A new approach to IRMPD using selective ion dissociation in a quadrupole ion trap.
Infrared multiphoton photodissociation (IRMPD) in a quadrupole ion trap is not selective for a parent ion. Product ions are decreased in abundance by continuous sequential dissociation and may be lost below the low mass cut-off. The IRMPD process is made selective by resonantly exciting trapped ions into an axially offset laser path. Product ions form and collisionally relax out of the laser path to accumulate in the center of the trap. The technique, termed selective broadband (SB) IRMPD, limits sequential dissociation to preserve first generation product ion abundance. The abundances of larger product ions are maximized by completely dissociating the parent ion, but continuous sequential dissociation does not form small product ions below the low mass cut-off associated with conventional IRMPD. Smaller product ions are further increased in abundance in another tandem mass spectrum by performing sequential stages of SB-IRMPD, adjusting the trapping rf amplitude to dissociate larger product ions at the same q(z) range. Thermal assistance is used to perform SB-IRMPD at higher bath gas pressures for increased sensitivity.


Structural brain network connectivity in trichotillomania (hair-pulling disorder).
Neuroimaging studies suggest involvement of frontal, striatal, limbic and cerebellar regions in trichotillomania, an obsessive-compulsive related disorder. However, findings regarding the underlying neural circuitry remains limited and inconsistent. Graph theoretical analysis offers a way to identify structural brain networks in trichotillomania. T1-weighted MRI scans were acquired in adult females with trichotillomania (n = 23) and healthy controls (n = 16). Graph theoretical analysis was used to investigate structural networks as derived from cortical thickness and volumetric FreeSurfer output. Hubs, brain regions with highest connectivity in the global network, were identified, and group differences were determined. Regions with highest connectivity on a regional level were also determined. There were no differences in small-worldness or other network measures between groups. Hubs in the global network of trichotillomania patients included temporal, parietal, and occipital regions (at 2SD above mean network connectivity), as well as frontal and striatal regions (at 1SD above mean network connectivity). In contrast, in healthy controls hubs at 2SD represented different frontal, parietal and temporal regions, while at 1SD hubs were widespread. The inferior temporal gyrus, involved in object recognition as part of the ventral visual pathway, had significantly higher connectivity on a global and regional level in trichotillomania. The study included women only and sample size was limited. This study adds to the trichotillomania literature on structural brain network connectivity. Our study findings are consistent with previous studies that have implicated somatosensory, sensorimotor and frontal-striatal circuitry in trichotillomania, and partially overlap with structural connectivity findings in obsessive-compulsive disorder.


Nebulized surfactant for experimentally induced otitis media with effusion.
Eustachian tube dysfunction frequently results in clinical evidence of otitis media with effusion (OME). Surface active substances, surfactants, are hypothesized to play a role in normal eustachian tube function. Recent work in a rodent model has demonstrated improved eustachian tube function with topical application of surfactants to the middle ear. A novel, noninvasive, and clinically practical method of delivering surfactant to the eustachian tube was studied in a gerbil model of OME. Otitis media with effusion was experimentally induced in 20 gerbils by transtympanic inoculation of heat-killed Streptococcus pneumoniae. This represents a well established model for creating a serous effusion in the gerbil that significantly increases eustachian tube opening pressure. Effusion developed in 27 of 40 ears (67.5%) after inoculation. An inhaled nebulized surfactant was used to treat the animals with microscopically confirmed OME in one or both ears. The treatment period was 5 days. Eustachian tube opening studies were performed on both affected and nonaffected animals. Successful eustachian tube opening pressures were obtained in 30 of 36 ears (83.3%). The mean opening pressure for ears without effusion (healthy ears) was 42.8 mmHg. The mean opening pressure for ears with effusion in animals treated with nebulized surfactant was 41.4 mmHg. The difference between these mean values was not statistically significant (t = 0.32; p > 0.50). This pilot study suggests that inhaled nebulized surfactant may be efficacious in treating eustachian tube dysfunction when manifested in disorders such as OME.


Sex Differences and Gender Diversity in Stress Responses and Allostatic Load Among Workers and LGBT People.
Measuring biological sex differences and socio-cultural gender diversity provides insights into individual variation in stress physiology and the development of "sex-specific" diseases. PURPOSE OF REVIEW: In this selective review, we summarize recent findings that assess sex and gender in relation to the stress hormone cortisol and multi-systemic physiological dysregulation called allostatic load. The focus of this research centers on workers as well as sexual and gender minorities as these populations provide unique insights into sex and gender at various levels of analysis from the micro-level to the macro-level. RECENT FINDINGS: Male/female sex, sex hormones, gender identity, gender roles, and sexual orientation are all variables that are distinctly correlated with stress physiology. Beyond identifying patterns of vulnerability to stress-related diseases, pathways towards resilience are of high priority in emerging literature. Stress scientists must account for both sex and gender in biobehavioral research. Future directions should assess macro-level constructs like institutionalized gender, occupational sex composition, and structural stigma to better understand the social determinants of health.


Elevated EGF Levels in the Blood Serum of Dogs with Periodontal Diseases and Oral Tumours.
Paradontopathy and neoplasms of the oral cavity represent one of the greatest challenges in human and animal dentistry. EGF plays a key role in maintaining the integrity and proper rate of cell proliferation in normal oral epithelium. The aim of the present study was to study serum levels of EGF in dogs diagnosed with periodontal diseases and oral cavity tumours. The samples comprised of cancerous tissue sections and serum obtained from dogs of various breeds, aged between 5-13 years. Serum EGF concentrations were measured by an immunoenzymatic method. The median for EGF concentration in serum of dogs suffered from severe periodontal diseases was greater when compared to the control group. EGF concentration in dogs with malignant tumours was significantly higher than in those with non-malignant growths. A positive correlation between EGF concentration and tumour size was also observed. EGF level in dogs diagnosed with benign tumours was comparable to the control group. The blood serum level of EGF increases significantly in patients with malignant oral tumours and advanced periodontal disease. In malignant tumours, the high level of EGF correlates with the size and invasiveness of the neoplasm.


Removal of ofloxacin from wastewater by chloride electrolyte electro-oxidation: Analysis of the role of active chlorine and operating costs.
Electro-oxidation (EO) has received increasing attention as an efficient and green method for removing pollutants from wastewater. Chloride anions (Cl-), which commonly exist in wastewater, can act as an electrolyte for the EO process. However, the role of reactive chlorine species (RCS) generated near electrodes is often underestimated. In this study, we generated hydroxyl radicals (OH) and RCS in a boron-doped diamond (BDD) electrode system and investigated its degradation mechanism for ofloxacin (OFX) removal. The findings suggested that OFX degradation was dominated by OH existing near the anode in solution, with RCS playing a supporting role. Based on the produced intermediates, we proposed an OFX decomposition pathway. The biological toxicities of the intermediates were evaluated through the ECOSAR and T.E.S.T. procedure. Nearly half of the intermediates are less toxic than the parent compound. After optimizing the operating parameters by the response surface methodology, 20 mg/L OFX was almost completely degraded after 10 min of reaction in 1.45 g/L NaCl with a current density (j) of 18 mA/cm2, and the total organic carbon was decreased by 30.55 %. The energy consumption and current efficiency were 0.648 kW·h/gTOC and 8.65 %, respectively. Comparing the operating costs of the proposed and other EO methods, our method emerged as a viable new treatment scheme for similar polluted wastewaters. This study aims to comprehensively understand the potential application value of BDD electrodes in the treatment of Cl- containing organic wastewater.


Uptake, bioaccumulation, and biodegradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and its reduced metabolites (MNX and TNX) by the earthworm (Eisenia fetida).
Uptake and accumulation kinetics of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and its two major N-nitroso metabolites, hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX), in earthworms was investigated. Results indicated that RDX and its N-nitroso metabolites were rapidly absorbed into earthworms (Eisenia fetida), reaching the highest concentrations within a few days. Accumulation of RDX was greater than its N-nitroso metabolites, as evidenced by a higher bioconcentration factor (BCF); BCFs were 1.86, 0.39, and 0.05 for RDX, MNX, and TNX, respectively. RDX and its N-nitroso metabolites were also rapidly eliminated from the earthworm and/or transformed to other metabolites, as evidenced by the rapid decrease of test compounds in earthworms after reaching their highest concentrations. The uptake of MNX and TNX increased as exposure concentration increased. Although these earthworms might (anaerobically) degrade RDX to MNX and MNX to TNX, it is hypothesized that this process would be slow. Other biotransformation pathways may be involved in biodegradation of RDX and its N-nitroso metabolites due to the fact that concentrations of tested compounds decreased in both soil and earthworms. It is hoped that these data can be used to refine environmental management strategies for RDX and for performing specific risk assessments of RDX and its N-nitroso metabolites.


Effect of common inorganic anions on iron-catalyzed secondary brown carbon formation from guaiacol.
Brown carbon (BrC) is the important component of aerosol with strong UV-visible absorbance. However, the formation of BrC is still elusive. Inorganic anions, e.g., Cl-, NO3- and SO42-, exist ubiquitously in the atmosphere, while their effects on the formation of BrC are poorly understood. In this study, we have systematically investigated the effects of pH (1, 2 and 3), inorganic anion (Cl-, NO3- and SO42-) and ionic strength (0.1, 0.5 and 1.0 M) on BrC generation process by measuring the optical, aggregation and product properties. Our results clearly show that the three factors strongly affect the BrC formation by influencing the oxidation activity and the complexation capability of different Fe(III) species. Marcus theory was used in this research to calculate the oxidation activity of different Fe(III) species. Among all the species of Fe(III), FeOH2+ is the most reactive form in the BrC formation reaction. Furthermore, the aggregation process of BrC was also studied, which is affected by different anions due to their different concentration and hydrability, and SO42- exhibits the highest efficiency to induce the aggregation of BrC. This study will deepen our understanding about the natural formation of BrC under environmentally relevant conditions, and be beneficial for controlling the production of atmospheric particulates and the subsequent health effects.


Apicoplast triose phosphate transporter (TPT) gene knockout is lethal for Plasmodium.
The C3, C5, C6 type sugar phosphate transporters bring sugars inside apicoplast, thus providing energy, reducing power and elements like carbon to apicoplast. Plasmodium berghei has two C3 type sugar phosphate transporters in the membrane of apicoplast: triose phosphate transporter (TPT) and phosphoenolpyruvate transporter (PPT). Here we report that P. berghei TPT knockout parasites failed to survive. However, PPT knockout parasite behaved similar to the wild type in the blood stages. The absence of PPT in other life stages, leads to defects in the development of parasite and was required at both mosquito as well as liver stages. This study also underlines the essentiality of triose transporters for apicoplast and its downstream pathways.


Drug treatment of rheumatic diseases in the 1990s. Achievements and future developments.
There have been several advances in the therapy of arthritis. These are based on better understanding of the pathogenesis of rheumatic diseases, re-evaluation of previous therapeutic concepts such as combination therapy, and developments within biotechnology. There are 4 main areas of development, mainly involving the treatment of inflammatory synovitis. The first is with anti-inflammatory drugs, where there has been a focus on reducing gastrointestinal toxicity through the use of combination preparations such as diclofenac-misoprostol, and the introduction of drugs with more selectivity for cyclo-oxygenase-2 inhibition such as meloxicam. An additional approach has been the development of anti-inflammatory drugs such as tenidap which also control cytokine metabolism. The second area is slow-acting antirheumatic drugs with the introduction of cyclosporin as a single agent or in combination with methotrexate, the development of immunomodulating drugs such as leflunomide, and the demonstration that some antibiotics such as minocycline have slow-acting effects. The third area is the use of corticosteroids including the development of deflazacort as a bone sparing agent, the greater use of intramuscular depot steroids and the validation of low-dose oral corticosteroids in early rheumatoid arthritis. Finally, there have been advances in the biotechnology area with the demonstration that cytokine immunotherapy such as antibodies to tumour necrosis factor can rapidly improve the symptoms of rheumatoid arthritis, and that T cell immunotherapy with antibodies to the CD4 receptor may be effective in reducing synovitis. Many of these agents have not yet been introduced into clinical practice but they show the diversity of drug development and suggest the likelihood of major therapeutic benefits in the next few years.


Effect of intracoronary verapamil on infarct size in the ischemic, reperfused canine heart: critical importance of the timing of treatment.
In an effort to determine whether the beneficial effect of calcium blocking drugs occurs only during ischemia or during reperfusion as well, anesthetized dogs were subjected to 3 hours of occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion. In protocol A, intracoronary verapamil (0.01 mg/kg/min) was begun 90 minutes after coronary occlusion and continued for 1 hour into the reperfusion phase (n = 6) while a control group received an infusion of saline solution (n = 6). In vivo area at risk determined by dye injection was 29 +/- 3% of the left ventricle (+/- standard error of the mean) in the control group and 30 +/- 3% in the verapamil group (difference not significant [NS]), whereas the area of necrosis determined by triphenyltetrazolium staining and expressed as a percent of area at risk was smaller in the verapamil group (29 +/- 8%) than in the control group (57 +/- 8%, p less than 0.05). In protocol B, verapamil infusion into the left anterior descending coronary was begun 5 minutes before blood reperfusion and continued throughout the 3-hour reperfusion phase. Area at risk was similar in both groups (control, 25 +/- 1%, n = 8; verapamil, 28 +/- 2%, n = 8, NS); area of necrosis expressed as a percentage of area at risk was 49 +/- 6% in the control group and 45 +/- 10% in the verapamil group (NS). Therefore, calcium blockade of ischemic myocytes delays death and enhances salvage produced by reperfusion. However, calcium blockade begun after prolonged coronary occlusion does not enhance reperfusion-induced myocardial salvage.


Access to spirocyclic oxindoles via N-heterocyclic carbene-catalyzed reactions of enals and oxindole-derived α,β-unsaturated imines.
A diastereoselective access to β-lactam fused spirocyclic oxindoles and related compounds bearing all carbon spiro centers is described. This N-heterocyclic carbene-catalyzed process employed challenging β,β-disubstituted α,β-unsaturated imines to react with enals.


Virus-associated arthritis.
The occurrence of arthritis in patients who were infected by a virus has been widely observed. In some cases, the clinical appearance seems to resemble that of rheumatoid arthritis. The mechanism by which the viral infection proceeds to the arthritic manifestation is, however, still to be investigated. Several biological and immunological pathways are suggested to be involved in the pathogenesis. The representatives of such potentially 'arthritogenic' viruses include human T-cell lymphotropic virus type I (HTLV-I), which causes destructive inflammatory arthritis in model animals. Other examples are hepatitis C virus and rubella virus. Clinical and pathological features of these virus-induced forms of arthritis are discussed.


Experimental and clinical evidence of the antidepressant effect of a beta-adrenergic stimulant.
A group of 49 patients with depressive illness were treated in an uncontrolled study by the intravenous administration of the beta-adrenergic stimulant, salbutamol. The results suggested a rapid antidepressant action in the majority of cases without significant adverse effects.


Shape configuration and category-specificity.
We examined the neural correlates of visual shape configuration, the binding of local shape characteristics into wholistic object descriptions, by comparing the regional cerebral blood flow associated with recognition of outline drawings and fragmented drawings. We found no areas that responded more to fragmented drawings than to outline drawings even though fragmentation had a clear impact on recognition performance. Instead, a region extending from the inferior occipital gyri to the middle parts of the fusiform gyri was activated during shape configuration of both outline drawings and fragmented drawings. We also examined whether fragmentation had different impact on the recognition of natural objects and artefacts and found that recognition of artefacts was more affected by fragmentation than recognition of natural objects. Thus, the usual finding of an advantage for artefacts in difficult object decision tasks, which is also found in the present experiments with outlines, is reversed when the stimuli are fragmented. This interaction between category (natural versus artefacts) and stimulus type (outlines versus fragmented forms) is in accordance with predictions derived from a recent account of category-specificity and lends support to the notion that category-specific impairments can occur for both natural objects and artefacts following damage to pre-semantic stages in visual object recognition. The implications of the present findings are discussed in relation to theories of perceptual organization, visual object recognition and category-specificity.


Transition effects from laparocscopic to robotic surgery skills in small cavities.
Conventional laparoscopic surgery (LS) is being challenged by the ever-increasing use of robotic surgery (RS) to perform reconstructive procedures. The purpose of this study was to assess the acquisition of skills in both techniques and the potential transfer of skills from one technique to the other when restricted spaces are involved. A preclinical randomized crossover study design was implemented. Twelve subjects performed two different reproducible drill procedures: "Thread the Ring" (TR) and "Transfer the Plot" (TP). To assess surgical proficiency in confined workspaces, these exercises were performed with LS and RS technology in a pediatric laparoscopic surgery (PLS) simulator. Each performance was recorded and evaluated by two reviewers using objective structured assessment of technical skills (OSATS). The times to complete the TP and the TR procedure were significantly shorter with RS compared to LS (64 s vs. 319 s; p < 0.0001 for both TP and TR). A significant transfer effect of skills between LS and RS was noted for the TP exercise (p = 0.006). The percentage improvement was greater overall with LS, meaning a higher number of trials were required to adequately master the procedure. This study demonstrated that RS performed significantly better compared to LS on pediatric simulation devices. A transfer effect was identified from LS to RS exclusively. The learning curves showed that progression was definitely longer with LS. These results, indicate that novice surgeons should be encouraged to persist with learning LS, and they support the use of a pediatric robotic simulation device.


Binding mechanisms of pesticides to soil humic substances.
This review-paper summarizes and discusses the nature of the binding forces involved and the types of mechanisms operating, often simultaneously, in the adsorption processes of several pesticides onto soil humic substances, humic acids and fulvic acids. These include ionic, hydrogen and covalent bonding, charge-transfer or electron donor-acceptor mechanisms, Van der Waals forces, ligand exchange, and hydrophobic bonding or partitioning. Experimental evidence obtained and interpretation provided for the various adsorption processes proposed are briefly presented and commented. The review ends with some concluding remarks and recommendations for future work needed to be done.


The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: clinical, seminal and biochemical characteristics.
Infertility affects 7%-12% of men, and its etiology is unknown in half of cases. To fill this gap, use of the male genital tract color-Doppler ultrasound (MGT-CDUS) has progressively expanded. However, MGT-CDUS still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study ("EAA ultrasound study") to assess MGT-CDUS characteristics of healthy, fertile men to obtain normative parameters. To report (a) the development and methodology of the "EAA ultrasound study," (b) the clinical characteristics of the cohort of healthy, fertile men, and (c) the correlations of both fertility history and seminal features with clinical parameters. A cohort of 248 healthy, fertile men (35.3 ± 5.9 years) was studied. All subjects were asked to undergo, within the same day, clinical, biochemical, and seminal evaluation and MGT-CDUS before and after ejaculation. The clinical, seminal, and biochemical characteristics of the cohort have been reported here. The seminal characteristics were consistent with those reported by the WHO (2010) for the 50th and 5th centiles for fertile men. Normozoospermia was observed in 79.6% of men, while normal sperm vitality was present in almost the entire sample. Time to pregnancy (TTP) was 3.0[1.0-6.0] months. TTP was negatively correlated with sperm vitality (Adj.r =-.310, P = .011), but not with other seminal, clinical, or biochemical parameters. Sperm vitality and normal morphology were positively associated with fT3 and fT4 levels, respectively (Adj.r = .244, P < .05 and Adj.r = .232, P = .002). Sperm concentration and total count were negatively associated with FSH levels and positively, along with progressive motility, with mean testis volume (TV). Mean TV was 20.4 ± 4.0 mL, and the lower reference values for right and left testes were 15.0 and 14.0 mL. Mean TV was negatively associated with gonadotropin levels and pulse pressure. Varicocoele was found in 33% of men. The cohort studied confirms the WHO data for all semen parameters and represents a reference with which to assess MGT-CDUS normative parameters.


Two deletion variants of Middle East respiratory syndrome coronavirus found in a patient with characteristic symptoms.
Significant sequence variation of Middle East respiratory syndrome coronavirus (MERS CoV) has never been detected since it was first reported in 2012. A MERS patient came from Korea to China in late May 2015. The patient was 44 years old and had symptoms including high fever, dry cough with a little phlegm, and shortness of breath, which are roughly consistent with those associated with MERS, and had had close contact with individuals with confirmed cases of MERS.After one month of therapy with antiviral, anti-infection, and immune-enhancing agents, the patient recovered in the hospital and was discharged. A nasopharyngeal swab sample was collected for direct sequencing, which revealed two deletion variants of MERS CoV. Deletions of 414 and 419 nt occurred between ORF5 and the E protein, resulting in a partial protein fusion or truncation of ORF5 and the E protein. Functional analysis by bioinformatics and comparison to previous studies implied that the two variants might be defective in their ability to package MERS CoV. However, the mechanism of how these deletions occurred and what effects they have need to be further investigated.


Diffusion-reaction model of positron annihilation for complex defect pattern.
The increasing structural complexity in modern material science is often associated with grain sizes in theµm- and the sub-µm-regime. Therefore, when positron annihilation is applied for studying free-volume type defects in such materials, positron trapping at grain boundaries (GBs) cannot be neglected, even when other defect types are in the primary focus. For this purpose, the available diffusion-reaction model for positron trapping and annihilation at GBs is extended to competitive trapping at two different types of intragranular defects. Closed-form expressions for the mean positron lifetime and the relative intensities of the defect-specific positron lifetime components are given. The model is presented for cylindrical-shaped crystallites, but is valid in the general sense for spherical symmetry as well with appropriate replacements. The model yields the basis for properly determining defect concentrations, even for the inconvenient but common case that one intragranular defect type exhibits a lifetime component similar to that in GBs. It turns out, that positron trapping at GBs matters even forµm-sized crystallites and should not be neglected for precise studies of intragranular defects.


Phenotypic methods for screening carbapenem-resistant Enterobacteriaceae and assessment of their antimicrobial susceptibility profile.
In this study, we used phenotypic methods to screen carbapenem-resistant Enterobacteriaceae (CREs) and evaluated their antimicrobial sensitivity profile. One hundred and seventy-eight CREs were isolated at a university hospital in south Brazil in a one-year period. Samples were assessed using disk diffusion tests with inhibitors of β-lactamases such as phenylboronic acid (AFB), cloxacillin (CLOXA), and ethylenediaminetetraacetic acid (EDTA). Strains with differences in zone diameters ≥ 5mm for disks supplemented or not were considered producers of carbapenemases. Klebsiella pneumoniae was the most prevalent CRE, which appeared in 80.3% cases (n = 143). Among clinical materials, the rectal swab was responsible for 43.4% of the isolations (n = 62), followed by urine (18.9%; n = 27). Among the CREs identified in this study, the growth of 56.7% (n = 101) isolates, which were putative producers of Klebsiella pneumoniae carbapenemase (KPC), were inhibited by AFB, whereas 7.3% (n = 13) isolates were inhibited by both AFB and CLOXA and were considered as putative producers of plasmid-mediated AmpC; approximately 3.4% (n = 6) were inhibited by EDTA, which possibly produced metallo-β-lactamase. Lastly, 32.6% (n = 58) cases showed negative results for AFB, CLOXA, and EDTA sensitivity, and represented another class of β-lactamases and/or mechanism of resistance. Phenotypic screening of CREs is important for clinical laboratories that monitor outbreaks of resistant microbes. Phenotypic tests that use carbapenemase inhibitors and enhancers such as AFB, CLOXA, and EDTA are necessary since they are good screening methods for the detection of carbapenemases.


Determination of human IgG and IgM class antibodies to West Nile virus by enzyme linked immunosorbent assay (ELISA).
An enzyme-linked immunosorbent assay (ELISA) was developed and used for the detection of IgG and IgM antibodies to West Nile virus in human sera. Thirteen paired sera of clinical cases and 24 control sera taken randomly from a blood bank repository were tested. The sera were reacted in microtiter plates coated with PEG-treated WNV antigen. IgG or IgM antibodies were quantitated by the use of alkaline-phosphatase-conjugated anti-human IgG or IgM antibodies. Of the 24 randomly collected serum samples, 7 were positive in the IgG-ELISA test. One positive by the IgM-ELISA was found to contain rheumatoid factor. In 12 of 13 paired sera of clinical cases, IgM as well as IgG antibodies were detected in the second serum sample taken about 3 wk after the onset of clinical signs. The IgM positive sera were screened for rheumatoid factor (RF) on IgG-coated plates. None of them contained RF. Antibody titers obtained by ELISA showed a good correlation with titers obtained by hemagglutination inhibition, complement fixation, and neutralization tests. The ELISA tests for detection of IgM and IgG antibodies to WNV therefore can replace the other serological methods for epidemiological surveillance and diagnostic purposes.


Differential effects of intra-midbrain raphe and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats.
Intra-median raphe nucleus (MRN) administration of the 5-HT(1A) receptor agonist 8-OH-DPAT decreases lateral hypothalamic self-stimulation thresholds and is reported to have biphasic effects following systemic administration. These experiments attempted to extend the previous findings to mesolimbic pathway self-stimulation at ventral tegmental area (VTA) electrodes. This study was conducted to provide comparative data for systemic and intra-dorsal raphe nucleus (DRN) and intra-MRN effects of 8-OH-DPAT on VTA self-stimulation. Male Sprague-Dawley rats with VTA electrodes were trained to respond for electrical stimulation. Systemic and intra-midbrain raphe 8-OH-DPAT effects on rate-frequency thresholds were measured. Systemic administration of WAY 100635 was used to confirm 5-HT(1A) receptor mediation of 8-OH-DPAT effects. 8-OH-DPAT (0.003-0.3 mg kg(-1) SC) increased rate-frequency thresholds and decreased maximal response rates. WAY 100635 alone (0.0125-0.1 mg kg(-1) SC) did not alter these measures. Intra-DRN and intra-MRN 8-OH-DPAT (5.0 microg) decreased rate-frequency thresholds without altering maximal response rates. Intra-DRN 8-OH-DPAT (0.1-5.0 microg) induced a slight decrease and intra-MRN 8-OH-DPAT a slight increase in locomotor activity. WAY 100635 (0.1 mg kg(-1)) blocked effects of 8-OH-DPAT on VTA self-stimulation. These results confirm threshold-decreasing effects of intra-MRN 8-OH-DPAT and extend this to the DRN and to VTA thresholds. Monophasic dose dependent increases in VTA thresholds following systemic 8-OH-DPAT are not equivalent to reports for hypothalamic self-stimulation. Differences between studies may be attributable to stimulation site and/or differences in threshold measurement procedures. Effects of WAY 100635 in this study indicate 5-HT(1A) receptor mediation of these 8-OH-DPAT effects.


Seasonal variation of chromophore composition in the eye of the Japanese dace, Tribolodon hakonensis.
The relationship between seasonal variation and the effect of several different environmental factors on chromophore composition was investigated in the eye of the Japanese dace, Tribolodon hakonensis which lives either in rivers or in the sea. Eyes obtained from river and sea populations had both retinal (A1) and 3,4-didehydroretinal (A2) all through the year but the ratio of these chromophores showed seasonal variation the relative amount of A2 was higher in winter and lower in summer. Besides seasonal variation, A2 showed marked differences depending on habitat: the highest proportion of A2 was 67% in January and the lowest 13% in July, in the river population, whereas in the sea population the highest and the lowest values were only 30 and 6%, respectively, during the same months. The seasonal variation in gonadosomatic index showed no correlation to variations in A2 proportion, and the maximum difference in water temperature between summer and winter was ca. 15 degrees C for both habitats. Because spectral conditions at the locations of capture of both river and sea populations were similar, we conclude that Japanese dace eyes are affected by exogenous factors related to differences between freshwater and seawater environments.


Induction of the shaking phenomenon by IgA class antispermatozoal antibodies from serum.
Serum was obtained from a woman with a high (greater than 1000) titre of antispermatozoal antibody of IgA immunoglobulin class determined by the indirect immunobead test (IBT). It was found that the serum could sensitize normal sperm to give a strong shaking reaction in the semen-cervical mucus contact test (SCMCT). The capacity to induce shaking was retained after absorption of the serum with protein A-sepharose, but lost after absorption with rabbit antihuman IgA. The results therefore suggest that antispermatozoal antibodies of IgA class from serum can induce shaking, and are consistent with the possibility that the Fc fragment (rather than secretory component or J-chain) may be important for induction of shaking in the conventional SCMCT.


Bipolar affective disorder and borderline personality disorder: Differentiation based on the history of early life stress and psychoneuroendocrine measures.
Borderline Personality Disorder (BPD) and Bipolar Affective Disorder (BD) have clinical characteristics in common which often make their differential diagnosis difficult. The history of early life stress (ELS) may be a differentiating factor between BPD and BD, as well as its association with clinical manifestations and specific neuroendocrine responses in each of these diagnoses. Assessing and comparing patients with BD and BPD for factors related to symptomatology, etiopathogenesis and neuroendocrine markers. The study sample consisted of 51 women, divided into 3 groups: patients with a clinical diagnosis of BPD (n = 20) and BD (n = 16) and healthy controls (HC, n = 15). Standardized instruments were used for the clinical evaluation, while the history of ELS was quantified with the Childhood Trauma Questionnaire (CTQ), and classified according to the subtypes: emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect. The functioning of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring a single plasma cortisol sample. Patients with BPD presented with more severe psychiatric symptoms of: anxiety, impulsivity, depression, hopelessness and suicidal ideation than those with BD. The history of ELS was identified as significantly more prevalent and more severe in patients (BPD and BP) than in HC. Emotional abuse, emotional neglect and physical neglect also showed differences and were higher in BPD than BD patients. BPD patients had greater severity of ELS overall and in the subtypes of emotional abuse, emotional neglect and physical neglect than BD patients. The presence of ELS in patients with BPD and BP showed significant difference with lower cortisol levels when compared to HC. The endocrine evaluation showed no significant differences between the diagnoses of BPD and BD. Cortisol measured in patients with BPD was significantly lower compared to HC in the presence of emotional neglect and physical neglect. A significant negative correlation between the severity of hopelessness vs cortisol; and physical neglect vs cortisol were found in BPD with ELS. The single cortisol sample showed a significant and opposite correlations in the sexual abuse diagnosis-related groups, being a negative correlation in BD and positive in BPD. Considering the need for a multi-factorial analysis, the differential diagnosis between BPD and BD can be facilitated by the study of psychiatric symptoms, which are more severe in the BPD patients with a history of early life stress. The function of the HPA axis assessed by this cortisol measure suggests differences between BPD and BP with ELS history. The integrated analysis of psychopathology, ELS and neuroendocrine function may provide useful indicators to differentiate BPD and BD diagnoses. These preliminary data need to be replicated in a more significant sample with improved and multiple assessments of HPA axis activity.


Focused utilization review strategies.
Researchers from the Michigan Health Care Education and Research Foundation, a research affiliate of Blue Cross and Blue Shield of Michigan, compared three focused utilization review (UR) strategies to determine which method most effectively and efficiently identifies nonacute inpatient hospital admissions. Intensity, Severity, Discharge-Appropriateness (ISD-A) criteria were used to identify nonacute admissions in 8,973 cases in 73 Michigan hospitals. Significant proportions of nonacute admissions were found in medical, psychiatric, and substance abuse cases; surgical admissions had the lowest rates. Strategies involving the concentration ratio were most effective at indicating potential efficiency gains. Focused UR on Diagnosis-Related Groups (DRGs) with nonacute rates greater than 15% captured 41% of admissions and accounted for 85% of nonacute admissions, 85% of nonacute days, and 80% of potential dollar savings. This suggests that UR efforts focused primarily on DRGs with high nonacute rates would significantly improve the efficiency and effectiveness of the overall UR process.


The site of synthesis and functions of acute phase plasma proteins: close relationship with the reticulo-endothelial system.
The evidence that the acute phase glycoproteins of plasma are synthesized by the liver parenchymal cells is critically examined, and is found to be inconclusive. Some evidence is cited which favors the reticulo-endothelial system (RES) in general, and Kupffer cells in particular, as the site of synthesis of these proteins: 1. The entire RES contains non-glycogenic periodic acid Schiff-positive substances. 2. The diseases which affect glycoprotein levels are also known to affect the function of the RES. 3. When the animal is subjected to stress, the RES function is initially depressed and then stimulated. A similar biphasic behavior is shown by plasma glycoprotein levels. 4. Adrenal cortico-steriods are the major regulators of the RES function and of the synthesis of acute phase proteins. Moreover, both are stimulated at low concentrations, and depressed at high concentrations of the hormone. Some of the glycoproteins of the acute phase (prothrombin, the third component of complement, haptoglobin, transferrin and ceruloplasmin) have defense-related functions. The others seem to participate in phenomena like detoxification, promotion of phagocytosis, wound healing, prevention of tissue injury by lysosomal enzymes, prevention of trauma and recovery from inflammation. It is proposed that the acute phase proteins, together with antibodies, form major components of the definse system, and the RES attempts to deal with injury by mobilization of increased amounts of these substances.


Probable adverse drug reactions in a rural geriatric nursing home population: a four-year study.
To quantitate probable adverse drug reactions (ADRs) in a geriatric nursing homes population. A repeated measures prospective study. Two nursing home populations in rural Georgia. All 332 residents present for 30 or more days over a 4-year period. Admission and monthly drug regimen review for each resident, Naranjo algorithm assessment of each ADR, with monthly reports to attending physicians and follow-up within the next month. There were 444 probable ADRs in 217 of 332 residents (67.4%) during this period. The 217 residents had a mean 1.9 +/- 1.3 probable adverse drug reactions (range, 1-9). The ADR group differed statistically from the rest of the population only in the number of drugs per patient (7.8 +/- 2.6 vs 3.3 +/- 1.3), which was almost twice the number of active problems present in both the ADR (4.0 +/- 0.9) and non-ADR populations (3.8 +/- 1.4). The organ systems most commonly involved in the 444 ADRs observed were cardiovascular (188), central nervous system (129), gastrointestinal (82), endocrine (41), immune (17), hematologic (7), pulmonary (6), and renal (5). The drugs most commonly implicated in ADRs were, in decreasing order, diuretics, antipsychotics, anxiolytics, potassium supplements, digoxin, NSAIDs, insulin, theophylline, H2-receptor antagonists, antiinfectives, anticonvulsants, and thyroid supplements. There were 39 multiple drug ADRs in 34 patients. In decreasing order the drug classes in multiple ADRs were CNS depressants, antihypertensives, potassium-altering therapy, and NSAIDs. Numerous patients had repetitions of the same ADR, especially with antipsychotics, NSAIDs, and insulin. ADRs are a common occurrence in a geriatric nursing home population, and may be related to inadequate attention to the patients history as well as to unrealistic therapeutic endpoints.


Model-informed precision dosing to optimise immunosuppressive therapy in renal transplantation.
Immunosuppressive therapy is pivotal for sustained allograft and patient survival after renal transplantation. However, optimally balanced immunosuppressive therapy is challenged by between-patient and within-patient pharmacokinetic (PK) variability. This could warrant the application of personalised dosing strategies to optimise individual patient outcomes. Pharmacometrics, the science that investigates the xenobiotic-biotic interplay using computer-aided mathematical modelling, provides options to describe and quantify this PK variability and enables identification of patient characteristics affecting immunosuppressant PK and treatment outcomes. Here, we review and critically appraise the available pharmacometric model-informed dosing solutions for the typical immunosuppressants in modern renal transplantation, to guide their initial and subsequent dosing.


Global ocean redox changes before and during the Toarcian Oceanic Anoxic Event.
Mesozoic oceanic anoxic events are recognized as widespread deposits of marine organic-rich mudrocks temporally associated with mass extinctions and large igneous province emplacement. The Toarcian Oceanic Anoxic Event is one example during which expanded ocean anoxia is hypothesized in response to environmental perturbations associated with emplacement of the Karoo-Ferrar igneous province. However, the global extent of total seafloor anoxia and the relative extent of euxinic (anoxic and sulfide-rich) and non-euxinic anoxic conditions during the Toarcian Oceanic Anoxic Event are poorly constrained. Here we present estimates of the global total anoxic and euxinic seafloor areas before and during the Toarcian Oceanic Anoxic Event based on rhenium and molybdenum enrichments, respectively, in organic-rich mudrocks of the Fernie Formation (British Columbia, Canada). We find that mass balance models depict an expansion of up to ~7% total seafloor anoxia, which was dominated by euxinia, at the onset of the Toarcian Oceanic Anoxic Event, followed by a contraction before the end of the event. The global ocean redox trends revealed by the rhenium data mirrors the collapse and recovery patterns of global ammonite and foraminiferal biodiversity.


Discovery of a novel native bacterium of Providencia sp. with high biosorption and oxidation ability of manganese for bioleaching of heavy metal contaminated soils.
Heavy metal removal from contaminated soils is a long-term challenging problem important for global economics, environment, and human health. Marine and freshwater-originated Mn(II)-oxidizing bacteria are considered as the promising bioremediation agents for environmental applications. However, practical application of soil-originated Mn(II)-oxidizing bacteria remains to be developed for contaminated soil remediation. In this work, the Mn(II) biosorption/oxidation mechanism of a new soil-originated bacterium and its bioleaching efficiency of heavy metals from soils was studied in detail. First, we found, isolated and identified a new highly Mn(II)-tolerant bacterial strain Providencia sp. LLDRA6 from heavy metal-contaminated soils. Next, strain LLDRA6 demonstrated its high Mn(II) biosorption capacity in aqueous solution. Then, Mn(II) adsorption by LLDRA6 was largely proven to be a synergistic effect of (i) Mn(II) precipitation on the cell surface, (ii) oxidation of Mn(II) into BioMnOx on the cell surface, and (iii) intracellular accumulation of insoluble MnCO3. Finally, combination bioleaching by the bacterium of Providencia sp. LLDRA6 and its formed BioMnOx was proposed to develop a potential environment-friendly and cost-effective technique to remediate severely heavy metal-contaminated soils. The bioleaching tests demonstrated that the combination of Providencia sp. LLDRA6 and BioMnOx exhibited an excellent removal efficiency for heavy metals of Pb (81.72%), Cr (88.29%), Cd (90.34%), Cu (91.25%), Mn (56.13%), and Zn (59.83%) from contaminated soils, resulting in an increase of removal efficiency in the range of 1.68-26.4% compared to Providencia sp. LLDRA6 alone. Moreover, the bacterial leachate facilitated the residual fraction of metals to transform into the easily migratory fractions in soils. These findings have demonstrated that strain LLDRA6 has high adsorption ability to remove heavy metals from contaminated soils, thus providing a promising bio-adsorbent for environmental bioremediation.


Endoscope or microscope-guided pediatric tympanoplasty? Comparison of grafting technique and outcome.
To review experience from the introduction of totally endoscopic ear surgery (TEES) to a pediatric tympanoplasty practice to identify factors influencing technique selection and successful outcome. Prospective cohort study. Analysis of prospectively acquired data from a consecutive series of 295 surgeries for tympanic membrane perforation over a 12-year period. Success of perforation closure was compared between microscope and TEES grafting techniques. Impact of the acquisition of endoscopic techniques and equipment were compared with annual proportion of cases completed by TEES. Of 267 tympanoplasties, 109 (41%) were completed with TEES and 158 by a postauricular approach. The proportion completed with TEES increased gradually to 97% of cases as equipment and expertise were acquired. Young age did not prevent TEES tympanoplasty. Two hundred nineteen of 250 (88%) perforations were closed successfully by tympanoplasty, with equivalent closure rates between TEES and postauricular approaches. Underlay of tragal perichondrium was less successful than lateral graft technique using TEES (P = .04, Fisher exact test). "Push-through" myringoplasty using a microscope or endoscope was least successful (19 of 28 (68%), P = .005). The median length of stay was 13 hours shorter for TEES than postauricular tympanoplasty (P = .04, Mann-Whitney rank sum test). Wound complications occurred in five (3%) postauricular cases and one TEES case. TEES tympanoplasty is feasible in a large majority of children given appropriate equipment and surgical experience. Nonautogenous graft material is ideal for this minimally invasive approach. TEES is recommended as providing equivalent likelihood of perforation closure to the post-auricular approach but with less postoperative morbidity. 2b. Laryngoscope, 127:2659-2664, 2017.


Electron spin resonance investigations of membrane proteins in erythrocytes in muscle diseases. Duchenne and myotonic muscular dystrophy and congenital myotonia.
Comparison of electron spin resonance spectra of spin labeled erythrocyte membranes from patients with the dystrophic conditions Duchenne and myotonic muscular dystrophy with those of normal controls suggests that alterations in membrane protein conformation and/or organization are present in these disease states. These protein alterations are not apparent in the non-dystrophic disease congenital myotonia. The results suggest a correlation between changes in the physical state of proteins in membranes with the presence of dystrophy. In addition, the present results from erythrocytes lend support for the concept of a generalized membrane defect in these diseases.


Effects of triiodothyronine on the synthesis of sulfolipids by oligodendrocyte-enriched glial cultures.
Glial cultures were obtained from the brains of 1-week-old rats and were grown in a chemically defined, serum-free medium. We investigated the development of oligodendrocytes in these cultures and the synthesis of sulfolipids in the presence and absence of triiodothyronine (T3) in the medium: (1) In the presence of T3, the incorporation of [35S]sulfate into sulfolipids exhibited a developmental profile which is comparable to that found in the developing brain in vivo. A sharp peak of sulfolipid synthesis was observed at day 5 in vitro, which is equivalent to day 12 after birth. As observed in vivo, the percentage of label incorporated into sulfogalactosyldiradylglycerols decreased with time in culture. (2) Addition of T3 to the medium stimulated sulfolipid synthesis by oligodendrocytes in a dose-related manner (optimal T3 concentration, 30 nM). The hormone also enhanced the rates of cholesterogenesis and lipogenesis but to a lesser extent than sulfolipid synthesis. (3) The temporary omission of T3 from the medium resulted in lower rates of sulfolipid synthesis that could not be restored by readdition of T3. This inhibitory effect was most pronounced if the hormone was omitted from the medium on days 2 and 3 in culture. (4) Omission of T3 also resulted in the development of fewer oligodendrocytes in the cultures. Our results show that T3 is essential for the development of oligodendrocytes in our neurone-free culture system. They also indicate that the stimulation of myelination by thyroid hormones can, at least partially, be explained as a direct effect of T3 on oligodendrocytes, independent of an effect of T3 on neuronal growth.


Critical care in East Asia. Little dragons and sleeping giants.
Southeast Asia is the world's region of most rapid economic growth. The countries in the region vary widely in annual per capita income and health expenditure. In the less wealthy countries, intensive care must compete for resources with basic public health programs and primary care, limiting public sector resources. In the wealthier countries and private hospitals in the region, intensive care units are well established but the organizational structure is still evolving, and there are few full-time intensivists. Most countries now have a Society of Intensive or Critical Care Medicine. Specialist training and examination systems for Intensive Care are established in Hong Kong, Taiwan, and the Philippines.


The role of non-commercial cyprinids in maintenance and spread of the opisthorchiasis focus in the middle Ob River basin (Tomsk region, Russia).
The study assessed the role of non-commercial cyprinid species in maintaining the opisthorchiasis focus in the middle Ob River basin, Tomsk region, Russia. The source of O. felineus infection for humans and carnivores is fish of the family Cyprinidae. This is the most numerous family, 14 species live in the middle Ob River basin, which includes 6 commercial species and 8 non-commercial species. This study aimed to investigate the current situation on infestation of non-commercial cyprinids with O. felineus metacercariae and their role in maintaining and spreading the natural focus of opisthorchiasis in the middle Ob River basin. We investigated 4 non-commercial species (tench, sunbleak, common bleak, gudgeon), which are highly abundant in water bodies. Tench, common bleak and gudgeon are objects of amateur fishing. These species are traditionally included in the diet of the local population. Opisthorchis felineus metacercariae were recorded in muscles of all the examined fish species. The identification of metacercariae was confirmed by morphological methods and PCR diagnostics. Tench and sunbleak are the main sources of opisthorchiasis infection in the floodplain lakes of the Ob River basin (the prevalence of tench infection is 89.3% and mean intensity of infection is 11.2 metacercariae per fish, the prevalence of sunbleak infection is 50.9% and the intensity of infection is 4.25 metacercariae per fish). The prevalence of infection in the introduced common bleak from the rivers of the middle Ob River basin is rapidly increasing from 2.4 (2016-2018) to 37.5% (2020-2021), and mean intensity of infection increased from 1 to 4.15. The epizootic state of water bodies in the middle Ob River basin remains unfavorable in relation to opisthorchiasis. Tench, common bleak and sunbleak, along with ide and dace, are the main source of infection for humans and animals, which is evidenced by high infection with Opisthorchis felineus metacercariae in these numerous fish species. They pose the greatest danger of infection of people and animals with opisthorchiasis. These species should be included in the campaign to avoid raw and poorly cooked fish in the diet. In addition, such species as roach, bream and sunbleak also pose the danger of infection with opisthorchiasis, but to a lesser extent.


Rhenium-Catalyzed Reduction of Carboxylic Acids with Hydrosilanes.
Re2(CO)10 efficiently catalyzes the direct reduction of various carboxylic acids under mild conditions (rt, irradiation 350 or 395 nm). While aliphatic carboxylic acids were readily converted to the corresponding disilylacetals with low catalyst loading (0.5 mol %) in the presence of Et3SiH (2.2 equiv), aromatic analogues required more drastic conditions (Re2(CO)10 5 mol %, Ph2MeSiH 4.0 equiv) to afford the corresponding aldehydes after acid treatment.


Simulation of conformational possibilities of DNA via calculation of nonbonded interactions of complementary dinucleoside phosphate complexes.
Using classical potential functions, we carried out potential-energy calculations on the complementary deoxydinucleoside phosphate complexes dApdA:dUpdU, dUpdA:dUpdA, and dApdU:dApdU. All dihedral and bond angles, except those of the nitrogen bases, were varied. The resulting minimum-energy conformations of the complexes are close to DNA A- and B-family conformations, with a typical arrangement of the nitrogen bases. The dihedral and bond angles of one of the molecules forming the complex can thereby differ by several degrees from those of the other molecule. For different base sequences, some dihedral and bond angles may vary over a range of several degrees without appreciably changing the total energy of the complex. Some low-energy conformations of the complexes corresponding to other regions of the conformational space are also found. The biological consequences of possible changes in dihedral and bond angles, occurring on interaction with other molecules, are discussed.


The "Make Surgical Pathology Easy" project: learning Pathology through tailored digital infographics - the case for renovation of an old teaching method.
The term 'infographics' is a blend of the two words "information" and "graphics". Infographics can be described as 'information visualizations', conceived as visual translation of data including text, numbers, graphs, charts, drawings and so on. Visual representations are a fundamental part of scientific communication. They match the need to organize different pieces of information in a coherent and synthetic structure and constitute one of the most effective methods scientists rely on to divulge their findings. In particular, infographics provide an overview of key points regarding specific topics in a form that promotes quick learning and knowledge retention. They can be presented in printed or digital formats, being the latter particularly suitable for a global-scale diffusion via social media or websites. In recent years, many pathologists have started developing digital infographics as a strategy for providing free educational contents on Facebook, Twitter or websites. In the present review, we focus on the value of digital infographics to summarize various aspects of Surgical and General Pathology. They shed light on diagnostic criteria, differentials and predictive/prognostic markers for many diseases, being a useful learning tool both for residents and practicing pathologists. In this paper, the model of infographics ideation, processing and sharing to an online audience is described and the impact of infographics on knowledge processes in Pathology is investigated.


Chronospeciation of uranium released in soil during a long-term DU shell weathering experiment.
Corrosion process was investigated of depleted uranium (DU) ammunition fragments buried for three years in aerobic soils continuously irrigated with water. The continuing corrosion process was triggered through formation of soluble uranyl oxyhydrate phases such as metaschoepite and becquerelite, which were identified by micro-Raman and X-ray diffraction spectroscopy. The soil was not amended by phosphates and, therefore, no uranyl phosphates were found as corrosion products on the DU surfaces by X-ray photoelectron spectroscopy. A speciation modelling at high temporal sequence (chronospeciation approach) indicated that the abundant Fe oxyhydroxides in the soil immobilized the U(IV) released through DU corrosion. During the first two years, therefore, only <10 mg of U(VI) was thus found in the leachates from the soil columns, even though >3 g of DU had been corroded. However, the degree of this immobilization was found to be controlled by the amount of dissolved inorganic and organic carbon (DIC and DOC) in the soil pore water providing for U(VI) complexation competing with surface complexation by the Fe hydroxides. The chronospeciation approach applied is useful to improve our understanding and ability to predict the long-term fate of U(VI) and the mechanisms controlling U(VI) mobility in soil contaminated with DU shells.


The place of B-mode ultrasonography, shear-wave elastography, and superb microvascular imaging in the pre-diagnosis of androgenetic alopecia.
Androgenetic alopecia (AGA) is the most common cause of hair loss in males. Physical examination and history are the most important examinations in diagnosis of the disease. As yet, there is no diagnostic method to be able to determine which individuals will develop AGA. Shear-wave elastography (SWE) is a novel diagnostic tool, which can evaluate tissue stiffness. Superb microvascular imaging (SMI) can determine low flow in microvessels. The aim of the current study was to determine whether or not AGA would develop in individuals with normal hair and a family history of AGA using B-mode US, SMI, and SWE. The study included 26 patients clinically diagnosed with AGA and a control group of 26 volunteers. Thickness with the distance from the epidermis to the calvarium (ECD) on the hairline and cranial subcutaneous tissue thickness (CSTD) were determined to be statistically significantly thinner in the AGA group than in the control group (p < 0.0001). For the differentiation of the AGA patients, the cutoff value was determined to be 5.5 mm for ECD and 4.05 mm for CSTD. The cranial epidermis-dermis (CED) stiffness values both as meter/second (m/s) and kilopascals (kPa) were statistically significantly lower in the AGA patients than in the control group (p < 0.0001). The cutoff values were 6.075 as m/s and 104.4 as kPa. The results of this study demonstrated that differentiation could be made of individuals before the development of AGA from normal healthy individuals with CSTD measurement on B-mode US and CED stiffness measurement on SWE.


Ten years after Dublin: principal trends in HIV surveillance in the EU/EEA, 2004 to 2013.
In 2004, the 31 countries of the European Union and European Economic Area (EU/EEA) adopted the Dublin Declaration on Partnership to Fight HIV/AIDS in Europe and Central Asia. In 2013, 29,157 persons were diagnosed with HIV in 30 EU/EEA countries (adjusted rate: 6.2/100,000); new diagnoses have increased by 33% since 2004 among men who have sex with men and late diagnosis remains common. Evidence-based prevention measures and efforts towards earlier testing need to be expanded.


IL-33 Promotes ST2-Dependent Fibroblast Maturation via P38 and TGF-β in a Mouse Model of Epidural Fibrosis.
Recent evidence suggests that IL-33, a novel member of the IL-1β family, is involved in organ fibrosis. However, the roles of IL-33 and its receptor ST2 in epidural fibrosis post spine operation remain elusive. A mouse model of epidural fibrosis was established after laminectomy. IL-33 in the wound tissues post laminectomy was measured with Western blotting, ELISA and immunoflurosence imaging. The fibroblast cell line NIH-3T3 and primary fibroblasts were treated with IL-33 and the mechanisms of maturation of fibroblasts into myofibroblasts were analyzed. To explore roles of IL-33 and its receptor ST2 in vivo, IL-33 knockout (KO) and ST2 KO mice were employed to construct the model of laminectomy. The epidural fibrosis was evaluated using H&E and Masson staining, western-blotting, ELISA and immunohistochemistry. As demonstrated in western blotting and ELISA, IL-33 was increased in epidural wound tissues post laminectomy. The immunoflurosence imaging revealed that endothelial cells (CD31+) and fibroblasts (α-SAM+) were major producers of IL-33 in the epidural wound tissues. In vitro, IL-33 promoted fibroblast maturation, which was blocked by ST2 neutralization antibody, suggesting that IL-33-promoted-fibroblasts maturation was ST2 dependent. Further, IL-33/ST2 activated MAPK p38 and TGF-β pathways. Either p38 inhibitor or TGF-β inhibitor decreased fibronectin and α-SAM production from IL-33-treated fibroblasts, suggesting that p38 and TGF-β were involved with IL-33/ST2 signal pathways in the fibroblasts maturation. In vivo, IL-33 KO or ST2 KO decreased fibronectin, α-SMA and collagen deposition in the wound tissues of mice that underwent spine surgery. In addition, TGF-β1 was decreased in IL-33 KO or ST2 KO epidural wound tissues. In summary, IL-33/ST2 promoted fibroblast differentiation into myofibroblasts via MAPK p38 and TGF-β in a mouse model of epidural fibrosis after laminectomy.


The medium and the message.
Communication between doctor and patient is examined in relation to ways of describing the institution of medicine, the rules of engagement between doctor and patient, and the language they employ. Medicine and its institutions are presented in metaphorical terms; a theatrical taxonomy of consultations between patient and doctor is suggested; and patient-doctor communication is considered in the light of the pervasiveness of mistranslation. Because it is possible to invent a wide range of alternative metaphors for medical institutions, to envisage many different sorts of dramatic possibilities in the patient-doctor encounter, and to develop a respect for the particularity of all language, optimism is expressed about the future of research, teaching and practice in doctor-patient communication.


An electrophoretic device concentrating charged macromolecules to a predetermined final solution volume.
An apparatus for electrophoretic concentration of charged macromolecules to a predetermined final solution volume has been developed. The concentration process has a yield of near 100%, which implies that it is possible to predetermine the final macromolecule concentration as well. Both the final macromolecule solution volume and concentration are nearly independent of the electrophoresis time when it exceeds a certain minimum value. The electric field strength across the boundary containing the concentrated macromolecule solution is very low. This considerably reduces macromolecule aggregation, adsorption, and denaturation at this boundary compared to conventional electrophoretic concentrator designs. Both one-stage and two-stage versions of the apparatus have been developed. The one-stage version easily yields a 10-fold and the two-stage version a 50-fold concentration of the macromolecules. Typical macromolecule solution start volumes are 20-50 ml.


The Sphingosine-1 Phosphate receptor agonist FTY720 dose dependently affected endothelial integrity in vitro and aggravated ventilator-induced lung injury in mice.
Lung barrier protection by Sphingosine-1 Phosphate (S1P) has been demonstrated experimentally, but recent evidence suggests barrier disruptive properties of high systemic S1P concentrations. The S1P analog FTY720 recently gained an FDA approval for treatment of multiple sclerosis. In case of FTY720 treated patients experiencing multiple organ dysfunction syndrome the drug may accumulate due to liver failure, and the patients may receive ventilator therapy. Whereas low doses of FTY720 enhanced endothelial barrier function, data on effects of increased FTY720 concentrations are lacking. We measured transcellular electrical resistance (TER) of human umbilical vein endothelial cell (HUVEC) monolayers, performed morphologic analysis and measured apoptosis by TUNEL staining and procaspase-3 degradation in HUVECs stimulated with FTY720 (0.01-100 μM). Healthy C57BL/6 mice and mice ventilated with 17 ml/kg tidal volume and 100% oxygen for 2 h were treated with 0.1 or 2 mg/kg FTY720 or solvent, and lung permeability, oxygenation and leukocyte counts in BAL and blood were quantified. Further, electron microscopic analysis of lung tissue was performed. We observed barrier protective effects of FTY720 on HUVEC cell layers at concentrations up to 1 μM while higher concentrations induced irreversible barrier breakdown accompanied by induction of apoptosis. Low FTY720 concentrations (0.1 mg/kg) reduced lung permeability in mechanically ventilated mice, but 2 mg/kg FTY720 increased pulmonary vascular permeability in ventilated mice accompanied by endothelial apoptosis, while not affecting permeability in non-ventilated mice. Moreover, hyperoxic mechanical ventilation sensitized the pulmonary vasculature to a barrier disrupting effect of FTY720, resulting in worsening of ventilator induced lung injury. In conclusion, the current data suggest FTY720 induced endothelial barrier dysfunction, which was probably caused by proapoptotic effects and enhanced by mechanical ventilation.


Requirements for stimulation of T cell responses against virus-infected cells: nature of ectromelia virus-infected cells capable of stimulating cytotoxic T cells in a secondary response in vitro.
The nature of infected stimulator cells in the in vitro secondary cytotoxic T cell response to ectromelia infection was investigated. It was found that macrophages were better stimulator cells than spleen cells. B cells (Ig-positive cells) were superior to T cells (Ig-negative cells) both on a relative proportion and on a cell-to-cell basis. Concanavalin A and lipopolysaccharide-stimulated lymphocytes were also effective stimulator cells but appeared to be slightly inferior to spleen cells. Spleen cells depleted of Ia-positive cells were markedly inferior to normal spleen cells as stimulators. It was also found that primary and secondary cytotoxic T cells were largely Ia-negative. These findings are discussed in relation to the likely events during T cell responses to infection in vivo.


Comparison of the toxic effects of non-task-specific and task-specific ionic liquids on zebrafish.
Ionic liquids (ILs) are composed of only anions and cations and are liquid solvents at room temperature. Different functional groups were introduced into the ILs, conferring them with specific functions or purposes and thus forming special ILs, namely task-specific ILs (TSILs). Imidazolium-based ILs are the most widely used ILs in industrial production. To date, there have been some studies on the toxic effects of ILs on different organisms. However, the effect of functionalized groups on the toxicity of ILs is still unclear. In the present study, zebrafish were used as model organisms to study the toxic effects of 1-ethyl-3-methylimidazolium nitrate ([C2mim]NO3) and 1-hydroxyethyl-3-methylimidazolium nitrate ([HOC2mim]NO3). The results showed that both promoted an increase in reactive oxygen species (ROS) contents, leading to lipid peroxidation and DNA damage. Furthermore, integrated biological response analysis showed that [HOC2mim]NO3 was less toxic to zebrafish than [C2mim]NO3, which indicated that adding functional groups decreased the toxicity of ILs to organisms. The influence of chemical structure on IL toxicity was also reported. These results could provide a scientific basis for better synthesis and utilization of ILs in the future.


Perils of human remains examination in COVID-19 times.
The novel coronavirus, SARS-CoV-2 has surged globally bringing the whole world virtually to a standstill. Due to its highly contagious nature, various guidelines, protocols and preventive strategies have been devised for the safety of healthcare workers during management of the living as well as the dead. However, guidelines and precautions to be followed during the examination of the human skeletal remains are largely lacking. The present communication intends to address the issue of safe handling of human remains during medicolegal investigations in the COVID-19 pandemic times.


Francisella tularensis Infection of Mice as a Model of Sepsis.
Sepsis results from the dysregulated immune response to infection. While the stimulator and progression of the septic response is poorly understood, the systemic production of a storm of cytokines is common in all etiologies of sepsis. While the complexity of this uncontrolled cascade is difficult to replicate using single molecule agonist, for example, lipopolysaccharide (LPS), several whole organism models can stimulate this cytokine storm. Herein, we detail protocols developed to trigger and analyze the systemic septic response in mouse models using the bacterium Francisella tularensis.


Mechanisms of spontaneous hypertension in rats.
Studies on the Kyoto (SHR) and the New Zealand (GHR) strains of genetically predisposed hypertensive rats have shown that in the SHR neurogenic influences, primarily of higher central origin, play an important role in the initiation of hypertension. Studies on human essential hypertension indicate that this may also be true for man, although it is far from being the sole explanation. Brookhaven hypertension-prone rats illustrate the interaction between genetic and exogenous factors since they require an overload of salt for the development of high blood pressure. The Milan hypertensive rats (MHS), on the other hand, illustrate a genetic deviation of renal function with imbalance between glomerular filtration and tubular resorption of sodium and water, which may simulate at least some variants of the relatively mild forms of low renin hypertension in man. Structural adaptive vascular changes have been demonstrated in SHR and GHR and in nongenetic renal hypertension in rats, and there are several indications of their presence in MHS. Thus, regardless of the nature of the initiating factors, these secondary but rapidly established changes occur and greatly contribute to the maintenance and acceleration of the hypertensive state. The vascular changes can even be regarded as a common denominator for chronic hypertension and serve as an element which, in fact, reinforces the initiating mechanisms. The progress of the vascular changes can be interfered with by reducing the pressure load. Lowering the blood pressure by pharmacologic treatment is most effective when the treatment is initiated as such an early age when the cardiovascular structural adaptation is still minimal. Treatment in later phases is less successful since the adaptive increases in cardiac and vessel wall thickness can then no longer be fully normalized by pressure reduction because of increased amounts of collagen and other connective tissue elements in the vessel wall, which regress poorly. An increased wall thickness of the resistance vessels implies a vascular hyperreactivity to constricting influences which, in turn, rapidly brings the blood pressure back to supranormal levels as soon as therapy is stopped.


Effect of preemptive topical diclofenac on postoperative pain relief after photorefractive keratectomy.
To assess the prophylactic effect of preoperative application of topical diclofenac on postoperative pain control in patients having photorefractive keratectomy (PRK). Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran. Randomized masked clinical trial. In this paired-eye study, patients having bilateral PRK received 1 drop of diclofenac 0.1% in 1 eye and 1 drop of placebo in the fellow eye 2 hours before PRK. Postoperatively, both arms of the trial (both eyes of each patient) received topical diclofenac every 6 hours for 2 days. One day and 2 days postoperatively, patients were asked to rate the perceived pain in each eye using an 11-point verbal numerical rating scale. A trained examiner noted the eye-specific responses. All 70 patients (140 eyes) completed the study and were included in the statistical analysis. Twenty-four hours after PRK, patients reported pain scores that were clinically and statistically significantly lower in the eyes pretreated with diclofenac than in the fellow eyes (0.97 versus 2.09) (P=.018). Pain scores at 2 days did not differ significantly (P=.877). Administration of a single drop of topical diclofenac 0.1% 2 hours before PRK seemed to increase the efficacy of postoperative pain management in a clinically and statistically significant manner. No author has a financial or proprietary interest in any material or method mentioned.


Effect of combining features generated through non-linear analysis and wavelet transform of EEG signals for the diagnosis of encephalopathy.
Electroencephalogram (EEG) signals portray hidden neuronal interactions in the brain and indicate brain dynamics. These signals are dynamic, complex, chaotic and nonlinear, the nature of which is represented with features - fractal dimensions, entropies and chaotic features. This study aims at examining the discriminative power of individual features and their combination in the diagnosis of a neuro-pathological condition called encephalopathy. Feature combination is accomplished with the help of feature selection using Gini impurity score that improves discriminative power and keeps redundancy minimal. Further, three widely used non-parametric classifiers which are known to be effective with wavelet features on EEG signals - Support Vector Machine, Random Forest, Multilayer Perceptron - are employed for disease classification. The models created by the combination of aforementioned stages are analysed and evaluated with performance scores, leading to an optimal model for automated diagnostic applications.


Combined phenotyping of glucose 6-phosphate dehydrogenase (G6PD; EC 18.104.22.168) and 6-phosphogluconate dehydrogenase (PDG; EC 18.104.22.168).
The addition of negroid phenotypes to the already heterogeneous population of Israel caused us to reuse the enzymes G6PD and PGD which are known to have a better discrimination power in a negroid population than in caucasians. We have developed a system for combined phenotyping of G6PD and PGD. This system answers the requirements of the above enzymes and results in a negroid population than in caucasians. We have developed a system for combined phenotype-amount of sample and reagents needed and time spent.


Sucrose controls storage lipid breakdown on gene expression level in germinating yellow lupine (Lupinus luteus L.) seeds.
This study revealed that cytosolic aconitase (ACO, EC 188.8.131.52) and isocitrate lyase (ICL, EC 18.104.22.168, marker of the glyoxylate cycle) are active in germinating protein seeds of yellow lupine. The glyoxylate cycle seems to function not only in the storage tissues of food-storage organs, but also in embryonic tissue of growing embryo axes. Sucrose (60mM) added to the medium of in vitro culture of embryo axes and cotyledons decreased activity of lipase (LIP, EC 18.104.22.168) and activity of glutamate dehydrogenase (NADH-GDH, EC 188.8.131.52). The opposite effect was caused by sucrose on activity of cytosolic ACO, ICL as well as NADP(+)-dependent (EC 126.96.36.199) and NAD(+)-dependent (EC 184.108.40.206) isocitrate dehydrogenase (NADP-IDH and NAD-IDH, respectively); activity of these enzymes was clearly stimulated by sucrose. Changes in the activity of LIP, ACO, NADP-IDH, and NAD-IDH caused by sucrose were based on modifications in gene expression because corresponding changes in the enzyme activities and in the mRNA levels were observed. The significance of cytosolic ACO and NADP-IDH in carbon flow from storage lipid to amino acids, as well as the peculiar features of storage lipid breakdown during germination of lupine seeds are discussed.


Are the same or different amino acid residues responsible for correct and incorrect protein folding?
It has been shown for 20 proteins that amino acid residues included into the protein folding nucleus, determined experimentally, are often involved in the theoretically determined amyloidogenic fragments. For 18 proteins, Phi-values indicative of the extent of residue involvement into the folding nucleus are on average higher for amino acid residues within amyloidogenic regions. Amyloidogenic fragments were predicted for 20 proteins by two methods chosen from four on the basis of comparison of prediction of amyloidogenic regions known from experimental data. Since theoretical folding nuclei are detected by the protein three-dimensional structure and amyloidogenic regions by the protein chain primary structure, the detected regularity makes possible predictions of folding nucleation sites on the basis of amino acid sequence.


Skeletal muscle fatty acids shift from oxidation to storage upon dexamethasone treatment in chickens.
The effect of an exogenous glucocorticoid on the lipid metabolism and fatty acid pattern of skeletal muscle in broiler chickens (Gallus gallus domesticus) was investigated in vivo and in vitro. Male Arbor Acres chickens were subjected to dexamethasone (DEX) treatment for 3days. We found that DEX retarded body growth, facilitated lipid accumulation in adipose and skeletal muscle tissues, and elevated the thigh monounsaturated fatty acids (MUFA) to saturated fatty acids (SFA) ratio at fasted state. DEX-treated chickens exhibited increased stearoyl-CoA desaturase-1 (SCD1) activity and decreased carnitine palmitoyltransferase-1 (CPT1) activity in the thigh muscle under fasting conditions and in primary cultured myoblasts. Phosphorylation of AMP-activated protein kinase alpha at Thr172 did not occur in vivo but was increased in vitro by DEX. In cells exposed to DEX, fatty acid transport protein-1 mRNA expression and fatty acid storage were enhanced while fatty acid oxidation was repressed. In conclusion, in oxidative muscle of fasted chickens, DEX stimulated uptake of myocellular fatty acids which was stored with the modified MUFA to SFA ratio in a process that maybe involved SCD1 activation. The altered fatty acid composition together with the inactivation of CPT1 showed an increased tendency towards fatty acid accumulation as opposed to oxidation. These findings provide important insight concerning the influence of glucocorticoids on lipid metabolism.


Reduced expression of the LRP16 gene in mouse insulinoma (MIN6) cells exerts multiple effects on insulin content, proliferation and apoptosis.
This study assessed the effects of leukemia-related protein 16 (LRP16) on the regulation of pancreatic functions in mouse insulinoma (MIN6) cells. Cells with down-regulated expression of LRP16 were obtained by a shRNA interference strategy. Insulin content and glucose-stimulated insulin secretion (GSIS) were examined by radioimmunoassay. Western blotting was applied to detect protein expression. Glucose-stimulated sub-cellular localization of PDX-1 was immunocytochemically determined. Cell proliferation and apoptosis were detected by flow cytometry. Our results showed that LRP16 regulated insulin content in MIN6 cells by controlling expression of insulin and insulin transcription factors. LRP16 gene silence in MIN6 cells led to reduced cell proliferation and increased apoptosis. The observation of phosphorylation of serine-473 Akt and the localization of PDX-1 to the nucleus under glucose-stimulation exhibited that LRP16 was a component mediating Akt signaling in MIN6 cells. These results suggest that LRP16 plays a key role in maintaining pancreatic β-cell functions and may help us to understand the protective effects of estrogen on the functions of pancreatic β-cells.


Degree and stability of tolerance to penicillin in Streptococcus pyogenes.
The degree of antibiotic tolerance may be assessed by determining the tolerance percentage of a bacterial strain, defined as the surviving fraction of an inoculum that has been exposed for 24 hours to a high concentration of a beta-lactam antibiotic. In 61 clinical isolates of Streptococcus pyogenes, tolerance percentages ranged from 0 to 0.43. From the slopes of the killing curves it can be deduced that killing starts to be delayed at a tolerance percentage of 0.1. Although a tolerance percentage exceeding 0.1 was observed in 41.4% of the strains, the incidence of clinically relevant forms of tolerance is expected to occur in a smaller fraction of the strains. Tolerance percentages of two strains stored at 20 degrees C, 4 degrees C or -70 degrees C (tolerance percentages 0.43 and 0.36) decreased to 0.03 or less in six weeks. Tolerance percentages could be completely restored in these strains, but not in sensitive strains, by successive selection for this property on penicillin gradients of increasing concentration. In four strains isolated from a family outbreak, identical levels of tolerance percentage could be selected for with the same technique.


Identification by monoclonal antibody of a major (28 kDa) surface membrane antigen of Schistosoma mansoni.
Monoclonal antibody M.1 was generated from mice immunized with membrane enriched extracts of mechanically transformed schistosomula. M.1 bound to the surface membranes of cercariae and young (0-24 h post-transformation) schistosomula but did not bind to older schistosomula or cultured worms. M.1 immunoprecipitated an antigen of approximate molecular weight 27-28 kDa from schistosomula. Experiments using metabolic labeling showed that the antigen was actively synthesized by developing schistosomula. Further M.1 immunoprecipitated a similar 27-28 kDa antigen from membrane-enriched extracts of miracidia, lung and adult worms as well as from schistosomula.


Ionic modulation of electrically induced fusion of mammalian cells.
During the last few years, a new technique has been developed for the "electrofusion" of mammalian cells. No previous treatment of the culture is needed, for the contact between cells is spontaneous. Short DC electric pulses are applied directly to a culture growing in monolayers on a culture dish. When the cell density is high enough, contacts occur between cells giving the so-called contact inhibition. In the present study, a systematic investigation of the modulation of the extent of the fusion by the ionic content of the bathing medium during the pulsation is described. An increase in the content in monovalent ions decreases the fusion yield. But this decrease is modulated by the nature of the ion; Li+, a potent "water structure maker," is less effective than Na+ or K+. Ca2+, when present in the millimolar range, leads to the lysis of the cells. Mg2+, when present at concentrations smaller than 4 mM, promotes the fusion but prevents it at larger concentrations. Microelectrophoresis measurements show that the electric surface charge is not strongly affected by these changes in ionic content. Our observations are relevant of a modulation of the cell-cell interactions by the ionic content of the bathing medium.


Beauty ideals, social media, and body positivity: A qualitative investigation of influences on body image among young women in Japan.
Body image and eating concerns are prevalent among Japanese young women and result in part from exposure to unrealistic media imagery. In Western contexts, a growing body of research has explored the impact of social media on body image and eating disorder risk, and the potential for body positive media to mitigate these harmful effects. However, similar research in Japan is lacking. The aim of the present study was to qualitatively explore media and social media influences on body image and associated behaviors among young women in Japan, with a specific focus on body positive media content. Female university students in Japan (n = 29) participated in majority group and some individual interviews. Thematic analysis revealed four primary themes: (1) media appearance pressures: additive pressures of Japanese and Western ideals through globalization, (2) criticism of, resistance to, and negotiating appearance ideals, and (3) presence of body positivity in Japan, and (4) media as a background for interpersonal appearance pressures. High pressure towards thinness emerged, perceived as contributing to weight control behaviors that were calibrated to avoid being "unhealthy." Desire for greater body diversity in Japanese media emerged; however, findings suggest body positive messaging is scarce and mainly limited to high-profile celebrities.


A novel class of sulfur-containing aminolipids widespread in marine roseobacters.
Marine roseobacter group bacteria are numerically abundant and ecologically important players in ocean ecosystems. These bacteria are capable of modifying their membrane lipid composition in response to environmental change. Remarkably, a variety of lipids are produced in these bacteria, including phosphorus-containing glycerophospholipids and several amino acid-containing aminolipids such as ornithine lipids and glutamine lipids. Here, we present the identification and characterization of a novel sulfur-containing aminolipid (SAL) in roseobacters. Using high resolution accurate mass spectrometry, a SAL was found in the lipid extract of Ruegeria pomeroyi DSS-3 and Phaeobacter inhibens DSM 17395. Using comparative genomics, transposon mutagenesis and targeted gene knockout, we identified a gene encoding a putative lyso-lipid acyltransferase, designated salA, which is essential for the biosynthesis of this SAL. Multiple sequence analysis and structural modeling suggest that SalA is a novel member of the lysophosphatidic acid acyltransferase (LPAAT) family, the prototype of which is the PlsC acyltransferase responsible for the biosynthesis of the phospholipid phosphatidic acid. SAL appears to play a key role in biofilm formation in roseobacters. salA is widely distributed in Tara Oceans metagenomes and actively expressed in Tara Oceans metatranscriptomes. Our results raise the importance of sulfur-containing membrane aminolipids in marine bacteria.


The theoretical systems of OFDI location determinants in global north and global south economies.
With economic transformation and industrial development, Outward Foreign Direct Investment (OFDI) from southern countries has increased rapidly. The theoretical system established by global north countries with their dominant position in the international investment market has been impacted by global south countries. The existing OFDI theory has always been based on developed countries and can only explain some international investment behavior of southern countries. The Vector Error Correction Model (VECM) is applied to conduct empirical analysis for the impact of the target country's investment climate on the location determinants of OFDI, by applying China and the United States as example which is focusing on 172 countries from 2005 to 2019. The results reveal significant differences in the theoretical system of foreign investment between China and the United States. For China, investment climate factors such as energy, logistics infrastructure, and politics are discover as the main drivers of China's OFDI. However, USA's OFDI is a corporate behavior aimed at economic interests. The differences in OFDI theoretical systems and provides policy advice for northern and southern countries and departments is the major contribution of this research.


Characterization of a Rab7-like GTPase, EhRab7: a marker for the early stages of endocytosis in Entamoeba histolytica.
We have identified a 667 base pair Rab7-like cDNA (EhRab7) from Entamoeba histolytica. The EhRab7 cDNA predicts a polypeptide of at least 206 amino acids with a molecular mass of at least 24.5 kDa. Alignment of EhRab7 with other Rab proteins demonstrated that EhRab7 shared significant homology at the amino acid level with Rab7-like proteins from a number of other eukaryotes, suggesting that EhRab7 is a Rab7 homolog for E. histolytica. Using immunofluorescence microscopy, EhRab7 was demonstrated to be associated with early fluid-phase endosomes (<30 min) and secretory vesicles. The association of EhRab7 with early endosomes disappeared 1 h after their formation. Immunofluorescence microscopy also revealed that this GTPase did not colocalize significantly with phagosomes nor with markers for other organelles including the endoplasmic reticulum, Golgi and late endosomes. These results, together with the known function for Rab7 in other systems, suggest that EhRab7 is bound to vesicles, and that it may participate in vesicle docking and fusion in secretory events, and in the early stages of fluid-phase endocytosis in E. histolytica.


Exploring natural microbial resources for the discovery of anti-malarial compounds.
Microorganisms in nature are highly diverse biological resources, which can be explored for drug discovery. Some countries including Brazil, Columbia, Indonesia, China, and Mexico, which are blessed with geographical uniqueness with diverse climates and display remarkable megabiodiversity, potentially provide microorganismal resources for such exploitation. In this review, as an example of drug discovery campaigns against tropical parasitic diseases utilizing microorganisms from such a megabiodiversity country, we summarize our past and on-going activities toward discovery of new antimalarials. The program was held in a bilateral collaboration between multiple Indonesian and Japanese research groups. In order to develop a new platform of drug discovery utilizing Indonesian bioresources under an international collaborative scheme, we aimed at: 1) establishment of an Indonesian microbial depository, 2) development of robust enzyme-based and cell-based screening systems, and 3) technology transfer necessary for screening, purification, and identification of antimalarial compounds from microbial culture broths. We collected, characterized, and deposited Indonesian microbes. We morphologically and genetically characterized fungi and actinomycetes strains isolated from 5 different locations representing 3 Indonesian geographical areas, and validated genetic diversity of microbes. Enzyme-based screening was developed against two validated mitochondrial enzymes from Plasmodium falciparum, dihydroorotate dehydrogenase and malate:quinone oxidoreductase, while cell-based proliferation assay was developed using the erythrocytic stage parasite of 3D7 strain. More than 17 thousands microbial culture extracts were subjected to the enzyme- and cell-based screening. Representative anti-malarial compounds discovered in this campaign are discussed, including a few isolated compounds that have been identified for the first time as anti-malarial compounds. Our antimalarial discovery campaign validated the Indonesian microbial library as a powerful resource for drug discovery. We also discuss critical needs for selection criteria for hits at each stage of screening and hit deconvolution such as preliminary extraction test for the initial profiling of the active compounds and dereplication techniques to minimize repetitive discovery of known compounds.


QA/QC as a tool for improvement of analytical process in case of determination of tritium specific activity by electrolytic enrichment.
Electrolytic enrichment is used as a method for measuring tritium in environmental waters. All measurement data and parameters are collected in control charts. Together with measurements and modelling of temperatures in the electrolytic cooling system, these charts were used to optimise the entire process. After modification, the scatter of the final sample masses was considerably reduced. Enrichment factor scatter was reduced by 33%, and overall enrichment can now be increased by up to 64%.


Greater reliance on proprioceptive information during a reaching task with perspective manipulation among children with autism spectrum disorders.
Difficulties with visual perspective-taking among individuals with autism spectrum disorders remain poorly understood. Many studies have presumed that first-person visual input can be mentally transformed to a third-person perspective during visual perspective-taking tasks; however, existing research has not fully revealed the computational strategy used by those with autism spectrum disorders for taking another person's perspective. In this study, we designed a novel approach to test a strategy using the opposite-directional effect among children with autism spectrum disorders. This effect refers to how a third-person perspective as a visual input alters a cognitive process. We directly manipulated participants' visual perspective by placing a camera at different positions; participants could watch themselves from a third-person perspective during a reaching task with no endpoint feedback. During a baseline task, endpoint bias (with endpoint feedback but no visual transformation) did not differ significantly between groups. However, the endpoint was affected by extrinsic coordinate information in the control group relative to the autism spectrum disorders group when the visual perspective was transformed. These results indicate an increased reliance on proprioception during the reaching task with perspective manipulation in the autism spectrum disorders group.


Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD).
Despite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD). A modified water box (locomotor activity may be provide a limiting factor in this method of SD) or multiple platforms were used for induction of TSD or RSD, respectively. Inhibitory passive avoidance apparatus has been used to determine the effects of SD and its changes by physostigmine (as cholinesterase inhibitor) or scopolamine (muscarinic receptor antagonist) on memory formation. Because locomotor activity and pain perception induce critical roles in passive avoidance memory formation, we also measured these factors by open field and hot-plate instruments, respectively. The results showed that TSD and RSD for 24 hours impaired memory formation but they did not alter locomotor activity. TSD also induced analgesia effect, but RSD did not alter it. Intra-CA1 injection of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) did not alter memory acquisition in the sham-TSD or sham-RSD, by themselves. Moreover, intra-CA1 injection of sub-threshold dose of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) could restore the memory acquisition deficit induced by RSD, while scopolamine could restore TSD-induced amnesia. Both drugs reversed analgesia induced by TSD. None of previous interventions altered locomotor activity. According to this study, CA1 cholinergic muscarinic receptors play an important role in amnesia induced by both TSD and RSD. However further studies are needed for showing cellular and molecular mechanisms of surprising result of similar pharmacological effects using compounds with opposite profiles.