Comments and hypotheses on the mechanism of methane against ischemia/reperfusion injury.
As we all know, methane is a kind of fuel. Previous studies have shown that methanogens in the colon can react with carbon dioxide and hydrogen to produce methane. In a recent study, the anti-inflammatory effects of methane were shown in a dog model of small intestinal ischemia/reperfusion. The mechanism of this anti-inflammatory effect needs further investigation. Recently, studies have shown anti-inflammatory, anti-apoptotic and anti-oxidative effects of methane on different organic injuries. According to the results of these studies, we hypothesize that the initial effects of methane are to react with free radicals and enhance expression of antioxidase through forkhead box transcription factor class O pathway. The anti-inflammatory effect is following the anti-oxidative effect, and the anti-apoptotic effect relies on anti-inflammatory and anti-oxidative effects.


Cutaneous mucormycosis in a heart transplant patient.
We present the first case of cutaneous mucormycosis reported in a patient who had undergone a heart transplant operation. This appeared to be a localized infection without a predisposing local factor such as a surgical adhesive and without evidence of dissemination. Prompt treatment with intravenous amphotericin B resulted in an apparent cure.


The prevalence of endometriosis in premenopausal women undergoing gynecological surgery.
Endometriosis is a disease of the female pelvic mesenchyme in which tissue with epithelial and stromal characteristics of the endometrium develops in a situation other than in the uterus. The aim of this study was to evaluate the prevalence of endometriosis in premenopausal women submitted to laparoscopy and/or laparotomy for infertility, chronic pelvic pain, benign ovarian cysts and uterine myomas. The prevalence of the disease was higher in patients with infertility (30.5%), chronic pelvic (45%) and benign ovarian cysts (43%) than in patients with uterine mvomas (8.5%).


Interfacial tryptophan residues: a role for the cation-pi effect?
Integral membrane proteins are characterized by having a preference for aromatic residues, e.g., tryptophan (W), at the interface between the lipid bilayer core and the aqueous phase. The reason for this is not clear, but it seems that the preference is related to a complex interplay between steric and electrostatic forces. The flat rigid paddle-like structure of tryptophan, associated with a quadrupolar moment (aromaticity) arising from the pi-electron cloud of the indole, interacts primarily with moieties in the lipid headgroup region hardly penetrating into the bilayer core. We have studied the interaction between the nitrogen moiety of lipid molecule headgroups and the pi-electron distribution of gramicidin (gA) tryptophan residues (W9, W11, W13, and W15) using molecular dynamics (MD) simulations of gA embedded in two hydrated lipid bilayers composed of 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) and 1-palmitoyl-2-oleoylphosphatidyl-choline (POPC), respectively. We use a force field model for tryptophan in which polarizability is only implicit, but we believe that classical molecular dynamics force fields are sufficient to capture the most prominent features of the cation-pi interaction. Our criteria for cation-pi interactions are based on distance and angular requirements, and the results from our model suggest that cation-pi interactions are relevant for W(PE)1), W(PE)13, W(PE)15, and, to some extent, W(PC)11 and W(PC)13. In our model, W9 does not seem to engage in cation-pi interactions with lipids, neither in POPE nor POPC. The criteria for the cation-pi effect are satisfied more often in POPE than in POPC, whereas the H-bonding ability between the indole donor and the carbonyl acceptor is similar in POPE and POPC. This suggests an increased affinity for lipids with ethanolamine headgroups to transmembrane proteins enriched in interfacial tryptophans.


Morphology and immunology of circulating cells in leukaemic phase of follicular lymphoma.
Ten patients with follicular lymphoma presented with a high white cell count (45-220 x 10(9)/l) which resembled chronic lymphocytic leukaemia (CCL): all had pronounced splenomegaly and, except one, generalised lymphadenopathy. The blood lymphocytes were small with scanty cytoplasm, densely condensed nuclear chromatin, and deep clefts originating in sharp angles from the nuclear surface. CLL cells are larger, have more cytoplasm, a different pattern of chromatin condensation, and may have shallow nuclear indentations or foldings rather than clefts. The circulating follicular lymphoma cells had moderate to strong membrane immunoglobulins (SmIg), low mouse (M)-rosettes, strong reactivity with the monoclonal antibody FMC7, and occasional expression of the CD5-antigen; at least one third of cells in each case were positive with anti-cALLa (J5,CD10). Half the cases were referred as B-CLL but none had the typical B-CLL immunophenotype: weak SmIg, M-rosettes of greater than 50%, CD5 positive, FMC7 and J5 negative. The diagnosis of follicular lymphoma was confirmed by lymph node biopsy in seven of the 10 cases. The overall response to treatment was poor and five patients died within three years of diagnosis. This aggressive form of follicular lymphoma needs to be distinguished from B-CLL as different management is required.


Functional changes of neural circuits in stroke patients with dysphagia: A meta-analysis.
Dysphagia is a common problem in stroke patients with unclear pathogenesis. Several recent functional magnetic resonance imaging (fMRI) studies had been carried out to explore the cerebral functional changes in dysphagic stroke patients. The aim of this study was to analysis these imaging findings using a meta-analysis. We used seed-based d mapping (SDM) to conduct a meta-analysis for dysphagic stroke patients prior to any kind of special treatment for dysphagia. A systematic search was conducted for the relevant studies. SDM meta-analysis method was used to examine regions of increased and decreased functional activation between dysphagic stroke patients and healthy controls. Finally, six studies including 81 stroke patients with dysphagia and 78 healthy controls met the inclusion standards. When compared with healthy controls, stroke patients with dysphagia showed hyperactivation in left cingulate gyrus, left precentral gyrus and right posterior cingulate gyrus, and hypoactivation in right cuneus and left middle frontal gyrus. The hyperactivity of precentral gyrus is crucial in stroke patients with dysphagia and may be associated with the severity of stroke. Besides the motor areas, the default-mode network regions (DMN) and affective network regions (AN) circuits are also involved in dysphagia after stroke.


[Ventilator bundle guided by context of JCI settings can effectively reduce the morbidity of ventilator-associated pneumonia].
To observe the impact of improving the compliance of ventilator bundle on morbidity of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients undergoing mechanical ventilation (MV) guided by context of Joint Commission International (JCI) settings, and to study the oral care efficacy of suction tube sponge brush. A prospective study was conducted. The patients who needed MV admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Xiamen University from January 2013 to December 2016 were enrolled. In the context of JCI settings, necessary measurements were taken to enhance the compliance of ventilator bundle each year. In 2013, the preventive measures were set up and the education was strengthened. In 2014, the compliance of hand hygiene and bedside elevation was strengthened. In 2015, a control study was conducted to evaluate the effect between the traditional cotton dipped in chlorhexidine and the suction tube sponge brush rinsed with chlorhexidine on oral health impact parameters. The suction tube sponge brush rinsed with chlorhexidine oral care was introduced to improve compliance. In 2016, electronic bundle checklist for daily self-audits was conducted. The annually morbidity of VAP through the software of hospital and ICU was collected and calculated. The annual incidence of VAP was indicated by the VAP cases per 1 000 MV days. Based on the VAP incidence rate in 2013 as 1, the VAP incidence-rate ratio (IRR) of each year was calculated. During the study period, a total of 2 733 patients admitted to the ICU, including 1 403 patients undergoing MV. Ninety-four of the 1 403 patients with community-acquired pneumonia (CAP), aspiration pneumonia, back elevation ban, incomplete information, and withdrew from the study were excluded. 1 399 patients undergoing MV were enrolled in the final analysis, with total MV days of 11 012 days, and 94 patients occurred VAP. The annual incidence of VAP was progressively declined from 2013 to 2016, and the VAP cases per 1 000 MV days were 17.0, 10.0, 5.9, 3.5 cases, respectively. Based on the VAP incidence rate in 2013, the IRR of VAP from 2014 to 2016 was also progressively declined, which was 0.59 [95% confidence interval (95%CI) = 0.35-0.98], 0.35 (95%CI = 0.18-0.64), and 0.21 (95%CI = 0.09-0.41), with statistical significance (all P < 0.05). In 2013, ICU patients had the lowest rates of bedside elevation and hand hygiene compliance, which were 28.57% and 54.29%, respectively. Compared with 2013, by the implementation of two quality control circle (QCC) projects for bedside elevation and hand hygiene, the rates of bedside elevation and hand hygiene compliance were improved significantly in 2014, which were 82.35%, 91.18%, respectively (both P < 0.05). In 2015, the compliance of chlorhexidine oral care which was the worst performed in 2014 had been improved by the method of QCC, and the rate of the compliance was significantly higher than that in 2013 (87.10% vs. 62.86%, P < 0.05). Compared with 2013, bundle compliance was significantly increased in 2016, except for the sterile operation of the suction tube [daily wake and weaning: 95.00% vs. 71.43%, bedside elevation for over 30degree angle: 92.50% vs. 28.57%, hand hygiene: 97.50% vs. 54.29%, chlorhexidine mouth care once per 6-8 hours: 95.00% vs. 62.86%, turned back and posture drainage: 97.50% vs. 80.00%], the differences were statistically significant (all P < 0.05). The incidences of bad breath, dirt residue and plaque were significantly lower in the group of oral care by using suction tube sponge brush with chlorhexidine (30 cases) compared with the group of traditional cotton pad with chlorhexidine (30 cases; bad breath: 10.0% vs. 40.0% %, dirt residue: 16.7% vs. 70.0%, plaque: 3.3% vs. 30.0%, all P < 0.05). There was no significant difference in the incidence of oral ulcers between the oral brush group and the traditional group (10.0% vs. 30.0%, P > 0.05). Ventilator bundle can effectively reduce the morbidity of VAP in the context of JCI settings, and the oral care by using suction tube sponge brush and chlorhexidine can effectively improve oral hygiene.


Heparin Induced Thrombocytopenia - Pathophysiology, Diagnosis and Treatment: A Narrative Review.
Heparin-induced thrombocytopenia (HIT) is a life-threatening, immune-mediated complication following heparin exposure and is considered to be the most severe adverse reaction to heparin treatment that is not associated with bleeding. Development of autoantibodies against platelet factor 4 (PF4) - heparin complex constitutes the basis of the pathophysiological changes in patients suffering from HIT, which then binds to the surface of platelets and monocytes, thus provoking their activation and subsequent aggregation, ultimately leading to the formation of thrombosis. Formation of arterial and venous thrombosis is aggravated by the simultaneous activation of platelets and monocytes with a substantial mortality rate. The incidence of HIT is reported to be significantly lower in pediatric patients compared with adults. Diagnosis of HIT in pediatric population remains a clinical entity supplemented by laboratory evaluation. The positive predictive value of laboratory evaluation is further elevated by the use of scoring systems and predictive models used for hastening the diagnosis of HIT. Use of alternative anticoagulants like direct thrombin inhibitors and factor Xa inhibitors form the mainstay of treatment in cases of HIT, however, more prospective studies would be required in the pediatric population to delineate definitive guidelines for proper management of patients in this age-group. This article delivers diagnostic and treatment approach in case of patients with HIT, wherein the pathophysiology, clinical manifestations, diagnostic approach and the management of patients with HIT has been described.


Dihydrofolate reductase from Escherichia coli: the kinetic mechanism with NADPH and reduced acetylpyridine adenine dinucleotide phosphate as substrates.
Kinetic studies on the reaction catalyzed by dihydrofolate reductase from Escherichia coli have been undertaken with the aim of characterizing further the kinetic mechanism of the reaction. For this purpose, the kinetic properties of substrates were determined by measurement of (a) initial velocities over a wide range of substrate concentrations and (b) the stickiness of substrates in ternary enzyme complexes. Stickiness is defined as the rate at which a substrate reacts to give products relative to the rate at which that substrate dissociates. Stickiness was determined by varying the viscosity of reaction mixtures and the concentration of one substrate in the presence of a saturating concentration of the other substrate. The results indicate that NADPH is sticky in the enzyme-NADPH-dihydrofolate complex, while dihydrofolate is much less sticky in this complex. At higher concentrations, NADPH functions as an activator through the formation of an enzyme-NADPH-tetrahydrofolate from which tetrahydrofolate is released more rapidly than from an enzyme-tetrahydrofolate complex. Higher concentrations of dihydrofolate also cause enzyme activation, and it appears that this effect is due to the ability of dihydrofolate to displace tetrahydrofolate from a binary enzyme complex through the formation of a transitory enzyme-tetrahydrofolate-dihydrofolate complex. As NADPH and dihydrofolate function as activators and as NADPH behaves as a sticky substrate, the kinetic mechanism of the dihydrofolate reductase reaction with the natural substrates is steady-state random. By contrast with NADPH, reduced 3-acetylpyridine adenine dinucleotide phosphate exhibits only slight stickiness and does not function as an activator.(ABSTRACT TRUNCATED AT 250 WORDS)


Panicolytic-like effect of µ1-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers.
The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µ1-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of µ1-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. Specific pathogen-free Wistar rats were treated with microinjection of the selective µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) and then confronted with rattlesnakes ( Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. The blockade of µ1-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. Taken together, these results suggest that a decrease in µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.


Analysis of mutations in pncA reveals non-overlapping patterns among various lineages of Mycobacterium tuberculosis.
Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, resistance to which occurs primarily due to mutations in pncA (Rv2043c) that encodes the pyrazinamidase enzyme responsible for conversion of pro-drug PZA into its active form. Previous studies have reported numerous resistance-conferring mutations distributed across the entire length of pncA without any hotspot regions. As different lineages of Mycobacterium tuberculosis display a strong geographic association, we sought to understand whether the genetic background influenced the distribution of mutations in pncA. We analyzed the whole genome sequence data of 1,480 clinical isolates representing four major M. tuberculosis lineages to identify the distribution of mutations in the complete operon (Rv2044c-pncA-Rv2042c) and its upstream promoter region. We observed a non-overlapping pattern of mutations among various lineages and identified a lineage 3-specific frame-shift deletion in gene Rv2044c upstream of pncA that disrupted the stop codon and led to its fusion with pncA. This resulted in the addition of a novel domain of unknown function (DUF2784) to the pyrazinamidase enzyme. The variant molecule was computationally modelled and physico-chemical parameters determined to ascertain stability. Although the functional impact of this mutation remains unknown, its lineage specific nature highlights the importance of genetic background and warrants further study.


The effects of lidocaine and bupivacaine on protein expression of cleaved caspase 3 and tyrosine phosphorylation in the rat hippocampal slice.
Severe neurologic sequelae have been reported with the use of lidocaine after spinal anesthesia. This is considered a consequence of the high concentrations reached in the cerebrospinal fluid. We have previously shown that lidocaine increases the phosphorylation of focal adhesion kinase (FAK, a nonreceptor tyrosine kinase playing a role in neuronal plasticity and cell death). Here, we compared the effects of lidocaine and bupivacaine on FAK phosphorylation and cleaved caspase 3 expression in rat hippocampal slices. Slices were treated with increasing concentrations of lidocaine (4.3 nM to 4.3 mM) or bupivacaine (3.4 nM to 3.4 mM) in the presence or absence of the specific inhibitor of the FAK tyrosine kinase PP2 (10 microM). Caspase 3 expression and FAK phosphorylation were examined by immunoblotting. Lidocaine induced a concentration-related increase in FAK phosphorylation while the bupivacaine effect was biphasic. The maximal effect observed with millimolar lidocaine concentrations was significantly more than with clinically equipotent bupivacaine concentrations (4.3 x 10(-3) M lidocaine: 168% +/- 20%, mean value +/- sd; 10(-3) M bupivacaine: 145% +/- 19% P < 0.001). The expression of cleaved caspase 3 was increased by lidocaine, but not bupivacaine, at millimolar concentrations and was blocked by PP2. Our results indicate that millimolar concentrations of lidocaine, but not bupivacaine, increase cleaved caspase 3 expression. The role of FAK phosphorylation in this effect remains to be clarified.


HLA class II SNP interactions and the association with type 1 diabetes mellitus in Bengali speaking patients of Eastern India.
Several studies have demonstrated a fundamental role for the HLA in the susceptibility of, or protection to, type 1 diabetes mellitus (T1DM). However, this has not been adequately studied in Asian Indian populations. To assess the frequency of HLA class II (DPA1, DPB1, DQA1, DQB1 and DRB1) associated to susceptibility or protection toT1DM in a Bengali population of India with diabetes. Single nucleotide polymorphism study. The HLA genotyping was performed by a polymerase chain reaction followed by their HLA-DP, DQ, and DRB1 genotypes and haplotypes by sequencing method. The results are studied by Plink software. The χ2 tests were used for the inferential statistics. To our knowledge, this study is the first of a kind which has attempted to check the HLA association with T1DM by SNPs analysis. The study recruited 151 patients with T1DM and same number of ethno-linguistic, sex matched non-diabetic controls. The present study found a significant SNP rs7990 of HLA-DQA1 (p = 0.009) negative correlation, again indicating that risk from HLA is considerably more with T1DM. This study demonstrates that the HLA class-II alleles play a major role in genetic basis of T1DM.


Underwater drag-reducing effect of superhydrophobic submarine model.
To address the debates on whether superhydrophobic coatings can reduce fluid drag for underwater motions, we have achieved an underwater drag-reducing effect of large superhydrophobic submarine models with a feature size of 3.5 cm × 3.7 cm × 33.0 cm through sailing experiments of submarine models, modified with and without superhydrophobic surface under similar power supply and experimental conditions. The drag reduction rate reached as high as 15%. The fabrication of superhydrophobic coatings on a large area of submarine model surfaces was realized by immobilizing hydrophobic copper particles onto a precross-linked polydimethylsiloxane (PDMS) surface. The pre-cross-linking time was optimized at 20 min to obtain good superhydrophobicity for the underwater drag reduction effect by investigating the effect of pre-cross-linking on surface wettability and water adhesive property. We do believe that superhydrophobic coatings may provide a promising application in the field of drag-reducing of vehicle motions on or under the water surface.


Open Trimalleolar Fractures Treated with Ilizarov External Fixator.
Open trimalleolar fractures are some of the most severe fractures of the ankle joint region and some of the most difficult in trauma surgery. Repositioning with internal fixation is the most common surgical treatment method. There is little published data on primary repositioning and external fixation. Five patients with open trimalleolar were fitted with Ilizarov external fixators in single-stage procedures. Full weight bearing was possible following surgical treatment in all five patients. None of the patients developed malunion, infections or vein thrombosis. For all patients, the Ilizarov apparatus was remodelled after six weeks to allow movement in the ankle. Three patients developed posttraumatic arthrosis requiring joint fusion. Arthrodesis was performed in two patients, and another patient will require it in the future. None of the patients developed any inflammatory complications. The mean duration of treatment with an external fixator was 11.6 weeks (range: 9-15 weeks). Radiological and clinical outcomes were satisfactory in all patients. The Ilizarov method allows for early and definitive treatment of open trimalleolar fractures with a low risk of complications and a good clinical outcome.


Localized temporal change of the Earth's inner core boundary.
Compressional waves of an earthquake doublet (two events occurring in the South Sandwich Islands on 1 December 1993 and 6 September 2003), recorded at three seismic stations in Russia and Kyrgyzstan and reflected off Earth's inner core boundary, arrived at least from 39 to 70 milliseconds earlier in the 2003 event than in the 1993 event. Such changes indicate that Earth's inner core radius enlarged locally beneath middle Africa by 0.98 to 1.75 kilometers between the times of these two events. Changes of the inner core radius may be explained by either a differential motion of the inner core, assuming that irregularities are present at the inner core boundary and fixed to the inner core, or a rapid growth of the inner core by this amount.


Women's knowledge and use of prenatal screening tests.
The aim of the study was to determine the rate of use of prenatal screening tests and the factors affecting the decision to have a prenatal screening test in pregnant women in Turkey. Prenatal genetic screening as an optional service is commonly used to determine a level of risk for genetic conditions in the foetus. A quantitative cross-sectional survey. Pregnant women (n = 274) who sought prenatal care from one hospital in Turkey were recruited and asked to complete questionnaires that were developed by the researchers. Descriptive and inferential statistics were used to analyse the data. Almost half (44·2) % of the women were primiparas, and the majority (97·8%) were in the third trimester of pregnancy. Only 36·1% of the women reported that they had prenatal screening by either the double test or triple test. Women had a low level of knowledge regarding prenatal screening: the mean knowledge score was 3·43 ± 3·21 of a possible score of 10. Having consanguineous marriage, a history of spontaneous abortion, a child with genetic disorder, multiparity or a longer marriage duration were positively correlated with accepting a prenatal screening test. This study has provided baseline data on the uptake and reasons for accepting or declining a prenatal screening in a cohort of Turkish women. There is evidence to suggest that more education is needed to improve knowledge and provide comprehensive nursing care to promote informed consent in this context. Perinatal nurses are ideally situated to inform pregnant women about prenatal screening tests to improve access to healthcare services and to ensure informed decisions are made by pregnant women and their partners.


Effects of context on eye movements when reading about possible and impossible events.
Plausibility violations resulting in impossible scenarios lead to earlier and longer lasting eye movement disruption than violations resulting in highly unlikely scenarios (K. Rayner, T. Warren, B. J. Juhasz, & S. P. Liversedge, 2004; T. Warren & K. McConnell, 2007). This could reflect either differences in the timing of availability of different kinds of information (e.g., selectional restrictions, world knowledge, and context) or differences in their relative power to guide semantic interpretation. The authors investigated eye movements to possible and impossible events in real-world and fantasy contexts to determine when contextual information influences detection of impossibility cued by a semantic mismatch between a verb and an argument. Gaze durations on a target word were longer to impossible events independent of context. However, a measure of the time elapsed from first fixating the target word to moving past it showed disruption only in the real-world context. These results suggest that contextual information did not eliminate initial disruption but moderated it quickly thereafter.


Smooth muscle cell-specific transcription is regulated by nuclear localization of the myocardin-related transcription factors.
On the basis of our previous studies on RhoA signaling in smooth muscle cells (SMC), we hypothesized that RhoA-mediated nuclear translocalization of the myocardin-related transcription factors (MRTFs) was important for regulating SMC phenotype. MRTF-A protein and MRTF-B message were detected in aortic SMC and in many adult mouse organs that contain a large SMC component. Both MRTFs upregulated SMC-specific promoter activity as well as endogenous SM22alpha expression in multipotential 10T1/2 cells, although to a lesser extent than myocardin. We used enhanced green fluorescent protein (EGFP) fusion proteins to demonstrate that the myocardin factors have dramatically different localization patterns and that the stimulation of SMC-specific transcription by certain RhoA-dependent agonists was likely mediated by increased nuclear translocation of the MRTFs. Importantly, a dominant-negative form of MRTF-A (DeltaB1/B2) that traps endogenous MRTFs in the cytoplasm inhibited the SM alpha-actin, SM22alpha, and SM myosin heavy chain promoters in SMC and attenuated the effects of sphingosine 1-phosphate and transforming growth factor (TGF)-beta on SMC-specific transcription. Our data confirmed the importance of the NH(2)-terminal RPEL domains for regulating MRTF localization, but our analysis of MRTF-A/myocardin chimeras and myocardin RPEL2 mutations indicated that the myocardin B1/B2 region can override this signal. Gel shift assays demonstrated that myocardin factor activity correlated well with ternary complex formation at the SM alpha-actin CArGs and that MRTF-serum response factor interactions were partially dependent on CArG sequence. Taken together, our results indicate that the MRTFs regulate SMC-specific gene expression in at least some SMC subtypes and that regulation of MRTF nuclear localization may be important for the effects of selected agonists on SMC phenotype.


Antinociceptive Activity of Borreria verticillata: In vivo and In silico Studies.
Borreria verticillata (L.) G. Mey. known vassourinha has antibacterial, antimalarial, hepatoprotective, antioxidative, analgesic, and anti-inflammatory, however, its antinociceptive action requires further studies. Aim of the study evaluated the antinociceptive activity of B. verticillata hydroalcoholic extract (EHBv) and ethyl acetate fraction (FAc) by in vivo and in silico studies. In vivo assessment included the paw edema test, writhing test, formalin test and tail flick test. Wistar rats and Swiss mice were divided into 6 groups and given the following treatments oral: 0.9% NaCl control group (CTRL), 10 mg/kg memantine (MEM), 10 mg/kg indomethacin (INDO), 500 mg/kg EHBv (EHBv 500), 25 mg/kg FAc (FAc 25) and 50 mg/kg FAc (FAc 50). EHBv, FAc 25 and 50 treatments exhibited anti-edematous and peripheral antinociceptive effects. For in silico assessment, compounds identified in FAc were subjected to molecular docking with COX-2, GluN1a and GluN2B. Ursolic acid (UA) was the compound with best affinity parameters (binding energy and inhibition constant) for COX-2, GluN1a, GluN2B, and was selected for further analysis with molecular dynamics (MD) simulations. In MD simulations, UA exhibited highly frequent interactions with residues Arg120 and Glu524 in the COX-2 active site and NMDA, whereby it might prevent COX-2 and NMDA receptor activation. Treatment with UA 10 mg/Kg showed peripheral and central antinociceptive effect. The antinociceptive effect of B. verticillata might be predominantly attributed to peripheral actions, including the participation of anti-inflammatory components. Ursolic acid is the main active component and seems to be a promising source of COX-2 inhibitors and NMDA receptor antagonists.


[A case of right liver atrophy].
The authors report a case of right liver atrophy. This rare anomaly was suspected during post-operative period on abnormalities of cholangiogram. This biliary tract anomaly was diagnosed by CT scan. This congenital abnormality may be associated with biliary tract abnormalities, portal hypertension and other congenital abnormalities.


Immobilization of proteins on organic polymer beads.
A new method is described for the immobilization of biologically active proteins onto several types of organic polymer beads. First, the soluble protein is modified by reaction with an excess of a hydrophobic imidoester, for example methyl 4-phenyl-butyrimidate, at ca. pH 9 and 0 degrees . Excess imidoester and side products resulting from imidoester hydrolysis are separated from the hydrophobic protein derivative by exclusion chromatography or dialysis. A suspension of polymer beads (e.g. Amberlite XAD-7) is then added to a solution of the modified protein at room temperature or below and stirred gently for 1-2 h. The polymer beads are allowed to settle, separated from the solution by decantation or filtration, washed, and resuspended in an appropriate buffer. Quantitative adsorption of protein to the polymer beads is observed under such conditions. The synthesis of seven hydrophobic imidoesters and their use for the immobilization of trypsin onto several types of porous polymer beads is described. The immobilizations of trypsin, yeast alcohol dehydrogenase, and E. coli asparaginase by this procedure with high recoveries of catalytic activity, suggests that it will be applicable to a large number of biologically active proteins.


Visible-light-induced thiotrifluoromethylation of terminal alkenes with sodium triflinate and benzenesulfonothioates.
An unconventional reductive quenching cycle was developed to realize the visible-light-induced thiotrifluoromethylation of terminal alkenes. CF3SO2Na was used as an easy to handle CF3 radical source to afford the desired products in moderate to good yields. Mild reaction conditions and a broad substrate scope feature in this transformation.


Analysis of fracture prevalence in kidney-pancreas allograft recipients.
Fractures occur in 11 to 26% of renal allograft recipients after transplantation despite improvements in bone and mineral disorders. This high fracture rate is likely a consequence of accelerated osteopenia. The cause of posttransplant bone loss is multifactorial, and patients with insulin-dependent diabetes mellitus and renal failure may have additional fracture risks such as low turnover bone disease. This retrospective cohort study was undertaken to determine the long-term incidence and the potential risk factors of posttransplant fractures in patients with insulin-dependent diabetes mellitus undergoing combined kidney-pancreas allograft transplantation. Thirty-five patients with insulin-dependent diabetes mellitus who received a combined kidney-pancreas allograft between 1987 and 1992 were evaluated. Thirty-five kidney allograft recipients matched for age, gender, and the date of transplant were also reviewed. The fracture incidence in the kidney-pancreas group was 49% after transplantation. The rate of first fracture after kidney-pancreas transplantation was 12.1% per patient year, resulting in a 5-yr fracture-free rate of 48%. The initial fracture occurred at a mean of 31.06 +/- 19.9 mo. Steroid exposure was found to increase the risk of fracture, and analysis by means of a Cox regression model estimated that an increase in cumulative steroid exposure of 10 mg/kg at any given month increased the hazard of sustaining a fracture by 9% (95% confidence interval for hazard ratio, 1.01 to 1.18; P = 0.031). This analysis suggests that kidney-pancreas recipients are at significant risk of sustaining a fracture within a few years after transplantation.


Lightweight reduced graphene oxide-Fe3O4 nanoparticle composite in the quest for an excellent electromagnetic interference shielding material.
This work reports a detailed study of reduced graphene oxide (rGO)-Fe3O4 nanoparticle composite as an excellent electromagnetic (EM) interference shielding material in GHz range. A rGO-Fe3O4 nanoparticle composite was synthesized using a facile, one step, and modified solvothermal method with the reaction of FeCl3, ethylenediamine and graphite oxide powder in the presence of ethylene glycol. Various structural, microstructural and optical characterization tools were used to determine its synthesis and various properties. Dielectric, magnetic and EM shielding parameters were also evaluated to estimate its performance as a shielding material for EM waves. X-ray diffraction patterns have provided information about the structural and crystallographic properties of the as-synthesized material. Scanning electron microscopy micrographs revealed the information regarding the exfoliation of graphite into rGO. Well-dispersed Fe3O4 nanoparticles over the surface of the graphene can easily be seen by employing transmission electron microscopy. For comparison, rGO nanosheets and Fe3O4 nanoparticles have also been synthesized and characterized in a similar fashion. A plot of the dielectric and magnetic characterizations provides some useful information related to various losses and the relaxation process. Shielding effectiveness due to reflection (SER), shielding effectiveness due to absorption (SEA), and total shielding effectiveness (SET) were also plotted against frequency over a broad range (8-12 GHz). A significant change in all parameters (SEA value from 5 dB to 35 dB for Fe3O4 nanoparticles to rGO-Fe3O4 nanoparticle composite) was found. An actual shielding effectiveness (SET) up to 55 dB was found in the rGO-Fe3O4 nanoparticle composite. These graphs give glimpses of how significantly this material shows shielding effectiveness over a broad range of frequency.


The relationship of serum IgG antibody titers to periodontal pathogens to indicators of the host response in crevicular fluid.
In this study; the relationship of indicators of the local host response in gingival crevicular fluid (GCF) to the serum antibody titer to periodontal pathogens was examined. 15 patients with chronic adult periodontitis were studied. GCF was collected and analyzed for the total amount of IgG, IgM, the lysosomal enzyme B-glucuronidase (BG) and alpha-2-macroglobulin (alpha 2M). At the same examination, serum from these patients was collected, and enzyme-linked immunosorbent assays used to determine the serum IgG antibody titer to a panel of 17 periodontal pathogens (Actinobacillus actinomycetemcomitans (3 strains), Bacteroides gingivalis (4), Eikenella corrodens (2), Wolinella recta, Bacteroides intermedius (3), Fusobacterium nucleatum, and 3 Capnocytophaga species). Using Spearman rank order correlation analysis, correlation coefficients were calculated to relate the 4 indicators of host response in GCF to the serum IgG antibody titer to each of the 17 micro-organisms. The mean correlation between total IgG in GCF and the serum IgG antibody titer was positive (r = +0.30), and statistically significant correlations between total IgG in GCF and serum IgG antibody titer were observed for one strain of B. intermedius and C. ochracea. A weaker positive correlation was observed for IgM (r = 0.18). In contrast, the mean correlation between total BG in GCF and the serum antibody titer was negative (r = -0.34). Statistically significant negative correlations were observed for all 3 strains of A. actinomycetemcomitans, one strain of E. corrodens and W. recta. The mean correlation for alpha 2M was r = -0.06. These data suggest that elevated BG activity in GCF, believed to be a marker for lysosomal enzyme released from polymorphonuclear leukocytes in the crevicular environment, may be associated with a reduced serum IgG antibody response to suspected periodontal pathogens. Furthermore, these findings imply that the development of a serum IgG antibody response to suspected periodontal pathogens is consistent with a protective host response.


[Seven days of intermittent terbinafine 250 mg treatment in Tinea pedis].
Tinea pedis responds well to topical antifungal therapy, however, relapse of the disease is not uncommon. Long-term application of antifungals is usually necessary to control relapse. We conducted an open trial of a 7 day intermittent course of oral terbinafine treatment at 250 mg/day for plantar type and interdigital type of tinea pedis. Seventy-five patients of plantar type and 49 patients of interdigital tinea pedis were treated with a 7 day course of terbinafine 250 mg/day. Clinical assessments were made at baseline and every 4 weeks. Another 7 day course of the same amount of terbinafine were given depending on the clinical and the mycological response. Of the 75 plantar type tinea pedis with 8 patients excluded, 66 of the remaining 67 (98.5%) were evaluated as cured. Of the 49 interdigital tinea pedis (3 excluded), 43 of 46 patients (93.5%) cured. Relapse of the disease was observed in 4 of 51 patients at 1 year after treatment, 4 of 25 at 2 years, and 2 of 9 at 3 years in the plantar type, and in 4 of 30 at 1 year, 0 of 14 at 2 years, and 0 of 6 at 3 years in the interdigital tinea pedis group. Intermittent terbinafine therapy is thus effective in the treatment of tinea pedis.


Generation and maintenance of immune interferon-producing cells induced by allogeneic stimulation in mice.
When spleen cells derived from C57BL/6 mice immunized with L cells 7 days previously were cocultured with antigenic cells, immune interferon appeared in the culture fluid. We analyzed the tissue distribution of the immune interferon-producing cells (IIPC) which appeared in various lymphoid organs after allogeneic stimulation. Although fluid from cocultures of L-cell-sensitized thymocytes and L-cells could not detect interferon activity consistently, small numbers of IIPC could be detected by using the enumeration method of IIPC. The generation, maintenance, and nature of IIPC emerging in the spleen were different depending on how the host mice were immunized. Multiple antigenic stimulations were more effective and induced longer-lasting immune interferon production than a single stimulation. IIPC induced by a single stimulation appeared to be sensitive to cortisone, vinblastine, and cyclophosphamide and were relatively short lived. In contrast, IIPC induced by multiple stimulations seemed to be partially resistant to these drugs and long lived. When mice were immunized with intact L-cells, carrageenan, a known antimacrophage agent, had no effect on immune interferon production. However, when mice were immunized with solubilized L-cell antigen, this drug displayed a suppressive effect on immune interferon production.


Terminology, concepts, and models in genetic epidemiology.
Genetic epidemiology brings together approaches and techniques developed in mathematical genetics and statistics, medical genetics, quantitative genetics, and epidemiology. In the 1980s, the focus was on the mapping and identification of genes where defects had large effects at the individual level. More recently, statistical and experimental advances have made possible to identify and characterise genes associated with small effects at the individual level. In this chapter, we provide a brief outline of the models, concepts, and terminology used in genetic epidemiology.


Persistent bleeding after laparoscopic supracervical hysterectomy.
In our clinical experience, there seemed to be a correlation between cervical stump bleeding and adenomyosis. Therefore, we wanted to conduct a study to determine whether there was an actual correlation and to identify other risk factors for persistent bleeding after a laparoscopic supracervical hysterectomy. The study included women who underwent laparoscopic supracervical hysterectomy from January 1, 2003, through December 31, 2012. Data were collected on age, postmenopausal status, body mass index (BMI), uterine weight, indication for hysterectomy, concomitant bilateral salpingo-oophorectomy (BSO), presence of endometriosis, surgical ablation of the endocervix, adenomyosis, presence of endocervix in the specimen, and postoperative bleeding. The study included 256 patients, of whom 187 had no postoperative bleeding after the operation, 40 had bleeding within 12 weeks, and 29 had bleeding after 12 weeks. The 3 groups were comparable in BMI, postmenopausal status, uterine weight, indication for hysterectomy, BSO, surgical ablation of the endocervix, adenomyosis, and the presence of endocervix. However, patients who had postoperative bleeding at more than 12 weeks were significantly younger (P = .002) and had a higher rate of endometriosis (P < .001). Risks factors for postoperative bleeding from the cervical stump include a younger age at the time of hysterectomy and the presence of endometriosis. Therefore, younger patients and those with endometriosis who desire to have no further vaginal bleeding may benefit from total hysterectomy over supracervical hysterectomy. All patients who are undergoing supracervical hysterectomy should be counseled about the possible alternatives, benefits, and risks, including continued vaginal bleeding from the cervical stump and the possibility of requiring future treatment and procedures.


Clinical results of primary low contact stress cementless total knee arthroplasty.
The published clinical and radiographic outcomes data for primary cementless low-contact stress (LCS) total knee arthroplasty (TKA) were examined. The majority of patients (92.6%) were pain free or had only mild pain, and excellent or good knee scores (99.1%) at follow-up. Patella difficulties and significant radiolucent lines were rare, occurring in less than 1% of patients. The average range of motion (ROM) for patients without a history of previous knee surgeries was 112.1 degrees. Previous knee procedures had a negative impact on ROM. Overall, primary cementless LCS TKA achieves excellent clinical nd radiographic results.


[Physiological and pathological conditions of the prepuce in childhood: treatment methods].
The authors analyse treatment of 3235 patients with prepuce pathology aged from 8 days to 16 years, the results of the treatment of preputial sac pathology; describe clinical manifestations of phimosis (physiological, hypertrophic, cicatricial) in children; formulate treatment policy, indications and contraindications for conservative and surgical treatment; provide practical recommendations on hygiene and care for infant and young age boys.


The long-term effects of the health coaching self-management program for nursing-home residents.
Little is known about whether a self-management program for nursing-home residents (NHR) with cognitive impairment is likely to have an impact on the care of this growing population. This study aimed to evaluate the effects of the health-coaching self-management program for NHR (HCSMP-NHR) on 1) self-efficacy and goal attainment scaling (GAS), 2) health status and quality of life (QoL) among older people, including those with cognitive impairment, in Korean nursing homes. This was a cluster-randomized controlled trial. Participants in the intervention group (n=43, mean age =80.91±7.65 years) received the HCSMP-NHR intervention, composed of group health education and individual coaching, for 8 weeks. Conventional care was provided to the conventional group (n=47, mean age =80.19±7.53 years) during the same period. The effects of the HCSMP-NHR were measured three times: at baseline, week 9, and week 20. The intervention group showed better results for self-efficacy (P=0.007), health distress (P=0.007), depression (P<0.001), and QoL (P=0.04) at week 9. Mean GAS score of the intervention group gradually increased from -0.38 to 0.74. The time × group interaction showed that the intervention group had significant improvements in QoL (P=0.047), and significant reductions in health distress (P=0.016) and depression (P<0.001), while showing no deterioration in shortness of breath (P<0.001). Our study findings indicate that the HCSMP-NHR improved self-efficacy and GAS and enhanced the health status and QoL of NHR with chronic conditions who also had mild-to-moderate cognitive impairment. Moreover, these effects were successfully maintained over the 5 months of the trial. Further research is needed to establish the optimum intervention period and to assess the possibility of nationwide implementation of the HCSMP-NHR.


Ghrelin antagonizes MPTP-induced neurotoxicity to the dopaminergic neurons in mouse substantia nigra.
Ghrelin, a stomach-derived hormone which induces growth hormone release and promotes positive energy balance, has been reported to inhibit cell apoptosis in endotheliocytes, osteoblasts and cardiocytes. Recent evidence has shown that ghrelin can also inhibit neuronal apoptosis of the hypothalamus and the hippocampus. However, little is known about the effects of ghrelin on the substantia nigra pars compacta (SNpc) neurons in which ghrelin's receptor, growth hormone secretagogue receptor (GHSR)-1a, is highly expressed. In the present study, we investigated whether ghrelin could protect nigral dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. We observed that ghrelin, acting through GHS-R 1a, inhibited MPTP-induced dopaminergic neuronal loss in the SNpc as well as dopamine depletion in the striatum. Ghrelin could also reverse the down-regulated the expression of Bcl-2, up-regulated the expression of Bax, and caspase-3 activation caused by MPTP. This study demonstrated that ghrelin might be a potential protector of dopaminergic neurons in a therapeutic strategy for Parkinson's disease.


[International Classification of Functioning, Disability and Health (ICF) in the most important diseases and conditions of rheumatology practice].
Musculoskeletal conditions are common throughout the world and their impact on individuals and society is enormous. The integrative and bio-psycho-socialy based model, the International Classification of Functioning, Disability and Health (ICF) is highly useful for structuring determinants of disability in these conditions. ICF encompasses health and health-related domains: body functions and structure, activity and participation and environmental factors. In clinical settings ICF is used for functional status assessment, goal setting and treatment planning and monitoring, as well as outcome measurement. In clinical practice the implementation of ICF is facilitated by the use of the ICF-based applications, such as ICF sheets or ICF Core Sets. In this article it is reported on the most important musculoskeletal conditions in rheumatology practice from the point of view of ICF and is complementary to the article by the same author that appeared in the previous issue of this journal.


What happens to women with chronic pelvic pain after a negative [normal] laparoscopy?
Chronic pelvic pain remains unexplained in one third of women who have negative [normal] findings at diagnostic laparoscopy. This paper investigates the history of chronic pelvic pain after a negative laparoscopy and to assess the effect of negative laparoscopy on self perceived quality of life. The results of this study show that chronic pelvic pain persists in the majority of women who had negative laparoscopy in the medium to long term. It also shows that laparoscopy is beneficial in such group of women when findings are negative, due to its reassuring effect. A few quality of life issues also seem to improve despite persistence of chronic pelvic pain after a negative [normal] laparoscopy.


The role of parental personality traits in differential parenting.
Significant relationships have been demonstrated between parental personality and parenting toward individual children, but there is little research exploring the relationship between parental personality and differential parenting (DP). The present study examined the relationship between the Big Five personality dimensions and differential positivity and negativity in parenting (observed and self-report measures). The analyses are based on a sample of 867 children nested within 381 families. Using multilevel modeling and controlling for child age, gender, birth order, behavior, and family socioeconomic status analyses revealed that maternal and paternal agreeableness were inversely related to reports of differential positivity. Agreeableness predicted observed differential negativity, and the relationship was curvilinear (at both high and low levels of agreeableness, differential negativity was higher). Finally, mothers with the most openness to experience exhibited the highest levels of reported differential negativity. The findings suggest that parental personality is a modest yet important influence to consider when conceptualizing the sources of DP.


Neutrophil gelatinase-associated lipocalin levels in chronic haemodialysis patients.
Neutrophil gelatinase-associated lipocalin (NGAL), a small 25 kDa protein strongly induced in injured renal tubular cells, represents an interesting emerging biomarker in the field of clinical nephrology. The aim of the present pilot study was to analyze circulating NGAL levels in a small cohort of 30 patients on chronic haemodialysis (HD), in order to assess any relationships with different laboratory and clinical parameters. Pre- and post-HD levels were higher in patients than in healthy subjects (485.2 +/- 49.7 vs 51.2 +/- 4.6 ng/mL; P < 0.001; and 167.4 +/- 48.0 vs 51.2 +/- 4.6 ng/mL; P = 0.01). Furthermore, a single HD session decreased NGAL levels by approximately fourfold (485.2 +/- 49.7 vs 167.4 +/- 48.0 ng/mL; p:0.01), with a reduction ratio of 73 +/- 14%. At baseline, direct and independent correlations were found between NGAL and, respectively, high-sensitivity C-reactive protein (beta = 0.34; P = 0.03) and spKt/V (beta = 0.35; P = 0.02). The findings showed that HD patients have chronically increased levels of circulating NGAL. However, with a single HD session, a marked reduction was achieved in circulating NGAL values, probably as a result of an important dialytic removal, similar to that observed for other cytokines. Finally, the direct independent correlation found between NGAL and spKt/V raises the question of whether, in the future, NGAL may also become a useful tool in predicting the adequacy of dialysis and in guiding the management of dialysis prescriptions.


Photon diffusion in a homogeneous medium bounded externally or internally by an infinitely long circular cylindrical applicator. VI. Time-domain analysis.
Part VI analytically examines time-domain (TD) photon diffusion in a homogeneous medium enclosed by a "concave" circular cylindrical applicator or enclosing a "convex" circular cylindrical applicator, both geometries being infinite in the longitudinal dimension. The aim is to assess characteristics of TD photon diffusion, in response to a spatially and temporally impulsive source, versus the line-of-sight source-detector distance along the azimuthal or longitudinal direction on the concave or convex medium-applicator interface. By comparing to their counterparts evaluated along a straight line on a semi-infinite medium-applicator interface versus the same source-detector distance, the following patterns are indicated: (1) the peak photon fluence rate is always reached sooner in concave and later in convex geometry; (2) the peak photon fluence rate decreases slower along the azimuthal and faster along the longitudinal direction on the concave interface, and conversely on the convex interface; (3) the total photon fluence decreases slower along the azimuthal and faster along the longitudinal direction on the concave interface, and conversely on the convex interface; (4) the ratio between the peak photon fluence rate and the total fluence is always greater in concave geometry and smaller in convex geometry. The total fluence is equivalent to the steady-state photon fluence analyzed in Part I [J. Opt. Soc. Am. A27, 648 (2010)10.1364/JOSAA.27.000648JOAOD61084-7529]. The patterns of peak fluence rate, time to reaching peak fluence rate, and the ratio of these two, correspond to those of AC amplitude, phase, and modulation depth of frequency-domain results demonstrated in Part IV [J. Opt. Soc. Am. A29, 1445 (2012)10.1364/JOSAA.29.001445JOAOD61084-7529].


[The operative videothoracosopy in rendering emergency surgical care in penetrating gunshot chest wounds].
The modern doctrine of military surgery is based on the concept of maximal and, if possible, simultaneous surgical aid to the wounded in the shortest period of time after the injury. It could be achieved by approximation of specialized surgical section to the zone of fighting and improvement of medical evaluation. These are conditions for applicability of modern methods of treatment and for perfecting of surgical strategies to the wounded, such as videothoracoscopy. To report the experience of the usage of videothoracoscopy in the treatment of the wounded with penetrating gunshot wounds of chest (PFAWT) in military hospital. 23 patients with PFWAT was administer surgical therapy: 19 patients had pleural draining at previous stages of medical evacuation, 4 patients were delivered directly from the battle Geld 1.5 hours after the injury. 11 patients with pleural drains and 4 patients, delivered from battle Geld, had indications for videothoracoscopy. These indications included ongoing intrapleural bleeding, clotted hemothorax and prolonged leakage of the air through the drain. Suturing of the lung wounds was performed by Endo-GIA-30 stapler. If it was impossible, manual suture EndoStitch USSC was used. In 2 cases was performed wedge-like resection by EndoGIA-30. The bleeding from the thoracic wall wounds was controlled by electrocautery. The clotted hemothorax was removed by fragmentation with EndoBabcock, washing out and aspiration through large diameter tubes. The duration of the procedure ranged from 40 to 90 minutes. None had suppurative complications. All patients was survived. The mean duration of inpatient period was 20 days, rehabilitation period-14 days.


[ACUTE CHOLECYSTITIS: COMPARATIVE STUDEY OF THREE MEDICAL-SURGICAL ALTERNATIVES]
Three alternatives of surgical treatment for acute cholescystitis were studied. The 40 patients integrating Group I were studied in a retrospective way and received conservative medical treatment and deferred conventional surgery. The 40 patients integrating Group II were studied in a prospective way and they were operated according to conventional technique 72 hours before the beginning of the acute vesicular condition. The 40 patients integrating Group III were studied in a prospective way and they were operated using laparoscopic technique. The operation time, fall of temperature, the removal of the nasogastric tube, the postoperative pain, the oral tolerance and the postoperative hospitalization time were compared. We find out that there is a significant difference between all the aforementioned parameters and, particularly, between the conventional technique and the laparoscopic technique.


Modeling in manual materials handling.
Manual materials handling (MMH) account for approximately $15.0 billion of injuries cost in the United States alone. Because of the need to establish manual handling guidelines, different approaches to achieve this goal were pursued. Such approaches are based on biomechanics, work physiology, and psychophysics. In order to better understand the MMH system's behavior, models were developed. These models can be divided into biomechanical models, physiological models, psychophysically based capacity models, safe load handling models, and simulation models. This paper will present a sample of these models and discusses their advantages and disadvantages.


[Radical surgery with mini-thoracolaparotomy for esophageal cancer].
In our institute, radical esophagectomy through mini-thoracolaparotomy has been performed as a less-invasive surgery for esophageal cancer since 1996. We describe the indications for and operative procedures of mini-thoracolaparotomy. Next we report the preliminary results of a prospective randomized trial that compared mini-thoracolaparotomy with conventional thoracolaparotomy in 30 patients without neoadjuvant therapy. There were no differences between the two groups in operative time, bleeding volume, and number of dissected lymph nodes. Thoracolaparotomy was effective in decreasing the quantity of morphinerequired in the ICU and shortening hospitalization after surgery. Thoracolaparotomy was effective in preventing a decrease in and early recovery of postoperative vital capacity. In clinical data on radical esophagectomy performed through a right thoracotomy and reconstruction with a stomach tube from 1996 to 2000, the 5-year survival rate of 63 patients in the thoracolaparotomy group (67.6%) did not differ from that of 124 patients in the conventional surgery group (49.9%).


Missing-in-metastasis protein downregulates CXCR4 by promoting ubiquitylation and interaction with small Rab GTPases.
Surface expression of chemokine receptor CXCR4 is downregulated by missing-in-metastasis protein (MIM; also known as MTSS1), a member of the inverse BAR (I-BAR)-domain protein family that recognizes and generates membranes with negative curvature. Yet, the mechanism for the regulation is unknown. Here, we show that MIM forms a complex with CXCR4 by binding to E3 ubiquitin ligase AIP4 (also known as ITCH) in response to stromal cell-derived factor 1 (SDF-1; also known as CXCL12). Overexpression of MIM promoted CXCR4 ubiquitylation, inhibited cellular response to SDF-1, caused accumulation and aggregation of multivesicular bodies (MVBs) in the cytoplasm, and promoted CXCR4 sorting into MVBs in a manner depending on binding to AIP4. In response to SDF-1, MIM also bound transiently to the small GTPase Rab5 at 5 min and to Rab7 at 30 min. Binding to Rab7 requires an N-terminal coiled-coil motif, deletion of which abolished MIM-mediated MVB formation and CXCR4 internalization. Our results unveil a previously unknown property of MIM that establishes the linkage of protein ubiquitylation with Rab-guided trafficking of CXCR4 in endocytic vesicles.


Animal-related injuries in veterinary services personnel, U.S. Army, 2001-2018.
Limited data exist on animal-related injuries in the U.S. Army veterinary service (VS). The purpose of this study was to determine the incidence of animalrelated injuries and the associated risk factors in VS personnel. A retrospective cohort study was conducted using military healthcare surveillance data on animal- related injuries in VS personnel from 2001-2018. Yearly incidence of medically diagnosed animal-related injuries ranged from 25-50 injuries per 1,000 person-years from 2001-2018. Linear regression showed no significant trend in the incidence rate per year over the study period (R2=0.005). Bites were the most common injury (86.5%), with dog bites (44.3%) being the most common injury type and dogs the most common species implicated. After controlling for sex, age group, race/ethnicity group, and occupation, adjusted incidence rate ratios (AIRRs) showed significantly elevated risk for animal-related injuries among females compared to males (AIRR=1.69; 95% confidence interval [CI]: 1.45-1.99), soldiers aged 17-29 compared to those aged 30 years or older (AIRR=2.55; 95% CI: 2.12-3.08), and technicians compared to veterinarians (AIRR=1.57; 95% CI: 1.30-1.89). Unlike the majority of published literature on veterinary occupational health and safety, this study showed a clear increased risk of diagnoses of injury among females compared to males.


Male choice, willingness to mate and body size in seaweed flies (Diptera: Coelopidae).
The mating system of seaweed flies is characterized by scramble competition and a premating struggle during which females vigorously attempt to remove mounted males and prevent copulation. Here we investigate factors affecting the willingness of males to mate in five species of Coelopa : C. frigida, C. nebularum, C. ursina, C. pilipes and C. vanduzeei. The data from 2000 individual observations of pairs of flies revealed no association between female size and the willingness of males to mate, suggesting that males do not exhibit mate choice for larger, more fecund females. Male willingness to mount was associated with male size in C. frigida, C. nebularum and C. ursina, although not in C. pilipes and C. vanduzeei. There is considerable intraspecific variation in male size in the former three species, including the presence of two almost discrete size classes within C. nebularum. We suggest that males of different sizes in these species may be adopting alternative reproductive strategies. Large males may benefit from increased longevity and their ability to withstand female rejection responses, whereas small males are more active and thus likely to encounter and mount more females. In addition small males develop faster and thus gain earlier access to females. Copyright 1999 The Association for the Study of Animal Behaviour.


Agreement of four competing guidelines on prevention of venous thromboembolism and comparison with observed physician practices: a cross-sectional study of 1,032 medical inpatients.
To assess the degree of agreement between four competing guidelines regarding the recommendation for prophylactic heparin therapy and to report to what extent actual practice agreed with or differed from the recommendations made before these guidelines were disseminated. Four French guidelines were applied to data from a cross-sectional study conducted before their dissemination. Twenty-six medical units of a teaching and a nonteaching hospital. One thousand thirty-two medical inpatients. Interguideline agreement rated by the kappa coefficient and percentage of patients receiving prophylactic heparin treatment. The percentage of patients requiring prophylactic treatment ranged from 35.4% to 54.6% (overall kappa coefficient, 0.65 [0.63 to 0.68]), depending on the guideline. The four guidelines agreed in recommending prophylactic heparin treatment in 330 patients (32.0%). The corresponding rate of prophylactic treatment use was 57.0% (188/330). None of the guidelines recommended prophylactic heparin treatment in 385 patients (37.3%). The physicians did not order prophylactic treatment in 80.3% of these patients (309/385). The guidelines disagreed in recommending prophylactic treatment in 317 patients (30.7%). The corresponding rate of prophylactic treatment use was 32.8% (104/317). The four guidelines agreed in 69.3% of patients but physician practices were already quite appropriate in these patients before the guidelines were disseminated. Active dissemination of the guidelines can be expected to improve physician practices in the treatment of these patients, but likely with limited impact. In contrast, the four guidelines disagreed in 30.7% of patients. Further clinical trials are needed in this subgroup of patients.


Occurrence in Saccharomyces cerevisiae of a gene homologous to the cDNA coding for the alpha subunit of mammalian G proteins.
From cross-hybridization studies with cDNAs that code for the alpha subunits of rat brain guanine nucleotide-binding regulatory (G) proteins, we have isolated a gene from yeast Saccharomyces cerevisiae encoding an amino acid sequence that is highly homologous to the alpha subunit of the G protein that mediates inhibition of adenylate cyclase (Gi alpha) from rat brain. The gene, tentatively designated as GPA1, contains a contiguous, single open reading frame of 1416 nucleotides that codes for a protein of 472 amino acids with a calculated Mr of 54,075. The predicted amino acid sequence of the protein encoded by the GPA1 gene (tentatively designated as G protein 1 alpha or GP1 alpha) is remarkably homologous to the amino acid sequence of rat brain Gi alpha and the alpha subunit of the G protein of unknown function (Go alpha); the primary structure of the sites for GTP hydrolysis as well as GTP interaction are nearly identical. The main difference in the molecular sizes of yeast GP1 alpha (472 amino acids) and rat brain Gi alpha (355 amino acids) is due to the presence of a stretch of 110 extra amino acid residues in yeast GP1 alpha, which are inserted near the NH2-terminal one-third of mammalian Gi alpha. From blot-hybridization analysis, the size of the GP1 alpha mRNA was estimated as 1.7 kilobases.


Cortical network architecture for context processing in primate brain.
Context is information linked to a situation that can guide behavior. In the brain, context is encoded by sensory processing and can later be retrieved from memory. How context is communicated within the cortical network in sensory and mnemonic forms is unknown due to the lack of methods for high-resolution, brain-wide neuronal recording and analysis. Here, we report the comprehensive architecture of a cortical network for context processing. Using hemisphere-wide, high-density electrocorticography, we measured large-scale neuronal activity from monkeys observing videos of agents interacting in situations with different contexts. We extracted five context-related network structures including a bottom-up network during encoding and, seconds later, cue-dependent retrieval of the same network with the opposite top-down connectivity. These findings show that context is represented in the cortical network as distributed communication structures with dynamic information flows. This study provides a general methodology for recording and analyzing cortical network neuronal communication during cognition.


HIV Risk, Prevalence, and Access to Care Among Men Who Have Sex with Men in Lebanon.
Little is known about HIV prevalence and risk among men who have sex with men (MSM) in much of the Middle East, including Lebanon. Recent national-level surveillance has suggested an increase in HIV prevalence concentrated among men in Lebanon. We undertook a biobehavioral study to provide direct evidence for the spread of HIV. MSM were recruited by respondent-driven sampling, interviewed, and offered HIV testing anonymously at sites located in Beirut, Lebanon, from October 2014 through February 2015. The interview questionnaire was designed to obtain information on participants' sociodemographic situation, sexual behaviors, alcohol and drug use, health, HIV testing and care, and experiences of stigma and discrimination. Individuals not reporting an HIV diagnosis were offered optional, anonymous HIV testing. Among the 292 MSM recruited, we identified 36 cases of HIV (12.3%). A quarter of the MSM were born in Syria and recently arrived in Lebanon. Condom use was uncommon; 65% reported condomless sex with other men. Group sex encounters were reported by 22% of participants. Among the 32 individuals already aware of their infection, 30 were in treatment and receiving antiretroviral therapy. HIV prevalence was substantially increased over past estimates. Efforts to control future increases will have to focus on reducing specific risk behaviors and experience of stigma and abuse, especially among Syrian refugees.


Peripheral OCT Assisted by Scleral Depression in Retinopathy of Prematurity.
To determine whether handheld widefield optical coherence tomography (OCT) can be used to document retinopathy of prematurity (ROP) stage while using scleral depression to improve peripheral views. Prospective observational study. Consecutive neonates admitted to the neonatal intensive care unit (NICU) in a single academic medical center who also met criteria for ROP screening and consented for research imaging. Scleral depression was combined with widefield OCT using an investigational 400-kHz, 55-degree field of view handheld OCT during routine ROP screening from October 28, 2020 to March 03, 2021. Acquisition of en face and B-scan imaging of the peripheral retina to objectively assess early vitreoretinal pathology, including the demarcation between vascularized and anterior avascular retina, the presence of early ridge formation, and small neovascular tufts. Various stages of ROP were detected using a rapid acquisition OCT system. In one neonate, serial OCT imaging over a five-week period demonstrated accumulation of neovascular tufts with progression to stage 3 ROP with extraretinal fibrovascular proliferation along the ridge. Videography of this technique is included in this report for instructional purposes. Serial examinations using widefield OCT and scleral depression is feasible and may improve detection and documentation of ROP disease progression. Earlier detection of ROP-related proliferation may prevent vitreoretinal traction, retinal detachment, and blindness.


Haemodynamic effects of alinidine, a specific sinus node inhibition, in patients with unstable angina or myocardial infarction.
Alinidine is a new sinus node inhibitor which does not interact with the beta adrenergic receptors. Its haemodynamic effects were studied in 57 patients; 24 with unstable angina, 9 with myocardial infarction and heart rate greater than 100 bpm but without heart failure. 10 with myocardial infarction treated with vasodilators and 14 with severe heart failure or shock. After dosages up to 40 mg alinidine, heart rate decreased by 14 +/- 7 bpm, mean arterial pressure was reduced by 3 +/- 6 mmHg, stroke volume remained unchanged while cardiac output decreased 0.5 +/- 0.61 min-1 and systemic vascular resistance increased. Signs of heart failure developed in 3 patients, although overall left ventricular filling pressure remained unchanged. The haemodynamic response to alinidine warrants further studies of its efficacy in patients with angina or sinus tachycardia.


F-block N-heterocyclic carbene complexes.
N-Heterocyclic carbenes (NHCs) can bind as two-electron sigma-donor ligands to lanthanide and actinide metal cations. In this review we summarise how the incorporation of an anionic group (alkoxide or amido), to form heterobidentate NHC ligands, allows the synthesis of a range of f-block NHC adducts. The tethering group also allows the lability of the NHC group, and its subsequent reactivity, to be studied. We include a brief survey of the known, structurally characterised f-element-NHC bond distances, and a range of substrates that react to displace the metal-bound NHC group.


[Polymorphism C366G of gene GRIN2B and verbal episodic memory: No association with schizophrenia].
The present study searched for associations between gene GRIN2B (glutamate receptor, ionotropic, N-methyl-D-aspartate, subunit 2B) and component processes of verbal episodic memory in schizophrenic patients. The Rey Auditory Verbal Learning Test (RAVLT) as a part of a large neuropsychological battery was administered to 302 patients with schizophrenic spectrum disorders (sample PI). Also, 285 patients (sample P2) and 243 healthy controls (sample C2) performed the "10 words" test that measures short-term memory. The GRIN2B rs7301328 (C366G) polymorphism was genotyped for each subject. There were no associations between the polymorphism and any measure of the RAVLT either in the whole PI sample or in a subsample of patients with a severe cognitive deficit. The GRIN2B influenced immediate recall and proactive interference in the "10 words" test in the control group: homozygotes CC recalled fewer words and showed a lower effect of proactive interference than carriers of other genotypes. The results suggest that the C366G polymorphism could influence verbal episodic memory in the general population, but this influence is absent in schizophrenic patients.


Skin metastases in metastatic uveal melanoma: GNAQ/GNA11 mutational analysis as a valuable tool.
Uveal melanomas represent 3.1% of all melanomas, with a high potential of metastatic disease of up to 50%, where the median survival time is 6 months. Though liver metastases dominate as the primary site for metastasis, the existence of primary skin metastases is still under discussion but has been reported in only a few studies. We present two cases in which patients with a known history of uveal melanoma developed melanoma skin metastases. Mutational analysis was performed to clarify the origin of the metastases (uvea or skin). The analyses revealed GNA11 mutations, which are typical for uveal melanoma. These cases strongly suggest the skin to be the primary site of uveal melanoma. Knowledge about the mutational status of uveal melanomas opens the opportunity for future targeted therapies that directly interact with the mutation and its activated signal cascades. First trials in uveal melanoma have shown promising results with MEK inhibitors.


Response to immune complex vaccine in chronic hepatitis B patients is associated with lower baseline level of serum IgG galactosylation.
The composition of glycan in immunoglobulin G (IgG) has shown to affect various diseases and can be regulated by drugs and preventive vaccination. A hepatitis B surface antigen (HBsAg)-hepatitis B immunoglobulin (HBIG) immune complex (YIC) therapeutic vaccine for chronic hepatitis B (CHB) patients has undergone clinical trials. To explore for markers of CHB, which could be associated with responsiveness to YIC therapeutic vaccine, serum IgG glycosylation in CHB patients was analyzed.Kinetic changes of serum galactosylated IgG in 53 hepatitis Be antigen (HBeAg)-positive CHB patients treated with YIC were monitored by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis. Whole blood cytokines were assayed by cytokine binding assay kits. All samples were back assayed before treatment, during therapy and follow-up for 6 months from a previous completed clinical trial.During YIC treatment, 26 patients with lower IgG galactosylation level at baseline [galactosylation level (Gal-ratio) = -0.29, 0.18 (mean, SD)] showed sustained increase of serum galactosylated IgG, and responded to YIC treatment by HBeAg seroconversion. While those who did not respond to YIC treatment [Gal-ratio = -0.40, 0.15 (mean, SD)] failed to show similar changes. Furthermore, this kinetic increase of galactosylated IgG correlated with marked up-regulated IL-2 level, confirming that effective cellular immune responses have participated in responsiveness.For HBeAg-positive CHB patients lower serum IgG galactosylation level may serve as an indicator for selecting a suitable subpopulation of candidates for YIC therapeutic vaccination.


Validation of the Frenchay activity index on stroke victims.
To evaluate the inter-rater reliability and predictive validity of the Frenchay Activities Index (FAI) in patients after stroke. One hundred sixty-one patients were selected for consecutive application of the FAI and National Institutes of Health Stroke Scale (NIHSS). Spearman's test was used for correlation between different scales. The FAI and NIHSS association was evaluated using ordinal logistic regression. Additionally, 36 patients underwent FAI rating on the same day by two independent evaluators. A negative correlation between the FAI and the NIHSS scores (p = 0.017 r = -0.22) was found. Adjusting all variables with possible association with the NIHSS, ordinal logistic regression showed that the FAI had a significant association with NIHSS scores (OR 0.93, 95% CI 0.87 to 0.99, p: 0.033). The inter-rater agreement was considered good, k = 0.66 (0.54 to 0.78), p < 0.001. The FAI is a valid and useful method to assess instrumental activities before acute stroke in a Brazilian population.


Fracture risk assessment and evaluation of femoroplasty in metastatic proximal femurs. An in vivo CT-based finite element study.
The goal of this study was twofold. First, we aimed to evaluate the accuracy of a finite element (FE) model to predict bone fracture in cancer patients with proximal femoral bone metastases. Second, we evaluated whether femoroplasty could effectively reduce fracture risk. A total of 89 patients were included, with 101 proximal femurs affected with bone metastases. The accuracy of the model to predict fracture was evaluated by comparing the FE failure load, normalized for body weight, against the actual occurrence of fracture during a 6-month follow-up. Using a critical threshold, the model could identify whether femurs underwent fracture with a sensitivity of 92% and a specificity of 66%. A virtual treatment with femoroplasty was simulated in a subset of 34 out of the 101 femurs; only femurs with one or more well-defined lytic lesions were considered eligible for femoroplasty. We modeled their lesions, as well as the surrounding 4 mm of trabecular bone, to be augmented with bone cement. The simulation of femoroplasty increased the median failure load of the FE model by 57% for lesions located in the head/neck of the femur. At this lesion location, all high risk femurs that had fractured during follow-up effectively moved from a failure load below the critical threshold to a value above. For lesions located in the trochanteric region, no definite improvement in failure load was found. Although additional validation studies are required, our results suggest that femoroplasty can effectively reduce fracture risk for several osteolytic lesions in the femoral head/neck.


Melanoma epidemiology.
New data show plateaus and even declines in rates of incidence and mortality due to melanoma among some age groups. Increased rates persist among older men, creating needs for health care planning. Early detection presents a paradox: screening activities, which may be more prevalent among those with higher socioeconomic status, may both increase incidence and decrease mortality (by diagnosing melanoma earlier and through the removal of precursor lesions). Studies of the development of nevi show that they are robust risk markers for melanoma and share some epidemiologic features with melanoma. Multiple primary melanomas develop in 5% to 10% of subjects with melanoma and may reflect genetic predisposition. Combined analyses and methodologic studies have refined estimation of the effects of risk factors.


[Expression of adhesion molecules in hepatic graft-versus-host disease].
I investigated effects of spleen cells on hepatic graft-versus-host disease (GVHD) and expression of adhesion molecules in a murine bone marrow transplant model, since these cells contain abundant T cells and induce severe GVHD. Furthermore, I investigated effects of tumor necrosis factor alpha (TNF alpha) on liver damage and expression of adhesion molecules in a murine bone marrow transplant model. By injection of spleen cells, the dotty, partially focal T cell infiltration with necrosis of hepatocytes was found in the liver parenchyma. Expression of leukocyte function associated antigen-1 (LFA-1) and cluster of differentiation-44 (CD44) was observed mainly on T cells and macrophages and expression of intercellular adhesion molecules-1 (ICAM-1) was observed on sinusoidal endothelial cells (SEC). T cells were in contact with SEC or hepatocytes and shedding of hepatocyte was found by electron microscopy. On the other hand, by injection of recombinant mouse TNF alpha the numbers of enlarged macrophages were increased in the liver parenchyma but the necrosis of hepatocytes was not apparent. Expression of LFA-1 and CD44 was mainly observed on macrophages and expression of ICAM-1 was found on SEC. Activated macrophages were observed in contact with SEC or hepatocytes by electron microscopy. No expression of ICAM-1 on interlobular bile duct epithelia was observed in any groups. This study suggests that the expression of adhesion molecules play an important role in developing hepatic GVHD. TNF alpha appeared to be one of the factors which deteriorate hepatic GVHD through an activation of macrophages and expression of adhesion molecules.


Real-World Rib Fracture Patterns in Frontal Crashes in Different Restraint Conditions.
The purpose of this study was to use the detailed medical injury information in the Crash Injury Research and Engineering Network (CIREN) to evaluate patterns of rib fractures in real-world crash occupants in both belted and unbelted restraint conditions. Fracture patterns binned into rib regional levels were examined to determine normative trends associated with belt use and other possible contributing factors. Front row adult occupants with Abbreviated Injury Scale (AIS) 3+ rib fractures, in frontal crashes with a deployed frontal airbag, were selected from the CIREN database. The circumferential location of each rib fracture (with respect to the sternum) was documented using a previously published method (Ritchie et al. 2006) and digital computed tomography scans. Fracture patterns for different crash and occupant parameters (restraint use, involved physical component, occupant kinematics, crash principal direction of force, and occupant age) were compared qualitatively and quantitatively. There were 158 belted and 44 unbelted occupants included in this study. For belted occupants, fractures were mainly located near the path of the shoulder belt, with the majority of fractures occurring on the inboard (with respect to the vehicle) side of the thorax. For unbelted occupants, fractures were approximately symmetric and distributed across both sides of the thorax. There were negligible differences in fracture patterns between occupants with frontal (0°) and near side (330° to 350° for drivers; 10° to 30° for passengers) crash principal directions of force but substantial differences between groups when occupant kinematics (and contacts within the vehicle) were considered. Age also affected fracture pattern, with fractures tending to occur more anteriorly in older occupants and more laterally in younger occupants (both belted and unbelted). Results of this study confirmed with real-world data that rib fracture patterns in unbelted occupants were more distributed and symmetric across the thorax compared to belted occupants in crashes with a deployed frontal airbag. Other factors, such as occupant kinematics and occupant age, also produced differing patterns of fractures. Normative data on rib fracture patterns in real-world occupants can contribute to understanding injury mechanisms and the role of different causation factors, which can ultimately help prevent fractures and improve vehicle safety.


Nanodiamond-mediated drug delivery and imaging: challenges and opportunities.
The field of nanoparticle-based therapeutic systems is rapidly expanding encompassing a wide variety of practices ranging from detection to diagnosis to treatment. Recently a great potential of nanodiamond (ND) particles as a multimodal imaging/therapy platform has been demonstrated. This review describes a unique set of properties of ND particles attractive for drug delivery and imaging applications and highlights the most recent ND-based multimodal imaging/therapy approaches and related biocompatibility studies. The spectrum of major advancements includes marked improvements in tumor treatment efficacy and safety based on integration of ND with doxorubicin (DOX). Recent progress of ND-mediated drug delivery in orthopedic, dental and ophthalmic applications is also discussed. ND particles possess a unique set of properties attractive for drug delivery applications, including exceptional biocompatibility, large carrier capacity and versatile surface chemistry properties, which enhance drug binding and provide sustainable drug release. Other unique attributes of NDs embrace bright stable fluorescence based on crystallographic defects. A roadmap toward a clinical translation comprises identification of ND-therapeutic compounds that display marked improvements over clinical standards with respects to efficacy, safety and cost.


Role of cAMP-PKA-PLC signaling cascade on dopamine-induced PKC-mediated inhibition of renal Na(+)-K(+)-ATPase activity.
We studied the molecular events set into motion by stimulation of D(1)-like receptors downstream of Na(+)-K(+)-ATPase, while measuring apical-to-basal ouabain-sensitive, amphotericin B-induced increases in short-circuit current in opossum kidney (OK) cells. The D(1)-like receptor agonist SKF-38393 decreased Na(+)-K(+)-ATPase activity (IC(50), 130 nM). This effect was prevented by the D(1)-like receptor antagonist SKF-83566, overnight cholera toxin treatment, the protein kinase A (PKA) antagonist H-89, or the PKC antagonist chelerythrine, but not the mitogen-activated PK inhibitor PD-098059 or phosphatidylinositol 3-kinase inhibitors wortmannin and LY-294002. Dibutyryl cAMP (DBcAMP) and phorbol 12,13-dibutyrate (PDBu) both effectively reduced Na(+)-K(+)-ATPase activity. PKA downregulation abolished the inhibitory effects of SKF-38393 and DBcAMP but not those of PDBu. PKC downregulation abolished inhibition by PDBu, SKF-38393, and DBcAMP. The phospholipase C (PLC) inhibitor U-73122 prevented inhibition by SKF-38393 and DBcAMP. However, DBcAMP increased PLC activity. Although OK cells express both G(s)alpha and G(q/11)alpha proteins, D(1)-like receptors are coupled to G(s)alpha proteins only, as evidenced by studies in cells treated overnight with specific antibodies raised against G(s)alpha and G(q/11)alpha proteins. We conclude that PLC and Na(+)-K(+)-ATPase are effector proteins for PKA and PKC, respectively, after stimulation of D(1)-like receptors coupled to G(s)alpha proteins, in a sequence of events that begins with adenylyl cyclase-PKA system activation followed by PLC-PKC system activation.


The Effects of Objective and Subjective Socioeconomic Status on Subjective Well-Being among Rural-to-Urban Migrants in China: The Moderating Role of Subjective Social Mobility.
Although previous investigations have agreed that Chinese rural-to-urban migrants' socioeconomic status (SES) increases with their migration, the association between SES and subjective well-being is uncertain. To address this research gap, the present study proposed that the association between objective SES and subjective well-being is mediated by subjective SES. This model was tested with a sample of 432 Chinese rural-to-urban migrants. The results indicate a significant association between objective SES and subjective well-being and a partial mediating effect of subjective SES. Furthermore, subjective social mobility, which is one's expectation about the possibility to move upward in the social hierarchy, was found to moderate both the direct path from objective SES to subjective well-being and the indirect path from subjective SES to subjective well-being. These findings suggest that Chinese rural-to-urban migrants gained in subjective well-being not only because of direct financial achievement but also because of their perceptions and beliefs about their relative social status.


The return of individual genomic results to research participants: design and pilot study of Tohoku Medical Megabank Project.
Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results, we extracted the potential challenges and obstacles. Major challenges include the determination of genes/disorders based on the current medical system in Japan, the storage of results, prevention of misunderstanding, and collaboration of medical professionals. To overcome these challenges, we plan to conduct multilayer pilot studies, which deal with different disorders/genes. We finally chose familial hypercholesterolemia (FH) as a target disease for the first pilot study. Of the 665 eligible candidates, 33.5% were interested in the pilot study and provided consent after an educational "genetics workshop" on the basic genetics and medical facts of FH. The genetics professionals disclosed the results to the participants. All positive participants were referred to medical care, and a serial questionnaire revealed no significant psychosocial distress after the disclosure. Return of genomic results to research participants was implemented using a well-prepared protocol. To further elucidate the impact of different disorders, we will perform multilayer pilot studies with different disorders, including actionable pharmacogenomics and hereditary tumor syndromes.


Molecular fundamentals of nitrogen uptake and transport in trees.
Nitrogen (N) is frequently a limiting factor for tree growth and development. Because N availability is extremely low in forest soils, trees have evolved mechanisms to acquire and transport this essential nutrient along with biotic interactions to guarantee its strict economy. Here we review recent advances in the molecular basis of tree N nutrition. The molecular characteristics, regulation, and biological significance of membrane proteins involved in the uptake and transport of N are addressed. The regulation of N uptake and transport in mycorrhized roots and transcriptome-wide studies of N nutrition are also outlined. Finally, several areas of future research are suggested.


Coma blisters in two postoperative patients.
Coma blisters are self-limited cutaneous bullae that occur in the setting of loss of consciousness because of a drug, illness, or accident, with the most common settings being barbiturate overdose and neurological disorders. The etiology behind coma blisters is poorly understood and is not related to underlying infections or autoimmune conditions. The clinical presentation consists of bullae, erosions, and violaceous plaques usually involving sites of pressure. The skin lesions usually occur within 48-72 hours of the start of a coma and resolve within 2-4 weeks. We present one case of a 5-month-old infant with severe valvular disease who required surgical repair. He was placed on extra corporeal membrane oxygenation and developed multiple tense coma blisters during the course of therapy. Skin biopsy revealed a noninflammatory subepidermal blister with necrosis of the overlying epidermis and necrosis of the eccrine ducts. We also present a second case of an 18-year-old female patient who underwent surgical resection of a benign mandibular tumor. She subsequently developed bullae on both arms 4 days after surgery. The skin biopsy showed a necrotic epidermis, a subepidermal blister, and diffuse necrosis of the eccrine coils.


Infected thoracoabdominal aortic aneurysms including the major abdominal branches in 4 cases.
We present four cases of infected thoracoabdominal aortic aneurysm (TAAA), including abdominal branches that underwent surgical repair. The mean age of patients at the time of operation was 61+/-18 (range: 39-83) years. The extent of the aneurysm was Crawford type III in 1 case and type IV in the other 3. They all underwent an emergency or urgent operation, which consisted of a debridement of the infected tissue, in situ four-branched Dacron graft replacement, and iodine gauze packing for 48 h followed by omental wrapping of the graft. To prevent postoperative spinal ischemia, intercostal and lumbar arteries were reimplanted under motor-evoked potential (1.25 pairs per patient). There was one (25%) hospital death, but postoperative graft infection did not occur in these present cases during a mean follow-up period of 15+/-43 (1-96) months. Antibiotics were administered intravenously for 8 weeks after the operation, then continued orally for a lifelong period. Postoperatively, paraplegia occurred in one (25%) patient. Our strategy for infected TAAA including major abdominal branches may prevent postoperative graft infection.


Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages.
Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis.


Differential Effects of Ca2+ Channel Blockers Nifedipine and Cilnidipine on Arterial Elasticity in the Aortic and Femoral Arterial Segments of Anesthetized Rabbits.
Ca2+ channel blockers have potent vasodilatory effects and excellent efficacy in preserving organ blood flow. These hemodynamic actions may be partly controlled by the functional stiffness of conduit arteries. In this study, we assessed the effects of the L-type Ca2+ channel blocker nifedipine on aortic and femoral arterial stiffness (referred to as aortic β and femoral β, respectively) in anesthetized rabbits. To further clarify the involvement of the autonomic nervous system, we compared the effects of nifedipine with those of the L/N-type Ca2+ channel blocker cilnidipine. Further, the effect of the α-adrenergic receptor blocker doxazosin on the effects of nifedipine on arterial elasticity was examined. An antihypertensive dose of nifedipine (300 µg/kg, administered intravenously) was found to increase the aortic β but hardly affected the femoral β. An antihypertensive dose of cilnidipine (30 µg/kg, administered intravenously) increased the aortic β but decreased the femoral β. Interestingly, nifedipine decreased the femoral β in the presence of the α-adrenoceptor blocker doxazosin (1 mg/kg, administered intravenously). These effects suggest that L-type Ca2+ channel blockers essentially increase vascular elasticity via the decrement in arterial stiffness in the femoral artery segment, which is modified by the presence or absence of the inhibitory effect of each drug on reflex sympathetic nerve activity, while decreasing vascular elasticity via the increment in arterial stiffness in the aortic segment independently of sympathetic nerve activity.