Mixed substituted porphyrins: structural and electrochemical redox properties.
To examine the influence of mixed substituents on the structural, electrochemical redox behavior of porphyrins, two new classes of beta-pyrrole mixed substituted free-base tetraphenylporphyrins H2(TPP(Ph)4X4) (X = CH3, H, Br, Cl, CN) and H2(TPP(CH3)4X4) (X = H, Ph, Br, CN) and their metal (M = Ni(II), Cu(II), and Zn(II)) complexes have been synthesized effectively using the modified Suzuki cross-coupling reactions. Optical absorption spectra of these porphyrins showed significant red-shift with the variation of X in H2(TPPR4X4), and they induce a 20-30 nm shift in the B band and a 25-100 nm shift in the longest wavelength band [Q(x)(0,0)] relative to the corresponding H2TPPR4 (R = CH3, Ph) derivatives. Crystal structure of a highly sterically crowded Cu(TPP(Ph)4(CH3)4).2CHCl3 complex shows a combination of ruffling and saddling of the porphyrin core while the Zn(TPP(Ph)4Br4(CH3OH)).CH3OH structure exhibits predominantly saddling of the macrocycle. Further, the six-coordinated Ni(TPP(Ph)4(CN)4(Py)2).2(Py) structure shows nearly planar geometry of the porphyrin ring with the expansion of the core. Electrochemical redox behavior of the MTPPR4X4 compounds exhibit dramatic cathodic shift in first ring oxidation potentials (300-500 mV) while the reduction potentials are marginally cathodic in contrast to their corresponding MTPPX4 (X = Br, CN) derivatives. The redox potentials were analyzed using Hammett plots, and the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap decreases with an increase in the Hammett parameter of the substituents. Electronic absorption spectral bands of H2TPPR4X4 are unique that their energy lies intermediate to their corresponding data for the H2(TPPX8) (X = CH3, Ph, Br, Cl) derivatives. The dramatic variation in redox potentials and large red-shift in the absorption bands in mixed substituted porphyrins have been explained on the basis of the nonplanarity of the macrocycle and substituent effects.


Modulating Room-Temperature Phosphorescence-To-Phosphorescence Mechanochromism by Halogen Exchange.
Modulating the stimulus-responsiveness of a luminescent crystal is challenging owing to the complex interdependent nature of its controlling factors, such as molecular structure, molecular conformation, crystal packing, optical properties, and amorphization behavior. Herein, we demonstrate a halogen-exchange approach that disentangles this problem, thereby realizing the modulation of room-temperature phosphorescence-to-phosphorescence mechanochromism. Replacing the bromine atoms in a brominated thienyl diketone with chlorine atoms afforded isostructural crystals; i.e., molecules with different halogen atoms exhibited the same molecular conformation and crystal packing. Consequently, amorphization behavior toward mechanical stimulation was also the same, and the phosphorescence of amorphous states originated from the same conformer of each diketone. In contrast, the phosphorescence properties of each conformer were modulated differently, which is ascribable to heavy atom effects, resulting in the modulation of the mechanochromism. Thus, halogen exchange is a promising approach for modulating the stimulus-responsive photofunctions of crystals involving spin-forbidden processes.


Tuberculosis.
Tuberculosis (TB) is a disease of antiquity, caused by Mycobacterium tuberculosis, which principally affects the lungs. It is a major public-health problem, with around 9 million new cases and 2 million deaths estimated to occur each year. Patients with pulmonary TB whose sputum is smear-positive for M. tuberculosis form the main source of infection in communities. About 5%-10% of infected individuals are likely to develop symptomatic TB during their lives but the risk of developing the clinical manifestations of the disease is greatly increased by HIV co-infection. The strong association between HIV and TB in sub-Saharan Africa is responsible for the massive increase in the incidence of TB observed in that region in the last 20 years. Diagnosis of TB in resource-poor countries is largely based on sputum-smear microscopy and chest radiography, although these methods lack sensitivity or specificity, especially when used on HIV-infected patients. Effective treatment has existed for 40 years but TB-attributable mortality remains high among HIV-infected patients in Africa, who are also particularly likely to develop TB again after receiving drug treatment for the disease. In Eastern Europe it is drug resistance in the local M. tuberculosis that makes the treatment of TB relatively ineffective. The approach to TB control that is now internationally recommended is the DOTS ('directly-observed treatment, short-course') strategy, which aims to prevent the transmission of M. tuberculosis, and the related illness and death, by using combinations of anti-TB drugs to treat patients with the active disease. Unfortunately, countries in sub-Saharan Africa are falling short of the World Health Organization's targets for case detection and treatment. This failure is, in turn, making the achievement of the Millennium Development Goals for TB--to ensure that the incidence of TB is falling by 2015 and to halve the prevalence of TB and the annual number of TB-attributable deaths between 1990 and 2015--less likely. To improve the performance and impact of TB-control programmes, in the face of HIV co-infection and other constraints on DOTS, the World Health Organization has launched the revised 'Stop TB Strategy'. The new strategy, to be implemented via the Global Plan to Stop TB (2006-2015), includes intensified TB-case finding, treatment of latent TB infection with isoniazid, prevention of HIV infection, cotrimoxazole preventive therapy, and antiretroviral therapy.


Citations for the Human Rights and Nursing Awards 2016.
The International Care Ethics Observatory is pleased to announce that on 14 September 2016 the Human Rights and Nursing Awards will be given at a short ceremony at the University of São Paulo at Ribeirão Preto, Brazil. The awards will be presented at the 17th annual Nursing Ethics and 2nd Ethics in Care conference, organised in conjunction with the PAHO/WHO Collaborating Centre for Nursing Research Development, the College of Nursing at the University of São Paulo at Ribeirão Preto, and Nursing Ethics.


Observation of chiral edge states in gapped nanomechanical graphene.
Emerging in diverse areas of physics, edge states have been exploited as an efficient strategy of manipulating electrons, photons, and phonons for next-generation hybrid electro-optomechanical circuits. Among various edge states, gapless chiral edge states harnessing quantum spin/valley Hall effects in graphene or graphene-like materials are especially unique. Here, we report on an experimental demonstration of chiral edge states in gapped "nanomechanical graphene"-a honeycomb lattice of free-standing silicon nitride nanomechanical membranes with broken spatial inversion symmetry. These chiral edge states can emerge from the conventional flat-band edge states by tuning the on-site boundary potentials. We experimentally demonstrated that they are backscattering-immune against sharp bends and exhibit the "valley-momentum locking" effect. We further realized smooth transition between the chiral edge states and the well-known valley kink states. Our results open the door to experimental investigation of exotic graphene-related physics in the very-high-frequency integrated nanomechanical systems.


Anisotropy in the electrical resistivity and susceptibility of superconducting BaFe2As2 single crystals.
We report that sizable single crystals of BaFe2As2 have been grown with the self-flux method. Measurements and anisotropy of intrinsic transport and magnetic properties from high-quality single crystal are first presented. The resistivity anisotropy (rho{c}/rho{ab}) is as large as 150 and independent of temperature. In contrast to the susceptibility behavior observed in polycrystalline samples, no Curie-Weiss behavior is observed, and a linear-T dependent susceptibility occurs from the spin-density-wave transition temperature, (T{s}), to 700 K. This result suggests that strong antiferromagnetic correlations are present well above T{s}. A twofold symmetry of susceptibility in the ab plane indicates a stripelike spin structure as observed by neutron scattering. The resistivity minimum is strongly dependent on the magnetic field, suggesting that the upturn of the resistivity at low temperatures should be related to spin fluctuation.


A review on golimumab in the treatment of psoriatic arthritis.
Psoriatic arthritis (PsA) causes inflammation in and around the joints and usually affects people who already have psoriasis. However, some patients develop the joint problems before the psoriasis. Currently, there are five anti-TNF-α agents licensed for use in patients with PsA: adalimumab, certolizumab pegol, etanercept, golimumab and infliximab. Golimumab, a human monoclonal antibody, has been approved by the US FDA for the treatment of PsA and is targeted against the pro-inflammatory molecule TNF-α. The Phase III GO-REVEAL study confirmed this drug was well tolerated and showed significant improvement in disease activity compared with placebo.


Hepatitis B virus replication in southern Africa blacks with HBsAg-positive hepatocellular carcinoma.
Sera from 106 southern African blacks with hepatocellular carcinoma and hepatitis B surface antigenemia (HBsAg) were tested for hepatitis B viral DNA (HBV-DNA) activity, HBV-DNA polymerase concentrations, and HBV e antigen (HBeAg) and antibody (anti-HBe) to investigate the state of viral replication in these patients. HBeAg and anti-HBe were detected by radioimmunoassay, HBV-DNA by molecular hybridization using a 32p-labeled HBV-DNA probe, and HBV-DNA polymerase was measured by incorporation of 3H-labeled thymidine triphosphate into double-stranded HBV-DNA. HBeAg was present in 30.2% (32/106) of the patients, almost always in low titer; 63.8% of the patients were anti-HBe positive. Circulating HBV-DNA was detected in 18.8% (20/106) of patients, including 14 of 32 (43.7%) who were HBeAg positive and 6 of 74 (8.1%) who were anti-HBe positive. In most patients, only trace amounts of HBV-DNA were evident. Raised HBV-DNA polymerase activity was found in 5.6% (6/106) of the patients, all of whom were HBeAg positive and 4 of whom had detectable amounts of circulating HBV-DNA. The HBV-DNA polymerase activity was relatively low in these patients. HBV replication thus appears to be present in only a minority of southern African Blacks with HBV-related hepatocellular carcinoma, and when present is of low grade activity.


[The outcome and prognosis of catheter ablation for atrial fibrillation].
The effect of radiofrequency catheter ablation for atrial fibrillation (AF-ABL) has been established in the last decade and has become one of the major therapeutic options. As for the outcome of AF-ABL, there exit wide varieties in the success rate among the reports published so far, mainly due to the differences in the patient characteristics, ablation methods, and the observation manner/periods. In general, approximately 90% of success can be obtained in paroxysmal AF by a single procedure without the use of antiarrhythmic drugs, while it is around 60 to 80 % in persistent AF even with both repeat sessions and the use of drugs. The success rate has been shown to be constantly reduced during the long-term followup periods irrespective of the AF-type. Although AF-ABL has been shown to be effective to maintain sinus-rhythm compared to the pharmacological method, its impact on the prognosis has not been established yet.


Congener-specific dechlorination of dissolved PCBs by microscale and nanoscale zerovalent iron in a water/methanol solution.
Polychlorinated biphenyl (PCB)-contaminated sediments remain a significantthreatto humans and aquatic ecosystems. Dredging and disposal is costly, so viable in situ technologies to dechlorinate PCBs are needed. This study demonstrates that nanoscale zerovalent iron (ZVI) dechlorinates PCBs to lower-chlorinated products under ambient conditions, provides insight into structure-activity relationships between PCB isomers, and compares the reactivity of nanoscale ZVI to that of palladized microscale ZVI. Six PCB congeners were studied (22', 34', 234, 22'35', 22'45', and 33'44') to compare the initial rate of dechlorination of each and to monitor the order in which chlorines are removed. Using 200 g/L of nanoscale ZVI in a 30% MeOH/water mixture, observed surface-area-normalized pseudo-first-order PCB dechlorination rate constants ranged from 1 x 10(-6) to 5.5 x 10(-4) L yr(-1) m(-2) depending on the PCB congener tested. Using 200 g/L of palladized (0.05 wt %) microscale ZVI, surface-area-normalized pseudo-first-order PCB dechlorination rate constants were significantly faster and ranged from 3.8 x 10(-2) to 1.7 x 10(-1) L yr(-1) m(-2), but these rates were not sustainable. For nanoscale ZVI, nonorthosubstituted congeners had faster initial dechlorination rates than orthosubstituted congeners in the same homologue group. Chlorines in the para and meta position were predominantly removed over chlorines in the ortho position, which suggests that more-toxic coplanar PCB congeners are not likely to form from less-toxic noncoplanar, orthosubstituted congeners. Complete dechlorination was not observed over the course of the experiments. PCB dechlorination is rapid enough that nanoscale ZVI may offer novel in situ remedial alternatives for PCB-contaminated sediments.


Burn trauma induces anorexia and aberrations in CNS amine neurotransmitters.
A 30% surface area, full-thickness, open-flame burn of guinea pigs induced significant anorexia and rapid loss of body weight. Analysis of regional brain concentrations of amine neurotransmitters suggested burn-specific elevation of serotonergic neurotransmission, reduction of dopamine metabolism, and elevation of norepinephrine concentrations in brain areas thought to control feeding. These data suggest that specific regional aberrations in each of these amine neurotransmitters may contribute to the anorexia associated with major thermal injury.


Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: findings from the COMMIT cohort.
Smoking many cigarettes per day (CPD) and short interval to first cigarette (TTF) after waking are two of the most heritable smoking phenotypes and comprise the Heavy Smoking Index (HSI). These phenotypes are often used as proxies for nicotine dependence (ND) and are associated with smoking cessation outcomes. Case-control and genome-wide association studies have reported links between single nucleotide polymorphisms (SNPs) in the alpha-5 and -3 nicotinic receptor subunit (CHRNA5 and CHRNA3) genes and CPD but few have examined TTF or cessation outcomes. In this study we longitudinally assessed 1301 European-American smokers at four time-points from 1988 to 2005. One CHRNA5 (rs16969968) and two CHRNA3 (rs1051703, rs6495308) SNPs were examined for their ability to predict smokers who "ever" reported ND based on three phenotypic classifications: (1) 25+ CPD, (2) TTF < 10 min, and (3) HSI ≥ 4. In a subsample of 1157 quit attempters, we also examined each SNP's ability to predict "ever" quitting for a period of >6 months. Demographically adjusted logistic regressions showed significant allelic and genotypic associations between all three SNPs and CPD but not TTF, HSI, or smoking cessation. Carriers of both the rs16969968-AA and rs6495308-TT genotypes had approximately twofold greater odds for ND defined using CPD or TTF. Results suggest nicotinic receptor variants are associated with greater odds of ND according to CPD and to a lesser extent TTF. Research examining the effect of nicotinic receptor genetic variation on ND phenotypes beyond CPD is warranted.


FcTp(R) (R = iPr or tBu): third-generation ferrocenyl scorpionates.
Scorpionate (or trispyrazolylborate) ligands have seen much structural variation due to the relative ease of modifying their electronic and steric effects. Second-generation scorpionates were created by increasing the bulk in the 3-position of the pyrazole (pz) ring. A new class of third-generation scorpionates was obtained by modifying the remaining boron substituent. A series of thallium(I) and cobalt(II) complexes of the ferrocenyltris(3-R-pyrazolyl)borate ligand [FcTpR; R = isopropyl (iPr) or tert-butyl (tBu)] have been synthesized in order to expand the range of redox-active third-generation scorpionates. These are [ferrocenyltris(3-tert-butylpyrazol-1-yl-κN2)borato]thallium(I), [FeTl(C5H5)(C26H37BN6)], [ferrocenyltris(3-isopropylpyrazol-1-yl-κN2)borato]thallium(I), [FeTl(C5H5)(C23H31BN6)], chlorido[ferrocenyltris(3-tert-butylpyrazol-1-yl-κN2)borato]cobalt(II), [CoFe(C5H5)(C26H37BN6)Cl], [ferrocenyltris(3-tert-butylpyrazol-1-yl-κN2)borato]iodidocobalt(II) benzene disolvate, [CoFe(C5H5)(C26H37BN6)I]·2C6H6, and [ferrocenyltris(3-isopropylpyrazol-1-yl-κN2)borato]iodidocobalt(II), [CoFe(C5H5)(C23H31BN6)I]. The structures demonstrate that the metal coordination site can easily be modified by using bulkier substituents at the pz 3-position.


Reported Goals For Knowledge to be Learned in Responsible Conduct of Research Courses.
EDUCATION IN RESPONSIBLE CONDUCT OF RESEARCH (RCR) has been a required part of training for students on U. S. National Institutes of Health (NIH) training grants for over 15 years. However, there is little evidence of commonly accepted goals for RCR instruction, making it difficult to assess effectiveness. As part of a larger study examining RCR instructors' goals for RCR education, this report focuses on those reported goals categorized as knowledge. To identify RCR instructors, e-mail requests were sent to the 116 recipients of NIH training grants awarded in 2000. Of 67 verified RCR instructors, 50 (75% response rate) from 37 different institutions were successfully interviewed. Despite a shared sense of the basics to be taught in RCR courses, these instructors were diverse in their views and understanding of goals for RCR education. This diversity suggests a challenge to be overcome not only for improving the effectiveness of RCR education, but also for attempts to assess that effectiveness.


[Proposal of a rating scale of posture for simple dysfunctional dysphonia: "S-TRAV"].
This work aims to create a scale to evaluate posture, quick and easy to perform during the assessment of voice in patients with simple dysfunctional dysphonia. The "S-TRAV" scale was evaluated on 60 subjects with dysphonia and 60 control subjects. It assesses "the overall severity" of the alteration of posture, the "Tension", the "Breathing", the "Ground anchoring" and the "Verticality" both quantitatively (score 0-3) and qualitatively. The patient also assesses his voice disorder and his posture. Postural observation was carried out in five conditions: at rest, conversational voice, reading, projected voice and singing voice. The comparison between the dysphonic subjects and control subjects was used to assess the sensitivity of this tool. Two reviewers rated the scale to determine its reproducibility. The scale is sensible for the majority of criteria with a significance coefficient less than 0.05. The most discriminate criteria relate to the cervical spine, the overall score of postural severity assessed by the therapist and verticality. All criteria have a low level of variability between the reviewers under all conditions. Most criteria are correlated with the criterion "Overall Severity" of postural alterations under all conditions. Non-sensible criteria were eliminated from the final scale). This tool is sensitive, reproducible and relevant in assessing the severity of postural alterations and their location. Further studies will validate the scale on a consistent population.


The effect of health on acute care supplemental insurance ownership: an empirical analysis.
The empirical effect of health status on private insurance ownership is a mixture of the effect of health on the demand for insurance (subjected to adverse selection) and its effect on the insurer's underwriting practice (subjected to risk-selection). Using bivariate partial observability probit models, this paper provides an empirical identification of health effects on the probability of application and on the probability of rejection in the Israeli market for acute care supplemental health insurance. The analysis shows that while the reduced-form health effect on ownership is negligible, the structural effects are sizeable and indicate that sicker individuals are more likely to apply, but are also more likely to be rejected. The policy implications of the above findings are discussed in the context of the Israeli health system.


Comparative study of the efficacy of the Songkla uterine manipulator and the Hulka controlling tenaculum in laparoscopic tubal ligation.
To compare the efficacy of the Songkla uterine manipulator (SUM) and the Hulka controlling tenaculum for manipulation of the uterus for laparoscopy. Forty women scheduled for laparoscopic tubal ligation were randomized to the SUM group (n=20) or the Hulka group (n=20) as uterine manipulator. Laparoscopic evidence of antevertion and lateral uterine movements and organ exposure was video recorded. Assessment of organ exposure and degree of lateral uterine deviation were subsequently evaluated. The characteristics of the women were similar in both groups. Right, left and range of lateral uterine motion were greater in the SUM group than the Hulka group (59 vs 42 degrees, 60 vs 47 degrees, and 118 vs 89 degrees, respectively, p<0.0001). The SUM group had 2.4 times better cul-de-sac exposure than the Hulka controlling tenaculum (95% CI: 0.51-11.51, p= 0.475). The SUM exposed fallopian tubes better than the Hulka tenaculum (p=0.022) but other structures were not significantly better visualized. There were no complications in the SUM group but two had cervical bleeding in the Hulka group. The SUM has advantages over the Hulka controlling tenaculum in giving a wider angle of lateral uterine deviation and better exposure of the fallopian tubes.


Studying the rhodopsin-like G protein-coupled receptors by atomic force microscopy.
Rhodopsin-like G protein-coupled receptors (GPCRs), widely distributed in microorganisms, invertebrates, and vertebrates, are the largest class in GPCRs, and are involved in many important physiological and pathological processes, including the photosensitivity, regulation of behavior and emotion, and so on. Atomic force microscopy (AFM) is a powerful and multifunctional toolkit in bionanotechnology, as it can image the morphology of membrane proteins at subnanometer spatial resolution and detect forces related with membrane proteins down to piconewton level by single-molecule force spectroscopy (SMFS) mode under physiological conditions. Herein, the achievements of AFM in the study of rhodopsin-like GPCRs, including observing the high-resolution topography and structural changes, revealing the interaction forces, binding kinetics, and mechanical properties (such as modulus), are reviewed and summarized. Finally, the challenges, outlook, and prospects of AFM in the study of rhodopsin-like GPCRs are discussed.


A perinuclear theca substructure is formed during epididymal guinea pig sperm maturation and disappears in acrosome reacted cells.
The perinuclear theca (PT) is a unique cytoskeletal mammalian sperm structure that surrounds the nucleus. Using negatively stained whole-mount preparations, we detected a PT substructure on the apical region of the postacrosomal theca layer of guinea pig spermatozoa. The PT substructure consists of projections resembling eyelashes, circling the sperm head. The PT substructure was absent in caput but appeared in corpus epidydimal spermatozoa. The same finding was observed in sheep and rabbit spermatozoa. The PT substructure persisted in capacitating spermatozoa, but was absent in acrosome reacted gametes. No labeling of the PT substructure was observed by the immunogold technique using antibodies against calmodulin, spectrin, myosin, and vimentin. A 34-kDa band appeared as a possible PT substructure protein. The PT was positive to the antibodies and the presence of the above-mentioned proteins was confirmed by Western blot. F-actin gold label was observed in mature spermatozoa on the PT substructure base zone. Results using cytochalasin D and phalloidin point to a role of F-actin in the PT substructure formation/disassembly processes. Ca(2+), bicarbonate, and proteases might be involved in the mechanism of the substructure disassembly. Novel PT morphological changes occurring during sperm epidydimal maturation and at acrosome reaction, respectively, are discussed in relation to the PT stability and function.


Early anteroposterior division of the presumptive neurectoderm in Xenopus.
We analyze the timing of neural patterning in Xenopus and the mechanism by which the early pattern is generated. With regard to timing, we show that by early gastrula, two domains of the anteroposterior (A/P) pattern exist in the presumptive neurectoderm, since the opl gene is expressed throughout the future neural plate, while the fkh5 gene is expressed only in more posterior ectoderm. By mid-gastrula, this pattern has become more elaborate, with an anterior domain defined by expression of opl and otx2, a middle domain defined by expression of opl and fkh5, and a posterior domain defined by expression of opl, fkh5 and HoxD1. Explant assays indicate that the late blastula dorsal ectoderm is specified as the anterior domain, but is not yet specified as middle or posterior domains. With regard to the mechanism by which the A/P pattern is generated, gain and loss of function assays indicate that quantitatively and qualitatively different factors may be involved in inducing the early A/P neural pattern. These data show that neural patterning occurs early in Xenopus and suggest a molecular basis for initiating this pattern.


Immunohistochemical markers in fibrohistiocytic lesions: factor XIIIa, CD34, S-100 and p75.
The distinction between dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP), and other benign and malignant cutaneous spindle cell lesions frequently requires immunohistochemical staining. CD34 and factor XIIIa are the most commonly used immunostains; however, they may exhibit aberrant expression and introduce the potential for misdiagnosis. There is some data supporting that p75 and S100A6 may be additional helpful immunohistochemical markers. We undertook a large case series examining the use of CD34 and factor XIIIa as well as p75 and S100A6 in DF, cellular DF, DFSP, indeterminate fibrohistiocytic lesion, and scar. As expected, CD34 stained DFSP, although it was usually negative in DF. Factor XIIIa was generally positive in DF and negative in DFSP. There were exceptions in both cases of DF and DFSP. S100A6 was routinely negative in all entities studied. P75 was negative in all cases except DFSP, approximately half of which showed weak and/or patchy positivity. We conclude that to date, CD34 and factor XIIIa remain the most reliable immunohistochemical markers for DF and DFSP.


Maternal Education, Early Child Care and the Reproduction of Advantage.
The social and human capital that educational attainment provides women enables them to better navigate their children's passages through school. In this study, we examine a key mechanism in this intergenerational process: mothers' selection of early child care. Analyses of the NICHD Study of Early Child Care and Youth Development revealed that maternal education was positively associated with configurations of child-care characteristics (i.e., type, quality, quantity) most closely linked to children's school readiness. This association was not solely a function of mother's income or employment status, persisted despite controls for many observable confounds (e.g., maternal cognitive and psychological skills, paternal characteristics), and, according to post-hoc indices, was fairly robust in terms of unobservable confounds.


Activation of xenobiotic receptors: driving into the nucleus.
Xenobiotic receptors (XRs) play pivotal roles in regulating the expression of genes that determine the clearance and detoxification of xenobiotics, such as drugs and environmental chemicals. Recently, it has become increasingly evident that most XRs shuttle between the cytoplasm and nucleus, and activation of such receptors is directly associated with xenobiotic-induced nuclear import. The scope of this review covers research literature that discusses nuclear translocation and activation of XRs, as well as unpublished data generated from this laboratory. Specific emphasis is given to the constitutive androstane receptor (CAR), the pregnane X receptor and the aryl hydrocarbon receptor. A number of molecular chaperons presumably associated with cellular localization of XRs have been identified. Primary hepatocyte cultures have been established as a unique model retaining inactive CAR in the cytoplasm. Moreover, several splicing variants of human CAR exhibit altered cellular localization and chemical activation. Nuclear accumulation is an essential step in the activation of XRs. Although great strides have been made, much remains to be understood concerning the mechanisms underlying intracellular localization and trafficking of XRs, which involve both direct ligand-binding and indirect pathways.


Tween 80 enhanced TNT mineralization by Phanerochaete chrysosporium.
The effect of a nonionic surfactant (Tween 80) on 2,4,6-trinitrotoluene (TNT) mineralization by the white-rot fungus Phanerochaete chrysosporium strain BKM-F-1767, was investigated in a liquid culture at 20, 50, and 100 mg TNT.L-1. The presence of 1% (w/v) Tween 80, at 20 mg.L-1 TNT, added to a 4-d-old culture, allowed the highest TNT mineralization level, that is 29.3% after 24 d, which is two times more than the control culture, without Tween 80 (13.9%). The mineralization of TNT resumed upon additional Tween 80 supplementation, consequently, 39.0% of the TNT was respired on day 68. Orbital agitation of the fungal culture was found detrimental to TNT mineralization, with or without Tween 80 in the culture medium. The surfactant also stimulated the growth of P. chrysosporium without any notable effect on either the glycerol consumption rate or the extracellular LiP and MnP activity levels. Respirometric assays highlighted some differences between the oxygen uptake rate of the fungal culture supplemented with or without Tween 80.


[Preliminary research on the differentiation of human amniotic epithelial cells into female germ cells].
To establish the method for isolation and culturation of human amniotic epithelial cells (hAECs) in vitro, and to investigate the differentiation potential of hAECs towards germ cells. hAECs were isolated from human term placenta and identified by immunocytochemistry. hAECs were sequential induced to form germ cells in medium supplemented with 5% human follicular fluid. Morphological changes were observed by inverted microscope. The oestradiol levels in the spent media were assayed. The expression of germ cell special genes and protein were examined by Real-time PCR and Western blot separately. Most of the isolated hAECs were polygon and of typical alabstone-like appearance, could express cytokeratin 19, the specific marker of epithelial cells, as well as octamer-binding protein 4 (Oct-4), a specific marker of embryonic stem cells (ESCs). After induced in medium supplemented with 5% human follicular fluid for 14 days, these stem cells grew as aggregates morphologically. Aliquots of supernatant of culture were collected and were assayed for oestradiol using chemiluminescence immunoassay (CLIA), although oestradiol was absent in the control group, the levels of the induction group were increased by day 8 and reached the maxima by day 10. Our study showed that hAECs treated with human follicular fluid were able to express germ cell genes, including growth differentiation factor 9 (GDF9) and deleted in azoospermia-like (DAZL) (P < 0.05), but without synaptonemal complex protein 3 (SCP3) (P > 0.05). The DAZL protein were also examined (P < 0.05). Germ cells could be induced in vitro from hAECs by human follicular fluid.


Utilization of 4T score to determine the pretest probability of heparin-induced thrombocytopenia in a community hospital in upstate New York.
Thrombocytopenia is common in hospitalized patients. Heparin-induced thrombocytopenia (HIT) is a life-threatening condition which can lead to extensive thrombosis. Diagnosis of HIT relies on clinical suspicion determined by 4T score and immunoassays through testing for anti-PF4/heparin antibodies. Clinical practice guidelines published by the American Society of Hematology in 2013 recommended use of the 4T score before ordering the immunoassays as a measure of pretest probability. The purpose of this study was to evaluate the utilization of 4T score before ordering anti-PF4/heparin antibodies at Unity Hospital. We did a retrospective chart review for patients who are 18 years or older, admitted to Unity Hospital between July 1, 2013, and December 31, 2014, and had anti-PF4/heparin antibodies ordered. Subjects who had prior history of HIT or had end-stage renal disease on hemodialysis were excluded. After calculating 4T score retrospectively, we calculated the proportion of patients who had 4T score documented prior to ELISA testing and proportion of ELISA tests, which were not indicated due to a 4T score less than or equal to 3 using Minitab 16. Review of 123 patients, with an average age of 69.4 years, showed that testing was indicated in 18 patients. Six subjects had positive results, and testing was indicated in all of them. 4T score was documented in three patients. This quality improvement study showed that 4T score documentation rate at Unity Hospital is 2.4%. Anti-PF4/heparin antibody testing was indicated in 14.6%. This test is being overused in thrombocytopenia work up at Unity Hospital, costing $9,345. The topic was reviewed for residents. A prompt and calculator for 4T score were added to electronic medical records before ordering the test as a step to improve high value care.


Antibodies to core lipopolysaccharide determinants: absence of cross-reactivity with heterologous lipopolysaccharides.
Using monoclonal antibodies directed against defined epitopes of endotoxin core, this study demonstrated that the presentation of lipopolysaccharide (LPS) to antibodies is critical for measuring the specific binding of antibodies to LPS structures. False cross-reactive reactions apparently were observed when free core LPS or lipid A were used as antigens in ELISA, whereas coating with complexes of high-density lipoproteins with core LPS increased both the sensitivity and the specificity of the test compared with coating with free core LPS, so that nonspecific binding of antibodies was largely avoided. Using this technique, it was not possible to find broadly cross-reactive core LPS antibodies after immunization of rabbits and humans with rough mutants of gram-negative bacteria. These observations underscore the need for careful evaluation of the potential for cross-reactivity of antisera and of monoclonal antibodies directed against endotoxin core.


Case Report: Need for Caution in the Diagnosis of GFAP Astrocytopathy-A Case of GFAP Astrocytopathy Coexistent With Primary Central Nervous System Lymphoma.
We reported a case of primary central nervous system lymphoma (PCNSL) coexistent with glial fibrillary acidic protein (GFAP) astrocytopathy, and discussed the problems needing attention in the diagnosis and differential diagnosis of GFAP astrocytopathy. Our patient was a 51-year-old female who presented with somnolence for a month, and memory declination for 10 days. Brain magnetic resonance imaging (MRI) demonstrated multiple abnormal enhancement lesions in bilateral basal ganglia and around the third ventricle, as well as transient T2-weighted hyper-intensity lesions at the splenium of the corpus callosum during the course of the disease. The cerebrospinal fluid (CSF) was positive for anti-GFAP antibodies by antigen-transfected HEK293 cell-based assay (indirect immunofluorescence assay). She was initially diagnosed with autoimmune GFAP astrocytopathy. After treatment with corticosteroids for about 2 months, she displayed poor response and even worsened clinical manifestations when the dose of prednisone reduced to 45 mg. Stereotactic brain biopsy was adopted and the diagnosis of large B-cell lymphoma, non-germinal center type was established on pathological examination. The results of brain biopsy also showed perivascular inflammation and CD8+ T cell infiltration, which also accorded with GFAP astrocytopathy. After chemotherapy with rituximab and methotrexate, the patient showed clinical and radiological improvement significantly. Our findings suggest that positivity of GFAP antibody calls for cautious interpretation. Cancer screening appropriate for age, sex, and risk factors is recommended for GFAP antibody-positive patients, especially for patients with atypical clinical and radiologic manifestations.


Peroxidase, an alternate pathway to cytochrome P-450 for xenobiotic metabolism in skin: partial purification and properties of the enzyme from neonatal rat skin.
Peroxidase activity was partially purified from neonatal (3 to 6 days old) rat skin. The membrane-bound peroxidase activity was extracted with 0.5 M calcium chloride and was monitored spectrophotometrically at 470 nm with 2-methoxyphenol (guaiacol) and hydrogen peroxide as substrates. Subcellular distribution studies indicated the activity to be highest and comparable in nuclei and mitochondria, lowest in microsomes, and absent in cytosol. The peroxidase activity was partially purified by affinity chromatography on concanavalin A-sepharose 4B and by gel filtration using Bio-Gel P-150. Purification factors from these two steps were about 25 and 4, respectively. Peroxidase extraction in the presence of 2 mM N-ethylmaleimide increased activity about twofold. The combination of 2 mM N-ethylmaleimide and 10% (w/v) glycerol was found to be optimal for preservation of activity. Peroxidase activity increased linearly with increases in protein concentration, time, and guaiacol concentration. Activity was inhibited approximately 75% by 0.1 mM potassium cyanide or 0.05 mM sodium azide. Pyrogallol, hydroquinone, p-cresol, catechol, benzidine, 3,3'-dimethoxybenzidine, tetramethylbenzidine and p-phenylenediamine also acted as substrates for the rat cutaneous peroxidase.


Medical relief activities, medical resourcing, and inpatient evacuation conducted by Nippon Medical School due to the Fukushima Daiichi Nuclear Power Plant accident following the Great East Japan Earthquake 2011.
On March 11, 2011, after the Great East Japan Earthquake and tsunami, the government declared a nuclear emergency following damage to the Fukushima Daiichi Nuclear Power Plant. A second hydrogen explosion occurred on March 14 at the plant's No. 3 reactor and injured 11 people. At that time the prime minister urged people living 20 to 30 km from the Daiichi plant to stay indoors. Under these circumstances, many residents of Iwaki City, which was largely outside the 30-km zone, left the city, making it difficult to get supplies to the remaining residents. The only transportation route open for supplies and medical resources was roads, and many drivers feared the rumor that the city was contaminated by radioactive materials and, so, refused to go there. Nippon Medical School (NMS) heard that medical resources were running short at Iwaki Kyoritsu Hospital, which requested water, medications, food, fuel (gasoline), medical support, and the evacuation of 300 inpatients. As a first step, NMS decided to evaluate the situation at the hospital and, on March 16, the director of the NMS Advanced Emergency Center visited the hospital and helped provide triage for about 200 patients. Critically ill patients receiving ventilatory support were given priority for evacuation because they would be most at risk of not being able to evacuate should the Japanese government order an immediate evacuation of the city. We tried to evacuate the inpatients via an official framework, such as the Disaster Medical Assistance Team (DMAT), but DMAT could not support this mission because this hospital was not within the 30-km evacuation zone. Moreover, the Iwaki City government could not support the evacuation efforts because they were fearful of the rumor that Iwaki was contaminated by radioactive material. Ultimately, we realized that we had to conduct the mission ourselves and, so, contacted our colleagues in the Tokyo metropolitan area to prepare enough hospital beds. We evacuated 15 patients to 8 hospitals over a 5-day period. As a result, we could reduce the number of patients at Iwaki Kyoritsu Hospital, and, thereby, the collapse of medical services in the city was avoided. In retrospect, someone might say the government--either central or local--should ideally have carried out this mission and created a system by which to do it. At the same time, however, to overcome any future bureaucratic issues, we should also prepare private networks, such as those used by NMS, because they can respond flexibly to unexpected large-scale disasters.


Identification and Functional Implications of Sodium/Myo-Inositol Cotransporter 1 in Pancreatic β-Cells and Type 2 Diabetes.
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, although the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and, specifically, β-cells. Genetic or pharmacological inhibition of SMIT1 impaired glucose-stimulated insulin secretion by INS-1E cells, probably via downregulation of PI signaling. In addition, SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions. In corroboration, chronic MI treatment improved the disease phenotypes of diabetic rats and islets. On the basis of our results, we postulate that the MI transporter SMIT1 is required to maintain a stable PI pool in β-cells in order that PI remains available despite its rapid turnover.


Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine.
Radiolabeled metaiodobenzylguanidine (MIBG), an analog of norepinephrine (NE), serves as an index of adrenergic neuron integrity and function. Using a rat model of adriamycin-induced cardiomyopathy, we tested the hypothesis that abnormal cardiac adrenergic neuron activity may appear and be exacerbated dose-dependently in adriamycin cardiomyopathy. The degree of vacuolar degeneration of myocardial cells was analyzed in relation to the duration of adriamycin treatment (2 mg/kg, once a week). There were no abnormalities or only isolated degeneration in the 1- or 2-wk treatment groups, isolated or scattered degeneration in half of the 3-wk group, frequent scattered degeneration in the 4-wk group, scattered or focal degeneration in the 5-wk group, and extensive degeneration in the 8-wk group. Myocardial accumulation of [125I]MIBG 4 hr after intravenous injection did not differ between the controls and the groups treated 3 wk or less. However, the 4-wk group had a slightly lower accumulation in the right ventricular wall (82% of the control) and significantly lower accumulation in the left ventricular wall (about 66% of the control: p less than 0.05). In the 5-wk group, MIBG accumulation in the right and left ventricular wall was 35% and 27% of that in controls, respectively (p less than 0.001). In the 8-wk group, MIBG accumulation in the right and left ventricular wall was 18% and 14% of that in controls, respectively (p less than 0.001). Thus, MIBG accumulation in the myocardium decreased in an adriamycin dose-dependent manner. The appearance of impaired cardiac adrenergic neuron activity in the presence of slight myocardial impairment (scattered or focal vacuolar degeneration) indicates that MIBG scintigraphy may be a useful method for detection of adriamycin-induced cardiomyopathy.


Removal of carbon black particles from polymer substrates in water/ethanol mixtures.
The removal of the carbon black (CB) particles from the polymer substrates was investigated in water/ethanol mixtures. As substrates, the films and the fibrous assemblies of polyethylene, nylon 6 and cellulose acetate were used. The ultrasonic wave was applied as a mechanical action for cleaning. The detergency of the CB particles for the films and the fibrous assemblies was assessed with the quartz crystal microbalance (QCM) technique and the reflectometry, respectively. The detergency for the films was discussed with the wetting force calculated from the experimentally determined contact angle on the substrate and surface tension of the water/ethanol mixture.


[Persistent renal bleeding treated with selective vascular embolisation with preservation of renal function].
In three patients with persistent blood loss from bleeding or abnormal renal vessels, kidney function was preserved by treatment with selective embolisation. The first patient, a 42-year-old woman, suffered from persistent haematuria after undergoing percutaneous nephrolithotripsy on the left side. Because conservative methods had failed and renal artery bleeding as a result of the lithotripsy was suspected, angiography with selective coil embolisation of a segmental branch of the lower pole artery of the kidney was performed. The second patient, a 40-year-old man with severe haemophilia A had been suffering from recurring macroscopic haematuria for a few months. CT showed an arteriovenous malformation in the right kidney. Angiography in combination with embolisation with two detachable balloons resulted in occlusion of the malformation. The third patient, a 23-year-old woman with tuberous sclerosis, presented with left abdominal pain, haematuria and decreasing haemoglobin concentrations. CT revealed a left renal angiomyolipoma, 10 cm in size, with a large internal haematoma. Three pathological branches of the upper pole renal artery were successfully occluded with Gianturco coils. At follow-up after 2, 2.5 and 2.5 years respectively, no recurrence of bleeding had occurred. Selective embolisation should be attempted as means of treatment for persistent renal bleeding if conservative treatment fails. Selective embolisation is minimally invasive and has the important advantage of preserving renal function.


[Controlled clinical trials of cost-effectiveness analysis on poking reduction and open reduction for the treatment of sanders type II calcaneal fractures].
To evaluate cost-effectiveness of poking reduction and open reduction for the treatment of Sanders type II calcaneal fractures, in order to provide evidence for standard treatment. From 2006.10 to 2008.10, 80 patients with Sanders type II calcaneal fractures were selected from Shandong Provincial Hospital of Traditional Chinese Medicine and randomly divided into poking reduction group and open reduction group with 40 cases in each group. There were 26 males and 14 females in poking reduction group and 30 males and 10 females in open reduction group. The average age of patients in poking reduction group was (36.60+/-3.15) years, and (37.10+/-3.45) years in open reduction group. Bohler angle, Gissane angle, the width of central calcaneus, stance phase of gait, HM-HL,arch index and subtalair joint flexibility were measured. The clinical results and expenses of the two treatment schemes were compared and concluded with the method of cost-effetiveness analysis. In the poking reduction group and open reduction group, the Böhler angle were (30.32+/-1.72) degree and (30.54+/-3.13) degree, Gissane angle were (133.73+/-6.73) degree and (134.86+/-4.90) degree, the width of central calcaneus were (30.18+/-1.59) mm and (30.24+/-1.25) mm, stance phase of gait were (0.679+/-0.070) s and (0.715+/-0.090) s, HM-HL were--(36.49+/-7.56) N and -(34.32+/-6.50) N,arch index were (30.26+/-2.69) and (30.47+/-1.89), and subtalair joint flexibility were (10.53+/-2.30) degree and (10.89+/-1.86) degree respectively. The cost-effectiveness ratio (C/E) were 6.06 and 136.19 respectively. Cost-effectiveness ratio of the poking reduction is superior to that of the open reduction in treating Sanders type II calcaneal fractures. Poking reduction is a useful method to treat Sanders type II calcaneal fractures with rapid wound healing and less cost.


Synthesis and Properties of Plasma-Polymerized Methyl Methacrylate via the Atmospheric Pressure Plasma Polymerization Technique.
Pinhole free layers are needed in order to prevent oxygen and water from damaging flexible electrical and bio-devices. Although polymerized methyl methacrylate (polymethyl methacrylate, PMMA) for the pinhole free layer has been studied extensively in the past, little work has been done on synthesizing films of this material using atmospheric pressure plasma-assisted electro-polymerization. Herein, we report the synthesis and properties of plasma-PMMA (pPMMA) synthesized using the atmospheric pressure plasma-assisted electro-polymerization technique at room temperature. According to the Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and time of flight-secondary ion mass spectrometry (ToF-SIMS) results, the characteristic peaks from the pPMMA polymer chain were shown to have been detected. The results indicate that the percentage of hydrophobic groups (C⁻C and C⁻H) is greater than that of hydrophilic groups (C⁻O and O⁻C=O). The field emission-scanning electron microscope (FE-SEM) and thickness measurement results show that the surface morphology is quite homogenous and amorphous in nature, and the newly proposed pPMMA film at a thickness of 1.5 µm has high transmittance (about 93%) characteristics. In addition, the results of water contact angle tests show that pPMMA thin films can improve the hydrophobicity.


Substance use, injury, and risk-taking dispositions in the general population.
Alcohol consumption has been found to be associated with injury occurrence and with risk-taking dispositions, and these dispositions, themselves, have been found to be associated with injury. Few studies have analyzed both alcohol consumption and risk-taking dispositions, or illicit drug use, on risk of injury across all types of injuries. Data on risk perception, risk-taking/impulsivity, sensation seeking, alcohol and drug use, demographic characteristics, and injury in the last year are reported from the 1995 National Alcohol Survey of 4925 respondents living in households in the 48 contiguous states. Moderate drinking, alcohol treatment, drug use, simultaneous use of alcohol and drugs, and risk-taking dispositions were all positively associated with reporting an injury. In multiple logistic regression, only risk-taking dispositions maintained significance when other variables were controlled. In separate regressions by ethnicity, risk-taking dispositions were significant predictors of injury for whites, whereas none of the variables were significant for blacks or Hispanics. Data suggest that risk-taking dispositions may be more important predictors of injury than either drinking or drug use variables, but this may vary by ethnicity. Risk-taking disposition may influence the effectiveness of strategies to reduce alcohol-related injuries; future research is important, therefore, for informing intervention and prevention efforts.


Problems concerning the concept of reactive psychoses.
The problems of reactive psychoses are discussed from the following perspectives: terminology, prevalence, psychogenesis and trauma, predisposition and vulnerability, as well as outcome. Four definitions of reactive psychoses, which are used in Scandinavia, are presented and discussed. Each of them is beset with problems. The authors argues that the term 'reactive psychoses' should be limited to those functional psychoses which are not typically schizophrenic, manic-depressive or paranoid.


Manifesto on the Value of Adult Immunization: "We Know, We Intend, We Advocate".
Immunization through vaccination is a milestone achievement that has made a tremendous contribution to public health. Historically, immunization programs aimed firstly to protect children, who were disproportionally affected by infectious diseases. However, vaccine-preventable diseases can have significant impacts on adult mortality, health, and quality of life. Despite this, adult vaccinations have historically been overlooked in favor of other health priorities, because their benefits to society were not well recognized. As the general population is aging, the issue of vaccination in older adults is gaining importance. In high-income countries, recommendations for the routine vaccination of older adults have been gradually introduced. The Italian National Immunization Plan is considered to be among the most advanced adult vaccination plans in Europe. However, available data indicate there is low adherence to vaccination recommendations in Italy. The COVID-19 pandemic has exposed the damage that can be caused by an infectious disease, especially among adults and individuals with comorbidities. The aim of this "Manifesto", therefore, is to provide an overview of the existing evidence on the value of adult vaccination, in the Italian context, with a call to action to healthcare providers and health authorities.


Polarity-based fluorescence probes: properties and applications.
Local polarity can affect the physical or chemical behaviors of surrounding molecules, especially in organisms. Cell polarity is the ultimate feedback of cellular status and regulation mechanisms. Hence, the abnormal alteration of polarity in organisms is closely linked with functional disorders and many diseases. It is incredibly significant to monitor and detect local polarity to explain the biological processes and diagnoses of some diseases. Because of their in vivo safe and real-time monitoring, several polarity-sensitive fluorophores and fluorescent probes have gradually emerged and been used in modern research. This review summarizes the fluorescence properties and applications of several representative polarity-sensitive fluorescent probes.


Soft X-ray Spectroscopy Simulations with Multiconfigurational Wave Function Theory: Spectrum Completeness, Sub-eV Accuracy, and Quantitative Reproduction of Line Shapes.
Multireference methods are known for their ability to accurately treat states of very different nature in many molecular systems, facilitating high-quality simulations of a large variety of spectroscopic techniques. Here, we couple the multiconfigurational restricted active space self-consistent field RASSCF/RASPT2 method (of the CASSCF/CASPT2 methods family) to the displaced harmonic oscillator (DHO) model, to simulate soft X-ray spectroscopy. We applied such an RASSCF/RASPT2+DHO approach at the K-edges of various second-row elements for a set of small organic molecules that have been recently investigated at other levels of theory. X-ray absorption near-edge structure (XANES) and X-ray photoelectron spectroscopy (XPS) are simulated with a sub-eV accuracy and a correct description of the spectral line shapes. The method is extremely sensitive to the observed spectral shifts on a series of differently fluorinated ethylene systems, provides spectral fingerprints to distinguish between stable conformers of the glycine molecule, and accurately captures the vibrationally resolved carbon K-edge spectrum of formaldehyde. Differences with other theoretical methods are demonstrated, which show the advantages of employing a multireference/multiconfigurational approach. A protocol to systematically increase the number of core-excited states considered while maintaining a contained computational cost is presented. Insight is eventually provided for the effects caused by removing core-electrons from a given atom in terms of bond rearrangement and influence on the resulting spectral shapes within a unitary orbital-based framework for both XPS and XANES spectra.


Stereospecific synthesis of a twinned alanine ester.
Reaction between 1,2-bis(2-hydroxyphenyl)-ethylenediamine (hpen) and methyl pyruvate gives the diaza-Cope rearrangement product with good yield and excellent stereospecificity. The product containing two chiral quaternary carbon centers is characterized by high performance liquid chromatography and X-ray crystallography. DFT computation provides insight into why the diaza-Cope rearrangement takes place readily with methyl pyruvate but not with other ketones like acetone and substituted acetophenones.


Meconium-induced periorchitis.
A testicular tumour-like lesion or a solid extratesticular mass are serious postnatal problems with a broad spectrum of inflammatory or tumorous causes and possible differential diagnoses. In this case report, an extraordinary case of a newborn boy with a rare cause of a periorchitis is described.A premature boy infant (25-year-old mother with obesity) was diagnosed as having a disturbance of prosperity. A plain film of the abdomen showed a dilated intestine (no pathological findings in abdominal ultrasound, in particular, no ascites). After 3 postnatal months of clinical observation at the hospital including temporary parenteral nutrition, hydrocele at both sides was diagnosed. Therefore, the boy underwent surgical exploration. Intraoperatively, the processus vaginalis peritonei was surprisingly filled with meconium; because of that, the situs was extensively rinsed. In addition, the boy underwent an operation for the right and left hydrocele. The testes were preserved (on follow-up investigation there were no further problems).Pathohistological investigation confirmed meconium periorchitis, which is a rare postnatal disease and which can only develop in cases of former meconium peritonitis and if the processus vaginalis peritonei is open. The precise details of cause and pathophysiology in this case may significantly help in avoiding unnecessary orchiectomy.


Paramagnetic hexacyanometalates. The diversity of spin distribution studied by 13C and 15N MAS NMR spectroscopy.
With the aim of probing the spin density distribution in the open-shell cyanometallates Cs2K[M(CN)6] (M = Cr, Mn, Fe), K3[M(CN)6] (M = Mn, Fe), K4[M(CN)6] (M = Cr, Mn), and K4[V(CN)7] have been studied by solid-state (13)C and (15)N NMR spectroscopy. The signals appear in strongly shifted and broad ranges ((13)C, -2100 to -8900 ppm; (15)N, -1900 to 2400 ppm) except K4[V(CN)7], which is NMR-silent. Analysis of the isotropic signal shifts yields negative spin density in all carbon 2s orbitals (up to 12.2% at the six ligands of [Mn(CN)6](3-)) and positive spin density in all nitrogen 2s orbitals (up to 1.1% at the six ligands of [Mn(CN)6](4-) and [Fe(CN)6](3-)). This is in accord with the induction of alternating spin at the CN ligands by successive polarization of σ bonds triggered by the spin center M(n+). The signal shift anisotropies are related to spin in the carbon and nitrogen 2pπ and 2pσ orbitals. In the case of Cs2K[Cr(CN)6] and K4[Cr(CN)6] much positive spin is found in the nitrogen 2pπ orbitals, which corresponds to direct M → N spin transfer. On Cs2K[M(CN)6] (M = Mn, Fe), the 2pπ spin density at nitrogen is negative. The results are in accord with and extend the data of polarized neutron diffraction and EPR spectroscopy. Owing to high signal resolution, small deviations of the [M(CN)6](n-) ions from octahedral symmetry and disorder of crystal layers have been detected. This corresponds to the crystal symmetry and to Jahn-Teller distortion. The disorder entails a scatter of spin densities. In the case of K4[Mn(CN)6] it reaches 19% for the C 2s orbitals and 80% for the N 2s orbitals with regard to the respective smallest spin population.


[A comparison of the penetration characteristics of latamoxef and cephalothin into the right atrial appendage and pericardial fluid of adult patients undergoing open-heart surgery].
A comparative study of the serum, atrial muscle, and pericardial fluid concentrations of latamoxef (LMOX) and cephalothin (CET) was performed in 18 adult patients having cardiac surgery. Patients were randomly assigned to receive either a single dose of CET 30 mg/kg, LMOX 30 mg/kg, or LMOX 20 mg/kg. Each drug was administered intravenously soon after anesthetic maintenance was achieved. After each drug administration, serum samples were obtained at various time intervals before, during, and after extracorporeal circulation (ECC), and assayed for CET and LMOX concentration. A sample of pericardial fluid was collected immediately after the pericardium was opened. The right atrial appendage tissue samples were obtained at the time of heart cannulation. The pharmacokinetics and penetration characteristics of each drug were analysed by the method of two-compartment model. Serum concentrations of CET following a single intravenous injection of 30 mg/kg were the high values, 172.4 +/- 35.6 micrograms/ml at 5 minutes, and 92.9 +/- 33.8 micrograms/ml at 15 minutes after injection. The initial (before bypass) half-life was 0.22 +/- 0.11 hour (13.1 minutes) while half-lives during and after ECC were prolonged significantly. In the cases of CET group, the myocardial tissue concentration value of 4.86 micrograms/g was obtained in only 1 case. The mean pericardial fluid concentration was 4.69 +/- 3.35 micrograms/ml at 5 to 30 minutes after injection. Serum concentration of LMOX following a injection of 30 mg/kg were 253.6 +/- 67.4 micrograms/ml at 5 minutes, and 176.3 +/- 64.1 micrograms/ml at 15 minutes after injection.(ABSTRACT TRUNCATED AT 250 WORDS)


Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate.
Measurement of the fraction of exhaled nitric oxide (FENO) has been proposed as a noninvasive assessment of asthmatic airway inflammation. The influence of the expiratory flow rate during the collection maneuver on the ability of FENO to discriminate healthy subjects from those with asthma is unknown. We compared online and offline measurement of FENO at different flow rates. FENO was collected with expiratory flows of 50-500 ml/second in 34 patients with asthma (PC(20) of less than 8 mg/ml) and 28 healthy subjects (PC(20) of more than 10 mg/ml) using offline collection techniques. In a subgroup of 18 individuals with asthma and 17 healthy subjects, we additionally measured FENO at multiple expiratory flow rates (47-250 ml/second) using online methods. FENO fell with an increasing expiratory flow rate; FENO was higher in subjects with asthma as compared with healthy subjects at each flow rate studied with both techniques (p < 0.001). Receiver operating characteristic (ROC) curves for the diagnosis of asthma indicated that FENO is a robust discriminator between individuals with asthma and healthy subjects (area under the ROC curves 0.79 +/- 0.06 to 0.86 +/- 0.06, p for significant discrimination < 0.0001). Neither expiratory flow rate nor collection technique (online versus offline) significantly altered this discriminatory capacity (area under the ROC curves = 0.84 +/- 0.07 with the slowest online method versus 0.80 +/- 0.07 with the fastest offline method, p = 0.46). These data indicate that the choice of expiratory flow rate and collection method can be based on practicality and patient comfort without compromising the utility of this test for asthma.


Comparison of intrapleural use of urokinase and tissue plasminogen activator/DNAse in pleural infection.
Fibrinolysis can be used to improve fluid drainage in pleural infection. Treatment with either urokinase or tissue plasminogen activator (t-PA) in association with DNAse via a chest tube has been effective at reducing the need for surgery. This study is the first to compare the efficacy of these two treatments. We performed a single-centre, controlled, prospective cohort study. All individuals with pleural infection admitted to our hospital between January 2014 and December 2017 who were treated with antibiotics, a chest tube and fibrinolysis were included in this study. The rate of additional procedure requirements (additional chest tube or surgery) after initial fibrinolysis, complications, costs, and radiological and biological outcomes were analysed. Among the 93 patients included in this study, 34% required additional procedures after an initial fibrinolysis, including 21% who received an additional chest tube and 13% who underwent thoracoscopy. The need for additional procedures arose due to presence of multiple pleural collections (p=0.01) and was associated with the use of large-bore drain (p=0.01). The success rate of fibrinolysis was not significantly different between urokinase and t-PA/DNAse (p=0.35). The differences in drainage duration and in length of hospital stay were not significant either (p=0.05 and p=0.12, respectively). Treatment with t-PA/DNAse was cheaper (p=0.04) but was associated with a higher rate of haemothorax (p=0.002). In conclusion, treatment with urokinase is safer and equally effective when compared with treatment with t-PA/DNAse.


The evolution of brain neuron numbers in amniotes.
SignificanceThe evolution of brain processing capacity has traditionally been inferred from data on brain size. However, similarly sized brains of distantly related species can differ in the number and distribution of neurons, their basic computational units. Therefore, a finer-grained approach is needed to reveal the evolutionary paths to increased cognitive capacity. Using a new, comprehensive dataset, we analyzed brain cellular composition across amniotes. Compared to reptiles, mammals and birds have dramatically increased neuron numbers in the telencephalon and cerebellum, which are brain parts associated with higher cognition. Astoundingly, a phylogenetic analysis suggests that as few as four major changes in neuron-brain scaling in over 300 million years of evolution pave the way to intelligence in endothermic land vertebrates.


Association of Acute Venous Thromboembolism With In-Hospital Outcomes of Coronary Artery Bypass Graft Surgery.
Background While venous thromboembolism (VTE) prophylaxis is a strong recommendation after most surgeries, it is controversial in cardiac surgeries such as coronary artery bypass grafting (CABG), because of perceived low VTE incidence and increased bleeding risk. Prior studies may not have been adequately powered to study outcomes of VTE in this population. We sought to investigate the postoperative incidence and outcomes of CABG patients using a large national inpatient database. Methods and Results We utilized the 2013 to 2014 National Inpatient Sample to identify all patients >18 years of age who underwent CABG (without concomitant valvular procedures), and had VTE during the hospital stay. We then compared clinically relevant outcomes in patients with and without VTE. We identified 331 950 CABG procedures. Of these, 1.3% (n=4205) had VTE. Patients with VTE were more likely to be older (mean 67.2±10.4 years versus 65.2±10.4 years, P<0.001). VTE was associated with higher incidence of inpatient mortality (6.8% versus 1.7%; adjusted odds ratio 1.92 [95% CI 1.40-2.65]; P<0.001) and complications. VTE was also associated with higher cost (mean±SE $81 995±$923 versus $48 909±$55) and longer length of stay (mean±SE 17.06±0.16 days versus 8.52±0.01 days). Conclusions Our analysis of >330 000 CABG procedures suggests that while postoperative VTE after CABG is rare, it is associated with increased morbidity and mortality. Randomized controlled trials are needed to identify optimal strategies for VTE prophylaxis in these patients.


Social Support and a Sense of Purpose: The Role of Personal Growth Initiative and Academic Self-Efficacy.
Objective: Studies have consistently found a positive relationship between social support and a sense of purpose; however, less is known about the underlying mechanisms of this relationship. The present study bridges this gap by proposing and testing a path model illustrating the mediating effects of personal growth initiative and academic self-efficacy on the linkage between social support and a sense of purpose. Method: A total of 2,085 Chinese college students completed the revised versions of the Social Support, Personal Growth Initiative, Academic Self-Efficacy, and Sense of Purpose Scales. Results: The results show that social support, personal growth initiative, and academic self-efficacy were all significantly associated with a sense of purpose. As predicted, personal growth initiative and academic self-efficacy mediated the relationship between social support and a sense of purpose, respectively. The results also support the hypothesized serial mediating effect. Conclusion: Individuals who feel more social support have a higher level of personal growth initiative, their academic self-efficacy is stronger, and their academic self-efficacy further enhances their sense of purpose. Additionally, comparisons among the three indirect effects indicated that the effect of personal growth initiative was significantly greater than those of the other two measures. Thus, it can be concluded that personal initiative plays a greater role in enhancing a sense of purpose. These findings not only help to understand how social support enhances the sense of purpose, but also provide insight into the underlying mechanism.


Cardiovascular response to blood loss during high intracranial pressure.
The authors hypothesized that the combination of hemorrhage and increased intracranial pressure (ICP) has deleterious effects on cardiovascular function. The effect of blood loss during normal and increased ICP was studied in eight pigs. The mean arterial pressure (MAP), pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, and cerebrospinal fluid (CSF) pressure were measured. The regional tissue blood flow was determined with radioactive microspheres labeled with four different nuclides. High ICP (80% of MAP) was induced by infusion of artificial CSF into the cisterna magna. The response to rapid arterial bleeding of 25% of blood volume was measured. The decrease in blood flow to the intestine, skeletal muscle, and the kidneys after blood loss was significantly greater during high ICP. The decrease in blood flow to the spleen and pancreas tended to be greater during high ICP, whereas the changes in blood flow to the liver, adrenal glands, and heart muscle showed no such tendency. The fall in cardiac output and heart stroke volume after blood loss were more pronounced when the ICP was high, and the increase in systemic vascular resistance was considerably greater. These observations suggest that during high ICP the physiological protective mechanisms against blood loss are impaired in the systemic circulation, and a loss of 25% of the blood volume, normally well compensated for, may induce a state of shock.


A cell-line-specific defect in the intracellular transport and release of assembled retroviral capsids.
Retrovirus assembly involves a complex series of events in which a large number of proteins must be targeted to a point on the plasma membrane where immature viruses bud from the cell. Gag polyproteins of most retroviruses assemble an immature capsid on the cytoplasmic side of the plasma membrane during the budding process (C-type assembly), but a few assemble immature capsids deep in the cytoplasm and are then transported to the plasma membrane (B- or D-type assembly), where they are enveloped. With both assembly phenotypes, Gag polyproteins must be transported to the site of viral budding in either a relatively unassembled form (C type) or a completely assembled form (B and D types). The molecular nature of this transport process and the host cell factors that are involved have remained obscure. During the development of a recombinant baculovirus/insect cell system for the expression of both C-type and D-type Gag polyproteins, we discovered an insect cell line (High Five) with two distinct defects that resulted in the reduced release of virus-like particles. The first of these was a pronounced defect in the transport of D-type but not C-type Gag polyproteins to the plasma membrane. High Five cells expressing wild-type Mason-Pfizer monkey virus (M-PMV) Gag precursors accumulate assembled immature capsids in large cytoplasmic aggregates similar to a transport-defective mutant (MA-A18V). In contrast, a larger fraction of the Gag molecules encoded by the M-PMV C-type morphogenesis mutant (MA-R55W) and those of human immunodeficiency virus were transported to the plasma membrane for assembly and budding of virions. When pulse-labeled Gag precursors from High Five cells were fractionated on velocity gradients, they sedimented more rapidly, indicating that they are sequestered in a higher-molecular-mass complex. Compared to Sf9 insect cells, the High Five cells also demonstrate a defect in the release of C-type virus particles. These findings support the hypothesis that host cell factors are important in the process of Gag transport and in the release of enveloped viral particles.


Building collagen molecules, fibrils, and suprafibrillar structures.
Fibril-forming collagens are synthesized in precursor form, procollagens, with N- and C-terminal propeptide extensions. The C-propeptides direct chain association during intracellular assembly of the procollagen molecule from its three constituent polypeptide chains. Following or during secretion into the extracellular matrix, propeptides are cleaved by specific procollagen proteinases, thereby triggering fibril formation. The recent determination of the low-resolution structure of the C-propeptide trimer gives insights into the mechanism of procollagen chain association. In the extracellular matrix, the procollagen C-propeptides ensure procollagen solubility, while persistence of the N-propeptides controls fibril shape. Mechanisms for the control of fibril diameter are reviewed in terms of the radial packing model for collagen fibril structure. Finally, procollagen molecules have recently been shown to undergo liquid crystalline ordering in solution, prior to fibril assembly. This may provide an explanation for the liquid crystal-like suprafibrillar architectures of different connective tissues.


The study of p53 and CA19-9 prognostic molecular markers in colorectal carcinomas.
Immunohistochemistry represents a relatively new identification technique of cellular and tissular antigens due to an antigen-antibody binding interactions, applied more and more in the pathology laboratories for positive and differential diagnosis of premalignant and malignant lesions and also for evolutive prognosis of tumoral formations. Immunohistochemistry coloration is based on the antigen-antibody affinity, the antibody binding situs being identified either by antibody coloration direct methods or by using an indirect method where the marking is supplied by antibodies called secondary or even tertiary. The present study is based on the immunohistochemical investigation of some molecular markers with a prognosis value in colorectal cancers (CCR), like the antibody p53 immune expression and of some factors supposed to have prognosis value, such as CA19-9 (carcinoembryonic antigen, carbohydrate antigen or Lewis antigen). In the last decade, the studies have tried to define the prognosis of the molecular markers that allow the identification of the patients with recurrent risk after surgical treatment and who can benefit from chemotherapy in an efficient way. The purpose of the study on immunohistochemical markers is to aim towards the treatment based on molecular phenotypes of colorectal tumors. In 2000, according to the Consensus Conference of the Colorectal Working Group of the American Joint Committee on Cancer Prognostic Factors (AJC), there were established four categories of prognosis factors in colorectal cancers based on the practical importance and the number of studies referring to them. The present study is centered on the prognosis factors from the second B category (p53 oncoprotein expression) and the fourth category (CA19-9 immunomarker expression).


Rituximab (anti-CD20 monoclonal antibody) as consolidation of first-line CHOP chemotherapy in patients with follicular lymphoma: a phase II study.
Advanced stages of follicular lymphoma are deemed incurable by conventional approaches. Immunotherapy with the humanised monoclonal anti-CD20 antibody rituximab represents a new therapeutic option. The aim of our study was to determine the effectiveness and safety of rituximab in the consolidation setting of first-line treated patients with follicular lymphomas. Thus the goal was first to reduce tumour burden using the CHOP regimen as induction treatment followed by consolidation with rituximab administered on a standard 4 wk schedule at a dosage of 375 mg m-2 body surface area. Between August 1998 and April 2001, 41 patients were enrolled in the study. All patients were evaluable with regard to tumour response and toxicity. The overall remission rate in the intent-to-treat analysis was 100%. On subgroup analysis, 20 [83% (95% CI: 63-95%)] of the 24 patients with grade 1 or 2 histology entered complete remission (CR), in 10 cases (42%) after additional rituximab therapy. Rituximab thus led to CR in 10/14 patients [71% (95% CI: 42-92%)] who had merely achieved partial remission (PR) with CHOP. Of 16 evaluable patients with grade 3 histology (excluding one patient achieving CR on CHOP who refused further treatment with rituximab), 15 [94% (95% CI: 63-97%)] achieved CR, 13 (81%) of these while still receiving CHOP. Two of the three patients achieving only PR on CHOP entered CR following rituximab. Thirty-four patients (83%) continued to be in remission during a median follow-up period of 24.3 (9-40) months. Our data suggest that the use of rituximab for consolidation after CHOP may improve CHOP-induced remission and thus increase the CR rate. Furthermore, it was accompanied by a reduced rate of infusion-related side-effects.


The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress.
Asparagine (N)-linked glycosylation is required for endoplasmic reticulum (ER) homeostasis, but how this co- and posttranslational modification is maintained during ER stress is unknown. Here, we introduce a fluorescence-based strategy to detect aberrant N-glycosylation in individual cells and identify a regulatory role for the heterotetrameric translocon-associated protein (TRAP) complex. Unexpectedly, cells with knockout of SSR3 or SSR4 subunits restore N-glycosylation over time concurrent with a diminished ER stress transcriptional signature. Activation of ER stress or silencing of the ER chaperone BiP exacerbates or rescues the glycosylation defects, respectively, indicating that SSR3 and SSR4 enable N-glycosylation during ER stress. Protein levels of the SSR3 subunit are ER stress and UBE2J1 dependent, revealing a mechanism that coordinates upstream N-glycosylation proficiency with downstream ER-associated degradation and proteostasis. The fidelity of N-glycosylation is not static in both nontransformed and tumor cells, and the TRAP complex regulates ER glycoprotein quality control under conditions of stress.


[Osteoid osteoma in the distal phalanx of the thumb].
We present a rare case of osteoid osteoma in the distal phalanx of the thumb. Symptoms had started seven months prior with pain and swelling and later progressed to enlargement of the nail. The patient lacked the classic symptoms of nocturnal pain and relief from NSAID. The ostoid osteoma was located in relation to the physis and was on the initial X-rays believed to be normal closure of the physis. MRI showed abnormality but the CT scan gave the right diagnosis and was used to plan en-bloc surgery.


Establishment of an erythroid progenitor cell line capable of enucleation achieved with an inducible c-Myc vector.
A robust scalable method for producing enucleated red blood cells (RBCs) is not only a process to produce packed RBC units for transfusion but a potential platform to produce modified RBCs with applications in advanced cellular therapy. Current strategies for producing RBCs have shortcomings in the limited self-renewal capacity of progenitor cells, or difficulties in effectively enucleating erythroid cell lines. We explored a new method to produce RBCs by inducibly expressing c-Myc in primary erythroid progenitor cells and evaluated the proliferative and maturation potential of these modified cells. Primary erythroid progenitor cells were genetically modified with an inducible gene transfer vector expressing a single transcription factor, c-Myc, and all the gene elements required to achieve dox-inducible expression. Genetically modified cells had enhanced proliferative potential compared to control cells, resulting in exponential growth for at least 6 weeks. Inducibly proliferating erythroid (IPE) cells were isolated with surface receptors similar to colony forming unit-erythroid (CFU-Es), and after removal of ectopic c-Myc expression cells hemoglobinized, decreased in cell size to that of native RBCs, and enucleated achieving cultures with 17% enucleated cells. Experiments with IPE cells at various levels of ectopic c-Myc expression provided insight into differentiation dynamics of the modified cells, and an optimized two-stage differentiation strategy was shown to promote greater expansion and maturation. Genetic engineering of adult erythroid progenitor cells with an inducible c-Myc vector established an erythroid progenitor cell line that could produce RBCs, demonstrating the potential of this approach to produce large quantities of RBCs and modified RBC products.


A Neurodynamic Approach to Distributed Optimization With Globally Coupled Constraints.
In this paper, a distributed neurodynamic approach is proposed for constrained convex optimization. The objective function is a sum of local convex subproblems, whereas the constraints of these subproblems are coupled. Each local objective function is minimized individually with the proposed neurodynamic optimization approach. Through information exchange between connected neighbors only, all nodes can reach consensus on the Lagrange multipliers of all global equality and inequality constraints, and the decision variables converge to the global optimum in a distributed manner. Simulation results of two power system cases are discussed to substantiate the effectiveness and characteristics of the proposed approach.


Will Africans take COVID-19 vaccination?
The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans. An online cross-sectional African-wide survey was administered in Arabic, English, and French languages. Questions on demographics, self-reported health status, vaccine literacy, knowledge and perception on vaccines, past experience, behavior, infection risk, willingness to receive and affordability of the SARS-COV-2 vaccine were asked. Data were subjected to descriptive and inferential statistics. A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the other Africans live in the Diaspora. Only 63% of all participants surveyed were willing to receive the COVID-19 vaccination as soon as possible and 79% were worried about its side effects. Thirty-nine percent expressed concerns of vaccine-associated infection. The odds of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed otherwise. The odds of vaccine hesitancy was one-fifth (OR = 0.21, 95% CI: 0.16, 0.28) among those who believed their risk of falling sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Participants want the vaccines to be mandatory (40%), provided free of charge (78%) and distributed in homes and offices (44%). COVID-19 vaccine hesitancy is substantial among Africans based on perceived risk of coronavirus infection and past experiences.


Two cheers for physicians' conflicts of interest.
This paper will attempt to demonstrate that conflict of interest is an unavoidable feature of medical practice, medical institutions, medical publications, and medical research. It also seeks to show how and why current regulations are ineffective in curbing fraud and abuse. The paper goes on to argue that, in light of the incentives incorporated into current reimbursement arrangements, physicians have to learn how to manage the conflicts they face and keep true their fiduciary responsibility to patients.


[Subacute sclerosing panencephalitis in Poland in the years 1990-1993. Stage V of epidemiologic studies].
The authors summarize the results of the fifth stage of epidemiological investigation on SSPE. The first stage covered the years 1971-1976, the next stages covered the periods: 1977-1983; 1984-1986; 1987-1989. In the period 1990-1993 data on 95 patients with SSPE were obtained. Morbidity rates continued to show a decreasing tendency (from 0.8 to 0.6 per 1,000,000 population) in the years 1990-1993, being lower the median morbidity (amounting to 0.98) in 1985-1989. Morbidity rates continued to shift towards older age groups: while the peak morbidity (25.7%) in the years 1990-1992 was noted in the 14-15 age range, in 1993 the peak (28.6%) was found in the age group of 16 to 19 years.


Sodium channelopathies and pain.
Chronic pain often represents a severe, debilitating condition. Up to 10% of the worldwide population are affected, and many patients are poorly responsive to current treatment strategies. Nociceptors detect noxious conditions to produce the sensation of pain, and this signal is conveyed to the CNS by means of action potentials. The fast upstroke of action potentials is mediated by voltage-gated sodium channels, of which nine pore-forming alpha-subunits (Nav1.1-1.9) have been identified. Heterogeneous functional properties and distinct expression patterns denote specialized functions of each subunit. The Nav1.7 and Nav1.8 subunits have emerged as key molecules involved in peripheral pain processing and in the development of an increased pain sensitivity associated with inflammation and tissue injury. Several mutations in the SCN9A gene encoding for Nav1.7 have been identified as important cellular substrates for different heritable pain syndromes. This review aims to cover recent progress on our understanding of how biophysical properties of mutant Nav1.7 translate into an aberrant electrogenesis of nociceptors. We also recapitulate the role of Nav1.8 for peripheral pain processing and of additional sodium channelopathies which have been linked to disorders with pain as a significant component.


ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts.
Background: Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great antitumor characteristics by targeting tumor cell apoptosis. The objective of this study was to explore whether ABT-263 could target apoptosis of overactivated myofibroblasts in hypertrophic scar. Methods: In vivo, we used ABT-263 to treat scars in a rabbit ear scar model. Photographs and ultrasound examination were taken weekly, and scars were harvested on day 42 for further Masson trichrome staining. In vitro, the expression levels of BCL-2 family members, including prosurvival proteins, activators, and effectors, were detected systematically in hypertrophic scar tissues and adjacent normal skin tissues, as well as in human hypertrophic scar fibroblasts (HSFs) and human normal dermal fibroblasts (HFBs). The roles of ABT-263 in apoptosis and proliferation of HSFs and HFBs were determined by annexin V/PI assay, CCK-8 kit, and cell cycle analysis. Mitochondrial membrane potential was evaluated by JC-1 staining and the expression of type I/III collagen and α-SMA was measured by PCR, western blotting, and immunofluorescence staining. Furthermore, immunoprecipitation was performed to explore the potential mechanism. Results: In vivo, ABT-263 could significantly improve the scar appearance and collagen arrangement, decrease scar elevation index (SEI), and induce cell apoptosis. In vitro, the expression levels of BCL-2, BCL-XL, and BIM were significantly higher in scar tissues and HSFs than those in normal skin tissues and HFBs. ABT-263 selectively induced HSFs apoptosis by releasing BIM from binding with prosurvival proteins. Moreover, ABT-263 inhibited HSFs proliferation and reduced the expression of α-SMA and type I/III collagen in a concentration- and time- dependent manner. Conclusion: HSFs showed increased mitochondrial priming with higher level of proapoptotic activator BIM and were primed to death. ABT-263 showed great therapeutic ability in the treatment of hypertrophic scar by targeting HSFs.


[Myocardial revascularization and ischemic heart failure].
Ischaemic heart failure is the cause of an increased number of hospital admissions and death rate. In severe heart failure and cardiogenic shock, coronary reperfusion associated or not with aortic balloon pump counter-pulsation, seems to be beneficial. Moreover, it has recently shown that coronary bypass surgery may be a reasonable alternative to cardiac transplantation in coronary patients with severe heart failure. In the chronic phase, two physiopathological conditions have been proposed to explain the mechanism of ischaemic left-ventricular dysfunction: myocardial hibernation and stunning. Only hibernation requires revascularisation to avoid irreversible myocardial damage. The CASS group and others have demonstrated a real benefit from surgery although the operative risk is greater. Angioplasty has also been shown to be effective in terms of primary success with a relatively low complication rate. Compared one with another, angioplasty seems to provide better immediate results whereas surgery is associated with more long-term benefits. Myocardial revascularisation is therefore part of the therapeutic arsenal in cases of ischaemic heart failure.


p53 Immunohistochemical Patterns in HPV-Independent Squamous Cell Carcinomas of the Vulva and the Associated Skin Lesions: A Study of 779 Cases.
Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour TP53 mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with TP53 mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor.


[Assessment of the acquisition, use and needs of plasma derivatives in Asturias (1990-1995)].
To estimate the effectiveness of the Asturias transfusion network in achieving self-sufficiency in plasma, derivatives, blood and blood components in the period from 1990 to 1995. A retrospective study of the indicators of blood donation, production, management and transfusion of fresh frozen plasma and of the clinical usage of plasma derivatives in 1990 and 1995 was carried out. In 1990, 26.1% of the plasma and derivatives used were produced in Asturias (108% of the plasma transfused and 15.9% of that equivalent to the plasma derivatives). On the other hand, an estimated 112.4% of the plasma needed was used (FFP, 153%; plasma derivatives, 108.7%). In 1995, 32.2% of all the plasma and derivatives used were produced here (118% of the FFP transfused and 27.2% of the equivalent to the plasma derivatives used). The usage of the plasma necessary for clinical supplies was estimated in 149.0% of the needs (FFP, 138.9%; plasma derivatives, 149.6%). The volume of plasma-equivalent used in both years was higher for albumin than for factor VII. The Consulting Commission of the Blood Centre, with the participation of the Services of Pharmacy, has to establish a programme aimed to monitor all the aspects related with the use of plasma and to evaluate the degree of accomplishment of the obligation of attaining self-sufficiency in plasma.


MicroRNA-93 inhibits ischemia-reperfusion induced cardiomyocyte apoptosis by targeting PTEN.
MicroRNAs have been implicated in some biological and pathological processes, including the myocardial ischemia/reperfusion (I/R) injury. Recent findings demonstrated that miR-93 might provide a potential cardioprotective effect on ischemic heart disease. This study was to investigate the role of miR-93 in I/R-induced cardiomyocyte injury and the potential mechanism. In this study, we found that hypoxia/reoxygenation (H/R) dramatically increased LDH release, MDA contents, ROS generation, and endoplasmic reticulum stress (ERS)-mediated cardiomyocyte apoptosis, which were attenuated by co-transfection with miR-93 mimic. Phosphatase and tensin homolog (PTEN) was identified as the target gene of miR-93. Furthermore, miR-93 mimic significantly increased p-Akt levels under H/R, which was partially released by LY294002. In addtion, Ad-miR-93 also attenuated myocardial I/R injury in vivo, manifested by reduced LDH and CK levels, infarct area and cell apoptosis. Taken together, our findings indicates that miR-93 could protect against I/R-induced cardiomyocyte apoptosis by inhibiting PI3K/AKT/PTEN signaling.


Discrimination between cross-country and downhill skiers by pulmonary and local 31PNMR evaluations.
The purpose of the present study was to correlate data on calf muscle metabolism using 31P nuclear magnetic resonance spectroscopy with measurements of whole body maximal oxygen consumption and maximal power output, and to determine whether the combination of these data could be used to predict athletic ability. Experiments were performed in a 2.35 Tesla, 35 cm diameter electromagnet on the leg muscle of sedentary human subjects (N = 6) and groups of athletes trained for endurance (cross-country skiers, N = 7) or strength performance (downhill skiers, N = 5). The exercise protocol consisted of successive plantar flexions performed at graded fractions of the maximal voluntary contraction (MVC). The results obtained from NMR investigation (changes in content of inorganic phosphate: Pi, phosphocreatine: PC and muscle ATP, and intracellular pH) were then compared with those of maximal O2 consumption (VO2max) and maximal power (MP). When the data on athletes were compared with those obtained on sedentary subjects, the curves illustrating the relationship between the imposed load and the Pi/PC ratio were significantly shifted toward high output power for a given Pi/PC value. It also appeared from this study that specific training in force development (downhill skiing) induced a slighter decrease in PC level than for endurance (cross-country skiers) despite improvement in physical performance. A slight but significant intracellular acidification was observed in the muscles of sedentary subjects and downhill skiers for contraction at, respectively, 50% and 80% of MVC, but not in the skeletal muscles of cross-country skiers.(ABSTRACT TRUNCATED AT 250 WORDS)


Comprehensive Evaluation of Parameters Affecting One-Step Method for Quantitative Analysis of Fatty Acids in Meat.
Despite various direct transmethylation methods having been published and applied to analysis of meat fatty acid (FA) composition, there are still conflicting ideas about the best method for overcoming all the difficulties posed by analysis of complex mixtures of FA in meat. This study performed a systematic investigation of factors affecting a one-step method for quantitative analysis of fatty acids in freeze-dried animal tissue. Approximately 280 reactions, selected using factorial design, were performed to investigate the effect of temperature, reaction time, acid concentration, solvent volume, sample weight and sample moisture. The reaction yield for different types of fatty acids, including saturated, unsaturated (cis, trans and conjugated) and long-chain polyunsaturated fatty acids was determined. The optimised condition for one-step transmethylation was attained with four millilitres 5% sulfuric acid in methanol (as acid catalyst), four millilitres toluene (as co-solvent), 300 mg of freeze-dried meat and incubation at 70 °C for 2 h, with interim mixing by inversion at 30, 60 and 90 min for 15 s. The optimised condition was applied to meat samples from different species, covering a broad range of fat content and offers a simplified and reliable method for analysis of fatty acids from meat samples.