Antithymocyte globulin for prevention of graft-versus-host disease.
This review aims to discuss current clinical trial using antithymocyte globulin in the context of hematopoietic stem cell transplantation. Published papers, as well as abstracts from European and American meetings, have been used together with original data. The review shows that antithymocyte globulin is used frequently in Europe in the setting of unrelated or family mismatched donor transplants. This may not be the case for American centers, reluctant to introduce antithymocyte globulin possibly due to known side effects such as prolonged immune deficiency and increased incidence of infections, including life threatening Epstein-Barr virus-associated lymphoproliferative disorders. Results from few randomized trials show that antithymocyte globulin reduces acute and chronic graft-versus-host disease, and this is in keeping with results from retrospective analysis on large number of patients. Several issues remain open, such as optimal dose, optimal timing with respect to infusion of stem cells and whether the commercially available agents have comparable effects. Prospective trials are needed to answer these important questions.


Vortices and their relation to ring currents and magnetic moments in nanographenes in high magnetic field.
Much attention has been paid to the role of vortices in the magnetic response properties of superconductors, but less so for molecular systems. Here we present a theoretical analysis on nanographenes subject to a strong homogeneous magnetic field. The analysis is based on the simple Hückel-London model, for which we derive the topological definition of vorticity. The results are confirmed by a more elaborate model that includes nonnearest neighbor interaction, the explicit presence of nuclei and all terms due to the magnetic field. We find that due to frontier orbital intersections, large changes in magnetic dipole moments occur. Orbital energy minima and maxima can be related to change of vortex patterns with flux.


Time-scale separation of a class of robust PD-type tracking controllers for robot manipulators.
In this paper, the trajectory tracking control of robot manipulators is studied from the theoretical and practical point of view. By using the theory of singularly perturbed systems, a class of PD-type robust controllers is introduced. Our analysis departs from parameterizing the proportional and derivative gains with a perturbing parameter. We prove that the smaller the value of perturbing parameter, the smaller the ultimate bound of the joint position tracking error. Derived from the introduced analysis, two forms of extending the proposed class of controllers are discussed. In one, error-varying PD gains are considered while in the another one, a dynamic extension to avoid joint velocity measurements is incorporated. An experimental study in a planar two degrees-of-freedom direct-drive robot is also presented. Under similar implementation conditions, four controllers are tested. The best performance is obtained for a nonlinear PD controller derived from the proposed class of controllers.


Radiological Features in Type II Odontoid Fractures in Older Adults After High- and Low-Energy Trauma.
Retrospective study. Although type II odontoid fractures mainly occur due to high-energy trauma (HET), the number of odontoid type II fractures after low-energy trauma (LET) in the elderly is on the rise. However, there is a paucity of conclusive evidence on the relationship between trauma mechanism and cervical spine alignment in the elderly population. Consequently, we examined cervical alignment and osteoporotic and osteoarthritic patterns in elderly individuals (aged ≥65 years) with type II odontoid fractures. We retrospectively assessed cervical spine alignment in 76 elderly individuals who experienced type II odontoid fractures after HET (n = 36) and LET (n = 40) between 2005 and 2020. Osteoporotic and osteoarthritic changes on computed tomography and cervical alignment parameters on sagittal plane radiographs were examined. Moderate and severe osteoporosis of the dens-body junction and osteoarthritis of the atlanto-odontoid joint were more prevalent in the LET than the HET group (P<.005). The anterior atlantodental interval (ADI) was significantly smaller in the LET group than in the HET group (.7 [.7] millimeter vs 1.2 [.8] mm; P=.003). An ADI equal 0 mm indicative for anterior fusion of C1/C2 was present in 37.5% of patients of the LET group. The C0-C2 angle, C1-C2 lordosis, and C2-C7 sagittal vertical axis were significantly different (HET vs LET: 33.2 [7.2]° vs 41.6 [11.4]°, P=.005; 28.1 [7.0]° vs 34.0 [8.0]°, P=.002; and 16.1 [11.1] millimeter vs 27.1 [12.4] mm, P=.008; respectively). Significantly higher rates of osteoporotic and degenerative changes were observed after LET. Furthermore, previous cervical malalignment represents a risk factor for type II odontoid fractures after LET.


The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes.
In the present study, we tested the hypothesis that chronic treatment with the direct rennin inhibitor aliskiren improves the remodelling of resistance arteries in dTGR (double-transgenic rats). dTGR (5 weeks) were treated with aliskiren (3 mg/kg of body mass per day) or ramipril (1 mg/kg of body mass per day) for 14 days and compared with age-matched vehicle-treated dTGR. BP (blood pressure) was similarly reduced in both aliskiren-treated and ramipril-treated rats compared with control dTGR (167±1 and 169±2 mmHg compared with 197±4 mmHg respectively; P<0.05). The M/L (media-to-lumen) ratio assessed on pressurized preparations was equally reduced in aliskiren-treated and ramipril-treated rats compared with controls (6.3±0.5 and 6.4±0.2% compared with 9.8±0.4% respectively; P<0.05). Endothelium-dependent and -independent relaxations were similar among the groups. L-NAME (N(G)-nitro-L-arginine methyl ester) significantly reduced acetylcholine-induced dilation in drug-treated dTGR. This effect was significantly more prominent in aliskiren-treated rats. eNOS (endothelial NO synthase) expression showed a 2-fold increase only in aliskiren-treated dTGR as compared with controls (P<0.01) and ramipril-treated dTGR (P<0.05). Plasma nitrite, as an index of NO production, was significantly increased in dTGR treated with either aliskiren or ramipril compared with controls. Only aliskiren induced a 2-fold increase in plasma nitrite, which was significantly greater than that induced by ramipril (P<0.05). gp91(phox) expression and ROS (reactive oxygen species) production in aorta were significantly and similarly reduced by both drugs. In conclusion, equieffective hypotensive doses of aliskiren or ramipril reduced the M/L ratio of mesenteric arteries and improved oxidative stress in dTGR. However, only aliskiren increased further NO production in the vasculature. Hence, in dTGR, direct renin inhibition induces favourable effects similar to that induced by ACE (angiotensin-converting enzyme) inhibition in improving vascular remodelling through different mechanisms.


TIMP-3 deficiency leads to dilated cardiomyopathy.
Despite the mounting clinical burden of heart failure, the biomolecules that control myocardial tissue remodeling are poorly understood. TIMP-3 is an endogenous inhibitor of matrix metalloproteinases (MMPs) that has been found to be deficient in failing human myocardium. We hypothesized that TIMP-3 expression prevents maladaptive tissue remodeling in the heart, and accordingly, its deficiency in mice would alone be sufficient to trigger progressive cardiac remodeling and dysfunction similar to human heart failure. Mice with a targeted timp-3 deficiency were evaluated with aging and compared with age-matched wild-type littermates. Loss of timp-3 function triggered spontaneous LV dilatation, cardiomyocyte hypertrophy, and contractile dysfunction at 21 months of age consistent with human dilated cardiomyopathy. Its absence also resulted in interstitial matrix disruption with elevated MMP-9 activity, and activation of the proinflammatory tumor necrosis factor-alpha cytokine system, molecular hallmarks of human myocardial remodeling. TIMP-3 deficiency disrupts matrix homeostasis and the balance of inflammatory mediators, eliciting the transition to cardiac dilation and dysfunction. Therapeutic restoration of myocardial TIMP-3 may provide a novel approach to limit cardiac remodeling and the progression to failure in patients with dilated cardiomyopathy.


[Histopathogenesis of goiters].
The basic mechanisms acting in the transformation of a normal thyroid gland into a toxic or nontoxic goiter are summarized: 1) Any goiter arises from multiplication of follicular epithelial cells forming new follicles. 2) In the follicular epithelium there are cell families with much higher than average growth potential. 3) Cells of an individual follicle are not identical but heterogeneous. 4) Each follicular cell has a certain level of autonomy of growth and of function.


HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator.
The accessory protein, Vpr, is a virion-associated protein that is required for HIV-1 replication in macrophages and regulates viral gene expression in T cells. Vpr causes arrest of cell cycle progression at G2/M, presumably through its effect on cyclin B1.Cdc2 activity. Here, we show that the ability of Vpr to activate HIV transcription correlates with its ability to induce G2/M growth arrest, and this effect is mediated by the p300 transcriptional co-activator, which promotes cooperative interactions between the Rel A subunit of NF-kappaB and cyclin B1.Cdc2. Vpr cooperates with p300, which regulates NF-kappaB and the basal transcriptional machinery, to increase HIV gene expression. Similar effects are seen in the absence of Vpr with a kinase-deficient Cdc2, and overexpression of p300 increases levels of HIV Vpr+ replication. Taken together, these data suggest that p300, through its interactions with NF-kappaB, basal transcriptional components, and Cdks, is modulated by Vpr and regulates HIV replication. The regulation of p300 by Vpr provides a mechanism to enhance viral replication in proliferating cells after growth arrest by increasing viral transcription.


Fluorescent dye prelabelled microglial cells migrate into organotypic hippocampal slice cultures and ramify.
Microglial cells with their characteristic ramified morphology are exclusively found in healthy CNS tissue, whereas various pathologies are associated with the occurrence of amoeboid, macrophage-like cells. It is still a matter of discussion whether amoeboid cells are blood-derived macrophages, or whether a characteristic change in morphology, reflecting activation of previously ramified microglia, takes place. Cells in dissociated microglia culture obtained from healthy rat brains, inevitably developing this amoeboid morphology, were labelled with a fluorescent dye and transferred onto organotypic hippocampal slice cultures. Prelabelled cells with amoeboid morphology invaded these slice cultures and had, after 9 days in vitro, gradually transformed into highly ramified cells. Our findings strengthen the hypothesis that the observed amoeboid and ramified cells belong to a single population of microglia, appearing with different morphologies depending on the presence of stimuli provided by the CNS microenvironment. Microglial cells obviously appear in different shapes and can switch from immunologically resting to activated modes and vice versa.


Merkel cell carcinoma metastatic to the testis.
Tumor metastases to the testes are rare and are usually found incidentally at autopsy or after orchiectomy for prostatic carcinoma. It is even more unusual for testicular metastases to be clinically detected or symptomatic. The authors report two cases of clinically detected testicular metastases from Merkel cell carcinoma of the skin. Merkel cell carcinoma metastatic to the testes has not been reported previously. The two tumors, to some degree, resembled testicular lymphomas and the interstitial type of seminoma.


HLA antigens in juvenile dermatitis herpetiformis.
The incidence of histocompatibility antigens HLA-A, B, C, DR was studied in 32 Italian children with dermatitis herpetiformis. A significantly increased relative risk was found for B8 (R.R.=6.2), which was present in 50% of the patients as against 14% of the controls and for DR3 (R.R.=11.7), present in 69% of the patients as against 16%. DR7 also appeared to be increased, but only among DR3-negative patients. There was no significant difference in the incidence of DR3 between children with abnormal and normal jejunal biopsy, though there does seem to be a difference in expressivity of the intestinal involvement between DR3 apparent homozygous, DR3 heterozygous and DR3-negative patients.


Engineering the Structural Defects of Spinel Oxide Nanoneedles by Doping of V for a Highly Efficient Oxygen Evolution Reaction.
Rational design of multi-structural defects in the transition-metal oxides is a very alluring and challenging strategy to significantly improve its oxygen evolution reaction (OER) performance. Herein, a simple and promising element doping approach is demonstrated to fabricate a poor-crystalline V-doping CuCo2O4 (V-CuCo2O4) nanoneedle with rich oxygen vacancies (Vo), partially amorphous phase, and Co2+ defects on the carbon fiber (CF) (V-CuCo2O4/CF). The results indicate that the V doping could further weaken the crystallinity of V-CuCo2O4, providing the thoroughfares for the convenience of electrolyte penetration and the exposure of active sites. Meanwhile, [CoO6] octahedron in the V-CuCo2O4 lattice is gravely distorted due to a strong electronic interaction between the doped V and Co atoms, creating more Co2+ active species. With the merits of these multiple structural defects, V-CuCo2O4/CF exhibits rich active sites, and its intrinsically electrocatalytic activity is significantly enhanced. The optimized V-CuCo2O4/CF electrocatalyst has a significantly enhanced OER activity with a required low overpotential of ∼204 and ∼246 mV at a current density of 100 and 300 mA cm-2, respectively, a small Tafel slope of 40.7 mV dec-1, and excellent stability in an alkaline medium. Furthermore, the results from the projected partial density of states calculation not only demonstrate that the 3-fol-coordinated Co near Vo bonded with Cu and V sites (Cu-Co(surf-Vo)-V) exhibits an enhanced electronic transfer activity but also reveal that the doped V could protect the Co sites from the deactivation by intermediates overbinding on the V sites. This work provides new insights into structure engineering of spinel phase copper cobaltite, resulting in significantly boosting electrocatalytic OER activity.


S2k-Guideline "Prolonged Weaning".
All mechanically ventilated patients must be weaned from the ventilator at some stage. According to an International Consensus Conference the criteria for "prolonged weaning" are fulfilled if patients fail at least 3 weaning attempts (i. e. spontaneous breathing trial, SBT) or require more than 7 days of weaning after the first SBT. This occurs in about 15 - 20 % of patients.Because of the growing number of patients requiring prolonged weaning a German guideline on prolonged weaning has been developed. It is an initiative of the German Respiratory Society (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin e. V., DGP) in cooperation with other societies (see acknowledgement) engaged in the field chaired by the Association of Scientific and Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF).This guideline deals with the definition, epidemiology, weaning categories, underlying pathophysiology, therapeutic strategies, the weaning unit, transition to out-of-hospital ventilation and therapeutic recommendations for end of life care. This short version summarises recommendations on prolonged weaning from the German guideline.


Formability of ABX3 (X = F, Cl, Br, I) halide perovskites.
In this study a total of 186 complex halide systems were collected; the formabilities of ABX3 (X = F, Cl, Br and I) halide perovskites were investigated using the empirical structure map, which was constructed by Goldschmidt's tolerance factor and the octahedral factor. A model for halide perovskite formability was built up. In this model obtained, for all 186 complex halides systems, only one system (CsF-MnF2) without perovskite structure and six systems (RbF-PbF2, CsF-BeF2, KCl-FeCl2, TlI-MnI2, RbI-SnI2, TlI-PbI2) with perovskite structure were wrongly classified, so its predicting accuracy reaches 96%. It is also indicated that both the tolerance factor and the octahedral factor are a necessary but not sufficient condition for ABX3 halide perovskite formability, and a lowest limit of the octahedral factor exists for halide perovskite formation. This result is consistent with our previous report for ABO3 oxide perovskite, and may be helpful to design novel halide materials with the perovskite structure.


Age-related changes in lung collagen metabolism. A role for degradation in regulating lung collagen production.
Lung collagen levels are determined by a balance between synthesis and degradation, processes known to have rapid rates in young animals. Here, we report age-related changes in lung collagen synthesis and degradation in rats at five ages from 1 month to 2 yr. Synthesis rates were determined after injection of [14C]proline with a flooding dose of unlabeled proline, and its appearance as hydroxy-[14C]proline in protein. To determine degradation of newly synthesized collagen, the appearance of hydroxy-[14C]proline, either free or in low-molecular-weight peptides, was compared with hydroxy-[14C]proline in protein. Fractional collagen synthesis rates decreased from 13.51 +/- 0.54%/day at 1 month to 0.97 +/- 0.14%/day at 2 yr of age (p less than 0.05). Total lung collagen production also fell, but only after 15 months, when it decreased from 2.01 +/- 0.16 mg/day at 15 months to 0.54 +/- 0.10 mg/day at 2 yr of age (p less than 0.05). Fractional rates of total collagen degradation, calculated from the difference between rates of synthesis and rates of collagen deposition, decreased 20-fold from 1 month to 2 yr of age. The proportion of newly synthesized collagen degraded increased from 27.6 +/- 3.2% at 1 month to a maximum of 82.3 +/- 1.1% at 15 months. These results suggest that lung collagen synthesis and degradation occur throughout life, and that degradative pathways may play important roles in regulating collagen production during growth and ageing.


Inflammatory Pathways Regulated by Tumor Necrosis Receptor-Associated Factor 1 Protect From Metabolic Consequences in Diet-Induced Obesity.
The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor-associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-α, IL (interleukin)-1β, and TLRs (toll-like receptors). Mice deficient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1-/- mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance-an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic and proinflammatory cues were synergistically driven by β3-adrenergic and inflammatory signaling and required the presence of both TRAF-1-deficient adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were upregulated. Enhancing TRAF-1-dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These findings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.


Contemporary retrograde approach for the recanalisation of coronary chronic total occlusion: on behalf of the Japanese Retrograde Summit Group.
The retrograde approach to CTO is promising, but questions remain with regard to its wider application and the potential risks. This study evaluated the feasibility and efficacy of retrograde recanalisation of chronic total occlusion (CTO) of the coronary arteries. A total of 378 consecutive patients (previously failed PCI 32.0%) who enrolled in 27 institutions in Japan underwent retrograde recanalisation for CTO. We analysed the data on lesion characteristics, procedural materials, technique used, complications and clinical outcomes. Successful retrograde recanalisation was achieved in 70.4% and the overall procedural success was 83.6%. Collateral crossing was achieved via a septal route in 68.9%, epicardial in 27.2% and bypass grafts in 2.6%, respectively. The retrograde approach was completed with implementation of reverse CART in 42.5%, direct wire crossing in 23.1%, bilateral wiring in 22.7%, and CART in 11.7%. Major and minor collateral injuries and coronary perforations were noted in 1.3%, 10.3% and 2.9% of cases, respectively. Stroke occurred in 0.3%, QWMI and emergency PCI in 0.3% of patients with successful recanalisation. Wider application of retrograde CTO PCI achieved a high rate of success in recanalisation with an acceptable rate of complications in Japan.


Association of LncRNA-GAS5 gene polymorphisms and PBMC LncRNA-GAS5 level with risk of systemic lupus erythematosus in Chinese population.
Growth arrest-specific 5 (GAS5) is a kind of long non-coding RNAs (lncRNAs). Previous studies showed that down-regulation of LncRNA-GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down-expressed LncRNA-GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA-GAS5 polymorphism with SLE risk. And further explore how LncRNA-GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5-base pair (AGGCA/-) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA-GAS5 promoter region. A custom 36-Plex SNPscan kit was used for genotyping the LncRNA-GAS5 polymorphisms. The LncRNA-GAS5 and miR-21 target prediction was performed using bioinformatics software. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) were performed to assess GAS5 and miR-21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30-0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46-0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46-0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53-0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36-0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43-0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A-A-C-G-D haplotype (OR = 0.67, 95% CI, 0.49-0.91, P = .010). Also, patients in the SLE group showed a down-regulated expression of LncRNA-GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up-regulated expression of LncRNA-GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR-21 levels were considerably up-regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR-21 levels than the ones with the II genotype. Thus, we found that the LncRNA-GAS5/miR-21/PTEN signalling pathway was involved in the development of SLE, where LncRNA-GAS5 acted as an miR-21 target, and miR-21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA-GAS5 gene promoter region may be protected against SLE by up-regulating the expression of LncRNA-GAS5, which consecutively regulated miR-21 and PTEN levels.


The consequences of UV-induced immunosuppression for human health.
Exposure to UV radiation can cause suppression of specific immune responses. The pathways leading to the down-regulation are complex, starting from the absorption of UV photons by chromophores in the skin and ending with local and systemic changes in immune mediators, the generation of T and B regulatory cells and inhibition of effector and memory T cell activation. The consequences for human health are thought to be both beneficial and adverse. The former are illustrated by protection against polymorphic light eruption, and possible protection against T cell-mediated autoimmune diseases and asthma. The latter are illustrated by skin cancer, cutaneous lupus erythematosus and infectious diseases including vaccination. Many outstanding questions remain in this rapidly developing and controversial area, not least what advice to give the general public regarding their sun exposure. While considerable advances have been made in the development of strategies that preserve the health benefits of sunlight exposure and decrease its detrimental effects, further research is required before optimal levels of protection are achieved.


Feline calicivirus: recovery of wild-type and recombinant viruses after transfection of cRNA or cDNA constructs.
The RNA genome of the vaccine strain 2024 of feline calicivirus was cloned as cDNA and analyzed by nucleotide sequencing. A full-length DNA copy of the viral genome was established and proved to be a source of infectious cRNA after in vitro transcription and RNA transfection. Virus could also be recovered when the DNA construct was introduced into cells containing phage T7 RNA polymerase that was provided by vaccinia virus MVA-T7. After insertion of the sequence encoding the green fluorescent protein into the structural protein-encoding region of the infectious cDNA clone, a defective replicon was recovered that was able to replicate autonomously and was packaged into virus particles when the structural proteins were provided in trans.


Effects of DNA damage in smooth muscle cells in atherosclerosis.
DNA damage and the DNA damage response have been identified in human atherosclerosis, including in vascular smooth muscle cells (VSMCs). However, although double-stranded breaks (DSBs) are hypothesized to promote plaque progression and instability, in part, by promoting cell senescence, apoptosis, and inflammation, the direct effects of DSBs in VSMCs seen in atherogenesis are unknown. To determine the presence and effect of endogenous levels of DSBs in VSMCs on atherosclerosis. Human atherosclerotic plaque VSMCs showed increased expression of multiple DNA damage response proteins in vitro and in vivo, particularly the MRE11/RAD50/NBS1 complex that senses DSB repair. Oxidative stress-induced DSBs were increased in plaque VSMCs, but DSB repair was maintained. To determine the effect of DSBs on atherosclerosis, we generated 2 novel transgenic mice lines expressing NBS1 or C-terminal deleted NBS1 only in VSMCs, and crossed them with apolipoprotein E(-/-) mice. SM22α-NBS1/apolipoprotein E(-/-) VSMCs showed enhanced DSB repair and decreased growth arrest and apoptosis, whereas SM22α-(ΔC)NBS1/apolipoprotein E(-/-) VSMCs showed reduced DSB repair and increased growth arrest and apoptosis. Accelerating or retarding DSB repair did not affect atherosclerosis extent or composition. However, VSMC DNA damage reduced relative fibrous cap areas, whereas accelerating DSB repair increased cap area and VSMC content. Human atherosclerotic plaque VSMCs show increased DNA damage, including DSBs and DNA damage response activation. VSMC DNA damage has minimal effects on atherogenesis, but alters plaque phenotype inhibiting fibrous cap areas in advanced lesions. Inhibiting DNA damage in atherosclerosis may be a novel target to promote plaque stability.


Alopecia Associated with Use of Methylphenidate: A Case Series.
In this case series, we report three cases of alopecia associated with use of methylphenidate for ADHD (Attention deficit hyperactivity disorder), that reversed with discontinuation of methylphenidate.


Towards automatic calibration of Fourier-Domain OCT for robot-assisted vitreoretinal surgery.
We present a new real-time automatic spectral calibration (ASC) method for Fourier domain optical coherence tomography (FD OCT) that can be automatically performed by the system. The ASC method proposed can be performed during OCT scanning operation and does not require an external calibrating light source or a commercial optical spectrum analyzer. Spectral data used for calibration can be interferograms obtained from an arbitrary sample which may have complicated internal structures, such as ones found in biological tissue. Moreover, our ASC method incorporates known robot motion to calibrate physical pixel spacing of the A-scan in static or dynamic environments. Experimental results show that our ASC method can provide high-performance calibration for FD OCT in terms of axial resolution and ranging accuracy without increasing hardware complexity.


Embolic myocardial infarction in a pregnant woman with a mechanical heart valve on low molecular weight heparin.
Even with continuing technical improvements in prosthesis design and the development of less thrombogenic materials, mechanical valve prostheses still carry a thromboembolic risk significant enough to warrant long-term anticoagulation therapy. Optimal anticoagulation is especially crucial during pregnancy due to the hypercoagulable state that rapidly develops after conception. Conventional anticoagulation therapy with coumarin derivatives is associated with risks of teratogenicity and hemorrhage for the fetus, and thromboembolic and hemorrhagic complications for the mother. As a result, other forms of anticoagulation, such as unfractionated or low molecular weight heparin, have been advocated as an alternative in selected cases. The present report describes a case of embolic myocardial infarction occurring in a pregnant woman with an aortic bileaflet mechanical valve prosthesis while on therapeutic low molecular weight heparin after only one dose was withheld before amniocentesis.


Arthritis in the prehistoric Southeastern United States: biological and cultural variables.
Recent research shows that a bacterial life form, Erysipelothrix insidiosa, can produce rheumatoid arthritis in deer, swine, and dogs, and that a number of animals, including man, birds, and fish, may be infected by the organism. Examination of the archaeological record suggests that both cultural and biological variables may be interrelated in the maintenance of some forms of arthritis over long periods of time in geographically disparate populations. Re-examination of Cherokee folk beliefs concerning arthritis suggests that they had some recognition of this connection, and it also suggests that they had some recognition of this connection, and it also suggests that the term "magical" may relate more to the world view of the observer than to any actual inability of preliterate peoples to draw causal relations on the basis of their own intimate knowledge of their environments.


New species and synonymy in the genus Corotoca Schiødte, 1853 (Coleoptera, Aleocharinae, Corotocini).
Corotoca Schiødte, 1853 is a Neotropical genus of termitophiles beetles, with five species, and its description marks the first record of insects associated with termites. A new species, Corotoca fontesi sp. nov., from Brazil, is described and illustrated, and a taxonomical problem regarding to the identification and nomenclatural status of two species, Corotoca phylo Schiødte, 1853 and Corotoca seeversi Fontes, 1977, is solved. Therefore, Corotoca seeversi is proposed as a new junior synonym of C. phylo, and the material identified as C. phylo housed in the Museum of Zoology of the University of São Paulo, Brazil (MZUSP) is recognized as a new species, Corotoca fontesi sp. nov. New morphological and sexual dimorphism data in the species, and solution of some messy informations about the genus present in the literature are also present.


3alpha,5alpha-THP: a potential plasma neurosteroid biomarker in Alzheimer's disease and perhaps non-Alzheimer's dementia.
A plasma biomarker for neurodegenerative disease is desirable because blood is relatively simple to obtain compared with other biological samples such as cerebrospinal fluid. Recent literature suggests that neurosteroid metabolism may be altered in Alzheimer's disease (AD). We sought to measure the plasma levels of seven steroids to assess their potential as biomarkers for dementia and AD. Steroids were measured using validated radioimmunoassay methods in AD (n=15), non-AD dementia (n=4), and control subjects (n=20). Demented subjects were in the mild-to-moderate stages of illness. Measurements were done blind to subject status in an independent laboratory. The notable finding was the significantly lower 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) level in demented subjects compared with controls (25% decrease; p=0.004); 3alpha,5alpha-THP was the only one of the steroids demonstrating an effect of dementia. Lowered 3alpha,5alpha-THP levels appear promising as a biomarker in dementia, but further work is needed to establish the sensitivity and specificity of these findings in AD.


Two new species of Spadicoides from Brunei and Hong Kong.
Spadicoides hodgkissa sp. nov. and Spadicoides arengae sp. nov., recorded from submerged decaying wood in Hong Kong and from decaying palm fronds in Brunei, are described and illustrated. Spadicoides hodgkissa is characterized by versicolored, obovoid conidia with up to 2 septa, including a distal distoseptum and a proximal euseptum, while Spadicoides arengae is characterized by unicellular, ellipsoidal conidia with verruculose walls that are relatively large. Eight genera, including Dendrographium, Helminthosporium, Luzfridiella, Paliphora, Polyschema, Polytretophora, Porosubramaniania, and Weufia, have the same conidiogenesis as Spadicoides. A key to these genera is provided.


The development of distance estimation in optic flow.
In three experiments we tested the ability of children aged 8 to 12 years and adults to locate a target in an optic texture flow projected onto the ground. During the exposure phase, a static target (diode) was lit up at 6 m or 8 m on the ground in front of the subject. During the pointing phase, the subject was asked to indicate the perceived location of the target with a laser pointer as soon as the target was switched off. In the first experiment, during both phases the optic texture (environment) was either motionless or approaching the subject. Results showed that target locations were significantly more underestimated within the moving texture than within the still texture. In the second experiment, a detailed error analysis showed that the differences of performance between children and adults were not due to differences in eye height. Errors can be described by a linear fit with the retinal speed of the optic flow surrounding the targets. Distance judgments improved from the age of 8 years onwards. In the last experiment we found the same kind of results with a receding texture and without stimulation in central vision. Results are discussed in terms of subject's capacity to compensate for the effect of linear vection produced by the optic flow.


mHealth program for patients with advanced cancer receiving treatment in a public health hospital in Brazil.
Previous studies have suggested the benefit of routine screening for biopsychosocial symptoms among patients with cancer. In recognition of the lack of data from low- and middle-income countries, this study sought to test and determine the effect of a mHealth program to screen biopsychological symptoms among patients with advanced breast or gynecological cancer. This was a quasi-experimental pre-post study conducted in a public hospital located in central western Brazil. Patients diagnosed with advanced breast of gynecological cancer who were about to initiate chemotherapy treatment at this institution and had access to Internet by smartphone, computer or tablet were invited to participate. Patients received training on using the app Comfort, a program developed to rate their physical and emotional symptoms during the 6-month of the proposed study. Patients were also asked to complete the EuroQOL 5D (EQ-5D-3L) every month. Mann-Whitney U test was used to determine differences among groups of patients (engaged and non-engaged). RM-ANOVA was used to determine the effect of time on mean visual analog scale (VAS) score. A total of 125 patients were recruited (median age = 46.6 years old, 41.6% married). Mostly, patients possessed lower levels of education and had relatively low monthly incomes. Notably, 67.2% of patients engaged with the Comfort program, and few patients (4%) withdrew due to lack of engagement with the program or issues with internet connection. In general, patients who engaged with the program reported improvement in physical and emotional symptoms (p < 0.01), as well as in their overall quality of life (VAS; p = 0.009), compared with patients who did not engage with the program. This is the first mHealth program developed in Brazil for patients in a low resource setting. Our findings suggest that Comfort could be an effective resource to assist patients and health care providers track symptoms and improve patients' quality of life.


Malignant peripheral nerve sheath tumor of the heart.
A 32-year-old man presented with dyspnea, chest pain, palpitations and ankle edema and was found to have a tumor involving the heart. This was diagnosed as malignant peripheral nerve sheath tumor, a rare sarcoma of the heart. Immunohistochemistry was utilized to establish the diagnosis. The details of the patient's clinical course, and imaging findings with morphological and immunohistochemistry data are reported.


Intervening in the residential mobility process: neighborhood outcomes for low-income populations.
Neighborhoods have become the focus of questions about how they affect the families that live within them. A current working assumption of some federal policies is that, with help, households can escape poverty neighborhoods and change their spatial context. How true is this, especially for low-income households, and does changing neighborhoods have measurable benefits? The study uses data from the Moving to Opportunity program, initiated by the Department of Housing and Urban Development, to test whether policy interventions by means of housing vouchers have aided moves away from low-poverty areas and into integrated residential settings. By examining the neighborhood demography of the initial and subsequent locations of the samples, it is possible to assess the success of the objectives of decreasing poverty and increasing integration. Although the program has shown some success in assisting households to live in lower-poverty neighborhoods, the findings here emphasize just how difficult it is to intervene in dynamic processes such as housing choice and mobility to create policy outcomes.


Site-specific methylation inhibits transcriptional activity of platelet-derived growth factor A-chain promoter.
Expression of the platelet-derived growth factor (PDGF) A-chain gene is temporally and spatially restricted in development and highly regulated in selected normal and tumor cell lines. Because DNA methylation appears to be important in regulating tissue specific gene expression, we tested the influence of in vitro methylation of the human PDGF A-chain promotor on its activity in vivo in transient transfection assays. We now report that PDGF A-chain promoter activity is strongly repressed by DNA methylation in a DNA sequence-specific manner and that the repression of promoter activity by methylation requires a methyl CpG-binding protein(s). We also report that incubation of HeLa cells with 5-azacytidine sharply increases levels of endogenous PDGF A-chain gene transcripts. These results indicate that the promoter activity of the PDGF A-chain gene is sharply and selectively reduced by in vitro DNA methylation and that DNA methylation in vivo also may reduce its function in selected cell lines.


Professionals with delivery skills: backbone of the health system and key to reaching the maternal health Millennium Development Goal.
The attainment of the fifth Millennium Development Goal requires adequate national reserves of skilled birth attendants. Nurses, midwives, and their equivalents form the frontline of the formal health system are a critical element of global efforts to reduce ill-health and poverty in the poorest areas of the world. Planning and policies supporting these cadres of workers must be placed high on the development agenda and championed by key international and national players. This article first sets forth an argument for the equity and efficiency of nurses, midwives, and their equivalents as the cadre largely responsible for maternal health. Second, it traces the root causes of neglect of this critical cadre, including a vacuum in political will in the context of poverty, lack of protections for frontline workers, the historical political position of the field of midwifery, lack of a pipeline of secondary school graduates, and gender inequity. Investment in the largely female cadre that cares for the majority of the world's poorer women has simply not been a high enough priority. Five key policy recommendations include harnessing political will and adequate metrics, protection of frontline workers' safety and livelihoods, ensuring an adequate pipeline with a focus on girls' education, donor support for training and professional organizations, and a rapid scale-up of a robust cadre of delivery care professionals. Finally, a call for unified international support of rapid scale-up of cadres of delivery care workers is put forth.


Testicular sperm aspiration (TESA) in 327 ICSI cycles.
To evaluate the efficiency of testicular sperm recovery by testicular sperm aspiration (TESA) in an IVF program. Retrospective Data Analysis. The Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, Reggio Emilia, Italy. Couples undergoing TESA/ICSI for obstructive or nonobstructive azoospermia. ESA/ICSI. Efficiency of testicular sperm recovery, fertilization rate, implantation rate and clinical pregnancy rate. Between March 1, 1997 and March 31, 2005, 327 cycles of TESA/ICSI were performed in couples in which the male had obstructive or nonobstructive azoospermia. The efficiency of testicular sperm recovery was 99.4% and 99.3%, fertilization rate 57.1% and 49.1%, implantation rate 5.7% and 6.2%, and the clinical pregnancy rate 12.9% and 15.4% in men with obstructive and nonobstructive infertility, respectively. The efficiency of TESA is very high in both obstructive and nonobstructive azoospermia. Because TESA is less invasive than TESE, it should be considered a valuable alternative to TESE in IVF programs, especially in setting where resources are limited.


A method for direct fabrication of a lingual splint for management of pediatric mandibular fractures.
Pediatric mandibular fractures have successfully been managed in various ways. The use of a lingual splint is one such option. The typical indirect method for acrylic lingual splint fabrication involves obtaining dental impressions. Dental models are produced from those impressions so that model surgery may be performed. The splint is then made on those models using resin powder and liquid monomer in a wet laboratory and transferred to the patient. Obvious limitations to this technique exist for both patient and operator. We present a technique for direct, intraoperative, fabrication of a splint using commercially available light-cured material that avoids some of the shortcomings of the indirect method. Recommendations are made based on available material safety information.


Sexually transmitted diseases and pregnancy.
The association of adverse pregnancy outcome with Treponema pallidum, Neisseria gonorrhoeae and herpes simplex infections is well known and specific recommendations for management have been formulated. However, other agents that are not so well known can be transmitted sexually and threaten an otherwise healthy pregnancy. These agents are discussed in order to make the nurse more aware of related maternal and fetal diseases.


Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats.
Cholesterol may have a role in the pathophysiology of depression. Lowering cholesterol levels with statins reduces risks for cardiovascular events, and there is clinical evidence that statins exert neuroprotective properties not fully explained by their effects on serum cholesterol levels. Altered cholesterol levels can affect serotonergic neurotransmission, which might be involved in the clinical efficacy of standard antidepressants. We examined interactions between a statin (lovastatin) and a selective serotonin reuptake inhibitor (fluoxetine) using the forced swim test (FST) in rats, a behavioral assay that identifies treatments with antidepressant effects in humans. Specifically, we determined if the addition of lovastatin to the diet would increase the efficacy of a subeffective dose of fluoxetine. Rats maintained on a lovastatin-enriched diet for 30 days were more sensitive to the antidepressant-like effects of a low (subthreshold) dose of fluoxetine. The behavior of rats treated with this combination resembled that normally seen with higher doses of fluoxetine. No effects were observed in rats maintained on a lovastatin-enriched diet for 3 days. Lovastatin can augment the antidepressant-like effects of a low dose of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans.


Nuclear Force Imprints Revealed on the Elastic Scattering of Protons with ^{10}C.
How does nature hold together protons and neutrons to form the wide variety of complex nuclei in the Universe? Describing many-nucleon systems from the fundamental theory of quantum chromodynamics has been the greatest challenge in answering this question. The chiral effective field theory description of the nuclear force now makes this possible but requires certain parameters that are not uniquely determined. Defining the nuclear force needs identification of observables sensitive to the different parametrizations. From a measurement of proton elastic scattering on ^{10}C at TRIUMF and ab initio nuclear reaction calculations, we show that the shape and magnitude of the measured differential cross section is strongly sensitive to the nuclear force prescription.


Viral Specific Factors Contribute to Clinical Respiratory Syncytial Virus Disease Severity Differences in Infants.
There is a wide range of severity of respiratory syncytial viral (RSV) disease in previously healthy infants. Host factors have been well demonstrated to contribute to disease severity differences. However the possibility of disease severity differences being produced by factors intrinsic to the virus itself has rarely been studied. Low-passage isolates of RSV collected prospectively from infants with different degrees of RSV disease severity were evaluated in vitro, holding host factors constant, so as to assess whether isolates induced phenotypically different cytokine/chemokine concentrations in a human lung epithelial cell line. Sixty-seven RSV isolates from previously healthy infants (38 hospitalized for acute RSV infection (severe disease) and 29 never requiring hospitalization (mild disease)) were inoculated into A549, lung epithelial cells at precisely controlled, low multiplicity of infection to mimic natural infection. Cultures were evaluated at 48 hours, 60 hours, and 72 hours to evaluate area under the curve (AUC) cytokine/chemokine induction. Cells infected with isolates from severely ill infants produced higher mean concentrations of all cytokine/chemokines tested (IL-1α, IL-6, IL-8 and RANTES) at all-time points tested. RSV isolates collected from infants with severe disease induced significantly higher AUCIL-8 and AUCRANTES secretion in infected cultures than mild disease isolates (p=0.028 and p=0.019 respectively). IL-8 and RANTES concentrations were 4 times higher at 48 hours for these severely ill infant isolates. Additionally, 38 isolates were evaluated at all-time points for quantity of virus. RSV concentration significantly correlated with both IL-8 and RANTES at all-time points. Neither cytokine/chemokine concentrations nor RSV concentrations were associated with RSV subgroup. Infants' RSV disease severity differences may be due in part to intrinsic viral strain-specific characteristics.


Toxicological evaluation of propane expanded tobacco.
A tiered testing strategy has been developed to evaluate the potential for tobacco processes, ingredients, and other technological developments to increase or decrease the biological activity resulting from burning tobacco. The strategy is based on comparative chemical and biological testing. Propane expanded tobacco is an example of a processed tobacco used in the modern manufacture of cigarettes. Test cigarettes containing propane expanded tobacco were compared to control cigarettes containing tobacco expanded with a traditional expansion agent (Freon-11). The toxicological evaluation included chemistry studies using mainstream cigarette smoke (determination of selected constituent yields), in vitro studies using cigarette smoke condensate (Ames study in Salmonella typhimurium and sister chromatid exchange study in Chinese hamster ovary cells) and in vivo studies (13-week inhalation study of mainstream cigarette smoke in Sprague-Dawley rats and 30-week dermal tumor promotion study of cigarette smoke condensate in SENCAR mice). Although statistically significant differences in several smoke constituents were observed, most constituents from cigarettes containing 100% propane expanded tobacco were within market survey ranges. Furthermore, biological tests indicated that the cigarettes containing propane or Freon-11 expanded tobacco were not significantly different.


Asymmetry-driven structure formation in pair plasmas.
The nonlinear propagation of electromagnetic waves in pair plasmas, in which the electrostatic potential plays a very important but subdominant role of a "binding glue" is investigated. Several mechanisms for structure formation are investigated, in particular, the "asymmetry" in the initial temperatures of the constituent species. It is shown that the temperature asymmetry leads to a (localizing) nonlinearity that is qualitatively different from the ones originating in ambient mass or density difference. The temperature-asymmetry-driven focusing-defocusing nonlinearity supports stable localized wave structures in 1-3 dimensions, which, for certain parameters, may have flat-top shapes.


The therapeutic efficacy of endoscopic optic nerve decompression and its effects on the prognoses of 96 cases of traumatic optic neuropathy.
Traumatic optic neuropathy (TON) is an important cause of severe loss of vision due to blunt or penetrating head trauma. The pathogenesis of TON remains unclear, and there are several potential causes for the observed loss in vision. Endoscopic optic nerve decompression (EOND) has been reported to improve the visual prognosis in TON cases, but its efficacy remains controversial. It is important to investigate the therapeutic efficacy of EOND in the treatment of TON and to evaluate the relevant prognostic factors. A retrospective study was conducted to analyze the clinical characteristics and prognoses of 96 TON cases. The χ(2) test and multiple logistic regression analyses were used to evaluate potential prognostic factors. : The overall rate of EOND effectiveness was 40.6% (39 of 96). A significantly higher effective rate (83.3%) was observed for patients with light perception compared with those without light perception (26.4%, p < 0.05). Univariate and multiple logistic regression analyses identified three variables (no light perception, undergoing EOND 3 days after trauma, and hemorrhage within the ethmoid and/or sphenoid sinus) that were significantly associated with unrecovered visual acuity. Age, loss of consciousness, optic canal fracture, preoperative steroid megadose treatment, and optic nerve sheath incision were all factors that showed no significant correlation with therapeutic efficacy. However, patients with fractures in a single medial wall of the optic canal appeared to have better prognoses than patients with multiple fractures or those with a single fracture in a lateral wall. The overall therapeutic efficacy of EOND for the treatment of TON is far from satisfactory, especially for patients without light perception. The factors that impact TON prognoses are complex and may be interrelated. The indication for EOND must be individualized. III, epidemiological study.


Valid and invalid implementations of GOR secondary structure predictions.
GOR algorithms have long been a standard methodology for predicting protein secondary structure from primary sequence. We have developed two short validation sequences for the GOR I and GOR II algorithms. Use of these sequences with seven commercial and non-commercial implementations of these algorithms demonstrated that several were incorrect implementations, including two of the three commercial modules implementing the GOR I algorithm. This may be due to an easy misinterpretation of the GOR I algorithm and related data tables. We present the validation sequences and discuss implications of this widely propagated error on secondary and tertiary structure prediction, using several proteins of known structure in three different structural classes as examples. A valid GOR I implementation predicts secondary structure increases the accuracy of predictions by from 1-13 percentage points over an invalid implementation based on the easy misinterpretation. A valid implementation of the GOR I and GOR II algorithms is available from the authors.


Pindolol increases plasma norepinephrine concentration by stimulation of beta 2-adrenoceptors in conscious spontaneously hypertensive rats.
The beta-adrenoceptor antagonist pindolol [10-1,000 micrograms/kg subcutaneously (s.c.)] caused dose-related decreases in mean arterial pressure (MAP) and increased heart rate (HR) in conscious spontaneously hypertensive rats (SHR). The lowest dose of pindolol (10 micrograms/kg) decreased MAP by 25 mm Hg (-16%) without affecting plasma norepinephrine (NE) or plasma renin concentration (PRC). However, higher doses of pindolol elicited dose-related increases in plasma NE concentration and PRC. Plasma epinephrine concentration was not altered by pindolol. The selective beta 2-adrenoceptor antagonist ICI 118,551 (3 mg/kg, s.c.) prevented the tachycardia but not the increase in PRC caused by 100 micrograms/kg pindolol. Treatment with ICI 118,551 completely eliminated the 45% increase in plasma NE elicited by 100 micrograms/kg of pindolol even though the decrease in MAP caused by this dose of pindolol was the same in the presence (-33 mm Hg) and absence (-34 mm Hg) of beta 2-adrenoceptor blockade. These results indicate that the vasodepressor action of pindolol in SHR does not result from an agonistic effect at postjunctional beta 2-adrenoceptors in the vasculature. In addition, the increases in plasma NE concentration produced by pindolol result from stimulation of beta 2-adrenoceptors. These beta 2-adrenoceptors may be located prejunctionally on sympathetic neurons.


Where is the optimum far-point for a presbyopic eye?
To resolve the presbyope's dilemma by determining the optimum location of the far-point that maximizes depth-of-field for reading printed text. Geometrical optical analysis of defocused retinal images was used to compute the size of retinal blur circles relative to object size. Functional consequences of changes in viewing distance, pupil diameter, and far-point location were assessed using the blur ratio concept. Depth-of-field was specified by the ratio of the maximum distance to the minimum distance for which printed text of a given size is legible. For the emmetropic patient, text that is legible at one viewing distance remains legible at all shorter distances. Conversely, text that is illegible at one distance is illegible at all distances. For myopic (or undercorrected) patients, the location of the far-point determines the center of the depth-of-field, but not its size. The depth-of-field is shown numerically and analytically to be given by the approximate formula: log(far distance/near distance) = 0.174* blur ratio threshold* letter height/pupil diameter. Location of the far-point is a free parameter that can be adjusted to suit a patient's needs without affecting depth-of-field. This suggests a theoretically based clinical strategy for presbyopic refractive correction that takes account of reading needs, pupil size, text size, and habitual reading distance for the benefit of the presbyopic patient.


Expertise in the clinical interview: a cognitive analysis.
The present study evaluates differences between subjects at three levels of expertise in acquiring and using information obtained from a patient during the clinical review. The results of the study suggest that the selective acquisition and the efficient utilization of information are hallmarks of expertise in the clinical review.


Sudden quadriplegia after acute cervical disc herniation.
Acute neurological deterioration secondary to cervical disc herniation not related to external trauma is very rare, with only six published reports to date. In most cases, acute symptoms were due to progression of disc herniation in the presence of pre-existing spinal canal stenosis. A 42-year-old man developed weakness and numbness in his arms and legs immediately following a sneeze. On physical examination he had upper motor neuron signs that progressed over a few hours to a complete C5 quadriplegia. An emergent magnetic resonance imaging study revealed a massive C4/5 disc herniation. He underwent emergency anterior cervical discectomy and fusion. Postoperatively, the patient remained quadriplegic. Eighteen days later, while receiving rehabilitation therapy, he expired secondary to a pulmonary embolus. Autopsy confirmed complete surgical decompression of the spinal cord. Our case demonstrates that acute quadriplegia secondary to cervical disc herniation may occur without a history of myelopathy or spinal canal stenosis after an event as benign as a sneeze.


Comparison of short scales to measure depressive symptoms in elders with diabetes.
Depression is the most common mental health problem among American elders and it is also prevalent among those with diabetes. The 20-item Center for Epidemiological Studies Depression Scale (CES-D) is commonly used to measure depressive symptoms in elders, but its length is potentially burdensome. Twelve short forms of the CES-D (4 to 16 items) exist, but they have not been tested with elders with diabetes. This study compared reliability and validity estimates across the 12 short forms and investigated similarities in classifying elders with diabetes as clinically depressed using standardized cut scores. Beck's theory provides a framework for identifying the affective, cognitive, behavioral, and somatic symptoms that are measured by the CES-D. Data were merged from two studies, which yielded 80 elders with diabetes who completed the CES-D items during structured interviews. Cronbach's alpha was .87 for the CES-D; it ranged from .60 (5 items) to .84 (16 items) for shorter forms. Correlations of the full CES-D and short forms ranged from .82 (4 items) to .98 (16 items). Using the CES-D cut score, 14% of the elders with diabetes had clinically significant depressive symptoms: 21% men, 11% women, 17% African Americans, and 13% Caucasians. A 5-item scale overestimated 29% as clinically depressed: 33% men, 27% women, 25% African Americans, and 29% Caucasians. The findings suggest that shortened scales to measure depressive symptoms may be potentially useful with elders with diabetes. Further psychometric studies of the CES-D short forms are recommended with elders with chronic conditions.


Aspects of Oral Language, Speech, and Written Language in Subjects with Temporal Lobe Epilepsy of Difficult Control.
Introduction About 50 million people have epilepsy and 30% of them have epilepsy that does not respond to properly conducted drug treatment. Objective Verify the incidence of language disorders in oral language, speech, and written language of subjects with difficult to control temporal lobe epilepsy (TLE) and compare the occurrence of these disorders in subjects before and after surgery. Methods Cross-sectional study with quantitative analysis, exploratory type. A questionnaire for data collection was administered covering the following aspects: oral language, speech complaints, and writing production and comprehension. Criteria for inclusion of subjects were a diagnosis of TLE refractory to drug treatment and at least 4 years of schooling. Results The sample of 63 patients with TLE was divided into two groups: presurgical (n = 31) and postsurgical (n = 32). In the postsurgical group, there was a higher frequency of left lobectomy (75%) than right (25%). Conclusion Statistical analysis was performed with the chi-square test (significance level of 0.05). Complaints related to speech-language attention were more predominant in postsurgical subjects. Analysis of oral language, speech, and written language in subjects with epilepsy who underwent temporal lobectomy or not showed findings consistent with symptoms related to transient aphasia, with the presence of paraphasias, as well as changes in speech prosody and melody. These symptoms appeared more associated with recurrence after having a temporal lobectomy.


[Isolation and ultrastructure of Yersinia spheroplasts and protoplasts].
The conditions suitable for the cultivation of Yersinia and the inhibition of their cell-wall synthesis have been selected with the aim of obtaining spheroplasts and protoplasts of these microorganisms. Penicillin, streptomycin and lithium chloride have proved to be not very suitable for this purpose as they induce essential changes in the structure of the cytoplasmic membrane in altered Yersinia forms. The addition of 1% of glycine (for Y. pseudotuberculosis), 1-1.5% of methionine in combination with growth stimulators has made it possible to obtain Yersinia spheroplasts and protoplasts with the intact cytoplasmic membrane, thus permitting the isolation and purification of the cytoplasmic membrane fraction.


[Determinants of urgency of nursing home placement].
The aim of this paper was to identify factors affecting the urgency of nursing home placement after introduction of public long-term care insurance. The subjects were families including at least one disabled elderly person and one another family member in two cities in Chugoku Prefecture. The measure of the urgency of placement was 0 if the family did not submit any application for placement, 1 if the care managers judged that the elderly person should enter in the future when she/he really needs placement, 2 if the care managers judged that she/he might be able to wait for a short while, and 3 if the care managers judged that she/he should enter as early as possible. Our estimation method was by ordered logit model. The dependent variable was the measure of the urgency and the independent variables were several attributes of the families. In the estimation, we considered the possibility that the coefficients depend on categories of dependent variable. We obtained data for 146 waiting families and 494 others (total 640). There were differences in the urgency of placement among waiting elderly as follows "she/he should enter as early as possible" (28.8%); "she/he can wait for a while" (32.2%), "she/he should enter in the future when she/he really needs placement" (39.0%). The results of multivariate analyses showed that the urgency of placement correlated significantly with the severity of the elderly persons disabilities, the number of primary caregivers' self-symptoms, the family members' negative attitude toward caregiving, residing in city A, not having one's own house and limited use of short-stay facilities due to the circumstances of the providers. When judging the urgency of placement, we should consider not only whether the applicant has submitted a request for a nursing home or not, but also differences among the waiting families. The urgency of placement correlates significantly with severity of disability of the elderly person, the number of primary caregivers' self-symptoms, the family members' negative attitude for caregiving, residing in city A, not having one's own house, and limited use of short-stay facilities due to the circumstances of the providers.


Kinetic evidence for folding and unfolding intermediates in staphylococcal nuclease.
The complex kinetic behavior commonly observed in protein folding studies suggests that a heterogeneous population of molecules exists in solution and that a number of discrete steps are involved in the conversion of unfolded molecules to the fully native form. A central issue in protein folding is whether any of these kinetic events represent conformational steps important for efficient folding rather than side reactions caused by slow steps such as proline isomerization or misfolding of the polypeptide chain. In order to address this question, we used stopped-flow fluorescence techniques to characterize the kinetic mechanism of folding and unfolding for a Pro- variant of SNase in which all six proline residues were replaced by glycines or alanines. Compared to the wild-type protein, which exhibits a series of proline-dependent slow folding phases, the folding kinetics of Pro- SNase were much simpler, which made quantitative kinetic analysis possible. Despite the absence of prolines or other complicating factors, the folding kinetics still contain several phases and exhibit a complex denaturant dependence. The GuHCl dependence of the major observable folding phase and a distinct lag in the appearance of the native state provide clear evidence for an early folding intermediate. The fluorescence of Trp140 in the alpha-helical domain is insensitive to the formation of this early intermediate, which is consistent with a partially folded state with a stable beta-domain and a largely disordered alpha-helical region. A second intermediate is required to model the kinetics of unfolding for the Pro- variant, which shows evidence for a denaturant-induced change in the rate-limiting unfolding step. With the inclusion of these two intermediates, we are able to completely model the major phase(s) in both folding and unfolding across a wide range of denaturant concentrations using a sequential four-state folding mechanism. In order to model the minor slow phase observed for the Pro- mutant, a six-state scheme containing a parallel pathway originating from a distinct unfolded state was required. The properties of this alternate unfolded conformation are consistent with those expected due to the presence of a non-prolyl cis peptide bond. To test the kinetic model, we used simulations based on the six-state scheme and were able to completely reproduce the folding kinetics for Pro- SNase across a range of denaturant concentrations.


Measurement of microorganisms with PHA production capability in activated sludge and its implication in activated sludge model no. 3.
In Activated Sludge Model No.3 (ASM3), it is hypothesized that all heterotrophic microorganisms (X(H)) can store substrate. However, in reality, both microorganisms with and without substrate storage capability (X(H/STO) and X(H/S), respectively) could exist. If the ratio of X(H/STO) in activated sludge is influenced by operational and environmental conditions, kSTO (storage rate constant of heterotrophic microorganisms which is defined in ASM3) may not be a universal parameter and can change from case to case. In this study, polyhydroxyalkanoate (PHA) is assumed as the principal storage product, and the ratio of microorganisms with PHA production capability (X(H/PHA)) in various activated sludges was estimated by the dual staining of Nile Blue A (NB) and DAPI. It was shown that the ratio of X(H/PHA) in sludge varied among different municipal and laboratory activated sludges.


Implicit and explicit forgetting: when is gist remembered?
Recognition (YES/NO) and stem completion (cued: complete with a word from the list; and uncued: complete with the first word that comes to mind) were tested following either semantic or non-semantic processing of a categorized input list. Item/instance information was tested by contrasting target items from the input list with new items that were categorically related to them; gist/categorical information was tested by comparing target items semantically related to the input items with unrelated new items. For both recognition and stem completion, regardless of initial processing condition, item information decayed rapidly over a period of one week. Gist information was maintained over the same period when initial processing was semantic but only in the cued condition for completion. These results are discussed in terms of dual process theory, which postulates activation/integration of a representation as primarily relevant to implicit item information and elaboration of a representation as mainly relevant to semantic (i.e. categorical) information.


Pathophysiological Changes During Ischemia-reperfusion Injury in Rodent Hepatic Steatosis.
Ischemia and reperfusion injuries may produce deleterious effects on hepatic tissue after liver surgery and transplantation. The impact of ischemia-reperfusion injury (IRI) on the liver depends on its substrate, the percentage of liver ischemic tissue subjected to IRI and the ischemia time. The consequences of IRI are more evident in pathologic liver substrates, such as steatotic livers. This review is the result of an extended bibliographic PubMed search focused on the last 20 years. It highlights basic differences encountered during IRI in lean and steatotic livers based on studies using rodent experimental models. The main difference in cell death between lean and steatotic livers is the prevalence of apoptosis in the former and necrosis in the latter. There are also major changes in the effect of intracellular mediators, such as TNFα and IL-1β. Further experimental studies are needed in order to increase current knowledge of IRI effects and relevant mechanisms in both lean and steatotic livers, so that new preventive and therapeutic strategies maybe developed.


Hierarchically Designed Cathodes Composed of Vanadium Hexacyanoferrate@Copper Hexacyanoferrate with Enhanced Cycling Stability.
Prussian blue analogues (PBAs) have been highlighted as electrode materials for aqueous rechargeable batteries (ARBs) because of their favorable crystal structure and electrochemical activity. However, dissolution of the transition-metal ions during cycling degrades the materials and hinders the development of long-life-span batteries. To overcome this limitation, a strategy to revive the capacity degradation of PBA-based cathodes was developed herein based on designing all-PBA-based core@shell materials, while specific reduction upon introducing the shell layers was minimized. The core@shell materials were constructed using a V/Fe PBA (high capacity) core and a Cu/Fe PBA (high cycling stability) shell via a two-step co-precipitation method. The electrochemical performances including specific capacity, cycling stability, and rate capability as a function of the Cu/Fe PBA shell thickness were explored. At the optimal Cu/Fe PBA thickness, improved capacity retention after 200 cycles of >90% (72% for the core only) was attained with negligible capacity reductions from 94 (core only) to 90 (core@shell) mA h g-1, arising from the high electrochemical activity and stability of the Cu/Fe PBA shell and stabilized interfaces due to the crystallographic coherence between the core and shell materials. In addition, the power performance of the core@shell materials was significantly improved, e.g., C38.4C/C0.6C for a core@shell of 80% and core only of 62%, arising from the unique chemical coordination and facile ion diffusion kinetics of the Cu/Fe PBA shell. The newly developed V/Fe@Cu/Fe PBA-based cathodes offer an effective strategy for fabricating sustainable and low-cost ARBs.


[Chapter 10. The embryo, a particular thing].
By allowing a woman to terminate the life of the embryo, the law of 17 January 1975 leads us to ask the question about how to qualify the embryo. Is it a thing or a person ? Subordinate to the birth of a viable, living being, the embryo can have no acknowledged legal personality. Its particularity must nevertheless be noted : it is the only thing in law that is likely to become a person. So, conjugated in the present (The reality of the present : the embryo is a thing), the embryo is without doubt a thing.This qualification is implicit and results from an a contrario interpretation of article 16 CC. By not qualifying the human being from the start of his life as a person, the legislator treats him as a thing. That explains why the term homicide cannot be used against someone whose fault has provoked the termination of the pregnancy of a pregnant woman.The qualification as a thing does not prevent the protection of the embryo, attached to its quality as a human being. This protection is different from that applied to a person. In fact, it does not present an obstacle to the destruction of the embryo. It only consists in providing a framework for any violations that the embryo might suffer. The protection is variable according to whether it applies to the embryo in vitro or in utero and increases as the parental project progresses.Conjugated in the future, the embryo will become a person (The fiction taken from the future : the embryo is a person). This perspective allows us to qualify it fictitiously as a person, from conception, by means of an analysis, either retrospective or prospective.The retrospective analysis allows, once the child is born alive, a ?return to the future? by recognising that the embryo has rights, from conception, by applying the adage infans conceptus.The prospective analysis leads to anticipating the future and the quality as a person that will be acknowledged for the embryo at birth. Inspired by the law of goods and in particular the notion of thing by anticipation, the embryo can thus be qualified as ?person by? : this is a ?thing by nature? fictitiously qualified as a person because of the perspective of his birth. The interest of this qualification is that it explains the exceptional application of the legal regime of persons to the embryo, which limits the powers of the woman over her embryo. Indeed, the woman without doubt has absolute power to dispose of her body materially during the first weeks of the pregnancy, which confers on her the ability to destroy the embryo which is an element of her body. However, if she should wish to give birth to the child, the woman is deprived of the power to conclude legal acts of disposition by which she would commit herself to transfer the child to someone else at birth.


Total syntheses of linear polythiazole/oxazole plantazolicin A and its biosynthetic precursor plantazolicin B.
Plantazolicin A, a linear decacyclic natural product, exhibits desirable selective activity against the causative agent of anthrax toxicity. The total synthesis of plantazolicin A and its biosynthetic precursor plantazolicin B was successfully achieved by an efficient, unified, and highly convergent route featuring dicyclizations to form 2,4-concatenated oxazoles and the mild synthesis of thiazoles from natural amino acids. This report represents the first synthesis of plantazolicin B and includes the first complete characterization data for both natural products.


Simulation of Fixed-Bed Chromatographic Processes Considering the Nonlinear Adsorption Isotherms.
This paper presents the numerical approximation of a nonlinear equilibrium-dispersive (ED) model of multicomponent mixtures for simulating single-column chromatographic processes. Using Danckwerts boundary conditions (DBCs), the ED is studied for both generalized and standard bi-Langmuir adsorption isotherms. Advection-diffusion partial differential equations are used to represent fixed-bed chromatographic processes. As the diffusion term is significantly weaker than the advection term, sophisticated numerical techniques must be applied for solving such model equations. In this study, the model equations are numerically solved by using the Runge-Kutta discontinuous Galerkin (RKDG) finite element method. The technique is designed to handle sudden changes (sharp discontinuities) in solutions and to produce highly accurate results. The method is tested with several case studies considering different parameters, and its results are compared with the high-resolution finite volume scheme. One-, two-, and three-component liquid chromatography elutions on fixed beds are among the case studies being considered. The dynamic model and its accompanying numerical case studies provide the initial step toward continuous monitoring, troubleshooting, and effectively controlling the chromatographic processes.


Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction.
A decade has passed since the first topical prostaglandin analog was prescribed to reduce intraocular pressure (IOP) for the treatment of glaucoma. Now four prostaglandin analogs are available for clinical use around the world and more are in development. The three most efficacious of these drugs are latanoprost, travoprost, and bimatoprost, and their effects on IOP and aqueous humor dynamics are similar. A consistent finding is a substantial increase in uveoscleral outflow and a less consistent finding is an increase in trabecular outflow facility. Aqueous flow appears to be slightly stimulated as well. Prostaglandin receptors and their associated mRNAs have been located in the trabecular meshwork, ciliary muscle, and sclera, providing evidence that endogenous prostaglandins have a functional role in aqueous humor drainage. Earlier evidence found that topical PG analogs release endogenous prostaglandins. One well-studied mechanism for the enhancement of outflow by prostaglandins is the regulation of matrix metalloproteinases and remodeling of extracellular matrix. Other proposed mechanisms include widening of the connective tissue-filled spaces and changes in the shape of cells. All of these mechanisms alter the permeability of tissues of the outflow pathways leading to changes in outflow resistance and/or outflow rates. This review summarizes recent (since 2000) animal and clinical studies of the effects of topical prostaglandin analogs on aqueous humor dynamics and recent cellular and molecular studies designed to clarify the outflow effects.


The British Society for Rheumatology biologics register.
The British Society for Rheumatology (BSR) established a nationwide register for patients with rheumatological disorders treated with biologic agents. The register is designed as a national prospective study whose primary purpose is to assess long term toxicity from the use of these agents in routine practice. In addition, the data will be capable of addressing the benefits from their use in relation to their toxicity. One specific feature of the BSR register is the recruitment and collection of data from a parallel comparison group, comprising patients with active rheumatoid arthritis treated with conventional disease modifying agents. Both class specific and drug specific analyses of the group treated with biologicals are planned.


Astragaloside IV Blunts Epithelial-Mesenchymal Transition and G2/M Arrest to Alleviate Renal Fibrosis via Regulating ALDH2-Mediated Autophagy.
Previous studies show that astragaloside IV (ASIV) has anti-renal fibrosis effects. However, its mechanism remains elusive. In this study, we investigated the anti-fibrosis mechanisms of ASIV on chronic kidney disease (CKD) in vivo and in vitro. A CKD model was induced in rats with adenine (200 mg/kg/d, i.g.), and an in vitro renal fibrosis model was induced in human kidney-2 (HK-2) cells treated with TGF-β1. We revealed that ASIV significantly alleviated renal fibrosis by suppressing the expressions of epithelial-mesenchymal transition (EMT)-related proteins, including fibronectin, vimentin, and alpha-smooth muscle actin (α-SMA), and G2/M arrest-related proteins, including phosphorylated p53 (p-p53), p21, phosphorylated histone H3 (p-H3), and Ki67 in both of the in vivo and in vitro models. Transcriptomic analysis and subsequent validation showed that ASIV rescued ALDH2 expression and inhibited AKT/mTOR-mediated autophagy. Furthermore, in ALDH2-knockdown HK-2 cells, ASIV failed to inhibit AKT/mTOR-mediated autophagy and could not blunt EMT and G2/M arrest. In addition, we further demonstrated that rapamycin, an autophagy inducer, reversed the treatment of ASIV by promoting autophagy in TGF-β1-treated HK-2 cells. A dual-luciferase report assay indicated that ASIV enhanced the transcriptional activity of the ALDH2 promoter. In addition, a further molecular docking analysis showed the potential interaction of ALDH2 and ASIV. Collectively, our data indicate that ALDH2-mediated autophagy may be a novel target in treating renal fibrosis in CKD models, and ASIV may be an effective targeted drug for ALDH2, which illuminate a new insight into the treatment of renal fibrosis and provide new evidence of pharmacology to elucidate the anti-fibrosis mechanism of ASIV in treating renal fibrosis.


Applying multiple computerized text-analytic measures to single psychotherapy cases.
The authors applied five different computer-assisted measures for the analysis of textual data to the transcripts of two brief psychotherapies. The five measures involved different computational procedures and were derived from different theoretical backgrounds. The two cases when compared did not show uniform results in their trends over time for any one method. However, examination and comparison of the five measurements for each case yielded convergent phenomena, which could then be validated by other data available for these cases.


Lipedema: an inherited condition.
Lipedema is a condition characterized by swelling and enlargement of the lower limbs due to abnormal deposition of subcutaneous fat. Lipedema is an under-recognized condition, often misdiagnosed as lymphedema or dismissed as simple obesity. We present a series of pedigrees and propose that lipedema is a genetic condition with either X-linked dominant inheritance or more likely, autosomal dominant inheritance with sex limitation. Lipedema appears to be a condition almost exclusively affecting females, presumably estrogen-requiring as it usually manifests at puberty. Lipedema is an entity distinct from obesity, but may be wrongly diagnosed as primary obesity, due to clinical overlap. The phenotype suggests a condition distinct from obesity and associated with pain, tenderness, and easy bruising in affected areas.


Surface stress anisotropy of Ge(001).
By analyzing the equilibrium shape of vacancy islands on the Ge(001) surface we have determined the surface stress anisotropy, i.e., the difference between the compressive stress component along the substrate dimer rows and the tensile stress component perpendicular to the substrate dimer rows. In order to extract the surface stress anisotropy we have used a model recently put forward by Li et al. [Phys. Rev. Lett. 85, 1922 (2000)]. The surface stress anisotropy of the clean Ge(001) surface is found to be 80+/-30 meV/A(2). This value is comparable to the surface stress anisotropy of the closely related Si(001) surface.


The promise of the World Wide Web and other telecommunication technologies within deaf education.
The authors summarize a national survey that collected information on instructional technology resources available at schools serving deaf students in the United States. Results indicated that over 70% of these schools have access to the Internet and World Wide Web. The authors also explore innovative uses of the Internet and provide examples of specific applications for deaf students.


Coordinated control of connexin 26 and connexin 30 at the regulatory and functional level in the inner ear.
Connexin 26 (Cx26) and connexin 30 (Cx30) are encoded by two genes (GJB2 and GJB6, respectively) that are found within 50 kb in the same complex deafness locus, DFNB1. Immunocytochemistry and quantitative PCR analysis of Cx30 KO mouse cultures revealed that Cx26 is downregulated at the protein level and at the mRNA level in nonsensory cells located between outer hair cells and the stria vascularis. To explore connexin coregulation, we manipulated gene expression using the bovine adeno-associated virus. Overexpression of Cx30 in the Cx30 KO mouse by transduction with bovine adeno-associated virus restored Cx26 expression, permitted the formation of functional gap junction channels, and rescued propagating Ca(2+) signals. Ablation of Cx26 by transduction of Cx26(loxP/loxP) cultures with a Cre recombinase vector caused concurrent downregulation of Cx30 and impaired intercellular communication. The coordinated regulation of Cx26 and Cx30 expression appears to occur as a result of signaling through PLC and the NF-kappaB pathway, because activation of IP(3)-mediated Ca(2+) responses by stimulation of P2Y receptors for 20 min with 20 nM ATP increased the levels of Cx26 transcripts in Cx30 KO cultures. This effect was inhibited by expressing a stable form of the IkappaB repressor protein that prevents activation/translocation of NF-kappaB. Thus, our data reveal a Ca(2+)-dependent control in the expression of inner ear connexins implicated in hereditary deafness as well as insight into the hitherto unexplained observation that some deafness-associated DFNB1 alleles are characterized by hereditable reduction of both GJB2 and GJB6 expression.


Effect of carboplatin on the functional integrity of the human sperm membrane in vitro.
Although it is well known that carboplatin is a drug that binds directly to DNA, causing DNA-DNA and DNA-protein cross-links, which is the presumptive method for killing cells, the whole mechanism of action of carboplatin on spermatozoa is unclear. There are no published data in peer-reviewed journals focused on the interaction between carboplatin and cell membranes. Therefore, the purpose of this study was to investigate the minimal concentration of carboplatin that would affect the functional integrity of the human sperm membrane in an in vitro model. Human-ejaculated spermatozoa were obtained from 20 healthy normozoospermic donors. Solutions (SOL) of 0.5 mL of the semen samples and 0.5 mL NaCl (0.9%) containing increasing concentrations (7.5, 15, 30, and 60 ng) of carboplatin per 1 mL of SOL were prepared. Then, the hypoosmotic-swelling (HOS) test and the eosin test were performed on these samples and compared with the control (no carboplatin) group. Significant damage to the plasma membrane in the head region (eosin test positive) and in the tail region of spermatozoa, as assessed by the HOS test, was observed in concentrations of 30 and 60 ng carboplatin per 1 mL of SOL in comparison to the values evaluated in the control group. The results demonstrate that a minimal carboplatin concentration of 30 ng/mL causes significant damage to membrane integrity of spermatozoa in healthy volunteers.


Bioactive-glass ceramic with two crystalline phases (BioS-2P) for bone tissue engineering.
We aimed to evaluate the in vitro osteogenic and osteoinductive potentials of BioS-2P and its ability to promote in vivo bone repair. To investigate osteogenic potential, UMR-106 osteoblastic cells were cultured on BioS-2P and Bioglass 45S5 discs in osteogenic medium. The osteoinductive potential was evaluated using mesenchymal stem cells (MSCs) cultured on BioS-2P, Bioglass 45S5 and polystyrene in non-osteogenic medium. Rat bone calvarial defects were implanted with BioS-2P scaffolds alone or seeded with MSCs. UMR-106 proliferation was similar for both materials, while alkaline phosphatase (ALP) activity and mineralization were higher for BioS-2P. Bone sialoprotein (BSP), RUNX2 and osteopontin (OPN) gene expression and BSP, OPN, ALP and RUNX2 protein expression were higher on BioS-2P. For MSCs, ALP activity was higher on Bioglass 45S5 than on BioS-2P and was lower on polystyrene. All genes were highly expressed on bioactive glasses compared to polystyrene. BioS-2P scaffolds promoted in vivo bone formation without differences in the morphometric parameters at 4, 8 and 12 weeks. After 8 weeks, the combination of BioS-2P with MSCs did not increase the quantity of new bone compared to the BioS-2P alone. To stimulate osteoblast activity, drive MSC differentiation and promote bone formation, BioS-2P is a good choice as a scaffold for bone tissue engineering.


Analysis on scattering characteristics of Love-type wave due to surface irregularity in a piezoelectric structure.
Surface irregularity in piezoelectric sensors causes scattering of Love-type waves, which may lead to significant signal insertion loss. Also, as the reflected wave field in the piezoelectric sensor is increased due to surface irregularity, the input interdigital transducer (IDT) can be damaged. The present analysis confers the characteristics of Love-type waves scattered through surface irregularity in piezoelectric composite structures with different shaped surface irregularity, e.g., rectangular shaped, parabolic shaped, and triangular notch shaped. The expressions of phase and group velocities of scattered Love-type waves are derived for electrically open and short conditions. Also, expressions of mechanical displacement and electrical potential function due to incident and scattered Love-type waves are deduced for both electrical conditions. It is reported from the analysis that the increase in vertical irregularity parameter causes stronger reflected wave fields. Also, with the increase in piezoelectricity of the superficial layer, signal insertion loss and strength of reflected wave field diminish.


Protecting adults at risk of pneumococcal infection and influenza from exposure to SARS-CoV-2.
There is a paucity of evidence linking pneumococcal infection and influenza with SARS-CoV-2 and COVID-19. There is circumstantial evidence of the possibility of an association between S. pneumoniae and SARS-CoV-2 such as the increased binding of S. pneumoniae to coronavirus-infected human airway epithelium, the frequent use of broad-spectrum antibiotics in the management of COVID-19 which could mask secondary bacterial infection, and the observation that pneumococcal vaccination is associated with decreased SARS-CoV-2 nasopharyngeal swab positivity. We performed a targeted literature review for the year 2020, using search terms S. pneumoniae, influenza, SARS-CoV-2, and found 25 relevant articles of a total of 291. Pneumococcal and influenza vaccinations have the potential to contribute toward efforts aimed at reducing the health burden of SARS-CoV-2, especially by reducing preventable admissions to hospital for pneumonia and the consequent risk of nosocomial SARS-CoV-2 transmission.


Principles and problems underlying testing the effectiveness of blast protective footwear.
Anti-personnel landmines are a continuing threat to soldiers and civilians working overseas in post conflict situations. Several groups of governmental and commercial scientists are currently designing and/or testing footwear to protect the lower leg from the effects of close proximity blast. The general principles surrounding testing of protective footwear are examined together with an assessment of the known progress to date and the strengths and weaknesses of the designs produced.


Developmental changes of fetal rat lung Na-K-ATPase after maternal treatment with dexamethasone.
Late in gestation, the prenatal fetal alveolar epithelium switches from fluid secretion to resorption of salt and water via apical sodium channels and basal Na-K-ATPase. The amounts of lung sodium pump activity protein and mRNA increase in the lung just before birth. Because maternal glucocorticoids (GC) may promote maturation of the alveolar epithelium and augment fetal surfactant apoprotein levels, we hypothesized that GC increase the fetal lung Na-K-ATPase alpha- and beta-subunit gene expression in development. Timed-pregnant Sprague-Dawley rats were injected daily with intraperitoneal dexamethasone (1 mg/kg) or saline for 1, 3, or 5 days before death at fetal day (FD) 17 or 19. Maternal GC treatment altered the fetal lung wet to dry weight, decreasing it at FD17 and increasing it at FD19. Northern analysis of total lung RNA for the alpha1- and beta1-pump subunits demonstrated differential regulation of the mRNA in response to GC. At FD17, beta1-mRNA increased after 1 (FD16) or 3 days (FD14-FD16) of GC treatment, whereas alpha1-mRNA was not altered. There were accompanying increases in beta1-, but not alpha1-, protein. At FD19, GC treatment for 5 days (FD14-FD18) increased beta1- and decreased alpha1-mRNA levels, but treatment for 1 (FD18) or 3 days (FD16-FD18) had no effect. In all groups, the alpha1-Na-K-ATPase protein was predominantly on the basolateral surface of airspace epithelium by immunofluorescence. In summary, maternal dexamethasone differentially affected the fetal lung mRNA levels of the two sodium pump subunits in a complex manner, with increased beta1-mRNA levels dependent on duration of treatment and fetal age.


Endoscopic Versus Open Surgical Intervention for Congenital Laryngeal Webs: A Systematic Review and Meta-Analysis.
To examine and compare the outcomes of various surgical interventions for congenital laryngeal webs in terms of avoidance of tracheostomy, rate of decannulation, web recurrence, revision surgery, and mortality in children. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted on December 10, 2021, using a comprehensive search in PubMed, Web of Science, Cochrane library, and Embase with no date restriction. Articles on surgical intervention for congenital laryngeal webs in pediatric (<18 years) patients were included in the analysis. Articles including acquired laryngeal webs, no surgical intervention, or exclusively adult population were excluded. 9027 articles were reviewed, 24 articles met the inclusion criteria and 126 patients were included. In patients with Grades I and II webs, there was no significant difference in rates of tracheostomy or decannulation, between endoscopic (100%) versus open approach (100%). For Grades III and IV webs, 96% of patients who received open surgery were decannulated or avoided tracheostomy compared to 84% of those managed endoscopically (p = 0.081). There were significantly lower rates of revision surgery in the open group compared to the endoscopic group (77.8% vs 30.9%, p = 0.008). This study showed no difference in rates of tracheostomy, decannulation, web recurrence, revision, or mortality between endoscopic and open approaches for the treatment of Grades I and II webs. For Grades III and IV, open surgical techniques achieved a lower revision rate. Results should be interpreted in light of associated increased morbidity with open procedures.


Systemic inflammation in glucocerebrosidase-deficient mice with minimal glucosylceramide storage.
Gaucher disease, the most common lysosomal storage disease, is caused by a deficiency of glucocerebrosidase resulting in the impairment of glucosylceramide degradation. The hallmark of the disease is the presence of the Gaucher cell, a macrophage containing much of the stored glucosylceramide found in tissues, which is believed to cause many of the clinical manifestations of the disease. We have developed adult mice carrying the Gaucher disease L444P point mutation in the glucocerebrosidase (Gba) gene and exhibiting a partial enzyme deficiency. The mutant mice demonstrate multisystem inflammation, including evidence of B cell hyperproliferation, an aspect of the disease found in some patients. However, the mutant mice do not accumulate large amounts of glucosylceramide or exhibit classic Gaucher cells in tissues.


Immunological studies of the human placenta: functional and morphological analysis of pregnancy-associated plasma protein A (PAPP-A).
A blood protein, pregnancy-associated plasma protein A (PAPP-A), has been isolated from the plasma of pregnant women. An antiserum to this protein has been prepared and used to localize the protein within the placenta by immunofluorescence. It was found to be inconstantly present in the syncytiotrophoblast and intervillous fibrin. Neither antiserum nor antigen exerts a cytotoxic effect on peripheral blood lymphocytes, and neither affected blastogenic responses of lymphocytes to mitogens or in mixed lymphocyte culture reactions.