Effect of different forms of transcutaneous electrical nerve stimulation on experimental pain.
The purpose of this study was to compare the effects of five different types of transcutaneous electrical nerve stimulation on experimentally induced pain threshold and tolerance in healthy subjects. Fourteen subjects received the following treatments on different days: low frequency TENS, burst frequency TENS, hyperstimulation TENS, high frequency TENS with a low voltage galvanic stimulator, and high frequency TENS with a high voltage galvanic stimulator to the left upper extremity. Pain threshold and tolerance were tested with electric current on a fingertip of the left upper extremity before each treatment, immediately after each treatment, and 20 minutes after the end of each treatment. Data were analyzed using separate two-by-five analyses of variance with repeated measures for pain threshold and tolerance. No significant effects of treatment or time for pain threshold or tolerance were found. A significant interaction between treatment and time for pain threshold was found. Further study is needed to compare the effects of these treatments in patients with clinical pain.


Sutureless Medtronic 3f Enable aortic valve replacement in a heavily calcified aortic root.
The case is reported of a surgical aortic valvular stenosis with a severely calcified ascending aortic root in a 76-year-old woman. The morphology and size of the aortic annulus were unsuitable for transcatheter aortic valve implantation (TAVI); thus, surgery was scheduled. Aortic calcifications allowed a transverse aortotomy 4 cm superior to the sinotubular junction, with a remote endoaortic view of the valve. A Medtronic 3f Enable sutureless bioprosthesis was then implanted after aortic annular decalcification. Sutureless bioprostheses are new tools that promise to reduce technical difficulties and cross-clamp times in minimally invasive aortic valve replacement surgery. In addition, sutureless techniques may have other possible advantages in special circumstances requiring full sternotomy access, such as in the present case.


Alternarialone A, a new curvularin-type metabolite from the mangrove-derived fungus Alternaria longipes.
Alternarialone A (1), one new curvularin derivative, and two known compounds (2 and 3) were isolated from the crude extract of the mangrove-derived fungus Alternaria longipes. Their structures were elucidated by comprehensive spectroscopic analyses, including MS and NMR spectroscopic data. The absolute configuration of 1 was assigned by 13C NMR calculations and a comparison of electronic circular dichroism (ECD) spectra. All compounds were evaluated for their antibacterial activities against Helicobacter pylori. Compounds 2 and 3 showed antibacterial activities against H. pylori G27 with MIC values of 8 and 16 µg/ml, respectively, while compound 3 also displayed antibacterial activity against H. pylori BHKS159 with the MIC value of 16 µg/ml.


Changes in care and outcome of very preterm babies in the Parisian region between 1998 and 2003.
To assess evolution in the care and health of very preterm babies between 1998 and 2003 after implementation of a regionalisation policy in France. Comparison of two population-based cohorts. The Parisian region. All live births at 24-31 weeks of gestation in 1997 (EPIPAGE study, n=488) and in 2003 (MOSAIC study, n=580). Interventions Implementation of regionalised perinatal networks. Main outcome measures In-hospital mortality and morbidity, including intraventricular haemorrhage (IVH) grade III and IV, cystic periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD). Over this period, babies born in level III units rose from 67% to 77% and use of antenatal corticosteroids, indicated deliveries and surfactant increased. In-hospital mortality and IVH grades III/IV declined, ORs of 0.66 (95% CI 0.46 to 0.95) and 0.27 (95% CI 0.15 to 0.47), respectively, while PVL and BPD stayed constant. The rate of very preterm babies discharged alive per 1000 total births increased by 18%, but declined for babies with severe brain lesions. The authors found improvements in mortality and morbidity for very preterm babies and changes in their care over a 6-year period following reinforcement of regionalisation policies.


Enhancing Computerized Provider Order Entry (CPOE) for neonatal intensive care.
The authors describe design, implementation, and use of a new order entry system module for neonatal intensive care. WizOrder is a Computerized Provider Order Entry (CPOE) system developed at Vanderbilt University Medical Center. Since WizOrder's introduction in 1995, it has been continually refined and enhanced; especially when new hospital units and specialties are implemented. Recently, in March 2003, WizOrder was updated and implemented in the Neonatal Intensive Care Unit (NICU).


UL26 Attenuates IKKβ-Mediated Induction of Interferon-Stimulated Gene (ISG) Expression and Enhanced Protein ISGylation during Human Cytomegalovirus Infection.
Viruses must negotiate cellular antiviral responses in order to replicate. Human cytomegalovirus (HCMV) is a prevalent betaherpesvirus that encodes a number of viral gene products that modulate cellular antiviral signaling. The HCMV UL26 gene has previously been found to attenuate cytokine-activated NF-κB signaling, yet the role that UL26 plays in modulating the host cell's global transcriptional response to infection is not clear. Here, we find that infection with a UL26 deletion virus (ΔUL26) induces a proinflammatory transcriptional environment that includes substantial increases in the expression of cytokine signaling genes relative to wild-type HCMV. These increases include NF-κB-regulated genes as well as interferon-stimulated genes (ISGs), such as ISG15 and bone marrow stromal cell antigen 2 (BST2). The ΔUL26 mutant-mediated induction of ISG15 expression was found to drive increases in global protein ISGylation during ΔUL26 mutant infection. However, short hairpin RNA (shRNA) and CRISPR-mediated targeting of ISG15 indicated that its induction does not restrict HCMV infection. In contrast, shRNA-mediated targeting of BST2 demonstrated that BST2 restricts HCMV cell-to-cell spread. In addition, the increased expression of both of these ISGs and the global enhancement in protein ISGylation were found to be dependent on the activity of the canonical inhibitor of NF-κB kinase beta (IKKβ). Both CRISPR-based and pharmacologically mediated inhibition of IKKβ blocked the induction of ISG15 and BST2. These results suggest significant cross-talk between the NF-κB and interferon signaling pathways and highlight the importance of IKK signaling and the HCMV UL26 protein in shaping the antiviral response to HCMV.IMPORTANCE Modulation of cellular antiviral signaling is a key determinant of viral pathogenesis. Human cytomegalovirus (HCMV) is a significant source of morbidity in neonates and the immunosuppressed that contains many genes that modulate antiviral signaling, yet how these genes contribute to shaping the host cell's transcriptional response to infection is largely unclear. Our results indicate that the HCMV UL26 protein is critical in preventing the establishment of a broad cellular proinflammatory transcriptional environment. Further, we find that the host gene IKKβ is an essential determinant governing the host cell's antiviral transcriptional response. Given their importance to viral pathogenesis, continuing to elucidate the functional interactions between viruses and the cellular innate immune response could enable the development of therapeutic strategies to limit viral infection.


Primitive neuroectodermal tumor: rare, highly aggressive differential diagnosis in urologic malignancies.
Peripheral primitive neuroectodermal tumor (PNET) is a highly aggressive neoplasm belonging to the Ewing family of tumors. It is characterized by the expression of MIC2 and neural markers (eg, neuron-specific enolase, synaptophysin, S-100, vimentin, Leu-7), and the presence of the EWS-FLI1 translocation. We performed a MEDLINE search for PNET in urologic malignancies. Additionally, we report on 2 cases of renal and 1 case of bladder PNET. The data obtained by reviewing patients with renal PNET were analyzed using Kaplan-Meier analysis. Renal PNET is diagnosed in young adults (median age 24 years). In contrast, the incidence of bladder PNET seems to be dependent on a defective immune mechanism. Patients often present with pain (84%), palpable tumor (60%), and hematuria (38%). The radiologic findings are uncharacteristic; therefore, the diagnosis should be based on the histologic and immunohistochemistry findings. Renal and bladder PNET are both often diagnosed at an advanced stage and, therefore, the prognosis is poor, despite aggressive multimodal treatment (surgery, polychemotherapy, radiotherapy). We identified palpable tumor masses (log-rank test, P = 0.0027) and synaptophysin expression (log-rank test, P = 0.0422) as prognostic unfavorable markers for renal PNET. Renal PNET should be considered in young patients who present with the classic triad of renal cancer, hematuria, and pain and palpable tumor. Once PNET is diagnosed, multimodal treatment (radical surgery, multidrug chemotherapy, radiotherapy) must be initiated. Despite this, the prognosis is poor if distant metastases are present. Furthermore, palpable tumor masses and synaptophysin expression are associated with a shorter cancer-specific survival.


Deposition of Colloidal Zinc Sulfide on Glass Substrate.
The effect of colloidal forces involved in the deposition of spherical zinc sulfide colloidal particles on a packed bed of glass has been studied. Experiments were performed by pumping a suspension of monodisperse colloidal ZnS particles through a cylindrical plug of ground glass, and by continuous determination of the outgoing suspension concentration. The flux density of adhered particles, jexp (number of particles deposited per unit time and unit surface area of glass collector), decreased with both pH and ionic strength of the aqueous electrolyte solution. Qualitative explanation of the experiments has been given in terms of the total energy of interaction between the dispersed particles and the substrate, and between the particles themselves, computed from the extended DLVO theory, including acid-base interactions. The contributions to the total free energy of interaction were determined from the zeta potential and surface free energy of ZnS and glass, measured under different experimental conditions. It was found that at pH 4 (below the isoelectric point of ZnS) the efficiency of the deposition of ZnS on glass was maximum. At higher pH values the amount of ZnS deposited on glass clearly decreased. Increasing NaCl concentration at fixed pH (>/=6) decreased the efficiency of the deposition. Adhesion experiments were also performed at pH 4 in the presence of increasing concentrations of CaCl2 or La(NO3)3 in the dispersion medium. In these cases, the rate of adhesion was qualitatively well correlated with the computed ZnS-glass interactions. Copyright 1999 Academic Press.


[Ureteral stents].
Due to the increasing clinical importance of ureteral stents, the advantages and disadvantages of the different materials used are described and discussed. The spectrum of indications includes palliative, curative and auxiliary uses of ureteral stents. In spite of the low complication rate, the advisability of clinical application of stents should always be critically considered before the final decision is made. The possibility of treating the basic disease should be considered in each patient, to lessen the likelihood of "permanent stent patients".


Alternative Routes for the Synthesis of 5-Aminolevulinic Acid in Maize Leaves : I. Formation from 2-Ketoglutarate via 4,5-Dioxovaleric Acid.
Cell-free extracts from greening maize (Zea mays L.) leaves catalyze the conversion of [(14)C]2-ketoglutarate (KG) to [(14)C]5-aminolevulinic acid (ALA) in a reaction which requires NADH and an amino donor and shows maximal activity around pH 6.5. The enzymic system is located in the cytosol. This cell fraction contains a low level of ;KG dehydrogenase' activity and a transaminase which catalyzes the conversion of 4,5-dioxovaleric acid (DOVA) to ALA. The transaminase can use glutamate, aspartate, or alanine as amino donor. It is effectively inhibited by aminooxyacetate and ethylenediamine tetraacetate and shows maximal activity at pH 6.7. The activity of DOVA transaminase is only slightly affected by preillumination of leaves and can also be detected in green leaves and in roots.DOVA was isolated from leaves and roots and determined as its benzoquinoxaline derivative. Significant amounts were found only in tissues in which ALA had accumulated or after it was exogenously supplied. DOVA was labeled in vivo by both [(14)C]ALA and [(14)C]KG. Small amounts were also formed from ALA in a cell-free system.It is suggested that DOVA may be an intermediate in the diversion of ALA to respiratory metabolism and that it is not involved in the biosynthesis of this porphyrin precursor.


[Involvement of endogenous nitric oxide in the regulation of distal colonic motility in anaesthetized rat].
The contribution of the endogenous nitric oxide (NO) to the distal colonic motility was investigated by inhibiting NO production using NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). The experiment was carried out in the anaesthetized rat, which was vagotomized and pretreated with guanethidine, phentolamine and propranolol. The colonic motility was evaluated by changes in the increase in intraluminal pressure of the distal colon. L-NMMA infusion (100mg/kg iv) in the presence of atropine (1 mg/kg iv) resulted in a significant increase in arterial blood pressure and intraluminal pressure. The following L-arginine infusion (100mg/kg iv) restored blood pressure and intraluminal pressure to the control level. In contrast, L-NMMA infusion in the absence of atropine resulted in no change in intraluminal pressure with a significant increase in arterial blood pressure. These results indicate that there are NO-dependent and nondependent mechanisms to regulate the distal colonic motility.


Mucinous borderline-like tumor of the gastrointestinal type arising from mature cystic teratoma of the ovary and its immunohistochemical cytokeratin and mucin phenotype.
Malignant transformation is rarely seen in the disease course of mature cystic teratoma (MCT) of the ovary. Adenocarcinoma arising from MCT is especially rare. We herein present the case of a premenopausal woman with a mucinous borderline-like tumor arising from a MCT. Based on the histological transition between the borderline-like tumor and gastrointestinal elements of the MCT, we consider that the tumor derived from teratomatous gastrointestinal epithelium. Immunohistochemistry showed that the proliferating mucinous cells were diffusely positive for cytokeratin 20 and partially positive for cytokeratin 7. MUC5AC was partially positive, whereas MUC2 and MUC6 were positive in a small number of tumor cells. The immunophenotype of cytokeratins and mucins in the present case was compatible with malignant transformation of the teratomatous gastrointestinal epithelium.


Does investment into "expensive" tissue compromise anti-parasitic defence? Testes size, brain size and parasite diversity in rodent hosts.
Species richness of parasite assemblages varies among host species. Earlier studies that searched for host-related determinants of parasite diversity mainly considered host traits that affect the probability of host encounter with parasites, whereas host traits related to defensibility against parasites have rarely been investigated. From the latter perspective, evolutionary investment in "expensive" tissue or organs (like testes or brain) may trade off against energetically costly anti-parasitic defences. If so, richer parasite assemblages are expected in hosts with larger testes and brains. We studied the relationships between testes and brain size and diversity of parasites (fleas, gamasid mites and helminths) in 55 rodent species using a comparative approach and application of two methods, namely the method of independent contrasts and generalized least-squares (GLS) analysis. Both phylogenetically correct methods produced similar results for flea and helminth species richness. Testes size positively correlated with flea and helminth species richness but not gamasid mite species richness. No correlation between brain size and species richness of any parasite group was found by the method of independent contrasts. However, GLS analysis indicated negative correlation between brain size and mite species richness. Our results cast doubt on the validity of the expensive tissue hypothesis, but suggest instead that larger testes are associated with higher parasite diversity via their effect on mobility and/or testosterone-mediated immunosuppression.


Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice.
Mitogen-activated protein (MAP) kinase cascades play a central role in mediating extracellular stimuli-induced intracellular signaling during cell activation. The fourth and least studied mammalian MAP kinase pathway, big MAP kinase 1 (BMK1), also known as extracellular signal regulated kinase 5 (ERK5), is activated in response to growth factors and stress. Activation of this signaling pathway has been implicated not only in physiological functions such as cell survival, proliferation and differentiation but also in pathological processes such as carcinogenesis, cardiac hypertrophy and atherosclerosis. In recent years a series of gene-targeted mice lacking components within the BMK1 cascade have been generated, which have enabled us to investigate the role of the BMK1 pathway within different tissues. Analyses of these knockout mice have led to major discoveries in the role of BMK1 signaling in angiogenesis and in cardiac development. Moreover, studies using conditional BMK1 knockout mice, which circumvent the early embryonic lethality of BMK1 knockouts, have unveiled the importance of BMK1 in endothelial survival and maintenance of vascular integrity during adulthood. Here we summarize current understanding of the function of BMK1, as well as include new data generated from a series of tissue-specific BMK1 knockout mice in an attempt to dissect the role of the BMK1 pathway in various cell types in animals.


Academic appointment and the process of promotion and tenure.
A critical component of a successful academic career is the understanding of institutional criteria and guidelines for academic appointment, promotion, and tenure. It is important to point out that these criteria and guidelines may vary from institution to institution; however, they are uniform for all clinical faculty within a single institution and do not differ from department to department. The purpose of this article is to provide the aspiring academic colon and rectal surgeon with a basic understanding of academic faculty appointments, promotion, and tenure.


Judgments of sexual orientation and masculinity-femininity based on thin slices of behavior: a cross-cultural comparison.
Studies of North Americans suggest that laypeople can judge the sexual orientation of others with greater than chance accuracy based on brief observations of their behavior (i.e., "gaydar" exists). One factor that appears to contribute to these judgments is targets' degree of masculinity-femininity. However, behaviors related to sexual orientation and to masculinity-femininity might vary across cultures. Thus, cross-cultural work is needed to test whether judgments of sexual orientation are more accurate when targets and raters are from the same culture. American and Czech male targets, 38 homosexual and 41 heterosexual, were videotaped and brief segments of the videotapes were presented to American and Czech raters. Overall, raters' judgments of targets' sexual orientation were related to targets' self-reported sexual orientation. However, the relationship was stronger when targets were judged by raters from their own country. In general, results suggest that there are both cross-cultural similarities and differences in gaydar and in cues related to sexual orientation.


Reaction Mechanism of the Symmetry-Forbidden [2+2] Addition of Ethylene and Acetylene to Amido-Substituted Digermynes and Distannynes Ph2N-EE-NPh2, (E = Ge, Sn): A Theoretical Study.
Quantum chemical calculations of reaction mechanisms for the formal [2+2] addition of ethylene and acetylene to the amido-substituted digermyne and distannyne Ph2N-EE-NPh2 (E = Ge, Sn) have been carried out by using density functional theory at the BP86/def2-TZVPP level. The nature and bonding situations were studied with the NBO method and with the charge and energy decomposition analysis EDA-NOCV. The addition of ethylene to Ph2N-EE-NPh2 takes place through an initial [2+1] addition to one metal atom and consecutive rearrangement to four-membered cyclic species, which feature a weak E-E bond. Rotation about the C-C bond with concomitant rupture of the E-E bond leads to the 1,2-disubstituted ethanes, which have terminal E(NPh2) groups. The overall reaction Ph2N-EE-NPh2+C2H4→(Ph2N)E-C2H4-E(NPh2) has very low activation barriers and is slightly exergonic for E = Ge but slightly endergonic for E = Sn. The analysis of the electronic structure shows that there is charge donation of nearly one electron to the ethylene moiety already in the first part of the reaction. The energy partitioning analysis suggests that the HOMO(Ph2N-EE-NPh2)→LUMO(C2H4) interaction has a similar strength as the HOMO(C2H4)→LUMO(Ph2N-EE-NPh2) interaction. The [2+2] addition of acetylene to Ph2N-EE-NPh2 also takes place through an initial [2+1] approach, which eventually leads to 1,2-disubstituted olefins (Ph2N)E-C2H2-E(NPh2). The formation of the energetically lowest lying conformations of cis-(Ph2N)E-C2H2-E(NPh2), which occurs with very low activation barriers, is clearly exergonic for the germanium and the tin compound. The trans-coordinated isomers of (Ph2N)E-C2H2-E(NPh2) are slightly lower in energy than the cis form but they are separated by a substantial energy barrier for the rotation about the C-C bond. The energy decomposition analysis indicates that the initial reaction takes place under formation of electron-sharing bonds between triplet fragments rather than HOMO-LUMO interactions.


Urbanization favors the proliferation of Aedes aegypti and Culex quinquefasciatus in urban areas of Miami-Dade County, Florida.
Urbanization processes are increasing globally. Anthropogenic alterations in the environment have profound effects on biodiversity. Decreased biodiversity due to biotic homogenization processes as a consequence of urbanization often result in increased levels of mosquito vector species and vector-borne pathogen transmission. Understanding how anthropogenic alterations in the environment will affect the abundance, richness, and composition of vector mosquito species is crucial for the implementation of effective and targeted mosquito control strategies. We hypothesized that anthropogenic alterations in the environment are responsible for increasing the abundance of mosquito species that are adapted to urban environments such as Aedes aegypti and Culex quinquefasciatus. Therefore, our objective was to survey mosquito relative abundance, richness, and community composition in Miami-Dade County, Florida, in areas with different levels of urbanization. We selected 24 areas, 16 remote areas comprised of natural and rural areas, and 8 urban areas comprised of residential and touristic areas in Miami-Dade County, Florida. Mosquitoes were collected weekly in each area for 24 h for 5 consecutive weeks from August to October 2020 using BG-Sentinel traps baited with dry ice. A total of 36,645 mosquitoes were collected, from which 34,048 were collected in the remote areas and 2,597 in the urban areas. Our results show a clear and well-defined pattern of abundance, richness, and community composition according to anthropogenic modifications in land use and land cover. The more urbanized a given area the fewer species were found and those were primary vectors of arboviruses, Ae. aegypti and Cx. quinquefasciatus.


Evaluation of heterogeneity in the association between congenital heart defects and variants of folate metabolism genes: conotruncal and left-sided cardiac defects.
Genetic variation in the folate metabolic pathway may influence the risk of congenital heart defects. This study was undertaken to assess the associations between the inherited and maternal genotypes for variants in folate-related genes and the risk of a composite heart phenotype that included two component phenotypes: conotruncal heart defects (CTDs) and left-sided cardiac lesions (LSLs). Nine folate-related gene variants were evaluated using data from 692 case-parent triads (CTD, n = 419; LSL, n = 273). Log-linear analyses were used to test for heterogeneity of the genotype-phenotype association across the two component phenotypes (i.e., CTD and LSLs) and, when there was no evidence of heterogeneity, to assess the associations of the maternal and inherited genotypes with the composite phenotype. There was little evidence of heterogeneity of the genotype-phenotype association across the two component phenotypes or of an association between the genotypes and the composite phenotype. There was evidence of heterogeneity in the association of the maternal MTR A2756G genotype (p = 0.01) with CTDs and LSLs. However, further analyses suggested that the observed associations with the maternal MTR A2756G genotype might be confounded by parental imprinting effects. Our analyses of these data provide little evidence that the folate-related gene variants evaluated in this study influence the risk of this composite congenital heart defect phenotype. However, larger and more comprehensive studies that evaluate parent-of-origin effects, as well as additional folate-related genes, are required to more fully explore the relation between folate and congenital heart defects.


[Significance of the laboratory diagnosis of hypercoagulability].
Alterations characteristic of the hypercoagulation syndrome such as changes in fibrinogen content, in FDP concentration and platelet counts as well as the presence of fibrinogen complexes were demonstrated by laboratory findings in 175 patients with severe diseases and disturbances of haemostasis. Twenty per cent of the patients showed no clinical signs of disturbances of haemostasis, in 32.5 per cent pronounced venous thrombosis occurred, bleeding complications arised in 28 per cent and microthrombosis developed in 20 per cent. The different findings in the individual groups are assumed to be due not only to haemostatic factors but also to other ones.


Erythema induratum of Bazin and renal tuberculosis: report of an association.
Erythema induratum of Bazin is a disease that usually affects women, in whom erythematous subcutaneous nodules and plaques appear on the posterior part of the lower extremities, some of which ulcerate. In many countries, tuberculosis is still the main etiologic factor. We report a case of a 40-year-old woman who presented a course of protracted and recurrent episodes over five years of cutaneous lesions on her legs. These tend to involute, but new crops appear at irregular intervals. It was painful, erythematous-violaceous nodules, some of which drained a reddish secretion. The histopathologic features of the lesions demonstrated inflammatory infiltration, with predominance of neutrophils in dermis and hypodermis, necrotizing vasculitis in the arterioles and septal fibrosis. There was no granuloma. The Ziehl-Neelsen stain did not revealed acid-fast bacilli, and the culture of biopsy specimen was negative. The tuberculin skin test was strongly positive (17 mm). The chest X-ray was normal. Few months later she presented adynamia and urinary complaints, such as polacyuria and dysuria. It has been done an urynalysis, which demonstrated acid pH urine, sterile pyuria and microscopic hematuria. It was then raised the diagnostic hypothesis of renal tuberculosis. The urine culture for M. tuberculosis was positive in two out of ten samples. The treatment was instituted with rifampin, isoniazid and pyrazinamide, with complete regression. This case illustrates a clear association between erythema induratum and renal tuberculosis, demonstrated by the remission of the cutaneous lesions after the treatment of the renal tuberculosis.


Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation.
The one-pot [3 + 2] cycloaddition of an azomethine ylide with a maleimide followed by another [3 + 2] cycloaddition of an azide with the second maleimide gives a 1,5-diamino intermediate which is used for a sequential aminomethylation reaction with formaldehyde through [5 + 1] annulation to afford a novel polycyclic scaffold bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide in stereoselective fashion.


Seasonality of symptoms in anorexia and bulimia nervosa.
Recent research has suggested that a large proportion of patients with bulimia nervosa have seasonal (winter) worsening of mood symptoms similar to seasonal affective disorder (SAD). The objectives of this study were to determine the specificity of this finding in anorexia and bulimia nervosa, and to further delineate the seasonal mood and eating patterns in bulimia nervosa. A modified Seasonal Pattern Assessment Questionnaire (SPAQ) was administered to consecutive female patients assessed at an Eating Disorders Clinic with DSM-III-R diagnoses of bulimia nervosa (BN, N = 60) and anorexia nervosa (AN, N = 31), and to female nonclinical comparison subjects (NC, N = 50). The BN group had higher global seasonality scores and more presumptive diagnoses of SAD than the other two groups; the AN patients, whether they had the restricting or binge eating/purging subtype, did not differ from the NC subjects. Thirty-two percent of the identified seasonal BN patients did not have parallel worsening of mood and eating symptoms in the same season. These results suggest that seasonality of symptoms is specific to BN and that there may be separate mechanisms for the seasonality of mood and eating symptoms in some BN patients.


[Influence of spiced feed additives on taste of hen's eggs].
The effect of the spices garlic (Allium sativum), extract from garlic, sage (Salvia officinalis), caraway (Carum carvi), peppermint (Mentha piperita), fennel (Foeniculum vulgare), thyme (Thymus vulgaris), paprika (Capsicum annuum), marjoram (Majorana hortensis), cardamom (Elettaria cardamomum) and sausage-mix fed to white hybrides on the quality of eggs (n = 705) was tested by 10 qualified persons. Changes in smell or taste were partly significant; a direct improvement is hard to induce. A well seasoned taste was obtained by feeding of garlic, fennel, peppermint and marjoram. They produce an aromatic flavor. A practical application is possible but limited by higher production prices. Further, it is uncertain if there is a need for "taste-manipulated" eggs.


Bacterial adherence: the attachment of group A streptococci to mucosal surfaces.
It is now recognized that bacteria bind to and colonize mucosal surfaces in a highly selective manner. After the organisms penetrate the nonspecific mechanical and cleansing forces, ligands (or adhesins) on the surface of the bacteria interact in a lock-and-key (or induced-fit) fashion with complementary receptors on mucosal surfaces of the host. The adhesins are usually composed of proteins in the form of fimbriae or fibrillae and the receptors of glycolipids or glycoproteins. In group A streptococci the adhesin, lipoteichoic acid (LTA), is anchored to one or more proteins on the surface of the bacterial cells and interacts through its lipid moiety with fibronectin molecules deposited on and bound to the epithelial cells. In an attempt to locate the region of fibronectin recognized by LTA and group A streptococci, fibronectin was cleaved with thermolysin and the fragment mixture adsorbed with Staphylococcus aureus or Streptococcus pyogenes. Staphylococci adsorbed several high-molecular-weight fragments as well as a 28-kilodalton and a 23-kilodalton fragment, whereas S. pyogenes cells adsorbed only the 28-kilodalton fragment completely. The adsorption of the fragments by S. pyogenes was blocked by LTA. Antibodies raised against a synthetic peptide copying the NH2 terminus of fibronectin reacted in a western blot with the 28-kilodalton fragment; this result indicated that S. pyogenes and its LTA react with the NH2-terminal region of fibronectin at a site distinct from that at which S. aureus reacts. Our findings are consistent with the idea that LTA mediates the attachment of group A streptococci to fatty acid binding sites of fibronectin deposited on mucosal epithelial cells.


[Culture and application of thymic organoids: a review].
The thymus is a pivotal immune organ of the human body, and it is the place where T cells differentiate and mature. The damage of thymus would easily induce autoimmune diseases and even malignant tumors. For years, researchers have been exploring the process of T cell development and revealing the mechanism of thymic injury and regeneration generally through the monolayer culture system of T cells in vitro. However, the classic monolayer culture system could neither reproduce the unique three-dimensional epithelial reticular structure of the thymus, nor provide the cytokines and growth factors required for the directed differentiation of hematopoietic stem cells into T cells. Thymic organoid technology utilizes cells with stem cell potential to simulate the anatomical structure of the thymus and the signaling pathway mediated by thymic epithelial cells in vitro through three-dimensional culture, which is particularly close to the microenvironment of the thymus in vivo. Thymic organoids show great potential in the study of T cell differentiation and development, thymus-related diseases, reconstruction of immune function, and cell therapy. This paper summarizes the methods for culturing thymic organoids, followed by comparing the advantages and disadvantages of the scaffolds used for culturing. The applications of thymic organoids in the disease model, tumor-targeting therapy, regenerative medicine, and organ transplantation were also discussed, with possible future research directions prospected.


Confronting Threats to Meaning: A New Framework for Understanding Responses to Unsettling Events.
We all have models of the world, and when these models fit with what goes on around us we have a sense of meaning. Unfortunately, we are often faced with situations that violate, or threaten, our models, and when this happens we attempt to resolve these inconsistencies to restore a sense of meaning. It is well documented that we often try to reduce threats in indirect ways-ways that, at first glance, seem to reduce the negative feelings without actually solving the problem. This article explores the possibility that threats can be interpreted in different ways depending on the person and context, and suggests that because of this, different threat reduction approaches can be adaptive in different situations. Specifically, it presents the hypothesis that concrete construal of threats should result in compensation efforts that are relatively direct, whereas abstract construals should expand the possibilities for compensation to include indirect strategies. It describes the existing evidence, where evidence is lacking, and potentially fruitful avenues of future exploration.


Medicare Program; hospital inpatient prospective payment systems for acute care hospitals and the long-term care hospital prospective payment system changes and FY2011 rates; provider agreements and supplier approvals; and hospital conditions of participation for rehabilitation and respiratory care services; Medicaid program: accreditation for providers of inpatient psychiatric services. Final rules and interim final rule with comment period.
: We are revising the Medicare hospital inpatient prospective payment systems (IPPS) for operating and capital-related costs of acute care hospitals to implement changes arising from our continuing experience with these systems and to implement certain provisions of the Affordable Care Act and other legislation. In addition, we describe the changes to the amounts and factors used to determine the rates for Medicare acute care hospital inpatient services for operating costs and capital-related costs. We also are setting forth the update to the rate-of-increase limits for certain hospitals excluded from the IPPS that are paid on a reasonable cost basis subject to these limits. We are updating the payment policy and the annual payment rates for the Medicare prospective payment system (PPS) for inpatient hospital services provided by long-term care hospitals (LTCHs) and setting forth the changes to the payment rates, factors, and other payment rate policies under the LTCH PPS. In addition, we are finalizing the provisions of the August 27, 2009 interim final rule that implemented statutory provisions relating to payments to LTCHs and LTCH satellite facilities and increases in beds in existing LTCHs and LTCH satellite facilities under the LTCH PPS. We are making changes affecting the: Medicare conditions of participation for hospitals relating to the types of practitioners who may provide rehabilitation services and respiratory care services; and determination of the effective date of provider agreements and supplier approvals under Medicare. We are also setting forth provisions that offer psychiatric hospitals and hospitals with inpatient psychiatric programs increased flexibility in obtaining accreditation to participate in the Medicaid program. Psychiatric hospitals and hospitals with inpatient psychiatric programs will have the choice of undergoing a State survey or of obtaining accreditation from a national accrediting organization whose hospital accreditation program has been approved by CMS. We are also issuing an interim final rule with comment period to implement a provision of the Preservation of Access to Care for Medicare Beneficiaries and Pension Relief Act of 2010 relating to Medicare payments for outpatient services provided prior to a Medicare beneficiary's inpatient admission.


Spontaneous vertebrovertebral arteriovenous fistulae clinical features, angioarchitecture and management of twelve patients.
Spontaneous vertebrovertebral arteriovenous fistula (SVVAVF) is a rare condition which often presents as a bruit. We reviewed the clinical and imaging records of 12 patients with 13 SVVAVF fistulae who were managed at our institution over the last 14 years. Two patients had predisposing conditions, neurofibromatosis in one and Ehlers-Danlos syndrome in the other. Nine of the patients presented with a bruit; one patient presented with a myelopathy and one with congestive cardiac failure. Six of the 13 fistulae were at Cl and five of these six were children. 1n seven of the fistulae there was retrograde flow in the distal vertebral artery. Eight patients underwent endovascular treatment. Six required both contralateral and ipsilateral vertebral artery approaches. Coils (two patients), balloons (three patients), or a combination of agents including liquid adhesives (three patients) were used. Preservation of the vertebral artery was possible in three of the eight patients. Angiographic obliteration was obtained in all eight patients. There were no significant procedure-related complications. Embolisation is the primary treatment of SVV AVF and can be performed successfully with low morbidity. Preservation of the vertebral artery, although desired, is often not possible.


Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review).
Recent studies have found that somatic gene mutations and environmental tumor‑promoting factors are both indispensable for tumor formation. Telomeric repeat‑binding factor (TRF)2 is the core component of the telomere shelterin complex, which plays an important role in chromosome stability and the maintenance of normal cell physiological states. In recent years, TRF2 and its role in tumor formation have gradually become a research hot topic, which has promoted in‑depth discussions into tumorigenesis and treatment strategies, and has achieved promising results. Some cells bypass elimination, due to either aging, apoptosis via mutations or abnormal prolongation of the mitotic cycle, and enter the telomere crisis period, where large‑scale DNA reorganization occurs repeatedly, which manifests as the precancerous cell cycle. Finally, at the end of the crisis cycle, the mutation activates either the expression level of telomerase or activates the alternative lengthening of telomere mechanism to extend the local telomeres. Under the protection of TRF2, chromosomes are gradually stabilized, immortal cells are formed and the stagewise mutation‑driven transformation of normal cells to cancer cells is completed. In addition, TRF2 also shares the characteristics of environmental tumor‑promoting factors. It acts on multiple signal transduction pathway‑related proteins associated with cell proliferation, and affects peripheral angiogenesis, inhibits the immune recognition and killing ability of the microenvironment, and maintains the stemness characteristics of tumor cells. TRF2 levels are abnormally elevated by a variety of tumor control proteins, which are more conducive to the protection of telomeres and the survival of tumor cells. In brief, the various regulatory mechanisms which tumor cells rely on to survive are organically integrated around TRF2, forming a regulatory network, which is conducive to the optimization of the survival direction of heterogeneous tumor cells, and promotes their survival and adaptability. In terms of clinical application, TRF2 is expected to become a new type of cancer prognostic marker and a new tumor treatment target. Inhibition of TRF2 overexpression could effectively cut off the core network regulating tumor cell survival, reduce drug resistance, or bypass the mutation under the pressure of tumor treatment selection, which may represent a promising therapeutic strategy for the complete eradication of tumors in the clinical setting. Based on recent research, the aim of the present review was to systematically elaborate on the basic structure and functional characteristics of TRF2 and its role in tumor formation, and to analyze the findings indicating that TRF2 deficiency or overexpression could cause severe damage to telomere function and telomere shortening, and induce DNA damage response and chromosomal instability.


Critical care of the patient with acute pancreatitis.
Acute pancreatitis is an inflammatory process of the pancreas with variable involvement of regional tissues and remote organs. This review gives a comprehensive overview of the aetiology, pathophysiology, diagnosis and therapy of acute pancreatitis relevant to the intensivist. Recent international guidelines on the management of acute pancreatitis are summarised. Eighty percent of acute pancreatitis episodes are related either to gallstones or to alcohol abuse. Independent of its aetiology, the pathophysiologic hallmark of acute pancreatitis is the premature activation of trypsin, which leads to massive pancreas inflammation, systemic overproduction of pro-inflammatory mediators and ultimately remote organ dysfunction. All guidelines agree that the diagnosis of acute pancreatitis should include clinical symptoms, increased serum amylase or lipase levels and/or characteristic findings on computed tomography. Endoscopic retrograde cholangiopancreatography is recommended as a causative therapy in patients with acute cholangitis or a strong suspicion of gallstones. All guidelines underline the importance of vigorous fluid resuscitation and supplemental oxygen therapy and prefer enteral over parenteral nutrition, with the majority favouring the nasojejunal route. In view of lacking scientific evidence, antibiotic prophylaxis to prevent infection of pancreatic necroses is discouraged by most guidelines. Computed tomography-guided fine needle aspiration is the technique of choice to differentiate between sterile and infected pancreas necrosis. While sterile pancreatic necrosis should be managed conservatively, infected pancreatic necrosis requires debridement and drainage supplemented by antibiotic therapy. Surgical necrosectomy is the traditional approach, but less invasive techniques (retroperitoneal or laparoscopic necrosectomy, computed tomography-guided percutaneous catheter drainage) may be equally effective.


Thermodynamic stability considerations for isostructural dehydrates.
Nonstoichiometric channel hydrates are a class of crystalline hydrates that can incorporate a range of water levels as a function of temperature and relative humidity (RH). When a nonstoichiometric channel hydrate can dehydrate to yield a physically stable isostructural crystalline lattice, it may become challenging to accurately evaluate the thermodynamic stability relationship associated with a polymorphic system using traditional methods. This work demonstrates application of a eutectic-melting method to determine the stability relationship between a nonstoichiometric channel dehydrate and an anhydrous form. A transition temperature (122°C) between the isostructural dehydrate of the nonstoichiometric channel hydrate and the anhydrous polymorph was identified, with the nonstoichiometric channel hydrate being the thermodynamically stable anhydrous form at room temperature (RT). Solid-state storage at a range of RH conditions demonstrated that the nonstoichiometric channel hydrate is also the stable form at RT above an RH of 94%. These results demonstrate that the nonstoichiometric channel hydrate is the stable form at low temperatures, independent of its hydration state. It has been demonstrated that the eutectic-melting method is applicable to the study of thermodynamic stability relationships between anhydrous forms and dehydrated channel hydrates.


Biomonitoring of arylamines: haemoglobin adducts of aniline derivatives.
Aromatic amines are important intermediates in industrial manufacturing. They are used in a large number of products, such as pesticides, dyes, plastics and pharmaceuticals. The parent arylamines can be metabolically released from these arylamine-based compounds and form DNA and protein adducts after N-oxidation to N-hydroxy arylamines. Aromatic amine derivatives, including the industrial intermediates acetoacetanilide, acetoacet-m-xylidide and N-ethylaniline, were examined for their ability to form Hb adducts in rats as potential biomarkers of exposure. The haemoglobin binding indices (HBI=binding [mmol mol(-1) Hb]/dose [mmol kg(-1) body weight]) of the arylamines were determined 24 h after oral administration to female Wistar rats. The precipitated haemoglobin was dissolved in 0.1 M sodium hydroxide in the presence of internal standards. After hexane extraction the released arylamines were analysed by gas chromatography-mass spectrometry (GC-MS). For aniline released from acetoacetanilide an HBI of 15 and for 2,4-dimethylaniline released from acetoacet-m-xylidide an HBI of 0.129 were determined. The HBIof aniline released from N-ethylaniline was 45.


High efficient and non-invasive collection of ejaculates from rats using penile vibratory stimulation.
The rat is one of the most important experimental animals, which plays an indispensable role in biomedical research, particularly in reproduction. However, according to our best knowledge, there is no easy and efficient method available for semen collection from rats. In this study, we successfully collected semen through penile vibratory stimulation ejaculation (PVSE) from laboratory rats. This is an easier and more efficient method compared with rectal probe electro-ejaculation (RPE). We found that the ejaculation rate, volume, concentration and motility of semen collected with PVSE were substantially better than those of RPE. Although PVSE was time-consuming compared to RPE, the quality of semen was better; additionally, sperm concentration and motility of semen were significantly higher with a two-day interval between collections compared to a five-day interval. Moreover, we found that electrical stimulation, use of anesthesia and increased age of rats have a negative effect on sperm quality. In the last experiment, four fertile female rats were artificially inseminated with PVSE-collected semen, and healthy offspring were born. Here, for the first time, we established the repeated collection of semen using the PVSE method in rats.


Family structure effects on early sexual debut among adolescent girls in Rakai, Uganda.
This study assessed the association between household family structure and early sexual debut among adolescent girls, ages 15-19, in rural Rakai District, Uganda. Early sexual debut is associated with detrimental physical, emotional and social outcomes, including increased risk of HIV. However, research on the family's role on adolescents' sexual risk behaviors in sub-Sahara Africa has been minimal and rarely takes into account the varying family structures within which African adolescents develop. Using six rounds of survey data (2001-2008) from the Rakai Community Cohort Study, unmarried adolescent girls (n=1940) aged 15-17 at their baseline survey, were followed until age 19. Parametric survival models showed that compared to adolescent girls living with both biological parents, girls who headed their own household and girls living with step-fathers, grandparents, siblings, or other relatives had significantly higher hazards of early sexual debut before age 16. Adolescent girls were significantly more likely to debut sexually if neither parent resided in the household, either due to death or other reasons. In addition, absence of the living biological father from the home was associated with higher risk of sexual debut, regardless of the biological mother's presence in the home. Our study's findings suggest that family structure is important to adolescent girls' sexual behavior. There is need for research to understand the underlying processes, interactions and dynamics of both low and high risk family structures in order to devise and strategically target interventions targeted for specific types of family structures.


Mitchell's osteotomy using internal fixation and early mobilisation.
We present the results of a prospective trial of osteotomy of the metatarsal neck for hallux valgus in 31 feet of 23 women, using a new stapling device with no plaster splintage and early weight-bearing. Surgery was performed for pain (29 feet) and difficulty with footwear (nine feet). The average time for return to light work was 3.3 weeks, and to full work 8.3 weeks after operation. Seventeen patients had full recovery within three months and 21 of the 23 patients had complete relief of pain. Shoes were more comfortable in 17 feet and 9 patients could wear narrower shoes. Only two patients were unsatisfied with the appearance of the foot. All the osteotomies united, and the average hallux valgus angle was improved on radiographs from 35 degrees to 23 degrees. The mean first metatarsal angle was reduced from 16 degrees to 11 degrees. The new technique allows more accurate surgery and easier postoperative management.


Debunking some judicial myths about epidemiology and its relevance to UK tort law.
Due to the limitations of current medical knowledge, claimants in complicated disease litigation often experience difficulties in proving causation. This paper aims to demonstrate that in some instances these difficulties could be overcome through greater use of epidemiological evidence. To encourage greater use of such evidence, it is first of all necessary to address and correct a series of common judicial misconceptions of epidemiology as a scientific discipline. By distinguishing epidemiology from the application of bare statistics, and by explaining that the courts are not automatically bound by an epidemiological result of 51+% to hold that causation has been established, this paper seeks to allay common judicial concerns about epidemiological evidence. It further seeks to demonstrate that the current judicial approach to determining questions of probabilistic causation is fundamentally flawed and that it could be significantly improved through greater use of specialist epidemiological expert witnesses. On the issue of expertise, the paper goes on to highlight the problems associated with the tendency of UK lawyers to turn to clinicians as experts on all matters of biomedical science.


Endoscopic telerobotics for neurosurgery: preliminary study for optimal distance between an object lens and a target.
To overcome limited maneuverability and procedures in the endoscopic neurosurgery, and to utilize its maximum potential ability, the HUMAN (hyper-utility mechatronic assistant) system has been developed. The system has a rigid three-dimensional endoscope with built-in three guiding-manipulators completely controlled as a slave robot by a surgeon in a remote place. To use this system most efficiently, we investigated the suitable distance between an object lens of the endoscope and a target. Actual working territory (AWT) and actual working angle (AWA) of the forceps in the endoscopical operative field (EOF) were measured by changing the distance between the lens and the target. AWT ratio (AWT/EOF) and AWA ratio (AWA/360) decreased from 58% to 12% and increased from 39% to 85% respectively as the distance became longer. When the distance exceeds 13 mm, AWA did not increase more than 85%, and AWT kept decreasing. For the effective use of the system, the optimal distance between the lens and the target should be within 13 mm, and the system will demonstrate its ability to the maximum at the distance of 8mm.


A comparison of the local anesthetic efficacy of the extraoral versus the intraoral infraorbital nerve block.
The efficacy of the extraoral infraorbital nerve block has not been studied sufficiently to ensure its appropriate clinical use. To compare the local anesthetic efficacy of the extraoral versus the intraoral infraorbital nerve block, the authors conducted a prospective, randomized crossover study. Forty adult participants randomly received extraoral infraorbital nerve blocks of 1.8 milliliters of 2 percent lidocaine with 1:100,000 epinephrine at one appointment and intraoral infraorbital nerve blocks of 1.8 mL of 2 percent lidocaine with 1:100,000 epinephrine at another appointment in a crossover design. After administering the injections, the authors used an electric pulp tester to assess the maxillary central and lateral incisors, canine, premolars and first molar for pulpal anesthesia in four-minute cycles for 60 minutes. They considered anesthesia to be successful when the participant had no response to two consecutive 80 readings (the maximum output) with the electric pulp tester. The authors found that the extraoral and intraoral infraorbital nerve blocks were ineffective in providing profound pulpal anesthesia of the maxillary central incisor (15 percent success rate) and lateral incisor (22 percent success rate). The pulpal anesthesia success rate was 92 percent for the canine for both types of nerve blocks, 80 to 90 percent for first and second premolars and 65 to 70 percent for the first molar, with no significant differences (P < .05) between the two nerve blocks. Pulpal anesthesia did not last for an hour in any of the teeth. Needle insertion pain and postoperative sequelae were more common after the extraoral infraorbital nerve block was administered. Both nerve blocks would be ineffective in the central and lateral incisors. Both nerve blocks would be somewhat successful in the canine and premolars but not in the first molar.


Retroperitoneal perforation during ERCP and endoscopic sphincterotomy: causes, clinical features and management.
Eleven patients with retroperitoneal perforation complicating endoscopic management of bile duct obstruction were seen over a seven-year period. In nine patients endoscopic sphincterotomy or pre-cut papillotomy had been performed, but in two who had not undergone sphincterotomy perforation occurred because of the penetration of a guidewire during attempts to negotiate a malignant bile duct stricture. Eight out of eleven patients remained asymptomatic, and all recovered with conservative management. Asymptomatic retroperitoneal perforation can complicate therapeutic ERCP even when sphincterotomy is not performed, but conservative management is usually effective if the complications is recognized immediately.


Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate: evidence for generation of nitric oxide.
1. The effect on platelet aggregation of glyceryl trinitrate in the presence of cultured vascular smooth muscle cells was determined turbidometrically. U46619 (a thromboxane mimetic) was used as agonist and experiments were performed in the presence of aspirin. Inorganic nitrite production from glyceryl trinitrate by vascular smooth muscle cells was also measured, to provide an indirect index of nitric oxide synthesis. 2. The combination of vascular smooth muscle cells together with glyceryl trinitrate, at concentrations that had little effect individually, profoundly inhibited platelet aggregation. 3. The inhibitory effect on platelet aggregation of vascular smooth muscle cells together with glyceryl trinitrate was markedly attenuated by haemoglobin, an inhibitor of nitric oxide. 4. These results show that vascular smooth muscle cells inhibit platelet aggregation when exposed to glycerol trinitrate and suggest that this is due to generation of nitric oxide from glyceryl trinitrate by vascular smooth muscle.


[The serum MBP, myelin sheath immunohistochemistry and electromicroscope of expetrimental epilepsy rats].
We detected the level of myelin basic protein (MBP) in the serum of experimental epilepsy rats using simplified MBP ELISA, and the myelin sheaths of their brain with MBP immuno-histochemistry (IHC) and transmitted electronmicroscopy (TEM) in order to explore the relation of brain myelin sheaths and MBP to the pathogenic mechanism of epileptic seizure. The results show that the serum MBP level in the experimental epilepsy group is significantly higher than that in the control groups (P < 0.05), and is similar to that in some patients with generalized myoclonic seizures reported by us previously. The IHC and TEM findings in the brain of epilepsy rats indicate that the lamelliform structure of myelin sheaths in some part of hippocampus region becomes relaxing, disorderly and homogenized. Our studies imply that epileptic seizures are associated with MBP release from the subtle damaged regions of myelin sheaths during epileptic seizures, and the change of MBP component in myelin sheath may play and important role in the pathogenesis of epilepsy.


Anionic-nonionic surfactants coupled micellar thin-layer chromatography: synergistic effect on simultaneous separation of hydrophilic vitamins.
A micellar thin-layer chromatographic system comprising of silica layer impregnated with 0.01% sodium dodecyl sulphate (SDS) as stationary phase and 0.1% aqueous solution of Cween 80 as mobile phase was identified as the most favorable system for the mutual separation of five water-soluble vitamins (folic acid, cyanocobalamin, thiamine, pyridoxine, and riboflavin). Effects of the presence of metal cations, inorganic anions, and amines as impurities was determined. The detection and dilution limits, given in parenthesis for folic acid (1 microg and 1:0.1 x 10(4)), cyanocobalamin (0.08 microg and 1:1.25 x 10(4)), thiamine (0.05 microg and 1:2.0 x 10(4)), pyridoxine (0.5 microg and 1:0.2 x 10(4)), and riboflavin (0.5 microg and 1:0.2 x 10(4)) were determined.


Shape Programming Using Triangular and Rectangular Soft Robot Primitives.
This paper presents fabric-based soft robotic modules with primitive morphologies, which are analogous to basic geometrical polygons-trilateral and quadrilateral. The two modules are the inflatable beam (IB) and fabric-based rotary actuator (FRA). The FRA module is designed with origami-inspired V-shaped pleats, which creates a trilateral outline. Upon pressurization, the pleats unfold, which enables propagation of angular displacement of the FRA module. This allows the FRA module to be implemented as a mobility unit in the larger assembly of pneumatic structures. In the following, we examine various ways by which FRA modules can be connected to IB modules. We studied how different ranges of motion can be achieved by varying the design of the rotary joint of the assemblies. Using a state transition-based position control system, movement of the assembled modules could be controlled by regulating the pneumatic pressurization of the FRA module at the joint. These basic modules allow us to build different types of pneumatic structures. In this paper, using IB and FRA modules of various dimensions, we constructed a soft robotic limb with an end effector, which can be attached to wheelchairs to provide assistive grasping functions for users with disabilities.


Optical Coherence Tomography Angiography Reveals Distinct Retinal Structural and Microvascular Abnormalities in Cerebrovascular Disease.
Cerebrovascular disease (CeVD) is one of the leading global causes of death and severe disability. To date, retinal microangiopathy has become a reflection of cerebral microangiopathy, mirroring the vascular pathological modifications in vivo. To evaluate the retinal structure and microvasculature in patients with CeVD, we conducted a cross-sectional study in Zhongshan Ophthalmic Center and Department of Neurology of Third Affiliated Hospital, Sun Yat-sen University using optical coherence tomography angiography (OCTA). CeVD patients (n = 121; 238 eyes) and healthy controls (n = 44; 57 eyes) were included in the analysis. The CeVD group showed significant thinning of the peripapillary retinal nerve fiber layer (pRNFL) thickness in the temporal and nasal quadrants, and thinning of the macular ganglion cell-inner plexiform layer (GC-IPL) in the inferior quadrant, while macular microvasculature reduction was prominent in all nine quadrants. There were significant correlations between OCTA parameters, visual acuity, and transcranial doppler parameters in the CeVD group. The specific structural parameters combining microvasculature indices showed the best diagnostic accuracies (AUC = 0.918) to discriminate CeVD group from healthy controls. To conclude, we proved that OCTA reveals specific patterns of retinal structural changes and extensive macular microvascular changes in CeVD. Additionally, these retinal abnormalities could prove useful disease biomarkers in the management of individuals at high risk of debilitating complications from a cerebrovascular event.


Consequences of increased third-party payments for health care services.
The growth of third-party programs to pay the costs of health care has occurred in an unplanned manner. As a result, the country presently is faced with a number of uncoordinated payment programs that sometimes work against each other. While the expansion of health insurance programs has provided the financing necessary to keep our health care system up-to-date, and while such programs doubtlessly have reduced the financial barriers to seeking health care for some population segments, health insurance also has produced some problems. Generally, the contribution of health insurance to these problems is subtle and cannot be quantified. Yet, policymakers increasingly are recognizing that there are factors at work in our health care system that, if continued unabated, will exacerbate the country's health care cost problem. Many of these factors owe their existence to the socially unacceptable incentives provided by most health insurance programs. This article focuses on some of the adverse consequences of health insurance programs and indicates that the future of private health insurance depends upon how these problems are addressed.


Polymorph specific RMSD local order parameters for molecular crystals and nuclei: α-, β-, and γ-glycine.
Crystal nucleation is important for many processes including pharmaceutical crystallization, biomineralization, and material synthesis. The progression of structural changes which occur during crystal nucleation are often described using order parameters. Polymorph specific order parameters have been developed for crystallization of spherically symmetric particles; however, polymorph specific order parameters for molecular crystals remain a challenge. We introduce template based polymorph specific order parameters for molecular crystals. For each molecule in a simulation, we compute the root mean squared deviation (RMSD) between the local environment around the molecule and a template of the perfect crystal structure for each polymorph. The RMSD order parameters can clearly distinguish the α-, β-, and γ-glycine polymorph crystal structures in the bulk crystal and also in solvated crystallites. Surface melting of glycine crystallites in supersaturated aqueous solution is explored using the newly developed order parameters. The solvated α-glycine crystallite has a thinner surface melted layer than the γ-glycine crystallite. α-glycine forms first out of aqueous solution, so surface melted layer thickness may provide insight into interfacial energy and polymorph selection.


How to deal with benign hilar or interlobar lymphadenopathy during video-assisted thoracoscopic surgery lobectomy-firing the bronchus and pulmonary artery together.
Anatomic lung resection for lung cancer by video-assisted thoracoscopic surgery (VATS) has become popular for resectable lung cancer. However, complicated situations with hilar or interlobar lymphadenopathy were tough for surgeons. We'd like to introduce a method of "firing the bronchus and pulmonary artery together" via a video demo demonstration for troubleshooting situations with severe inflammatory or calcified peri-arterial/peri-bronchial lymphadenopathy. The inflammatory and calcified lymph nodes surrounding the target bronchus and artery were firstly dissected via sharp dissection using scissors. There was no clearance between the right lower bronchus and artery, then we fired them together using endo-stapler. At last, the stumps were shortened and reinforced via complementary cross mattress suture. This video shows a classic three portal VATS right lower lobectomy, which was complicated with severe inflammatory and calcified lymph nodes. The operation went through smoothly. The postoperative course of the patient was uneventful. If there was no clearance between the target bronchus and artery during a complicated VATS lobectomy caused by severe lymphadenopathy, firing the bronchus and pulmonary artery together was an optimal option.


Renoprotective effect of pravastatin in salt-loaded Dahl salt-sensitive rats.
The pathophysiological features of nephrosclerosis may be analogous to those of atherosclerosis, which is intimately related to lipid metabolism. Thus, we examined whether a lipid-lowering agent, pravastatin, would ameliorate renal damage in hypertensive model animals. Salt-loaded Dahl salt-sensitive (S) rats were given pravastatin (2 mg/ml in drinking water) for 5 weeks. Pravastatin decreased systolic blood pressure. Although pravastatin did not influence the serum total, high-density, or low-density lipoprotein cholesterol, serum triglycerides were decreased. Pravastatin decreased urinary protein excretion and ameliorated histopathological damage in salt-loaded Dahl S rats. Increased urinary excretion of 8-iso-prostagaldin F2alpha and 8-hydroxy-2'-deoxyguanosine and renal superoxide overproduction and decreased reduced glutathione in the renal parenchyma were ameliorated with pravastatin in Dahl S rats fed a high salt diet. Therefore, pravastatin inhibited the progression of renal injury in salt-loaded Dahl S rats, through its antioxidant as well as its depressor effects.


Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.
The design of immunogens that elicit broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to assess potential immunogens is to use mice expressing precursors of human bnAbs as vaccination models. The bnAbs of the VRC01-class derive from the IGHV1-2 immunoglobulin heavy chain and neutralize a wide spectrum of HIV-1 strains via targeting the CD4 binding site of the envelope glycoprotein gp120. We now describe a mouse vaccination model that allows a germline human IGHV1-2(∗)02 segment to undergo normal V(D)J recombination and, thereby, leads to the generation of peripheral B cells that express a highly diverse repertoire of VRC01-related receptors. When sequentially immunized with modified gp120 glycoproteins designed to engage VRC01 germline and intermediate antibodies, IGHV1-2(∗)02-rearranging mice, which also express a VRC01-antibody precursor light chain, can support the affinity maturation of VRC01 precursor antibodies into HIV-neutralizing antibody lineages.


Integrated assessment of oil pollution using biological monitoring and chemical fingerprinting.
A full assessment of the impact of oil and chemical spills at sea requires the identification of both the polluting chemicals and the biological effects they cause. Here, a combination of chemical fingerprinting of surface oils, tissue residue analysis, and biological effects measures was used to explore the relationship between spilled oil and biological impact following the grounding of the MSC Napoli container ship in Lyme Bay, England in January 2007. Initially, oil contamination remained restricted to a surface slick in the vicinity of the wreck, and there was no chemical evidence to link biological impairment of animals (the common limpet, Patella vulgata) on the shore adjacent to the oil spill. Secondary oil contamination associated with salvage activities in July 2007 was also assessed. Chemical analyses of aliphatic hydrocarbons and terpanes in shell swabs taken from limpet shells provided an unequivocal match with the fuel oil carried by the ship. Corresponding chemical analysis of limpet tissues revealed increased concentrations of polycyclic aromatic hydrocarbons (PAHs) dominated by phenanthrene and C1 to C3 phenanthrenes with smaller contributions from heavier molecular weight PAHs. Concurrent ecotoxicological tests indicated impairment of cellular viability (p < 0.001), reduced immune function (p < 0.001), and damage to DNA (Comet assay, p < 0.001) in these animals, whereas antioxidant defenses were elevated relative to un-oiled animals. These results illustrate the value of combining biological monitoring with chemical fingerprinting for the rapid identification of spilled oils and their sublethal impacts on biota in situ.


Unclassified mucinous renal cell carcinoma: a rare histopathological entity.
Renal cell carcinoma (RCC) with mucin production is extremely rare. We present the case of a previously healthy 76-year-old woman who underwent a robotic-assisted laparoscopic right nephrectomy for a 5-cm heterogeneously enhancing right renal mass. Pathology revealed mucin-producing epithelial RCC. We discuss the presentation and pathological features of this case and comment on its definitive treatment.


Ultralong-Life Cathode for Aqueous Zinc-Organic Batteries via Pouring 9,10-Phenanthraquinone into Active Carbon.
Organic carbonyl electrode materials have shown a great potential in various rechargeable batteries but limited by the problems of poor cycling and rate performance owing to their high solubility in aqueous electrolytes and low conductivity. To address these problems, the 9,10-phenanthraquinone (PQ)@active carbon (AC) composite fabricated by melting PQ molecules into porous AC is considered as a superstable cathode material for aqueous zinc batteries. The introduction of AC improves the structural stability and restrains the PQ dissolution in an aqueous electrolyte. As a result, the PQ@AC composite electrode delivers a reversible discharge capacity of 150.0 mA h g-1 at a current density of 0.1 A g-1, and it also features an unprecedented cycling performance of 36 000 cycles with a capacity retention of 96.3% at 5 A g-1. Moreover, the Zn2+ and H+ in an aqueous electrolyte are verified to co-insert into the PQ@AC composite electrode using various ex situ characterizations and electrochemical test. This strategy provides a new avenue for organic carbonyl compounds with quinone substructures to improve their electrochemical performance of other batteries.


[Intraoperative radiofrequency ablation of liver metastases: age of reason].
Intraoperative radiofrequency ablation (IORA) is a surgical technique used to destroy liver metastases by heat. It is performed by a surgeon experienced in intraoperative ultrasounds. It has been officially registered in the French nomenclature of medical acts in 2009. Indications and results of IORA are very different from those of the percutaneous route used by radiologists. Ten years of experience have allowed to define IORA indications in complement to resection which remains the gold standard of liver surgery: 1) lesion no greater than 30 mm in diameter; 2) no proximity to a major portal structure; 3) use of a straight needle with overlapping heat volumes; 4) complete vascular exclusion (portal and sus-hepatic circulation) to treat para-sus-hepatic lesions; 5) requirement to spare parenchymal liver volume. Positive preliminary data of two prospective studies, the EORTCC CLOCC study and the ARF2003 study confirm that IORA complements surgery to obtain complete resection in a larger proportion of patients after chemotherapy induction.


Validation of a White-light 3D Body Volume Scanner to Assess Body Composition.
Estimating body fat content has shown to be a better predictor of adiposity-related cardiovascular risk than the commonly used body mass index (BMI). The white-light 3D body volume index (BVI) scanner is a non-invasive device normally used in the clothing industry to assess body shapes and sizes. We assessed the hypothesis that volume obtained by BVI is comparable to the volume obtained by air displacement plethysmography (Bod-Pod) and thus capable of assessing body fat mass using the bi-compartmental principles of body composition. We compared BVI to Bod-pod, a validated bicompartmental method to assess body fat percent that uses pressure/volume relationships in isothermal conditions to estimate body volume. Volume is then used to calculate body density (BD) applying the formula density=Body Mass/Volume. Body fat mass percentage is then calculated using the Siri formula (4.95/BD - 4.50) × 100. Subjects were undergoing a wellness evaluation. Measurements from both devices were obtained the same day. A prediction model for total Bod-pod volume was developed using linear regression based on 80% of the observations (N=971), as follows: Predicted Bod-pod Volume (L)=9.498+0.805*(BVI volume, L)-0.0411*(Age, years)-3.295*(Male=0, Female=1)+0.0554*(BVI volume, L)*(Male=0, Female=1)+0.0282*(Age, years)*(Male=0, Female=1). Predictions for Bod-pod volume based on the estimated model were then calculated for the remaining 20% (N=243) and compared to the volume measured by the Bod-pod. Mean age among the 971 individuals was 41.5 ± 12.9 years, 39.4% were men, weight 81.6 ± 20.9 kg, BMI was 27.8 ± 6.3kg/m2. Average difference between volume measured by Bod-pod- predicted volume by BVI was 0.0 L, median: -0.4 L, IQR: -1.8 L to 1.5 L, R2=0.9845. Average difference between body fat measured-predicted was-1%, median: -2.7%, IQR: -13.2 to 9.9, R2=0.9236. Volume and BFM can be estimated by using volume measurements obtained by a white- light 3D body scanner and the prediction model developed in this study.


Pulmonary valve replacement after tetralogy of Fallot repair in preadolescent patients.
After tetralogy of Fallot (TOF) repair, severe pulmonary insufficiency is known to impair biventricular function. Pulmonary valve replacement (PVR) alleviates symptoms, normalizes right ventricular volumes, and improves ventricular function. Most studies addressing the role of PVR have examined older adolescents or adults. Less is known about the potential benefits of PVR in preadolescents with TOF and significant right ventricular dilatation. We reviewed the clinical data for all preadolescents (< or = 13 years) with TOF who underwent cardiac magnetic resonance imaging (cMRI) or PVR, or both. Serial cMRI data were analyzed to determine the change in indexed right ventricular end-diastolic volume (RVEDV) and biventricular ventricular ejection fractions. Available cMRI data after PVR were compared with data before PVR. During the study period, 101 preadolescents with TOF had cMRI. The median age of complete repair was 6 months (range, 6 days to 3.4 years). The mean RVEDV at the first study was 135 +/- 39 mL/m(2). For 32 with serial cMRI studies, the RVEDV increased at a mean yearly rate of 9 mL/m(2). Ventricular systolic function was impaired in 46 (46%). Forty-two patients underwent PVR at a mean age of 8 +/- 3 years. No hospital deaths occurred, and no pulmonary valve reinterventions have been required. Significant right ventricular dilatation is common in preadolescents after transannular patch repair of TOF. Routine follow-up of this population should incorporate cMRI. Further studies will be needed to determine whether a strategy of early PVR might improve intermediate-term outcome.


Risk of relapse of multiple myeloma following kidney transplantation.
Autologous stem cell transplantation (ASCT) and novel therapies have improved the prognosis for patients with multiple myeloma (MM). For those who undergo ASCT while on dialysis, a similar survival compared with the overall MM population has been reported. Therefore, for patients achieving remission following ASCT, kidney transplantation is an attractive option, offering an improved quality of life and significant economic advantage. This case series investigates the outcome of five patients who underwent an ASCT for MM with subsequent kidney transplantation between 2006 and 2012. Four patients presented with end-stage renal disease (ESRD) and one progressed to ESRD shortly after diagnosis. Induction chemotherapy regimens with novel agents including thalidomide and bortezomib were utilized. Following attainment of very good partial remission or complete remission, high-dose melphalan ASCTs were performed after a median of 10 months. Kidney transplantation (living donor n = 3, deceased donor n = 2) with tacrolimus-based immunosuppression regimens was completed at a median of 27 months after ASCT. Patients 1 and 3 experienced relapse of myeloma at 6 and 16 months after kidney transplantation. Patients 2, 4 and 5 remain alive at 55 months (median) after kidney transplantation with no evidence of relapse. Forty percent of our cohort experienced a relapse in MM within 2 years of kidney transplantation. Death-censored graft survival and patient survival were 80% at 4 years. Our study adds to the growing literature supporting kidney transplantation following successful ASCT for MM and is useful when counselling patients regarding renal and haematological outcomes.


9.4T Magnetic Resonance Imaging of the Mouse Circle of Willis Enables Serial Characterization of Flow-Induced Vascular Remodeling by Computational Fluid Dynamics.
The neurovasculature dynamically responds to changes in cerebral blood flow by vascular remodeling processes. Serial imaging studies in mouse models could help characterize pathologic and physiologic flow-induced remodeling of the Circle of Willis (CoW). We induced flow-driven pathologic cerebral vascular remodeling in the CoW of mice (n=3) by ligation of the left Common Carotid Artery (CCA), and the right external carotid and pterygopalatine arteries, increasing blood flow through the basilar and the right internal carotid arteries. One additional mouse was used as a wild-type control. Magnetic Resonance Imaging (MRI) at 9.4 Tesla (T) was used to serially image the mouse CoW over three months, and to obtain threedimensional images for use in Computational Fluid Dynamic (CFD) simulations. Terminal vascular corrosion casting and scanning electron microscope imaging were used to identify regions of macroscopic and microscopic arterial damage. We demonstrated the feasibility of detecting and serially measuring pathologic cerebral vascular changes in the mouse CoW, specifically in the anterior vasculature. These changes were characterized by bulging and increased vessel tortuosity on the anterior cerebral artery and aneurysm- like remodeling at the right olfactory artery origin. The resolution of the 9.4T system further allowed us to perform CFD simulations in the anterior CoW, which showed a correlation between elevated wall shear stress and pathological vascular changes. In the future, serial high-resolution MRI could be useful for characterizing the flow environments corresponding to other pathologic remodeling processes in the mouse CoW, such as aneurysm formation, subarachnoid hemorrhage, and ischemia.


Schistosoma japonicum MiRNA-7-5p Inhibits the Growth and Migration of Hepatoma Cells via Cross-Species Regulation of S-Phase Kinase-Associated Protein 2.
MicroRNAs (miRNAs) play important roles in human diseases, such as cancer. Human miRNA-7-5p is a tumor suppressor miRNA that inhibits tumor growth by regulating multiple oncogenic signal pathways. Recently, studies revealed that plant miRNAs could regulate mammalian gene expression in a cross-kingdom manner. Schistosoma japonicum miRNA-7-5p (designated as sja-miR-7-5p) is conserved between the parasites and mammals. Thus, we investigated whether sja-miR-7-5p has similar antitumor activity to its mammalian counterpart. We first showed that sja-miR-7-5p was detected in host hepatocytes during S. japonicum infection. The sja-miR-7-5p mimics significantly inhibited the growth, migration, and colony formation of mouse and human hepatoma cell lines in vitro, and induced G1/G0 cell cycle arrest. In a xenograft animal model, the tumor volume and weight were significantly reduced in mice inoculated with hepatoma cells transfected with sja-miR-7-5p mimics compared with those transfected with NC miRNAs. Furthermore, the antitumor activity of sja-miR-7-5p was suggested by cross-species downregulation of the S-phase kinase-associated protein 2 gene in the host. Thus, sja-miR-7-5p is translocated into hepatocytes and exerts its anti-cancer activities in mammals, implying that sja-miR-7-5p might strengthen host resistance to hepatocellular carcinoma during schistosome infection.


Progression of Danon disease with medical imaging: two case reports.
Danon disease is a rare X-linked dominant genetic disorder caused by loss-of-function mutations in the lysosome-associated membrane protein 2 gene. Progression of Danon disease is unknown because of its rare incidence in a diverse ethnic population. We report longitudinal data from two patients who were diagnosed with Danon disease by a genetic test. The evaluation protocol included electrocardiographic monitoring, echocardiography, and magnetic resonance imaging. Progression of hypertrophic cardiomyopathy to dilated cardiomyopathy was observed in the first patient. He died from sudden cardiac arrest. The second patient is currently suffering from hypertrophic cardiomyopathy. Development of the hypertrophic phase progressing into the dilated phase in Danon disease may provide useful information for early identification and clinical decisions in patients with this disease.


Surgical treating lumbar intraspinal tumor through a para-split laminotomy.
to explore the feasibility and effectiveness of para-split laminotomy in the treatment of lumbar intraspinal tumors. We retrospectively review the clinical data of 15 patients suffering lumbar intraspinal tumors, who underwent tumor resection using the para-split laminotomy, from October 2016 to May 2018. Observation indicators were as follows: (1) surgical and postoperative recovery situations; (2) the neurological function of the spinal cord and the follow-up situations. Mean blood loss was 95.3 ± 58.2 ml, and the mean duration of the surgical procedure was 176.7 ± 35.2 min. All lumbar intraspinal tumors were resected completely. There were no operative complications. The postoperative CT scans showed no pedicle or vertebral fractures. During the follow-up period of 6-18 months (average 10.8 ± 3.9 months), no tumor recurrence or spinal deformation was found according to the imaging examination. CT 3D reconstructions showed that the split laminae tended to heal. The average preoperative JOA score was 15.5 ± 4.9 and the average postoperative JOA score improved to 24.0 ± 3.5 (average improvement rate 65.9 ± 19.6%). The para-split laminotomy could reduce the damage to the posterior spinal tension band and help to protect the stability of the spine. It is feasible and effective to apply the para-split laminotomy to the operation of a lumbar intraspinal tumor, and this technique may be a promising option when considering surgical methods for some multilevel well-circumscribed intraspinal tumors.


Validation of an online assessment of orthopedic surgery residents' cognitive skills and preparedness for carpal tunnel release surgery.
Surgical competence requires both cognitive and technical skills. Relatively little is found in the literature regarding the value of Web-based assessments to measure surgery residents' mastery of the competencies. To determine the validity and reliability of 2 online instruments for predicting the cognitive preparedness of residents for performing carpal tunnel release surgery. Twenty-eight orthopedic residents and 2 medical school students responded to an online measure of their perception of preparedness and to an online cognitive skills assessment prior to an objective structured assessment of technical skills, in which they performed carpal tunnel release surgery on cadaveric specimens and received a pass/fail assessment. The 2 online assessments were analyzed for their internal reliability, external correlation with the pass/fail decision, and construct validity. The internal consistency of the perception of preparedness measure was high (α = .92) while the cognitive assessment was less strong (α = .65). Both instruments demonstrated moderately strong correlations with the pass/fail decision, with Spearman correlation of .606 (P = .000) and .617 (P = .000), respectively. Using logistic regression to analyze the predictive strength of each instrument, the perception of preparedness measure demonstrated a 76% probability (η(2) = .354) and the cognitive skills assessment a 73% probability (η(2) = .381) of correctly predicting the pass/fail decision. Analysis of variance modeling resulted in significant differences between levels at P < .005, supporting good construct validity. The online perception of preparedness measure and the cognitive skills assessment both are valid and reliable predictors of readiness to successfully pass a cadaveric motor skills test of carpal tunnel release surgery.


Achilles Tendon Ruptures in Middle-Aged Rats Heal Poorly Compared With Those in Young and Old Rats [Formula: see text].
Achilles tendon ruptures are painful and debilitating injuries and are most common in middle-aged patients. There is a lack of understanding of the underlying causes for increased rupture rates in middle-aged patients and how healing outcomes after a rupture might be affected by patient age. Therefore, the objective of this study was to define age-specific Achilles tendon healing by assessing ankle functional outcomes and Achilles tendon mechanical and histological properties after a rupture using a rat model. Rats representing the middle-aged patient population would demonstrate reduced healing capability after an Achilles tendon rupture, as demonstrated by a slower return to baseline ankle functional properties and inferior biomechanical and histological tendon properties. Controlled laboratory study. Fischer 344 rats were categorized by age to represent young, middle-aged, and old patients, and Achilles tendon ruptures were induced in the right hindlimb. Animals were allowed to heal and were euthanized at 3 or 6 weeks after the injury. In vivo functional assays and ultrasound imaging were performed throughout the healing period, and ex vivo tendon mechanical and histological properties were assessed after euthanasia. Rats representing middle-aged patients displayed reduced healing potential compared with the other age groups, as they demonstrated decreased recovery of in vivo functional and ultrasound assessment parameters and inferior mechanical and histological properties after an Achilles tendon rupture. These findings may help explain the increased rupture rate observed clinically in middle-aged patients by suggesting that there may be altered tendon responses to daily trauma. The results provide novel data on age-specific healing outcomes after an Achilles tendon rupture, which underscores the importance of considering a patient's age during treatment and expectations for outcomes.


[Civilization stress, cardiovascular risk, evidence-based medicine, guidelines].
Cardiovascular diseases have the pole-position on the list of morbidity and mortality statistics. Despite the great advances have been made in management of cardiovascular diseases, prevalence of these disorders increases worldwide, and even younger and younger ages are threatened. This phenomenon is strongly related to obesity and type 2 diabetes pandemic, which shows an unequivocal association with expansion of modernized life-style. The pathomechanism proposed to have central role is the chronic stress induced by civilized life-conduct. The authors criticizes the everyday practice suggested for management of cardiovascular diseases, focusing on normalization of cardiovascular risk factors, instead of fighting against the primary cause ie. chronic stress. There is growing evidence, that achieving the target values defined in guide-lines will not necessarily result in improvement of patient related clinical outcomes. The statistical approach generally practiced in randomized clinical trials is primarily striving for the drug-sale, instead of discovering novel pathophysiological relations. Pharmaceutical industry having decisive role in research and patient-care is mainly interested in profit-sharing, therefore patients' interest can not be optimally realized, and costs are unnecessarily augmented. Separation of patient-, and business-oriented medical care is an ethical question of fundamental importance.


Effects of pretreatment on morphology, chemical composition and enzymatic digestibility of eucalyptus bark: a potentially valuable source of fermentable sugars for biofuel production - part 1.
In recent years, the growing demand for biofuels has encouraged the search for different sources of underutilized lignocellulosic feedstocks that are available in sufficient abundance to be used for sustainable biofuel production. Much attention has been focused on biomass from grass. However, large amounts of timber residues such as eucalyptus bark are available and represent a potential source for conversion to bioethanol. In the present paper, we investigate the effects of a delignification process with increasing sodium hydroxide concentrations, preceded or not by diluted acid, on the bark of two eucalyptus clones: Eucalyptus grandis (EG) and the hybrid, E. grandis x urophylla (HGU). The enzymatic digestibility and total cellulose conversion were measured, along with the effect on the composition of the solid and the liquor fractions. Barks were also assessed using Fourier-transform infrared spectroscopy (FTIR), solid-state nuclear magnetic resonance (NMR), X-Ray diffraction, and scanning electron microscopy (SEM). Compositional analysis revealed an increase in the cellulose content, reaching around 81% and 76% of glucose for HGU and EG, respectively, using a two-step treatment with HCl 1%, followed by 4% NaOH. Lignin removal was 84% (HGU) and 79% (EG), while the hemicellulose removal was 95% and 97% for HGU and EG, respectively. However, when we applied a one-step treatment, with 4% NaOH, higher hydrolysis efficiencies were found after 48 h for both clones, reaching almost 100% for HGU and 80% for EG, in spite of the lower lignin and hemicellulose removal. Total cellulose conversion increased from 5% and 7% to around 65% for HGU and 59% for EG. NMR and FTIR provided important insight into the lignin and hemicellulose removal and SEM studies shed light on the cell-wall unstructuring after pretreatment and lignin migration and precipitation on the fibers surface, which explain the different hydrolysis rates found for the clones. Our results show that the single step alkaline pretreatment improves the enzymatic digestibility of Eucalyptus bark. Furthermore, the chemical and physical methods combined in this study provide a better comprehension of the pretreatment effects on cell-wall and the factors that influence enzymatic digestibility of this forest residue.


Polyclonal human T lymphocyte activation results in the secondary functional activation of the human B lymphocyte.
The polyclonal T lymphocyte activators Con A and PHA were demonstrated to induce secretion of IgM and IgG as well as IgA antibodies in cultures of human peripheral blood lymphocytes. A similar response was seen in one-way mixed lymphocyte cultures and the kinetics, dose-response characteristics and optimal culture conditions are presented. The presence of functional T lymphocytes is a prerequisite for in vitro B lymphocyte activation in response to T lymphocyte mitogens. A narrow dose-response profile is a characteristic for both Con A and PHA and polyclonal B cell activation occurred at what have been previously regarded as suboptimal concentrations of these agents. The use of higher doses of these activators failed to generate immunoglobulin-secreting cells despite the presence of early and optimal levels of DNA synthesis in the cultures.


Chimpanzee and pig-tailed macaque iPSCs: Improved culture and generation of primate cross-species embryos.
As our closest living relatives, non-human primates uniquely enable explorations of human health, disease, development, and evolution. Considerable effort has thus been devoted to generating induced pluripotent stem cells (iPSCs) from multiple non-human primate species. Here, we establish improved culture methods for chimpanzee (Pan troglodytes) and pig-tailed macaque (Macaca nemestrina) iPSCs. Such iPSCs spontaneously differentiate in conventional culture conditions, but can be readily propagated by inhibiting endogenous WNT signaling. As a unique functional test of these iPSCs, we injected them into the pre-implantation embryos of another non-human species, rhesus macaques (Macaca mulatta). Ectopic expression of gene BCL2 enhances the survival and proliferation of chimpanzee and pig-tailed macaque iPSCs within the pre-implantation embryo, although the identity and long-term contribution of the transplanted cells warrants further investigation. In summary, we disclose transcriptomic and proteomic data, cell lines, and cell culture resources that may be broadly enabling for non-human primate iPSCs research.


The attentional demands of encoding and retrieval in younger and older adults: 2. Evidence from secondary task reaction time distributions.
Three studies examined the effects of encoding or retrieval on properties of secondary task reaction time (RT) distributions in younger and older adults. Relative to full attention conditions, encoding and retrieval increased secondary task RT medians and standard deviations more for older adults than for younger adults, and the age-related RT increase was most pronounced among the slowest RTs. Hierarchical regression analyses revealed two age-related mechanisms underlying these effects, which were interpreted as cognitive slowing and reductions in attentional resources. Cognitive slowing affects the entire RT distribution regardless of the memory task. By contrast, reduced attentional resources result in very long RTs, especially when the tasks require self-initiated encoding or retrieval operations.


Drinking patterns among individuals with and without DSM-IV alcohol use disorders.
The purpose of this study was to compare alcohol consumption patterns among individuals with and without alcohol use disorders, using a representative sample of the general population that would not exaggerate differences as a result of selection biases associated with treatment for alcohol problems. Based on data from 18,352 past-year drinkers selected from a nationally representative sample of U.S. households, 11 measures of past-year alcohol consumption were compared for three diagnostic groups: (1) individuals who did not meet the criteria for either alcohol abuse or dependence, i.e., those without a DSM-IV alcohol use disorder (AUD); (2) those classified with abuse only; and (3) those classified with alcohol dependence, with or without abuse. For all measures reflecting frequency and quantity of drinking, frequency of heavy drinking and intoxication, and frequency of atypical temporal drinking patterns, the values for abusers lay midway between those for individuals without an AUD and those with dependence. Individuals with alcohol use disorders drank a greater proportion of their ethanol intake in the form of beer and a lower proportion in the form of wine than did those without an AUD. Of all the consumption measures considered, frequency of intoxication showed the strongest association with the probability of having an AUD, followed by frequency of drinking 5 + drinks, prevalence of morning drinking and total volume of intake. The ratios of consumption measures for individuals with disorders relative to those without an AUD showed relatively little significant variation across demographic subgroups of the population. The findings supported the distinction between the disorders of alcohol abuse and dependence, and implicated loss of control as an important element of this distinction. They also indicated that even among individuals with alcohol use disorders, demographic differentials reflecting cultural, physiological and normative forces were maintained and should be considered in approaches to treatment.