Coronavirus (COVID-19) Infection-Induced Chilblains: A Brisk Perieccrine Inflammatory Response.
The varying cutaneous and pathological manifestations of coronavirus 2 (SARS-CoV-2 or COVID-19) may have prognostic implications. Acral ischemic findings present with a hypercoagulable state in critically ill COVID-19 patients. Pathologically confirmed varicella-like exanthem and perniosis COVID-19 cases have correlated with paucisymptomatic and asymptomatic patients in previous reports. We present the second case of biopsy-proven COVID-19 infection-induced chilblains (pernio) in a paucisymptomatic patient with a brisk perieccrine lymphocytic response. Based on an antecedent pathological study, we know coronavirus particles have been seen in the eccrine gland associated with a brisk peri-inflammatory response. The prominent perieccrine inflammation is helpful in the diagnosis of COVID-19 infections. Currently, nonischemic pathological findings correlate with a good prognosis based on the paucisymptomatic or asymptomatic nature of their disease courses. Patients presenting with suspected COVID-19 infection-induced chilblains who are paucisymptomatic or asymptomatic should be isolated and immediately tested with polymerase chain reaction (PCR) testing (as there is a delay in diagnosis based on the poor sensitivity of the current rapid test). We continue to stress the importance of early diagnosis and quarantining to prevent spread to the older and immunocompromised patients.


Antagonistic peptides specifically inhibit proliferation, cytokine production, CD40L expression, and help for IgE synthesis by Der p 1-specific human T-cell clones.
Allergic disorders are characterized by IgE antibody responses to a multitude of allergens as a result of the ability of these antibodies to specifically bind to high-affinity IgE receptors on mast cells and basophils. This interaction results in receptor activation and release of soluble mediators such as histamine and leukotrienes, which cause allergic reactions in various target organs. Because the synthesis of IgE is tightly regulated by cytokines and CD40 ligand (L) interactions, CD4+ helper T cells are obvious targets, with the aim to modulate allergen-induced IgE responses. Because of the central role of allergen-specific T-helper type 2 (TH2) cells in the pathway leading to IgE synthesis in vitro and in vivo, we have evaluated the possibility of inhibiting allergen-induced activation of these cells by using allergen-derived peptides that have been modified by single amino acid substitutions. Three cloned human TH2-like CD4+ T-cell lines, specific for Der p 1, the major allergen in house dust, were used in this study. Upon activation with Der p 1 or specific Der p 1-derived wild-type peptides, these T-cell clones produce high levels of IL-4 and IL-5 and low levels of interferon-gamma and IL-2, respectively, and furthermore give help to B cells for the production of IgE in vitro. Modified synthetic peptides were generated by the introduction of single amino acid substitutions into two different T-cell activation-inducing epitopes on Der p 1. The effects of these modified peptides were studied in Der p 1-induced proliferation, cytokine production, and in vitro IgE production assays. Several substituted Der p 1-derived peptides failed to induce T-cell proliferation, in contrast to the native peptides. In addition, some of these peptides acted as antagonists by strongly inhibiting wild-type peptide-induced proliferation as well as the production of interferon-gamma, IL-2, IL-4, and IL-5, although the production of the latter two cytokines was less affected than that of interferon-gamma, even at a 100-fold molar excess of the antagonistic peptides. In addition, the presence of an excess of each of the antagonistic peptides during the activation of Der p I-specific T-cell clones prevented induction of CD40L expression, resulting in a failure of these cells to give help to B cells for the production of IgE in vitro, even in the presence of exogenous IL-4. Substitution of certain amino acid residues in immunogenic Der p 1-derived peptides results in the generation of peptides that fail to induce proliferation of Der p 1-specific T-cell clones. In addition, these modified peptides have strong antagonistic activities on Der p 1-induced proliferation, cytokine production, and CD40L expression by allergen-specific T-cell clones as well as on T cell-mediated IgE production by B cells. These findings suggest that modified peptides interfere with allergen-induced activation of T cells, including the production of cytokines and the expression of surface molecules important for successful T cell-B cell interactions, and may therefore have therapeutic potential by inhibiting the expansion and function of allergen-specific TH2 cells.


[Treatment of malignant melanoma (clinical stages I and II) (author's transl)].
The uncorrected cumulative five-year survival rate ("actuarial method") among 195 patients with infiltrative malignant melanoma of the skin was 58% (160 cases) in clinical stage I, 26% (35 cases) in clinical stage II. In addition to clinical staging, microstaging - i.e. the histologically determined depth of invasion of the primary tumour - is of great prognostic significance. In microstages 2 and 3 with the largest vertical tumour diameter below 0.76 mm, five-year survival rate was 100% while in microstage 3 with greater vertical tumour diameter it was 66% in microstage 4 55% and microstage 5 31%. Results of treatment can be reliably interpreted only if they are divided according to microstage. Propylactic dissection of the regional lymph-nodes (dissection in clinical stage I) need not be undertaken in microstages 2 and 3 with vertical tumours diameter below 0.76 mm. Whether prophylactic dissection was done in one or two sessions has apprarently no significant influence on survival rate. A single X-radiation dose to the primary tumour of 4 000 -6000 R immediately before excision of the tumour did not significantly increase the results. The results were particularly bad when the primary tumour was removed after inadequate manipulation.


Kinetic Isotope Effect Probes the Reactive Spin State, As Well As the Geometric Feature and Constitution of the Transition State during H-Abstraction by Heme Compound II Complexes.
What do experimentally measured kinetic isotope effects (KIEs) tell us about H-abstraction reactions with multispin-state reactivity options? Using DFT calculations with tunneling corrections for experimentally studied H-abstraction reactions of porphyrin-Compound II species (Chem.-Eur. J. 2014, 20, 14437; Angew. Chem., Int. Ed. 2008, 47, 7321) with cyclohexane, dihydroanthracene (DHA), and xanthene (Xan), we show here that KIE is a selective probe that identifies the experimentally reactive spin state. At the same time, comparison of calculated and experimental KIE values permits us to determine the structural orientation of the transition states, as well as the presence/absence of an axial ligand, and the effect of porphyrin substituents. The studied compound II (Cpd II) species involve porphine, and porphyrin ligands with different meso-substituents, TPFPP (tetrakis(pentafluorophenyl)porphyrin dianion) and TMP (tetramesitylporphyrin dianion), with and without imidazole axial ligands. The DFT calculations reveal three potential pathways: quintet and triplet σ-pathways (5Hσ and 3Hσ) that possess linear transition state (TS) structures, and a triplet π -pathway (3Hπ) having a bent TS structure. Without an axial ligand, the 5Hσ pathways for these Cpd II complexes cross below the triplet states. The axial ligand raises the barriers for the quintet and triplet σ-pathways and quenches any chances for two-state reactivity, thus proceeding via the 3Hπ pathway. All of these pathways exhibit characteristic KIE values: very large for 3Hπ (48-200), small for 5Hσ (3-9), and intermediate for 3Hσ (23-51). The calculated KIEs for (TPFPP)FeIV═O without an axial ligand reveal that 3Hσ is the only pathway having a KIE that matches the experimental values, for the reactions with DHA and Xan (Angew. Chem., Int. Ed. 2008, 47, 7321). Indeed, theory shows that tunneling significantly lowers the 3Hσ barrier rendering it the sole reactive state for the reaction. A prediction is made for the reactivity and KIE of (TMP)FeIV═O complex, and a comparison is made with the analogous nonheme complexes.


Effect of lyophilization and storage temperature on the activity of salivaricin CRL 1328, a potential bioactive ingredient of a urogenital probiotic product.
Bacteriocins are antimicrobial peptides with potential applications as therapeutic agents for the treatment of microbial infections. The aim of this work was to investigate the effect of different protectors on the activity of salivaricin CRL1328, a bacteriocin produced by Lactobacillus salivarius CRL1328, during the lyophilization process and subsequent storage at different temperatures for 18 months using statistical models. Different protectors such as mannitol, Tween 80, polyethylene glycol 8000 (PEG), monosodium glutamate (MSG), reconstituted skim milk, sucrose and ascorbic acid were used for the lyophilization and storage of salivaricin. The biplot of principal component analysis was used for the interpretation of the interactions between the different factors studied. The antimicrobial activity of salivaricin was dependent mainly on temperature, and also on the time of storage and protector assayed. The stability of salivaricin was higher at -20°C and 4°C than 25°C and decreased during the time of storage; however, salivaricin was active after 18 months of storage at 25°C. Sucrose, mannitol plus sucrose, PEG plus sucrose and MSG were the most effective agents in protecting the bacteriocin during the lyophilization process. Effective maintenance of the activity of the bacteriocin was observed by storage with sucrose and ascorbic acid at -20°C as well as with PEG plus sucrose at 4°C and -20°C. The results obtained suggest that sucrose alone or combined with PEG can effectively maintain the activity of salivaricin during lyophilization and storage. This study provides useful information for the potential application of salivaricin as a bioactive principle for a pharmaceutical formulation.


The Effect of Ingested Glucose Dose on the Suppression of Endogenous Glucose Production in Humans.
Insulin clamp studies have shown that the suppressive actions of insulin on endogenous glucose production (EGP) are markedly more sensitive than for stimulating glucose disposal (Rd). However, clamp conditions do not adequately mimic postprandial physiological responses. Here, using the variable infusion dual-tracer approach, we used a threefold range of ingested glucose doses (25, 50, and 75 g) to investigate how physiological changes in plasma insulin influence EGP in healthy subjects. Remarkably, the glucose responses were similar for all doses tested, yet there was a dose-dependent increase in insulin secretion and plasma insulin levels. Nonetheless, EGP was suppressed with the same rapidity and magnitude (∼55%) across all doses. The progressive hyperinsulinemia, however, caused a dose-dependent increase in the estimated rates of Rd, which likely accounts for the lack of a dose effect on plasma glucose excursions. This suggests that after glucose ingestion, the body preferentially permits a transient and optimal degree of postprandial hyperglycemia to efficiently enhance insulin-induced changes in glucose fluxes, thereby minimizing the demand for insulin secretion. This may represent an evolutionarily conserved mechanism that not only reduces the secretory burden on β-cells but also avoids the potential negative consequences of excessive insulin release into the systemic arterial circulation.


Increased skin inflammation and blood vessel density in human and experimental diabetes.
Systemic inflammation is associated with impaired wound healing in diabetes mellitus (DM) patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all DM animal models compared with their non-DM controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around preexisting skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes.


Improvement of prognosis for unresectable biliary tract cancer.
To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer. A total of 186 consecutive patients with unresectable biliary tract cancer, who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan, were retrospectively analyzed. These patients were divided into three groups based on the year beginning chemotherapy: Group A (2000-2003), Group B (2004-2006), and Group C (2007-2009). The data were fixed at the end of December 2011. Overall survival and time-to-progression were analyzed and compared chronologically. No patient characteristics were significantly different among the three groups. The gallbladder was involved in about half of the patients in each group, and metastatic biliary tract cancer was present in three quarters of the enrollees. In Group A, 5-fluorouracil-based chemotherapies were primarily selected as first-line chemotherapy, and only 24% were treated with second-line chemotherapy. In Group B, gemcitabine or S-1 monotherapy was mainly introduced as first-line chemotherapy, and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy. In Group C, the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy, and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy. The median time-to-progressions were 4.4 mo, 3.5 mo and 5.9 mo in Groups A, B and C, respectively (4.4 mo vs 3.5 mo vs 5.9 mo, P < 0.01). The median overall survivals were 7.1, 7.3, and 11.7 mo in Groups A, B and C (7.1 mo vs 7.3 mo vs 11.7 mo, P = 0.03). Induction rates of all three drugs (gemcitabine, platinum analogs, and fluoropyrimidine) in Groups A, B and C were 4%, 2% and 27% (4% vs 2% vs 27%, P < 0.01). The prognosis of unresectable biliary tract cancer has improved recently. Using three effective drugs (gemcitabine, platinum analogs, and fluoropyrimidine) may improve the prognosis of this cancer.


Quantitative Evaluation of Protein Heterogeneity within Herpes Simplex Virus 1 Particles.
Several virulence genes have been identified thus far in the herpes simplex virus 1 genome. It is also generally accepted that protein heterogeneity among virions further impacts viral fitness. However, linking this variability directly with infectivity has been challenging at the individual viral particle level. To address this issue, we resorted to flow cytometry (flow virometry), a powerful approach we recently employed to analyze individual viral particles, to identify which tegument proteins vary and directly address if such variability is biologically relevant. We found that the stoichiometry of the UL37, ICP0, and VP11/12 tegument proteins in virions is more stable than the VP16 and VP22 tegument proteins, which varied significantly among viral particles. Most interestingly, viruses sorted for their high VP16 or VP22 content yielded modest but reproducible increases in infectivity compared to their corresponding counterparts containing low VP16 or VP22 content. These findings were corroborated for VP16 in short interfering RNA experiments but proved intriguingly more complex for VP22. An analysis by quantitative Western blotting revealed substantial alterations of virion composition upon manipulation of individual tegument proteins and suggests that VP22 protein levels acted indirectly on viral fitness. These findings reaffirm the interdependence of the virion components and corroborate that viral fitness is influenced not only by the genome of viruses but also by the stoichiometry of proteins within each virion.IMPORTANCE The ability of viruses to spread in animals has been mapped to several viral genes, but other factors are clearly involved, including virion heterogeneity. To directly probe whether the latter influences viral fitness, we analyzed the protein content of individual herpes simplex virus 1 particles using an innovative flow cytometry approach. The data confirm that some viral proteins are incorporated in more controlled amounts, while others vary substantially. Interestingly, this correlates with the VP16 trans-activating viral protein and indirectly with VP22, a second virion component whose modulation profoundly alters virion composition. This reaffirms that not only the presence but also the amount of specific tegument proteins is an important determinant of viral fitness.


Thermodynamical scaling of the glass transition dynamics.
Classification of glass-forming liquids based on the dramatic change in their properties upon approach to the glassy state is appealing, since this is the most conspicuous and often-studied aspect of the glass transition. Herein, we show that a generalized scaling, log (tau) proportional, variant T-1 V-gamma, where gamma is a material constant, yields superpositioning for ten glass formers, encompassing van der Waals molecules, associated liquids, and polymers. The exponent gamma reflects the degree to which volume governs the temperature and pressure dependence of the relaxation times.


Psychiatry in the emergency room: one year period of clinical experience.
We examined the psychiatric consultations carried out over one year at the Emergency Room (ER) of the hospital of Perugia, with the aim of describing the epidemiologic characteristics of patients with any psychiatric illness and their management. We also assessed the distribution of psychiatric emergencies over this year of observation. We recruited patients admitted to the ER, between July 2011 and June 2012, for which a psychiatric consultation was required. We used the t-test for continuous variables. Categorical variables were analyzed with the chi-squared test and the Fisher exact test. We considered significant test results with p<0.05. The post-hoc analyses were carried out with Bonferroni or Sidak correction. Statistical analyses were performed using STATA 12.0. Neurotic, stress-related and somatoform disorders were the most represented. The most frequent approach to patients with psychiatric complaints did not imply the use of psychopharmacological treatments or coercive interventions. No particular seasonality of psychopathology was observed. One of the fundamental aspects of the psychiatric intervention is empathy along with the attempt to enter into a relationship with the patient, in order to share, where possible, the therapeutic project, particularly in the case the of patients with acute and severe psychiatric illnesses.


Remission of porphyria cutanea tarda after anastrozole treatment of breast cancer.
Porphyria cutanea tarda (PCT) is sometimes precipitated or aggravated by increased exposure to estrogen, estrogen-like compounds, or tamoxifen. We report the case of a 37-year-old white woman who developed sporadic PCT after she took oral contraceptives for 10 years. She was heterozygous for the common H63D mutation of the hemochromatosis-associated HFE gene. The PCT responded partially to the cessation of oral contraceptives and to phlebotomy therapy to maintain low iron stores, but only remitted after she received anastrozole therapy for management of adenocarcinoma of the breast at age 59 years. The pertinence of HFE mutations, anastrozole and tamoxifen treatment, and chemotherapy to the development and management of PCT in women with breast cancer is discussed.


Bulk and interfacial properties in colloid-polymer mixtures.
Large-scale Monte Carlo simulations of a phase-separating colloid-polymer mixture are performed and compared to recent experiments. The approach is based on effective interaction potentials in which the central monomers of self-avoiding polymer chains are used as effective coordinates. By incorporating polymer nonideality together with soft colloid-polymer repulsion, the predicted binodal is in excellent agreement with recent experiments. In addition, the interfacial tension as well as the capillary length are in quantitative agreement with experimental results obtained at a number of points in the phase-coexistence region, without the use of any fit parameters.


Radioautographic localization of 3H-fucose incorporation into bone cells in cultured calvaria.
Radioautographic procedures were used to examine the incorporation of 3H-fucose into macromolecular material in bone organ cultures. Radioautography demonstrated that silver grains were first apparent in the paranuclear area of osteoclasts, and continued to increase in number over osteoclasts throughout the culture period. Silver grains associated with osteoclasts were later found on the side adjacent to bone and the adjacent bone surface. Osteoblasts, pre-osteoblasts and fibroblasts of the fibrous periosteum incorporated some 3H-fucose as evidenced by labelling in the later time periods. At later incubation periods, labelled material was found in the underlying bone below osteoblasts, demonstrating the active elaboration of bone matrix glycoproteins. Osteocytes were labelled only after the longest period of incubation.


Ultra-thin alumina and silicon nitride MEMS fabricated membranes for the electron multiplication.
In this paper we demonstrate the fabrication of large arrays of ultrathin freestanding membranes (tynodes) for application in a timed photon counter (TiPC), a novel photomultiplier for single electron detection. Low pressure chemical vapour deposited silicon nitride (Si x N y ) and atomic layer deposited alumina (Al2O3) with thicknesses down to only 5 nm are employed for the membrane fabrication. Detailed characterization of structural, mechanical and chemical properties of the utilized films is carried out for different process conditions and thicknesses. Furthermore, the performance of the tynodes is investigated in terms of secondary electron emission, a fundamental attribute that determines their applicability in TiPC. Studied features and presented fabrication methods may be of interest for other MEMS application of alumina and silicon nitride as well, in particular where strong ultra-thin membranes are required.


Identification of SNP loci and candidate genes genetically controlling norisoprenoids in grape berry based on genome-wide association study.
Obtaining new grapevine varieties with unique aromas has been a long-standing goal of breeders. Norisoprenoids are of particular interest to wine producers and researchers, as these compounds are responsible for the important varietal aromas in wine, characterized by a complex floral and fruity smell, and are likely present in all grape varieties. However, the single-nucleotide polymorphism (SNP) loci and candidate genes genetically controlling the norisoprenoid content in grape berry remain unknown. To this end, in this study, we investigated 13 norisoprenoid traits across two years in an F1 population consisting of 149 individuals from a hybrid of Vitis vinifera L. cv. Muscat Alexandria and V. vinifera L. cv. Christmas Rose. Based on 568,953 SNP markers, genome-wide association analysis revealed that 27 candidate SNP loci belonging to 18 genes were significantly associated with the concentrations of norisoprenoid components in grape berry. Among them, 13 SNPs were confirmed in a grapevine germplasm population comprising 97 varieties, including two non-synonymous mutations SNPs within the VvDXS1 and VvGGPPS genes, respectively in the isoprenoid metabolic pathway. Genotype analysis showed that the grapevine individuals with the heterozygous genotype C/T at chr5:2987350 of VvGGPPS accumulated higher average levels of 6-methyl-5-hepten-2-one and β-cyclocitral than those with the homozygous genotype C/C. Furthermore, VvGGPPS was highly expressed in individuals with high norisoprenoids concentrations. Transient overexpression of VvGGPPS in the leaves of Vitis quinquangularis and tobacco resulted in an increase in norisoprenoid concentrations. These findings indicate the importance of VvGGPPS in the genetic control of norisoprenoids in grape berries, serving as a potential molecular breeding target for aroma.


Cytochrome P-450 mediated metabolism in active murine systemic lupus erythematosus.
In a comparison of NZB/NZW female mice either with active systemic lupus erythematosus (SLE) (28-33 weeks of age) or without overt SLE (7-13 weeks), the hepatic microsomal activities of ethoxycoumarin O-deethylation and aminopyrine N-demethylation were decreased 32% (p less than 0.05) and 28% (p less than 0.03), respectively, and cytochrome P-450 levels were decreased 34% (p less than 0.01) in the mice with active SLE. These changes were not associated with age differences alone in 2 nonautoimmune strains. Active murine SLE is thus associated with significant depressions in both hepatic cytochrome P-450 levels and microsomal enzyme activities. The metabolism of drugs and endogenous substrates may thus be impaired in active SLE.


Effectiveness of an AIDS education program on knowledge, attitudes, and practices of state employees.
While the number of companies employing HIV infected workers has more than tripled since 1985, only 10% of American corporations have policies for dealing with persons infected with HIV. The occupational health nurse is in a unique position to influence the attitudes, knowledge, and behaviors of workers in promoting a safe and productive work environment and reducing high risk activities. While the number of all individuals with AIDS has increased 4,000% in the last 6 years, there has been no reported increase in the percentage of HIV infected health care workers as compared with other occupations. An evaluation of an AIDS educational program revealed that while knowledge base was fairly high, statistically significant improvements were noted from pretest to retest in specific knowledge, attitude, and practice items.


Rheumatoid vasculitis: an update.
Rheumatoid vasculitis is the most serious extra-articular complication of rheumatoid arthritis, with high morbidity and mortality noted in multiple prior reports. Recent studies have expanded our understanding of this entity in the era of modern immunosuppressive therapy. New clinical predictors and possible protective factors have also been identified. This review provides an update on the epidemiology, clinical correlates, predictors, therapy and outcomes of rheumatoid vasculitis over the past decade. During this time, there has been increasing use of the treat-to-target management practices and incorporation of biologic response modifiers that have revolutionized rheumatoid arthritis treatment with better disease control and overall improved outcomes. The incidence of rheumatoid vasculitis has declined significantly in the past several decades, but morbidity and mortality continue to remain high, despite aggressive treatment with cyclophosphamide or biologic agents. Hydroxychloroquine and low-dose aspirin may have a protective role. There is ongoing debate about the role of newer biological therapies in prevention, treatment or even as a trigger for rheumatoid vasculitis. Rheumatoid vasculitis remains a rare yet challenging extra-articular manifestation of rheumatoid arthritis with high morbidity and mortality, despite aggressive use of disease-modifying therapy.


Remarkable improvement of hemodynamics by continuous hemodiafiltration in patients after operation for thoracic aortic dissection.
Severe circulatory failure after cardiovascular surgery is occasionally difficult to treat and the mortality risk is high. Systemic inflammatory response syndrome (SIRS) is one of the complications resulting in circulatory failure and, continuous hemodiafiltration (CHDF) seems to be a potentially effective treatment to improve the critical condition by removing proinflammatory cytokines. We present two recent cases of SIRS with critical circulatory failure which were successfully treated by CHDF after operation for thoracic aortic dissection.


Optimum Screw Configuration for the Fixation of Sanders Type IIC Tongue-Type Fractures? A Biomechanical Study.
The minimally invasive technique (percutaneous screw fixation) is one of the options for treating tongue-type IIC fractures successfully. The aim of this study was to assess the biomechanics of four different screw configurations used for the fixation of tongue-type IIC calcaneal fractures. Identical osteotomies, recapitulating a type IIC injury, were created in synthetic calcaneus specimens using a saw. The specimens were randomly assigned to one of the four fixation groups (n = 7 per group): two divergent screws, two parallel screws, two parallel screws plus one screw axially oriented toward the sustentaculum tali, and three parallel screws. A load test was performed on all of the groups, and the specimens were then tested using offset axial loading until 2, 4, and 5 mm of fracture displacement occurred. Mean force values for the three-parallel screw construct at 2-, 4-, and 5-mm fracture displacements were found to be significantly higher compared with those for the other groups. The use of a three-parallel screw construct seems to provide more stability in the treatment of tongue-type IIC fractures.


Influenza vaccine effectiveness in households with children during the 2012-2013 season: assessments of prior vaccination and serologic susceptibility.
There are recognized needs to identify determinants of influenza vaccine effectiveness (VE), including the effect of repeated annual vaccination. We recruited 321 households with 1426 members, including 833 children, and followed them during the 2012-2013 influenza season; specimens were collected from subjects with reported acute respiratory illnesses. We estimated the effectiveness of documented influenza vaccination in preventing laboratory-confirmed influenza, using adjusted Cox proportional hazards models. Antibody titers in a subset of subjects were determined by a hemagglutination inhibition assay to determine the subjects' preseason susceptibility to influenza. Influenza was identified in 76 (24%) households and 111 (8%) individuals. VE point estimates indicated significant protection in adults (48%; 95% confidence interval [CI], 1%-72%), similar protection in children aged 9-17 years (49%; 95% CI, -16% to 78%), but no evidence of effectiveness in children aged <9 years (-4%; 95% CI, -110% to 49%). Lower VE was observed in those vaccinated in both the current and prior seasons, compared with those vaccinated in the current season only; susceptibility titers against type A but not type B were consistent with this observation. Residual protection from vaccination in the prior season was indicated by both VE and serologic results. Prior vaccination appears to modify VE by both residual protection and reduced vaccine response.


Macroalbuminuria and microalbuminuria: do both predict renal and cardiovascular events with similar strength?
Until recently, most attention given to patients with macroalbuminuria has focused on their worse renal prognosis, while in contrast, patients with microalbuminuria were mostly considered to be at increased cardiovascular risk. In recent years, however, evidence has been accumulating that this distinction between the 2 -- either large or small quantities of albumin in the urine -- is not that clear. On the one hand, various studies have reported that macroalbuminuria also bears an increased cardiovascular risk. Interestingly, the extent to which albumin loss can be reduced in patients with macroalbuminuria is associated not only with a better renal prognosis, but also similarly with a better cardiovascular prognosis. On the other hand, patients with microalbuminuria not only have an impaired cardiovascular, but also an impaired renal, prognosis. These latter findings in microalbuminuria are especially of importance for the renal community, as screening for albuminuria is not carried out systematically even in patients with increased risk for microalbuminuria, such as those with diabetes and those with essential hypertension. When promoting routine screening for albuminuria, one should realize, moreover, that such projects will most likely be much more cost-effective when directed to preventing not only renal end points, but also CV end points.


Functional mapping of GABA(B)-receptor subtypes in the thalamus.
The thalamus plays an important role in attention mechanisms and the generation of brain rhythms. gamma-Aminobutyric acid type B (GABA(B)) receptors are known to regulate the main output neurons of the thalamus, the thalamocortical relay (TCR) cells. However, the contributions of the two predominant GABA(B)-receptor subtypes, GABA(B(1a,2)) and GABA(B(1b,2)), to the control of TCR cell activity are unknown. Here, we used genetic and electrophysiological methods to investigate subtype-specific GABA(B) effects at the inputs to TCR cells. We found that mainly GABA(B(1a,2)) receptors inhibit the release of glutamate from corticothalamic fibers impinging onto TCR cells. In contrast, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors efficiently inhibit the release of GABA from thalamic reticular nucleus (TRN) neurons onto TCR neurons. Likewise, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors efficiently activate somatodendritic K(+) currents in TCR cells. In summary, our data show that GABA(B(1b,2)) receptors cannot compensate for the absence of GABA(B(1a,2)) receptors at glutamatergic inputs to TCR cells. This shows that the predominant association of GABA(B(1a,2)) receptors with glutamatergic terminals is a feature that is preserved at several brain synapses. Furthermore, our data indicate that the cognitive deficits observed with mice lacking GABA(B(1a,2)) receptors could to some extent relate to attention deficits caused by disinhibited release of glutamate onto TCR neurons.


The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines.
The cardiac potassium channel encoded by the human ether-à-go-go related gene (HERG) is blocked by a diverse array of common therapeutic compounds. Even transient exposure to such agents may provoke the life-threatening cardiac arrhythmia torsades de pointes in some, but not all, individuals. Although the molecular and genetic factors predicting such wide variability in drug response remain unclear, known sequence variations within the coding region of HERG do not explain the adverse drug response in many cases. Although other proteins can modulate HERG function, no studies have identified protein partners capable of limiting the pharmacological sensitivity of HERG. Here we show that KCR1, a protein identified previously in rat cerebellum, is a plasma membrane-associated protein expressed at the RNA level in the human heart and can be immunoprecipitated with HERG. Functionally, KCR1 reduces the sensitivity of HERG to classic proarrhythmic HERG blockers (sotalol, quinidine, dofetilide) in both cardiac and noncardiac cell lines. We propose that KCR1, when coupled to HERG, may limit the sensitivity of HERG to proarrhythmic drug blockade and may be a rational target for modifying the proarrhythmic effects of otherwise clinically useful compounds.


One-day FISH approach for the high-speed determination of HER2 gene copy status in breast carcinoma.
Fluorescence in situ hybridization (FISH) is a commonly used method to detect chromosomal aberrations, for example, to assess human epidermal growth factor receptor 2 (HER2) gene status in breast carcinoma. The classical FISH approach requires overnight incubation for proper hybridization result. Tissue morphologic features are varying because of aggressive pretreatment and application of high temperatures. To eliminate some of the methodological problems, a new 1-day FISH method was recently introduced. The aim of our study was to evaluate the utility of the Instant Quality FISH with the conventional FISH kit from the same provider (Dako pharmDx) for determination of HER2 status. We performed in situ hybridization on the same 40 invasive breast carcinoma samples with both probe kits, and HER2/CEN17 and chromosome 17/cell nucleus ratios were calculated. FISH signal stability was also tested by the reassessment of the slides after 2 months storage. The accordance regarding HER2 gene amplification status between the 2 FISH kits tested was 100%. There was an excellent correlation between HER2/CEN17 ratios with a concordance correlation coefficient of 0.958 and correlation coefficient (R) of 0.959. The 1-day HER2 Instant Quality FISH diagnostic kit points with fast and stable reaction showing the same result in the diagnostic practice when compared with the conventional overnight FISH method.


Characteristics of minimal hepatic encephalopathy.
The term minimal hepatic encephalopathy refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy. Use of this term emphasizes the fact that the entity of hepatic encephalopathy is a single syndrome with quantitatively distinct features relating to severity. The absence of clinical evidence of hepatic encephalopathy is key to the diagnosis and can only be determined by a detailed assessment of the patients' history and a comprehensive neurological assessment of consciousness, cognitive, and motor function. The neuropsychological features of minimal hepatic encephalopathy point to a disorder of executive functioning, particularly selective attention and psychomotor speed, but other abnormalities may be observed. Alterations in electrophysiological variables have been described; endogenous evoked potentials are, in principle, more likely to reflect the presence of minimal hepatic encephalopathy, since they reflect cognitive phenomena rather than mere stimulus conduction but the specificity of the changes observed is unclear at present. Changes have also been described in the execution of diadochokinetic movements and in the capacity to discriminate flickering light, both of which may have diagnostic potential. The changes observed in cerebral blood flow and metabolism in SPET, PET, and 1H and 31P MRS studies reflect the pathogenic process that underlies the condition rather than providing diagnostic information. Similarly, the morphological brain abnormalities identified in this population, including mild brain oedema, hyperintensity of the globus pallidus and other subcortical nuclei observed in cerebral MR studies, and the central and cortical atrophy observed in neural imaging studies, are unlikely to have diagnostic utility. The presence of minimal hepatic encephalopathy is not without clinical consequence; it has a detrimental effect on health-related quality of life, the ability to perform complex tasks such as driving, and on outcome.


Superluminal pulse propagation through one-dimensional photonic crystals with a dispersive defect.
The propagation of a pulse through one-dimensional photonic crystals that contain a dispersive and absorptive defect layer doped with two-level atoms is discussed. The dynamical evolution of the pulse inside the photonic crystal is presented. Superluminal negative group velocity (the peak appears at the exit end before it reaches the input end) is discovered. Although the group velocity is larger than c and even negative, the velocity of energy propagation never exceeds the vacuum light speed. The appearance of the superluminal advance or subluminal delay of the pulse peak inside the photonic crystal or at the exit end is due to the wave interference from Bragg reflections.


The effect of endodontic access cavity preparation and subsequent restorative procedures on incisor crown retention.
Endodontic treatment often will require access through existing crowns. This study was undertaken to determine whether endodontic access cavity preparation affected the retention of crowns in anterior teeth and then to determine whether this retention can be regained by amalgam or post-retained amalgam restorations. Twenty extracted human incisors were mounted in acrylic blocks and prepared for crowns. Metal copings were fabricated and cemented with zinc phosphate cement and the forces required to displace the copings after various procedures were measured with a tensile testing machine. Retention values for all stages were compared with the initial retentive value for each coping without an access cavity which was set at 100 per cent. Group one specimens had the following means: copings with access cavity, 85.64 +/- 28.65 per cent of the initial values; amalgam flush with lingual dentine, 95.81 +/- 36.2 per cent; amalgam flush with coping, 114.89 +/- 34.5 per cent. Group two means were: copings with access cavity, 89.95 +/- 21.42 per cent; posts and amalgam, 177.37 +/- 77.5 per cent. Statistical analysis with the two sample t test showed that retention with post-retained amalgam restorations showed significantly higher values when compared with access cavities without restorations (p < 0.05). Retention values for post-retained restorations were significantly different from those just using amalgam. This study demonstrated that endodontic access cavities reduced the retention of the crowns, and subsequent restoration with amalgam or a post can regain the retention.(ABSTRACT TRUNCATED AT 250 WORDS)


[Influence of BCG on the production of antibody-forming cells in the primary and secondary immune response against sheep erythrocytes in the mouse].
Adult mice react with an increased production of PFC (plaque-forming cells) against sheep erythrocytes (SE). in the primary immune response after application of BCG. Animals receiving 0,5 mg of BCG 10 days before SE show an increase in direct PFC of more than 50%. No effect was observed after injecting BCG 14 or 5 days before SE or using a dose of 0,1 mg of BCG. The results indicate that the effect of BCG on the humoral immune response is influenced by the interval between application of BCG and the SE as well as the BCG-dose. By contrast, BCG had no significant influence on the secondary humoral immune response. In a few cases the immune response seemed to be suppressed.


The association of promoter gene polymorphisms of the tumor necrosis factor-α and interleukin-10 with severity of lactic acidosis during liver transplantation surgery.
Orthotopic liver transplantation (OLT) is a major operation, causing cytokine release and other inflammatory responses that can contribute to postreperfusion syndrome occurrence. During the systemic inflammatory response syndrome, increased lactate levels result from excessive cytokine production despite normal oxygen delivery and carbohydrate metabolism. The goal of the study was to determine the relationship between genetic polymorphisms in interleukin (IL)-10 (-1082G/A) or tumor necrosis factor (TNF)-α (-376 G/A) and lactate levels in patients during OLT surgery. This prospective observational study in 40 consecutive adult patients who underwent OLT documented lactic acid levels at 5 times: Immediately after induction of anesthesia, at the end of the pre-anhepatic phase, at the end of the anhepatic phase, 1 hour after reperfusion, and at the end of surgery. Polymerase chain reaction (PCR; RFLP methodology) was used to examine IL-10 (-1082G/A) and TNF-α (-376 G/A) gene polymorphisms. Carriers of the IL-10/TNF-α genotype combination GG/GG showed significantly different changes in lactate levels at 1 hour after reperfusion and at the end of surgery. Lactate levels were significantly higher among patients heterozygous for TNF-α (AG genotype) compared with patients homozygous for TNF-α (GG genotype) at same times. In contrast, there was no significant difference among IL-10 polymorphic genotypes (-1082G/A). Genetic factors play a role in the development of lactic acidosis after OLT. IL-10 (-1082G/A) and TNF-α (-376 G/A) gene polymorphisms could influence the variability of lactate levels after liver transplantation surgery.


Thermal stress in teeth.
Observations of crack damage in the tooth structure from in vivo studies and in vitro experimental thermal cycling studies were combined with numerical analysis techniques to identify and isolate the influence of thermal stresses on the creation and propagation of cracks in teeth. The factors considered in this study included: (a) variations in tooth type or geometry (molar, bicuspid, etc.), (b) tooth age, (c) material properties of the tooth, (d) the magnitude of the change in the temperature of the environment surrounding the tooth, and (e) the thermal resistance between the tooth and the medium surrounding the tooth.


Tetracycline-regulated expression of VEGF-A in beta cells induces angiogenesis: improvement of engraftment following transplantation.
Early revascularization of pancreatic islet cells after transplantation is crucial for engraftment, and it has been suggested that vascular endothelial growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to vascular tumor formation. Here we have explored the role of temporal VEGF expression, controlled by a tetracycline (TC)-regulated promoter, on revascularization and engraftment of genetically modified beta cells following transplantation. To this end, we modified the CDM3D beta cell line using a lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell proliferation, and stimulated insulin secretion were assessed in vitro. VEGF secretion was increased in TET and PGK cells, and VEGF delivery resulted in angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion by the three cell types was similar. We used a syngeneic mouse model of transplantation to assess the effects of this controlled VEGF expression in vivo. Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular density, and cellular mass were evaluated. Increased expression of VEGF resulted in significantly better revascularization and engraftment after transplantation when compared to control cells. In vivo, there was a significant increase in vascular density in grafted TET and PGK cells versus control cells. Moreover, the time for diabetic mice to return to normoglycemia and the stimulated plasma glucose clearance were also significantly accelerated in mice transplanted with TET and PGK cells when compared to control cells. VEGF was only needed during the first 2-3 weeks after transplantation; when removed, normoglycemia and graft vascularization were maintained. TC-treated mice grafted with TC-treated cells failed to restore normoglycemia. This approach allowed us to switch off VEGF secretion when the desired effects had been achieved. TC-regulated temporal expression of VEGF using a gene therapy approach presents a novel way to improve early revascularization and engraftment after islet cell transplantation.


Domain- and site-specific phosphorylation of bovine NF-L by Rho-associated kinase.
Rho-associated kinase (Rho-kinase), the putative target of the small GTP-binding protein Rho, phosphorylated neurofilament protein (NF-L) in vitro with approximately 1 mole phosphate per mole NF-L. Phosphorylated NF-L no longer formed the 10 nm filaments, and NF-L filaments were phosphorylated with a result of nearly complete disassembly. NF-L phosphorylated by Rho-kinase was digested with trypsin, and digested fragments were assigned by MALDI/TOF. Unique phosphorylation sites were found at Ser-26 and Ser-57 in the head domain of NF-L. These results indicate that domain- and site-specific phosphorylation by Rho-kinase may regulate the assembly-disassembly of NF-L filaments.


Functional characterisation of mycobacterial DNA gyrase: an efficient decatenase.
A rapid single step immunoaffinity purification procedure is described for Mycobacterium smegmatis DNA gyrase. The mycobacterial enzyme is a 340 kDa heterotetrameric protein comprising two subunits each of GyrA and GyrB, exhibiting subtle differences and similarities to the well-characterised Escherichia coli gyrase. In contrast to E.coli gyrase, the M.smegmatis enzyme exhibits strong decatenase activity at physiological Mg2+ concentrations. Further, the enzymes exhibited marked differences in ATPase activity, DNA binding characteristics and susceptibility to fluoroquinolones. The holoenzyme showed very low intrinsic ATPase activity and was stimulated 20-fold in the presence of DNA. The DNA-stimulated ATPase kinetics revealed apparent K0.5 and kcat of 0.68 mM and 0.39 s(-1), respectively. The dissociation constant for DNA was found to be 9.2 nM, which is 20 times weaker than that of E.coli DNA gyrase. The differences between the enzymes were further substantiated as they exhibited varied sensitivity to moxifloxacin and ciprofloxacin. In spite of these differences, mycobacterial DNA gyrase is a functionally and mechanistically conserved enzyme and the variations in activity seem to reflect functional optimisation for its physiological role during mycobacterial genome replication.


Predictors of weight change in overweight patients with myocardial infarction.
Weight loss is recommended among overweight survivors of myocardial infarction (MI). This study describes patterns of weight change among overweight patients with MI and identifies factors associated with weight change. A prospective cohort of 1253 overweight or heavier (body mass index [BMI] > or = 25 kg/m2) post-MI patients were enrolled in the 19-center PREMIER study and followed up for 1 year to determine changes in weight. Patients were categorized at 1 month as overweight (BMI = 25-29.9 kg/m2), obese (BMI = 30-39.9 kg/m2), or morbidly obese (BMI > or = 40 kg/m2). Unadjusted percent weight change was assessed at 1 year, and multivariable linear regression was used to identify independent correlates of change. Mean weight change was -0.2% and varied by the severity of baseline obesity (+0.4% for overweight patients, -0.5% for obese patients, and -3.7% for morbidly obese patients [P < .001]). Multivariable analyses revealed the following to be significantly associated with weight change: depression 1 month post-MI (+2.7%, P = .001), lack of health insurance (+2%, P = .01), smoking cessation 1 month post-MI (+2.7% vs current smokers, P < .001), morbid obesity (+4.7% vs overweight patients, P < .0001), and increasing age (-0.8% per decade, P = .001). An interaction between smoking cessation and weight class was detected in that overweight patients who quit had a mean increase of 5.3% (95% CI 3.1%-7.4%), whereas no significant change was observed among obese and morbidly obese patients who quit. Although post-MI patients had negligible weight loss over 1 year, several sociodemographic, clinical, and lifestyle characteristics were associated with weight change. New, targeted interventions will likely be needed to improve weight management after an MI.


Myocardial infarction without coronary occlusion. A study with a new experimental method in sheep.
An experimental method for induction of myocardial infarction in sheep is described. This leads to local infarction without arteriographically demonstrable lesions in the coronary arteries. A 0.95 mm thick thermosonde is introduced into a coronary artery through a catheter. The tip of the thermosonde is heated to 45-65 degrees C for 1-2 min and the thermosonde is then removed. On heating of the tip, infarction occurs instantaneously, as observed both macro- and microscopically and at left ventricular angiography. The thermosonde method described makes it possible to induce myocardial infarction in sheep in a reproducible way and is therefore applicable to studies of the pathogenesis of infarction. This justifies its use in investigations of the effect of myocardial infarction on the anatomy and function of the left ventricle and coronary arteries.


Absorption, distribution, and excretion of [14C]patulin by rats.
Adult rats of both sexes were given a single oral dose of [14C] patulin and were sacrificed at various time intervals from 4 hr to 7 days following administration of the mycotoxin. Two groups of rats were employed; the treated group had been exposed to daily oral doses of unlabeled patulin (dissolved in pH 5.0 citrate buffer) in utero and for 41-66 wk after weaning, while the controls were given the buffer only throughout gestation and for 38-81 wk after weaning. Approximately 49% of the administered 14C radioactivity was recovered from feces and 36% from urine within 7 days after dosing. Most of the excretion of labeled material occurred within the first 24 hr. All of the 14C activity detected in the urine samples was either metabolites and/or conjugates of the original [14C]patulin. About 1-2% of the total radioactivity was recovered as 14CO2 from expired air. Carbon-14 radioactivity in various tissues and organs was determined throughout the 7 day period; the most significant retention site was the red blood cells.


PAH degradation and redox control in an electrode enhanced sediment cap.
Capping is typically used to control contaminant release from the underlying sediments. However, the presence of conventional sediment caps will often eliminate or slow natural degradation that might otherwise occur at the surface sediment. The objective of this study was to explore the potential of a novel reactive capping, an electrode enhanced cap for the remediation of PAH contaminated sediment. The study on electrode enhanced biodegradation of PAH in slurries showed that naphthalene concentration decreased from ~1000 μg/L to ~50 μg/L, and phenanthrene decreased from ~150 μg/L to ~30 μg/L in ElectroBioReactor within 4 days, and the copy numbers of PAH degrading genes increased by almost 2 orders of magnitude. In a cap microcosm, two carbon electrodes were emplaced within a sediment cap with an applied potential of 2 V. The anode was placed at the sediment-cap interface encouraging oxidizing conditions. Oxidation and Reduction Potential (ORP) profiles showed redox potential approximately 60-100 mV higher at the sediment-cap interface with the application of voltage than in controls. Vertical profiles of phenanthrene porewater concentration were obtained by PDMS-coated fiber, and results showed that phenanthrene at the depth of 0-0.5 cm below the anode was degraded to ~70% of the initial concentration within 10 weeks. PAH degrading genes showed an increase of approximately 1 order of magnitude at the same depth. The no power controls showed no degradation of PAH. These findings suggest that electrode enhanced capping can be used to control redox potential, provide microbial electron acceptor, and stimulate PAH degradation.


Hemodilution--possibilities and safety aspects.
Normovolemic hemodilution is an essential part of the overall strategy to avoid exposure of patients to the hazards of homologous blood transfusions. It includes beneficial effects on the flow properties and flow conditions of blood. A hematocrit of 30% can be regarded as an optimal compromise between the fluidity and the oxygen content of the blood. Compensatory responses such as increased cardiac output and stroke volume occur following hemodilution. In patients with compromised coronary reserve the degree of hemodilution that is tolerated has to be carefully considered. Therefore specific selection criteria for patients to be preoperatively hemodiluted are needed. For reasons of safety, efficiency and practicability colloid solutions rather than crystalloid solutions should be used for intentional hemodilution.


Effect of MK-507 on aqueous humor dynamics in normal human eyes.
The effects of the topical carbonic anhydrase inhibitor, MK-507, on aqueous humor dynamics were studied in 6 normal volunteers. As a baseline study, intraocular pressure (IOP) was determined and aqueous protein concentration was checked hourly by laser flare-cell photometry from 0900 to 1800 hours. One week later, IOP and aqueous protein concentration were determined in the same subjects on the same time schedule with instillation of 1% MK-507 at 1100 hours. After one more week, the same experiment was carried out with oral administration of acetazolamide at a dose of 250 mg at 1100 hours. Topical MK-507 showed the maximum IOP reduction at 3 hours and increased aqueous protein concentration reaching its maximum at 4 hours. Oral acetazolamide showed the maximum IOP reduction at 2 hours and the maximum increase in aqueous protein concentration was at 3 hours. Although the peak effect on IOP or aqueous protein concentration did not significantly differ between topical MK-507 and oral acetazolamide, only oral acetazolamide showed a significant effect at 1 hour. These results suggested that topical MK-507 reduced the aqueous humor production, but it took more time for the ocular effect to become manifest than after administration of oral acetazolamide.


Relationship between the Central and Regional Pulse Wave Velocity in the Assessment of Arterial Stiffness Depending on Gender in the Geriatric Population.
Artery stiffness is a risk factor for cardiovascular disease (CVD). The measurement of pulse wave velocity (PWV) between the carotid artery and the femoral artery (cfPWV) is considered the gold standard in the assessment of arterial stiffness. A relationship between cfPWV and regional PWV has not been established. The aim of this study was to evaluate the influence of gender on arterial stiffness measured centrally and regionally in the geriatric population. The central PWV was assessed by a SphygmoCor XCEL, and the regional PWV was assessed by a new device through the photoplethysmographic measurement of multi-site arterial pulse wave velocity (MPPT). The study group included 118 patients (35 males and 83 females; mean age 77.2 ± 8.1 years). Men were characterized by statistically significantly higher values of cfPWV than women (cfPWV 10.52 m/s vs. 9.36 m/s; p = 0.001). In the measurement of regional PWV values using MPPT, no such relationship was found. Gender groups did not statistically differ in the distribution of atherosclerosis risk factors. cfPWV appears to be more accurate than regional PWV in assessing arterial stiffness in the geriatric population.


Science, hormesis and regulation.
While hormesis is an intriguing scientific hypothesis, this paper argues that it is not yet an acceptable basis for policy-making. Two reasons are given for this assessment. First, although hormesis has suggestive explanatory power, it does not yet have the predictive successes that indicate a general reliability sufficient for policy-making. Second, the regulatory agenda for chemical exposures is usually focused, for good ethical reasons, on protecting people from involuntary and potentially harmful exposures, rather than focused on maximizing public health benefits.


Nutritional status affects the microRNA profile of the hypothalamus of female sheep.
Recent studies on the seasonal regulation of the oestrous cycle in sheep have focussed mainly on the responses to photoperiod. However, the brain systems that control reproductive activity also respond to nutritional inputs, although the molecular mechanisms involved are not completely understood. One possibility is that small, non-coding RNAs, such as micro-RNAs (miRNAs), have significant influence. In the present study, the amounts and characteristics of miRNAs in hypothalamus from oestrous and anestrous ewes, fed low- or high-nutrient diets, were compared using Illumina HiSeq sequencing technology. In total, 398 miRNAs, including 261 novel miRNAs, were identified in ewes with an enhanced nutritional status (HEN), whereas 384 miRNAs, including 247 novel miRNAs, were identified in the ewes with a lesser nutritional status (HAN). There were eight conserved and 140 novel miRNAs expressed differentially between the two libraries. Based on quantitative real-time polymerase chain reaction, six miRNAs were assessed to verify the accuracy of the library database. Moreover, the correlation between the miRNA target and several upstream and downstream genes in the oestrus-related pathways were also verified in hypothalamus nerve cells. According to the results, nutritional status plays an important role in oestrous regulation in sheep, and the hypothalamic processes and pathways induced by nutritional signals (folic acid and tyrosine) are different from those induced by photoperiodic regulation of oestrus. We have expanded the repertoire of sheep miRNAs that could contribute to the molecular mechanisms that regulate the initiation of oestrous cycles in anestrous ewes in response to the influence of nutritional status.


Antitumor and antimetastasis effects of carboplatin liposomes with polyethylene glycol-2000 on SGC-7901 gastric cell-bearing nude mice.
The present study aimed to analyze the characteristics of polyethylene glycol (PEG)ylated carboplatin liposomes (PL-CBPs), including size, stability, their release, entrapping and loading efficiencies, and their antitumor and antimetastatic effects on the lymph nodes. The PL-CBPs were prepared using PEG-2000 with the thin film hydration method. The liposome size and release, entrapping and loading efficiencies were detected by ultra-violet/visible spectrophotometry. A nude mouse model was established with the SGC-7901 gastric cell line to evaluate the antitumor effect of the PL-CBP. After 7 days, the mice were randomly divided into three groups (the control, CBP, and PL-CBP groups). CBP and PL-CBP were administered at a dose of 10 mg/kg for two consecutive cycles of treatment, 5 days apart, to their respective groups. In each group, two doses of 5 mg/kg were administered every 48 h. The tumor weight and volume were detected, and the food intake and body weight were measured during the administration. Apoptosis in the tumor cells was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and platinum (Pt) accumulation was detected by atomic absorption spectroscopy. Lastly, lymph node metastasis was evaluated by hematoxylin and eosin staining. The PL-CBPs were more stable when comapred with CBP alone, and the drug release efficiency was 0.7, 22.5, 48.7 and 65.1% at 37°C for 0, 12, 24 and 48 h. The results showed that the encapsulation efficiency was 85% and the loading efficiency was 0.15 mg/mg lipid. After 35 days, PL-CBP induced potent antitumor effects compared with the control and CBP groups (PL-CBP vs. control, P<0.01; PL-CBP vs. CBP, P<0.05). PL-CBP and CBP induced a lower and the lowest body weight and level of food intake, respectively, compared with the control group (CBP vs. control, P<0.05). The apoptosis rate and lymph node metastasis in the PL-CBP group was higher than that in the CBP and control groups (PL-CBP vs. control, P<0.01; PL-CBP vs. CBP, P<0.05). Pt accumulation in the tumors was higher in the PL-CBP group than in the CBP group (PL-CBP vs. CBP, P<0.05). The PL-CBPs were more stable in the circulation and could be released more slowly at the tumor site than compared with CBP injection. The PL-CBPs showed potent antitumor and antimetastatic effects on the lymph nodes.


Radiation-induced malignant mesenchymoma of the chest wall following treatment for breast cancer.
21 years after radiotherapy for breast cancer, a 63-year-old woman developed a malignant mesenchymoma of the chest wall. The total irradiation dose was 132 Gy. The first clinical symptom of this second malignancy was a slight irregular calcification around the implanted silicon protheses observed in a conventional chest X-ray. Radiation-induced sarcoma is a very rare complication of radiotherapy. In cases of chest wall calcification after radiation therapy further investigation should be carried out, because some patients with radiation-induced sarcoma could be saved, if an early diagnosis is reached.


[Reconstruction using pedicle and free flaps in partial or total resections of the hypopharyngeal-esophageal tract].
Modern surgical treatment of cancer of the hypopharyngo-esophageal cannot be conditioned by the reconstructive procedures. Reconstructive options are based on the size and position of the defect in this important anatomical region. Currently the reconstruction of the hypopharyngo-esophageal tract allows a rapid and suitable restoration of the vital functions, a low morbidity and shortened hospital stay. The purpose of this study was to compare the various reconstructive approaches in terms of morbidity and functional results. Between January 1990 and June 1994, 17 patients with hypopharyngo-esophageal tract malignancies and one with a stenosis received treatment. The reconstructive procedures included 19 flaps: five myocutaneous pectoralis major flaps, one myocutaneous trapezius flap, five deltopectoral flaps, one radial forearm free flap and seven free jejunal grafts. There were six complications: one total necrosis and two stenosis in the free jejunal grafts group, one partial necrosis and one dehiscence in two myocutaneous pectoralis major flaps and one stenosis in a deltopectoral flap. Based on our studies, we believe that the free jejunal graft is the first choice for total reconstruction of the hypopharyngo and cervical esophageal tract. However the radial forearm free flap is certainly a valid solution for subtotal hypopharyngo-esophageal reconstruction. Pedicled flaps and particularly the myocutaneous pectoralis major flaps are a good alternatives for limited reconstructions (< 50%) of the hypopharyngo-esophageal tract.


Synchronized imaging and acoustic analysis of the upper airway in patients with sleep-disordered breathing.
Progressive narrowing of the upper airway increases airflow resistance and can produce snoring sounds and apnea/hypopnea events associated with sleep-disordered breathing due to airway collapse. Recent studies have shown that acoustic properties during snoring can be altered with anatomic changes at the site of obstruction. To evaluate the instantaneous association between acoustic features of snoring and the anatomic sites of obstruction, a novel method was developed and applied in nine patients to extract the snoring sounds during sleep while performing dynamic magnetic resonance imaging (MRI). The degree of airway narrowing during the snoring events was then quantified by the collapse index (ratio of airway diameter preceding and during the events) and correlated with the synchronized acoustic features. A total of 201 snoring events (102 pure retropalatal and 99 combined retropalatal and retroglossal events) were recorded, and the collapse index as well as the soft tissue vibration time were significantly different between pure retropalatal (collapse index, 2 ± 11%; vibration time, 0.2 ± 0.3 s) and combined (retropalatal and retroglossal) snores (collapse index, 13 ± 7% [P ≤ 0.0001]; vibration time, 1.2 ± 0.7 s [P ≤ 0.0001]). The synchronized dynamic MRI and acoustic recordings successfully characterized the sites of obstruction and established the dynamic relationship between the anatomic site of obstruction and snoring acoustics.


Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review.
Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike. A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014. The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi. ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority. CRD42014009103.


[Jean-martin charcot].
Charcot created a system for the classification and diagnosis of neurological patients in the 1850s. His methodology consisted of listening to a patient's family history and present history, observing the patient scrupulously, and confirming lesions by autopsy once the patient was dead. He compared two different diseases in order to make their differences clear. Once he understood the fundamental form of a disease, he proceeded to study less perfect forms that had a single symptom. By this process, Charcot developed many new symptomatologies in Neurology.


LSDP5 enhances triglyceride storage in hepatocytes by influencing lipolysis and fatty acid β-oxidation of lipid droplets.
Lipid storage droplet protein 5 (LSDP5) is a lipid droplet-associated protein of the PAT (perilipin, adipophilin, and TIP47) family that is expressed in the liver in a peroxisome proliferator-activated receptor alpha (PPARα)-dependent manner; however, its exact function has not been elucidated. We noticed that LSDP5 was localized to the surface of lipid droplets in hepatocytes. Overexpression of LSDP5 enhanced lipid accumulation in the hepatic cell line AML12 and in primary hepatocytes. Knock-down of LSDP5 significantly decreased the triglyceride content of lipid droplets, stimulated lipolysis, and modestly increased the mitochondrial content and level of fatty-acid β-oxidation in the mitochondria. The expression of PPARα was increased in LSDP5-deficient cells and required for the increase in the level of fatty acid β-oxidation in LSDP5-deficient cells. Using serial deletions of LSDP5, we determined that the lipid droplet-targeting domain and the domain directing lipid droplet clustering overlapped and were localized to the 188 amino acid residues at the N-terminus of LSDP5. Our findings suggest that LSDP5, a novel lipid droplet protein, may contribute to triglyceride accumulation by negatively regulating lipolysis and fatty acid oxidation in hepatocytes.


Scissors: are they an infection control risk?
Increasing bacterial resistance means that nurses must re-examine infection control procedures. Bacteria were cultured from 59% of scissors swabbed. Some were still contaminated after cleaning. Some nurses do not appear to recognise the risk of infection from using their scissors for a variety of purposes.


Effects of gestation and lactation on rat gastric fundus.
This study evaluated the effects of gestation and lactation on stomach growth in rats. Constant increases were observed in gastric fundus weight during pregnancy and lactation, with a maximum obtained after 3 weeks of lactation. This increase in tissue weight was not associated with hyperplasia of the gastric fundus as in no instance did total DNA contents from mated females differ significantly from those of the unmated controls. Mild hypertrophy, as evidenced by significant increases in cellular mass and RNA and protein concentrations, was observed during late lactation. Gastrin might be responsible for these modest changes in the gastric fundus.


Practice and performance of domestic waste source segregation in Chinese universities: A case study in Shanghai.
The importance and urgency of domestic solid waste (DSW) source segregation in universities is self-evident. Although many universities have carried out waste management, however, a comprehensive summary for successful implementation work of DSW segregation is lacking. This study summarizes the mechanism of DSW segregation in Chinese university based on questionnaire survey, on-site inquiry and sampling analysis in a comprehensive university in Shanghai. Questionnaire survey show that it is critical for encouraging students to participate in waste segregation to build convenient segregation facilities and humanized segregation reward and punishment method. The strengthened publicity and education due to the advantages in environmental discipline, easy-operating waste dumping site/facility as well as personalized solutions for different functional areas (teaching building) were considerably important strategies for implementing efficient waste segregation. The recyclables that were collected by intelligent recycling device and mobile recycling enterprise were dominated by paper, and the amounts increased dramatically during the graduation season. Therefore, the university correspondingly increased the collection frequencies of waste and the number of segregation guiders in the period to decrease the potential risk of fire safety. The study could provide a valuable reference for efficient implementation of waste segregation on university/college in China.


Suppression of DNA synthesis and induction of apoptosis in rat prostate by human seminal plasma inhibin (HSPI).
In vivo administration of HSPI (10.7 kDa FSH suppressing peptide of prostate) to intact adult male rats was found to suppress the basal levels of incorporation of 3H-thymidine into DNA of ventral and dorsolateral lobes of the prostate, in a dose-dependent manner. Interestingly, microscopic examination of the prostate histology of HSPI treated rats revealed a significantly increased incidence of apoptotic bodies which are indicative of cell death. In another experiment, HSPI was also found to suppress the active DNA synthesis in testosterone-induced regrowth of prostate in castrated rats. Thus HSPI can suppress the basal and stimulated DNA synthesis and also induce apoptotic cell death in rat prostate.


Long-term effect of physical inactivity on thoracic and lumbar disc degeneration-an MRI-based analysis of 385 individuals from the general population.
The correlation between physical inactivity, thoracolumbar disc degeneration, and back pain remains unclear. This study investigated the relationship between short- and long-term physical inactivity and degenerative changes of the thoracic and lumbar spine in a southern German cohort from the general population over a time period of 14 years. This study was designed as a cross-sectional case-control study, nested in a prospective cohort from the "Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung in der Region Augsburg" (KORA) study. All participants in the population-based KORA study were assessed using a physical activity questionnaire to establish a baseline in 1999-2001 (exam 1), within an initial follow up questionnaire in 2006-2008 (exam 2), and a second follow-up questionnaire between 2013 and 2014 (exam 3). A subsample of this group (400 subjects) underwent full body MR scan performed on a 3T magnetic resonance imaging scanner current with exam 3. Data regarding physical inactivity over a time period of 14 years and back pain, and quantification of thoracic and lumbar disc degeneration on magnetic resonance imaging. Quantification of thoracic and lumbar disc degeneration was performed using the Pfirrmann score. Physical activity was grouped as no physical activity, irregularly for 1 hour, regularly for 1 hour, or regularly for ≥2 hours. This was used to calculate another variable "physical inactivity," with the options of irregular activity ≤1 hour per week or regularly ≥1 hour. Physical labor, walking, and cycling activity were additionally investigated. Correlations between physical inactivity measurements and thoracic and lumbar disc degeneration were analyzed via linear regression models adjusted for age, sex, BMI, hypertension, diabetes, and back pain. In total, 385 individuals (mean age: 56 years, SD ± 9.19; 58.2% male) were included in this study. Mean summed Pfirrmann score was 2.41 (SD ± 4.19) in the thoracic and 1.78 (SD ± 1.81) in the lumbar spine. The level of current exercise in our cohort varied with 113 (29.4%) subjects exercising regularly ≥2 hours per week, 118 (30.7%) regularly 1 hour per week, 57 (14%) irregularly for about 1 hour per week, and 97 (25.2%) stated not to exercise at exam 3. Disc degeneration was more apparent in those with irregular activity <1 hour compared to those with regular activity of ≥1 hour and more per week (p<.01) and in those with no activity compared to those with regular activity of ≥2 (p<.001) measured using exam 3. Less physical activity over a time period of 14 years correlated with an increase of disc degeneration of the thoracic and lumbar spine after adjustment for age, sex, BMI, hypertension and diabetes mellitus (p<.05). There was no statistically significant association between physical labor, walking activity, or cycling activity with disc degeneration. Additionally, no significant correlations between degree of disc degeneration (p=.990), degree of physical inactivity (p=.158), and back pain were observed. Degree of physical inactivity as measured over a time period of 14 years demonstrated a strong correlation with disc degeneration of the thoracic and lumbar spine.


Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy.
We studied 231 acute leukemia patients relapsing after allogeneic (n = 114) or autologous (n = 117) BMT to assess the outcome of further therapy. In general, all patients in good condition were eligible for second transplants except for post-allograft relapses from 1993-1994 onwards who received cytokine- or cell-mediated immunotherapy. The major reason for patients not progressing to second graft was death from progressive disease or toxicity of salvage chemotherapy. Seventeen of 231 patients (7%) were alive at the last follow-up. Six of 14 post-autograft relapses treated with second transplants were alive and well, compared with five of 103 not undergoing second grafts (P < 0.0001). One of 23 post-allograft recipients treated with second allografts was alive with an extramedullary relapse, compared with five of 13 receiving immunotherapy and none of 78 receiving standard-dose or palliative therapy (P < 0.0001). We conclude that only a small proportion of highly selected acute leukemia patients relapsing after a transplant reach the stage of a conventional second transplant. In our experience, second allografts after myeloablative therapy in patients relapsing after one allograft are associated with very poor results, and immunotherapy may be a better approach in such cases. Selected patients relapsing after an autograft may become long-term survivors following a second autograft or an allograft.


Assessment of public health perspectives on responding to an emerging pathogen: carbapenem-resistant Enterobacteriaceae.
Public health has an important and critical role in responding to emerging multidrug-resistant organisms, such as carbapenem-resistant Enterobacteriaceae. The Centers for Disease Control and Prevention developed a survey as a tool for state health departments to determine carbapenem-resistant Enterobacteriaceae prevalence within their region. This report summarizes an assessment of the health department experience with the survey, their perceived roles and responsibilities in responding to an emerging health care-associated pathogen, and potential barriers to public health engagement of acute care facilities in response activities. Key informant interviews consisting of open-ended and 5-point Likert scale questions were conducted. Interviewees represented state health departments that administered the survey and select states that did not. Of 11 states interviewed, 7 (64%) had administered the survey to acute care facilities. Despite similar competing priorities and concerns about administering the survey, different perspectives emerged among the 11 states; those that administered the survey regarded it as a learning opportunity, whereas other states emphasized concerns about survey logistics and other public health demands. All 11 states perceived the prevention of an emerging pathogen to be a public health priority, but the degree of their action depended on availability of resources and existing relationships with infection preventionists. Health departments had less interaction with other hospital personnel (eg, facility leadership) and limited knowledge of the roles and associated responsibilities of other health care partners (eg, Quality Improvement Organizations). Although considered a public health priority, response efforts to emerging pathogens were reported to vary among state health departments. A better understanding is needed of the factors that motivate and facilitate state health departments to engage in a public health activity despite the challenges of competing priorities and limited resources. Efforts should also focus on improving the relationship between health departments and hospital leadership and other health care partners.


Crystalloid versus colloid fluid therapy after cardiac surgery.
Differences in hemodynamic stability and fluid requirements were examined in patients randomly assigned to receive either normal saline crystalloid solution (N = 10) or hetastarch colloid solution (N = 11) after coronary artery bypass or valve operation. Both solutions were administered in the same manner for 8 hours after surgery, with hourly assessment of hemodynamic parameters and intake/output data. Infusion rates and 8-hour intake were higher for the group receiving normal saline solution (p less than 0.001), as was postoperative weight gain (p less than 0.01), although urine and chest tube outputs did not differ. Despite lower filling pressures, subjects receiving hetastarch exhibited higher systolic blood pressures and cardiac outputs (p less than 0.05). Hematocrits on postoperative day 1 were lower in the group given hetastarch (p less than 0.001), suggesting prolonged intravascular expansion. The subjects given hetastarch also required significantly less time in the intensive care unit (p less than 0.001). Thus, cardiac surgical patients receiving colloids exhibited reduced fluid requirements, superior hemodynamic performance, and shortened intensive care stay when compared with those given crystalloid resuscitation.


Postparathyroidectomy hypocalcemia as an accurate indicator of preparathyroidectomy bone histology in the uremic patient.
19 chronic renal failure patients underwent iliac crest bone biopsy prior to total parathyroidectomy with autotransplantation. The preoperative serum calcium concentration did not correlate with the number of osteoclasts/mm2 present on the preparathyroidectomy iliac biopsy. However, the postparathyroidectomy decrement in serum calcium (mg/dl and percent change) and the osteoclasts/mm2 were strongly correlated (p less than 0.001). In addition, the postoperative fall in serum calcium also correlated with the postoperative change in serum alkaline phosphatase (p less than 0.001). The nadir in postparathyroidectomy serum calcium was attained in a mean of 4.4 +/- 2.7 days. Our results indicate that the preoperative serum calcium concentration does not necessarily reflect active bone resorption, but the postoperative decrement in serum calcium provides an accurate index of preoperative histologic activity. The available data do not provide information with respect to the mechanism of postparathyroidectomy hypocalcemia since either the cessation of bone resorption, continued bone deposition, or a combination of both may be operative.


Examining the impact of patient characteristics and symptomatology on knowledge, attitudes, and beliefs among foreign-born tuberculosis cases in the US and Canada.
Foreign-born individuals represent the majority of TB cases in the US/Canada. Little is known about their TB knowledge, attitudes, and beliefs (KAB). Cross-sectional survey was conducted in 22 sites in the US/Canada among foreign-born adults with active TB. Multiple regression was used to examine KAB factors against covariates. Of 1,475 participants interviewed, most answered the six knowledge items correctly. Significant predictors of correct knowledge included region of origin, education, income, age, visa status, place of diagnosis, BCG vaccination, and TB symptoms. Significant predictors of higher perceived risk/stigma scores included region of origin, age, place of diagnosis, English fluency, time in the US/Canada, TB symptoms, and household rooms. This study examines associations between TB KAB and patient and disease characteristics in foreign-born individuals in the US/Canada. The findings call for improved health education, along with efforts to reduce stigma and enhance realistic risk assessments.


Confabulations in remembering past and planning future are associated with psychiatric symptoms in Alzheimer's disease.
Psychiatric symptoms such as delusions and aggression are frequently observed in patients with Alzheimer's disease (AD), but few studies examined the association of these symptoms with confabulations. We studied 32 AD patients and 10 age- and education-matched healthy older adults. The AD patients were divided into delusion/aggression and non-delusion/non-aggression groups based on their behavioral pathology in AD frequency-weighted severity scale score. Confabulations were assessed using questions about temporality (personal past, orientation, and future planning), and cognitive functions were determined using the mini-mental state examination and the cognitive abilities screening instrument. The AD patients showed confabulations on all types of questions, and their confabulation scores for the past and future were strongly correlated. Cognitive functions were not significantly correlated with confabulation scores for any type of questions. The delusion/aggression group had significantly more confabulations on past and future questions compared to the non-delusion/non-aggression group. These findings suggested that confabulations in remembering the past and planning the future were affected by psychiatric symptoms such as delusion and aggression.


[Chronic perianal pyoderma with urethrocutaneous fistula: a case report].
A 65-year-old male was hospitalized because of micturition pain and urinary oozing from several fistulas on the perineal and the left gluteal skin. Oozing had been present for about 50 years, after receiving mass resection of his left scrotum or perineum, and left orchiectomy. The main focus was on the left dorsal site of the anus. Compression around this area produced malodorous grayish pus discharge from many fistulas, although the anus was intact. Although he had histories of spinal caries and renal tuberculosis, both pus and urine cultures showed Staphylococcus spp. and no growth of Mycobacterium tuberculosis. Urethrocystography showed urethral stenosis at bulbar urethra and leakage from a site just proximal to the stenosis. Antibiotics for tuberculosis were administrated for fear of recurrent tuberculosis for 6 months. Cystostomy formation and debridement were performed, followed by en-bloc resection and mesh-skin graft after two weeks. Internal urethrotomy was performed six months after the surgery, and subsequently cystostomy removed. After three and a half years, although there was no local recurrence and no difficulty of urination, he died of cholangio-carcinoma. There are many reports of chronic perianal pyoderma subsequent to hemorrhoid or subcutaneous abscess; however, this might be the first report on a case originating from fistulas in the urinary tract.


Safety in Senhance™ Robotic Gastrointestinal Surgery in 530 Patients.
The Senhance Robotic System™ (Asensus Surgical, Durham, NC, USA) has been used in abdominal surgery since 2016, and provides an eye-tracker for camera movement and haptic tactile feedback. Safety aspects are very important in robotic surgery, such as regarding the presence of system malfunctions and surgical outcomes. The data for robotic function in gastrointestinal surgical procedures in 530 patients (colorectal surgery, fundoplication, others) were prospectively listed in the TRUST registry after informed patient consent in three German gastrointestinal surgery centers (center A, N = 46 patients; center B, N = 457; center C, N =27). Adverse events were noted in 14.3% (76/530 patients) of the overall surgeries, with an equal distribution among the procedures. Robotic malfunctions, such as console/camera/arm malfunctions, collisions, or limited motion, were experienced in 5.5 % (29/530 patients), with some differences among the centers (A, 0.0%; B, 4.2%; C, 37%). These differences were explained in terms of team experience and case load. In conclusion, the Senhance™ Robotic System can be safely applied to routine abdominal surgery procedures.


One-step oxidation preparation of unfolded and good soluble graphene nanoribbons by longitudinal unzipping of carbon nanotubes.
A simple one-step method to prepare graphene nanoribbon (GNR) is reported in this paper. Compared with water steam etching, the oxidation and co-etching of dilute sulfuric acid can result in the more complete longitudinal unzipping of carbon nanotube, although there is no other strong oxidant. As-prepared GNRs are more flat and have more oxygenated functional groups along the edge. Moreover, they can steadily disperse in a water system. These make them suitable as a carrier for supporting palladium (Pd) nanoparticles. The Pd/GNR composite exhibits a superior electrocatalytic activity for ethanol oxidation.


Sulfur-Enhanced Field-Effect Passivation using (NH4)2S Surface Treatment for Black Si Solar Cells.
We demonstrated surface passivation of a black Si-based solar cell using an (NH4)2S solution to mitigate surface recombination velocity. Incorporated S at the interface between atomic-layer-deposited Al2O3 and black Si by (NH4)2S solution treatment boosted the density of negative fixed charges, S-enhanced field-effect passivation. Furthermore, NH4OH generated during (NH4)2S solution treatment removed the defective Si phase at the black Si surface, the surface cleaning effect. The optimized (NH4)2S solution treatment significantly enhanced the internal quantum efficiency up to ∼17.2% in the short wavelength region, suggesting suppressed surface recombination. As a result, photoconversion efficiency of the cell increased from 11.6 to 13.5%, by 16% compared to the control cells without (NH4)2S solution treatment.


Time-motion analysis in men's breaking: A longitudinal study.
Quantifying the effort of a sport confrontation by determining its temporal structure is of concern to the scientific community. In breaking this has not yet been sufficiently studied. The objectives of the study were to longitudinally analyze the temporal and sequential parameters of male breaking battles to determine the evolution of these parameters and to establish a model of temporal structure. All Red Bull BC One dancers from 2011 to 2021 (n = 152 dancers) participated. By using observational methodology, all battles were analyzed (n = 142). To obtain the results, we employed different analysis techniques: descriptive, normality tests, Student's t-test or Mann-Whitney, one factor ANOVA or Kruskall-Wallis and effect size (Cohen's d or Hedges' g). The significance level established for the study was ρ ≤ 0.05. The results define the temporal and sequential structure of the battles. With these, breaking professionals will be able to develop precise and adequate training for these athletes. We conclude that approaches to dancing and battling have evolved. The effort that the athlete must exert is increasing and will therefore require better preparation to cope with the physical demands required for a sport that will be incorporated into the Olympics program in 2024.


Combination of MALDI-MSI and cassette dosing for evaluation of drug distribution in human skin explant.
Study of skin penetration and distribution of the drug compounds in the skin is a major challenge in the development of topical drug products for treatment of skin diseases. It is crucial to have fast and efficacious screening methods which can provide information concerning the skin penetration and the distribution of the drug molecules in the region of the target. Mass spectrometry imaging (MSI) such as matrix-assisted laser desorption/ionization (MALDI)-MSI offers the opportunity to analyze the drug distribution at micrometer scale, but is a low throughput technique. Cassette dosing of drug molecules has been widely used for two decades as a high throughput screening tool for plasma pharmacokinetic analysis. The purpose of this study is to evaluate the utility of combining MALDI-MSI with cassette dosing to obtain a medium throughput screening technique for drug distribution in the skin directly from thin tissue sections. Excised fresh human skin was treated with two different formulation types containing both single drugs and a cassette with four drugs. Biopsies were taken and analyzed with traditional UHPLC-MS/MS and MALDI-MSI. The results reveal that skin penetration data of the four drugs administered together were in agreement with skin penetration data obtained when the molecules were administered individually. Furthermore, the MALDI-MSI data reveal different distribution profiles of the four drugs which were not possible to deduce from the UHPLC-MS/MS bioanalysis. These findings suggest that combination of MALDI-MSI and cassette dosing can be used as a medium throughput screening tool at an early stage in the drug discovery/development process. Graphical abstract Investigation of drug distribution in human skin explant by MALDI-MSI after cassette dosing.


Specificity in the interaction of natural products with their target proteins--a biochemical and structural insight.
Natural products are an abundant source of anti cancer agents. They act as cytotoxic drugs, and inhibitors of apoptosis, transcription, cell proliferation and angiogenesis. While pathways targeted by natural products have been well studied, there is paucity of information about the in vivo molecular target/s of these compounds. This review summarizes some of the natural compounds for which the molecular targets, mechanism of action and structural basis of specificity have been well documented. These examples illustrate that 'off target' binding can be explained on the basis of diversity inherent to biomolecular interactions. There is enough evidence to suggest that natural compounds are potent and versatile warheads that can be optimized for a multi targeted therapeutic intervention in cancer.


Cancer risk factors among people living with HIV/AIDS in China: a systematic review and meta-analysis.
Cancer is a leading cause of death among people living with HIV/AIDS (PLWHA). We conducted a systematic review and meta-analysis to evaluate prevalence of cancer risk factors among Chinese PLWHA based on 102 articles. Random effects meta-analysis was used to calculate the summary prevalence estimate (sPrev) and 95% confidence interval (CI) for each cancer risk factor by demographic group. Overall, the sPrev for each risk factor among Chinese PLWHA was: 41.1% (95% CI: 35.3-46.9%) for current smoking; 30.3% (95% CI: 23.3-37.4%) for current alcohol consumption; 24.4% (95% CI: 14.7-30.2%) for overweight and obesity; 12.5% (95% CI: 10.6-14.3%) for hepatitis B virus infection; 29.1% (95% CI: 23.6-34.5%) for hepatitis C virus infection; 33.9% (95% CI: 24.3-43.5%) for high-risk human papillomavirus infection from cervical samples and 78.6% (95% CI: 69.4-87.7%) from anal samples; 2.7% (95% CI: 0.7-4.7%) for Epstein-Barr virus (EBV) immunoglobulin M (IgM) positivity, 94.7% (95% CI: 90.7-98.8%) for EBV IgG positivity and 25.6% (95% CI: 12.4-38.8%) for EBV DNA positivity; 14.9% (95% CI: 12.4-17.4%) for human herpes virus 8 infection. The prevalence of major cancer risk factors was high among PLWHA in China, suggesting an urgent need for interventions to reduce cancer risk in this high-risk group.