Aldosterone induces myofibroblastic transdifferentiation and collagen gene expression through the Rho-kinase dependent signaling pathway in rat mesangial cells.
There is accumulating evidence indicating the role of aldosterone in the pathogenesis of hypertension and renal injury. In this study, we investigated the role of the Rho-kinase dependent signaling pathway in aldosterone-induced myofibroblastic transdifferentiation and collagen gene expression in rat mesangial cells (RMCs). Stimulation with aldosterone (1 nmol/L) significantly increased phosphorylation of myosin phosphatase target subunit-1 (MYPT-1), a marker of Rho-kinase activity, with a peak at 20 min in RMCs. Pre-incubation with a selective mineralocorticoid receptor antagonist, eplerenone (10 micromol/L), or a specific Rho-kinase inhibitor, Y27632 (10 micromol/L), attenuated the aldosterone-induced increase in MYPT-1 phosphorylation. Aldosterone also induced hypertrophy in RMCs, accompanied by an increase in actin polymerization and expression of alpha-smooth muscle actin (alpha-SMA), a myofibroblastic transdifferentiation marker. Collagen type I, III and IV mRNA levels were also increased with aldosterone stimulation. Pre-treatment with eplerenone or Y27632 prevented the aldosterone-induced cell hypertrophy, actin polymerization, the increase in alpha-SMA expression and the increases of collagen type I, III, IV mRNA levels in RMCs. These results suggest that aldosterone-induced mesangial cell hypertrophy is associated with cell transformation, leading to an increase in collagen gene expression via the Rho-kinase dependent signaling pathway.


Serological and cellular definition of a new HLA-DR associated determinant, MC1, and its association with rheumatoid arthritis.
A new serological HLA-DR associated determinant was defined by a cluster of six B cell alloantisera. This determinant, designated as MC1, was strongly associated with DR1 and DR4 and appeared unrelated to MB, MT, and SB. The antigen frequency of MC1 was 47% in Caucasoids and 43% in Blacks. Mixed leukocyte culture cloning yielded an alloreactive T cell clone with PLT specificity associated with MC1. We have also observed that certain alloreactive clones may also acquire expression of MC1 but not DR4 during long-term culture maintenance in the presence of DR4, MC1-positive feeder cells. Disease association studies showed a significantly increased frequency of MC1 in adult rheumatoid arthritis patients (93.5% vs 47.4% in normals; relative risk 16.1). These findings suggest that MC1 represents a novel HLA-D encoded determinant.


Physician's Prescribing Preference as an Instrumental Variable: Exploring Assumptions Using Survey Data.
Physician's prescribing preference is increasingly used as an instrumental variable in studies of therapeutic effects. However, differences in prescribing patterns among physicians may reflect differences in preferences or in case-mix. Furthermore, there is debate regarding the possible assumptions for point estimation using physician's preference as an instrument. A survey was sent to general practitioners (GPs) in The Netherlands, the United Kingdom, New Zealand, Ireland, Switzerland, and Germany, asking whether they would prescribe levothyroxine to eight fictitious patients with subclinical hypothyroidism. We investigated (1) whether variation in physician's preference was observable and to what extent it was explained by characteristics of GPs and their patient populations and (2) whether the data were compatible with deterministic and stochastic monotonicity assumptions. Levothyroxine prescriptions varied substantially among the 526 responding GPs. Between-GP variance in levothyroxine prescriptions (logit scale) was 9.9 (95% confidence interval: 8.0, 12) in the initial mixed effects logistic model, 8.3 (6.7, 10) after adding a fixed effect for country and 8.2 (6.6, 10) after adding GP characteristics. The occurring prescription patterns falsified the deterministic monotonicity assumption. All cases in all countries were more likely to receive levothyroxine if a different case of the same GP received levothyroxine, which is compatible with the stochastic monotonicity assumption. The data were incompatible with this assumption for a different definition of the instrument. Our study supports the existence of physician's preference as a determinant in treatment decisions. Deterministic monotonicity will generally not be plausible for physician's preference as an instrument. Depending on the definition of the instrument, stochastic monotonicity may be plausible.


Tadpole competition in a desert anuran community.
Five interspecific competition experiments performed in artificial ponds under temporary pond-like conditions established that temporary and permanent pond tadpoles interact. Temporary pond species typically lowered survivorship and reduced progress towards metamorphosis of permanent pond tadpoles. These results suggest that competitive interactions may partially determine the local distribution of tadpoles in the Chihuahuan Desert by preventing some permanent pond anurans from using temporary ponds. Predation by Scaphiopus multiplicatus tadpoles (a temporary pond species) may also prevent permanent pond tadpoles from using temporary ponds.


Body mass decline in a Mediterranean community of solitary bees supports the size shrinking effect of climatic warming.
The long-known, widely documented inverse relationship between body size and environmental temperature ("temperature-size rule") has recently led to predictions of body size decline following current climatic warming ("size shrinking effect"). For keystone pollinators such as wild bees, body shrinking in response to warming can have significant effects on pollination processes but there is still little direct evidence of the phenomenon because adequate tests require controlling for confounding factors linked to climate change (e.g., habitat change). This paper assesses the shrinking effect in a community of solitary bees from well-preserved habitats in the core of a large nature reserve experiencing climatic warming without disturbances or habitat changes. Long-term variation in mean body mass was evaluated using data from 1704 individual bees (137 species, 27 genera, 6 families) sampled over 1990-2023. Climate warmed at a fast rate during this period, annual mean of daily maximum temperature increasing 0.069°C/year on average during 2000-2020. Changes in bee body mass verified expectations from the size shrinking effect. The mean individual body mass of the community of solitary bees declined significantly, irrespective of whether the analysis referred to the full species sample or only to the subset of species that were sampled in both the old (1990-1997) and recent (2022-2023) periods. On average, body mass declined ~0.7%·year-1 , or an estimated average cumulative reduction of ~20 mg per individual bee from 1990 to 2023. Proportional size reduction was greatest among large-bodied species, ranging from around -0.6%·year-1 for the smallest species to -0.9%·year-1 for the largest ones. Declining rate was steeper for cavity-nesting than ground-nesting species. The pollination and mating systems of bee-pollinated plants in the study region are probably undergoing significant alterations as a consequence of supra-annual decline in bee body mass.


Shoulder replacement in the chimpanzee: surgical and post-operative management.
A modified "Floating-Socket" total shoulder replacement was implanted in an adult male chimpanzee using an anterior surgical approach. The surgical technique and the post-operative course are described. Clinical and X-ray follow-up for 17 months reveals satisfactory function of the implant with no apparent loosening of either glenoid or humeral components.


Upper-limb contracture development in children with cerebral palsy: a population-based study.
The aim of this study was to investigate the longitudinal development of passive range of motion (ROM) in the upper limbs in a population-based sample of children with cerebral palsy (CP), and to investigate which children are more likely to develop contractures related to functional level, CP subtype, and age. Registry data of annual passive ROM measurements of the upper limbs from 771 children with CP (417 males, 354 females; mean age 11y 8mo, [SD 5mo] range 1-18y) were analysed. Mixed models were used to investigate at what age decreased passive ROM occurs. Odds ratios were calculated to compare risks and logistic regression analysis was used to predict contracture development. Thirty-four per cent of the children had developed contractures. Among these children, decreased passive ROM was significant at a mean age of 4 years for wrist extension and 7 years for shoulder flexion, elbow extension, and supination. Children at Manual Ability Classification System (MACS) level V had a 17-times greater risk of contractures than children at MACS level I. One-third of the children in the total population developed upper-limb contractures while passive ROM decreased with age. MACS level was the strongest predictor of contracture development. In a population-based sample of 771 children with cerebral palsy, 34% developed an upper-limb contracture. Contracture development started at preschool age. The first affected movements were wrist extension and supination. Passive range of motion decreased with age. High Manual Ability Classification System level was the most important predictor of contractures.


Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond.
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted - for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.


Oscillations in the reproductive condition of Diaptomus leptopus (Copepoda: Calanoida) and their relation to rates of egg-clutch production.
Isolated female D. leptopus oscillate between gravid and nongravid reproductive conditions. When gravid, the oviducts are visible as a pair of dark bands lateral to the digestive tract. Periodically the females revert to a nongravid condition by releasing all the unfertilized oocytes into the environment. The oviducts then remain transparent until they refill with ripe gametes.The characteristics of this gametogenic cycle were defined at 18° C using females cultured under controlled conditions. The average period of the cycle was 4.4 days, with a gravid phase (dark oviducts) of 3.4 days and a nongravid phase (clear oviducts) of 0.9 days. Observations made in situ confirmed the oscillatory nature of the changes in reproductive status.The duration of the nongravid phase was shown to represent the minimal time interval between successive clutches of fertilized eggs. Estimates of maximal rates of clutch production based on this measure were more than three times higher than those based on the duration of embryonic development.Since unfertilized oocytes disintegrate upon extrusion, a considerable amount of reproductive material may be wasted regularly. A turnover rate of 5.6% body weight (dry) day-1 was calculated for isolated females at 18° C. A model used to estimate the frequency of mating interactions indicated that the probability of oocyte extrusion in lakes may be high and the impact on nutrient pools could be substantial. Up to 0.12 μg phosphorus mg-1 h-1 may be released in the form of unfertilized oocytes.


Purification of Lipase from Pseudomonas aeruginosa VSJK R-9 and Its Application in Combination with the Lipolytic Consortium for Bioremediation of Restaurant Wastewater.
Microorganisms are very important in biodegradation of edible oil contaminated effluents, and they find an excellent scope in restaurant wastewater bioremediation. The edible oil in such wastewater harms the environment in a number of ways. The native bacteria in the wastewater are less effective in degrading edible oil. It leads to the formation of blockage along the sewer line. This narrows the diameter of line and forms partial to complete blockage causing overflows of wastewater exposing humans and animals to diverse pathogens. A consortium of lipolytic bacteria and lipase enzyme gives a new approach for effective and environment friendly degradation of waste oil in restaurant wastewater. In the present study, the lipase produced by Pseudomonas aeruginosa VSJK-R9 isolated from restaurant wastewater was purified by ammonium sulfate precipitation, dialysis and gel exclusion chromatography-Sephadex G-100, with 11.45-fold purification to obtain a yield of 35.08%. Its molecular mass was around 50 kDa as determined by SDS-PAGE analysis. The bioremediation of restaurant wastewater supplemented with 0.5% NH4Cl and 0.8% K2HPO4 was studied with lipolytic consortium formed by the combination of lipolytic isolates Acinetobacter junii VSJK-R6, Pseudomonas composti VSJK-R8 and Pseudomonas aeruginosa VSJK-R9. Further, the impact of lipase supplementation was also evaluated, and it was found that the action of consortium was boosted by lipase. The oil and chemical oxygen demand value of the restaurant wastewater was considerably decreased. These findings have shown the application of lipase for bioremediation of restaurant wastewater and its positive impact on the performance of lipolytic consortium.


Two kinesin-like Kin I family proteins in fission yeast regulate the establishment of metaphase and the onset of anaphase A.
Metaphase is thought to be a force-equilibrium state of "tug of war," in which poleward forces are pulling kinetochores and counteracting the cohesive forces between the centromeres. Unlike conventional kinesins, members of the Kin I family are microtubule-depolymerizing enzymes, which are expected to be molecules that could generate poleward forces. We have characterized mitotic roles of two Kin I homologs, Klp5 and Klp6, in fission yeast. Klp5 and Klp6 colocalize to the mitotic kinetochores and the spindle midzone. These two proteins form a heterocomplex, but not a homocomplex. Albeit not essential, both proteins are required for accurate chromosome segregation and normal morphology of interphase microtubules. Time-lapse live analysis using GFP-alpha-tubulin indicates that these mutants spend a much longer time (2-fold) in mitosis before the initiation of anaphase B. Further observation using kinetochore and centromere markers shows that, in these mutants, sister centromeres move back and forth between the two poles, indicating that entry into anaphase A is delayed. This is supported by live image analysis showing that Cut2 securin is retained during the prolonged mitosis. Furthermore, the mitotic extension is dependent upon the Mad2 spindle checkpoint. We discuss two models of Kin I function in fission yeast. One proposes that Klp5 and Klp6 are required for efficient capturing of kinetochores by the spindles, while the other proposes that they are required to generate tension upon kinetochore capturing. Kin I, therefore, plays a fundamental role in the establishment of metaphase, probably by generating poleward forces at the kinetochores.


Tumor growth potential after tumoral and instrumental contamination: an in-vivo comparative study of T-saw, Gigli saw, and scalpel.
In the field of spinal tumors, intralesional tumor cutting is sometimes inevitable. The purpose of this study was to compare the potential for tumor growth after intralesional cutting by T-saw, Gigli saw, and scalpel. Tumors, prepared by the subcutaneous injection of human HT 1080 fibrosarcoma cells in nude mice, were harvested and cut with a T-saw, Gigli saw, or scalpel. A 3-cm wound was created in the skin on the back in another group of nude mice. The cut surface of the tumor was rubbed for 10 s against the subcutaneous tissue in this second group of nude mice. In the same manner, the instrument used for tumor cutting was rubbed against the subcutaneous tissue in the 3-cm wound in the back of a third group of nude mice for 10 s. Other instruments used for tumor cutting were immediately washed in culture medium, and the total number of tumor cells was counted. Tumor blocks and single-cell suspensions prepared from tumor tissues of the same weight were inoculated and injected into a fourth group of nude mice. The incidence of tumor growth after the rubbing of the subcutaneous tissue with the tumor surface cut with a T-saw, Gigli saw, and scalpel was 16.7%, 50.0%, and 33.3%, respectively. The corresponding figures after the rubbing of the subcutaneous tissue with a T-saw, Gigli saw, and scalpel was 16.7%, 33.3%, and 33.3%, respectively. The mean numbers of tumor cells attached to the T-saw, Gigli saw, and scalpel were 1.88 x 105, 5.02 x 105, and 4.92 x 105, respectively. Finally, the incidence of tumor growth after the inoculation of tumor blocks and single-cell suspensions was 100% and 77.8%, respectively. These findings show that tumor recurrence is less likely after intralesional tumor cutting with a T-saw than after such cutting with a Gigli saw or scalpel.


The importance of chemical potential in the determination of water slip in nanochannels.
We investigate the slip properties of water confined in graphite-like nanochannels by non-equilibrium molecular dynamics simulations, with the aim of identifying and analyze separately the influence of different physical quantities on the slip length. In a system under confinement but connected to a reservoir of fluid, the chemical potential is the natural control parameter: we show that two nanochannels characterized by the same macroscopic contact angle--but a different microscopic surface potential--do not exhibit the same slip length unless the chemical potential of water in the two channels is matched. Some methodological issues related to the preparation of samples for the comparative analysis in confined geometries are also discussed.


Effect of closed incision negative pressure wound therapy on incidence rate of surgical site infection after stoma reversal: a pilot study.
The stoma reversal (SR) procedure is associated with a relatively high risk of perioperative complications with surgical site infection (SSI) as the most common. Recently closed incision negative pressure wound therapy (ciNPWT) was applied widely to prevent SSI. To investigate the efficiency of ciNPWT in terms of the incidence rate of SSI after SR surgery. As an exploratory observational cohort study patients were treated either with ciNPWT (n = 15) or standard sterile dressing (SSD) (n = 15). CiNPWT was applied every 3 days whereas SSD was changed every day. Clinical evaluation for SSI signs, C-reactive protein level and pain assessment using the visual analogue scale (VAS) were analyzed. The incidence rate of SSI was in 13% (2/15) in the ciNPWT group and 26% (4/15) in the SSD group (p = 0.651, OR = 0.44, 95% CI: 0.03-3.73). All patients in the SSD group who developed SSI presented both local and generalized signs of infection. Pain-VAS levels assessed on the 1st (MdnciNPWT = 4, MdnSSD = 5, p = 0.027, W = 51.5) and 3rd postoperative day (MdnciNPWT = 2, MdnSSD = 4, p = 0.014, W = 45.5) were significantly lower in the ciNPWT group than in the SSD group. CiNPWT seems not to have a benefit to reduce SSI after the SR procedure. Further investigation is needed to establish firmly the benefit of using ciNPWT in this group of patients.


Comparative ecotoxicity of single and binary mixtures exposures of cadmium and nickel on growth and biomarkers of Lemna gibba.
The aim of the present study was to investigate the toxicity effects of cadmium-nickel (Cd-Ni) after single and mixtures exposures over the macrophyte Lemna gibba. Effects were assessed on growth, as frond number and fresh weight and biochemical parameters, such as total protein content and activity of antioxidant enzymes. Plants were exposed to single Cd and Ni in concentrations that ranged between 0.13-33 mg/L and 0.18 and 11.82 mg/L, respectively. For binary mixtures, individual metal IC50 values were used for selection of the evaluated concentrations. The experimental design consisted in three different ratios based on the concept of toxic units (TU), each ratio was evaluated by five different concentrations. Both single and mixture treatments were performed for 7 days following the conditions according to OECD (2006). Single and mixture exposures affected plant growth and the biomarkers of the antioxidant response. Growth parameters showed a differential sensitivity after individual metal exposures. Cd was more toxic for L. gibba plants when fresh weight was considered, but on the contrary, considering frond number, Ni was the most toxic metal. IC50-7d, based on growth rate calculated on frond number were 17.8 and 2.47 mg/L, and on fresh weight were 1.08 and 3.89 mg/L, for Cd and Ni respectively. LOEC values for Cd were obtained at 2.06 and 1.03 mg/L, for frond number and fresh weight, respectively; while for Ni, these values were 0.92 and 11.82 mg/L. The three evaluated ratios for binary mixtures resulted in a high toxicity considering the same response variables in single metal exposures. Ratio 1 (2/3 TU Cd-1/3 TU Ni) was the most toxic considering both frond number and fresh weight, showing percentage inhibition of growth rates of 96 and 90%, respectively for the highest concentration. A modification of the protein content was observed in single, but especially in the mixture treatments. The activity of catalase (CAT; EC 126.96.36.199), ascorbate peroxidase (APOX; EC 188.8.131.52) and guaiacol peroxidase (GPOX; EC 126.96.36.199) was also affected in single and mixtures assays. APOX and GPOX showed a higher increase of its activities respect the controls after mixture treatments than for single metal treatments. Such optimization of the antioxidant system could be one of the causes of the antagonistic toxicity observed in mixture exposures. Concentration addition (CA) reference model, based on frond number, in Cd-Ni mixtures was not a good predictor to evaluate toxicity from dissolved metal concentration since the results showed that toxicity was less than additive, with an average of ΣTU = 2.17. The observed antagonisms resulted to be stronger in mixtures with higher metal concentrations.


The Role of Adjuvant Chemotherapy in Non-Metastatic Goblet Cell Carcinoid of the Appendix: An 11-Year Experience from the National Cancer Database.
Goblet cell carcinoids (GCC) are an aggressive, albeit rare, subtype of appendiceal tumors that exhibit distinct histologic features and lack clear treatment guidelines. We aimed to ascertain the impact of adjuvant chemotherapy (AC) for GCC in a national cohort of patients. Patients who underwent a right hemicolectomy for stage I-III GCC of the appendix between 2006 and 2016 were selected from the National Cancer Database (NCDB). Stratification based on AC receipt was performed. Kaplan-Meier survival estimates and Cox proportional hazard regression were used to identify predictors of overall survival (OS). A total of 867 patients were identified, of whom 124 (14%) received AC. Patients in the AC group were significantly younger (54 vs. 57 years; p = 0.006) and were predominantly of male sex (60 vs. 48%; p = 0.012). On histopathology, patients in the AC group had a higher proportion of poorly/undifferentiated grade (27 vs. 5%; p < 0.001), T4 disease (35 vs. 11%; p < 0.001), and lymph node-positive disease (45 vs. 7%; p < 0.001) than patients who did not receive AC. After excluding patients diagnosed in 2016 due to a lack of follow-up data (n = 162), a survival advantage for the AC group was detected only after stratification for lymph node-positive disease (p = 0.007). On Cox proportional hazard regression, AC demonstrated an independent association with improved OS (hazard ratio 0.24, 95% confidence interval 0.084-0.683; p = 0.007). The current analysis from the NCDB supports the role of AC for GCC of the appendix, chiefly for patients with lymph node metastatic disease.


S1 glycoprotein gene analysis of infectious bronchitis viruses isolated in Korea.
Fifteen isolates of Infectious bronchitis virus (IBV) were obtained from the kidney, trachea, and cecal tonsil of IB suspected chickens between 2001 and 2002 years in Korea. The S1 glycoprotein gene of IBV isolates were amplified by reverse transcriptase - polymerase chain reaction (RT-PCR) and analyzed by restriction fragment length polymorphism (RFLP) analysis. Fifteen Korean IBV isolates were classified into 4 groups by their RFLP patterns using restriction enzymes, HaeIII, BstYI, and XcmI. The RFLP patterns for 3, 1, and 1 of 15 isolates corresponded to the patterns of IBV Arkansas, Connecticut, and Massachusetts strains, respectively. Ten of 15 isolates generated unique KM91 RFLP pattern that was observed in the IBV KM 91 strain previously isolated in Korea. To confirm genetic diversity in the S1 genes of IBV isolates, viral RNAs of representative 9 of 15 IBV isolates were amplified, cloned, sequenced and compared with published sequences for non-Korean IBV strains. Korean IBV isolates showed amino acid sequence similarity between 61.8% (K446-01 and K161-02) and 96.1% (K281-01 and K210-02) with each other and they showed amino acid sequence similarity between 42.9% (K161-02 and GA980470) and 96.5% (K203-02 and KB8523) compared to non-Korean IBV strains. By phylogenetic tree analysis, Korean IBV field isolates were branched into five clusters in which 3 clusters were differentiated from non-Korean IBV strains. Especially, Korean IBV isolates K069-01, K507-01, K774-01 and K142-02 formed a separate cluster. It seems that IBVs continue to evolve and IBVs showing various genetic differences may cocirculate in Korea.


Association between synesthetic colors and sensitivity to physical colors changed by type of synesthetic experience in grapheme-color synesthesia.
Grapheme-color synesthesia is a condition in which visual perception of letters induces simultaneous perception of a specific color. Previous studies indicate that grapheme-color synesthetes are more sensitive to physical colors than non-synesthetes. Synesthetic colors are found to be concentrated in multiple regions of the color space, forming "synesthetic color clusters". The present study investigated whether color sensitivity corresponding to synesthetic color clusters (clustered colors) is higher than color sensitivity that does not correspond to synesthetic color clusters (non-clustered colors). However, we found no difference in the color sensitivity for clustered and non-clustered colors. We also investigated whether the color sensitivity is dependent on the synesthetic experience (associators and projectors). We found that the greater the tendency toward associator characteristics, the greater the sensitivity for clustered colors compared to that for non-clustered colors. Our findings suggest an association between synesthetic colors and physical color sensitivity that is modulated by synesthetic experience.


The Impact of Magnesium Sulfate Therapy on Angiogenic Factors in Preeclampsia.
OBJECTIVE: The objective was to evaluate whether intravenous magnesium sulfate (magnesium) alters levels of angiogenic factors in women with preeclampsia. STUDY DESIGN: This was a prospective cohort study comparing women with preeclampsia treated with magnesium for seizure prophylaxis to those who were not. Serum levels of angiogenic factors, soluble fms-like tyrosine kinase 1, soluble endoglin and placental growth factor, were measured at the time of diagnosis and approximately 24 hours later. Secondary analysis compared women receiving magnesium for preeclampsia to women receiving magnesium for preterm labor. Analysis of covariance was used to compare levels at 24 hours, adjusting for levels at enrollment and potential confounders. RESULTS: Angiogenic factor levels did not differ between preeclampsia groups with and without magnesium or between preeclampsia and preterm labor groups treated with magnesium (all P > 0.05). CONCLUSION: Magnesium likely decreases seizure risk in preeclampsia by a mechanism other than altering angiogenic factor levels.


Influence of autophagy on the efficacy of radiotherapy.
Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly, autophagy could play both pro-death and pro-survival roles in influencing the development of cancer via various signal pathways. As radiotherapy is one of the main treatment modalities for cancer, we reviewed the effect of autophagy modulations on radiosensitivity and radiotherapy efficacy in various cancer types. The future development of autophagy modifications for improving radiotherapy efficacy and cancer prognosis will also be discussed.


Analysis of adenomatous polyposis coli gene in thyroid tumours.
Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma.


Effect of dynamic change in body mass index on the risk of hypertension: Results from the Rural Chinese Cohort Study.
To examine the effect of change in body mass index (BMI) on incident hypertension by gender and age groups. A total of 10,145 non-hypertensive participants 18-75years old from rural areas in the middle of China were selected for this cohort study. Questionnaire interview and anthropometric and laboratory measurements were performed at baseline (during July to August 2007 and July to August 2008) and follow-up (during July to August 2013 and July to October 2014). Multiple logistic regression analysis was used to examine the relationship between change in BMI and incident hypertension. During a mean follow-up of 6.03±0.69years, hypertension developed in 794 of 3986 men and 1184 of 6159 women. Both genders who were obese (BMI ≥28kg/m2 for Chinese people) at follow-up, regardless of their obesity status at baseline, showed greater risk of hypertension than those who were non-obese (BMI <28kg/m2) at both baseline and follow-up. We found a dose-response relationship between change in BMI and incident hypertension. Risk of hypertension was markedly greater with a BMI gain of the highest quartile or more as compared with a BMI reduction of the lowest quartile or more, except for women 60-75years old. Risk of hypertension was high for non-hypertensive people in rural China with stable obesity. BMI dynamic gain may be related to incident hypertension for men of all ages and young and middle-aged women.


Healthcare providers as sources of vaccine-preventable diseases.
Vaccine-preventable infectious diseases may be introduced into the healthcare setting and pose a serious risk to vulnerable populations including immunocompromised patients. Healthcare providers (HCPs) are exposed to these pathogens through their daily tasks and may serve as a reservoir for ongoing disease transmission in the healthcare setting. The primary method of protection from work-related infection risk is vaccination that protects not only an individual HCP from disease, but also subsequent patients in contact with that HCP. Individual HCPs and healthcare institutions must balance the ethical and professional responsibility to protect their patients from nosocomial transmission of preventable infections with HCP autonomy. This article reviews known cases of HCP-to-patient transmission of the most common vaccine-preventable infections encountered in the healthcare setting including hepatitis B virus, influenza virus, Bordetella pertussis, varicella-zoster virus, measles, mumps and rubella virus. The impact of HCP vaccination on patient care and current recommendations for HCP vaccination against vaccine-preventable infectious diseases are also reviewed.


Common immunopathogenesis of central nervous system diseases: the protein-homeostasis-system hypothesis.
There are hundreds of central nervous system (CNS) diseases, but there are few diseases for which the etiology or pathogenesis is understood as well as those of other organ-specific diseases. Cells in the CNS are selectively protected from external and internal insults by the blood-brain barrier. Thus, the neuroimmune system, including microglia and immune proteins, might control external or internal insults that the adaptive immune system cannot control or mitigate. The pathologic findings differ by disease and show a state of inflammation that reflects the relationship between etiological or inflammation-inducing substances and corresponding immune reactions. Current immunological concepts about infectious diseases and infection-associated immune-mediated diseases, including those in the CNS, can only partly explain the pathophysiology of disease because they are based on the idea that host cell injury is caused by pathogens. Because every disease involves etiological or triggering substances for disease-onset, the protein-homeostasis-system (PHS) hypothesis proposes that the immune systems in the host control those substances according to the size and biochemical properties of the substances. In this article, I propose a common immunopathogenesis of CNS diseases, including prion diseases, Alzheimer's disease, and genetic diseases, through the PHS hypothesis.


Cardiac magnetic resonance imaging in suspected blunt cardiac injury: A prospective, pilot, cohort study.
The aim of this study was to evaluate the incidence and severity of blunt cardiac injury (BCI) as determined by cardiac magnetic resonance imaging (CMR), and to compare this to currently used diagnostic methods in severely injured patients. We conducted a prospective, pilot cohort study of 42 major trauma patients from July 2013 to Jan 2015. The cohort underwent CMR within 7 days, enrolling 21 patients with evidence of chest injury and an elevated Troponin I compared to 21 patients without chest injury who acted as controls. Major adverse cardiac events (MACE) including ventricular arrhythmia, unexplained hypotension requiring inotropes, or a requirement for cardiac surgery were recorded. 6/21 (28%) patients with chest injuries had abnormal CMR scans, while all 21 control patients had normal scans. CMR abnormalities included myocardial oedema, regional wall motion abnormalities, and myocardial haemorrhage. The left ventricle was the commonest site of injury (5/6), followed by the right ventricle (2/6) and tricuspid valve (1/6). MACE occurred in 5 patients. Sensitivity and specificity values for CMR at predicting MACE were 60% (15-95) and 81% (54-96), which compared favourably with other tests. In this pilot trial, CMR was found to give detailed anatomic information of myocardial injury in patients with suspected BCI, and may have a role in the diagnosis and management of patients with suspected BCI.


Stereocontrolled regeneration of olefins from epoxides.
Through treatment with NaI and trifluoroacetic anhydride, which presumably forms trifluoroacetyl iodide in situ, epoxides can be converted to olefins. This reaction now has been shown to tolerate remote olefins without loss of their individual stereochemistry. A reaction sequence involving regiospecific epoxidation of an isoprenoid alcohol, conversion of the alcohol to an azide, and cycloaddition with an acetylene, followed by conversion of the epoxide back to the original olefin, has allowed stereocontrolled preparation of triazole bisphosphonates with a farnesyl or a geranylgeranyl substituent. This strategy may be applicable selective protection of an alkene in other polyolefins, including substrates for metathesis reactions.


Pseudomonas aeruginosa necrotizing infection of the abdominal flap in a post-bariatric patient undergoing body contouring surgery.
Pseudomonas aeruginosa infections may involve any organ or body district and may give serious clinical sequelae. We report the case of an infection of the abdominoplasty flap that compromised wound closure and jeopardized the aesthetic outcome. To the best of our knowledge, this is the first such case reported in the literature for this group of patients. We have presented this case in order to alert plastic and general surgeons who may encounter this complication in future, such that they may be aware of the need to adopt an aggressive approach to manage these patients. This consisted of the accurate monitoring of the patient's clinical condition, prescribing appropriate antibiotics, and performing serial debridement of necrotic tissue.


Nano-sized layered Mn oxides as promising and biomimetic water oxidizing catalysts for water splitting in artificial photosynthetic systems.
One challenge in artificial photosynthetic systems is the development of artificial model compounds to oxidize water. The water-oxidizing complex of Photosystem II which is responsible for biological water oxidation contains a cluster of four Mn ions bridged by five oxygen atoms. Layered Mn oxides as efficient, stable, low cost, environmentally friendly and easy to use, synthesize, and manufacture compounds could be considered as functional and structural models for the site. Because of the related structure of these Mn oxides and the catalytic centre of the active site of the water oxidizing complex of Photosystem II, the study of layered Mn oxides may also help to understand more about the mechanism of water oxidation by the natural site. This review provides an overview of the current status of layered Mn oxides in artificial photosynthesis and discuss the sophisticated design strategies for Mn oxides as water oxidizing catalysts.


Evidence-based systematic review on the efficacy and safety of botulinum toxin-A therapy in post-stroke spasticity.
Botulinum toxin type A (BoNTA) has been suggested as an effective anti-spastic drug. In this article, we summarized the data of randomized, placebo-controlled, double- blind trials and conducted a meta-analysis to assess if BoNTA is an adequate treatment for spasticity following stroke. To evaluate the relevant literature and assess the effectiveness and safety of BoNTA in (1) reducing spasticity based on mean change in the Modified Ashworth Scale (MAS) for upper and lower limb spasticity from baseline; (2) reducing spasticity based on the percent of patients having > or = 1point(s) change in the MAS; (3) improving the patient's or caregivers' Global Assessment Scale (GAS); and (4) total adverse events. We selected all randomized, placebo controlled, double-blind clinical trials or previous meta-analyses evaluating the efficacy and safety of BoNTA (Botox or Dysport) for the treatment of spasticity in both upper and lower limbs after stroke. Validity assessment of studies was performed, and Revman 4.2.7 from Cochrane Collaboration and SPSS (statistical package for the social sciences), v 9.0, were applied for analysis. Overall analysis showed clinical improvement between baseline and 4-6 weeks after application of BoNTA of the patient's spasticity score using the MAS (weighted mean difference [WMD] = 0.87, 95% CI = 0.52-1.22). The odds ratio of the MAS spasticity score showing one or more points improvement at 4-6 weeks after giving BoNTA showed clinically significant improvement (OR = 4.5, 95% CI = 2.79-7.25). The odds ratio of having an improved GAS at 4-6 weeks after injecting BoNTA showed clinically significant improvement (Odds ratio = 5.85, 95% CI = 3.12-10.95). The odds ratio of having an adverse event during the entire study did not show any significant difference between placebo and BoNTA (odds ratio = 0.84, 95% CI = 0.55-1.28). BoNTA improves muscle tone in upper and lower limb spasticity following stroke. A global assessment of improvement was noted by the patients or the caregivers following BoNTA injection. BoNTA is considered a safe therapeutic agent.


Mesangial hypercellularity in children: presenting features and outcomes.
Mesangial hypercellularity (MH), in the absence of sclerosis or immune deposition, was a common finding on renal biopsy in our center. We studied 66 children with predominant MH. Among all patients older than 2.7 years, blood pressure (BP) percentile and glomerular filtration rate (GFR) remained stable. Serum albumin (Alb) trended higher (3.0+/-0.2 start vs. 3.4+/-0.2 end g/dl, p=0.06) and urine protein/creatinine lower (4.2+/-0.9 start vs. 2.3+/-0.9 end mg/mg, p=0.18) at the end of the study period. The proportion with stage 1 CKD remained constant: 94% start vs. 92% end. At end, Alb was lower in patients referred for nephrotic syndrome (NS): 4.4+/-0.3 hematuria vs. 4.2+/-0.2 proteinuria vs. 2.8+/-0.3 NS g/dl, p<0.05 vs. both. Alb was lower (p=0.03) and urine protein/creatinine trended higher in patients with diffuse foot-process fusion (FPF). Twenty-five percent of patients with focal FPF developed NS, all had relapses, and 63% were steroid sensitive (SS). All but one with diffuse FPF presented with NS; 86% had relapses (mean 1 year) and 63% were SS. GFR trended higher at the end in those with matrix thickening (mat) (119.6+/-4.7 no mat vs. 129.1+/-2.6 mat ml/min per 1.73 m2, p=0.1). Those without mat were less SS (59% no mat vs. 80% mat) and were more likely to require alkylating agents (Alk) for NS. Among those with positive immunofluorescence (IF), 82% had immunoglobulin M (IgM) alone; those with positive IF were more SS and needed Alk for NS. MH predicts a favorable prognosis. FPF predicts NS and multiple relapses.


Silk sericin as building blocks of bioactive materials for advanced therapeutics.
Silk sericin is a class of protein biopolymers produced by silkworms. Increasing attention has been paid to silk sericin for biomedical applications in the last decade, not only because of its excellent biocompatibility and biodegradability but also due to the pharmacological activities stemming from its unique amino acid compositions. In this review, the biological properties of silk sericin, including curing specific diseases and promoting tissue regeneration, as well as underlying mechanisms are summarized. We consider the antioxidant activity of silk sericin as a fundamental property, which could account for partial biological activities, despite the exact mechanisms of silk sericin's effect remaining unknown. Based on the reactive groups on silk sericin, approaches of bottom-up fabrication of silk sericin-based biomaterials are highlighted, including non-covalent interactions and chemical reactions (reduction, crosslinking, bioconjugation, and polymerization). We then briefly present the cutting-edge advances of silk sericin-based biomaterials applied in tissue engineering and drug delivery. The challenges of silk sericin-based biomaterials are proposed. With more bioactivities and underlying mechanisms of silk sericin uncovered, it is going to boost the therapeutic potential of silk sericin-based biomaterials.


Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice.
Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.


US Attenuation Imaging for the Evaluation and Diagnosis of Fatty Liver Disease.
This study aimed to determine whether the attenuation coefficient (AC) from attenuation imaging (ATI) was correlated with visual US assessment in patients with hepatic steatosis. Moreover, it aimed to assess whether the patient's blood chemistry results and CT attenuation were correlated with AC. Patients who underwent abdominal US with ATI between April 2018 and December 2018 were included in this study. Patients with chronic liver disease or cirrhosis were excluded. The correlation between AC and other parameters, such as visual US assessment, blood chemistry results, liver attenuation, and liver-to-spleen (L/S) ratio, were analyzed. AC values according to visual US assessment grades were compared using analysis of variance. A total of 161 patients were included in this study. The correlation coefficient between US assessment and AC was 0.814 (p < 0.001). The mean AC values for the normal, mild, moderate, and severe grades were 0.56, 0.66, 0.74, and 0.85, respectively (p < 0.001). Alanine aminotransferase levels were significantly correlated with AC (r = 0.317, p < 0.001). The correlation coefficients between liver attenuation and AC and between L/S ratio and AC were -0.702 and -0.626, respectively (p < 0.001). Visual US assessment and AC showed a strong positive correlation with the discriminative value between the groups. Computed tomography attenuation and AC showed a strong negative correlation.


Porcine alpha-1,3-galactosyltransferase: full length cDNA cloning, genomic organization, and analysis of splicing variants.
Full length cDNA and genomic DNA of porcine alpha-1,3-galactosyltransferase were isolated, and their structures were analysed. The coding region was encoded by six exons as in the mouse, and the length of each exon was conserved between the two species. The porcine exons were designated Exon 4-9, since in the mouse coding exons started from Exon 4. Introns tended to be longer in the porcine gene; the distance from Exon 4 to the 3'-end of Exon 9 was 24 kb, while this region was 18 kb in the mouse gene. The cDNA structure was extended from the previous data to the 3'-end and to the 5' side of the cDNA. In addition to a cDNA clone with all coding exons, clones lacking parts of these exons were isolated and their structures were determined. One variant lacked Exon 5; the second, Exons 5 and 6; and the third, Exons 5, 6 and 7. The last variant was not found in the mouse, and cDNA transfection of this variant yielded scarcely any enzymatic activity using asialo alpha1-acid glycoprotein as a substrate, and decreased activity using N-acetyllactosamine as a substrate.


Immunological cross-reactivity between H-2Dk product and DTIC-treated H-2d lymphoma.
The experiments reported here concern the characterization by techniques of in vitro cell-mediated immunity of the antigens induced by 5-(3,3' dimethyl-1-triazine)-imidazole-4-carboxamide (DTIC) on L1210, a chemically-induced lymphoma of DBA/2 mice (H-2d). This series of experiments with the DTIC-treated L1210 tumour show the presence of an 'H-2D'-like antigen which resembles the Dk gene product/s of the H-2k haplotype.


Nursing Students in Crisis Mode: Fluctuations in Anxiety During the COVID-19-Related Lockdown.
The COVID-19 pandemic initiated a period of new and difficult challenges for nursing students. The aim of this study was to assess the change in levels of anxiety and ways of coping when the lockdown was being lifted compared with the period of the most severe lockdown restrictions. First- to fourth-year nursing students in Israel (N = 244) completed 2 surveys conducted during the initial lockdown and 5 weeks later. When the restrictions were lightened, the mean anxiety score decreased from 9.3 to 7.5 (P < .0001). Among Muslims students, the trend was the opposite, and anxiety levels increased. Stronger resilience was associated with lower odds for anxiety. Mental disengagement and information seeking were associated with higher anxiety levels. The pandemic created unparalleled stressful situations for nursing students. Faculty should have heightened awareness of these stressors and act to implement innovative resolutions for the problems that arise.


Induction of second trimester abortion by intraamniotic instillation of Rivanol (ethacridine) combined with oxytocin infusion.
We report our experience of 0.1% intraamniotic Rivanol in the interruption of 100 midtrimester pregnancies (15-24 gestation weeks). The mean injection to abortion interval was 37.2h and there were no complications. Intraamniotic Rivanol injection combined with oxytocin infusion seemed an effective and safe method for terminating second trimester pregnancies.


Coping strategies predict post-traumatic stress in patients with head and neck cancer.
Evidence suggests that patients with head and neck cancer (HNC) are susceptible to post-traumatic stress disorder (PTSD). However, research is yet to examine predictors of PTSD symptoms in this patient group. The objective of this study was to investigate whether coping strategies at HNC diagnosis were related to outcomes of post-traumatic stress and health-related quality of life (HRQL) 6 months later. Sixty-five patients with HNC completed an assessment of coping, distress, and health-related quality of life at diagnosis and again 6 months later, and an assessment of post-traumatic stress at 6 months. Correlations and regression analyses were performed to examine relationships between coping and outcomes over time. Regression analyses showed that denial, behavioural disengagement and self-blame at diagnosis predicted post-traumatic stress symptoms. Self-blame at diagnosis also predicted poor HRQL. Results have implications for the development of psychological interventions that provide alternative coping strategies to potentially reduce PTSD symptoms and improve HRQL.


The contribution of musculoskeletal factors to physical frailty: a cross-sectional study.
Musculoskeletal conditions and physical frailty have overlapping constructs. We aimed to quantify individual contributions of musculoskeletal factors to frailty. Participants included 347 men and 360 women aged ≥60 yr (median ages; 70.8 (66.1-78.6) and 71.0 (65.2-77.5), respectively) from the Geelong Osteoporosis Study. Frailty was defined as ≥3, pre-frail 1-2, and robust 0, of the following; unintentional weight loss, weakness, low physical activity, exhaustion, and slowness. Measures were made of femoral neck BMD, appendicular lean mass index (ALMI, kg/m2) and whole-body fat mass index (FMI, kg/m2) by DXA (Lunar), SOS, BUA and SI at the calcaneus (Lunar Achilles Insight) and handgrip strength by dynamometers. Binary and ordinal logistic regression models and AUROC curves were used to quantify the contribution of musculoskeletal parameters to frailty. Potential confounders included anthropometry, smoking, alcohol, prior fracture, FMI, SES and comorbidities. Overall, 54(15.6%) men and 62(17.2%) women were frail. In adjusted-binary logistic models, SI, ALMI and HGS were associated with frailty in men (OR = 0.73, 95%CI 0.53-1.01; OR=0.48, 0.34-0.68; and OR = 0.11, 0.06-0.22; respectively). Muscle measures (ALMI and HGS) contributed more to this association than did bone (SI) (AUROCs 0.77, 0.85 vs 0.71, respectively). In women, only HGS was associated with frailty in adjusted models (OR = 0.30 95%CI 0.20-0.45, AUROC = 0.83). In adjusted ordinal models, similar results were observed in men; for women, HGS and ALMI were associated with frailty (ordered OR = 0.30 95%CI 0.20-0.45; OR = 0.56, 0.40-0.80, respectively). Muscle deficits appeared to contribute more than bone deficits to frailty. This may have implications for identifying potential musculoskeletal targets for preventing or managing the progression of frailty.


Scale invariant features of differential spatial displacement discrimination.
For a configuration of three blobs, with Gaussian spatial contrast profiles, at threshold luminance contrast, differential spatial displacement discrimination thresholds were determined. The blobs were arranged one above the other, at equal spatial intervals. Thresholds were determined for displacements of the middle blob both orthogonal to and along the axis joining the outer two blobs. Thresholds for both tasks were obtained as a function of both the resolution and the separation of the blobs. The thresholds for both tasks increased linearly with decreasing resolution (increasing blur), for a constant ratio of the resolution parameter and the separation of the outer two blobs. At all levels of resolution there are two blob-separation regimes, in which different strategies are used to compute differential spatial displacements. Independent of the level of resolution, transition between those regions occurs when the separation of the outer two blobs is a constant multiple (approx. 25) of their blur parameter. We interpret these results as further evidence for a scale-invariant mechanism for differential spatial displacement computation.


Biodegradable polyesters for controlled release of trypanocidal drugs: in vitro and in vivo studies.
Copolymers of epsilon-caprolactone and L-lactide P(CL-LLA), epsilon-caprolactone and D,L-lactide P(CL-DLLA) and epsilon-caprolactone and trimethylene carbonate P(CL-TMC) were synthesized. The composition of comonomers and their sequence lengths were determined by means of 1H and 13C NMR measurements. The effect of the comonomer on the thermal properties was investigated by differential scanning calorimetry (DSC) analysis. The in vitro degradation of the rods obtained by melt extrusion of the synthesized copolymers and the commercial homopolymers poly(epsilon-caprolactone) P(CL) and poly(D,L-lactide) P(DLLA) was carried out in phosphate buffer (PB) pH 7.4 at 37 degrees C. The rate of degradation depends on comonomers and polymer composition. The in vitro release of the selected drugs, isometamidium chloride (IMM) and ethidium bromide (EtBr), from such devices was carried out under the same conditions as used for the in vitro degradation. The release experiments show that the release of IMM is faster than for EtBr. During the first stage, for IMM the release is governed by osmotic pressure whereas for EtBr the release is mainly diffusion-controlled. The in vitro release of these drugs is governed by polymer matrix degradation at the later stage of the release process. Comparative in vitro release study from the different polymers showed that the release depends mainly on the physical properties of the polymer. The in vivo experiments carried out in the field on cattle and in the laboratory on rabbits using the classical treatment (intramuscular injection) and the sustained release devices (SRD) subcutaneously implanted, showed that the prophylactic period is significantly enhanced in the case of SRD as compared to intramuscular injection. The comparative efficacy of SRD containing IMM and EtBr evaluated in the case of rabbits showed that, the SRD (IMM) prophylactic period is much longer than for SRD (EtBr).


Estrogen facilitates osteoblast differentiation by upregulating bone morphogenetic protein-4 signaling.
Imbalanced functions of osteoclasts and osteoblasts are involved in various types of bone damage including postmenopausal osteoporosis. In the present study, we investigated the cellular mechanism by which estrogen interacts in the process of osteoblastic differentiation regulated by BMP-4 using mouse MC3T3-E1 cells that express estrogen receptors (ER) and BMP-4. Estradiol enhanced BMP-4-induced Runx2, osterix, ALP and osteocalcin expression in MC3T3-E1 cells. BMP-4-induced mineralization shown by Alizarin red staining was also facilitated by estrogen treatment. It was revealed that estrogen upregulated BMP-4-induced Smad1/5/8 phosphorylation, BRE-Luc activity and Id-1 mRNA expression. The expression of BMPRII was increased by estrogen in MC3T3-E1 cells, and inhibition of BMPRII or ALK-2/3 signaling impaired the effect of estrogen on BMP-4 signaling. Of note, the enhanced expression of osterix, ALP and osteocalcin mRNAs induced by BMP-4 and estrogen was reversed in the presence of an ER antagonist. Given that membrane-impermeable estrogen also upregulated BMP-4-induced expression of osteoblastic markers and Id-1 mRNA, non-genomic ER activity is involved in the mechanism by which estrogen enhances BMP-4-induced osteoblast differentiation in MC3T3-E1 cells. On the other hand, the expression of ERα and endogenous BMP-4 was suppressed by BMP-4 treatment regardless of the presence of estrogen, implying the presence of a negative feedback loop for osteoblast differentiation. Thus, estrogen is functionally involved in the process of osteoblast differentiation regulated by BMP-4 through upregulating BMP sensitivity of MC3T3-E1 cells.


Compensatory behavior of the postural control system to flexion-relaxation phenomena.
Laxity of the passive tissues of the spine during prolonged spinal flexion has been shown to disturb spinal stability. This study investigated the effects of short periods of static lumbar flexion and short rest periods on the flexion-relaxation angle for the erector spinae muscles in 36 healthy female college students. The surface electromyographic activity of the erector spinae muscles was measured in three states before the onset of creep, immediately after 7 min of static lumbar flexion, and after a 10 min rest. The results showed that 7 min of static lumbar flexion will produce relaxation of the erector spinae muscles that occurs at greater absolute lumbar and trunk angles, during the forward bending activity (P<0.05), while the corresponding relative angles did not change before and after creep. The results also indicate that postural compensations are dominant over the muscular compensations for load sharing in flexion-relaxation phenomena of asymptomatic healthy participants. This further highlights the importance of postural modulation in the control of movement and preservation of skeletal stability. Considering spinal posture in the upright condition, and its changes by phenomena such as creep, can reduce postural injuries by instructing subjects to approach a more vertical posture, after periods of bending, to compensate the stretching effects of the tissues and thus regaining the normal muscular activity pattern.


Seismic Survey Footprints in Irish Waters: A Starting Point for Effective Mitigation.
The noise footprint of a given activity is defined as the area where the noise from the activity spreads into the ocean at levels above the existing statistical ambient noise. The noise footprints of seismic surveys in Irish waters from 2,000 to 2,011 have been estimated using Quonops, a global ocean noise prediction service. Noise footprints are converted into sound exposure levels to evaluate the cumulative risks toward high-, mid-, and low-frequency marine mammals. The results demonstrate large variability in risk areas as a function of existing ambient-noise levels, season, survey location, and characteristics of the survey.


Vegetation pattern shift as a result of rising atmospheric CO2 in arid ecosystems.
Arid ecosystems are expected to be among the ecosystems most sensitive to climate change. Here, we explore via model calculations how regular vegetation patterns, widely observed in arid ecosystems, respond to projected climatic shifts as provided by general circulation model output. In our model, the photosynthesis and respiration terms are explicitly linked to physiological attributes of the plants and are forced with the primary climatic drivers: atmospheric CO(2), air temperature, and precipitation. Under future climate scenarios, our simulations show that the system's fate depends on whether the enhancements to photosynthesis due to elevated atmospheric CO(2) outweigh the increases in respiration due to higher air temperatures and the increases in water stress due to lower rainfall. A scalar measure is proposed to quantify this balance between the changes in the three climate drivers. Our model results suggest that knowing how the three primary climate drivers are evolving may provide hints as to whether the ecosystem is approaching desertification.


ABR frequency tuning curves in dolphins.
Tone-tone masking was used to determine auditory brain-stem response tuning curves in dolphins (Tursiops truncatus) in a simultaneous-masking paradigm. The Q10 of the curves was as large as 16-19 in the frequency range 64-128 kHz. In the range 45-16 kHz, Q10 decreased proportionally to the frequency with the bandwidth of the curves being constant, about 3.5-4 kHz at the 10-dB level. Tuning curves below 45 kHz are supposed to reflect broad spectral bandwidth of the probe's effective part which is no longer than 0.5 ms, irrespective of actual probe duration. Tuning curves above 64 kHz are supposed to reflect the real frequency tuning of the dolphin's auditory system.


Be careful of splenic rupture caused by hit by a pitch during a baseball game: a case report.
To the best of our knowledge, splenic rupture caused by hit by a pitch (HBP) has not been previously reported. We present a patient who underwent emergency laparotomy for splenic rupture after being HBP during a baseball game. A 41-year-old male was HBP in the left abdomen during his first at-bat during a baseball game. During the operation, vascular injury of the splenic hilum and a deeply extending parenchymal injury were observed, and splenectomy was performed. Histologic findings were consistent with splenic rupture. The patient's postoperative course was uneventful. Although extremely rare, the possibility of intra-abdominal organ injury should be considered in batters who are hit in the abdomen by a pitched baseball, as illustrated by our patient.


[The main reasons behind variability in detection of prolactin and causes of true or apparent discordance with clinical state].
Both the "hook" effect and macroprolactinaemia, are the main reasons behind the discrepancy of serum prolactin level results in various laboratories. They can cause the diagnostic dilemmas or even completely faulty diagnosis resulting with undertaking of unnecessary investigations and/or an inappropriate method of treatment. Therefore, a review article on this matters may be of some help for clinical practice.


Detection of amine impurity and quality assessment of the MALDI matrix α-cyano-4-hydroxy-cinnamic acid for peptide analysis in the amol range.
We have studied sample preparation conditions to increase the reproducibility of positive UV-MALDI-TOF mass spectrometry of peptides in the amol range. By evaluating several α-cyano-4-hydroxy-cinnamic acid (CHCA) matrix batches and preparation protocols, it became apparent that two factors have a large influence on the reproducibility and the quality of the generated peptide mass spectra: (1) the selection of the CHCA matrix, which allows the most sensitive measurements and an easier finding of the "sweet spots," and (2) the amount of the sample volume deposited onto the thin crystalline matrix layer. We have studied in detail the influence of a contaminant, coming from commercial CHCA matrix batches, on sensitivity of generated peptide mass spectra in the amol as well as fmol range of a tryptic peptide mixture. The structure of the contaminant, N,N-dimethylbutyl amine, was determined by applying MALDI-FT-ICR mass spectrometry experiments for elemental composition and MALDI high energy CID experiments utilizing a tandem mass spectrometer (TOF/RTOF). A recrystallization of heavily contaminated CHCA batches that reduces or eliminates the determined impurity is described. Furthermore, a fast and reliable method for the assessment of CHCA matrix batches prior to tryptic peptide MALDI mass spectrometric analyses is presented.


Development and Implementation of an Online Education Program on Advanced Breast Cancer for European Cancer Nurses: ABC4Nurses Project: a Brief Report.
Breast cancer is now the most commonly diagnosed cancer worldwide. Approximately 30% of those who present with early breast cancer later develop advanced breast cancer (ABC). Additionally, approximately 6% have advanced breast cancer at diagnosis. New treatment options result in an extended lifespan dominated by cycles of deterioration and stable disease. Specialist nurse knowledge is key to multidisciplinary care of people with ABC; however, access to education on ABC for nurses is not universally available in Europe. This paper describes the development and implementation of an online bespoke program on ABC care for specialist and generalist nurses in Europe. The project team is affiliated with the European Oncology Nurses Society (EONS) and comprises specialist breast cancer nurses, oncology nurse academics and breast cancer advocates associated with EUROPA DONNA Turkey, an independent non-profit European breast cancer organisation. The program development involved (1) a systematic review of ABC educational resources for cancer nurses; (2) a modified four-round Delphi study to seek agreement on curriculum content and (3) curriculum development, conversion to an interactive online platform and translation into four European languages. The program evaluation will be guided by Kirkpatrick's framework. The phases described in this short report could guide others involved in developing bespoke cancer education programs.


Pooled analysis of the HLA-DRB1 by smoking interaction in Parkinson disease.
Inflammatory response plays an important role in Parkinson disease (PD). Previous studies have reported an association between human leukocyte antigen (HLA)-DRB1 and the risk of PD. There has also been growing interest in investigating whether inflammation-related genes interact with environmental factors such as smoking to influence PD risk. We performed a pooled analysis of the interaction between HLA-DRB1 and smoking in PD in 3 population-based case-control studies from Denmark and France. We included 2,056 cases and 2,723 controls from 3 PD studies (Denmark, France) that obtained information on smoking through interviews. Genotyping of the rs660895 polymorphism in the HLA-DRB1 region was based on saliva or blood DNA samples. To assess interactions, we used logistic regression with product terms between rs660895 and smoking. We performed random-effects meta-analysis of marginal associations and interactions. Both carrying rs660895-G (AG vs AA: odds ratio [OR] = 0.81; GG vs AA: OR = 0.56; p-trend = 0.003) and ever smoking (OR = 0.56, p < 0.001) were inversely associated with PD. A multiplicative interaction was observed between rs660895 and smoking using codominant, additive (interaction parameter = 1.37, p = 0.005), and dominant (interaction parameter = 1.54, p = 0.001) genetic models without any heterogeneity (I² = 0.0%); the inverse association of rs660895-(AG+GG) with PD seen in never smokers (OR = 0.64, p < 0.001) disappeared among ever smokers (OR = 1.00, p = 0.99). Similar interactions were observed when we investigated light and heavy smokers separately. Our study provides the first evidence that smoking modifies the previously reported inverse association of rs660895-G with PD, and suggests that smoking and HLA-DRB1 are involved in common pathways, possibly related to neuroinflammation. Ann Neurol 2017;82:655-664.


Quantification of BK viral load in asymptomatic renal allograft recipients.
Polyoma BK virus (BKV) has recently been identified to cause renal allograft dysfunction, which manifests as polyomavirus-associated nephropathy (PVAN). However, the presence and level of BKV DNA in renal allograft patients with good and stable renal function have remained undetermined. In this prospective study, serum samples were collected from a total of 45 renal allograft recipients with serum creatinine <155 μmol/L. In 17 patients, whose duration of transplantation was under 2 years, samples were collected at 3-4-month intervals for up to 2 years after transplantation. BK viral load was quantified using quantitative polymerase chain reaction (Q-PCR). The BK viral load in asymptomatic renal allograft recipients was independent of the duration of transplantation and did not correlate with allograft function. The mean (± SD) level of viremia was 552.80 ± 1931.00 genome copies/mL, with 92.9% of patients having low levels of viremia corresponding to <1 × 10(3) copies/mL. In contrast, patients with proven PVAN had levels in the range of 10(6) copies/mL. The prevailing BK viral load in asymptomatic renal allograft patients is quantifiably low. Our findings may guide optimal immunosuppressive modulation in PVAN cases, where judicious manipulation of immunosuppression is required without inciting allograft rejection.


Youth unemployment--individual and societal consequences, and new research approaches.
The social effects of youth unemployment must be described in connection with the special unemployment situations which this condition implies for youths. Periods of joblessness are in general short and alternate with job programmes or educational programmes, a situation which can be characterised as a 'permanent impermanence'. Unemployment must also be seen in light of its occurrence during a central stage of a youth's development. The social effects are primarily of three kinds: those limited to the individual welfare, those concerning the individual's connection to his group and those concerning the individual's relationship with society. The first mentioned is most commonly expressed psychosomatically or socio-medically, the second socio-psychologically and the third socio-culturally or societally.


Regenerative strategies for the consequences of myocardial infarction: Chronological indication and upcoming visions.
Heart muscle injury and an elevated troponin level signify myocardial infarction (MI), which may result in defective and uncoordinated segments, reduced cardiac output, and ultimately, death. Physicians apply thrombolytic therapy, coronary artery bypass graft (CABG) surgery, or percutaneous coronary intervention (PCI) to recanalize and restore blood flow to the coronary arteries, albeit they were not convincingly able to solve the heart problems. Thus, researchers aim to introduce novel substitutional therapies for regenerating and functionalizing damaged cardiac tissue based on engineering concepts. Cell-based engineering approaches, utilizing biomaterials, gene, drug, growth factor delivery systems, and tissue engineering are the most leading studies in the field of heart regeneration. Also, understanding the primary cause of MI and thus selecting the most efficient treatment method can be enhanced by preparing microdevices so-called heart-on-a-chip. In this regard, microfluidic approaches can be used as diagnostic platforms or drug screening in cardiac disease treatment. Additionally, bioprinting technique with whole organ 3D printing of human heart with major vessels, cardiomyocytes and endothelial cells can be an ideal goal for cardiac tissue engineering and remarkable achievement in near future. Consequently, this review discusses the different aspects, advancements, and challenges of the mentioned methods with presenting the advantages and disadvantages, chronological indications, and application prospects of various novel therapeutic approaches.


How I do it: robotic-assisted Ivor Lewis esophagectomy.
Advances in minimally invasive techniques, including robotic surgical technology, have led to improved outcomes in esophagectomy. In this article, we detail our approach to the robotic Ivor Lewis esophagectomy.


Ultrasonography and return to play of the different clinical grading of quadriceps contusions: a case series.
Prognostication of quadriceps contusion is based on the patient's active knee flexion after the injury. Unlike ultrasonography, clinical grading does not define the extent of soft tissue injury and may provide inaccurate time for return to play. The purposes of this report are to describe the ultrasound findings of the different clinical grading of quadriceps contusion and document the return to play of each case. Seven patients were evaluated in this series. Results showed discrepancies in the disability time between clinical grading and ultrasound findings. Clinical grading did not consistently estimate the return to play as described in previously published literature. Contusions with hyperechoic lesions had earlier return to play compared to patients with hypoechoic findings. Contusions with hypoechoic lesions might require aggressive monitoring and therapy to decrease disability time and avoid complications such as myositis ossificans.


Nephroblastoma and neuroblastoma--histology and prognosis.
Statistically evaluating the influence of a histological grading, respectively of morphological differences on prognosis of nephroblastomas and neuroblastomas, better chances for survival become evident not only for earlier clinical stages, but also for nephroblastomas with high differentiation, or neuroblastomas with signs for differentiation. Only for neuroblastomas a relevant predeliction of tumors with signs of differentiation for the early clinical stage I is present. Combined subclassification according to clinical stages and histological grades results in 3 risk groups with different chances for survival. These 3 groups may play a role for specific therapeutic considerations.


A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS Clinical Trials Group Protocol 135 Study Team.
To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients. A randomized, open-labeled, comparative trial. Outpatient clinics. Seventy-four patients with HIV and symptomatic bacteremic M. avium infection. Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium. No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups. The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.


Oxidized low-density lipoprotein promotes vascular endothelial cell dysfunction by stimulating miR-496 expression and inhibiting the Hippo pathway effector YAP.
Oxidized low-density lipoprotein (ox-LDL) can damage vascular endothelial cells and cause atherosclerosis, but its epigenetic regulatory mechanism has not been fully elucidated. We show that ox-LDL induced significant apoptosis and loss of function in human umbilical vascular endothelial cells (HUVECs). At the same time, ox-LDL significantly decreased the expression of Hippo-YAP/ZAP (Yes-associated protein/YLP motif-containing 1) pathway proteins as compared to that of the control. The luciferase reporter system confirmed that microRNA (miR)-496 silenced YAP gene expression by binding to its 3' untranslated region (3' UTR). Ox-LDL-treated miR-496 overexpression HUVECs had a higher apoptosis rate and more severe dysfunction compared to the control cells. This in-depth study shows that ox-LDL inhibits YAP protein expression by inducing miR-496 expression, leading to its inability to enter the nucleus, thereby losing its function as a transcriptional cofactor for activating the downstream genes. Our findings reveal that, through epigenetic modification, ox-LDL can inhibit the normal expression of Hippo-YAP/ZAP pathway proteins via miR-496 expression and induce vascular endothelial cell dysfunction.


Diagnostic dilemmas resulting from the immunoreactive trypsinogen/DNA cystic fibrosis newborn screening algorithm.
To quantitate the proportion of infants identified through cystic fibrosis (CF) newborn screening (NBS) by an immunoreactive trypsinogen (IRT)/DNA screening algorithm who have an unclear diagnosis as defined by the findings of an elevated IRT level and either 1) 2 CF gene (CFTR) mutations detected and sweat chloride level <60 mEq/L; or 2) 0 or 1 CFTR mutations and a "borderline" sweat chloride level >or=30 and <60 mEq/L. Using the 4-year cohort of CF-affected infants recently described by the Massachusetts CF NBS program, we identified and described the number of infants with the diagnostic characteristics (diagnostic dilemmas) aforementioned. Of infants with positive results on CF NBS who had 1 CFTR mutation detected and a borderline sweat chloride concentration, nearly 20% displayed a second CFTR mutation on further evaluation. Of all infants with positive CF NBS results considered affected with CF, 11% had a diagnosis that fell into 1 of the diagnostic dilemma categories aforementioned. Four problematic diagnostic categories generated by CF NBS are defined. In the absence of data on the natural history of such infants, careful follow-up is recommended for infants in whom a definitive diagnosis is elusive.


Biomarkers for isolated congenital heart disease based on maternal amniotic fluid metabolomics analysis.
Congenital heart disease (CHD) is one of the most prevalent birth defects in the world. The pathogenesis of CHD is complex and unclear. With the development of metabolomics technology, variations in metabolites may provide new clues about the causes of CHD and may serve as a biomarker during pregnancy. Sixty-five amniotic fluid samples (28 cases and 37 controls) during the second and third trimesters were utilized in this study. The metabolomics of CHD and normal fetuses were analyzed by untargeted metabolomics technology. Differential comparison and randomForest were used to screen metabolic biomarkers. A total of 2472 metabolites were detected, and they were distributed differentially between the cases and controls. Setting the selection criteria of fold change (FC) ≥ 2, P value < 0.01 and variable importance for the projection (VIP) ≥ 1.5, we screened 118 differential metabolites. Within the prediction model by random forest, PE(MonoMe(11,5)/MonoMe(13,5)), N-feruloylserotonin and 2,6-di-tert-butylbenzoquinone showed good prediction effects. Differential metabolites were mainly concentrated in aldosterone synthesis and secretion, drug metabolism, nicotinate and nicotinamide metabolism pathways, which may be related to the occurrence and development of CHD. This study provides a new database of CHD metabolic biomarkers and mechanistic research. These results need to be further verified in larger samples.


Clinical impact of bloodstream infection on acute cholecystitis indicated for emergency cholecystectomy.
The significance of blood culture for acute cholecystitis remains unclear. A retrospective cohort study was conducted on patients who underwent emergency cholecystectomy at Hyogo Prefectural Amagasaki General Medical Center to examine the clinical impact of bloodstream infection (BSI), focusing on the association of BSI with bactibilia and severity grade based on the Tokyo guidelines 2018 (TG18). Among 177 patients included in the study, 32 had positive and 145 had negative BSI. Significant differences were observed between the positive and negative BSI in terms of age, body mass index (BMI), the American Society of Anesthesiologists physical status (ASA-PS) and TG18 severity score. The odds ratios of BSI for patients aged ≥72 years, with a BMI of ≤21.8, an ASA-PS of ≥3E, and grade III acute cholecystitis were 3.45, 3.23, 2.43 and 4.51, respectively. In the multivariate analysis, lower BMI and grade III were significantly associated with BSI with odds ratios of 2.53 (95% confidence interval: 1.07-6.21, P = .037) and 3.03 (95% confidence interval: 1.02-8.82, P = .041). Bacterial species that could not be isolated in the bile culture alone were identified in blood culture on 10 (38.5%) of 26 patients. Bloodstream infection is associated with grade III acute cholecystitis. Blood culture enables the identification of bacteria that cannot be isolated in bile culture. Blood culture should be obtained for patients with grade III acute cholecystitis who undergo emergency cholecystectomy.


A Virtual Cohort Study of Individuals at Genetic Risk for Parkinson's Disease: Study Protocol and Design.
The rise of direct-to-consumer genetic testing has enabled many to learn of their possible increased risk for rare diseases, some of which may be suitable for gene-targeted therapies. However, recruiting a large and representative population for rare diseases or genetically defined sub-populations of common diseases is slow, difficult, and expensive. To assess the feasibility of recruiting and retaining a cohort of individuals who carry a genetic mutation linked to Parkinson's disease (G2019S variant of LRRK2); to characterize this cohort relative to the characteristics of traditional, in-person studies; and to evaluate this model's ability to create an engaged study cohort interested in future clinical trials of gene-directed therapies. This single-site,3-year national longitudinal observational study will recruit between 250 to 350 LRRK2 carriers without Parkinson's disease and approximately 50 with the condition. Participants must have undergone genetic testing by the personal genetics company, 23andMe, Inc., have knowledge of their carrier status, and consent to be contacted for research studies. All participants undergo standardized assessments, including video-based cognitive and motor examination, and complete patient-reported outcomes on an annual basis. 263 individuals living in 33 states have enrolled. The cohort has a mean (SD) age of 56.0 (15.9) years, 59% are female, and 76% are of Ashkenazi Jewish descent. 233 have completed the baseline visit: 47 with self-reported Parkinson's disease and 186 without. This study establishes a promising model for developing a geographically dispersed and well-characterized cohort ready for participation in future clinical trials of gene-directed therapies.


Cross-country discrepancies on public understanding of stress concepts: evidence for stress-management psychoeducational programs.
Negative effects of stress have pose one of the major threats to the health and economic well being of individuals independently of age and cultural background. Nevertheless, the term "stress" has been globally used unlinked from scientificevidence-based meaning. The discrepancies between scientific and public stress knowledge are focus of concern and little is know about it. This is relevant since misconceptions about stress may influence the effects of stress-management psychoeducational programs and the development of best practices for interventions. The study aimed to analyze stress knowledge among the Canadian and Brazilian general public and to determine the extent to which scientific and popular views of stress differ between those countries. We evaluated 1156 healthy participants between 18 and 88 years of age recruited from Canada (n = 502) and Brazil (n = 654). To assess stress knowledge, a questionnaire composed of questions regarding stress concepts ("stress is bad" versus "stress-free life is good") and factors capable of triggering the stress response ("novelty, unpredictability, low sense of control and social evaluative threat versus "time pressure,work overload, conflict, unbalance and children") was used. Both Canadian and Brazilian participants showed misconceptions about stress and the factors capable of triggering a stress response. However, the rate of misconceptions was higher in Brazil than in Canada (p < 0.05). These findings suggest a lack of public understanding of stress science and its variance according to a country's society. Psychoeducational programs and vulnerability of stress-related disorder are discussed.


A novel matrix protein PNU5 facilitates the transformation from amorphous calcium carbonate to calcite and aragonite.
For both nacre formation and biomineralization in mollusks, understanding the molecular mechanism is imperative. Biomineralization, especially shell formation, is dedicatedly regulated by multiple matrix proteins. However, ACC conversion to stable crystals still lacks positive factors. In this research, we found a novel matrix protein named PNU5 in Pinctada fucata that plays a regulatory role in both prismatic layer and nacreous layer formation. Functional studies in vivo and in vitro have shown that it might be involved in shell formation in a positive manner. RT-qPCR analysis showed that pnu5 was highly expressed in mantle pallial and participated in shell repairing and regeneration. RNAi-mediated repression of pnu5 could affect the normal structure of prismatic layer and nacreous layer. The recombinant protein rPNU5 significantly enhanced the precipitation rate of CaCO3 both in the calcite and aragonite crystallization systems, as well as altering the morphology of the crystals. Based on ACC transition experiments, the recombinant protein rPNU5 facilitated amorphous calcium carbonate (ACC) transformation into stable calcite or aragonite. This study could provide us with a better understanding of how positive regulatory mechanisms contribute to biomineralization.


Muscle activation and time to task failure differ with load type and contraction intensity for a human hand muscle.
Time to failure for sustained isometric contractions of the elbow flexors is briefer when maintaining a constant elbow angle while supporting an inertial load (position task) compared with exerting an equivalent torque against a rigid restraint (force task). Our primary purpose was to determine whether the effects of load type on time to task failure exist when motor unit recruitment cannot be enhanced during a sustained submaximal contraction of an intrinsic hand muscle. A second purpose was to determine whether a greater reserve remains in the muscle after early failure of the position task. Two groups of 10 strength-matched men performed the force and position tasks at either 20% or 60% of maximal force (MVC) with the first dorsal interosseus, followed by a second force task at the same relative intensity. The rate of increase in surface EMG was greater (P = 0.002) and time to failure was briefer (P = 0.005) for the position task (593 +/- 212 s) compared with the force task (983 +/- 328 s) at 20% MVC, whereas there were no task differences in these variables at 60% MVC (P >or= 0.200). Time to failure for the second force tasks did not differ at either contraction intensity (P>or=0.743). These results demonstrate that previously observed effects of load type generalize to a hand muscle, although only for low-intensity contractions. For the position task at low forces, muscle activity increased more rapidly and no additional reserve remained in the muscle at failure compared with the force task. We propose that the briefer time to failure for the position task during sustained, low-intensity contractions is due to earlier recruitment of the motor unit pool.


Use of a problem-based learning discussion format to teach anesthesiology residents research fundamentals.
To present a new research problem-based learning discussion (PBLD) conference and to evaluate its effect on residents. Retrospective observational study of resident education before and after implementation of a research PBLD. Large U.S. academic anesthesiology department. 93 anesthesiology residents with research PBLD exposure in the academic year (AY) 2010 and AY 2011, and 85 residents without research PBLD exposure in AY 2008 and AY 2009. Since AY 2010, a PBLD format has been used to teach residents clinical research fundamentals. The annual 90-minute PBLD addressed residents' perceived barriers to research and introduced research resources available via the Clinical and Translational Science Institute (CTSI). Data recorded were: 1) number of residents who made CTSI consultation solicitations as a new investigator, and 2) number of new research projects proposed by the residents and designed with CTSI consultation. Each outcome was compared between the prePBLD group (AY 2008 [n=43] and AY 2009 [n=42]) and the postPBLD group (AY 2010 [n=43] and AY 2011 [n=50]). The number of residents who consulted the CTSI as new investigators increased from 4 of 85 residents (4.7%) in the prePBLD group to 13 of 93 residents (14.0%) in the postPBLD group (P = 0.042). The number of new research projects for which the residents consulted CTSI increased from 10 to 20 (100% increase). A PBLD format for research education of anesthesiology residents is effective.


Ecology dictates the value of memory for foraging bees.
"Ecological intelligence" hypotheses posit that animal learning and memory evolve to meet the demands posed by foraging and, together with social intelligence and cognitive buffer hypotheses, provide a key framework for understanding cognitive evolution.1-5 However, identifying the critical environments where cognitive investment reaps significant benefits has proved challenging.6-8 Here, we capitalize upon seasonal variation in forage availability for a social insect model (Bombus terrestris audax) to establish how the benefits of short-term memory, assayed using a radial arm maze (RAM), vary with resource availability. Following a staggered design over 2 years, whereby bees from standardized colonies at identical life-history stages underwent cognitive testing before foraging in the wild, we found that RAM performance predicts foraging efficiency-a key determinant of colony fitness-in plentiful spring foraging conditions but that this relationship is reversed during the summer floral dearth. Our results suggest that the selection for enhanced cognitive abilities is unlikely to be limited to harsh environments where food is hard to find or extract,5,9-11 highlighting instead that the challenges of rich and plentiful environments, which present multiple options in short succession, could be a broad driver in the evolution of certain cognitive traits. VIDEO ABSTRACT.


Bioactive marine peptides: nutraceutical value and novel approaches.
Marine organisms represent a valuable source of nutraceuticals and functional compounds. The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of novel active substances for the development of bioactive products. Recently, a great deal of interest has been expressed in marine-derived bioactive peptides because of their numerous beneficial health effects. Moreover, several studies have reported that marine bioactive peptides can be used as antihypertensive, antioxidative, anticoagulant, and antimicrobial components in functional foods or nutraceuticals and pharmaceuticals due to their therapeutic potential in the treatment or prevention of disease. In this chapter, we provide an overview of bioactive peptides derived from marine organisms as well as information about their biological properties and mechanisms of action with potential applications in different areas.


Pure cellulose nanofiber separator with high ionic conductivity and cycling stability for lithium-ion batteries.
Conventional polyolefin separators are constrained by poor electrolyte wettability, inferior thermal stability, and low ionic conductivity, which seriously restrict their application in high-performance lithium-ion batteries (LIBs). Herein, cellulose nanofiber (CNF) as the matrix and tert-butyl alcohol (TBA) as the dispersion medium were used to prepare the pure CNF separators for LIBs by a facile filtration method. The effects of the drying temperature on the pore structure, electrolyte wettability, mechanical properties, thermal stability, and ionic conductivity of the separators were comprehensively investigated. The results showed that the freeze-dried separator at -80 °C with TBA as the dispersion medium (TBA-FD) had the best overall performance, with the porosity and electrolyte uptake up to 70.8 % and 296 %, respectively, as well as the ionic conductivity up to 1.90 mS/cm. The CNF separators had no apparent thermal shrinkage at 160 °C, illustrating good thermal stability. Moreover, the LiFePO4/lithium metal battery assembled with the TBA-HD (tert-butyl alcohol as the dispersion medium for heat-drying at 80 °C) and TBA-FD separators displayed superior cycling stability (with a capacity retention rate up to 97.5 % and 96.4 %, respectively) and rate performance. The pure CNF separators with good performance prepared by the facile method are greatly promising for high-performance LIBs.


Comparative histopathological study of the venous wall of chronic venous insufficiency and varicose disease.
To investigate venous histopathology of chronic venous insufficiency and varicose patients (C2). Retrospective review of venous histopathology of 52 patients (13, 8, 2, and 28 were C2, C4, C5 and C6). The intimal thickness, intimal fibrosis, total thickness and intimal/total thickness ratio were highest in venous clinical severity score 0, 1 chronic venous insufficiency (no or minimal varicosity) follow by Venous Clinical Severity Score 2,3 chronic venous insufficiency (trunkal varice) and C2 veins (mean intimal thickness 62, 36, 26 µm, mean intimal fibrosis 74%, 72%, 65%, mean total thickness 184, 159, 133 µm, mean intimal/total thickness ratio 0.32, 0.20, 0.21). The statistical significances were found when comparing intimal thickness, intimal fibrosis, intimal/total thickness ratio and total thickness of Venous Clinical Severity Score 0, 1 chronic venous insufficiency veins and C2 veins. The medial changes are relatively constant among groups. Compared with C2 vein, the intimal changes in chronic venous insufficiency venous wall differ, particularly in the VCSS 0, 1 chronic venous insufficiency.


A LIKELIHOOD JUSTIFICATION OF PARSIMONY.
Abstract- A connection is established between maximally parsimonious cladograms and trees of highest likelihood. The assumptions needed to prove this are derivable from the structure of evolutionary theory and are independent of the frequency of homoplasy. The bearing of this justification on alternative methods of phylogenetic inference and on Felsenstein's (1978) proof that parsimony and other phylogenetic methods can be statistically inconsistent is discussed.


Sarcolectin: an interferon antagonist extracted from hamster sarcomas and normal muscles. Isolation, characterization, and purification.
In the present work we show that sarcoma and normal hamster tissues contain a protein which agglutinates normal and transformed cells. The inhibition of agglutination by galacturonic acid and occasionally by fucose suggests a resemblance of this protein with vegetal lectins. When added 5 h after interferon, the crude semipurified and electrophoretically homogeneous preparations reduce within 20 h the antiviral state pre-established by interferon. These two biological tests have enabled us to monitor the subsequent purification steps. The isolation of the biologically active protein is greatly facilitated by its resistance to pepsin and nucleases, whereas its sensitivity to trypsin and Pronase suggests its proteinaceous character. Furthermore, the molecule is stable when heated 1-2 min at 100 degrees C in the presence or absence of sodium dodecyl sulfate. After pepsin treatment, Sephacryl G-200 gel filtration, and ion exchange chromatography on DEAE-cellulose, 25-40-fold purification can be obtained. When controlled by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a double band (DEAE-cellulose sample) or single band (octyl-agarose sample) is detected in the 65,000-dalton region and no other contaminator is present. The eluted protein retains full biological activity when assayed by the degradation of the interferon-induced antiviral protection in the cell or titrated by cell agglutination.