Balloon dilatation following tracheal reconstruction for congenital microtrachea.
A male infant presented with failed extubation was diagnosed with congenital microtrachea. After primary combined surgery with excision of a left pulmonary artery sling and microtracheal resection with anastomosis incorporating the excised microtrachea as an autologous anterior tracheal graft he was treated with balloon dilatation of the re-stenosed segment on three occasions during the following year. During the 4 years follow-up, stridor has been minimal and intermittent. His feeding and growth have been normal. We have found balloon dilatation to be a useful adjunct to tracheal reconstructive surgery in this difficult condition.


Selecting efficient methodologies for estimation of As and Hg availability in a brownfield.
The determination of soil metal(loid) availability presents controversy and there is no consensus or uniformity on used analytical methods. In this study nine single extraction methods (H2O, CaCl2, NaNO3, NH4NO3, DTPA, EDTA, HCl, LMWOA, TCLP) and four sequential extraction procedures (Tessier, BCR, Wenzel and Fernández-Martínez) have been compared to estimate the availability of As and Hg in two soils from a highly polluted brownfield, especially with As. The metal(loid) concentrations were also determined in three native plant species (Lotus corniculatus, Betula celtiberica and Dactylis glomerata) collected in the habitat under study. Each single extractant showed a particular capacity of As/Hg extraction because they do not extract the same forms of each element. The availability of As and Hg depended on the element characteristics, soil properties, type of extractant and degree of pollution, thus the use of a single extraction procedure provides limited information of metal(loid) availability and to reach general conclusions is difficult. Regarding the sequential extractions, each procedure showed a specific pattern for As and Hg regardless of the soil. Thus, the choice of one or other method depends on the environmental conditions, metal(loid) and soil properties. In risk assessment studies it would be recommendable to select one of the more aggressive extractants, so as not to underestimate the environmental risk. In this regard, the sequential extraction procedures render more detailed information about metal(loid) potential availability in relation to soil properties. The analysis of native plant species showed higher metal(loid) concentrations in roots than in aerial parts and differences were observed depending on the metal(loid) and the species. In general, plants showed a higher BCFs for Hg than As even though the total and available As concentrations were higher than those found for Hg, which highlights the influence of plant species on the metal(loid) uptake.


Radiofrequency treatment induces fibroblast growth factor 2 expression and subsequently promotes neocollagenesis and neoangiogenesis in the skin tissue.
Radiofrequency (RF) treatment appears to be involved in production of new collagen fibrils and the improvement of existing collagen structures; however, the molecular bases of the effect of non-invasive RF on the skin tissue have not been fully elucidated. This study reports the effects of RF associated or not with hydrolyzed collagen (HC) in the skin tissue. Wistar rats were randomly divided into four groups, according to the treatment received: control group (G1, n = 5), no treatment; subjects in group G2 (n = 5) were treated with HC; and capacitive RF was applied to the back of each subject in G3 (n = 5) and RF associated with HC in G4 (n = 5). Biopsies were taken 30 days after treatment and then were histologically processed and studied for inflammatory cell counting, collagen content, and morphometry. In addition, FGF2, CD105, and COX-2 expression was assessed by immunohistochemical staining. The most relevant changes were the increase in cellularity and accumulation of intercellular substance in RF-treated animals (G3 and G4). The greatest dermis thickness rate was observed in G4, followed by G3 and G2 (p < 0.05). RF-treated skins (G3 and G4) exhibited a significant overexpression of FGF2 (p < 0.0001) and increased microvessel density (p < 0.0001) in comparison with G1 and G2. Moreover, the amount of COX-2 was significantly higher (p < 0.0001) in dermis of RF-treated areas compared to G1 and G2, and demonstrated differences in G3 (RF) compared to G4 (RF + HC) (p < 0.0001). Our results suggests that RF treatment associated or not with HC induces FGF2 overexpression, promotes neoangiogenesis and modulates the COX-2 expression, subsequently promotes neocollagenesis, and increased thickness rate of dermis.


Plasticity in the cockroach neuromuscular system.
The retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase extracellularly injected into a leg muscle was used to identify the regenerating cockroach motor neurons that have grown an axonal branch into that muscle. At least 66% of the animals with crushed nerve roots eventually reform the original innervation pattern of this muscle with no mistakes. In spite of this apparent specificity the cockroach neuromuscular system can express plasticity as evidenced by the correction of mistakes made at early stages of regeneration. These mistakes are corrected through elimination during the time interval between 40 and 60 days after nerve crush. In addition, when the distal segments of the leg are removed, thus depriving some motor neurons of their normal target muscles, many of them form stable inappropriate axonal branches in denervated as well as fully innervated muscles. These observations are discussed in terms of possible mechanisms responsible for the specificity of the cellular interactions and in terms of their relevance to understanding the development of vertebrate neuromuscular systems.


Ki-67 labelling index is related to the risk classification and prognosis of gastrointestinal stromal tumours: a retrospective study.
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract with malignant potential. The current risk classification standard is unable to accurately evaluate the invasiveness and clinical outcomes of GISTs. Ki-67 labelling index (LI) may be an effective indicator in assessing tumour invasiveness and prognosis, however, its exact value in GISTs is still uncertain. The aims of our study were to evaluate the correlation of the Ki-67 LI and clinicopathological features of GISTs and to assess the potential value of the Ki-67 LI in GISTs classification and prognosis. The clinical, pathological and prognostic data were collected and analysed to identify the independent influential factors of GISTs risk stratification and the predictors of GISTs prognosis. The Ki-67 LI was significantly associated with the clinicopathological features of tumour progression (P<0.05). It was an independent influential factor of GISTs risk classification (odds ratio: 1.322; 95% confidence interval: 1.031-1.696) (P=0.028), and the area under the curve (AUC) value of the Ki-67 LI on the discrimination ability of GISTs risk stratification was 0.906 (P<0.001). The optimal cutoff value of the Ki-67 LI was 6% (sensitivity of 87.5% and specificity of 76.2%), and patients with Ki-67 LI≥6% exhibited significantly poorer progression-free survival (PFS) than those with Ki-67 LI<6% (P<0.001). The AUC value of the Ki-67 LI for predicting PFS in postoperative patients was 0.813 (P=0.03). The Ki-67 LI has appreciated value to predict the risk grade and prognosis of GISTs. Patients with Ki-67 LI≥6% are prone to recurrence and metastasis after operation and may need a close follow-up.


Developing applied medical anthropology in Third World countries: problems and actions.
Recognition of the usefulness of ethnographic research in Third World community health projects and programs developed rapidly during the 1980s. As a result, the various agencies and organizations promoting community health programs (UNICEF, WHO, NGOs) have greatly increased their recruiting of social scientists, particularly medical anthropologists, for research and other programmatic activities in primary health care, child survival (especially diarrhea, acute respiratory infections, maternal and child nutrition, infectious disease, and AIDS). However, it has proved very difficult to identify well-trained anthropologists and/or other social scientists for these roles, particularly in Third World countries. This paper examines some of the background of this problem, and presents examples of methodological training (in both qualitative and quantitative research techniques) that seek to increase the skills of social scientists and other researchers in the arena of international community health.


Renal injury of diet-induced hypercholesterolemia in rats.
Abnormalities in lipid metabolism frequently accompany renal disease and may be important in the pathogenesis of progressive renal injury. In the present study, the effects of a high cholesterol diet on renal histology, cortical lipids, and glomerular hemodynamic function were examined in normal rats with and without reduced renal mass. Cholesterol feeding for 19 weeks increased serum cholesterol from 66 +/- 10 mg/dl to 256 +/- 93 mg/dl in two-kidney rats, and from 73 +/- 15 mg/dl to 407 +/- 274 mg/dl in nephrectomy rats (P less than 0.01). Both sham-operated and unilateral nephrectomy rats fed a high cholesterol diet had a greater amount of glomerulosclerosis and tubulointerstitial damage than rats fed standard chow. Cortical cholesteryl esters were increased by the cholesterol diet, and correlated with the amount of glomerulosclerosis (r = 0.90, P less than 0.01) and tubulointerstitial injury (r = 0.64, P less than 0.05). Cholesterol feeding and nephrectomy both caused alterations in tissue essential fatty acids, and a panel of specific monoclonal antibodies indicated that renal injury and cortical lipid alterations were associated with an increase in glomerular macrophages. Finally, micropuncture experiments carried out in a separate group of rats fed high cholesterol for 8 to 10 weeks demonstrated increases in glomerular capillary pressure. These results suggest that additional investigations may ultimately determine how cholesterol deposition, altered fatty acid metabolism, macrophages, and increased glomerular pressure might combine to cause chronic progressive renal injury.


New findings on green sweet pepper (Capsicum annum) pectins: Rhamnogalacturonan and type I and II arabinogalactans.
Polysaccharides were extracted from sweet pepper (Capsicum annum) with hot water and named ANW (9% yield). Starch was precipitated by freeze-thaw treatment, while pectic polysaccharides (8% yield) remained soluble and consisted of GalA (67.0%), Rha (1.6%), Ara (6.4%), Xyl (0.3%), Gal (6.7%) and Glc (4.4%). A highly methoxylated homogalacturonan (HG, degree of methylesterification of 85% and degree of acetylation of 5%), and type I and type II arabinogalactans (AG-I and AG-II) were observed in NMR analyses. These were fractionated with Fehling's solution to give HG (5.5% yield) and AG fractions (0.6% yield). AG-I and AG-II were further separated by ultrafiltration. AG-II (0.2% yield) consisted of Ara (17.1%), Gal (36.0%), Rha (5.6%) and GalA (12.0%), had a molecular weight of 5.3×104g/mol and methylation and 1H/13C HSQC-DEPT-NMR analyses showed that it was anchored in type I rhamnogalacturonan. This is the first study that reports the presence of AG-I and AG-II in sweet pepper fruits.


Suppression of cytokine production in T helper type 2 cells by nitric oxide in comparison with T helper type 1 cells.
We examined the effect of nitric oxide (NO) on cytokine production in T helper (Th) cell subsets, using murine splenic CD4+ T cells and two types of Th clones. Interferon-gamma-treated murine peritoneal exudate cells (IFN-PEC) suppressed DNA synthesis to 60% of the control level in CD4+ T cells stimulated with the anti-CD3 monoclonal antibody. The production of IL-2 and IL-4 in the CD4+ T cells decreased to 63.2% and 9.2%, respectively, of the control value by co-culture with IFN-PEC. The addition of NG-monomethyl-L-arginine (L-NMMA) partially recovered the suppression of DNA synthesis. In the presence of indomethacin, the suppression of DNA synthesis was partially inhibited and the reduction in the cytokine production caused by IFN-PEC was partially recovered. The simultaneous addition of NG-monomethyl-L-arginine (L-NMMA) and indomethacin completely inhibited not only the suppression of DNA synthesis but also the reduction in the cytokine production caused by IFN-PEC. Moreover, DNA synthesis in the Th2 clone was suppressed to a greater extent than that in the Th1 clone by co-culture with IFN-PEC. This suppression in the Th1 clone was inhibited by the addition of L-NMMA, whereas the DNA synthesis in the Th2 clone was not recovered by L-NMMA. In addition, sodium nitroprusside (SNP) suppressed IL-4 production in the Th2 clone but had no effect on IL-2 production in the Th1 clone. In the experiment of the co-culture with IFN-PEC, the inhibitory-effect of NO on T cell activation was not clarified by the influence of prostaglandins. However, in conclusion, cytokine production in Th2 cells may be more susceptible to NO than that in Th1 cells.


Avulsion fracture of the coracoid process in a patient with chronic anterior shoulder instability treated with the Latarjet procedure: a case report.
Shoulder dislocations can cause acute and chronic instabilities that need to be addressed in order to restore joint functioning. The transfer of the coracoid process has become a feasible surgical procedure in patients with shoulder instability. Several concomitant injuries after recurrent dislocations have been described. A 32-year-old German man presented to our department with a history of recurrent shoulder dislocations. He was diagnosed with an avulsion fracture of the coracoid process and dislocation of an osseous piece with attachment to the conjoined tendons during the surgical transfer of the coracoid process. Therefore, we performed an open Latarjet procedure and reattached the bony piece with the conjoined tendons to the glenoid rim. Three months after the operation the patient presented with a satisfying range of motion and without instabilities or pain. He was able to return to his job. Patients suffering from anterior shoulder dislocation might develop accompanying lesions after numerous dislocations that are not present upon first visit. Different techniques for the reconstruction of the glenoid rim and the restoration of shoulder joint stability have been described in the literature. We opted for a coracoid transfer and achieved an optimal reconstruction, as shown on the postoperative computed tomography scan. An avulsion fracture of the coracoid process with dislocation of the conjoined tendons can not only be found in patients suffering a direct trauma as pointed out in the literature, but also in patients with anterior shoulder instability with recurrent anterior shoulder dislocation.


Small bowel GIST with hemorrhagic shock diagnosed by capsule endoscopy and double-balloon endoscopy, angiography-guided hemostasis, and laparoscopic-assisted resection.
Small bowel tumors presenting with hemorrhagic shock require urgent treatment with angiographic embolization to achieve hemostasis. Capsule endoscopy and double-balloon endoscopy are useful for localizing the tumor, diagnosis, and guiding surgery.


Male hamster sociosexual behaviors: effects of testosterone and its metabolites.
Male hamsters were tested for copulatory behavior (CB) with receptive females, for investigatory responses to the females' ano-genital region (A/G), and for attraction to female hamster vaginal secretion (FHVS). After castration, the males received Silastic capsules containing one of two doses of testosterone (T), 5 alpha-dihydrotestosterone (DHT), estradiol (E2) or DHT + E2, and the maintenance of their copulatory and chemoinvestigatory responsiveness was assessed during weekly tests for the next month. The major findings were: (1) T thresholds for the maintenance of CB were lower than they were for the maintenance of A/G behavior and FHVS attraction; (2) DHT + E2 or DHT alone were more effective in maintaining A/G and FHVS attraction than was E2 alone; (3) DHT + E2 or DHT alone maintained ejaculatory behavior in some animals but E2 did not; (4) the posttreatment maintenance of normal ejaculation latencies and intromissions to ejaculation shown by intact and T-treated males was not demonstrated by males receiving DHT or DHT + E2. These results are consistent with the hypothesis that copulatory and chemoinvestigatory behaviors may be subserved by distinct neuroendocrine mechanisms in male hamsters.


Electrophysiologic effects of cocaine on subendocardial Purkinje fibers surviving 1 day of myocardial infarction.
Cocaine has been shown to have broad cardiovascular effects that could be life threatening. Most of the reported electrophysiologic effects of cocaine have been studied in normal but not infarcted myocardium. Using microelectrode techniques, we investigated the electrophysiologic effects of cocaine on endocardial canine Purkinje fibers that survived 1 day of myocardial infarction. In quiescent infarcted preparations, stimulated trains were followed by subthreshold delayed afterdepolarizations (DADs), in the presence of propranolol (1 microM). Cocaine (10 microM) decreased the amplitude of DADs from 6.1 +/- 1.8 mV to 3.0 +/- 1.3 mV (P < 0.05, n = 6). When stimulated preparations (n = 23) showing no triggered activity during control (+propranolol) were superfused with a low concentration of caffeine (1 mM) or high extracellular Ca2+ (8.1 mM), triggered activity was induced. Subsequent cocaine (10 microM) superfusion prevented the induction of caffeine- and high Ca(2+)-induced triggered activity. Cocaine's effects were reversible upon washout. In preparations that showed triggered activity during control conditions (+propranolol), the mean cycle length of triggered activity was 755 +/- 45 msec. Cocaine (10 microM) superfusion lengthened the cycle length to 1030 +/- 141 msec and terminated triggered activity with a subthreshold DAD (n = 12). In addition, cocaine and ryanodine (10 microM) suppressed triggered activity in a similar manner when tested in the same preparations (n = 4). During control conditions, cocaine did not cause any significant change on the rate of rise of action potential upstroke (from 55.6 +/- 24.3 to 54.5 +/- 28.6 V/sec, n = 8) and maximum diastolic potential (from -58.4 +/- 4.3 to -56.6 +/- 6.5 mV, n = 8). In the absence of propranolol, 50 microM but not 10 microM cocaine induced early afterdepolarizations in 62% of the preparations exhibiting triggered activity during control conditions. The results suggest that cocaine modulates DADs and triggered activity in infarcted endocardial fibers via direct inhibition of cyclic release of Ca2+ from sarcoplasmic reticulum (SR) independently from a local anesthetic or sympathomimetic effect. This SR inhibition could account for the myocardial depressant effect of cocaine. However, while cocaine suppressed DADs, its induction of EADs can precipitate malignant ventricular arrhythmias in the setting of cocaine overdose and infarction.


A Prospective Study of Childhood Predictors of Traumatic Brain Injuries Sustained in Adolescence and Adulthood.
Traumatic brain injuries (TBIs) are sustained by approximately 17% of males in the general population, many of whom subsequently present mental disorders, cognitive, and physical problems. Little is known about predictors of TBIs and how to prevent them. The present study aimed to determine whether inattention-hyperactivity and/or all externalizing problems presented by boys at age 10 predict subsequent TBIs to age 34 after taking account of previous TBIs and family social status (FSS). 742 Canadian males were followed, prospectively, from age 6 to 34. Diagnoses of TBIs were extracted from health files, parents-reported sociodemographic and family characteristics at participants' age 6, and teachers-rated participants' behaviors at age 10. Separate logistic regression models predicted TBIs sustained from age 11 to 17 and from age 18 to 34. For each age period, two models were computed, one included previous TBIs, inattention-hyperactivity, FSS, and interaction terms, the second included previous TBIs, externalizing problems, FSS, and interaction terms. In models that included inattention-hyperactivity, TBIs sustained from age 11 to 17 were predicted by age 10 inattention-hyperactivity (odds ratio [OR] = 1.46, 1.05 to 2.05) and by TBIs prior to age 11 (OR = 3.50, 1.48 to 8.24); TBIs sustained from age 18 to 34 were predicted by age 10 inattention-hyperactivity (OR = 1.31, 1.01 to 170). In models that included all externalizing problems, TBIs from age 11 to 17 were predicted by prior TBIs (OR = 3.66, 1.51 to 8.39); TBIs sustained from age 18 to 34 were predicted by age 10 externalizing problems (OR = 1.45, 1.12 to 1.86). Neither FSS nor interaction terms predicted TBIs in any of the models. Among males, using evidence-based treatments to reduce inattention-hyperactivity and externalizing problems among boys could, potentially, decrease the risk of TBIs to age 34. Further, boys who sustain TBIs in childhood require monitoring to prevent recurrence in adolescence.


The Incidence and Mortality Ratio of Ischemic Cerebrovascular Accidents in COVID-19 Cases: A Systematic Review and Meta-Analysis.
Coronavirus disease 2019 (COVID-19) is primarily known as a respiratory illness; however, a wide variety of symptoms and complications of the central nervous system (CNS), such as ischemic cerebrovascular accidents (CVA) have been reported. Hereby, we provide a systematic review and a meta-analysis of the literature, investigating the incidence of ischemic CVA and the mortality due to it in the setting of COVID-19. Our search databases included Google Scholar, MEDLINE via PubMed, and Scopus. We searched the databases up to July 22, 2020. The primary outcome was the incidence of ischemic CVA in COVID-19 cases, while the secondary outcomes were the ratio of mortality in these cases. Standard meta-analysis methods used to measure the pooled incidence and mortality rates of ischemic CVA in COVID-19 cases. After excluding studies with reasons, only 20 articles were eligible to be included in our qualitative synthesis, and 17 studies were evaluated quantitatively in our meta-analysis. Included studies reported a pooled average incidence of 1.7% for ischemic CVA, ranging from 1.3% to 2.3%. Mortality in patients of ischemic CVA to all COVID-19 cases was 0.5%, ranging from 0.4% to 0.6%. The mortality rate of patients with CVA to those who suffered from COVID-19 infection and ischemic CVA simultaneously was 29.2% ranging from 21.6% to 38.2%. Overall, the heterogeneity of the studies was high. Our analysis revealed a pooled incidence of 1.7% for ischemic CVA in the setting of COVID-19 infection, with a mortality rate of 29.2% amongst the COVID-19 patients who are suffering ischemic CVA.


Diagnosis and treatment of retroperitoneal hematoma in multiple trauma patients.
From 1984 to 1991 20 multiple trauma patients with pelvic fractures and retroperitoneal bleeding from pelvic vessels underwent angiographic localization and embolization of massively bleeding arterial vessels. Nine patients survived (multiple trauma index grade III, Hanover polytrauma index), three patients with very severe injuries died immediately (multiple trauma index grade IV). After successful control of bleeding by embolization, three other patients died from severe brain injuries and five patients from septic multiorgan failure. The interval to definite localization and treatment of the bleeding source was three times shorter in the group of survivors, and the amount of transfusions needed was less by a factor of three. This underlines the importance of early angiography in multiple trauma patients with pelvic fractures and persisting hemorrhage. Embolization has proven to be effective in the treatment of such injuries.


Healthfulness Assessment of Recipes Shared on Pinterest: Natural Language Processing and Content Analysis.
Although Pinterest has become a popular platform for distributing influential information that shapes users' behaviors, the role of recipes pinned on Pinterest in these behaviors is not well understood. This study aims to explore the patterns of food ingredients and the nutritional content of recipes posted on Pinterest and to examine the factors associated with recipes that engage more users. Data were collected from Pinterest between June 28 and July 12, 2020 (207 recipes and 2818 comments). All samples were collected via 2 new user accounts with no search history. A codebook was developed with a raw agreement rate of 0.97 across all variables. Content analysis and natural language processing sentiment analysis techniques were employed. Recipes using seafood or vegetables as the main ingredient had, on average, fewer calories and less sodium, sugar, and cholesterol than meat- or poultry-based recipes. For recipes using meat as the main ingredient, more than half of the energy was obtained from fat (277/490, 56.6%). Although the most followed pinners tended to post recipes containing more poultry or seafood and less meat, recipes with higher fat content or providing more calories per serving were more popular, having more shared photos or videos and comments. The natural language processing-based sentiment analysis suggested that Pinterest users weighted taste more heavily than complexity (225/2818, 8.0%) and health (84/2828, 2.9%). Although popular pinners tended to post recipes with more seafood or poultry or vegetables and less meat, recipes with higher fat and sugar content were more user-engaging, with more photo or video shares and comments. Data on Pinterest behaviors can inform the development and implementation of nutrition health interventions to promote healthy recipe sharing on social media platforms.


PIP2 and septin control STIM1/Orai1 assembly by regulating cytoskeletal remodeling via a CDC42-WASP/WAVE-ARP2/3 protein complex.
Store-operated calcium entry (SOCE) is triggered by assembly of Orai1 with STIM proteins in ER-PM junctions. Plasma membrane PIP2 as well as PIP2-binding protein, SEPT4, significantly impact Orai1-STIM1 interaction. While septins and PIP2 can organize the actin cytoskeleton, it is unclear whether the status of actin within the junctions contributes to SOCE. We report herein that actin remodeling modulates STIM1 clustering. Our findings show that a PIP2- and SEPT4-dependent mechanism involving CDC42, WASP/WAVE, and ARP2 regulates actin remodeling into a ring-like structure around STIM1 puncta. CDC42 localization in the ER-plasma membrane region is enhanced following ER-Ca2+ store depletion. PIP2 depletion or knockdown of SEPT4 attenuate the recruitment of CDC42 to the ER-PM region. Importantly, knockdown of SEPT4, or CDC42+ARP2, disrupts the organization of actin as well as STIM1 clustering. Consequently, Orai1 recruitment to STIM1 puncta, SOCE, and NFAT translocation to the nucleus are all attenuated. Ca2+ influx induced by STIM1-C terminus is not affected by CDC42 knockdown. In aggregate, our findings reveal that PIP2 and SEPT4 affect Orai1/STIM1 clustering by coordinating actin remodeling within ER-PM junctions. This dynamic reorganization of actin has an important role in regulation of SOCE and downstream Ca2+-dependent effector functions.


2,2,5,7,8-Penta-methyl-chroman-6-yl 2,3,4,6-tetra-O-acetyl-α-d-glucopyran-oside from synchrotron data.
The crystal structure of the title compound, C(28)H(38)O(11), solved and refined against synchrotron diffraction data, contains two formula units in the asymmetric unit. In both mol-ecules, the dihydro-pyran ring along with its methyl substituents is disordered and adopts two alternative half-chair conformations. The occupancy of the major conformers of the two mol-ecules refined to 0.858 (5) and 0.523 (5).


Predicting word-recognition performance in noise by young listeners with normal hearing using acoustic, phonetic, and lexical variables.
To analyze the 50% correct recognition data that were from the Wilson et al (this issue) study and that were obtained from 24 listeners with normal hearing; also to examine whether acoustic, phonetic, or lexical variables can predict recognition performance for monosyllabic words presented in speech-spectrum noise. The specific variables are as follows: (a) acoustic variables (i.e., effective root-mean-square sound pressure level, duration), (b) phonetic variables (i.e., consonant features such as manner, place, and voicing for initial and final phonemes; vowel phonemes), and (c) lexical variables (i.e., word frequency, word familiarity, neighborhood density, neighborhood frequency). The descriptive, correlational study will examine the influence of acoustic, phonetic, and lexical variables on speech recognition in noise performance. Regression analysis demonstrated that 45% of the variance in the 50% point was accounted for by acoustic and phonetic variables whereas only 3% of the variance was accounted for by lexical variables. These findings suggest that monosyllabic word-recognition-in-noise is more dependent on bottom-up processing than on top-down processing. The results suggest that when speech-in-noise testing is used in a pre- and post-hearing-aid-fitting format, the use of monosyllabic words may be sensitive to changes in audibility resulting from amplification.


Comparison of day 2 and overnight day 3 frozen embryo transfers: A prospective randomized controlled trial.
In certain patients cleavage stage embryos may be preferred. The relationship between an additional day in culture and pregnancy outcomes is not well established. We aimed to compare outcomes of day 2 versus overnight day 3 frozen embryo transfer (FET). In this randomized controlled trial, patients with day 2 cryopreserved embryos were allocated to two groups. In group A embryos were transferred on day 2, the same day of thawing. In group B embryos were transferred one day after thawing, on day 3 after overnight incubation. Out of 410 patients eligible, 92 were recruited. Finally, 72 patients participated, 39 in group A and 33 in group B. No significant difference in implantation (11 % in group A and 14 % in group B, p = 0.81), clinical pregnancy (18 % in group A and 21 % in group B, p = 0.73) or live birth rates (13 % in group A and 18 % in group B, p = 0.53) was found. To conclude, no significant difference in reproductive outcomes was found when comparing patients with day 2 or overnight day 3 FET. Considering published data on blastocyst transfer, cleavage stage ET may still be a relevant option and the decision between day 2 or overnight day 3 ET depends on patients' and physicians' preference and recommendation.


The effect of antithrombotic therapy on the recurrence and outcome of chronic subdural hematoma after burr-hole craniostomy in a population-based cohort.
To study the effect of antithrombotic therapy (ATT) on the outcome of operatively treated chronic subdural hematomas (CSDH). A retrospective population-based cohort study from Eastern Finland including all adult patients who underwent a burr-hole craniostomy (BHC) for CSDH during 2016 and 2017. The follow-up time for recurrence was 6 months and for mortality 3 years. A total of 301 CSDH patients were included in the study. ATT (antithrombotic therapy; antiplatelet or anticoagulant medication) was used by 164 patients (54.5%) at the time of diagnosis. The hematoma was bilateral in 102 patients (33.9%). Forty-seven patients (15.8%) encountered hematoma recurrence. Bilateral CSDHs required reoperations more often than unilateral hematomas (12.6% vs. 22.0%; p = 0.036) regardless of the primary operation (uni- or bilateral). A bivariate logistic regression analysis showed that bilateral hematoma (OR 1.918; 95% CI 1.013-3.630; p = 0.045) and male gender (OR 2.363; 95% CI 1.089-5.128; p = 0.030) independently predicted hematoma recurrence. The overall three-year mortality was 27.9%. The use of ATT was not associated with CSDH recurrence, and the length of the temporary postoperative ATT discontinuation did not correlate with the rate of thromboembolic events. ATT did not affect CSDH recurrence in our study population, and the duration of the temporary postoperative ATT discontinuation was not associated with the rate of thromboembolic complications. Male gender and bilateral hematomas were more frequently associated with recurrences.


Age-associated changes in mitogen-induced lymphoproliferation and lymphokine production in the long-lived brown-Norway rat: effect of caloric restriction.
We have previously demonstrated that age-related declines in Concanavalin A (ConA), induced proliferation and lymphokine production, occur in ad-libitum fed Brown Norway (AL BN) rats. Since caloric restriction (CR) extends lifespan, we expected that the age related changes in immune parameters would be delayed by CR. CR does act to delay age-related changes in proliferation in response to ConA. In addition, CR postpones the plateau in ConA induced interferon (IFN) production seen after 23 months of age in AL rats. However, CR does not postpone the age-related decline in ConA induced interleukin-2 (IL-2) production. Therefore, ConA induced IFN production maybe a good candidate as an early marker of physiologic aging, while ConA induced proliferative response is a possible candidate for a marker of late stages of aging.


Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6.
Optimal targeted treatment in rheumatoid arthritis requires early identification of failure to respond. This post hoc analysis explored the relationship between early disease activity changes and the achievement of low disease activity (LDA) and remission targets with tofacitinib. Data were from 2 randomized, double-blind, phase III studies. In the ORAL Start trial, methotrexate (MTX)-naive patients received tofacitinib 5 or 10 mg twice daily, or MTX, for 24 months. In the placebo-controlled ORAL Standard trial, MTX inadequate responder patients received tofacitinib 5 or 10 mg twice daily or adalimumab 40 mg every 2 weeks, with MTX, for 12 months. Probabilities of achieving LDA (using a Clinical Disease Activity Index [CDAI] score ≤10 or the 4-component Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] ≤3.2) at months 6 and 12 were calculated, given failure to achieve threshold improvement from baseline (change in CDAI ≥6 or DAS28-ESR ≥1.2) at month 1 or 3. In ORAL Start, 7.2% and 5.4% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to show improvement in the CDAI ≥6 at month 3; of those who failed, 3.8% and 28.6%, respectively, achieved month 6 CDAI-defined LDA. In ORAL Standard, 18.8% and 17.5% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 0% and 2.9%, respectively, achieved month 6 CDAI-defined LDA. Findings were similar when considering improvements at month 1 or DAS28-ESR thresholds. In patients with an inadequate response to MTX, lack of response to tofacitinib after 1 or 3 months predicted a low probability of achieving LDA at month 6. Lack of an early response may be considered when deciding whether to continue treatment with tofacitinib.


Coal-based ultrathin N-doped carbon nanosheets synthesized by molten-salt method for high-performance lithium-ion batteries.
Coal is a typical fossil fuel and it is also a natural carbon material, therefore, converting it to functional carbon materials is an effective way to enhance the economic advantages of coal. Here, ultrathin N-doped carbon nanosheets were prepared from low-cost coal via a handy and green molten-salt method, which shown excellent performance for lithium-ion batteries (LIBs). The formation mechanism of ultrathin nanosheets was studied in detail. The eutectic molten salts possess low melting points and become a strong polar solvent at the calcined temperature, making the acidified coal miscible with them in very homogeneously state. Therefore, they can play a gigantic role inin situpore-forming during the carbonization and induce the formation of ultrathin nanosheets due to the salt ions. Simultaneously, the ultrathin N-doped carbon nanosheets with rich defects and controllable surface area was smoothly prepared without any more complex process while revealing brilliant electrochemical performance due to rich ion diffusion pathways. It delivers reversible capacity of 727.0 mAh g-1at 0.2 A g-1after 150 cycles. Thus, the molten-salt method broadens the avenue to construct porous carbon materials with tailor-made morphologies. Equally important, this approach provides a step toward the sustainable materials design and chemical science in the future.


The criterion-related validity of the IADL Profile with measures of executive functions, indices of trauma severity and sociodemographic characteristics.
To examine relationships between classical measures of executive functions (EF) and indices of traumatic brain injury (TBI) severity with the IADL Profile, a new performance-based measure of independence in instrumental activities of daily living (IADL) based on EF. This study hypothesized the presence of correlations between classical tests of EF and the IADL Profile, as the latter aims to establish whether the subject's main difficulties pertain to goal formulation, planning, carrying out the task and/or attaining the initial task goal; all important components of EF. One hundred subjects with a moderate/severe TBI aged 16-65 years (convenience sample) were recruited. Subjects were tested with the IADL Profile and three measures of EF within their home environment. Data was analysed using Pearson correlations, t-tests and multiple stepwise regressions. Post-traumatic amnesia and working memory emerged as the major determinants of IADL Profile scores. Together, indices of injury severity, measures of EF, education, age and environmental factors accounted for 12-28% of the variance in IADL Profile scores. This study has shown that the IADL Profile's non-structured approach permits the observation of a broad range of behaviours related to EF deficits and thus provides a closer approximation of the person's independence in IADL. Further study is required to demonstrate the IADL Profile's ability to inform more targeted treatment interventions.


ChREBP deficiency alleviates apoptosis by inhibiting TXNIP/oxidative stress in diabetic nephropathy.
In the present study, we investigated the effect of carbohydrate responsive element binding protein (ChREBP) on the TXNIP/oxidative stress and apoptosis in diabetic nephropathy. ChREBP-/- mice (8-week old) were produced using the CRISPR/Cas9 gene editing approach. Diabetes was induced in C57BL/6 mice with streptozotocin. HK-2 cells was transfected with plasmid containing either ChREBP shRNA or TXNIP siRNA. Renal expression of ChREBP and thioredoxin-interacting protein (TXNIP) was increased in patients with type 2 diabetes mellitus (T2DM) and diabetic mice. ChREBP deficiency improved renal function, apoptosis as well as endoplasmic reticulum (ER) stress in diabetic mice. In addition, ChREBP deficiency prevented expression levels of TXNIP and NADPH oxidase 4 (Nox4), 8-hydroxydeoxyguanosine (8-OHdG) and heme oxygenase-1 (HO-1) in diabetic kidneys. The increased urinary 8-OHdG level induced by diabetes was also attenuated in ChREBP deficiency mice. Similarly, HG was shown to induce ChREBP expression and nuclear translocation in HK-2 cells. HG-induced apoptosis was inhibited by transfection of ChREBP shRNA plasmid. Moreover, we found that knockdown of ChREBP suppressed HG-induced TXNIP and Nox4 expression, reactive oxygen species (ROS) generation and ER stress in HK-2 cells. Furthermore, TXNIP knockdown effectively abrogated HG-induced apoptosis in HK-2 cells. These results suggest that ChREBP deficiency prevents diabetes-induced apoptosis via inhibiting oxidative stress and ER stress, highlighting ChREBP as a potential therapy target for diabetic nephropathy.


Lymphokine-like activity in the serum of patients with haemopoietic malignancies.
Serum from patients with haemopoietic malignancies was tested for the presence of migration inhibition factor (MIF) and leucocyte inhibition factor (LIF) activity by standard assays. There was no correlation between the specific disease state and positivity of the sera for MIF or LIF activity. MIF activity in the serum of one patient with myeloma was present in the isolated IgG cryoglobulin fraction.


Silent information regulator 1 suppresses epithelial-to-mesenchymal transition in lung cancer cells via its regulation of mitochondria status.
Silent information regulator 1 (SIRT1) is a NAD+-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, cell metabolism, and mitochondrial functions. Given that it acts as both a tumor promoter and suppressor, the complex mechanisms underlying SIRT1 signaling in cancer remain controversial. Epithelial-to-mesenchymal transition (EMT) plays a key role in the progression of carcinogenesis and tumors metastasis. Studies have shown that mitochondrial defects are critical in EMT process, and SIRT1 is found to regulate the generation and energy metabolism of mitochondria. Here, we elucidate a novel mechanism by which SIRT1 affects EMT in lung cancer cells via its regulation on mitochondria. SIRT1 signaling was detected in TGF-β1-induced EMT and was found to regulate mitochondria status, including mitochondrial biogenesis-related protein levels as detected by western blotting, mitochondrial structure observed by transmission electron microscopy, and respiratory functions analyzed by a respiration capacity assay. The effects of modulating SIRT1 expression on EMT and migration of lung cancer cells or normal cells were evaluated by in vitro and in vivo models. We found that the regulation of SIRT1 signaling on the biogenesis or functions of mitochondria was critical to EMT. Overexpression of SIRT1 reduced EMT or metastasis potential of lung cancer cells by improving the quantity and quality of mitochondria, whereas silencing SIRT1 promote EMT in cancer cells, even in normal cells by disturbing mitochondria status. Consequently, SIRT1 is an attractive therapeutic target for reversing EMT or tumor metastasis.


The induction of ferritin synthesis in circulating larval red blood cells.
The circulating red blood cells formed in bullfrog larvae, chicken embryos, and mouse embryos contain large amounts of ferritin and storage iron in excess of the need for hemoglobin. In contrast, the circulating red cells of adult animals contain little ferritin. Ferritin synthesis and iron storage are coordinated with differentiation and hemoglobin synthesis in the red cells of adults. In order to test the hypothesis that ferritin synthesis could be controlled independently of hemoglobin synthesis and differentiation in the red cells formed early in life, bullfrog larvae were injected with iron to determine if ferritin synthesis was increased in the circulating red cells. Within 17 h after the injection of iron, the synthesis of ferritin, assayed as the incorporation of [14C]leucine by cell suspensions prepared from circulating red cells, was increased from 2.9 to 10.2% of the total protein, and the specific activity of the ferritin synthesized increased from 1100 to 3000 cpm/A280. There was no change in the hematocrit of the animals nor in the specific activity of hemoglobin synthesized by suspensions of red cells (average, 720 cpm/A280). The results suggest that in mature, larval red cells, ferritin synthesis can be controlled by changes in the extracellular environment. The results also indicate that ferritin synthesis can be controlled independently of hemoglobin synthesis with which it is coordinated during erythroid differentiation in adult animals.


At-GDI1 from Arabidopsis thaliana encodes a rab-specific GDP dissociation inhibitor that complements the sec19 mutation of Saccharomyces cerevisiae.
Rab GTPases play a central role in the control of vesicular membrane traffic. These proteins cycle between cytosolic and membrane-bound compartments in a guanine nucleotide-dependent manner, a process that is regulated by several accessory proteins. Of particular interest are the Rab guanosine nucleotide diphosphate dissociation inhibitor proteins (Rab-GDI) which bind to prenylated Rab GTPases, slow the rate of GDP dissociation and escort GDP bound Rab proteins to their target membranes and retrieve them after completion of their catalytic cycle. We have cloned from Arabidopsis thaliana a cDNA coding for the Rab guanosine diphosphate dissociation inhibitor (AtGDI1) by functional complementation of the Saccharomyces cerevisiae sec19-1 mutant. The Arabidopsis cDNA potentially encodes a 49850 Da protein which is homologous to yeast GDI (49%) and to other members of the Rab-GDI family (49-63%). Northern blot analysis indicates that the mRNA is expressed in all tissues examined. The existence of a plant homologue of the Rab-GDI family indicates that the basic vesicle traffic control machinery may be highly conserved in plants as it is in yeast and mammals.


A novel shiga based immunotoxin against Fn-14 receptor on colorectal and lung cancer.
Immunotoxins are regarded as a type of targeted therapy for killing cells by highly potent bacterial, fungal or plant toxins. Shiga like toxins (SLTs) are a group of bacterial AB5 protein toxins that inhibit host cell protein synthesis through the removal of a single adenine residue from the 28S rRNA and lead to apoptosis. Here, we described the design and usage of a Stx-based immunotoxin that can induce the selective cytotoxicity and apoptosis in Fn-14-positive cells related to the colon and lung cancer. In the present study, the Stx2a-PE15-P4A8 fusion protein was expressed efficiently in E. coli (DE3) system when driven from inclusion bodies by 8 M urea. The Stx2a-PE15-P4A8 fusion protein was expressed efficiently in E. coli (DE3) system and then purified. The purified fusion protein could specifically target Fn-14 receptor existed on colon and lung cancer cell lines and suppress these cells in a dose-dependent manner. In addition, the protein was able to nearly 50 % of apoptotic cell death and maintains about 54 % of its stability after 24 h of incubation in mouse serum at 37 °C. Compared to PE38-P4A8 construct in our previous study, these results showed that the Stx2a-PE15-P4A8 construct can be an efficient therapeutic candidate for cancer immunotherapy.


Predesign of Catalytically Active Sites via Stable Coordination Cluster Model System for Electroreduction of CO2 to Ethylene.
Purposefully designing the well-defined catalysts for the selective electroreduction of CO2 to C2 H4 is an extremely important but challenging work. In this work, three crystalline trinuclear copper clusters (Cu3 -X, X=Cl- , Br- , NO3 - ) have been designed, containing three active Cu sites with the identical coordination environment and appropriate spatial distance, delivering high selectivity for the electrocatalytic reduction of CO2 to C2 H4 . The highest faradaic efficiency of Cu3 -X for CO2 -to-C2 H4 conversion can be adjusted from 31.90 % to 55.01 % by simply replacing the counter anions (NO3 - , Cl- , Br- ). The DFT calculation results verify that Cu3 -X can facilitate the C-C coupling of identical *CHO intermediates, subsequently forming molecular symmetrical C2 H4 product. This work provides an important molecular model system and a new design perspective for electroreduction of CO2 to C2 products with symmetrical molecular structure.


Neural tube formation in the mouse: a morphometric and computerized three-dimensional reconstruction study of the relationship between apical constriction of neuroepithelial cells and the shape of the neuroepithelium.
Morphometry and computerized three-dimensional reconstruction were used to study the relationship between apical constriction of neuroepithelial cells and the pattern of bending of the neuroepithelium in the developing neural tube of the 12-somite mouse embryo. The neuroepithelium of the mouse exhibits prominent regional variations in size and shape along the embryo axis. The complex shape of most of the cephalic neural tube (e.g., forebrain and midbrain) is due to the coexistence of concave and convex bending sites whereas more caudal regions (e.g., hindbrain and spinal cord) generally lack sites of convex bending and have a relatively simple shape. The apical morphology of neuroepithelial cells was found to be correlated more closely with the local status of bending of the neuroepithelium than with the specific region of the neural tube in which they are located. In areas of enhanced apical constriction, microfilament bundles were particularly prominent. Morphometry revealed that patterns of bending of the neuroepithelium were correlated almost exactly with those of apical constriction throughout the forming neural tube. These findings support the idea that apical constriction of neuroepithelial cells, resulting from tension generated by microfilament bundles, plays a major role in bending of the neuroepithelium during neural tube formation in the mouse.


DIRECTIONAL AND STABILIZING DENSITY-DEPENDENT NATURAL SELECTION FOR PUPATION HEIGHT IN DROSOPHILA MELANOGASTER.
Six populations of Drosophila melanogaster have been kept at extreme population densities, three high and three low, for 175 generations. Larvae from the high density populations pupate 50%-100% higher than larvae from the low density populations. At high larval test densities there is both a directional and a stabilizing component to selection, with viabilities ranging from 0.14 to 0.992, depending on the choice of pupation site. The directional component is stronger on the populations which have evolved at low densities, while the stabilizing component is stronger on the populations which have evolved at high densities. There is no indication that the evolution of this trait, in response to density, has altered its phenotypic plasticity.


Reduced graphene oxide as an effective adsorbent for removal of malachite green dye: Plausible adsorption pathways.
Efficient removal of malachite green (MG) dye from simulated wastewater is demonstrated using high surface area reduced graphene oxide (rGO). The plausible interaction pathways between MG dye and rGO are deduced from nanostructural features (HRTEM) of rGO and spectroscopic analyses (FTIR and Raman). The high surface area (931m2⋅gm-1) of rGO, π-π interaction between the aromatic rings of MG dye and graphitic skeleton, and electrostatic interaction of cationic centre of MG dye with π-electron clouds and negatively charged residual oxygen functionalities of rGO collectively facilitate the adsorption of MG dye on the rGO. The rGO displays adsorption capacity as high as 476.2mg⋅g-1 for MG dye. The thermodynamic parameters calculated from the temperature dependent isotherms suggested that the adsorption was a spontaneous and endothermic process. These results promise the potential of high surface area rGO for efficient removal of cationic dyes for wastewater treatment.


Risk of fetal infection from invasive procedures.
Recent technological advances have led to the development of several types of invasive procedures in the fetus principally for the diagnosis and management of fetal disorders. The risk of infection to the fetus related to these procedures needs evaluation. Although there are few reports of fetal infection, proper infection control procedures must be observed because the most common consequence of infection is fetal loss. Fetal blood sampling in the presence of chorioamnionitis is a risk factor that warrants prophylactic antibiotics. Conversely, clinical specimens taken from the fetus in the absence of chorioamnionitis are more likely to become contaminated with maternal skin flora, and a positive fetal blood culture is not necessarily significant. There is probably a small but finite risk of transmission of maternal viral infections such as human immunodeficiency virus, hepatitis B and C, cytomegalovirus and herpes simplex during invasive procedures. Obstetric departments undertaking invasive fetal diagnosis and treatment must have an adequate policy for infection control procedures.


Microglia inflammatory responses are controlled by an intrinsic circadian clock.
The circadian system regulates many physiological functions including inflammatory responses. For example, mortality caused by lipopolysaccharide (LPS) injection varies depending on the time of immunostimulation in mammals. The effects of more subtle challenges on the immune system and cellular mechanisms underlying circadian differences in neuroinflammatory responses are not well understood. Here we show that adult male Sprague-Dawley rats injected with a sub-septic dose of LPS during the light phase displayed elevated sickness behaviors and hippocampal cytokine production compared to rats injected during the dark phase. Microglia are the primary central nervous system (CNS) immune cell type and may mediate diurnal differences in sickness response, thus we explored whether microglia demonstrate temporal variations in inflammatory factors. Hippocampal microglia isolated from adult rats rhythmically expressed inflammatory factors and circadian clock genes. Microglia displayed robust rhythms of TNFα, IL1β and IL6 mRNA, with peak cytokine gene expression occurring during the middle of the light phase. Microglia isolated during the light phase were also more reactive to immune stimulation; such that, ex vivo LPS treatment induced an exaggerated cytokine response in light phase-isolated microglia. Treating microglia with corticosterone ex vivo induced expression of the circadian clock gene Per1. However, microglia isolated from adrenalectomized rats maintained temporal differences in clock and inflammatory gene expression. This suggests circadian clock gene expression in microglia is entrained by, but oscillates in the absence of, glucocorticoids. Taken together, these findings demonstrate that microglia possess a circadian clock that influences inflammatory responses. These results indicate time-of-day is an important factor to consider when planning inflammatory interventions such as surgeries or immunotherapies.


Renal bilirubin excretion in canine models of jaundice.
Renal handling of bilirubin and its relationship to blood bilirubin level were investigated for up to 2 weeks in two models of jaundiced dogs, namely, chronic bile duct ligation (CBDL), which are mildly icteric, and choledococaval anastomosis (CDCA), which develop deep jaundice. The mean (+/- SD) urinary bilirubin excretion in CBDL plateaued at 30.3 +/- 9.3 mg/24 hr whereas in CDCA it continued to increase above the normal bilirubin production rate (56-84 mg/24 hr) up to 130-150 mg/24 hr. The renal clearance of bilirubin in both models was inversely proportional to serum bilirubin concentration. It was approximately twice as high in the CDCA model, which induced also a moderate diuresis. It is suggested that higher serum bilirubin levels in CDCA dogs is due to the increased production of bilirubin which is not compensated by the renal clearance of bilirubin.


Lymphocyte glutathione status in relation to their Con A proliferative response.
We studied the intracellular total, oxidized and reduced glutathione levels in thymus and spleen rat lymphocytes cultured with or without Con A and 2-mercaptoethanol (2-ME). After 48 h culture, the total glutathione level decreased and the oxidized glutathione level increased in the two types of unstimulated and stimulated cells. In the presence of 2-ME, the tritiated thymidine incorporation increased in splenocytes but not in thymocytes; on the other hand, the two types of stimulated cells increased their total and oxidized glutathione content. The enhancement of the GSSG/GSH + GSSG ratio, irrespective of culture conditions, indicates a severely disturbed redox state of the cells. 2-ME acts on the glutathione synthesis of stimulated lymphocytes but is unable to maintain a normal redox state of these cells.


Long-term results of resection of renal cell cancer with extension into inferior vena cava.
From July 2, 1971 to April 1, 1985, 47 patients (median age 63 years) with renal cell cancer extending into the renal vein or inferior vena cava were evaluated and treated. Two-thirds of the tumors occurred in men and three-fourths were found in the right kidney. Of the 44 patients operated on 35 had no evidence of preoperative metastatic disease at operation. The patients were divided into ideal, favorable and unfavorable subgroups. The adjusted 5 and 10-year survival rates in the former 2 groups (32 patients) were 68.8 and 60.2 per cent, respectively. In contrast, 12 patients with nodal involvement or metastases had an adjusted median survival time of 1.2 years with no survival extending beyond 4.8 years. We believe that an extended operation for renal cell cancer with involvement of the vena cava is warranted and provides reasonable long-term survival in properly selected patients.


On the design of in situ forming biodegradable parenteral depot systems based on insulin loaded dialkylaminoalkyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) nanoparticles.
The feasibility to generate in situ forming parenteral depot systems from insulin loaded dialkylaminoalkyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) nanoparticles, was investigated. Biodegradable nanoparticles formed polymeric semi-solid depots upon injection into isotonic phosphate buffered saline (PBS) with no additional initiators. Nanoparticles (NP) prepared from the different amine-modified polyesters displayed a pronounced positive zeta-potential of >25 mV. Diethylaminopropyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DEAPA(68)-PVAL-g-PLGA(1:20)), diethylaminoethyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DEAEA(33)-PVAL-g-PLGA(1:20)), and dimethylaminopropyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DMAPA(33)-PVAL-g-PLGA(1:20)), formed in situ depots by an ion-mediated aggregation with subsequent fusion of nanoparticles, related to a decreased glass transition temperature in the presence of PBS. Moreover, two factors, namely, polymer and insulin-nanocomplex concentration, were evaluated using a response surface design with respect to nanoparticles formation and insulin loading. Nanoparticles and implants were investigated by atomic force microscopy (AFM). The in vitro release from implants loaded with 2% insulin was carried out in a flow trough cell and quantified by high performance liquid chromatography (HPLC). The release showed a triphasic profile with an initial burst, pore diffusion and diffusion from the swollen matrix over more than two weeks. Insulin distribution in the implants during the release was followed by confocal laser scanning microscopy (CLSM). These findings combined with the protection of the model peptide against competitive macromolecules and the possibility to get dry powders by lyophilization make these nanoparticles-based depots suitable candidates for the design of controlled release devices for bioactive macromolecules.


Two-step synthesis of hexaammonium triptycene: an air-stable building block for condensation reactions to extended triptycene derivatives.
A simple two-step synthesis of an air-stable hexaammoniumtriptycene is introduced, which can be used for a variety of transformations by condensation reactions, e.g., to benzimidazole, benzotriazole, and quinoxaline derivatives in high yields.


Measurement properties of completely and end labeled unipolar and bipolar scales in Likert-type questions on income (in)equality.
The measurement of respondents' attitudes is key in social science research and many adjacent research fields. A common method to measure this information is to use Likert-type questions that consist of a statement that is evaluated with a rating scale. As shown by previous research, the scale design of Likert-type questions can have a profound impact on respondents' answer behavior. In this study, we therefore investigate the measurement properties of scales that systematically vary with respect to polarity (i.e., unipolar and bipolar) and labeling (i.e., completely and end). We conducted a survey experiment in a probability-based online panel (N = 4851) and used questions on income (in)equality that were adopted from the European Social Survey (ESS). The results reveal considerable differences between the scales under investigation. They show that end labeled unipolar and bipolar scales accomplish the criteria of equidistance best. Completely labeled bipolar scales, in contrast, only show a poor performance in terms of equidistance. Completely labeled unipolar scales are somewhere in between. Overall, our findings suggest that researchers should be careful when using survey data measured with (slightly) different scales because the results might not be comparable.


Healthcare and Terrorism: The Lebanese Experience.
Due to the common instability caused by political and security issues, Lebanese hospitals have experienced acts of terrorism multiple times. The most recent Beirut Explosion even forced several hospitals to cease operations for the first time in decades-but studies show the preparedness levels for such attacks in similar countries are low. The aim of this study is to explore the experience of Lebanese hospitals with terrorist attacks. This qualitative study used semi-structured interviews with various stakeholders to assess their experience with terrorist bombings. Data was analyzed using the thematic analysis method. The researchers found that Lebanese hospitals vary greatly in their structures and procedures. Those differences are a function of 3 contextual factors: location, culture, and accreditation status. Hospitals found near 'dangerous zones' were more likely to be aware and to have better response to such events. A severe lack of communication, unity of command, and collaboration between stakeholders has made the process fragmented. The researchers recommend a larger role for the Ministry of Public Health (MOPH) in this process, and the creation of a platform where Lebanese organizations can share their experiences to improve preparedness and resilience of the Lebanese healthcare system in the face of terrorism.


Bovine lactoferrin induces interleukin-11 production in a hepatitis mouse model and human intestinal myofibroblasts.
Orally administered bovine lactoferrin (bLF) exerts an anti-inflammatory effect on hepatitis and colitis animal models. To investigate the mechanism underlying the action of bLF, we explored the expression of inflammation-related factors in the intestine of a hepatitis mouse model after the oral administration of bLF and in several human intestinal cell lines treated with bLF. The effects of bLF on the expression of interleukin-11 (IL-11) and bone morphogenetic protein 2 (BMP2) in the intestinal mucosa of a hepatitis mouse model as well as in cell cultures of human intestinal epithelial cells, myofibroblasts, and monocytes were examined using the real-time reverse transcription polymerase chain reaction. Epithelial cells and myofibroblasts were also cocultured using transwells. bLF transport, and IL-11 and BMP2 induction, as well as the interactions between the two cell types, were then analyzed after bLF treatment. In vivo, oral bLF administration increased the production of IL-11 and BMP2 in intestinal specimens. In vitro, bLF only stimulated the production of IL-11 in human intestinal myofibroblasts; i.e., it had no effect on BMP2 production in any cell type. In the transwell cocultures, bLF passed through the epithelium and directly stimulated IL-11 production in the myofibroblasts on the basolateral side. The IL-11 produced in the myofibroblasts subsequently acted protectively on the epithelial cells of the coculture. bLF upregulated the activity of anti-inflammatory factors, such as IL-11, in the intestine of a hepatitis mouse model and human intestinal myofibroblasts.


Postsaccadic eye position contributes to oculomotor error estimation in saccadic adaptation.
We investigated whether the proprioceptive eye position signal after the execution of a saccadic eye movement is used to estimate the accuracy of the movement. If so, saccadic adaptation, the mechanism that maintains saccade accuracy, could use this signal in a similar way as it uses visual feedback after the saccade. To manipulate the availability of the proprioceptive eye position signal we utilized the finding that proprioceptive eye position information builds up gradually after a saccade over a time interval comparable to typical saccade latencies. We confined the retention time of gaze at the saccade landing point by asking participants to make fast return saccades to the fixation point that preempt the usability of proprioceptive eye position signals. In five experimental conditions we measured the influence of the visual and proprioceptive feedback, together and separately, on the development of adaptation. We found that the adaptation of the previously shortened saccades in the case of visual feedback being unavailable after the saccade was significantly weaker when the use of proprioceptive eye position information was impaired by fast return saccades. We conclude that adaptation can be driven by proprioceptive eye position feedback.NEW & NOTEWORTHY We show that proprioceptive eye position information is used after a saccade to estimate motor error and adapt saccade control. Previous studies on saccadic adaptation focused on visual feedback about saccade accuracy. A multimodal error signal combining visual and proprioceptive information is likely more robust. Moreover, combining proprioceptive and visual measures of saccade performance can be helpful to keep vision, proprioception, and motor control in alignment and produce a coherent representation of space.


Genetic diagnosis of pancreatic cancer using specimens obtained by EUS-FNA.
We review the current situation concerning molecular biological analysis in respect of pancreatic cancer, using specimens obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). K-ras, p53, p16, DPC4/SMAD4, telomerase activity are used for discrimination between tumor-forming pancreatitis and pancreatic cancer. Examination of heat shock protein (HSP) 27, ribonucleotide reductase, and other factors are examined in order to test the sensitivity to Gemcitabin. Comparative genomic hybridization analysis for pancreatic cancer specimens obtained by EUS-FNA was reported to be useful for evaluate the biological characteristics of pancreatic cancer before treatment. It is expected that the genetic diagnosis using EUS-FNA specimens will not only positively contribute to improving the diagnostic performance, but it will also provide valuable information for carrying out tailor-made treatment.


A randomised trial of endobronchial ultrasound guided sampling in peripheral lung lesions.
The aim of the study was to evaluate endobronchial ultrasound (EBUS) for peripheral lung lesions and to find the most cost effective combination of sampling techniques. 264 patients with lesions suspicious of malignancy were recruited in Bergen and Aalesund, Norway from 2005 to 2008. The study was a prospective randomised cohort study. EBUS was performed with a 1.7 mm rotating probe. X-ray fluoroscopy was used in both arms. The different sampling techniques were evaluated in a cost-effectiveness analysis. The detection rate for cancer was 36% in the EBUS group, 44% in the non-EBUS group (ns). Lesions below 3 cm and lesions assumed difficult to reach had significant lower detection rates in the EBUS group. Lesions visualised by EBUS had a higher detection rate for cancer than lesions not visualised by EBUS (62% vs. 19%, p<0.01). The cost of one additional positive sample was 1211 euro when brushing was added to biopsy. It was not cost effective to add washing or TBNA. EBUS did not increase the detection rate for cancer in peripheral lung lesions when bronchoscopy was performed by bronchoscopists at all levels of expertise. Biopsy and brushing was the most cost effective combination of sampling techniques.


Identification of the active site serine of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis.
The active site serine of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis (PepX) was identified. The enzyme was labeled by [3H]DFP, treated by CNBr and the resulting peptides were separated by reverse-phase-HPLC. The main radiolabeled peptide was sequenced. Ser-348, in the following sequence, Gly-Lys-Ser-Tyr-Leu-Gly, was identified as the active site serine. A sequence comparison between the active site of PepX and other serine proteases was made, showing only limited sequence homologies in this area. The consensus sequence surrounding the active site serine in the three known X-prolyl dipeptidyl aminopeptidases (mammalian DPPIV, yeast DPAB and PepX) is G-X-S-Y-X-G, where X is a non-conserved amino acid.


Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis.
How cyclooxygenase-2 (COX-2) and its proinflammatory metabolite prostaglandin E2 (PGE2) enhance colon cancer progression remains poorly understood. We show that PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein betagamma subunits and the direct association of the G protein alphas subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3beta from its complex with axin, thereby relieving the inhibitory phosphorylation of beta-catenin and activating its signaling pathway. These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer.


Molecular diagnosis of nonaneurysmal infectious aortitis.
We report a 79-year-old patient who presented with a fever and abdominal pain. The patient was initially thought to have a retroperitoneal fibrosis or inflammatory abdominal aortitis in a normal-sized caliber aorta. Broad-range polymerase chain reaction (PCR) and DNA sequencing revealed the presence of Enterobacter. We finally diagnosed nonaneurysmal infectious aortitis, and we performed a successful surgical resection. Establishing a diagnosis of aortic infection before formation of an aneurysm is difficult. The molecular diagnostic technique was particularly useful in specifying the microbial species and diagnosis.


Biologically active compounds from marine organisms in the strategies for combating coronaviruses.
Despite the progress made in immunization and drug development, so far there are no prophylactic vaccines and effective therapies for many viral infections, including infections caused by coronaviruses. In this regard, the search for new antiviral substances continues to be relevant, and the enormous potential of marine resources are a stimulus for the study of marine compounds with antiviral activity in experiments and clinical trials. The highly pathogenic human coronaviruses-severe acute respiratory syndrome-related coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) remain a serious threat to human health. In this review, the authors hope to bring the attention of researchers to the use of biologically active substances of marine origin as potential broad-spectrum antiviral agents targeting common cellular pathways and various stages of the life cycle of different viruses, including coronaviruses. The review has been compiled using references from major databases such as Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to June 2020) and keywords such as 'coronaviruses', 'marine organisms', 'biologically active substances', 'antiviral drugs', 'SARS-CoV', 'MERS-CoV', 'SARS-CoV-2', '3CLpro', 'TMPRSS2', 'ACE2'. After obtaining all reports from the databases, the papers were carefully analysed in order to find data related to the topic of this review (98 references). Biologically active substances of marine origin, such as flavonoids, phlorotannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, lipids and others substances, can affect coronaviruses at the stages of penetration and entry of the viral particle into the cell, replication of the viral nucleic acid and release of the virion from the cell; they also can act on the host's cellular targets. These natural compounds could be a vital resource in the fight against coronaviruses.


Urinary excretion of type I collagen crosslinked N-telopeptides in healthy Japanese adults: age- and sex-related changes and reference limits.
A new immunoassay for measuring urinary excretion of type I collagen crosslinked N-telopeptides (NTx) has been reported to be a specific and sensitive method for assessing bone resorption. We have studied factors affecting biological variations in urinary NTx excretion in a population of 452 healthy Japanese adults, comprising 238 men and 214 women, 20-79 years of age. Urinary NTx excretion increased significantly with age in women (> or = 25 years of age) (r = 0.55, p < 0.0001) and modestly correlated with lumbar bone mineral density (L-BMD) in both sexes (> or = 25 years of age) (r = 0.31, p < 0.0001 for men; r = 0.50, p < 0.0001 for women). Urinary NTx levels in women were significantly higher than in the corresponding male age groups after the fifth decade (p < 0.0001). None of the anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary NTx excretion independent of age and L-BMD. In women, menopause was reflected by a twofold increase in urinary NTx excretion, from a mean of 28-59 pmol bone collagen equivalents (BCE)/mumol creatinine, and this menopause-related increase persisted for the entire postmenopausal period. In postmenopausal women, the interindividual variations of urinary NTx excretion were much more marked than in men and in premenopausal women. Moreover, in the subgroups of pre- and postmenopausal women, urinary NTx excretion correlated with neither age nor L-BMD. These data show that the major biological factor that modifies urinary NTx level is menopause and suggest that the bone turnover rates in the elderly women are increased, on average, irrespective of bone mineral density.


Surgery of the hand in severe systemic sclerosis.
Ten patients with scleroderma and severe hand problems required surgery, and seven were available for follow-up (two died from scleroderma-related complications and one was lost to follow-up). The mean duration of follow-up was 4 (range 1.5-9) years. Thirty-three procedures were carried out, including five metacarpophalangeal joint excisional arthroplasties, 13 proximal interphalangeal joint fusions, ten distal interphalangeal joint fusions, and one thumb interphalangeal joint fusion. The metacarpophalangeal joint excision arthroplasties and proximal interphalangeal joint fusions were performed for the correction of severe fixed "finger-in-palm" deformities. Lesions of cutaneous calcinosis were removed in four patients. Fixation was satisfactory in all cases of interphalangeal joint fusion, with no cases of nonunion. Wound healing was satisfactory in six of seven patients. A second surgical procedure was required in three patients for the removal of tension band wires following interphalangeal fusion. Calcinosis was effectively removed using a high-speed dental burr. The results of hand surgery for systemic sclerosis are reliable, but goals must be limited and patient expectations should be modest.


Comparison between respiratory variations in pulse oximetry plethysmographic waveform amplitude and arterial pulse pressure during major abdominal surgery.
To assess preload dependence, the variation of the plethysmographic waveform of pulse oximetry (ΔPOP) has been proposed as a surrogate of the pulse pressure variation (ΔPP). The aim of the study was to assess the ability of the pulse oximeter-derived plethysmographic analysis to accurately trend ΔPP in patients undergoing major abdominal surgery by using standard monitors. A continuous recording of arterial and plethysmographic waveform was performed in 43 patients undergoing abdominal surgery. ΔPP and ΔPOP were calculated on validated respiratory cycles. For analysis, 92,467 respiratory cycles were kept (73.5% of cycles recorded in 40 patients). The mean of intrapatient coefficients of correlation was low (r = 0.22). The Bland and Altman analysis showed a systematic bias of 5.21; the ΔPOP being greater than the ΔPP, this bias increased with the mean value of the two indices and the limits of agreement were wide (upper 21.7% and lower -11.3%). Considering a ΔPP threshold at 12% to classify respiratory cycles as responders and nonresponders, the corresponding best cutoff value of ΔPOP was 13.6 ± 4.3%. Using these threshold values, the observed classification agreement was moderate (κ = 0.50 ± 0.09). The wide limits of agreement between ΔPP and ΔPOP and the weak correlation between both values cast doubt regarding the ability of ΔPOP to substitute ΔPP to follow trend in preload dependence and classify respiratory cycles as responders or nonresponders using standard monitor during anesthesia for major abdominal surgery.


A farewell to phlebotomy-use of placenta-derived drugs Laennec and Porcine for improving hereditary hemochromatosis without phlebotomy: a case report.
Human hepcidin, produced by hepatocytes, regulates intestinal iron absorption, iron recycling by macrophages, and iron release from hepatic storage. Recent studies indicate that hepcidin deficiency is the underlying cause of the most known form of hereditary hemochromatosis. A 44-year-old Asian man who developed type 2 diabetes mellitus had elevated serum ferritin levels (10,191 ng/mL). Liver biopsy revealed remarkable iron deposition in the hepatocytes and relatively advanced fibrosis (F3). Chromosomal analysis confirmed the presence of transferrin receptor type 2 mutations (c.1100T>G, c.2008_9delAC, hereditary hemochromatosis type 3 analyzed by Kawabata). The patient received intravenous infusions of Laennec (672 mg/day, three times/week) or oral administration with Porcine (3.87 g/day) for 84 months as an alternative to repeated phlebotomy. At the end of the treatment period, serum ferritin level decreased to 428.4 ng/mL (below the baseline level of 536.8 ng/mL). Hemoglobin A1c levels also improved after treatment with the same or lower dose of insulin (8.8% before versus 6.8% after). Plural liver biopsies revealed remarkable improvements in the grade of iron deposition and fibrosis (F3 before versus F1 after) of the liver tissue. The discovery of hepcidin and its role in iron metabolism could lead to novel therapies for hereditary hemochromatosis. Laennec (parenteral) and Porcine (oral), which act as hepcidin inducers, actually improved iron overload in this hereditary hemochromatosis patient, without utilizing sequential phlebotomy. This suggests the possibility of not only improving the prognosis of hereditary hemochromatosis (types 1, 2, and 3) but also ameliorating complications, such as type 2 diabetes, liver fibrosis, and hypogonadism. Laennec and Porcine can completely replace continuous venesection in patients with venesection and may improve other iron-overloading disorders caused by hepcidin deficiency.


High-precision multiparameter estimation of mechanical force by quantum optomechanics.
A nanomechanical oscillator can be used as a sensitive probe of a small linearized mechanical force. We propose a simple quantum optomechanical scheme using a coherent light mode in the cavity and weak short-pulsed light-matter interactions. Our main result is that if we transfer some displacement to the mechanical mode in an initialization phase, then a much weaker optomechanical interaction is enough to obtain a high-precision multiparameter estimation of the unknown force. This approach includes not only estimating the displacement caused by the force but also simultaneously observing the phase shift and squeezing of the mechanical mode. We show that the proposed scheme is robust against typical experimental imperfections and demonstrate the feasibility of our scheme using orders of magnitude weaker optomechanical interactions than in previous related works. Thus, we present a simple, robust estimation scheme requiring only very weak light-matter interactions, which could open the way to new nanomechanical sensors.


Histological examination of the rat after long-term exposure to subtoxic automotive exhaust gas.
Regarding the potential impact of traffic-born air pollutants on public health, in recent years attention has increasingly been focused on the possible effects on the cardiovascular system. In order to investigate this problem further, the influence of long-term exhaust gas exposure on rats has been studied. One hundred Wistar rats of either sex were exposed 5 X 8 h/week up to 28 months to an atmosphere polluted by the emissions of an idling Otto engine, CO concentrations held constant at 90 ppm. A second group (50 rats) was exposed to 250 ppm for 6 months. Blood parameters and body weight were controlled. Specimens of CNS, heart, vessels, kidney etc. were investigated light microscopically. Focal necroses of the myocardium with inflammatory reactions as well as interstitial fibrosis were found in the heart muscle of the 90 ppm group. In the 250 ppm group endothelial proliferations, edema of the intima and deposits of proteoglycanes in the media were observed. We conclude that subtoxic concentrations of CO which only lead to slight morphologic changes may aggravate preexisting lesions caused by high risk conditions, e.g., hypertension or hypercholesteremia.


Three-dimensional determination of variability in colon anatomy: applications for numerical modeling of the intestine.
Precise knowledge of variability in colonic anatomy is of great importance for numerical modeling studies of the abdomen. This knowledge would allow the creation of personalized models for the gastrointestinal tract used for surgical simulations or in studies of virtual trauma. To determine the colonic configuration in the general population and define its variability by gender, age, and corpulence, the layout of the colon was determined via the following reference points: ileocecal junction, left and right colonic flexures, and colosigmoid junction (CSJ). Three-dimensional coordinates for each point were recorded on scanned sections of 100 healthy adults to examine the colonic layout under physiological conditions. Coordinates were repositioned in a new anatomical reference for comparison. The average points' coordinates, standard deviations, and distances between them were compared for each group. The right colonic flexure was the most variable point. The CSJ was the least variable. Gender affected mainly the height of the colonic flexures and the length of its segments. Age affected the length of the transverse mesocolon root. Corpulence affected both the position of the ileocecal and CSJs and the length of the right colon. Differences in size and perivisceral fat distribution between groups explained these differences. Three-dimensional anatomical models of the colon were defined for each group by statistical equations. These equations, combined with data concerning the actual lengths of the colonic segments, enable reconstruction of different anatomical models of the colon that are representative according to gender, age, and corpulence.


The accumulation and elimination of diflubenzuron by fish.
In summary, diflubenzuron is accumulated from water into fish tissues at levels up to 80 fold within 24 hr when fish are exposed to concentrations of 10 ppb. Within the concentration range of 1-10 ppb, the amount accumulated in a 24 hr exposure is proportional to concentration. After 24 to 48 hr exposure fish degrade and eliminate diflubenzuron and the excretory products are neither the parent compound nor p-chlorophenylurea. The amount of diflubenzuron remaining in fish tissues with time is dependent on the reduction of residue concentration in water; however, the potential for degradation and elimination is very great.


Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells.
Cytotoxic T cells play a key role in adaptive immunity by killing infected or cancerous cells. While the transcriptional control of CD8 T cell differentiation and effector function following T cell activation has been extensively studied, little is known about epigenetic regulation of these processes. Here we show that the histone deacetylase HDAC3 inhibits CD8 T cell cytotoxicity early during activation and is required for persistence of activated CD8 T cells following resolution of an acute infection. Mechanistically, HDAC3 inhibits gene programs associated with cytotoxicity and effector differentiation of CD8 T cells including genes encoding essential cytotoxicity proteins and key transcription factors. These data identify HDAC3 as an epigenetic regulator of the CD8 T cell cytotoxicity program.


Off-resonance correction using an estimated linear time map.
Images acquired in the presence of magnetic field deviations and reconstructed without taking into account the off-resonance, are distorted and corrupted with artifacts. Several post-processing algorithms have been developed for correcting the distortion when it is not possible to fix the field inhomogeneities. These off-resonance correction methods are, in general, slow and computing intensive. To make them faster they are usually adapted to a particular situation or approximated. One of these approximations is to assume that the field map is linear. Although this assumption makes the algorithm fast and robust it is not well suited for arbitrary field maps. On the other hand, there are k-space trajectories with an almost linear time map (time at which each k-space value is acquired), such as 2DFT and EPI. This paper presents an algorithm for off-resonance correction based on a linear time map approximation. This approximation allows a fast algorithm that takes advantage of the almost linearity of the time map and uses the whole field map to correct the images. The proposed correction algorithm reduces the off-resonance induced artifacts while being fast. The linear approximation of the time map needs to be done only once for each trajectory because it does not depend on the acquired image or field map data. The method can also be extended to a multi-plane approximation for sequences with more complex time maps.


Unregulated online sales of cardiac implantable electronic devices in the United States: A six-month assessment.
An estimated 1 million patients require cardiac implantable electronic devices (CIEDs) but go without annually. This disparity exists in low-to-middle-income nations largely owing to the cost of CIED hardware. Humanitarian reuse of CIEDs has been shown to be safe and feasible. However, recent publications have raised concern that promotion of CIED reuse may foster a CIED "black market," to the dismay of manufacturers, regulators, and clinicians alike. To determine if unregulated CIED sales for potential human use is a real issue by investigating unregulated public online CIED sale listings in the United States of America. An observational study was undertaken over 6 months using multiple internet search engines from May 1 to November 1, 2019. We cataloged usable CIEDs (still in packaging, manufactured <7 years) and pricing. Manufacturers were contacted to determine status of sellers and unregulated CIEDs using model/serial numbers. In total, 58 CIEDs-47 implantable cardioverter-defibrillators and 11 permanent pacemakers-from 4 manufacturers were listed for sale on 3 websites. During the study period, 8 of 11 pacemakers and 37 of 47 implantable cardioverter-defibrillators were sold (price range: $100-$1500 [US dollars]). No new listings were seen in the last 3 months of observation, possibly owing to concomitant industry investigation. There does exist a public online market for unregulated CIED sales in the United States. This specific market seems to be small and unlikely to significantly expand with active monitoring by manufacturers and regulators.


The costimulatory signal upregulation is associated with Th1 bias at the maternal-fetal interface in human miscarriage.
PROBLEM To evaluate whether the association of the costimulatory signal regulation with T helper 1/T helper 2 (Th1/Th2) bias at maternal-fetal interface in human pregnancy loss. METHOD OF STUDY The expression of CD80 and CD86 in decidual tissues and CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in the decidual T cells was compared between normal early pregnancy and miscarriage by qPCR and Western blot. The cytokine production in decidual T cells was performed by flow cytometry. The correlation of costimulatory molecule expression with Th1/Th2 cytokines was analyzed. RESULTS The CD80 mRNA and protein expression showed no significant difference between normal pregnancy and miscarriage. An increase in the expression of CD28 and CD86 was accompanied by a decrease in the expression of CTLA-4 in miscarriage in comparison with the early pregnancy. The higher expression of interleukin (IL)-2 and interferon-γ (IFN-γ), and lower expression of IL-4 and IL-10 in the decidual T cells were present in miscarriage. A correlation analysis showed a significant positive correlation of CD86 and CD28 expression with the Th1 cytokine production (IL-2 and IFN-γ), a significant negative correlation of CTLA-4 expression with the Th1 cytokine production. CONCLUSION The upregualtion of costimulatory signals on T cells might form an abnormal immune microenvironment, a shift to Th1 responses, at maternal-fetal interface, which leads to human miscarriage.


Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores.
PR loss in ER+/HER2- breast cancer indicates worse prognosis and insensitivity to anti-estrogen therapy, while the mechanisms of PR loss in ER+/HER2- breast cancer remain unrevealed. In this study, ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer cases from TCGA were used. 1387 pathways were analyzed and used as variables for classifying the two groups with LASSO regression. ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer groups can be classified by a combination of 13 pathways using their activity score. Among the 13 pathways, those involving growth factors and ion-channel transporters were most significant in the distinction, followed by pathways involving immune modulation and cell metabolism. Two growth factor pathways, EGF and IGF-1, were deferentially regulated in ER+/PR+/HER2- and ER+/PR-/HER2- groups. In conclusion, this study indicated in ER+/HER2- breast cancers the various status of PR expression can be an indication of molecular variation, particularly for the growth factor pathway activation.


The syndrome of mental handicap, cataracts, muscle wasting and skeletal abnormalities: report of a second case.
A severely mentally handicapped Caucasian male with cataracts, deafness, distal muscle wasting and skeletal abnormalities, including calcification of the pinnae, is described. The findings in this patient strongly resemble those in a male described in 1982 by Primrose, and it suggested that this unusual pattern of abnormalities constitutes a discrete entity, which we propose should be known as 'Primrose syndrome'.


Abatacept Improves Intractable Protein-Losing Enteropathy Secondary to AA Amyloidosis in a Patient With Rheumatoid Arthritis.
A 71-year-old Japanese woman with a history of rheumatoid arthritis of 50 years' duration was admitted to our hospital with refractory diarrhea. Endoscopic biopsy revealed AA amyloid deposition in the large intestine. Although the patient had been prescribed 5 tumor necrosis factor inhibitors over the past 10 years, rheumatoid arthritis was poorly controlled, with a Disease Activity Score 28 using C-reactive protein score of 6.52 on admission. Treatment with tocilizumab (8 mg/kg every 2 weeks) was initiated, but this was ineffective. After 3 months, abatacept (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin) was initiated (750 mg/mo) and the patient's diarrhea began to improve. After 3 months of abatacept treatment, serum albumin, C-reactive protein, and serum amyloid A levels had all decreased to within normal ranges. After 3 years of abatacept treatment, a repeat biopsy of the large intestine revealed a marked improvement in amyloid deposition. Interleukin 6 is a key factor in AA amyloid formation, but this case suggests that T-cell activation increases the production of cytokines (including interleukin 6) via a mechanism involving cytotoxic T-lymphocyte-associated antigen 4, resulting in a second key factor of AA amyloid formation.


Renal cortical uptake kinetics of gentamicin in rats with impaired renal function.
The renal cortical uptake kinetics of the aminoglycoside antibiotic gentamicin was determined in the remnant kidney model. Renal failure was induced by partial ablation of the right kidney followed by left nephrectomy in female Wistar rats. The animals received a six-hour gentamicin infusion at a constant rate yielding steady-state serum concentrations ranging from 0.5 to 150 micrograms/mL. The renal cortical gentamicin concentrations were determined and related to the serum concentrations achieved. This relationship was nonlinear and followed Michaelis-Menten kinetics. Gentamicin cortical uptake rate, however, did not show clear saturation in the range of gentamicin serum levels studied as was observed in rats with normal renal function. The Michaelis-Menten parameters determined by nonlinear regression were Km = 15.0, 73.9, and 135.7 micrograms/mL; and Vmax = 149.9, 213.7, and 239.2 micrograms/g cortex/h, respectively, for controls, rats with serum creatinine levels between 0.9 and 1.2 mg/dL, and those with levels between 1.3 and 1.8 mg/dL. It is concluded that at serum levels below 100 micrograms/mL, the gentamicin renal cortical uptake is diminished in rats with renal failure. This decrease in renal cortical uptake is more pronounced in the group of rats with more severe renal failure.


Dynamic multi-objective evolutionary optimization algorithm based on two-stage prediction strategy.
Tracking pareto-optimal set or pareto-optimal front in limited time is an important problem of dynamic multi-objective optimization evolutionary algorithms (DMOEAs). However, the current DMOEAs suffer from some deficiencies. In the early optimization process, the algorithms may suffer from random search. In the late optimization process, the knowledge which can accelerate the convergence rate is not fully utilized. To address the above issue, a DMOEA based on the two-stage prediction strategy (TSPS) is proposed. TSPS divides the optimization progress into two stages. At the first stage, multi-region knee points are selected to capture the pareto-optimal front shape, which can accelerate the convergence and maintaining good diversity at the same time. At the second stage, improved inverse modeling is applied to search the representative individuals, which can improve the diversity of the population and is beneficial to predicting the moving location of the pareto-optimal front. Experimental results on dynamic multi-objective optimization test suites show that TSPS is superior to the other six DMOEAs. In addition, the experimental results also show that the proposed method has the ability to respond quickly to environmental changes.


A multi-centre study of therapeutic efficacy and safety of platelet components treated with amotosalen and ultraviolet A pathogen inactivation stored for 6 or 7 d prior to transfusion.
Bacteria in platelet components (PC) may result in transfusion-related sepsis (TRS). Pathogen inactivation of PC with amotosalen (A-PC) can abrogate the risk of TRS and hence facilitate storage to 7 d. A randomized, controlled, double-blinded trial to evaluate the efficacy and safety of A-PC stored for 6-7 d was conducted. Patients were randomized to receive one transfusion of conventional PC (C-PC) or A-PC stored for 6-7 d. The primary endpoint was the 1 h corrected count increment (CCI) with an acceptable inferiority of 30%. Secondary endpoints included 1- and 24-h count increment (CI), 24-h CCI, time to next PC transfusion, red blood cell (RBC) use, bleeding and adverse events. 101 and 100 patients received A-PC or C-PC respectively. The ratio of 1-h CCI (A-PC:C-PC) was 0·87 (95% confidence interval: 0·73, 1·03) demonstrating non-inferiority (P = 0·007), with respective mean 1-h CCIs of 8163 and 9383; mean 1-h CI was not significantly different. Post-transfusion bleeding and RBC use were not significantly different (P = 0·44, P = 0·82 respectively). Median time to the next PC transfusion after study PC was not significantly different between groups: (2·2 vs. 2·3 d, P = 0·72). Storage of A-PCs for 6-7 d had no impact on platelet efficacy.