Serum Liver Fibrosis Markers in the Prognosis of Liver Cirrhosis: A Prospective Observational Study.
BACKGROUND The prognostic role of serum liver fibrosis markers in cirrhotic patients remains unclear. We performed a prospective observational study to evaluate the effect of amino-terminal pro-peptide of type III pro-collagen (PIIINP), collagen IV (CIV), laminin (LN), and hyaluronic acid (HA) on the prognosis of liver cirrhosis. MATERIAL AND METHODS All patients who were diagnosed with liver cirrhosis and admitted to our department were prospectively enrolled. PIIINP, CIV, LN, and HA levels were tested. RESULTS Overall, 108 cirrhotic patients were included. Correlation analysis demonstrated that CIV (coefficient r: 0.658, p<0.001; coefficient r: 0.368, p<0.001), LN (coefficient r: 0.450, p<0.001; coefficient r: 0.343, p<0.001), and HA (coefficient r: 0.325, p=0.001; coefficient r: 0.282, p=0.004) levels, but not PIIINP level (coefficient r: 0.081, p=0.414; coefficient r: 0.090, p=0.363), significantly correlated with Child-Pugh and MELD scores. Logistic regression analysis demonstrated that HA (odds ratio=1.00003, 95% confidence interval [CI]=1.000004-1.000056, p=0.022) was significantly associated with the 6-month mortality. Receiver operating characteristics analysis demonstrated that the area under the curve (AUC) of HA for predicting the 6-month mortality was 0.612 (95%CI=0.508-0.709, p=0.1531). CONCLUSIONS CIV, LN, and HA levels were significantly associated with the severity of liver dysfunction, but might be inappropriate for the prognostic assessment of liver cirrhosis.


Difference in thrombotic microangiopathy between concurrently and previously diagnosed systemic lupus erythematosus.
Thrombotic microangiopathy (TMA) syndromes are potentially life-threatening complications and are defined as integrated syndromes of microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect various organs, including the hematopoietic system. SLE can complicate with TMA and can be categorized into two distinct groups by chronological association: TMA occurring as the initial presentation and leading to a diagnosis of SLE concurrently (TMA-cSLE) or TMA developing in patients previously diagnosed as having SLE (TMA-pSLE). We examined the differences in clinical characteristics, treatment responses, and clinical outcomes between these groups. We reviewed data of patients diagnosed as having TMA and SLE at Taipei Veterans General Hospital between 2002 and 2013. We included 29 patients: 8 and 21 in TMA-cSLE and TMA-pSLE groups, respectively. All underwent plasma exchange. Patients' demographic and clinical characteristics, disease activity, and treatment modality were summarized. Overall survival (OS) from SLE or TMA diagnosis was poor for the TMA-cSLE group. Median OS from SLE diagnosis was 2.9 months in the TMA-cSLE group and 103.5 months in the TMA-pSLE group (p < 0.001). Median OS from TMA diagnosis was 2.9 months in the TMA-cSLE group and 10.7 months in the TMA-pSLE group (p = 0.58). Time to TMA remission after treatment appeared longer in the TMA-cSLE group (38.00 vs 10.76 days). Multivariate Cox analysis revealed TMA-cSLE and anti-RNP positivity were independent risk factors for mortality in SLE patients with TMA. The occurrence of TMA with SLE is rare, and its vigorous course results in high mortality and morbidity rates. In patients without a history of autoimmune disease, early suspicion of TMA and working-up for SLE under this condition are vital. Early recognition of TMA-cSLE and prompt plasma exchange with upfront immunosuppressive therapies for TMA-cSLE patients or anti-RNP-positive patients may improve their prognosis.


Hepatitis C infection is acquired pre-ESRD.
Hepatitis C is more prevalent in patients with end-stage renal disease (ESRD) than in the general population. Previously, infection from nosocomial sources was an important cause for this increase. In the past decade, the risk from these sources has lessened, but the estimated percentage of patients with ESRD with hepatitis C virus (HCV) antibody (anti-HCV) has not changed. This is a prospective observational study of hemodialysis patients in 4 urban units in Birmingham, AL. Testing for anti-HCV was performed at the initiation of dialysis therapy and then yearly from August 1998 through August 2004. Race, sex, age, ESRD date, comorbid conditions, and outcomes were recorded. The prevalence of anti-HCV was 16.8% in 860 patients (89% black). Patients new to ESRD had a prevalence of 14.4%. Seroconversion in previously anti-HCV-negative patients was 2.5%. Anti-HCV occurred in black men 3 times more than in black women (odds ratio, 3.3; 95% confidence interval, 2.2 to 5.0). Mean age at ESRD was significantly younger in anti-HCV-positive than HCV-negative patients (47.3 versus 54.1 years; P < 0.0001). Age, race, sex, and history of drug abuse were predictors of anti-HCV positivity. The prevalence of anti-HCV among patients with ESRD varies from community to community. New patients are major contributors to the prevalence of anti-HCV in patients with ESRD, particularly those who are younger, male, black, or have a history of drug use. Measuring anti-HCV levels in patients with chronic kidney disease may help identify those at risk for additional disorders.


The production of synthetic chemodisruptive peptides in planta disrupts the establishment of cyst nematodes.
Root exudates from transgenic potato plants expressing a chemoreception-disruptive peptide inhibit acetylcholinesterase by up to 63 +/- 3%. This inhibition correlates strongly with the efficacy of the exudates as a presoak solution for infective juveniles of Heterodera glycines that leads to reduced root invasion. The establishment of developing Globodera pallida at 21 days post-infection in these transgenic plants was also suppressed in containment trials. Relative to controls, the best line showed a 47 +/- 5% reduction in developing females and had 188 +/- 25% more undeveloped infective juveniles. This suggests that disorientation of chemoreception occurs after initial root invasion. Line (e) showed the highest level of resistance with 61 +/- 4% in glasshouse trials conducted over a 9-week period. This result represents the combined effect on the number of cysts produced and the number of eggs each cyst contains. The level of control shown to saccate females was consistent in both the 21-day and 9-week post-infection studies. Another chemoreception-disruptive peptide, that binds to nematode nicotinic receptors in cholinergic neurones, provided a 52.6 +/- 1% reduction in the number of nematodes able to establish in transgenic hairy roots that expressed the peptide. This confirms that both chemoreception-disruptive peptides have efficacy in suppressing parasitism by cyst nematodes when expressed in planta at low concentrations.


Genome sequence and description of Anaeromassilibacillus senegalensis gen. nov., sp. nov., isolated from the gut of patient with kwashiorkor.
Using the culturomics strategy, a wide range of anaerobic bacteria was discovered including Anaeromassilibacillus senegalensis strain mt9T (= CSUR P1511 = DSM 102954), isolated from the gut microbiota of a 1-year-old Senegalese patient with kwashiorkor. This Gram-negative strain is a strictly anaerobic, spore-forming rod motile by a polar flagellum. The 3 511 289 bp long genome of this strain contains 3046 protein-coding and 49 RNA genes, including 45 tRNA and four rRNA genes, and exhibits a G+C content of 52.94%. Here we describe the features of this organism, together with the complete genome sequence and annotation.


Aging augments renal vasoconstrictor response to orthostatic stress in humans.
The ability of the human body to maintain arterial blood pressure (BP) during orthostatic stress is determined by several reflex neural mechanisms. Renal vasoconstriction progressively increases during graded elevations in lower body negative pressure (LBNP). This sympathetically mediated response redistributes blood flow to the systemic circulation to maintain BP. However, how healthy aging affects the renal vasoconstrictor response to LBNP is unknown. Therefore, 10 young (25 ± 1 yr; means ± SE) and 10 older (66 ± 2 yr) subjects underwent graded LBNP (-15 and -30 mmHg) while beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), arterial BP (Finometer), and heart rate (HR; electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as mean BP/RBFV. All baseline cardiovascular variables were similar between groups, except diastolic BP was higher in older subjects (P < 0.05). Increases in RVR during LBNP were greater in the older group compared with the young group (older: -15 mmHg Δ10 ± 3%, -30 mmHg Δ20 ± 5%; young: -15 mmHg Δ2 ± 2%, -30 mmHg Δ6 ± 2%; P < 0.05). RBFV tended to decrease more (P = 0.10) and mean BP tended to decrease less (P = 0.09) during LBNP in the older group compared with the young group. Systolic and diastolic BP, pulse pressure, and HR responses to LBNP were similar between groups. These findings suggest that aging augments the renal vasoconstrictor response to orthostatic stress in humans.


NMR, PGSE diffusion, and X-ray diffraction studies of lithium and potassium salts derived from diphenylphosphino(o-cyanophenyl)aniline and their crown ether complexes.
1H, 31P, and 7Li pulsed-gradient spin-echo (PGSE) diffusion and variable-temperature NMR results for THF solutions of the lithium and potassium salts derived from diphenylphosphino(o-cyanophenyl)aniline are reported and compared to the solid-state results obtained via X-ray diffraction studies. The solution results favor mononuclear salts, sometimes strongly ion paired, whereas the solid-state data reveal dinuclear species. The structures of the products from reactions of these salts with crown ethers are determined via PGSE and 1H Overhauser NMR methods.


Adenovirus infection of the cornea causes histopathologic changes in the lacrimal gland.
To explore the effects on the lacrimal gland of adenovirus infection of the cornea. Rabbit corneas were inoculated with human adenoviruses Ad5, Ad14, or a rabbit adapted form of Ad 5, and in some instances booster inoculations were given. Sections of lacrimal glands removed 21-59 days post-inoculation were immunostained using antibodies against rabbit Class I and Class II MHC molecules, CD4, CD8, CD18, and rabbit thymic lymphocyte antigen (RTLA). Relative numbers of positively stained cells were quantified with a Metamorph image analysis system. RTLA and CD18 antigens were expressed on many interstitial cells in the normal lacrimal gland, but few expressed CD4 or CD8. The number of RTLA+ cells increased by 60-100% after inoculation of Ad5 and after boosting, and CD18+ cells increased from 33-100% after inoculation of Ad5 and after boosting. Booster inoculations also caused focal lymphocytic infiltration. MHC Class I was expressed on interstitial cells and duct epithelium, but not acinar cells, and there was no detectable difference after viral infection. In controls, MHC Class II was localized to a population of interstitial cells and a few acinar cells. A single inoculation of the Ad5 virus did not result in an increase in the total number of MHC Class II-positive cells at 21 days, but inoculation with the rabbit-adapted Ad 5 and booster inoculations caused a 30% increase. Ad5 and rabbit-adapted Ad5 infection of the cornea induce lymphocytic infiltration in the lacrimal gland, and the effect is enhanced by boosting. There is also an increase in expression of MHC Class II after inoculation with rabbit-adapted Ad5 and with booster inoculations.


A case of purpura fulminans caused by Hemophilus influenzae complicated by reversible cardiomyopathy.
Here, we report a case of a 41-year-old male diagnosed as septic shock with purpura fulminans (PF) infection. The causative organism was β-lactamase-negative ampicillin-resistant Hemophilus influenzae. He developed fulminant cardiac dysfunction approximately 1 h after admission, and the cause was considered to be septic cardiomyopathy. Blood pressure and oxygenation were maintained at adequate levels with the aid of extracorporeal membrane oxygenation (ECMO). The cardiac dysfunction was reversible, and he was successfully weaned from ECMO on day 12 of hospitalization. However, he needed amputation for all extremities because the infection spread to his limbs and eventually, succumbed to sepsis caused by empyema on day 34 of hospitalization. To the best of our knowledge, this is only the second case of PF caused by H. influenzae in an adult to be reported worldwide.


[Therapeutic efficacy of allogeneic hematopoietic stem cell transplantation in children with chronic myelogenous leukemia].
To investigate the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with chronic myelogenous leukemia (CML), and to analyze the possible prognostic factors. The clinical data of 20 children with CML who had received allo-HSCT was analyzed retrospectively to investigate possible prognostic factors, including age, sex, interval between diagnosis and transplantation, HLA matching between donors and recipients, illness status on transplantation and acute and chronic graft-versus-host disease (GVHD). At the end of follow-up, 13 of the 20 treated children had disease-free survival (DFS) and the rest (7 cases) died. Four died of severe acute GVHD, two of chronic GVHD and its complications, and one of relapse after transplantation. The three-year DFS was (64.6±1.1%). As shown by the univariate analysis, age was the most important prognostic factor in children with CML who had received allo-HSCT (P<0.05), and in children over 10 years, the prognosis was poor. No other of the above factors had a significant impact on prognosis (P>0.05). The multivariate logistic regression analysis also confirmed age as the only prognostic factor (P<0.01). Severe acute and/or chronic GVHD was the most important cause of patient death. 10/10 HLA-matched donors could improve the transplantation outcome. Allo-HSCT is an effective treatment for children with CML. To improve the prognosis and treatment outcome, children with CML aged over 10 years should receive allo-HSCT as early as possible. 10/10 HLA-matched donors are preferred in allo-HSCT and GVHD should be prevented.


Short term lead exposure induces a stress-like response in adult mice.
Developmental and perinatal lead exposure in rats affects the Hypothalamus-Pituitary-Adrenal Cortex (HPA) axis function resulting in elevated corticosterone blood levels thus affecting the level of stress responsivity of the offspring. The majority of the studies on lead exposure and stress have been done by exposing the animal indirectly during gestation, or lactation periods. This study presents evidence supporting that short term lead exposure affects a stress-like response in adult lead-exposed mice. DBA/2J mice were exposed to three different lead concentrations, 250, 500 and 1000 ppm, in the drinking water for a two week period. After the exposure period the animals were subjected to behavioral tests, i.e., social contact, and the plus maze using a computer-assisted videomonitoring system, Videomex-V (Columbia Instruments). The levels of ACTH and corticosterone in plasma were also measured using a Radioimmunoassay (RIA). Exposed animals displayed a significant decrease in the length of time the mice pairs spent within social contact distance (5.18 +/- 0.58 seconds for controls and 3.23 +/- 0.34 seconds for 1000 ppm exposure), and a significant decrease in the percent of time the mice stayed in the open arms of the plus maze (7% for controls and 1% for 1000 ppm exposure) a measure indicator of anxiety. In addition exposed mice showed increased blood levels of ACTH (573 +/- 106 microg/dL for 1000 ppm and 127 +/- 25 microg/dL for control mice) and corticosterone (195.12 +/- 52.47 controls and 87.33 +/- 10.94 for exposed). These results support the hypothesis that exposure to lead of the adult mice affects a behavioral and hormonal response consistent with stress.


Motor deficit in a Drosophila model of mucolipidosis type IV due to defective clearance of apoptotic cells.
Disruption of the Transient Receptor Potential (TRP) mucolipin 1 (TRPML1) channel results in the neurodegenerative disorder mucolipidosis type IV (MLIV), a lysosomal storage disease with severe motor impairments. The mechanisms underlying MLIV are poorly understood and there is no treatment. Here, we report a Drosophila MLIV model, which recapitulates the key disease features, including abnormal intracellular accumulation of macromolecules, motor defects, and neurodegeneration. The basis for the buildup of macromolecules was defective autophagy, which resulted in oxidative stress and impaired synaptic transmission. Late-apoptotic cells accumulated in trpml mutant brains, suggesting diminished cell clearance. The accumulation of late-apoptotic cells and motor deficits were suppressed by expression of trpml(+) in neurons, glia, or hematopoietic cells. We conclude that the neurodegeneration and motor defects result primarily from decreased clearance of apoptotic cells. Since hematopoietic cells in humans are involved in clearance of apoptotic cells, our results raise the possibility that bone marrow transplantation may limit the progression of MLIV.


Renal epithelioid angiomyolipoma: a malignant disease.
Renal angiomyolipomas are recognized as clonal neoplasms with clonal chromosomal aberrations and a common progenitor cell, the perivascular epithelial cell (PEC). The epithelioid variant is a recently identified entity, characterized by predominance of PEC and a unique morphologic and immunohistochemical profile. There is accumulating evidence suggesting that renal epithelioid angiomyolipoma (REA) is a malignant disease. We searched the literature for descriptions of clinical behavior of REA. A Pubmed search was performed using the following key words: angiomyolipoma, epithelioid, perivascular epithelial cell or/and renal tumors. We reviewed a case of fatal REA at our institution. A pathologist reviewed slides to confirm the diagnosis. Upon review of 140 articles, 37 eligible articles were found including 10 articles describing the clinical course of REA. Almost all of the patients described, for whom there was a follow-up available, died of neoplastic progression of the disease, with liver, lung and bone metastases. Four cases were reclassified after retrospective pathology review, and they were fatal. Three of these had been misdiagnosed as renal cell carcinoma (RCC), while 1 was diagnosed as classic angiomyolipoma. Unlike commonly benign classic angiomyolipoma, REA behaves aggressively. It is crucial for the clinician to be aware of and identify this epithelioid variant as a malignant disease. It should be carefully differentiated from RCC. Resection alone may not be curative, and adjuvant therapy should be considered. A multimodality treatment approach needs to be explored for this newly recognized malignant variant renal angiomyolipoma.


Postoperative Doppler echocardiographic evaluation in different sizes of Medtronic-Hall, Biocor and Carpentier-Edwards S.A.V. prosthetic aortic valves.
Doppler echocardiography was performed on 108 patients 4-15 days after implantation of a Medtronic-Hall, Biocor or Carpentier-Edwards S.A.V. prosthetic aortic valve because of aortic stenosis. Significant correlation was found between the in vitro (maker-declared) and the Doppler-estimated effective prosthetic valve orifice area (r = 0.70, p < 0.01). Doppler-estimated prosthetic valve orifice area, but not transprosthetic blood velocities, discriminated between different sizes of Medtronic-Hall and Biocor valves. The effective orifice area in these valves was 57% of the in vitro area, but in Carpentier-Edwards valves it was only 43%. Transprosthetic blood velocity was inversely related to orifice area in men, but not in women, who also had longer duration of systole and better preservation of systolic left ventricular function. The data suggest that the effective prosthetic valve areas found in patients are significantly smaller than the experimental in vitro areas. Prosthesis size and type, anatomic and hemodynamic variables and gender are important in Doppler estimation of effective valve area.


Management of hypertension: risk-benefit ratio.
The justification for drug treatment of mild hypertension rests upon epidemiological data demonstrating an increased risk of heart attack and stroke and a very small number of controlled clinical trials. These data provide a slender basis for mass treatment and leave many vital questions unanswered. The incidence of stroke (and heart attack in some countries) appears to be falling irrespective of antihypertensive therapy. Are historic epidemiological findings still relevant? The level of diastolic blood pressure where risk begins to increase appears to be about 95 mmHg. Ought this also to be the target value for blood pressure reduction? Do thiazide diuretics have added risks and beta-adrenergic blocking drugs added benefits over and above their effect upon blood pressure? If the MRC Hypertension trial turns out to be the last of the big placebo controlled trials in hypertension how shall we assess the effects of new types of drugs upon outcome?


Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis.
Fibroblast growth factor 1 (FGF-1) is a classical member of the FGF family and is produced by chondrocytes cultured from osteoarthritic patients. Also, this growth factor was shown to bind to CCN family protein 2 (CCN2), which regenerates damaged articular cartilage and counteracts osteoarthritis (OA) in an animal model. However, the pathophysiological role of FGF-1 in cartilage has not been well investigated. In this study, we evaluated the effects of FGF-1 in vitro and its production in vivo by use of an OA model. Treatment of human chondrocytic cells with FGF-1 resulted in marked repression of genes for cartilaginous extracellular matrix components, whereas it strongly induced matrix metalloproteinase 13 (MMP-13), representing its catabolic effects on cartilage. Interestingly, expression of the CCN2 gene was dramatically repressed by FGF-1, which repression eventually caused the reduced production of CCN2 protein from the chondrocytic cells. The results of a reporter gene assay revealed that this repression could be ascribed, at least in part, to transcriptional regulation. In contrast, the gene expression of FGF-1 was enhanced by exogenous FGF-1, indicating a positive feedback system in these cells. Of note, induction of FGF-1 was observed in the articular cartilage of a rat OA model. These results collectively indicate a pathological role of FGF-1 in OA development, which includes an insufficient cartilage regeneration response caused by CCN2 down regulation.


The effect of mass media campaigns on oral health knowledge: A systematic review and meta-analysis.
Knowledge and awareness gained from mass media can prepare people for lifestyle changes and impact their health and well-being. Considering the differences in the results of primary studies, we decided to conduct this study to evaluate the effect of mass media campaigns on oral health knowledge as a systematic meta-analysis and review. The databases such as the Web of Sciences (ISI), Scopus, PubMed/Medline, and the Cochrane Library were searched systematically until February 2022. Data pooling was performed using a random effects model. The effect sizes were estimated as odds ratios (ORs) with their 95% confidence intervals (CIs). Additional analyses, including sensitivity, subgroup, and publication bias analyses, were also conducted. Our meta-analysis comprised a total number of seven articles. The pooled results indicated significant increases in oral health knowledge among included studies (OR = 1.64, 95% CI: 1.20-2.24, p < 0.001). In subgroup analyses, the effects of mass media campaigns on oral health knowledge remained significant for the studies with follow-up of less than 150 weeks (OR = 1.69, 95% CI: 1.49-1.91) and working-age populations (OR = 1.80, 95% CI: 1.40-2.32) compared to other categories. In general, this study showed that mass media campaigns may have positive effects on oral health knowledge, especially in the working-age population; it seems that for improving health knowledge among children, more initiatives are needed. Besides, the effects of these campaigns seem to be time-dependent and higher in shorter follow-up periods.


Leveraging weather data for forecasting cases-to-mortality rates due to COVID-19.
There are several recent publications criticizing the failure of COVID-19 forecasting models, with swinging over predictions and underpredictions, which have made it difficult for decision and policy making. Observing the failures of several COVID-19 forecasting models and the alarming spread of the virus, we seek to use some stable response for forecasting COVID-19, viz., ratios of COVID-19 cases to mortalities, rather than COVID-19 cases or fatalities. A trend of low COVID-19 cases-to-mortality ratios calls for urgent attention: the need for vaccines, for instance. Studies have shown that there are influences of weather parameters on COVID-19; and COVID-19 may have come to stay and could manifest a seasonal outbreak profile similar to other infectious respiratory diseases. In this paper, the influences of some weather, geographical, economic and demographic covariates were evaluated on COVID-19 response based on a series of Granger-causality tests. The effect of four weather parameters, viz., temperature, rainfall, solar irradiation and relative humidity, on daily COVID-19 cases-to-mortality ratios of 36 countries from 5 continents of the world were determined through regression analysis. Regression studies show that these four weather factors impact ratios of COVID-19 cases-to-mortality differently. The most impactful factor is temperature which is positively correlated with COVID-19 cases-to-mortality responses in 24 out of 36 countries. Temperature minimally affects COVID-19 cases-to-mortality ratios in the tropical countries. The most influential weather factor - temperature - was incorporated in training random forest and deep learning models for forecasting the cases-to-mortality rate of COVID-19 in clusters of countries in the world with similar weather conditions. Evaluation of trained forecasting models incorporating temperature features show better performance compared to a similar set of models trained without temperature features. This implies that COVID-19 forecasting models will predict more accurately if temperature features are factored in, especially for temperate countries.


Tuning the Orchestra: HCMV vs. Innate Immunity.
Understanding how the innate immune system keeps human cytomegalovirus (HCMV) in check has recently become a critical issue in light of the global clinical burden of HCMV infection in newborns and immunodeficient patients. Innate immunity constitutes the first line of host defense against HCMV as it involves a complex array of cooperating effectors - e.g., inflammatory cytokines, type I interferon (IFN-I), natural killer (NK) cells, professional antigen-presenting cells (APCs) and phagocytes - all capable of disrupting HCMV replication. These factors are known to trigger a highly efficient adaptive immune response, where cellular restriction factors (RFs) play a major gatekeeping role. Unlike other innate immunity components, RFs are constitutively expressed in many cell types, ready to act before pathogen exposure. Nonetheless, the existence of a positive regulatory feedback loop between RFs and IFNs is clear evidence of an intimate cooperation between intrinsic and innate immunity. In the course of virus-host coevolution, HCMV has, however, learned how to manipulate the functions of multiple cellular players of the host innate immune response to achieve latency and persistence. Thus, HCMV acts like an orchestra conductor able to piece together and rearrange parts of a musical score (i.e., innate immunity) to obtain the best live performance (i.e., viral fitness). It is therefore unquestionable that innovative therapeutic solutions able to prevent HCMV immune evasion in congenitally infected infants and immunocompromised individuals are urgently needed. Here, we provide an up-to-date review of the mechanisms regulating the interplay between HCMV and innate immunity, focusing on the various strategies of immune escape evolved by this virus to gain a fitness advantage.


Determination of the chiral condensate from (2+1)-flavor lattice QCD.
We perform a precise calculation of the chiral condensate in QCD using lattice QCD with 2+1 flavors of dynamical overlap quarks. Up and down quark masses cover a range between 3 and 100 MeV on a 16{3}x48 lattice at a lattice spacing approximately 0.11 fm. At the lightest sea quark mass, the finite volume system on the lattice is in the regime. By matching the low-lying eigenvalue spectrum of the Dirac operator with the prediction of chiral perturbation theory at the next-to-leading order, we determine the chiral condensate in (2+1)-flavor QCD with strange quark mass fixed at its physical value as Sigma;{MS[over ]}(2 GeV)=[242(04)(+19/-18) MeV]{3} where the errors are statistical and systematic, respectively.


Four-year incidence and progression of visual impairment in a South Indian population with diabetes.
The aim of this study is to investigate the 4-year incidence and progression of visual impairment (VI) and the associated risk factors for incident VI in a South Indian population with type 2 diabetes. A total of 634 participants with type 2 diabetes were found eligible after 4 years. Visual acuity (VA) was estimated using the modified Early Treatment Diabetic Retinopathy Study protocol. VA in the better eye was considered for the assessment of VI based on the World Health Organization criteria. Mild VI was defined as VA <20/40 but up to 20/60, moderate VI as VA <20/60 but up to 20/200, severe VI as VA <20/200 but up to 10/200, and blindness as VA worse than 10/200. The 4-year incidence of any VI, mild VI, moderate VI, severe VI, and blindness was 21.7%, 18.3%, 3.4%, 0.0%, and 0.0%, respectively; of the 13 participants with VI at baseline, 12 (92%) showed worsening/progression of VI on follow-up. Multiple logistic regression showed that nuclear cataract of grades >4.0 (odds ratio [OR]: 2.612 [1.148-5.942], P = 0.022) and lower socioeconomic score (OR: 0.965 [95% confidence interval, (0.933-0.998)], P = 0.040) were associated with the risk of future incident VI. Refractive error (47%) and cataract (30%) were identified as the leading causes of incident VI at follow-up. VI seems to be a significant problem among diabetic participants in the South Indian population. Refractive error and cataract are the leading but treatable causes of incident VI in this population and would benefit from intervention.


Water loss control using pressure management: life-cycle energy and air emission effects.
Pressure management is one cost-effective and efficient strategy for controlling water distribution losses. This paper evaluates the life-cycle energy use and emissions for pressure management zones in Philadelphia, Pennsylvania, and Halifax, Nova Scotia. It compares water savings using fixed-outlet and flow-modulated pressure control to performance without pressure control, considering the embedded electricity and chemical consumption in the lost water, manufacture of pipe and fittings to repair breaks caused by excess pressure, and pressure management. The resulting energy and emissions savings are significant. The Philadelphia and Halifax utilities both avoid approximately 130 million liters in water losses annually using flow-modulated pressure management. The conserved energy was 780 GJ and 1900 GJ while avoided greenhouse gas emissions were 50 Mg and 170 Mg a year by Philadelphia and Halifax, respectively. The life-cycle financial and environmental performance of pressure management systems compares favorably to the traditional demand management strategy of installing low-flow toilets. The energy savings may also translate to cost-effective greenhouse gas emission reductions depending on the energy mix used, an important advantage in areas where water and energy are constrained and/or expensive and greenhouse gas emissions are regulated as in California, for example.


Right-left hand asymmetry in manual tracking: when poorer control is associated with better adaptation and interlimb transfer.
To date, interlimb transfer following visuomotor adaptation has been mainly investigated through discrete reaching movements. Here we explored this issue in the context of continuous manual tracking, a task in which the contribution of online feedback mechanisms is crucial, and in which there is a well-established right (dominant) hand advantage under baseline conditions. We had two objectives (1) to determine whether this preexisting hand asymmetry would persist under visuomotor rotation, (2) to examine interlimb transfer by assessing whether prior experience with the rotation by one hand benefit to the other hand. To address these, 44 right-handed participants were asked to move a joystick and to track a visual target following a rather unpredictable trajectory. Visuomotor adaptation was elicited by introducing a 90° rotation between the joystick motion and the cursor motion. Half of the participants adapted to the rotation first with the right hand, and then with the left, while the other half performed the opposite protocol. As expected during baseline trials, the left hand was less accurate while also exhibiting more variable and exploratory behavior. However, participants exhibited a left hand advantage during first exposure to the rotation. Moreover, interlimb transfer was observed albeit more strongly from the left to the right hand. We suggest that the less effective and more variable/exploratory control strategy of the left hand promoted its adaptation, which incidentally favored transfer from left to right hand. Altogether, this study speaks for further attention to the dominant/non-dominant asymmetry during baseline before examining interlimb transfer of adaptation.


Extinction and the optical theorem. Part I. Single particles.
We study the extinction caused by a single particle and present a conceptual phase-based explanation for the related optical theorem. Simulations of the energy flow caused by a particle's presence in a collimated beam of light demonstrate how the extinction process occurs. It is shown that extinction does not necessarily cause a reduction of the energy flow along the exact forward direction. Implications regarding the measurement of the single-particle extinction cross section are discussed. This work is extended to noninteracting and interacting multiparticle groups in Part II [J. Opt. Soc. Am. A25, pp. 1514 (2008)].


Footprints of a trypanosomatid RNA world: pre-small subunit rRNA processing by spliced leader addition trans-splicing.
The addition of a capped mini-exon [spliced leader (SL)] through trans-splicing is essential for the maturation of RNA polymerase (pol) II-transcribed polycistronic pre-mRNAs in all members of the Trypanosomatidae family. This process is an inter-molecular splicing reaction that follows the same basic rules of cis-splicing reactions. In this study, we demonstrated that mini-exons were added to precursor ribosomal RNA (pre-rRNA) are transcribed by RNA pol I, including the 5' external transcribed spacer (ETS) region. Additionally, we detected the SL-5'ETS molecule using three distinct methods and located the acceptor site between two known 5'ETS rRNA processing sites (A' and A1) in four different trypanosomatids. Moreover, we detected a polyadenylated 5'ETS upstream of the trans-splicing acceptor site, which also occurs in pre-mRNA trans-splicing. After treatment with an indirect trans-splicing inhibitor (sinefungin), we observed SL-5'ETS decay. However, treatment with 5-fluorouracil (a precursor of RNA synthesis that inhibits the degradation of pre-rRNA) led to the accumulation of SL-5'ETS, suggesting that the molecule may play a role in rRNA degradation. The detection of trans-splicing in these molecules may indicate broad RNA-joining properties, regardless of the polymerase used for transcription.


Beyond Safe Harbor: Automatic Discovery of Health Information De-identification Policy Alternatives.
Regulations in various countries permit the reuse of health information without patient authorization provided the data is "de-identified". In the United States, for instance, the Privacy Rule of the Health Insurance Portability and Accountability Act defines two distinct approaches to achieve de-identification; the first is Safe Harbor, which requires the removal of a list of identifiers and the second is Expert Determination, which requires that an expert certify the re-identification risk inherent in the data is sufficiently low. In reality, most healthcare organizations eschew the expert route because there are no standardized approaches and Safe Harbor is much simpler to interpret. This, however, precludes a wide range of worthwhile endeavors that are dependent on features suppressed by Safe Harbor, such as gerontological studies requiring detailed ages over 89. In response, we propose a novel approach to automatically discover alternative de-identification policies that contain no more re-identification risk than Safe Harbor. We model this task as a lattice-search problem, introduce a measure to capture the re-identification risk, and develop an algorithm that efficiently discovers polices by exploring the lattice. Using a cohort of approximately 3000 patient records from the Vanderbilt University Medical Center, as well as the Adult dataset from the UCI Machine Learning Repository, we also experimentally verify that a large number of alternative policies can be discovered in an efficient manner.


Microbiology in intraabdominal infections: what is the message for clinical studies? (Opinion paper).
Bacterial flora participating in intraabdominal infections are well known. Data are reviewed here documenting the constant antibiotic susceptibility of this flora despite many years of widespread use of antibiotics. The flaws inherent in the concept of "microbiologic efficacy" in evaluating antibiotic efficacy are examined. Among the possible results of a clinical trial, outcomes not in accord with antibiotic sensitivity data occur regularly. Factors such as host defense responses, source control and inoculum density also influence the outcome in a clinical trial but are not currently being measured. Recommendations for improved conduct of trails are made.


Morphology and clinical importance of epidural membrane and periradicular fibrous tissue in lumbar spinal stenosis.
Compared to the ligamentum flavum (LF), morphology of the epidural membrane (EM) and the periradicular fibrous tissue (PRFT) has been largely ignored in studies of lumbar spinal stenosis (LSS). The aim of this prospective study was to elucidate the morphologies and clinical importance of the EM and PRFT in LSS. Before starting this study, neural compressive EM (c-EM) and PRFT (c-PRFT) were defined as follows based on our microsurgical experience and a literature review. The c-EM is a constriction band or membrane obstructing dural tube expansion, and the c-PRFT is a fibrous tissue that compresses the nerve root and/or restricts its mobility. This study enrolled 134 patients who underwent microscopic decompression at L4/5. The morphologies of each patient's EM and PRFT were observed and recorded. Specimens were obtained from randomly selected patients for histological evaluation. The EM and PRFT exhibited a wide morphological spectrum, from a fine strand to a substantial membrane. The c-EM alone was observed in four cases, the c-PRFT alone in 37 cases, and both in three cases. The c-PRFT was more frequently observed in patients with degenerative spondylolisthesis than in those without olisthesis (P < 0.05). Several cases exhibited interesting histological findings including many small arteries, chondrometaplasia, ganglion-like cyst formation, and hyalinized collagen fibers. Some EM and PRFT transform into degenerative and substantial fibrous tissues during the process of symptomatic LSS development. Such morphological and histological changes can cause dural tear, symptomatic epidural hematoma, and/or inadequate decompression.


Serum irisin and myostatin levels after 2 weeks of high-altitude climbing.
Exposure to high-altitude hypoxia causes physiological and metabolic adaptive changes by disturbing homeostasis. Hypoxia-related changes in skeletal muscle affect the closely interconnected energy and regeneration processes. The balance between protein synthesis and degradation in the skeletal muscle is regulated by several molecules such as myostatin, cytokines, vitamin D, and irisin. This study investigates changes in irisin and myostatin levels in male climbers after a 2-week high-altitude expedition, and their association with 25(OH)D and indices of inflammatory processes. The study was performed in 8 men aged between 23 and 31 years, who participated in a 2-week climbing expedition in the Alps. The measurements of body composition and serum concentrations of irisin, myostatin, 25(OH)D, interleukin-6, myoglobin, high-sensitivity C-reactive protein, osteoprotegerin, and high-sensitivity soluble receptor activator of NF-κB ligand (sRANKL) were performed before and after expedition. A 2-week exposure to hypobaric hypoxia caused significant decrease in body mass, body mass index (BMI), free fat mass and irisin, 25-Hydroxyvitamin D levels. On the other hand, significant increase in the levels of myoglobin, high-sensitivity C-reactive protein, interleukin-6, and osteoprotegerin were noted. The observed correlations of irisin with 25(OH)D levels, as well as myostatin levels with inflammatory markers and the OPG/RANKL ratio indicate that these myokines may be involved in the energy-related processes and skeletal muscle regeneration in response to 2-week exposure to hypobaric hypoxia.


Fluorescence-based methods to image palmitoylated proteins.
A well known function of palmitoylation is to promote protein binding to cell membranes. Until recently, it was unclear what additional roles, if any, palmitoylation has in controlling protein localization in cells. Recent studies of palmitoylated forms of the small GTPase Ras have now revealed that palmitoylation plays multiple roles in the regulation of protein trafficking, including targeting proteins into the secretory pathway and recycling proteins between the plasma membrane and Golgi complex. We here describe how quantitative fluorescence microscopy and photobleaching approaches can be used to study the intracellular targeting and trafficking of GFP-tagged palmitoylated proteins in living cells. We discuss (1) general considerations for fluorescence recovery after photobleaching (FRAP) measurements of GFP-tagged proteins; (2) FRAP-based assays to test the strength of binding of palmitoylated proteins to cell membranes; (3) methods to establish the kinetics and mechanisms of recycling of palmitoylated proteins between the Golgi complex and the plasma membrane; (4) the use of the palmitoylation inhibitor 2-bromo-palmitate as a tool to study the dynamic regulation of protein targeting and trafficking by palmitate turnover.


Autobiographical memory and hierarchical search strategies in depressed and non-depressed participants.
There is a growing body of literature showing individuals with depression and other trauma-related disorders (e.g., posttraumatic stress disorder) recall more overgeneral and less specific autobiographical memories compared to normal participants. Although the mechanisms underlying overgeneral memory are quite clear, the search strategy operated within the autobiographical knowledge base, at time of recollection, requires further exploration. The current study aimed to examine the hierarchical search sequence used to recall autobiographical memories in depressed and non-depressed participants, with a view to determining whether depressed participants exhibited truncated search strategies. Thirteen depressed and an equal number of non-depressed participants retrieved 15 memories each, in response to 15 commonly used cue words. Participants reported the first memory that entered in their mind. All memory descriptions were recorded and later transcribed verbatim for content analysis. Depressed participants retrieved autobiographical memories faster, produced shorter memory descriptions and were less likely to recall positive memories than non-depressed participants. Non-depressed participants were more likely to commence retrieval by accessing lifetime period knowledge followed by general event and event specific knowledge, whereas depressed participants showed a tendency to terminate retrieval at the general event level. It is concluded that depressed participants do adhere to the same hierarchical search strategy as non-depressed participants when retrieving specific autobiographical memories, but that they terminate their search early, resulting in overgeneral memories.


Repertoire breadth of human CD4+ T cells specific for HIV gp120 and p66 (primary antigens) or for PPD and tetanus toxoid (secondary antigens)
Antigen derived peptides bound on MHC class II molecules on presenting cells stimulate specific CD4 lymphocytes that are in a naive state if antigen is given for the first time, or in a memory state if antigen has been previously encountered. In order to compare clonal heterogeneity of the human CD4+ T helper repertoire in primary vs. recall responses, we have generated T cell lines in vitro by repeated stimulation of peripheral lymphocytes with primary or with recall antigens. Clonal heterogeneity was broad in the case of recall response to tetanus toxoid or PPD, with a high frequency of specific precursors (> 100 cells/10(6) lymphocytes). In contrast, T cell lines responsive to primary antigens (HIV gp120 or HIV p66) were oligoclonal as defined by TCR V beta gene usage and by spectratyping, and the precursor frequency was low (< 2 cells/10(6) lymphocytes). Primary T cell lines generated from blood samples drawn at different times from the same donor showed that clones with identical TCR CDR3 region coding sequences were expanded, suggesting that in these individuals a large progeny derived from one single precursor is present, even though a previous encounter with the antigen was not documented. Assuming an even in vivo distribution of such cells, the presence of one precursor every 10(6) CD4 lymphocytes (within the CD4 T repertoire that comprises roughly 10(11) CD4 T cells) indicates that approximately 10(5) identical T cells from the same clonal precursor account for the primary response against the model antigens we have studied.


Rendezvin: An essential gene encoding independent, differentially secreted egg proteins that organize the fertilization envelope proteome after self-association.
Preventing polyspermy during animal fertilization relies on modifications to the egg's extracellular matrix. On fertilization in sea urchins, the contents of cortical granules are secreted and rapidly assemble into the egg's extracellular vitelline layer, forming the fertilization envelope, a proteinaceous structure that protects the zygote from subsequent sperm. Here, we document rendezvin, a gene whose transcript is differentially spliced to yield proteins destined for either cortical granules or the vitelline layer. These distinctly trafficked variants reunite after cortical granule secretion at fertilization. Together, they help coordinate assembly of the functional fertilization envelope, whose proteome is now defined in full.


Low back pain and yoga.
ABSTRACT Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is chronic low back pain, one of the most common reasons to visit one's primary care doctor. Complementary approaches, including yoga, will be addressed.


Half-sarcomere dynamics in myofibrils during activation and relaxation studied by tracking fluorescent markers.
To study the dynamics of individual half-sarcomeres in striated muscle contraction, myofibrils prepared from rabbit psoas muscle and left ventricles of guinea pig were immunostained with two conjugated antibody complexes consisting of a primary antibody against either alpha-actinin or myomesin and a secondary fluorescently labeled Fab-fragment. We simultaneously measured force kinetics and determined the positions of the Z-line and M-band signals by fluorescence video microscopy and sophisticated computer vision (tracking) algorithms. Upon calcium activation, sarcomeres and half-sarcomeres shortened nonuniformly. Shortening occurred first rapidly and exponentially during the force rise and then slowly during the force plateau. In psoas myofibrils, time-resolved displacements of the A-band in sarcomeres were observed, i.e., the two halves of individual sarcomeres behaved nonuniformly. Nonuniformity in length changes between the two halves of sarcomeres was comparable to that between two adjacent half-sarcomeres of neighboring sarcomeres. Sequential lengthening of half-sarcomeres was observed in cardiac myofibrils during the rapid phase of force relaxation. The independent dynamics of the halves in a sarcomere reveals the half-sarcomere as the functional unit rather than the structural unit, the sarcomere. The technique will facilitate the study of filament sliding within individual half-sarcomeres and the mechanics of intersegmental chemomechanical coupling in multisegmental striated muscles.


Visualization and quantification of de novo lipogenesis using a FASN-2A-GLuc mouse model.
De novo lipogenesis (DNL) is a dynamic process that converts excess carbohydrates into fatty acids to maintain cellular homeostasis. Dysregulation of DNL is associated with diverse obesity-related diseases and many tumor types. Therefore, monitoring DNL in real-time with high sensitivity should be highly beneficial when screening therapeutic agents for their potential use as obesity treatments. A sequence coding for Gaussia luciferase (GLuc) preceded by a 2A peptide was inserted into the murine fatty acid synthase (FASN) genetic locus by homologous recombination to generate FASN-2A-GLuc mice. The luciferase mouse model was evaluated in conditions of physical and pharmacological stimuli by in vivo and ex vivo imaging. The distribution of bioluminescence signals in different organs was identical to the FASN expression: high in white fat, brown fat, and the lungs. In addition, the bioluminescence signals accurately recapitulated the dynamic change of FASN in response to fasting and refeeding conditions. Moreover, with this murine reporter model, we also discovered that fatostatin, a synthetic inhibitor of sterol regulatory element-binding proteins, effectively inhibited DNL in multiple organs, especially in adipose tissues under a high-carbohydrate diet. Our FASN-2A-GLuc reporter mouse model proved to be a sensitive visualization tool for monitoring both systemic and organ-specific DNL in real time.


Genetic, structural, and antigenic analyses of glycan diversity in the O-linked protein glycosylation systems of human Neisseria species.
Bacterial capsular polysaccharides and lipopolysaccharides are well-established ligands of innate and adaptive immune effectors and often exhibit structural and antigenic variability. Although many surface-localized glycoproteins have been identified in bacterial pathogens and symbionts, it not clear if and how selection impacts associated glycoform structure. Here, a systematic approach was devised to correlate gene repertoire with protein-associated glycoform structure in Neisseria species important to human health and disease. By manipulating the protein glycosylation (pgl) gene content and assessing the glycan structure by mass spectrometry and reactivity with monoclonal antibodies, it was established that protein-associated glycans are antigenically variable and that at least nine distinct glycoforms can be expressed in vitro. These studies also revealed that in addition to Neisseria gonorrhoeae strain N400, one other gonococcal strain and isolates of Neisseria meningitidis and Neisseria lactamica exhibit broad-spectrum O-linked protein glycosylation. Although a strong correlation between pgl gene content, glycoform expression, and serological profile was observed, there were significant exceptions, particularly with regard to levels of microheterogeneity. This work provides a technological platform for molecular serotyping of neisserial protein glycans and for elucidating pgl gene evolution.


Physiological and genomic characterization of Arcobacter anaerophilus IR-1 reveals new metabolic features in Epsilonproteobacteria.
In this study we characterized and sequenced the genome of Arcobacter anaerophilus strain IR-1 isolated from enrichment cultures used in nitrate-amended corrosion experiments. A. anaerophilus IR-1 could grow lithoautotrophically on hydrogen and hydrogen sulfide and lithoheterothrophically on thiosulfate and elemental sulfur. In addition, the strain grew organoheterotrophically on yeast extract, peptone, and various organic acids. We show for the first time that Arcobacter could grow on the complex organic substrate tryptone and oxidize acetate with elemental sulfur as electron acceptor. Electron acceptors utilized by most Epsilonproteobacteria, such as oxygen, nitrate, and sulfur, were also used by A. anaerophilus IR-1. Strain IR-1 was also uniquely able to use iron citrate as electron acceptor. Comparative genomics of the Arcobacter strains A. butzleri RM4018, A. nitrofigilis CI and A. anaerophilus IR-1 revealed that the free-living strains had a wider metabolic range and more genes in common compared to the pathogen strain. The presence of genes for NAD(+)-reducing hydrogenase (hox) and dissimilatory iron reduction (fre) were unique for A. anaerophilus IR-1 among Epsilonproteobacteria. Finally, the new strain had an incomplete denitrification pathway where the end product was nitrite, which is different from other Arcobacter strains where the end product is ammonia. Altogether, our study shows that traditional characterization in combination with a modern genomics approach can expand our knowledge on free-living Arcobacter, and that this complementary approach could also provide invaluable knowledge about the physiology and metabolic pathways in other Epsilonproteobacteria from various environments.


Point-of-Care Platform Based on Solid-Phase Fluorescence Filter Effect for Urinary Iodine Testing in Children and Pregnant Women.
Iodine is an essential element that is used to make thyroid hormones. However, people usually ignore their iodine nutrition level, thus leading to a series of thyroid diseases, particularly in areas where medical resources are scarce. Thus, development of a portable, economical, and simple method for the detection of urinary iodine is of significant importance. Herein, a solid-phase fluorescence filter effect (SPFFE) induced by iodine was used to develop an SPFFE-based point-of-care testing (POCT) platform for the detection of urinary iodine by coupling with headspace sample introduction. This method can not only alleviate the matrix interference that occurred in the conventional inner filter effect (IFE) but also achieve high sensitivity. Furthermore, the urinary iodine (UI) POCT platform was developed through the integration of a sample pretreatment and fluorescence readout. This whole system costs less than US $20 and provides accurate temperature control and a portable fluorescence reading within 15-20 min. Compared to the traditional IFE-based assay, the SPFFE-based POCT platform allows the selective detection of iodine as low as 10 nM and has a linear range of 0.05-4 μM. In addition, it provides notable visualization from blue-violet to orange-red in the presence of iodine, which tends to indicate the iodine nutritional status of the human body. Eventually, the clinical applicability and feasibility of the UIPOCT platform as an early diagnostic test kit were confirmed by determining the iodine in urine samples from children and pregnant women.


Interfacial phenomena: an in vitro study of the effect of calcium phosphate (Ca-P) ceramic on bone formation.
In previous studies we developed a RF magnetron sputter technique for the production of thin Ca-P coatings. With this technique coatings can be produced that vary in Ca/P ratio as well as in structural appearance. The aim of this investigation was to obtain more understanding of the biological behavior of these coatings by way of in vitro experiments. The effect of noncoated titanium (Ti) and three different Ca-P-sputtered surfaces on the proliferation and differentiation (morphology and matrix production) of osteoblast-like cells was studied. Proliferation was determined using counting procedures; morphology was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fluorescent markers and energy-dispersive X-ray microanalysis (EDX) were used to obtain quantitative and compositional information about the resultant calcified extracellular matrix (ECM). Results demonstrated that proliferation of the osteoblast-like cells was significantly (p < 0.05) higher on noncoated than on Ca-P-coated samples. On the other hand, more mineralized ECM was formed on the coated surfaces. In addition, TEM confirmed that the cells on the coated substrates were surrounded by ECM with collagen fibers embedded in crystallized, needle-shaped structures. On the basis of these findings, we concluded that: (1) the investigated Ca-P sputter coatings possess the capacity to activate the differentiation and expression of osteogenic cells, and (2) bone formation proceeds faster on Ca-P surfaces than on Ti substrates. Further, this bone-inductive effect appeared to be dependent on the Ca-P ratio of the deposited coatings.


Correlations of Resource Bricolage and Exaptation With Low-Cost Breakthrough Innovations: Moderating Effect of Organizational Agility.
The mechanism influencing resource bricolage driving low-cost breakthrough innovations remains unclear. By introducing exaptation and organizational agility, this study creates a regulated mediation model, explores effects of resource bricolage on low-cost breakthrough innovations, and analyzes the moderating effect of organizational agility and mediation effect of exaptation. The results revealed that resource bricolage exerted a significant positive impact on low-cost breakthrough innovations, and exaptation played a mediation role between resource bricolage and low-cost breakthrough innovations. In addition, both marketing agility and operational agility positively regulated the correlation between resource bricolage and exaptation. Further research revealed that the mediation effect of exaptation was positively regulated by marketing agility and operational agility, respectively. Overall, this study enriches the discussion of the impact mechanism of breakthrough innovations by resource bricolage and provides valuable enlightenment for enterprises to implement innovation-driven development strategies in the context of economic transformation.


Experimental study on the flow structures and dynamics of turbulent Rayleigh-Bénard convection in an annular cell.
We conduct an experimental study on the flow structures and dynamics of turbulent Rayleigh-Bénard convection in an annular cell with radius ratio η≃0.5 and aspect ratio Γ≃4. The working fluid is water with a Prandtl number of Pr≃5.4, and the Rayleigh number (Ra) ranges from 5.05×10^{7} to 5.05×10^{8}. The multithermal-probe method and the particle image velocimetry technique are employed to measure the temperature profiles and the velocity fields, respectively. Two distinct states with multiroll standing waves are observed, which are the quadrupole state (QS) characterized by a four-roll structure and the sextupole state (SS) by a six-roll structure. The scaling exponents of Reynolds number Re with Ra are different for the two states, which are 0.56 for QS and 0.41 for SS. In addition, the standing waves become unstable upon tilting the cell by 1^{∘} in relation to the horizontal plane, and they evolve into traveling waves. At relatively high Ra, for instance, Ra⩾2.55×10^{8}, it is observed that the traveling wave state SS undergoes a transition to the traveling wave state QS. However, the opposite transition from QS to SS is not observed in our experiments. Our findings provide insights into the flow structures and dynamics in the convection flow with rotation symmetry.


EPO and alpha-MSH prevent ischemia/reperfusion-induced down-regulation of AQPs and sodium transporters in rat kidney.
Ischemia-induced acute renal failure (ARF) is known to be associated with significant impairment of urinary concentrating ability and down-regulation of renal aquaporins (AQPs) and sodium transporters in rats. We tested whether treatment with erythropoietin (EPO) or alpha-melanocyte-stimulating hormone (alpha-MSH) in combination with EPO reduces the renal ischemia/reperfusion (I/R) injury and prevents the down-regulation of renal AQPs and major sodium transporters. I/R-induced ARF was established in rats by 40-minute temporary bilateral obstruction of renal arteries, and rats were kept in metabolic cages for urine measurements. After 2 or 4 days following EPO and/or alpha-MSH treatment, kidneys were removed to determine the expression levels of AQPs and sodium transporters by semiquantitative immunoblotting. Rats with ARF showed significant renal insufficiency, increased urine output, and high fractional excretion of urinary sodium. Consistent with this, immunoblotting and immunocytochemistry revealed that the kidney expression of AQPs (AQP-1, -2 and -3) and sodium transporters [Na,K-ATPase, rat type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), Na/H exchanger type 3 (NHE3), and thiazide-sensitive sodium chloride cotransporter (TSC)] in ARF rats was significantly decreased compared to sham-operated control rats. In contrast, EPO treatment at the time of ischemia of rats with ARF significantly prevented the ischemia-induced down-regulation of renal AQPs and sodium transporters and in parallel improved the urinary concentrating capability and renal sodium reabsorption. Importantly, similar effects were observed following the initiation of EPO or alpha-MSH treatment 4 hours after the onset of ischemia injury. Moreover, the combination of EPO with alpha-MSH potentiated the beneficial effects of single compound treatment. EPO and/or alpha-MSH treatment significantly prevent I/R-induced injuries such as urinary-concentrating defects and down-regulation of renal AQPs and sodium transporters.


The bisphosphonate zoledronate prevents vertebral bone loss in mature estrogen-deficient rats as assessed by micro-computed tomography.
The effect of long-term treatment with the bisphosphonate zoledronate on vertebral bone architecture was investigated in estrogen-deficient mature rats. 4-month-old rats were ovariectomized and development of cancellous osteopenia was assessed after 1 year. The change of bone architectural parameters was determined with a microtomographic instrument of high resolution. After 1 year of estrogen-deficiency, animals lost 55% of vertebral trabecular bone in comparison to sham operated control animals. Trabecular number (Tb.N) and trabecular thickness (Tb.Th) were significantly reduced in ovariectomized animals, whereas trabecular separation (Tb.Sp), bone surface to volume fraction (BS/BV) and trabecular bone pattern factor (TBPf) were significantly increased, indicating a loss of architectural integrity throughout the vertebral body. 3 groups of animals were treated subcutaneously with zoledronate for 1 year with 0.3, 1.5 and 7.5 microgram/kg/week to inhibit osteoclastic bone degradation. Administration started immediately after ovariectomy and treatment dose-dependently prevented the architectural bone deterioration and completely suppressed the effects of estrogen deficiency at the higher doses. The results show that microtomographic determination of static morphometric parameters can be used to quantitate the effects of drugs on vertebral bone architecture in small laboratory animals and that zoledronate is highly effective in this rat model.


Effects of histone deacetylase inhibitors on the early development of bovine androgenetic embryos.
Histone acetylation is one of the most important posttranslational modifications that contribute to transcriptional initiation and chromatin remodeling. In our previous study, we enhanced sperm chromatin remodeling within the bovine sperm injection-derived androgenentic (SpI-AG) embryos by sperm pretreatment, and thereby improved their early developmental competence. In this study, we found that blastocyst development of SpI-AG embryos could be elevated by the histone deacetylase inhibitor (HDACi). First, we optimized the efficacy of two histone deacetylase inhibitors [trichostatin A (TSA) and Scriptaid (SCR)] in a dose (0, 5, 10, 20, 50, and 100 nM for TSA; 0, 50, 100, 200, 300, and 500 nM for SCR, respectively) and time-dependent (0, 10, 15, 20, and 25 h) manner on the developmental capacity of these embryos. Furthermore, we quantitatively assessed the alterations in histone H3 and H4 overall acetylation levels and blastocyst quality of SpI-AG embryos by immunofluorescence staining. We found a significantly improved morula and blastocyst development rate of SpI-AG embryos at a mild dose of TSA (20 nM) or SCR (200 nM) for 15 h after embryo activation. Furthermore, both HDACi noticeably increased the levels of acetylated histone H3 and H4 in SpI-AG blastocyst embryos, whereas, SCR treatment improved the quality of blastocysts when compared with control group. In conclusion, HDACi is beneficial for early development of bovine SpI-AG embryos and can be used to improve the efficiency of its in vitro production.


Biochemical screening of hospitalized geriatric patients.
Blood specimens were collected from 50 hospitalized geriatric patients with a range of chronic diseases. Analyses were conducted for 12 plasma components. Additional tests were performed on patients with abnormal results in the first tests. Of the 50 patients, 21 (42 per cent) had biochemical abnormalities, often unexpected on the basis of current diagnoses. It is suggested that routine biochemical screening should be conducted on geriatric patients at regular intervals.


AdaRTE: adaptable dialogue architecture and runtime engine. A new architecture for health-care dialogue systems.
Spoken dialogue systems have been increasingly employed to provide ubiquitous automated access via telephone to information and services for the non-Internet-connected public. In the health care context, dialogue systems have been successfully applied. Nevertheless, speech-based technology is not easy to implement because it requires a considerable development investment. The advent of VoiceXML for voice applications contributed to reduce the proliferation of incompatible dialogue interpreters, but introduced new complexity. As a response to these issues, we designed an architecture for dialogue representation and interpretation, AdaRTE, which allows developers to layout dialogue interactions through a high level formalism that offers both declarative and procedural features. AdaRTE aim is to provide a ground for deploying complex and adaptable dialogues whilst allows the experimentation and incremental adoption of innovative speech technologies. It provides the dynamic behavior of Augmented Transition Networks and enables the generation of different backends formats such as VoiceXML. It is especially targeted to the health care context, where a framework for easy dialogue deployment could reduce the barrier for a more widespread adoption of dialogue systems.


Sulfation and Desulfation Behavior of Pt-BaO/MgO-Al2O3 NOx Storage Reduction Catalyst.
The comparative study between Pt-BaO/Al2O3 and Pt-BaO/MgO-Al2O3 gives the information about the effect of MgO addition to Al2O3 support on the sulfation and desulfation behavior of Pt-BaO/MgO-Al2O3 NOx storage reduction catalyst. The sulfated two samples were analyzed by using element analysis (EA), X-ray diffraction (XRD), H2 temperature programmed reaction (H2 TPRX) and NOx uptake measurement. The amount of sulfur uptake on 2 wt% Pt-20 wt% BaO/Al2O3 and 2 wt% Pt-20 wt% BaO/MgO-Al2O3 are almost identical as 0.45 and 0.40 of S/Ba, respectively, which yields the drastic decrease in NOx uptake for both sulfated samples. However, after desulfa- tion with H2 at 600 degrees C, the residual sulfur amount on MgO-Al2O3 supported catalyst is three times larger than that on Al2O3 supported one, indicating that sulfur species formed on the former are more stable than those on the latter. It is also well corresponding to the H2 TPRX results where the main H2S peak from MgO-Al2O3 supported sample is observed at higher temperature than Al2O3 supported one, resulting in the lower NOx uptake activity of former sample than the latter one. Meanwhile, after desulfation of MgO-Al2O3 supported sample at 700 degrees C and 800 degrees C, the activity is recovered more significantly due to the removal of the large amount of sulfur while Al2O3 supported one decreases monotonically due to the sintering of Pt crystallite and the formation of BaAl2O4 phase. It is summarized that MgO-Al2O3 supported catalyst enhances the thermal stability of the catalyst, however, forms the stable sulfate species, which needs to be improved to develop the more sulfur resistant NSR catalyst system.


Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 5-Discontinuation of anticoagulant therapy in small animals.
To systematically evaluate the evidence supporting the timing and mechanisms of permanent or temporary discontinuation of antiplatelet or anticoagulant medications in small animals DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality (poor, fair, or good), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice. Academic and referral veterinary medical centers. Databases searched included Medline via PubMed and CAB abstracts. Two specific courses of inquiry were pursued, one focused on appropriate approaches to use for small animal patients receiving antiplatelet or anticoagulant drugs and requiring temporary discontinuation of this therapy for the purposes of invasive procedures (eg, surgery), and the other aimed at decision-making for the complete discontinuation of anticoagulant medications. In addition, the most appropriate methodology for discontinuation of heparins was addressed. To better define specific patient groups, a risk stratification characterization was developed. It is recommended to continue anticoagulant therapy through invasive procedures in patients at high risk for thrombosis that are receiving anticoagulant therapy, while consideration for discontinuation in patients with low to moderate risk of thrombosis is reasonable. In patients with thrombosis in whom the underlying cause for thrombosis has resolved, indefinite treatment with anticoagulant medication is not recommended. If the underlying cause is unknown or untreatable, anticoagulant medication should be continued indefinitely. Unfractionated heparin therapy should be slowly tapered rather than discontinued abruptly.


The burden of COVID-19 infection on medical doctors in the first year of the pandemic in Ghana.
To quantify and describe the burden of COVID-19 infection amongst doctors in Ghana. A quantitative and qualitative analysis of cross-sectional data was performed. All 16 regions in Ghana. Participants were medical doctors diagnosed with COVID-19 between March 2020 and March 2021. Data sources were Ghana Medical Association and Ministry of Health records. Demographics and workplace data included age, gender, the rank of the doctor, and location and type of current facility. Characteristics of the COVID-19 infection included the likely source, clinical and recovery status, and place of management. Doctors reported their desire for a general checkup and psychological support and described the challenges encountered. The prevalence of COVID-19 infection was 88.9 cases per 1000 doctor-population. Of 544 infected doctors, 59.2% were stable but symptomatic, and 1.7% were in critical condition, with a case fatality rate of 1.7%. Overall, 31.6% had recovered from their COVID-19 infection, and the majority (82.4%) were managed at home in self-isolation. Compared to medical officers, house officers (OR 1.36, p=0.03), senior house officers (OR 7.60, p<0.001), and consultants (OR 2.94, p=0.001) were more likely to have a COVID-19 infection. Desire for support was varied, with 13.0% desiring someone to check on them and 9.7% desiring psychological support. The majority (75.3%) reported facing a challenge, including difficulty obtaining needed vitamins and medications, and accessing daily necessities like groceries. In Ghana, COVID-19 infections greatly burden medical doctors. None declared.


Metal-Modified Nucleic Acids: Metal-Mediated Base Pairs, Triples, and Tetrads.
The incorporation of metal ions into nucleic acids by means of metal-mediated base pairs represents a promising and prominent strategy for the site-specific decoration of these self-assembling supramolecules with metal-based functionality. Over the past 20 years, numerous nucleoside surrogates have been introduced in this respect, broadening the metal scope by providing perfectly tailored metal-binding sites. More recently, artificial nucleosides derived from natural purine or pyrimidine bases have moved into the focus of AgI -mediated base pairing, due to their expected compatibility with regular Watson-Crick base pairs. This minireview summarizes these advances in metal-mediated base pairing but also includes further recent progress in the field. Moreover, it addresses other aspects of metal-modified nucleic acids, highlighting an expansion of the concept to metal-mediated base triples (in triple helices and three-way junctions) and metal-mediated base tetrads (in quadruplexes). For all types of metal-modified nucleic acids, proposed or accomplished applications are briefly mentioned, too.


Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques.
The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body's endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone's other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L'Héritier) DC.


The plant microbiota signature of the Anthropocene as a challenge for microbiome research.
One promise of the recently presented microbiome definition suggested that, in combination with unifying concepts and standards, microbiome research could be important for solving new challenges associated with anthropogenic-driven changes in various microbiota. With this commentary we want to further elaborate this suggestion, because we noticed specific signatures in microbiota affected by the Anthropocene. Here, we discuss this based on a review of available literature and our own research targeting exemplarily the plant microbiome. It is not only crucial for plants themselves but also linked to planetary health. We suggest that different human activities are commonly linked to a shift of diversity and evenness of the plant microbiota, which is also characterized by a decrease of host specificity, and an increase of r-strategic microbes, pathogens, and hypermutators. The resistome, anchored in the microbiome, follows this shift by an increase of specific antimicrobial resistance (AMR) mechanisms as well as an increase of plasmid-associated resistance genes. This typical microbiome signature of the Anthropocene is often associated with dysbiosis and loss of resilience, and leads to frequent pathogen outbreaks. Although several of these observations are already confirmed by meta-studies, this issue requires more attention in upcoming microbiome studies. Our commentary aims to inspire holistic studies for the development of solutions to restore and save microbial diversity for ecosystem functioning as well as the closely connected planetary health. Video abstract.


Motor function and incident dementia: a systematic review and meta-analysis.
cognitive and mobility decline are interrelated processes, whereby mobility decline coincides or precedes the onset of cognitive decline. to assess whether there is an association between performance on motor function tests and incident dementia. electronic database, grey literature and hand searching identified studies testing for associations between baseline motor function and incident dementia in older adults. of 2,540 potentially relevant documents, 37 met the final inclusion criteria and were reviewed qualitatively. Three meta-analyses were conducted using data from 10 studies. Three main motor domains-upper limb motor function, parkinsonism and lower limb motor function-emerged as associated with increased risk of incident dementia. Studies including older adults without neurological overt disease found a higher risk of incident dementia associated with poorer performance on composite motor function scores, balance and gait velocity (meta-analysis pooled HR = 1.94, 95% CI: 1.41, 2.65). Mixed results were found across different study samples for upper limb motor function, overall parkinsonism (meta-analysis pooled OR = 3.05, 95% CI: 1.31, 7.08), bradykinesia and rigidity. Studies restricted to older adults with Parkinson's Disease found weak or no association with incident dementia even for motor domains highly associated in less restrictive samples. Tremor was not associated with an increased risk of dementia in any population (meta-analysis pooled HR = 0.80, 95% CI 0.31, 2.03). lower limb motor function was associated with increased risk of developing dementia, while tremor and hand grip strength were not. Our results support future research investigating the inclusion of quantitative motor assessment, specifically gait velocity tests, for clinical dementia risk evaluation.


Use of the KT-MCC strategy to improve the quality of decision making for multidisciplinary cancer conferences: a pilot study.
Multidisciplinary Cancer Conferences (MCCs) are increasingly used to guide treatment decisions for patients with cancer, though numerous barriers to optimal MCC decision-making quality have been identified. We aimed to improve the quality of MCC decision making through the use of an implementation bundle titled the KT-MCC Strategy. The Strategy included use of discussion tools (standard case intake tool and a synoptic discussion tool), workshops, MCC team and chair training, and audit and feedback. Implementation strategies were selected using a theoretically-rooted and integrated KT approach, meaning members of the target population (MCC participants) assisted with the design and implementation of the intervention and strategies. We evaluated implementation quality of the KT-MCC Strategy and initial signals of impact on decision making quality. This was a before-and-after study design among 4 MCC teams. Baseline data (before-phase) were collected for a period of 2 months to assess the quality of MCC decision making. Study teams selected the intervention strategies they wished to engage with. Post-intervention data (after-phase) were collected for 4 months. Implementation quality outcomes included reach, adherence/fidelity and adaptation. We also evaluated feasibility of data management. Decision making quality was evaluated on a per-case and per-round level using the MTB-MODe and MDT-OARS tools, respectively. There were a total of 149 cases and 23 MCCs observed in the before phase and 260 cases and 35 MCCs observed in the after phase. Teams implemented 3/5 strategies; adherence to selected strategies varied by MCC team. The per-round quality of MCCs improved by 11% (41.0 to 47.3, p = < 0.0001). The quality of per-case decision-making did not improve significantly (32.3 to 32.6, p = 0.781). While per round MCC decision making quality improved significantly, per-case decision-making quality did not. We posit that the limited improvements on decision making quality may be attributed to implementation quality gaps, including a lack of uptake of and adherence to theoretically-identified implementation strategies. Our findings highlight the importance of evaluating implementation quality and processes, iterative testing, and engagement of key gatekeepers in the implementation process.


Thermally reversible formation of microspheres through non-covalent polymer cross-linking.
Bis-thymine units were used to noncovalently cross-link a complementary diamidopyridine-functionalized copolymer. Upon combination in noncompetitive solvents, discrete micron-scale spherical aggregates were formed arising from specific three-point polymer-cross-linker hydrogen bonding interactions. The diameter of these microspheres could be controlled through spacer structure. The cross-linking process was fully thermally reversible, with complete dissolution observed at 50 degrees C and reformation of the aggregates upon return to ambient temperature. This process could be repeated multiply, with lower particle dispersity observed arising from the annealing process.


Noninvasive insulin delivery: the great potential of cell-penetrating peptides.
Insulin, a potent therapeutic peptide used in the treatment of diabetes, is administered to patients via subcutaneous injections because of the poor pharmacokinetics associated with alternative routes of administration such as oral, nasal and pulmonary delivery. Noninvasive nasal and oral formulations are appealing to patients who need consecutive daily treatments of insulin. However, to achieve mucosal absorption of insulin via oral or nasal administration, two barriers must be overcome: the impermeability of insulin through the epithelial membranes and local digestion and enzymatic degradation. Cell-penetrating peptides (CPPs), which efficiently bring exogenous proteins and nucleic acids into cells, have great potential to facilitate insulin permeation from the intestinal lumen or nasal cavity into systemic circulation via efficient uptake by epithelial cells. In fact, the coadministration of insulin with the peptide penetratin, a typical CPP, increased intestinal and nasal insulin bioavailability to 35 and 50%, respectively. In this review, the authors describe recent findings using this novel CPP-based formulation for noninvasive delivery of insulin.


Expression of the lipopolysaccharide-modifying enzymes PagP and PagL modulates the endotoxic activity of Bordetella pertussis.
Lipopolysaccharide (LPS) is one of the major constituents of the gram-negative bacterial cell envelope. Its endotoxic activity causes the relatively high reactogenicity of whole-cell vaccines. Several bacteria harbor LPS-modifying enzymes that modulate the endotoxic activity of the LPS. Here we evaluated whether two such enzymes, i.e., PagP and PagL, could be useful tools for the development of an improved and less reactogenic whole-cell pertussis vaccine. We showed that expression of PagP and PagL in Bordetella pertussis leads to increased and decreased endotoxic activity of the LPS, respectively. As expected, PagP activity also resulted in increased endotoxic activity of whole bacterial cells. However, more unexpectedly, this was also the case for PagL. This paradoxical result may be explained, in part, by an increased release of LPS, which we observed in the PagL-expressing cells.


The diversity of ice algal communities on the Greenland Ice Sheet as revealed by oligotyping.
The Arctic is being disproportionally affected by climate change compared with other geographic locations, and is currently experiencing unprecedented melt rates. The Greenland Ice Sheet (GrIS) can be regarded as the largest supraglacial ecosystem on Earth, and ice algae are the dominant primary producers on bare ice surfaces throughout the course of a melt season. Ice-algal-derived pigments cause a darkening of the ice surface, which in turn decreases albedo and increases melt rates. The important role of ice algae in changing melt rates has only recently been recognized, and we currently know little about their community compositions and functions. Here, we present the first analysis of ice algal communities across a 100 km transect on the GrIS by high-throughput sequencing and subsequent oligotyping of the most abundant taxa. Our data reveal an extremely low algal diversity with Ancylonema nordenskiöldii and a Mesotaenium species being by far the dominant taxa at all sites. We employed an oligotyping approach and revealed a hidden diversity not detectable by conventional clustering of operational taxonomic units and taxonomic classification. Oligotypes of the dominant taxa exhibit a site-specific distribution, which may be linked to differences in temperatures and subsequently the extent of the melting. Our results help to better understand the distribution patterns of ice algal communities that play a crucial role in the GrIS ecosystem.


The influence of gapped positions in multiple sequence alignments on secondary structure prediction methods.
All currently leading protein secondary structure prediction methods use a multiple protein sequence alignment to predict the secondary structure of the top sequence. In most of these methods, prior to prediction, alignment positions showing a gap in the top sequence are deleted, consequently leading to shrinking of the alignment and loss of position-specific information. In this paper we investigate the effect of this removal of information on secondary structure prediction accuracy. To this end, we have designed SymSSP, an algorithm that post-processes the predicted secondary structure of all sequences in a multiple sequence alignment by (i) making use of the alignment's evolutionary information and (ii) re-introducing most of the information that would otherwise be lost. The post-processed information is then given to a new dynamic programming routine that produces an optimally segmented consensus secondary structure for each of the multiple alignment sequences. We have tested our method on the state-of-the-art secondary structure prediction methods PHD, PROFsec, SSPro2 and JNET using the HOMSTRAD database of reference alignments. Our consensus-deriving dynamic programming strategy is consistently better at improving the segmentation quality of the predictions compared to the commonly used majority voting technique. In addition, we have applied several weighting schemes from the literature to our novel consensus-deriving dynamic programming routine. Finally, we have investigated the level of noise introduced by prediction errors into the consensus and show that predictions of edges of helices and strands are half the time wrong for all the four tested prediction methods.


A novel energy recovery system for parallel hybrid hydraulic excavator.
Hydraulic excavator energy saving is important to relieve source shortage and protect environment. This paper mainly discusses the energy saving for the hybrid hydraulic excavator. By analyzing the excess energy of three hydraulic cylinders in the conventional hydraulic excavator, a new boom potential energy recovery system is proposed. The mathematical models of the main components including boom cylinder, hydraulic motor, and hydraulic accumulator are built. The natural frequency of the proposed energy recovery system is calculated based on the mathematical models. Meanwhile, the simulation models of the proposed system and a conventional energy recovery system are built by AMESim software. The results show that the proposed system is more effective than the conventional energy saving system. At last, the main components of the proposed energy recovery system including accumulator and hydraulic motor are analyzed for improving the energy recovery efficiency. The measures to improve the energy recovery efficiency of the proposed system are presented.


A comparison of Doppler flow measurements, ultrasonic and arteriographic imaging in the evaluation of stenoses of the carotid artery.
To determine the value of Doppler periorbital flow measurements (DOP) and real-time ultrasonic in the analysis of carotid artery occlusive disease, 1,203 carotid arteries were evaluated in 669 consecutive patients from 1 June 1980 to 1 July 1981. The results of DOP and US were compared with biplane carotid arteriograms using the Seldinger technique. The stenoses were graded: Grade I (zero to 25 per cent), Grade II (25 to 50 per cent), Grade III (50 to 75 per cent) and Grade IV (75 to 100 per cent). Both US and CA agreed in 71.3 per cent of 209 arteries. US and DOP were performed together in 1,203 arteries and agreed in 83.2 per cent. The flow surfaces of an additional 29 arteries were visually inspected at operation to determine the capacity of US to predict ulceration. All of the arteries demonstrated visible ulceration, but only six (20.7 per cent) were predicted by US. The deepest ulcerations that were not detected by US were 2 millimeters in depth. US images were unsatisfactory in 44 arteries (3.7 per cent) because of excessive sound reflection and in 60 (5.0 per cent) because of a "high bifurcation." We conclude that Doppler periorbital flow studies are not as accurate as carotid sonography nor do they add to the accuracy of sonography when the two examinations are combined. Sonography identified significant stenoses but failed to grade the stenoses well and was unreliable in detecting shallow to moderately deep ulcerations.


Deep Vein Thrombosis Is Facilitated by Endothelial-Derived Extracellular Vesicles via the PDI-GRP94-GPIIb/IIIa Pathway in Mice.
Deep vein thrombosis (DVT) is a prevalent cardiovascular condition. Endothelial-derived extracellular vesicles (EVs) may play a crucial role in platelet-dependent DVT development via platelet activation, but the mechanism is not clear yet. This research aims to understand how platelets and endothelial-derived EVs work in DVT. The interaction between protein disulfide isomerase (PDI) and glucose-regulated protein 94 (GRP94) was founded by molecular docking. Inferior vena cava stasis-induced mice received PDI and GRP94 inhibitor treatments. Platelet activation, endothelial-derived EVs, and PDI were measured using flow cytometry. The expression of PDI and dimetric GRP94 in platelets co-cultured with hypoxic endothelial cells was confirmed by Western blot or native PAGE. The fluorescence resonance energy transfer assay shows conformational changes in GPIIb/IIIa on platelet surfaces. A tracking experiment was performed using PKH26, which labelled endothelial-derived EVs, and the endocytosis of EVs by platelets was tracked by confocal microscope. In a DVT mouse model, platelets enhance venous thrombus formation in a coagulation-independent manner, instead, platelet activation and the length of the thrombus are related to PDI and GRP94 activity. Next, we found that the expression level of endothelial-derived EVs carrying PDI is significantly increased in plasma. Endothelial-derived EVs carrying PDI are endocytosed by platelets, in which the content of GRP94 dimer is elevated, and consequently increases the expression of surface GPIIb/IIIa. In addition, PDI allosterically interacts with GPIIb/IIIa, which is re-configurated into an activated form. Endothelial-derived EVs carrying PDI induce DVT via interplay with GRP94 and GPIIb/IIIa in platelets. These findings emphasize the significance of platelets in DVT formation, and PDI may be a suitable target in DVT prevention.


Influence of cholesterol screening and nutritional counseling in reducing cholesterol levels in children. The American Heart Association.
The purpose of this study was to determine whether cholesterol screening and nutritional counseling can reduce cholesterol concentrations in populations of otherwise unrecognized hypercholesterolemic children. A large pediatric practice in Parma Heights, Ohio, has conducted cholesterol surveillance of children over 2 years of age since 1986. The importance of cholesterol and other recognized risk factors for the progression of atherosclerosis is discussed with all families, and the American Heart Association's Step-One diet is recommended. The present study examines data from a cohort of 894 children (473 boys, 421 girls) who had cholesterol concentrations above 185 mg/dL (4.79 mmol/L) (the 90th percentile) at baseline and, after counseling, had a repeat measurement an average of 2.2 years later. Their mean ages were 7 years at the first testing and 9.2 years at the second. Children who had cholesterol concentrations above 200 mg/dL (5.18 mmol/L) (the 95th percentile) had lipoprotein profiles done, and if their LDL cholesterol exceeded 130 mg/dL (3.37 mmol/L) (the 95th percentile), they were referred to a nutritionist, and family members were advised to have their blood lipids analyzed. Mean cholesterol concentration for all 894 children over this time period decreased by 9.4% (19.5 mg/dL [0.51 mmol/L]; 95% CI = 17.5 mg/dL [0.45 mmol/L] to 21.5 mg/dL [0.56 mmol/L]; P < 0.001). A similar decrease of 8.6% (16.6 mg/dL [0.43 mmol/L); 95% CI = 14.0 mg/dL [0.36 mmol/L] to 19.3 mg/dL [0.50 mmol/L); P < 0.001) was observed for the 463 children who had initial cholesterol concentrations between 185 and 200 mg/dL (4.79 and 5.18 mmol/L) and who therefore received a less intense intervention. Cholesterol concentrations in groups of otherwise unidentified hypercholesterolemic children can be significantly reduced as a result of cholesterol screening and nutritional counseling in a pediatric practice setting.


Tumor induction in mice administered neonatally with N-bis(2-hydroxypropyl)nitrosamine (BHPN).
Two subcutaneous injections of N-bis(2-hydroxypropyl)nitrosamine (BHPN) to mice on day 1 and 8 induced tumors of the lung, liver, nasopharynx and pancreas, when animals were killed at the end of one year. The tumor incidences of lung were 90-100%; those of liver 60-92%; those of nasopharynx 3-13%; those of pancreas 2-3%, respectively. The average tumor nodules of lung and those of liver increased in a dose-dependent manner. Two doses of 50 mg/g body weight of BHPN induced one duct cell carcinoma and one acinar cell adenoma of pancreas in a mouse, respectively.


Piezoelectricity in secondary explosives.
A theory for the formation of "hot spots" necessary for the initiation of an explosion is discussed in light of experimental evidence that most solid explosives are highly piezoelectric.


Estrogen-receptor-related protein p29 in primary nonsmall cell lung carcinoma: pathologic and prognostic correlations.
Estrogen-dependent intracellular processes are important in the growth regulation of normal tissue and may play a role in the regulation of malignancies. Utilization of estrogen receptor assays in breast carcinoma is well established, but the role of such evaluation in other cancers largely is unknown. In this study, immunohistochemical expression of estrogen receptor (ER) and the ER-related protein p29 was correlated with survival of patients with nonsmall cell carcinoma of the lung. All patients with a tissue diagnosis of primary nonsmall cell bronchogenic carcinoma diagnosed over a 6-year period at the Medical Center Hospital of Vermont were reviewed. Assays for p29 and ER using a streptavidin-biotin immunoperoxidase method were performed on each tumor. Results were correlated with clinical data, including survival. Of 111 tumors examined, 109 (98%) were positive for p29 whereas none of the tumors reacted with ER (ER1D5). The relation between p29 expression and survival time was different for men and women. A statistically significant negative relation for women was observed; this relation was most pronounced in patients with Stage I and II tumors. A positive but not statistically significant relation was observed for men. The ER-related protein p29 commonly is expressed in nonsmall cell carcinomas of the lung. The relation between p29 and survival time is different for males and females, suggesting the presence of gender specific factors that may influence tumor growth and overall patient survival, especially in patients with early stage lung carcinoma.