Association between portal vein color Doppler findings and the severity of disease in cirrhotic patients with portal hypertension.
Doppler ultrasound is the accepted gold standard for assessing direction of flow in the portal vein (PV). Moreover, it is non-invasive; therefore, it is well accepted by the patients and does not interfere with flow hemodynamics. The present study was aimed to evaluate the association between color Doppler findings and the severity of portal hypertension in patients with cirrhosis. The study group included 50 patients referred for ultrasound (US) evaluation over a period of six months from March to August, 2007. The patients were divided into three groups (Child' A, B and C) based on Child Pugh classification. The direction of flow in the main portal vein (hepatopetal or nonhepatopetal) and peak venous velocity (PVV) in the main portal vein were measured and correlated with the presence or absence of ascites, splenomegaly, splenic and esophageal varices (assessed by Doppler US). These findings were correlated with clinical features and laboratory findings (using Child Pugh's criteria). There was significant association between the decrease of peak portal venous velocity (PVV) and the increase in Child Pugh score. Hepatofugal flow was seen only in patients with more advanced disease. There was also significant association between PVV and splenic varices and ascites, while PVV was not affected by the presence or absence of esophageal varices or splenomegaly. Presence of a recanalized umbilical vein (UV) was associated with increased PVV even in advanced disease. Color Doppler is an excellent modality for detecting and characterizing the complex hemodynamics of portal hypertension in cirrhosis and they correlate with the clinical stage of disease.


Prevention of Gallstones After Bariatric Surgery using Ursodeoxycholic Acid: A Narrative Review of Literatures.
Obesity by itself is a factor in the development of gallstone disease, and periods of weight loss after bariatric surgery further increase the risk of gallstone formation. In patients with obesity, hypersecretion of cholesterol may increase the risk of gallstone formation, which is approximately five-fold higher than that in the general population. The incidence of gallstone formation after bariatric surgery is 10-38% and often associated with a proportional increase in the risk of developing biliary complications. Routine postoperative administration of ursodeoxycholic acid (UDCA) is recommended to prevent gallstone formation. Several randomized trials have indicated that UDCA can effectively prevent gallstones and reduce the risk of cholecystectomy after bariatric procedures. The effective daily dose of UDCA in each study ranged from 500 to 1,200 mg, and it may be considered at least during the period of rapid weight loss (first 3-6 months postoperatively) to decrease the incidence of symptomatic gallstones.


Assessing falls in older people.
For an older person in hospital a fall can have devastating consequences, prolonging hospital stay and leading to loss of confidence. Falls cost the NHS between pounds 5340 and pounds 12,500 per patient in delayed discharge, and can cause nurses to question their own practice and blame themselves. Further, the efforts of clinicians and researchers implementing falls prevention interventions are hampered because of inconsistencies in assessing risk. The use of falls risk assessment tools varies throughout the U.K. In Scotland some hospitals use them while others do not. Unlike England and Wales, Scotland has no national guidelines. To deal with this problem, the authors conclude that it is important to develop an evidence-based guideline that covers the whole of the UK.


Compressed oxygen in drug stability experiments.
A drug stability experiment accelerated by compressed oxygen was established. The stability of 10% ascorbic acid solution as a model was studied and the kinetic parameters were obtained with the newly established experimental method. Because ascorbic acid degrades under both anaerobic and aerobic conditions, the total rate constant k(total) can be expressed as: k(total)=k(anaerobic) + k(aerobic), where k(anaerobic) and k(aerobic) are the rate constants of anaerobic and aerobic degradations, respectively. The k(anaerobic) can be expressed as k(anaerobic) = A(anaerobic) x exp(-E(a,anaerobic)/RT) according to Arrhenius equation, and the k(aerobic) was found to be k(aerobic) = A(aerobic) x exp(-E(a,aerobic)/RT) x p(O2) in our study.


Extracellular calcium promotes bone formation from bone marrow mesenchymal stem cells by amplifying the effects of BMP-2 on SMAD signalling.
Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo. Moreover, we analysed the molecular mechanisms involved and observed an antagonistic effect between Ca2+ and BMP-2 on SMAD1/5, ERK and S6K signalling after 24 hours. More importantly, a cooperative effect between Ca2+ and BMP-2 on the phosphorylation of SMAD1/5, S6, GSK3 and total levels of β-CATENIN was observed at a later differentiation time (10 days). Furthermore, Ca2+ alone favoured the phosphorylation of SMAD1, which correlates with the induction of Bmp2 and Bmp4 gene expression. These data suggest that Ca2+ and BMP-2 cooperate and promote an autocrine/paracrine osteogenic feed-forward loop. On the whole, these results demonstrate the usefulness of calcium-based bone grafts or the addition of exogenous Ca2+ in bone tissue engineering.


Survivors of an Acute Coronary Syndrome With Lower Patient Activation Are More Likely to Experience Declines in Health-Related Quality of Life.
Patient activation comprises the knowledge, skills, and confidence for self-care and may lead to better health outcomes. We examined the relationship between patient activation and changes in health-related quality of life (HRQOL) after hospitalization for an acute coronary syndrome (ACS). We studied patients from 6 medical centers in central Massachusetts and Georgia who had been hospitalized for an ACS between 2011 and 2013. At 1 month after hospital discharge, the patients completed the 6-item Patient Activation Measure and were categorized into 4 levels of activation. Multinomial logistic regression analyses compared activation level with clinically meaningful changes (≥3.0 points, generic; ≥10.0 points, disease-specific) in generic physical (SF-36v2 Physical Component Summary [PCS]), generic mental (SF-36v2 Mental Component Summary [MCS]), and disease-specific (Seattle Angina Questionnaire [SAQ]) HRQOL from 1 to 3 and 1 to 6 months after hospitalization, adjusting for potential sociodemographic and clinical confounders. The patients (N = 1042) were, on average, 62 years old, 34% female, and 87% non-Hispanic white. A total of 10% were in the lowest level of activation. The patients with the lowest activation had 1.95 times (95% confidence interval, 1.05-3.62) and 2.18 times (95% confidence interval, 1.17-4.05) the odds of experiencing clinically significant declines in MCS and SAQ HRQOL, respectively, between 1 and 6 months than the most activated patients. The patient activation level was not associated with meaningful changes in PCS scores. Hospital survivors of an ACS with lower activation may be more likely to experience declines in mental and disease-specific HRQOL than more-activated patients, identifying a group at risk of poor outcomes.


[Ibopamine--clinical results].
Recently, major advances have been made in the therapy of chronic congestive heart failure. New vasodilatory and positive inotropic drugs as well as specific antagonists to activated neurohormones have added new therapeutic dimensions. Dopaminergic stimulation, which has been used in acute heart failure for many years has now been introduced with the new substance ibopamine into the therapy of chronic heart failure. The therapeutic efficacy of new drugs in the treatment of chronic congestive heart failure has to be evaluated in terms of their prognostic and therapeutic impact for improvement and symptomatology, which sometimes does not necessarily lead to improvement of prognosis. Ibopamine has potential in improving prognosis by its major effects: vasodilatation, decrease in vasoactive hormones and improvement in renal blood flow and water diuresis. In the long-term therapy of chronic congestive heart failure ibopamine has been useful in mobilization of edema in acute decompensation, improvement of symptoms according to the New York Heart Classification and of exercise tolerance. In addition improvement of hemodynamics with an increase in cardiac output, a decrease in filling pressures and in peripheral resistance has been demonstrated. Efficacy of diuretics is improved and ibopamine has been a valuable adjunct in the pre-operative therapy before cardiac transplantation. Major positive inotropic effects in the usual dose of 100 mg tid, as well as other potentially dangerous effects of beta-receptor-stimulation (such as malignant, ventricular arrhythmias) can be largely excluded. Historically, controls of patients with heart failure of similar severity do not suggest any unfavorable effect of this drug on prognosis.


Biogeochemistry of Lead. Its Release to the Environment and Chemical Speciation.
Lead (Pb) is a metal that is not essential for life processes and proves acutely toxic to most organisms. Compared to other metals Pb is rather immobile in the environment but still its biogeochemical cycling is greatly perturbed by human activities. In this review we present a summary of information describing the physical and chemical properties of Pb, its distribution in crustal materials, and the processes, both natural and anthropogenic, that contribute to the metal's mobilization in the biosphere. The relatively high volatility of Pb metal, low melting point, its large ionic radius, and its chemical speciation in aquatic systems contributes to its redistribution by anthropogenic and natural processes. The biogeochemical cycle of Pb is significantly altered by anthropogenic inputs. This alteration began in antiquity but accelerated during the industrial revolution, which sparked increases in both mining activities and fossil fuel combustion. Estimates of the flux of Pb to the atmosphere, its deposition and processing in soils and freshwater systems are presented. Finally, the basin scale distribution of dissolved Pb in the ocean is interpreted in light of the chemical speciation and association with inorganic and organic particulate matter. The utility of stable radiogenic Pb isotopes, as a complement to concentration data, to trace inputs to the ocean, better understand the biogeochemical cycling of Pb and track water mass circulation in the ocean is discussed. An ongoing international survey of trace elements and their isotopes in seawater will undoubtedly increase our understanding of the deposition, biogeochemical cycling and fate of this infamous toxic metal.


Evidence for the existence of distinct biophases for alpha- and beta-adrenoceptors in the vascular tissue.
In dog mesenteric artery and saphenous vein strips, the inhibition of neuronal uptake by cocaine increased the potency of exogenous adrenaline for alpha-effects and did not change its potency for beta-effects, whereas inhibition of catechol-O-methyltransferase (COMT) by U-0521 enhanced the beta-effects more than the alpha-ones. On the other hand, cocaine prolonged the duration of adrenaline-induced contraction more than it prolonged the adrenaline-induced relaxation, while U-0521 prolonged the duration of the relaxation much more than that of the contraction. Cocaine and U-0521 also caused differential influences on alpha- and beta-effects caused by endogenous adrenaline, i.e., on alpha- and beta-effects caused by electrical stimulation of strips previously preloaded with adrenaline. It was also observed that the time elapsing between the beginning of the electrical stimulation and the onset of the response (latency) is longer for beta- than for alpha-responses when both are evoked by electrical stimulation. Furthermore, in these strips, alpha-adrenoceptor blocking agents more easily antagonized the contractions caused by exogenous adrenaline than contractions caused by electrical stimulation, whereas propranolol antagonized beta-responses caused by exogenous adrenaline as easily as beta-responses caused by electrical stimulation. It is concluded that there is a biophase for alpha-adrenoceptors, which is under greater influence of neuronal uptake, and another for beta-adrenoceptors, which is under greater influence of COMT activity.


[A case of deep vein thrombosis].
The case of a woman admitted to hospital various times because of the onset of a mantle-like oedematous syndrome is reported. Observations revealed a narrowing at the level of the internal jugular and right subclavian veins with total obliteration of the right anonymous vein caused by previous thrombosis induced by intravenous implantation of a pace-maker.


Mutualists and antagonists mediate frequency-dependent selection on floral display.
Theory predicts that, with conflicting selection pressures mediated by mutualists and antagonists, alternative reproductive strategies can be maintained by negative frequency-dependent selection if it results in rare-morph advantage. We combined field experiments and surveys of natural populations to determine whether selection on floral display is frequency dependent in the self-incompatible herb Primula farinosa, which is polymorphic for inflorescence height and occurs in a short-scaped and a long-scaped morph. Among short-scaped plants, both pollination success, quantified as initiation of fruits and seeds, and seed predation were positively correlated with the relative frequency of the long-scaped morph. The relative strength of these effects and the direction of the resulting frequency-dependent selection on scape morph varied among years and populations. The results suggest that both mutualists and antagonists may mediate frequency-dependent selection and that frequency dependence may vary from positive to negative with rare-morph advantage, depending on the relative strength of these interactions.


An improved procedure for the isolation of glia maturation factor.
A procedure for the bulk isolation of glia maturation factor (GMF) in high yield and high purity from bovine brains is outlined. The method involves extraction by homogenization and centrifugation, followed by ammonium sulfate precipitation and column chromatography with diethylaminoethyl (DEAE) Sephacel, Sephadex G-75, and hydroxylapatite. The method results in a 10,000-fold purification, a purity exceeding that of previously published procedures, and enables us to handle as much as 2.8 kg brain tissue or eight brains/week. The ability to mass-produce GMF with this method greatly facilitates its biological studies, further purification, and chemical characterization. The isolated GMF shows a molecular weight of 13,000 on Bio-gel P-30 column and an isoelectric point of about 5.4 on isoelectric focusing. The isolated GMF is heat labile and susceptible to papain and ficin but relatively resistant to trypsin, neuraminidase, and endoglycosidase.


Patient-reported outcomes and surgical triage: A gap in patient-centered care?
To help address wait times for elective surgery, British Columbia has implemented a triaging system that assigns priority levels to patients based on their diagnoses. The extent to which these priority levels concords with patients' assessment of their health status is not known. The purpose of this study was to measure the association between the priority levels assigned to patients and their patient-reported outcomes data collected at the time of being enrolled on the surgical wait list. Patients waiting for elective surgery in the Vancouver Coastal Health Authority were sampled. Participants completed a set of generic and condition-specific patient-reported outcome instruments, including: the EQ-5D(3L) (general health), PEG (pain), and the PHQ-9 (depression). A multivariate ordered logistic model was used to regress patient-reported outcome values on the priority level assigned at the time of wait list registration. A total of 2725 participants completed the survey package (response rate 49 %). Using the EQ-5D(3L), 63 % reported having problems with pain or discomfort, 41 % problems performing usual activities, 36 % problems with depression or anxiety, 28 % problems with mobility, and 8 % a problem with self-care. The results from the ordered logistic model indicated very little association between the patient-reported outcomes and wait list priority levels, when adjusted for patient factors. This study observed no relationship between patients' self-reported health status and their assigned priority level for elective surgery. A more patient-centered approach to triaging patients for surgical treatment would incorporate patients' perspective in surgical wait list prioritization systems.


Staphylococcus aureus small colony variants in prosthetic joint infection.
Small colony variants of Staphylococcus aureus tend to persist despite antimicrobial therapy, especially when involved in implant-associated infections. We analyzed 5 cases of hip prosthesis-associated infections due to small colony variants, including their course prior to identification of the pathogen. Biopsy investigations included microbiological examination and, in 1 case, transmission electron microscopy to detect intracellular bacteria in nonprofessional phagocytes. A treatment concept was elaborated on the basis of a published algorithm and patients were managed accordingly. The patients' mean age was 62.2 years. All patients experienced treatment failures prior to isolation of small colony variants, despite as many as 3 surgical revisions and up to 22 months of antibiotics. Transmission electron microscopy performed on biopsy specimens from periprosthetic tissue revealed intracellular cocci in fibroblasts. All prostheses were removed without implanting a spacer, and antimicrobial agents were administered for 5.5-7 weeks. Reimplantation of the prosthesis was performed for 4 patients. Follow-ups were uneventful in all 5 cases. In the case of a poor response to adequate antimicrobial and surgical treatment in implant-associated staphylococcal infections, small colony variants should be considered and actively sought. In our case series, a 2-stage exchange without implantation of a spacer combined with antimicrobial therapy for an implant-free interval of 6-8 weeks was associated with successful outcome, with a mean follow-up of 24 months.


Efficient neocentromere formation is suppressed by gene conversion to maintain centromere function at native physical chromosomal loci in Candida albicans.
CENPA/Cse4 assembles centromeric chromatin on diverse DNA. CENPA chromatin is epigenetically propagated on unique and different centromere DNA sequences in a pathogenic yeast Candida albicans. Formation of neocentromeres on DNA, nonhomologous to native centromeres, indicates a role of non-DNA sequence determinants in CENPA deposition. Neocentromeres have been shown to form at multiple loci in C. albicans when a native centromere was deleted. However, the process of site selection for CENPA deposition on native or neocentromeres in the absence of defined DNA sequences remains elusive. By systematic deletion of CENPA chromatin-containing regions of variable length of different chromosomes, followed by mapping of neocentromere loci in C. albicans and its related species Candida dubliniensis, which share similar centromere properties, we demonstrate that the chromosomal location is an evolutionarily conserved primary determinant of CENPA deposition. Neocentromeres on the altered chromosome are always formed close to the site which was once occupied by the native centromere. Interestingly, repositioning of CENPA chromatin from the neocentromere to the native centromere occurs by gene conversion in C. albicans.


Bacterial biofilms and implantable prosthetic devices.
Erectile dysfunction afflicts millions of men. A group of patients with advanced degeneration of their erectile tissue do not respond to pharmacological therapy, and surgical prosthetic reconstruction represents an attractive and highly satisfying alternative. Yet many men are unwilling to take this step due to fear of infection. Implanted prosthetic devices are at risk for infection because they provide a platform for the development of a bacterial biofilm, an organized bacterial colony that grows on the surface of the implanted material. The biofilm is resistant to all efforts to eradicate it short of removal of the foreign material. Bacteria may attach to the surface of the foreign material by surface charge attraction, hydrophilic/hydrophobic interactions, and by specific attachment by fimbrae. Growth, colonization, and maturation follow bacterial attachment. A mature biofilm is composed of three layers: a linking film binding the biofilm to the surface; a base film made up of a compact layer of bacteria; and a surface film from which free-floating bacteria can arise and spread. The majority of the surface layer is made up of exopolysaccharide matrix. Bacteria deep within the biofilm matrix live in a protected environment; diffusion of antibiotics is difficult, low oxygen tension leads to a lower bacterial metabolic rate rendering the bacteria functionally resistant to high levels of antibiotics. Effective strategies to reduce prosthetic infection levels must rely on the prevention of biofilm formation through surface modification. Possible mechanisms include the addition of antimicrobials to the surface of the device, or chemical modifications, which reduces bacterial attachment.


Anticonvulsant Medication Use in Veterans With Posttraumatic Stress Disorder.
Anticonvulsants have been studied for many indications, including posttraumatic stress disorder (PTSD). The limited efficacy research on anticonvulsants for PTSD is mixed. However, anticonvulsants are prescribed widely to veterans with PTSD. Our objective was to measure trends and factors associated with anticonvulsant prescriptions among veterans with PTSD. We obtained administrative and pharmacy data for veterans who initiated PTSD treatment in the US Department of Veterans Affairs (VA) between 2004 and 2013 (N = 731,520). We identified those who received anticonvulsants during the year following their initial clinical PTSD diagnosis and examined common indications for anticonvulsant use, patient characteristics, and service use characteristics. Using logistic regression, we determined the predictors of anticonvulsant initiation among those without an indication. Although 24.9% of patients in the cohort received an anticonvulsant during their initial year of PTSD treatment, 94.6% had an indication unrelated to PTSD and 51.2% initiated anticonvulsant use before their PTSD diagnosis. While there was growth in anticonvulsant initiation over the 10-year period, this was explained both by growth in indications unrelated to PTSD and by increased use of anticonvulsants for these indications. The rate of anticonvulsant initiation without an indication was stable at approximately 5% throughout the period, with patient and service use characteristics driving the selection of individual agents. A large and increasing proportion of veterans with PTSD receives anticonvulsant prescriptions. However, this may be appropriate use driven by increased prevalence of comorbid conditions that may be an indication for anticonvulsant use, including pain and headache disorders.


Seroepidemiology of human T-cell lymphotropic virus type-I in blood donors of Northeastern Iran, Sabzevar.
Human T-cell lymphotropic virus type-I (HTLV-I) infection is considered as a public health challenge in endemic areas. The virus is associated with severe diseases, such as adult T-cell leukemia/lymphoma, and HTLV-I-associated myelopathy/tropical spastic paraparesis. One of the major routes of the HTLV-I transmission includes blood transfusion. Sabzevar is located in the endemic region of HTLV-I infection. The aim of the present study was to determine the seroprevalence of HTLV-I infection in the blood donors in Sabzevar. A total of 35,067 blood donors in Sabzevar from March 2009 to April 2012 who were screened with HTLV-I on the enzyme-linked immunosorbent assay screening test were included in this survey. Reactive samples that confirmed by western blot were considered to be seropositive cases. The required data were obtained from blood donors' database of blood transfusion service. The overall prevalence of HTLV-1 based on the positive result of western blot test was 0.14%. The seropositive donors aged 17-59 years with a mean age of 38.10 ± 11.82. The prevalence rates of HTLV-I infection in 3 years of study were 0.19%, 0.14%, and 0.09%, respectively. A significant relation between age, sex, educational level, and history of blood donation was observed with seropositivity of HTLV-I. The improvement of donor selection and laboratory screening caused a decline in the prevalence of infection in blood donors. Given the lower prevalence of infection in regular donors with lower age and higher educational level, more efforts should be done to attract blood donors from these populations.


A simple superimposition method for anatomical adjustments of CT and SPECT images.
A technique for superimposition of CT and single photon emission CT (SPECT) images is described. Regions of interest can be placed on SPECT images and projected to CT images. In this way, anatomical registration of regions of increased or decreased activity is possible. The equipment is easy to handle and available at low cost.


Lymphangioma in children.
The topic of lymphangioma is reviewed. Included in the text are the embryology, classification, clinical presentation, and treatment. Eight case reports are included. One case involved the skin, two presented with a submandibular mass, one had both a facial lymphangioma and a cystic hygroma of the floor of the mouth, and there are two cases of involvement of the tongue, and two cases of classical cystic hygroma of the neck. The rate of involution is probably higher than previously thought. Indications for surgery are suggested. This diagnosis must be considered in the differential diagnosis of a mass presenting in the head and neck of a child.


Innovative light collimator with afocal lens and total internal reflection lens for daylighting system.
This research presents a novel design of the collimator, which uses total internal reflection (TIR), convex, and concave lenses for the natural light illumination system (NLIS). The concept of the NLIS is to illuminate building interiors with natural light, which saves energy consumption. The TIR lens is used to collimate the light, and convex and concave lenses are used to converge the light to the required area. The results have shown that the efficiency in terms of achieving collimated light using the proposed collimator at the output of the light collector is better than that of a previous system without a collimator.


Insights into Antifungal Mechanisms of Bacillus velezensis S141 against Cercospora Leaf Spot in Mungbean (V. radiata).
Cercospora leaf spot (CLS) is caused by Cercospora canescens and is one of the most important diseases of mungbean (Vigna radiata). Cercospora leaf spot may result in economic loss in production areas. The present study investigated the potential of Bacillus velezensis S141 as a biocontrol agent for C. canescens PAK1 growth on culture plates. Cell-free secretions from a dual culture of S141+PAK1 inhibited fungal growth more than those from a single culture of S141. The biocontrol efficiency of S141 against Cercospora leaf spot on mungbean was then evaluated by spraying. The disease severity of Cercospora leaf spot was significantly reduced in plants treated with S141, with a control efficiency of 83% after 2 days of infection. Comparative transcriptomics and qRT-PCR ana-lyses of S141 during C. canescens inhibition were performed to elucidate the antifungal mechanisms underlying its antifungal activity against Cercospora leaf spot. According to the differentially expressed genes, most up-regulated genes involved in the biosynthetic genes encoding enzymatic hydrolases, including protease, β-glucanase, and N-acyl glucosaminase, were detected in strain S141 following its interaction. Moreover, genes related to secondary metabolites (surfactin, bacilysin, and bacillomycin D) were up-regulated. Collectively, these results suggest that S141 exhibited strong antifungal activity against C. canescens due to multiple enzymatic hydrolases and secondary metabolites. Therefore, the present study provides insights into the biological network responsible for the antifungal activity of B. velezensis S141 against C. canescens.


Toward the development of a versatile functionalized silicone coating.
The development of a versatile silicone copolymer coating prepared by the chemical coupling of trichlorosilane (TCS) to the vinyl groups of poly(vinylmethylsiloxane) (PVMS) is reported. The resultant PVMS-TCS copolymer can be deposited as a functional organic layer on a hydrophobic poly(dimethylsiloxane) substrate and its mechanical modulus can be regulated by varying the TCS coupling ratio. In this paper, several case studies demonstrating the versatile properties of these PVMS-TCS functional coatings on PDMS elastomer substrates are presented. Numerous experimental probes, including optical microscopy, Fourier-transform infrared spectroscopy, surface contact angle, ellipsometry, and nanoindentation, are utilized to interrogate the physical and chemical characteristics of these PVMS-TCS coatings.


Building a children's health network: city-wide computer linkages among heterogeneous sites for pediatric primary care.
For many infants and children in our cities, quality of care and health status outcomes suffer due to poor continuity and coordination among ambulatory care sites. Despite proximity to technologically-advanced secondary and tertiary institutions, primary care services for children are fragmented, multiple-site use is common, and data flow among providers serving the same patients is primitive. Preventive and acute health care is often incomplete or redundant, and aggregate information for public health purposes is insufficient. This paper focuses on the development of a city-wide computer-based pediatric health care network to improve provider decision-making and follow-through, parent role in their children's care, and community-wide data. A process of building consensus for a regional system is presented, addressing issues of establishing a uniform data base, coordination among heterogeneous institutions, system development, confidentiality, and integration with public health reporting and planning functions.


Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.
Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Current studies have identified the roles of CPA4 in cancer biology and insulin sensitivity. However, the roles of CPA4 in other diseases are not known. In the present study, we investigated the roles of CPA4 in cardiac hypertrophy. The expression of CPA4 was significantly increased in the hypertrophic heart tissues of human patients and isoproterenol (ISO)-induced hypertrophic heart tissues of mice. We next knocked down Cpa4 with shRNA or overexpressed Cpa4 using adenovirus in neonatal rat cardiomyocytes and induced cardiomyocyte hypertrophy with ISO. We observed that Cpa4 overexpression promoted whereas Cpa4 knockdown reduced ISO-induced growth of cardiomyocyte size and overexpression of hypertrophy marker genes, such as myosin heavy chain β (β-Mhc), atrial natriuretic peptide (Anp), and brain natriuretic peptide (Bnp). Our further mechanism study revealed that the mammalian target of rapamycin (mTOR) signaling was activated by Cpa4 in cardiomyocytes, which depended on the phosphoinositide 3-kinase (PI3K)-AKT signaling. Besides, we showed that the PI3K-AKT-mTOR signaling was critically involved in the roles of Cpa4 during cardiomyocyte hypertrophy. Collectively, these results demonstrated that CPA4 is a regulator of cardiac hypertrophy by activating the PI3K-AKT-mTOR signaling, and CPA4 may serve as a promising target for the treatment of hypertrophic cardiac diseases.


[Incidence of acute pancreatitis in children with inflammatory bowel disease].
The aim of our study was to estimate the frequency of acute pancreatitis and the frequency of increased activity of pancreatic enzymes in serum of children with inflammatory bowel disease (IBD). Analysis comprises 101 children aged from 3 to 18-years treated because of IBD in the period of 1998-2002: 79 children with ulcerative colitis (UC) and 22 children Crohn's disease (CD). The authors analyzed together 191 admissions because of UC and 51 because of CD. Acute pancreatitis was observed in 4.5% of children with CD and in 5.1% of children with UC. Significantly more often acute pancreatitis was recognized in children with moderate and severe stage of UC. Hyperamylasemia was observed in 27.3% of children with CD and in 12.7% of children with UC. Hyperlipasemia was observed only in children with UC (3.8%), elevated urinary amylase was observed in 4.5% of children with CD and in 8.86% children with UC. No correlations between the frequency of acute pancreatitis and medication were observed.


[S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology].
Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.


Effect of reperfusion on electrocardiographic and enzymatic infarct size: results of a randomized multicenter study of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) versus intracoronary streptokinase in acute myocardial infarction.
The effect of early coronary artery reperfusion on ECG and enzymatic parameters was examined in 240 patients with acute myocardial infarction. These patients had participated in a randomized trial comparing intravenous anisoylated plasminogen streptokinase activator complex (APSAC) (n = 123) and intracoronary streptokinase (n = 117) therapy. Reperfusion occurred in 59 of 115 (51%) patients receiving APSAC and 67 of 111 (60%) patients receiving streptokinase (p = NS). There was greater early resolution of ST segment elevation in the reperfused than in the nonreperfused patients (p less than or equal to 0.003) and more rapid Q wave evolution (p less than or equal to 0.03). Sigma Q was lower in reperfused than in nonreperfused patients at 8 hours (1.41 +/- 1.18 versus 2.11 +/- 2.10 mV; p less than or equal to 0.05) and at 24 hours (1.43 +/- 1.25 mV versus 2.08 +/- 1.88 mV; p less than or equal to 0.02). Time to peak level was shorter in the reperfused patients for creatine kinase (CK) (10.7 +/- 5.5 hours versus 14.9 +/- 5.9 hours; p less than 0.0001) and lactic acid dehydrogenase (LDH) (29.6 +/- 13.6 hours versus 34.4 +/- 10.5 hours; less than or equal to 0.03) enzymes. Peak LDH-1 was lower in the reperfused group (274 +/- 149 U/L versus 341 +/- 173 U/L; p less than or equal to 0.04). Reperfusion at a mean of 3.9 hours after the onset of infarction was associated with more rapid resolution of ST segment elevation, faster Q wave evolution, smaller ECG infarct size, earlier cardiac enzyme release, and smaller enzymatic infarct size than later or no reperfusion.


[Guillain-Bare syndrome in a patient with tuberculous].
The article reports on the rarest case of Guillain-Barré syndrome in the form of acute motor-sensory polyneuropathy in a female patient with tuberculous meningitis, disseminated pulmonary tuberculosis, and tuberculous pleurisy. In the neurological status at the exit from the coma, the patient was diagnosed with tetraplegia, bulbar syndrome, and respiratory disorders. Further, within a week, pronounced muscle atrophy appeared. Active etiotropic, pathogenetic therapy, including plasmapheresis, gave a dramatic effect with a significant improvement in the condition and a gradual regression of neurological disorders. The differential diagnosis was carried out primarily with critical illness polyneuropathy. The authors emphasize the rarity of the presented case: to date, such a combination of pathologies has never been described in the literature.


Analysis of differentially-regulated genes within a regulatory network by GPS genome navigation.
A critical challenge of the post-genomic era is to understand how genes are differentially regulated even when they belong to a given network. Because the fundamental mechanism controlling gene expression operates at the level of transcription initiation, computational techniques have been developed that identify cis regulatory features and map such features into expression patterns to classify genes into distinct networks. However, these methods are not focused on distinguishing between differentially regulated genes within a given network. Here we describe an unsupervised machine learning method, termed GPS for gene promoter scan, that discriminates among co-regulated promoters by simultaneously considering both cis-acting regulatory features and gene expression. GPS is particularly useful for knowledge discovery in environments with reduced datasets and high levels of uncertainty. Application of this method to the enteric bacteria Escherichia coli and Salmonella enterica uncovered novel members, as well as regulatory interactions in the regulon controlled by the PhoP protein that were not discovered using previous approaches. The predictions made by GPS were experimentally validated to establish that the PhoP protein uses multiple mechanisms to control gene transcription, and is a central element in a highly connected network. The scripts and programs used in this work are accessible from the gps-tools.wustl.edu website. Data and predictions are available by request.


[Death and dying process: evidences from the literature of nursing].
The objective was to identify the profile of production and analyze perceptions, feelings and confrontations on the process of death and dying in the practice evidenced in nursing scientific production in the period 1994 to 2009. There was a qualitative, descriptive research, developed through a systematic literature review with metasynthesis from the meta-ethnographic method. Ten studies met the inclusion criteria, this set was subjected to quality assessment checklist with Critical Appraisal Skills Programme. Subjects perceive this process as a transition, separation and finitude. This is permeated with feelings of frustration and powerlessness and the most effective interventions to this issue is the development of coping strategies that vary with the reality of each individual.


Unmet visual needs of children with Down syndrome in an African population: implications for visual and cognitive development.
To determine the magnitude and types of ocular disorders in children with Down syndrome in an African population and to assess to what extent these visual needs have been met. This is a cross-sectional study of children with Down syndrome attending a school for the mentally challenged in Southeastern Nigeria. Visual acuity, ocular examination, and cycloplegic refraction were done on all cooperative participants. Information was sought from parents/caregivers to ascertain previous ocular treatment/spectacle usage. A total of 30 children with Down syndrome aged 5-15 years were examined. Uncorrected refractive errors were detected in 76.4% of them. Other lesions included mongoloid slant (53.5%), strabismus (33.3%), ptosis (33.3%), nystagmus (13.3%), and cataract (3.3%). None of the children with refractive errors had ever worn spectacles. Refractive error is a common finding in this population. There is a high unmet visual need in these children. This may have implications for visual and cognitive development. Early screening for ocular disorders in Down syndrome is recommended to detect and treat them.


A prospective, multicenter evaluation of point-of-care ultrasound for appendicitis in the emergency department.
The main objective of this study was to evaluate the accuracy of point-of-care ultrasound (POCUS) for the diagnosis of appendicitis in a general emergency department (ED) population as performed by emergency physicians with variable ultrasound experience. We performed a prospective, multicenter, observational study examining a convenience sample of adult patients with potential appendicitis presenting to the ED between July 2014 and February 2020. Each emergency physician-performed POCUS was interpreted at the bedside and retrospectively by an expert reviewer. Test characteristics were calculated for POCUS and blinded expert interpretation compared to surgical pathology in patients undergoing appendectomy and advanced imaging in patients managed nonoperatively. A total of 256 subjects were included in the primary analysis with an overall appendicitis prevalence of 28.1%. For the diagnosis of appendicitis, POCUS demonstrated an overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 0.85 (95% confidence interval [CI] = 0.74 to 0.92), 0.63 (95% CI = 0.56 to 0.70), 2.29 (95% CI = 1.85 to 2.84), and 0.24 (95% CI = 0.14 to 0.42), respectively. Expert review yielded a lower sensitivity (0.74 [95% CI = 0.62 to 0.83]) with a similar specificity (0.63 [95% CI = 0.56 to 0.70]). POCUS is moderately accurate for acute appendicitis as performed by emergency physicians with a wide range of ultrasound expertise, but lacks adequate sensitivity and specificity to function as a definitive test in an undifferentiated ED population. Further study is warranted to elucidate the optimal role of integrated POCUS in the general approach to suspected appendicitis.


Micropatterning of silver nanoclusters embedded in polyvinyl alcohol films.
Direct laser writing has been utilized to fabricate highly photostable fluorescent nanocluster microstructures in an organic polymer poly(methacrylic acid), where the carboxyl functional group is reported to play a vital role in nanocluster stabilization. In this Letter, we demonstrate that not only the polymer containing the carboxyl functional group, but also the polymer comprising the hydroxyl group, namely polyvinyl alcohol (PVA), can act as an appropriate stabilizer matrix for laser-induced synthesis and patterning of silver nanoclusters. The as-formed nanoclusters in the PVA film exhibit broadband emission and photostability comparable to the nanoclusters formed in the poly(methacrylic acid) polymer. As PVA is a widely used, nontoxic, biocompatible and biodegradable polymer, the technique of patterning fluorescent nanoclusters in PVA thin films is expected to find numerous applications in fields like fluorescence imaging, biolabeling, and sensing.


[Medical Academy of Lodz during the Stalinist period (1949-1953)].
During the Stalinist period especially between 1949-1953 the Medical Academy in Lodz was under constant ideological pressure of the Communist Party (PZPR). It was trying to stir-up students and workers in the spirit of marxist and the leninist ideology. The main PZPR's methods of influence were to reduce and importunate indoctrination. They exterminated all impulses of protest and opposition, also they investigated and penetrated academic life. On admission to the university, countryman and workman youth was preferred. People who had different conviction and opinion were removed. On every step the party's authority was flatten in the face of Soviet's dictate.


[Phylogeny and divergence time estimation of Schizothoracinae fishes in Xinjiang].
Based on combined data of mitochondrial COI, ND4 and 16S RNA genes, molecular phylogeny of 4 genera, 10 species or subspecies of Schizothoracinae fishes distributed in Xinjiang were analyzed. The molecular clock was calibrated by divergence time of Cyprininae and geological segregation event between the upper Yellow River and Qinghai Lake. Divergence time of Schizothoracinae fishes was calculated, and its relationship with the major geological events and the climate changes in surrounding areas of Tarim Basin was discussed. The results showed that genus Aspiorhynchus did not form an independent clade, but clustered with Schizothorax biddulphi and S. irregularis. Kimura 2-parameter model was used to calculate the genetic distance of COI gene, the genetic distance between genus Aspiorhynchus and Schizothorax did not reach genus level, and Aspiorhynchus laticeps might be a specialized species of genus Schizothorax. Cluster analysis showed a different result with morphological classification method, and it did not support the subgenus division of Schizothorax fishes. Divergence of two groups of primitive Schizothoracinae (8.18Ma) and divergence of Gymnodiptychus dybowskii and Diptychus maculates (7.67Ma) occurred in late Miocene, which might be related with the separation of Kunlun Mountain and north Tianshan Mountain River system that was caused by the uplift of Qinghai-Tibet Plateau and Tianshan Mountain, and the aridification of Tarim Basin. The terrain of Tarim Basin that was affected by Quaternary Himalayan movement was high in west but low in east, as a result, Lop Nor became the center of surrounding mountain rivers in Tarim Basin, which shaped the distribution pattern of genus Schizothorax.


Countercurrent multistage fluidized bed reactor for immobilized biocatalysts: I. Modeling and simulation.
For the application of immobilized enzymes, fixed bed reactors are used almost exclusively. Fixed bed reactors have specific disadvantages, especially for processes with a deactivating catalyst. Therefore, we have studied a novel reactor type with continuous transport of the immobilized biocatalyst. Flow of biocatalyst is countercurrent to the substrate solution. Because of a stagewise reactor design, back-mixing of biocatalyst is very limited and transport is nearly plug flow. The reactor operates at a constant flow rate and conversion, due to constant holdup of catalytic activity. The reactor performance is compared with a configuration of fixed bed reactors. For reactions in the first-order regime, enzyme requirements in this new reactor are slightly less than for fixed bed processes. The multistage fluidized bed appears to be an attractive reactor design to use biocatalyst to a low residual activity. However, nonuniformity of the particles might affect plug flow transport of the biocatalyst. A laboratory scale reactor and experiments are described in Part II(1) of this series. Hydrodynamic design aspects of a multistage fluidized bed are discussed in more detail in Part III.(2).


[Outcomes of perisurgery and short-time follow-up of pelvic exenteration for 17 cases with locally recurrent cervical cancer].
Objective: To investigate the perioperative situation and recent effect of pelvic exenteration for patients with locally recurrent cervical cancer. Methods: A total of 17 patients with locally recurrent cervical cancer who underwent pelvic exenteration in Peking University People's Hospital from October 2015 to May 2018 were retrospectively analyzed for their clinical and pathological characteristics, surgical conditions, hospitalization costs, postoperative complications, and survival situation. Results: (1) The median age of 17 patients with locally recurrent cervical cancer was 51 years (range 27-64 years). Pathological type: 13 cases of squamous cell carcinoma, 2 cases of adenocarcinoma, and 2 cases of adenosquamous carcinoma. Thirteen patients received radiotherapy during the initial treatment and 4 patients did not receive radiotherapy. (2) Pelvic exenteration was performed in 17 patients with locally recurrent cervical cancer, of which 9 cases were performed with total pelvic exenteration (operation range including radical cystectomy, partial urethrectomy rectectomy and partial vaginalectomy), and 8 cases with anterior pelvic exenteration operation (operation range including: radical cystectomy, part of urethrectomy and part of vaginalectomy). Of the 17 patients successfully completed the operation. The median operation time was 450 minutes (range 240-760 minutes), the median intraoperative blood loss was 2 200 ml (range 200- 8 400 ml), the median postoperative hospital stay was 17 days (range 9-55 days), the median hospital cost was 83 857 yuan (range 41 588-296 354 yuan). (3) Of the 17 patients underwent pelvic exenteration, 16 of them had early complications, the most common one was fever (14 cases). Fourteen of them had late complications, and the most common one was a urinary system infection (12 cases). (4) The median overall survival time was 26.0 months (range 3-44 months), the median progression-free survival (PFS) time was 9.0 months (range 2-44 months). Among them, 13 patients received radiation therapy during the initial treatment, the median PFS time was 9.0 months (range 2-30 months); 4 patients did not receive radiation therapy in the initial treatment, the median PFS time was 10.5 months (range 2-44 months).Eleven patients received adjuvant therapy after pelvic exenteration, the median PFS time was 12.0 months (range 2-44 months); 6 patients did not receive adjuvant therapy, the median PFS time was 5.0 months (range 2-9 months). Conclusions: Pelvic exenteration has a wide range of operations, many postoperative complications, and high hospitalization costs. Adjuvant treatment after pelvic exenteration could improve the PFS time for some patients. Its clinical value and health economic value need to be further explored.


Role of revascularization in the treatment of claudication.
Intermittent claudication is a relative indication for vascular reconstruction. Conservative management with a combination of risk factor control, exercise training and medical therapy will relieve or at least improve claudication in some patients. If claudication precludes gainful employment or imposes an unacceptable alteration in lifestyle, surgical revascularization should be considered. Surgical bypass for claudication will produce optimal results in younger patients, in whom near-normalization of the ankle/brachial index can be anticipated. Proximal axial (in-line) reconstructions maintain their patencies longer than more distal, and often technically more challenging, bypasses. These tenets also apply well to percutaneous transluminal angioplasty. Both surgical and catheter-based interventions carry potential risks of short- and long-term morbidity, although overall morbidity associated with surgery for claudication is acceptably low. Interventions are justified only if they are safe, effective and durable, and if they are performed after the long-term prognosis for both life and limb is considered.


Synthesis and reactivity of a conveniently prepared two-coordinate bis(amido) nickel(II) complex.
A strictly two-coordinate nickel(II) bis(amido) complex has been prepared and its reactivity towards a variety of small molecules is described. Ni[N(SiMe(3))(DIPP)](2) reacts with DMAP and acetonitrile to form T-shaped three-coordinate complexes, and preliminary results show that Ni[N(SiMe(3))(DIPP)](2) is a catalyst for the hydrosilation of olefins with secondary silanes at ambient temperature.


Evaluation of a Commercial Enzyme-Linked Immunosorbent Assay Kit and In-House Fasciola gigantica Cysteine Proteinases-Based Enzyme-Linked Immunosorbent Assays for Diagnosis of Human Fascioliasis.
Fascioliasis, caused by Fasciola hepatica and Fasciola gigantica infection, is a major food-borne trematodiasis in many places of the world, with the central region of Vietnam being reported as a highly endemic area. Stool examination for Fasciola eggs is not a sensitive method, and immunodiagnostic methods are preferable. We investigated various enzyme-linked immunosorbent assays (ELISAs) to evaluate their efficacy for fascioliasis diagnosis. Test sera used are primarily screened using an ELISA kit produced in Vietnam (VN kit; Viet Sinh Chemical Producing & Trading Co. Ltd., Ho Chi Minh City, Vietnam): Seropositive individuals having symptoms compatible with fascioliasis were regarded as clinically diagnosed fascioliasis cases. A commercial Fasciola IgG ELISA kit from Diagnostic Automation/Cortez Diagnostics, Inc. (USA kit; Woodland Hills, CA), which has been commonly used in Vietnam, was assessed and compared with in-house ELISA systems, including a cystatin-capture (CC) ELISA using crude worm extract (CWE) and an indirect ELISA using a synthetic peptide Ac-TPTCHWECQVGYNKTYDEE-NHMe designed from the F. gigantica cathepsin B (FgCB5) molecule. The USA kit was suitable for routine diagnosis after recalibration of the manufacturer's suggested cutoff point. Cystatin-capture ELISA with CWE provided good sensitivity and specificity with perfect agreement to the results of the USA kit. In dot-blot ELISA, recombinant FgCB5 reacted more strongly with human antisera than did other F. gigantica antigens tested. Enzyme-linked immunosorbent assay using the synthetic peptide fragment of the FgCB5 exhibited nearly 80% sensitivity and specificity, but the test results showed low agreement with CC-ELISA or the USA kit. In conclusion, the commercially available Fasciola IgG ELISA kit from the United States and the in-house CC ELISA using CWE are suitable for practical diagnosis for fascioliasis.


[Treatment results of pancoast tumor].
To study the clinical characteristics, treatment modalities, and outcome of patients with Pancoast tumors who underwent surgery over 11-year period. From January 1994 to May 2005, 13 patients (12 men, 1 woman) with Pancoast tumor and histology of non-small cell lung cancer underwent surgical resection. Nine patients were received induction therapy (8 chemoradiation, 1 radiation only), and there were no treatment-related deaths. Twelve lobectomies, 1 pneumonectomy, and none of wedge resections or partial resection were performed. The number of ribs resected ranged from 2-6 (median 2.8). Chest wall reconstruction was performed in 2 patients, total vertebrectomy in 2, bronchoplasty in 2, and pulmonary arterioplasty in 1. Twelve of 13 patients (92.3%) had a complete resection. Pathologic stages were IB, IIB, IIIA and IIIB in 1, 7, 2, and 1, respectively, and pathologic complete responses was noted in 1. After a median follow-up of 34 months, the 3-year survival was 78.6% for all 13 patients and 85.7% for patients who had a complete resection. It is thought that induction chemoradiation for Pancoast tumors have potential to be able to become the treatment strategy in the future.


Professionals' reported provision and recommendation of psychosocial interventions for youth with autism spectrum disorder.
Children and adolescents with autism spectrum disorder (ASD) receive intervention services from multiple professionals across disciplines. Little is known about services for youth with ASD in community settings. The purpose of this study was to provide data on professionals' self-reported practices across different classes of psychosocial interventions for youth with ASD. A multidisciplinary (medicine/nursing, education, occupational/physical therapy, psychology, social work, and speech-language pathology/audiology) sample (N=709; 86% female; 86% White) of professionals who endorsed providing clinical services to youth with ASD was recruited through convenience sampling (listservs, etc.) and stratified random sampling (online provider listings). Professionals completed a survey on intervention practices with youth with ASD, specifically on their own provision of, as well as their recommendation/referral of, psychosocial interventions (focused intervention practices [FIPs], comprehensive treatment models [CTMs], and other interventions). Hierarchical multiple regression models showed discipline differences in self-reported provision and recommendation of evidence-based FIPs; training variables and unfamiliarity with FIPs predicted rates of providing and recommending. FIPs were reportedly provided and recommended at higher rates than CTMs. Descriptive data are presented on professionals' reported practice of other psychosocial interventions (e.g., cognitive-behavioral therapy). This study highlights the usefulness of examining not only provision of services but also recommendation/referral practices: professionals are important sources of information for families. Implications of the results are discussed in terms of the importance of disseminating intervention information to professionals and the need for consensus on terminology used to classify interventions and on criteria used to evaluate intervention efficacy.


Early Serum and Hematological Responses to Pembrolizumab Therapy as Predictors of Survival in Metastatic Urothelial Cancer.
In order to search for predictive biomarkers of efficacy of pembrolizumab therapy for metastatic urothelial cancer (UC), we investigated the relationship between treatment outcomes and early neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP) responses. Medical records of 101 patients with metastatic UC who started pembrolizumab as a second-line or later treatment were reviewed. NLR, LDH, and CRP were recorded after 3 weeks of therapy. In addition, we investigated whether these factors had an association with prolonged progression-free (PFS) or overall (OS) survival. The objective response rate, median PFS, and median OS were 25.7%, 6.3 months, and 15.2 months, respectively. PFS and OS were significantly shorter in patients with NLR>3, LDH>upper limit of normal (ULN), and CRP>0.5 mg/dl after 3 weeks of pembrolizumab treatment (p<0.05). A predictive model comprising these factors (favorable risk group: 0 risk factors; intermediate-risk group: 1-2 risk factors; poor-risk group: 3 risk factors) revealed distinct PFS and OS curves (p<0.001). In the favorable risk group, 12-month OS was 79.6%; in the poor-risk group, it was 12.8%. Harrell's C-indices for NLR >3, LDH >ULN, CRP >0.5 mg/dl, and all three combined for predicting OS were 0.656, 0.625, 0.633 and 0.678, respectively. Early responses were also non-significantly associated with ORR (p=0.37). Pembrolizumab treatment outcomes are associated with early NLR, LDH, and CRP responses in metastatic urothelial cancer.


Efficacy of a triple therapy for Helicobacter pylori eradication in a well-developed urban area in Brazil.
Helicobacter pylori eradication has become the standard treatment for peptic ulcer disease. Triple therapy with omeprazole plus two antibiotics has been used. Due to the lack of ideal treatment and the high rates of primary resistance to nitroimidazoles, the use of clarithromycin has been adopted. To determine the Helicobacter pylori eradication rates using lansoprazole, amoxicillin and clarithromycin for seven days, in patients with peptic ulcer disease in a well developed urban area in Brazil. This was a retrospective, open-label study carried out at the School of Medicine of the Fundação ABC. It included 130 patients with peptic ulcer disease (upper endoscopy) who had been tested positive for Helicobacter pylori infection (urease test, histology or breath test), without previous treatment. Patients were treated with lansoprazole 30 mg, amoxicillin 1,000 mg and clarithromycin 500 mg b.i.d., for seven days. Eradication was verified after 90 days. Follow-up data were available for 94 patients. Their mean age was 52.23 years; 51.54% were woman, 84.31% white, 37.69% smokers, 20.77% using nonsteroidal anti-inflammatory drugs and 8.46% alcoholics. Upper endoscopy revealed that 78.46% had duodenal ulcers and 21.53% had gastric ulcers (a 4:1 DU:GU ratio). The eradication rates were 85.11% per protocol and 61.54% by intention to treat; 97% had no adverse effects. Triple therapy using lansoprazole, amoxicillin and clarithromycin is well tolerated with high eradication rates and forms a good alternative for developing countries.


Towards reproducible MRM based biomarker discovery using dried blood spots.
There is an increasing interest in the use of dried blood spot (DBS) sampling and multiple reaction monitoring in proteomics. Although several groups have explored the utility of DBS by focusing on protein detection, the reproducibility of the approach and whether it can be used for biomarker discovery in high throughput studies is yet to be determined. We assessed the reproducibility of multiplexed targeted protein measurements in DBS compared to serum. Eighty-two medium to high abundance proteins were monitored in a number of technical and biological replicates. Importantly, as part of the data analysis, several statistical quality control approaches were evaluated to detect inaccurate transitions. After implementing statistical quality control measures, the median CV on the original scale for all detected peptides in DBS was 13.2% and in Serum 8.8%. We also found a strong correlation (r = 0.72) between relative peptide abundance measured in DBS and serum. The combination of minimally invasive sample collection with a highly specific and sensitive mass spectrometry (MS) technique allows for targeted quantification of multiple proteins in a single MS run. This approach has the potential to fundamentally change clinical proteomics and personalized medicine by facilitating large-scale studies.


[Schistosoma japonicum: protective immunity induced in mice immunized with SjGST-Sj32].
Schistosoma japonicum glutathione-s-transferase (SjGST), Schistosoma japonicum 32,000 protein (Sj32) and SjGST - Sj32 were expressed and purified to study on protective immunity against Schistosoma japonicum. The result showed that compared with the adjuvant control group, the worm burden was decreased significantly in mice immunized with recombinant SjGST - Sj32, Sj32 and Sj32 + SjGST (P < 0.05). At the same time, the liver egg per gram(EPG) was decreased in mice immunized with SjGST - Sj32, Sj32, Sj32 + SjGST and SjGST. It is concluded that Sj32 significantly induces both protective immunity and anti-fecundity immunity, but SjGST only has an anti-fecundity effect.


PFT1-controlled ROS balance is critical for multiple stages of root hair development in Arabidopsis.
Reactive oxygen species (ROS) have been shown to play key roles in cellular decision making and signal integration in multicellular organisms. In roots, ROS levels are managed by the action of peroxidases and NAPDH oxidases, resulting in a distinct spatial distribution of hydrogen peroxide (H₂O₂) and superoxide (O₂(-)) that is critical for the balance between cell proliferation and differentiation. In addition, ROS is required for the determination of the cell shape of root hairs. Mutations in the Mediator subunit MED25/PFT1 result in compromised root hair development, due to altered expression of a suite of H₂O₂-producing class III peroxidases. pft1-1 mutants form shorter root hairs than wild-type plants. Analysis of pft1-1 cross-sections revealed that also root hair initiation is compromised, probably by impeding local cell wall loosening. It is suggested that ROS homeostasis is critical throughout the development of root hairs, controlling various processes via PFT1-regulated transcription of genes encoding redox-active enzymes.


High order reflectivity of highly oriented pyrolytic graphite crystals for x-ray energies up to 22 keV.
We used Kr K alpha (12.6 keV), Zr K alpha (15.7 keV), and Ag K alpha (22.2 keV) x-rays, produced by petawatt-class laser pulses, to measure the integrated crystal reflectivity R(int) of flat highly oriented pyrolytic graphite (HOPG) up to the fifth order. The maximum R(int) was observed in first order (3.7 mrad at 12.6 keV), decreasing by a factor of 3-5 for every successive order, and dropping by a factor of 2-2.5 at 22.2 keV. The current study indicates that HOPG crystals are suitable for measuring scattering signals from high energy x-ray sources (E > or = 20 keV). These energies are required to penetrate through the high density plasma conditions encountered in inertial confinement fusion capsule implosions on the National Ignition Facility.


On Making Statistical Inferences Regarding the Relationship between Spawners and Recruits and the Irresolute Case of Western Atlantic Bluefin Tuna (Thunnus thynnus).
Forecasts of the future abundance of western Atlantic bluefin tuna (Thunnus thynnus) have, for nearly two decades, been based on two competing views of future recruitment potential: (1) a "low" recruitment scenario based on hockey-stick (two-line) curve where the expected level of recruitment is set equal to the geometric mean of the recruitment estimates for the years after a supposed regime-shift in 1975, and (2) a "high" recruitment scenario based on a Beverton-Holt curve fit to the time series of spawner-recruit pairs beginning in 1970. Several investigators inferred the relative plausibility of these two scenarios based on measures of their ability to fit estimates of spawning biomass and recruitment derived from stock assessment outputs. Typically, these comparisons have assumed the assessment estimates of spawning biomass are known without error. It is shown here that ignoring error in the spawning biomass estimates can predispose model-choice approaches to favor the regime-shift hypothesis over the Beverton-Holt curve with higher recruitment potential. When the variance of the observation error approaches that which is typically estimated for assessment outputs, the same model-choice approaches tend to favor the single Beverton-Holt curve. For this and other reasons, it is argued that standard model-choice approaches are insufficient to make the case for a regime shift in the recruitment dynamics of western Atlantic bluefin tuna. A more fruitful course of action may be to move away from the current high/low recruitment dichotomy and focus instead on adopting biological reference points and management procedures that are robust to these and other sources of uncertainty.


Conceptualizations of illness among relatives of patients diagnosed with schizophrenia.
Family concepts of a relative's illness are an important part of the coping process and reveal the cultural construction of the experience of illness. As part of a qualitative study conducted in the Schizophrenia Outpatient Clinic of the Department of Psychiatry, Escola Paulista de Medicina - UNIFESP, 14 relatives of eight outpatients diagnosed with schizophrenia were interviewed and invited to talk freely about their ideas and feelings concerning their relative's problem. Qualitative analysis was used to identify categories of illness representations. Three main categories were discussed, including Problema de Nervoso, Problema na Cabeça and Problema Espiritual (Problem of the Nerves, Problem in the Head and Spiritual Problem). The authors present evidence of these categories as cultural constructions, and discuss the relevance of popular notions of illness to the understanding of the course and outcome of schizophrenia, and the planning of culturally meaningful interventions.


Contribution of ionization and lipophilicity to drug binding to albumin: a preliminary step toward biodistribution prediction.
Understanding the molecular mechanisms governing albumin binding is a major challenge in absorption-distribution-metabolism-excretion prediction. To gain insight into this complex field, an ultracentrifugation method to measure the drug fraction bound to bovine serum albumin [%B(DAB)] is presented. The second part of the study shows the dependence of the experimental binding parameter on ionization and lipophilicity descriptors (pK(a) and log D(oct)(7.4) for a series of 14 structurally diverse drugs. Finally, a docking strategy is used to rationalize the findings; the results confirm the mostly nonspecific nature of the interaction of albumin with neutral ligands.


Pigment interactions in light-harvesting complex II in different molecular environments.
Extraction of plant light-harvesting complex II (LHCII) from the native thylakoid membrane or from aggregates by the use of surfactants brings about significant changes in the excitonic circular dichroism (CD) spectrum and fluorescence quantum yield. To elucidate the cause of these changes, e.g. trimer-trimer contacts or surfactant-induced structural perturbations, we compared the CD spectra and fluorescence kinetics of LHCII aggregates, artificial and native LHCII-lipid membranes, and LHCII solubilized in different detergents or trapped in polymer gel. By this means we were able to identify CD spectral changes specific to LHCII-LHCII interactions, at (-)-437 and (+)-484 nm, and changes specific to the interaction with the detergent n-dodecyl-β-maltoside (β-DM) or membrane lipids, at (+)-447 and (-)-494 nm. The latter change is attributed to the conformational change of the LHCII-bound carotenoid neoxanthin, by analyzing the CD spectra of neoxanthin-deficient plant thylakoid membranes. The neoxanthin-specific band at (-)-494 nm was not pronounced in LHCII in detergent-free gels or solubilized in the α isomer of DM but was present when LHCII was reconstituted in membranes composed of phosphatidylcholine or plant thylakoid lipids, indicating that the conformation of neoxanthin is sensitive to the molecular environment. Neither the aggregation-specific CD bands, nor the surfactant-specific bands were positively associated with the onset of fluorescence quenching, which could be triggered without invoking such spectral changes. Significant quenching was not active in reconstituted LHCII proteoliposomes, whereas a high degree of energetic connectivity, depending on the lipid:protein ratio, in these membranes allows for efficient light harvesting.


Vitamin D supplementation and glycemic control in type 2 diabetes patients: A systematic review and meta-analysis.
Low vitamin D status has been found to be associated with impaired glycemic control in patients who suffer from type 2 diabetes; however, whether vitamin D supplementation is associated with improved glycemic status remains controversial. The aim of this study was to summarize evidence from randomized controlled trials (RCTs) to assess the efficacy of vitamin D supplementation in reducing glycosylated haemoglobinA1c (HbA1c) and fasting blood glucose (FBG) levels. We searched PubMed, Web of Science and the Cochrane Library for reports published up to March 2017. We selected parallel RCTs investigating the effect of vitamin D or vitamin D analogues on HbA1c or FBG levels in type 2 diabetes patients. Cohen's d was calculated to represent the standardized mean difference (SMD) for each study, and the SMDs with 95%confidence intervals (CIs) were pooled using a random effects model. Twenty-four studies were included that evaluated HbA1c levels and 18 studies were included that evaluated FBG levels. Meta-analyses showed that vitamin D supplementation was associated with reduced HbA1c levels (standardized mean difference (SMD) -0.25 [-0.45 to -0.05]) but had no influence on FBG levels (SMD -0.14 [-0.31 to 0.03]). However, the subgroup analyses suggested that vitamin D supplementation was associated with reduced HbA1c levels (SMD -0.39 [-0.67 to -0.10]) and FBG (SMD -0.27 [-0.46 to -0.07]) among patients with 25-hydroxyvitamin D (25(OH) D) deficiency at baseline. Significantly reduced HbA1c levels were also observed in association with vitamin D supplementation in the subgroup including type 2 diabetes patients with a body mass index (BMI) <30kg m-2 (SMD -0.30 [-0.54 to -0.07]). Vitamin D supplementation could be effective at improving glycemic control in vitamin D deficient or non-obese type 2 diabetes patients.


Morphological variation in the appendicular skeleton of Atlantic Forest sigmodontine rodents.
Rodents of the subfamily Sigmodontinae comprise a highly diversified group in the Atlantic Forest, with semifossorial, terrestrial, semiaquatic, scansorial, and arboreal forms. In this study, we analyzed morphometric variation in humerus, scapula, ulna, radius, femur, tibia, and pelvis to investigate its possible relationship with the different types of locomotion recorded in the literature. Skeletal characters were measured in 321 specimens belonging to 29 species and 19 genera either restricted to or recorded in this ecoregion. Multivariate morphometric analyses (principal component and canonical variate analyses) arranged individuals of different genera in groups congruent with the different types of locomotion. This arrangement was more clearly defined when analyses included only forelimb measurements, indicating that most of the variation in appendicular traits associated with the different locomotor modes occurs in the forelimb skeleton. Semifossorial forms exhibited the most distinct appendicular morphology, as well as the greatest frequency of endemism among analyzed species. These results suggest that this mode of locomotion led to greater differentiation in semifossorial Atlantic forest sigmodontines than in terrestrial and arboreal forms, which were found to have more subtle differentiation and fewer endemics. Scansorial species could not be set apart from terrestrial ones in terms of appendicular morphology, suggesting that these two modes of locomotion are the most similar and generalized for the group, as they occur in most lineages in the subfamily. The results of this study corroborate previous observations on the relevance of appendicular characters in the differentiation of species and genera in the subfamily Sigmodontinae.


The effects of obesity on fall efficacy in elderly people.
[Purpose] The aim of this study was to identify the effects of obesity on falls as a practical verification of the importance of obesity-targeting interventions as part of future fall prevention programs. [Subjects and Methods] The study involved 351 elderly people (172 men, 179 women) living in rural areas. The dependent variable, fall efficacy, was measured using the Falls Efficacy Scale, while the independent variables, body mass index (BMI) and visceral fat, were measured using the InBody 720. The Faces Pain Scale was used to measure pain. Mobility was measured using the Timed Up and Go Test, and balance ability was measured according to the duration subjects could stand on one foot with their eyes closed. Hierarchical multiple regression analysis was performed for the final data analysis. [Results] Investigation of the correlations between the variables revealed a negative correlation between fall efficacy and the other variables. Ultimatley, investigation of the causality of fall efficacy revealed that the BMI, pain, and mobility were influential factors. In other words, fall efficacy tends to be lower when there are higher degrees of obesity, increased pain, and decreased mobility. [Conclusion] To improve the fall efficacy of elderly people living in rural areas, pain management and the maintenance of physical functionality are required. The present study confirms that the elderly need continuous obesity management to lead healthy lives.


Structural Neuroimaging Genetics Interactions in Alzheimer's Disease.
This article investigates late-onset cognitive impairment using neuroimaging and genetics biomarkers for Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. Eight-hundred and eight ADNI subjects were identified and divided into three groups: 200 subjects with Alzheimer's disease (AD), 383 subjects with mild cognitive impairment (MCI), and 225 asymptomatic normal controls (NC). Their structural magnetic resonance imaging (MRI) data were parcellated using BrainParser, and the 80 most important neuroimaging biomarkers were extracted using the global shape analysis Pipeline workflow. Using Plink via the Pipeline environment, we obtained 80 SNPs highly-associated with the imaging biomarkers. In the AD cohort, rs2137962 was significantly associated bilaterally with changes in the hippocampi and the parahippocampal gyri, and rs1498853, rs288503, and rs288496 were associated with the left and right hippocampi, the right parahippocampal gyrus, and the left inferior temporal gyrus. In the MCI cohort, rs17028008 and rs17027976 were significantly associated with the right caudate and right fusiform gyrus, rs2075650 (TOMM40) was associated with the right caudate, and rs1334496 and rs4829605 were significantly associated with the right inferior temporal gyrus. In the NC cohort, Chromosome 15 [rs734854 (STOML1), rs11072463 (PML), rs4886844 (PML), and rs1052242 (PML)] was significantly associated with both hippocampi and both insular cortices, and rs4899412 (RGS6) was significantly associated with the caudate. We observed significant correlations between genetic and neuroimaging phenotypes in the 808 ADNI subjects. These results suggest that differences between AD, MCI, and NC cohorts may be examined by using powerful joint models of morphometric, imaging and genotypic data.


Degesting the remodeled cardiovascular wall: role of cysteinyl cathepsins in cardiovascular disease.
Cardiovascular disease (CVD) is characterized by extensive remodeling of the extracellular matrix (ECM) architecture of the cardiovascular system. Among the many extracellular proteolytic enzymes present in cardiovascular cells and inflammatory cells and involved in ECM remodeling, members of the matrix metalloproteinase family and serine protease family have received the most attention. However, recent findings from laboratory and clinical studies have indicated that lysosomal cysteinyl cathepsins also participate in pathogenesis of CVD. This review summarizes recent knowledge on discoveries regarding the relationship between cysteinly cathepsins and CVD.


Chain Modeling of Molecular Communications for Body Area Network.
Molecular communications provide an attractive opportunity to precisely regulate biological signaling in nano-medicine applications of body area networks. In this paper, we utilize molecular communication tools to interpret how neural signals are generated in response to external stimuli. First, we propose a chain model of molecular communication system by considering three types of biological signaling through different communication media. Second, communication models of hormonal signaling, Ca 2 + signaling and neural signaling are developed based on existing knowledge. Third, an amplify-and-forward relaying mechanism is proposed to connect different types of signaling. Simulation results demonstrate that the proposed communication system facilitates the information exchange between the neural system and nano-machines, and suggests that proper adjustment can optimize the communication system performance.


Health outcomes of unpaid care workers in low-income and middle-income countries: a protocol for a systematic review.
The literature on health outcomes of unpaid care work has included studies coming from high-income countries, and has reported gender inequalities that make caregiving women more vulnerable to physical and mental health problems. The impact of unpaid care work on the health of those living in low-income and middle-income countries, where women's autonomy is more limited, is unknown. We will conduct a systematic review of observational studies on health outcomes according to unpaid caregiving status and sex of people living in low-income and middle-income countries. Cumulative Index to Nursing and Allied Health Literature, PubMed and Scientific Electronic Library Online Citation Index will be searched for reports in English or Spanish with published results from inception to 1 June 2017. We expect the studies to have recruited individuals in low-income and middle-income countries, including exposed and non-exposed groups to participation in unpaid care to members if their households or community reporting either physical and/or mental health problems, self-reported health-related quality of life, self-care skills/behaviours or use of any healthcare services in the participants. Data extraction, the assessment of risk of bias and confounding, and qualitative synthesis will be carried out by two independent reviewers with the assistance of a third party. Results are expected to be published in peer-reviewed journals from the field of health and gender, or health and inequality. CRD42017071785.


Lifestyle, Physical Activity and Cognitive Functions: the impact on the scores of Montreal Cognitive Assessment (MoCa).
The Montreal Cognitive Assessment (MoCA) is a rapid screening tool, including subtests to assess several cognitive domains, developed to detect MCI from normal ageing cognitive changes. Several validation and normative studies have conducted around the world considering the influences of age and education on the MoCA score, but none takes into account the lifestyle and habits. However, lifestyles, and particularly physical activity (PA) have been positively associated with both physical and mental health in elderly. The aim of the present study is to investigate the influence of regularly practiced PA on the MoCA scores in a sample of Italian healthy elderly males. For this purpose sixty-five healthy adult males, aged 65-81 years were assigned to two groups, physically active group (PAG, N=33), and sedentary group (SG, N=32), according to recommended levels of physical activity by the World Health Organization. The Italian version of MoCA was administered to each participant. Raw data were analysed by a multiple regression model in which the independent variables were PA, age and education. Results showed a highly significant influence of PA on MoCA total score and on several cognitive domain sub-scores. Furthermore, multiple regression analysis indicated a larger impact on scores by PA than both age and education. In the light of these findings, it is advisable to pay attention to the life style of subject that undergoing a neuropsychological evaluation like the MoCa and in particular the level of PA practiced, as well as age and education.


Sequencing polymers to enable solid-state lithium batteries.
Rational designs of solid polymer electrolytes with high ion conduction are critical in enabling the creation of advanced lithium batteries. However, known polymer electrolytes have much lower ionic conductivity than liquid/ceramics at room temperature, which limits their practical use in batteries. Here we show that precise positioning of designed repeating units in alternating polymer sequences lays the foundation for homogenized Li+ distribution, non-aggregated Li+-anion solvation and sequence-assisted site-to-site ion migration, facilitating the tuning of Li+ conductivity by up to three orders of magnitude. The assembled all-solid-state batteries facilitate reversible and dendrite-mitigated cycling against Li metal from ambient to elevated temperatures. This work demonstrates a powerful molecular engineering means to access highly ion-conductive solid-state materials for next-generation energy devices.


Impact of Obesity on Left Ventricular Thickness in Children with Hypertrophic Cardiomyopathy.
Obesity is associated with additional left ventricular hypertrophy (LVH) in adults with hypertrophic cardiomyopathy (HCM). It is not known whether obesity can lead to further LVH in children with HCM. Echocardiographic LV dimensions were determined in 504 children with HCM. Measurements of interventricular septal thickness (IVST) and posterior wall thickness (PWT), and patients' weight and height were recorded. Obesity was defined as a body mass index (BMI) ≥ 99th percentile for age and sex. IVST data was available for 498 and PWT data for 484 patients. Patient age ranged from 2 to 20 years (mean ± SD, 12.5 ± 3.9) and 340 (68%) were males. Overall, patient BMI ranged from 7 to 50 (22.7 ± 6.1). Obesity (BMI 18-50, mean 29.1) was present in 140 children aged 2-19.6 (11.3 ± 4.1). The overall mean IVST was 20.5 ± 9.6 mm and the overall mean PWT was 11.0 ± 8.4 mm. The mean IVST in the obese patients was 21.6 ± 10.0 mm and mean PWT was 13.3 ± 14.7 mm. The mean IVST in the non-obese patients was 20.1 ± 9.5 mm and mean PWT was 10.4 ± 4.3 mm. Obesity was not significantly associated with IVST (p = 0.12), but was associated with increased PWT (0.0011). Obesity is associated with increased PWT but not IVST in children with HCM. Whether obesity and its impact on LVH influences clinical outcomes in children with HCM needs to be studied.


Simple Scalable Protein Expression and Extraction Using Two-stage Autoinducible Cell Autolysis and DNA/RNA Autohydrolysis in Escherichia coli.
Recombinant protein expression is extensively used in biological research. Despite this, current protein expression and extraction methods are not readily scalable or amenable for high-throughput applications. Optimization of protein expression conditions using traditional methods, reliant on growth-associated induction, is non-trivial. Similarly, protein extraction methods are predominantly restricted to chemical methods, and mechanical methods reliant on expensive specialized equipment more tuned for large-scale applications. In this article, we outline detailed protocols for the use of an engineered autolysis/autohydrolysis E. coli strain, in two-stage fermentations in shake-flasks. This two-stage fermentation protocol does not require optimization of expression conditions and results in high protein titers. Cell lysis in an engineered strain is tightly controlled and only triggered post-culture by addition of a 0.1% detergent solution. Upon cell lysis, a nuclease digests contaminating host oligonucleotides, which facilitates sample handling. This method has been validated for use at different scales, from microtiter plates to instrumented bioreactors. Graphic abstract: Two-stage protein expression, cell autolysis and DNA/RNA autohydrolysis. Reprinted with permission from Menacho-Melgar et al. (2020a). Copyright 2020 John Wiley and Sons.


Grifolin induces apoptosis and promotes cell cycle arrest in the A2780 human ovarian cancer cell line via inactivation of the ERK1/2 and Akt pathways.
Grifolin, a secondary metabolic product isolated from the mushroom Albatrellus confluence, has been demonstrated to possess antitumor activities in a variety of malignant cells. However, the signaling pathways and the molecular mechanisms underlying the anticancer effects of the agent in human ovarian cancer remain to be elucidated. The aim of the present study was to examine the effect of grifolin treatment on the human ovarian cancer cell line, A2780. MTT and flow cytometry analysis were used to analyze the viability of A2780 cells following treatment with grifolin. Western blotting was used analyze the expression of apoptosis-associated and cell cycle arrest-associated proteins. The results of MTT assays and flow cytometry analysis revealed that grifolin suppressed cell viability, induced apoptosis and triggered cell cycle arrest. Western blotting revealed that grifolin treatment resulted in inactivation of protein kinase B (Akt) and extracellular signal-related kinase 1/2 (ERK1/2), accompanied by upregulation of Bcl-2 associated X, apoptosis regulator, cleaved-caspase-3 and cleaved-poly (ADP-ribose) polymerase, and downregulation of B cell lymphoma-2, cyclin dependent kinase 4 and cyclinD1. The results of the present study indicated that grifolin had significant anti-cancer effects on the human ovarian cancer A2780 cells, which occurred via the Akt and ERK1/2 signaling pathways to at least a certain extent. These results demonstrate the therapeutic potential of grifolin as a treatment for ovarian cancer.


Design and control of a fast steering mirror based on flexible supports and piezoelectric ceramic actuators.
The use of the fast steering mirror in an optical path requires strict volume control, and traditional structures have low space-utilization efficiency, resulting in traditional actuators having limited output in narrow spaces. The design in this paper adopts a combination of flexible universal supports and piezoelectric ceramic actuators, greatly reducing the layout space of the rotating-shaft system. We accurately model the design structure and develop closed-loop control methods to further improve the closed-loop control accuracy of the system. The experimental results indicate that the developed control method effectively improves the response speed and bandwidth and thus has good potential for use in engineering applications.


Reliability analysis of the electrical control system of subsea blowout preventers using Markov models.
Reliability analysis of the electrical control system of a subsea blowout preventer (BOP) stack is carried out based on Markov method. For the subsea BOP electrical control system used in the current work, the 3-2-1-0 and 3-2-0 input voting schemes are available. The effects of the voting schemes on system performance are evaluated based on Markov models. In addition, the effects of failure rates of the modules and repair time on system reliability indices are also investigated.


Growth factors for silver nanoplates formed in a simple solvothermal process.
We synthesized both big and ultra-small silver nanoplates through a simple solvothermal process in a common autoclave. Using this approach, we achieved the reduction of silver nitrate in DMF or ethanol in the presence of PVP as a capping agent. The reduction capacity of PVP was also investigated. Growth factors such as the concentration of silver precursor, quantity of capping agent, reaction time, and temperature have been shown to play important roles in the formation of different sizes and shapes of silver nanoplates. The big plates, over 100 nm in edge length, were found mainly in the shape of a connected triangular. Single triangle plates, truncated triangular plates, and hexangular plates were also found under different reaction conditions. The ultra-small silver nanoplates, 20-100 nm in edge length, were successfully extracted from the solution under different centrifugation conditions. The UV-vis spectrum exhibited intense in-plane dipole absorption peaks varying from 470-630 nm, as reflected by the gradual color change of the solution from orange to red, and finally to blue.


Apolipoprotein E Isoform-specific changes related to stress and trauma exposure.
Post-Traumatic Stress Disorder (PTSD) is a highly prevalent mental health disorder. Due to the high level of variability in susceptibility and severity, PTSD therapies are still insufficient. In addition to environmental exposures, genetic risks play a prominent role and one such factor is apolipoprotein E. The protein (apoE) is functionally involved in cholesterol transport and metabolism and exists as 3 major isoforms in humans: E2, E3, and E4. To model the role of apolipoprotein E isoform in stress-related changes in behavior and cognition, female and male mice (3-5 months of age) expressing E2, E3, or E4 were used. Mice were either placed into control groups or exposed to chronic variable stress (CVS), which has been shown to induce PTSD-like behavioral and neuroendocrine changes. E2 mice showed a unique response to CVS compared to E3 and E4 mice that included impaired spatial learning and memory, increased adrenal gland weight, and no increase in glucocorticoid receptor protein levels (normalized to apoE levels). In addition, the cholesterol metabolite 7-ketocholesterol was elevated in the cortex after CVS in E3 and E4, but not E2 female mice. E2 confers unique changes in behavioral, cognitive, and biomarker profiles after stress exposure and identify 7-ketocholesterol as a possible novel biomarker of the traumatic stress response. We further explored the relationship between E2 and PTSD in an understudied population by genotyping 102 patients of Cambodian and Vietnamese ethnicity. E2 carriers demonstrated a higher odds ratio of having a PTSD diagnosis compared to E3/E3 carriers, supporting that the E2 genotype is associated with PTSD diagnosis after trauma exposure in this population.


Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation.
Andersen-Tawil syndrome (ATS) is an uncommon form of channelopathy linked to mutations in the KCNJ2 gene. Currently, little is known about the long-term arrhythmic prognosis of this disease. We conducted a retrospective multicentre study in nine French hospitals. Patients were recruited only if they were KCNJ2 mutation carriers. Thirty-six patients (female n = 22, 61%) from 20 unrelated kindred were included with a mean follow-up of 9.5 ± 8.2 years. We found 12 distinct KCNJ2 mutations in the 20 probands. Three of them were novel. Thirteen patients (36%) experienced syncope and one patient was resuscitated from cardiac arrest before diagnosis. The mean QTc interval was 439 ± 57 ms and QUc was 642 ± 64 ms. All patients had normal ejection fraction. Holter recordings in 33 patients found 11 272 premature ventricular complexes (PVCs) per day on average, 25 patients had episodes of bigeminy, and 25 patients had polymorphic PVCs. Twenty-three patients (70%) had non-sustained polymorphic ventricular tachycardia (VT), and six sustained polymorphic VT. Only one patient presented with torsades de pointes. Patients were treated with beta-blocker (n = 20), beta-blocker and amiodarone (n = 2), beta-blocker and flecainide (n = 6), or acetazolamide (n = 6). Radiofrequency ablation was attempted in five patients without clinical success. An implantable cardiac defibrillator was implanted in three patients. During follow-up, none of the patients died, four patients experienced syncope under treatment, and one patient had non-fatal cardiac arrest. Despite a severe clinical presentation with a very high rate of ventricular arrhythmias, the arrhythmic prognosis of the ATS patients is relatively good under treatment.


Relapsing acute kidney injury associated with pegfilgrastim.
We report a previously unrecognized complication of severe acute kidney injury (AKI) after the administration of pegfilgrastim with biopsy findings of mesangioproliferative glomerulonephritis (GN) and tubular necrosis. A 51-year-old white female with a history of breast cancer presented to the hospital with nausea, vomiting and dark urine 2 weeks after her third cycle of cyclophosphamide and docetaxel along with pegfilgrastim. She was found to have AKI with a serum creatinine (Cr) level of 6.9 mg/dl (baseline 0.7). At that time, her AKI was believed to be related to prior sepsis and/or daptomycin exposure that had occurred 5 weeks earlier. She was dialyzed for 6 weeks, after which her kidney function recovered to near baseline, but her urinalysis (UA) still showed 3.5 g protein/day and dysmorphic hematuria. Repeat blood cultures and serological workup (complement levels, hepatitis panel, ANA, ANCA and anti-GBM) were negative. She received her next cycle of chemotherapy with the same drugs. Two weeks later, she developed recurrent AKI with a Cr level of 6.7 mg/dl. A kidney biopsy showed mesangioproliferative GN, along with tubular epithelial damage and a rare electron-dense glomerular deposit. Pegfilgrastim was suspected as the inciting agent after exclusion of other causes. Her Cr improved to 1.4 mg/dl over the next 3 weeks, this time without dialysis. She had the next 2 cycles of chemotherapy without pegfilgrastim, with no further episodes of AKI. A literature review revealed a few cases of a possible association of filgrastim with mild self-limited acute GN. In conclusion, pegfilgrastim may cause GN with severe AKI. Milder cases may be missed and therefore routine monitoring of renal function and UA is important.


Who Deserves Endoscopic Screening for Esophageal Neoplasia?
Despite the availability of safe and effective endoscopic treatment of Barrett's esophagus (BE)-related dysplasia and neoplasia, the incidence and mortality from esophageal adenocarcinoma (EAC) have continued to increase. This likely stems from the large population of patients that develop EAC outside of a BE screening and surveillance program. Identification of BE with screening followed by enrollment in an appropriate surveillance/risk stratification program could be a strategy to address both the incidence of and mortality from EAC. This article summarizes the rationale and challenges for BE screening, the risk factors for BE, and the currently described BE risk assessment tools.


The PRP6-like splicing factor STA1 is involved in RNA-directed DNA methylation by facilitating the production of Pol V-dependent scaffold RNAs.
DNA methylation is a conserved epigenetic marker in plants and animals. In Arabidopsis, DNA methylation can be established through an RNA-directed DNA methylation (RdDM) pathway. By screening for suppressors of ros1, we identified STA1, a PRP6-like splicing factor, as a new RdDM regulator. Whole-genome bisulfite sequencing suggested that STA1 and the RdDM pathway share a large number of common targets in the Arabidopsis genome. Small RNA deep sequencing demonstrated that STA1 is predominantly involved in the accumulation of the siRNAs that depend on both Pol IV and Pol V. Moreover, the sta1 mutation partially reduces the levels of Pol V-dependent RNA transcripts. Immunolocalization assay indicated that STA1 signals are exclusively present in the Cajal body and overlap with AGO4 in most nuclei. STA1 signals are also partially overlap with NRPE1. Localization of STA1 to AGO4 and NRPE1 signals is probably related to the function of STA1 in the RdDM pathway. Based on these results, we propose that STA1 acts downstream of siRNA biogenesis and facilitates the production of Pol V-dependent RNA transcripts in the RdDM pathway.