Immunocytochemical localization of ProANF 1-30, ProANF 31-67, atrial natriuretic factor and urodilatin in the human kidney.
Whether ProANF 1-30 [first 30 amino acids (a.a.) of the 126-a.a. atrial natriuretic factor (ANF) prohormone] and ProANF 31-67 (a.a. 31-67 of this prohormone) with their natriuretic and diuretic properties are present within the human kidney is unknown. In the present investigation, ProANFs 1-30 and 31-67 as well as ANF (a.a. 99-126) of the ANF prohormone localized to the subbrush border of the pars convoluta and pars recta of the proximal tubules of the human kidney with immunoperoxidase staining. Immunofluorescent studies revealed that each of these peptides had a strong inclination for the perinuclear region in the proximal and distal tubules. ProANFs 1-30, 31-67 and 99-126 (i.e. ANF) also localized with both immunoperoxidase and immunofluorescent staining to the coritcal collecting ducts, glomeruli, and peritubular and interstitial blood vessels. ANF immunoperoxidase staining was particularly striking in the endothelium of interstitial arteries and vasa recta. In the glomeruli, prominent staining was noted in the peripheral glomerular capillary wall and in some of the visceral epithelial cells. In contrast, urodilatin (i.e. a.a. 95-126 of the ANF prohormone) was not found in the proximal tubules, but weak staining was found in the distal tubules and interstitial vessels with some but not all glomeruli, peritubular vessels, cortical collecting tubules and outer medullary nephrons weakly staining by immunoperoxidase and immunofluorescent methods. The whole prohormone being present in the kidney was suggested by immunological recognition of both the N- and C-termini of the ANF prohormone by radioimmunoassays.(ABSTRACT TRUNCATED AT 250 WORDS)


Sonographic evaluation of biliary ascariasis.
In a prospective 6-month study, sonographic diagnosis of biliary ascariasis was made in 14 patients; in nine patients, the diagnosis was confirmed by endoscopic retrograde cholangiopancreatography and bile analysis, while in five patients, confirmation was obtained by proven intestinal infestation. No false-positive or false-negative cases were encountered. Ascariasis of the biliary tract was seen on ultrasound as echogenic, non-shadowing images, either as single or multiple strips, with visualization of the digestive tract of the worm as an anechoic inner tube, or as amorphous fragments. Follow-up sonograms helped in detection of worm expulsion following medical therapy in five patients, while endoscopic extraction of the worm was performed in four patients. In three patients, disappearance of the worm from the biliary tract was noted following a therapeutic sphincterotomy, and two patients detected to have a worm within the gall-bladder were operated on. In all patients, serial sonograms revealed disappearance of the worm, and the regression of biliary tract dilatation.


Comparison of prostaglandin E2 gel, prostaglandin E2 pessary and extra-amniotic saline infusion with oxytocin for induction of labour.
Induction of labour is the intentional initiation of cervical ripening and uterine contraction for the purpose of accomplishing delivery, prior to onset of spontaneous parturition. This study was conducted to compare maternal and neonatal outcome in women induced with Prostaglandin E2 gel, Prostaglandin E2 pessary and extra-amniotic saline infusion with oxytocin at Bishops score < 5. It was a quasi-experimental which was conducted at the Department of Gynaecology and Obstetrics Unit-I, Mother and Child Health Care Centre, Pakistan Institute of Medical Sciences, Islamabad during one year of time. Eighty cases in each group (prostaglandin gel, prostaglandinE2 pessary and extra-amniotic saline infusion with oxytocin) were collected. Systematic sampling was done. First woman admitted was induced with prostaglandin gel, the second one with prostaglandin pessary and the third was induced with extra amniotic saline infusion and oxytocin. The most common indication for induction was post dates followed by PIH. The induction labour interval was less in EASI with oxytocin group (5.18 +/- 3.4) hours, as compared to prostaglandin pessary (8.81 +/- 5.60) hours and prostaglandin gel (8.32 +/- 5.18) hours. Induction delivery interval in EASI with oxytocin was (10 +/- 5.6) hours as compared to prostaglandin pessary (14 +/- 6.3) hours and prostaglandin gel (13 +/- 7.1) hours. This difference was statistically significant. The primigravidas had longer duration of labour than multigravidas. Induction labour interval in primigravidas was (8.2 +/- 5.1) hours while in multigravidas it was (6.7 +/- 5.02) hours. Induction delivery interval was also more in primigravidas (13.6 +/- 6.80) hours as compared to multigravidas (11.4 +/- 6.20) hours. Vaginal delivery rate was 89.2% while the caesarean section rate was 10.4%. The most common indication for caesarean section was foetal distress. There was no significant difference in perinatal morbidity and mortality in the three groups. EASI with oxytocin is a better method of induction than prostaglandin E2 gel and pessary. Moreover it is more economical in our country.


Racial difference in cardiovascular outcomes following percutaneous coronary intervention in a public health service patient population.
Prior studies have reported conflicting findings regarding racial disparities in long-term cardiovascular outcomes after percutaneous coronary intervention (PCI). Our aim was to compare major adverse cardiac events (MACE) following PCI in black versus non-black patients in a Public Health Service (PHS) setting. A cohort of 1,438 consecutive patients undergoing intended PCI at a large public teaching hospital between April 2002 and September 2006 were followed for the development of MACE, defined as a composite of death, myocardial infarction (MI) and urgent target vessel revascularization. The study population consisted of 47.4% blacks, 21.3% whites, 15.2% Hispanics and 16.1% Asians. Overall, 17.4% of patients developed MACE over the mean followup period of 2.9 years. The rate of MACE was significantly higher in blacks compared with non-blacks (21.7% vs. 13.6%, log-rank p < 0.001). After adjusting for age, gender, cardiovascular risk factors, socioeconomic status (SES) and potential confounding factors, black race remained a strong and independent predictor of MACE (adjusted HR, 1.52; CI, 1.18-1.96; p = 0.001). Blacks had higher rates of death (12.3% vs. 5.2%, log-rank p < 0.001) and MI (8.7% vs. 4.4%, log rank p = 0.002). There were no racial differences in in-hospital mortality and 3-month and 6-month MACE. In this PHS population, blacks were found to have worse long-term cardiovascular outcomes and mortality following PCI, irrespective of differences in baseline cardiovascular risk factors, SES and health-care access.


Synthesis of tyrocidine A and its analogues by spontaneous cyclization in aqueous solution.
[reaction: see text] Head-to-tail cyclization of peptides is a multistep process involving tedious C-terminal activation and side chain protection. Here we report a facile, quantitative cyclization method in aqueous ammonia solution for the total syntheses of the cyclic decapeptide antibiotic Tyrocidine A and its analogues from their fully deprotected linear thioester precursors on a solid support. This novel aqueous method is conformation-dependent and may be applicable to syntheses of other natural cyclic peptides.


Maternal gestational weight gain and adverse pregnancy outcomes in non-diabetic women.
This study investigated the relationship between maternal gestational weight gain (GWG) and the risk of adverse pregnancy outcomes in gestational diabetes mellitus (GDM)-negative pregnant women. We did a retrospective cohort study between 1 July 2017, and 1 January 2020, at Women's Hospital, Zhejiang University School of Medicine. Firstly, pregnant women were divided into subgroups according to the entire GWG (inadequate GWG, adequate GWG, and excessive GWG) and GDM status (positive and negative) during pregnancy. Secondly, the whole population of pregnant women with GDM was used as a reference to evaluate the relationship between GWG and adverse pregnancy outcomes in GDM-negative pregnant women. Lastly, subgroup analysis was conducted based on pre-pregnancy body mass index (pp-BMI). A total of 30,910 pregnant women were analysed. Included pregnancy women were divided into three groups based on GWG: 7569 (24.49%) pregnancy women had inadequate GWG, 13088 (42.34%) had adequate GWG, and 10,253 (33.17%) had excessive GWG. In addition to preterm birth and small for gestational age (SGA), the incidence of macrosomia and large for gestational age (LGA) continues to increase from inadequate GWG to excessive GWG groups. Pregnant women without GDM who have excessive GWG are at higher risk of macrosomia and LGA than pregnant women with GDM. Moreover, this risk increased with increasing pp-BMI. Pregnant women without GDM with inadequate GWG were at risk of preterm birth regardless of pp-BMI. Only those with inadequate GWG and pp-BMI < 18.5 kg/m2 had an increased risk of SGA. In conclusion, inappropriate GWG is strongly associated with adverse pregnancy outcomes, even if they do not have GDM. Therefore, this population should receive attention and management before and during pregnancy.Impact StatementWhat is already known on this subject? Several studies have focused on the GDM population and the risk of adverse pregnancy outcomes, but few have focused on GDM-negative populations. This is because GDM-negative women are perceived to be "safe," leading to less focus on themselves, which can lead to subsequent excessive weight gain during pregnancy. Whether this factor increases the risk of adverse pregnancy outcomes in this population remains unknown.What do the results of this study add? Our study found an inverse relationship between GWG and GDM. Therefore, our study focuses on this group of GDM-negative pregnant women. Their excessive weight gain increases the risk of adverse pregnancy outcomes, even higher than GDM pregnant women.What are the implications of these findings for clinical practice and/or further research? GWG is associated with adverse pregnancy outcomes. Therefore, pregnant women without GDM also need increased attention and management of their weight before and during pregnancy. Prenatal care providers can utilise tools such as diet, exercise counselling, weight tracking, and setting weight gain goals to reduce inappropriate weight gain and mitigate its adverse effects on pregnancy outcomes.


Capsaicin-loaded nanolipoidal carriers for topical application: design, characterization, and in vitro/in vivo evaluation.
Capsaicin has been used in clinical applications for the treatment of pain disorders and inflammatory diseases. Given the strong pungency and high oil/water partition coefficient of capsaicin, capsaicin-loaded nanolipoidal carriers (NLCs) were designed to increase permeation and achieve the analgesic, anti-inflammatory effect with lower skin irritation. Capsaicin-loaded NLCs were prepared and later optimized by the Box-Behnken design. The physicochemical characterizations, morphology, and encapsulation of the capsaicin-loaded NLCs were subsequently confirmed. Capsaicin-loaded NLCs and capsaicin-loaded NLCs gel exhibited sustained release and no cytotoxicity properties. Also, they could significantly enhance the penetration amount, permeation flux, and skin retention amounts of capsaicin due to the application of NLCs. To study the topical permeation mechanism of capsaicin, 3,3'-dioctadecyloxacarbocyanine perchlorate (Dio) was used as a fluorescent dye. Dio-loaded NLCs and Dio-loaded NLCs gel could effectively deliver Dio up to a skin depth of 260 and 210 μm, respectively, primarily through the appendage route on the basis of version skin sections compared with Dio solution, which only delivered Dio up to 150 μm. In vivo therapeutic experiments demonstrated that capsaicin-loaded NLCs and capsaicin-loaded NLCs gel could improve the pain threshold in a dose-dependent manner and inhibit inflammation, primarily by reducing the prostaglandin E2 levels in the tissue compared with capsaicin cream and capsaicin solution. Meanwhile, skin irritation was reduced, indicating that application of NLCs could decrease the irritation caused by capsaicin. Overall, NLCs may be a potential carrier for topical delivery of capsaicin for useful pain and inflammation therapy.


[Protein kinases involved in the meiotic maturation and fertilization of oocyte].
The meiosis and fertilization of vertebrate oocyte are extensively regulated by various protein kinases. Recently, a great progress has been achieved in the studies on the molecular mechanisms of oocyte maturation, activation and fertilization. MPF and MAPK were found to be the key modulators of the cell cycle in oocyte, whose activation and inactivation result in the entry, arrest and exit of meiosis. Many protein kinases influence the meiosis by stimulating or inhibiting the activity of MPF and MAPK. Polo-like kinase activates MPF, whereas Mos initiates oocyte maturation and sustains MII arrest by activating MAPK. CaMK II down-regulates the MPF level through an ubiquitin-dependent pathway, which leads to the breakthrough of M phase arrest. Furthermore, p90(rsk) is involved in themeiosis regulation as a downstream regulator of MAPK; protein kinase C induces cortical granule exocytosis after fertilization and inhibits MAPK activity during maturation; and tyrosine protein kinase family members modulate the calcium release induced by fertilization. The cooperation of these protein kinases is essential to the development and fertilization of the oocyte.


The evaluation of motivation for sexual health among women.
This study conducted a psychometric evaluation of the construct validity of the Health Self-Determinism Index-Sexual (HSDI-S). The instrument was modified to measure motivation related to sexual health rather than motivation of general health in the Health Self-Determinism Index (HSDI). The HSDI-S was completed by 260 conveniently selected women (between the ages of 18 and 44) attending primary-care clinics in the southeastern United States. Confirmatory factor analysis using LISREL did not validate the four subscales of the original HSDI. Subsequent exploratory and confirmatory factor analysis isolated a single-factor model composed of eight items: four judgment items and four external/internal cues items. This finding is suggestive that changes in wording appear to have shifted the responses from motivation for sexual health to that of women's perception of their role in intimate relationships. The eight extrinsically worded items isolate a single-factor model of social and cultural influences of child-bearing-age women's intimate relationships.


Comparison of three methods for determination of N-nitrosopyrrolidine in fried dry-cured bacon.
The recently developed Eastern Regional Research Center ( ERRC ) dry column chromatographic procedure for determining N-nitrosopyrrolidine (NPYR) in fried cure-pumped bacon was evaluated for its applicability to fried dry-cured bacon. The method was then compared with 2 established procedures for volatile nitrosamine analysis in cured meat products: the multidetection thermal energy analyzer (MD) method and the mineral oil distillation (MOD) screening procedure. No significant difference (P less than 0.05) in NPYR values was found between the ERRC and MD procedures, but significant differences were found between the ERRC and MOD procedures and between the MOD and MD procedures. No artifactual nitrosamine formation was found in the ERRC procedure, but significant amounts were found in samples analyzed by the MOD procedure. The ERRC method was demonstrated to be rugged and very rapid. It is proposed that the ERRC method replace the MOD method as the official screening procedure for NPYR in fried bacon.


Sexual Violence in America: Public Funding and Social Priority.
We compared lifetime risk, annual incidence, and annual economic burden of sexual violence with other major public health issues in the United States: cardiovascular disease, cancer, diabetes, and HIV/AIDS. With public funding data from 2013, we examined how much public funding is allocated to these public health issues as a proxy of the social priority of addressing each of them. Although sexual violence is as prevalent as and more costly than are these other major public health issues, it receives a fraction of the public funds that they receive.


OPAL: prediction of MoRF regions in intrinsically disordered protein sequences.
Intrinsically disordered proteins lack stable 3-dimensional structure and play a crucial role in performing various biological functions. Key to their biological function are the molecular recognition features (MoRFs) located within long disordered regions. Computationally identifying these MoRFs from disordered protein sequences is a challenging task. In this study, we present a new MoRF predictor, OPAL, to identify MoRFs in disordered protein sequences. OPAL utilizes two independent sources of information computed using different component predictors. The scores are processed and combined using common averaging method. The first score is computed using a component MoRF predictor which utilizes composition and sequence similarity of MoRF and non-MoRF regions to detect MoRFs. The second score is calculated using half-sphere exposure (HSE), solvent accessible surface area (ASA) and backbone angle information of the disordered protein sequence, using information from the amino acid properties of flanks surrounding the MoRFs to distinguish MoRF and non-MoRF residues. OPAL is evaluated using test sets that were previously used to evaluate MoRF predictors, MoRFpred, MoRFchibi and MoRFchibi-web. The results demonstrate that OPAL outperforms all the available MoRF predictors and is the most accurate predictor available for MoRF prediction. It is available at http://www.alok-ai-lab.com/tools/opal/. email@example.com or firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Dissociated effect of buserelin on luteinizing hormone (LH) and alpha subunit in men.
Chronic treatment with LHRH analogs is known to depress testosterone (T) values to castration levels. In contrast to results from animal experiments, studies in humans indicate that a pituitary-dependent mechanism predominates in the suppression of plasma T. However, this reduction in T levels may occur when LH values are within or below the normal range. One explanation for this result has been that while absolute values of LH in serum may not change, the bioactivity of LH is reduced. The present study has been performed to determine whether this discrepancy between LH and T values is obscured by the hypersecretion of the alpha-subunit which is devoid of any biological activity but crossreacts in most RIAs with LH. Following 2 days of blood collection to establish basal serum hormone levels, six men with prostatic cancer were treated with the LHRH agonist, Buserelin (500 micrograms sc, daily injection) for 15 days. The most significant endocrine responses at the end of this treatment were as follows: 1) T levels were depressed to the castration range; 2) no change was seen in the LH values with a conventional RIA procedure which crossreacted with the alpha-subunit; 3) a significant decrease was found in the LH values evaluated with an immunoradiometric (IRMA) method, which shows no cross-reactivity with the alpha-subunit; 4) there was a significant increase in the alpha-subunit levels; and 5) serum FSH levels were significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)


Is interferon with or without vinblastine the "treatment of choice" in metastatic renal cell carcinoma? The Norwegian Radium Hospital's experience 1983-1986.
Fifty-seven of 66 patients with metastatic renal cell carcinoma (RCC) were evaluable for response after treatment with Interferon (IFN) - Alfa 2a (Roferon A, Roche) with or without Vinblastine (VB). Three different dose schedules were used in 3 subsequent trials: protocol 1: (18 evaluable patients): IFN 36 X 10(6) U tiw +/- VB 0.1-0.15 mg/kg/2-3 week; protocol 2: (13 patients): IFN 18 X 10(6) U tiw +/- VB 0.1 mg/kg/3 week; protocol 3: (26 patients): IFN 18 X 10(6) U tiw +/- VB 0.1 mg/kg/3 week. Twelve of the 57 patients obtained an objective response (CR:1; PR:11). Regarding the main indicator lesions responses were seen in lung metastases (10), lymph node metastases (1), and bone metastases (1). The median response duration was 243 days. No significant impact of the IFN/VB treatment on survival could be demonstrated. Flulike symptoms represented the main toxicity. Four patients developed mental confusion, and in 2 patients with visual disturbances retinal exudation was observed. In more than half of the patients, the drug(s) had to be reduced, delayed, or finally discontinued due to toxicity. It is concluded that IFN with or without VB yields a 15-20% response rate in metastatic RCC. Due to the considerable toxicity of the treatment and the lack of proof of survival improvement, the clinical usefulness of IFN therapy in RCC remains questionable. However, on the background of the present therapeutic nihilism in metastatic RCC, additional clinical trials using IFN in RCC are justified.


Project Wildfish: rewarding through innovation.
The appropriateness of a reward system depends, in part, on the developmental level of the staff. Based on a model developed at Shadyside Hospital, Pittsburgh, PA, called the Transformational Model for the Practice of Professional Nursing, we have determined that the potential for innovation becomes a highly valued reward for a healthy, well-developed nursing unit. Project Wildfish illustrates the energy, commitment, and enthusiasm that innovation can inspire.


Stromal cells regulate mechanics of tumour spheroid.
The remarkable contractility and force generation ability exhibited by cancer cells empower them to overcome the resistance and steric hindrance presented by a three-dimensional, interconnected matrix. Cancer cells disseminate by actively remodelling and deforming their extracellular matrix (ECM). The process of tumour growth and its ECM remodelling have been extensively studied, but the effect of the cellular tumour microenvironment (TME) has been ignored in most studies that investigated tumour-cell-mediated ECM deformations and realignment. This study reports the integration of stromal cells in spheroid contractility assays that impacts the ECM remodelling and invasion abilities of cancer spheroids. To investigate this, we developed a novel multilayer in vitro assay that incorporates stromal cells and quantifies the contractile deformations that tumour spheroids exert on the ECM. We observed a negative correlation between the spheroid invasion potential and the levels of collagen deformation. The presence of stromal cells significantly increased cancer cell invasiveness and altered the cancer cells' ability to deform and realign collagen gel, due to upregulation of proinflammatory cytokines. Interestingly, this was observed consistently in both metastatic and non-metastatic cancer cells. Our findings contribute to a better understanding of the vital role played by the cellular TME in regulating the invasive outgrowth of cancer cells and underscore the potential of utilising matrix deformation measurements as a biophysical marker for evaluating invasiveness and informing targeted therapeutic opportunities.


Type IX secretion: the generation of bacterial cell surface coatings involved in virulence, gliding motility and the degradation of complex biopolymers.
The Type IX secretion system (T9SS) is present in over 1000 sequenced species/strains of the Fibrobacteres-Chlorobi-Bacteroidetes superphylum. Proteins secreted by the T9SS have an N-terminal signal peptide for translocation across the inner membrane via the SEC translocon and a C-terminal signal for secretion across the outer membrane via the T9SS. Nineteen protein components of the T9SS have been identified including three, SigP, PorX and PorY that are involved in regulation. The inner membrane proteins PorL and PorM and the outer membrane proteins PorK and PorN interact and a complex comprising PorK and PorN forms a large ring structure of 50 nm in diameter. PorU, PorV, PorQ and PorZ form an attachment complex on the cell surface of the oral pathogen, Porphyromonas gingivalis. P. gingivalis T9SS substrates bind to PorV suggesting that after translocation PorV functions as a shuttle protein to deliver T9SS substrates to the attachment complex. The PorU component of the attachment complex is a novel Gram negative sortase which catalyses the cleavage of the C-terminal signal and conjugation of the protein substrates to lipopolysaccharide, anchoring them to the cell surface. This review presents an overview of the T9SS focusing on the function of T9SS substrates and machinery components.


Pediatric Magnetic Resonance Enterography: Focused on Crohn's Disease.
Crohn's disease is a chronic idiopathic inflammatory disease of the intestines characterized by frequent relapse and remission. It often develops in children and adolescents, who are vulnerable to repeated exposure to ionizing radiations. Magnetic resonance enterography (MRE) is an increasingly important radiation-free imaging modality that is used to evaluate pediatric patients with Crohn's disease. MRE can evaluate extraluminal and extraintestinal abnormalities as well as the status of the bowel wall. In addition, MRE has an advantage in the evaluation of the small bowel involvement. MRE can be used for the initial diagnosis of Crohn's disease, and can aid in the assessment of disease activity and complications such as penetrating and fibrostenotic diseases. The aims of this article are to review the MRE technique for obtaining diagnostic and high-quality images and to discuss interpretations of imaging findings in patients with Crohn's disease.


The subchondral bone in osteoarthritis and rheumatoid arthritis of the knee. A histological and microradiographical study.
Specimens of the joint surfaces of the tibia from patients with OA and RA were exposed were examined for bone mineralization, bone formation, osteoid tissue and bone resorption. Judging from the appearance of the osteoblasts in OA the sclerotic changes are mainly focal with relatively little osteogenesis. No osteoclasia was seen in the sclerotic areas. Breakdown of the mineralized cartilage is followed by the development of cysts with highly cellular connective tissue with high osteoblastic activity and osteoclasia. Osteoid tissue is relatively sparse. The changes in RA are more diffuse with a more active osteoblastic activity and widespread zones of osteoid tissue as well as resorption by osteoclasts. It appears as if the increased uptake of 85Sr in OA is more dependent on the occurrence of relatively inert osteosclerosis than on a rapid turnover of the bone tissue.


Transient receptor potential canonical 5 channels plays an essential role in hepatic dyslipidemia associated with cholestasis.
Transient receptor potential canonical 5 (TRPC5), a calcium-permeable, non-selective cation channel is expressed in the periphery, but there is limited knowledge of its regulatory roles in vivo. Endogenous modulators of TRPC5 include a range of phospholipids that have an established role in liver disease, including lysophosphatidylcholine (LPC). Cholestasis is characterized by impairment of excretion of bile acids, leading to elevation of hepatic bile acids. We investigated the contribution of TRPC5 in a murine model of cholestasis. Wild-type (WT) and TRPC5 knock-out (KO) mice were fed a diet supplemented with 0.5% cholic acid (CA) for 21 days. CA-diet supplementation resulted in enlargement of the liver in WT mice, which was ameliorated in TRPC5 KO mice. Hepatic bile acid and lipid content was elevated in WT mice, with a reduction observed in TRPC5 KO mice. Consistently, liver enzymes were significantly increased in cholestatic WT mice and significantly blunted in TRPC5 KO mice. Localized dyslipidaemia, secondary to cholestasis, was investigated utilizing a selected lipid analysis. This revealed significant perturbations in the lipid profile following CA-diet feeding, with increased cholesterol, triglycerides and phospholipids, in WT, but not TRPC5 KO mice. Our results suggest that activation of TRPC5 contributes to the development of cholestasis and associated dyslipidemia. Modulation of TRPC5 activity may present as a novel therapeutic target for liver disease.


Revealing Surface Elemental Composition and Dynamic Processes Involved in Facet-Dependent Oxidation of Pt3Co Nanoparticles via in Situ Transmission Electron Microscopy.
Since catalytic performance of platinum-metal (Pt-M) nanoparticles is primarily determined by the chemical and structural configurations of the outermost atomic layers, detailed knowledge of the distribution of Pt and M surface atoms is crucial for the design of Pt-M electrocatalysts with optimum activity. Further, an understanding of how the surface composition and structure of electrocatalysts may be controlled by external means is useful for their efficient production. Here, we report our study of surface composition and the dynamics involved in facet-dependent oxidation of equilibrium-shaped Pt3Co nanoparticles in an initially disordered state via in situ transmission electron microscopy and density functional calculations. In brief, using our advanced in situ gas cell technique, evolution of the surface of the Pt3Co nanoparticles was monitored at the atomic scale during their exposure to an oxygen atmosphere at elevated temperature, and it was found that Co segregation and oxidation take place on {111} surfaces but not on {100} surfaces.


Community Health Workers During COVID-19: Supporting Their Role in Current and Future Public Health Responses.
Community health workers advance health equity and foster community-clinical linkages. By promoting culturally relevant care, sharing their own stories, and bridging gaps, they can reach populations burdened with higher rates of chronic diseases due to adverse social determinants of health and structural racism. Given the disproportionate impacts of COVID-19, lessons learned from a forum, an expert group, and a survey showed a need by community health workers for (1) training, (2) health and safety practices, (3) workplace guidance, and (4) mental health resources. Community health workers are integral to expanding access to services and require a robust infrastructure for their growth.


Geographic variation in body size and sexual size dimorphism of a seed-feeding beetle.
Body size of many animals varies with latitude: body size is either larger at higher latitudes (Bergmann's rule) or smaller at higher latitudes (converse Bergmann's rule). However, the causes underlying these patterns are poorly understood. Also, studies rarely explore how sexual size dimorphism varies with latitude. Here we investigate geographic variation in body size and sexual size dimorphism of the seed-feeding beetle Stator limbatus, collected from 95 locations along a 38 degrees range in latitude. We examine 14 variables to test whether clines in environmental factors are adequate to explain geographic patterns of body size. We found that body size and sexual size dimorphism of S. limbatus varied considerably with latitude; beetles were smaller but more dimorphic at lower latitudes. Body size was not correlated with a gradient in mean temperature, contrary to the commonly accepted hypothesis that clines are produced by latitudinal gradients in temperature. Instead, we found that three factors were adequate to explain the cline in body size: clinal variation in host plant seed size, moisture (humidity), and seasonality (variance in humidity, precipitation, and temperature). We also found that the cline in sexual size dimorphism was partially explainable by a gradient in moisture, though moisture alone was not sufficient to explain the cline. Other ecological or environmental variables must necessarily contribute to differences in selection on male versus female body size. The main implications of our study are that the sexes differ in the magnitude of clinal variation in body size, creating latitudinal variation in sexual size dimorphism, and that clines in body size of seed beetles are likely influenced by variation in host seed size, water availability, and seasonality.


Fluorescent nanocrystals as colloidal probes in complex fluids measured by fluorescence correlation spectroscopy.
The diffusion properties of fluorescent colloidal CdSe and CdSe/ZnS nanocrystals (QDs) with different hydrophilic coatings were characterized in complex fluids such as actin solutions using fluorescence correlation spectroscopy (FCS). The hydrodynamic radii of the QDs were determined both in organic solvents and water. Attention was given to the potential artifacts arising from the fluorescence properties of the QDs. With increasing excitation intensities, the apparent particle concentration and diffusion times are overestimated if using a simple diffusion model. This can be explained by a numerical simulation. The diffusion behavior of QDs in actin networks of different concentrations was determined to demonstrate the potential use of nanocrystals as probes in soft biological matter. The decreasing diffusion coefficient of the nanocrystals with increasing actin concentration results in an intrinsic polymer viscosity of 0.12+/-0.02 ml mg(-1), in accordance with literature values.


The C-terminal region of the Turnip mosaic virus P3 protein is essential for viral infection via targeting P3 to the viral replication complex.
Like other positive-strand RNA viruses, plant potyviruses assemble viral replication complexes (VRCs) on modified cellular membranes. Potyviruses encode two membrane proteins, 6K2 and P3. The former is known to play pivotal roles in the formation of membrane-associated VRCs. However, P3 remains to be one of the least characterized potyviral proteins. The P3 cistron codes for P3 as well as P3N-PIPO which results from RNA polymerase slippage. In this study, we show that the P3N-PIPO of Turnip mosaic virus (TuMV) is required for viral cell-to-cell movement but not for viral replication. We demonstrate that the C-terminal region of P3 (P3C) is indispensable for P3 to form cytoplasmic punctate inclusions and target VRCs. We reveal that TuMV mutants that lack P3C are replication-defective. Taken together, these data suggest that the P3 cistron has two distinct functions: P3N-PIPO as a dedicated movement protein and P3 as an essential component of the VRC.


Motor neurons control blood vessel patterning in the developing spinal cord.
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF). We describe that motor neurons express the VEGF trapping receptor sFlt1 via a Neuropilin-1-dependent mechanism. Using a VEGF gain-of-function approach in mice and a motor neuron-specific sFlt1 loss-of-function approach in chicken, we show that motor neurons control blood vessel patterning by an autocrine mechanism that titrates motor neuron-derived VEGF via their own expression of sFlt1.


The use of human dental pulp stem cells for in vivo bone tissue engineering: A systematic review.
Dental pulp represents a promising and easily accessible source of mesenchymal stem cells for clinical applications. Many studies have investigated the use of human dental pulp stem cells and stem cells isolated from the dental pulp of human exfoliated deciduous teeth for bone tissue engineering in vivo. However, the type of scaffold used to support the proliferation and differentiation of dental stem cells, the animal model, the type of bone defect created, and the methods for evaluation of results were extremely heterogeneous among these studies conducted. With this issue in mind, the main objective of this study is to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of human dental pulp stem cells and stem cells from human exfoliated deciduous teeth (SHED) for bone regeneration was evaluated. The article search was conducted in PubMed/MEDLINE and Web of Science databases. Original research articles assessing potential of human dental pulp stem cells and SHED for in vivo bone tissue engineering, published from 1984 to November 2017, were selected and evaluated in this review according to the following eligibility criteria: published in English, assessing dental stem cells of human origin and evaluating in vivo bone tissue formation in animal models or in humans. From the initial 1576 potentially relevant articles identified, 128 were excluded due to the fact that they were duplicates and 1392 were considered ineligible as they did not meet the inclusion criteria. As a result, 56 articles remained and were fully analyzed in this systematic review. The results obtained in this systematic review open new avenues to perform bone tissue engineering for patients with bone defects and emphasize the importance of using human dental pulp stem cells and SHED to repair actual bone defects in an appropriate animal model.


[Application of intraoperative optical coherence tomography in deep lamellar keratoplasty].
Objective: To evaluate the clinical application value of intraoperative optical coherence tomography (iOCT) in deep anterior lamellar keratoplasty (DALK) using the big-bubble technique to bare Descemet's membrane. Methods: Retrospective case series. Clinical data of 92 patients (92 eyes) with monocular stromal corneal diseases who underwent big-bubble DALK in the Eye Hospital of Shandong First Medical University from January 2020 to August 2021 were collected. There were 53 males and 39 females. The average age was (53.2±16.0) years old. All patients underwent iOCT scanning to determine the location and depth of the injection needle after initial removal of the corneal lesion, to observe the integrity of the recipient bed, Descemet's membrane, after complete lesion removal, and to observe the adhesion between the corneal graft and the recipient bed and check folds on the recipient bed after suturing of the corneal graft. The intraoperative perforation of Descemet's membrane, postoperative thickness of the cornea and the recipient bed, visual acuity, and corneal astigmatism were recorded. Results: By iOCT, the thickness of the recipient bed was found to be about 1/2 of the corneal thickness and relatively uniform in all directions in 62 eyes (67.4%), so the sterile air was injected from the center of the recipient bed to separate it from the stromal layer. In 30 eyes (32.6%) with an uneven thickness of the recipient bed, the sterile air was injected from the paracentral area of the recipient bed. Under the guidance of iOCT scanning, 89 eyes (96.7%) did not experience any perforation of Descemet's membrane during surgery. The Descemet's membrane folds in the central 5-mm area of the recipient bed was observed and flattened in 20 eyes with the assistance of iOCT scanning. The postoperative corneal thickness was (578.95±108.26) μm, and the recipient bed thickness was (36.06±23.11) μm. The best corrected visual acuity of all patients at 6 months after surgery was 0.57±0.25 logMAR, which was significantly better than that before surgery (1.61±1.27 logMAR; P<0.001). The average corneal astigmatism at 6 months after surgery was (2.72±2.44) diopters. Conclusions: The application of iOCT scanning in DALK surgery assisted by the big-bubble method can provide safe guidance for surgeons to adopt correct surgical procedures, decrease the risk of Descemet's membrane perforation, reduce the recipient bed folds, and facilitate corneal interlayer adhesion, thereby improving the visual prognosis.


Prevalence of Neisseria gonorrhoeae infection in patients attending an antenatal clinic.
Neisseria gonorrhoeae infection was diagnosed by culture using a selective medium (Thayer-Martin) in 140 (11.7%) of 1 200 pregnant black women attending an antenatal clinic in 1981. The study confirmed the need for specimens from three sites (endocervix, urethra and rectum)--endocervical cultures were positive in only 75.9% of infected women, in the remainder only the urethral and/or rectal cultures were positive. Rectal cultures were positive in 41.6%. Cultures of throat swabs from 200 women were all negative for N. gonorrhoeae. In comparison with endocervical specimens directly plated, high vaginal swab specimens placed in Stuart's transport medium before plating gave a lower yield of positive cultures. No penicillinase-producing N. gonorrhoeae strains were detected.


Engineering muscle cell alignment through 3D bioprinting.
Processing of hydrogels represents a main challenge for the prospective application of additive manufacturing (AM) to soft tissue engineering. Furthermore, direct manufacturing of tissue precursors with a cell density similar to native tissues has the potential to overcome the extensive in vitro culture required for conventional cell-seeded scaffolds seeking to fabricate constructs with tailored structural and functional properties. In this work, we present a simple AM methodology that exploits the thermoresponsive behavior of a block copolymer (Pluronic® ) as a means to obtain good shape retention at physiological conditions and to induce cellular alignment. Pluronic/alginate blends have been investigated as a model system for the processing of C2C12 murine myoblast cell line. Interestingly, C2C12 cell model demonstrated cell alignment along the deposition direction, potentially representing a new avenue to tailor the resulting cell histoarchitecture during AM process. Furthermore, the fabricated constructs exhibited high cell viability, as well as a significantly improved expression of myogenic genes vs. conventional 2D cultures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2582-2588, 2017.


ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes.
The precise glycosyltransferase enzymes that mediate selectin-ligand biosynthesis in human leukocytes are unknown. This knowledge is important because selectin-mediated cell tethering and rolling is a critical component of both normal immune response and various vascular disorders. We evaluated the role of 3 α(2,3)sialyltransferases, ST3Gal-3, -4, and -6, which act on the type II N-Acetyllactosamine structure (Galβ1,4GlcNAc) to create sialyl Lewis-X (sLe(X)) and related sialofucosylated glycans on human leukocytes of myeloid lineage. These genes were either silenced using lentiviral short hairpin RNA (shRNA) or functionally ablated using the clustered regularly interspaced short palindromic repeat/Cas9 technology. The results show that ST3Gal-4, but not ST3Gal-3 or -6, is the major sialyltransferase regulating the biosynthesis of E-, P-, and L-selectin ligands in humans. Reduction in ST3Gal-4 activity lowered cell-surface HECA-452 epitope expression by 75% to 95%. Glycomics profiling of knockouts demonstrate an almost complete loss of the sLe(X) epitope on both leukocyte N- and O-glycans. In cell-adhesion studies, ST3Gal-4 knockdown/knockout cells displayed 90% to 100% reduction in tethering and rolling density on all selectins. ST3Gal-4 silencing in neutrophils derived from human CD34(+) hematopoietic stem cells also resulted in 80% to 90% reduction in cell adhesion to all selectins. Overall, a single sialyltransferase regulates selectin-ligand biosynthesis in human leukocytes, unlike mice where multiple enzymes contribute to this function.


Mechanical compression regulates tumor spheroid invasion into a 3D collagen matrix.
Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stress within the tumor. Although the effects of tension within 3D extracellular matrices on tumor growth and invasion are well established, the role of compression in tumor mechanics and invasion is largely unexplored. In this study, we modified a Transwell assay such that it provides constant compressive loads to spheroids embedded within a collagen matrix. We used microscopic imaging to follow the single cell dynamics of the cells within the spheroids, as well as invasion into the 3D extracellular matrices (EMCs). Our experimental results showed that malignant breast tumor (MDA-MB-231) and non-tumorigenic epithelial (MCF10A) spheroids responded differently to a constant compression. Cells within the malignant spheroids became more motile within the spheroids and invaded more into the ECM under compression; whereas cells within non-tumorigenic MCF10A spheroids became less motile within the spheroids and did not display apparent detachment from the spheroids under compression. These findings suggest that compression may play differential roles in healthy and pathogenic epithelial tissues and highlights the importance of tumor mechanics and invasion.


Neuroendocrine carcinomas of the skin: light microscopic, ultrastructural, and immunohistochemical analysis.
Three primary skin carcinomas were analyzed by light microscopy, immunohistochemistry, and electron microscopy. In all cases, local recurrences, regional lymph node metastases, distant metastases, or all three developed. One patient had elevated serum calcitonin levels that did not decrease after thyroidectomy but did return to normal after removal of the skin tumor recurrences, its metastases, or both. The tumor cells were arranged in solid clusters; a trabecular arrangement was occasionally seen. In 2 cases the cells were of intermediate size and showed vesicular central nuclei and pale, moderately abundant cytoplasm. In the remaining case the cells were distinctly smaller and either round or fusiform. Mitoses were more abundant in the latter case than in the former two. By immunohistochemistry, calcitonin- and somatostatin-containing cells were demonstrated in all cases and ACTH in one. By electron microscopy, the cases consisting of intermediate-size cells displayed moderately abundant neurosecretory-type granules irregularly dispersed throughout the cytoplasm. The case consisting of smaller cells displayed fewer and smaller granules that tended to concentrate in slender cytoplasmic processes. We conclude that these tumors constitute parts of the broadening spectrum of neuroendocrine skin carcinomas that may derive from Merkel cells.


[On acupuncture-moxibustion research needing dependence on clinical practice].
In this present paper, the current situation and the main features in acupuncture-moxibustion clinic are analyzed. The preliminary conclusion is that acupuncture-moxibustion research should proceed from the actual situation, take the treatment as the carrier, be scientifically designed and study in a deep-going way according to the methods of medical science for the acupuncture-moxibustion treatment with obvious clinical effect and specific action, then can get the scientific data and conclusion to illustrate the clinical problem and increase the therapeutic effect with important instruction significance for clinical practice. Clinical practice of acupuncture and moxibustion is the basis of all acupuncture-moxibustion research.


Dry Synthesis of Binder-Free Ruthenium Nitride-Coated Carbon Nanotubes as a Flexible Supercapacitor Electrode.
Ruthenium nitride was successfully deposited on a multiwalled carbon nanotube (MWCNT) forest grown on a stainless-steel mesh substrate by radiofrequency plasma-assisted pulsed laser deposition. This novel dry fabrication method for flexible supercapacitor electrodes eliminates toxic byproducts and the need for any binder component. Experimental results show a successful thin film coating of the individual MWCNTs with RuNx under various synthesis conditions. The electrochemical characterization demonstrates a significant improvement in capacitance of the synthesized RuNx-MWCNT electrode compared to the bare MWCNT forest, with a large potential window of 1.2 V. Capacitance values as high as 818.2 F g-1 (37.9 mF cm-2) have been achieved.


Label-free monitoring of cell death induced by oxidative stress in living human cells using terahertz ATR spectroscopy.
We demonstrated that attenuated total reflectance terahertz time-domain spectroscopy (ATR THz-TDS) is able to monitor oxidative stress response of living human cells, which is proven in this work that it is an efficient non-invasive, label-free, real-time and in situ monitoring of cell death. Furthermore, the dielectric constant and dielectric loss of cultured living human breast epithelial cells, and along with their evolution under oxidative stress response induced by high concentration of H2O2, were quantitatively determined in the work. Our observation and results were finally confirmed using standard fluorescence-labeled flow cytometry measurements and visible fluorescence imaging.


Dysphagia, medicines and older people: the need for education.
Dysphagia is particularly common in elderly patients and may contribute towards difficulties in swallowing solid dose medications. Two recent community surveys have revealed that the problem might be more prevalent in primary care than previously thought. The community nurse is particularly well placed to help identify patients with dysphagia and provide appropriate support and advice.


Conformational variability of nucleo-cytoplasmic transport factors.
The transport of macromolecules between the nucleus and cytoplasm of eukaryotic cells is largely mediated by a single family of transport factors, the karyopherin or importin beta-like family. Structural and biochemical evidence suggests conformational flexibility of these modular HEAT-repeat proteins is crucial for their regulation. Here we use small angle x-ray scattering to assess the extent of conformational variation within a set of nuclear import and export factors. The study reveals that importin beta, transportin, and the exportin Xpo-t share a similar S-like superhelical conformation in their unbound state. There are no obvious differences in the overall structures that might generally distinguish nuclear export from nuclear import mediators. Two other members of the family, the exportins Cse1 and Xpo1, possess a significantly more globular conformation, indicating that the extended S-like architecture is not a hallmark of all karyopherins. Binding of RanGTP/cargo to importin beta, transportin, and Xpo-t triggers distinct conformational responses, suggesting that even closely related karyopherins employ different mechanisms of conformational regulation and that cargo and nuclear pore-interacting surfaces of the different receptors may be unique.


The Effect of Irrigation Solutions on Recurrence of Chronic Subdural Hematoma: A Consecutive Cohort Study of 234 Patients.
Chronic subdural hematomas (CSDHs) occur often in elderly persons and can occur with mild head trauma. With burr-hole irrigation as standard treatment, symptoms usually improve and can be cured, and outcomes are good, but postoperative recurrences are a common problem. This study investigated the effectiveness and recurrence rates when using artificial cerebrospinal fluid (ACF) instead of normal saline (NS) as an irrigation solution for burr-hole irrigation in patients with CSDH. This prospective study included 234 consecutive patients who underwent initial surgical treatment by burr-hole irrigation for a CSDH between April 2008 and June 2015. The irrigation solution used was changed from NS to ACF in June 2011. Factors examined with regard to recurrence included age, sex, unilateral or bilateral surgery, computed tomography (CT) findings, antiplatelet or anticoagulant drug use, past history, and irrigation solution (NS or ACF). These were analyzed by univariate and multivariate analyses. Univariate analyses (chi-square test) with a significance level <5% showed that recurrence rates were significantly lower in the ACF group than in the NS group (P = 0.003). Multivariate analysis (multiple logistic regression analysis) showed that the risk of recurrence was reduced 3.14-fold in the ACF group compared to the NS group (odds ratio, 3.143; 95% confidence interval, 0.1504-0.6733; P = 0.0028). None of the other factors were significantly different. In burr-hole irrigation for CSDH, the use of ACF instead of NS as an irrigation solution significantly reduces recurrence rates.


Rising prevalence of non-B HIV-1 subtypes in North Carolina and evidence for local onward transmission.
HIV-1 diversity is increasing in North American and European cohorts which may have public health implications. However, little is known about non-B subtype diversity in the southern United States, despite the region being the epicenter of the nation's epidemic. We characterized HIV-1 diversity and transmission clusters to identify the extent to which non-B strains are transmitted locally. We conducted cross-sectional analyses of HIV-1 partial pol sequences collected from 1997 to 2014 from adults accessing routine clinical care in North Carolina (NC). Subtypes were evaluated using COMET and phylogenetic analysis. Putative transmission clusters were identified using maximum-likelihood trees. Clusters involving non-B strains were confirmed and their dates of origin were estimated using Bayesian phylogenetics. Data were combined with demographic information collected at the time of sample collection and country of origin for a subset of patients. Among 24,972 sequences from 15,246 persons, the non-B subtype prevalence increased from 0% to 3.46% over the study period. Of 325 persons with non-B subtypes, diversity was high with over 15 pure subtypes and recombinants; subtype C (28.9%) and CRF02_AG (24.0%) were most common. While identification of transmission clusters was lower for persons with non-B versus B subtypes, several local transmission clusters (≥3 persons) involving non-B subtypes were identified and all were presumably due to heterosexual transmission. Prevalence of non-B subtype diversity remains low in NC but a statistically significant rise was identified over time which likely reflects multiple importation. However, the combined phylogenetic clustering analysis reveals evidence for local onward transmission. Detection of these non-B clusters suggests heterosexual transmission and may guide diagnostic and prevention interventions.


4-Hydroxynonenal inhibits interleukin-1 beta converting enzyme.
Lipid peroxidation results from the interaction of reactive oxygen species and polyunsaturated fatty acids. Metabolites generated from oxidative stress play an important role in the pathogenesis of a variety of diseases and biologic processes. One such product generated from lipid peroxidation in 4-hydroxynonenal (HNE). HNE is thiol reactive and exhibits numerous cellular effects. In this study, the inhibition of the cysteine protease, interleukin-1 beta (IL-1 beta) converting enzyme (ICE), by HNE in human blood mononuclear cells was investigated. HNE blocked the release of lipopolysaccharide (LPS)-stimulated IL-1 beta (EC50 5 microM) and IL-10 (EC50 2 microM) in a dose-dependent manner and, to a lesser extent, tumor necrosis factor-alpha (TNF-alpha) (EC50 15 microM) release. However, LPS-stimulated elevation of intracellular proIL-1 beta levels was not affected by HNE treatment. HNE inhibited ICE activity in lysed cells in a similar dose-dependent manner, measured by hydrolysis of the fluorogenic substrate YVAD-AMC and recombinant proIL-1 beta. To confirm that the inhibition of ICE activity by HNE was not an indirect effect, ICE activity was examined using purified recombinant human ICE (rHu-ICE). HNE inhibited rHu-ICE activity in a dose-dependent manner. Thus, low levels of HNE can suppress mononuclear cell release of IL-1 beta, probably by interacting with the active site cysteine of ICE. These results have implications for modulating mononuclear cell function during oxidative stress conditions.


Silanizing agent for semipermanent wall coating in micellar electrokinetic capillary chromatography.
In this paper, the long-chained, silanizing agent chloro(dodecyl)dimethylsilane (CDDS) was investigated as a semipermanent coating in micellar electrokinetic capillary chromatography (MEKC). CDDS coating had great stability due to the formation of covalent bonding with the silanol groups on the surface of fused-silica capillary and remained stable for over 100 min after removal of the rinse step of CDDS solution. Anionic surfactant sodium dodecyl sulfate (SDS) could aggregate at this CDDS coating by the hydrophobic group and formed a SDS layer which could increase the electroosmotic flow (EOF). The separation was performed with the running buffer composed of 60mM sodium tetraborate, 12 mM SDS at pH 9.9, with the applied voltage of 20 kV and capillary temperature 25 degrees C. The effect of the coating agent was investigated by the analysis of amino acids. Compared with previous no-coating method, the EOF increases from 4.34 x 10(-4)cm(2)V(-1)s(-1) to 7.02 x 10(-4)cm(2)V(-1)s(-1). Migration time reproducibility was less than 0.97% R.S.D. from run to run and less than 1.56% R.S.D. from day to day.


Human papillomavirus (HPV) infections involved in the neoplastic process of the uterine cervix as established by prospective follow-up of 513 women for two years.
A total of 513 women with cervical HPV infections have been followed-up since 1981 (mean 25.6 months) to establish the biological potential of HPV in cervical carcinogenesis. On each attendance, the patients were subjected to colposcopy accompanied by Papanicolaou (PAP) smears and/or punch biopsies. The latter were analysed for HPV particles on TEM, for the cytopathic changes of HPV, as well as for HPV structural proteins. The local immunocompetent cell (ICC) infiltrates are enumerated using ANAE-technique to define B-, MPS- and T cells, and monoclonal antibodies for T cell subsets, NK and K cells and Langerhans cells. HPV DNA typing was accomplished by Southern blot and spot hybridization using the DNA probes for HPV 6, 11, 16 and 18. Antibody titres for HSV were measured, and Chlamydia trachomatis isolations completed in cervical swabs. No correlation with the clinical course, e.g. regression (RE), persistence (PE), progression (PR) or recurrence (RC) of the HPV lesions could be established for the following factors; expression of HPV antigens, presence of HPV particles on TEM, Chlamydia in cervical swabs, the levels of HSV antibodies, and the levels of the ICCs. The OKT4+/OKT8+ cell ratio, however, was inversely correlated with PR, being most markedly reduced in recurrent lesions. Of the 513 lesions, 24.8% regressed, 59.8% remained persistent, and 14.1% progressed, 11.9% having been coned due to progression into CIS. So far, 1.1% of lesions have recurred after such a treatment. The progression rate was highest (45.5%) in HPV 16 lesions, followed by that (27.3%) in HPV 18 lesions, as contrasted to 0% and 13.3% for HPV 6 and 11, respectively. The results clearly confirm that cervical HPV infections are capable of progressing into CIS and thus show a natural history equivalent to that of classical CIN. The inherent potential of HPV 16 and HPV 18 lesions for clinical progression was clearly established, supporting the concept on HPV 16 and HPV 18 as the high risk HPV types in cervical carcinogenesis.


Quantification of wrist joint laxity.
Laxity may be a trigger for chronic unidentified wrist pain. To determine whether this is the case, first an objective method to quantify wrist laxity needs to be defined. This study investigates different quantification methods (reference tests) from the literature and compares these with the judgment of 2 independent experienced clinicians (index test, or gold standard). Fifty healthy women (ages 19-43 y) without wrist complaints were included. For each subject, both clinicians were asked to give a laxity score for both wrists on a Likert scale of 1 to 5 (1 = very stiff, 5 = very lax). Subjects also had 3 reference tests: the Garcia-Elias method (passive range of motion), the Beighton method (general hypermobility), and the active range of motion method (specially designed measurement device). There was no significant difference between the average laxity scores of clinicians 1 and 2. The intraclass correlation between clinician 1 and clinician 2 was significant but low. Correlation between the clinicians with the Garcia-Elias test as well as the Beighton method was significant but low (0.431 and 0.378). The correlation between reference tests was higher but still moderate. This study showed that the index test used (clinical assessment) did not produce a satisfactory quantification of wrist laxity. Also, the reference tests are not suitable for quantification of laxity and seem to measure mobility rather than laxity. To quantify wrist laxity in a reliable and clinically relevant manner, it seems that consensus needs to be established between clinicians as to what elements of (abnormal) wrist motion define the wrist as "lax." In addition the development and testing of a measurement device that quantifies wrist translation might be needed for determining an objective score for wrist laxity.


Tubulins and brain development - The origins of functional specification.
The development of the vertebrate central nervous system is reliant on a complex cascade of biological processes that include mitotic division, relocation of migrating neurons, and the extension of dendritic and axonal processes. Each of these cellular events requires the diverse functional repertoire of the microtubule cytoskeleton for the generation of forces, assembly of macromolecular complexes and transport of molecules and organelles. The tubulins are a multi-gene family that encode for the constituents of microtubules, and have been implicated in a spectrum of neurological disorders. Evidence is building that different tubulins tune the functional properties of the microtubule cytoskeleton dependent on the cell type, developmental profile and subcellular localisation. Here we review of the origins of the functional specification of the tubulin gene family in the developing brain at a transcriptional, translational, and post-transcriptional level. We remind the reader that tubulins are not just loading controls for your average Western blot.


High-Resolution Finger MRI: What Should You Look for in Trauma of the Fingers?
The fingers are among the most commonly injured structures in traumatic injuries resulting from sports and work. Finger injuries encompass a broad spectrum of injuries to bone and soft tissues, including tendons, ligaments, and cartilage. The high resolution of 3T MRI with dedicated surface coils allows for optimal assessment of the intricate soft tissue structures of the fingers. There have been several reports on detailed MRI features of the basic anatomy and common pathological findings of the finger and hand. Understanding the normal anatomy and familiarization with common traumatic lesions of the ligaments, tendons, and pulleys of the fingers on high-resolution MRI will allow radiologists to perform accurate preoperative evaluations of traumatic hand lesions. The purpose of this study is to review the normal hand anatomy and common traumatic lesions of the finger on high-resolution MRI and correlate them with surgical findings.


Mathematical descriptions of hybridoma culture kinetics: I. Initial metabolic rates.
The lack of quantitative descriptions of mammalian culture kinetics limits the ability to optimally design and control cell culture bioreactors. This limitation is ad dressed by developing mathematical equations relating the initial growth rate and the antibody productivity of the hybridoma cell line, CRL-1606, to its environmental state. This initial rate approach, in contrast with steady state analysis of chemostat cultures, approximates steady state behavior, since the rates were measured over brief time intervals and at low cell concentrations (< 50,000 cells/mL). The advantage of this approach is that it is much faster than the chemostat approach.An equation for the growth rate was developed that superimposed Monod equations in serum and glutamine with "noncompetitive" -type inhibition constants were inversely proportional to the lactate and ammonium concentrations. The Monod constant is critical for relating initial, low cell level culture states to other states.Lactate was found to be the only environmental parameter that significantly inhibited antifibronectin monoclonal antibody production by the CRL-1606 hybridomas. Volumetric productivity was strictly related to culture viability, which was observed to decline at growth rates below 0.02 h(-1). Lactate was also found to significantly inhibit ammonium production.


Embryonic origin of hemocytes and their relationship to cell death in Drosophila.
We have studied the embryonic development of Drosophila hemocytes and their conversion into macrophages. Hemocytes derive exclusively from the mesoderm of the head and disperse along several invariant migratory paths throughout the embryo. The origin of hemocytes from the head mesoderm is further supported by the finding that in Bicaudal D, a mutation that lacks all head structures, and in twist snail double mutants, where no mesoderm develops, hemocytes do not form. All embryonic hemocytes behave like a homogenous population with respect to their potential for phagocytosis. Thus, in the wild type, about 80-90% of hemocytes become macrophages during late development. In mutations with an increased amount of cell death (knirps; stardust; fork head), this figure approaches 100%. In contrast, in these mutations, the absolute number of hemocytes does not differ from that in wild type, indicating that cell death does not 'induce' the formation of hemocytes. Finally, we show that, in the Drosophila embryo, apoptosis can occur independently of macrophages, since mutations lacking macrophages (Bicaudal D; twist snail double mutants; torso4021) show abundant cell death.


A peptide from insects protects transgenic tobacco from a parasitic weed.
Parasitic plants present some of the most intractable weed problems for agriculture in much of the world. Species of root parasites such as Orobanche can cause enormous yield losses, yet few control measures are effective and affordable. An ideal solution to this problem is the development of parasite-resistant crops, but this goal has been elusive for most susceptible crops. Here we report a mechanism for resistance to the parasitic angiosperm Orobanche based on expression of sarcotoxin IA in transgenic tobacco. Sarcotoxin IA is a 40-residue peptide with antibiotic activity, originally isolated from the fly, Sarcophaga peregrina. The sarcotoxin IA gene was fused to an Orobanche-inducible promoter, HMG2, which is induced locally in the host root at the point of contact with the parasite, and used to transform tobacco. The resulting transgenic plants accumulated more biomass than non-transformed plants in the presence of parasites. Furthermore, plants expressing sarcotoxin IA showed enhanced resistance to O. aegyptiaca as evidenced by abnormal parasite development and higher parasite mortality after attachment as compared to non-transformed plants. The transgenic plants were similar in appearance to non-transformed plants suggesting that sarcotoxin IA is not detrimental to the host.


Genetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carriers.
In this report, we have tried to gain molecular insight into a single nucleotide polymorphism (SNP) in the NEIL2 gene previously identified as "cancer risk modifier" for BRCA2 mutation carriers. To that end, we studied the role of this SNP (rs804271) on NEIL2 transcriptional regulation, oxidative DNA damage and genome instability in two independent set of samples: The first one was a series of eighty-six BRCA1 and BRCA2 mutation carriers and eighty non-carrier controls in which we evaluated the effect of the SNP on NEIL2 gene expression and oxidative DNA damage accumulation. The second was a set of twenty lymphoblastoid cell lines (LCLs), thirteen BRCA1 mutation carriers and seven non-carriers control, that were used to analyze the correlation between NEIL2 mRNA and/or protein levels, the oxidative and the double stranded break (DSB) DNA damage levels. Our results suggest that an excessive production of NEIL2 enzyme, associated with the SNP, may have a deleterious effect modifying cancer risk susceptibility in BRCA2 mutation carriers. We hypothesize that due to the SNP impact on NEIL2 transcriptional upregulation, a cascade of events may converge in the accumulation of oxidative DNA damage and its posterior conversion into DSBs for this specific group of patients.


The Predictive Role of Low Spatial Frequencies in Automatic Face Processing: A Visual Mismatch Negativity Investigation.
Visual processing is thought to function in a coarse-to-fine manner. Low spatial frequencies (LSF), conveying coarse information, would be processed early to generate predictions. These LSF-based predictions would facilitate the further integration of high spatial frequencies (HSF), conveying fine details. The predictive role of LSF might be crucial in automatic face processing, where high performance could be explained by an accurate selection of clues in early processing. In the present study, we used a visual Mismatch Negativity (vMMN) paradigm by presenting an unfiltered face as standard stimulus, and the same face filtered in LSF or HSF as deviant, to investigate the predictive role of LSF vs. HSF during automatic face processing. If LSF are critical for predictions, we hypothesize that LSF deviants would elicit less prediction error (i.e., reduced mismatch responses) than HSF deviants. Results show that both LSF and HSF deviants elicited a mismatch response compared with their equivalent in an equiprobable sequence. However, in line with our hypothesis, LSF deviants evoke significantly reduced mismatch responses compared to HSF deviants, particularly at later stages. The difference in mismatch between HSF and LSF conditions involves posterior areas and right fusiform gyrus. Overall, our findings suggest a predictive role of LSF during automatic face processing and a critical involvement of HSF in the fusiform during the conscious detection of changes in faces.


Can we predict if patients with SLE will require more than one cycle of rituximab?
To identify clinical and serological features that distinguish patients with SLE who require single as opposed to repeated rituximab (RTX) cycles. All 175 SLE patients followed up at University College Hospital from 2000 onwards were retrospectively reviewed. They were divided into a one-RTX-cycle group and a multiple-cycle group (2 or more cycles). Patients included had a follow-up of at least 3 years after their first RTX cycle, unless they needed a second infusion sooner. A total of 131 patients were included; 44 (33.6%) received one cycle of RTX and 87 (66.4%) received two or more. The former were older at diagnosis (31.4 vs 21 years, P < 0.001) and at first RTX infusion (39.9 vs 29 years, P < 0.001). This group of patients had more organs/systems involved (P = 0.044), more leukopenia, lymphopenia and thrombocytopenia (P = 0.001, P < 0.0001 and P = 0.003, respectively) and lower C3 levels (P = 0.035). They also had fewer immunosuppressive drugs before RTX therapy compared with those who required multiple RTX cycles (P = 0.003). There was no statistical difference in either the clinical or serological response after the first RTX cycle between both groups. Furthermore, patients who had received more immunosuppressive treatments were more likely to require more than one cycle of RTX infusions (P = 0.007). RTX is an effective option for SLE patients with severe flares. Patients who received more immunosuppressive drugs were more likely to receive more than one set of RTX infusions. This suggests that RTX is best used for SLE patients with no history of refractory disease.


Cardiovascular Risk Profile of Chimeric Antigen Receptor T-cell Therapy.
Chimeric antigen receptor (CAR) T-cell therapy is a novel form of immunotherapy that has been recently introduced in clinical practice for the treatment of leukemias and lymphomas after being approved by United States Food and Drug Administration (USFDA). The risk profile of this treatment modality is not yet fully explored. As the survival of cancer patients is expected to rise due to new therapies being brought into practice, physicians are going to encounter side effects of these therapies. This may include both short-term and long-term effects. Having a good knowledge of these side effects can help the physicians recognize in advance the at-risk population and risk stratify them accordingly. Cardiac oncology is a growing field that involves the study of interaction between novel immunotherapies and their cardiac side effects. Knowing the cardiotoxicity profile of CAR T-cell therapy will help us choose the most appropriate patient population (those who can benefit the most without being at risk of harmful effects including cardiotoxicity) for the therapy. It will also help us recognize various cardiac complications, as they arise later during the lifetime of these cancer survivors.


Calcitonin and postmenopausal osteoporosis.
Fasting serum calcitonin levels were measured in 54 postmenopausal women who had for 10 years been taking part in a double blind trial to assess the effect of the synthetic oestrogen, mestranol, on postmenopausal bone loss. There were no differences in calcitonin levels between mestranol treated and placebo groups. Fifteen of the women were challenged with a calcium infusion to measure the secretory reserve of calcitonin. Oestrogen treatment did not increase the calcitonin response to calcium infusion. The three patients who exhibited the greatest responses were placebo treated. Bone density was measured by gamma-ray absorptiometry over the ten year period and the annual rate of change of bone density calculated. No correlation could be found between basal calcitonin level or calcitonin reserve and change in bone density. Our results indicate that postmenopausal osteoporosis is not caused by a deficiency of calcitonin and that the action of oestrogen therapy to prevent bone loss does not involve calcitonin.


Alcohol and health in Central and Eastern European Union countries - status quo and alcohol policy options.
The aim of this narrative review is to give an overview of alcohol consumption, attributable health harm, and potential alcohol control policies to reduce this harm in five Central and Eastern European Union countries: Czech Republic, Estonia, Latvia, Lithuania, and Poland. The overall level of alcohol consumption was high, with the two highest-consuming countries in the world being situated in Central and Eastern Europe (Czech Republic, Latvia), and all five of these countries being in the top 15% of World Health Organization member states with respect to consumption. Accordingly, alcohol-attributable health harm was high. Implementation of alcohol control policies could be improved, especially the implementation of pricing policies such as taxation increases. A moderate increase of the tax share on alcohol could result in thousands of lives being saved in Central and Eastern Europe in a single year. As taxation increases not only save lives, but also increase state revenue, the implementation of this alcohol control measure should be made a priority.


The effect of dopamine on renal microcirculation in hemorrhagic shock in dogs.
Dopamine, a naturally occuring catecholamine, was infused at the rate of 6 micrograms per kilogram per minute on an hemorrhagic shock model in dogs. Urinary output was continuously recorded, with arterial pressure being maintained at 50 millimeters of mercury. At the termination of the experiment, the dogs were sacrificed, and renal microcirculation was studied by an angiomicrohistologic technique. There was a dramatic increase in urinary output following the infusion of dopamine. Results of the microcirculatory study of the renal vasculature showed markedly increased cortical perfusion and dilation of vessels, particularly at a level of afferent arterioles; however, findings on efferent arterioles were inconsistent. Also, changes in the microvasculature of the medulla were less striking than those of the cortex following the administration of dopamine.


Mutation of the Carboxy-Terminal Processing Protease in Acinetobacter baumannii Affects Motility, Leads to Loss of Membrane Integrity, and Reduces Virulence.
Motility plays an essential role in the host-parasite relationship of pathogenic bacteria, and is often associated with virulence. While many pathogenic bacteria use flagella for locomotion, Acinetobacter baumannii strains do not have flagella, but have other features that aid in their motility. To study the genes involved in motility, transposon mutagenesis was performed to construct A. baumannii mutant strains. Mutant strain MR14 was found to have reduced motility, compared to wild-type ATCC 17978. NCBI BLAST analysis revealed that the Tn10 transposon in the MR14 genome is integrated into the gene that encodes for carboxy-terminal processing protease (Ctp). Additionally, MR14 exhibits a mucoidy, sticky phenotype as the result of increased extracellular DNA (eDNA) caused by bacterial autolysis. Transmission and scanning electron microscopy revealed cytoplasmic content leaving the cell and multiple cell membrane depressions, respectively. MR14 showed higher sensitivity to environmental stressors. Mutation of the ctp gene reduced invasion and adhesion of A. baumannii to airway epithelial cells, potentially due to increased hydrophobicity. In the zebrafish model of infection, MR14 increased the survival rate by 40% compared to the wild-type. Taken together, the ctp gene in A. baumannii has a pivotal role in maintaining membrane integrity, adaptation to environmental stress, and controlling virulence.


Diabetes self-management education interventions in the WHO African Region: A scoping review.
Diabetes mellitus (DM) is one of the commonest chronic diseases worldwide. Self-Management Education (SME) is regarded as a critical element of treatment for all people with diabetes, as well as those at risk of developing the condition. While a great variety of diabetes self-management education (DSME) interventions are available in high-income countries, limited information exists on educational programs for the prevention and management of diabetes complications in Africa. This study, therefore, aimed at synthesizing information in the literature to describe the state of the science of DSME interventions in the WHO African Region. The study is a scoping review, which followed the standard PRISMA guidelines for conducting and reporting scoping reviews. A systematic keyword and subject headings searches were conducted on six electronic databases (PubMed, Scopus, MEDLINE, EMBASE, PsychINFO and the Cochrane Central Register of Controlled Trials) to identify relevant English language publications on DSME from 2000 through 2020. Titles and abstracts of the search results were screened to select eligible papers for full text reading. All eligible papers were retrieved and full text screening was done by three independent reviewers to select studies for inclusion in the final analysis. Nineteen studies were included in the review. The interventions identified were individually oriented, group-based, individually oriented & group-based, and information technology-based DSME programs. Outcomes of the interventions were mixed. While the majority yielded significant positive results on HbA1c, diabetes knowledge, blood pressure, blood sugar and foot care practices; few demonstrated positive outcomes on self-efficacy, BMI, physical activity; self-monitoring of blood glucose, medication adherence, smoking and alcohol consumption. The limited studies available indicate that DSME interventions in the WHO African Region have mixed effects on patient behaviors and health outcomes. That notwithstanding, the majority of the interventions demonstrated statistically significant positive effects on HbA1c, the main outcome measure in most DSME intervention studies.


Fatty acid transport: difficult or easy?
Transport of unesterified fatty acids (FA) into cells has been viewed either as a simple diffusion process regulated mainly by lipid physical chemistry or as a more complex process involving protein catalysis. In this review FA transport in cell membranes is broken down into three essential steps: adsorption, transmembrane movement, and desorption. The physical properties of FA in aqueous, membrane, and protein environments relevant to transport mechanisms are discussed, with emphasis on recent information derived from NMR and fluorescence studies. Because of their low solubility in water and high hydrophobicity, FA bind rapidly and avidly to model membranes (phospholipid bilayers); if albumin is a donor, FA desorb rapidly to reach their equilibrium distribution between the membrane and albumin. The ionization properties of FA in a phospholipid bilayer result in a high population of the un-ionized form (approximately 50%) at pH 7.4, which diffuses across the lipid bilayer (flip-flops) rapidly (t(1/2) < 1 sec). Desorption of FA from a phospholipid surface is slower than transmembrane movement and dependent on the FA chain length and unsaturation, but is rapid for typical dietary FA. These physical properties of FA in model systems predict that proteins are not essential for transport of FA through membranes. The only putative FA transport protein to be purified and reconstituted into phospholipid bilayers, the mitochondrial uncoupling protein (UCP1), was shown to transport the FA anion in response to FA flip-flop. New experiments with cells have found that FA movement into cells acidifies the cytosol, as predicted by the flip-flop model.


Atypical information-use in children with autism spectrum disorder during judgments of child and adult face identity.
Unusual patterns of fixation behavior in individuals with autism spectrum disorder during face tasks hint at atypical processing strategies that could contribute to diminished face expertise in this group. Here, we use the Bubbles reverse correlation technique to directly examine face-processing strategies during identity judgments in children with and without autism, and typical adults. Results support a qualitative atypicality in autistic face processing. We identify clear differences not only in the specific features relied upon for face judgments, but also more generally in the extent to which they demonstrate a flexible and adaptive profile of information use.


Optical coherence tomography as an adjunct to white light cystoscopy for intravesical real-time imaging and staging of bladder cancer.
Optical coherence tomography (OCT) is a novel, real-time endoscopic imaging modality that permits delineation of microarchitectural features of bladder lesions. It may provide an extension of conventional cystoscopy by allowing noninvasive examination of bladder tissue at microscopic resolution (10 to 20 microm). The purpose of this study was to examine the application of OCT in augmenting the diagnosis and staging of bladder lesions. We conducted a retrospective institutional review board-approved, single-institution, single-user review on the use of OCT as an adjunct to conventional cystoscopy in 32 patients with a history of bladder cancer (24), primary tumor (6), prostate cancer (1), or hematuria (1). We obtained OCT images of suspicious areas before biopsy or resection, interpreted them in real time, and subsequently compared them with pathology results. We obtained 94 images in 32 patients undergoing bladder biopsy or transurethral resection of bladder tumor. Age of the patients ranged from 49 to 84 years (mean, 59 years), with 25 men (78%) and 7 women (22%). We correlated 38 suspicious areas with biopsy findings. OCT imaging correctly identified tumors confined to the mucosa with a sensitivity and specificity of 90% and 89%, respectively. Muscle-invasive tumors were detected in 7 of 7 lesions with 100% sensitivity, 90% specificity, and 92% accuracy. Optical coherence tomography is a rapid, easy-to-use tool that can help differentiate Ta and T1 tumors and identify muscle-invasive bladder tumors. It provides real-time microarchitectural information that can aid in the evaluation of bladder tumors and adjacent and remote urothelium.


Effect of four thiol-containing chelators on disposition of orally administered mercuric chloride.
Acute toxicity and the disposition of inorganic mercury depends on the route of exposure. Most previous studies on effect of chelators on inorganic mercury toxicity and toxicokinetics employed parenteral administration of both metal and chelator. However, the most prominent routes for human inorganic mercury exposure are the oral or pulmonary. BAL was previously considered the drug of choice in human intoxications with most heavy metals. This recommendation has been questioned during recent years due to the advent of the less toxic hydrophilic BAL analogues DMSA and DMPS. The present study, using oral administration of HgCl2 labelled with 203Hg, demonstrates that DMPS is superior to the other chelators in preventing mortality. Moreover, both DMSA and DMPS are superior to BAL and NAPA in alleviating acute toxicity and in preventing the undesirable distribution of orally administered mercury, especially to the brain. Further, oral administration of these chelators were more efficient than parenteral administration in reducing whole-body retention and organ deposition of orally administered mercuric chloride, most likely due to the prevention of intestinal uptake of mercury.


Targeting T cell activation in immuno-oncology.
The years since 2009 have seen tremendous progress in unlocking the curative potential of the immune system for the treatment of cancer. Much of that revolution in immuno-oncology has been fueled by the clinical success of immune checkpoint inhibitors, particularly those targeting the PD-1 axis. Unfortunately, many patients still fail to benefit from checkpoint blockade or other immunotherapies. An inability to fully activate antitumour T cells contributes in part to the failure of those therapies. Here, we review the basic biology of T cell activation, with particular emphasis on the essential role of the dendritic cell and the innate immune system in T cell activation. The current understanding of the multiple factors that govern T cell activation and how they impinge on tumour immunotherapy are also discussed. Lastly, treatment strategies to potentially overcome barriers to T cell activation and to enhance the efficacy of immunotherapy are addressed.


Aberrant right subclavian artery presenting as tracheoesophagial fistula in a 50-year-old lady: Case report of a rare presentation of a common arch anomaly.
A 50-year-old, woman with a 2-year history of progressive dysphagia and 2-month history of chronic cough was referred to our center in a state of generalized sepsis. Provisional diagnosis of carcinoma esophagus with tracheoesophagial fistula was made. Evaluation of the patient revealed an aberrant right subclavian artery with retroesophageal course with compression of the esophagus and trachea with fistulous communication in between. The patient was managed with medical stabilization and with feeding jejunostomy, but she succumbed to underlying severe sepsis. This presentation of aberrant subclavian artery at this advanced age rare and is therefore reported.


Individualized early goal-directed therapy in systemic inflammation: is full utilization of preload reserve the optimal strategy?
In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals. Prospective, randomized animal study. University animal research laboratory. Thirty domestic pigs. After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal. Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (-90.76% [study group] vs -130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025). Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.


Multi-frequency, multi-technique pulsed EPR investigation of the copper binding site of murine amyloid β peptide.
Copper-amyloid peptides are proposed to be the cause of Alzheimer's disease, presumably by oxidative stress. However, mice do not produce amyloid plaques and thus do not suffer from Alzheimer's disease. Although much effort has been focused on the structural characterization of the copper- human amyloid peptides, little is known regarding the copper-binding mode in murine amyloid peptides. Thus, we investigated the structure of copper-murine amyloid peptides through multi-frequency, multi-technique pulsed EPR spectroscopy in conjunction with specific isotope labeling. Based on our pulsed EPR results, we found that Ala2, Glu3, His6, and His14 are directly coordinated with the copper ion in murine amyloid β peptides at pH 8.5. This is the first detailed structural characterization of the copper-binding mode in murine amyloid β peptides. This work may advance the knowledge required for developing inhibitors of Alzheimer's disease.


Health-promotion research over three decades: The social-ecological model and challenges in implementation of interventions.
This debate paper traces the development of innovative methods for undertaking health promotion research with a socialecological orientation, with a few examples drawn from 30 years of research on adolescent health promotion research at the University of Bergen. We aim to show how the social-ecological model is becoming more evident as a guide to research, using three cases that illustrate progress and potential. The first case is the Norwegian part of the European Network of Health Promoting Schools. The second case is a project just underway, The COMPLETE study, which is a community-led effort to promote students' mental health and create a good psychosocial learning environment. The third case is a developing idea for the next generation of social-ecological research on adolescent well-being, using an asset approach to foster social inclusion and sense of community in multiple settings.


Lens Densitometry after Corneal Cross-linking in Patients with Keratoconus Using a Scheimpflug Camera.
To evaluate changes in crystalline lens densitometry following corneal cross-linking (CXL) in keratoconic patients. In a quasi-experimental study, three-dimensional lens densitometry was performed using the Pentacam Scheimpflug camera (Oculus Optikgerate GmbH, Wetzlar, Germany) at baseline and six months after CXL. Densitometry was performed in a fixed area of 2 inch × 1 inch of the anterior capsule and anterior lens cortex. The subject group included patients with progressive keratoconus who underwent CXL (n = 40) and the control group was comprised of aged-matched patients with non-progressive keratoconus (n = 36). Mean age of the case and control groups was 25.8 ± 4.0 and 25.0 ± 4.1 years, respectively (P = 0.392). Mean lens density in the CXL group was 6.68% ± 0.58% at baseline and 6.77% ± 0.53% at the last visit (P = 0.352). Corresponding figures in the control group were 6.53% ± 0.27% and 6.39% ± 0.31%, respectively (P = 0.213). There was no significant difference between the study groups at baseline or six months later (P = 0.96). In this short term study with six months' follow-up, we observed no significant impact on lens density following exposure of the crystalline lens to ultraviolet A and riboflavin free radicals in the CXL procedure.


Field trial efficacy of Anvil 10+10 and Biomist 31:66 against Ochlerotatus sollicitans in Delaware.
Anvil 10+10 (hereafter Anvil) and Biomist 31:66 (hereafter Biomist) were applied by ground ultra-low volume (ULV) methods to determine the effectiveness of each formulation against Ochlerotatus sollicitans. Each formulation was tested at 50, 67, and 100% of respective maximum label dosage rates. Mosquitoes were exposed in cages on a 3 x 3 grid at distances of 30.5, 60.9, and 91.4 m. Mortality data were collected at intervals of 1, 4, and 12 h after treatment. No significant differences (P > or = 0.05) were found among formulations at applications of 100% of the label rate and no significant differences (P > or = 0.05) were found between Anvil applied at 100% of the label rate and Biomist applied at 50 and 67% of label rates. Ground ULV applications of Anvil at 100% label rate and Biomist at all tested rates were effective (> or = 95% mortality) adulticides. Applications of Anvil at 50 and 67% label rates were significantly less effective (P < or = 0.05) than applications of Biomist at equal percentages of the maximum label rate. Applications of Anvil at rates of 50 and 67% were not effective.


Wavelength dependence of inactivation and membrane damage to Saccharomyces cerevisiae cells by monochromatic synchrotron vacuum-uv radiation (145-190 nm).
Using an electron storage ring as a source of radiation, the wavelength dependence of inactivation and membrane damage in yeast cells (Saccharomyces cerevisiae) was investigated in the range from 145 to 254 nm, with special reference to the effects of vacuum-uv radiation. The cells were irradiated on a Millipore filter in a moist chamber filled with water vapor (deoxygenated) at saturation pressure. Fluence-survival curves taken at 5-nm intervals were generally sigmoidal. Action spectra of the two types of effects were nearly identical in shape. The maximum occurred in both spectra at 160 nm, decreasing sharply toward 180 nm. The spectra remarkably resembled the calculated absorption spectrum of (liquid) water in the range from 145 to 170 nm; the spectra had no similarity at all to the absorption spectra of DNA, proteins, or lipids. These data support the theory that inactivation of wet cells by vacuum-uv radiation may be attributable to damage in the cell membrane initiated by the absorption of water molecules. Above 210 nm the spectrum for inactivation paralleled the absorption of DNA. Genetic changes (induction of gene conversion) were also observed above 210 nm. Photoreversion for the induced convertants was detectable only above 220 nm. These characteristics are consistent with the expectation that above 210 nm the site of major lethal damage shifts to DNA.


Unusual renal manifestation of Caroli disease: AA amyloidosis.
Congenital hepatic fibrosis is a fairly uncommon disorder and it is usually associated with other fibropolycystic disorders, including renal involvement. Main clinical features are hepatic fibrosis, portal hypertension, and renal cystic disease. There are multifocal saccular dilatations of segmental bile ducts, usually with accompanying calculi formation and recurrent bacterial cholangitis. Renal cystic disorders are common complications of Caroli disease (CD), but renal amyloidosis is fairly uncommon. We present a patient who was diagnosed with CD at the age of 31 years and in whom renal AA amyloidosis developed at the age of 45 years due to recurrent bacterial cholangitis.