The association between the serum concentration of CXC subfamily chemokine 13 and post-surgical clinical outcomes in cervical cancer patients.
This study aimed to investigate the relationship between serum levels of CXC subfamily chemokine 13 (CXCL13) and clinical outcomes following radical surgery for cervical cancer. A total of 70 cervical cancer patients admitted to our hospital between August 2021 and December 2022 were selected as the study group, while 30 healthy individuals who underwent regular physical examinations during the same period were selected as the control group. The levels of CXCL13 were measured in both groups, and a comparison was made between pre- and post-operative CXCL13 levels in the study group and the control group. Follow-up data on clinical outcomes were collected for the study group, and clinical data were compared between the recurrence/metastasis group and the non-recurrence/metastasis group. Logistic regression analysis was performed to identify factors influencing recurrence and metastasis by incorporating variables showing significant differences. Additionally, Pearson's correlation analysis was used to examine the relationship between CXCL13 and clinical data. Postoperative levels of CXCL13 in the study group showed a significant decrease compared to preoperative levels, and they were lower than those in the control group (p<0.05). Among the 70 patients in the study group, 23 experienced recurrence or metastasis, while 47 did not. Significant differences were observed between the recurrence/metastasis group and the non-recurrence/metastasis group in terms of histological grade, depth of cervical invasion, FIGO stage, parametrial infiltration, lymph node metastasis, and CXCL13 (p<0.05). Logistic regression analysis revealed that CXCL13, histological grade, depth of cervical invasion, FIGO stage, parametrial infiltration, and lymph node metastasis were all factors influencing recurrence and metastasis. There was a positive correlation between CXCL13 and histological grade, depth of cervical invasion, FIGO stage, parametrial infiltration, and lymph node metastasis (p<0.05). The level of CXCL13 is closely associated with the clinical outcome of cervical cancer after radical surgery and can serve as an important indicator for predicting clinical outcomes. Its application in clinical practice is highly recommended.


Triptan nonresponder studies: implications for clinical practice.
The maximum absolute response rate with oral triptans, as measured in clinical trials by the incidence of relief from migraine pain at 2 hours after taking medication, is approximately 70%. Therefore around 30% of patients fail to respond to a particular triptan. Nonresponse is likely to be due to a variety of factors, including low and inconsistent absorption, use of the medication late in an attack, inadequate dosing, and variability in individual response. Evidence from recent clinical trials, however, confirms the common clinical observation that patients with a poor response to one triptan can benefit from subsequent treatment with a different triptan. Two-hour pain-relief rates of 25% to 81% using alternative triptans (naratriptan, almotriptan, eletriptan, zolmitriptan, and rizatriptan) have been reported in patients who were described as poor responders to sumatriptan. Physicians should remain vigilant in assessing the response to acute therapy and take advantage of simple clinical questionnaires that have been developed to facilitate the recognition of those patients who require and may benefit from a change in acute therapy.


Examining the meaning of the language used to communicate the nursing hand-off.
The miscommunication and inconsistent recall of patient information due to cognitive lapses that occur during the hand-off between healthcare providers account for 80% of sentinel events in acute care. Cognitive lapses are a consequence of the nurse experiencing cognitive overload, which impedes the nurse's ability to recall relevant information during and after the hand-off communication. The primary cognitive and human factor contributing to cognitive overload in the hand-off is language. The purpose of this study was to examine the meaning of the language used to communicate the nurse-to-nurse change of shift hand-off occurring at bedside and nonbedside on a medical-surgical unit in an urban medical center. A qualitative descriptive design was used. The sample was 10 audio-recorded hand-offs (five bedside and five nonbedside), with a total of 19 nurses participating. A natural language process program was used to analyze the data. The hand-off is a narrative story centered on communicating patient information delivered with a high degree of confidence. The hand-off is focused on past and current events with minimal focus on future or anticipated events. The drive to communicate is minimally based on concern, fear, or danger. There is a difference in the language used to communicate the nursing hand-off message at bedside as compared to the nonbedside hand-off.


Channeling and dampening: The role of political ties in information disclosure and concealment.
Non-profit organizations (NPOs) help the state achieve its social objectives. At the same time, they often depend on the private-sector actors for donations. The different beliefs of public- and private-sector actors regarding which practices are desirable for NPOs can affect the transparency of these organizations. We propose that political ties influence NPOs to comply with state-mandated disclosure requirements, while simultaneously dampening their willingness to voluntarily disclose sensitive information that may jeopardize their legitimacy in the eyes of private-sector stakeholders. The impact of political ties on disclosure is contingent upon two factors. First, market institutions moderate such effects because expectations of public- and private-sector actors may diverge more in freer markets than where the state has inordinate power. Second, financial dependence on the state amplifies both effects as dependence on the state exerts more pressure for compliance whilst making politically connected organizations appear even more questionable in the eyes of the private-sector stakeholders. Leveraging a policy shock that weakened political ties, we found that following the policy shock, charities in China reduced their compliance to state-mandated information disclosure, but increased their voluntary disclosure. The opposing roles of political ties in mandatory versus voluntary disclosure is further supported by a policy capturing study involving private donors in China. This study has important implications for research on political ties and information disclosure.


Comparison of the Efficacy of Tibolone and Transdermal Estrogen in Treating Menopausal Symptoms in Postmenopausal Women.
This study aimed to compare the efficacy of tibolone and transdermal estrogen in treating menopausal symptoms in postmenopausal women with an intact uterus. Overall, 26 women consumed tibolone orally and 31 women received transdermal estrogen gel mixed with progestogen. The menopause rating scale (MRS) was used to assess their menopausal symptoms at their first outpatient visit and 6 months later. The transdermal estrogen group showed significant improvements in more items of the MRS questionnaire. There was a favorable change in body weight in the transdermal estrogen group compared with that in the tibolone group. Depressive mood, irritability, physical and mental exhaustion, sexual and bladder problems, and joint and muscular discomfort improved only in the transdermal estrogen group, whereas heart discomfort and vaginal dryness improved only in the tibolone group. Nevertheless, the intergroup differences in each item were insignificant after adjusting for body mass index and hypertension, which differed before treatment. Both the therapeutic options improved menopausal symptoms within 6 months of use. However, transdermal estrogen appeared to be more effective in preventing weight gain in menopausal women than tibolone.


cAMP immunocytochemistry provides evidence for functional VIP receptors in trachea.
Vasoactive intestinal peptide (VIP), first isolated from porcine intestine (S. I. Said and V. Mutt, Science Wash. DC 169: 1217-1218, 1970), has been identified in postganglionic autonomic axons of many tissues. VIP has potent regulatory effects on the function of various cell types within these tissues, ranging from relaxation of smooth muscle to ion transport. Recently, VIP has been implicated in the regulation of mucus secretion in the respiratory tract, a process involving release of macromolecules from exocrine cells and transport of ions and water across the airway mucosa. However, because airway glands and mucosa both consist of mixed cell populations, it was unclear which specific cells contained VIP receptors and contributed to VIP-evoked responses. We identified these specific cells by using immunocytochemical techniques to monitor concentration changes in adenosine 3',5'-cyclic monophosphate (cAMP), the intracellular compound known to mediate VIP responses. Serous and mucous cells of ferret tracheal submucosal glands and ciliated and basal cells of dog tracheal mucosa all increased cAMP in response to VIP stimulation. We conclude that these cell types possess VIP receptors and thus participate in VIP-stimulated responses. In contrast, ferret tracheal epithelium and dog epithelial goblet cells showed little or no reactivity after VIP, and thus we believe that these cells lack VIP receptors.


Bioactive Alkaloids as Secondary Metabolites from Plant Endophytic Aspergillus Genus.
Alkaloids represent a large family of natural products with diverse structures and bioactivities. These compounds and their derivatives have been widely used in clinics to treat various diseases. The endophytic Aspergillus is a filamentous fungus renowned for its extraordinary ability to produce active natural products of high therapeutic value and economic importance. This review is the first to focus on Aspergillus-derived alkaloids. Through an extensive literature review and data analysis, 263 alkaloids are categorized according to their structural features into those containing cytochalasans, diketopiperazine alkaloids, quinazoline alkaloids, quinoline alkaloids, indole alkaloids, pyrrolidine alkaloids, and others. These metabolites exhibited diverse biological activities, such as antibacterial activity, cytotoxicity, anti-inflammatory activity, and α-glucosidase, ACE, and DPPH inhibitory activities. The bioactivity, structural diversity, and occurrence of these alkaloids are reviewed in detail.


Epithelial Na(+) channel (ENaC) expression in the developing normal and abnormal human perinatal lung.
Impaired lung epithelial Na(+) channel (ENaC) activity at the time of birth results in respiratory distress. To investigate potential mechanisms, the ontogeny and cellular distribution of the alphaENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lungs using nonradioisotopic in situ hybridization. Surprisingly, alphaENaC expression was detected at the embryonic stage of normal lung development (4 to 5 wk gestation) when expression was localized to the fetal lung bud epithelium. By late gestation, ENaC was expressed in the conductive and respiratory airway epithelium, serous cells, and the distal lung unit in an alveolar type II (ATII) epitheliumlike distribution. Significant alphaENaC expression was found in newborn lung diseases associated with respiratory distress. One explanation is that alphaENaC mRNA is constitutively expressed, and that activity is regulated, at least in part, at the post-transcriptional level. Alternative explanations are that the expression of the beta or gammaENaC subunits may be impaired in certain newborn lung diseases or that alternate Na(+) permeant channels or transporters are important to lung liquid absorption in humans at birth.


Thoracic wall trauma-misdiagnosed lesions on radiographs and usefulness of ultrasound, multidetector computed tomography and magnetic resonance imaging.
Blunt injuries to the chest wall are an important chapter on emergency room (ER) departments, being the third most common injuries in trauma patients which ominous complications could appear. This article describes different types of traumatic events affecting the chest wall, which maybe misdiagnosed with conventional X-ray. Special emphasis has been done in computed tomography (CT) and multidetector CT (MDCT) imaging. This technique is considered the "gold-standard" for those traumatic patients, due to its fast acquisition covering the whole area of interest in axial plane, reconstructing multiplanar (2D, 3D) volume-rendered images with a superb quality and angiographic CT capabilities for evaluating vascular damage. Complementary techniques such as ultrasonography (US) and magnetic resonance imaging (MRI) may improve the diagnostic accuracy due to its great capacity in visualising soft-tissue trauma (muscle-tendinous tears) and subtle fractures. All these imaging methods have an important role in quantifying the severity of chest wall trauma. The findings of this study have been exposed with cases of our archives in a didactic way.


Red blood cell lifespan, erythropoiesis and hemoglobin control.
Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.


An International Virtual COVID-19 Critical Care Training Forum for Healthcare Workers.
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in redeployment of non-critical care-trained providers to intensive care units across the world. Concurrently, traditional venues for delivery of medical education faced major disruptions. The need for a virtual forum to fill knowledge gaps for healthcare workers caring for patients with coronavirus disease (COVID-19) was apparent in the early stages of the pandemic. Objective: The weekly, open-access COVID-19 Critical Care Training Forum (CCCTF) organized by the American Thoracic Society (ATS) provided a global audience access to timely content relevant to their learning needs. The goals of the forum were threefold: to aid healthcare providers in assessment and treatment of patients with COVID-19, to reduce provider anxiety, and to disseminate best practices. Methods: The first 13 ATS CCCTF sessions streamed live from April to July 2020. Structured debriefs followed each session and participant feedback was evaluated in planning of subsequent sessions. A second set of 14 sessions streamed from August to November 2020. Content experts were recruited from academic institutions across the United States. Results: As of July 2020, the ATS CCCTF had 2,494 live participants and 7,687 downloads for a total of 10,181 views. The majority of participants had both completed training (58.6%) and trained in critical care (53.8%). Physicians made up a majority (82.2%) of the audience that spanned the globe (61% were international attendees). Conclusion: We describe the rapid and successful implementation of an open-access medical education forum to address training and knowledge gaps among healthcare personnel caring for patients with COVID-19.


Probing the interaction of the diarylquinoline TMC207 with its target mycobacterial ATP synthase.
Infections with Mycobacterium tuberculosis are substantially increasing on a worldwide scale and new antibiotics are urgently needed to combat concomitantly emerging drug-resistant mycobacterial strains. The diarylquinoline TMC207 is a highly promising drug candidate for treatment of tuberculosis. This compound kills M. tuberculosis by binding to a new target, mycobacterial ATP synthase. In this study we used biochemical assays and binding studies to characterize the interaction between TMC207 and ATP synthase. We show that TMC207 acts independent of the proton motive force and does not compete with protons for a common binding site. The drug is active on mycobacterial ATP synthesis at neutral and acidic pH with no significant change in affinity between pH 5.25 and pH 7.5, indicating that the protonated form of TMC207 is the active drug entity. The interaction of TMC207 with ATP synthase can be explained by a one-site binding mechanism, the drug molecule thus binds to a defined binding site on ATP synthase. TMC207 affinity for its target decreases with increasing ionic strength, suggesting that electrostatic forces play a significant role in drug binding. Our results are consistent with previous docking studies and provide experimental support for a predicted function of TMC207 in mimicking key residues in the proton transfer chain and blocking rotary movement of subunit c during catalysis. Furthermore, the high affinity of TMC207 at low proton motive force and low pH values may in part explain the exceptional ability of this compound to efficiently kill mycobacteria in different microenvironments.


Twice-daily applications of benzoyl peroxide 5%/clindamycin 1% gel versus vehicle in the treatment of pseudofolliculitis barbae.
Pseudofolliculitis barbae (PFB) is an inflammatory disorder characterized by the formation of papules, pustules, and hyperpigmentation as a result of ingrown hairs. It is estimated that PFB affects 45% to 83% of black men who shave regularly. In this multicenter, double-blind pilot study, men with 16 to 100 combined papules and pustules on the face and neck were randomized to receive twice-daily benzoyl peroxide 5%/ clindamycin 1% (BP/C) gel (BenzaClin)(n = 47) or vehicle (n = 41) for 10 weeks. Sixty-eight (77.3%) of the participants were black. All patients were required to shave at least twice a week and to use a standardized shaving regimen throughout the study. Clinical evaluations were performed at 2-week intervals. The primary efficacy parameter was the percentage change from baseline in lesion counts. At weeks 2, 4, and 6, mean percentage reductions from baseline in combined papule and pustule counts were significantly greater with BP/C gel compared with vehicle (P < or = .029). Treatment differences in favor of active therapy were more pronounced in the subpopulations of black patients, with least squares mean percentage reductions in papule and pustule counts ranging from 38.2% at week 2 to 63.9% at week 10. Study medication was well tolerated. These positive findings warrant further investigation of BP/C gel in the treatment of patients with PFB.


CD45 protein-tyrosine phosphatase inhibitor development.
The protein-tyrosine phosphatase (PTP) CD45 serves both positive and negative signaling elements by dephosphorylating regulatory pTyr residues on Src-family protein-tyrosine kinases. Although its physiological participation in immune function makes it an important point of intervention for treatment of a variety of inflammatory and immune disorders, comparatively little has been reported on development of CD45 inhibitors. Frequently, when inhibitory data against CD45 is reported, the data has been generated secondarily to other target PTPs. The focus of the current review is to summarize the types of structures that have been found to inhibit CD45, even in cases the compounds themselves were designed as antagonists of other PTPs. The review's organization begins with generic broad spectrum PTP inhibitors and progresses from peptide-based inhibitors and small molecule peptide mimetics to inhibitors that have resulted from screening hits. Although potent and moderately selective CD45 inhibitors have been reported, no single dominant theme has yet emerged in the design of these CD45-directed agents.


Prenatal indicators of congenital cytomegalovirus infection.
To assess the validity of a diagnostic protocol designed to predict the outcome of newborns of mothers suspected to have primary cytomegalovirus (CMV) infection during the first 4 months of pregnancy. Anti-CMV immunoglobulin (Ig) M detection by enzyme immunoassay and immunoblot together with the determination of anti-CMV IgG avidity allowed us to classify 456 women as (1) uninfected, (2) undergoing either a primary or a recurrent infection, or (3) having an undefined serologic condition. Prenatal diagnosis was carried out at 21 to 23 weeks' gestation for women. The presence of the virus in the amniotic fluid was determined by culture, polymerase chain reaction, and quantitative polymerase chain reaction. Macroscopic and histologic examinations were undertaken on tissue from aborted fetuses, whereas for newborns culture was performed on urine sampled during the first week of life. Congenital infections were found exclusively among women undergoing a primary infection. The quantitative determination of CMV DNA in the amniotic fluid of at least 10(3) genome equivalents gave a 100% certainty of detecting an infected fetus. Higher viral loads were associated with fetuses or newborns with symptoms. IgM tests and the IgG avidity determination can identify all women at risk of transmitting CMV. Furthermore, a high CMV DNA load in amniotic fluid could be an indicator of symptomatic congenital infection at a relatively early stage of pregnancy.


Urea permeability of human red cells.
The rate of unidirectional [14C]urea efflux from human red cells was determined in the self-exchange and net efflux modes with the continuous flow tube method. Self-exchange flux was saturable and followed simple Michaelis-Menten kinetics. At 38 degrees C the maximal self-exchange flux was 1.3 X 10(-7) mol cm-2 s-1, and the urea concentration for half-maximal flux, K1/2, was 396 mM. At 25 degrees C the maximal self-exchange flux decreased to 8.2 X 10(-8) mol cm-2 s-1, and K1/2 to 334 mM. The concentration-dependent urea permeability coefficient was 3 X 10(-4) cm s-1 at 1 mM and 8 X 10(-5) cm s-1 at 800 mM (25 degrees C). The latter value is consonant with previous volumetric determinations of urea permeability. Urea transport was inhibited competitively by thiourea; the half-inhibition constant, Ki, was 17 mM at 38 degrees C and 13 mM at 25 degrees C. Treatment with 1 mM p-chloromercuribenzosulfonate inhibited urea permeability by 92%. Phloretin reduced urea permeability further (greater than 97%) to a "ground" permeability of approximately 10(-6) cm s-1 (25 degrees C). This residual permeability is probably due to urea permeating the hydrophobic core of the membrane by simple diffusion. The apparent activation energy, EA, of urea transport after maximal inhibition was 59 kJ mol-1, whereas in control cells EA was 34 kJ mol-1 at 1 M and 12 kJ mol-1 at 1 mM urea. In net efflux experiments with no extracellular urea, the permeability coefficient remained constantly high, independent of a variation of intracellular urea between 1 and 500 mM, which indicates that the urea transport system is asymmetric. It is concluded that urea permeability above the ground permeability is due to facilitate diffusion and not to diffusion through nonspecific leak pathways as suggested previously.


Familial partial lipodystrophy: two types of an X linked dominant syndrome, lethal in the hemizygous state.
Familial lipodystrophy (referred to in publications as the Köbberling-Dunnigan syndrome) comprises at least two clinical phenotypes which are consistent within each pedigree. In type 1 familial lipodystrophy, loss of subcutaneous fat is confined to the limbs, sparing the face and trunk. In type 2 familial lipodystrophy, the trunk is also affected with the exception of the vulva, giving an appearance of labial hypertrophy. Diabetes mellitus, hyperlipoproteinaemia, and acanthosis nigricans are present to a variable degree in some but not all patients with familial lipodystrophy, and the abnormal distribution of subcutaneous fat is the essential hallmark of the syndrome. In addition to a survey of published reports, new cases with the syndrome are described. Both types of partial lipodystrophy, occurring either as familial disease or as sporadic cases, have only been observed in female patients. Study of the pedigrees of five families with familial lipodystrophy (two Scottish and three German) suggests an X linked dominant mode of transmission, lethal in the hemizygous (XY) state. The two clinical phenotypes with their variably expressive metabolic abnormalities are consistent either with different mutants of the same allele or with two genes on adjacent loci. Other clinical phenotypes of familial lipodystrophy may exist due to further mutations of the same allele or of genes on adjacent loci. The nature of the disorder in patients with familial lipodystrophy usually escapes recognition for many years and the syndrome is almost certainly much commoner than the few families described to date suggest.


Overcoming Heroin Addiction without the Use of Pharmaceuticals: A Qualitative Interview Study.
Although opioid maintenance treatment lowers mortality and has proven efficacy in reducing opioid use, it is not an option for every person with an opioid addiction. Studies of the experiences of those who have overcome their addiction without pharmaceuticals are rare, but vital to understanding the quitting process and how it can be facilitated. This study investigated what persons with a previous heroin addiction perceived as helpful when overcoming their addiction without the use of pharmaceuticals, and what they consider important for health services to consider. Eleven adults with former heroin addiction participated. Most described the leaving process as prolonged and including many attempts. Experiences such as being worn out and numb, life-threatening overdoses, personal losses or a growing feeling of missing important stages in life fueled the decision process. Envisioning a future without drugs was described as an important component. To maintain the decision to refrain from heroin use the possibility to gain a new social context was crucial. Results imply that health care professionals should be proactive by seizing the moment of opportunity for change (e.g., after an overdose), and should be empathetic and never give up on a person. Those concerned with care, welfare and other support or control systems in society must cooperate to offer more personalized support.


Increased uridine diphosphate-glucuronyltransferase activity in preneoplastic liver nodules and Morris hepatomas.
In preneoplastic rat liver nodules produced by 2-acetylaminofluorene, certain uridine diphosphate-glucuronyltransferase (UDP-GT) activities, which are ascribed to a distinct enzyme form, were selectively increased (5-fold). This enzyme form, operationally termed UDP-GT1, accepts 1-naphthol,4-methylumbelliferone, and 3-hydroxybenzo(a)pyrene as substrates and is chiefly inducible in liver by 3-methylcholanthrene-type inducers. Glucuronidation of other substrates (morphine, 4-hydroxybiphenyl, chloramphenicol, bilirubin, and estrone) was only slightly enhanced or decreased in nodular tissue. Differentially increased UDP-GT1 activities were also found in Morris hepatomas 9121 and 7777. Rabbit antibodies to rat liver UDP-GT1, purified from 3-methylcholanthrene-treated rats, demonstrated immunological similarity between the enzymes from liver, nodular tissue, and Morris hepatoma 9121. Rocket immunoelectrophoresis ascertained that enhanced enzyme activity in nodular tissue reflected an increased level of enzyme protein. Increased activity of UDP-GT1 together with decreased cytochrome P-450-dependent monooxygenase may contribute to the resistance of preneoplastic hepatocytes to the cytotoxic actions of chemical carcinogens.


Identification of quantitative trait loci underlying seed protein content of soybean including main, epistatic, and QTL × environment effects in different regions of Northeast China.
The objective here was to identify QTL underlying soybean protein content (PC), and to evaluate the additive and epistatic effects of the QTLs. A mapping population, consisting of 129 recombinant inbred lines (RILs), was created by crossing 'Dongnong 46' and 'L-100'. Phenotypic data of the parents and RILs were collected for 4 years in three locations of Heilongjiang Province of China. A total of 213 SSR markers were used to construct a genetic linkage map. Eight QTLs, located on seven chromosomes (Chr), were identified to be associated with PC among the 10 tested environments. Of the seven QTLs, five QTLs, qPR-2 (Satt710, on Chr9), qPR-3 (Sat_122, on Chr12), qPR-5 (Satt543, on Chr17), qPR-7 (Satt163, on Chr18), and qPR-8 (Satt614, on Chr20), were detected in six, seven, seven, six, and seven environments, respectively, implying relatively stable QTLs. qPR-3 could explain 3.33%-11.26% of the phenotypic variation across eight tested environments. qPR-5 and qPR-8 explained 3.64%-10.1% and 11.86%-18.40% of the phenotypic variation, respectively, across seven tested environments. Eight QTLs associated with PC exhibited additive and (or) additive × environment interaction effects. The results showed that environment-independent QTLs often had higher additive effects. Moreover, five epistatic pairwise QTLs were identified in the 10 environments.


Triazine based eccentric Piedfort units towards a single source hydrogen bonded network.
Herein we report a hydrogen-bonded three-dimensional network originating from a single source precursor, sym-triisopropylaminotriazine, that is both a donor and an acceptor of hydrogen bonds. The C3h symmetric design allowed the formation of intermolecular hydrogen bonds leading to helices in all three directions. The eccentric Piedfort units present in the framework with a distance of 8.15 Å between the two triazine rings allowed the CHCl3 guest to be parked.


Should coronary artery bypass grafting be performed at the same time as repair of a post-infarct ventricular septal defect?
The value of coronary artery bypass grafting (CABG) at the time of repair of a post-infarct ventricular septal defect (VSD) remains controversial. The aim of this study was to analyse the effect of CABG on early mortality and survival following repair of an acquired VSD. Over 23 years, 179 patients, 118 male, 61 female, mean age 66 years (range 43-80), have undergone repair of a post-related VSD in our unit. A total of 29 patients, who predominantly form the earlier part of the series, were operated on greater than 1 month after the infarct and are, therefore, excluded. Coronary angiography was performed in 98 (65.3%) of the remaining 150 patients. Of these, 41 had coronary artery disease (CAD) limited to the infarct-related vessel and 57 had additional significant CAD. Those with CAD limited to the infarct-related vessel were not grafted (Group A). Of those, 40 with significant CAD underwent CABG at the time of VSD repair (Group B) and 17 did not (Group C). In 52 patients the coronary anatomy was not documented (Group D). Risk factors for early mortality were evaluated using logistic regression. Actuarial survival was compared using log rank and Wilcoxon tests. Cox's proportional hazards method was used to determine factors affecting survival. Overall, 30 day mortality was 32%. CABG did not significantly decrease operative mortality (logistic regression). There was no statistically significant difference in early mortality or actuarial survival between the four groups. CABG was not associated with an increased survival (Cox's method). Concomitant CABG at the time of VSD repair does not affect early mortality nor confer survival benefits. There seems to be no demonstrable benefit in revascularisation at the time of repair and, therefore, it may be unnecessary to perform CABG or coronary angiography in these patients.


Accuracy of multi-unit implant impression: traditional techniques versus a digital procedure.
The objective of this study was to evaluate the accuracy of different impression techniques on multiple implants. A master cast simulating a jaw with four implants was used. Eight impression techniques were tested: open tray-polyether#1, open tray plus splint of impression copings with acrylic resin-polyether#1, closed tray-polyether#1, open tray-polyether#2, open tray-splint-polyether#2, closed tray-polyether#2, open tray-impression plaster, and digital impression (DI). Five impressions of the master cast were taken with each traditional impression (TI) technique, pouring 35 sample casts. Three different clinicians took 5 DI each (n = 15). A three-dimensional coordinate measurement machine (CMM) was used to measure implant angulation and inter-implant distances on TI casts. TI data and DI Standard Tessellation Language datasets were compared with the master cast. The best and the worst impressions made with TI and DI were selected to fabricate four milled titanium frameworks. Passive fit was evaluated through Sheffield test, screwing each framework on the master cast. Gaps between framework-implant analogs were measured through a stereomicroscope (×40 magnification). Statistically significant differences in accuracy were found comparing the different impression techniques by CMM (p < 0.01). DI performed the best, while TI techniques revealed a greater variability in the results. Sheffield test revealed a mean gap of 0.022 ± 0.023 mm (the best TI), 0.063 ± 0.059 mm (the worst TI), 0.015 ± 0.011 mm (the best DI), and 0.019 ± 0.015 mm (the worst DI). Within the limits of this in vitro study, the digital impression showed better accuracy compared to conventional impressioning. The digital impression might offer a viable alternative to traditional impressions for fabrication of full-arch implant-supported prostheses with satisfactory passive fit.


A Critical Scrutiny on Liposomal Nanoparticles Drug Carriers as Modelled by Topotecan Encapsulation and Release in Treating Cancer.
The medical field is looking for drugs and/or ways of delivering drugs without harming patients. A number of severe drug side effects are reported, such as acute kidney injury (AKI), hepatotoxicity, skin rash, and so on. Nanomedicine has come to the rescue. Liposomal nanoparticles have shown great potential in loading drugs, and delivering drugs to specific targeted sites, hence achieving a needed bioavailability and steady state concentration, which is achieved by a controlled drug release ability by the nanoparticles. The liposomal nanoparticles can be conjugated to cancer receptor tags that give the anticancer-loaded nanoparticles specificity to deliver anticancer agents only at cancerous sites, hence circumventing destruction of normal cells. Also, the particles are biocompatible. The drugs are shielded by attack from the liver and other cytochrome P450 enzymes before reaching the desired sites. The challenge, however, is that the drug release is slow by these nanoparticles on their own. Scientists then came up with several ways to enhance drug release. Magnetic fields, UV light, infrared light, and so on are amongst the enhancers used by scientists to potentiate drug release from nanoparticles. In this paper, synthesis of liposomal nanoparticle formulations (liposomal-quantum dots (L-QDs), liposomal-quantum dots loaded with topotecan (L-QD-TPT)) and their analysis (cytotoxicity, drug internalization, loading efficiency, drug release rate, and the uptake of the drug and nanoparticles by the HeLa cells) are discussed.


Epigenetics in adipose tissue, obesity, weight loss, and diabetes.
Given the role that diet and other environmental factors play in the development of obesity and type 2 diabetes, the implication of different epigenetic processes is being investigated. Although it is well known that external factors can cause cell type-dependent epigenetic changes, including DNA methylation, histone tail modifications, and chromatin remodeling, the regulation of these processes, the magnitude of the changes and the cell types in which they occur, the individuals more predisposed, and the more crucial stages of life remain to be elucidated. There is evidence that obese and diabetic people have a pattern of epigenetic marks different from nonobese and nondiabetic individuals. The main long-term goals in this field are the identification and understanding of the role of epigenetic marks that could be used as early predictors of metabolic risk and the development of drugs or diet-related treatments able to delay these epigenetic changes and even reverse them. But weight gain and insulin resistance/diabetes are influenced not only by epigenetic factors; different epigenetic biomarkers have also been identified as early predictors of weight loss and the maintenance of body weight after weight loss. The characterization of all the factors that are able to modify the epigenetic signatures and the determination of their real importance are hindered by the following factors: the magnitude of change produced by dietary and environmental factors is small and cumulative; there are great differences among cell types; and there are many factors involved, including age, with multiple interactions between them.


The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.


Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study.
To re-examine the epidemiology of acute lung injury (ALI) in European intensive care units (ICUs). A 2-month inception cohort study in 78 ICUs of 10 European countries. All patients admitted for more than 4 h were screened for ALI and followed up to 2 months. Acute lung injury occurred in 463 (7.1%) of 6,522 admissions and 16.1% of all mechanically ventilated patients; 65.4% cases occurred on ICU admission. Among 136 patients initially presenting with "mild ALI" (200< PaO2/FiO2 < or =300), 74 (55%) evolved to acute respiratory distress syndrome (ARDS) within 3 days. Sixty-two patients (13.4%) remained with mild ALI and 401 had ARDS. The crude ICU and hospital mortalities were 22.6% and 32.7% (p<0.001), and 49.4% and 57.9% (p=0.0005), respectively, for mild ALI and ARDS. ARDS patients initially received a mean tidal volume of 8.3+/-1.9 ml/kg and a mean PEEP of 7.7+/-3.6 cmH2O; air leaks occurred in 15.9%. After multivariate analysis, mortality was associated with age (odds ratio (OR) =1.2 per 10 years; 95% confidence interval (CI): 1.05-1.36), immuno-incompetence (OR: 2.88; Cl: 1.57-5.28), the severity scores SAPS II (OR: 1.16 per 10% expected mortality; Cl: 1.02-1.31) and logistic organ dysfunction (OR: 1.25 per point; Cl: 1.13-1.37), a pH less than 7.30 (OR: 1.88; Cl: 1.11-3.18) and early air leak (OR: 3.16; Cl: 1.59-6.28). Acute lung injury was frequent in our sample of European ICUs (7.1%); one third of patients presented with mild ALI, but more than half rapidly evolved to ARDS. While the mortality of ARDS remains high, that of mild ALI is twice as low, confirming the grading of severity between the two forms of the syndrome.


Efficacy of a topical agent SS-cream in the treatment of premature ejaculation: preliminary clinical studies.
SS-cream is a topical agent for treating premature ejaculation (PE) which is made with extracts from 9 natural products. We evaluated the efficacy of SS-cream in the treatment of PE. An open pilot study was performed in 186 patients with PE. The mean ejaculatory latency from intromission to ejaculation was 1.5 minutes. Sixty-four of the 186 patients (34.4%) were combined with mild erectile dysfunction in whom penile rigidity was not sufficient to be satisfied in sexual activity. Patients were instructed to apply 0.1 gm. of SS-cream on the glans penis 1 hour before sexual contact and to wash out the cream before sexual intromission. Patients were asked to complete a report form including ejaculatory latency, the degree of satisfaction in the sexual lives of both themselves and their partners, and any adverse effects after each application. One hundred and sixty-six out of 186 patients (89.2%) reported they were satisfied with the application of the SS-cream and the mean ejaculatory latency was significantly prolonged to 10.89 +/- 5.60 minutes. The mean ejaculatory latency was 9.85 +/- 3.58 minutes in 52 out of 64 patients (81.2%) with mild erectile dysfunction. There was no significant difference in the changes of ejaculatory latencies between patients with pure PE and patients with mild erectile dysfunction. Twenty patients (10.8%) claimed to have no changes of ejaculatory latencies after the application of SS-cream. Adverse effects were noted in 11 patients (5.9%), which were mild local irritation symptoms in 7 patients, and delayed ejaculation of more than 30 minutes in 4 patients, the symptoms subsided spontaneously within 4 hours. These results indicate SS-cream is effective in the treatment of PE and also PE combined with mild erectile dysfunction with a few side effects. Further studies on the action mechanisms of SS-cream and a double blind placebo-controlled trial are needed.


Assessment of the Interelectrode Distance Effect over the Omnipole with High Multielectrode Arrays.
The development of high-density multielectrode catheters has significantly advanced cardiac electrophysiology mapping. High-density grid catheters have enabled the creation of a novel technique for reconstructing electrogram (EGM) signals known as "omnipole," which is believed to be more reliable than other methods, especially in terms of orientation independence. This study aims to evaluate how distance affects the omnipolar reconstruction of EGMs by comparing different configurations. Using an animal set up of perfused isolated rabbit hearts, recordings were taken using an ad hoc high-density epicardial multielectrode catheter. Inter-electrode distances ranging from 1 to 4 mm were analysed for their effect on the quality of resulting EGMs. Two biomarkers were computed to evaluate the robustness of the reconstructions: the areas contained within the bipolar loops and the amplitudes of the omnipoles. We hypothesised that both bipolar and omnipolar electrograms would be more robust at shorter inter-electrode distances. The results showed that an increase in distance triggers an increase in loop areas and amplitudes, which supports the hypothesis. This finding provides a more reliable estimate of wavefront propagation for the cross-omnipolar reconstruction method. These results emphasise the importance of distance in cardiac electrophysiology mapping and provide valuable insights into the use of high-density multielectrode catheters for EGM reconstruction.Clinical Relevance- The results of this study have direct clinical relevance in the application of the described techniques to recording systems in the cardiac electrophysiology laboratory, enabling clinicians to obtain more precise characterisation of signals in the myocardium.


HIV-related stigma, depression, and social support are associated with health-related quality of life among patients newly entering HIV care.
Entering HIV care is a vulnerable time for newly diagnosed individuals often exacerbating psychosocial difficulties, which may contribute to poor health-related quality of life (HRQOL) ultimately influencing health behaviors including ART adherence, the driver of viral load suppression. Understanding HRQOL in people newly entering HIV care is critical and has the potential to guide practice and research. This exploratory cross-sectional study examined demographic, clinical, and psychosocial factors associated with limitations in four specific domains of HRQOL among persons initially entering outpatient HIV care at four sites in the United States (n = 335). In the unadjusted analysis, female gender was significantly associated with sub-optimal HRQOL with women having increased odds of reporting HRQOL challenges with pain, mood, mobility, and usual activity when compared to men. The adjusted models demonstrated attenuation of parameter estimates and loss of statistical significance for the associations with impaired HRQOL observed among women in unadjusted analyses, suggesting psychosocial factors related to HRQOL are complex and interrelated. Findings are consistent with a robust literature documenting gender-related health disparities. Programs aimed at improving HRQOL for persons initially entering HIV care are warranted generally, and specifically for women, and must address modifiable psychosocial factors via mechanisms including coping and social support.


Resistance of insecticide-treated foam board insulation against the eastern subterranean termite and the Formosan subterranean termite (Isoptera: Rhinotermitidae).
Three foam board types, one untreated control, one containing 2,000 ppm disodium octaborate tetrahydrate (DOT), and one containing 1,000 ppm deltamethrin, were exposed to field populations of the eastern subterranean termite, Reticulitermes flavipes (Kollar), and the Formosan subterranean termite, Coptotermes formosanus Shiraki. There was no significant difference in termite damage between foam boards treated with 2,000 ppm DOT and the untreated control. Form boards containing 1,000 ppm deltamethrin were not damaged by R. flavipes, whereas only minor damage occurred after exposure to C. formosanus.


Leveraging Physiological Markers to Quantify the Transient Effects of Traumatic Stress and Non-Invasive Neuromodulation.
Millions around the world suffer from traumatic stress (stress caused by traumatic memories). Transcutaneous cervical vagus nerve stimulation (tcVNS) has been shown to counteract physiological changes associated with traumatic stress. However, little is known regarding the approximate timecourse of tcVNS effects. This knowledge of how quickly tcVNS takes effect is needed to optimize closed-loop tcVNS systems that can mitigate traumatic stress in a timely manner. To address this gap, we studied N=26 participants with history of prior trauma. Participants wore electrocardiogram, photoplethysmogram, seismocardiogram, and respiratory effort sensors throughout a double-blind protocol involving traumatic stress and active tcVNS (n=12) or sham stimulation (n=14). From the physiological signals, we extracted cardiovascular and respiratory markers and studied their dynamics during the traumatic stress and stimulation conditions. We decoupled the short-term transient responses from longer-term cumulative changes by centering each condition's response with respect to data immediately prior to the condition. We thereby elucidate a diverse set of transient physiological responses to tcVNS and traumatic stress. These responses demonstrate that tcVNS-induced changes occur within seconds and have the potential to reduce acute physiological manifestations of traumatic stress.Clinical relevance- Traumatic stress can overpower an individual within seconds and often occurs outside the clinic. This analysis focuses on transient physiological responses to traumatic memories and tcVNS captured using multimodal physiological sensing. We demonstrate that tcVNS-induced changes occur within seconds and have the potential to mitigate some of the short-term effects of traumatic stress.


Using antiubiquitin antibodies to probe the ubiquitination state within rhTRIM5α cytoplasmic bodies.
The first line of defense protecting rhesus macaques from HIV-1 is the restriction factor rhTRIM5α, which recognizes the capsid core of the virus early after entry and normally blocks infection prior to reverse transcription. Cytoplasmic bodies containing rhTRIM5α have been implicated in the ubiquitin-proteasome pathway, but the specific roles these structures play remain uncharacterized. Here, we examine the ubiquitination status of cytoplasmic body proteins. Using antibodies specific for different forms of ubiquitin, we show that ubiquitinated proteins are present in cytoplasmic bodies, and that this localization is altered after proteasome inhibition. A decrease in polyubiquitinated proteins localizing to cytoplasmic bodies was apparent after 1 h of proteasome inhibition, and greater differences were seen after extended proteasome inhibition. The decrease in polyubiquitin conjugates within cytoplasmic bodies was also observed when deubiquitinating enzymes were inhibited, suggesting that the removal of ubiquitin moieties from polyubiquitinated cytoplasmic body proteins after extended proteasome inhibition is not responsible for this phenomenon. Superresolution structured illumination microscopy revealed finer details of rhTRIM5α cytoplasmic bodies and the polyubiquitin conjugates that localize to these structures. Finally, linkage-specific polyubiquitin antibodies revealed that K48-linked ubiquitin chains localize to rhTRIM5α cytoplasmic bodies, implicating these structures in proteasomal degradation. Differential staining of cytoplasmic bodies seen with different polyubiquitin antibodies suggests that structural changes occur during proteasome inhibition that alter epitope availability. Taken together, it is likely that rhTRIM5α cytoplasmic bodies are involved in recruiting components of the ubiquitin-proteasome system to coordinate proteasomal destruction of a viral or cellular protein(s) during restriction of HIV-1.


Lymphocyte enzymes in the detection of Niemann-Pick Carriers.
An improved method for the detection of Niemann-Pick disease type A and B carriers is described. Niemann-Pick disease is a genetic disorder characterized by the accumulation of sphingomyelin in several organs, among them spleen, liver and brain. A deficiency in sphingomyelinase activity is the characteristic defect in this lipid storage disorder, and the decreased enzyme activity in these types can be demonstrated in various cells and tissues. Low activity levels of enzymes were found in leukocyte fractions of peripheral blood from patients screened for Niemann-Pick disease. In heterozygote patients levels were within the lower range of control values. We therefore determined sphingomyelinase activity in discrete cell types isolated by two different methods from the total leukocyte fraction. In normal subjects sphingomyelinase activity is five to ten-fold higher in lymphocytes than in granulocytes. Monocytes have an intermediate level. pH profile and stability to heat inactivation were tested in separated lymphocytes and granulocytes and were found to be insignificantly different. Detection of carriers for Niemann-Pick type A and B by using separated lymphocyte as enzyme source, overcomes the difficulty of overlapping values with normal controls and serves as an excellent tool to detect heterozygotes.


Management of smoking cessation in patients with psychiatric disorders.
There is a close relationship between tobacco smoking and psychiatric disorders, and a higher proportion of individuals with mental health conditions smoke compared with the general population. Due to the increased smoking prevalence in this population, patients with psychiatric conditions are at greater risk of smoking-related morbidity and mortality and experience detrimental effects on their quality of life. However, while the majority of individuals with a history of mental health conditions appreciate that smoking is detrimental to their health, they are less likely to quit smoking and have a lower success rate during quit attempts compared with the general population. Peer-reviewed articles were identified from PubMed using the inclusive date-range of 1990 - October 2008 and the search terms; depression, mental health, psychiatric disorders, schizophrenia, and smoking cessation. Articles were selected from the search results to provide a general overview of some of the main issues for smokers with psychiatric disorders in general and specifically, those with schizophrenia and depression. The evidence from smoking cessation trials within these populations was also reviewed. Nicotine has some positive effects on symptoms of psychiatric disorders and it has been proposed that patients with mental health conditions may smoke as a form of self-medication. Further, several studies have shown that some symptoms of psychiatric disorders may be exacerbated by nicotine withdrawal. Therefore, attempts to quit smoking pose additional problems to patients with mental health problems. Traditional programmes for smoking cessation may not always be suitable for psychiatric patients due to their neuropsychological profile. Preliminary evidence suggests that more flexible, open-ended, combination approaches of pharmacotherapy and counselling may be more successful. In addition, identification and treatment of nicotine addiction remains very low in patients with mental health conditions and far more needs to be done to raise the awareness and ability of psychiatrists to diagnose and treat patients with nicotine problems.


Reduced cadmium transport determined by a resistance plasmid in Staphylococcus aureus.
The presence of a plasmid harboring a gene for Cd2+ resistance led to markedly reduced Cd2+ uptake via the energy-dependent Mn2+ transport system in Staphylococcus aureus strain 17810R. Cd2+ uptake by the resistant strain via this high-affinity system was seen only at very low Cd2+ concentrations. At high concentrations, Cd2+ was taken up by the resistant strain via a different low-affinity uptake system. Cd2+ uptake via this system was energy dependent but was not blocked by Mn2+. Loss of the plasmid from the resistant strain resulted in Cd2+ sensitivity and unblocking of Cd2+ transport via the Mn2+ carrier in the plasmidless derivative strain 17810S. The energy-dependent Cd2+ uptake by the sensitive strain was inhibited by Mn2+ with kinetics indicating competitive inhibition. It is suggested that the second, low-affinity uptake system for Cd2+ in the resistant strain is the energy-dependent cadmium/proton antiporter, which at low Cd2+ concentrations functions in net Cd2+ efflux.


Supramolecularly Dimeric Assemble of Planar Cu13 Clusters Controlled by the Length of Spacers of Diphosphine.
The controlled formation of dimeric clusters is challenging. Three copper(I) clusters, labeled as {Cu13[o-Ph(C≡C)2]6(L)4}(ClO4), were synthesized by using three different ligands, including 1,4-bis(diphenylphosphino)butane (dppb), 1,5-bis(diphenylphosphino)pentane (dpppe), and bis(diphenylphosphino)hexane (dpph). By increasing the flexibility of alkyl spacers in the diphosphine ligands, the relative positions of the phenyl rings could be optimized to achieve efficient packing with maximized intercluster interactions. In the crystal structures, cluster 1 with dppb ligands did not display interlocked structures. In contrast, cluster 2 with dpppe ligands formed supramolecularly interlocked polymers through weak π-π interactions and C-H···π interactions, while cluster 3 employing dpph ligands formed supramolecularly interlocked dimers with strong π-π interactions and C-H···π interactions. The supramolecular dimer of 3 was also evidenced by analyses through electrospray ionization mass spectrometry and transmission electron microscopy. Density functional theory calculation was used to understand the electronic structure and transitions. Supramolecularly interlocked polymers/dimers with rigid structures exhibited higher quantum efficiency. The solution of these clusters demonstrated remarkable aggregation-induced emission enhancements. This study presents unique examples of planar luminescent copper clusters, featuring the first serial dialkynyl-protected cluster. It underlines the importance of ligand flexibility in creating supramolecular cluster dimers.


Comparative effectiveness and prognostic factors for outcome of surgical and non-surgical management of lumbar spinal stenosis in an elderly population: protocol for an observational study.
Lumbar spinal stenosis is a common cause of low back and leg pain in the elderly and affects both physical activity and quality of life. First-line treatments are non-surgical options but if unsuccessful, surgery is advocated. The literature is not clear as to the outcome of surgery compared with non-surgical treatment, and the optimal time for surgery is not explicit. This observational study is designed to investigate the course of treatment, compare effectiveness of surgical and non-surgical management in patients with lumbar spinal stenosis and identify prognostic factors for outcome in the context of current clinical practice. Prospectively registered data on treatment, outcome and patient characteristics are collected from nationwide registers on health and social issues, a clinical registry of people with chronic back pain and hospital medical records. Primary outcome is change in physical function measured by the Zurich Claudication Questionnaire. Secondary outcomes are changes in symptom severity, pain-related function, health-related quality of life and general self-efficacy. Outcomes are assessed at baseline and 6 and 12 months. Outcomes at 12 months will be compared for patients who undergo surgery for lumbar spinal stenosis and patients managed non-surgically, using different analytical approaches. Prespecified prognostic factors of interest at baseline include treatment allocation, back and leg pain intensity, comorbidity, duration of symptoms, pretreatment function, self-rated health, income, general self-efficacy and MRI-graded severity of central stenosis. The study has been evaluated by the Regional Committees on Health Research for Southern Denmark (S-20172000-200) and notified to the Danish Data Protection Agency (18/22336). All participants provide consent. Findings will be disseminated in peer-reviewed publications and presented at national and international conferences according to the Strengthening the Reporting of Observational Studies in Epidemiology and Prognosis Research Strategy statements. Potential sources of bias will be addressed using Risk of Bias in Non-randomised Studies of Interventions. NCT03548441; Pre-results.


[Amyloid-plaque imaging of the brain using PET].
Alzheimer's disease (AD) is neuropathologically characterized by the presence of senile plaques. The formation of these plaques is caused by the accumulation of amyloid-beta protein (Aβ), a process that begins decades before the onset of the first clinical symptoms. Senile plaques can be visualized by using positron emission tomography (PET) and the tracer 11C-PIB. Such 'amyloid imaging' can contribute significantly to both early and differential diagnosis of Alzheimer's disease. In the future, amyloid imaging could also be useful for selecting patients for clinical trials and in evaluating the effects of disease modifying agents tailored at lowering Aβ burden.


Hypophosphatemic rickets caused by a novel splice donor site mutation and activation of two cryptic splice donor sites in the PHEX gene.
X-linked hypophosphatemic rickets (XLH) is the most common inherited form of rickets. XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder. We investigated PHEX mutation in a sporadic Turkish girl with hypophosphatemic rickets. The patient was 2 years of age with a complaint of inability to walk. She had bowing of legs and growth retardation. Laboratory data showed normal calcium, low phosphate with markedly elevated ALP, and low phosphate renal tubular reabsorption. She was treated with Calcitriol 0.5 mg/kg/day and oral phosphate supplement with good response. The entire coding region of PHEX gene was sequenced from patient's peripheral leukocyte DNA and a novel 13 bp deletion at the donor splice site of exon5 was found (c.663+12del). Instead of using the donor splice site of intron 4 to splice out exon 5 and intron 5, the spliceosome utilized two nearby cryptic donor splice sites (5' splice site) to splice out intron 4, resulting in two smaller transcripts. Both of them could not translate into functional proteins due to frameshift. Her parents did not carry the mutation, indicating that this is a de novo PHEX mutation likely resulting from mutagenesis of X chromosome in paternal germ cells. We conclude that c.663+12del is a novel mutation that can activate nearby cryptic 5' splice sites. The selection of cryptic 5' splice sites adds the complexity of cell's splicing mechanisms. The current study extends the database of PHEX mutation and cryptic 5' splice sites.


Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond.
Although its prevalence is declining, gastric cancer remains a significant public health issue. The bacterium Helicobacter pylori is known to colonize the human stomach and induce chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Results using a Mongolian gerbil model revealed that H. pylori infection increased the incidence of carcinogen-induced adenocarcinoma, whereas curative treatment of H. pylori significantly lowered cancer incidence. Furthermore, some epidemiological studies have shown that eradication of H. pylori reduces the development of metachronous cancer in humans. However, other reports have warned that human cases of atrophic metaplastic gastritis are already at risk for gastric cancer development, even after eradication of these bacteria. In this article, we discuss the effectiveness of H. pylori eradication and the morphological changes that occur in gastric dysplasia/cancer lesions. We further assess the control of gastric cancer using various chemopreventive agents.


Isotretinoin's action against cisplatin-induced ototoxicity in rats.
Current data do not support the routine use of any agent to prevent cisplatin ototoxicity. Although there are various diseases in which derivatives of vitamin A are used due to their antioxidant effects, there is no study for prevention from ototoxicity. In this study, the protective effect of isotretinoin was investigated on cisplatin ototoxicity in rats. 21 Wistar Albino rats were divided randomly into 3 groups. Group I: cisplatin, Group II: cisplatin + isotretinoin and Group III was the control group. Hearing assessment of all rats was done with ABR and DPOAE tests before and after the procedure. After the procedure, cochleas were resected and transmission electron microscopic examination was performed. Our DPOAE and ABR findings showed that isotretinoin has protective effects on cisplatin ototoxicity. According to transmission electron microscopic findings, isotretinoin has protective effects on cell integrity. We think that new experimental and clinical studies to be carried out in this regard may give us a new option on prevention of cochlea from ototoxicity.


Morphometric grading of squamous cell carcinoma.
Histological grading of squamous cell carcinoma is subjective and suffers from poor observer reproducibility. We investigated the feasibility of quantifying histological differentiation via point counting, using both the degree of keratinization and a novel definition of differentiation that was based on architectural features of the tumour. Multiple recounts of 20 cases of human oral squamous cell carcinoma were performed at several magnifications (X100, X160 and X250). Six lines of human squamous cell carcinoma tumour lines were examined for changes in differentiation following transplantation to athymic nude mice. Observer reproducibility was extremely high for all recounts except at the highest magnification, where the tumour architecture may have been obscured. Of the human squamous cell carcinomas transplanted to nude mice, five of six tumour lines showed significant histological changes, most commonly toward decreased differentiation. The changes were usually present in the initial transplant and were similar to those we have reported for transplants of adenocarcinomas. We conclude that histological differentiation can be quantified in squamous cell carcinomas with a high degree of observer reproducibility, even in the absence of keratinization; the method employed is sufficiently sensitive to be applied to practical problems of biological significance.


Ivabradine in Postural Orthostatic Tachycardia Syndrome: A Review of the Literature.
Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by symptoms such as palpitations, dyspnea, chest discomfort, and lightheadedness affecting various systems. The pathophysiology of POTS is not completely understood due to a variety of symptoms showing that the disease is multifactorial. There is no approved uniform management strategy for POTS and hence, no drug has been approved by the United States (US) Food and Drug Administration (FDA) for it. Ivabradine is an FDA-approved drug for stable symptomatic heart failure (HF) and patients with an ejection fraction (EF) of ≤35%. Previous studies have depicted improvement in symptoms of POTS with the use of ivabradine. It is a selective inhibitor of funny sodium channels (If) in the sinoatrial (SA) node cells resulting in the prolongation of the slow diastolic depolarization (phase IV) and reduction in the heart rate (HR). Although beta-adrenoceptor blockers are commonly used to lower HR in patients with POTS, they are less ideal due to numerous adverse effects. This review aims to provide a comprehensive and up-to-date picture of all the studies and case reports that utilized ivabradine for the treatment of POTS along with a precise overview of epidemiology, pathophysiology, and types of POTS. To conclude, we recommend further research on the effectiveness of ivabradine in patients who experience symptoms of POTS. Other than stable chronic angina pectoris, its application in this setting has been proven to be effective and safe. Further evaluation by means of randomized control trials is required to encourage use of this HR-lowering agent in common disorders other than HF and stable angina, i.e. POTS.


Recurrence of Fever After Initial Intravenous Immunoglobulin Treatment in Children With Kawasaki Disease.
The standard treatment for Kawasaki disease (KD) is high-dose intravenous immunoglobulin (IVIG). Some patients experienced recurrent fever after IVIG following defervescence. However, little is known about the frequency of such episodes and the clinical outcome for such patients. We classified 195 KD patients into 4 groups based on their fever patterns after initial IVIG treatment: group NR (no response), group EF (early recurrent fever within 72 hours after defervescence), group LF (late recurrent fever >72 hours after defervescence), and group GR (good response). We compared the clinical characteristics and laboratory data among these groups retrospectively. Nearly a third of patients had recurrent fever (group EF, n = 45; group LF, n = 11). In two-thirds of these patients, the fever had subsided spontaneously without retreatment; 2 patients in Group LF with smoldering KD symptoms had developed coronary artery lesions (CALs) even after additional IVIG. Recurrent fever and smoldering symptoms might be risk factors for CAL.


L-Threonine Supplementation During Colitis Onset Delays Disease Recovery.
Dietary nutrients have emerged as potential therapeutic adjuncts for inflammatory bowel disease (IBD) given their impact on intestinal homeostasis through the modulation of immune response, gut microbiota composition and epithelial barrier stability. Several nutrients have already been associated with a protective phenotype. Yet, there is a lack of knowledge toward the most promising ones as well as the most adequate phase of action. To unveil the most prominent therapy candidates we characterized the colon metabolic profile during colitis development. We have observed a twofold decrease in threonine levels in mice subjected to DSS-induced colitis. We then assessed the effect of threonine supplementation in the beginning of the inflammatory process (DSS + Thr) or when inflammation is already established (DSS + Thr D8). Colitis progression was similar between the treated groups and control colitic mice, yet threonine had a surprisingly detrimental effect when administered in the beginning of the disease, with mice displaying a delayed recovery when compared to control mice and mice supplemented with threonine after day 8. Although no major changes were found in their metabolic profile, DSS + Thr mice displayed altered expression in mucin-encoding genes, as well as in goblet cell counts, unveiling an impaired ability to produce mucus. Moreover, IL-22 secretion was decreased in DSS + Thr mice when compared to DSS + Thr D8 mice. Overall, these results suggest that supplementation with threonine during colitis induction impact goblet cell number and delays the recovery period. This reinforces the importance of a deeper understanding regarding threonine supplementation in IBD.


[Experimental coronavirus encephalomyelitis in mice].
A combined comparative virological, morphological, and immunological study of experimental coronavirus encephalomyelitis was carried out in mice in order to elucidate the pathogenetic mechanisms involved in the formation of the foci of lesions in acute and chronic forms of the disease. Intracerebral inoculation of C3H mice with the neurotropic JHM strain of murine hepatitis virus induces a disease with demyelinization foci in the CNS running acute, subacute, or chronic course. This model underlies a concept that demyelinating diseases are caused by viruses producing immunopathologic responses realized via certain histocompatibility loci. The long-term persistence of viral antigen in the CNS and liver may be explained by virus replication in hepatocytes and oligodendrocytes at low levels, and exacerbations of the disease are prevented by the immune system.


Femtosecond pulse generation with voltage-controlled graphene saturable absorber.
We report, for the first time to our knowledge, the demonstration of a graphene supercapacitor as a voltage-controlled saturable absorber for femtosecond pulse generation from a solid-state laser. By applying only a few volts of bias, the Fermi level of the device could be shifted to vary the insertion loss, while maintaining a sufficient level of saturable absorption to initiate mode-locked operation. The graphene supercapacitor was operated at bias voltages of 0.5-1V to generate sub-100 fs pulses at a pulse repetition rate of 4.51 MHz from a multipass-cavity Cr(4+):forsterite laser operating at 1255 nm. The nonlinear optical response of the graphene supercapacitor was further investigated by using pump-probe spectroscopy.


Current conceptualizations of narcissism.
Definitions of narcissism have traditionally differed across psychiatry and subfields of psychology. This review aims to highlight emerging points of consensus and suggest further directions needed to obtain a more comprehensive and cohesive conceptualization of the construct. An emerging consensus is that stable individual differences in the phenotypic expression of narcissism are best captured with a taxonomy that includes the core traits of entitlement, grandiosity, and vulnerability. Recent work has also begun to conceptualize and assess narcissistic states matched with these dimensions. We combine emerging taxonomic knowledge with principles from Whole Trait Theory to propose a multilevel conceptualization of narcissism that focuses on its manifestation at the trait level, state level, and within-situation level. Efforts to understand the phenotypic structure of the core traits associated with narcissism have been successful. As the field moves forward, it will become critical for researchers studying narcissism at multiple levels to align and integrate these perspectives so that a more comprehensive and cohesive conceptualization of the construct can be developed.


Molecular Insights into the Mechanisms Underlying the Cholesterol- Lowering Effects of Phytosterols.
Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma Low-Density Lipoprotein-Cholesterol (LDL-C) levels when given 2 g/day. Since this dose has not been reported to cause health-related side effects in long-term human studies, food products containing these plant compounds are used as potential therapeutic dietary options to reduce LDL-C and cardiovascular disease risk. Several mechanisms have been proposed to explain the cholesterol-lowering action of phytosterols. They may compete with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption. Recent evidence indicates that phytosterols may also regulate other pathways. Impaired intestinal cholesterol absorption is usually associated with reduced cholesterol transport to the liver, which may reduce the incorporation of cholesterol into Very-Low- Density Lipoprotein (VLDL) particles, thereby lowering the rate of VLDL assembly and secretion. Impaired liver VLDL production may reduce the rate of LDL production. On the other hand, significant evidence supports a role for plant sterols in the Transintestinal Cholesterol Excretion (TICE) pathway, although the exact mechanisms by which they promote the flow of cholesterol from the blood to enterocytes and the intestinal lumen remains unknown. Dietary phytosterols may also alter the conversion of bile acids into secondary bile acids, and may lower the bile acid hydrophobic/hydrophilic ratio, thereby reducing intestinal cholesterol absorption. This article reviews the progress to date in research on the molecular mechanisms underlying the cholesterol-lowering effects of phytosterols.


Shape transformation of erythrocyte ghosts depends on ion concentrations.
Resealed human erythrocyte ghosts undergo shape transformations similar to those of intact erythrocytes. The results indicate that the shape of these ghosts depends on the inner as well as on the outer NaCl concentration. A correlation between shape and calculated transmembrane potential was established similar to that for intact human erythrocytes.


A reconnaissance survey of farmers' awareness of hypomagnesaemic tetany in UK cattle and sheep farms.
Hypomagnesaemic tetany (HypoMgT) in ruminants is a physiological disorder caused by inadequate intake or impaired absorption of magnesium (Mg) in the gut. If it is not detected and treated in time, HypoMgT can cause the death of the affected animal. A semi-structured questionnaire survey was conducted from July 2016-2017 to assess farmers' awareness of HypoMgT in cattle and sheep in the UK. The questionnaire was distributed to farmers at farm business events and agricultural shows, and through a collaborative group of independent veterinary practices to their clients. Farmers were asked about (i) the incidence of presumed HypoMgT (PHT); (ii) their strategies to treat or prevent HypoMgT; (iii) mineral tests on animals, forage and soil, and (iv) farm enterprise type. A total of 285 responses were received from 82 cattle, 157 mixed cattle and sheep, and 46 sheep farmers, of whom 39% reported HypoMgT in their livestock, affecting 1-30 animals. Treatment and/or prevention against HypoMgT was reported by 96% respondents with PHT and 79% of those without. Mineral tests on animal, forage, and soil was conducted by 24%, 53%, and 66% of the respondents, respectively, regardless of PHT. There was a highly significant association between the use of interventions to tackle HypoMgT and the incidence of PHT (p < 0.01). The top three treatment/prevention strategies used were reported as being free access supplementation (149), in feed supplementation (59) and direct to animal treatments (drenches, boluses and injections) (45) although these did vary by farm type. Although some (9) reported using Mg-lime, no other pasture management interventions were reported (e.g., Mg-fertilisation or sward composition). Generally, the results indicate that UK farmers are aware of the risks of HypoMgT. A more integrated soil-forage-animal assessment may improve the effectiveness of tackling HypoMgT and help highlight the root causes of the problem.


Osteosarcomatous differentiation in lung metastases from a malignant phyllodes tumour of the breast.
Osteosarcomatous differentiation of a phyllodes tumour in the breast is extremely rare. A 54 year old woman presented with a painless lump in her left breast and a mastectomy was performed. Microscopically, the tumour was diagnosed as a malignant phyllodes tumour, where no osteosarcomatous component was found. One year later, two lung tumours were revealed upon chest x ray and were surgically treated. The tumours revealed osteosarcomatous features, and were thought to be metastases from the phyllodes tumour. The present case is very unusual in that osteosarcomatous features are present only in the metastatic lesion of the phyllodes tumour.


Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.
Human S100A7 (psoriasin) is overexpressed in inflammatory diseases. The recently discovered, co-evolved hS100A15 is almost identical in sequence and up-regulated with hS100A7 during cutaneous inflammation. The functional role of these closely related proteins for inflammation remains undefined. By generating specific Abs, we demonstrate that hS100A7 and hS100A15 proteins are differentially expressed by specific cell types in the skin. Although highly homologous, both proteins are chemoattractants with distinct chemotactic activity for leukocyte subsets. We define RAGE (receptor for advanced glycation end products) as the hS100A7 receptor, whereas hS100A15 functions through a Gi protein-coupled receptor. hS100A7-RAGE binding, signaling, and chemotaxis are zinc-dependent in vitro, reflecting the previously reported zinc-mediated changes in the hS100A7 dimer structure. When combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus, proinflammatory synergism in disease may be driven by the diverse biology of these almost identical proteins that have just recently evolved. The identified S100A7 interaction with RAGE may provide a novel therapeutic target for inflammation.


Oxidative depolymerization of lignin in ionic liquids.
Beech lignin was oxidatively cleaved in ionic liquids to give phenols, unsaturated propylaromatics, and aromatic aldehydes. A multiparallel batch reactor system was used to screen different ionic liquids and metal catalysts. Mn(NO(3))(2) in 1-ethyl-3-methylimidazolium trifluoromethanesulfonate [EMIM][CF(3)SO(3)] proved to be the most effective reaction system. A larger scale batch reaction with this system in a 300 mL autoclave (11 g lignin starting material) resulted in a maximum conversion of 66.3 % (24 h at 100 degrees C, 84x10(5) Pa air). By adjusting the reaction conditions and catalyst loading, the selectivity of the process could be shifted from syringaldehyde as the predominant product to 2,6-dimethoxy-1,4-benzoquinone (DMBQ). Surprisingly, the latter could be isolated as a pure substance in 11.5 wt % overall yield by a simple extraction/crystallization process.


Characterization of Sedentary Behavior in Heart Failure Patients With Arthritis.
Arthritis is one of the most common comorbidities in heart failure (HF) patients, and is associated with decreased activity levels. Few studies have examined sedentary behavior (SB) in HF patients with arthritis, and little is known about the factors that may influence SB in this population. This is a retrospective, secondary analysis using data collected from a randomized control trial. SB was measured by the daily sedentary time collected by accelerometers. Structural equation modeling was performed to examine relationships between key concepts based on social cognitive theory, and elucidate the potential pathways by which demographic, clinical and sociobehavioral factors that influence SB. A total of 101 participants' data were used for this analysis. Participants were mainly female (n = 64, 63%) with a mean age of 70 years (standard deviation (SD) = 12.2) and an average of 13 years of education (SD = 2.3). SB was highly prevalent at baseline (mean value: 21.0 h/day), 3 months (mean value: 20.6 h/day) and 6 months (mean value: 20.8 h/day) in study participants. Factors with statistically significant positive association with sedentary time include age and retirement, while significant negative association was found with current employment. HF self-care efficacy and behavior were also significantly associated with SB. Most HF patients with arthritis in this study lived a sedentary lifestyle. Additional studies are needed to identify feasible and effective exercise programs for HF participants with arthritis.


A novel metalloproteinase-derived cryptide from Bothrops cotiara venom inhibits angiotensin-converting enzyme activity.
Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara, including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin. Using FRET (fluorescence resonance energy transfer) substrate assays, we demonstrated that Bc-7a strongly inhibits the two domains of angiotensin converting enzyme (Ki < 1 μM). Our findings contribute to the repertoire of biologically active peptides from snake venoms capable of inhibiting angiotensin-converting enzyme (ACE), beyond current known structural motifs and precursors. In summary, we report a novel snake venom peptide with ACE inhibitory activity, suggesting its potential contribution to the hypotensive effect observed in envenomation.


Assessment of the cytotoxicity of photocrosslinked dextran and hyaluronan-based hydrogels to vascular smooth muscle cells.
The cytotoxicity of polysaccharide-based hydrogels and solutions was studied in vitro after 48h of indirect exposure of the materials with vascular smooth muscle cells. Dextran and/or hyaluronan were derivatized using glycidyl methacrylate, and hydrogels were formed in the presence of photoinitiators and ultraviolet radiation in multiwell inserts to avoid direct contact with cell monolayers. Observation of cell morphology indicated that dextran hydrogels, a blend of non-derivatized hyaluronan into dextran hydrogel. and a hyaluronan solution were highly cytocompatible. However, hydrogels made of derivatized hyaluronan were cytotoxic when compared to unexposed sham controls that contained multiwell inserts but no hydrogels. Results from quantitative assays for proliferation and viability corroborated the qualitative observations, and scrape wound assays revealed a significant increase in smooth muscles cell migration/proliferation after indirect exposure to several of the polysaccharide-based materials. Results from this study demonstrate that hydrogels made of dextran and hyaluronan solution show good cytocompatibility in vitro. making these degradable matrices interesting candidates for drug delivery purposes.


Multiparametric CT for Noninvasive Staging of Hepatitis C Virus-Related Liver Fibrosis: Correlation With the Histopathologic Fibrosis Score.
The objective was to develop a multiparametric CT algorithm to stage liver fibrosis in patients with chronic hepatitis C virus (HCV) infection. Abdominal CT and laboratory measures in 469 patients with HCV (340 men and 129 women; mean age, 50.1 years) were compared against the histopathologic Metavir fibrosis reference standard (F0, n = 49 patients; F1, n = 69 patients; F2, n = 102 patients; F3, n = 76 patients; F4, n = 173 patients). From the initial candidate pool, nine CT and two laboratory measures were included in the final assessment (CT-based features: hepatosplenic volumetrics, texture features, liver surface nodularity [LSN] score, and linear CT measurements; laboratory-based measures: Fibrosis-4 [FIB-4] score and aspartate transaminase-to-platelets ratio index [APRI]). Univariate logistic regression and multivariate logistic regression were performed with ROC analysis, proportional odds modeling, and probabilities. ROC AUC values for the model combining all 11 parameters for discriminating significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (F4) were 0.928, 0.956, and 0.972, respectively. For all nine CT-based parameters, these values were 0.905, 0.936, and 0.972, respectively. Using more simplified panels of two, three, or four parameters yielded good diagnostic performance; for example, a two-parameter model combining only LSN score with FIB-4 score had ROC AUC values of 0.886, 0.915, and 0.932, for significant fibrosis, advanced fibrosis, and cirrhosis. The LSN score performed best in the univariate analysis. Multiparametric CT assessment of HCV-related liver fibrosis further improves performance over the performance of individual parameters. An abbreviated panel of LSN score and FIB-4 score approached the diagnostic performance of more exhaustive panels. Results of the abbreviated panel compare favorably with elastography, but this approach has the advantage of retrospective assessment using preexisting data without planning.


Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion.
The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila, we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout (Robo) receptor-mediated repulsive axon guidance. CrGAP physically associates with the Robo receptor. Too much or too little CrGAP activity leads to defects in Robo-mediated repulsion at the midline choice point. The CrGAP gain-of-function phenotype mimics the loss-of-function phenotypes of both Robo and Rac. Dosage-sensitive genetic interactions among CrGAP, Robo, and Rac support a model in which CrGAP transduces signals downstream of Robo receptor to regulate Rac-dependent cytoskeletal changes.


Dynamic Monte Carlo simulations of a new lattice model of globular protein folding, structure and dynamics.
A long-standing problem of molecular biology is the prediction of globular protein tertiary structure from the primary sequence. In the context of a new, 24-nearest-neighbor lattice model of proteins that includes both alpha and beta-carbon atoms, the requirements for folding to a unique four-member beta-barrel, four-helix bundles and a model alpha/beta-bundle have been explored. A number of distinct situations are examined, but the common requirements for the formation of a unique native conformation are tertiary interactions plus the presence of relatively small (but not irrelevant) intrinsic turn preferences that select out the native conformer from a manifold of compact states. When side-chains are explicitly included, there are many conformations having the same or a slightly greater number of side-chain contacts as in the native conformation, and it is the local intrinsic turn preferences that produce the conformational selectivity on collapse. The local preference for helix or beta-sheet secondary structure may be at odds with the secondary structure ultimately found in the native conformation. The requisite intrinsic turn populations are about 0.3% for beta-proteins, 2% for mixed alpha/beta-proteins and 6% for helix bundles. In addition, an idealized model of an allosteric conformational transition has been examined. Folding occurs predominantly by a sequential on-site assembly mechanism with folding initiating either at a turn or from an isolated helix or beta-strand (where appropriate). For helical and beta-protein models, similar folding pathways were obtained in diamond lattice simulations, using an entirely different set of local Monte Carlo moves. This argues strongly that the results are universal; that is, they are independent of lattice, protein model or the particular realization of Monte Carlo dynamics. Overall, these simulations demonstrate that the folding of all known protein motifs can be achieved in the context of a single class of lattice models that includes realistic backbone structures and idealized side-chains.


Using a Spanish surname match to improve identification of Hispanic women in Medicare administrative data.
To assess the effectiveness of a Spanish surname match for improving the identification of Hispanic women in Medicare administrative data in which Hispanics are historically underrepresented. We collected self-identified race/ethnicity data (N=2,997) from a mailed survey sent to elderly Medicare beneficiaries who resided in 11 geographic areas consisting of eight metropolitan counties and three nonmetropolitan areas (171 counties) in the fall of 2004. The 1990 Census Spanish Surname list was used to identify Hispanics in the Medicare data. In addition, we used data published on the U.S. Census Bureau website to obtain estimates of elderly Hispanics. We used self-identified race/ethnicity as the gold standard to examine the agreement with Medicare race code alone, and with Medicare race code+Spanish surname match. Additionally, we estimated the proportions of Hispanic women and men, in each of the 11 geographic areas in our survey, using the Medicare race code alone and the Medicare race code+Spanish surname match, and compared those estimates with estimates derived from U.S. Census 2000 data. The Spanish surname match dramatically increased the accuracy of the Medicare race code for identifying both Hispanic and white women, producing improvements comparable with those seen for men. We recommend the addition of a proxy race code in the Medicare data using the Spanish surname match to improve the accuracy of racial/ethnic representation.To assess the effectiveness of a Spanish surname match for improving the identification of Hispanic women in Medicare administrative data in which Hispanics are historically underrepresented. We collected self-identified race/ethnicity data (N=2,997) from a mailed survey sent to elderly Medicare beneficiaries who resided in 11 geographic areas consisting of eight metropolitan counties and three nonmetropolitan areas (171 counties) in the fall of 2004. The 1990 Census Spanish Surname list was used to identify Hispanics in the Medicare data. In addition, we used data published on the U.S. Census Bureau website to obtain estimates of elderly Hispanics. We used self-identified race/ethnicity as the gold standard to examine the agreement with Medicare race code alone, and with Medicare race code+Spanish surname match. Additionally, we estimated the proportions of Hispanic women and men, in each of the 11 geographic areas in our survey, using the Medicare race code alone and the Medicare race code+Spanish surname match, and compared those estimates with estimates derived from U.S. Census 2000 data. The Spanish surname match dramatically increased the accuracy of the Medicare race code for identifying both Hispanic and white women, producing improvements comparable with those seen for men. We recommend the addition of a proxy race code in the Medicare data using the Spanish surname match to improve the accuracy of racial/ethnic representation.


Laser Nano-Neurosurgery from Gentle Manipulation to Nano-Incision of Neuronal Cells and Scaffolds: An Advanced Neurotechnology Tool.
Current optical approaches are progressing far beyond the scope of monitoring the structure and function of living matter, and they are becoming widely recognized as extremely precise, minimally-invasive, contact-free handling tools. Laser manipulation of living tissues, single cells, or even single-molecules is becoming a well-established methodology, thus founding the onset of new experimental paradigms and research fields. Indeed, a tightly focused pulsed laser source permits complex tasks such as developing engineered bioscaffolds, applying calibrated forces, transfecting, stimulating, or even ablating single cells with subcellular precision, and operating intracellular surgical protocols at the level of single organelles. In the present review, we report the state of the art of laser manipulation in neuroscience, to inspire future applications of light-assisted tools in nano-neurosurgery.


Idiopathic stroke in a normal parturient.
A 34-year-old Chinese woman was admitted to the labour suite for induction of labour. She had no history of hypertension, vascular disease or coagulapathy. She was induced for less fetal movement at 38 weeks of gestation. Labour progressed smoothly, but immediately after delivery the patient had symptoms of facial neurological deficit, slurred speech and heaviness in the left side of the body. After completion of the third stage of labour, her condition soon deteriorated with left-sided facial palsy and left-sided dense hemiplegia. The patient was then transferred to the intensive care unit where an urgent CT scan was arranged for her. She was diagnosed as a case of right-sided stroke with dense left-sided hemiplegia and left facial palsy. She was placed under the care of the neurosurgical team for 2 weeks and was discharged on regular physiotherapy treatment. She had completely recovered 6 months later.


Biphasic effect of extracellular [K] on isoproterenol-stimulated renin secretion from rat kidney slices.
It is known that large changes in extracellular K concentration [K], in either direction from normal, lead to depolarization of the cell and it has been suggested that depolarization inhibits the secretion of renin from juxtaglomerular cells. In the present experiments, renin secretion of rat kidney slices was examined as a function of [K]. Increases in [k] (from 4-45 or to 60mM) inhibited basal and isoproterenol-stimulated renin secretion, independently of changes in [Na], [Cl] and osmolality. At 4, 45 and 60 mM K, reductions in extracellular [Na] also inhibited secretion; the combined effect of isoproterenol. The Ca antagonist D-600 antagonized the inhibitory effects of high [K], restoring both the basal and the isoproterenol-stimulated secretory rates to normal values. Decreasing [K] (from 2.5-1.0 mM) also inhibited basal and isoproterenol-stimulated secretion, and this effect was not antagonized by D-600. On the basis of the known actions of D-600 and the present observations, it is suggested that depolarization per se does not inhibit renin secretion but that increases in intracellular [Ca] (resulting from depolarization-induced Ca influx in the presence of high [K] or from changes in the rate of Na-Ca exchange in the presence of low [K]) antagonize both basal and isoproterenol-stimulated renin secretion.


Stable DOPG/Glycyrrhizin Vesicles with a Wide Range of Mixing Ratios: Structure and Stability as Seen by Scattering Experiments and Cryo-TEM.
Phosphatidylglycerols represent a large share of the lipids in the plasmamembrane of procaryotes. Therefore, this study investigates the role of charged lipids in the plasma membrane with respect to the interaction of the antiviral saponin glycyrrhizin with such membranes. Glycyrrhizin is a natural triterpenic-based surfactant found in licorice. Vesicles made of 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1'-glycerol) (DOPG)/glycyrrhizin are characterized by small-angle scattering with neutrons and X-rays (SANS and SAXS). Small-angle scattering data are first evaluated by the model-independent modified Kratky-Porod method and afterwards fitted by a model describing the shape of small unilamellar vesicles (SUV) with an internal head-tail contrast. Complete miscibility of DOPG and glycyrrhizin was revealed even at a ratio of lipid:saponin of 1:1. Additional information about the chain-chain correlation distance of the lipid/saponin mixtures in the SUV structures is obtained from wide-angle X-ray scattering (WAXS).