Novel Parathyroid Hormone-Based Bone Graft, KUR-113, in Treatment of Acute Open Tibial Shaft Fracture: A Phase-2 Randomized Controlled Trial.
Treatment of an open tibial shaft fracture (TSF) is complex, and many cases are associated with delayed bone union or malunion. Parathyroid hormone (PTH) plays a key role in bone metabolism. A peptide fragment of PTH (PTH1-34) has been shown to promote bone healing. The objective of this study was to evaluate the safety and efficacy of a novel PTH-based bone graft (KUR-113) in the treatment of subjects with an open TSF. The study was a randomized, controlled, open-label (dose-blinded), dose-finding study of 200 subjects who had an open TSF secondary to trauma. Subjects were randomized into 1 of 4 groups to receive the standard of care (SoC) alone (control) or the SoC plus a single application of 4 mL of KUR-113 containing TGplPTH1-34 in fibrin at a concentration of 0.133 mg/mL (KUR-113-low), 0.4 mg/mL (KUR-113-mid), or 1.0 mg/mL (KUR-113-high). KUR-113 was administered at the fracture site after internal fracture fixation and before wound closure. Subjects were followed for up to 12 months after treatment. The primary outcome measure was fracture healing at 6 months assessed by the study investigator using radiographic and clinical measures. The primary end point was the proportion of subjects with fracture healing at 6 months. A total of 200 subjects were enrolled and randomized to 1 of the 4 treatments. The primary end point was met in the KUR-113-mid group, which showed a significantly higher prevalence of healing at 6 months than the control group (37 of 46; 80.4% versus 31 of 48; 64.6%). By 12 months, healing had occurred in the majority of subjects in all treatment groups, with the control group requiring more surgical interventions to achieve fracture healing. Adverse events occurred at similar frequencies between the KUR-113 groups and the SoC group. No ectopic bone formation or abnormal bone resorption at the fracture site was observed in any of the treatment groups. KUR-113 has the potential to be a good adjunctive therapy in the treatment of open TSFs. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway.
To verify whether amyloid precursor protein (APP) affects the migration and invasion of breast cancer cell lines, and to understand its underlying mechanisms, epithelial‑mesenchymal transition (EMT), the mitogen‑activated protein kinase (MAPK) signaling pathway and the matrix metalloproteinase (MMP) family were investigated in MDA‑MB‑231, MCF‑7 and BT474 human breast cancer cells. Breast cancer cell lines were transfected with plasmids containing APP coding sequences (pEGFP‑n1‑APP) and APP short hairpin RNA (pENTR APP shRNA). APP overexpression efficiency, knockout efficiency and the expression levels of related genes were tested using reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analyses. The effects of APP and mitogen‑activated protein kinase kinase (MEK) inhibitor on cell migration and invasion were examined using Transwell assays. The results demonstrated that APP was significantly upregulated in the pEGFP‑n1‑APP group (P<0.05), and significantly downregulated in the pENTR APP shRNA group (P<0.05), compared with the control group. APP overexpression increased the migratory and invasive ability of human breast cancer cells (P<0.05), whereas APP silencing significantly inhibited cell migration and invasion (P<0.05). RT‑qPCR and western blot analysis results suggested that APP overexpression significantly increased the expression of MMP‑9, MMP‑2, MMP‑3, N‑cadherin and vimentin (P<0.05). In addition, the enhanced expression of APP markedly affected the phosphorylation of mitogen‑activated protein kinase kinase kinase 11 (MLK3), mitogen‑activated protein kinase kinase 4 (MEK4) and mitogen‑activated protein kinase 10 (JNK3; P<0.05). Additionally, APP overexpression had no effect on the total expression levels of MLK3, MEK4, and JNK3; however, APP overexpression significantly decreased the expression levels of E‑cadherin and cytokeratin (P<0.05). Conversely, APP silencing had the opposite effects. When cells were treated with the MEK inhibitor PD0325901, the expression of APP was not altered, nor was the expression levels of MEK and its upstream signaling molecules. Taken together, the present findings suggested that APP could affect the migration and invasion of human breast cancer cells by mediating the activation of the MAPK signaling pathway, thereby promoting the EMT process.


Impact of Communicating With Doctors Via Social Media on Consumers' E-Health Literacy and Healthy Behaviors in China.
This study investigated the relationship between consumers' communication with doctors and their e-Health literacy and healthy behaviors based on the theory of reasoned action. Five communication activities were identified: following doctors' social media accounts, reading doctors' posts, responding to doctors' posts, favoring (clicking "like" of) doctors' posts, and recommending doctors to other patients. E-Health literacy and healthy behaviors were measured based on instruments used in previous literature. Survey method was used to collect data and a hierarchical regression analysis was used to analyze the relationship between communication activities and consumers' e-Health literacy and healthy behaviors. We found that following doctors' accounts (r = 0.127, P < .001), responding to doctors' posts (r = 0.141, P < .001) and recommending doctors to others (r = 0.133, P < .001) were significantly associated with e-Health literacy, while following doctors' accounts (r = 0.091, P < .001), responding to doctors' post (r = 0.072, P < .01), favoring doctors' posts (r = 0.129, P < .001), and recommending doctors to others (r = 0.220, P < .001) were significantly associated with healthy behaviors. Our study demonstrated that the social network communication between doctors and consumers could be cost-effective in improving intermediary consumers' health outcomes. To be specific, following doctors' posts, responding to doctors' posts, favoring doctors' posts, and recommending doctors to others were positively associated with consumers' e-Health literacy and healthy behaviors. The results suggested that leveraging information technology could be an important tool to health policymakers and health providers in order to improve outcomes.


Starting dialysis is dangerous: how do we balance the risk?
Recent studies of timing of dialysis initiation have challenged the recent trend to earlier initiation of therapy. The observed outcomes though are a consequence of the balance between the risks of advanced uremia versus the inherent dangers relating to dialysis therapy itself. Many of these risks are inherent in how dialysis treatment is currently carried out, and may indeed be amenable to mitigation, through refinement of clinical practice (and potentially modality choice). This article aims to lay out a discussion relating to patient outcomes being the composite result of this balance, pivoting on the vulnerability of a particular patient to these attendant risks.


Factors influencing brood sex ratios in polyembryonic Hymenoptera.
Copidosoma sp. is a polyembryonic encyrtid wasp which parasitizes isolated hosts. Most broods of this wasp are unisexual, but some contain both sexes and the secondary sex ratio of these is usually highly female biased. The overall population secondary sex ratio is female biased. Walter and Clarke (1992) argue that because the majority of individuals must mate outside the natal patch, the bias in the population secondary sex ratio contradicts predictions made by Hamilton's (1967) theory of local mate competition (LMC). We suggest that the primary sex ratio is unbiased and that Walter and Clarke's results do not cast doubt on LMC. Instead these results imply that ovipositing females make a combined clutch size and sex ratio decision influencing whether individuals developing from a particular brood will outbreed or largely inbreed; for each case the predictions of LMC theory are not violated. If this interpretation is correct, what is of interest is the basis on which this decision is made rather than the population secondary sex ratio. We show that host encounter rate influences the proportions of mixed and single sex broods laid by Copidosoma floridanum, a related polyembryonic parasitoid. Among single-sex broods the primary sex ratio is female biased, but our results are in agreement with LMC theory since offspring developing from these broods will probably mate with siblings from adjacent hosts. We consider the egg load of females to be of major influence on oviposition behaviour, and that the mating structure of parasitoid offspring, potentially differential costs of male and female broods and the natural distributions of hosts both at oviposition and eclosion, require further study.


The maturation of the central auditory conduction in preterm infants until three months post term. IV. Composite group averages of the cortical auditory evoked responses (ACRs).
Composite group averages were constructed from cortical auditory evoked responses (ACRs), which are recorded sequentially at maximally 8 conceptional age levels in 5 groups of 49 preterm infants, with additional inclusion of the records of 16 prematures obtained at different conceptional age levels. The group averages for the 5 gestational age groups showed replicable waveforms at all conceptional age (CA) levels reflecting the intragroup stability of the ACR complex. From the earliest age levels, from 25 weeks CA on, ACR group averages can be obtained, containing relative low voltage fast waves and high voltage slow waves. The most outstanding developmental changes in the ACR complex are the waveform changes. Until about 36 weeks CA a premature waveform is found, followed by a transitional phase with low voltage noisy records. Finally the adult waveform is found in the measurements at three months after term date. The latency values of the group averages are determined by the waveform changes. Persistent amplitude differences are found for the slow late waves between the vertex and the central temporal derivations.


Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL).
TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).


Potent, non-thiol inhibitors of farnesyltransferase.
The structure-activity relationship of a series of non-thiol CaaX analogs, which are inhibitors of farnesyltransferase, is described. These inhibitors contain a substituted phenyl group at the N terminus, which may occupy a novel binding domain on the Ras protein.


Clinical Characteristics and Treatment of Langerhans Cell Histiocytosis.
Langerhans cell histiocytosis (LCH) is a disease caused by clonal proliferation of CD1a+/CD207+ cells that is characterized by a spectrum of varying degrees of organ involvement and dysfunction. Treatment of LCH is risk adapted; patients with single lesions may respond well to local treatment, whereas patients with multi-system disease and risk-organ involvement require more intensive therapy. Although survival for patients without organ dysfunction is excellent, mortality rates for patients with organ dysfunction may reach 30% to 40%. For patients with low-risk disease, although cure is almost universal, disease reactivation rates are in excess of 30%.


Biochemical evidence of the functional recovery and regeneration of adrenal autotransplants in the rat spleen.
Adrenal transplantation may restore adrenal function after bilateral adrenalectomy or when adrenal function is lost. Thus, animal experiments could provide useful information before clinical application of adrenal transplantation. Using an experimental model of autotransplantion of a complete adrenal gland in the spleen of adrenalectomized rats, several biochemical and hormonal parameters were studied to evaluate the function of transplanted adrenal tissue compared to control and adrenalectomized animals. Three weeks after surgery, the animals were sacrificed and plasma and tissue samples were obtained for biochemical studies. In the autotransplanted rats, plasma glucose, hepatic glycogen, plasma, and hepatic proteins, which were decreased in adrenalectomized rats, increased to values close to those of the control group; whereas muscle and thymus proteins, which were increased in adrenalectomized animals, decreased and reached normal levels. Corticosterone plasma levels in autotransplanted rats showed a 50% recovery compared to control animals, whereas plasma aldosterone concentrations were low, with similar values to those of the adrenalectomized group. These results provide evidence that the adrenal grafts secrete corticosterone in quantities enough to overcome hepatic inactivation. On the other hand, aldosterone plasma concentrations remain very low, plasma potassium levels are increased, and plasma sodium levels are decreased in animals with intrasplenic adrenal grafts, indicating that aldosterone production is insufficient to avoid hypoaldosteronism.


The Neural Representation of Sequences: From Transition Probabilities to Algebraic Patterns and Linguistic Trees.
A sequence of images, sounds, or words can be stored at several levels of detail, from specific items and their timing to abstract structure. We propose a taxonomy of five distinct cerebral mechanisms for sequence coding: transitions and timing knowledge, chunking, ordinal knowledge, algebraic patterns, and nested tree structures. In each case, we review the available experimental paradigms and list the behavioral and neural signatures of the systems involved. Tree structures require a specific recursive neural code, as yet unidentified by electrophysiology, possibly unique to humans, and which may explain the singularity of human language and cognition.


Methods for the absolute quantification of N-glycan biomarkers.
Many treatment options especially for cancer show a low efficacy for the majority of patients demanding improved biomarker panels for patient stratification. Changes in glycosylation are a hallmark of many cancers and inflammatory diseases and show great potential as clinical disease markers. The large inter-subject variability in glycosylation due to hereditary and environmental factors can complicate rapid transfer of glycan markers into the clinical practice but also presents an opportunity for personalized medicine. This review discusses opportunities of glycan biomarkers in personalized medicine and reviews the methodology for N-glycan analysis with a specific focus on methods for absolute quantification. The entry into the clinical practice of glycan markers is delayed in large part due to a lack of adequate methodology for the precise and robust quantification of protein glycosylation. Only absolute glycan quantification can provide a complete picture of the disease related changes and will provide the method robustness required by clinical applications. Glycan biomarkers have a huge potential as disease markers for personalized medicine. The use of stable isotope labeled glycans as internal standards and heavy-isotope labeling methods will provide the necessary method precision and robustness acceptable for clinical use. This article is part of a Special Issue entitled "Glycans in personalized medicine" Guest Editor: Professor Gordan Lauc.


Rapid diagnosis of Rift Valley fever: a comparison of methods for the direct detection of viral antigen in human sera.
Human sera collected during the 1987 Rift Valley fever (RVF) epidemic in the Senegal River basin were analysed using three enzyme immunoassays to establish the best method for rapid diagnosis of RVF. A biotin-avidin-enhanced antigen detection method utilizing monoclonal antibodies proved most sensitive. Eighty-two viremic human sera were tested, and this assay detected antigen in 29.3% of the samples.


[Proteolytic system of Aspergillus ochraceus studied in relation to its plasma-coagulating and fibrinolytic activities].
The culture of Aspergillus ochraceus HP-19 accumulates two types of proteolytic enzymes in the cultural broth. One group of proteases coagulates blood while the other has the fibrinolytic activity. The enzymes can be separated by gel filtration on Sephadex G-100. The first group of enzymes consists of several proteases with the coagulase activity and an inert protein.


The formins: active scaffolds that remodel the cytoskeleton.
Evolutionarily conserved in eukaryotes, formin homology (FH) proteins, or formins, exert their effects on the actin and microtubule (MT) networks during meiosis, mitosis, the maintenance of cell polarity, vesicular trafficking, signaling to the nucleus and embryonic development. Once thought to be only molecular scaffolds that indirectly affected cellular functions through the binding of other proteins, recent in vitro studies have illustrated that they can function as actin nucleators in the formation of new filaments. The connection between formins and MTs is less well understood. In yeast, the MT effects appear to be dependent on the ability of formins to generate polarized actin cables whereas, in mammalian cells, formin signals that cause MT stabilization and polarization might be more direct. A subclass of formins, the Diaphanous-related formins (Drfs), can act as effectors for Rho small GTPases, yet it is not clear what GTPase binding contributes to formin function.


Identification of potential radiation-responsive biomarkers based on human orthologous genes with possible roles in DNA repair pathways by comparison between Arabidopsis thaliana and homo sapiens.
Rapid and reliable ionization radiation (IR) exposure estimation has become increasingly important in environment due to the urgent requirement of medical evaluation and treatment in the event of nuclear accident emergency. Human DNA repair genes can be identified as important candidate biomarkers to assess IR exposure, while how to find the enough sensitive and specific biomarkers in the DNA repair networks is still challenged and not fully determined. The conserved features of DNA repair pathways may facilitate interdisciplinary studies that cross the traditional boundaries between animal and plant biology, with the aim of identifying undiscovered human DNA repair genes for potential radiation-responsive biomarkers. In this work, an in silico method of homologous comparison was performed to identify the human orthologues of A. thaliana DNA repair genes, and thereby to explore the sensitive and specific human radiation-responsive genes to evaluate the IR exposure levels. The results showed that a total of 16 putative candidate genes were involved in the human DNA repair pathways of homologous recombination (HR) and non-homologous end joining (NHEJ), and most of them were confirmed by previous experiments. Additionally, we analyzed the gene expression patterns of these 16 candidate genes in several human transcript microarray datasets with different IR treatments. The results indicated that most of the gene expression levels for these candidate genes were significantly changed under different radiation treatments. Based on these results, we integrated these putative human DNA repair genes into the DNA repair pathways to propose new insights of the HR and NHEJ pathways, which can also provide the potential targets for the development of radiation biomarkers. Notably, two putative DNA repair genes, named ERCC1 and ESCO2, were identified and were considered to be the sensitive and specific biomarkers in response to γ-ray exposures.


A synchrotron study of microstructure gradient in laser additively formed epitaxial Ni-based superalloy.
Laser additive forming is considered to be one of the promising techniques to repair single crystal Ni-based superalloy parts to extend their life and reduce the cost. Preservation of the single crystalline nature and prevention of thermal mechanical failure are two of the most essential issues for the application of this technique. Here we employ synchrotron X-ray microdiffraction to evaluate the quality in terms of crystal orientation and defect distribution of a Ni-based superalloy DZ125L directly formed by a laser additive process rooted from a single crystalline substrate of the same material. We show that a disorientation gradient caused by a high density of geometrically necessary dislocations and resultant subgrains exists in the interfacial region between the epitaxial and stray grains. This creates a potential relationship of stray grain formation and defect accumulation. The observation offers new directions on the study of performance control and reliability of the laser additive manufactured superalloys.


Control of arthropod abundance by Anolis lizards on St. Eustatius (Neth. Antilles).
The two Anolis lizard species of St. Eustatius (Neth. Antilles) have large effects on the abundance of arthropods. Over a six-month period, we excluded Anolis lizards from three experimental areas and maintained three other areas with natural densities of lizards. Exclusion of anoles resulted in a two to three-fold increase in the abundance of arthropods on the forest floor (mainly Dipterans), and a twenty to thirty-fold increase in the abundance of three large web-building spiders. These abundant web-building spiders, in turn, caused approximately a 25% decrease in the abundance of insects between the forest floor and canopy. Exclusion of anoles had no observed effect on the degree of herbivory as assayed by the amount of leaf damage on two plant species.


Effect of vagotomy on biliary-tract motor activity in the opossum.
In this study, we evaluated the effect of truncal vagotomy in the opossum on changes in gallbladder and sphincter-of-Oddi (SO) contractile activity that occur normally during fasting and after a meal. In six animals, bipolar electrodes were implanted on the SO, gastric antrum, duodenum, and jejunum. A catheter secured in the gallbladder fundus was used to monitor gallbladder volume. After control studies, truncal vagotomy and pyloroplasty were done in each animal. Before vagotomy, the SO exhibited cyclic changes in spike-burst rate, from 2 to 5/min, that were synchronized with corresponding phases of the duodenal MMC cycle. The gallbladder exhibited partial emptying during the second half of the duodenal MMC cycle with refilling during the first half of the next cycle. By two weeks after vagotomy, the MMC-related changes in SO and gallbladder contractile activity were normal. In contrast, vagotomy retarded the increase in SO spike-burst rate and delayed as well as diminished the pronounced gallbladder emptying that normally occurs after a meal. The same effects were observed for changes in SO and gallbladder activity induced by intraduodenal infusion of Isocal. After vagotomy, the SO and gallbladder exhibited exaggerated responses to intravenous infusion of CCK-OP or motilin. We conclude that truncal vagotomy in the opossum does not affect the fasting pattern of SO and gallbladder contractile activity, but it significantly alters the normal postprandial pattern of enhanced SO spike-burst rate and pronounced gallbladder emptying. The precise mechanism(s) whereby vagotomy produces these changes remains to be determined.


Assessing survival in a multi-population system: a case study on bat populations.
In long-lived animals, adult survival is among the most important determinants of population dynamics. Although it may show considerable variation both in time and among populations and sites, a single survival estimate per species is often used in comparative evolutionary studies or in conservation management to identify threatened populations. We estimated adult survival of the isabelline serotine bat Eptesicus isabellinus using capture-recapture data collected on six maternity colonies scattered over a large area (distance 8-103 km) during periods varying from 8 to 26 years. We modelled temporal and inter-colony variations as random effects in a Bayesian framework and estimated mean annual adult survival of females on two scales and a single survival value across all colonies. On a coarse scale, we grouped colonies according to two different habitat types and investigated the effect on survival. A difference in adult survival was detected between the two habitat types [posterior mean of annual survival probability 0.71; 95% credible interval (CI) 0.51-0.86 vs. 0.60; 0.28-0.89], but it was not statistically supported. On a fine scale, survival of the six colonies ranged between 0.58 (95% CI 0.23-0.92) and 0.81 (0.73-0.88), with variation between only two colonies being statistically supported. Overall survival was 0.72 (95% CI 0.57-0.93) with important inter-colony variability (on a logit scale 0.98; 95% CI 0.00-8.16). Survival varied temporally in a random fashion across colonies. Our results show that inference based solely on single colonies should be treated with caution and that a representative unbiased estimate of survival for any species should ideally be based on multiple populations.


In vitro degradation behaviour, cytocompatibility and hemocompatibility of topologically ordered porous iron scaffold prepared using 3D printing and pressureless microwave sintering.
Biodegradable porous iron having topologically ordered porosity and tailorable properties as per the required application has been the major requirement in the field of biodegradable biomaterials. Hence, in the present study, iron scaffolds with the topologically ordered porous structure were developed and for the first time, the effect of the variation in the topology on the in vitro degradation behaviour, cytocompatibility and hemocompatibility were investigated. Iron scaffold samples were fabricated using a novel process based on the combination of 3D printing and pressureless microwave sintering. To investigate the effect of topology, two different types of topological structures namely Truncated Octahedron (TO) (with variable strut size) and Cubic (C) were used. From the morphological characterization, it was found that fabricated iron scaffold possessed interconnected porosity varying from 50.70%-80.97% which included the random microporosities in the strut and designed macroporosity. Furthermore, it was inferred that the topology of the iron scaffold significantly affected its degradation properties and cytocompatibility. Increase in the weight loss, corrosion rate and reduction in cell viability with the reduction in porosity were obtained. The maximum corrosion rate and weight loss achieved was 1.64 mmpy and 6.4% respectively. Direct cytotoxicity test results revealed cytotoxicity, while prepared iron scaffold samples exhibited excellent hemocompatibility and anti-platelet adhesion property. A comparative study with relevant literature was performed and it was established that the developed iron scaffold exhibited favorable degradation and biological properties which could be tailored to suit appropriate bone tissue engineering applications.


Immunogenicity and protective efficacy of a novel foot-and-mouth disease virus empty-capsid-like particle with improved acid stability.
Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects cloven-hoofed animal species. The FMDV capsid is highly acid labile and viral particles lose their immunogenicity when they disassemble at mildly acidic pHs. The viral capsid of FMDV serotype O is more sensitive than those of other serotypes, making it more difficult to acquire enough empty-capsid-like particles in the acidic insect cell environment for research. In this study, novel FMDV mutants with increased acid resistance were isolated using BHK-21 cell cultured under low-pH conditions. Amino acid substitutions Q25R, K41E, and N85A in the VP1 capsid protein and K154Q in the VP3 capsid protein were detected in all six mutants. Based on these amino acid replacements, empty-capsid-like particles of FMDV serotype O, which were resistant to the acid-induced dissociation of the capsid into pentameric subunits, were produced in insect cells. We characterized the protective immunity induced by these acid-resistant empty capsid particles. Significant humoral and cellular immune responses were elicited in mice after immunization with the acid-resistant empty capsid particles. The acid-resistant empty-capsid-like particles also induced strong neutralizing antibodies in guinea pigs and protected all the guinea pigs from FMDV challenge. Our results suggest that these acid-resistant empty-capsid-like particles have potential utility as a vaccine against serotype O FMDV infection.


Strategies for making regular contact with the scholarly literature.
Behavior analysts are obligated by the conventions of the academic discipline and guidelines of professional conduct to stay in close contact with the scholarly literature. However, a number of variables can interfere with this obligation. We discuss several barriers to searching the literature, accessing journal content, and making contact with the contemporary literature and provide solutions for eliminating them.


Promoting Self-Management and Independent Living of Older Individuals with Chronic Diseases through Technology: A Study of Self-Reported Needs, Priorities, and Preferences.
Background and Objectives: Older patients' needs are rarely examined beforehand, and thus, although technology-based tools can enhance self-management, acceptability rates are still low. This study aimed to examine and compare self-reported needs, priorities, and preferences of older patients with heart failure (HF), diabetes mellitus type II (DM2), and chronic obstructive pulmonary disease (COPD) toward technology use to enhance self-management. Materials and Methods: A convenience sample of 473 participants over 60 s (60.5% females), diagnosed with HF (n= 156), DM2 (n = 164), or COPD (n = 153) was recruited. They were administered a questionnaire about the usefulness of technology in general and in specific areas of disease management. Results: Most participants (84.7%) admitted that technology is needed for better disease management. This was equally recognized across the three groups both for the overall and specific areas of disease management (in order of priority: "Information", "Communication with Physicians and Caregivers", and "Quality of Life and Wellbeing"). Sociodemographic differences were found. Cell phones and PCs were the devices of preference. The four common features prioritized by all three groups were related to 'information about disease management' (i.e., monitoring symptoms, reminders for medication intake, management and prevention of complications), whereas the fifth one was related to 'communication with physicians and caregivers (i.e., in case of abnormal or critical signs). The top disease-specific feature was also monitoring systems (of respiratory rate or blood sugar or blood pressure, and oxygen), whereas other disease-specific features followed (i.e., maintaining normal weight for HF patients, adjusting insulin dose for DM2 patients, and training on breathing exercises for COPD patients). Conclusions: Older individuals in these three groups seem receptive to technology in disease management. mHealth tools, incorporating both common and disease-specific features and addressing different chronic patients, and also being personalized at the same time, could be cost-saving and useful adjuncts in routine clinical care to improve self-management.


Synthetic analogues of mycobacterial arabinogalactan linkage-disaccharide part II: synthesis and preliminary screening of lipophilic O-alkyl glycosides.
Lipophilic analogues of the linkage-disaccharide found in the mycobacterial cell wall were synthesized and the synthetic analogues when biologically evaluated showed promising antimycobacterial property with MIC value in the range 3.13-12.50 μg/mL against Mycobacterium tuberculosis H(37)Rv.


Paralinguistic abilities of adults with intellectual disability.
The aim of this research was to determine the ability level of paralinguistic production and comprehension in adults with intellectual disability (ID) with regard to the level of their intellectual functioning and presence of co-morbid psychiatric conditions or dual diagnosis (DD). The sample consisted of 120 participants of both genders, ranging in age between 20 and 56 years (M=31.82, SD=8.702). Approximately 50% of the sample comprised participants with a co-existing psychiatric condition. Each of these two sub-samples (those with ID only and those with DD) consisted of 25 participants with mild ID and 35 participants with moderate ID. The paralinguistic scale from The Assessment Battery for Communication (ABaCo; Sacco et al., 2008) was used to assess the abilities of comprehension and production of paralinguistic elements. The results showed that the participants with mild ID are more successful than the participants with moderate ID both in paralinguistic comprehension tasks (p=.000) and in paralinguistic production tasks (p=.001). Additionally, the results indicated the presence of separate influences of both ID levels on all of the paralinguistic abilities (F [116]=42.549, p=.000) and the existence of DD (F [116]=18.215, p=.000).


Analysis of the Type II-A CRISPR-Cas System in Streptococcus canis Isolated from Diseased Companion Animals and One Human Patient in Japan.
We determined the whole-genome sequence (WGS) of Streptococcus canis strain TA4 harboring the M-like protein gene (scm); the strain was isolated from a human patient presenting with bacteremia. The potential of type II-A clustered regularly interspaced short palindromic repeats (CRISPR) array-based typing was evaluated, and the genetic relation was elucidated between spacer genogroups and scm prevalence and/or polymorphisms among the isolates from 19 diseased companion animals and the human patient. CRISPRFinder and CRISPRCasFinder detected the type II-A locus with the same repeat sequences in strain TA4 and another WGS of S. canis strain, isolated from a cow with mastitis. An optimized PCR-based amplification method was used to sequence the region covering the locus around the leader and terminal repeat sequences. Among the 20 isolates sequenced, 16 strains (including TA4) were identified with the CRISPR array. We conducted comparative analysis of the homologous spacer sequences and performed grouping based on the successive common ancestral spacer types. These 16 isolates were assigned to five genogroups (A to E) with scm being absent in genogroup A. We found a relationship between genogroups C and E and allele type 1 of the deduced M-like protein. These preliminary findings suggest the feasibility of CRISPR array-based typing and a genetic relation between the spacer genogroups and scm prevalence and/or polymorphisms in the isolates.


The oncoprotein and stem cell renewal factor BMI1 associates with poor clinical outcome in oesophageal cancer patients undergoing preoperative chemoradiotherapy.
The polycomb group (PcG) family BMI1, acting downstream of the hedgehog (Hh) pathway, plays an essential role in the self-renewal of haematopoietic, neural, and intestinal stem cells, and is dysregulated in many types of cancer. Our recent report has demonstrated that Hh signalling activation can predict very earlier relapse of oesophageal cancers. As data were not available on the clinical role of BMI1 expression in oesophageal cancers after chemoradiotherapy (CRT), we analysed whether it could be also used to predict disease progression and prognosis in oesophageal cancer patients undergoing trimodality therapy of preoperative CRT and oesophagectomy. Expressions of BMI1 and p16INK4A, a downstream target of PcG, were analysed in 78 patients with histologically confirmed oesophageal squamous cell carcinoma (ESCC) after preoperative CRT by immunohistochemical staining. The association of BMI1 and p16INK4A expression with clinicopathologic characteristics was analysed by χ2-test. Survival analysis was carried out by the log-rank test using Kaplan-Meier method. Among 78 ESCC patients, 24 patients (30.8%) showed BMI1 positivity, mainly localised in the nuclei of tumour cells. Patients harbouring BMI1-positive tumour cells showed significantly poorer prognoses than those without such cells or residual tumours (mean disease-free survival (DFS) time 16.8 vs 71.2 months; 3-yr DFS 13.3% vs 49.9%, P=0.002; mean OS time 21.8 vs 76.6 months; 3-yr OS 16.2% vs 54.9%, P=0.0005). There was no significant correlation between p16INK4A expression and BMI1 expression. Our study shows that BMI1 expression is a predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that BMI1 signal activation might be involved in promoting cancer regrowth and progression after CRT, and might be indicative of emergence of 'more aggressive' cancer progenitor cells.


Application of step and beat alignment approaches and its effect on gait in progressive multiple sclerosis with severe cerebellar ataxia: A proof of concept case study.
In a case report of a progressive multiple sclerosis with cerebellar impairments, we reported that synchronisation of steps to beats was possible only at -12% of usual walking cadence during 1 minute of walking. Here, we investigate the effect of synchronisation using two different alignment approaches on the patient's gait pattern over 2 minutes of walking, compared to walking in silence. This proof of concept showed that the adaptive approach was successful resulting in an improved gait pattern compared to the other conditions, providing preliminary evidence to support a full-scale intervention study.


Effect of sequential or ternary starters-assisted fermentation on the phenolic and glucosinolate profiles of sauerkraut in comparison with spontaneous fermentation.
This study investigated the effectiveness of two novel started-assisted sauerkraut fermentations in comparison with spontaneous fermentation. Three lactic acid bacteria strains were selected as best starters for sauerkraut processing, based on the complementarity of pro-technological (kinetics of growth and acidification) traits, phenotypic fingerprints through OmniLog Phenotype MicroArray, and phenolics metabolism. The selected strains were applied according to two different fermentation methods based on steering sequential and temporally deferred inoculum of three strains, and ternary simultaneous inoculum. Sequential and ternary starters-assisted fermentations lasted 9 and 7 days, respectively, and were compared to conventional spontaneous fermentation lasting 35 days. Sequential and ternary fermentations resulted in a higher and constant number of lactic acid bacteria compared to spontaneous fermentation, which reflected on the acidification and sugar utilization. Ternary fermentation enhanced phenolic compounds conversion (hydrocaffeic acid, hydroferulic acid, 4-ethyl catechol), ensuring at the same time higher level of aliphatic (glucobrassicanapin) and indole glucosinolates (glucobrassicin) and derivatives(ascorbigen). Short fermentation of sequential and ternary starters-assisted processing caused only slight changes in the sensory profile compared to the spontaneous process, preserved the structural integrity of sauerkraut, and did not affect the colour lightness.


Falls From Height, Facial Injuries and Fatalities: An Institutional Review.
Retrospective cohort review. To investigate the relationship between falls from height and facial injuries. This is a retrospective cohort study, conducted over a 7-year period, of the medical records of all patients who presented to hospital for a maxillofacial injury following a fall from height. Fall heights were classified as low falls (1-3 m), high falls (3-10 m) and very high falls (≥10 m). A total of 111 patients with 218 facial bone fractures were identified (78 men, 33 women and mean age 50.3 years). High falls were the most common (n = 58, 52.3%). Multiple fractures were identified in 51 (46.0%) patients. Orbital and middle third fractures were the most prevalent. Nasal, mandible, bilateral and fractures involving more than one facial third, increased as fall height increased, as did the requirement for operative fixation. The majority of patients had an associated injury (n = 100, 90.1%) and overall mortality was 6.3%. Falls from height are prevalent and there is a trend towards increased severity of facial injury, surgical intervention and associated morbidity as fall height increases. Falls from height are a significant public health concern and an important facet of maxillofacial trauma to recognise, as is the requirement for an interdisciplinary approach as they present to hospital.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) counteracts the inhibiting effect of monocytes on natural killer (NK) cells.
GM-CSF is known to accelerate haematopoietic recovery following allogeneic bone marrow transplantation (BMT). In addition, it may restore and enhance both granulocyte and monocyte functions. Stimulation of monocyte functions may induce a direct or an indirect anti-leukaemic activity due to an increase of cellular cytotoxicity and production of cytokines which may result in a reduction of the relapse rate after BMT. NK cells may play a crucial role in this activity. Therefore we studied the influence of monocytes on NK activity in combination with GM-CSF. Lymphocytes and monocytes were isolated from buffy coats of healthy individuals by counterflow centrifugation elutriation (CCE). NK activity was exerted by CD3-CD56+ cell populations and could be enhanced by IL-2 incubation overnight. Incubation of CD3-CD56+ cells with GM-CSF in the presence or absence of IL-2 hardly influenced NK activity of the lymphocyte population. Low amounts of monocytes enhanced NK activity. NK activity in lymphocyte population in the presence of equivalent numbers of monocytes with or without IL-2 was strongly decreased irrespective of the effector:target ratio (ETR). This appeared not to result from sterical hindrance effects of the present number of cells. However, addition of GM-CSF abrogated the inhibition of NK activity by monocytes in the presence of IL-2. In monocyte fractions neither IL-2 nor GM-CSF yielded NK activity. Our findings indicate that GM-CSF can affect NK activity by counteracting the suppressing effects of monocytes, and hence may improve the outcome after BMT.


Life histories of two desert species of the bulbous genus Bellevalia : The relation between biomass partitioning and water availability.
Annual biomass increment and biomass partitioning to leaves, roots and reproduction, and biomass storage in the below-ground bulb was measured in plants of two species of the geophytic genus Bellevalia grown outdoors at three levels of soil moisture. The differences between the species were in accordance with the hypothesis that plants of more arid environments should rely more on internal reserves than plants of more productive environments. In Bellevalia desertorum, a shallow rooted species of the most arid habitats in the Central Negev, leaf and root development during outgrowth at the beginning of winter was rather variable, and followed soil moisture availability to a certain degree. A small portion of its biomass budget was committed to seed production, which varied little among the irrigation regimes. The rest of the biomass was stored in the bulb. The amount of biomass devoted annually to reproduction was mainly determined by the amount of reserves already present in the bulb. In contrast, in B. eigii, which grows in the more productive wadis with its bulb at a depth of 15 to 30 cm, leaf and root growth was not only determined by water availability, but also by initial bulb mass. This resulted in a greater potential relative growth rate than in B. desertorum, but also in a greater risk of accumulating less biomass than it spent in root and leaf construction under poor soil moisture conditions. In this species, reproductive biomass and seed yield were proportional to current biomass gain and, in contrast to B. desertorum, independent of initial bulb mass, provided that the bulb was large enough to initiate flowering.


Neoadjuvant therapy for gastric cancer.
Complete surgical resection remains the primary curative treatment option for patients with early stage gastric adenocarcinoma appropriately staged with an adequate lymphadenectomy. Unfortunately, only 40% patients who undergo curative resection at the authors' institution will have early stage (i.e., stage IA or T2N0M0) disease; thus, the majority of patients will remain at high risk for recurrence after complete resection. At present, the authors advocate rigorous preoperative staging studies to identify patients with high-risk gastric cancer who are unlikely to benefit from single modality therapy, namely surgery alone, and assign them to undergo neoadjuvant chemotherapy before an attempt at curative resection. Patients who are determined to have high-risk disease postoperatively should be offered adjuvant therapy that will address the site of recurrence most likely to affect survival.


Cryptic HBV Replicative Activity Is Frequently Revealed in Anti-HBc-Positive/HBsAg-Negative Patients with HIV Infection by Highly Sensitive Molecular Assays, and Can Be Predicted by Integrating Classical and Novel Serological HBV Markers.
The anti-HBc-positive/HBsAg-negative status is frequent in HIV-infection and correlates with poor survival. Here, by highly-sensitive assays, we evaluate cryptic HBV replication and factors correlated with its detection in 81 anti-HBc-positive/HBsAg-negative HIV-infected patients. Patients were treated for >12 months with HBV-active modern combined antiretroviral-therapy (cART) and had serum HBV-DNA < 20 IU/mL by commercial Real-Time PCR. Serum HBV-DNA was quantified by droplet digital PCR, serum HBV-RNA by an Abbott research assay, and anti-HBc titer (proposed to infer intrahepatic cccDNA) by Lumipulse/Fujirebio. Cryptic serum HBV-DNA was detected in 29.6% of patients (median (IQR): 4(1-15) IU/mL) and serum HBV-RNA in 3.7% of patients despite HBsAg-negativity and HBV-active cART. Notably, cryptic serum HBV-DNA correlated with an advanced CDC-stage (p = 0.01) and a lower anti-HBs titer (p = 0.05), while serum HBV-RNA correlated with lower nadir CD4+ cell-count (p = 0.01). By analyzing serological HBV-markers, the combination of anti-HBs < 50 mIU/mL (indicating lower immune response) plus anti-HBc > 15COI (reflecting higher HBV replicative activity) was predictive of cryptic serum HBV-DNA (OR: 4.7(1.1-21.7), p = 0.046, PPV = 62.5%, and NPV = 72%). In conclusion, cryptic HBV-replication (not detected by classical assays) characterizes a conspicuous set of anti-HBc-positive HIV-infected patients despite HBsAg-negativity and HBV-active combined antiretroviral therapy (cART). The integration of classical and novel markers may help identify patients with cryptic HBV-replication, thus optimizing the monitoring of anti-HBc-positive/HBsAg-negative HIV-infected patients.


Validation of ICD-10 codes for the identification of paediatric out-of-hospital cardiac arrest patients.
There is a need for large-scale epidemiological studies of paediatric out-of-hospital cardiac arrest (POHCA). To enable this, we developed and validated international classification of disease (ICD-10) search algorithms for the identification of POHCA patients from health administrative data. We validated the algorithms with a registry of POHCA (CanRoc) as the reference standard. The reference standard included all atraumatic POHCA in Middlesex-London region for January 2012-June 2020. All algorithms included 1 day to <18-year-old patients transported to emergency department (ED) by ambulance and excluded trauma. We tested three algorithms, which were applied to the National Ambulatory Care Reporting System and Discharge Abstract Database. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ration (NLR) were calculated for each algorithm. During the study period, 17,688 children presented to the ED by ambulance. The reference standard included 51 POHCA patients. The algorithm using only ICD-10 code for cardiac arrest had a sensitivity of 65.5% and PPV of 90%. The algorithm with the highest sensitivity of 87.3% added sudden infant death syndrome, drowning or asphyxiation with CPR in addition to the cardiac arrest codes for inpatient and ED records. This algorithm had a specificity of 99.9%, PPV of 81.4% and NPV of ∼100.0%. It is important that algorithms used for cohort identification are validated prior to use. The ICD-10 code for cardiac arrest alone misses many POHCA cases but the use of additional codes can improve the sensitivity while maintaining specificity.


Evaluation of attitudes and opinions of medical faculty students against the use of cadaver in anatomy education and investigation of the factors affecting their emotional responses related thereto.
The encounter with the cadaver is one of the few experiences that have a profound effect on the educational life of the medical students. The objective of this study was to investigate medical student's attitudes and opinions towards the use of cadaver in anatomy education, as well as the factors affecting the emotional reactions they demonstrate in their repeated encounter with the cadaver. Before the study, ethics committee approval for the study was obtained from the Gaziantep University Clinical Researches Ethical Committee (decision date and number: 2016/40). Two different questionnaires were administered to 351 students who participated in the study. Questionnaire-I was administered before the student's first encounter with the cadaver, whereas Questionnaire-II was administered twice, one after student's first encounter with the cadaver and the other after student's fifth encounter with the cadaver. The females got significantly more excited before their first encounter with the cadaver, and that they felt more fear and more sadness for the cadaver (p = 0.001, p = 0.002, and p = 0.019, respectively). On the other hand, the males felt significantly readier to see the cadaver (p = 0.002). It was found that statements of emotional shock, excitement, sadness, and fear coming from the participants decreased significantly after their fifth encounter with the cadaver (p = 0.028, p = 0.001, p = 0.048, and p = 0.039, respectively). Repeated encounters with cadavers were found to have reduced the negative emotions felt by the students, but have negatively affected the thoughts of the students in respect of donating their bodies.


[Experimental study of the transferred keratinocytes transplanted on biomembrane].
To search an ideal carrier of transferred keratinocytes for transplantation. The transferred keratinocytes were seeded on the surfaces of the artificial dermis and the silicone membrane and cultured in vitro for 2 weeks. The growth of the keratinocytes was observed by microscope and scanning electron microscope. The keratinocytes implanted on the artificial dermis began to rupture and died after 2 to 3 days. While the keratinocytes adhered well on the surface of silicone membrane with pseudopodia formation after 1 week under scanning electron microscope, and the cells kept normal morphological and proliferative properties 2 weeks later. The silicone membrane can be applied as an useful carrier for the keratinocytes transplantation.


Lethal vascular leak syndrome after denileukin diftitox administration to a patient with cutaneous gamma/delta T-cell lymphoma and occult cirrhosis.
Denileukin diftitox (Ontak) is an immunotoxin used in the treatment of cutaneous T-cell lymphomas. Vascular leak syndrome is a known complication of this therapy, although the syndrome is most often self-limited. We report the case of a patient with cutaneous gamma/delta (gammadelta) T-cell lymphoma and previous undiagnosed liver disease treated with denileukin diftitox. Just 4 days after initiating drug therapy, the patient developed profound vascular leak syndrome characterized by a rapid fall in his previously normal serum albumin to levels below the limit of detection. The patient then quickly deteriorated into rhabdomyolysis and eventual death. To our knowledge, this is the first report of a death directly related to denileukin diftitox therapy. The purpose of this case is to increase awareness and improve management of patients who are treated with denileukin diftitox with resulting vascular leak syndrome leading to hypoalbuminemia.


Stimulus conflict triggers behavioral avoidance.
According to a recent extension of the conflict-monitoring theory, conflict between two competing response tendencies is registered as an aversive event and triggers a motivation to avoid the source of conflict. In the present study, we tested this assumption. Over five experiments, we examined whether conflict is associated with an avoidance motivation and whether stimulus conflict or response conflict triggers an avoidance tendency. Participants first performed a color Stroop task. In a subsequent motivation test, participants responded to Stroop stimuli with approach- and avoidance-related lever movements. These results showed that Stroop-conflict stimuli increased the frequency of avoidance responses in a free-choice motivation test, and also increased the speed of avoidance relative to approach responses in a forced-choice test. High and low proportions of response conflict in the Stroop task had no effect on avoidance in the motivation test. Avoidance of conflict was, however, obtained even with new conflict stimuli that had not been presented before in a Stroop task, and when the Stroop task was replaced with an unrelated filler task. Taken together, these results suggest that stimulus conflict is sufficient to trigger avoidance.


The Ethical Acceptability of a Recipient's Choice of Donor in Directed and Nondirected Transplantation: Japanese Perspective.
In organ transplantation, there is a lack of ethical discussion about the recipient's right not to receive a transplant. Using the current situation of living organ transplantation and deceased organ transplantation in Japan as an example, we prospectively discussed to what extent the recipient's right not to receive a transplant is ethically acceptable. In directed transplantation from a living donor, a recipient may refuse organ donation from a particular donor. It is preferable that a recipient's request for organ donation from a donor occurs as part of a transparent process. In nondirected transplantation from a deceased donor, refusal of transplantation from a particular type of donor appears potentially justifiable. There are both moral and pragmatic considerations. Certain refusals based solely on belief are morally unacceptable, and refusal to transplant a recipient based on the donor's age jeopardizes the entire transplant system. When religious beliefs affect mental and physical health, individualized measures are required for transplant rejection. We also deductively developed a prospective argument based on the current status of donor-recipient communication in living organ transplantation in Japan and the 2010 amendment of the law allowing relatives to be given priority in organ transplantation from deceased donors.


Tensor electrical impedance myography identifies bulbar disease progression in amyotrophic lateral sclerosis
Electrical impedance myography (EIM) is a promising biomarker for amyotrophic lateral sclerosis (ALS). A key issue is how best to utilise the complex high dimensional, multi-frequency data output by EIM to fully characterise the progression of disease. Muscle volume conduction properties were obtained from EIM recordings of the tongue across three electrode configurations and 14 input frequencies (76 Hz-625 kHz). Analyses of individual frequencies, averaged EIM spectra and non-negative tensor factorisation were undertaken. Longitudinal data were collected from 28 patients and 17 healthy volunteers at 3-monthly intervals for a maximum of 9 months. EIM was evaluated against the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) bulbar sub-score, tongue strength and an overall bulbar disease burden score. Longitudinal changes to individual patient EIM spectra demonstrated complex shifts in the spectral shape. At a group level, a clear pattern emerged over time, characterised by an increase in centre frequency and general shift to the right of the spectral shape. Tensor factorisation reduced the spectral data from a total of 168 data points per participant per recording to a single value which captured the complexity of the longitudinal data and which we call tensor EIM (T-EIM). The absolute change in tensor EIM significantly increased within 3 months and continued to do so over the 9-month study duration. In a hypothetical clinical trial scenario tensor EIM required fewer participants (n = 64 at 50% treatment effect), than single frequency measures (n range 87-802) or ALSFRS-R bulbar subscore (n = 298). Changes to tongue EIM spectra over time in ALS are complex. Tensor EIM captured and quantified disease progression and was more sensitive to changes than single frequency EIM measures and other biomarkers of bulbar disease. Objective biomarkers for the assessment of bulbar disease in ALS are lacking. Tensor EIM enhances the biomarker potential of EIM data and can improve bulbar symptom monitoring in clinical trials.


Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents.
The rising epidemic worldwide in overweight and obese children requires urgent attention. Leptin has been found to be associated with body weight control and possibly affects insulin sensitivity. Since insulin resistance is associated with obesity in adults and possibly in adolescents, we set out to investigate the association of plasma leptin level with various anthropometric indices, body fat mass (FM), lipids, and insulin resistance (IR) index in nondiabetic adolescents. A cross-sectional study from three high schools in Taipei City in Taiwan. A total of 402 nondiabetic subjects (162 boys and 240 girls; age range, 10-19 y; mean age, 15.8+/-1.9 y, and mean body mass index (BMI), 24.8+/-4.6 kg/m(2)) were recruited. The fasting plasma leptin, plasma glucose, insulin, lipids, and anthropometric indices including height, weight, waist (WC) and hip circumferences, and waist-to-hip ratio (WHR) were examined. Total body FM and percentage body fat (FM%) were obtained from dual-energy X-ray absorptiometry. The homeostasis model was applied to estimate the degree of IR. The plasma leptin levels were significantly higher in girls (17.45+/-10.13 ng/ml) than boys (8.81+/-6.71 ng/ml, P<0.001). The plasma leptin levels were positively correlated to BMI, WC, WHR, FM, FM%, and triglycerides (TG). The IR index was positively correlated to BMI, WC, WHR, FM, FM%, TG, and leptin. Using the multivariate linear regression models, we found that plasma leptin remains significantly associated with IR index even after adjusting for age, gender, BMI, FM, WC, Tanner stage, and TG. Plasma leptin was associated with IR index independent of age, gender, BMI, FM, WC, Tanner stage, and TG. Plasma leptin levels in adolescents could be a predictor for the development of the metabolic syndrome disorders and cardiovascular diseases.


Effects of FPL-55712 or indomethacin on leukotriene-induced coronary constriction in the intact pig heart.
Intracoronary leukotriene D4, 0.1-3.0 micrograms (0.2-6.0 nmol), produced dose-dependent decreases in coronary flow of anesthetized pigs. Pretreatment with intracoronary FPL-55712 (0.1, 0.3 and 1.0 mg) reduced coronary constriction due to 1.0 micrograms leukotriene D4 by up to 77%. FPL-55712 did not produce sustained alterations in coronary flow, left ventricular end-diastolic pressure, systemic arterial pressure, or heart rate. Indomethacin pretreatment (6 mg/kg i.v.) had no effect on leukotriene-induced coronary constriction. Inhibition produced by FPL-55712 may be useful in disease states involving leukotriene-mediated coronary constriction.


Endothelin-1 contributes to the sexual differences in renal damage in DOCA-salt rats.
We investigated whether gender differences in renal damage in DOCA-salt hypertension are associated with effects of ovarian hormones and/or endothelin-1 (ET-1). Renal injuries and renal pre-pro-ET-1 mRNA expression were enhanced in male and female ovariectomized (OVX) DOCA rats versus female DOCA rats. Treatment with estrogen plus progesterone or progesterone, but not estrogen alone, attenuated renal damage and pre-pro-ET-1 mRNA expression in OVX DOCA rats. The ETA antagonist BMS182874 greatly ameliorated renal damage in male and OVX DOCA rats. In conclusion, the ovarian hormones have a protective role on the renal structural alterations in female DOCA rats by modulating effects of ET-1, via ETA receptors.


Successful treatment of near-fatal asthma with ECMO: A case report and literature review.
Near-fatal asthma (NFA) can lead to severe hypercapnia and sudden cardiac arrest; however, it can be reversed by extracorporeal membrane oxygenation (ECMO). We report a case of a 37-year-old male diagnosed with NFA. After fluid rehydaration, spasmolysis, and treatment with glucocorticoid and mechanical ventilation, the patient's condition improved temporarily. However, his condition worsened rapidly, and the patient presented with progressive respiratory distress, a sharp increase in airway pressure, decreased tidal volume, and barotrauma. The patient was treated with venovenous ECMO in the prone position. Five days later, the patient was successfully weaned from ECMO. Hence, ECMO could be used for NFA at the right time to provide adequate gas exchange for patients in order to reduce lung damage and prevent death.


Agglutination tests and their modifications in the diagnosis of bovine brucellosis.
This article reviews the effects of using Yersinia enterocolitica serotype: 09 somatic antigen in diagnostic tests for brucellosis. The tests employed include the standard tube agglutination test, the microplate agglutination test, the quantitative plate agglutination test, the growth agglutination test and the indirect hemagglutination technique. Only the growth agglutination technique demonstrated an increased sensitivity over the STAT. Neither the microplate agglutination test nor quantitative plate tests offered any significant advantages over the STAT. The QPAT using Brucella O antigen was clearly subject to false negative results. The indirect hemagglutination technique showed extreme variation in results, the significance of which (if any) was unclear.


Effects of cis- and trans-platinum complexes on RNA transcription.
Current thinking concerning the anti-cancer actions of platinum complexes view cis-platinum agents as active and trans-complexes as not being anti-neoplastic. It is generally accepted that the active cis forms exert their effects by binding to the DNA template. Data is presented here showing trans-Pt(NH3)2Cl2(trans-PDD) to be much more active than cis-Pt(NH3)2Cl2(cis-PDD) in inhibiting in vitro RNA transcription using both bacterial and eukaryotic enzyme sources. It is further shown that the polymerase enzyme is a much more sensitive target for these platinum agents than the DNA template under the conditions employed.


Effect of dietary Ergosan on growth performance, digestive enzymes, intestinal histology, hematological parameters and body composition of rainbow trout (Oncorhynchus mykiss).
Present study examined the effects of Ergosan on growth performance, digestive enzyme activities, hematological parameters and gastrointestinal structure of rainbow trout. Rainbow trout (mean weight 100-110 g) were fed basal diet (control) and diet treated with Aquavac Ergosan (5 g kg⁻¹ of diet) for 50 days. Results of this study showed that Ergosan supplementation significantly increased weight gain (94.27 g vs. 65.04 g), specific growth rate (4.09 vs. 3.10) and feed intake (136.85 g vs. 111.22 g) and decreased feed conversion ratio (1.43 vs. 2.03) compared to control (P<0.05). Lipase activity and leukocyte and erythrocyte count also increased in juvenile fish fed Ergosan-treated diet compared to control (P<0.05). Light microscopy demonstrated that both groups of fish displayed normal morphology of proximal intestine and pyloric caeca. In Ergosan-treated group, higher percentage of goblet cell was shown in proximal intestine and pyloric caeca. Present study suggests that Ergosan effectively promotes growth performance, lipase activity and gastrointestinal structure in rainbow trout.


Sodium Glucose Transporter, Type 2 (SGLT2) Inhibitors (SGLT2i) and Glucagon-Like Peptide 1-Receptor Agonists: Newer Therapies in Whole-Body Glucose Stabilization.
Diabetes is a worldwide epidemic that is increasing rapidly to become the seventh leading cause of death in the world. The increased incidence of this disease mirrors a similar uptick in obesity and metabolic syndrome, and, collectively, these conditions can cause deleterious effects on a number of organ systems including the renal and cardiovascular systems. Historically, treatment of type 2 diabetes has focused on decreasing hyperglycemia and glycated hemoglobin levels. However, it now is appreciated that there is more to the puzzle. Emerging evidence has indicated that newer classes of diabetes drugs, sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1-receptor agonists, improve cardiovascular and renal function, while appropriately managing hyperglycemia. In this review, we highlight the recent clinical and preclinical studies that have shed light on sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1-receptor agonists and their ability to stabilize blood glucose levels while offering whole-body protection in diabetic and nondiabetic patient populations.


Prospects for targeting protein kinase C isozymes in the therapy of drug-resistant cancer--an evolving story.
The seminal discovery in 1988 that selective protein kinase C (PKC) activators induce multidrug resistance (MDR) in human cancer cells spawned several years of intensive investigations; these studies were primarily directed at the question of whether isozyme-selective PKC antagonism could reverse MDR phenotypes produced in cancer cells by P-glycoprotein and other ATP-binding cassette (ABC) transporters. The first section of this commentary provides a succinct overview of those studies. In the second section, we evaluate why the enthusiasm for studies of the involvement of PKC in transport-related drug resistance is currently diminished, and we offer an assessment of whether the PKC/MDR field should be revisited. The final section of the commentary highlights recent developments in studies of PKC targeting in experimental cancer therapeutics, which continues to be a vibrant field. Highlights include the sensitization of cancer cells to radiation- and drug-induced apoptosis by PKC inhibition.


Cosmetic gynecology-An emerging field for the dermatologist.
Cosmetic gynecology is an expanding field with a steep rise in awareness and demand for procedures to enhance the aesthetic appearance of female genitalia. This article aims to provide an overview of aesthetic gynecology for a practicing dermatologist. A study conducted in India showed a rising trend in the demand of aesthetic vaginal procedures from 3.9% in 2012 to 28.97% in 2015. Several aesthetic modalities such as peels, platelet rich plasma, and energy-based devices and surgical modalities have been in use, though serious evidence for efficacy of many of these procedures is lacking.


Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and peritoneum).
Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and peritoneum) Ovarian serous carcinoma (OSC) is the most common of the ovarian epithelial malignancies, and accounts for most of the mortality. Traditionally, ovarian cancer has been considered to be one disease; however, it is now apparent that it actually consists of many different entities. OSC can be further segregated into two processes: high-grade serous carcinoma (HGSC) and low-grade serous carcinoma. This classification is supported by molecular changes, morphological appearance, clinical behaviour, and distinct precursor lesions. This review will describe in detail these features of OSC, differential diagnosis, prognosis, and recent challenges to the existing hypotheses regarding the origin of these tumours. Special attention will be paid to HGSC and its relationship with BRCA abnormalities, especially those seen in hereditary breast and ovarian cancer syndrome. Finally, treatment options based on specific molecular targets will be discussed.


The reaction of chemical probes with the erythrocyte membrane.
Trinitrobenzenesulfonate (TNBS), fluorodinitrobenzene (FDNB) and suberimidate have been reacted with intact human erythrocytes. TNBS does not penetrate the cell membrane significantly at 23 degrees C in bicarbonate-NaCl buffer, pH 8.6, as estimated by the labeling of the N-terminal valine of hemoglobin. Hence, under these conditions it can be used as a vectorial probe. However, at 37 degrees C, especially in phosphate buffer, at pH 8.6, TNBS does penetrate the cell membrane. FDNB and suberimidate both penetrate the erythrocyte membrane. The time course reaction of TNBS with intact erythrocytes over a 24-hr period at 23 degrees C is complex and shows transition zones for both membrane phosphatidylethanolamine (PE) and membrane proteins. No significant cell lysis occurs up to 10 hr. The fraction of total PE or phosphatidylserine (PS) which reacts with TNBS by this time period can be considered to be located on the outer surface of the cell membrane. Under these conditions it can be located on the outer surface of the cell membrane. Under these conditions it can be shown that 10 to 20% of the total PE and no PS is located on the outer surface of the membrane and hence these amino phospholipids are asymmetrically arranged. The pH gradient between the inside and outside of the cell in our system is 0.4 pH units. Nigericin has no effect on the extent of labeling of PE or PS by TNBS. Isotonic sucrose gives a slight enhancement of the labeling of PE by TNBS. Hence, the inability of PE and PS to react with the TNBS is considered not due to the inside of the cell having a lower pH. The extent of reaction of TNBS with PE is not influenced by changing the osmolarity of the medium or by treatment of cells with pronase, trypsin, phospholipase A or phospholipase D. However, bovine serum albumin (BSA) does protect some of the PE molecules from reacting with TNBS. Cels treated with suberimidate were suspended in either isotonic NaCl or in distilled water. In both cases the suberimidate-treated cells became refractory to hypotonic lysis. Pretreatment of cells with TNBS did not prevent them from interacting with suberimidate and becoming refractory to lysis. However, pretreatment of cells with the penetrating probe FDNB abolished the suberimidate effect. Electron-microscopic analysis of the cells showed a continuous membrane in the case of cells suspended in isotonic saline. The cells suspended in water did not lyse but their membranes had many large holes, sufficient to let the hemoglobin leak out. Since the hemoglobin did not leak out we know that the hemoglobin is cross-linked into a large supramolecular aggregate.


Elective Labor Induction at 39 Weeks of Gestation Compared With Expectant Management: Factors Associated With Adverse Outcomes in Low-Risk Nulliparous Women.
To evaluate characteristics associated with adverse outcomes in low-risk nulliparous women randomized to elective labor induction at 39 weeks of gestation or expectant management. We conducted a secondary analysis of women randomized during the 38th week to induction at 39 weeks of gestation or expectant management. Deliveries before 39 weeks of gestation and those not adherent to study protocol or with fetal anomalies were excluded. A composite of adverse outcomes (perinatal death or severe neonatal complications), third- or fourth-degree lacerations, and postpartum hemorrhage were evaluated. Log binomial regression models estimated relative risks and 95% CIs for associations of outcomes with patient characteristics including randomly assigned treatment group. Interactions between patient characteristics and treatment group were tested. Of 6,096 women with outcome data, 5,007 (82.1%) met criteria for inclusion in this analysis. Frequency of the perinatal composite was 252 (5.0%), 166 (3.3%) for third- or fourth-degree perineal laceration, and 237 (4.7%) for postpartum hemorrhage. In multivariable analysis, intended labor induction at 39 weeks of gestation was associated with a reduced perinatal composite outcome (4.1% vs 6.0%; adjusted relative risk [aRR] 0.71; 95% CI 0.55-0.90), whereas increasing body mass index (BMI) was associated with an increased perinatal composite outcome (aRR 1.04/unit increase; 95% CI 1.02-1.05). Decreased risk of third- or fourth-degree perineal laceration was observed with increasing BMI (aRR 0.96/unit increase; 95% CI 0.93-0.98) and in Black women compared with White women (1.2% vs 3.9%; aRR 0.34; 95% CI 0.19-0.60). Increased risk of postpartum hemorrhage was observed in Hispanic women compared with White women (6.3% vs 4.0%; aRR 1.64; 95% CI 1.18-2.29). Patient characteristics associated with adverse outcomes were similar between treatment groups (P for interaction >.05). Compared with expectant management, intended induction at 39 weeks of gestation was associated with reduced risk of adverse perinatal outcome. Patient characteristics associated with adverse outcomes were few and similar between groups. ClinicalTrials.gov, NCT01990612.


Biomarker changes with systolic anterior motion of the mitral valve in cats with hypertrophic cardiomyopathy.
N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) are biomarkers commonly evaluated in cats with suspected heart disease. Many cats with hypertrophic cardiomyopathy (HCM) have systolic anterior motion of the mitral valve (SAM), but its influence on circulating NT-proBNP or cTnI concentrations is currently unknown. Cats with HCM and SAM (HCMSAM+ ) have higher NT-proBNP and cTnI concentrations than do cats with HCM but without SAM (HCMSAM- ). One hundred forty cats with HCM: 70 with SAM and 70 without SAM. Retrospective case-to-case study. Cats were recruited if diagnosed with HCM by echocardiography and results were available for NT-proBNP or cTnI concentrations or both. Cats with SAM were matched to those without SAM for clinical presentation, left atrial (LA) size and left ventricular (LV) fractional shortening. A total of 119 NT-proBNP and 123 cTnI results were available. The HCMSAM+ cats had higher median concentrations than did HCMSAM- cats for NT-proBNP (729 pmoL/L; interquartile range [IQR], 275-1467 versus 65 pmoL/L; IQR, 25-271; P < .001) and cTnI (0.27 ng/mL; IQR, 0.10-0.81 versus 0.07 ng/mL; IQR, 0.01-0.43; P = .002). In general linear models for both NT-proBNP and cTnI, the independent explanatory variables were SAM, congestive heart failure, maximal LV wall thickness, and LA size. For cats with HCM and equivalent LA size and LV systolic function, those with SAM had higher NT-proBNP and cTnI concentrations than did those without SAM. Presence of SAM should be considered when interpreting biomarker concentrations in cats with HCM.


Ability of rosetting or non-rosetting individual control and inflammatory macrophages to kill Escherichia coli X43 intracellularly.
An autoradiographic method combined with a rosette technique was used to assess the bactericidal activity of individual control and inflammatory peritoneal macrophages (PM phi) in the presence or absence of expression of Fc receptor for IgG (FcR). There was a lack of FcR reactivity in a certain percentage of both categories of PM phi exposed to E. coli X43, a bacterium which is readily phagocytosed in the presence of specific antibody. Both rosetting and non-rosetting PM phi were capable of phagocytosing E. coli X43, but inflammatory PM phi showed a marked reduction in their capacity to ingest these bacteria compared with control PM phi. Once ingested the E. coli X43 were killed equally well by non-rosetting and rosetting control and inflammatory PM phi.


Numerical analysis of the 3-dimensional aortic root morphology during the cardiac cycle.
The aim was to define the 3-dimensional (3D) geometrical changes of the aortic root and to determine the local shear stress profile of aortic root elements during the cardiac cycle. Six sonomicrometric crystals (200 Hz) were implanted into the aortic root of five pigs at the commissures and at the aortic root base (AoB). 3D aortic root deformation including volume, torsion and tilt angle were determined. Geometrical data with measured local flow and pressure conditions was used for computed fluid dynamics modelling of the aortic root. Compared with end-diastole, the sinotubular junction and AoB have maximal expansion at peak ejection: 16.42 ± 6.36 and 7.60 ± 2.52%, and minimal at isovolaemic relaxation: 2.87 ± 1.62 and 1.85 ± 1.79%. Aortic root tilt and rotation angle were maximal at the end of diastole: 17.7 ± 8.8 and 21.2 ± 2.09°, and decreased to 15.24 ± 8.14 and 18.3 ± 0.1.94° at peak ejection. High shear stress >20 Pa was registered at peak ejection at coaptations, and during diastole at the superior two-thirds of the leaflets and intervalvular triangles (IVTs). The leaflet body, inferior one-third of the IVTs and valve nadir were exposed to moderate shear stress (8-16 Pa) during the cardiac cycle. Aortic root geometry demonstrates precise 3D changes of tilt and rotation angle. Reduction of angles during ejection results in a straight cylinder with low shear stress that facilitates the ejection; the increase during diastole results in a tilted frustum with elevated shear stress. Findings can be used for comparative analysis of native and synthetic structures with individual compliance.


Data and performances evaluation of the SPIDIA-DNA Pan-European External Quality Assessment: 2nd SPIDIA-DNA laboratory report.
Within the EU-SPIDIA project (www.spidia.eu), the quality parameters of blood genomic DNA were defined [SPIDIA-DNA: an External Quality Assessment for the pre-analytical phase of blood samples used for DNA-based analyses - [1]; Influence of pre-analytical procedures on genomic DNA integrity in blood samples: the SPIDIA experience - [2]; Combining qualitative and quantitative imaging evaluation for the assessment of genomic DNA integrity: the SPIDIA experience - [3]. DNA quality parameters were used to evaluate the laboratory performance within an External Quality Assessment (EQA) [Second SPIDIA-DNA External Quality Assessment (EQA): Influence of pre-analytical phase of blood samples on genomic DNA quality - [4]. These parameters included DNA purity and yield by UV spectrophotometric measurements, the presence of PCR interferences by Kineret software and genomic DNA integrity analysis by Pulsed Field Gel Electrophoresis. Here we present the specific laboratory report of the 2nd SPIDIA-DNA EQA as an example of data and performances evaluation.


Infection of the human orbit by Aspergillus stromatoides. Case report.
We report a case of human infection due to Aspergillus stromatoides. To our knowledge this organism has not previously been described as causing human infections. The infection of sino-orbital tissues was of 3 1/2 years duration and the patient died following cerebral involvement despite seven months of hospitalisation and therapy including amphotericin B, 5-fluorocytosine and rifampicin.


Monoclonal antibodies to Neurospora adenylate cyclase.
A monoclonal antibody against Neurospora soluble adenylate cyclase was obtained. The antibody inhibits cyclase activities from several lower eucaryotic organisms but not activities associated to testicular cytosol or turkey erythrocyte membranes.


Clinical outcome of biportal endoscopic revisional lumbar discectomy for recurrent lumbar disc herniation.
Although literature provides evidence regarding the superiority of surgery over conservative treatment in patients with lumbar disc herniation, recurrent lumbar disc herniation (RLDH) was the indication for reoperation in 62% of the cases. The major problem with revisional lumbar discectomy (RLD) is that the epidural scar tissue is not clearly isolated from the boundaries of the dura matter and nerve roots; therefore, unintended durotomy and nerve root injury may occur. The biportal endoscopic (BE) technique is a newly emerging minimally invasive spine surgical modality. However, clinical evidence regarding BE-RLD remains limited. We aimed to compare the clinical outcomes after performing open microscopic (OM)-RLD and BE-RLD to evaluate the feasibility of BE-RLD. This retrospective study included 36 patients who were diagnosed with RLDH and underwent OM-RLD and BE-RLD. RLDH is defined as the presence of herniated disc material at the level previously operated upon in patients who have experienced a pain-free phase for more than 6 months. BE-RLD was performed as follows: two independent surgical ports were made inside the medial pedicular line of the target segment and on the intact upper and lower laminas. Peeling off the soft tissue from the vertebral lamina helps to easily identify the traversing nerve root and the recurrent disc material without dealing with the fibrotic scar tissue. Clinical outcomes were obtained using a visual analog scale (VAS) and the modified Macnab criteria before and at 2 days, 2 and 6 weeks, and 3, 6, and 12 months after surgery. The data of 20 and 16 patients who underwent OM-RLD and BE-RLD, respectively, were evaluated. The demographic and perioperative data were comparable between the groups. During the year following the surgery, in the BE-RLD group, the VAS scores at each point were significantly improved over the baseline and remained improved up to 2 weeks after surgery (p < 0.05); however, no statistical difference between the two groups was observed after 6 weeks of surgery (p > 0.05). According to the modified Macnab criteria on the follow-up, the excellent or good satisfaction rates reported at 2 weeks, 6 weeks, 6 months, and 12 months after surgery were 81.25%, 81.25%, 75%, and 81.25%, respectively, in the BE-RLD group, and 50%, 75%, 75%, and 80%, respectively, in the OM-RLD group. BE-RLD yielded similar outcomes to OM-RLD, including pain improvement, functional improvement, and patient satisfaction, at 1 year after surgery. However, faster pain relief, earlier functional recovery, and better patient satisfaction were observed when applying BE-LRD. Retrospectively registered.


Hepatitis C virus infection in the Middle East and North Africa "MENA" region: injecting drug users (IDUs) is an under-investigated population.
Investigation of the injecting drug users (IDUs) population is becoming extremely critical and timely in light of the recent evidence that IDUs now act as the core of hepatitis C virus (HCV) epidemics in developed countries. The purpose of this article, therefore, is not only to review the epidemiology of HCV in the Middle East and North Africa (MENA) region, but also to see whether IDUs were adequately studied and whether harm reduction strategies to be applied for their protection have been set. A literature review was carried out of articles published within the last decade on HCV infection. The gathered data showed that the population of IDUs is severely under-investigated throughout the whole region, possibly due to religious and cultural impediments. In order to reduce the risk of HCV infection in IDUs, a set of recommendations are advanced emphasizing the urgent need for bio-behavioral studies in this population in order to help identify the source and mode of transmission and the genotypes of HCV involved. These results may allow the development of effective and, yet, socially acceptable intervention strategies. We believe that the role which IDUs play in sustaining HCV infection is also an under-investigated topic in many developing countries. Similar reviews and, hence, interventions should be initiated in these regions.


Linear and nonlinear modeling of antifungal activity of some heterocyclic ring derivatives using multiple linear regression and Bayesian-regularized neural networks.
Antifungal activity was modeled for a set of 96 heterocyclic ring derivatives (2,5,6-trisubstituted benzoxazoles, 2,5-disubstituted benzimidazoles, 2-substituted benzothiazoles and 2-substituted oxazolo(4,5-b)pyridines) using multiple linear regression (MLR) and Bayesian-regularized artificial neural network (BRANN) techniques. Inhibitory activity against Candida albicans (log(1/C)) was correlated with 3D descriptors encoding the chemical structures of the heterocyclic compounds. Training and test sets were chosen by means of k-Means Clustering. The most appropriate variables for linear and nonlinear modeling were selected using a genetic algorithm (GA) approach. In addition to the MLR equation (MLR-GA), two nonlinear models were built, model BRANN employing the linear variable subset and an optimum model BRANN-GA obtained by a hybrid method that combined BRANN and GA approaches (BRANN-GA). The linear model fit the training set (n = 80) with r2 = 0.746, while BRANN and BRANN-GA gave higher values of r2 = 0.889 and r2 = 0.937, respectively. Beyond the improvement of training set fitting, the BRANN-GA model was superior to the others by being able to describe 87% of test set (n = 16) variance in comparison with 78 and 81% the MLR-GA and BRANN models, respectively. Our quantitative structure-activity relationship study suggests that the distributions of atomic mass, volume and polarizability have relevant relationships with the antifungal potency of the compounds studied. Furthermore, the ability of the six variables selected nonlinearly to differentiate the data was demonstrated when the total data set was well distributed in a Kohonen self-organizing neural network (KNN).


Nanoparticle Cookies Derived from Metal-Organic Frameworks: Controlled Synthesis and Application in Anode Materials for Lithium-Ion Batteries.
The capacity of anode materials plays a critical role in the performance of lithium-ion batteries. Using the nanocrystals of oxygen-free metal-organic framework ZIF-67 as precursor, a one-step calcination approach toward the controlled synthesis of CoO nanoparticle cookies with excellent anodic performances is developed in this work. The CoO nanoparticle cookies feature highly porous structure composed of small CoO nanoparticles (≈12 nm in diameter) and nitrogen-rich graphitic carbon matrix (≈18 at% in nitrogen content). Benefiting from such unique structure, the CoO nanoparticle cookies are capable of delivering superior specific capacity and cycling stability (1383 mA h g(-1) after 200 runs at 100 mA g(-1) ) over those of CoO and graphite.


Electron microscopic cytochemical demonstration of adenyl cyclase activity in psoriatic epidermis.
Isoproterenol and sodium fluoride stimulated adenyl cyclase activity was detected in epidermal tissue from 2 patients with untreated psoriasis by an electron microscopic cytochemical technique. Adenyl cyclase activity was present on the outer surface of the cell membranes, predominantly in the basal cells and in the 4-5 lower Malpighian cell layers, while the superficial layers, stratum granulosum and stratum corneum showed no activity. The precipitates (lead-PPi complexes) after isoproterenol stimulation were larger and fewer in number than those seen after sodium fluoride stimulation. Isoproterenol stimulation was abolished by propranolol. Neither the uninvolved epidermis from the 2 patients with psoriasis nor the normal skin from 2 volunteer individuals showed any difference from the psoriatic epidermis.


Comparison of the Stanford ECG Left Atrial Criteria With the International ECG Criteria for Sports Screening.
Because the International left atrial enlargement electrocardiographic (ECG) screening criteria (ECG-LAE) for athletes are rarely fulfilled in young athletes, we compared it with evidence-based criteria from a recent clinical outcome study of ECG left atrial abnormality (ECG-LAA). Retrospective analyses. Routine preparticipation ECG screening in California. Four thousand four hundred thirty-eight young individuals (18.5 ± 5.4 years, 40% women). The International criteria for ECG-LAE were applied: prolonged P wave duration of ≥120 ms in leads I or II AND negative portion of ≥1 mm in depth in lead V1. This was compared with Stanford criteria for ECG-LAA: prolonged P wave duration of ≥140 ms odds ratio (OR) negative portion in V1 and V2 greater than 1 mm. Differences in the classification of abnormal ECGs between the 2 criteria applied to the same population of young athletes. Only 33 (0.7%) of our subjects fulfilled the International criteria for ECG-LAE while 110 (2.5%) fulfilled the ECG-LAA criteria. Adding our new ECG-LAA criterion and considering it a major criterion raised the abnormal ECG prevalence and athletes referred for further evaluation from 2.9% to 4.4%. The Stanford evidence-based criterion for ECG-LAA incorporating V2 and replacing "or" for "and" regarding P wave duration increased the yield of abnormal classification for P waves. Future follow-up studies are needed to confirm that this new criterion should be included in future ECG screening consensus documents.


Prevalence of depression, anxiety and their risk factors in German women with breast cancer in general and gynecological practices.
To analyze the prevalence of depression, anxiety and their risk factors in German women with breast cancer (BC) in general and gynecological practices (GP, GYP). Women initially diagnosed with BC between 2009 and 2013 were identified by 1202 general practitioners and 244 gynecologists in the IMS Disease Analyzer database. They were included only if they had not suffered from depression or an anxiety disorder within the 12 months prior to the index date. The main outcome was the first diagnosis of depression or an anxiety disorder within 5 years after index date. A multivariate Cox regression model was used to predict these diagnoses on the basis of patient characteristics. A total of 24,537 patients in GP were available for the study, as well as 20,018 patients in GYP. The mean age was 65.8 and 62.5 years in GP and GYP, respectively (p value <0.0001). The proportions of depressive or anxiety episodes in the past and the proportion of metastases were higher in GP than in GYP (7.9 vs. 3.6%, and 10.1 vs. 8.6%, p values <0.0001). Within 5 years of follow-up, 36.9% of GP patients and 35.1% of GYP patients had been diagnosed with depression or anxiety. There was a significantly higher risk of depression and/or anxiety in women in the age groups 51-60, 61-70 and >70 years than in women = <50 years (OR between 1.05 and 1.27, all p values lower than 0.0359). Patients with metastases or with previous episodes of depression/anxiety had a higher risk of depression/anxiety (OR = 1.21 and 1.97, p values <0.0001). Finally, women with private health insurance had a lower risk of depression and anxiety (OR = 0.45, p value <0.0001). The present study indicates that levels of depression and anxiety increase in German women after diagnosis of BC and may be predicted on the basis of several demographic and clinical characteristics.


Power, professions and evidence-based guidelines: lessons from an organizational case study.
This paper addresses the issues of evidence-based practice (EBP) in relation to power, professionalism and the British National Health Service reforms. There has been little discussion at organizational level over issues of professional boundaries, roles and tensions, which are inextricably linked with the drive for an evidence-based culture. The paper is a reflection on the findings of a recent case study, which examined the management and organization of an independent sector provider of mental health services in its drive to address issues of EBP. New managerial hegemony had altered the balance of power within the organization, there was an extension of managerial surveillance, competing political relationships and a general decline in medical dominance. Organizations should avoid 'personalizing' the debate on establishing a research-based culture. EBP requires structures to support it and groups representing the health care professions within the organization should be involved in identifying and making recommendations on EBP issues.


Reliability of three-dimensional measurements of the upper airway on cone beam computed tomography images.
The aim of this study was (1) to assess intra- and interobserver reliability of the localization of anatomic landmarks of the upper airway on cone beam computed tomography (CBCT) images; and (2) to assess intra- and interobserver reliability of the three-dimensional measurements of the upper airway based on these landmarks. Fifteen NewTom 5G (QR systems, Verona, Italy) CBCT data sets were randomly selected from the archives of the Department of Oral Radiology, Academic Centre for Dentistry (ACTA) at University of Amsterdam and VU University, Amsterdam, The Netherlands. Three observers localized six anatomic landmarks that are relevant for upper airway analysis twice, with a 10-day interval, using 3Diagnosys software (v5.3.1, 3diemme, Cantu, Italy). Subsequently, the observers performed upper airway volume measurement based on those landmarks twice as well, again with a 10-day interval, using Amira software (v4.1, Visage Imaging Inc., Carlsbad, CA). The upper airway measurements also included the minimum cross-sectional area (CSAmin), location of the CSAmin, and anteroposterior and lateral dimensions of the CSAmin. Both intraobserver reliability and interobserver reliability were excellent for the localization of the anatomic landmarks of the upper airway (intraclass correlation coefficients = 0.97-1.00) as well as for the three-dimensional upper airway measurements (intraclass correlation coefficients = 0.78-1.00). The methodology of landmark localization and upper airway measurements, as used in this study, showed an excellent reliability and can thus be recommended for upper airway analysis on CBCT images.


MRI Fat-Saturated T2-Weighted Radiomics Model for Identifying the Ki-67 Index of Soft Tissue Sarcomas.
Ki-67 expression has been shown to be an important risk factor associated with prognosis in patients with soft tissue sarcomas (STSs). Its assessment requires fine-needle biopsy and its accuracy can be influenced by tumor heterogeneity. To develop and test an MRI-based radiomics nomogram for identifying the Ki-67 status of STSs. Retrospective. A total of 149 patients at two independent institutions (training cohort [high Ki-67/low ki-67]: 102 [52/50], external validation cohort [high Ki-67/low ki-67]: 47 [28/19]) with STSs. Fat-saturated T2-weighted imaging (FS-T2WI) with a fat-suppressed fast spin/turbo spin echo sequence at 1.5 T or 3 T. After radiomics feature extraction, logistic regression (LR), random forest (RF), support vector machine (SVM), and k-nearest neighbor (KNN) were used to construct radiomics models to distinguish between high and low Ki-67 status. Clinical-MRI characteristics included age, gender, location, size, margin, and MRI morphological features (size, margin, signal intensity, and peritumoral hyperintensity) were assessed. Univariate and multivariate logistic regression analysis were applied for screening significant risk factors. Radiomics nomogram was constructed by radiomics signature and risk factors. Model performances (discrimination, calibration, and clinical usefulness) were validated in the validation cohort. The nomogram was assessed using the Harrell index of concordance (C-index), calibration curve analysis. The clinical utility of the model was assessed by decision curve analysis (DCA). LR, RF, SVM, and KNN models represented AUCs of 0.789, 0.755, 0.726, and 0.701 in the validation cohort (P > 0.05). The nomogram had a C-index of 0.895 (95% CI: 0.837-0.953) in the training cohort and 0.852 (95% CI: 0.796-0.957) in the validation cohort and it demonstrated good calibration and clinical utility (P = 0.972 for the training cohort and P = 0.727 for the validation cohort). This MRI-based radiomics nomogram developed showed good performance in identifying Ki-67 expression status in STSs. 2.


Growth of Klebsiella aerogenes on xylitol: implications for bacterial enzyme evolution.
When Klebsiella aerogenes was grown in continuous culture with xylitol. an unnatural pentitol, as the growth limiting substrate, the structural gene which codes for ribitol dehydrogenase, an enzyme which gratuitously catalyzes the oxidation of xylitol to D-xylulose, was duplicated. It appears that the duplication mechansim only duplicates the gene which is subjected to selective pressure and not any of the other closely linked genes. The degree to which the ribitol dehydrogenase gene is duplicated does not appear to be strictly correlated with the ability to grow faster on xylitol. Duplication mutants do, in fact, grow faster than their parent strain, but when challenged to grow at even higher growth rates there is a catabolic repression of enzyme activity. Thus a situation is created in which a structural gene is duplicated in response to selective pressure; these mutants can grow faster on the new substrate, but faster growth results in a "silencing" of a portion of the genes by catabolite repression.