Cholesterics of colloidal helices: predicting the macroscopic pitch from the particle shape and thermodynamic state.
Building a general theoretical framework to describe the microscopic origin of macroscopic chirality in (colloidal) liquid crystals is a long-standing challenge. Here, we combine classical density functional theory with Monte Carlo calculations of virial-type coefficients to obtain the equilibrium cholesteric pitch as a function of thermodynamic state and microscopic details. Applying the theory to hard helices, we observe both right- and left-handed cholesteric phases that depend on a subtle combination of particle geometry and system density. In particular, we find that entropy alone can even lead to a (double) inversion in the cholesteric sense of twist upon changing the packing fraction. We show how the competition between single-particle properties (shape) and thermodynamics (local alignment) dictates the macroscopic chiral behavior. Moreover, by expanding our free-energy functional, we are able to assess, quantitatively, Straley's theory of weak chirality, which is used in several earlier studies. Furthermore, by extending our theory to different lyotropic and thermotropic liquid-crystal models, we analyze the effect of an additional soft interaction on the chiral behavior of the helices. Finally, we provide some guidelines for the description of more complex chiral phases, like twist-bend nematics. Our results provide new insights into the role of entropy in the microscopic origin of this state of matter.


Purification and cardiovascular activity of [Met1, Met5]-bradykinin from the plasma of a sturgeon (Acipenseriformes).
The sturgeons (Order Acipenseriformes) are extant representatives of a group of primitive Actinopterygian (ray-finned) fish that probably shared a common ancestor with present-day teleosts. Incubation of heat-denatured plasma from a sturgeon (a hybrid of the shovelnosed sturgeon Scaphirhynchus platorynchus and the pallid sturgeon Scaphirhynchus albus) with either trypsin or porcine pancreatic kallikrein generated bradykinin-like immunoreactivity. The primary structure of sturgeon bradykinin was established as Met-Pro-Pro-Gly-Met-Ser-Pro-Phe-Arg. This amino acid sequence contains two amino acid substitutions (Arg1 --> Met and Phe5 --> Met) compared with mammalian bradykinin. Bolus injections of synthetic sturgeon bradykinin in doses as low as 1 pmol/kg into the dorsal aorta of unanesthetized sturgeon resulted in an immediate and significant fall in arterial blood pressure with a maximum depressor response at 300 pmol/kg. Thus, the cardiovascular response of the sturgeon to bradykinin resembles more closely the response of mammals rather than the predominantly pressor response seen in teleost fish. Sturgeon bradykinin produced a strong and concentration-dependent (EC50 = 4.7 +/- 0.7 x 10(-10) M) relaxation of rings of vascular tissue from the sturgeon ventral aorta that had been pre-contracted with acetylcholine. The data indicate that sturgeon tissues are particularly responsive to native bradykinin and suggest that the kallikrein-kinin system may have evolved before the appearance of the neopterygians (gars, bowfin and teleosts).


Predictors and effect of physical symptom status on health-related quality of life in patients with heart failure.
Physical symptoms are common and distressing problems for patients with heart failure and may be the strongest predictor of health-related quality of life. Identification of variables predictive of physical symptom status is needed to develop effective interventions to improve health-related quality of life. A total of 84 patients discharged after being hospitalized for exacerbation of heart failure were followed up for 3 months. The Minnesota Living With Heart Failure Questionnaire and the Dyspnea-Fatigue Index were used to assess health-related quality of life and physical symptom status, respectively. Relationships of health-related quality of life and physical symptom status to baseline demographic, behavioral, biophysiological, and psychological variables were examined with bivariate correlations and stepwise multiple regression analyses. Patients with better physical symptom status and those who worked, were older, and were less anxious at baseline reported better health-related quality of life (F=12.4, P<.001); physical symptom status was the strongest predictor. Patients who had less depression, worked, had higher perceived control, and were younger at baseline reported better physical symptom status (F=14.4, P<.001); depression was the strongest predictor. Physical symptom status is the most important predictor of health-related quality of life, and baseline depression and perceived control are the best predictors of physical symptom status. Interventions targeted to improve psychological status may improve physical symptom status and thereby improve health-related quality of life.


Beyond destructive and constructive interparental conflict: Children's psychological vulnerability to interparental disorganization.
Guided by models of family unpredictability, this study was designed to identify the distinctive sequelae of disorganized interparental conflict, a dimension of interparental conflict characterized by abrupt, inexplicable changes in parental emotional lability, conflict tactics, and verbalizations. Participants included 208 kindergarten children (M age = 5.74 years; 56% girls), mothers, and their caregiving partners from racially diverse backgrounds (e.g., 44% Black) who participated in a longitudinal study with two annual measurement occasions. At Wave 1, trained observers assessed disorganized interparental conflict. Observational and survey assessments were used to assess several family (i.e., interparental conflict, parenting difficulties, parent psychopathology, family instability) and demographic (i.e., children's gender, household income, parent education) characteristics. Assessments of child functioning at each wave included psychological adjustment (i.e., externalizing and internalizing symptoms, prosocial behavior), social information processing difficulties, and attention to emotion cues. Findings from structural equation modeling analyses indicated disorganized interparental conflict significantly predicted decreases in children's prosocial behavior and increases in their externalizing problems, angry reactivity to social problems, and biased attention to angry and sad cues over a one-year period. Results were significant while controlling for established measures of interparental conflict, parenting difficulties, parent psychopathology, family instability, and demographic characteristics. The findings suggest that disorganized characteristics of interparental conflict may be an important domain of clinical change beyond the established targets of family harshness and adversity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


[Pharyngeal A-streptococcal infection encountered in the practical work of an internal medicine specialist].
The problem of pharyngeal infections caused by beta-hemolytic streptococci of group A (BHSA) remains a challenge for both health providers and general medicine. The present paper was designed to provide the data suggesting the "reappearance" of a highly virulent BHSA infection and a rise in the frequency of its complications (such as acute rheumatic fever and toxic shock syndrome) and to substantiate the necessity of rational antibacterial therapy for the management of this pathology. The agents of choice for the treatment of acute forms of BHSA (tonsillitis and pharyngitis) include penicillins (amoxicillin, benzathine-penicillin, phenoxymethyl penicillin) and cephalosporins of the first generation (cephadroxyl) as well as macrolids (spiramycin, azithromycin, roxithromycin, midecamycin, josamycin) for the patients who do not tolerate beta-lactam antibiotics. Inhibitor-protected penicillins (amoxicillin, clavulanate) or cephalosporins of the second generations (cefuroxime-axetil) should be prescribed to the patients presenting with chronic recurring BHSA characterized by the rather high probability of colonization of the site of infection by beta-lactamase producing microorganisms. Lincosamine-derived antibiotics, such as lincomycin and clindamycin, are reserved for the patients with acute and chronic BHSA (tonsillitis and pharyngitis).


Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line.
Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype.


Gene therapy for restenosis after balloon angioplasty and stenting.
Percutaneous coronary revascularization is an increasingly attractive alternative to medical therapy and surgical revascularization for coronary artery disease. The leading drawback of this procedure continues to be restenosis-the process of late arterial renarrowing at the site of initially successful intervention. Restenosis after balloon angioplasty seems to be determined primarily by the direction and magnitude of vessel wall remodeling. In contrast, the major limitation of stent implantation is the initiation of neointimal tissue proliferation within and adjacent to the stent. The goal of this review is to summarize recent laboratory and clinical investigations of the transmission of mitogenic signals from the membrane to the nucleus in smooth muscle cells. The mechanisms responsible for restenosis after balloon angioplasty and stenting and the possibility of transferring specific genes into somatic vascular cells with molecular tools to inhibit smooth muscle cell proliferation also will be reviewed.


Prostaglandin F2 alpha-induced estrus in open cows and presumed abortion in pregnant cows with unobserved estrus in a herd monitored by milk progesterone assay.
Data were obtained in a large Florida herd of about 1800 Holstein cows. All cows were inseminated by the herdsman who did the pregnancy checks and who also administered drugs. The herdsman injected 103 cows with prostaglandin F2 alpha during the time this herd was under continuous observation by the authors who were conducting an unrelated research project. These cows consisted of 86 open (never bred) cows which had no estrus observed during the first 70 days postpartum, or no second estrus observed within 30 days after a previous estrus, and 17 cows previously inseminated. Two-thirds (57) of the 86 open cows were in estrus within 4 days. The 17 previously inseminated cows appeared to be pregnant, based upon progesterone profiles, when these were inadvertently given prostaglandin F2 alpha by the herdsman. Progesterone declined in all cows and they were in estrus in 7 +/- 4 days (mean +/- standard error). This result of presumed abortion reflects the luteolytic effectiveness of the drug and the importance of instructing any laymen users to follow necessary precautions to avoid undesirable effects.


The pseudokinase MLKL contributes to host defense against Streptococcus pluranimalium infection by mediating NLRP3 inflammasome activation and extracellular trap formation.
Host innate immunity plays a pivotal role in the early detection and neutralization of invading pathogens. Here, we show that pseudokinase mixed lineage kinase-like protein (MLKL) is required for host defence against Streptococcus pluranimalium infection by enhancing NLRP3 inflammasome activation and extracellular trap formation. Notably, Mlkl deficiency leads to increased mortality, increased bacterial colonization, severe destruction of organ architecture, and elevated inflammatory cell infiltration in murine models of S. pluranimalium pulmonary and systemic infection. In vivo and in vitro data provided evidence that potassium efflux-dependent NLRP3 inflammasome signalling downstream of active MLKL confers host protection against S. pluranimalium infection and initiates bacterial killing and clearance. Moreover, Mlkl deficiency results in defects in extracellular trap-mediated bactericidal activity. In summary, this study revealed that MLKL mediates the host defence response to S. pluranimalium, and suggests that MLKL is a potential drug target for preventing and controlling pathogen infection.


Campylobacter enteritis in 188 hospitalized patients.
The clinical picture and epidemiologic characteristics of infection due to Campylobacter fetus subspecies jejuni were studied in 188 patients hospitalized in Finland during a three-year period. All but two patients had diarrhea; 90% had abdominal pain, fever, and fatigue; half had vomiting and headache; one third experienced electrolyte disturbances; and one fifth of the patients had other complications, most commonly pancreatitis (6%) and arthritis (5%). All age groups were affected, most usually those who were 0 to 9 years old and 20 to 29 years old. The incidence of domestic cases increased during the summer months. With only three exceptions (1.3%), all jejuni strains were sensitive to erythromycin. Among Finns who visited ten popular tourist countries, the incidence of hospitalized C jejuni enteritis cases varied from 0 to 63 per 100,000 travelers.


Delirium in critical care unit patients: prevalence and associated risk factors.
A large number of critically ill patients experience physical and mental distress, resulting from systemic illness, multiple interventions, and environmental factors, during their stay in the Intensive Care Unit (ICU). Delirium is a common medical problem related to prolonged critical care. ICU delirium is linked to higher mortality as well as morbidity. The majority of patients suffering from delirium in the ICU experience hypoactive delirium, which remains relatively undiagnosed. Multiple tools have been devised for ICU delirium screening and early diagnosis. This short report aimed to assess the prevalence of delirium using a validated screening tool in medical ICU patients and determine the associated modifiable and non-modifiable risk factors.


Asap: a framework for over-representation statistics for transcription factor binding sites.
In studies of gene regulation the efficient computational detection of over-represented transcription factor binding sites is an increasingly important aspect. Several published methods can be used for testing whether a set of hypothesised co-regulated genes share a common regulatory regime based on the occurrence of the modelled transcription factor binding sites. However there is little or no information available for guiding the end users choice of method. Furthermore it would be necessary to obtain several different software programs from various sources to make a well-founded choice. We introduce a software package, Asap, for fast searching with position weight matrices that include several standard methods for assessing over-representation. We have compared the ability of these methods to detect over-represented transcription factor binding sites in artificial promoter sequences. Controlling all aspects of our input data we are able to identify the optimal statistics across multiple threshold values and for sequence sets containing different distributions of transcription factor binding sites. We show that our implementation is significantly faster than more naïve scanning algorithms when searching with many weight matrices in large sequence sets. When comparing the various statistics, we show that those based on binomial over-representation and Fisher's exact test performs almost equally good and better than the others. An online server is available at http://servers.binf.ku.dk/asap/.


High-resolution nucleic acid detection using online polyacrylamide gel electrophoresis platform.
Polyacrylamide gel electrophoresis (PAGE) is one of the most popular techniques for the separation and detection of nucleic acids. However, it requires a complicated detection procedure and offline detection format, which inevitably leads to band broadening and thus compromises the separation resolution. To overcome this problem, we developed an online PAGE (OPAGE) platform by integrating the gel electrophoresis apparatus with the gel imaging system, so as to obviate the need for the complicated detection procedure. Notably, OPAGE enabled the real-time monitoring of the separation process and the immediate imaging of the separation results once the electrophoresis ended. Using a series of synthetic DNAs with different lengths as samples, we demonstrated that the OPAGE platform enhanced 32-64 % of the number of theoretical plates, showed a robust dynamic range of 0.1-12.5 ng/μL, and realized a limit of detection as low as 0.08 ng/μL DNA. Based on our results, we anticipate that the OPAGE platform is a promising alternative to traditional nucleic acid gel electrophoresis for simple and high-resolution detection and quantification and nucleic acid.


THE ROLE OF SERUM CK-18, MMP-9 AND TIPM-1 LEVELS IN PREDICTING R0 RESECTION IN PATIENTS WITH GASTRIC CANCER.
Gastric cancer is the 3rd most common cause of death in men and the 5th common in women worldwide. Today, surgery is the only curative therapy. Currently available advanced imaging modalities can predict R0 resection in most patients, but it can only be detected with certainty in the perioperative period. To determine the role of serum CK18, MMP9, TIMP1 levels in predicting R0 resection in patients with gastric cancer. Fifty consecutive patients scheduled for curative surgery with gastric adenocarcinoma diagnosed between 2013-2015 were included. One ml of blood was taken from the patients to analyze CK18, MMP9 and TIMP1. CK18, MMP9 and TIMP1 levels were positively correlated with pathological N and the stage (p<0,05). CK-18, MMP-9 and TIMP-1 averages in positive clinical lymph nodes and in clinical stage 3, were found to be higher than the averages of those with negative clinical lymph nodes and in clinical stage 2 (p<0,05). Although serum CK-18, MMP-9 and TIMP-1 preoperatively measured in patients scheduled for curative surgery did not help to evaluate gastric tumor resectability, they were usefull in predicting N3-stage.


The use of panniculectomy in morbidly obese patients undergoing gynecological surgery.
Panniculectomy is a surgical procedure that involves removal of the skin and fat excess which facilitates access to the peritoneal cavity. In the paper we present three cases of morbidly obese women (BMI: 46.3-59.5) who were treated in the Department of Gynecology and Oncological Gynecology in Lodz. One of the patients underwent an operation due to the presence of a large cervical myoma. Two another women were treated for endometrial cancer. During all of the three procedures panniculectomy was the first stage of the operation.


Anti-EGFR Therapy in Metastatic Small Bowel Adenocarcinoma: Myth or Reality?
Due to the relative rarity of small bowel adenocarcinoma (SBA), prospective trials, helping to guide therapeutic decisions, are lacking and the optimal therapy for advanced SBA is unknown. The role of targeted agents, such as anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor (VEGF), is unknown. This is a retrospective multicenter observational study that included patients with metastatic SBA treated with anti-EGFR antibodies (cetuximab or panitumumab) ± chemotherapy in the first (I) or second (II) line. Thirteen patients with metastatic SBA, recruited from 5 Italian referral institutions, were included in the present retrospective analysis. All patients received anti-EGFR inhibitors as a single agent or in association with chemotherapy. More common G2 treatment-related side effects were skin reaction (8 patients, 53.8%), hypomagnesemia (6 patients, 46.2%), and diarrhea (8 patients, 61.5%). Grade 3 diarrhea was observed in only 1 patient. Conjunctivitis was not reported in any patients. Grade 4 toxicity was not reported. In the overall population, median progression-free survival was 5.526 months (95% confidence interval [CI]: 3.684-12.467). Median overall survival was 15.86 months (95% CI: 14.43-24.30). Complete response was observed in 15% of patients, partial response in 39% of patients, stable disease in 23% of patients, and progression disease in 15% of patients. In this retrospective analysis, anti-EGFR inhibitors showed to be a suitable addendum to chemotherapy in the I and II line, with an excellent tolerance and safety profile both in I and II line.


Two-step formulation of magnetic nanoprobes for microRNA capture.
MicroRNAs (miRs) belong to a family of short non-coding endogenous RNAs. Their over-expression correlates with various pathologies: for instance, miRNA-155 (miR-155) is over-expressed upon the development of breast cancers. However, the detection of miRs as disease biomarkers suffers from insufficient sensitivity. In the present study, we propose a protocol for a rapid and efficient generation of magnetic nanoprobes able to capture miR-155, with the aim of increasing its concentration. As a nanoprobe precursor, we first synthesized superparamagnetic iron oxide nanoparticles (SPIONs) coated with covalently attached polyethylene glycol carrying a free biotin terminus (PEG-bi). Using streptavidin-biotin interactions, the nanoprobes were formulated by functionalizing the surface of the nanoparticles with the miR sequence (CmiR) complementary to the target miR-155 (TmiR). The two-step formulation was optimized and validated using several analytical techniques, in particular with Size-Exclusion High Performance Liquid Chromatography (SE-HPLC). Finally, the proof of the nanoprobe affinity to TmiR was made by demonstrating the TmiR capture on model solutions, with the estimated ratio of 18 : 22 TmiR : CmiR per nanoprobe. The nanoprobes were confirmed to be stable after incubation in serum.


Collection and use of cancer family history in primary care.
This systematic review was undertaken to: (1) evaluate the accuracy of patient reporting of cancer family history, (2) identify and evaluate tools designed to capture cancer family history that are applicable to the primary care setting, and (3) identify and evaluate risk assessment tools (RATs) in promoting appropriate management of familial cancer risk in primary care settings. MEDLINE, EMBASE, CINAHL, and Cochrane Central from 1990 to July 2007. Standard systematic review methodology was employed. Eligibility criteria included English studies evaluating breast, colorectal, ovarian, or prostate cancers. All primary study designs were included. For family history tools (FHxTs) and RATs, studies were limited to those applicable to primary care settings. RATs were excluded if they calculated the risk of mutation only, required specialist genetics knowledge, or were stand-alone guidelines. Reporting Accuracy: Of 19 eligible studies, 16 evaluated the accuracy of reporting family history and three on reliability. Reporting accuracy was better for relatives free of cancer (specificity) than those with cancer (sensitivity). Accuracy was better for breast and colorectal than for ovarian and prostate cancers. Family History Tools: Of 40 eligible studies, 18 FHxTs were applicable to primary care. Most collected information on more than one cancer, employed self-administered questionnaires, and favored paper-based formats to collate family information. Details collected were often focused on specific conditions and affected relatives. Eleven tools were evaluated relative to current practice and seven were not. Irrespective of study design, compared to best current practice (genetic interviews) and standard primary care practice (family history in medical records) the FHxTs performed well. Risk Assessment Tools: Of 15 eligible studies, three RATs were identified for patient use and eight for use by professionals. They were presented in a range of computer-based and paper-based formats, and preliminary evidence indicated potential efficacy, but not definitive effectiveness in practice. Although limited in generalizability, informants reporting their cancer family history have greater accuracy for relatives free of cancer than those with cancer. Reporting accuracy may vary among different cancer types. FHxTs varied in the extent of family enquiry depending on the tool's purpose. These tools were primarily developed as an integral part of risk assessment. The few tools that were evaluated performed well against both best and standard clinical practice. A number of RATs designed for primary care settings exist, but evidence is lacking of their effectiveness in promoting recommended clinical actions.


Confinement of Dyes inside Boron Nitride Nanotubes: Photostable and Shifted Fluorescence down to the Near Infrared.
Fluorescence is ubiquitous in life science and used in many fields of research ranging from ecology to medicine. Among the most common fluorogenic compounds, dyes are being exploited in bioimaging for their outstanding optical properties from UV down to the near IR (NIR). However, dye molecules are often toxic to living organisms and photodegradable, which limits the time window for in vivo experiments. Here, it is demonstrated that organic dye molecules are passivated and photostable when they are encapsulated inside a boron nitride nanotube (dyes@BNNT). The results show that the BNNTs drive an aggregation of the encapsulated dyes, which induces a redshifted fluorescence from visible to NIR-II. The fluorescence remains strong and stable, exempt of bleaching and blinking, over a time scale longer than that of free dyes by more than 104 . This passivation also reduces the toxicity of the dyes and induces exceptional chemical robustness, even in harsh conditions. These properties are highlighted in bioimaging where the dyes@BNNT nanohybrids are used as fluorescent nanoprobes for in vivo monitoring of Daphnia Pulex microorganisms and for diffusion tracking on human hepatoblastoma cells with two-photon imaging.


Insulin-like growth factor binding proteins-3 and -5: central mediators of fibrosis and promising new therapeutic targets.
Fibrosis involves an orchestrated cascade of events including activation of fibroblasts, increased production and deposition of extracellular matrix components, and differentiation of fibroblasts into myofibroblasts. Epithelial-mesenchymal cross-talk plays an important role in this process, and current hypotheses of organ fibrosis liken it to an aberrant wound healing response in which epithelial-mesenchymal transition (EMT) and cellular senescence may also contribute to disease pathogenesis. The fibrotic response is associated with altered expression of growth factors and cytokines, including increased levels of transforming growth factor-β1 (TGF-β1) and the more recent observation that increased levels of several insulin-like growth factor binding proteins (IGFBPs) are associated with a number of fibrotic conditions. IGFBPs have been implicated in virtually every cell type and process associated with the fibrotic response, making the IGFBPs attractive targets for the development of novel anti-fibrotic therapies. In this review, the current state of knowledge regarding the classical IGFBP family in organ fibrosis will be summarized and the clinical implications considered.


Cellular inhibitor of apoptosis protein 2 promotes the epithelial-mesenchymal transition in triple-negative breast cancer cells through activation of the AKT signaling pathway.
Triple-negative breast cancer (TNBC) represents approximately 10-17% of all breast cancers, and patients with TNBC show a poorer short-term prognosis than patients with other types of breast cancer. TNBCs also have a higher tendency for early distant metastasis and cancer recurrence due to induction of the epithelial-mesenchymal transition (EMT). Several recent reports have suggested that inhibitor of apoptosis (IAP) proteins function as regulators of the EMT. However, the roles of these proteins in TNBC are not clear. Accordingly, we investigated the roles of cIAP2 in TNBC. Among eight IAP genes, only cIAP2 was upregulated in TNBC cells compared with that in other breast cancer subtypes. Analysis of TMAs revealed that expression of cIAP2 was upregulated in TNBCs. In vitro studies showed that cIAP2 was highly expressed in TNBC cells compared with that in other types of breast cancer cells. Furthermore, silencing of cIAP2 in TNBC cells induced mesenchymal-epithelial transition (MET)-like processes and subsequently suppressed the migratory ability and invasion capacity of the cells by regulation of Snail through the AKT signaling pathway. In contrast, ectopic expression of cIAP2 in luminal-type breast cancer cells induced activation of the AKT signaling pathway. These results collectively indicated that cIAP2 regulated the EMT in TNBC via activation of the AKT signaling pathway, contributing to metastasis in TNBC. Our study proposes a novel mechanism through which cIAP2 regulates the EMT involving AKT signaling in TNBC cells. We suggest that cIAP2 may be an attractive candidate molecule for the development of targeted therapeutics in the future.


[Impairment of the immune system caused by drugs].
The immune response and the ensuing inflammation relies on a complex interaction of cells and mediators. Various drugs can interfere with individual steps of the immune response, and in so doing they often imitate regulatory mechanisms of the immune system itself. The immunosuppressive effect of corticosteroids is based on changes in cell migration, reduced responsiveness of monocytes/macrophages to various stimuli and diminished production of interleukin-2. Cyclosporin A appears to block prolactin binding to prolactin receptors on lymphocytes, thus interfering with the immunostimulatory effect of prolactin. It also appears to have a Calmodulin antagonism and might thus block lymphokine production. Anticoagulants may block delayed type hypersensitivity reactions, since activation of the coagulation cascade is involved in this type of immune reaction. Attempts to use calcium channel blockers as immunosuppressive agents, or to take advantage of the immunoregulatory effects of adrenergic substances/blockers or other neurotransmitters, are of experimental value only.


Increased neutrophil-lymphocyte ratio in delirium: a pilot study.
Delirium is a common and severe complication among older hospitalized patients. The pathophysiology is poorly understood, but it has been suggested that inflammation and oxidative stress may play a role. The aim of this pilot study was to investigate levels of the neutrophil-lymphocyte ratio (NLR) - a marker of systemic inflammation and oxidative stress - in patients with and without delirium. This pilot study was performed within a retrospective chart review study that included acutely ill patients, 65 years and older, who were admitted to the ward of geriatrics of the Erasmus University Medical Center. All patients in whom the differential white blood cell (WBC) counts as well as the C-reactive protein (CRP) level were determined within 24 h after admission were included in the present study. Differences in NLR between patients with and without delirium were investigated using univariate analysis of variance, with adjustments for age, sex, comorbidities, CRP level, and total WBC count. Eighty-six patients were included. Thirteen patients were diagnosed with delirium. In adjusted models, higher mean NLR values were found in patients with, than in those without, delirium (9.10 vs 5.18, P=0.003). In this pilot study, we found increased NLR levels in patients with delirium. This finding might suggest that an inadequate response of the immune system and oxidative stress may play a role in the pathogenesis of delirium. Further studies are needed to confirm the association between NLR and delirium.


Computing relative motion with complex cells.
Contextual influences shape our perception of local visual stimuli. Relative-motion stimuli represent an important contextual influence, yet the mechanism subserving relative-motion computation remains largely unknown. In the present work, we investigated the responses of an established model for simple and complex cells to relative-motion stimuli. A straightforward mathematical analysis showed that relative-motion computation is inherent in the nonlinear transformation of the complex-cell model. Tuning to relative velocity is achieved by applying a temporal filter to the complex-cell response. The mathematical inference is supported by simulations that quantitatively reproduce measured complex-cell responses in both cat and monkey to a variety of relative-motion stimuli. Importantly, the posited mechanism for cortical computation of relative motion does not require an intermediate neural representation of local velocities and does not require lateral or feedback interactions within a network.


Trajectories of PTSD symptoms following sexual assault: is resilience the modal outcome?
Theoretical frameworks positing qualitatively distinct trajectories of posttrauma outcome have received initial empirical support, but have not been investigated in cases of severe interpersonal trauma. To address this limitation, we conducted latent class growth analysis with longitudinal data collected from 119 female sexual assault survivors at 1-, 2-, 3-, and 4-months postassault. Participants' mean age was 33 years; 63% were White. We hypothesized that given the severity of exposure associated with sexual assault, resilience would not be the modal course of adaptation. Four distinct PTSD growth trajectories, representing unique latent classes of participants, best fit the data: a high chronic trajectory, a moderate chronic trajectory, a moderate recovery trajectory, and a marked recovery trajectory. Contrary to previous studies and recent theoretical models, resilience and resistance trajectories were not observed, as high levels of distress were evident in nearly all participants at 1-month postassault. These results suggest that theoretical models of posttrauma response positing resilience as the modal outcome may not generalize to cases of sexual assault.


Log-linear model based behavior selection method for artificial fish swarm algorithm.
Artificial fish swarm algorithm (AFSA) is a population based optimization technique inspired by social behavior of fishes. In past several years, AFSA has been successfully applied in many research and application areas. The behavior of fishes has a crucial impact on the performance of AFSA, such as global exploration ability and convergence speed. How to construct and select behaviors of fishes are an important task. To solve these problems, an improved artificial fish swarm algorithm based on log-linear model is proposed and implemented in this paper. There are three main works. Firstly, we proposed a new behavior selection algorithm based on log-linear model which can enhance decision making ability of behavior selection. Secondly, adaptive movement behavior based on adaptive weight is presented, which can dynamically adjust according to the diversity of fishes. Finally, some new behaviors are defined and introduced into artificial fish swarm algorithm at the first time to improve global optimization capability. The experiments on high dimensional function optimization showed that the improved algorithm has more powerful global exploration ability and reasonable convergence speed compared with the standard artificial fish swarm algorithm.


Colin Fraser Brockington (1903-2004) and the revolution in nurse-education.
Colin Fraser Brockington was Professor of Social and Preventive Medicine at the University of Manchester from 1952 to 1965. During that time he developed the Diploma in Community Nursing, the first pre-registration training course for nurses at a British University. This paper traces Brockington's education and career and explores his commitment to university-based nursing education which appears to have stemmed from his desire to enhance and broaden the role of the health visitor. It also considers the implications of the innovative course at Manchester and evaluates the way in which it influenced the gradual movement of nursing education into the university sector throughout the UK.


[Influencing factors and reaction mechanism of chloroacetic acid reduction by cast iron].
The chloroacetic acids are ubiquitous present as a class of trace chlorinated organic pollutants in surface and drinking water. Most of chloroacetic acids are known or suspected carcinogens and, when at high concentrations, are of great concern to human health. In order to economically remove chloroacetic acids, the degradation of chloroacetic acids by cast iron was investigated. Moreover, the effect of iron style, pretreatment process, shocking mode and dissolved oxygen on chloroacetic acids reduced by cast iron was discussed. Compared to iron source and acid pretreatment, mass transfer was more important to chloroacetic acid removal. Dichloroacetic acid (DCAA) and monochloroacetic acid (MCAA) were the main products of anoxic and oxic degradation of trichloroacetic acid (TCAA) by cast iron during the researched reaction time, respectively. With longtitudinal shock, the reaction kinetics of chloroaectic acid removal by cast iron conformed well to the pseudo first order reaction. The anoxic reaction constants of TCAA, DCAA and MCAA were 0.46 h(-1), 0.03 h(-1) and 0, and their oxic constants were 1.24 h(-1), 0.79 h(-1) and 0.28 h(-1), respectively. The removal mechanisms of chloroacetic acids were different under various oxygen concentrations, including sequential hydrogenolysis for anoxic reaction and sequential hydrogenolysis and direct transformation possible for oxic reaction, respectively.


Immunoreactive beta-endorphin and adrenocorticotropin in human cerebrospinal fluid.
To elucidate the significance of beta-endorphin in human cerebrospinal fluid (CSF), CSF levels of beta-endorphin-like immunoreactivity (beta-EP-LI) in various diseases were determined by a specific radioimmunoassay and compared with simultaneously determined ACTH-like immunoreactivity (ACTH-LI) levels in CSF. CSF beta-EP-LI and ACTH-LI in the control group, consisting of 5 normal subjects and 19 patients with nonendocrine diseases, were 22.2+/-1.3 and 14.6+/-0.4 fmol/ml, respectively. CSF levels of these peptides in patients with schizophrenia (n = 19) and acromegaly (n = 10) were not significantly different from those in the control group. Patients with Cushing's disease (n = 7) had significantly lower CSF beta-EP-LI and ACTH-LI levels than those in the control group. Four of them showed a parallel increase in CSF beta-EP-LI and CSF ACTH-LI levels after the complete removal of pituitary microadenomas (P < 0.05). Gel chromatography of CSF beta-EP-LI from a normal volunteer, a control patient, and one patient each with catatonia, Nelson's syndrome, Cushing's syndrome (adrenal adenoma), and acromegaly gave similar patterns consisting of three peaks with the elution positions comparable to those of authentic beta-endorphin, beta-lipotropin, and possibly their precursor molecule. Gel chromatographic patterns of CSF beta-EP-LI and ACTH-LI were compared in a normal volunteer. The first peaks of beta-EP-LI and ACTH-LI eluted at the same position and the second peak of ACTH-LI coincided with the elution position of authentic ACTH.CSF beta-EP-LI and ACTH-LI levels determined every 5 min over a period of 80 min in three normal volunteers did not show moment-to-moment variability.A significant correlation (r = 0.75, P < 0.001) was seen between CSF beta-EP-LI and ACTH-LI levels in normal subjects and patients studied (n = 73). This suggests that beta-endorphin and ACTH in human CSF share the common regulatory mechanism in normal and pathologic conditions.


The effect of mitochondrial complex I inhibitor on longevity of short-lived and long-lived seed beetles and its mitonuclear hybrids.
Mitochondria are suggested to play a central role in ageing and evolution of longevity. Gradual decline in mitochondrial function during ageing and concomitant increase in production of reactive oxygen species (ROS) leads to oxidative damage of macromolecules and impairment of ATP synthesis. To assess relationship between ageing and oxidative stress resistance we exposed different longevity lines of the seed beetle (Acanthoscelides obtectus) to four concentrations of tebufenpyrad, mitochondrial complex I inhibitor. Complex I is one of main sites of ROS production during normal respiration and its inhibition elevates oxidative stress. Our results showed that 24 h of exposure to tebufenpyrad decreased survival and post-stress longevity due to increased baseline mortality. Higher resistance was recorded in beetles from lines selected for late reproduction and extended longevity (L) than in early reproducing beetles (E). Also, females were more resistant than males. Since complex I is under dual genetic control, our second aim was to disentangle relative contribution of nuclear and mitochondrial genes to the variation in longevity. We used crossed combinations of distinct mitochondrial and nuclear genotypes (E × L, L × E) and compared them to control hybrids where mitochondrial genome was "transplanted" onto the original background (E × E, L × L). Our study revealed significant effect of nucleus, i.e. higher survival and post-stress longevity in beetles harbouring L nucleus. Mitochondrion effect was significant only within L nuclear background where E mitochondrion gave advantage.


Educating medical professionals about suicide prevention among military veterans.
The aim of this paper was to discuss the results of a review of literature related to suicide in military veteran populations. Suicide in veteran populations has been increasing in recent years, and continues to be a medical and social problem across the globe. For medical health professionals, knowledge of the risk factors for suicide, careful assessment, and appropriate interventions are key to suicide prevention. The main aim of this review is to better understand the risk factors present in veteran suicide and find ways by which to educate medical professionals in suicide prevention. Key suicide risk factors found in veteran populations include posttraumatic stress disorder, major depressive disorder, physical injuries, substance use disorders, traumatic brain injury, combat-related guilt, access to firearms, and insufficient social support. Some psychosocial difficulties are unique to veteran populations, and medical professionals should be culturally sensitive to these factors. Psychosocial changes upon discharge from active duty, as well as stigma against mental health disorders and treatment, should also be considered and assessed. Given that general practitioners may be the first line of defense for these veterans, they should be educated in risk factors for veteran suicide and proper assessment techniques. Any suicide risk in a veteran population should be taken very seriously, and responded to appropriately.


Clinical evaluation of SARS-CoV-2 lung HRCT and RT-PCR Techniques: Towards risk factor based diagnosis of infectious diseases.
This study uses image analysis techniques for comparative analysis of the lung HRCT features and RT-PCR of 325 suspected patients to COVID-19 pneumonia. Our findings propose more caution in the interpretation of RT-PCR data, promoting, instead, also the quantification of age and sex-based risk factors using HRCT images. Statistical analysis of our methodology reveals a direct relation between intensity, skewness and kurtosis of the radiological features and the gender of patients. Moreover, we investigate the effect of the age of patients on the appearance of COVID-19 pneumonia in the HRCT images. We have also applied our methodology to investigate the effect of time on the severity of COVID-19 pneumonia within the lungs. Subsequently, we find a strong relationship between image analysis and the informed medical diagnosis asserted by the radiologists. Additionally, our results also indicate increase in the severity of lung infection in the first and second week after the onset of the SARS-CoV-2 symptoms. Thereafter, a gradual decrease in the lung damage is observed during the third week. The proposed image analysis methodology can be used as a simple complementary tool for infectious disease diagnostics as demonstrated in this study with an example of SARS-CoV-2 to provide better understanding of the disease for drug and vaccine development.


Carriage burden, multiple colonization and antibiotic pressure promote emergence of resistant vaccine escape pneumococci.
Pneumococcal conjugate vaccines target the limited subset of the more than 90 known serotypes of Streptococcus pneumoniae responsible for the greatest burden of pneumococcal disease and antibiotic resistance. Following the introduction of these vaccines, serotypes not targeted were able to expand and resistance became more common within these types. Here we use a stochastic dynamic model of pediatric pneumococcal carriage to evaluate potential influences on the emergence of new resistant lineages following the introduction of a vaccine targeting more common resistant types. Antibiotic pressure was the strongest driver, with no emergence at low levels and universal emergence at high levels. At intermediate levels of antibiotic pressure, higher carriage burden and a greater degree of dual carriage promoted emergence. This may have implications for current plans to introduce childhood pneumococcal vaccination in several high-burden countries.


Skeletal growth in early and late Neolithic foragers from the Cis-Baikal region of Eastern Siberia.
Skeletal growth is explored between Early Neolithic (EN) (8000 to 6800 BP) and Late Neolithic (LN) (6000 to 5200 BP) foragers from the Cis-Baikal region of Eastern Siberia. Previous studies suggest that increased systemic stress and smaller adult body size characterize the EN compared to LN. On this basis, greater evidence for stunting and wasting is expected in the EN compared to LN. Skeletal growth parameters assessed here include femoral and tibial lengths, estimated stature and body mass, femoral midshaft cortical thickness, total bone thickness, and medullary width. Forward selection was used to fit polynomial lines to each skeletal growth parameter relative to dental age in the pooled samples, and standardized residuals were compared between groups using t tests. Standardized residuals of body mass and femoral length were significantly lower in the EN compared to LN sample, particularly from late infancy through early adolescence. However, no significant differences in the standardized residuals for cortical thickness, medullary width, total bone thickness, tibial length, or stature were found between the groups. Age ranges for stunting in femoral length and wasting in body mass are consistent with environmental perturbations experienced at the cessation of breast feeding and general resource insecurity in the EN compared to LN sample. Differences in relative femoral but not tibial length may be associated with age-specific variation in growth-acceleration for the distal and proximal limb segments. Similarity in cortical bone growth between the two samples may reflect the combined influences of systemic and mechanical factors on this parameter.


Calculating cost savings in utilization management.
A major motivation for managing the utilization of laboratory testing is to reduce the cost of medical care. For this reason it is important to understand the basic principles of cost accounting in the clinical laboratory. The process of laboratory testing includes three distinct components termed the pre-analytic, analytic and post-analytic phases. Utilization management efforts may impact the cost structure of these three phases in different ways depending on the specific details of the initiative. Estimates of cost savings resulting from utilization management programs reported in the literature have often been fundamentally flawed due to a failure to understand basic concepts such as the difference between laboratory costs versus charges and the impact of reducing laboratory test volumes on the average versus marginal cost structure in the laboratory. This article will provide an overview of basic cost accounting principles in the clinical laboratory including both job order and process cost accounting. Specific examples will be presented to illustrate these concepts in various different scenarios.


Value as the key concept in the health care system: how it has influenced medical practice and clinical decision-making processes.
In the last 10 years, value has played a key role in the health care system. In this concept, innovations in medical practice and the increasing importance of patient centeredness have contributed to draw the attention of the medical community. Nonetheless, a large consensus on the meaning of "value" is still lacking: patients, physicians, policy makers, and other health care professionals have different ideas on which component of value may play a prominent role. Yet, shared clinical decision-making and patient empowerment have been recognized as fundamental features of the concept of value. Different paradigms of health care system embrace different meanings of value, and the absence of common and widely accepted definition does not help to identify a unique model of care in health care system. Our aim is to provide an overview of those paradigms that have considered value as a key theoretical concept and to investigate how the presence of value can influence the medical practice. This article may contribute to draw attention toward patients and propose a possible link between health care system based on "value" and new paradigms such as patient-centered system (PCS), patient empowerment, and P5 medicine, in order to create a predictive, personalized, preventive, participatory, and psycho-cognitive model to treat patients. Indeed, patient empowerment, value-based system, and P5 medicine seem to shed light on different aspects of a PCS, and this allows a better understanding of people under care.


Octacosanol Attenuates Inflammation in Both RAW264.7 Macrophages and a Mouse Model of Colitis.
Octacosanol has multiple biological functions. In this study, the anti-inflammatory effect and molecular mechanism of octacosanol were evaluated by using dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. The colitis mouse model was induced by 3.0% DSS in 8-week ICR mice and octacosanol orally administered with 100 mg/kg/day. The results showed that octacosanol significantly improved the health status of mice and reduced DSS-induced pathological damage in the colonic tissues. Octacosanol obviously inhibited the mRNA and protein expression levels of pro-inflammatory factors of colonic tissues. In vitro, octacosanol administration significantly reduced the expression of mRNA or protein of pro-inflammatory cytokines and the phosphorylation of c-Jun N-terminal kinase and p38, and it also partly prevented LPS-induced translocations of NF-κB and AP-1. Octacosanol has anti-inflammatory effect, and its molecular mechanism may be involved in downregulating the expression of inflammatory factors and blocking of MAPK/NF-κB/AP-1 signaling pathway.


Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis.
Macroautophagy (hereafter autophagy) is a cellular "self-eating" process that is implicated in many human cancers, where it can act to either promote or suppress tumorigenesis. However, the role of autophagy in regulation of inflammation during tumorigenesis remains unclear. Here we show that autophagy is induced in the epidermis by ultraviolet (UV) irradiation and autophagy gene Atg7 promoted UV-induced inflammation and skin tumorigenesis. Atg7 regulated UV-induced cytokine expression and secretion, and promoted Ptgs2/Cox-2 expression through both a CREB1/CREB-dependent cell autonomous mechanism and an IL1B/IL1β-dependent non-cell autonomous mechanism. Adding PGE2 increased UV-induced skin inflammation and tumorigenesis, reversing the epidermal phenotype in mice with Atg7 deletion in keratinocytes. Similar to ATG7 knockdown in human keratinocytes, ATG5 knockdown inhibited UVB-induced expression of PTGS2 and cytokines. Furthermore, ATG7 loss increased the activation of the AMPK pathway and the phosphorylation of CRTC1, and led to endoplasmic reticulum (ER) accumulation and reduction of ER stress. Inducing ER stress and inhibiting calcium influx into the ER by thapsigargin reverses the inflammation and tumorigenesis phenotype in mice with epidermal Atg7 deletion. Taken together, these findings demonstrate that deleting autophagy gene Atg7 leads to a suppression of carcinogen-induced protumorigenic inflammatory microenvironment and tumorigenesis of the epithelium.


Energetics of gramicidin hybrid channel formation as a test for structural equivalence. Side-chain substitutions in the native sequence.
To determine whether amino acid side-chain substitutions in linear gramicidins after the structure of membrane-spanning channels formed by the modified peptides, we have developed a quantitative measure of structural equivalence of the peptide backbone among gramicidin channels based on functional (single-channel) measurements. The experiments exploit the fact that gramicidin channels are symmetrical dimers, and that channels formed by different gramicidin analogues can be distinguished on the basis of their single-channel current amplitudes or durations. It is thereby possible to determine whether hybrid channels can form between chemically dissimilar peptides, i.e. whether the peptides can adapt to each other. Further, since the relative rates of channel formation as well as the relative concentrations of pure and hybrid channel types can be measured in the same membrane, these experiments provide a quantitative measure of the energetic cost of hybrid channel formation relative to the formation of the pure channels. For a wide variety of different side-chains, we find that substitutions as extreme as glycine to phenylalanine at position 1, at the join between the two monomers in a membrane-spanning dimer, incur no energetic cost for channel formation, which implies that channels formed by each of the modified peptides are structurally equivalent. In addition, the average durations of the hybrid channels (except those having tyrosine or hexafluorovaline at position 1) are intermediate to the average durations of the respective pure channel types, thus providing further evidence for structural equivalence among channels formed by sequence-substituted gramicidins.


Transcriptomic Features of T Cell-Barren Tumors Are Conserved Across Diverse Tumor Types.
Background: Understanding how tumors subvert immune destruction is essential to the development of cancer immunotherapies. New evidence suggests that tumors limit anti-tumor immunity by exploiting transcriptional programs that regulate intratumoral trafficking and accumulation of effector cells. Here, we investigated the gene expression profiles that distinguish immunologically "cold" and "hot" tumors across diverse tumor types. Methods: RNAseq profiles of tumors (n = 8,920) representing 23 solid tumor types were analyzed using immune gene signatures that quantify CD8+ T cell abundance. Genes and pathways associated with a low CD8+ T cell infiltration profile (CD8-Low) were identified by correlation, differential expression, and statistical ranking methods. Gene subsets were evaluated in immunotherapy treatment cohorts and functionally characterized in cell lines and mouse tumor models. Results: Among different cancer types, we observed highly significant overlap of genes enriched in CD8-Low tumors, which included known immunomodulatory genes (e.g., BMP7, CMTM4, KDM5B, RCOR2) and exhibited significant associations with Wnt signaling, neurogenesis, cell-cell junctions, lipid biosynthesis, epidermal development, and cancer-testis antigens. Analysis of mutually exclusive gene clusters demonstrated that different transcriptional programs may converge on the T cell-cold phenotype as well as predict for response and survival of patients to Nivo treatment. Furthermore, we confirmed that a top-ranking candidate belonging to the TGF-β superfamily, BMP7, negatively regulates CD8+ T cell abundance in immunocompetent murine tumor models, with and without anti-PD-L1 treatment. Conclusions: This study presents the first evidence that solid tumors of diverse anatomical origin acquire conserved transcriptional alterations that may be operative in the T cell-cold state. Our findings demonstrate the potential clinical utility of CD8-Low tumor-associated genes for predicting patient immunotherapy outcomes and point to novel mechanisms with potential for broad therapeutic exploitation.


Ionic Conduction through Reaction Products at the Electrolyte-Electrode Interface in All-Solid-State Li+ Batteries.
All-solid-state lithium-ion batteries have attracted significant research interest for providing high power and energy densities with enhanced operational safety. Despite the discoveries of solid electrolyte materials with superionic conductivities, it remains a challenge to maintain high rate capability in all-solid lithium-ion batteries in long-term operation. The observed rate degradation has been attributed to reactivity and resistance at the electrode-electrolyte interfaces. We examine interfaces formed between eight electrolytes including garnet, LiPON, and Li10GeP2S12 (LGPS) and seven electrode materials including an NCM cathode and a metallic Li anode and identify the most rapid lithium-ion diffusion pathways through metastable arrangements of product phases that may precipitate out at each interface. Our analysis accounts for possible density functional theory (DFT) error, metastability, and finite-temperature effects by statistically sampling thousands of possible phase diagrams for each interface. The lithium-ion conductivities in the product phases at the interface are evaluated using machine-learned interatomic potentials trained on the fly. In nearly all electrode-electrolyte interfaces we evaluate, we predict that lithium-ion conduction in the product phases making up the interphase region becomes the rate-limiting step for battery performance.


Omalizumab for severe atopic keratoconjunctivitis.
A 35-year-old patient received omalizumab (300 mg twice a month) for 2 years for a severe atopic keratoconjunctivitis (AKC) in order to reduce the risk for steroid-induced keratitis. After 4 months, quality of life and ocular symptoms improved, and the use of oral steroids was strongly reduced. The treatment was well tolerated. This observation suggests that omalizumab may be a good option for the treatment of severe AKC, especially to avoid side effects of immunosuppressive treatments, as suggested for other allergic diseases. Specific trials should be designed for allergic eye diseases.


Nonreciprocal lasing in topological cavities of arbitrary geometries.
Resonant cavities are essential building blocks governing many wave-based phenomena, but their geometry and reciprocity fundamentally limit the integration of optical devices. We report, at telecommunication wavelengths, geometry-independent and integrated nonreciprocal topological cavities that couple stimulated emission from one-way photonic edge states to a selected waveguide output with an isolation ratio in excess of 10 decibels. Nonreciprocity originates from unidirectional edge states at the boundary between photonic structures with distinct topological invariants. Our experimental demonstration of lasing from topological cavities provides the opportunity to develop complex topological circuitry of arbitrary geometries for the integrated and robust generation and transport of photons in classical and quantum regimes.


Vitreous dynamics: vitreous flow analysis in 20-, 23-, and 25-gauge cutters.
To evaluate porcine vitreous flow and balanced saline solution (BSS) flow rates in different vitrectomy systems. Porcine vitreous was obtained within 24 hours of slaughter. A high-speed (2 samples/s) balance, precise to 0.01 g, was used. Variable cut rates and vacuum pressures were analyzed in vitreous and BSS. The vitreous was labeled with glass microspheres and triamcinolone acetonide. A high-speed (400 frames/s) camera was used to record cutting for each condition. For all cutters, there was no vitreous flow at zero cut rates (off). In 25-gauge cutters, at 500 mmHg of vacuum, the electric cutter produced higher average flow rates at high cut rates (600 cpm, 0.004 mL/s, and 1500 cpm, 0.013 mL/s) than pneumatic, which demonstrated a decreased flow at speeds higher than 1000 cpm (1000 cpm, 0.015 mL/s, and 1500 cpm, 0.006 mL/s). The percentage of vitreous flow rate/BSS flow rate in different aspiration and cut rates showed an ascending curve. This demonstrates evidence of flow obstruction in 25- (all cut rates), 23- (all cut rates), and 20-gauge (all cut rates). Flow obstruction and surge movements were seen in the high-speed videos. The vitrectomy systems each illustrate different performances of vitreous removal. The physical characteristics of vitreous resulted in nonuniform flow in all vitreous cutters.


Glycosylation analysis of IgLON family proteins in rat brain by liquid chromatography and multiple-stage mass spectrometry.
IgLON family proteins, including limbic-associated membrane protein (LAMP), opioid-binding cell adhesion molecule (OBCAM), neurotrimin, and Kilon, are immunoglobulin (Ig) superfamily cell adhesion molecules. These molecules are composed of three Ig domains and a glycosylphosphatidylinositol (GPI) anchor and contain six or seven potential N-glycosylation sites. Although their glycosylations are supposed to be associated with the development of the central nervous system like other Ig superfamily proteins, they are still unknown because of difficulty in isolating individual proteins with a high degree of homology in performing carbohydrate analysis. In this study, we conducted simultaneous site-specific glycosylation analysis of rat brain IgLON proteins by liquid chromatography and multiple-stage mass spectrometry (LC-MS ( n )). The rat brain GPI-linked proteins were enriched and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The four proteins were extracted from the gel, and subjected to LC-MS ( n ) after proteinase digestions. A set of glycopeptide MS data, including the mass spectrum, the mass spectrum in the selected ion monitoring mode, and the product ion spectra, was selected from all data based on carbohydrate-related ions in the MS/MS spectrum. The peptide portion and the carbohydrate structure were identified on the basis of peptide-related ion and carbohydrate-related ions, and the accurate mass. The site-specific glycosylations of four proteins were elucidated as follows. N-Glycans near the N-terminal were disialic acid-conjugated complex- and hybrid-type oligosaccharides. The first Ig domains were occupied by Man-5-9. Diverse oligosaccharides, including Lewis a/x-modified glycans, a brain-specific glycan known as BA-2, and Man-5, were found to be attached to the third Ig domain. Three common structures of glycans were found in the GPI moiety of LAMP, OBCAM, and neurotrimin.


Prevalence and risk factors for extended-spectrum β-lactamase- and AmpC-producing Escherichia coli in dairy farms.
A cross-sectional study was conducted to evaluate the prevalence of extended-spectrum β-lactamase (ESBL)- and plasmid-mediated AmpC-producing Escherichia coli and associated risk factors in dairy herds. One hundred dairy herds were randomly selected and sampled to study the presence of ESBL- and AmpC-producing E. coli in slurry samples. The sensitivity of testing slurry samples for ESBL/AmpC herd status is less than 100%, especially for detecting herds with a low ESBL/AmpC prevalence. Therefore, whereas herds that tested positive for ESBL/AmpC-producing E. coli in slurry were defined as positive herds, herds with negative slurry samples were defined as unsuspected. Isolates of ESBL- and AmpC-producing E. coli were further characterized by detection and typing of their ESBL/AmpC gene. At the initial sampling, a comprehensive questionnaire was conducted at the participating farms. The farmers were asked questions about management practices potentially associated with the ESBL/AMPC herd status. Also, data on antimicrobial purchases during 2011 were acquired to evaluate whether the animal-defined daily dose of antimicrobials per year at farm level was associated with the ESBL/AmpC herd status. Multivariable logistic regression models were used to determine the association between management practices and the ESBL/AmpC herd status. Six months after the initial slurry sampling, 10 positive herds and 10 herds that had an unsuspected ESBL/AmpC herd status during the first visit were resampled. At each farm, slurry samples and feces from 24 individual cows were collected to evaluate within herd dynamics. During the first sampling, ESBL/AmpC-producing E. coli were isolated from the slurry samples collected at 41% of the herds. In total, 37 isolates were further characterized, revealing 7 different ESBL genes (blaCTX-M-1, -2, -14, -15, -32, -55 and blaTEM-52), 1 plasmid-encoded AmpC gene (blaCMY-2), and 1 chromosomally encoded ampC gene (ampC type 3). The total animal-defined daily dose of antimicrobials per year at farm level was not significantly different between ESBL/AmpC-positive and unsuspected dairy herds. The use of third- and fourth-generation cephalosporins, however, was found to be associated with ESBL/AmpC status, with higher use of these antimicrobials resulting in a significant higher odds to be ESBL/AmpC-positive. Management factors that were associated with a higher odds of being ESBL/AmpC-positive were treatment of all cases of clinical mastitis with antimicrobials, a higher proportion of calves treated with antimicrobials, not applying teat sealants in all cows at dry off, and the use of a floor scraper. This last association, however, was considered a methodological effect rather than a true risk factor. On 5 of the 10 initially positive farms, no ESBL/AmpC-producing E. coli were cultured from the slurry or any of the individual cow samples collected during the second sampling. In 4 of the initially unsuspected farms, slurry or individual cow samples tested positive during the second sampling. In conclusion, ESBL/AmpC could frequently be cultured from slurry samples collected from Dutch dairy farms and the ESBL/AmpC genes carried by the isolates were consistent with those reported earlier. The use of third- and fourth-generation cephalosporins appeared to be associated the ESBL/AmpC herd status.


Cotton Fibers with A Lactic Acid-like Surface for Re-establishment of Protective Lactobacillus Microbiota by Selectively Inhibiting Vaginal Pathogens.
Failure to reconstruct the Lactobacillus microbiota is the major reason for the recurrence of vaginal infection. However, most empiric therapies focus on the efficacy of pathogen elimination but do not sufficiently consider the viability of Lactobacillus. Herein, cotton fibers with a lactic acid-like surface (LC) are fabricated by NaIO4 oxidation and L-isoserine grafting. The lactic acid analog chain ends and imine structure of LC can penetrate cell walls to cause protein cleavage in Escherichia coli and Candida albicans and inhibit vaginal pathogens. Meanwhile, the viability of Lactobacillus acidophilus is unaffected by the LC treatment, thus revealing a selective way to suppress pathogens as well as provide a positive route to re-establish protective microbiota in the vaginal tract. Moreover, LC has excellent properties such as good biosafety, anti-adhesion, water absorption, and weight retention. The strategy proposed here not only is practical, but also provides insights into the treatment of vaginal infections. This article is protected by copyright. All rights reserved.


A review of the anti-inflammatory properties of clindamycin in the treatment of acne vulgaris.
This article reviews anti-inflammatory properties of clindamycin, which is often used topically for the management of acne vulgaris, usually in combination with other agents. The efficacy of clindamycin in acne treatment has been shown to be sustained for more than 3 decades. It is likely that anti-inflammatory effects play an important role in the therapeutic activity of topical clindamycin.


Accuracy of reproducing angles: is a right angle special?
The ability to set the angle of a 'V' to a designated value in the following three conditions was compared: (1) verbal designation of V angle; (2) initial 30 s visual demonstration of the designated V angle; (3) verbal designation of V angle plus feedback after every setting. The designated angles were 90 degrees and 45 degrees plus three arbitrary angles (65 degrees, 125 degrees, and 145 degrees). Each run comprised thirty consecutive settings. To ensure that our observers based their settings entirely on V angle it was arranged that line orientation did not provide a reliable cue to V angle. In condition (1), accuracy of setting V angle was significantly worse when the designated angle was other than 90 degrees or 45 degrees. This was not the case in condition (2), indicating that observers maintained a memory of the initial demonstration throughout a run of thirty settings. Setting error was not significant in condition (3) for any of the five angles. However, even in condition (3), setting-to-setting variability was significantly lower for the 90 degrees angle than for the other angles.


Human papillomavirus type 11 neutralization in the athymic mouse xenograft system: correlation with virus-like particle IgG concentration.
Neutralization of virus is likely to be necessary for development of an effective prophylactic vaccine against genital human papillomavirus (HPV) infection. Two New Zealand white rabbits were immunized with purified HPV type 11 (HPV 11) virions in Freund's adjuvant. An enzyme linked immunoassay (ELISA) was used to determine the quantity of IgG which recognized the HPV 11 major capsid protein (L1 protein) virus-like particles (VLPs) in the two anti-HPV 11 sera (serum A and serum B). The concentration of HPV 11 L1 VLP-specific IgG in the A and B sera were determined to be 37 and 90 micrograms per ml, respectively. The A and B sera were used in neutralization experiments in the athymic mouse xenograft system with known quantities of purified HPV 11 virions. The concentration of HPV 11 L1 VLP-specific IgG required to neutralize HPV 11 was determined for each antiserum. This concentration of IgG was approximately 700 to 900 ng per ml. This study demonstrates a positive correlation between the level of HPV 11 L1 VLP-specific IgG in animals immunized with HPV 11 virions and neutralization of HPV 11 in the athymic mouse model. Further studies are needed 1) to determine if sera or genital secretions from other species are neutralizing in the athymic mouse xenograft system, and 2) to determine if the VLP ELISA can be used as a reliable substitute for more cumbersome neutralization assays.


Inhibition of spontaneous apoptosis in human breast cancer.
Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptosis, a genetically programed process of autonomous cell death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer samples. We found there is a great inhibition of spontaneous apoptosis in breast cancer cells compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.


Splashing transients of 2D plasmons launched by swift electrons.
Launching of plasmons by swift electrons has long been used in electron energy-loss spectroscopy (EELS) to investigate the plasmonic properties of ultrathin, or two-dimensional (2D), electron systems. However, the question of how a swift electron generates plasmons in space and time has never been answered. We address this issue by calculating and demonstrating the spatial-temporal dynamics of 2D plasmon generation in graphene. We predict a jet-like rise of excessive charge concentration that delays the generation of 2D plasmons in EELS, exhibiting an analog to the hydrodynamic Rayleigh jet in a splashing phenomenon before the launching of ripples. The photon radiation, analogous to the splashing sound, accompanies the plasmon emission and can be understood as being shaken off by the Rayleigh jet-like charge concentration. Considering this newly revealed process, we argue that previous estimates on the yields of graphene plasmons in EELS need to be reevaluated.


Graphene-Based Composites for Biomedical Applications: Surface Modification for Enhanced Antimicrobial Activity and Biocompatibility.
The application of graphene-based materials in medicine has led to significant technological breakthroughs. The remarkable properties of these carbon materials and their potential for functionalization with various molecules and compounds make them highly attractive for numerous medical applications. To enhance their functionality and applicability, extensive research has been conducted on surface modification of graphene (GN) and its derivatives, including modifications with antimicrobials, metals, polymers, and natural compounds. This review aims to discuss recent and relevant studies related to advancements in the formulation of graphene composites, addressing their antimicrobial and/or antibiofilm properties and evaluating their biocompatibility, with a primary focus on their biomedical applications. It was concluded that GN surface modification, particularly with compounds intrinsically active against bacteria (e.g., antimicrobial peptides, silver and copper nanomaterials, and chitosan), has resulted in biomaterials with improved antimicrobial performance. Furthermore, the association of GN materials with non-natural polymers provides composites with increased biocompatibility when interfaced with human tissues, although with slightly lower antimicrobial efficacy. However, it is crucial to highlight that while modified GN materials hold huge potential, their widespread use in the medical field is still undergoing research and development. Comprehensive studies on safety, long-term effects, and stability are essential before their adoption in real-world medical scenarios.


Fertility Preservation Preferences and Perspectives Among Adult Male Survivors of Pediatric Cancer and Their Parents.
Purpose: In this study, we set out to determine the preferences, concerns, and attitudes toward fertility preservation of adult male survivors of pediatric cancer and their parents. Methods: We conducted 3 focus groups with a total of 15 male survivors of pediatric cancer (age at diagnosis: mean=14, range: 10-20; age at study: mean=35, range: 25-47) and 2 groups with a total of 7 parents of survivors. Grounded theory methodology was used for the identification and analysis of recurrent themes expressed by survivors and their parents in the course of focus group discussions. Results: Themes most frequently expressed by survivors included concern regarding long-term treatment effects and a retrospective desire for fertility impairment to have been discussed when they were originally diagnosed with cancer. Parental themes included the same hindsight desire, as well as reliance upon the treating oncologist for direction in selecting the course of treatment, and an acknowledgment that input from a specialist in fertility preservation would have been beneficial. Conclusions: Although future reproductive potential was not consistently reported as a source of apprehension when diagnosed with cancer, both survivors and their parents noted it to be a paramount concern later in life. Parents and survivors both reported that fertility preservation discussions should be routinely incorporated in the clinical context of a pediatric cancer diagnosis.


Referral of newly diagnosed chronic hepatitis B and C patients in six EU countries: results of the HEPscreen Project.
Effective linkage to specialist care following screening is crucial for secondary prevention of chronic viral hepatitis-related consequences. To explore the frequency of referral of patients to secondary care from the health services involved in screening and to gather information on the services responsible for the provision of post-test counselling and contact tracing, four online surveys were conducted among general practitioners (GP), and experts working in sexual health services (SHS), antenatal care (ANC) and specialist secondary care in Germany, Hungary, Italy, The Netherlands, Spain and the UK. Overall, 60% of GPs report referring all patients to specialist care. Although 67% of specialists commonly receive patients referred by GPs, specialists in Germany rarely or never receive patients from ANC or from centres testing injecting drug users; and specialists in the Netherlands, Hungary and Germany rarely receive patients from SHS. Gastroenterologists/hepatologists are the professionals mainly responsible for the provision of counselling following a positive diagnosis of viral hepatitis according to two-thirds of specialists, 14% of SHS providers and 11% of ANC providers. Almost half of ANC providers (45%) stated that gynaecologists are the professionals responsible for the provision of counselling to positive pregnant women; among SHS providers, only 14% identified SHS as the services responsible. Our findings suggest the existence of complex/ineffective referral practices or that opportunities to screen risk groups are missed. Recommendations clarifying the services responsible at each step of the referral pathway are needed in order to increase the success of screening programmes.


Identification and characterization of a novel adiponectin receptor agonist adipo anti-inflammation agonist and its anti-inflammatory effects in vitro and in vivo.
Adiponectin (APN) is an adipokine secreted from adipocytes that binds to APN receptors AdipoR1 and AdipoR2 and exerts an anti-inflammatory response through mechanisms not fully understood. There is a need to develop small molecules that activate AdipoR1 and AdipoR2 and to be used to inhibit the inflammatory response in lipopolysaccharide (LPS)-induced endotoxemia and other inflammatory disorders. We designed 10 new structural analogues of an AdipoR agonist, AdipoRon (APR), and assessed their anti-inflammatory properties. Bone marrow-derived macrophages (BMMs) and peritoneal macrophages (PEMs) were isolated from mice. Levels of pro-inflammatory cytokines were measured by reverse transcription and real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and microarray in LPS-induced endotoxemia mice and diet-induced obesity (DIO) mice in which systemic inflammation prevails. Western blotting, immunohistochemistry (IHC), siRNA interference and immunoprecipitation were used to detect signalling pathways. A novel APN receptor agonist named adipo anti-inflammation agonist (AdipoAI) strongly suppresses inflammation in DIO and endotoxemia mice, as well as in cultured macrophages. We also found that AdipoAI attenuated the association of AdipoR1 and APPL1 via myeloid differentiation marker 88 (MyD88) signalling, thus inhibiting activation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and c-Maf pathways and limiting the production of pro-inflammatory cytokines in LPS-induced macrophages. AdipoAI is a promising alternative therapeutic approach to APN and APR to suppress inflammation in LPS-induced endotoxemia and other inflammatory disorders via distinct signalling pathways.


5-Hydroxytryptamine-1 receptor activation inhibits endocrine pancreatic secretion in humans.
The selective 5-hydroxytryptamine-1 receptor agonist sumatriptan inhibits exocrine pancreatic function in humans. No data are available on the effect of sumatriptan on fasting and postprandial endocrine pancreatic function in humans. To elucidate the influence of 5-hydroxytryptamine-1 receptor activation by sumatriptan on endocrine pancreatic function and blood glucose homeostasis, we determined plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin, and C-peptide before and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers, and we measured blood glucose and insulin plasma levels during an oral glucose tolerance test after placebo and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers. Sumatriptan significantly decreased the mean plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin and C-peptide (P < 0.001) and also significantly decreased mean and peak plasma levels of insulin after an oral glucose challenge (P < 0.02 and P = 0.04, respectively) without affecting glucose homeostasis. From our study, we speculate that activation of the 5-hydroxytryptamine-1 receptor inhibits endocrine pancreatic secretion.


Cardiovascular variability during treatment with haloperidol, olanzapine or risperidone in recent-onset schizophrenia.
This study aimed to investigate the effects of treatment with haloperidol, olanzapine and risperidone on cardiovascular variability in patients with recent-onset schizophrenia by means of spectral analysis. Unmedicated patients (n = 18) had a higher mean heart rate and a tendency for a lower high-frequency power of heart rate variability than healthy control subjects (n = 57), indicating a decreased cardiac vagal control in unmedicated patients with schizophrenia. Patients treated with haloperidol (n = 10) showed significantly lower low-frequency power of heart rate and systolic blood pressure variability compared with olanzapine-treated patients, suggesting that haloperidol attenuated sympathetic functioning. On the contrary, olanzapine-treated patients (n = 10) showed the highest power in the low-frequency range of heart rate and systolic blood pressure variability, suggesting an increased sympathetic cardiac functioning. No significant effects of risperidone (n = 13) were found. None of the antipsychotic agents differed in their parasympathetic cardiovascular effects. We conclude that young, unmedicated patients with schizophrenia differed from controls in their parasympathetic functioning, but the antipsychotic agents haloperidol, risperidone and olanzapine induced only minor cardiovascular side effects.


Psychosocial interventions for self-harm, suicidal ideation and suicide attempt in children and young people: What? How? Who? and Where?
We reviewed the evidence for the effectiveness of indicated individual psychosocial interventions for the treatment of self-harm, suicidal ideation and suicide attempts in children and young people, with a particular emphasis on the emerging use of electronic methods to deliver psychological interventions. In total, 16 randomised controlled trials (RCTs) were identified, none of which included children under the age of 12 years. Cognitive-behavioural therapy is the most commonly implemented approach in RCTs until now, although problem-solving therapy, interpersonal psychotherapy, social support and distal support methods by provision of a green card and regular receipt of postcards have also been investigated. Young people have been recruited into RCTs within schools, outpatient clinics, emergency departments and inpatient facilities. Face-to-face delivery of therapy has dominated the intervention trials thus far; however, the use of the internet, social media and mobile devices to deliver interventions to young people and other family members allows for a more novel approach to suicide prevention in youth going forward.


Cross-pinning: the philosophy of retrievability applied practically to fixed, implant-supported prostheses.
Biologic and technical complications are widely reported in the dental literature and often compromise the functional and/or aesthetic features of fixed, implant-supported prostheses. Managing complications without damaging or destroying a restoration is an obvious advantage of implant-based dentistry where the option of prosthetic retrievability is almost always available. The technique of cross-pinning uses a transverse screw to secure a prosthesis to a milled implant abutment, allowing prosthetic retrievability irrespective of dental implant alignment. This study presents guidelines for cross-pinning implant-supported prostheses based on resistance form, screw mechanics and natural tooth contours. The technical aspects of cross-pinning are also discussed using examples from four implant systems.


Validity and reproducibility of cephalometric measurements obtained from digital photographs of analogue headfilms.
The emerging market of digital cephalographs and computerized cephalometry is overwhelming the need to examine the advantages and drawbacks of manual cephalometry, meanwhile, small offices continue to benefit from the economic efficacy and ease of use of analogue cephalograms. The use of modern cephalometric software requires import of digital cephalograms or digital capture of analogue data: scanning and digital photography. The validity of digital photographs of analogue headfilms rather than original headfilms in clinical practice has not been well established. Digital photography could be a fast and inexpensive method of digital capture of analogue cephalograms for use in digital cephalometry. The objective of this study was to determine the validity and reproducibility of measurements obtained from digital photographs of analogue headfilms in lateral cephalometry. Analogue cephalometric radiographs were performed on 15 human dry skulls. Each of them was traced on acetate paper and photographed three times independently. Acetate tracings and digital photographs were digitized and analyzed in cephalometric software. Linear regression model, paired t-test intergroup analysis and coefficient of repeatability were used to assess validity and reproducibility for 63 angular, linear and derivative measurements. 54 out of 63 measurements were determined to have clinically acceptable reproducibility in the acetate tracing group as well as 46 out of 63 in the digital photography group. The worst reproducibility was determined for measurements dependent on landmarks of incisors and poorly defined outlines, majority of them being angular measurements. Validity was acceptable for all measurements, and although statistically significant differences between methods existed for as many as 15 parameters, they appeared to be clinically insignificant being smaller than 1 unit of measurement. Validity was acceptable for 59 of 63 measurements obtained from digital photographs, substantiating the use of digital photography for headfilm capture and computer-aided cephalometric analysis.


Low CSF oxytocin reflects high intent in suicide attempters.
Data from animal studies suggest that oxytocin is an important modulating neuropeptide in regulation of social interaction. One human study has reported a negative correlation between CSF oxytocin levels, life history of aggression and suicidal behaviour. We hypothesized that CSF oxytocin levels would be related to suicidal behaviour, suicide intent, lifetime interpersonal violence and suicide risk. 28 medication free suicide attempters and 19 healthy volunteers participated in this cross sectional and longitudinal study. CSF and plasma morning basal levels of oxytocin were assessed with specific radio-immunoassays. The Beck Suicide Intent Scale (SIS), the Freeman scale and the Karolinska Interpersonal Violence Scale (KIVS) were used to assess suicide intent and lifetime violent behaviour. All patients were followed up for cause of death. The mean follow-up was 21 years. Suicide attempters had lower CSF oxytocin levels compared to healthy volunteers p=0.077. In suicide attempters CSF oxytocin showed a significant negative correlation with the planning subscale of SIS. CSF oxytocin showed a significant negative correlation with suicide intent, the planning subscale of SIS and Freeman interruption probability in male suicide attempters. Correlations between plasma oxytocin levels and the planning subscale of SIS and Freeman interruption probability were significant in male suicide attempters. Lifetime violent behaviour showed a trend to negative correlation with CSF oxytocin. In the regression analysis suicide intent remained a significant predictor of CSF oxytocin corrected for age and gender whereas lifetime violent behaviour showed a trend to be a predictor of CSF oxytocin. Oxytocin levels did not differ significantly in suicide victims compared to survivors. CSF oxytocin may be an important modulator of suicide intent and interpersonal violence in suicide attempters.


Myelin basic protein is affected by reduced synthesis of myelin proteolipid protein in the jimpy mouse.
Myelin basic proteins (MBPs) from 6-day-old, 10-day-old, 20-day-old and adult normal mouse brain were compared with those from 20-day-old jimpy (dysmyelinating mutant) mouse brain to determine the effect of reduced levels of proteolipid protein (PLP) on MBPs. Alkaline-urea-gel electrophoresis showed that 6-day-old and 10-day-old normal and jimpy MBPs lacked charge microheterogeneity, since C8 (the least cationic of the components; not be confused with complement component C8) was the only charge isomer present. In contrast, MBPs from 20-day-old and adult normal mouse brain displayed extensive charge microheterogeneity, having at least eight components. A 32 kDa MBP was the major isoform observed on immunoblots of acid-soluble protein from 6-day-old and 10-day-old normal and 20-day-old jimpy mouse brain. There were eight bands present in 20-day-old and adult normal mouse brain. Purified human MBP charge heteromers C1, C2, C3 and C4 reacted strongly with rat 14 kDa MBP antiserum, whereas the reaction with human C8 was weak. This suggested that MBPs from early-myelinating and jimpy mice did not react to MBP antisera because C8 was the major charge isomer in these animals. Purification of MBPs from normal and jimpy brain by alkaline-gel electrophoresis showed that both normal and jimpy MBPs have size heterogeneity when subjected to SDS/PAGE. However, the size isoforms in normal mouse brain (32, 21, 18.5, 17 and 14 kDa) differed from those in jimpy brain (32, 21, 20, 17, 15 and 14 kDa) in both size and relative amounts. Amino acid analyses of MBPs from jimpy brain showed an increase in glutamic acid, alanine and ornithine, and a decrease in histidine, arginine and proline. The changes in glutamic acid, ornithine and arginine are characteristic of the differences observed in human C8 when compared with C1.


Determination of sterol and fatty acid compositions, oxidative stability, and nutritional value of six walnut (Juglans regia L.) cultivars grown in Portugal.
Six cultivars (Franquette, Marbot, Mayette, Mellanaise, Lara, and Parisienne) of walnuts (Juglans regia L.) were collected during the 2001 crop, from Bragança, Portugal. Chemical composition, including moisture, total oil content, crude protein, ash, carbohydrates, and nutritional value, was evaluated. Fat was the predominant component, ranging from 62.3 to 66.5%. Total oil was extracted and analyzed for fatty acids, sterols, oxidative stability, and peroxide value. Fatty acids and sterols were determined by gas-liquid chromatography coupled to a flame ionization detector. Eighteen fatty acids were quantified. Polyunsaturated fatty acids and, in particular, linoleic acid were predominant. Beta-Sitosterol, delta(5)-avenasterol, and campesterol were the major sterols found. Differences were observed among the studied cultivars, especially in peroxide values and in the sterol profile.


Growth optimization and organogenesis of Gerbera jamesonii Bolus ex. Hook f. in vitro.
Regeneration potentials in Gerbera jamesonii Bolus ex. Hook f. from tissues culture system was studied using leaf, petiole and root explants. In vitro regeneration, callus induction and root formation were optimized by manipulation of growth regulators during organogenesis. Various kinds of plant growth regulators such as 6-Benzylaminopurine (BAP), alpha-Naphthalene acetic acid (NAA), 2, 4-Dichlorophenoxyacetic acid (2,4-D), Indole-3-acetic acid (IAA), Indole-3-Butyric acid (IBA), N6-[2-Isopentenyl]adenine (2iP), Kinetin and Zeatin were used to initiate cultures. These plant growth regulators were added to Murashige and Skoog medium in different combinations and concentrations. Adventitious shoots were obtained from petiole explants cultured on Murashige and Skoog (MS) medium supplemented with 2.0 mg L(-1) BAP and 0.5 mg L(-1) NAA. Effectiveness of shoot regeneration medium, type of growth regulator used and duration of induction period were investigated. Leaf explants cultured on MS medium supplemented with 1.0 mg L(-1) BAP and 2.0 mg L(-1) 2, 4-D showed the best results for callus induction. Root explants were found to be non-regenerative in all experiments conducted. Petiole segment was identified as the best explant for regeneration of this species. Regenerated plants were rooted on Murashige and Skoog basal medium. Plantlets were then transferred to field with 75% survival rate.


[Determination of the early antigens induced by herpes simplex virus in human tumors by a radioimmunological binding method].
It is very difficult to produce specific antibody to individual antigens comprising the multicomponent antigenic system of a cell. It is particularly true of the antigens present in the cell in small amounts and characterized by low immunogenic potency, among them early antigens of herpes simplex virus (HSV). To overcome these difficulties the authors propose a method of preparation of a specific serum using specific immune complexes as immunogens. The use of the radioimmune binding method and a new specific serum to early HSV antigen has proved that HSV could be associated not only with cervical carcinoma, as believed by many research workers, but also with tumors of other localization, in particular, lung carcinoma and malignant melanomas.


Plasma 1-carbon metabolites and academic achievement in 15-yr-old adolescents.
Academic achievement in adolescents is correlated with 1-carbon metabolism (1-CM), as folate intake is positively related and total plasma homocysteine (tHcy) negatively related to academic success. Because another 1-CM nutrient, choline is essential for fetal neurocognitive development, we hypothesized that choline and betaine could also be positively related to academic achievement in adolescents. In a sample of 15-yr-old children (n= 324), we measured plasma concentrations of homocysteine, choline, and betaine and genotyped them for 2 polymorphisms with effects on 1-CM, methylenetetrahydrofolate reductase (MTHFR) 677C>T, rs1801133, and phosphatidylethanolamineN-methyltransferase (PEMT), rs12325817 (G>C). The sum of school grades in 17 major subjects was used as an outcome measure for academic achievement. Lifestyle and family socioeconomic status (SES) data were obtained from questionnaires. Plasma choline was significantly and positively associated with academic achievement independent of SES factors (paternal education and income, maternal education and income, smoking, school) and of folate intake (P= 0.009,R(2)= 0.285). With the addition of thePEMTrs12325817 polymorphism, the association value was only marginally changed. Plasma betaine concentration, tHcy, and theMTHFR677C>T polymorphism did not affect academic achievement in any tested model involving choline. Dietary intake of choline is marginal in many adolescents and may be a public health concern.-Nilsson, T. K., Hurtig-Wennlöf, A., Sjöström, M., Herrmann, W., Obeid, R., Owen, J. R., Zeisel, S. Plasma 1-carbon metabolites and academic achievement in 15-yr-old adolescents.


Management of Infections and Osteomyelitis in Patients With Charcot Foot Arthropathy.
There is growing interest in performing reconstruction of deformities associated with Charcot foot arthropathy. At least half of the patients undergoing this reconstruction will have chronic wounds and osteomyelitis overlying the deformity. It is important to provide orthopaedic surgeons with tools for making the diagnosis of osteomyelitis in this patient population and creating a strategy for treatment.


Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences.
Hepatitis B virus (HBV) is a diverse, partially double-stranded DNA virus, with 9 genotypes (A-I), and a putative 10th genotype (J), characterized thus far. Given the broadening interest in HBV sequencing, there is an increasing requirement for a consistent, unified approach to HBV genotype and subgenotype classification. We set out to generate an updated resource of reference sequences using the diversity of all genomic-length HBV sequences available in public databases. We collated and aligned genomic-length HBV sequences from public databases and used maximum-likelihood phylogenetic analysis to identify genotype clusters. Within each genotype, we examined the phylogenetic support for currently defined subgenotypes, as well as identifying well-supported clades and deriving reference sequences for them. Based on the phylogenies generated, we present a comprehensive set of HBV reference sequences at the genotype and subgenotype level. All of the generated data, including the alignments, phylogenies and chosen reference sequences, are available online (https://doi.org/10.6084/m9.figshare.8851946) as a simple open-access resource.