Enhancing Plant Disease Resistance without R Genes.
Crop plants encounter constant biotic challenges, and these challenges have historically been best managed with resistance (R) genes. However, the rapid evolution of new pathogenic strains along with the nonavailability or nonidentification of R genes in cultivated crop species against a large number of plant pathogens have led researchers to think beyond R genes. Biotechnological tools have shown promise in dealing with such challenges. Technologies such as transgenerational plant immunity, interspecies transfer of pattern recognition receptors (PRRs), pathogen-derived resistance (PDR), gene regulation, and expression of antimicrobial peptides (AMPs) in host plants from other plant species have led to enhanced disease resistance and increased food security.


An epidemiological study of work-related violence experienced by physicians who graduated from a medical school in Japan.
Healthcare workers are at high risk of being victim of verbal and physical violence perpetrated by patients. There are only a few studies on work related violence among physicians. The aim of this study was to determine how prevalent work-related violence against physicians is and whether gender, age, specializations and workplaces are associated with verbal and physical violence against physicians in Japan. A questionnaire was mailed to all the 1,705 physicians who had graduated from one medical school in Japan and had practiced for a minimum of 3 yr by the time of this study. The verbal and physical violence experienced by physicians at the hands of their patients and/or clients in the last 6 months preceding this study were collected. We defined ;verbal violence' as ;any threatening statement or complaint' while ;physical violence' referred to ;the attempted or actual exercise by persons of any physical force so as to cause injury to a physician'. Multiple logistic regression analysis was used to determine the independent contribution of each factor with violence. A total of 540 men and 158 women responded. The adjusted response rate was 41.8%. Among the participants, 168 (24.1%) physicians had experienced verbal violence and 15 (2.1%) physicians had experienced physical violence in the prior 6 months. Verbal violence was positively associated with physicians who were under 30 yr old (odds ratio [OR] = 2.1; 95% confidence interval [CI], 1.0-4.1 for 27-29 yr old) and, psychiatry (OR, 2.4; 95% CI, 1.1-5.4). Physical violence was significantly associated with women (OR, 3.8; 95% CI, 1.1-13.5), specializations such as emergency and anesthesiology (OR, 18.9; 95% CI, 2.8-126.1), and psychiatry (OR, 7.6; 95% CI, 1.6-35.4). There was a considerable number of physicians exposed to violence. Younger physicians and psychiatrists are likely to be exposed to verbal violence. Female physicians, psychiatrists, and emergency physicians are likely to be exposed to physical violence. Education on avoiding from violence should be provided for physicians early in their career.


Arbitrarily spin-orientated and super-resolved focal spot.
In this Letter, we propose a facile approach for achieving a robust focal spot bearing both super-resolution and arbitrary spin orientation. Toward this aim, we meticulously devise a structured incident light consisting of three sorts of beams, which can be produced definitely by the superposition of a radially polarized beam and an azimuthally polarized beam. Based on the vectorial diffraction integral and spin density theory, such newly configurable beams are tightly focused and isotropically interfered in a 4π microscopic configuration to create three polarized field components perpendicular to each other beyond the diffraction limit, thus enabling us to yield a super-resolved focal spot possessing spatial spin axis. By further willfully adjusting the amplitude factors of the reconstituent fields, the photonic spin direction can be freely tunable. The demonstrated results in this Letter may hold great potential for the spin photonics.


[Experience with registration of purulent-septic diseases in newborn infants].
The recording or urgent reports in Moscow since 1974 allowed analyzing the cases of purulent and septic diseases for the period of 1974-1978. The features of the time course and morbidity pattern of the disease, its seasonal fluctuations and the time of onset are presented. Thus, a tendency towards a decrease in morbidity was noted during the above period. The leading role of the diseases of the skin and the subcutaneous fat was established, the morbidity reports were found to fall mostly on the first 2 weeks of the infants' life, and the morbidity rate varied in different maternity hospitals. The recording ensured obtaining current data on morbidity, thus allowing forecast and prevention of the disease.


Novel Variants in LRRK2 and GBA Identified in Latino Parkinson Disease Cohort Enriched for Caribbean Origin.
Background: The Latino population is greatly understudied in biomedical research, including genetics. Very little information is available on presence of known variants originally identified in non-Hispanic white patients or novel variants in the Latino population. The Latino population is admixed, with contributions of European, African, and Amerindian ancestries. Therefore, the ancestry surrounding a gene (local ancestry, LA) can be any of the three contributing ancestries and thus can determine the presence or risk effect of variants detected. Methods: We sequenced the major exons and exons of reported Latino-specific variants in GBA and LRRK2 and performed genome-wide genotyping for LA assessments in 79 Latino Parkinson disease (PD) patients, of which ~80% identified as Caribbean Latino. Results: We observed five carriers of LRRK2 p.G2019S, one GBA p.T408M, and three GBA p.N409S on European as well as three GBA p.L13R on African LA backgrounds. Previous Latino variant GBA p.K237E was not observed in this dataset. A novel highly conserved and predicted damaging variant LRRK2 p.D734N was identified in two unrelated individuals with African LA. Additionally, we identified rare, functional variants LRRK2 p.P1480L and GBA p.S310G in one individual each heterozygous for European/Amerindian LA. Discussion: Additional functional analysis will be needed to determine the pathogenicity of the novel variants in PD. However, the identification of novel disease variants in the Latino cohort potentially contributing to PD supports to importance of inclusion of Latinos in genetics research to provide insight in PD genetics in Latinos specifically as well as other populations with the same ancestral contributions.


Hypoxia and hyperbaric oxygen therapy: a review.
Hypoxia causes a cascade of activity from the level of the individual down to the regulation and function of the cell nucleus. Prolonged periods of low oxygen tension are a core feature of several disease states. Advances in the study of molecular biology have begun to bridge the gap between the cellular response to hypoxia and physiology. Hyperbaric oxygen therapy is a treatment for hypoxic- and inflammatory-driven conditions, in which patients are treated with 100% oxygen at pressures greater than atmospheric pressure. This review discusses hypoxia, the physiologic changes associated with hypoxia, the responses that occur in the cells during hypoxic conditions, and the role that hyperbaric oxygen therapy can play as part of the treatment for many patients suffering from diseases with underlying hypoxia.


Establishing a diagnosis of benign paroxysmal positional vertigo through the dix-hallpike and side-lying maneuvers: a critically appraised topic.
Many patients consult neurologists because of vertigo. Benign paroxysmal positional vertigo (BBPV) is one of the most common types of vertigo. Although the clinical presentation of this common condition is straightforward, the diagnosis and diagnostic maneuvers can be challenging. How useful is the Dix-Hallpike test in establishing the diagnosis of BPPV? How useful is an alternative positional test, such as the side-lying maneuver, in the diagnosis of BPPV? We addressed the question through development of a structured critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarian, and clinical content expert in the field of otolaryngology. Participants started with a clinical scenario and structured questions, devised search strategies, located and compiled the best evidence, performed critical appraisals, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. A single study comparing the Dix-Hallpike and side-lying tests was identified. For the Dix-Hallpike test, the estimated sensitivity was 79% [95% confidence interval (CI) 65-94], specificity was 75% (33-100), positive likelihood ratio (LR) was 3.17 (95% CI 0.58-17.50), negative LR was 0.28 (95% CI 0.11-0.69). For the side-lying test, the estimated sensitivity was 90% (95% CI 79-100), specificity was 75% (33-100), positive LR was 3.59 (95% CI 0.65-19.67), negative LR was 0.14 (95% CI 0.04-0.46). The study employed very weak methodology, and therefore the results had limited validity. The Dix-Hallpike test is the standard from which the diagnosis of posterior semicircular canal BPPV is made. Hence evaluations of its diagnostic test properties and utility are challenging. For patients unable to move into the Dix-Hallpike test positions, alternative tests such as the side-lying test can be attempted. These modifications, however, are rarely necessary.


Prognosis of invasive squamous cell carcinoma of the uterine cervix: a comparative study of the predictive values of clinical staging IB--III and a histopathologic malignancy grading system.
The prognostic values of clinical staging IB--III and a histopathologic malignancy grading system have been compared in a retrospective study on 338 women with invasive squamous cell carcinoma of the uterine cervix. The superiority of the grading system to staging was significant (p less than 0.01). However, staging had an additional prognostic value. Using both the malignancy grading system and clinical staging together provided a better capacity to predict the clinical outcome in individual patients. Prognostication according to clinical staging alone will result in a considerable loss of information.


Focus of attention modulates the heartbeat evoked potential.
Theoretical frameworks such as predictive coding suggest that the perception of the body and world - interoception and exteroception - involve intertwined processes of inference, learning, and prediction. In this framework, attention is thought to gate the influence of sensory information on perception. In contrast to exteroception, there is limited evidence for purely attentional effects on interoception. Here, we empirically tested if attentional focus modulates cortical processing of single heartbeats, using a newly-developed experimental paradigm to probe purely attentional differences between exteroceptive and interoceptive conditions in the heartbeat evoked potential (HEP) using EEG recordings. We found that the HEP is significantly higher during interoceptive compared to exteroceptive attention, in a time window of 524-620 ms after the R-peak. Furthermore, this effect predicted self-report measures of autonomic system reactivity. Our study thus provides direct evidence that the HEP is modulated by pure attention and suggests that this effect may provide a clinically relevant readout for assessing interoception.


Outer membrane protein BamA-based ELISA differentiates Salmonella-vaccinated chickens from naturally infected chickens.
Salmonella often causes subclinical infection in chickens, but antibody tests can find infected individuals and control the spread of infection. In this study, the S. Typhimurium-specific outer membrane, β-barrel assembly machinery protein A (BamA), was overexpressed in Escherichia coli and purified as a coating antigen to develop a BamA-based enzyme-linked immuno sorbent assay for detecting Salmonella infection. The presence of anti-BamA IgG was detected in the sera of infected BALB/c mice, but not in that of heat-killed Salmonella-vaccinated mice. The assay was validated using White Leghorn chickens and showed similar results. The detection of BamA antibodies in the sera can differentiate infected chickens from vaccinated chickens. This assay will be useful for monitoring Salmonella infection in chickens and possibly in other animals.


Hemocytic sarcoma of the body wall in a California king crab Paralithodes californiensis.
Neoplasia is rarely reported in decapod crustaceans, and sarcoma has not been previously reported in any crab species. A California king crab Paralithodes californiensis with a recent history of autotomy (4 legs lost) and anorexia was found dead. Grossly, the crab had a pigmented ulcer on the right cheliped merus. Necropsy tissue samples were placed in 10% neutral buffered formalin and processed routinely for histology. Both histochemical (i.e. Brown and Brenn Gram, Fite-Faraco acid fast, Fontana-Masson, Giemsa, hematoxylin and eosin, Masson's trichrome, periodic acid-Schiff [PAS], phosphotungstic acid-hematoxylin, and von Kossa) and immunohistochemical (i.e. cytokeratin, vimentin, and lysozyme) stains were performed. The body wall (presumably of the right cheliped merus) was ulcerated and subtended by a densely cellular, unencapsulated, invasive neoplasm composed of spindle cells arranged in intersecting streams and bundles embedded in a small to moderate amount of fibromatous stroma. Neoplastic cells were oval to elongate with fibrillar, pale eosinophilic cytoplasm that occasionally contained moderate numbers of small, spherical, brightly eosinophilic granules that were highlighted with PAS and Giemsa stains. Neoplastic cells had mild atypia and no evident mitoses. Immunohistochemical stains were noncontributory. This neoplasm is consistent with hemocytic sarcoma of semi-granulocytic origin. Decapod crustaceans have 3 types of hemocytes: hyalinocytes, granulocytes, and semi-granulocytes. Neoplastic cells had PAS- and Giemsa-positive granules, which are present in both semi-granulocytes and granulocytes. Semi-granulocytes can elongate and are associated with deposition of extracellular matrix during some immune responses. Neoplastic cells were elongate and associated with deposition of matrix. These findings suggest neoplastic cells were of semi-granulocytic origin.


Detection and management of mental health problems of older patients by primary care providers.
Evidence is accruing that older individuals receive little attention for mental health problems and that any attention that is given is most often within the primary care setting. A randomized clinical trial was carried out at a primary care clinic of The Johns Hopkins University, Baltimore, testing the ability of feedback of the results of a screening instrument (the General Health Questionnaire) to increase awareness in clinicians of the emotional and psychological problems of their patients. This report contrasts those aged 65 years and older with younger patients. Detection and management of mental morbidity were lower for older individuals, but the feedback intervention increased the likelihood of attention to these problems. This was not true for younger patients. Detection was significantly higher for older patients when screening data were made available, as was management, although the latter difference was not statistically significant. There was evidence as well that the intervention moved clinicians to greater congruence with their older patients in the perception that current mental health problems existed. These findings have important implications for primary care.


Purinergic P2X7 Receptor Mediates the Elimination of Trichinella spiralis by Activating NF-κB/NLRP3/IL-1β Pathway in Macrophages.
Trichinellosis is one of most neglected foodborne zoonoses worldwide. During Trichinella spiralis infection, the intestinal immune response is the first line of defense and plays a vital role in the host's resistance. Previous studies indicate that purinergic P2X7 receptor (P2X7R) and pyrin domain-containing protein 3 (NLRP3) inflammasome are involved in the intestinal immune response in T. spiralis infection. However, the precise role of P2X7R and its effect on NLRP3 remains largely underdetermined. In this study, we aimed to investigate the role of P2X7R in the activation of NLRP3 in macrophages during the intestinal immune response against T. spiralis We found that T. spiralis infection upregulated expression of P2X7R and activation of NLRP3 in macrophages in mice. In vivo, P2X7R deficiency resulted in increased intestinal adult and muscle larval burdens, along with decreased expression of NLRP3/interleukin-1β (IL-1β) in macrophages from the infected mice with T. spiralis In In vitro experiments, P2X7R blockade inhibited activation of NLRP3/IL-1β via NF-κB and thus reduced the capacity of macrophages to kill newborn larvae of T. spiralis These results indicate that P2X7R mediates the elimination of T. spiralis by activating the NF-κB/NLRP3/IL-1β pathway in macrophages. Our findings contribute to the understanding of the intestinal immune mechanism of T. spiralis infection.


Assessment of physiological state of microorganisms in activated sludge with flow cytometry: application for monitoring sludge production minimization.
Many sludge reduction processes have been studied for the minimization of sludge production in biological wastewater treatment. The investigations on most of these processes have monitored the increase of the soluble chemical oxygen demand, the sludge mass reduction, or the decrease of the floc size, but little information has been obtained on cell lysis and the change of the biological cell activity. However, employing any strategy for reducing sludge production may have an impact of microbial community in biological wastewater treatment process. This impact may influence the sludge characteristics and the quality of effluent. The objective of this study concerns the determination of the physiological state of activated sludge microorganisms during a sludge minimization process. A thermal treatment at 80 degrees C for 5, 20, 40 and 60 min was chosen in this study. Staining bacteria with CTC and SYTOX green was used to evaluate biological cell activity and viability of cell types contained in activated sludge, respectively. The monitoring of cell activity and viability was performed using flow cytometry (FCM) analysis before and after thermal treatment of activated sludge. Results indicated an increase in the number of permeabilized cells and a decrease in the number of active cells, subsequent to the thermal treatment. The study also confirms the potential of FCM to successfully evaluate the physiological heterogeneity of an activated sludge bacterial population. Moreover, the experimentally observed correlations between the FCM results and the organic matter solubilization in activated sludge samples during thermal treatment revealed that the increase in the soluble organic matter concentration was predominantly due to an intracellular material release. Identifying the increase in activated sludge hydrolysis requires a precise knowledge of the involved mechanisms, and this study indicated that the FCM, used in conjunction with specific probes, could be a useful tool.


Utilization of transferrin and salmon serum as sources of iron by typical and atypical strains of Aeromonas salmonicida.
The ability of typical and atypical strains of Aeromonas salmonicida to utilize non-haem sources of protein-bound iron was evaluated. (i) In a plate bioassay, the suppression of growth imposed on typical and atypical A. salmonicida by addition of the high-affinity iron chelator ethylenediamine-di(o- hydroxyphenylacetic acid) (EDDA) to the growth medium was reversed by the addition of 30% or 90% iron-saturated bovine or human transferrin (Tf) or lactoferrin (Lf) to the growth medium. (ii) The mechanism of obtaining iron from Tf was investigated by the addition of bovine Tf contained within a dialysis bag. The reversal of iron-restricted growth suppression differed between the strains in that the atypical strains were unable to utilize Tf contained within a dialysis bag while the typical strains were able to do so. This suggested a siderophore-mediated uptake of iron from Tf by the typical strains, which are known to produce siderophores while atypical strains do not. (iii) A solid-phase binding assay using horseradish-peroxidase-conjugated or biotinylated Tf or Lf failed to detect Tf/Lf-binding activity using whole typical or atypical cells. (iv) When atypical extracellular products (ECP) plus bovine Tf or salmon serum were enclosed in a dialysis bag, diffusible products were released which could reverse the EDDA-imposed growth suppression of an atypical strain. This reversal was negated by inhibition of the ECP metalloprotease with EDTA. (v) Purified 70 kDa serine protease of a typical strain was able to digest bovine Tf to low molecular mass fragments as observed in SDS-PAGE. These results indicate that typical and atypical strains of A. salmonicida differ in their mechanism of utilization of non-haem protein- bound sources of iron. Typical strains utilize Tf via a siderophore-mediated mechanism and are also able to digest Tf with the extracellular serine protease. Atypical strains utilize Tf by a siderophore-independent mechanism probably involving the proteolytic degradation of Tf by the extracellular metalloprotease.


Comparative analysis of the modified enclosed energy metric for self-focusing holograms from digital lensless holographic microscopy.
A comparative analysis of the performance of the modified enclosed energy (MEE) method for self-focusing holograms recorded with digital lensless holographic microscopy is presented. Notwithstanding the MEE analysis previously published, no extended analysis of its performance has been reported. We have tested the MEE in terms of the minimum axial distance allowed between the set of reconstructed holograms to search for the focal plane and the elapsed time to obtain the focused image. These parameters have been compared with those for some of the already reported methods in the literature. The MEE achieves better results in terms of self-focusing quality but at a higher computational cost. Despite its longer processing time, the method remains within a time frame to be technologically attractive. Modeled and experimental holograms have been utilized in this work to perform the comparative study.


Joint modelling of longitudinal and competing risks data.
Available methods for joint modelling of longitudinal and survival data typically have only one failure type for the time to event outcome. We extend the methodology to allow for competing risks data. We fit a cause-specific hazards sub-model to allow for competing risks, with a separate latent association between longitudinal measurements and each cause of failure.The method is applied to data from the SANAD trial of anti-epileptic drugs (AEDs), as a means of investigating the effect of drug titration on the relative effects of lamotrigine (LTG) and carbamazepine (CBZ) on treatment failure. Concern had been expressed that differential titration rates may have been to the disadvantage of CBZ. The beneficial effect of LTG on unacceptable adverse events leading to drug withdrawal did not lessen and indeed increased slightly when a calibrated dose was accounted for in the joint model. Adjustment for the titration rate of LTG relative to CBZ resulted in an unchanged effect of the former on drug withdrawals due to inadequate seizure control. LTG remains the AED of choice from this analysis.


A comparison of surgical intervention and stereotactic body radiation therapy for stage I lung cancer in high-risk patients: a decision analysis.
We sought to compare the relative cost-effectiveness of surgical intervention and stereotactic body radiation therapy in high risk patients with clinical stage I lung cancer (non-small cell lung cancer). We compared patients chosen for surgical intervention or SBRT for clinical stage I non-small cell lung cancer. Propensity score matching was used to adjust estimated treatment hazard ratios for the confounding effects of age, comorbidity index, and clinical stage. We assumed that Medicare-allowable charges were $15,034 for surgical intervention and $13,964 for stereotactic body radiation therapy. The incremental cost-effectiveness ratio was estimated as the cost per life year gained over the patient's remaining lifetime by using a decision model. Fifty-seven patients in each arm were selected by means of propensity score matching. Median survival with surgical intervention was 4.1 years, and 4-year survival was 51.4%. With stereotactic body radiation therapy, median survival was 2.9 years, and 4-year survival was 30.1%. Cause-specific survival was identical between the 2 groups, and the difference in overall survival was not statistically significant. For decision modeling, stereotactic body radiation therapy was estimated to have a mean expected survival of 2.94 years at a cost of $14,153 and mean expected survival with surgical intervention was 3.39 years at a cost of $17,629, for an incremental cost-effectiveness ratio of $7753. In our analysis stereotactic body radiation therapy appears to be less costly than surgical intervention in high-risk patients with early stage non-small cell lung cancer. However, surgical intervention appears to meet the standards for cost-effectiveness because of a longer expected overall survival. Should this advantage not be confirmed in other studies, the cost-effectiveness decision would be likely to change. Prospective randomized studies are necessary to strengthen confidence in these results.


In vitro and in vivo pathogenicity of Plesiomonas shigelloides.
Epidemiologic evidence suggests that Plesiomonas shigelloides is an enteric pathogen. We conducted in vitro, animal, and volunteer studies on P. shigelloides isolates from patients with diarrhea. Five strains gave a negative keratoconjunctivitis reaction in guinea pigs and did not invade HeLa cells. Genetic probes for heat-stable enterotoxins related to those of enterotoxigenic Escherichia coli and for gene sequences common to the invasiveness plasmids of Shigella spp. and enteroinvasive E. coli were negative. Heat-labile enterotoxins were not found when a modified GM1-enzyme-linked immunosorbent assay was used. Rabbits did not develop diarrhea but were transiently colonized when inoculated with up to 10(11) P. shigelloides CFU using the reversible intestinal tie adult rabbit diarrhea model. A very large plasmid (between 118 and 312 megadaltons) was found in all isolates. Strain P012 was cured of its plasmid by novobiocin. This strain, but not its cured derivative, invaded the mucosa of the distal ileum of gnotobiotic piglets given 10(10) CFU. At a lower inoculum (10(9) CFU), strain P012 induced inflammation of the colonic mucosa and diarrhea at day 6. The same isolate was fed to 33 healthy volunteers in doses of 1 X 10(3) to 4 X 10(9) CFU. Thirty-six percent of the volunteers shed the organism, but none became ill. These data are only weakly supportive of a role for P. shigelloides in diarrheal illness and suggest the need for more studies with other strains to better understand its pathogenicity.


A case report of thyroid-associated Orbitopathy with elevated TPO antibodies.
Thyroid associated orbitopathy (TAO) is defined as an immune mediated inflammatory process affecting the extraocular muscles, connective and adipose tissue of uncertain etiopathogenesis. TAO are classically described in Grave's disease (GD) however it may occur in euthyroid and hypothyroid patients. Those patients usually test positive for Thyroid Stimulating Hormone receptor antibodies (TRAb). For instance, only few cases of severe Hashimoto's thyroiditis (HT) associated orbitopathy with negative TRAb are reported to date. Herewith we report a rare case of a middle-aged female who presented with bilateral progressive upper and lower palpebral edema and a unilateral marked proptosis associated with asthenia, headache and decrease in visual acuity. Biological investigation was notable for high levels of anti-thyroid peroxidase antibodies (Anti-TPO) in an otherwise euthyroid patient with negative TRAb. Orbital Magnetic resonance imaging revealed edema of the extraocular muscles and inflammation of periorbital soft tissue. The patient received a treatment with intravenous methylprednisolone followed by oral treatment with prednisone. This regimen was both effective and safe with minimal metabolic side effects in our patient. Minor ocular manifestations of HT are common; however, severe sight threatening ophtalmopathy in the absence of TRAb is rare. Multiple differential diagnosis should be considered and investigated before diagnosing this rare entity. Management of similar cases is currently based on reports and no clear guidelines have been elaborated, corticosteroids is the mainstream of treatment with a potential benefit of selenium supplementation in mild to moderate cases.


Effect of Hydrophobic Interactions on Lower Critical Solution Temperature for Poly(N-isopropylacrylamide-co-dopamine Methacrylamide) Copolymers.
For the preparation of thermoresponsive copolymers, for e.g., tissue engineering scaffolds or drug carriers, a precise control of the synthesis parameters to set the lower critical solution temperature (LCST) is required. However, the correlations between molecular parameters and LCST are partially unknown and, furthermore, LCST is defined as an exact temperature, which oversimplifies the real situation. Here, random N-isopropylacrylamide (NIPAM)/dopamine methacrylamide (DMA) copolymers were prepared under a systematical variation of molecular weight and comonomer amount and their LCST in water studied by calorimetry, turbidimetry, and rheology. Structural information was deduced from observed transitions clarifying the contributions of molecular weight, comonomer content, end-group effect or polymerization degree on LCST, which were then statistically modeled. This proved that the LCST can be predicted through molecular structure and conditions of the solutions. While the hydrophobic DMA lowers the LCST especially the onset, polymerization degree has an important but smaller influence over all the whole LCST range.


The effect of posture on body circumferences in older adults.
Standards for anthropometrical assessment define that measurements must be carried out with the subject in the standing position, although this is not always possible. The effect of body position on girth measurement has not been evaluated, even though this issue is clinically relevant because it may bias nutritional assessment results. The present study aimed to evaluate the effect of body position and symmetry on girth measurement. A cross-sectional study was conducted on 102 older adults aged ≥65 years from care homes and tertiary hospitals. Right and left arm, waist, hip mid-thigh and calf girths were obtained with the subject standing or in the supine position. Mini-Nutritional Assessment Short-Form (MNA-SF) score and reference data percentiles (NHANES IV) misclassification according to girths assessed in the supine position was evaluated. A high intraclass correlation coefficient (ICC > 0.97) and quartiles agreement (k > 0.89) were found between girth measurements conducted on participants in the standing and supine positions. According to MNA-SF, 23.5% of the participants were undernourished and 51% were at risk of undernutrition. A high agreement between MNA-SF score using calf circumference measured on standing or supine position was found (k = 0.96). A relevant agreement for NHANES IV girth percentiles by sex and age was also found (ICC > 0.89). Agreement between girth measurements on standing and supine positions among older adults is high and differences do not have any clinically relevant impact on MNA-SF classification and reference data percentiles.


Why do I treat my patients with mild hepatitis C?
The major advances achieved in the treatment of HCV by the development of new direct-acting antiviral agents (DAAs) allow treatment of almost the entire spectrum of patients with chornic infection. As a result of the exceedingly high cost of DAAs in many countries, IFN-free DAA regimens are mostly reserved to patients with advanced fibrosis or cirrhosis. Hence, treatment of patients with milder liver disease is often deferred. This could ultimately result in an increased burden of advanced liver disease and in increased long-term costs of management. Moreover, studies performed during the 'interferon era' and the early data on interferon-free regimens show that patients without severe fibrosis achieve higher rates of sustained virological response with less treatment-related adverse events. Unfortunately, there is no univocal way to predict the progression of liver fibrosis and therefore to identify the patients with early disease who would require urgent HCV treatment. Many studies have also demonstrated that treatment-induced HCV clearance reduces all-cause mortality regardless of the stage of liver fibrosis, pointing to an effect on extrahepatic manifestations of HCV infection. Last but not least, pharmacoeconomic studies show that DAA treatment of patients with mild HCV disease is cost-effective even at high prices of drugs, thus suggesting the opprtunity to treat regardless of the stage of liver disease.


"Combined Diagnostic Tool" APPlication to a Retrospective Series of Patients Undergoing Total Joint Revision Surgery.
Background: Differentiating between septic and aseptic joint prosthesis may be challenging, since no single test is able to confirm or rule out infection. The choice and interpretation of the panel of tests performed in any case often relies on empirical evaluation and poorly validated scores. The "Combined Diagnostic Tool (CDT)" App, a smartphone application for iOS, was developed to allow to automatically calculate the probability of having a of periprosthetic joint infection, on the basis of the relative sensitivity and specificity of the positive and negative diagnostic tests performed in any given patient. Objective: The aim of the present study was to apply the CDT software to investigate the ability of the tests routinely performed in three high-volume European centers to diagnose a periprosthetic infection. Methods: This three-center retrospective study included 120 consecutive patients undergoing total hip or knee revision, and included 65 infected patients (Group A) and 55 patients without infection (Group B). The following parameters were evaluated: number and type of positive and negative diagnostic tests performed pre-, intra- and post-operatively and resultant probability calculated by the CDT App of having a peri-prosthetic joint infection, based on pre-, intra- and post-operative combined tests. Results: Serological tests were the most common performed, with an average 2.7 tests per patient for Group A and 2.2 for Group B, followed by joint aspiration (0.9 and 0.8 tests per patient, respectively) and imaging techniques (0.5 and 0.2 test per patient). Mean CDT App calculated probability of having an infection based on pre-operative tests was 79.4% for patients in Group A and 35.7 in Group B. Twenty-nine patients in Group A had > 10% chance of not having an infection, and 29 of Group B had > 10% chance of having an infection. Conclusion: This is the first retrospective study focused on investigating the number and type of tests commonly performed prior to joint revision surgery and aimed at evaluating their combined ability to diagnose a peri-prosthetic infection. CDT App allowed us to demonstrate that, on average, the routine combination of commonly used tests is unable to diagnose pre-operatively a peri-prosthetic infection with a probability higher than 90%.


Hypothesis: Immunotherapy by Selective Convalescent Blood Engineering to Stifle Diseases like COVID-19.
Current standard vaccine testing protocols take approximately 10-24 months of testing before a vaccine can be declared successful. Sometimes by the time a successful vaccine is out for public use, the outbreak may already be over. With no vaccine or antiviral drug available to treat the infected, we are left with the age-old methods of isolation, quarantine, and rest, to arrest such a viral outbreak. Convalescent blood therapy and covalent plasma therapy have often proved effective in reducing mortality, however, the role of innate and adaptive immune cells in these therapies have been overlooked. Antigen presenting cells (APCs), CD4+ T memory cells, CD8+ T memory cells, and memory B-Cells all play a vital role in sustainable defense and subsequent recovery. This report incorporates all these aspects by suggesting a novel treatment therapy called selective convalescent leukapheresis and transfusion (SCLT) and also highlights its potential in vaccination. The anticipated advantages of the proposed technique outweigh the cost, time, and efficiency of other available transfusion and vaccination processes. It is envisioned that in the future this new approach could serve as a rapid emergency response to subdue a pathogen outbreak and to stop it from becoming an epidemic, or pandemic.


How Neoliberalism Is Shaping the Supply of Unhealthy Commodities and What This Means for NCD Prevention.
Alcohol, tobacco, and unhealthy foods contribute greatly to the global burden of non-communicable disease (NCD). Member states of the World Health Organization (WHO) have recognized the critical need to address these three key risk factors through global action plans and policy recommendations. The 2013-2020 WHO action plan identifies the need to engage economic, agricultural and other relevant sectors to establish comprehensive and coherent policy. To date one of the biggest barriers to action is not so much identifying affective policies, but rather how a comprehensive policy approach to NCD prevention can be established across sectors. Much of the research on policy incoherence across sectors has focused on exposing the strategies used by commercial interests to shape public policy in their favor. Although the influence of commercial interests on government decisions remains an important issue for policy coherence, we argue, that the dominant neoliberal policy paradigm continues to enable the ability of these interests to influence public policy. In this paper, we examine how this dominant paradigm and the way it has been enshrined in institutional mechanisms has given rise to existing systems of governance of product environments, and how these systems create structural barriers to the introduction of meaningful policy action to prevent NCDs by fostering healthy product environments. Work to establish policy coherence across sectors, particularly to ensure a healthy product environment, will require systematic engagement with the assumptions that continue to structure institutions that perpetuate unhealthy product environments.


Protein arginine methyltransferase 1 interacts with and activates p38α to facilitate erythroid differentiation.
Protein arginine methylation is emerging as a pivotal posttranslational modification involved in regulating various cellular processes; however, its role in erythropoiesis is still elusive. Erythropoiesis generates circulating red blood cells which are vital for body activity. Deficiency in erythroid differentiation causes anemia which compromises the quality of life. Despite extensive studies, the molecular events regulating erythropoiesis are not fully understood. This study showed that the increase in protein arginine methyltransferase 1 (PRMT1) levels, via transfection or protein transduction, significantly promoted erythroid differentiation in the bipotent human K562 cell line as well as in human primary hematopoietic progenitor CD34(+) cells. PRMT1 expression enhanced the production of hemoglobin and the erythroid surface marker glycophorin A, and also up-regulated several key transcription factors, GATA1, NF-E2 and EKLF, which are critical for lineage-specific differentiation. The shRNA-mediated knockdown of PRMT1 suppressed erythroid differentiation. The methyltransferase activity-deficient PRMT1G80R mutant failed to stimulate differentiation, indicating the requirement of arginine methylation of target proteins. Our results further showed that a specific isoform of p38 MAPK, p38α, promoted erythroid differentiation, whereas p38β did not play a role. The stimulation of erythroid differentiation by PRMT1 was diminished in p38α- but not p38β-knockdown cells. PRMT1 appeared to act upstream of p38α, since expression of p38α still promoted erythroid differentiation in PRMT1-knockdown cells, and expression of PRMT1 enhanced the activation of p38 MAPK. Importantly, we showed for the first time that PRMT1 was associated with p38α in cells by co-immunoprecipitation and that PRMT1 directly methylated p38α in in vitro methylation assays. Taken together, our findings unveil a link between PRMT1 and p38α in regulating the erythroid differentiation program and provide evidence suggesting a novel regulatory mechanism for p38α through arginine methylation.


A meta-analysis of clinical outcomes in the treatment of aphasia.
An extensive search of aphasia-treatment literature yielded 55 reports of clinical outcomes satisfying the essential criteria for inclusion in a meta-analysis. The results confirmed those of an earlier meta-analysis in demonstrating the utility of aphasia treatments, generally considered, for bringing about desirable clinical outcomes. Beyond the general case, the new findings address clinical utility in finer detail than was previously possible. Effects of treatment for aphasia are synthesized and assessed for each of four important dimensions: amount of treatment, type of treatment, severity of aphasia, and type of aphasia.


[Primary signet cell adenocarcinoma of the bladder].
The primary signet-ring cell adenocarcinoma of the bladder is a rare tumor, with great biological aggressivity and bad prognosis. We report a clinical case of a 65 years old patient, starting with bladder irritative symptoms and suffering from advanced disease at the initial diagnosis. We review clinical and etiopathogenic aspects about this entity.


[Antithrombogenic activity of blood vessel walls in the pathogenesis of metastasis in tumor-bearing animals].
The purpose of this work was to examine the relationship between the antiaggregatory activity of the vascular wall and the metastatic spread of experimental tumors. Rats with the tumor "Myosarcoma-1" displayed, on the average, a 30% reduction in the antiaggregatory activity of the aortic wall. Three-week of the animals with a combination of the drugs dipyridamole (0.84 mg/kg per os), phytin (14 mg/kg per os), glutamic acid (28 mg/kg per os) restored the antiaggregatory properties of the vascular wall virtually up to the control values. The similar result was observed with cordarone (60 mg/kg intraperitoneally): the antiaggregatory properties of the vascular wall increased on the average by 50%. The metastatic spread of tumor cells in mice with Lewis carcinoma of the lung decreased on the average twice while treating them with these agents. The findings point to the fact that drug correction of the antiaggregatory activity of the vascular wall reduces the rate of metastatic spread.


Yersinia enterocolitica infection in diarrheal patients.
In this study, we hoped to provide valuable clinical information on yersiniosis for clinicians. Two thousand six hundred stool samples were collected from in- and outpatients with diarrhea, which were tested with both culture method and real-time polymerase chain reaction (RT-PCR). In total, 188 positive samples were detected by RT-PCR (178) and culture method (160), while the incidence was about 7.23%. The detection rate of RT-PCR was significantly higher than culture method and a higher incidence in autumn-winter was also noticeably identified than in spring-summer. Infection sources mostly focused on unboiled foods (101) and pets (45), while clinical manifestation mainly presented as gastroenteritis (156), pseudoappendicitis (32), and extraintestinal complications (46). The morbidity of extraintestinal complications in adults was significantly higher than in children and it was the same for high-risk patients between adults over the age of 60 years (4.7%) and children under the age of 3 years (1.4%), whereas the constituent ratio of children versus adults with yersiniosis in different systems was not significant. Of 160 isolates tested for antimicrobial susceptibility, the majority were susceptible to third-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, whereas only a small portion was susceptible to the first-generation cephalosporins and penicillins. During autumn-winter months, clinicians should pay more attention to clinical manifestation, early diagnosis, and treatment with susceptible antibiotics of yersiniosis and its complications, targeting high-risk patients.


SPI2 T3SS effectors facilitate enterocyte apical to basolateral transmigration of Salmonella-containing vacuoles in vivo.
Salmonella pathogenicity island (SPI) 2 type three secretion system (T3SS)-mediated effector molecules facilitate bacterial survival in phagocytes but their role in the intestinal epithelium in vivo remains ill-defined. Using our neonatal murine infection model in combination with SPI2 reporter technology and RNA-Seq of sorted primary enterocytes, we demonstrate expression of SPI2 effector molecules by intraepithelial Salmonella Typhimurium (S. Typhimurium). Contrary to expectation, immunostaining revealed that infection with SPI2 T3SS-mutants resulted in significantly enlarged intraepithelial Salmonella-containing vacuoles (SCV) with altered cellular positioning, suggesting impaired apical to basolateral transmigration. Also, infection with isogenic tagged S. Typhimurium strains revealed a reduced spread of intraepithelial SPI2 T3SS mutant S. Typhimurium to systemic body sites. These results suggest that SPI2 T3SS effector molecules contribute to enterocyte apical to basolateral transmigration of the SCV during the early stage of the infection.


Role of supplementary eye field in saccade initiation: executive, not direct, control.
The goal of this study was to determine whether the activity of neurons in the supplementary eye field (SEF) is sufficient to control saccade initiation in macaque monkeys performing a saccade countermanding (stop signal) task. As previously observed, many neurons in the SEF increase the discharge rate before saccade initiation. However, when saccades are canceled in response to a stop signal, effectively no neurons with presaccadic activity display discharge rate modulation early enough to contribute to saccade cancellation. Moreover, SEF neurons do not exhibit a specific threshold discharge rate that could trigger saccade initiation. Yet, we observed more subtle relations between SEF activation and saccade production. The activity of numerous SEF neurons was correlated with response time and varied with sequential adjustments in response latency. Trials in which monkeys canceled or produced a saccade in a stop signal trial were distinguished by a modest difference in discharge rate of these SEF neurons before stop signal or target presentation. These findings indicate that neurons in the SEF, in contrast to counterparts in the frontal eye field and superior colliculus, do not contribute directly and immediately to the initiation of visually guided saccades. However the SEF may proactively regulate saccade production by biasing the balance between gaze-holding and gaze-shifting based on prior performance and anticipated task requirements.


Cross-sectional survey of cat handling practices in veterinary clinics throughout Canada and the United States.
To assess handling techniques commonly used during routine examinations and procedures used for calm, fearful, and aggressive cats by veterinarians and nonveterinarian staff at Canadian and US veterinary practices and to evaluate demographic factors associated with those handling techniques. 310 veterinarians and 944 nonveterinarians who handle cats at Canadian and US veterinary practices. An online questionnaire was developed to evaluate respondent demographics and use of common cat handling practices and techniques. A snowball sampling method was used to send a link to the questionnaire to members of Canadian and US veterinary-affiliated groups. Descriptive statistics were generated; logistic regression was used to identify demographic factors associated with the use of minimal and full-body restraint with scruffing during routine examination and procedures for fearful and aggressive cats. Full-body restraint was used to handle cats of all demeanors, although its frequency of use was greatest for fearful and aggressive cats. Veterinarians and nonveterinarians who graduated from veterinary training programs before 2006 were less likely to use full-body restraint for cats of all demeanors, compared with nonveterinarians who did not graduate or graduated between 2006 and 2015. Other factors associated with decreased use of full-body restraint included working at an American Association of Feline Practitioners-certified practice and working at a Canadian practice. Results suggested that full-body restraint is commonly used to handle cats. Further research is necessary to determine whether current handling recommendations are effective in decreasing stress for cats during veterinary visits.


[SWE elastography in assessment of liver fibrosis].
Liver fibrosis is a relatively common consequence of chronic liver diseases, especially chronic viral hepatitis B and C. Biopsy still remains the gold standard in the assessment of liver fibrosis. However, due to its invasiveness and possible complications, less or even non-invasive methods are being developed, e.g. using biochemical parameters (Fibrotest) or elastography. Elastography is a new diagnostic tool that aims to evaluate stiffness of the tissues. Elastography techniques that are used in the assessment of liver fibrosis are transient elastography (TE), acoustic radiation force impulse (ARFI) and shear-wave elastography (SWE). SWE is a novel real-time two-dimensional elastography technique, which allows one to estimate stiffness quantitatively in kilopascals (kPa). Moreover, lapping elastography over regular B-mode allows precise choice of the region of interest. Therefore SWE creates the opportunity for accurate assessment of liver fibrosis. In this paper we describe processes leading to liver fibrosis as well as methods of liver fibrosis assessment, e.g. liver biopsy, biochemical tests or elastography. The main goal of this paper is to present the SWE technique, its role in liver fibrosis assessment and a short review of the most important clinical studies on SWE. We also present several examples of SWE examinations performed on patients with different stages of liver fibrosis - F0 to F4 on the METAVIR scale.


Inducible nuclear translocation of a STAT protein in Dictyostelium prespore cells: implications for morphogenesis and cell-type regulation.
Dd-STATa, the Dictyostelium STAT (signal transducer and activator of transcription) protein, is selectively localised in the nuclei of a small subset of prestalk cells located in the slug tip. Injection of cAMP into the extracellular spaces in the rear of the slug induces rapid nuclear translocation of a Dd-GFP:STATa fusion protein in prespore cells surrounding the site of injection. This suggests that cAMP signals that emanate from the tip direct the localised nuclear accumulation of Dd-STATa. It also shows that prespore cells are competent to respond to cAMP, by Dd-STATa activation, and it implies that cAMP signalling is in some way limiting in the rear of the slug. Co-injection of a specific inhibitor of the cAR1 serpentine cAMP receptor almost completely prevents the cAMP-induced nuclear translocation, showing that most or all of the cAMP signal is transduced by cAR1. Dd-GFP:STATa also rapidly translocates into the nuclei of cells adjoining the front and back cut edges when a slug is bisected. Less severe mechanical disturbances, such as pricking the rear of a slug with an unfilled micropipette, also cause a more limited nuclear translocation of Dd-GFP:STATa. We propose that these signalling events form part of a repair mechanism that is activated when the migrating slug suffers mechanical damage.


Clinical advances and ongoing trials on mRNA vaccines for cancer treatment.
Years of research exploring mRNA vaccines for cancer treatment in preclinical and clinical trials have set the stage for the rapid development of mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and the inherent advantage in ease of production, which rivals the best available conventional vaccine manufacture methods, renders mRNA vaccines a promising option for cancer immunotherapy. Technological advances have optimised mRNA-based vaccine stability, structure, and delivery methods, and multiple clinical trials investigating mRNA vaccine therapy are now enrolling patients with various cancer diagnoses. Although therapeutic mRNA-based cancer vaccines have not yet been approved for standard treatment, encouraging results from early clinical trials with mRNA vaccines as monotherapy and in combination with checkpoint inhibitors have been obtained. This Review summarises the latest clinical advances in mRNA-based vaccines for cancer treatment and reflects on future perspectives and challenges for this new and promising treatment approach.


Effect of Anserine and Carnosine on Sperm Motility in the Japanese Quail.
Sperm motility is considered as one of the most important traits for successful fertilization, but the motility of an ejaculated sperm decreases with time when stored as liquid. It is reported that seminal plasma serves as a nutrient rich medium for sperm and plays an important role in sperm motility and its fertilization ability. Several studies have reported that imidazole dipeptides such as anserine and carnosine affect sperm motility and its fertilization ability in mammals. In this study, we report the presence of anserine and carnosine in the male reproductive tract of the Japanese quail. Abundant levels of anserine (44.46 µM) and carnosine (41.75 µM) were detected in the testicular fluid and seminal plasma respectively using the amino acid analyzer; however, seminal plasma solely contained carnosine. When the ejaculates were incubated with anserine or carnosine, we found that both the dipeptides improve sperm motility parameters such as straight line velocity, curvilinear velocity, average path velocity and amplitude of lateral head displacement after in vitro sperm storage at 15°C. These results indicate that imidazole dipeptides are present in the male reproductive tract and may improve sperm quality during in vitro sperm storage in the liquid states.


Architecture of the microtubule component of mitotic spindles from Dictyostelium discoideum.
Ten mitotic spindles from Dictyostelium discoideum have been studied by electron microscopy of serial sections. We have used computer graphics to track individual microtubules (MTs) in three dimensions and to compare seven spindles at different stages of anaphase and telophase. The central spindle of early anaphase is formed by the interdigitation of two sets of pole-associated MTs. The distribution of MT lengths at this stage is hetero-disperse. During anaphase total MT length decreases by a factor of about 2 as a result of two opposing changes in MT length: the longer MTs that interdigitate become even longer, while the short MTs, including those attached to kinetochores, become shorter still and decrease in number. The extent of MT interdigitation is less in longer spindles than in short ones. In metaphase and early anaphase, the MTs are not in an ordered arrangement as seen in spindle cross-sections, but as anaphase proceeds the MTs cluster into a square-packed, paracrystalline bundle in which most of the nearest neighbours come from opposite poles. This arrangement and the condensation-like increase in order suggest the existence of specific interactions between antiparallel MTs. A quantitative analysis of MT positions supports this interpretation, but direct evidence for convincing bridges between MTs is lacking. The pole-distal ends of the MTs that interdigitate show an irregular termination (C-shaped ends in transverse view), as is characteristic of MTs that are either adding or losing subunits. Since it is these interdigitating MTs that elongate, and since the shortening MTs show the customary blunt endings, we conclude that subunits add to the interdigitating MTs at their pole-distal ends. This inference, combined with other structural data, suggests that the interdigitating MTs of Dictyostelium are sliding over one another as they polymerize in anaphase. It also suggests a simple model for why the spindle becomes thinner as it elongates. We propose that MT interdigitation defines a region where MTs bind a factor that will associate only with antiparallel MTs. This factor biases the MT assembly equilibrium toward polymer. As the shorter MTs slide out of this region, they lose their polymerization advantage and depolymerize, releasing subunits to contribute to the further elongation of the already longer MTs. The properties of the Dictyostelium spindle are compared with those of both higher and lower eukaryotes.


The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis.
Conflicting results regarding the impact of repeated vaccination on influenza vaccine effectiveness (VE) may cause confusion regarding the benefits of receiving the current season's vaccine. We systematically searched MEDLINE, Embase, PubMed, and Cumulative Index to Nursing and Allied Health Literature from database inception to August 17, 2016, for observational studies published in English that reported VE against laboratory-confirmed influenza for the following four vaccination groups: current season only, prior season only, both seasons, and neither season. We pooled differences in VE (∆VE) between vaccination groups by influenza season and type/subtype using a random-effects model. The study protocol is registered with PROSPERO (registration number: CRD42016037241). We identified 3435 unique articles, reviewed the full text of 634, and included 20 for meta-analysis. Compared to prior season vaccination only, vaccination in both seasons was associated with greater protection against influenza H1N1 (∆VE = 25%; 95% CI 14%, 35%) and B (∆VE = 18%; 95% CI 3%, 33%), but not H3N2 (∆VE = 7%; 95% CI - 7%, 21%). Compared to no vaccination for either season, individuals who received the current season's vaccine had greater protection against H1N1 (∆VE = 62%; 95% CI 51%, 70%), H3N2 (∆VE = 45%; 95% CI 35%, 53%), and B (∆VE = 64%; 95% CI 57%, 71%). We observed no differences in VE between vaccination in both seasons and the current season only for H1N1 (∆VE = 3%; 95% CI - 8%, 13%), but less protection against influenza H3N2 (∆VE = - 20%; 95% CI - 36%, - 4%), and B (∆VE = - 11%; 95% CI - 20%, - 2%). Our results support current season vaccination regardless of prior season vaccination because VE for vaccination in the current season only is higher compared to no vaccination in either season for all types/subtypes, and for H1N1 and influenza B, vaccination in both seasons provides better VE than vaccination in the prior season only. Although VE was lower against H3N2 and B for individuals vaccinated in both seasons compared to those vaccinated in the current season only, it should be noted that past vaccination history cannot be altered and this comparison disregards susceptibility to influenza during the prior season among those vaccinated in the current season only. In addition, our results for H3N2 were particularly influenced by the 2014-2015 influenza season and the impact of repeated vaccination for all types/subtypes may vary from season to season. It is important that future VE studies include vaccination history over multiple seasons to evaluate repeated vaccination in more detail.


Beyond responsible conduct in research: new pedagogies to address macroethics of nanobiotechnologies.
A team of engineers, scientists, ethicists, and educational specialists are enhancing Duke University's Responsible Conduct of Research (RCR) program to ensure that graduate-level researchers in emerging fields are adequately prepared when confronted with macroethical issues associated with applications of new and emerging medical technologies. The focus is on nanoscale laboratory research conducted in the Center for Biologically Inspired Materials and Material Systems and the Center for Biological Tissue Engineering. Most present RCR programs address methodological ethics of the individual researcher or practitioner (i.e., microethical) issues, analogous to Kohlberg's theory of moral development. The resultant model from this project is the basis for departmental, center, and other more targeted ethical challenges stemming from research in emerging technologies, designed to provide comprehensive RCR training. The research successfully identified new ways of teaching students about macroethical issues (i.e., those that affect society). Three main dimensions of ethics in nanotechnology-related research are being stressed, namely, awareness, ethical decision making, and behavior. Workshops appear to enhance awareness of the ethical issues associated with emerging technologies. To date, attempts to affect decision making have been difficult, although in this study workshops were an effective means of identifying strategies to address ethical issues. A principal lesson learned has been the importance of providing a context for macroethical issues. For example, the workshop where an expert presented the technical aspects of environmental consequences of carbon nanotubes led to statistically significant differences between pre- and postworkshop understanding of societal risks. Conversely, in a workshop without the technical introduction, little difference was observed. This indicates that the stage of students' ethical understanding is an important determinant of effectiveness of the education method needed.


Result of surgery for ruptured intracranial aneurysms in Nepal.
Although aneurysmal subarachnoid haemorrhage appears to be fairly common in the developing countries, the data on the results of management appear to be relatively sparse. This is a retrospective study of 40 patients with 44 intracranial aneurysms operated upon at the National Neurosurgical Referral Centre in Kathmandu, Nepal from 1991 to 1999. The female male ratio was 1.5:1. Age ranged from 16 to 69 years with a mean of 43.2. In location, 18 (41%) were anterior communicating, 10 (23%) posterior communicating, nine (20%) middle cerebral, five (11%) internal carotid other than posterior communicating, two (5%) distal anterior cerebral and one (2%) posterior circulation. Multiple aneurysms were present in four (10%) and giant in three (8%). The timing of surgery ranged from 3 days to 3 months from the day of bleeding. Microsurgical clipping was possible in 37 (93%) and wrapping had to be done in three (7%). Overall mortality was four (10%), two (5%) had a surgery-related death and a further two (5%) died later due to pulmonary embolism. The remaining (90%) made a good recovery. The results compare favourably with that of the International Cooperative Study. Further reduction in mortality will have to await the introduction of endovascular techniques.


A bioinspired flexible organic artificial afferent nerve.
The distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. We used flexible organic electronics to mimic the functions of a sensory nerve. Our artificial afferent nerve collects pressure information (1 to 80 kilopascals) from clusters of pressure sensors, converts the pressure information into action potentials (0 to 100 hertz) by using ring oscillators, and integrates the action potentials from multiple ring oscillators with a synaptic transistor. Biomimetic hierarchical structures can detect movement of an object, combine simultaneous pressure inputs, and distinguish braille characters. Furthermore, we connected our artificial afferent nerve to motor nerves to construct a hybrid bioelectronic reflex arc to actuate muscles. Our system has potential applications in neurorobotics and neuroprosthetics.


Bioartificial nerve graft for bridging extended nerve defects in rat sciatic nerve based on resorbable guiding filaments.
A long defect (15 mm) in rat sciatic nerve was repaired with a bioartificial nerve graft composed of a silicone tube and seven synthetic filaments of five types (polyamide, catgut, polydioxanone, and two types of polyglactin, normal and quickly-absorbed) inserted longitudinally into the tube. In all cases in which filaments were used a regenerating bridge was obtained in the tube after three months in contrast to empty silicone tubes, in which no structure was observed. There was a 6%-46% recovery of isometric muscle contractility of the anterior tibial and gastrocnemius muscles with positive pinch reflex test in most cases. Myelinated axons were seen in the regenerating tissue between the filaments but not directly in contact with them, and there were varying numbers of macrophages close to the filaments. Silicone tubes with filaments, regardless of type of filament, induced nerve tissue to regenerate and resulted in functional recovery through a 15 mm nerve gap not achieved with empty tubes. Nerve promoting factors may be applied to the filaments and the model is a valuable tool for further development of artificial nerve grafts.


Skeletal Fragility in Type 2 Diabetes Mellitus.
Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.


Radio frequency magnetic field effects on a radical recombination reaction: a diagnostic test for the radical pair mechanism.
The photoinduced electron-transfer reaction of chrysene with isomers of dicyanobenzene is used to demonstrate the sensitivity of a radical recombination reaction to the orientation and frequency (5-50 MHz) of a approximately 300 muT radio frequency magnetic field in the presence of a 0-4 mT static magnetic field. The recombination yield is detected via the fluorescence of the exciplex formed exclusively from the electronic singlet state of the radical ion pair Chr*+/DCB*-. Magnetic field effects are simulated using a modified version of the gamma-COMPUTE algorithm, devised for the simulation of magic angle spinning NMR spectra of powdered samples. The response of a chemical or biological system to simultaneously applied radio frequency and static or extremely low-frequency magnetic fields could form the basis for a diagnostic test for the operation of the radical pair mechanism that would not require prior knowledge of the nature and properties of the radical reaction.


[The management of gout].
We describe the case of a patient with a history of gout, who presents with a new episode of acute gout. Based on this clinical case, we will discuss the management of acute gout. We will then address the management of chronic gout, i.e., the indications for a hypouricemic treatment and the caution required when starting this treatment. Finally, we will address the need for a holistic care, discussing the change of certain co-medications, screening for cardiovascular comorbidities and providing diet and life-style recommendations.


Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years.
To examine the impact of newer neuropathological techniques on the power of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria for Alzheimer disease (AD) to detect AD at later postmortem study. We examined clinical and postmortem diagnoses of persons evaluated postmortem with thioflavin-S staining for plaques and tangles and immunohistochemical staining techniques for alpha synuclein, uhiquitin, and tau protein. Alzheimer Disease Center. Clinically evaluated persons for whom tissue diagnosis was available. Of 313 evaluees, 166 met criteria for probable AD. An additional 59 subjects had clinical diagnoses that included AD, e.g., possible AD, Lewy body variant of AD, AD and Parkinsonism, and mixed AD and vascular dementia. Of the 166 probable AD cases, 147 of 166 (88.6%) met pathologic criteria for AD. When all five AD groups were combined, 194 of 225 subjects (86.2%) met pathologic criteria for AD. There were five cases diagnosed pathologically as tangle-only dementia, which was considered a variant of AD. A pathologic diagnosis of Lewy body variant of AD was made in 56 (17.9%) of cases, including 44 of 313 (14.1%) cases diagnosed as probable or possible AD. Pure dementia with Lewy bodies was seen in 13 (4.2%). There were 9 (2.9%) cases of mixed AD and vascular dementia, and 37 (11.4%) cases of frontotemporal dementia. McKhann et al. criteria for probable and possible AD are valid for AD but do not exclude additional Lewy body pathology.


Targeting a polyepitope protein incorporating multiple class II-restricted viral epitopes to the secretory/endocytic pathway facilitates immune recognition by CD4+ cytotoxic T lymphocytes: a novel approach to vaccine design.
The role of CD4+ and CD8+ cells in the generation of an effective immune response against viral infections is well established. Moreover, there is an increasing realization that subunit vaccines which include both CD4+- and CD8+-T-cell epitopes are highly effective in controlling viral infections, as opposed to those which are designed to activate a CD8+- or CD4+-T-cell response alone. One of the major limitations of epitope-based vaccines designed to stimulate virus-specific CD4+ T cells is that endogenously expressed class II-restricted minimal cytotoxic-T-lymphocyte (CTL) epitopes are poorly recognized by CD4+ CTLs. In the present study we attempted to enhance the efficiency of class II-restricted endogenous presentation of minimal class II-restricted CTL epitopes by specifically targeting a polyepitope protein to class II processing compartments through the endosomal and/or lysosomal pathway. A significantly enhanced stimulation of virus-specific CD4+-T-cell clones by antigen-presenting cells (APC) expressing the recombinant polyepitope protein targeted to the endocytic/secretory pathway was readily demonstrated in cytotoxicity assays. In addition, in vitro activation of Epstein-Barr virus- and influenza virus-specific CD4+ memory CTLs by the recombinant constructs encoding the polyepitope protein, specifically targeted to the lysosomal compartment, was also demonstrated. The enhanced stimulatory capacity of APC expressing a lysosome-targeted polyepitope protein has important implications for vaccine design.


An Atlas of Plant Transposable Elements.
Advances in genomic sequencing have recently offered vast opportunities for biological exploration, unraveling the evolution and improving our understanding of Earth biodiversity. Due to distinct plant species characteristics in terms of genome size, ploidy and heterozygosity, transposable elements (TEs) are common characteristics of many genomes. TEs are ubiquitous and dispersed repetitive DNA sequences that frequently impact the evolution and composition of the genome, mainly due to their redundancy and rearrangements. For this study, we provided an atlas of TE data by employing an easy-to-use portal ( APTE website ). To our knowledge, this is the most extensive and standardized analysis of TEs in plant genomes. We evaluated 67 plant genomes assembled at chromosome scale, recovering a total of 49,802,023 TE records, representing a total of 47,992,091,043 (~47,62%) base pairs (bp) of the total genomic space. We observed that new types of TEs were identified and annotated compared to other data repositories. By establishing a standardized catalog of TE annotation on 67 genomes, new hypotheses, exploration of TE data and their influences on the genomes may allow a better understanding of their function and processes. All original code and an example of how we developed the TE annotation strategy is available on GitHub ( Extended data).


Delayed pericardial tamponade after penetrating chest trauma.
Delayed pericardial tamponade (PT) after penetrating heart trauma is now a rare condition as a result of advances in medical and surgical management. We report the case of a 32-year-old man with delayed PT after a stab wound from a knife. The initial evaluation was consistent with a traumatic apical myocardial infarction. After an uneventful initial course, the patient developed acute PT, which required emergency surgery. A thrombus was discovered over a laceration in the mid-segment of the left anterior descending artery and a simple suture was performed.


Incorporation of a β-AgVO3 Semiconductor in Resin Cement: Evaluation of Mechanical Properties and Antibacterial Efficacy.
This in vitro study aimed to investigate the effect of incorporating the semiconductor nanostructured silver vanadate decorated with silver nanoparticles (β-AgVO3) in a dual-cure resin cement on the degree of conversion (DC), microhardness, roughness, color, adhesion properties before and after artificial aging, and antimicrobial efficacy. Three test groups were established: control (without β-AgVO3), with the incorporation of 2.5% and 5% (by weight) of β-AgVO3 in dual-cure resin cement (Allcem, FGM). The degree of conversion was measured using Fourier transform infrared spectroscopy (FTIR). To evaluate roughness (n = 10), microhardness (n = 10), color (n = 10), and to perform agar disk diffusion (n = 8), disks of 6-mm diameter and 2-mm height were manufactured using the same concentrations. For the color and shear bond strength test (n = 6), orthodontic brackets (Morelli) were used, which were cemented to natural human enamel and evaluated before and after artificial aging via thermocycling at 5°C and 55°C for 1000 cycles. For color measurements, a portable spectrocolorimeter and the CIE-Lab method were used. Data were analyzed using Student's t-test, ANOVA, and Tukey's multiple comparisons with significance set at α = 0.05. Semiconductor incorporation did not influence the cements's DC. The incorporation of 2.5% and 5% of β-AgVO3 resulted in a significant increase in Knoop microhardness and surface roughness. Significant changes were observed in the color of the specimens when the semiconductor was incorporated. Adhesion after aging remained within the clinically recommended values in all groups, and antimicrobial activity was observed against Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis at both concentrations tested. It is suggested to incorporate the semiconductor β-AgVO3 in the dual-cure resin cement at both concentrations. Moreover, the physical-mechanical properties remained satisfactory for the proposed application.


Effects of high altitude mountaineering on body composition: a systematic review.
High altitude mountaineering is characterized by high energetic requirements due to the environment in which the activity is developed: negative energy balance, extreme cold, high altitude and the assumption of potential risks can be found during the practice of this sport. High altitude mountaineering, as a result of the previous factors, induces changes in body composition which have never been studied previously in a systematic review. A search within four different databases (PubMed, SportDiscus, Scopus and Medline) was performed using the thesaurus terms "Mountaineering" and "Body composition". A second search was performed using the following terms "Altitude" and "Body composition". The selection criteria included studies with healthy adults which evaluated the effects of at least 14 days of uninterrupted stays at altitudes above 4,000 m. The studies included in the review assessed body composition through different methods such as anthropometry, bioimpedance, dual energy x-ray absorptiometry, hydrostatic weighing and air displacement plethysmography. The search was performed up to and including December 1st 2018. Eleven observational studies met the inclusion criteria. All studies reported weight loss, of which five reported significant reductions in lean mass and six reported reductions in fat mass. Also, three studies reported reductions in both fat mass and lean mass. Current evidence is limited to observational studies with important confounding factors affecting the final conclusions. Longitudinal studies with a better methodological design and control groups are needed in order to verify these results.


Does age at adoption and geographic origin matter? A national cohort study of cognitive test performance in adult inter-country adoptees.
Inter-country adoptees run risks of developmental and health-related problems. Cognitive ability is one important indicator of adoptees' development, both as an outcome measure itself and as a potential mediator between early adversities and ill-health. The aim of this study was to analyse relations between proxies for adoption-related circumstances and cognitive development. Results from global and verbal scores of cognitive tests at military conscription (mandatory for all Swedish men during these years) were compared between three groups (born 1968-1976): 746 adoptees born in South Korea, 1548 adoptees born in other non-Western countries and 330 986 non-adopted comparisons in the same birth cohort. Information about age at adoption and parental education was collected from Swedish national registers. South Korean adoptees had higher global and verbal test scores compared to adoptees from other non-European donor countries. Adoptees adopted after age 4 years had lower test scores if they were not of Korean ethnicity, while age did not influence test scores in South Koreans or those adopted from other non-European countries before the age of 4 years. Parental education had minor effects on the test performance of the adoptees - statistically significant only for non-Korean adoptees' verbal test scores - but was prominently influential for non-adoptees. Negative pre-adoption circumstances may have persistent influences on cognitive development. The prognosis from a cognitive perspective may still be good regardless of age at adoption if the quality of care before adoption has been 'good enough' and the adoption selection mechanisms do not reflect an overrepresentation of risk factors - both requirements probably fulfilled in South Korea.


Proteomics Reveals Cell-Surface Urokinase Plasminogen Activator Receptor Expression Impacts Most Hallmarks of Cancer.
While metastasis is the primary cause of colorectal cancer (CRC) mortality, the molecular mechanisms underpinning it remains elusive. Metastasis is propagated through driver oncogene/suppressor gene mutations, accompanied by passenger mutations and underlying genomic instability. To understand cancer biology, a unifying framework called the "hallmarks of cancer" (HoCs) has been developed, which organizes cell biological alterations under ten key hallmarks. Underlying these HoCs, genome instability generates mutational diversity that is amplified by inflammation. Recognizing how critical cancer cell-surface proteins influence, these HoCs have been proposed to accelerate precision medicine therapeutic development. A moderate decrease (43%↓) in HCT116 cell surface urokinase plasminogen activator receptor (uPAR) expression mitigates against many HoCs driven by these cell's KRAS and PIK3CA mutational signature. Comprehensive proteomics (whole cell lysis with two membrane protein enrichments) coupled with ingenuity pathway analysis (IPA) demonstrates that uPAR negates essential pathways across the HoC spectrum, particularly those associated with metastasis, resisting cell death, and sustaining proliferation, and parallels Cancer Hallmarks Analytics Tool analysis. Decreasing uPAR predominantly alters metastasis-related and uPAR-interactome protein expression (e.g., EGFR, caveolin, vitronectin, integrin β4). Collectively, it is demonstrated that uPAR is a lynchpin protein capable of regulating several HoC pathways in a classical CRC mutational background.


Lipid analysis in nerve biopsy specimens of hypertrophic neuropathy.
We performed a lipid analysis on nerve biopsy specimens in two cases of degenerative hypertrophic neuropathy. Quantitative analysis of the major lipid classes, ie, cholesterol, cerebrosides, sulfatides, ethanolamine phospholipids, phosphatidyl-choline, phosphatidyl-serine, phosphatidyl-inositol, sphingomyelin, and gangliosides, were performed. The two cases exhibited extreme decreases in levels of lipids that could be related to the very low myelin content of these nerves. Cholesterol and phospholipid levels were especially reduced. Cerebrosides and sulfatides were not modified in the same proportion, as could have been predicted from the degree of demyelination. This relative glycolipid increase could be due to the very high Schwann cell proliferation.


Cell cannibalism in oral cancer: A sign of aggressiveness, de-evolution, and retroversion of multicellularity.
According to Darwin's theory of evolution, complex creatures evolve from more simplistic ancestors. Dollo's law of irreversibility states that evolution is irreversible. However, cancer cells tend to follow anti-Dollo's law. Unfavorable conditions such as hypoxia, acidic pH and low nutrients cause the cancer cells to switch their lifestyle atavistically in order to survive. They start behaving like a unicellular organism. There is a switch from normal metabolism to Warburg effect and finally cannibalism. Cannibalism is a cell eating cell phenomenon. It is defined as a large cell enclosing a smaller one within its cytoplasm and is known by odd names such as "bird's eye cells" or "signet ring cells." Smaller tumor cells are found in the cytoplasm of larger tumor cells with crescent-shaped nucleus. Cannibalistic cells (CCs) are a feature of aggressive tumors. These cell types are vulnerable to metastasis. The aim of this study is to identify CCs in various histological grades of oral squamous cell carcinoma (OSCC) and to relate them with the pattern of invasion, lymphocytic response (LR), and mitotic figures (Mfs). The purpose of the article is to establish it as a marker of aggressiveness and metastasis and as an evidence of de-evolution and retroversion of multicellularity. Sixty-five histologically confirmed cases of OSCC were studied. Pattern of invasion, LR, number of CCs, and Mfs were recorded on 5 μ hematoxylin and eosin-stained tissue sections. ANOVA and t-test were applied; P < 0.05 was considered statistically significant. CCs were more in sections with patchy LR, increased Mfs, and grade IV pattern of invasion. With increase in dedifferentiation, tumor cells start behaving like unicellular organisms with cell eating cell characteristics.


Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial.
Findings of preclinical and clinical trials in colorectal cancer have shown promising antitumour effects of the co-formulation trifluridine/tipiracil and VEGF inhibition. We aimed to investigate the safety and activity of trifluridine/tipiracil and ramucirumab for previously treated advanced gastric cancer. We did an open-label, single-arm, two-cohort, phase 2 study at eight centres in Japan. We enrolled patients with unresectable advanced gastric cancer or gastro-oesophageal junction adenocarcinoma. Cohort A included patients previously treated with one line of chemotherapy without ramucirumab and cohort B included patients previously treated with two to four lines of chemotherapy, including ramucirumab. Patients received trifluridine/tipiracil (35 mg/m2) orally twice daily on days 1-5 and days 8-12 of each 28-day treatment cycle, plus intravenous ramucirumab (8 mg/kg) on days 1 and 15. The primary endpoint was the disease control rate, assessed by investigators and defined as the proportion of patients with a confirmed best overall response, according to Response Evaluation Criteria in Solid Tumors version 1.1. This trial is registered on JapicCTI (JapicCTI-194596) and is ongoing but not recruiting. Between April 8 and Oct 11, 2019, 64 patients were enrolled and included in the safety and activity analyses, 33 in cohort A and 31 in cohort B. In cohort A, the disease control rate was 85% (95% CI 68-95; 28 of 33 patients) and in cohort B it was 77% (59-90; 24 of 31 patients). Common treatment-related adverse events of grade 3 or worse were neutrophil count decreased (27 [82%] in cohort A and 23 [74%] in cohort B), white blood cell count decreased (eight [24%] and seven [23%]), and platelet count decreased (eight [24%] and four [13%]). Serious treatment-related adverse events were recorded in three patients in cohort A (fatigue and neutrophil count decreased; large intestine perforation; and febrile neutropenia, platelet count decreased, and anaemia). No patients in cohort B had a serious treatment-related adverse event, and no treatment-related deaths were reported in either cohort. Trifluridine/tipiracil and ramucirumab showed an acceptable safety profile and clinical activity in patients with previously treated advanced gastric cancer regardless of previous ramucirumab exposure. Taiho Pharmaceutical and Eli Lilly.


Implications of natural organic matter binding heterogeneity on understanding lead(II) complexation in aquatic systems.
A critical analysis of data published for complexation (conditional stability constants and complexation capacities) of lead(II) by natural organic matter (NOM) is presented. The same patterns are observed for the different types of NOM, i.e. isolated humic-type substances, isolated algae- and bacteria derived ligands and cell walls, and filtered whole water systems: apparent stronger binding sites are utilised at lower metal ion loadings, progressively weaker sites contribute to metal complexation at higher loadings. Continuous binding functions should thus be used to adequately describe lead-NOM complexation in natural waters. Two important observations arising from our analysis are that: (i) the binding curves (binding affinity as a function of metal ion loading) for whole natural water samples lie between those for compounds representative of the two main NOM types, viz., isolated humic compounds and biota, and (ii) binding constants commonly used in speciation codes probably underestimate the actual extent of lead(II) binding by NOM at natural concentration levels.


In vivo assessment of grafted cortical neural progenitor cells and host response to functionalized self-assembling peptide hydrogels and the implications for tissue repair.
Tissue specific scaffolds formed from minimalist N-fluorenylmethyloxycarbonyl self-assembling peptides (Fmoc-SAPs) have emerged as promising biomaterials due to their ease of synthesis and capacity to self-assemble via simple, non-covalent interactions into complex nanofibrous hydrogels. However, concerns remain over their biocompatibility and cytotoxicity for in vivo applications. Here, we demonstrate that these Fmoc-SAPs are biocompatible in vivo and well suited as a delivery vehicle for cell transplantation. In order to determine the effect of tissue specific parameters, we designed three Fmoc-SAPs containing varying bioactive peptide sequences derived from extracellular matrix proteins, laminin and fibronectin. Fmoc-SAPs delivering cortical neural progenitor cells into the mouse brain display a limited foreign body response, effective functionalization and low cytotoxicity for at least 28 days. These results highlight the suitability of Fmoc-SAPs for improved neural tissue repair through the support of grafted cells and adjacent host parenchyma. Overall, we illustrate that Fmoc-SAPs are easily engineered materials for use as a tool in cell transplantation, where biocompatibility is key to promoting cell survival, enhancing the graft-host interface and attenuation of the inflammatory response for improved tissue repair outcomes.


Components of executive functioning in metamemory.
This study examined metamemory in relation to three basic executive functions (set shifting, working memory updating, and response inhibition) measured as latent variables. Young adults (Experiment 1) and middle-aged adults (Experiment 2) completed a set of executive functioning tasks and the Prospective and Retrospective Memory Questionnaire (PRMQ). In Experiment 1, source recall and face recognition tasks were included as indicators of objective memory performance. In both experiments, analyses of the executive functioning data yielded a two-factor solution, with the updating and inhibition tasks constituting a common factor and the shifting tasks a separate factor. Self-reported memory problems showed low predictive validity, but subjective and objective memory performance were related to different components of executive functioning. In both experiments, set shifting, but not updating and inhibition, was related to PRMQ, whereas source recall showed the opposite pattern of correlations in Experiment 1. These findings suggest that metamemorial judgments reflect selective effects of executive functioning and that individual differences in mental flexibility contribute to self-beliefs of efficacy.


[A network meta-analysis of the efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors for the treatment of influenza in otherwise healthy patients].
Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis (NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients. A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals. The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI [3.23, 39.07]). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI [28.18, 73.86] and 56.03 h [33.74, 87.86], respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir. The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.


Assessing Quality of Syndesmotic Reduction in Surgically Treated Acute Syndesmotic Injuries: A Systematic Review.
There is no universal method with cutoff values for the assessment of distal tibiofibular joint reduction in acute syndesmotic injuries. It is important to detect malreductions because they may lead to impaired functional outcome and may demand reoperations. The aim of this study was to systematically review the literature to evaluate the appropriateness of different image techniques in determining syndesmotic malalignment. A literature search was conducted in Medline, Embase, and the Cochrane Library to search for articles assessing syndesmotic reduction. Excluded were articles where no criteria and/or measurements for syndesmotic reduction were provided, only normative values were provided and reviews. In total, 2157 articles were found, of which 1421 studies were screened for title and abstract after exclusion of duplicates. One hundred ten studies were eligible for full-text analysis. Of these, 61 were excluded. Three studies where added after screening the included references. Fifty-two studies were included, of which 32 were original publications and 20 were publications referring to the original publications. From the original publications, 14 used plains radiographs, 19 computed tomographic (CT) scans, and 5 used 3-dimensional CT scans (some authors used >1 modality in their study). For each modality, a large number of parameters and different cutoff values were reported. CT scanning is superior to plain radiography in the assessment of the quality of joint reduction. Parameters used the most were fibular position in the incisura and fibular rotation. The criteria for adequate reduction should at least include the position of the fibula in the incisura and rotation of the fibula, while ensuring adequate fibular length, all equaling or at least approaching the values of the uninjured contralateral side.


[Differential medium for selection of bacterial L-asparaginase producer strains].
A specific, fast, and easy method for revelation of active plate producers of L-asparaginase using differential medium on the basis of LB or M9 with 1.5% agar was developed. Each 100 ml of LB or M9 medium additionally contained 6-7 ml ofglycerol, 4 g of L-asparagine, 0.2 g of CaCO3, and diagnostic components: 3 ml of 0.2 M CuSO4 x 5H2O and 2.5 ml of 0.1 M K3Fe(CN)6, pH 7.6-7.8. The results were counted 12-20 or 24-48 h after strain growth at 37 degrees C in corresponding mediums. Red color of colonies and colored zone around them showed the ability of the strain under study to destroy asparaginic complexes. The recommended method allows revealing bacterial strains producing L-asparaginase with specific activity of not less than 0.1-3.0 MU/mg of protein.


Orchiectomy performed in two patients with Brucella orchitis mimicking testicular tumour.
Brucellosis is a zoonosis caused by gram negative coccobacilli and it is an endemic infectious disease in Turkey. Infection is usually acquired as a result of direct contact with infected animals or by consuming milk or cheese freshly made from them. There exists a wide spectrum of clinical signs and symptoms in brucellosis. Many systems including musculoskeletal, gastrointestinal, cardiovascular and genitourinary may be involved in brucellosis. The genitourinary system is affected in 2% to 20% of the cases with brucellosis. The most common forms of brucellosis are epididymo-orchitis, testicular abscess and atrophy. The serum agglutination test to detect the presence of antibodies is a reliable test in patients with urogenital symptoms. Long-term and combined antibacterial therapy have been found to be effective in brucellosis. We present two cases undergoing orchiectomy because of testicular mass before the diagnosis of brucellosis was made.


A continuous wavelet transform-based method for time-frequency analysis of artefact-corrected heart rate variability data.
Time-frequency analysis of heart rate variability (HRV) provides relevant clinical information. However, time-frequency analysis is very sensitive to artefacts. Artefacts that are present in heart rate recordings may be corrected, but this reduces the variability in the signal and therefore adversely affects the accuracy of calculated spectral estimates. To overcome this limitation of traditional techniques for time-frequency analysis, a new continuous wavelet transform (CWT)-based method was developed in which parts of the scalogram that have been affected by artefact correction are excluded from power calculations. The method was evaluated by simulating artefact correction on HRV data that were originally free of artefacts. Commonly used spectral HRV parameters were calculated by the developed method and by the short-time Fourier transform (STFT), which was used as a reference. Except for the powers in the very low-frequency and low-frequency (LF) bands, powers calculated by the STFT proved to be extremely sensitive to artefact correction. The CWT-based calculations in the high-frequency and very high-frequency bands corresponded well with their theoretical values. The standard deviations of these powers, however, increase with the number of corrected artefacts which is the result of the non-stationarity of the R-R interval series that were analysed. The powers calculated in the LF band turned out to be slightly sensitive to artefact correction, but the results were acceptable up to 20% artefact correction. Therefore, the CWT-based method provides a valuable alternative for the analysis of HRV data that cannot be guaranteed to be free of artefacts.