[Effect of foodstuff on healthy longevity].
The author models the human organism as complex chromatograph column, such that upon digestion of food-stuffs, in which some part of sustenance first reacts with hydrochloric acid and enzymes to break-down in the stomach. The nutritive particle molecules will then each migrate to different parts of the human molecular structure based on their relative thermodynamic stability and their relative chemical affinities for different intra-molecular attachment sites within the human molecule - the body. Hence, by way of correlating these theories and subsequent data to longevity statistics the author wish to assign gerontological values to food-stuffs based on enthalpy or heats (Gibbs function) of supramolecular interaction measurements. So, essentially, the author patented the idea that all items of food intake can be assigned an anti-aging value based on thermodynamic parameters.


Intubating laryngeal mask airway allows tracheal intubation when the cervical spine is immobilized by a rigid collar.
An intubating laryngeal mask airway (ILMA) facilitates tracheal intubation with the neck in neutral position, which is similar to the neck position maintained by a rigid cervical collar. However, a cervical collar virtually obliterates neck movement, even small movements that normally facilitate airway insertion. We therefore tested the hypothesis that the ILMA will allow tracheal intubation even in patients wearing a rigid cervical collar. We performed blind tracheal intubation via an ILMA under general anaesthesia in 50 patients with a rigid Philadelphia collar in place undergoing cervical spine surgery and 50 general surgical patients. Time required for intubation, intubation success rate, and numbers and type of adjusting manoeuvres used were recorded. Inter-incisor distance was significantly smaller (4.1 (0.8) vs 4.6 (0.7) cm, mean (sd), P<0.01) and Mallampati scores were significantly greater (P<0.001) in the patients with collars. ILMA insertion took longer (30 (25) vs 22 (6) s), more patients required two insertion attempts (15 vs 3; P<0.005), and ventilation adequacy with ILMA was worse (P<0.05) in collared patients. However, there were no significant differences between the collars and control patients in terms of total time required for intubation (60 (41) vs 50 (30) s), number of intubation attempts, overall intubation success rate (96 vs 98%), or the incidence of intubation complications. Blind intubation through an ILMA is thus a reasonable strategy for controlling the airway in patients who are immobilized with a rigid cervical collar.


Mianserin hydrochloride: a new anti-depressant drug.
The tetracyclic anti-depressant drug mianserin hydrochloride has been assessed in an open clinical study in 24 psychiatric out-patients, who were prescribed 30 mg. mianserin daily, and were rated on the Hamilton Rating Scale and on the Wakefield Self-Assessment Inventory on day 0, before starting therapy, and on days 7 and 28 of their treatment. The results support the view that mianserin has anti-depressant properties, and the patients' self-rating scores confirm that the level of anti-depressant action is similar to amitriptyline. Drowsiness was the only side effect reported.


Biochemical characterization and molecular cloning of a novel endothelial-specific sialomucin.
We have generated rat monoclonal antibodies (MoAbs) against cell surface antigens of the mouse endothelioma cell line bEND.3. Three antibodies (V.1A7, V.5C7, and V.7C7) were selected, all of which recognize a 75-kD antigen on bEND.3 cells and bind selectively to endothelial cells in cryostat sections of mouse tissues. A cDNA for the antigen was isolated from a bEND.3 pCDM8 expression library by using transient expression in COS-7 cells and immunoselection with the three MoAbs. This cDNA coded for a novel, type I membrane protein of 248 amino acids with an extracellular domain rich in threonine and serine residues (35%). The protein is sensitive to O-sialoglycoprotein endopeptidase, indicating that it belongs to the class of sialomucin-like proteins. Therefore, we suggest the name endomucin. Treatment of isolated endomucin by sialidase and O-glycosidase reduced the apparent molecular weight to 45 kD and abolished binding of all three antibodies, indicating that carbohydrates are directly or indirectly involved in the formation of the antibody epitopes. Immunohistological analysis of all examined mouse tissues showed that endomucin is an endothelial antigen found in venous endothelium as well as in capillaries, but not on arterial endothelium. Interestingly, high endothelial venules of peripheral and mesenteric lymph nodes as well as of Peyers's patches were negative for staining with the three MoAbs.


Longitudinal examination of pathways to peer problems in middle childhood: A siblings-reared-apart design.
To advance research from Dishion and others on associations between parenting and peer problems across childhood, we used a sample of 177 sibling pairs reared apart since birth (because of adoption of one of the siblings) to examine associations between parental hostility and children's peer problems when children were ages 7 and 9.5 years (n = 329 children). We extended conventional cross-lagged parent-peer models by incorporating child inhibitory control as an additional predictor and examining genetic contributions via birth mother psychopathology. Path models indicated a cross-lagged association from parental hostility to later peer problems. When child inhibitory control was included, birth mother internalizing symptoms were associated with poorer child inhibitory control, which was associated with more parental hostility and peer problems. The cross-lagged paths from parental hostility to peer problems were no longer significant in the full model. Multigroup analyses revealed that the path from birth mother internalizing symptoms to child inhibitory control was significantly higher for birth parent-reared children, indicating the possible contribution of passive gene-environment correlation to this association. Exploratory analyses suggested that each child's unique rearing context contributed to his or her inhibitory control and peer behavior. Implications for the development of evidence-based interventions are discussed.


Availability and use of palliative care and end-of-life services for pediatric oncology patients.
Palliative care prevents or relieves the symptoms caused by life-threatening medical conditions. Previous surveys have shown both underuse and lack of availability of these services for children with cancer throughout North America. We sought to investigate the current practices and resources surrounding palliative and end-of-life care among participating institutions of the Children's Oncology Group (COG). A survey regarding practices and resources was developed by the COG palliative care subcommittee and was sent to all 232 institutions to complete for the calendar year 2005. The survey was completed by 81% of the institutions. Per institution, there were a mean of 64.6 newly diagnosed patients and 17.7 patients experiencing relapse. A palliative care team was available in 58% of institutions, a pain service in 90%, a hospice in 60%, a psychosocial support team in 80%, and a bereavement program in 59%. Complementary and alternative medicine was available in 39% of institutions and in 95% of the COG institution's community. Most services, even when available, were not well used by patients. Despite the well-established benefit of pediatric palliative care, it is only offered in 58% of COG institutions caring for children with cancer. In an era where the benefit of palliative care has been clearly established, this number should approach 100%. Efforts should be directed toward understanding barriers to provision of such services, so that they are available and well used at all childhood cancer centers.


A theoretical investigation of the plausibility of reactions between ammonia and carbonyl species (formaldehyde, acetaldehyde, and acetone) in interstellar ice analogs at ultracold temperatures.
We have reexamined the reaction between formaldehyde and ammonia, which was previously studied by us and other workers in modestly sized cluster calculations. Larger model systems with up to 12H(2)O were employed, and reactions of two more carbonyl species, acetaldehyde and acetone, were also carried out. Calculations were performed at the B3LYP/6-31+G** level with bulk solvent effects treated with a polarizable continuum model; limited MP2/6-31+G** calculations were also performed. We found that while the barrier for the concerted proton relay mechanism described in previous work remains modest, it is still prohibitively high for the reaction to occur under the ultracold conditions that prevail in dense interstellar clouds. However, a new pathway emerged in more realistic clusters that involves at least one barrierless step for two of the carbonyl species considered here: ammonia reacts with formaldehyde and acetaldehyde to form a partial charge transfer species in small clusters (4H(2)O) and a protonated hydroxyamino intermediate species in large clusters (9H(2)O, 12H(2)O); modest barriers that decrease sharply with cluster size are found for the analogous processes for the acetone-NH(3) reaction. Furthermore, if a second ammonia replaces one of the water molecules in calculations in the 9H(2)O clusters, deprotonation can occur to yield the same neutral hydroxyamino species that is formed via the original concerted proton relay mechanism. In at least one position, deprotonation is barrierless when zero-point energy is included. In addition to describing the structures and energetics of the reactions between formaldehyde, acetaldehyde, and acetone with ammonia, we report spectroscopic predictions of the observable vibrational features that are expected to be present in ice mixtures of different composition.


pH dependence of short-circuit current and active phosphate transport by toad bladder.
The effect of changing the pH of the mucosal and serosal bathing solutions on active Na transport (estimated by the short-circuit current) and active inorganic phosphate (Pi) transport was studied in the toad bladder. The short-circuit current was unaffected by lowering the pH from 7.6 to 7.1 but was inhibited (29-45%) at pH 6.6, 8.1, 8.6, 9.1, or 9.6. The Pi transport was not changed when the pH was increased from 7.6 to 8.1, but was totally inhibited at pH 6.6, 7.1, 8.6, 9.1 or 9.6. Thus, active transport of Pi occurs only when most of the Pi is HPO4(-2), but the effect of varying pH on active Pi transport in the toad bladder is more complicated than a simple titration of Pi.


[Statistical analysis of pharmacological data: use of cumulative chi-squared statistic].
The cumulative chi-squared statistic has been proposed for testing against ordered alternatives in various statistical models. As usual statistical tests of ordered column categorical data, the chi 2 test, Fisher's exact test and Wilcoxon test are used. Pharmacological studies often are performed by multiple dosing. Data obtained from these studies are called ordered categorical data. The cumulative chi-squared statistic, which has been proposed by Hirotsu and Shibuya for testing against ordered alternatives in various statistical models, is little used in spite of its good applicability in the field of pharmacology. This method was too difficult for the general pharmacologist and biological scientists because it requires the use of a complex matrix and a powerful computer to carry out the analysis. However since a more simple method was proposed by Matsumoto and Yoshimura this method has been used more frequently in the biological sciences. In this paper, the one way cumulative chi-squared statistic test and two way chi-squared statistic test are compared with the chi-squared statistic test and Wilcoxon test.


Living Alone and Depressive Symptoms Among Older Japanese: Do Urbanization and Time Period Matter?
Previous research has suggested cross-national differences in the association between living alone and well-being among older adults. This study examined whether the association varied across social contexts within the country, Japan, in terms of varying degree of urbanization and differential time periods. Data were obtained from a nine-wave nationwide longitudinal survey with a probability sample of Japanese adults aged 60 years and over. Respondents belonged to one of the three periods (around 1990, 2000, and 2015) according to the year they commenced participation. As many as 4,655 individuals from 575 municipalities provided 9,016 observation sets of two consecutive waves (t - 1 and t). Within a framework of the Hierarchical Generalized Linear Model, depressive symptoms at t were predicted based on changes in living arrangements from t - 1 to t and their cross-level interactions with gender, level of urbanization, and time period, controlling for various covariates at t - 1. In general, older adults living alone continuously as well as those who started living alone between the waves showed more depressive symptoms than those coresiding with someone continuously. However, this tendency was more prominent among rural residents than their urban counterparts, especially for men. Moreover, the effect of continuously living alone on depressive symptoms became smaller in Period 2015 than that in Period 1990, because of the increase in depressiveness in coresident older adults. Our findings indicate that living alone has a differential effect on older adults' well-being depending on the social context where residents' preferences for living arrangements and availability of formal services could vary.


A roadmap for starting, growing and sustaining a comprehensive pediatric surgery service in a low resource area.
The Tanzania-Oxford Children's Surgery Partnership is a longstanding capacity building and research collaboration. Over a 21-year period, this non-hierarchical partnership has worked to develop from service delivery to children surgical system strengthening in Tanzania. This has directly impacted the children's surgery and workforce by increasing the number of pediatric surgeons in the country and upskilling nurses, anesthetists, and pediatricians. Clinical skills acquisition has been complemented by the development of leadership, mentorship, and research acumen. The partnership has also delivered critical upgrading of infrastructure which has significantly increased operative volume and allowed for the provision of minimally invasive children's surgery. A children's research network has been established, with a focus on research equity and local data ownership adhering to local ethics, leading to prolific academic output. At the core of this partnership has been the recognition that achieving sustainable change requires local leadership, long-term commitment, and 'bottom-up' change. We described the historical events and steps taken by our partners to achieve the universal provision of children's surgery in Tanzania.


Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar-I disorder: A double-blind, randomized, placebo-controlled clinical trial.
Treatment of mood and cognitive symptoms of patients with bipolar disorder is associated with many complications and is generally not associated with therapeutic satisfaction. In this clinical trial, we evaluated the effectiveness of spironolactone in controlling mood and cognitive symptoms, sleep quality, appetite, and body mass index in patients with bipolar disorder in manic episodes. Sixty inpatients with bipolar disorder in manic episodes were treated with spironolactone/placebo in an 8-week randomized, double-blind, placebo-controlled clinical trial. They were evaluated using the Young Mania Rating Scale (YMRS), mini-mental state examination (MMSE), Pittsburgh sleep quality index, Simplified Nutritional Appetite Questionnaire, and body mass index in weeks 1, 4, and 8. For cognitive impairment (MMSE), there were significant interaction effects of group and time at week 8 (B = -1.60, SE = 0.69, t = -2.33, p = .021) such that individuals in the spironolactone group experienced more improvement in their cognitive performance. For manic symptoms (YMRS), there were no significant interaction effects of group and time at week 8 (B = -2.53, SE = 1.46, t = -1.73, p = .085). Considering the promising findings in this clinical trial, further study of spironolactone as adjunctive therapy in bipolar disorder in manic episodes with larger sample sizes, multicenter settings, and longer follow-ups are recommended.


In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers.
Quercetin, a commonly occurring flavonoid and well known antioxidant, has been suggested to possess other beneficial activities. The present study investigated the possible anti-inflammatory effects of physiologically attainable quercetin concentrations. The effects of quercetin were tested in vitro, i.e., added to blood in the test tube, and ex vivo and in vivo, i.e., in blood taken after 4 wk of administration of quercetin in an intervention study. Quercetin dose-dependently inhibited in vitro lipopolysaccharide-induced tumor necrosis factor-alpha production in the blood of healthy volunteers. At a concentration of 1 muM, quercetin caused a 23% reduction. The in vitro lipopolysaccharide-induced interleukin-10 production remained unaffected by quercetin. A 4-wk quercetin intervention resulted in a significant increase in plasma quercetin concentration. The supplementation also increased total plasma antioxidant status but did not affect glutathione, vitamin C, and uric acid plasma concentrations. Basal and ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha levels were not altered by the intervention. The present study shows that quercetin increases antioxidant capacity in vivo and displays anti-inflammatory effects in vitro, but not in vivo or ex vivo, in the blood of healthy volunteers. This lack of effect is probably due to their low cytokine and high antioxidant levels at baseline, indicating that neither inflammation nor oxidative stress is present. Only in people with increased levels of inflammation and oxidative stress, e.g., patients with a disease of which the pathology is associated with these two processes, might antioxidant supplementation be fruitful.


Implicit Associations and Explicit Expectancies toward Cannabis in Heavy Cannabis Users and Controls.
Cognitive biases, including implicit memory associations are thought to play an important role in the development of addictive behaviors. The aim of the present study was to investigate implicit affective memory associations in heavy cannabis users. Implicit positive-arousal, sedation, and negative associations toward cannabis were measured with three Single Category Implicit Association Tests (SC-IAT's) and compared between 59 heavy cannabis users and 89 controls. Moreover, we investigated the relationship between these implicit affective associations and explicit expectancies, subjective craving, cannabis use, and cannabis related problems. Results show that heavy cannabis users had stronger implicit positive-arousal associations but weaker implicit negative associations toward cannabis compared to controls. Moreover, heavy cannabis users had stronger sedation but weaker negative explicit expectancies toward cannabis compared to controls. Within heavy cannabis users, more cannabis use was associated with stronger implicit negative associations whereas more cannabis use related problems was associated with stronger explicit negative expectancies, decreasing the overall difference on negative associations between cannabis users and controls. No other associations were observed between implicit associations, explicit expectancies, measures of cannabis use, cannabis use related problems, or subjective craving. These findings indicate that, in contrast to other substances of abuse like alcohol and tobacco, the relationship between implicit associations and cannabis use appears to be weak in heavy cannabis users.


Colony size predicts division of labour in attine ants.
Division of labour is central to the ecological success of eusocial insects, yet the evolutionary factors driving increases in complexity in division of labour are little known. The size-complexity hypothesis proposes that, as larger colonies evolve, both non-reproductive and reproductive division of labour become more complex as workers and queens act to maximize inclusive fitness. Using a statistically robust phylogenetic comparative analysis of social and environmental traits of species within the ant tribe Attini, we show that colony size is positively related to both non-reproductive (worker size variation) and reproductive (queen-worker dimorphism) division of labour. The results also suggested that colony size acts on non-reproductive and reproductive division of labour in different ways. Environmental factors, including measures of variation in temperature and precipitation, had no significant effects on any division of labour measure or colony size. Overall, these results support the size-complexity hypothesis for the evolution of social complexity and division of labour in eusocial insects. Determining the evolutionary drivers of colony size may help contribute to our understanding of the evolution of social complexity.


Treatment for patients with newly diagnosed multiple myeloma in 2015.
Multiple myeloma is the second most frequent haematological disease. The introduction of high-dose melphalan followed by autologous haematopoietic cell transplant (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want to definitively cure the disease. Treatment goals for transplant-eligible and non-transplant-eligible patients should be to prolong survival by achieving the best possible response, while ensuring quality of life. The treatment should be individualized on the basis of host and disease features and better monitoring of the response upon use of high-sensitivity techniques for evaluating residual disease. For young patients, HDT/ASCT is a standard of care for treatment and its efficacy has been enhanced and challenged by the new drugs. For elderly patients, treatment options were limited to alkylators, but new upfront treatment combinations based on novel agents (proteasome inhibitors and immunomodulatory drugs) combined or not with alkylators have significantly improved outcomes.Extended treatment for young and elderly patients improves the quality and duration of clinical responses; however,the optimal scheme, appropriate doses and duration of long-term therapy have not yet been fully determined.This review summarises the progress in the treatment of patients with newly diagnosed multiple myeloma, addressing critical questions such as the optimal induction, early versus late ASCT, consolidation and/or maintenance for young patients, and how we can choose the best option for non-transplant-eligible patients.


A roentgenographic evaluation of frozen allografts versus autografts in anterior cervical spine fusions.
Serial roengenograms of 53 patients who had 76 cervical interspaces grafted with frozen, bone marrrow-free cadaver bone were compared to those obtained from 45 patients who received 63 iliac crest autografts for anterior cervical spine fusion. The roentgenograms were evaluated on the basis of achieving union, delayed union, non-union, and the presence of graft collapse and extrusion. No significant difference was noted in the union rate, with allografts (94%) or with autografts (97%). In 21 patients a higher rate of graft collapse was noted with allografts as compared to autografts in multilevel fusions. In these patients, allograft rejection or the biomechanical properties of the allograft may have contributed to a difference in the rate of graft collapse with cadaver bone. No difference in collapse rate was noted between allografts and autografts in 32 patients with single level fusions. Insertion of frozen bone allografts into intervertebral spaces of the cervical spine has not produced adverse reactions.


Embryo development of porcine oocytes after injection with miniature pig sperm and their extracts.
This study examined embryo development of porcine oocytes after microinjection of sperm extracts (SE) in porcine intracytoplasmic sperm injection (ICSI). SE was prepared from miniature pig sperm by a nonionic surfactant, and various concentrations (0.02, 0.04 and 0.08 mg/mL) of SE were injected into the matured oocytes with a first polar body. In the pronuclear stage, the rate of oocytes with two pronuclei and a second polar body (21.4%) in the sperm and SE (0.04 mg/mL) injection group was significantly higher (P < 0.05) compared to other groups. The rate of 2-4-cell stage in sperm and SE (0.04 mg/mL) injection group was 38.1%, and it was significantly higher than that in the sperm injection group (22.9%). The rate of blastocyst stage in sperm and SE (0.04 mg/mL) injection group was 21.4%, the value was significantly higher than those in SE (0.08 mg/mL) injection group (0%), sperm injection group (5.7%), and sperm and SE (0.08 mg/mL) injection group (2.6%). These results suggest that SE induces activation of porcine oocytes and their further embryonic development, and that SE is effective for porcine ICSI.


Consensus Report on Destination Therapy in Japan - From the DT Committee of the Council for Clinical Use of Ventricular Assist Device Related Academic Societies.
Destination therapy (DT) is the indication to implant a left ventricular assist device (LVAD) in a patient with stage D heart failure who is not a candidate for heart transplantation. The implantable LVAD has been utilized in Japan since 2011 under the indication of bridge to transplant (BTT). After almost 10 year lag, DT has finally been approved and reimbursed in May 2021 in Japan. To initiate the DT program in Japan, revision of the LVAD indication from BTT is necessary. Also, in-depth discussion of caregiver issues as well as end-of-life care is indispensable. For that purpose, we assembled a DT committee of multidisciplinary members in August 2020, and started monthly discussions via web-based communication during the COVID-19 pandemic. This is a summary of the consensus reached after 6 months' discussion, and we have included as many relevant topics as possible. Clinical application of DT has just started, and we are willing to revise this consensus to meet the forthcoming issues raised during real-world clinical experience.


Restriction in activity associated with fear of falling among community-based seniors using home care services.
Fear of falling may lead to avoidance of activities for seniors, even though they may be able to perform these activities. Specific risk factors for fear of falling that are amenable to change among various populations have been identified within the literature; however, detailed information about the risk factors for fear of falling, specifically among community-based seniors receiving home care services, is limited. The aim of this cross-sectional study was to examine the factors associated with restriction of activity resulting from fear of falling among 2,300 seniors receiving home care services. All participants (n = 2,304) in this study were receiving home care services between 1999 and 2001 from a sample of 10 volunteering community-based agencies (Community Care Access Centres) representing the major geographic regions of Ontario, Canada. Community care access centres act as gatekeeping organisations assessing need and contracting out for a broad range of community-based services. The Minimum Data Set for Home Care, a comprehensive and standardised assessment tool used to evaluate the needs and ability levels of older adults utilising home care services, covers several key domains, such as service use, function, health and social support. Nurses trained to administer the Minimum Data Set for Home Care assessed each of the participants within their homes. Of the 2,304 seniors within the study, 41.2% of participants expressed they restricted their activity for fear of falling. Percentages reporting fear of falling within the literature are considerably lower than the presentfindings, and probably attributable to the frailer, home care population within the present study. In the final logistic regression model, being female, having various impairments/limitations, lack of support and being a multiple faller significantly increased risk of fear of falling, whereas individuals that used antipsychotics and individuals that had Alzheimer's disease were less likely to report restricting their activity. The results from this study provide information about a group void in the literature pertaining to activity restriction from fear of falling - community-based seniors receiving home care services. The comprehensive nature of the Minimum Data Set for Home Care allowed for a myriad of factors to be assessed and subsequently analysed with respect to the outcome variable. The inclusion of items on falls, fear of falling, and risk factors for both adverse outcomes means that home care professionals using this instrument will have a unique opportunity to identify and respond to problems that have an important impact on the client's quality of life.


Leaky scanning translation generates a second A49 protein that contributes to vaccinia virus virulence.
Vaccinia virus (VACV) strain Western Reserve gene A49L encodes a small intracellular protein with a Bcl-2 fold that is expressed early during infection and has multiple functions. A49 co-precipitates with the E3 ubiquitin ligase β-TrCP and thereby prevents ubiquitylation and proteasomal degradation of IκBα, and consequently blocks activation of NF-κB. In a similar way, A49 stabilizes β-catenin, leading to activation of the wnt signalling pathway. However, a VACV strain expressing a mutant A49 that neither co-precipitates with β-TrCP nor inhibits NF-κB activation, is more virulent than a virus lacking A49, indicating that A49 has another function that also contributes to virulence. Here we demonstrate that gene A49L encodes a second, smaller polypeptide that is expressed via leaky scanning translation from methionine 20 and is unable to block NF-κB activation. Viruses engineered to express either only the large protein or only the small A49 protein both have lower virulence than wild-type virus and greater virulence than an A49L deletion mutant. This demonstrates that the small protein contributes to virulence by an unknown mechanism that is independent of NF-κB inhibition. Despite having a large genome with about 200 genes, this study illustrates how VACV makes efficient use of its coding potential and from gene A49L expresses a protein with multiple functions and multiple proteins with different functions.


H2O2 sensing through oxidation of the Yap1 transcription factor.
The yeast transcription factor Yap1 activates expression of antioxidant genes in response to oxidative stress. Yap1 regulation involves nuclear accumulation, but the mechanism sensing the oxidative stress signal remains unknown. We provide biochemical and genetic evidence that upon H2O2 treatment, Yap1 is activated by oxidation and deactivated by enzymatic reduction with Yap1-controlled thioredoxins, thus providing a mechanism for autoregulation. Two cysteines essential for Yap1 oxidation are also essential for its activation by H2O2. The data are consistent with a model in which oxidation of Yap1 leads to disulfide bond formation with the resulting change of conformation masking recognition of the nuclear export signal by Crm1/Xpo1, thereby promoting nuclear accumulation of the protein. In sharp contrast to H2O2, diamide does not lead to the same Yap1 oxidized form and still activates mutants lacking cysteines essential for H2O2 activation, providing a molecular basis for differential activation of Yap1 by these oxidants. This is the first example of an H2O2-sensing mechanism in a eukaryote that exploits the oxidation of cysteines in order to respond rapidly to stress conditions.


Acute onset of tetraparesis, arreflexia and respiratory distress in an otherwise healthy male.
The patient is a previously healthy Eastern-African man in his late 20s, with unknown vaccination status who presented to a US Army Combat Hospital in Iraq with acute upper and lower extremity weakness progressing to respiratory distress requiring intubation over the course of 12 h. His only antecedent symptoms were weakness and nausea. Laboratories including complete blood count, C reactive protein, cerebrospinal fluid analysis, venous blood gas, rapid HIV and chemistry were normal. Non-contrast head CT was normal. The patient was extubated after 24 h but continued to exhibit 2/5 strength in bilateral upper and lower extremities with absence of deep-tendon reflexes. At 48 h of illness it was discovered that the prior to his presentation the patient had a significant life stressor which had since been resolved. Upon discovery that this stressor had been resolved, the patient's symptoms improved over the subsequent 4-6 h and was discharged after 24 h without further complication.


Involving decision-makers in the research process: Challenges of implementing the accountability for reasonableness approach to priority setting at the district level in Tanzania.
The past two decades have seen a growing call for researchers, policy-makers and health care providers to collaborate in efforts to bridge the gaps between research, policy and practice. However, there has been a little attention focused on documenting the challenges of dealing with decision-makers in the course of implementing a research project. This paper highlights a collaborative research project aiming to implement the accountability for reasonableness (AFR) approach to priority setting in accordance with the Response to Accountable Priority Setting for Trust in Health Systems (REACT) project in Tanzania. Specifically, the paper examines the challenges of dealing with decision-makers during the project-implementation process and shows how the researchers dealt with the decision-makers to facilitate the implementation of the REACT project. Key informant interviews were conducted with the Council Health Management Team (CHMT), local government officials and other stakeholders, using a semi-structured interview guide. Minutes of the Action Research Team and CHMT were analysed. Additionally, project-implementation reports were analysed and group priority-setting processes in the district were observed. The findings show that the characteristics of the REACT research project, the novelty of some aspects of the AFR approach, such as publicity and appeals, the Action Research methodology used to implement the project and the traditional cultural contexts within which the project was implemented, created challenges for both researchers and decision-makers, which consequently slowed down the implementation of the REACT project. While collaboration between researchers and decision-makers is important in bridging gaps between research and practice, it is imperative to understand the challenges of dealing with decision-makers in the course of implementing a collaborative research project. Such analyses are crucial in designing proper strategies for improved communication and for the utilisation of research projects over time.


The Interaction Between Neuromuscular Forces, Aerodynamic Forces, and Anatomical Motion in the Upper Airway Predicts the Severity of Pediatric OSA.
Upper airway neuromuscular response to air pressure during inhalation is an important factor in assessing pediatric subjects with obstructive sleep apnea (OSA). The neuromuscular response's strength, timing, and duration all contribute to the potential for airway collapses and severity of OSA. This study quantifies these factors at the soft palate, tongue, and epiglottis to assess the relationship between neuromuscular control and OSA severity in 20 pediatric subjects with and without trisomy 21, under dexmedetomidine-induced sedation. The interaction between neuromuscular force and airflow pressure force was assessed based on power transferred between the airway wall and airflow calculated from airway wall motion (from cine magnetic resonance images) and air pressure acting on the airway wall (from computational fluid dynamics simulations). Airway wall motion could be asynchronous with pressure forces due to neuromuscular activation, or synchronous with pressure forces, indicating a passive response to airflow. The obstructive apnea-hypopnea index (oAHI) quantified OSA severity. During inhalation, the normalized work done through asynchronous dilation of the airway at the soft palate, tongue, and epiglottis correlated significantly with oAHI (Spearman's ρ=0.54, 0.50, 0.64; p=0.03, 0.03, 0.003). Synchronous collapse at the epiglottis correlated significantly with oAHI (ρ=0.52; p=0.02). Temporal order of synchronous and asynchronous epiglottis motion during inhalation predicted severity of OSA (moderate vs. severe) with 100% sensitivity and 70% specificity. Subjects with severe OSA and/or trisomy 21 have insufficient neuromuscular activation during inhalation, leading to collapse and increased neuromuscular activation. Airflow-driven airway wall motion during late inhalation likely is the main determinant of OSA severity.


Merged Tacrine-Based, Multitarget-Directed Acetylcholinesterase Inhibitors 2015-Present: Synthesis and Biological Activity.
Acetylcholinesterase is an important biochemical enzyme in that it controls acetylcholine-mediated neuronal transmission in the central nervous system, contains a unique structure with two binding sites connected by a gorge region, and it has historically been the main pharmacological target for treatment of Alzheimer's disease. Given the large projected increase in Alzheimer's disease cases in the coming decades and its complex, multifactorial nature, new drugs that target multiple aspects of the disease at once are needed. Tacrine, the first acetylcholinesterase inhibitor used clinically but withdrawn due to hepatotoxicity concerns, remains an important starting point in research for the development of multitarget-directed acetylcholinesterase inhibitors. This review highlights tacrine-based, multitarget-directed acetylcholinesterase inhibitors published in the literature since 2015 with a specific focus on merged compounds (i.e., compounds where tacrine and a second pharmacophore show significant overlap in structure). The synthesis of these compounds from readily available starting materials is discussed, along with acetylcholinesterase inhibition data, relative to tacrine, and structure activity relationships. Where applicable, molecular modeling, to elucidate key enzyme-inhibitor interactions, and secondary biological activity is highlighted. Of the numerous compounds identified, there is a subset with promising preliminary screening results, which should inspire further development and future research in this field.


Neprilysin Inhibition and the Treatment of Heart Failure: Recent Steps in the Right Direction.
Numerous investigators have attempted to target the natriuretic peptide system in the treatment of heart failure since it was first described over 30 years ago. The history of neprilysin inhibition as a treatment for heart failure has been characterized by numerous setbacks. Recently, the PARADIGM-HF trial has shown favorable results, which may bring neprilysin inhibition into the mainstream of clinical practice. This article will review the history of the natriuretic peptide system and the investigations into it as a target for heart failure treatment, culminating in the positive results of the PARADIGM-HF trial, as well as planned and potential future directions for research.


Quantifying active diffusion in an agitated fluid.
Mixing of reactants in microdroplets predominantly relies on diffusional motion due to small Reynolds numbers and the resulting absence of turbulent flows. Enhancing diffusion in microdroplets by an auxiliary noise source is therefore a topical problem. Here we report on how the diffusional motion of tracer beads is enhanced upon agitating the surrounding aqueous fluid with miniaturized magnetic stir bars that are compatible with microdroplets and microfluidic devices. Using single-particle tracking, we demonstrate via a broad palette of measures that local stirring of the fluid at different frequencies leads to an enhanced but apparently normal and homogenous diffusion process, i.e. diffusional steps follow the anticipated Gaussian distribution and no ballistic motion is observed whereas diffusion coefficients are significantly increased. The signature of stirring is, however, visible in the power-spectral density and in the velocity autocorrelation function of trajectories. Our data therefore demonstrate that diffusive mixing can be locally enhanced with miniaturized stir bars while only moderately affecting the ambient noise properties. The latter may also facilitate the controlled addition of nonequilibrium noise to complex fluids in future applications.


Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work.
Decreases in melatonin production in human and animals are known to be caused by environmental lighting, especially short-wavelength lighting (between 470 and 525 nm). We investigated the novel hypothesis that the use of goggles with selective exclusion of all wavelengths less than 530 nm could prevent the suppression of melatonin in bright-light conditions during a simulated shift-work experiment. Salivary melatonin levels were measured under dim (<5 lux), bright (800 lux), and filtered (800 lux) light at hourly intervals between 2000 and 0800 h in 11 healthy young males and eight females (mean age, 24.7 +/- 4.6 yr). The measurements were performed during three nonconsecutive nights over a 2-wk period. Subjective sleepiness was measured by self-report scales, whereas objective performance was assessed with the Continuous Performance Test. All subjects demonstrated preserved melatonin levels in filtered light similar to their dim-light secretion profile. Unfiltered bright light drastically suppressed melatonin production. Normalization of endogenous melatonin production while wearing goggles did not impair measures of performance, subjective sleepiness, or alertness.


Cross-genome screening of novel sequence-specific non-LTR retrotransposons: various multicopy RNA genes and microsatellites are selected as targets.
Although most LINEs (long interspersed nuclear elements), which are autonomous non-long-terminal-repeat retrotransposons, are inserted throughout the host genome, three groups of LINEs, the early-branched group, the Tx group, and the R1 clade, are inserted into specific sites within the target sequence. We previously characterized the sequence specificity of the R1 clade elements. In this study, we screened the other two groups of sequence-specific LINEs from public DNA databases, reconstructed elements from fragmented sequences, identified their target sequences, and analyzed them phylogenetically. We characterized 13 elements in the early-branched group and 13 in the Tx group. In the early-branched group, we identified R2 elements from sea squirts and zebrafish in this study, although R2 has not been characterized outside the arthropod group to date. This is the first evidence of cross-phylum distribution of sequence-specific LINEs. The Dong element also occurs across phyla, among arthropods and mollusks. In the Tx group, we characterized five novel sequence-specific families: Kibi for TC repeats, Koshi for TTC repeats, Keno for the U2 snRNA gene, Dewa for the tRNA tandem arrays, and Mutsu for the 5S rRNA gene. Keno and Mutsu insert into the highly conserved region within small RNA genes and destroy the targets. Several copies of Dewa insert different positions of tRNA tandem array, which indicates a certain "site specifier" other than sequence-specific endonuclease. In all three groups, LINEs specific for the rRNA genes or microsatellites can occur as multiple families in one organism. This indicates that the copy number of a target sequence is the primary factor to restrict the variety of sequence specificity of LINEs.


Implementation of a municipality-based rehabilitation program for patients with neuritis vestibularis: lessons learned and derived snowball effects.
Patients with dizziness are severely affected in their daily life. The dizziness may be caused by vestibular neuritis and this condition may be severe and result in hospitalization. Qualified municipal rehabilitation services are warranted for these patients after edischarge from the hospital. However, very few specialized municipal initiatives in Denmark are targeting this patient group. This paper reports on the development of a clinically applicable municipality-based vestibular neuritis rehabilitation program and evaluates the acceptability of this initiative. The study recognized the need for a rehabilitation program after hospital discharge. However, the program was not evaluated as acceptable for multiple reasons. The exercise program was applicable and feasible but was experienced as a limitation for the practitioner, when addressing other balance issues was needed. It proved challenging to inform both the administrative staff and the clinicians about the new rehabilitation service to allow for sufficient implementation. Although the rehabilitation program was not considered an unequivocal success, there were several derived valuable snowball effects of the program. This paper advocates that focus should not only lie on the success of a single program, but also explore the derived benefits for patients and organizations, as well as the practice-oriented knowledge these programs generate.


Comparison of Stenting Versus Bypass Surgery According to the Completeness of Revascularization in Severe Coronary Artery Disease: Patient-Level Pooled Analysis of the SYNTAX, PRECOMBAT, and BEST Trials.
The aim of this study was to compare long-term survival between patients with severe coronary artery disease undergoing coronary artery bypass grafting (CABG) and those undergoing percutaneous coronary intervention (PCI) achieving complete revascularization (CR) or incomplete revascularization. The importance of CR in decision making regarding revascularization strategy in patients with severe coronary artery disease is unknown. Data were pooled from the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trials. The primary outcome was death from any cause and was compared in an as-treated analysis. The rate of CR was 61.7% (57.2% with PCI and 66.8% with CABG). During a median 4.9-year follow-up period (interquartile range: 4.5 to 5.0 years), compared with patients undergoing CABG with CR, those undergoing PCI with incomplete revascularization had a higher risk for death from any cause (adjusted hazard ratio [aHR]: 1.43; 95% confidence interval [CI]: 1.03 to 2.00; p = 0.036) and the composite of death, myocardial infarction, and stroke (aHR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003). However, there was no significant difference between patients undergoing CABG with CR and those undergoing PCI with CR regarding the risk for death from any cause (aHR: 1.16; 95% CI: 0.83 to 1.63; p = 0.39) and the composite of death, myocardial infarction, and stroke (aHR: 1.14; 95% CI: 0.87 to 1.48; p = 0.35). Subgroup analysis of multivessel coronary disease, high SYNTAX score (>32), and diabetes showed consistent findings. For the treatment of left main or multivessel coronary artery disease, PCI resulting in CR was associated with a similar long-term survival rate to CABG resulting in CR. Therefore, the ability to achieve CR should enter into the decision algorithm for choice of revascularization strategy.


MRI in early detection of prostate cancer.
The use of MRI in the early detection of prostate cancer (PCa) is increasing rapidly. In the last couple of years, there have been a number of key publications that have led to its adoption in the UK and European guidelines. PROMIS showed that standard biopsy missed up to half of clinically significant disease, compared with 5 mm template mapping biopsy. Three studies then compared the standard transrectal ultrasound (TRUS) pathway with an MRI with or without targeted biopsy pathway. These showed that MRI-targeted biopsies detect more clinically significant disease and reduce overdetection of indolent disease whilst allowing between one-third to one half of men to avoid an immediate biopsy. Cost-effectiveness data show that using MRI to determine who gets a biopsy and how that biopsy is done is a cost-neutral approach when men at lowest risk do not undergo biopsy. Prostate MRI is a useful and cost-effective tool for early detection of PCa that minimizes the impact of overdetection and overtreatment whilst maximizing the detection of PCa, which could benefit from treatment. The next challenge is to ensure that centres offering MRI are able to offer high-quality MRI acquisition and reporting.


Energy balance and emissions associated with biochar sequestration and pyrolysis bioenergy production.
The implications for greenhouse gas emissions of optimizing a slow pyrolysis-based bioenergy system for biochar and energy production rather than solely for energy production were assessed. Scenarios for feedstock production were examined using a life-cycle approach. We considered both purpose grown bioenergy crops (BEC) and the use of crop wastes (CW) as feedstocks. The BEC scenarios involved a change from growing winter wheat to purpose grown miscanthus, switchgrass, and corn as bioenergy crops. The CW scenarios consider both corn stover and winter wheat straw as feedstocks. Our findings show that the avoided emissions are between 2 and 5 times greater when biochar is applied to agricultural land (2--19 Mg CO2 ha(-1) y(-1)) than used solely for fossil energy offsets. 41--64% of these emission reductions are related to the retention of C in biochar, the rest to offsetting fossil fuel use for energy, fertilizer savings, and avoided soil emissions other than CO2. Despite a reduction in energy output of approximately 30% where the slow pyrolysis technology is optimized to produce biochar for land application, the energy produced per unit energy input at 2--7 MJ/MJ is greater than that of comparable technologies such as ethanol from corn. The C emissions per MWh of electricity production range from 91-360 kg CO2 MWh(-1), before accounting for C offset due to the use of biochar are considerably below the lifecycle emissions associated with fossil fuel use for electricity generation (600-900 kg CO2 MWh(-1)). Low-temperature slow pyrolysis offers an energetically efficient strategy for bioenergy production, and the land application of biochar reduces greenhouse emissions to a greater extent than when the biochar is used to offset fossil fuel emissions.


Autoantibody-induced intestinal inflammation and weight loss in experimental epidermolysis bullosa acquisita.
Type VII collagen (COL7) is a major constituent of the cutaneous basement membrane. Loss of tolerance to COL7 leads to the blistering skin disease epidermolysis bullosa acquisita (EBA). Antibodies to COL7 have also been detected in patients with inflammatory bowel disease (IBD), yet reports on the expression of COL7 in the gut are controversial and a pathogenic relevance of anti-COL7 autoantibodies in IBD has not been demonstrated. We therefore characterized the expression patterns of COL7 in murine gastrointestinal organs and investigated if anti-COL7 antibodies induce an inflammatory response in the gut. COL7 expression was analysed on the mRNA and protein levels. Mice were injected with rabbit anti-murine COL7 IgG (passive EBA) or immunized with a fragment of murine COL7 (active EBA). COL7 was found to be expressed in buccal mucosa, oesophagus, stomach, small intestine, and colon. In addition to skin blistering, in both passive and active EBA, autoantibodies bound to the gastrointestinal basement membrane, fixed complement, and led to recruitment of leukocytes. Furthermore, blister formation was observed in the oesophagus (40%/38% of mice in passive/active model), stomach (40%/63%), small intestine (20%/13%), and colon (20%/13%). Compared to control animals, we found a significantly reduced body weight in diseased mice, suggesting that autoantibody-induced gastrointestinal inflammation is clinically relevant. Those observations may help us to understand the co-incidence of IBD with EBA, and vice versa: The inflammatory response in IBD might expose novel antigens (COL7), which leads to the formation of anti-COL7 antibodies. On the contrary, anti-COL7 antibody-induced gastrointestinal inflammation might pave the way for IBD pathogenesis. In summary, our results provide strong evidence that COL7 is expressed in different portions of the gut and that anti-COL7 antibodies induce distinct gastrointestinal tissue damage.


The change in the fluoroscopy-guided transseptal puncture site and difficult punctures in catheter ablation of recurrent atrial fibrillation.
A second procedure for recurrent atrial fibrillation (AF) may be associated with the need for a different positioning of the puncture site and may increase the difficulty and complications. This study investigated whether the transseptal puncture site changed and whether the difficult punctures increased in the patients who received a repeat ablation procedure for recurrent AF. Twenty-nine AF patients (52 +/- 12 years old, 20 males) underwent catheter ablation for a recurrence of AF. Compared with the first procedure, the height between the transseptal puncture site and coronary sinus ostium was higher in the second procedure during both the atrial end-systolic phase (38.0 +/- 4.7 vs. 34.8 +/- 5.3 mm, P = 0.036), and end-diastolic phase (43.0 +/- 4.8 vs. 39.1 +/- 5.4 mm, P = 0.004) in the 30 degrees right anterior oblique view. No significant change in the vertical atrial diameter was noted between the first and second procedures. A higher incidence of a difficult puncture was noted during the second procedure than in the first procedure (28 vs. 7%, P = 0.014). All those difficult punctures were overcome by using a large-curved transseptal needle. No differences of age, gender, AF duration, interval between first and second procedures, procedure time of the first procedure, and left atrial anteroposterior diameter were noted between easy and difficult transseptal punctures during the second procedure. The incidence of a difficult puncture was higher in the second procedure compared with the first procedure. The transseptal puncture site moved higher in the second procedure. Chronic scarring over the previous transseptal site is a reasonable hypothesis to explain the observations. The difficult punctures experienced during the second procedure might be overcome by changing the needle curve from a small curve to a large curve design.


Tumor-associated urokinase-type plasminogen activator: significance in breast cancer.
Urokinase-type plasminogen activator (u-PA), a proteolitic enzyme, capable of degrading type 4 collagen, is supposed to be involved in degradation of extracellular matrix during cancer invasion. Evidence has been presented that primary breast cancer patients with tumors containing high levels of u-PA experience a worse prognosis. u-PA and its inhibitor, type 1 plasminogen activator inhibitor (PAI-1), are potentially important prognostic factors in breast cancer to identify patients at high risk for recurrence and also in the classification of clinically important subgroups.


Acute liver failure and self-medication.
Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. To warn about how the practice of self-medication can be responsible for acute liver failure. Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute liver failure [tiab] AND acetaminophen [tiab]; self-medication [tiab] AND acetaminophen [tiab]; acute liver failure [tiab] AND dietary supplements [tiab]; self-medication [tiab] AND liver failure [tiab] and self-medication [tiab] AND green tea [tiab]. In Lilacs and SciELO used the descriptor self medication in Portuguese and Spanish. From total surveyed were selected 27 articles and five sites specifically related to the purpose of this review. Legislation and supervision disabled and information inaccessible to people, favors the emergence of cases of liver failure drug in many countries. In the list of released drugs that deserve more attention and care, are some herbal medicines used for the purpose of weight loss, and acetaminophen. It is recommended that institutes of health intensify supervision and better orient their populations on drug seemingly harmless, limiting the sale of products or requiring a prescription for release them.


Biological activity of recombinant human interleukin-2 produced in Escherichia coli.
The gene for interleukin-2 was isolated from the Jurkat cell line and from normal peripheral blood lymphocytes and, when inserted in Escherichia coli, was expressed at high concentrations. This interleukin-2 was purified to apparent homogeneity and tested for biological activity in a variety of assays in vitro and in vivo. The recombinant lymphokine supports the growth of murine and human interleukin-2 dependent cell lines, enhances the generation of murine and human cytolytic cells in vitro, and generates lymphokine activated killer cells from murine and human lymphocytes. It has a serum half-life of 2 to 3 minutes in the mouse and significantly enhances the generation of cytolytic cells in vivo after alloimmunization. No functional differences between native and the recombinant interleukin-2 molecules have been detected.


Connexin expression in epidermal cell lines from SENCAR mouse skin tumors.
Alteration of gap-junctional intercellular communication (GJIC) has long been proposed to be involved in carcinogenesis. Previously, we reported that the level of gap junctional intercellular communication in mouse skin carcinoma cell lines is significantly lower than in papilloma cell lines and normal mouse keratinocytes Klann et al., Cancer Res 49:699-705, 1989). Here, we present data on expression of the gap-junctional protein connexins (Cx) 26, Cx31.1, and Cx43 in a comprehensive panel of keratinocyte cell lines representing different stages of mouse skin carcinogenesis and the effect of different conditions of propagation on Cx phenotype. Northern and western blot analyses and immunostaining showed that all cell lines studied in vitro expressed Cx43 but most did not express Cx31.1 or Cx26. The abundance of Cx43 expression on plasma membranes correlated well with the level of GJIC. In vivo expression of Cx43 and Cx26 was strongly increased. Whereas none of tumorigenic cell lines expressed Cx26 gap junctions in culture, those growing as tumors in nude mice began to express Cx26 protein. The comparison of Cx expression on the keratinocyte membranes in three different groups of tumors (papillomas and squamous cell and spindle cell carcinomas) clearly revealed that the abundance of Cx43 and Cx26 expression directly correlated with the level of tumor differentiation. All studied tumors were Cx31.1 negative. These results suggest that both Cx expression and gap-junction permeability are gradually reduced during the tumor progression stage of mouse skin carcinogenesis.


Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis.
Asbestos is known to induce malignant mesothelioma (MM) and other asbestos-related diseases. It is directly genotoxic by inducing DNA strand breaks and cytotoxic by promoting apoptosis in lung target cells. Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear zinc-finger protein with a function as a DNA damage sensor. To determine whether PARP1 is involved in asbestos-induced carcinogenesis, PARP1 expression and activity as well as DNA damage and repair were evaluated in circulating cells of asbestos-exposed subjects, MM patients and age-matched controls. PARP1 expression and activity were also evaluated in pleural biopsies of MM patients and compared with normal tissue. Accumulation of the pre-mutagenic 8-hydroxy-2'-deoxyguanosine and elevated PARP1 expression were found both in asbestos-exposed subjects and MM patients. Although PARP1 was highly expressed, its activity was relatively low. Low DNA repair efficiency was observed in lymphocytes from MM patients. High expression of PARP1 associated with low PARP activity was also found in MM biopsies. To mimic PARP1 dysfunction, PARP1 expression and activity were induced in immortalised mesothelial cells by their exposure to asbestos in the presence of a PARP1 inhibitor, which resulted in transformation of the cells. We propose that exposure to asbestos inhibits the PARP1 activity possibly resulting in higher DNA instability, thus causing malignant transformation.


Preparation of 2D molecularly imprinted materials based on mesoporous silicas via click reaction.
The two-dimensional (2D) molecular imprinting approach has attracted extensive research interest in recent years due to its potential advantages such as simple construction, fast template removal and rapid mass transfer. In this study, a new 2D imprinting approach based on the combination of mesoporous silica materials and molecular imprinting technology is reported. 2D molecularly imprinted materials (MIMs) for cholesterol were prepared by using cholesterol as the template, azide modified β-cyclodextrin (azide-β-CD) as the functional monomer and alkynyl-modified SBA-15 (alkyne-SBA-15) as the skeleton. In this method, azide-β-CD molecules were first assembled around the templates by formation of template-monomer complexes, and thus the mutual positions of azide-β-CD molecules were fixed. Then, azide-β-CD molecules were anchored to the walls of the nano-pores of SBA-15 via click chemistry. After removal of the template molecules, the resulting cavities, i.e., recognition sites were formed in the nano-pores of mesoporous silicas. The synthesized MIM was characterized by FT-IR, X-ray diffraction (XRD), elemental analysis (EA), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and so on. Binding kinetic experiments demonstrated that the 2D imprinting approach can improve site accessibility for the template effectively. The 2D MIM exhibited binding affinity and specificity for the template, as revealed by equilibrium binding experiments. When using MIM as a stationary phase for HPLC, baseline separation of cholesterol from other compounds can be achieved. In addition, the use of 2D imprinting significantly reduced the peak broadening and tailing.


Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor-directed therapies.
Seventy percent of breast cancers express the estrogen receptor (ER), and agents that target the ER are the mainstay of treatment. However, virtually all people with ER+ breast cancer develop resistance to ER-directed agents in the metastatic setting. Beyond mutations in the ER itself, which occur in 25-30% of people treated with aromatase inhibitors1-4, knowledge about clinical resistance mechanisms remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to aromatase inhibitors, tamoxifen or fulvestrant. Examination of treatment-naive primary tumors in five patients showed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. The HER2 mutations and ER mutations were mutually exclusive, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that the HER2 mutations conferred estrogen independence as well as-in contrast to ER mutations-resistance to tamoxifen, fulvestrant and the CDK4 and CDK6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib.


Interleukin-10 in combination with M-CSF and IL-4 contributes to development of the rare population of CD14+CD16++ cells derived from human monocytes.
Peripheral blood CD14(+)CD16(++) monocytes (Mo) are a rare Mo subpopulation known to undergo expansion in various diseases. We show here that IL-10 in the presence of M-CSF and IL-4 triggers the generation of CD14(+)CD16(++) cells from highly purified human cord blood (CB) and adult blood Mo. CB Mo were more sensitive to this cytokine combination than adult Mo. IL-10-induced CD14(+)CD16(++) cells that expressed dendritic cell markers: CD80, CD86, HLA-DR, and CD83 and initiated significantly decreased allogeneic mixed lymphocyte reactions (MLRs). Blockage of CD86, but not CD80, further down-modulated MLRs induced by CD14(+)CD16(++)cells. CD14(+)CD16(++) cells had similar features to CD14(+)CD16(++) Mo in that they expressed increased level of CCR5, efficiently produced TNF-alpha, and displayed higher MLR than CD14(+)CD16(-) Mo. Together, these results demonstrate that M-CSF, IL-4, and IL-10 drive Mo into CD14(+)CD16(++) cells similar to those identified in vivo, and CB Mo, due to their increased responsiveness, may be a useful starting cell source to study differentiation of CD14(+)CD16(++) cells.


Melatonin Prevents Chronic Kidney Disease-Induced Hypertension in Young Rat Treated with Adenine: Implications of Gut Microbiota-Derived Metabolites.
Melatonin, a signaling hormone with pleiotropic biofunctions, has shown health benefits. Trimethylamine-N-oxide (TMAO) and asymmetric dimethylarginine (ADMA) are uremic toxins involved in the development of hypertension. TMAO originates from trimethylamine (TMA), a gut microbial product. ADMA is an endogenous nitric oxide (NO) synthase inhibitor. We examined whether melatonin therapy could prevent hypertension and kidney disease by mediating gut microbiota-derived metabolites and the NO pathway using an adenine-induced chronic kidney disease (CKD) young rat model. Six-week-old young Sprague Dawley rats of both sexes were fed a regular diet (C group), a diet supplemented with 0.5% adenine (CKD group), or adenine plus 0.01% melatonin in their drinking water (CKD + M group) for three weeks (N = 8/group). Adenine-fed rats developed renal dysfunction, hypertension, renal hypertrophy and increased uremic toxin levels of TMAO and ADMA. Melatonin therapy prevented hypertension in both sexes and attenuated kidney injury in males. Melatonin reversed the changes to the plasma TMAO-to-TMA ratio induced by CKD in both sexes. Besides, the protective effects of melatonin were associated with restoration of gut microbiota alterations, including increased α-diversity, and enhancement of the abundance of the phylum Proteobacteria and the genus Roseburia in male rats. Melatonin therapy also partially prevented the increases in ADMA in male CKD rats. Melatonin sex-specifically protected young rats against hypertension and kidney injury induced by CKD. The results of this study contribute toward a greater understanding of the interaction between melatonin, gut microbiota-derived metabolites, and the NO pathway that is behind CKD, which will help to prevent CKD-related disorders in children.


Construction of hu-PBL/SCID chimeras and development of EBV-related lymphomas.
To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV). Human peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and transplanted intraperitoneally into severe combined immunodeficient (SCID) mice. Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected intraperitoneally with EBV-containing supernatant from suspension culture of B95-8 cell line (active infection), whereas mice receiving lymphocytes from healthy EBV seropositive donors were not re-infected with B95-8 derived EBV (latent infection). Pathological examination and molecular analysis were performed on experimental animals and induced neoplasms. In the early stage of this experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3% (12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID chimeric recipients from 12 healthy donors, tumor incidence was 84.2% (16/19 mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related neoplasms in SCID mice were nodular tumors with aggressive and fatal features. Histological morphology of tumors exhibited diffuse large cell lymphomas. Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1, and EBNA2 were expressed in a small number of tumor cells. EB virus particles were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA could be amplified in the tumor tissues by PCR. In situ hybridization indicated that the nuclei of tumor cells contained human-specific Alu sequence. EBV-induced tumors were human B-cell malignant lymphomas. We obtained direct causative evidence dealing with EBV-associated tumor deriving from normal human cells.


The incidence of pressure ulcers in surgical patients: a sample hospital in Turkey.
This research was conducted for the purpose of determining the incidence of surgery-related pressure ulcer formation. Patients undergoing surgery are prone to develop pressure ulcers during surgery. Pressure ulcer incidence in surgery population is reported between 3.5% and 29.5%. Some of these factors that occur during surgery are being under pressure for a long time, remaining wet, and metabolic and circulatory changes related to the surgery and anaesthesia. The research was conducted as a prospective-analytic-descriptive study with 84 patients who agreed to participate in the study and who were 20 years old or older, having elective surgery, having a surgical procedure lasting two or more hours under general anaesthesia, and who had no risk for pressure ulcer development before surgery according to the Braden Pressure Ulcer Risk Assessment Scale. Research data were obtained using a Data Collection Form that has places for pre-, intra- and postoperative factors that may be related to surgery-related pressure ulcer development; a Body Mass Index Data Form and the Braden Pressure Ulcer Risk Assessment Scale. The Braden Pressure Ulcer Risk Assessment Scale was used to determine that patients had no risk for pressure ulcer development pre- and postoperatively and it was used for the purpose of establishing the patients risk status and areas at risk. Patients were monitored for pressure ulcers until the sixth postoperative day and risk status and areas at risk were determined. Data obtained in the research were analysed using percentage, chi-squared, McNemar and Cohen's Kappa tests for reliability between dependent groups. At the conclusion of the research, the findings obtained showed that 54.8% of the patients (n = 46) were observed to have Stage 1 pressure ulcers. A total of 41.3% of the patients had pressure ulcers in more than one region and 56.5% of these were of the erythema type. During the six-day postoperative monitoring, 97.9% of the pressure ulcers were observed in the first three days. The study made clear that surgery-related pressure ulcers are an important problem. (i) Determining the incidence of pressure ulcers during surgery in Turkey; (ii) For nurses to be able to prevent surgery-related pressure ulcers, it is necessary for them to direct their care by knowing factors that have a role in the development of pressure ulcers during surgery therefore this study will be to call Turkish nurse's attention to pressure ulcers during surgery.


Iodide conversion to iodate in aqueous and solid aerosols exposed to ozone.
The aqueous-phase and surface reactions of ozone (O3) with iodide (I-) in/on seawater have been recently found to be a strong atmospheric source of iodine. In addition, ozone also reacts with I- in solid and aqueous sea-salt aerosol. However, the primary products of the heterogeneous reactions of ozone with I- have not been clarified. In this paper, solid and aqueous KI aerosols have been exposed to ozone in an aerosol flow tube system and I- and iodate (IO3-) concentrations have been measured by UV-Vis spectroscopy. The results of these experiments have been combined with a kinetic model to elucidate the primary products of the aqueous and surface reactions. The reaction of ozone with aqueous iodide has been inferred to originate different products depending on whether it occurs at the surface via O3 adsorption (product I2-) or in the aqueous phase via O3 solvation (product IO-). The surface reaction of ozone with solid KI in the presence of water vapor forms KIO3, and other species, which are likely to be gaseous. Although the reactions have been studied in aerosols, the results can be extrapolated to aqueous solutions as well.


Supporting a Culture of Evidence-Based Policy: Federal Funding for Public Health Law Evaluation Research, 1985-2014.
Law powerfully influences health and can be a critical tool for promoting population well-being. Evaluation research is needed to measure the health effects of law and guide policy making and implementation. The purpose of this study was to assess trends in National Institutes of Health (NIH) funding for scientific public health law research (PHLR). Using data from the UberResearch NIH grant repository, we collected and coded all grants with a focus on health law between FY'85 and FY'14 and then analyzed the grants by funding agency and topic areas. Between FY'85 and FY'14, NIH funded 510 research grants on health policy making, the health effects of laws or enforcement practices. On average, 4 PHLR grants were funded annually with a median total funding of $545 956 (range: $2535-$44 052 300) and a median annual funding of $205 223 (range: $2535-$7 019 517). National Institutes of Health has supported important PHLR but not nearly to the extent necessary to ensure that public health laws affecting the population are evaluated in a rigorous and timely manner. In addition to greater funding evaluation research, NIH can increase its support for creating legal datasets, fund training in PHLR, and work with the National Library of Medicine to create Medical Subject Headings (MeSH) terms related to PHLR.


Spatial mismatch between the Na+ flux and spike initiation in axon initial segment.
It is widely believed that, in cortical pyramidal cells, action potentials (APs) initiate in the distal portion of axon initial segment (AIS) because that is where Na(+) channel density is highest. To investigate the relationship between the density of Na(+) channels and the spatiotemporal pattern of AP initiation, we simultaneously recorded Na(+) flux and action currents along the proximal axonal length. We found that functional Na(+) channel density is approximately four times lower in the AP trigger zone than in the middle of the AIS, where it is highest. Computational analysis of AP initiation revealed a paradoxical mismatch between the AP threshold and Na(+) channel density, which could be explained by the lopsided capacitive load imposed on the proximal end of the AIS by the somatodendritic compartment. Favorable conditions for AP initiation are therefore achieved in the distal AIS portion, close to the edge of myelin, where the current source-load ratio is highest. Our findings suggest that cable properties play a central role in determining where the AP starts, such that small plastic changes in the local AIS Na(+) channel density could have a large influence on neuronal excitability as a whole.


[Value of ultrasound and magnetic resonance imaging in the control of the postoperative progress after Achilles tendon rupture].
A comparison of clinical examination, sonography and MRI in the follow-up of suture of the Achilles tendon. 60 patients were examined in a prospective study for 6-78 months following suture of the Achilles tendon repair; both sides were compared clinically and sonographically; in 30 patients MRI was also used. Morphometric measurements (antero-posterior and transverse measurements) and changes in morphological structure were correlated with clinical results. All patients showed thickening of the Achilles tendon postoperatively. Morphometric and morphological changes showed positive and significant correlation between sonography and MRI (p = < 0.001, p = 0.004). Structural changes in sonography had positive correlation with general symptoms (p = < 0.001), pain on movement (p = < 0.001), reduced function (p = 0.005), and reduced sporting activity (p = 0.034). MRI findings showed significant regression with time (p = 0.05). Following repair, the Achilles tendon remained thickened throughout the period of observation. Post-operative changes in the structure of the tendon regressed partially. Sonography and MRI correlate significantly with the clinical findings. Sonography is the imaging method of choice, MRI is an additional procedure.


Comparative study of unilateral and bilateral cages with respect to clinical outcomes and stability in instrumented posterior lumbar interbody fusion.
We sought to compare the clinical and radiological results of instrumented posterior lumbar interbody fusion (PLIF) using unilateral or bilateral polyetheretherketone cages and pedicle screws. One hundred eighty-seven cases of degenerative spine that had been followed for at least 18 months were reviewed retrospectively. In 88 cases (147 levels), one cage was inserted, and in 99 cases (152 levels), two cages were inserted. Visual analog scale, Oswestry disability index, and functional rating indices were measured. Lumbar lordosis, lumbar scoliotic and fusion level scoliotic angles, and stable fixation were determined before surgery and 12 months postoperatively on standing x-rays. Amounts of intra- and postoperative blood loss, total quantities transfused, and operation times were also evaluated. No significant differences were found between the two groups in terms of visual analog scale, Oswestry disability index, functional rating indices, lumbar lordosis, lumbar scoliotic angles, fusion level scoliotic angles, or fixation stabilities. However, the amounts of postoperative blood loss, total blood loss, and total transfusion for two-level PLIF using a unilateral cage were statistically smaller than those for two-level PLIF using bilateral cages. Times required for PLIF using a unilateral cage were also significantly shorter than those for PLIF using bilateral cages. Unilateral cage and bilateral pedicle screw insertion may be a good alternative surgical option because it provides adequate alignment, balance, and mechanical stability in addition to reducing operative time, blood loss, and transfusion requirements.


"I Have No Capacities That Can Help Me": Young Asylum Seekers in Norway and Serbia - Flight as Disturbance of Developmental Processes.
Most studies on refugee populations are organized around trauma-related issues and focus on explaining pathological factors. Few studies are anchored in general developmental psychology with the aim of exploring normal age-specific developmental tasks and how the special circumstances associated with forced migration can influence how developmental tasks are negotiated. This study is part of a larger mixed method study seeking to identify resilience-promoting and resilience-inhibiting factors, on individual and contextual levels, among asylum seekers and refugees on the move (passing through Serbia) and settled in reception centers in Norway. A strategic sample of 20 adolescent and young adult refugees/asylum seekers during flight in Serbia (10) and after arrival in Norway (10) was chosen from a sample of 178 refugees interviewed in depth in Serbia and at receptions centers in Norway. The sample reflects the focus of this paper, which is to explore adolescent and young adult refugees/asylum seekers' psychological and social needs and resources during flight to and after arrival in the host country, including how developmental tasks are negotiated. Through qualitative analysis, experiences associated with the developmental changes the participants experienced before, during, and after flight are contextualized. Their sense of self, their relationships with their families and their perceptions of their situation as adolescents or young adults in a highly unpredictable situation are presented in the light of relevant theory and findings from similar refugee studies. All the participants have fled from dangerous and intolerable situations in their home countries. They describe extreme dangers during flight in contexts that are unpredictable and where they feel lonely and unsupported. Most have unmet psychosocial needs and have received little support or help for their mental health issues during flight or after arrival in Norway. Suggestions for interventions and resilience-promoting actions are given based on the findings of the study.


The Value of CT Angiography Based on Intelligent Segmentation Algorithm for Survival of Hemodialysis Patients.
This study was to explore the application value for central venous stenosis and occlusion in hemodialysis patients under the CT angiography based on intelligent segmentation algorithm, so that patients can survive better. Spiral CT was used to examine upper limb swelling in 62 uremic hemodialysis patients at a speed of 3.8 mL/s. Nonionic iodine contrast agent was injected around the contralateral limb. The total dosage of 90-102 mL, it was scanned by intelligent trigger technology. The trigger scanning threshold was set. The monitoring point was located in the superior vena cava. CT with convolutional neural network intelligent segmentation algorithm was used to process image data. Finally, the quality of life and related biochemical levels of patients before and after hemodialysis were detected. Under the CT angiography of intelligent segmentation algorithm, 77 stenoses were found in 62 uremic patients, including 48 stenoses of the brachial vein and 17 stenoses of the superior vena cava. The correlation coefficient between CT angiography and digital subtraction angiography (DSA) imaging results of intelligent segmentation algorithm was 0.411. Segmentation effect of the algorithm in this study: automatic segmentation accuracy was greater than 79%. After hemodialysis treatment, the scores of physical fitness, pain, social function, and energy status of patients were significantly increased compared with those before treatment, and the levels of albumin, serum phosphorus, and parathyroid hormone were significantly decreased (P < 0.05). In summary, CT angiography with intelligent segmentation algorithm can obtain clear, intuitive, and complete vascular walking images, and better display subclavian vein, brachiocephalic vein, and superior vena cava. It can provide more valuable support for surgical intervention and has certain application value for better survival of hemodialysis patients.


Susceptibility of black soldier fly (Diptera: Stratiomyidae) larvae and adults to four insecticides.
Dosage-mortality regressions were determined for black soldier fly, Hermetia illucens (L.), larvae fed cyromazine or pyriproxifen treated media. Cyromazine LC50 for larvae dying before becoming prepupae ranged from 0.25 to 0.28 ppm with dosage-mortality regression slopes between 5.79 and 12.04. Cyromazine LC50s for larvae dying before emergence ranged from 0.13 to 0.19 ppm with dosage-mortality regression slopes between 3.94 and 7.69. Pyriproxifen dosage-mortality regressions were not generated for larvae failing to become prepupae since <32% mortality was recorded at the highest concentration of 1,857 ppm. LC50s for larvae failing to become adults ranged from 0.10 to 0.12 ppm with dosage mortality-regression slopes between 1.67 and 2.32. Lambda-cyhalothrin and permethrin dosage-mortality regressions were determined for wild adult black soldier flies and house flies, Musca domestica L., and for susceptible house flies. Our results indicate that the wild house fly, unlike the black soldier fly, population was highly resistant to each of these pyrethroids. Regression slopes for black soldier flies exposed to lambda-cyhalothrin were twice as steep as those determined for the wild house fly strain. Accordingly, LC50s for the black soldier fly and susceptible house fly were 10- to 30-fold lower than those determined for wild house flies. The differential sensitivity between wild black soldier flies and house flies might be due to behavioral differences. Adult house flies usually remain in animal facilities with the possibility of every adult receiving pesticide exposure, while black soldier fly adults are typically present only during emergence and oviposition thereby limiting their exposure.


Chemisorption of CO2 by diamine-tetraamido macrocyclic motifs: a theoretical study.
Although alkanolamines have been systematically utilized for CO2 capture, intensive research efforts are still required to ultimately design more efficient CO2 sorbents with appropriate sorption characteristics. In this article, we have explored a series of diamine-tetraamido macrocyclic molecules with different organic linkers, namely, pyridine, phenylene, pyrrole, furan, and thiophene, for the titled purpose using quantum chemical calculations. The optimized structures of the sequestration reaction revealed the formation of a carbamate anion within the macrocyclic cavity that was stabilized through several intramolecular interactions compared to parent amines. The reaction thermodynamics indicated that the macrocyclic compounds with pyridine, pyrrole and furan can effectively capture CO2. The results highlight the potential application of macrocyclic structures as efficient CO2 capturing agents.


Sex hormone receptors are present in the human suprachiasmatic nucleus.
The suprachiasmatic nucleus (SCN) is the clock of the brain that orchestrates circadian and circannual biological rhythms, such as the rhythms of hormones, body temperature, sleep and mood. These rhythms are frequently disturbed in menopause and even more so in dementia and can be restored in postmenopausal women by sex hormone replacement therapy (SHRT). Although it seems clear, both from clinical and experimental studies, that sex hormones influence circadian rhythms, it is not known whether this is by a direct or an indirect effect on the SCN. Therefore, using immunocytochemistry in the present study, we investigated whether the human SCN expresses sex hormone receptors in 5 premenopausal women and 5 young men. SCN neurons appeared to contain estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta) and progesterone receptors. Median ratings of ER immunoreactivity per individual and per gender group revealed a statistically significantly stronger nuclear ERalpha expression pattern in female SCN neurons (p < 0.05). No significant sexual dimorphic tendency was observed for nuclear ERbeta (p > 0.1) and progesterone receptors (p > 0.7). These data seem to support previously reported functional and structural SCN differences in relation to sex and sexual orientation and indicate for the first time that estrogen and progesterone may act directly on neurons of the human biological clock. In addition, the present findings provide a potential neuroendocrine mechanism by which SHRT can act to improve or restore SCN-related rhythm disturbances, such as body temperature, sleep and mood.


Viral and immunologic examination of human immunodeficiency virus type 1-infected, persistently seronegative persons.
Persons who were human immunodeficiency virus type 1 (HIV-1)-infected but who remained persistently seronegative (HIPS) on HIV-1 antibody tests were examined through AIDS case surveillance. Six such individuals (HIPS-1 to -4, -7, and -9) were examined to determine whether their persistent seronegativity was attributable to immune dysfunction or infection with atypical HIV. Of the 6, 4 had antibody titers to at least 1 other common pathogen. In vitro stimulation of peripheral blood mononuclear cells from HIPS-4 and HIPS-7 with pokeweed mitogen or phosphorothioate oligodeoxynucleotide (direct B cell mitogen) did not produce HIV-1-specific antibody. Reconstitution experiments with recombinant interleukin (rIL)-4 and rIL-12 also had no impact on antibody production. Virus isolates from HIPS-4 and -9 were R5X4-tropic, whereas HIPS-7 was CCR5-tropic only. Sequence analysis of long terminal repeat, p24, and env gp41 did not reveal any specific mutation, and phylogenetic analysis confirmed that all 6 virus specimens were HIV-1 subtype B. These data suggest that the lack of a detectable antibody response in these patients may be the result of immune dysfunction.


A retrospective analysis of balance control parameters in elderly fallers and non-fallers.
A cross-sectional retrospective study of parameters reflecting balance function in elderly fallers and non-fallers was conducted to better understand postural control mechanisms in individuals prone to falls. Ninety-nine old adults (65-91 years, mean age 78.4 (SD 5.7)) from two self-care residential facilities participated in the study. Foot center-of-pressure (CoP) displacement data were collected during narrow base upright stance eyes closed conditions and analyzed using summary statistics and Stabilogram-Diffusion Analysis (SDA) for mediolateral (ML) and anteroposterior (AP) directions. Subjects were instructed to minimize body sway. Twenty-nine of the subjects reported at least one fall and 69 subjects reported no falls in the past six months. The SDA showed significantly higher short-term diffusion coefficients and critical displacements in fallers in the ML but not the AP direction. Mean sway area and ML-CoP sway range were also larger in fallers. The greater ML critical displacement seen in fallers suggests that balance corrections on average occurred at higher sway amplitudes in this population. This is consistent with an ML decrease in the sensitivity of their postural control system. A higher short-term diffusion coefficient is consistent with increased muscle stiffness, a possible compensation for lost control sensitivity. Testing balance function under narrow stance conditions provides a modest increase in task difficulty that may help reveal pre-conditions of the balance control system that could increase the risk of falls.


Synthesis of biurets via TMSNCO addition to 1-aminosugars: application in the de novo synthesis of dC oxidation products.
The reaction between 1-aminosugars and trimethylisocyanate (TMSNCO) was optimised as a one-step synthetic strategy for the synthesis of sugar biurets. This protocol was successfully applied to a number of 1-aminosugars, which exclusively provided the corresponding biurets in 67-99% yields. The new methodology was applied in the de novo synthesis of N1-(2-deoxy-α/β-d-erythro-pentofuranosyl)biuret (dfBU) and N1-(2-deoxy-α/β-d-erythro-pentopyranosyl)biuret (dpBU), two known DNA lesions arising from the hydroxyl radical induced decomposition of 2'-deoxycytidine (dCyd).


The activated sludge bulking filament Eikelboom morphotype 0914 is a member of the Chloroflexi.
The filamentous bacterium Eikelboom morphotype type 0914 responsible for bulking in activated sludge plants is identified here for the first time as a member of the phylum Chloroflexi subgroup 1. Two FISH probes, CFX67a and CFX67b, targeting the 16S rRNA sequences of this filament morphotype were designed, validated and used successfully for its in situ identification. A survey of plants in eastern Australia with the CFX67a probe showed it targeted only the type 0914 morphotype that was common especially in long sludge age plants designed to remove phosphorus and nitrogen microbiologically, although being in very low abundance in many samples. Filaments responding to the CFX67b probe also exhibited the type 0914 morphology but were less frequent, although again occurring in similarly configured plants. All these filaments showed an uneven FISH signal suggesting their ribosomes are localized at the ends of their cells. Furthermore, some generated distinctive FISH signals in all biomass samples containing them, where only certain cells within any single trichome fluoresced with probes designed against different target sites. Helper probes for each of these were required before all cells fluoresced above the visual detection limits of FISH.


Interleukin-22 and Chemokine Interferon γ -Inducible-10 (IP-10) Levels in Chronic Hepatitis C Patients and Treatment Response to Pegylated Interferon and Ribavirin Therapy.
IL-22 plays a vital role in improving hepatic damage by targeting hepatocytes that express high levels of IL-22 receptor1. IP-10 is a chemokine that recruit mononuclear cells to liver parenchyma and improves the host immune response against hepatitis C virus. The study targeted 27 patients with chronic HCV who received pegylated Interferon and Ribavirin. IL-22 and IP-10 serum levels were measured by Elisa. The level of the serum IL-22 is higher in HCV patients groups receiving the antiviral treatment compared to control group and its levels significantly increased with response to treatment. The level of the serum IP-10 is higher in HCV patients groups compared to control group and its level significantly decreased with effective antiviral treatment. In conclusion, IL-22 and IP-10 levels could be used with a high sensitivity and specificity during antiviral treatment of HCV infected patients as predictive markers for treatment response.


Theoretical and experimental investigation of the antioxidative activity of monascin.
Monascin, a specific type of monascus pigments, exhibits many bioactivities. In this study, the antioxidative activity of monascin was investigated by theoretical and experimental methods. First, the antioxidant potential of six monascus pigments was predicted by density functional theory (DFT) and time-dependent density functional theory (TDDFT) at the B3LYP/6-31+G (d, p) level, and monascus yellow pigments were predicted to have strong antioxidant capacity, as they can transfer hydrogen to free radicals and accept electrons from radicals. Then, the free radical-scavenging capacity of monascin for 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide, and hydroxyl radicals was experimentally validated by electron spin resonance (ESR) measurement. Monascin exhibited a quenching effect on DPPH, superoxide, and hydroxyl radicals in a dose-dependent manner. Specifically, the scavenging activity of monascin for DPPH, superoxide, and hydroxyl radicals was 97.5%, 59.5%, and 68.6%, respectively, when 0.1 mg mL-1 monascin was present. Our study provides theoretical evidence for the strong antioxidative activity of monascin and offers a simple and reliable strategy to determine the antioxidative activity.


Classification and genetics of numeric anomalies of dentition.
A suggested classification of numeric anomalies of teeth is a trimodal classification: anodontia, hypodontia, and hyperdontia. A subclassification into nonsyndromic and syndromic cases would allow for uniform analysis. The limited data on anodontia and hyperdontia have made the genetic analysis of these anomalies difficult. The most suitable data for analysis on the genetics of numeric anomalies of dentition are on hypodontia. A reevaluation of this data, as presented in this report, suggests hypodontia follows an autosomal dominant mode of inheritance. However, the fact that penetrance is not complete suggests the presence of a mechanism whereby epistatic genes interfere with the phenotypic expression of the hypodontia gene. How this occurs is uncertain, but the available evidence suggests a major single gene defect, which is modified by genetic or environmental factors.


Plasma concentrations of neuroactive steroids before and after electroconvulsive therapy in major depression.
There is evidence that both cerebrospinal fluid (CSF) and plasma concentrations of 3alpha-reduced neuroactive steroids are decreased in major depressive disorder. Successful antidepressant pharmacotherapy, for example, with selective serotonin reuptake inhibitors (SSRIs), over several weeks is accompanied by an increase in CSF and plasma concentrations of these neuroactive steroids. However, no such increase has been observed during nonpharmacological treatments such as partial sleep deprivation or repetitive transcranial magnetic stimulation. In order to investigate whether concentration changes in neuroactive steroids are an important component of clinically effective antidepressant treatment, we examined plasma concentrations of the neuroactive steroids 3alpha,5alpha-tetrahydroprogesterone, 3alpha,5beta-tetrahydroprogesterone, 3beta,5alpha-tetrahydroprogesterone, and their precursors progesterone, 5alpha-dihydroprogesterone, and 5beta-dihydroprogesterone in 31 pharmacotherapy-resistant depressed in-patients before and after unilateral electroconvulsive therapy (ECT) as a monotherapy over 4 weeks. Samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. In all, 51.6% of the patients were treatment responders. There was no influence of ECT on the plasma concentrations of any neuroactive steroid studied. Moreover, neuroactive steroid levels did not differ between treatment responders and nonresponders. Our study shows that changes in neuroactive steroid plasma levels are not a mandatory factor for successful antidepressant treatment by ECT. Thus, the previously observed changes in plasma concentrations of neuroactive steroids following treatment with antidepressants such as SSRIs more likely reflect distinct pharmacological properties of these compounds rather than clinical improvement.