Novel recognition mode between Vav and Grb2 SH3 domains.
Vav is a guanine nucleotide exchange factor for the Rho/Rac family that is expressed exclusively in hematopoietic cells. Growth factor receptor-bound protein 2 (Grb2) has been proposed to play important roles in the membrane localization and activation of Vav through dimerization of its C-terminal Src-homology 3 (SH3) domain (GrbS) and the N-terminal SH3 domain of Vav (VavS). The crystal structure of VavS complexed with GrbS has been solved. VavS is distinct from other SH3 domain proteins in that its binding site for proline-rich peptides is blocked by its own RT loop. One of the ends of the VavS beta-barrel forms a concave hydrophobic surface. The GrbS components make a contiguous complementary interface with the VavS surface. The binding site of GrbS for VavS partially overlaps with the canonical binding site for proline-rich peptides, but is definitely different. Mutations at the interface caused a decrease in the binding affinity of VavS for GrbS by 4- to 40-fold. The structure reveals how GrbS discriminates VavS specifically from other signaling molecules without binding to the proline-rich motif.


DNA damage in fish (Anguilla anguilla) exposed to a glyphosate-based herbicide -- elucidation of organ-specificity and the role of oxidative stress.
Organophosphate herbicides are among the most dangerous agrochemicals for the aquatic environment. In this context, Roundup(®), a glyphosate-based herbicide, has been widely detected in natural water bodies, representing a potential threat to non-target organisms, namely fish. Thus, the main goal of the present study was to evaluate the genotoxic potential of Roundup(®) in the teleost fish Anguilla anguilla, addressing the possible causative involvement of oxidative stress. Fish were exposed to environmentally realistic concentrations of this herbicide (58 and 116 μgL(-1)) during one or three days. The standard procedure of the comet assay was applied to gill and liver cells in order to determine organ-specific genetic damage. Since liver is a central organ in xenobiotic metabolism, nucleoids of hepatic cells were also incubated with a lesion-specific repair enzyme (formamidopyrimidine DNA glycosylase - FPG), in order to recognise oxidised purines. Antioxidants were determined in both organs as indicators of pro-oxidant state. In general, both organs displayed an increase in DNA damage for the two Roundup(®) concentrations and exposure times, although liver showed to be less susceptible to the lower concentration. The enzyme-modified comet assay showed the occurrence of FPG-sensitive sites in liver only after a 3-day exposure to the higher Roundup(®) concentration. The antioxidant defences were in general unresponsive, despite a single increment of catalase activity in gills (116 μgL(-1), 3-day) and a decrease of superoxide dismutase activity in liver (58 μgL(-1), 3-day). Overall, the mechanisms involved in Roundup(®)-induced DNA strand-breaks showed to be similar in both organs. Nevertheless, it was demonstrated that the type of DNA damage varies with the concentration and exposure duration. Hence, after 1-day exposure, an increase on pro-oxidant state is not a necessary condition for the induction of DNA-damaging effects of Roundup(®). By increasing the duration of exposure to three days, ROS-dependent processes gained preponderance as a mechanism of DNA-damage induction in the higher concentration.


Structural and functional dissection of human cytomegalovirus US3 in binding major histocompatibility complex class I molecules.
The human cytomegalovirus US3, an endoplasmic reticulum (ER)-resident transmembrane glycoprotein, forms a complex with major histocompatibility complex (MHC) class I molecules and retains them in the ER, thereby preventing cytolysis by cytotoxic T lymphocytes. To identify which parts of US3 confine the protein to the ER and which parts are responsible for the association with MHC class I molecules, we constructed truncated mutant and chimeric forms in which US3 domains were exchanged with corresponding domains of CD4 and analyzed them for their intracellular localization and the ability to associate with MHC class I molecules. All of the truncated mutant and chimeric proteins containing the luminal domain of US3 were retained in the ER, while replacement of the US3 luminal domain with that of CD4 led to cell surface expression of the chimera. Thus, the luminal domain of US3 was sufficient for ER retention. Immunolocalization of the US3 glycoprotein after nocodazole treatment and the observation that the carbohydrate moiety of the US3 glycoprotein was not modified by Golgi enzymes indicated that the ER localization of US3 involved true retention, without recycling through the Golgi. Unlike the ER retention signal, the ability to associate with MHC class I molecules required the transmembrane domain in addition to the luminal domain of US3. Direct interaction between US3 and MHC class I molecules could be demonstrated after in vitro translation by coimmunoprecipitation. Together, the present data indicate that the properties that allow US3 to be localized in the ER and bind MHC class I molecules are located in different parts of the molecule.


Differentiation of mesophilic and thermophilic bacteria with fourier transform infrared spectroscopy.
In the present study the characterization and differentiation of mesophilic and thermophilic bacteria were investigated by using Fourier transform infrared (FT-IR) spectroscopy. Our results showed significant differences between the FT-IR spectra of mesophilic and thermophilic bacteria. The protein-to-lipid ratio was significantly higher for thermophiles compared to mesophiles. The absorption intensity of the CH(3) asymmetric stretching vibration was higher in thermophilic bacteria, indicating a change in the composition of the acyl chains. The higher intensity/area observed in the CH(2) symmetric stretching mode at 2857 cm(-1), and the CH(2) bending vibration band at 1452 cm(-1), indicated a higher amount of saturated lipids in thermophilic bacteria. The lipid C=O stretching vibration at 1739 cm(-1), which was observed in the mesophilic group, was not observed clearly in the thermophilic group, indicating a difference in packing that is presumably due to the decreased proportion of unsaturated acyl chains in thermophilic bacteria. In addition, the carbonyl groups become hydrogen bonded and the cellular DNA content was lower in thermophilic bacteria. Moreover, in the 1000-400 cm(-1) frequency region, the spectra of each bacterial species belonging to both the mesophilic and thermophilic bacterial groups, showed characteristic differences that were discriminated via dendrogram using cluster analysis. The current study implies that FT-IR spectroscopy could be successfully applied for the rapid comparison of bacterial groups and species to establish either similarities or discrepancies, as well as to confirm biochemical or physiological characteristics.


The common pain of surrealism and death: acetaminophen reduces compensatory affirmation following meaning threats.
The meaning-maintenance model posits that any violation of expectations leads to an affective experience that motivates compensatory affirmation. We explore whether the neural mechanism that responds to meaning threats can be inhibited by acetaminophen, in the same way that acetaminophen inhibits physical pain or the distress caused by social rejection. In two studies, participants received either acetaminophen or a placebo and were provided with either an unsettling experience or a control experience. In Study 1, participants wrote about either their death or a control topic. In Study 2, participants watched either a surrealist film clip or a control film clip. In both studies, participants in the meaning-threat condition who had taken a placebo showed typical compensatory affirmations by becoming more punitive toward lawbreakers, whereas those who had taken acetaminophen, and those in the control conditions, did not.


Matched unrelated donor stem cell transplant in 131 patients with follicular lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
Matched unrelated donor stem cell transplantation (MUD-SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD-SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced-intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD-SCT between 2000 and 2005 were included. Median time from diagnosis to MUD-SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD-SCT and had failed a previous autograft more frequently than CONV recipients. Non-relapse mortality (NRM) was 24% and 30% at 100-d and 1-year, respectively. After a median follow-up of 36 months, 17% of the patients developed disease progression, the 3-year progression-free survival (PFS) being 47%. Three-year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD-SCT results, even in heavily pre-treated populations, in a meaningful PFS and OS.


User Acceptance of Electronic Medical Record System: Implementation at Marie Stopes International, Myanmar.
This study assessed the technical feasibility and aimed to determine the factors influencing intention to use Electronic Medical Records (EMRs) at Marie Stopes International, Myanmar (MSI-M). A cross-sectional survey was conducted among 112 participants who were working at the clinics and head office of MSI-M. Demographic information, type of office, technical feasibility, information communication technology knowledge, computer usage, and user acceptance towards the proposed system were obtained from the participants. The results indicated low health information technology usage and network availability at MSI-M clinics. Positive perception of EMRs was found among the staff members of MSI-M, which was reflected by positive responses regarding perceived usefulness (average score of 4.15), perceived ease of use (average score of 4.03), and intention to use (average score of 4.10) on a 5-point Likert scale. Statistically, staff from the head office expressed less desire to implement an EMR system (odds ratio = 0.07; 95% confidence interval, 0.01-0.97), especially when they do not perceive the usefulness of the system (odds ratio = 5.05; 95% confidence interval, 2.39-10.69). Since health information technology usage and network availability were low in MSI-M, it is important to strengthen the information and communication technology infrastructure and introduce a policy for capacity building at MSI-M. Adequate training and strong leadership support are recommended for the successful initial implementation and sustainability of an EMR system at MSI-M.


What randomized trials and systematic reviews can offer decision makers.
It is important to recognize the studies that yield the most reliable evidence upon which to base treatment decisions. Randomized trials have a particular place in providing high-quality unbiased comparisons of different treatments, when carried out to a high methodological standard. Empirical evidence shows that such trials are not always done well, and also that poor methodology is associated with biased findings. Consumers of the published literature need to be able to recognize which trials can be trusted. Systematic reviews and meta-analyses offer an organized approach to assessing all the relevant literature on a topic, particularly when several randomized trials address the same treatment comparison. Like trials, systematic reviews and meta-analyses need to be carried out to a high standard. They offer particular potential for providing the most useful information for clinical decision making. Critical aspects of these types of study are considered in this paper.


Longitudinal assessment of von Willebrand factor antigen and von Willebrand factor propeptide in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.
The impact of commencing or changing antiplatelet therapy on von Willebrand factor antigen (VWF:Ag) and von Willebrand factor propeptide (VWF:Ag II) levels has not been comprehensively assessed following TIA or ischaemic stroke. In this pilot, longitudinal, observational analytical study, VWF:Ag and VWF:Ag II levels were simultaneously quantified in platelet poor plasma by ELISA in patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Ninety-one patients were recruited. Eighteen were initially assessed on no antiplatelet therapy, and then after 14d (N = 17) and 90d (N = 8) on aspirin monotherapy; 21 patients were assessed on aspirin and after 14d and 90d on clopidogrel; 52 were assessed on aspirin monotherapy, and after 14d and 90d on aspirin and dipyridamole combination therapy. VWF:Ag, VWF:Ag II levels and VWF:Ag/VWF:Ag II ratio were unchanged at 14d and 90d in the overall study population (p ≥ 0.1). VWF:Ag and VWF:Ag II levels remained stable at 14d and 90d after commencing aspirin (p ≥ 0.054), and after changing from aspirin to clopidogrel (p ≥ 0.2). Following the addition of dipyridamole MR to aspirin, there was a significant reduction in VWF:Ag levels at 14d (p = 0.03) and 90d (p = 0.005), but not in VWF:Ag II levels (p ≥ 0.3). The addition of dipyridamole to aspirin led to a persistent reduction in VWF:Ag but not in VWF:Ag II levels, suggesting that dipyridamole may inhibit release of platelet-derived VWF:Ag following TIA or ischaemic stroke.


Barriers to the routine collection of health outcome data in an Australian community care organization.
For over a decade, organizations have attempted to include the measurement and reporting of health outcome data in contractual agreements between funders and health service providers, but few have succeeded. This research explores the utility of collecting health outcomes data that could be included in funding contracts for an Australian Community Care Organisation (CCO). An action-research methodology was used to trial the implementation of outcome measurement in six diverse projects within the CCO using a taxonomy of interventions based on the International Classification of Function. The findings from the six projects are presented as vignettes to illustrate the issues around the routine collection of health outcomes in each case. Data collection and analyses were structured around Donabedian's structure-process-outcome triad. Health outcomes are commonly defined as a change in health status that is attributable to an intervention. This definition assumes that a change in health status can be defined and measured objectively; the intervention can be defined; the change in health status is attributable to the intervention; and that the health outcomes data are accessible. This study found flaws with all of these assumptions that seriously undermine the ability of community-based organizations to introduce routine health outcome measurement. Challenges were identified across all stages of the Donabedian triad, including poor adherence to minimum dataset requirements; difficulties standardizing processes or defining interventions; low rates of use of outcome tools; lack of value of the tools to the service provider; difficulties defining or identifying the end point of an intervention; technical and ethical barriers to accessing data; a lack of standardized processes; and time lags for the collection of data. In no case was the use of outcome measures sustained by any of the teams, although some quality-assurance measures were introduced as a result of the project.


The role of EHD proteins at the neuronal synapse.
Eps15 homology domain (EHD) proteins are conserved adenosine triphosphatases that are involved in membrane remodeling. EHD family members are structurally similar to the guanosine triphosphatase (GTPase) dynamin, and both are essential for the fission step of clathrin-mediated endocytosis. This Journal Club highlights a recent study by Jakobsson et al. that reports the unexpected finding that, rather than having a redundant function, EHD can regulate dynamin activity. Dynamin helices assemble around the neck of budding endocytic vesicles; as dynamin helices lengthen, the neck of the growing bud may become so long that GTP hydrolysis is no longer sufficient to promote fission. EHD increases the efficiency of dynamin-induced fission by restricting the length of dynamin helices. Furthermore, EHD is able to bind both dynamin and amphiphysin. Therefore, we propose a model whereby amphiphysin recruits both EHD and dynamin in neurons to regulate clathrin-dependent synaptic vesicle endocytosis.


Quality of life of cancer patients.
Cancer is a one of the major public health problem both in developed and developing countries around the globe. Quality-of-life (QOL) of a cancer patient before and after the treatment is an important issue especially for the cancer survivors, their families, and the care providers. In cancer prospective, Quality-of-life can been defined as a sense of well-being, it is a multidimensional perspective that includes dimensions such as physical, psychological, social, and spiritual, changes in one QOL dimension can influence perceptions in other dimensions also. Cancer patients should demand information related to adverse effects of chemotherapy and actions to be taken to reduce them, also there should be provision of providing sufficient information prior to beginning of the treatment procedure irrespective to type of treatment, so that patient is aware of all the treatment modalities and their side effects and self-care strategies so as to reduce treatment-related concerns.


The Effect of Glycemic Status on Kidney Stone Disease in Patients with Prediabetes.
While the evidence supporting a positive association between diabetes mellitus and kidney stone disease (KSD) is solid, studies examining the association between impaired fasting glucose (IFG) and KSD show inconsistent results. Currently, there are no studies examining the relationship between impaired glucose tolerance (IGT) and KSD. The objective of this study is to investigate the effects of different glycemic statuses on KSD. The results may help to motivate patients with diabetes to conform to treatment regimens. We conducted a cross sectional study of a population that underwent health check-ups between January 2000 and August 2009 at the Health Evaluation Center of National Cheng Kung University Hospital. A total of 14,186 subjects were enrolled. The following categories of glycemic status were used according to the criteria of the 2009 American Diabetes Association: normal glucose tolerance, isolated IGT, isolated IFG, combined IFG/IGT, and diabetes. The existence of KSD was evaluated using renal ultrasonography, and the presence of any hyperechoic structures causing acoustic shadowing was considered to be indicative of KSD. The prevalence of KSD was 7.4% (712/9,621), 9.3% (163/1,755), 10.8% (78/719), 12.0% (66/548), and 11.3% (174/1,543) in subjects with NGT, isolated IGT, isolated IFG, combined IFG/IGT, and diabetes, respectively. Isolated IFG, combined IFG/IGT, and diabetes were associated with KSD after adjusting for other clinical variables, but isolated IGT was not. Age (41 to 64 years vs. ≤40 years, ≥65 years vs. ≤40 years), male gender, hypertension, and hyperuricemia were also independently associated with KSD. Isolated IFG, combined IFG/IGT, and diabetes, but not isolated IGT, were associated with a higher risk of KSD.


Mixed land use and neighborhood crime.
The concentration of certain land uses has been linked to crime rates; yet, it remains to be seen whether mixed land use, defined as heterogeneity among several land uses, independently affects neighborhood crime. The goal of the current study, therefore, is to build upon the extant literature by examining how mixed land use influences crime, net of specific land uses and sociodemographic characteristics. Using data on Los Angeles block groups, a Herfindahl index was constructed of eight specific land uses to capture mixed land use, and a series of negative binomial regression models were estimated to assess the main and moderating effects of mixed land use on neighborhood crime. Although mixed land use was found to exert a deleterious influence on two crime types, concentrated disadvantage moderated the effect of mixed land use on all crime types. The implications of these findings for criminology, urban studies, and policy are discussed.


Human albumin: old, new, and emerging applications.
Human serum albumin has been widely used in an array of clinical settings for nearly 7 decades. Although there is no evidence to support the use of albumin rather than crystalloid in acute volume resuscitation, many clinicians continue to use albumin because it has other important physiologic effects besides the oncotic function. In keeping with the improved understanding of albumin physiology and pathophysiology of many acute and chronic diseases, use of albumin for medical applications has increased in recent years. This, along with increased costs of manufacturing and lower production volume of medical-grade albumin, has lead to an ongoing shortage and rapid increase in albumin prices. This review is based on the analysis of major publications, related to albumin chemistry, physiology, and medical uses including guidelines developed by professional and governmental organizations. Results reflect current knowledge about the role of albumin in health and disease and relevance of albumin therapy in specific clinical settings. Albumin therapy is currently recommended in spontaneous bacterial peritonitis with ascites, refractory ascites not responsive to diuretics, large-volume paracentesis, post-paracentesis syndrome, and the treatment of hepatorenal syndrome as an adjunct to vasoconstrictors. New indications for albumin therapy are linked to the antioxidant activity of albumin and its effects on capillary integrity. In recent years, large-pore hemofiltration and albumin exchange have emerged as promising liver support therapies for liver failure and other toxic syndromes. They are designed to remove a broad range of blood-borne toxins and to restore normal functions of the circulating albumin by replacing defective forms of albumin and albumin molecules saturated with toxins with normal albumin. In view of the ongoing worldwide shortage and high cost of human albumin (native and recombinant), new usage criteria, protocols, and guidelines for appropriate utilization of albumin are needed.


Understanding the Role of Hypoxia Inducible Factor During Neurodegeneration for New Therapeutics Opportunities.
Neurodegeneration (NDG) is linked with the progressive loss of neural function with intellectual and/or motor impairment. Several diseases affecting older individuals, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, stroke, Multiple Sclerosis and many others, are the most relevant disorders associated with NDG. Since other pathologies such as refractory epilepsy, brain infections, or hereditary diseases such as "neurodegeneration with brain iron accumulation", also lead to chronic brain inflammation with loss of neural cells, NDG can be said to affect all ages. Owing to an energy and/or oxygen supply imbalance, different signaling mechanisms including MAPK/PI3K-Akt signaling pathways, glutamatergic synapse formation, and/or translocation of phosphatidylserine, might activate some central executing mechanism common to all these pathologies and also related to oxidative stress. Hypoxia inducible factor 1-α (HIF-1α) plays a twofold role through gene activation, in the sense that this factor has to "choose" whether to protect or to kill the affected cells. Most of the afore-mentioned processes follow a protracted course and are accompanied by progressive iron accumulation in the brain. We hypothesize that the neuroprotective effects of iron chelators are acting against the generation of free radicals derived from iron, and also induce sufficient -but not excessive- activation of HIF-1α, so that only the hypoxia-rescue genes will be activated. In this regard, the expression of the erythropoietin receptor in hypoxic/inflammatory neurons could be the cellular "sign" to act upon by the nasal administration of pharmacological doses of Neuro-EPO, inducing not only neuroprotection, but eventually, neurorepair as well.


Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes.
Type 2 diabetes mellitus is frequently associated with hypertension, but the underlying mechanisms are not completely understood. We tested the hypothesis that activation of type 1 prostaglandin E(2) (PGE(2)) receptor (EP1) increases skeletal muscle arteriolar tone and blood pressure in mice with type 2 diabetes. In 12-week-old, male db/db mice (with homozygote mutation in leptin receptor), systolic blood pressure was significantly elevated, compared with control heterozygotes. Isolated, pressurized gracilis muscle arterioles ( approximately 90 microm) of db/db mice exhibited an enhanced pressure- and angiotensin II (0.1-10 nM)-induced tone, which was reduced by the selective EP1 receptor antagonist, AH6809 (10 microM), to the level observed in arterioles of control mice. Exogenous application of PGE(2) (10 pM-100 nM) or the selective agonist of the EP1 receptor, 17-phenyl-trinor-PGE(2) (10 pM-100 nM), elicited arteriolar constrictions that were significantly enhanced in db/db mice (max: 31 +/- 4 and 29 +/- 5%), compared with controls (max: 20 +/- 2 and 14 +/- 3%, respectively). In the aorta of db/db mice, an increased protein expression of EP1, but not EP4, receptor was also detected by western immunoblotting. Moreover, we found that oral administration of the EP1 receptor antagonist, AH6809 (10 mg/kg/day, for 4 days), significantly reduced the systolic blood pressure in db/db, but not in control mice. Activation of EP1 receptors increases arteriolar tone, which could contribute to the development of hypertension in the db/db mice.


Blind Quality Assessment of Iris Images Acquired in Visible Light for Biometric Recognition.
Image quality is a key issue affecting the performance of biometric systems. Ensuring the quality of iris images acquired in unconstrained imaging conditions in visible light poses many challenges to iris recognition systems. Poor-quality iris images increase the false rejection rate and decrease the performance of the systems by quality filtering. Methods that can accurately predict iris image quality can improve the efficiency of quality-control protocols in iris recognition systems. We propose a fast blind/no-reference metric for predicting iris image quality. The proposed metric is based on statistical features of the sign and the magnitude of local image intensities. The experiments, conducted with a reference iris recognition system and three datasets of iris images acquired in visible light, showed that the quality of iris images strongly affects the recognition performance and is highly correlated with the iris matching scores. Rejecting poor-quality iris images improved the performance of the iris recognition system. In addition, we analyzed the effect of iris image quality on the accuracy of the iris segmentation module in the iris recognition system.


Shared care: the barriers encountered by community-based palliative care teams in Ontario, Canada.
To meet the complex needs of patients requiring palliative care and to deliver holistic end-of-life care to patients and their families, an interprofessional team approach is recommended. Expert palliative care teams work to improve the quality of life of patients and families through pain and symptom management, and psychosocial spiritual and bereavement support. By establishing shared care models in the community setting, teams support primary healthcare providers such as family physicians and community nurses who often have little exposure to palliative care in their training. As a result, palliative care teams strive to improve not only the end-of-life experience of patients and families, but also the palliative care capacity of primary healthcare providers. The aim of this qualitative study was to explore the views and experiences of community-based palliative care team members and key-informants about the barriers involved using a shared care model to provide care in the community. A thematic analysis approach was used to analyse interviews with five community-based palliative care teams and six key-informants, which took place between December 2010 and March 2011. Using the 3-I framework, this study explores the impacts of Institution-related barriers (i.e. the healthcare system), Interest-related barriers (i.e. motivations of stakeholders) and Idea-related barriers (i.e. values of stakeholders and information/research), on community-based palliative care teams in Ontario, Canada. On the basis of the perspective of team members and key-informants, it is suggested that palliative care teams experience sociopolitical barriers in an effort to establish shared care in the community setting. It is important to examine the barriers encountered by palliative care teams to address how to better develop and sustain them in the community.


Genome sizes and the Benford distribution.
Data on the number of Open Reading Frames (ORFs) coded by genomes from the 3 domains of Life show the presence of some notable general features. These include essential differences between the Prokaryotes and Eukaryotes, with the number of ORFs growing linearly with total genome size for the former, but only logarithmically for the latter. Simply by assuming that the (protein) coding and non-coding fractions of the genome must have different dynamics and that the non-coding fraction must be particularly versatile and therefore be controlled by a variety of (unspecified) probability distribution functions (pdf's), we are able to predict that the number of ORFs for Eukaryotes follows a Benford distribution and must therefore have a specific logarithmic form. Using the data for the 1000+ genomes available to us in early 2010, we find that the Benford distribution provides excellent fits to the data over several orders of magnitude. In its linear regime the Benford distribution produces excellent fits to the Prokaryote data, while the full non-linear form of the distribution similarly provides an excellent fit to the Eukaryote data. Furthermore, in their region of overlap the salient features are statistically congruent. This allows us to interpret the difference between Prokaryotes and Eukaryotes as the manifestation of the increased demand in the biological functions required for the larger Eukaryotes, to estimate some minimal genome sizes, and to predict a maximal Prokaryote genome size on the order of 8-12 megabasepairs. These results naturally allow a mathematical interpretation in terms of maximal entropy and, therefore, most efficient information transmission.


Localized excitatory synaptic interactions mediate the sustained depolarization of electrographic seizures in developing hippocampus.
Repetitive synchronized neuronal discharging that lasts for seconds and even minutes in in vitro brain slice preparations are important new models in experimental epilepsy. In hippocampal slices from 1-2-week-old rats, individual CA3 pyramidal cells undergo a sustained depolarization during such electrographic seizures, induced by GABAA receptor antagonists. In experiments reported here these events were produced in small isolated segments of the CA3 subfield, measuring only 400-500 microns along the cell body layer. In such minisclices local application of either kynurenic acid or 6-cyano-7-nitroquinoxaline-2-3-dione (CNQX) to the proximal basilar dendrites abolished the synchronized discharges of electrographic seizures. Interictal spikes appeared unaffected by this treatment. Application of these excitatory amino acid receptor antagonists to distal basilar dendrites or apical dendrites was ineffective. In "larger" minislices, measuring 700-1000 microns along the cell body layer, application of kynurenic acid, CNQX, or TTX to the proximal basilar dendrites did not abolish electrographic seizures but instead selectively suppressed the intracellularly recorded sustained depolarization and the coincident slow negative field potential recorded in proximal basilar dendrites. Results of several experiments suggest that electrographic seizures recorded under these conditions were produced by a remote network of "generator cells." Since the remote neurons were unaffected by local application of the drugs, it seemed likely that they continued to undergo a sustained depolarization. Simultaneous blockade of basilar dendritic synapses in the "generator" population abolished electrographic seizures throughout these larger minislices. These results suggest that the sustained depolarization plays a central role in seizure generation and that it does not have to be generated in every neuron, only in a critical number of "generator cells" for a seizure to occur. Taken together, results presented here suggest that the sustained depolarization of electrographic seizures is a separate physiological process from the more rapid repetitive depolarizations of the seizure discharges and is required if electrographic seizures are to occur. This slow depolarization appears to be synaptically mediated and generated exclusively in proximal basilar dendrites. Therefore, in addition to the excitatory synaptic potentials involved in paroxysmal depolarization shift generation, a second form of recurrent excitation may exist in immature hippocampus. Not only is this physiological process critical for the genesis of seizures, but it also appears to be highly partitioned within the hippocampal laminae.


Proceedings of the 2020 GRAPPA Collaborative Research Network (CRN) Meeting.
At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Collaborative Research Network (CRN) annual meeting, the GRAPPA-CRN group presented a pilot investigator-initiated study protocol to test electronic case report forms (eCRFs) and proposed Standardized Operating Procedures (SOPs) to evaluate biomarkers of psoriatic arthritis (PsA) associated with axial disease. The progress on 3 studies was also presented: BioDAM PsA (Biomarkers as Predictors of structural DAMage in PsA; to validate soluble biomarkers as predictors of structural damage in PsA), PreventPsA (examining the development of PsA and risk factors among patients with psoriasis and no arthritis), and PredictORPsA (Predicting Treatment respOnse in patients with eaRly PsA; in collaboration with Pfizer using samples from the Oral Psoriatic Arthritis TriaL [OPAL], to identify biomarkers of treatment response). GRAPPA-CRN funding partnerships and applications are also underway with both the Innovative Medicines Initiative (IMI) in Europe and Accelerating Medicines Partnerships (AMP) 2.0 in the USA, and the progress of these applications and associated objectives were presented.


Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer.
Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RARβ2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between CDH13, SFRP1, and RASSF1A methylation and breast cancer subtypes and between SFRP1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced RASSF1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci (RASSF1A, RARβ2 and CDH13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients.


Poor sleep and emotion dysregulation mediate the association between depressive and premenstrual symptoms in young adult women.
A large portion of reproductive-aged women report experiencing distressing premenstrual symptoms. These symptoms can be exacerbated by concurrent mood problems and contribute to long-term depressive risk. However, difficulty sleeping and regulating emotional responses are also associated with the premenstrual phase and represent additional, well-established risk factors for depression. The aim of this study was to investigate whether habitual sleep problems and emotion regulation strategies serve to mediate the relationship between mood and premenstrual symptoms in non-treatment-seeking young women. Participants included 265 adult women between the ages of 18 and 25 who provided retrospective self-reports of depressive symptoms, habitual sleep quality, and premenstrual symptoms for the past month. Trait-based difficulties in regulating emotions were also assessed. Greater depressive symptoms significantly predicted greater premenstrual symptoms and both poor sleep and ineffective emotion regulation were shown to mediate this relationship. Poor sleep may enhance experience of premenstrual symptoms via its well-established impact on physical, cognitive, and/or affective functioning. Similarly, an inability to effectively regulate emotional responses in general may exacerbate experience or perception of somatic and mood symptoms during the premenstrual period, contributing to mood disturbances and risk. Findings require replication in future studies using prospective designs and more diverse samples of women.


High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy.
We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses. Cross-sectional on consecutive recruitment. Hospital sleep center and pediatric unit. Forty-three children and adolescents with NC versus 52 age-matched obese children as controls. N/A. Patients underwent clinical interview, polysomnographic recordings, cerebrospinal fluid hypocretin-1 measurement, and human leukocyte antigen typing. Height, weight, arterial blood pressure, and Tanner pubertal stage were evaluated. Plasma lipid and glucose profiles were analyzed. When an altered pubertal development was clinically suspected, plasma concentrations of hypothalamic-pituitary-gonadal axis hormones were determined. Children with NC showed a high prevalence of overweight/obesity (74%) and a higher occurrence of precocious puberty (17%) than obese controls (1.9%). Isolated signs of accelerated pubertal development (thelarche, pubic hair, advanced bone age) were also present (41%). Precocious puberty was significantly predicted by a younger age at first NC symptom onset but not by overweight/obesity or other factors. In addition, overweight/obesity was predicted by younger age at diagnosis; additional predictors were found for overweight/obesity (short disease duration, younger age at weight gain and lower high-density lipoprotein cholesterol), which did not include precocious puberty. NC symptoms, pubertal signs appearance, and body weight gain developed in close temporal sequence. NC occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction. The severity of these comorbidities and the potential related risks require a multidiagnostic approach and a tailored therapeutic management.


Inpatient recognition and management of HLH.
Hemophagocytic lymphohistiocytosis (HLH) is one of the life-threatening emergencies that a hematologist may be called upon to diagnose and manage. It is a hyperinflammatory process that develops in patients with genetic abnormalities, hematologic malignancies, chronic inflammatory states, or infections. The main clinical challenges are recognizing HLH, determining whether the immune response is aberrant or appropriate, and deciding upon therapy. Patients may present with fever, central nervous system symptoms, cytopenias, or elevated liver enzymes. Recognizing HLH is challenging because its features overlap with numerous systemic disorders, thus requiring a high level of suspicion and timely investigations to confirm the diagnosis and detect the underlying trigger. Once HLH is diagnosed, careful consideration of immunosuppressive therapy's potential benefit versus harm is necessary. Such therapy can sometimes be tailored to the underlying trigger. In the acute setting, the competing pressures of completing a thorough diagnostic process (including evaluation for the presence of lymphoma and infection) and the need for expedited treatment must be balanced. During the management of an HLH patient, continuous vigilance for the presence of as-yet unrecognized disease triggers, monitoring response, and identifying emerging complications is critical. This review will discuss the recognition and management of HLH in the inpatient setting.


Therapeutic Efficacy and Cost Effectiveness of High Cut-Off Dialyzers Compared to Conventional Dialysis in Patients with Cast Nephropathy.
High Cut-Off (HCO) dialysis membranes efficiently reduce serum free light chain (FLC) concentrations and may improve renal recovery and survival from multiple myeloma (MM) associated renal failure with cast nephropathy. However, clinical trials comparing dialysis with HCO versus conventional filters are lacking. The aim of this study was to assess clinical outcomes and economic impact of HCO dialyzers compared to conventional hemodialysis membranes in cast nephropathy. Multicenter retrospective analysis of 19 patients treated for renal failure from FLC associated cast nephropathy with standard induction chemotherapy (bortezomib/dexamethasone). We compared hemodialysis treatment with High Cut-Off (n = 12) versus conventional dialyzers (n = 7). Primary endpoint was survival; secondary endpoints were renal recovery, renal function and treatment costs. At 12 months, patient survival was 25% in the HCO group versus 0% in controls (p = NS). A tendency towards faster renal recovery (p = 0.066) and better renal function at 3, 6 and 12 months (p = 0.109) after diagnosis of MM was noted in the HCO group. Complete renal response rate was achieved in 10.5 and 0% of HCO and control patients, respectively, partial renal response in 15.8 and 5.3%, and minor renal response in 26.3 and 15.8%, respectively. Both patient survival and renal recovery were significantly correlated with the extent of free light chain (FLC) reduction in serum. Median treatment costs were CHF 230'000 and 223'000 (p = NS) in the HCO and control group, respectively. Hemodialysis treatment with HCO membranes for cast nephropathy tended towards better survival as well as faster and better recovery of renal function versus conventional dialyzers. Moreover, total medical costs were comparable between groups. In the absence of results from randomized prospective trials on this topic, the use of HCO dialyzers in patients with renal failure from cast nephropathy may be recommended. Prospective randomized trials are required.


Hepatitis B virus (HBV) envelope glycoproteins vary drastically in their sensitivity to glycan processing: evidence that alteration of a single N-linked glycosylation site can regulate HBV secretion.
The role of N-linked glycosylation and glycan trimming in the function of glycoproteins remains a central question in biology. Hepatitis B virus specifies three glycoproteins (L, M, and S) that are derived from alternate translation of the same ORF. All three glycoproteins contain a common N-glycosylation site in the S domain while M possesses an additional N-glycosylation site at its amino terminus. In the presence of N-butyl-deoxnojirimycin (an inhibitor of alpha-glucosidase) virions and the M protein are surprisingly retained. Preliminary evidence suggests that the retained M protein is hyperglucosylated and localized to lysosomal vesicles. In contrast, the S and L proteins are secreted, and their glycosylation state is unaffected by the presence of the inhibitor. Site-directed mutagenesis provides evidence that virion secretion requires the glycosylation sequon in the pre-S2 domain of M. This highlights the potential role of the M protein oligosaccharide as a therapeutic target.


A transcription network of interlocking positive feedback loops maintains intracellular iron balance in archaea.
Iron is required for key metabolic processes but is toxic in excess. This circumstance forces organisms across the tree of life to tightly regulate iron homeostasis. In hypersaline lakes dominated by archaeal species, iron levels are extremely low and subject to environmental change; however, mechanisms regulating iron homeostasis in archaea remain unclear. In previous work, we demonstrated that two transcription factors (TFs), Idr1 and Idr2, collaboratively regulate aspects of iron homeostasis in the model species Halobacterium salinarum. Here we show that Idr1 and Idr2 are part of an extended regulatory network of four TFs of the bacterial DtxR family that maintains intracellular iron balance. We demonstrate that each TF directly regulates at least one of the other DtxR TFs at the level of transcription. Dynamical modeling revealed interlocking positive feedback loop architecture, which exhibits bistable or oscillatory network dynamics depending on iron availability. TF knockout mutant phenotypes are consistent with model predictions. Together, our results support that this network regulates iron homeostasis despite variation in extracellular iron levels, consistent with dynamical properties of interlocking feedback architecture in eukaryotes. These results suggest that archaea use bacterial-type TFs in a eukaryotic regulatory network topology to adapt to harsh environments.


Radiobiological impact of planning techniques for prostate cancer in terms of tumor control probability and normal tissue complication probability.
The radiobiological models describe the effects of the radiation treatment on cancer and healthy cells, and the radiobiological effects are generally characterized by the tumor control probability (TCP) and normal tissue complication probability (NTCP). The purpose of this study was to assess the radiobiological impact of RapidArc planning techniques for prostate cancer in terms of TCP and normal NTCP. A computed tomography data set of ten cases involving low-risk prostate cancer was selected for this retrospective study. For each case, two RapidArc plans were created in Eclipse treatment planning system. The double arc (DA) plan was created using two full arcs and the single arc (SA) plan was created using one full arc. All treatment plans were calculated with anisotropic analytical algorithm. Radiobiological modeling response evaluation was performed by calculating Niemierko's equivalent uniform dose (EUD)-based Tumor TCP and NTCP values. For prostate tumor, the average EUD in the SA plans was slightly higher than in the DA plans (78.10 Gy vs. 77.77 Gy; P = 0.01), but the average TCP was comparable (98.3% vs. 98.3%; P = 0.01). In comparison to the DA plans, the SA plans produced higher average EUD to bladder (40.71 Gy vs. 40.46 Gy; P = 0.03) and femoral heads (10.39 Gy vs. 9.40 Gy; P = 0.03), whereas both techniques produced NTCP well below 0.1% for bladder (P = 0.14) and femoral heads (P = 0.26). In contrast, the SA plans produced higher average NTCP compared to the DA plans (2.2% vs. 1.9%; P = 0.01). Furthermore, the EUD to rectum was slightly higher in the SA plans (62.88 Gy vs. 62.22 Gy; P = 0.01). The SA and DA techniques produced similar TCP for low-risk prostate cancer. The NTCP for femoral heads and bladder was comparable in the SA and DA plans; however, the SA technique resulted in higher NTCP for rectum in comparison with the DA technique.


Knowledge, perception and practice towards oxytocin stability and quality: A qualitative study of stakeholders in three resource-limited countries.
Oxytocin is the gold standard drug for the prevention of postpartum haemorrhage, but limitations in cold chain systems in resource-constrained settings can severely compromise the quality of oxytocin product available in these environments. This study investigated the perspectives and practices of stakeholders in low and lower-middle income countries towards oxytocin, its storage requirements and associated barriers, and the quality of product available. Qualitative inquiries were undertaken in Ethiopia, India and Myanmar, where data was collected through Focus Group Discussions (FGDs) and In-Depth Interviews (IDIs). A total of 12 FGDs and 106 IDIs were conducted with 158 healthcare providers (pharmacists, midwives, nurses, doctors and obstetricians) and 40 key informants (supply chain experts, program managers and policy-makers). Direct observations of oxytocin storage practices and cold chain resources were conducted at 51 healthcare facilities. Verbatim transcripts of FGDs and IDIs were translated to English and analysed according to a thematic content analysis framework. Stakeholder awareness of oxytocin heat sensitivity and the requirement for cold storage of the drug was widespread in Ethiopia but more limited in Myanmar and India. A consistent finding across all study regions was the significant barriers to maintaining a consistent cold chain, with the lack of refrigeration facilities and unreliability of electricity cited as major challenges. Perceptions of compromised oxytocin quality were expressed by some stakeholders in each country. Knowledge of the heat sensitivity of oxytocin and the potential impacts of inconsistent cold storage on product quality is not widespread amongst healthcare providers, policy makers and supply chain experts in Myanmar, Ethiopia and India. Targeted training and advocacy messages are warranted to emphasise the importance of cold storage to maintain oxytocin quality.


Lymphatic osteopathic manipulative treatment reduces duration of deltoid soreness after Pfizer/BioNTech COVID-19 vaccine.
Pfizer-BioNTech BNT162b2 is one of the three U.S. Food and Drug Administration (FDA)-approved vaccines for the prevention of COVID-19. Its most common side effect, injection site pain, occurs because of locally recruited inflammatory mediators and is mitigated by the lymphatic system. Side effects may discourage individuals from receiving vaccines; therefore, reducing the duration of injection site pain can promote vaccination compliance. Osteopathic manipulative treatments (OMT) can directly affect the physiology underlying muscle soreness; however, there is currently no literature that supports the use of OMT in this scenario. In this case report, an otherwise healthy male presented with acute left deltoid soreness after receiving the Pfizer COVID-19 vaccine. The pain began 5 h prior to the visit. Three hours after being treated with lymphatic OMT, the severity of the pain was significantly reduced and was alleviated 8h after onset in comparison to the median duration of 24-48 h. He received his second dose 3 weeks later. This case report can provide future studies with the groundwork for further investigating the role of OMT in treating postvaccination muscle soreness, which can improve patient satisfaction and potentially promote vaccination compliance.


Determinants of weddellite formation: chondroitin sulfates and citrate determine weddellite formation in vitro.
In synthetic urine (SU), addition of oxalate tends to form monohydrates of calcium oxalate. However, addition of oxalate to natural urine preferably forms calcium oxalate dihydrate (COD). Urine apparently contains a determinant for COD formation. To identify the determinant, the effects of pH, temperature, oxalate, calcium, urate, citrate, magnesium, sulfate and chondroitin sulfates (CS) on calcium oxalate crystal formation were studied. Lower temperatures, higher oxalate concentrations and higher pH favored COD formation in a SU. Mixed CS in the presence of citrate were the most decisive determinant of COD formation. Substitution of CS for agar and gelatin produced similar results, indicating that the colloidal effect of the macromolecules determines COD formation. Identification of the determinants led to a simple, reproducible method of COD formation in SU without natural urine. Addition of strontium to SU resulted in dodecahedral bipyramids. Interpenetration twinning of bipyramids occur within seconds of the crystal formation.


Palatal height and dental arch dimensions in Turner syndrome karyotypes.
The aim of this project was to study the impact from Turner syndrome (TS) karyotype and age on dental arch morphology and palatal height and to compare the variables in TS with reference data from non-TS females with normal occlusion. Plaster casts from 76 females with TS (6-50 years) were analysed with respect to dentoalveolar arch dimensions and palatal height. The TS females were divided into the karyotype categories: i) 45,X ii) 45,X/46,XX iii) isochromosome, and iv) other. The 45,X/46,XX karyotype exhibited fewer statistically significant variables differing from the reference group compared with other karyotypes. TS females showed increased dentoalveolar depths, decreased maxillary but increased mandibular width, decreased posterior segments, and decreased mandibular circumference compared with the reference group. In opposition to previous reports, the palatal height did not differ compared with non-TS females. Age had an impact on nine of the variables. We conclude that the present dental arch deviations are reflecting the high frequency of malocclusions reported in TS and the subsequent need for orthodontic treatment, which might possibly be lower in the 45,X/46,XX karyotype. The palatal height did not differ from the reference group, but instead the narrow maxilla might contribute to an illusion of a higher palate. We therefore suggest using the nomination 'narrow palatal vault' instead of the commonly used term 'high palatal vault'.


Observational cross-sectional study of nasal staphylococcal species of medical students of diverse geographical origin, prior to healthcare exposure: prevalence of SCCmec, fusC, fusB and the arginine catabolite mobile element (ACME) in the absence of selective antibiotic pressure.
The aim of this study was to investigate co-located nasal Staphylococcus aureus and coagulase-negative staphylococci (CoNS) (mainly Staphylococcus epidermidis), recovered from healthy medical students in their preclinical year, prior to exposure to the healthcare environment, for the carriage of genes and genetic elements common to both species and that may contribute to S. aureus and methicillin-resistant S. aureus (MRSA) evolution. Prospective observational cross-sectional study. Carriage of antimicrobial resistance and virulence-associated genes in the absence of significant antibiotic selective pressure was investigated among healthy medical students from geographically diverse origins who were nasally co-colonised with S. aureus and CoNS. Clonal lineages of S. aureus isolates were determined. Dublin-based international undergraduate medical students. Nasal S. aureus carriage was identified in 137/444 (30.8%) students of whom nine (6.6%) carried MRSA (ST59-MRSA-IV (6/9), CC1-MRSA-V-SCCfus (3/9)). The genes mecA, fusB, ileS2, qacA/qacC and the arginine catabolic mobile element-arc were detected among colonising nasal staphylococci and had a significantly greater association with CoNS than S. aureus. The rate of co-carriage of any of these genes in S. aureus/CoNS pairs recovered from the same individual was <1%. The relatively high prevalence of these genes among CoNS of the healthy human flora in the absence of significant antibiotic selective pressure is of interest. Further research is required to determine what factors are involved and whether these are modifiable to help prevent the emergence and spread of antibiotic resistance among staphylococci.


Autoantibodies in myositis.
The discovery of novel autoantigen systems related to idiopathic inflammatory myopathies (collectively referred to as myositis) in adults and children has had major implications for the diagnosis and management of this group of diseases across a wide range of medical specialties. Traditionally, autoantibodies found in patients with myositis are described as being myositis-specific autoantibodies (MSAs) or myositis-associated autoantibodies (MAAs), depending on their prevalence in other, related conditions. However, certain MSAs are more closely associated with extramuscular manifestations, such as skin and lung disease, than with myositis itself. It is very rare for more than one MSA to coexist in the same individual, underpinning the potential to use MSAs to precisely define genetic and disease endotypes. Each MSA is associated with a distinctive pattern of disease or phenotype, which has implications for diagnosis and a more personalized approach to therapy. Knowledge of the function and localization of the autoantigenic targets for MSAs has provided key insights into the potential immunopathogenic mechanisms of myositis. In particular, evidence suggests that the alteration of expression of a myositis-related autoantigen by certain environmental influences or oncogenesis could be a pivotal event linking autoantibody generation to the development of disease.


Antifungal activities of the essential oil and its fractions rich in sesquiterpenes from leaves of Casearia sylvestris Sw.
Casearia genus (Salicaceae) is found in sub-tropical and tropical regions of the world and comprises about 160-200 species. It is a medicinal plant used in South America, also known as "guaçatonga", "erva-de-tiú", "cafezinho-do-mato". In Brazil, there are about 48 species and 12 are registered in the State of Rio de Janeiro, including Casearia sylvestris Sw. There are many studies related to the chemical profile and cytotoxic activities of extracts from these plants, although few studies about the antifungal potential of the essential oil have been reported. In this work, we have studied the antifungal properties of the essential oil of C. sylvestris leaves, as well as of their fractions, against four yeasts (Saccharomyces cerevisae, Candida albicans, C. glabrata and C. krusei) for the first time. The chemical analysis of the essential oil revealed a very diversified (n = 21 compounds) volatile fraction composed mainly of non-oxygenated sesquiterpenes (72.1%). These sesquiterpenes included α-humulene (17.8%) and α-copaene (8.5%) and the oxygenated sesquiterpene spathulenol (11.8%) were also identified. Monoterpenes were not identified. The fractions are mainly composed of oxygenated sesquiterpenes, and the most active fraction is rich in the sesquiterpene 14-hydroxy -9-epi-β-caryophyllene. This fraction was the most effective in inhibiting the growth of three yeast strains.


PGMS: a case study of collecting PDA-based geo-tagged malaria-related survey data.
Using mobile devices, such as personal digital assistants (PDAs), smartphones, tablet computers, etc., to electronically collect malaria-related field data is the way for the field questionnaires in the future. This case study seeks to design a generic survey framework PDA-based geo-tagged malaria-related data collection tool (PGMS) that can be used not only for large-scale community-level geo-tagged electronic malaria-related surveys, but also for a wide variety of electronic data collections of other infectious diseases. The framework includes two parts: the database designed for subsequent cross-sectional data analysis and the customized programs for the six study sites (two in Kenya, three in Indonesia, and one in Tanzania). In addition to the framework development, we also present our methods used when configuring and deploying the PDAs to 1) reduce data entry errors, 2) conserve battery power, 3) field install the programs onto dozens of handheld devices, 4) translate electronic questionnaires into local languages, 5) prevent data loss, and 6) transfer data from PDAs to computers for future analysis and storage. Since 2008, PGMS has successfully accomplished quite a few surveys that recorded 10,871 compounds and households, 52,126 persons, and 17,100 bed nets from the six sites. These numbers are still growing.


Inferring biochemical reaction pathways: the case of the gemcitabine pharmacokinetics.
The representation of a biochemical system as a network is the precursor of any mathematical model of the processes driving the dynamics of that system. Pharmacokinetics uses mathematical models to describe the interactions between drug, and drug metabolites and targets and through the simulation of these models predicts drug levels and/or dynamic behaviors of drug entities in the body. Therefore, the development of computational techniques for inferring the interaction network of the drug entities and its kinetic parameters from observational data is raising great interest in the scientific community of pharmacologists. In fact, the network inference is a set of mathematical procedures deducing the structure of a model from the experimental data associated to the nodes of the network of interactions. In this paper, we deal with the inference of a pharmacokinetic network from the concentrations of the drug and its metabolites observed at discrete time points. The method of network inference presented in this paper is inspired by the theory of time-lagged correlation inference with regard to the deduction of the interaction network, and on a maximum likelihood approach with regard to the estimation of the kinetic parameters of the network. Both network inference and parameter estimation have been designed specifically to identify systems of biotransformations, at the biochemical level, from noisy time-resolved experimental data. We use our inference method to deduce the metabolic pathway of the gemcitabine. The inputs to our inference algorithm are the experimental time series of the concentration of gemcitabine and its metabolites. The output is the set of reactions of the metabolic network of the gemcitabine. Time-lagged correlation based inference pairs up to a probabilistic model of parameter inference from metabolites time series allows the identification of the microscopic pharmacokinetics and pharmacodynamics of a drug with a minimal a priori knowledge. In fact, the inference model presented in this paper is completely unsupervised. It takes as input the time series of the concetrations of the parent drug and its metabolites. The method, applied to the case study of the gemcitabine pharmacokinetics, shows good accuracy and sensitivity.


Dental Workforce Trends: A National Study of Gender Diversity and Practice Patterns.
The dental workforce is increasingly gender diverse. This study analyzed gender differences in dental practice using the American Dental Association's 2010-2016 Masterfile and the 2017 Survey of Dental Practice. Between 2010 and 2016, the proportion of women working in dentistry increased from 24.5% to 29.8%. Overall, female dentists were more racially/ethnically diverse, more likely to be foreign-trained, and more likely to work in pediatric dentistry than male dentists. The likelihood of female dentists working as employees, part-time, and/or in metropolitan areas was 1.2 to 4.2 times greater compared with male dentists. Female solo practitioners were 1.2 to 1.8 times more likely to provide services to children and patients covered by public insurance than male solo practitioners. Gender diversification in dentistry and other factors, including generational differences and changes in the dental service delivery system and public policy, will continue to reshape the delivery of oral health services.


Patient related outcome measures for breast augmentation mammoplasty: a systematic review.
We review the current literature for validated patient related outcome measures (PROM) in breast augmentation mammoplasty (BAM). Using Medline search between 1966 to 2018, using the search strategy ("patient reported outcome measure" OR "surveys or questionnaires") AND "breast" AND ("augment" OR "implant") was performed. A manual search with Google Scholar using the search term "Patient Reported Outcome Measures in Bilateral Augmentation Mammaplasty" was also performed. Once the search yielded its results, a further search of bibliographic references within the articles was also performed. The Medline computer search produced 72 results, with a Google Scholar search yielding two results and a bibliographic search of all articles revealing a further single result. Ten studies were included as they used validated PROM. Three articles used the same PROM (Breast-Q) and seven used different PROM, therefore 8 validated PROM were discovered. Bilateral augmentation mammoplasty has been demonstrated to confer an increase in patient reported outcomes in domains of satisfaction with breasts and psychological well-being. There is some decrease in physical well-being following this procedure. Validated PROMs provide objective data relating to different aspects of BAM. Combined with traditional surgeon-based outcome measures and implant registry data, they may provide a more comprehensive insight into the patient journey.


High-throughput DNA barcoding of oligochaetes for abundance-based indices to assess the biological quality of sediments in streams and lakes.
Aquatic oligochaete communities are valuable indicators of the biological quality of sediments in streams and lakes, but identification of specimens to the species level based on morphological features requires solid expertise in taxonomy and is possible only for a fraction of specimens present in a sample. The identification of aquatic oligochaetes using DNA barcodes would facilitate their use in biomonitoring and allow a wider use of this taxonomic group for ecological diagnoses. Previous approaches based on DNA metabarcoding of samples composed of total sediments or pools of specimens have been proposed for assessing the biological quality of ecosystems, but such methods do not provide precise information on species abundance, which limits the value of resulting ecological diagnoses. Here, we tested how a DNA barcoding approach based on high-throughput sequencing of sorted and genetically tagged specimens performed to assess oligochaete species diversity and abundance and the biological quality of sediments in streams and lakes. We applied both molecular and morphological approaches at 13 sites in Swiss streams and at 7 sites in Lake Geneva. We genetically identified 33 or 66 specimens per site. For both approaches, we used the same index calculations. We found that the ecological diagnoses derived from the genetic approach matched well with those of the morphological approach and that the genetic identification of only 33 specimens per site provided enough ecological information for correctly estimating the biological quality of sediments in streams and lakes.


Magnolol and Honokiol Attenuate Apoptosis of Enterotoxigenic Escherichia Coli-Induced Intestinal Epithelium by Maintaining Secretion and Absorption Homeostasis and Protecting Mucosal Integrity.
BACKGROUND The cortex of Magnolia officinalis has long been used as an element of traditional Chinese medicine for the treatment of anxiety, chronic bronchitis, and gastrointestinal dysfunction. This study aimed to elucidate the underlying mechanism of its functional ingredients (magnolol and honokiol) in modifying the secretion and absorption homeostasis and protecting mucosal integrity in an Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea mouse model. MATERIAL AND METHODS This study established a diarrhea mouse model infected by ETEC at a dosage of 0.02 ml/g live body weight (BW) in vivo. Magnolol or honokiol was followed by an intraperitoneal administration at dosages of 100, 300, and 500 mg/kg BW according to a 3×3 factorial arrangement. The useful biomarkers for evaluating the integrity of intestinal tract and histologic injury were analyzed and morphological development (including villus height, crypt depth, and ratio of villus height to crypt depth) and the expressions of inflammatory cytokines were determined by real-time PCR. RESULTS The results showed that magnolol and honokiol (500 mg/kg BW) reduced the concentrations of NO, DAO, and DLA, and iNOS activity, and the mRNA expressions of the interferon gamma (IFN-γ) and interleukin 10 (IL-10), and inhibited intestinal epithelial cell apoptosis. Magnolol and honokiol (300 mg/kg BW) elongated the villus height and crypt depth and decreased the number of goblet cells and the ratio of villus height to crypt depth. CONCLUSIONS The current results indicate that magnolol and honokiol enhance the intestinal anti-inflammatory capacities, elongate the villus height and crypt depth, and reduce goblet cell numbers to inhibit the intestinal epithelium apoptosis and effectively protect the intestinal mucosa. These results show that magnolol and honokiol protect the intestinal mucosal integrity and regulate gastrointestinal dysfunction.


Field evaluation of seven products to control cyanobacterial blooms in aquaculture.
Harmful algal blooms negatively impact water quality in hypereutrophic systems that are common in aquaculture. However, few algaecides are approved for use in food-fish aquaculture. This study assessed the effectiveness of seven products, including hydrogen peroxide (as a concentrated liquid or in granular form (PAK-27)), peracetic acid (as VigorOx SP-15 and Peraclean), copper (as copper sulfate in unchelated (powder) or chelated (Captain) forms), and a clay-based product (as Phoslock) on phytoplankton (including cyanobacteria) and zooplankton biomass. Each product was tested in a 14-day laboratory and 35-day field experiment to assess their short- and long-term performance. Although some products (i.e., copper-based and liquid hydrogen peroxide) quickly reduced phytoplankton, effects were short-lived given that chlorophyll concentrations returned to starting concentrations within 21 days. In contrast, all but one product (i.e., concentrated liquid hydrogen peroxide) maintained low phycocyanin concentrations for 35 days. Zooplankton biomass trends showed large, negative effects for most algaecides; however, zooplankton rebounded for most treatments except for copper-based products. In general, copper-based products remain the most efficient and cheapest choice to reduce total phytoplankton biomass in aquaculture systems. However, peracetic acid-based products effectively and quickly reduced cyanobacteria while having marginal effects on beneficial algae and zooplankton. Such algaecides could be effective alternatives to copper-based products for aquaculture farmers.


Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer.
Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments. ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle. The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women.


Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy.
Total triterpenic fraction of Centella asiatica (TTFCA) is effective in improving venous wall alterations in chronic venous hypertension and in protecting the venous endothelium. TTFCA is active on connective tissue modulation, improves the synthesis of collagen and other tissue proteins by modulating the action of fibroblasts in the vein wall, and stimulates collagen remodeling in and around the venous wall. This is due to the modulating action of TTFCA on fibroblasts as shown by experiments on the growth of human embryonal fibroblasts. TTFCA has a moderate in-vitro and in-vivo stimulating effect on collagen synthesis and, at higher dosages, an inhibition on the synthesis of collagen and acid mucopolysaccharides. Studies have indicated the role of TTFCA on the synthesis of specific venous wall elements by cell cultures of human embryonal fibroblasts. The tissue-stimulating action is shown by the increased collagen production independent from the stimulation of cell proliferation (this differentiates the action of TTFCA from cell growth factors). TTFCA is active on the microcirculation in venous and diabetic microangiopathy. Signs and symptoms of venous hypertension and edema are improved by treatment. The remodeling on collagen synthesis could be one of the possible mechanisms of actions of TTFCA in the remodeling of echolucent (soft; therefore, with risk of thrombosis and embolization) plaques at the carotid and femoral bifurcation. This compound is safe and well tolerated. In conclusion, several actions of TTFCA in vascular diseases makes the use of this compound very interesting in venous and arterial problems.


Efficient preparation and analysis of membrane and membrane protein systems.
Molecular dynamics (MD) simulations have become a highly important technique to consider lipid membrane systems, and quite often they provide considerable added value to laboratory experiments. Rapid development of both software and hardware has enabled the increase of time and size scales reachable by MD simulations to match those attainable by several accurate experimental techniques. However, until recently, the quality and maturity of software tools available for building membrane models for simulations as well as analyzing the results of these simulations have seriously lagged behind. Here, we discuss the recent developments of such tools from the end-users' point of view. In particular, we review the software that can be employed to build lipid bilayers and other related structures with or without embedded membrane proteins to be employed in MD simulations. Additionally, we provide a brief critical insight into force fields and MD packages commonly used for membrane and membrane protein simulations. Finally, we list analysis tools that can be used to study the properties of membrane and membrane protein systems. In all these points we comment on the respective compatibility of the covered tools. We also share our opinion on the current state of the available software. We briefly discuss the most commonly employed tools and platforms on which new software can be built. We conclude the review by providing a few ideas and guidelines on how the development of tools can be further boosted to catch up with the rapid pace at which the field of membrane simulation progresses. This includes improving the compatibility between software tools and promoting the openness of the codes on which these applications rely. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.


A systematic review of complications and failures associated with medial patellofemoral ligament reconstruction for recurrent patellar dislocation.
Patellofemoral instability affects activities of daily living and hinders athletic participation. Over the past 2 decades, more attention has been paid to medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent patellar dislocations/subluxations. Numerous techniques have been reported; however, there is no consensus regarding optimal reconstruction. This study sought to report on the various techniques for MPFL reconstruction described in the literature and to assess the rate of complications associated with the procedure. Meta-analysis. A systematic review of the literature was performed in early October 2010 using keywords "medial patellofemoral ligament," "MPFL," "reconstruction," "complication(s)," and "failure(s)." Articles meeting the inclusion criteria were reviewed. Graft choice, surgical technique, outcome measures, and complications were recorded and organized in a database. Descriptive statistical analysis was performed on the data collected. Twenty-five articles were identified and reviewed. A total of 164 complications occurred in 629 knees (26.1%). These adverse events ranged from minor to major including patellar fracture, failures, clinical instability on postoperative examination, loss of knee flexion, wound complications, and pain. Twenty-six patients returned to the operating room for additional procedures. Medial patellofemoral ligament reconstruction has a high rate of success for patients with patellofemoral instability; however, the complication rate of 26.1% associated with this procedure is not trivial. This study quantified complications and documented the variety of complications reported in outcomes-based literature.


Novel ultrasensitive homogeneous electrochemical aptasensor based on dsDNA-templated copper nanoparticles for the detection of ractopamine.
Herein, we describe a novel homogenous electrochemical aptasensor for the ultrasensitive detection of ractopamine (RAC) based on the signal amplification of a hairpin DNA cascade amplifier (HDCA) and electrocatalysis of dsDNA-templated copper nanoparticles. The present electrochemical aptasensor employs a label-free "turn-on" strategy with enzyme-free amplification. Briefly, the target RAC triggers the HDCA autocatalytic process of two ingeniously designed complementary hairpin DNA, which results in the formation of nucleic-acid-stabilized copper nanoparticles (dsDNA/CuNPs). Thus, with the mimic oxidase catalytic character of the dsDNA/CuNPs and enzyme-free hairpin DNA cascade amplifier reactions, a remarkable electrochemical response can be achieved, which is dependent on the concentration of the target RAC. Taking advantage of the highly amplified efficiency of trigger recycling and the excellent electrochemical catalytic response of dsDNA/CuNPs, the proposed strategy is capable of detecting RAC ultrasensitively. Under optimal conditions, the electrochemical signal increases with an increase in the target RAC concentration in the wide dynamic range from 1 × 10-12 M to 3 × 10-7 M with a detection limit (LOD) of 3 × 10-13 M. The proposed system does not need any sophisticated operation procedures such as electrode immobilization and expensive labeling. Therefore, the devised label-free and enzyme-free amplification homogeneous electrochemical aptasensor strategy may become an alternative method for the simple, sensitive, and selective detection of biological small molecules, proteins, nucleic acids and nuclease activity.


A numerical framework for interstitial fluid pressure imaging in poroelastic MRE.
A numerical framework for interstitial fluid pressure imaging (IFPI) in biphasic materials is investigated based on three-dimensional nonlinear finite element poroelastic inversion. The objective is to reconstruct the time-harmonic pore-pressure field from tissue excitation in addition to the elastic parameters commonly associated with magnetic resonance elastography (MRE). The unknown pressure boundary conditions (PBCs) are estimated using the available full-volume displacement data from MRE. A subzone-based nonlinear inversion (NLI) technique is then used to update mechanical and hydrodynamical properties, given the appropriate subzone PBCs, by solving a pressure forward problem (PFP). The algorithm was evaluated on a single-inclusion phantom in which the elastic property and hydraulic conductivity images were recovered. Pressure field and material property estimates had spatial distributions reflecting their true counterparts in the phantom geometry with RMS errors around 20% for cases with 5% noise, but degraded significantly in both spatial distribution and property values for noise levels > 10%. When both shear moduli and hydraulic conductivity were estimated along with the pressure field, property value error rates were as high as 58%, 85% and 32% for the three quantities, respectively, and their spatial distributions were more distorted. Opportunities for improving the algorithm are discussed.


Structures of cefradine dihydrate and cefaclor dihydrate from DFT-D calculations.
The crystal structure of cefradine dihydrate, C16H19N3O4S·2H2O, is considered in the pharmaceutical sciences to be the epitome of an isolated-site hydrate. The structure from single-crystal X-ray data was described in 1976, but atomic coordinates were not published. The atomic coordinates are determined here by combining the information available from the published single-crystal data with a dispersion-corrected density functional theory (DFT-D) method that has been validated to reproduce molecular crystal structures very accurately. Additional proof for the correctness of the structure comes from comparison with cefaclor dihydrate, C15H14ClN3O4S·2H2O, which is isomorphous and for which more complete single-crystal data are available. H-atom positions have not previously been published for either compound. The DFT-D calculations confirm that both cefradine and cefaclor are present in the zwitterionic form in the two dihydrate structures. A potential ambiguity concerning the orientation of the cyclohexadienyl ring in cefradine dihydrate is also clarified, and on the basis of the calculated energies it is shown that disorder should not be expected at room temperature. The DFT-D methods can be applied to recover full structural data in cases where only partial information is available, and where it may not be possible or desirable to obtain new experimental data.


Modelling the ecological niche of hookworm in Brazil based on climate.
The distribution of hookworm in schistosomiasis-endemic areas in Brazil was mapped based on climate suitability. Known biological requirements of hookworm were fitted to data in a monthly long-term normal climate grid (18 x 18 km) using geographical information systems. Hookworm risk models were produced using the growing degree day (GDD) water budget (WB) concept. A moisture-adjusted model (MA-GDD) was developed based on accumulation of monthly temperatures above a base temperature of 15 °C (below which there is no lifecycle progression of Necator americanus) conditional on concurrent monthly values (rain/potential, evapotranspiration) of over 0.4. A second model, designated the gradient index, was calculated based on the monthly accumulation of the product of GDD and monthly WB values (GDD x WB). Both parameters had a significant positive correlation to hookworm prevalence. In the northeastern part of Brazil (the Caatinga), low hookworm prevalence was due to low soil moisture content, while the low prevalence in southern Brazil was related to low mean monthly temperatures. Both environmental temperature and soil moisture content were found to be important parameters for predicting the prevalence of N. americanus.


[Development and evaluation of food supplements for the education, health, and nutrition program].
To develop and evaluate nutritional supplements destined to a program of social assistance. In the design of the nutritional supplements a series of criteria were considered including nutrient composition, physicochemical properties and feasibility of production and utilization. Final products were initially evaluated to determine the level of acceptance in 40 children, 52 pregnant women and 62 lactating women in Mexico City. A community trial was also carried out to determine acceptance and consumption in 108 children and 128 women from a rural community in the state of Morelos. The specific formulation and technical processes of production of the nutritional supplements are presented. Products proved to be widely accepted, with average scores of 4.11-4.29 for the children's beverage, and 3.98-4.15 for a more viscous pap (range of scores was 1 to 5). Products for women received average scores from 4.75 to 5.70 in pregnant and from 4.8 to 5.4 in lactating women (range of scores from 1 to 7). In the community trial, supplements were very well accepted. Average consumption was > 75% among children and > 98% among women. Mean energy intake from supplements was 244 Kcal/day for women, and for children, 168 Kcal/day with the pap and 147 Kcal/day with the beverage. Consumption was consistent in all cases along the study. Nine nutritional supplements were developed and evaluated which comply with the necessary nutritional, physicochemical and hygienic characteristics for the target population, besides being relatively simple to prepare, and widely well accepted and consumed.


Cracking the bioelectric code: Probing endogenous ionic controls of pattern formation.
Patterns of resting potential in non-excitable cells of living tissue are now known to be instructive signals for pattern formation during embryogenesis, regeneration and cancer suppression. The development of molecular-level techniques for tracking ion flows and functionally manipulating the activity of ion channels and pumps has begun to reveal the mechanisms by which voltage gradients regulate cell behaviors and the assembly of complex large-scale structures. A recent paper demonstrated that a specific voltage range is necessary for demarcation of eye fields in the frog embryo. Remarkably, artificially setting other somatic cells to the eye-specific voltage range resulted in formation of eyes in aberrant locations, including tissues that are not in the normal anterior ectoderm lineage: eyes could be formed in the gut, on the tail, or in the lateral plate mesoderm. These data challenge the existing models of eye fate restriction and tissue competence maps, and suggest the presence of a bioelectric code-a mapping of physiological properties to anatomical outcomes. This Addendum summarizes the current state of knowledge in developmental bioelectricity, proposes three possible interpretations of the bioelectric code that functionally maps physiological states to anatomical outcomes, and highlights the biggest open questions in this field. We also suggest a speculative hypothesis at the intersection of cognitive science and developmental biology: that bioelectrical signaling among non-excitable cells coupled by gap junctions simulates neural network-like dynamics, and underlies the information processing functions required by complex pattern formation in vivo. Understanding and learning to control the information stored in physiological networks will have transformative implications for developmental biology, regenerative medicine and synthetic bioengineering.


Fatigue in psoriasis: a phenomenon to be explored.
Fatigue is a prevalent and substantial phenomenon in many patients with chronic inflammatory diseases, often rated by patients as the most troublesome symptom and aspect of their disease. It frequently interferes with physical and social functions and may lead to social withdrawal, long-standing sick leave and disability. Although psychological and somatic factors such as depression, sleep disorders, pain and anaemia influence fatigue, the underlying pathophysiological mechanisms by which fatigue is generated and regulated are largely unknown. Increasing evidence points towards a genetic and molecular basis for fatigue as part of the innate immune system and cellular stress responses. Few studies have focused on fatigue in dermatological diseases. Most of these studies describe fatigue as a phenomenon related to psoriatic arthritis and describe the beneficial effects of biological agents on fatigue observed in clinical studies. It is therefore possible that this problem has been underestimated and deserves more attention in the dermatological community. In this review, we provide a definition and explanation for chronic fatigue, describe some commonly used instruments for measuring fatigue, and present hypothetical biological mechanisms with an emphasis on activation of the innate immune system and oxidative stress. An overview of relevant clinical studies covering the theme 'psoriasis and fatigue' is given.


Ectopic expression of BABY BOOM triggers a conversion from vegetative to embryonic growth.
The molecular mechanisms underlying the initiation and maintenance of the embryonic pathway in plants are largely unknown. To obtain more insight into these processes, we used subtractive hybridization to identify genes that are upregulated during the in vitro induction of embryo development from immature pollen grains of Brassica napus (microspore embryogenesis). One of the genes identified, BABY BOOM (BBM), shows similarity to the AP2/ERF family of transcription factors and is expressed preferentially in developing embryos and seeds. Ectopic expression of BBM in Arabidopsis and Brassica led to the spontaneous formation of somatic embryos and cotyledon-like structures on seedlings. Ectopic BBM expression induced additional pleiotropic phenotypes, including neoplastic growth, hormone-free regeneration of explants, and alterations in leaf and flower morphology. The expression pattern of BBM in developing seeds combined with the BBM overexpression phenotype suggests a role for this gene in promoting cell proliferation and morphogenesis during embryogenesis.


Functional and morphologic alterations after anterior or inferior repositioning of the maxilla.
The purpose of this investigation was 1) to compare functional and morphologic measurements between controls and patients scheduled for anterior or inferior repositioning of the maxilla, and 2) to examine how these patients' oral function adapted after surgery. Nine male patients undergoing anterior and/or inferior repositioning of the maxilla were compared with 26 male controls preoperatively and up to 3 years after surgery. Measures of skeletal morphology, mandibular range of motion, maximum voluntary bite force, and levels of electromyographic (EMG) activity in the anterior and posterior temporalis and masseter muscles during isometric bites were made on all subjects over time. One-way ANOVA was used to compare the controls, the patients before surgery, and the patients after surgery. Before surgery, most of the patients had morphologic characteristics of mandibular prognathism and maxillary retrognathism. Surgery made the patients' skeletal morphology similar to controls except for mandibular length, upper facial height, and palatal plane angle, which were significantly greater than those of controls. There were no significant differences in jaw muscle mechanical advantage between controls and patients either before or after surgery. Hypomobility of the jaw was apparent at 6 weeks and 6 months after surgery, but returned to normal values within 1 to 2 years. Before surgery, the patients had maximum voluntary bite forces significantly less than those of controls. Bite forces in patients steadily increased after surgery, approaching significantly higher values than those of controls. Before surgery, patients' muscle activity levels per unit of bite force were not significantly different from those of controls. Most of the patients' muscle activity levels per unit of bite forces at all bite positions showed no significant change after surgery. The results of this study suggest that anterior or inferior repositioning of maxilla produces some significant functional benefits in patients.


Cancer prevention through weight control-where are we in 2020?
Growing data from epidemiological studies highlight the association between excess body fat and cancer incidence, but good indicative evidence demonstrates that intentional weight loss, as well as increasing physical activity, offers much promise as a cost-effective approach for reducing the cancer burden. However, clear gaps remain in our understanding of how changes in body fat or levels of physical activity are mechanistically linked to cancer, and the magnitude of their impact on cancer risk. It is important to investigate the causal link between programmes that successfully achieve short-term modest weight loss followed by weight-loss maintenance and cancer incidence. The longer-term impact of weight loss and duration of overweight and obesity on risk reduction also need to be fully considered in trial design. These gaps in knowledge need to be urgently addressed to expedite the development and implementation of future cancer-control strategies. Comprehensive approaches to trial design, Mendelian randomisation studies and data-linkage opportunities offer real possibilities to tackle current research gaps. In this paper, we set out the case for why non-pharmacological weight-management trials are urgently needed to support cancer-risk reduction and help control the growing global burden of cancer.


Integral imaging system using a dual-mode technique.
A new integral imaging system is proposed that uses a dual-mode technique, in which the elemental lens of the lens array is used not only as a convex lens but also as a convex mirror. The integral imaging system using dual modes can represent the real and the virtual integrated images simultaneously with improved viewing parameters. The lens array coated with thin aluminum is used to balance the ratio between the reflectance and the transmittance of lens array. The feasibility of the proposal is proved by the experiments.


Commentary on Almassalha et al., "The Greater Genomic Landscape: The Heterogeneous Evolution of Cancer".
In this issue of Cancer Research, Almassalha and colleagues have proposed a new concept of the development of malignancy, that of the greater genomic landscape. They propose a stressor-related exploration of intracellular genomic sites as a response mechanism. This process can express sites with beneficial or deleterious effects, among them those that promote cell proliferation. They point out that their conception is broader, although certainly inclusive, of the process of gene induction. The authors view the physical process of chromatin reorganization as central to the exploration of the genomic landscape. Accordingly, they advocate the development of agents to limit chromatin structural modification as a chemotherapeutic approach in cancer. We found their theory relevant to understand the phenotypic heterogeneity of malignancy, particularly in familial cancer syndromes. For example, the familial atypical multiple mole melanoma (FAMMM) syndrome, related to a gene mutation, is characterized by a diversity of melanocytic lesions, only some of which become malignant melanoma. This new conceptualization can do much to increase understanding of the diversity of malignancy in families with hereditary cancer. Cancer Res; 76(19); 5602-4. ©2016 AACR.


Enteric viruses in New Zealand drinking-water sources.
This study determined whether human pathogenic viruses are present in two New Zealand surface waters that are used as drinking-water sources. Enteric viruses were concentrated using hollow-fibre ultrafiltration and detected using PCR for adenovirus (AdV), and reverse transcription PCR for norovirus (NOV) genogroups I-III, enterovirus, rotavirus (RoV) and hepatitis E virus (HEV). Target viruses were detected in 106/109 (97%) samples, with 67/109 (61%) samples positive for three or more viral types at any one time. AdV, NoV and ROV were detected the most frequently, and HEV the least frequently. Human NoV was not usually associated with animal NOV. Our results suggest that New Zealand would be well served by assessing the ability of drinking-water treatment plants to remove viruses from the source waters, and that this assessment could be based on the viral concentration of AdV-NoV-RoV. The long-term aim of our work is to use this information to estimate the risk of waterborne viral infection.