Monitoring Population Size, Activity, and Distribution of gfp-luxAB-Tagged Pseudomonas fluorescens SBW25 during Colonization of Wheat.
Increasingly, focus has been directed towards the use of microorganisms as biological control agents to combat fungal disease, as an alternative to chemical fungicides. Pseudomonas fluorescens SBW25 is one bacterial strain that has been demonstrated to promote plant growth by biocontrol of pathogenic fungi. To understand the mode of action of this bacterium, information regarding its localization and metabolic activity on plants is important. In this study, a gfp/luxAB-tagged derivative of P. fluorescens SBW25, expressing the green fluorescent protein (GFP) and bacterial luciferase, was monitored during colonization of wheat starting from seed inoculation. Since bacterial luciferase is dependent on cellular energy reserves for phenotypic expression, metabolically active cells were detected using this marker. In contrast, the stable GFP fluorescence phenotype was used to detect the cells independently of their metabolic status. The combination of these two markers enabled P. fluorescens SBW25 cells to be monitored on wheat plants to determine their specific location and metabolic activity. Studies on homogenized wheat plant parts demonstrated that the seed was the preferred location of P. fluorescens SBW25 during the 65-day time period studied, but the leaves and roots were also colonized. Interestingly, the bacteria were also found to be metabolically active on all plant parts examined. In situ localization of P. fluorescens SBW25 using a combination of different microscopic techniques confirmed the preference for the cells to colonize specific regions of the seed. We speculate that the colonization pattern of P. fluorescens SBW25 can be linked to the mechanism of protection of plants from fungal infection.


Retention of a model pathogen in a porous media biofilm.
The inadvertent or the deliberate introduction of pathogens into drinking water can lead to public health consequences. Distribution system sampling strategies are needed to provide information on the identity, source and fate of the introduced pathogens. Porous media biofilm reactors conditioned with undefined drinking water biofilms were tested for their ability to immobilize Escherichia coli 0157:H7. Biofilms were established by applying continuous flow of biologically activated carbon treated water with natural microflora and supplemented nutrient solution (0.5 mg l(-1) C) for 2 or 3 weeks. Control reactors were clean and were not colonized with biofilm. All reactors were injected with slug doses of approximately 1 x 10(9) cfu E. coli O157:H7. On the basis of the plate count enumeration of the introduced pathogen, reactors pre-colonized for 2 or 3 weeks retained significantly more cells (0.75 and 9.37% of the introduced spike dose, respectively) compared with uncolonized control reactors (0.22%). Compared with cultivation, microscopic direct counts and quantitative PCR suggested significantly higher and lower numbers of pathogens, respectively. Plate counts were thus considered as the method of choice for pathogen enumeration in this study. In addition to providing general insights into interactions between pathogens and drinking water biofilms, the study concluded that engineered biofilm systems may be considered as a device to capture pathogens from the bulk flow for monitoring purposes.


How to help homeless youth suffering from first episode psychosis and substance use disorders? The creation of a new intensive outreach intervention team.
In Canada, about 6,000 youth are homeless every night, many of whom suffer from addiction and psychotic disorders. To facilitate the exit out of homelessness, access to care and to improve psychosis and addiction outcomes, a new intensive outreach intervention team (EQIIP SOL) was created in Montreal (2012). It offers intensive outreach services dedicated to homeless youth suffering from first episode psychosis and addiction (HYFEPA) in addition to an early psychosis intervention service (EIS) in collaboration with the Addiction Psychiatry Unit. Our aim is to describe the characteristics, clinical, functional and housing outcomes of HYFEPA followed by EQIIP SOL. This two years long prospective longitudinal study with all HYFEPA (n = 42) admitted to EQIIP SOL between 2012-2015 reports at multiple time points, clinical (CGI, GAF), functional (SOFAS, work/study, housing autonomy) and substance use disorder (DUS, AUS) outcomes and acute services use (hospitalizations, emergency room visits). We observed that, at baseline, HYFEPA showed poor prognostic factors (eg. cluster B personality, substance use disorders, legal problems, childhood trauma and lower education level). The majority reached housing stability after 6 months and their functioning and illness severity improved with time. This suggests that HYFEPA improve with an intensive outreach intervention team integrated to an EIS.


The precision of binocular and monocular depth judgments in natural settings.
We measured binocular and monocular depth thresholds for objects presented in a real environment. Observers judged the depth separating a pair of metal rods presented either in relative isolation, or surrounded by other objects, including a textured surface. In the isolated setting, binocular thresholds were greatly superior to the monocular thresholds by as much as a factor of 18. The presence of adjacent objects and textures improved the monocular thresholds somewhat, but the superiority of binocular viewing remained substantial (roughly a factor of 10). To determine whether motion parallax would improve monocular sensitivity for the textured setting, we asked observers to move their heads laterally, so that the viewing eye was displaced by 8-10 cm; this motion produced little improvement in the monocular thresholds. We also compared disparity thresholds measured with the real rods to thresholds measured with virtual images in a standard mirror stereoscope. Surprisingly, for the two naive observers, the stereoscope thresholds were far worse than the thresholds for the real rods-a finding that indicates that stereoscope measurements for unpracticed observers should be treated with caution. With practice, the stereoscope thresholds for one observer improved to almost the precision of the thresholds for the real rods.


Step Counts of Middle-Aged and Elderly Adults for 10 Months Before and After the Release of Pokémon GO in Yokohama, Japan.
Smartphones have been integrated into our society and are expected to serve as tools to improve health outcomes. In the summer of 2016, Pokémon GO, a location-based augmented reality game for smartphones was released; it attracted attention from the perspective of health, especially with its potential to increase physical activity (PA). A few studies have compared objectively measured step counts before and after the release of the game; however, they were conducted over a short study period and evaluated only young people. The objective of this study was to confirm whether there was a difference in step counts between middle-aged and elderly players and nonplayers before and after the release of Pokémon GO. A total of 46 players and 184 nonplayers aged ≥40 years were matched for sex, age group, and PA level; they were respondents to a questionnaire randomly sent to citizens who were given free pedometers by Yokohama city. Their play status was identified through the questionnaire. To investigate the change in step counts before and after the release of Pokémon GO according to play status, a 2-way repeated-measures analysis of variance was performed. Step counts 1 month before the release of the game were compared with those 8 months after the release. In addition, subgroup analyses according to sex, age group, PA level, and subjective health status were performed. The mean ages of players and nonplayers were 56.5 (SD 9.9) years and 57.3 (SD 9.6) years, respectively, and the mean baseline step counts of players and nonplayers were 7641.8 (SD 2754.5) and 7903.3 (SD 2674.7), respectively. There was no significant difference in the age and baseline step counts according to a t test (2-tailed). In the analysis of all samples, the interaction between play status and time effect was significant for 3 of 8 months after release. In the subgroup analyses, the interaction was significant for 3 months in men, 7 months in the 55-64-year-old group, 2 months in workers, 4 months in the active group in PA level, and 2 months in participants with subjectively good health. The interaction was significant for only 1 month, at most, in other subgroups. The present study confirmed a difference in step counts between players and nonplayers before and after the release of Pokémon GO. According to our analysis, step counts were higher until 7 months after the release. The player group maintained their step counts in winter, despite the decrease in step counts of nonplayers. In subgroup analyses, players were more likely to be men, aged <55 years, workers, active, and subjectively in good health.


Mycorrhizal Fungi Respond to Resource Inequality by Moving Phosphorus from Rich to Poor Patches across Networks.
The world's ecosystems are characterized by an unequal distribution of resources [1]. Trade partnerships between organisms of different species-mutualisms-can help individuals cope with such resource inequality [2-4]. Trade allows individuals to exchange commodities they can provide at low cost for resources that are otherwise impossible or more difficult to access [5, 6]. However, as resources become increasingly patchy in time or space, it is unknown how organisms alter their trading strategies [7, 8]. Here, we show how a symbiotic fungus mediates trade with a host root in response to different levels of resource inequality across its network. We developed a quantum-dot-tracking technique to quantify phosphorus-trading strategies of arbuscular mycorrhizal fungi simultaneously exposed to rich and poor resource patches. By following fluorescent nanoparticles of different colors across fungal networks, we determined where phosphorus was hoarded, relocated, and transferred to plant hosts. We found that increasing exposure to inequality stimulated trade. Fungi responded to high resource variation by (1) increasing the total amount of phosphorus distributed to host roots, (2) decreasing allocation to storage, and (3) differentially moving resources within the network from rich to poor patches. Using single-particle tracking and high-resolution video, we show how dynamic resource movement may help the fungus capitalize on value differences across the trade network, physically moving resources to areas of high demand to gain better returns. Such translocation strategies can help symbiotic organisms cope with exposure to resource inequality.


Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer.
We describe a cell-lineage marking system applicable to the vertebrate nervous system. The basis of the technique is gene transfer using the retroviral vector system. We used Escherichia coli beta-galactosidase as a marker gene and demonstrate a high level of expression of this marker from the viral long terminal repeat promoter, with simultaneous expression of the Tn5 neo gene from the simian virus 40 early promoter. This expression has allowed us to detect individual infected cells histochemically. We applied this marking technique to the study of lineage relationships in the developing vertebrate nervous system, both in vivo and in culture. In the rat retina, we injected virus in vivo and histochemically identified clones of marked neural cells. In addition, we used this virus to infect cultures of rat cerebral cortex and have analyzed the clonal relationships of morphologically different neural cell types. The host range of the marking system extends to avian as well as mammalian species. Thus, this system should have broad applicability as a means of gene transfer and expression in the nervous system.


[The roles of a nutrition support team].
In 1998, a new system called the potluck party method (PPM) for the operation of nutrition support teams (NSTs) was developed. In the PPM, just as at a potluck party where each participant brings a single dish of food to share, the NST is operated and managed by each department contributing a small amount of staff and resources at one time. Based on the PPM, 1 or 2 staff members are selected from each department and each ward and carry out the work of the NST as they continue to go about their routine duties. The roles of the NST are 1) nutritional assessments, 2) checking whether the nutritional support provided is adequate, 3) recommending the best nutritional therapy for each patient, 4) preventing complications during nutritional therapy, and 5) responding to consultations on nutritional support. NST performance based on the PPM have proven effective as demonstrated by the following results: 1) decreases in the number of problem cases in terms of nutritional management; 2) reductions in the incidence of catheter sepsis; 3) reductions in the numbers of patients with poor food intake; 4) prevention of pressure ulceration; 5) attempts to eradicate nosocomial infections; 6) decreases in mean length of hospital stay; and 7) a total cost benefit of at least 120,000,000 yen (US$1,000,000) per year.


Efficient wavelength converters with flattop responses based on counterpropagating cascaded SFG and DFG in low-loss QPM LiNbO3 waveguides.
A wavelength converter based on counterpropagating quasi-phase matched cascaded sum and difference frequency generation in lossy lithium niobate waveguide is numerically evaluated and compared to a single-pass scheme assuming a large pump wavelength difference of 75 nm. A double-pass device is proposed to improve the conversion efficiency while the response flattening is accomplished by increasing the wavelength tuning of one pump. The criteria for the design of the low-loss waveguide length, and the assignment of power in the pumps to achieve the desired efficiency, ripple and bandwidth are presented.


Spatial-Temporal Dependency Modeling and Network Hub Detection for Functional MRI Analysis via Convolutional-Recurrent Network.
Early identification of dementia at the stage of mild cognitive impairment (MCI) is crucial for timely diagnosis and intervention of Alzheimer's disease (AD). Although several pioneering studies have been devoted to automated AD diagnosis based on resting-state functional magnetic resonance imaging (rs-fMRI), their performance is somewhat limited due to non-effective mining of spatial-temporal dependency. Besides, few of these existing approaches consider the explicit detection and modeling of discriminative brain regions (i.e., network hubs) that are sensitive to AD progression. In this paper, we propose a unique Spatial-Temporal convolutional-recurrent neural Network (STNet) for automated prediction of AD progression and network hub detection from rs-fMRI time series. Our STNet incorporates the spatial-temporal information mining and AD-related hub detection into an end-to-end deep learning model. Specifically, we first partition rs-fMRI time series into a sequence of overlapping sliding windows. A sequence of convolutional components are then designed to capture the local-to-global spatially-dependent patterns within each sliding window, based on which we are able to identify discriminative hubs and characterize their unique contributions to disease diagnosis. A recurrent component with long short-term memory (LSTM) units is further employed to model the whole-brain temporal dependency from the spatially-dependent pattern sequences, thus capturing the temporal dynamics along time. We evaluate the proposed method on 174 subjects with 563 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with results suggesting the effectiveness of our method in both tasks of disease progression prediction and AD-related hub detection.


Big and mighty: preverbal infants mentally represent social dominance.
Human infants face the formidable challenge of learning the structure of their social environment. Previous research indicates that infants have early-developing representations of intentional agents, and of cooperative social interactions, that help meet that challenge. Here we report five studies with 144 infant participants showing that 10- to 13-month-old, but not 8-month-old, infants recognize when two novel agents have conflicting goals, and that they use the agents' relative size to predict the outcome of the very first dominance contests between them. These results suggest that preverbal infants mentally represent social dominance and use a cue that covaries with it phylogenetically, and marks it metaphorically across human cultures and languages, to predict which of two agents is likely to prevail in a conflict of goals.


Factors affecting the translucency of monolithic zirconia ceramics: A review from materials science perspective.
The use of monolithic [yttria (Y2O3)-stabilized tetragonal zirconia (ZrO2) polycrystalline] (Y-TZP) ceramics to restore teeth is expanding in dentistry. However, there are still some problems about color matching and the translucency of these ceramics. The employment of Y-TZP ceramics in aesthetically critical regions is questionable due to the insufficient translucency and opacity of the restorations. The objective of this review was to assess the factors affecting the translucency of monolithic Y-TZP ceramics for a better understanding the relevant parameters in restorations. The translucency of polycrystalline ceramics is a complex phenomenon. Apprehending the translucency regarding ceramics requires their knowledge of physical, chemical and microstructural characteristics with the light interactions among them.


Type VI secretion system killing by commensal Neisseria is influenced by expression of type four pili.
Type VI Secretion Systems (T6SSs) are widespread in bacteria and can dictate the development and organisation of polymicrobial ecosystems by mediating contact dependent killing. In Neisseria species, including Neisseria cinerea a commensal of the human respiratory tract, interbacterial contacts are mediated by Type four pili (Tfp) which promote formation of aggregates and govern the spatial dynamics of growing Neisseria microcolonies. Here, we show that N. cinerea expresses a plasmid-encoded T6SS that is active and can limit growth of related pathogens. We explored the impact of Tfp on N. cinerea T6SS-dependent killing within a colony and show that pilus expression by a prey strain enhances susceptibility to T6SS compared to a non-piliated prey, by preventing segregation from a T6SS-wielding attacker. Our findings have important implications for understanding how spatial constraints during contact-dependent antagonism can shape the evolution of microbial communities.


Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children.
The National Institutes of Health (NIH) Diagnostic Criteria for neurofibromatosis 1 (NF1) are very useful clinically, but some individuals who are later shown to have NF1 cannot be diagnosed in early childhood using these criteria. The aim of this study is to determine the value of the NIH Diagnostic Criteria for NF1 in early childhood, to determine the age at which diagnosis can confidently be made, and to clarify the age at onset of the cardinal clinical features used in the NIH Diagnostic Criteria. We studied 1893 NF1 patients under 21 years old from the National Neurofibromatosis Foundation International Database to determine the age at which the features included in the NIH Diagnostic Criteria appear. Approximately 46% of sporadic NF1 cases fail to meet the NIH Diagnostic Criteria by 1 year of age. Nearly all (97%; 95% confidence interval: 94-98) NF1 patients meet the criteria for diagnosis by 8 years old, and all do so by 20 years old. The usual order of appearance of the clinical features listed as NIH criteria is café-au-lait macules, axillary freckling, Lisch nodules, and neurofibromas. Symptomatic optic glioma is usually diagnosed by 3 years old, and characteristic osseous lesions are usually apparent within the first year of life. The diagnosis of NF1 cannot always be made in young children using the NIH Diagnostic Criteria. Modification of these criteria may be necessary for children under 8 years old.


Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.
This study examined renal and glycemic effects of chromium picolinate [Cr(pic)3] supplementation in the context of its purported potential for DNA damage. In preventional protocol, male obese diabetic db/db mice were fed diets either lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue advanced glycation end products, albuminuria, glomerular mesangial expansion, urinary 8-hydroxydeoxyguanosine (an index of oxidative DNA damage) and renal tissue immunostaining for γH2AX (a marker of double-strand DNA breaks) compared to db/m controls. Creatinine clearance was lower in untreated db/db mice than their db/m controls, while blood pressure was similar. High Cr(pic)3 intake (i.e., 100-mg/kg diet) mildly improved glycemic status and albuminuria without affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not increase DNA damage despite marked renal accumulation of chromium. In interventional protocol, effects of diets containing 0, 100 and 250 mg/kg supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice. The results generally revealed similar effects to those of the 100-mg/kg diet of the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse displays renal structural and functional abnormalities in association with DNA damage. High-dose Cr(pic)3 treatment mildly improves glycemic control, and it causes moderate reduction in albuminuria, without affecting the histopathological appearance of the kidney and increasing the risk for DNA damage.


[Peruvian experience in the treatment of chronic hepatites C with the new direct acting antiviral drugs].
The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.


Autoantibodies in sporadic Creutzfeldt-Jakob disease.
The diagnosis of autoimmune and neurodegenerative conditions can be unclear. Treatments such as removing the associated tumor, if present, and immunosuppression can halt or often reverse the progression of autoimmune conditions, but there is no curative treatment for neurodegenerative conditions. The presence of autoantibodies can sometimes be misleading. This report illustrates potential difficulties in differentiating autoimmune encephalopathies from sporadic Creutzfeldt-Jakob disease. In a clinical follow-up of an older man with rapidly evolving encephalopathy at a neuroscience center, unsuccessful treatment with immunosuppression based on the incorrect presumptive diagnosis of Morvan syndrome was followed by the correct histological diagnosis of sporadic Creutzfeldt-Jakob disease. Autoimmune encephalopathies raise important treatment options and potential for recovery. However, since neuronal antibodies may be positive in prion disease, interpretation can be complex and must be rooted in the clinical picture.


Stability of the fluorescence measurement of Foscan in the normal human oral cavity as an indicator of its content in early cancers of the esophagus and the bronchi.
Photodynamic therapy (PDT) with Foscan (mTHPC) is used to cure early cancers of the esophagus or the tracheobronchial tree. However, fixed PDT parameters (drug dose, light dose, etc.) do not permit an accurate prediction of the tissue damage. Large interpatient fluctuations in tissue drug level, at the time of light application, suggest that the light dose must be adjusted to the drug dose shortly before the PDT. This drug dose can be measured endoscopically by light-induced fluorescence spectroscopy, but this measurement is inconvenient and somewhat difficult. A better test site, yielding comparable information, is needed. The oral cavity seems ideal. However, it first had to be established to what extent the estimation of the drug dose was dependent upon the location of the measurement and the pressure applied to the probe. These measurements prove to be not only correlated to similar measurements in the esophagus or the bronchi but also more consistent and less sensitive to the location and the applied pressure. The buccal mucosa is therefore recommended as a test site for measuring the Foscan fluorescence signal at the time of PDT in the esophagus or the bronchi. This measurement is accurate enough for use in light-dose adjustment.


Assessing cathode property prediction via exchange-correlation functionals with and without long-range dispersion corrections.
We benchmark calculated interlayer spacings, average topotactic voltages, thermodynamic stabilities, and band gaps in layered lithium transition-metal oxides (TMOs) and their de-lithiated counterparts, which are used in lithium-ion batteries as positive electrode materials, against available experimental data. Specifically, we examine the accuracy of properties calculated within density functional theory (DFT) using eight different treatments of electron exchange-correlation: the strongly constrained and appropriately normed (SCAN) and Perdew-Burke-Ernzerhof (PBE) density functionals, Hubbard-U-corrected SCAN and PBE (i.e., SCAN+U and PBE+U), and SCAN(+U) and PBE(+U) with added long-range dispersion (D) interactions (i.e., DFT(+U)+D). van der Waals interactions are included respectively via the revised Vydrov-Van Voorhis (rVV10) for SCAN(+U) and the DFT-D3 for PBE(+U). We find that SCAN-based functionals predict larger voltages due to an underestimation of stability of the MO2 systems, while also predicting smaller interlayer spacings compared to their PBE-based counterparts. Furthermore, adding dispersion corrections to PBE has a greater effect on voltage predictions and interlayer spacings than with SCAN, indicating that DFT-SCAN - despite being a ground-state theory - fortuitously captures some short and medium-range dispersion interactions better than PBE. While SCAN-based and PBE-based functionals yield qualitatively similar band gap predictions, there is no significant quantitative improvement of SCAN-based functionals over the corresponding PBE-based versions. Finally, we expect SCAN-based functionals to yield more accurate property predictions than the respective PBE-based functionals for most TMOs, given SCAN's stronger theoretical underpinning and better predictions of systematic trends in interlayer spacings, intercalation voltages, and band gaps obtained in this work.


Bibliometric analysis of theranostics: two years in the making.
With the newly released impact factor from Thomson Reuters, we look at the first two years of the journal Theranostics under the scope of a new bibliometric designed for the analysis of emerging specialties and also for journals with a multidisciplinary approach. With this method, we are able to look at characteristics of an interdisciplinary field or a single journal subject area, and also, the bibliographic trends of their authors. We use this tool to examine authors from the journal Theranostics and compare them to similar authors in the field of theranostics, or theranosticians. Our document and co-citation analysis examines the growth and overlap of established knowledge networks with the incorporation of fields, topics, and disciplines; the quantification can also reflect the intellectual activity in combining leading edge developments in solidly grounded specialties. The quantification of junior authorship aims to gauge the promotion of fresh ideas and scientific development in the community, while productivity of overall authors is measured by citation analysis.


How physicians support children with disabilities and their families: Roles, responsibilities and collaborative partnerships.
The American Association of Pediatricians (AAP), in collaboration with the Council for Children with Disabilities and the Council on School Health, recommends that physicians learn special education law and practices in order to increase their ability to work with schools to support children with disabilities and their families. However, there is limited research that examines how doctors perceive their role as collaborators with families and school personnel. The purpose of this study was to explore the perceptions and collaborative experiences of doctors treating children with disabilities in order to develop an initial understanding of how doctors collaborate within the doctor/family/school triad. Semi-structured interviews with doctors (n = 13) from two states in the North Eastern United States were collected and analyzed using grounded theory methodology. Doctor specialty areas included general pediatrics, developmental pediatrics, rehabilitation pediatrics, and neurology. Analysis of the data revealed four key categories: (a) what doctors do with regard to children with disabilities and schools, (b) elements that interfere with doctor/family/school collaboration, (c) what doctors know and understand about topics related to special education, and (d) how doctors learned about topics related to special education. Doctors disclosed they learned about these topics through mentorship and on-the job training, not formally during medical school or residency. This research presents powerful evidence in support of a paradigm shift with regard to infusing a focus on doctor/family/school collaboration for children with disabilities into the medical school curriculum.


Coherent optical nanotweezers for ultracold atoms.
There has been a recent surge of interest and progress in creating subwavelength free-space optical potentials for ultracold atoms. A key open question is whether geometric potentials, which are repulsive and ubiquitous in the creation of subwavelength free-space potentials, forbid the creation of narrow traps with long lifetimes. Here, we show that it is possible to create such traps. We propose two schemes for realizing subwavelength traps and demonstrate their superiority over existing proposals. We analyze the lifetime of atoms in such traps and show that long-lived bound states are possible. This work allows for subwavelength control and manipulation of ultracold matter, with applications in quantum chemistry and quantum simulation.


[Relation of clinical and biochemical factors with clinical stage and type of surgery in a sample of patients with critical ischemia of limbs].
The term of critical ischemia of legs is used in patients with chronic ischemia and pain in rest, ulcer or tisular necrosis secondary to oclussive arterial disease. The objective of our work was to identify factors related with clinical stage and type of surgery in these patients. An observational study was performed during two years, from january 1999 to december 2000, with 330 patients with surgery secondary to critical ischemia of legs. The next parameters were recorded during the Hospital stance; age, sex, blood pressure, glycaemia, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, location of disease, type of surgery, arm-ankle index, and pharmacological treatment to cardiovascular risk factors. A regression logistic analyze was realized to study the influence of different variables in the clinical stage and in the type of surgery. The mean age was 74.78+/-10.35 years, with a higher age in females (78.88+/-10.45 years) than males (73.70+/-10.07) (p<0,0001), with 261 males (79.1%) and 69 females (20.9%). Logistic regression model to investigate clinical stage III/IV (adjusted by age and sex) showed that the independent variables related with stage IV were diabetes mellitus, location of arterial lesion, and low cholesterol levels. A patient with diabetes mellitus type 2 has 3,322 (CI 95%: 1,881-5,866) times more risk of stage IV than a non diabetic patient. Odds ratio of total cholesterol was 0,990, the risk to develop a IV stage is increased 0,990 times for each mg/dl of cholesterol. Distal lesion increased the risk of stage IV en 6,897 times (CI 95%: 3,509-13,557). Logistic regression model to investigate type of surgery (amputation/bypass) (adjusted by age and sex) showed that diabetes mellitus type 2 had Odds Ratio (OR) of 3,37, this means that diabetes increase 3,37 times (CI 95%: 1,940-5,866) the risk of amputation. Total cholesterol showed a OR of 0,986, this jeans an increase of amputation 0,986 time with each mg/dl of cholesterol. Distal location increase risk of amputation 2,585 times. Patients with more than one surgery had an OR of 3,013 (1,602-5,666) to increase amputation. Each day of hospital stance increase 0,8% risk of amputation. In multivariant análisis, diabetes mellitus, distal lesion, male sex and age over 75 years were positive related with stage IV, and cholesterol levels were inverse related. Diabetes mellitus, distal lesion, age over 75 years, days of hospital stance, number of surgeries were positive related with amputation as surgery technic and cholesterol levels were negative related.


Perioperative complications in liver transplantation using donation after cardiac death grafts: a propensity-matched study.
Donation after cardiac death (DCD) is an important source for expanding the donor pool for liver transplantation (LT). Although the long-term outcomes of LT using DCD grafts have been extensively studied, perioperative complications related to DCD grafts are rarely reported. The aim of this study was to determine whether DCD grafts were associated with a higher incidence of postreperfusion complications and worse outcomes in adult LT patients. After institutional review board approval, the medical records of all adult patients who underwent LT at our medical center between 2004 and 2011 were reviewed. Postreperfusion complications and posttransplant outcomes were compared between patients receiving DCD grafts and patients receiving donation after brain death (DBD) grafts. In all, 74 patients received DCD grafts during the study period, and 1369 patients received DBD grafts. An initial comparison showed that many preoperative, prereperfusion, and donor variables in the DCD group differed significantly from those in the DBD group. Propensity matching was chosen so that adjustments could be made for the differences. A postmatching analysis showed that the preoperative, prereperfusion, and donor variables no longer differed between the 2 groups. The postreperfusion requirements for blood products and vasopressors, the posttransplant ventilation times, the incidence of posttransplant acute renal injury, and the 30-day and 1-year patient and graft survival rates were comparable between the 2 groups. However, patients receiving DCD grafts experienced significantly higher rates of hyperkalemia (33.8% versus 18.9%, P < 0.05) and postreperfusion syndrome (PRS; 25.7% versus 12.3%, P < 0.05). In conclusion, after adjustments for preoperative and prereperfusion risks via propensity matching, DCD grafts remained a risk factor for postreperfusion hyperkalemia and PRS. A prophylactic regimen aimed at decreasing postreperfusion hyperkalemia and PRS is recommended for the management of LT using DCD grafts.


Molecular response of the bloom-forming cyanobacterium, Microcystis aeruginosa, to phosphorus limitation.
Cyanobacteria blooms caused by species such as Microcystis have become commonplace in many freshwater ecosystems. Although phosphorus (P) typically limits the growth of freshwater phytoplankton populations, little is known regarding the molecular response of Microcystis to variation in P concentrations and sources. For this study, we examined genes involved in P acquisition in Microcystis including two high-affinity phosphate-binding proteins (pstS and sphX) and a putative alkaline phosphatase (phoX). Sequence analyses among ten clones of Microcystis aeruginosa and one clone of Microcystis wesenbergii indicates that these genes are present and conserved within the species, but perhaps not the genus, as phoX was not identified in M. wesenbergii. Experiments with clones of M. aeruginosa indicated that expression of these three genes was strongly upregulated (50- to 400-fold) under low inorganic P conditions and that the expression of phoX was correlated with alkaline phosphatase activity (p < 0.005). In contrast, cultures grown exclusively on high levels of organic phosphorus sources (adenosine 5'-monophosphate, β-glycerol phosphate, and D: -glucose-6-phosphate) or under nitrogen-limited conditions displayed neither high levels of gene expression nor alkaline phosphatase activity. Since Microcystis dominates phytoplankton assemblages in summer when levels of inorganic P (P(i)) are often low and/or dominate lakes with low P(i) and high organic P, our findings suggest this cyanobacterium may rely on pstS, sphX, and phoX to efficiently transport P(i) and exploit organic sources of P to form blooms.


Preventing compulsory admission to psychiatric inpatient care using psycho-education and monitoring: feasibility and outcomes after 12 months.
The aim of this study was to evaluate an intervention programme for people with severe mental illness that targets the reduction in compulsory psychiatric admissions. In the current study, we examine the feasibility of retaining patients in this programme and compare outcomes over the first 12 months to those after treatment as usual (TAU). Study participants were recruited in four psychiatric hospitals in the Canton of Zurich, Switzerland. Patients were eligible if they had at least one compulsory admission during the past 24 months. Participants were assigned at random to the intervention or to the TAU group. The intervention programme consists of individualised psycho-education focusing on behaviours prior to illness-related crisis, crisis cards and, after discharge from the psychiatric hospital, a 24-month preventive monitoring. In total, 238 (of 756 approached) inpatients were included in the trial. After 12 months, 80 (67.2%) in the intervention group and 102 (85.7%) in the TAU group were still participating in the trial. Of these, 22.5% in the intervention group (35.3% TAU) had been compulsorily readmitted to psychiatry; results suggest a significantly lower number of compulsory readmissions per patient (0.3 intervention; 0.7 TAU). Dropouts are characterised by younger age and unemployment. This interim analysis suggests beneficial effects of this intervention for targeted psychiatric patients.


Field Resistance to the Ug99 Race Group of the Stem Rust Pathogen in Spring Wheat Landraces.
Wheat landraces provide a source of genetic variability for breeding. The emergence and spread of highly virulent races of the stem rust pathogen (Ug99 race group of Puccinia graminis f. sp. tritici) threaten wheat production globally. Spring wheat landraces were screened for resistance in eight field seasons at the Kenya Agricultural Research Institute, Njoro, where the Ug99 race group has become endemic. Accessions showing resistance in one season were retested and screened with molecular markers associated with resistance genes Sr2, Sr24, Sr36, and Lr34/Yr18; two height-reducing genes; and a photoperiod insensitivity allele. Of 2,509 accessions tested, 278 were categorized as resistant based on results from at least two seasons. Of these resistant accessions, 32 were positive for one or more markers for Sr2, Sr36, Rht-B1b, or Rht-D1b, indicating that they do not fit the definition of "landrace" because these genes were likely introduced via modern breeding practices. Thus, 246 resistant "landrace" accessions were identified. Of countries with more than five tested accessions, Afghanistan, Iran, Portugal, Ethiopia, Uzbekistan, Greece, Tajikistan, Bosnia and Herzegovina, and Serbia had at least 10% of tested accessions that were resistant to the Ug99 race group. Future research will characterize the resistance to determine its novelty and incorporate novel genes into improved lines.


Influence of an oxygen-inhibited layer on enamel bonding of dental adhesive systems: surface free-energy perspectives.
The influence of an oxygen-inhibited layer (OIL) on the shear bond strength (SBS) to enamel and surface free-energy (SFE) of adhesive systems was investigated. The adhesive systems tested were Scotchbond Multipurpose (SM), Clearfil SE Bond (CS), and Scotchbond Universal (SU). Resin composite was bonded to bovine enamel surfaces to determine the SBS, with and without an OIL, of adhesives. The SFE of cured adhesives with and without an OIL were determined by measuring the contact angles of three test liquids. There were no significant differences in the mean SBS of SM and CS specimens with or without an OIL; however, the mean SBS of SU specimens with an OIL was significantly higher than that of SU specimens without an OIL. For all three systems, the mean total SFE (γS), polarity force (γSp), and hydrogen bonding force (γSh) values of cured adhesives with an OIL were significantly higher than those of cured adhesives without an OIL. The results of this study indicate that the presence of an OIL promotes higher SBS of a single-step self-etch adhesive system, but not of a three-step or a two-step self-etch primer system. The SFE values of cured adhesives with an OIL were significantly higher than those without an OIL. The SFE characteristics of the OIL of adhesives differed depending on the type of adhesive.


Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor.
Xenopus egg extracts treated with the protein kinase inhibitor 6-dimethylaminopurine (6-DMAP) are unable to support the initiation of DNA replication. Nuclei assembled in 6-DMAP extracts behave as though they are in G2, and will not undergo another round of DNA replication until passage through mitosis. 6-DMAP extracts are functionally devoid of a replication factor that modifies chromatin in early G1 before nuclear envelope assembly, but which is itself incapable of crossing the nuclear envelope. This chromatin modification is capable of supporting only a single round of semiconservative replication. The behavior of this replication factor is sufficient to explain why eukaryotic DNA is replicated once and only once in each cell cycle, and conforms to the previous model of a Replication Licensing Factor. Cell cycle analysis shows that this putative Licensing Factor is inactive during metaphase, but becomes rapidly activated on exit from metaphase when it can modify chromatin before nuclear envelope assembly is complete.


Overexpression of plasminogen activator inhibitor type 2 in basal keratinocytes enhances papilloma formation in transgenic mice.
The serpin plasminogen activator inhibitor (PAI) type 2 is expressed in differentiated epidermal keratinocytes. To explore its role in this tissue, we studied the impact of PAI-2 overexpression on epidermal differentiation and skin carcinogenesis. A mouse PAI-2-encoding transgene was targeted to basal epidermis and hair follicles under the control of the bovine keratin type 5 gene promoter. Two mouse lines were established, one of which strongly expressed the transgene and produced elevated levels of PAI-2 in the epidermis. Although it had no manifest impact on cellularity or differentiation of skin or hair follicles, PAI-2 overexpression rendered the mice highly susceptible to skin carcinogenesis induced by a single application of 7,12-dimethylbenz(a)anthracene (initiation) followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate [TPA (promotion)]. In transgenic mice, papillomas could be observed after 3 weeks of promotion; after 8 weeks, 94% (31 of 33) of transgenic mice had developed readily visible papillomas, whereas only 35% (7 of 20) of control mice (transgene-negative littermates) had barely detectable lesions. After 11 weeks, all but 1 (32 of 33) of the transgenic mice had papillomas as compared with only 65% (13 of 20) of control mice. After 11 weeks of promotion, application of TPA was terminated. In control mice, papillomas regressed and eventually disappeared; in transgenic mice, there was continued growth of papillomas, some of which further progressed to carcinomas. In contrast to massive apoptosis in regressing papillomas of control mice, only a few apoptotic cells were detected in transgenic papillomas after the cessation of TPA application. The effect of PAI-2 on papilloma formation did not appear to involve inhibition of the secreted protease urokinase-type plasminogen activator (uPA): PAI-2 accumulated predominantly in cells, and PAI-2 overexpression failed to alleviate a phenotype induced by uPA secretion, as demonstrated by a double transgenic strategy. In addition, in situ hybridization revealed that uPA mRNA is not expressed concomitantly with PAI-2 in developing papillomas. We conclude that overexpression of PAI-2 promotes the development and progression of epidermal papillomas in a manner that does not involve inhibition of its extracellular target protease, uPA, but appears to be related to an inhibition of apoptosis.


Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease.
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. Ginkgo biloba dropping pill (GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids. Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment, the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP. These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.


Depth-Independent Reproduction in the Reef Coral Porites astreoides from Shallow to Mesophotic Zones.
Mesophotic coral ecosystems between 30-150 m may be important refugia habitat for coral reefs and associated benthic communities from climate change and coastal development. However, reduced light at mesophotic depths may present an energetic challenge to the successful reproduction of light-dependent coral organisms, and limit this refugia potential. Here, the relationship of depth and fecundity was investigated in a brooding depth-generalist scleractinian coral, Porites astreoides from 5-37 m in the U.S. Virgin Islands (USVI) using paraffin tissue histology. Despite a trend of increasing planulae production with depth, no significant differences were found in mean peak planulae density between shallow, mid-depth and mesophotic sites. Differential planulae production over depth is thus controlled by P. astreoides coral cover, which peaks at 10 m and ~35 m in the USVI. These results suggest that mesophotic ecosystems are reproductive refuge for P. astreoides in the USVI, and may behave as refugia for P. astreoides metapopulations providing that vertical larval exchanges are viable.


Role of the Lymphatic System in the Pathogenesis of Hypertension in Humans.
Recent studies, mainly on animal models, have suggested that negatively charged glycosaminoglycans, macrophages, and lymph vessels in the skin interstitium may serve as extrarenal control of sodium balance and blood pressure. The aim of the study was to prove the hypothesis that skin interstitium has a role in the pathogenesis of hypertension in humans. We have examined skin biopsies in 91 patients from the department of surgery who had elective surgery with abdominal skin incision: 43 were hypertensive, 14 had resistant hypertension, and 34 with normal blood pressure as control group (median patients' age in these groups estimated accordingly 64 vs. 64 vs. 61.5; p > 0.05). We have studied (1) the content of Na+, water, accumulation of macrophages (CD68), and density of lymphatic vessels (D2-40) and blood vessels (CD31) in the specimens of abdominal skin taken at the time of surgery and (2) plasma NT-proANP, vascular endothelial growth factor (VEGF)-C, and VEGF-D concentrations. The study groups differed in skin expression of CD68 (control vs. hypertension vs. resistant hypertension groups were accordingly: 3.33 vs. 4.00 vs. 8.33; p = 0.005) and in serum concentration of VEGF-C (5792 vs. 4348 vs. 3974 pg/mL; p = 0.026). Differences among groups in plasma NT-proANP levels were close to statistical significance (p = 0.056). Our results confirm that skin interstitium may be involved in the pathogenesis of essential hypertension in humans. Lower levels of VEGF-C in hypertensive groups suggest that impairment of lymphangiogenesis and protective function of the skin lymphatic system may play a role in the pathogenesis of hypertension.


Effects of Different Dosages of Interval Training on Glycemic Control in People With Prediabetes: A Randomized Controlled Trial.
High-intensity interval training (HIIT) has been used as an alternative to moderate-intensity exercise training. Research has shown that HIIT produces better effects on glycemic control and hence the cardiometabolic risk in prediabetes. This randomized controlled trial was conducted to compare the effect of low-volume HIIT (LV-HIIT) with high-volume HIIT (HV-HIIT) on A1C and fasting blood glucose (FBG) in overweight adults with prediabetes. The trial included 60 young adults with prediabetes (32 male, 28 female). Subjects were randomly assigned to one of three equal-sized groups (n = 20): an LV-HIIT group (10 × 1-minute intervals at an interval intensity of ∼90% HRmax on a treadmill separated by 1 minute of easy recovery, with total exercise of 25 minutes/session), an HV-HIIT group (4 × 4-minute intervals at 90% of HRmax with 3 minutes of active recovery at 70% of HRmax between intervals, with total exercise of 40 minutes/session), and a control group (no exercise intervention). Exercise programs consisted of 3 sessions/week for 12 successive weeks. All participants followed a low-calorie diet for the 12-week intervention period. A1C and FBG were measured before and at the end of the 12-week trial. There were statistically significant effects on A1C and FBG from both exercise interventions (P <0.05). LV-HIIT and HV-HIIT significantly reduced A1C and FBG; however, HV-HIIT yielded a greater reduction in A1C than LV-HIIT (26.07 vs. 14.50%) and in FBG (17.80 vs. 13.22%) after exercise training, respectively. HIIT was found to be effective for glycemic control in prediabetes, with HV-HIIT being more effective than LV-HIIT in reducing A1C, FBG, and progression to type 2 diabetes in young adults with prediabetes.


Obstructing giant post-inflammatory polyposis in ulcerative colitis: Case report and review of the literature.
Post-inflammatory polyps >15 mm in diameter or length are termed "giant". This benign and rare sequel of ulcerative colitis or colonic Crohn's disease can mimic colorectal carcinoma. To illustrate this rare complication of inflammatory bowel disease and outline the characteristic radiological, endoscopic and histopathological features, by reviewing all previously published cases of giant post-inflammatory polyps in the English literature. Reports of 81 giant post-inflammatory polyps in 78 patients were identified by systematic review of the literature. The incidence of giant post-inflammatory polyps is related to the extent of ulcerative colitis (incidence: 0%, 30%, and 70%, in proctitis, left-sided, and extensive disease, respectively). These lesions are typically located in the transverse or descending colon. Giant post-inflammatory polyps are as common in Crohn's disease (n=36) as in ulcerative colitis (n=42, 54%). Clinical presentations varies, including pain (n=29), rectal bleeding (n=20), diarrhoea (n=19), luminal obstruction (n=15), or a palpable mass (n=11). Symptomatic presentation results in surgical resection. Clinical details and outcomes are comprehensively tabulated. Recognition of this rare entity will prevent unnecessary radical surgical resection for presumed carcinoma. It highlights the need for clinical, radiological, endoscopic and histopathological correlation.


Temporal dynamics of the attentional spotlight: neuronal correlates of attentional capture and inhibition of return in early visual cortex.
A stimulus that suddenly appears in the corner of the eye inevitably captures our attention, and this in turn leads to faster detection of a second stimulus presented at the same position shortly thereafter. After about 250 msec, however, this effect reverses and the second stimulus is detected faster when it appears far away from the first. Here, we report a potential physiological correlate of this time-dependent attentional facilitation and inhibition. We measured the activity in visual cortex representations of the second (target) stimulus' location depending on the stimulus onset asynchrony (SOA) and spatial distance that separated the target from the preceding cue stimulus. At an SOA of 100 msec, the target yielded larger responses when it was presented near to than far away from the cue. At an SOA of 850 msec, however, the response to the target was more pronounced when it appeared far away from the cue. Our data show how the neural substrate of visual orienting is guided by immediately preceding sensory experience and how a fast-reacting brain system modulates sensory processing by briefly increasing and subsequently decreasing responsiveness in parts of the visual cortex. We propose these activity modulations as the neural correlate of the sequence of perceptual facilitation and inhibition after attentional capture.


A tailored multi-frequency EPR approach to accurately determine the magnetic resonance parameters of dynamic nuclear polarization agents: application to AMUPol.
To understand the dynamic nuclear polarization (DNP) enhancements of biradical polarizing agents, the magnetic resonance parameters need to be known. We describe a tailored EPR approach to accurately determine electron spin-spin coupling parameters using a combination of standard (9 GHz), high (95 GHz) and ultra-high (275 GHz) frequency EPR. Comparing liquid- and frozen-solution continuous-wave EPR spectra provides accurate anisotropic dipolar interaction D and isotropic exchange interaction J parameters of the DNP biradical AMUPol. We found that D was larger by as much as 30% compared to earlier estimates, and that J is 43 MHz, whereas before it was considered to be negligible. With the refined data, quantum mechanical calculations confirm that an increase in dipolar electron-electron couplings leads to higher cross-effect DNP efficiencies. Moreover, the DNP calculations qualitatively reproduce the difference of TOTAPOL and AMUPol DNP efficiencies found experimentally and suggest that AMUPol is particularly effective in improving the DNP efficiency at magnetic fields higher than 500 MHz. The multi-frequency EPR approach will aid in predicting the optimal structures for future DNP agents.


CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation.
We investigated the roles of CXC chemokine ligand 12a (CXCL12a), also known as stromal cell-derived factor-1α (SDF-1α), in endochondral bone growth, which can give us important clues to understand the role of CXCL12a in osteoarthritis (OA). Primary chondrocytes and tibial explants from embryonic 15.5 day-old mice were cultured with recombinant mouse CXCL12a. To assess the role of CXCL12a in chondrogenic differentiation, we conducted mesenchymal cell micromass culture. In tibia organ cultures, CXCL12a increased total bone length in a dose-dependent manner through proportional effects on cartilage and bone. In accordance with increased length, CXCL12a increased the protein level of proliferation markers, such as cyclin D1 and proliferating cell nuclear antigen (PCNA), in primary chondrocytes as well as in tibia organ culture. In addition, CXCL12a increased the expression of Runx2, Col10 and MMP13 in primary chondrocytes and tibia organ culture system, implying a role of CXCL12a in chondrocyte maturation. Micromass cultures of limb-bud mesenchymal progenitor cells (MPCs) revealed that CXCL12a has a limited effect on early chondrogenesis, but significantly promoted maturation of chondrocytes. CXCL12a induced the phosphorylation of p38 and Erk1/2 MAP kinases and IκB. The increased expression of cyclin D1 by CXCL12a was significantly attenuated by inhibitors of MEK1 and NF-κB. On the other hand, p38 and Erk1/2 MAP kinase and NF-κB signaling were associated with CXCL12a-induced expression of Runx2 and MMP13, the marker of chondrocyte maturation. CXCL12a promoted the proliferation and maturation of chondrocytes, which strongly suggest that CXCL12a may have a negative effect on articular cartilage and contribute to OA progression.


Identification of differentially expressed genes in sexed pig embryos during post-hatching development in primiparous sows exposed to differing intermittent suckling and breeding strategies.
The aim of commercial pig breeding programs is to maximize the number of pigs produced per sow per year. Given that sows exhibit an estrus during lactation is a potential means of increasing productivity of a pig breeding herd without reducing in lactation length, conventionally, weaning of piglets at a relatively young age is often related to post-weaning piglet performance which compromises piglet welfare. Therefore, intermittent suckling (IS) is a management technique in which lactating sows are separated from their piglets for a fixed period of the days and allowing sows to continue nursing piglets while exhibiting estrus and being breed during lactation, thereby promoting both piglet well-being and sow reproductive performance [1]. For this study, primiparous sows (PP) were exposed to 28 day (D28) lactation with intermittent suckling (IS) during the final week prior to weaning. The sows detected to be in estrus during lactation were either bred at this first estrus (FE) during lactation (IS21FE), or were "skipped" and bred at their second estrus which occurred after final weaning at D28 (IS21SE). Despite the benefits of IS, the effects of the maternal physiology related to breeding during lactation on embryonic transcriptome are largely unknown. Recent advances in the ability to assess embryonic gene expression in both sexes have made these analyses possible. Here, we describe the experimental procedures of two color microarray analyses and annotation of differentially expressed (DE) genes in detail corresponding to data deposited at NCBI in the Gene Expression Omnibus under accession number GSE53576 and GSE73020 for day 9 embryos (D9E) and day 30 embryos (D30E) respectively. Although only a few DE genes were discovered between IS21FE and IS21SE in both sexes from D9E or D30E, the raw data are still valuable for future use to understand the gene expression profiling from two different developmental stages.


Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts.
Glutaredoxin 5 (GLRX5) deficiency has previously been identified as a cause of anemia in a zebrafish model and of sideroblastic anemia in a human patient. Here we report that GLRX5 is essential for iron-sulfur cluster biosynthesis and the maintenance of normal mitochondrial and cytosolic iron homeostasis in human cells. GLRX5, a mitochondrial protein that is highly expressed in erythroid cells, can homodimerize and assemble [2Fe-2S] in vitro. In GLRX5-deficient cells, [Fe-S] cluster biosynthesis was impaired, the iron-responsive element-binding (IRE-binding) activity of iron regulatory protein 1 (IRP1) was activated, and increased IRP2 levels, indicative of relative cytosolic iron depletion, were observed together with mitochondrial iron overload. Rescue of patient fibroblasts with the WT GLRX5 gene by transfection or viral transduction reversed a slow growth phenotype, reversed the mitochondrial iron overload, and increased aconitase activity. Decreased aminolevulinate delta, synthase 2 (ALAS2) levels attributable to IRP-mediated translational repression were observed in erythroid cells in which GLRX5 expression had been downregulated using siRNA along with marked reduction in ferrochelatase levels and increased ferroportin expression. Erythroblasts express both IRP-repressible ALAS2 and non-IRP-repressible ferroportin 1b. The unique combination of IRP targets likely accounts for the tissue-specific phenotype of human GLRX5 deficiency.


Endothelin interactions with brain dopamine systems.
We examined the interactions of endothelin (ET) with dopaminergic systems in rat brain. Using HPLC and radioimmunoassay, we found that striatum contained the highest levels of predominantly ET-1, whereas highest levels of predominantly ET-3 were found in the pituitary. Dopamine depletion in the striatum did not change the levels of immunoreactive ET, even though we have previously found a decrease in the density of ET receptors. In a comparison of spontaneously hypertensive rats (SHR) with Wistar-Kyoto (WKY) rats, ET levels were lower in cerebellum and medulla, with no difference in striatum or in other brain areas. In conclusion, ET is present in high levels in striatum, but these levels are not affected by dopamine depletion or in SHR.


Strategies used in the clinical trials of gene therapy for cancer.
Advances in understanding and manipulating genes have set the stage for scientists to alter a person's genetic material to prevent or treat diseases. Over the past decade, somatic gene therapy has been increasingly applied in clinical trials where the genetic material (DNA and RNA) introduced into a person's cell. Mutation and inactivation of the tumor suppressor genes are the unified concept of the development of tumor in humans. Therefore, researchers have discovered potential of gene therapies in the treatment of cancer. Among the clinical trials of gene therapy conducted so far, approximately 66% were for the treatment of cancer which includes cancer of prostate, head and neck, kidneys, lungs, breast and skin. Introducing a wild type p53 gene, enhancing the immune system to protect against the cancer cells, enhancing the apoptosis of cancer cells and inhibiting the process of angiogenesis in the tumor are some of the clinical trials that are achieved through the gene therapy. Broad spectrum of delivery constructs, including viral vectors, liposomes, cationic polymers and dendrimers, cell-penetrating peptides, semiconductor quantum dots, and gold and magnetic nanoparticles have been investigated. A well designed vector is the most forward approach to increase the safety of gene therapy. Though, Gendicine and Oncorine have been marketed, gene therapy is still in its infancy stages in cancer research. More experimental and clinical trials using well-designed and effective doses of vectors are needed to ensure the therapeutic efficacy of gene therapy for its clinical use against a wide variety of cancers. This review article discuses about the various strategies used in clinical trials of gene therapy for cancer.


Heath-related quality of life in Spanish breast cancer patients: a systematic review.
Breast cancer is one of the oncological diseases in which health-related quality of life (HRQL) has been most studied. This is mainly due to its high incidence and survival. This paper seeks to: review published research into HRQL among women with breast cancer in Spain; analyse the characteristics of these studies; and describe the instruments used and main results reported. The databases consulted were MEDLINE, EMBASE, PsycINFO, Dialnet, IBECS, CUIDEN, ISOC and LILACS. The inclusion criteria required studies to: 1) include Spanish patients, and a breakdown of results where other types of tumours and/or women from other countries were also included; and, 2) furnish original data and measure HRQL using a purpose-designed questionnaire. The methodological quality of studies was assessed. Spain ranked midway in the European Union in terms of the number of studies conducted on the HRQL of breast cancer patients. Of the total of 133 papers published from 1993 to 2009, 25 met the inclusion criteria. Among them, only 12 were considered as having good or excellent quality. A total of 2236 women participated in the studies analysed. In descending order of frequency, the questionnaires used were the EORTC, FACT-B, QL-CA-Afex, SF-12, FLIC, RSCL and CCV. Five papers focused on validation or adaptation of questionnaires. Most papers examined HRQL in terms of type of treatment. Few differences were detected by type of chemotherapy, with the single exception of worse results among younger women treated with radiotherapy. In the short term, better results were reported for all HRQL components by women undergoing conservative rather than radical surgery. Presence of lymphedema was associated with worse HRQL. Three studies assessed differences in HRQL by patients' psychological traits. Psychosocial disorder and level of depression and anxiety, regardless of treatment or disease stage, worsened HRQL. In addition, there was a positive effect among patients who reported having a "fighting spirit" and using "denial" as a defence mechanism. One study found that breast cancer patients scored worse than did healthy women on almost all SF-12 scales. Research into health-related quality of life of breast-cancer patients is a little developed field in Spain.


Spiritual and religious interventions for well-being of adults in the terminal phase of disease.
As terminal disease progresses, health deteriorates and the end of life approaches, people may ask "Why this illness? Why me? Why now?" Such questions may invoke, rekindle or intensify spiritual or religious concerns. Although the processes by which these associations occur are poorly understood, there is some research evidence for associations that are mainly positive between spiritual and religious awareness and wellness, such as emotional health. This review aimed to describe spiritual and religious interventions for adults in the terminal phase of a disease and to evaluate their effectiveness on well-being. We searched 14 databases to November 2011, including the Cochrane Central Register of Controlled Trials and MEDLINE. We included randomised controlled trials (RCTS) if they involved adults in the terminal phase of a disease and if they evaluated outcomes for an intervention that had a spiritual or religious component. Primary outcomes were well-being, coping with the disease and quality of life. In accordance with the inclusion criteria, two review authors independently screened citations. One review author extracted data which was then checked by another review author. We considered meta-analysis for studies with comparable characteristics. Five RCTs (1130 participants) were included. Two studies evaluated meditation, the others evaluated multi-disciplinary palliative care interventions that involved a chaplain or spiritual counsellor as a member of the intervention team. The studies evaluating meditation found no overall significant difference between those receiving meditation or usual care on quality of life or well-being. However, when meditation was combined with massage in the medium term it buffered against a reduction in quality of life. In the palliative care intervention studies there was no significant difference in quality of life or well-being between the trial arms. Coping with the disease was not evaluated in the studies. The quality of the studies was limited by under-reporting of design features. We found inconclusive evidence that interventions with spiritual or religious components for adults in the terminal phase of a disease may or may not enhance well-being. Such interventions are under-evaluated. All five studies identified were undertaken in the same country, and in the multi-disciplinary palliative care interventions it is unclear if all participants received support from a chaplain or a spiritual counsellor. Moreover, it is unclear in all the studies whether the participants in the comparative groups received spiritual or religious support, or both, as part of routine care or from elsewhere. The paucity of quality research indicates a need for more rigorous studies.


Raman spectroscopy of primary bovine aortic endothelial cells: a comparison of single cell and cell cluster analysis.
There are many techniques that allow in vitro interactions among cells and their environment to be monitored, including molecular, biochemical and immunochemical techniques. Traditional techniques for the analysis of cells often require fixation or lysis from substrates; however, use of such destructive methods is not feasible where the expanded cell cultures are required to be used for clinical implantation. Several studies have previously highlighted the potential of Raman spectroscopy to provide useful information on key biochemical markers within cells. As such, we highlight the capability of Raman spectroscopy with different laser spot sizes for use as a non-invasive, rapid, and specific method to perform in situ analysis of primary bovine aortic endothelial cells (BAECs). Raman spectra were collected from both individual live cells cultured on fused silica substrates and on clusters of live cells placed on fused silica substrates, measured at 532 and 785 nm. The results obtained show notable spectral differences in DNA/RNA region indicative of the relative cytoplasm and nucleus contributions. Raman spectra of cell clusters show slight variations in the intensity of the phenylalanine peak (1004 cm(-1)) indicating variations in protein contribution. These spectra also highlight contributions from other cellular components such as, proteins, lipids, nucleic acids and carbohydrates, respectively.


Salvage of advanced squamous cell carcinomas of the head and neck: internal carotid artery sacrifice and extracranial-intracranial revascularization.
Squamous cell carcinoma (SCC) of the head and neck may involve the carotid artery (CA) in the neck or skull base. Whether tumor resection should be associated with sacrifice of the CA is debatable. Records obtained in five consecutive patients (three men, and two women; mean age 58 years, range 47-69 years) treated for recurrent or progressive SCC involving the internal carotid artery (ICA) at the skull base were reviewed retrospectively. The ICA was sacrificed, an extracranial-intracranial (EC-IC) bypass was performed using a saphenous vein graft, and the tumor and involved ICA segment were resected. Gross-total resection of the SCC was achieved in four cases. One patient died of an acute postoperative stroke due to bypass occlusion and did not undergo tumor resection. No other permanent ischemic or neurological deficits were noted. The other four patients died of tumor progression (survival range 2-40 months, mean 14 months). One patient survived for more than 2 years (2-year overall survival rate 20%). Histological tumor invasion of the CA wall was verified in one of the three evaluated specimens. A high rate of morbidity and mortality is associated with cases in which skull base CA sacrifice and an EC-IC bypass are performed. Not all resected arteries are shown to have malignant infiltration on histological examination. Better preoperative imaging criteria are needed to define malignant infiltration of the ICA at the skull base. Chemotherapy and radiotherapy without aggressive tumor resection may be an option for these patients.


GAP-43 in growth cones is associated with areas of membrane that are tightly bound to substrate and is a component of a membrane skeleton subcellular fraction.
To ascertain the subcellular localization of the growth-associated protein GAP-43 in growth cones, we isolated growth cones from the forebrains of neonatal rats. Anti-GAP-43 immunoreactivity in these isolated growth cones (IGCs) resembled that seen in cultured growth cones in 2 respects: First, in substrate-attached IGCs, as in cultured growth cones, immunoreactivity was intracellular, punctate, and extended throughout the IGCs and their processes. Second, when IGCs were dislodged from this substrate, patches of membrane that were highly immunoreactive for GAP-43 were left behind. Extracting IGCs in nonionic detergents revealed that almost all the particulate GAP-43 colocalized with a membrane skeleton fraction: It was not present in the cytoskeleton. The association of GAP-43 with the membrane skeleton was not due to nonspecific aggregation, nor was it calcium dependent. Examination of this fraction under the electron microscope showed it to consist of membrane fragments associated with amorphous material that could be visualized with tannic acid. Immunoelectron microscopy showed that anti-GAP-43 immunoreactivity was localized to this amorphous material. Fodrin, talin, and a-actinin immunoreactivity could be detected in the membrane skeleton fraction, and actin and tubulin were also identifiable from SDS gels. The association of GAP-43 with the membrane skeleton, which by analogy with other cell types is involved in the dynamic regulation of cell shape, implies that GAP-43 in growth cones may be involved in this function.


External cephalic version of term singleton breech presentations with tocolysis: a retrospective study in a community hospital.
External version with the use of tocolysis in low-risk patients has been shown to be relatively safe and effective. A retrospective analysis was undertaken to see if version was practical for a smaller community-based hospital. Thirty-two antepartum external cephalic versions with ritodrine tocolysis during a 4-year period were reviewed. Successful version occurred in 59.4% of attempts. Of patients with a successful version, 68.4% delivered vaginally. One successful version occurred spontaneously with ritodrine tocolysis alone. A stillbirth due to abruptio placentae occurred 20 hours after a failed version attempt.


Nursing students' attitudes toward care of dying patients: A pre- and post-palliative course study.
Many nursing students are not prepared to encounter death and care for patients who are at the end of life as newly educated nurses. The Frommelt Attitude Toward Care of Dying Scale (FATCOD) has been used to assess nursing students' attitudes during their education and changes have been noted. To examine nursing students' attitudes towards care of dying patients before and after a course in palliative care. A descriptive study with a pre and post design. Nursing students (n = 73) enrolled in a mandatory palliative course in the nursing programme at a Swedish university. Data were collected before and after a palliative care course using FATCOD and qualitative open-ended questions. Data from FATCOD were analysed using descriptive and analytical statistics. The open-ended questions were analysed with qualitative content analysis. The students' mean scores showed a statistically significant change toward a more positive attitude toward care of dying. Students with the lowest pre-course scores showed the highest mean change. The qualitative analysis showed that the students had gained additional knowledge, deepened understanding, and increased feelings of security through the course. A course in palliative care could help to change nursing students' attitudes towards care of patients who are dying and their relatives, in a positive direction. A course in palliative care is suggested to be mandatory in nursing education, and in addition to theoretical lectures include learning activities such as reflection in small groups, simulation training and taking care of the dead body.


Prevalence of hepatitis C virus infection among health-care workers: A 10-year survey.
Hepatitis C virus (HCV) is one of the most common blood-borne pathogens transmitted from patients to health-care workers (HCWs). HCV infection status among HCWs and occupational blood exposure accidents were monitored to assess the risk of HCV infection among 403 HCWs from a single institution between 1999 and 2009. Additionally, HCV-related malignancies were evaluated in the HCV-positive HCWs. HCV infection was detected in 3% of the subjects at the first survey. The HCWs that initially tested negative for HCV remained negative during the 10 years of the survey. Of note, a statistically significant decrease was observed in the number of HCWs that experienced occupational blood exposure accidents, from 116 in 1999 to 72 in 2009 (p=0.0002). One HCV-infected HCW developed B-cell non-Hodgkin lymphoma (NHL) of the liver. The heavy chain gene combinations detected in the DNA from the NHL tissue were of the type usually found in HCV-associated lymphomas, supporting the role of HCV infection in the lymphomagenesis of this patient. The set of universal precautions recommended by the US Center for Disease Control and Prevention aided in the prevention of HCV transmission from patients to HCWs, as all 390 HCV-negative HCWs remained negative for the duration of the survey. Consequently, these recommendations also serve to prevent the development of HCV-associated malignancies such as hepatocellular carcinoma or B-cell NHL.


Extreme (13)C depletion of carbonates formed during oxidation of biogenic methane in fractured granite.
Precipitation of exceptionally 13C-depleted authigenic carbonate is a result of, and thus a tracer for, sulphate-dependent anaerobic methane oxidation, particularly in marine sediments. Although these carbonates typically are less depleted in 13C than in the source methane, because of incorporation of C also from other sources, they are far more depleted in 13C (δ13C as light as -69‰ V-PDB) than in carbonates formed where no methane is involved. Here we show that oxidation of biogenic methane in carbon-poor deep groundwater in fractured granitoid rocks has resulted in fracture-wall precipitation of the most extremely 13C-depleted carbonates ever reported, δ13C down to -125‰ V-PDB. A microbial consortium of sulphate reducers and methane oxidizers has been involved, as revealed by biomarker signatures in the carbonates and S-isotope compositions of co-genetic sulphide. Methane formed at shallow depths has been oxidized at several hundred metres depth at the transition to a deep-seated sulphate-rich saline water. This process is so far an unrecognized terrestrial sink of methane.


Beta-blocker effect on ST-segment: a prespecified analysis of the EARLY-BAMI randomised trial.
The effect of early intravenous (IV) beta-blockers (BBs) administration in patients undergoing primary percutaneous coronary intervention (pPCI) on ST-segment deviation is unknown. We undertook a prespecified secondary analysis of the Early Beta-blocker Administration before primary PCI in patients with ST-elevation Myocardial Infarction (EARLY-BAMI) trial to investigate the effect of early IV BB on ST-segment deviation. The EARLY-BAMI trial randomised patients with ST-elevation myocardial infarction (STEMI) to IV metoprolol (2×5 mg bolus) or matched placebo before pPCI. The prespecified outcome, evaluated by an independent core laboratory blinded to study treatment, was the residual ST-segment deviation 1 hour after pPCI (ie, the percentage of patients with >3 mm cumulative ST deviation at 1 hour after pPCI). An ECG for the evaluation of residual ST-segment deviation 1 hour after pPCI was available in 442 out of 683 randomised patients. The BB group had a lower heart rate after pPCI compared with placebo (71.2±13.2 vs 74.3±13.6, p=0.016); however, no differences were noted in the percentages of patients with >3 mm cumulative ST deviation at 1 hour after pPCI (58.6% vs 54.1%, p=0.38, in BB vs placebo, respectively) neither a significant difference was found for the percentages of patients in each of the four prespecified groups (normalised ST-segment; 1-3 mm; 4-6 mm;>6 mm residual ST-deviation). In patients with STEMI, who were being transported for primary PCI, early IV BB administration did not significantly affect ST-segment deviation after pPCI compared with placebo. The neutral result of early IV BB administration on an early marker of pharmacological effect is consistent with the absence of subsequent improvement of clinical outcomes.


Short Review: The Use of Conventional X-rays in Mummy Studies.
X-raying is arguably the most well-known, non-invasive technique for visualising the internal structures of ancient mummies and bog bodies. There are several factors such as the easy availability, the relative cheapness as well as the high spatial resolution, which speaks for this diagnostic modality in ancient mummy research. The aim of this short review is to address the advantages and pitfalls of this particular technique for such unique samples. We recommend that when results of X-ray examination of mummies are presented, the specific recording data should be listed, and any given finds, for example, of Paleopathology, should be cross-checked against other sources, for example, CT-scanning, direct inspection (also by endoscopy), and so forth.


Detecting Dementia Through Interactive Computer Avatars.
This paper proposes a new approach to automatically detect dementia. Even though some works have detected dementia from speech and language attributes, most have applied detection using picture descriptions, narratives, and cognitive tasks. In this paper, we propose a new computer avatar with spoken dialog functionalities that produces spoken queries based on the mini-mental state examination, the Wechsler memory scale-revised, and other related neuropsychological questions. We recorded the interactive data of spoken dialogues from 29 participants (14 dementia and 15 healthy controls) and extracted various audiovisual features. We tried to predict dementia using audiovisual features and two machine learning algorithms (support vector machines and logistic regression). Here, we show that the support vector machines outperformed logistic regression, and by using the extracted features they classified the participants into two groups with 0.93 detection performance, as measured by the areas under the receiver operating characteristic curve. We also newly identified some contributing features, e.g., gap before speaking, the variations of fundamental frequency, voice quality, and the ratio of smiling. We concluded that our system has the potential to detect dementia through spoken dialog systems and that the system can assist health care workers. In addition, these findings could help medical personnel detect signs of dementia.


Proteomic analysis of follicular fluid during human ovulation.
Human ovulation is a biologically complex process that involves several biochemical factors, promoting follicular rupture and release of a fertilizable oocyte. Proteins which are present in follicular fluid at high concentrations during ovulation are likely to be active participants in the biochemical pathways of ovulation. The aim of the study was to identify, by use of a modern proteomic technique, proteins of human follicular fluid which are differentially regulated during ovulation of the natural menstrual cycle. This prospective experimental study over 3 years included women planned for laparoscopic sterilization. During surgery, retrieval of the dominant follicle was performed either at the preovulatory stage or during ovulation. Four women of preovulatory phase and four women of ovulatory phase met the predetermined criteria of hormone levels for respective phases, and samples of these were finally included out of the 15 women operated. Follicular fluid was aspirated from the excised follicle and subjected to mass spectrometry with the isobaric tags for relative and absolute quantification (iTRAQ) technology for isobaric tagging of peptides. This enables simultaneous identification and quantification of proteins. The protein profiles of the follicular fluid of the preovulatory phase and the ovulatory phase were analyzed, and proteins that were present were identified. A total of 502 proteins were identified, several of which previously have not been identified in human follicular fluid. Of the 115 proteins that were found in all samples, 20 proteins were at higher levels during ovulation. These were inflammatory-related proteins, coagulation factors, proteins in lipid metabolism, complement factors and antioxidants. Five proteins were present in lower levels during ovulation, with three being enzymes and the other two proteins of lipid metabolism and iron transport. Twenty-five follicular fluid proteins, with differential regulation during ovulation, were identified in human follicular fluid of the natural menstrual cycle. These proteins may have essential roles in the ovulatory cascade.


Hundreds of variants clustered in genomic loci and biological pathways affect human height.
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.


Epigallocatechin-3-gallate (EGCG) protects the oocytes from methyl parathion-induced cytoplasmic deformities by suppressing oxidative and endoplasmic reticulum stress.
Methyl parathion (MP) is a commonly used organophosphorus insecticide in commercial farming. It is well known that MP exposure can affect the function of nervous, respiratory, cardiovascular and reproductive systems. In our previous report we have demonstrated that MP exposure results in poor oocyte maturation and defective embryo development which is mainly mediated through oxidative stress. The present investigation was designed to explore whether using a potent free radical scavenger like Epigallocatechin-3-gallate (EGCG) can help in reducing the detrimental effects of MP on the oocytes. For the study, germinal vesicle (GV) stage oocytes collected from the ovaries of adult Swiss albino mice were subjected to in vitro maturation (IVM) in the presence or absence of MP (100 μg/mL) and/or EGCG (0.25 μM). MP significantly reduced the nuclear maturation rate, and resulted in poor cytoplasmic organization which was evident from the altered distribution pattern of mitochondria, endoplasmic reticulum and abnormal spindle organization. These changes were associated with significant elevation in oxidative stress and expression of ER stress markers such as 78 kDa Glucose regulated protein (GRP78) as well as X-box binding protein-1 (XBP1) in the oocytes. Further, the oocytes exposed to MP had lower activation rate and developmental potential. Supplementation of EGCG during IVM not only improved the nuclear maturation rate but also reduced the cytoplasmic abnormalities. These beneficial effects appear to be due to mitigation of oxidative and ER stress in oocytes. In conclusion, results of our study indicate that EGCG can help in alleviating MP-induced oocyte abnormalities.


Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model.
To investigate the survival of melanopsin-expressing retinal ganglion cells (mRGCs) after the induction of chronic ocular hypertension. Intraocular pressure (IOP) was elevated in adult Sprague-Dawley rats using an argon laser to photocoagulate the episcleral and limbal veins. IOP was measured with a calibrated tonometer and monitored for a period. Seven days before the animals were killed, a piece of sterile foam soaked with gold fluorescent dye was placed onto the superior colliculus (SC) to label the SC-projecting retinal ganglion cells (scRGCs) retrogradely. mRGCs were visualized by free floating immunohistochemistry on whole-mounted retinas. The number of surviving scRGCs and mRGCs were counted on flatmounted retinas. The branching pattern of dendrites and soma size of mRGCs were examined. An approximately 1.7-fold increase of IOP and a significant loss of scRGCs were found in experimental eyes after laser photocoagulation. However, no significant cell loss or morphologic changes on mRGCs and their dendrites after the induction of chronic ocular hypertension are noticed over a 12-week period. Although the degeneration of retinal ganglion cells (RGCs) is a major concern in glaucomatous damage, the findings show that mRGCs are less susceptible to death after the induction of chronic ocular hypertension. This result indicates that mRGCs carry some unique properties that are different from those of other subpopulations of RGCs. The immunohistochemistry approach can be used to distinguish easily these mRGCs from other subtypes. This method provides a useful tool to investigate their injury-resistant properties that are informative for the development of effective neuroprotective treatment for glaucoma.


Genome sequencing reveals widespread virulence gene exchange among human Neisseria species.
Commensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. However, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. The genus Neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. We undertook a comprehensive sequencing and analysis of human commensal and pathogenic Neisseria genomes. Commensals have an extensive repertoire of virulence alleles, a large fraction of which has been exchanged among Neisseria species. Commensals also have the genetic capacity to donate DNA to, and take up DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria serve as reservoirs of virulence alleles, and that they engage extensively in genetic exchange.


Statistical modelling and simulation of nanohybrid shish-kebab architecture of PE-b-PEG copolymers and carbon nanotubes.
Carbon nanotubes have been known to develop hierarchically ordered polymer nanocomposites by virtue of epitaxial crystallization. A unique product of CNT induced crystallization is generation of nanohybrid shish-kebab (NHSK) structure, which has gained tremendous attention owing to its unique applications. However, research faces major challenges in terms of producing tunable patterns on CNTs, which are largely governed by precise control of the crystallization parameters. Conventional methods of experimentation can mislead the effect of experimental conditions on NHSK structure. The effect of crystallization time, undercooling temperature and polymer concentration on the NHSK architecture of carbon nanotubes (CNTs) and on a block copolymer, polyethylene-b-polyethylene glycol (PE-b-PEG), was studied in this work by applying the Response Surface Methodology (RSM). The present novel investigation mainly reports the statistical models that can be used to predict the different NHSK structural features such as diameter, periodicity, and thickness by including the interaction and quadratic effects of experimental variables. The developed models are in very good agreement with the experimental data and are statistically significant. Our novel approach can be used to better understand the interplay between various crystallization parameters for periodic patterning on carbon nanotubes to generate tunable hierarchical structures.


Addition of meloxicam to the treatment of bovine clinical mastitis results in a net economic benefit to the dairy farmer.
Recently, it has been shown that the addition of meloxicam to standard antimicrobial therapy for clinical mastitis (CM) improves the conception rate of dairy cows contracting CM in the first 120 d in milk. The objective of our study was to assess whether this improved reproduction through additional treatment with meloxicam would result in a positive net economic benefit for the farmer. We developed a stochastic bio-economic simulation model, in which a dairy cow with CM in the first 120 d in milk was simulated. Two scenarios were simulated in which CM cases were treated with meloxicam in conjunction with antimicrobial therapy or with antimicrobial therapy alone. The scenarios differed for conception rates (31% with meloxicam or 21% without meloxicam) and for the cost of CM treatment. Sensitivity analyses were undertaken for the biological and economic components of the model to assess the effects of a wide range of inputs on inferences about the cost effectiveness of meloxicam treatment. Model results showed an average net economic benefit of €42 per CM case per year in favor of the meloxicam scenario. Cows in the no-meloxicam treatment scenario had higher returns on milk production, lower costs upon calving, and reduced costs of treatment. However, these did not outweigh the savings associated with lower feed intake, reduced number of inseminations, and the reduced culling rate. The net economic benefit favoring meloxicam therapy was a consequence of the better reproductive performance in the meloxicam scenario in which cows had a shorter calving to conception interval (132 vs. 143 d), a shorter intercalving interval (405 vs. 416 d), and fewer inseminations per conception (2.9 vs. 3.7) compared with cows in the no-meloxicam treatment scenario. This resulted in a shorter lactation, hence a lower lactational milk production (8,441 vs. 8,517 kg per lactation) with lower feeding costs in the meloxicam group. A lower culling rate (12 vs. 25%) resulted in lower replacement costs in the meloxicam treatment scenario. All of the scenarios evaluated in the sensitivity analyses favored meloxicam treatment over no meloxicam. This study demonstrated that improvements in conception rate achieved by the use of meloxicam, as additional therapy for mild to moderate CM in the first 120 d in milk, have positive economic benefits. This inference remained true over a wide range of technical and economic inputs, demonstrating that use of meloxicam is likely to be cost effective across many production systems.