Perfusion index-derived parameters as predictors of hypotension after induction of general anaesthesia: a prospective cohort study.
Induction of general anaesthesia is commonly associated with hypotension. This exposes patients to perioperative organ hypoperfusion and eventually damage. This study was designed to assess the ability of preoperative perfusion index (PI), plethysmographic variability index (PVI), and dicrotic plethysmography (Dicpleth) to predict hypotension after induction of general anaesthesia. In this cohort study, 95 ASA I and II adult patients who were scheduled for elective surgery under general anaesthesia were enrolled. The correlation between preoperative PI, PVI, Dicpleth and percentage decrease in mean arterial blood pressure after anaesthesia induction was investigated. Ability of PI, PVI, Dicpleth to detect post-induction hypotension was also analysed. The percent decrease in MAP after anaesthesia correlated with baseline PI (r = -0.45, P < 0.001), PVI (r = 0.45, P = 0.001) and Dicpleth (r = 0.16, P = 0.12). The PI cut-off value was ≤ 3.03 for a patient at risk for post-induction hypotension with 77.8% sensitivity, 75% specificity, positive and negative predictive values of 74.5% and 78.3%, respectively. Similarly, the ROC analysis revealed that baseline PVI (AUC = 0.73, 95% CI = 0.622-0.812) was suitable for detecting post-induction hypotension. Moreover, baseline Dicpleth (AUC = 0.63) showed significant predictive ability. The pre-anaesthetic PI and PVI 17, respectively, have a good ability to predict those at risk of developing post-induction hypotension in adult patients undergoing elective surgery under general anaesthesia. Future studies are needed in order to investigate the usefulness of Dicpleth in different circumstances during anaesthesia. Clinical trial registration ID: The study was registered at clinicaltrials.gov (NCT04217226).


A patient with persistent renal AL amyloid deposition after clinical remission by HDM/SCT therapy.
A 62-year-old female patient was admitted to our hospital for evaluation of nephrotic syndrome. Monoclonal gammopathy (IgG λ type) and urinary Bence Jones proteins were detected in the serum and urine by the immunofixation method. The initial renal biopsy revealed amyloid deposition in mesangial area, glomerular capillary walls and arterioles by Congo-red staining, and amyloid fibers were detected by electron microscopy. On the bone marrow test, plasma cells accounted for 8.6%. Based on these findings, we diagnosed as AL amyloidosis associated with multiple myeloma. We treated her by high-dose intravenous injection therapy of melphalan combined with autologous peripheral blood stem cell transplantation. She achieved complete hematologic response 27 months later, however. Urine M-protein disappeared 2 months after treatment, and proteinuria slowly disappeared 17 months after treatment. On the other hand, amyloid fibers remained in renal biopsied tissues at 17 and 53 months after therapy. Electron microscopic examination also revealed the similar amyloid fibers in glomeruli. These findings suggest that, in this case, immunoglobulin light chains may cause directly and/or indirectly glomerular epithelial injury and nephrotic range proteinuria rather than via amyloid fiber formation.


Clonotypic analysis of T cells in patients with autoimmune and viral hepatitis.
The immunopathogenesis of autoimmune hepatitis (AIH), and the role of T cells in the onset and maintenance of this disease, are still unclear. Since T cells expand clonally after stimulation by an antigen, it is important to analyze the behavior of T cells at a clonal level. We have established recently a novel system, using reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism (SSCP) that allows the identification of clonal accumulation of T cells in a lymphocyte population. Using this system, we demonstrated that oligoclonal T cells were accumulated in the liver of patients with AIH, and that identical T-cell clonotypes were detected in two different regions of the liver, although these features were also observed in cases with viral hepatitis. Only in cases with AIH, however, nearly all identical T cells were found to belong to CD8+ subset and there were very few CD4+ T cells in this population. Our results suggest that common antigens presented to CD8+ T cells in the context of HLA class I molecule are distributed diffusely in the liver of AIH. These findings also suggest that antigens recognized by CD4+ T cells may be relatively heterogeneous in the liver with AIH.


Reduction in insulin antibodies 42 months after transfer from porcine to human monocomponent insulins.
The present study was planned to evaluate if a longterm follow-up would show any modification of insulin antibodies in IDDs transferred from porcine to human monocomponent insulins. Nineteen IDDs, treated for more than one year with porcine monocomponent insulins, were transferred to the equivalent formulations of human insulin (Actrapid HM, Monotard HM); insulin antibodies, metabolic control, insulin dose, adverse drug reactions were evaluated during a 42-month follow-up. A reduction of IgG insulin antibodies was observed after 22 months of the follow-up and became significant (2p less than 0.05) at the 42nd month. No significant modification of metabolic control, insulin requirement, or hypoglycaemic episodes were recorded. No adverse events were reported.


The eighteenth-century scientific community: a prosopographical study.
The object of this note is to provide a prosopographical analysis of the eighteenth-century scientific community with a view to explaining the gradual breakdown over the course of that century of the traditional general categories of 'natural philosophy' and 'natural history', and their replacement by a wide range of separate scientific disciplines.


Uncontrolled Donation After Circulatory Determination of Death: A Systematic Ethical Analysis.
Uncontrolled donation after circulatory determination of death (uDCDD) refers to organ donation after a refractory cardiac arrest. We analyzed ethical issues raised by the uDCDD protocols of France, Madrid, and New York City. We recommend: (1) Termination of resuscitation (TOR) guidelines need refinement, particularly the minimal duration of resuscitation efforts before considering TOR; (2) Before enrolling in an uDCDD protocol, physicians must ascertain that additional resuscitation efforts would be ineffective; (3) Inclusion in an uDCDD protocol should not be made in the outpatient setting to avoid error and conflicts of interest; (4) The patient's condition should be reassessed at the hospital and reversible causes treated; (5) A no-touch period of at least 10 minutes should be respected to avoid the risk of autoresuscitation; (6) Once death has been determined, no procedure that may resume brain circulation should be used, including cardiopulmonary resuscitation, artificial ventilation, and extracorporeal membrane oxygenation; (7) Specific consent is required prior to entry into an uDCDD protocol; (8) Family members should be informed about the goals, risks, and benefits of planned uDCDD procedures; and (9) Public information on uDCDD is desirable because it promotes public trust and confidence in the organ donation system.


Review of the Effectiveness of Enteral Feeding in Pediatric Oncology Patients [Formula: see text].
Enteral supplementation for nutritional support in pediatric oncology patients remains nonstandardized across institutions and between providers. Pediatric oncology patients frequently fail to meet their growth curve percentiles, lose weight, and/or are malnourished due to both the oncologic process as well as side effects from chemotherapy and radiation treatments. Methods of increasing weight include enteral feeding (nasogastric, nasoduodenal/jejunal, or gastrostomy), parenteral intravenous feeding, and oral supplementation. Indications for feeding and feeding protocols are highly variable, in part due to parental and familial choices, and in part due to the lack of guidelines available for providers. This article provides a comprehensive literature review of 8 published studies regarding the effectiveness and safety of enteral feeding in maintaining or increasing weight in pediatric oncology patients to help inform practice. The review concludes that enteral feeding in pediatric oncology patients is an effective and safe method to affect weight positively. However, further research is needed for developing treatment guidelines, including establishing a timeline for initiation of feeding, and determining which patients are most likely to benefit from enteral feeding.


Cooperative Effect of Ni-Decorated Monolayer WS2, NiO, and AC on Improving the Flame Retardancy and Mechanical Property of Polypropylene Blends.
Improving the residual char of polypropylene (PP) is difficult due to the preferential complete combustion. Here, we designed a combination catalyst that not only provides physical barrier effects, but also dramatically promotes catalytic charring activity. We successfully synthesized WS2 monolayer sheets decorated with isolated Ni atoms that bond covalently to sulfur vacancies on the basal planes via thiourea. Subsequently, PP blends composed of 8 wt.% Ni-decorated WS2, NiO, and activated carbon (AC) were obtained (ENi-SWS2-AC-PP). Combining the physical barrier effects of WS2 monolayer sheets with the excellent catalytic carbonization ability of the ENi-SWS2-AC combination catalyst, the PP blends showed a remarkable improvement in flame retardancy, with the yield of residual char reaching as high as 41.6 wt.%. According to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations, it was revealed that the microstructure of residual char contained a large number of carbon nanotubes. The production of a large amount of residual char not only reduced the release of pyrolytic products, but also formed a thermal shield preventing oxygen and heat transport. Compared to pure PP, the peak heat release rate (pHRR) and total heat release rate (THR) of ENi-SWS2-AC-PP were reduced by 46.32% and 26.03%, respectively. Furthermore, benefiting from the highly dispersed WS2, the tensile strength and Young's modulus of ENi-SWS2-AC-PP showed similar values to pure PP, without sacrificing the toughness.


Science communication challenges about antimicrobial resistance in animal agriculture: insights from stakeholders.
Communicating about antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) requires technical knowledge, consideration of audience values and appropriate identification of communication strategies for multiple audiences. Within the context of animal agriculture, communicating about AMR represents an important and complex endeavour for veterinarians, governmental agencies, producers and the industry to convey policy and practice information regarding the use of antimicrobials in food animals. To assess the science communication challenges related to AMR by identifying the motivations, goals and struggles of animal agriculture stakeholders when communicating about AMR and AMS. Participants attending a meeting on AMR communication in animal agriculture (N = 80) completed a workshop on science communication, including small group meetings with oral/written comments collected. Participants included veterinarians, government agency representatives, industry stakeholders and producers. Results indicated participants believed providing more accurate information would resolve misunderstanding and concern about AMR to other stakeholders, counter to recommendations of science communicators. Other participants noted beliefs about the utility of stories in trying to explain how AMS is normative and consistent with the values of all parties interested in animal agriculture. Participants noted the importance of public engagement, even if the participants' perceived target audiences did not include the public. Communicating about AMR and AMS in animal agriculture contexts provide unique challenges. Few evidence-based recommendations are available for science communicators in these contexts and more research is needed to improve the quality of communication about AMR and AMS in animal agriculture.


Description of male, pupa and larva of Psorophora (Grabhamia) paulli and redescription of the female (Diptera: Culicidae).
The female of Psorophora (Grabhamia) paulli Paterson & Shannon is redescribed, and the pupa, fourth-instar larva and male genitalia are described and illustrated for the first time. Information about the distribution, bionomics and taxonomy is also included. Adults of Ps. paulli can be separated from the other species of the genus and subgenus by its small size. The larva of Ps. paulli is similar to that of Ps. varinervis Edwards and Ps. discolor (Coquillett) but can be separated based on the development of setae 1-X and 5-VIII, the length of the anal papillae and the comb on a sclerotized area.


MANAGEMENT OF ENDOCRINE DISEASE: l-Thyroxine replacement therapy in the frail elderly: a challenge in clinical practice.
The number of elderly people, mostly aged over 85 years (the 'oldest old'), is increasing worldwide. As a consequence, accompanying morbidity and disability have been increasing, and frailty, defined as an age-related condition of decline of physiological reserves and vulnerability, represents an emerging problem. Caring for older frail people may represent a challenge, since the elderly differ significantly from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions. Specific criteria of therapeutic appropriateness and modified goals of care are needed in such patients, also in endocrine care settings. Indeed, thyroid dysfunctions are among the most common conditions in older, multimorbid populations. The prevalence of overt and subclinical hypothyroidism is as high as 20% and thyroid hormone prescription is common in the elderly, with a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism. In addition, older patients have the highest rate of overtreatment during replacement therapy and are more susceptible to developing adverse effects from thyroid hormone excess. Recently, results of a multicentric randomized controlled trial, the TRUST-IEMO collaboration trial, added further insights to the debated question of whether and when levothyroxine treatment is required and if it is beneficial in the elderly. With this in mind, we revised the relevant literature on the impact of thyroid dysfunction and replacement therapy among older people, with the aim to better define indications, benefits and risks of l-T4 replacement therapy in the frail elderly.


[Objective roentgenologic diagnostics of anterior cruciform ligamentous disruption in servicemen].
The article is dedicated to the method of roentgenological diagnostics, developed at military traumatology and orthopaedics department of the S.M. Kirov Military medical academy, which allows objectively assessing degree of knee joint instability in consequence of anterior cruciform ligamentous disruption.


These studies were conducted to assess the effects of lead toxicity on exploratory behavior and running. Effects of lead on exploratory behavior and running speed in the shrew, Blarina brevicauda (Insectivora).
These studies were conducted to assess the effects of lead toxicity on exploratory behavior and running speed in the short-tailed shrew, Blarina brevicauda. Shrews from the experimental group received 25 mg/kg/day of lead acetate in their drinking water for a period of 90 days. Control subjects received sodium acetate. Exploratory behavior was determined using a computerized activity chamber where movements of test subjects broke infrared beams projected onto the floor of the apparatus. Time spent (sec) in exploration was recorded over eight 6-min intervals. Running speed (km/hr) was measured in a microprocessor-controlled rectangular racetrack fitted with photocell timers. With respect to time spent in exploration, there were significant differences between lead-exposed (20.5-23.9 sec per 6-min testing session) and control subjects (6.8-8.1 sec) after the sixth testing interval in the activity chamber. With respect to maximal running speed, control subjects ran significantly faster (mean: 14.8 km/hr) than their lead-exposed counterparts (5.83 km/hr). Lead-exposed animals exhibited hyperactivity and increased random locomotor movements. They would frequently bump into the walls and their movements were more random. Controls typically ran along the racetrack in a straight line. These results represent the first data for the effects of lead exposure on exploratory behavior and running speed for shrews.


Supporting Evidence-Informed Teaching in Biomedical and Health Professions Education Through Knowledge Translation: An Interdisciplinary Literature Review.
Phenomenon: The purpose of "systematic" reviews/reviewers of medical and health professions educational research is to identify best practices. This qualitative article explores the question of whether systematic reviews can support "evidence informed" teaching and contrasts traditional systematic reviewing with a knowledge translation (KT) approach to this objective. Degrees of freedom analysis (DOFA) is used to examine the alignment of systematic review methods with educational research and the pedagogical strategies and approaches that might be considered with a decision-making framework developed to support valid assessment. This method is also used to explore how KT can be used to inform teaching and learning. The nature of educational research is not compatible with most (11/14) methods for systematic review. The inconsistency of systematic reviewing with the nature of educational research impedes both the identification and implementation of "best-evidence" pedagogy and teaching. This is primarily because research questions that do support the purposes of review do not support educational decision making. By contrast to systematic reviews of the literature, both a DOFA and KT are fully compatible with informing teaching using evidence. A DOFA supports the translation of theory to a specific teaching or learning case, so could be considered a type of KT. The DOFA results in a test of alignment of decision options with relevant educational theory, and KT leads to interventions in teaching or learning that can be evaluated. Examples of how to structure evaluable interventions are derived from a KT approach that are simply not available from a systematic review. Insights: Systematic reviewing of current empirical educational research is not suitable for deriving or supporting best practices in education. However, both "evidence-informed" and scholarly approaches to teaching can be supported as KT projects, which are inherently evaluable and can generate actionable evidence about whether the decision or intervention worked for students, instructors, and the institution. A DOFA can also support evidence- and theory-informed teaching to develop an understanding of what works, why, and for whom. Thus KT, but not systematic reviewing, can support decision making around pedagogy (and pedagogical innovation) that can also inform new teaching and learning initiatives; it can also point to new avenues of empirical research in education that are informed by, and can inform, theory.


Mode mixing and losses in misaligned microcavities.
We present a study on the optical losses of Fabry-Pérot cavities subject to realistic transverse mirror misalignment. We consider mirrors of the two most prevalent surface forms: idealised spherical depressions, and Gaussian profiles generated by laser ablation. We first describe the mode mixing phenomena seen in the spherical mirror case and compare to the frequently-used clipping model, observing close agreement in the predicted diffraction loss, but with the addition of protective mode mixing at transverse degeneracies. We then discuss the Gaussian mirror case, detailing how the varying surface curvature across the mirror leads to complex variations in round trip loss and mode profile. In light of the severe mode distortion and strongly elevated loss predicted for many cavity lengths and transverse alignments when using Gaussian mirrors, we suggest that the consequences of mirror surface profile are carefully considered when designing cavity experiments.


IgD allotypic determinants. I. Determinants expressed on murine IgD of the a allotype.
Allotypes of membrane IgD of 27 strains of mice were determined with a series of anti-delta reagents, each capable of binding to the IgD of BALB/c spleen cells. One of these reagents is a newly defined allospecific rabbit anti-mouse-delta a. Typing with these reagents reveals the strain distribution of the previously described IgD.36 (Ig5.1) and IgD.43 (Ig5.4) specificities and demonstrates the existence of a new specificity, IgD.45 (Ig5.5). The results confirm the previous subdivision of the Igh-Ce haplotype into Igh-Ce, to which A mice are assigned, and Igh-Cn, to which NZB and NZW mice are assigned. In addition, it is shown that the Igh-Cd haplotype must also be subdivided. AKR mice, which express the a allele at the Igh-5(delta) locus, are designated as possessing the Igh-Cd haplotype while AL/N and C.AL20 mice, which have the e allele at the Igh-5(delta) locus, are assigned a new Igh-C haplotype designation, o.


Effect of starter culture on staphylococcal enterotoxin and thermonuclease production in dry sausage.
Different amounts of enterotoxin A-, B-, and C1-producing staphylococci were added to dry sausage prepared by normal processes, either alone or in conjunction with a starter culture (micrococci and lactobacilli). The sausage was examined after 0, 3, 7, 14, and 30 days for staphylococci, micrococci, and lactobacilli, and measurements were made of water activity, pH, enterotoxin, and thermostable nuclease. The results showed that in the absence of starter culture measurable amounts of enterotoxin A were formed in a 200-g sample of dry sausage in 3 days, the level of Staphylococcus aureus infection being over 10(6) cells/g. Enterotoxin B was not found, although the total number of staphylococci was over 10(8) cells/g. Enterotoxin C1 was observed when the Staphylococcus count was about 8 X 10(7) cells/g, but was no longer detectable after 7 days. The starter culture prevented the production of enterotoxin A in all cases investigated. By contrast, a very high-level inoculation of an enterotoxin C1-producing strain gave a positive result after 3 days of incubation even in the presence of a starter culture. Heat-stable nuclease was observed in all sausages to which enterotoxin-producing staphylococci were added. The cell count determined in a sample of sausage had no definite correlation with the thermonuclease activity of the sample.


Generation of Transfer-DNA-Free Base-Edited Citrus Plants.
To recover transgenic citrus plants in the most efficient manner, the use of selection marker genes is essential. In this work, it was shown that the mutated forms of the acetolactate synthase (ALS) gene in combination with the herbicide selection agent imazapyr (IMZ) added to the selection medium may be used to achieve this goal. This approach enables the development of cisgenic regenerants, namely, plants without the incorporation of those bacterial genes currently employed for transgenic selection, and additionally it allows the generation of edited, non-transgenic plants with altered endogenous ALS genes leading to IMZ resistance. In this work, the citrus mutants, in which ALS has been converted into IMZ-resistant forms using a base editor system, were recovered after cocultivation of the explants with Agrobacterium tumefaciens carrying a cytidine deaminase fused to nSpCas9 in the T-DNA and selecting regenerants in the culture medium supplemented with IMZ. Analysis of transgene-free plants indicated that the transient expression of the T-DNA genes was sufficient to induce ALS mutations and thus generate IMZ-resistant shoots at 11.7% frequency. To our knowledge, this is the first report of T-DNA-free edited citrus plants. Although further optimization is required to increase edition efficiency, this methodology will allow generating new citrus varieties with improved organoleptic/agronomic features without the need to use foreign genes.


Sleep Deprivation by Exposure to Novel Objects Increases Synapse Density and Axon-Spine Interface in the Hippocampal CA1 Region of Adolescent Mice.
Sleep has been hypothesized to rebalance overall synaptic strength after ongoing learning during waking leads to net synaptic potentiation. If so, because synaptic strength and size are correlated, synapses on average should be larger after wake and smaller after sleep. This prediction was recently confirmed in mouse cerebral cortex using serial block-face electron microscopy (SBEM). However, whether these findings extend to other brain regions is unknown. Moreover, sleep deprivation by gentle handling was reported to produce hippocampal spine loss, raising the question of whether synapse size and number are differentially affected by sleep and waking. Here we applied SBEM to measure axon-spine interface (ASI), the contact area between pre-synapse and post-synapse, and synapse density in CA1 stratum radiatum. Adolescent YFP-H mice were studied after 6-8 h of sleep (S = 6), spontaneous wake at night (W = 4) or wake enforced during the day by novelty exposure (EW = 4; males/females balanced). In each animal ≥425 ASIs were measured and synaptic vesicles were counted in ~100 synapses/mouse. Reconstructed dendrites included many small, nonperforated synapses and fewer large, perforated synapses. Relative to S, ASI sizes in perforated synapses shifted toward higher values after W and more so after EW. ASI sizes in nonperforated synapses grew after EW relative to S and W, and so did their density. ASI size correlated with presynaptic vesicle number but the proportion of readily available vesicles decreased after EW, suggesting presynaptic fatigue. Thus, CA1 synapses undergo changes consistent with sleep-dependent synaptic renormalization and their number increases after extended wake.SIGNIFICANCE STATEMENT Sleep benefits learning, memory consolidation, and the integration of new with old memories, but the underlying mechanisms remain highly debated. One hypothesis suggests that sleep's cognitive benefits stem from its ability to renormalize total synaptic strength, after ongoing learning during wake leads to net synaptic potentiation. Supporting evidence for this hypothesis mainly comes from the cerebral cortex, including the observation that cortical synapses are larger after wake and smaller after sleep. Using serial electron microscopy, we find here that sleep/wake synaptic changes consistent with sleep-dependent synaptic renormalization also occur in the CA1 region. Thus, the role of sleep in maintaining synaptic homeostasis may extend to the hippocampus, a key area for learning and synaptic plasticity.


Spinal Epidural Stimulation Strategies: Clinical Implications of Locomotor Studies in Spinal Rats.
Significant advancements in spinal epidural stimulation (ES) strategies to enable volitional motor control in persons with a complete spinal cord injury (SCI) have generated much excitement in the field of neurorehabilitation. Still, an obvious gap lies in the ability of ES to effectively generate a robust locomotor stepping response after a complete SCI in rodents, but not in humans. In order to reveal potential discrepancies between rodent and human studies that account for this void, in this review, we summarize the findings of studies that have utilized ES strategies to enable successful hindlimb stepping in spinal rats. Recent clinical and preclinical evidence indicates that motor training with ES plays a crucial role in tuning spinal neural circuitry to generate meaningful motor output. Concurrently administered pharmacology can also facilitate the circuitry to provide near optimal motor performance in SCI rats. However, as of today, the evidence for pharmacological agents to enhance motor function in persons with complete SCI is insignificant. These and other recent findings discussed in this review provide insight into addressing the translational gap, guide the design of relevant preclinical experiments, and facilitate development of new approaches for motor recovery in patients with complete SCIs.


Sex- and disease-specific inflammasome signatures in circulating blood leukocytes of patients with abdominal aortic aneurysm.
Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared to matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 vs 0.01 pg/ml) and IL-1β plasma levels (mean = 12.07 vs. 0.04 pg/ml) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients.


Cataract-preventing contact lens for in vivo imaging of mouse retina.
In vivo imaging of mouse retinas using two-photon or confocal laser scanning fluorescence microscopy is a powerful tool for time-lapse analyses of the dynamic movements of cell populations. However, acute and reversible opacification of the crystalline lenses of mouse eyes under anesthesia decreases the visibility of the ocular fundus. Therefore, we developed a customized contact lens for preventing cataract during continuous retinal imaging in anesthetized mice. This experimental approach will aid in the elucidation of cellular and molecular dynamics in the CNS under physiological and pathological conditions.


Experimental course of bioethics upon the bioethics core curriculum of UNESCO: methodoloy and result of investigation.
In October 2005 the General Conference of UNESCO adopted the Universal Declaration on Bioethics and Human Rights. The aim of this Declaration was to assist in the realization ofprinciples and support the thorough understanding of the consequences of the ethics of scientific and technical progress, especially for youth. In 2008, the Division of Ethics of Science and Technology Sector for Social and Human Sciences of UNESCO worked out an Educational Program (Bioethics Core Curriculum). On November 23, 2010 a Memorandum was signed between UNESCO and the Yerevan State Medical University after M. Heratsi. The Memorandum was aimed to test the Bioethics Core Curriculum of UNESCO. In this article we will analyze the aims and goals of studying the course, as well as disputable shortcomings of the Program, make recommendations for the improvement of the course of bioethics, and highlight the positive aspects of this Educational Program.


Passively Q-switched Nd:YAlO₃nanosecond laser using MoS₂as saturable absorber.
We report on the first passively Q-switched Nd:YAlO₃ laser at ~1079.5 nm using MoS₂ as saturable absorber. The MoS₂ saturable absorber is fabricated by transferring the liquid-phase-exfoliated MoS₂ nanosheets onto a BK7 glass substrate. By inserting the glass MoS₂ saturable absorber into a plano-concave Nd:YAlO₃ laser cavity, we obtain a stable Q-switched laser operation with a maximum average output power of 0.26 W corresponding to a pulse repetition rate of 232.5 kHz, a pulse width of 227 ns and a pulse energy of about 1.11 μJ. The results experimentally confirm the promising application of the new kind of 2D material, few-layer MoS₂, in solid state lasers.


Purification and characterization of a novel alcohol oxidase from Paenibacillus sp. AIU 311.
An oxidase catalyzing the conversion of glycolaldehyde to glyoxal was purified to the homogeneous state from Paenibacillus sp. AIU 311, and its properties were revealed. This enzyme was specific to glycolaldehyde and glyceraldehyde, and the reaction rates to other alcohols and aldehydes were less than 6% of that of glycolaldehyde. The Km values for glycolaldehyde and glyceraldehyde were estimated to be 13.2 and 7.5 mM, respectively. The glycolaldehyde oxidation was optimum at pH 6.5 and 50 degrees C. The molecular mass of this enzyme was 49 kDa, and it consisted of two identical subunits of 24 kDa. The NH2-terminal sequence was not homologous to those of alcohol oxidases. This is the first report of an oxidase exhibiting high specificity to a hydroxy group of aldehyde alcohols.


A nonvoxel-based dose convolution/superposition algorithm optimized for scalable GPU architectures.
Real-time adaptive planning and treatment has been infeasible due in part to its high computational complexity. There have been many recent efforts to utilize graphics processing units (GPUs) to accelerate the computational performance and dose accuracy in radiation therapy. Data structure and memory access patterns are the key GPU factors that determine the computational performance and accuracy. In this paper, the authors present a nonvoxel-based (NVB) approach to maximize computational and memory access efficiency and throughput on the GPU. The proposed algorithm employs a ray-tracing mechanism to restructure the 3D data sets computed from the CT anatomy into a nonvoxel-based framework. In a process that takes only a few milliseconds of computing time, the algorithm restructured the data sets by ray-tracing through precalculated CT volumes to realign the coordinate system along the convolution direction, as defined by zenithal and azimuthal angles. During the ray-tracing step, the data were resampled according to radial sampling and parallel ray-spacing parameters making the algorithm independent of the original CT resolution. The nonvoxel-based algorithm presented in this paper also demonstrated a trade-off in computational performance and dose accuracy for different coordinate system configurations. In order to find the best balance between the computed speedup and the accuracy, the authors employed an exhaustive parameter search on all sampling parameters that defined the coordinate system configuration: zenithal, azimuthal, and radial sampling of the convolution algorithm, as well as the parallel ray spacing during ray tracing. The angular sampling parameters were varied between 4 and 48 discrete angles, while both radial sampling and parallel ray spacing were varied from 0.5 to 10 mm. The gamma distribution analysis method (γ) was used to compare the dose distributions using 2% and 2 mm dose difference and distance-to-agreement criteria, respectively. Accuracy was investigated using three distinct phantoms with varied geometries and heterogeneities and on a series of 14 segmented lung CT data sets. Performance gains were calculated using three 256 mm cube homogenous water phantoms, with isotropic voxel dimensions of 1, 2, and 4 mm. The nonvoxel-based GPU algorithm was independent of the data size and provided significant computational gains over the CPU algorithm for large CT data sizes. The parameter search analysis also showed that the ray combination of 8 zenithal and 8 azimuthal angles along with 1 mm radial sampling and 2 mm parallel ray spacing maintained dose accuracy with greater than 99% of voxels passing the γ test. Combining the acceleration obtained from GPU parallelization with the sampling optimization, the authors achieved a total performance improvement factor of >175 000 when compared to our voxel-based ground truth CPU benchmark and a factor of 20 compared with a voxel-based GPU dose convolution method. The nonvoxel-based convolution method yielded substantial performance improvements over a generic GPU implementation, while maintaining accuracy as compared to a CPU computed ground truth dose distribution. Such an algorithm can be a key contribution toward developing tools for adaptive radiation therapy systems.


Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues.
A small family of structural analogues of the antimitotic tripeptides, hemiasterlins, have been designed and synthesized as potential inhibitors of tubulin polymerization. The effectiveness of a multicomponent approach was fully demonstrated by applying complementary versions of the isocyanide-based Ugi reaction. Compounds strictly related to the lead natural products, as well as more extensively modified analogues, have been synthesized in a concise and convergent manner. In some cases, biological evaluation provided evidence for strong cytotoxic activity (six human tumor cell lines) and for potent inhibition of tubulin polymerization.


A Modified Formula for Intraocular Lens Power Calculation Based on Aphakic Refraction in a Pediatric Population.
To investigate and optimize the accuracy of aphakic refraction (AR) techniques for secondary intraocular lens (IOL) power calculation in aphakic children. Thirty-three aphakic eyes of 18 patients who were candidates for secondary IOL implantation were enrolled in the present study. Axial length (AL) measured by optical biometry was used in the biometric formula (SRK-T, Holladay II, and Hoffer-Q). AR and spherical equivalent (SE) were used in two AR-based formulas (Ianchulev, Leccissotti). True power was calculated based on postoperative SE at three months' follow-up. Regarding the postoperative SE, 13 (40%) eyes were within ± 1.00 diopters (D) and 22 (66%) were within ± 2.00 D. Median absolute error (MedAE) was predicted to be 4.4 and 7.3 D with the use of Ianchulev and Leccissotti formulas, respectively. The corresponding value was 0.8 D with the biometric formula. All eyes were deemed to have myopic refraction when using the AR-based formulas except one eye with the Ianchulev formula. The coefficient of our modified formula was 1.7 instead of 2.01 in the Ianchulev formula. MedAE with the use of new formulae was 0.5 D and was comparable with the true IOL power (P = 0.22). Both Ianchulev and Leccissotti formulas resulted in a significant myopic surprise in aphakic children aged between 4.5 and 14 years. The modified formula proved to determine a more accurate SE that is comparable with biometric formulas.


Replication potential of cells via the protein kinase C-MAPK pathway: application of a mathematical model.
A mechanistically based mathematical model is used to investigate some of the important factors in priming hepatocytes to enter the G1 phase of the cell cycle. The model considers all of the relevant biochemical mechanisms from signal-receptor binding to the elevation of AP-1 (activation protein transcription factor) levels. Focus is centered on the chain of biochemical events governing the sequential activation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and AP-1. Factors such as amplitude and duration of growth factors signals, the kinetics of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) conversion, and the negative feedback control mechanisms governing initial steps in cellular replication were theoretically examined. The results of our theoretical assessments support the finding that specific mutations along the PKC-AP1 pathways can have a critical effect on the rate at which cells enter the division cycle.


Altered neurobiological function of brainstem hypoglossal neurons in DiGeorge/22q11.2 Deletion Syndrome.
DiGeorge/22q11.2 Deletion Syndrome (22q11DS) is a common genetic microdeletion syndrome that underlies several neurodevelopmental disorders including autism, attention deficit/hyperactivity disorder, and schizophrenia. In addition to cognitive impairments, those with 22q11DS have disrupted feeding and swallowing from birth onward. This perinatal dysphagia significantly compromises nutritional status, impairs appropriate weight gain, and can lead to life threatening aspiration-based infections. Appropriately timed excitation and inhibition of brainstem hypoglossal motor neurons, which innervate tongue muscles, is essential for proper feeding and swallowing. In this study we have examined changes in hypoglossal motor neuron function in the LgDel mouse model of 22q11DS. Hypoglossal motor neurons from LgDel mouse pups have action potentials with afterhyperpolarizations, mediated by a large conductance charybdotoxin-sensitive Ca-activated K current, that are significantly shorter in duration and greater in magnitude than those in wild-type pups. In addition, the amplitude, but not frequency, of glutamatergic excitatory glutamatergic postsynaptic currents (EPSCs) is diminished, and GABAergic, but not glycinergic, neurotransmission to hypoglossal motor neurons was reduced in LgDel animals. These observations provide a foundation for understanding the neurological changes in hypoglossal motor neuron function and their contribution to swallowing abnormalities that occur in DiGeorge/22q11.2 Deletion Syndrome.


Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors.
Over the last twenty years, tocotrienol analogues raised great interest because of their higher level and larger domain of biological activities when compared with tocopherols. Amongst the most promising therapeutic application, anti-inflammatory potency has been evaluated through the inhibition of various mediators of inflammation. Here, we worked on the isolation of two natural isoforms of garcinoic acid (i.e., δ and γ) from two different sources, respectively, Garcinia kola seeds and Garcinia amplexicaulis bark. We also developed semisynthetic strategies to access the other two non-natural α- and β-garcinoic acid isoforms. In the next stage of our work, microsomal prostaglandin E2 synthase was defined as a target to evaluate the anti-inflammatory potential of the four garcinoic acid isomers. Both dimethylated isoforms, β- and γ-garcinoic acid, exhibited the lowest IC50, 2.8 µM and 2.0 µM, respectively. These results showed that the affinity of tocotrienol analogues to microsomal prostaglandin E2 synthase-1 most probably contributes to the anti-inflammatory potential of this class of derivatives.


Influenza A community-acquired pneumonia in East London infants and young children.
Community-acquired pneumonia (CAP) is common in young children, but there are few data in Europe on influenza A virus as a cause of childhood CAP. The aim of this study was to determine the relative contributions of different etiologic agents to CAP in children. This was a 6-month prospective study of pediatric accident and emergency and general practice consultations with a diagnosis of CAP. Nasopharyngeal aspirates for viral immunofluorescence and PCR studies and blood cultures for bacterial studies were taken from 51 children with symptoms, signs and chest radiographic features that satisfied a diagnosis of pneumonia. An etiologic agent was isolated from 25 patients (49%). A viral cause was identified in 22 patients (43%), and influenza A virus and respiratory syncytial virus (RSV) were detected in 16 and 18% of all cases, respectively. Only four patients (8%) had a positive bacterial blood culture; three had Streptococcus pneumoniae and one had Neisseria meningitidis W135. Mycoplasma pneumoniae was detected in 2 children, and mixed infections were detected in 5 (10%). The use of viral PCR increased the detection rate of influenza A virus by 100%. Influenza A virus caused more than one-third of all viral CAP cases, a rate comparable with that of RSV CAP. Viral PCR doubled the diagnostic yield of influenza A virus. The clinical burden of influenza A CAP was comparable with that of RSV CAP, as measured by the duration of fever, hospital stay and total duration of illness.


The effect of Trichomonas vaginalis and the role of pH on cell culture monolayer viability.
In vitro, Trichomonas vaginalis produces contact-dependent cytotoxicity in which the monolayers are disrupted and monolayer cells die. In contrast, when cell-free filtrates of T. vaginalis culture supernatants are applied to a monolayer, detachment occurs but cell viability is maintained. Growth of T. vaginalis in culture results in a dramatic fall in pH. Both in systems where T. vaginalis grew in physical contact with McCoy cells and where they were physically separate, monolayers still disrupted; but the rate of death of McCoy cells significantly decreased when pH was rigidly controlled. This would indicate that cell death attributed to contact-dependent cytotoxicity is in part due to the drop in pH when T. vaginalis is grown in vitro.


Single-Molecule Investigations of Conformation Adaptation of Porphyrins on Surfaces.
The porphyrin macrocyclic core features dynamic conformational transformations in free space because of its structural flexibility. Once attached to a substrate, the molecule-substrate interaction often restricts this flexibility and stabilizes the porphyrin in a specific conformation. Here using molecular dynamic and density-functional theory simulations and scanning tunneling microscopy and spectroscopy, we investigated the conformation relaxation and stabilization processes of two porphyrin derivatives (5,15-dibromophenyl-10,20-diphenylporphyrin, Br2TPP, and 5,15-diphenylporphyrin, DPP) adsorbed on Au(111) and Pb(111) surfaces. We found that Br2TPP adopts either dome or saddle conformations on Au(111) but only the saddle conformation on Pb(111), whereas DPP deforms to a ruffled conformation on Au(111). We also resolved the structural transformation pathway of Br2TPP from the free-space conformations to the surface-anchored conformations. These findings provide unprecedented insights revealing the conformation adaptation process. We anticipate that our results may be useful for controlling the conformation of surface-anchored porphyrin molecules.


Theoretical and uniaxial experimental evaluation of human annulus fibrosus degeneration.
The highly organized structure and composition of the annulus fibrosus provides the tissue with mechanical behaviors that include anisotropy and nonlinearity. Mathematical models are necessary to interpret and elucidate the meaning of directly measured mechanical properties and to understand the structure-function relationships of the tissue components, namely, the fibers and extrafibrillar matrix. This study models the annulus fibrosus as a combination of strain energy functions describing the fibers, matrix, and their interactions. The objective was to quantify the behavior of both nondegenerate and degenerate annulus fibrosus tissue using uniaxial tensile experimental data. Mechanical testing was performed with samples oriented along the circumferential, axial, and radial directions. For samples oriented along the radial direction, the toe-region modulus was 2x stiffer with degeneration. However, no other differences in measured mechanical properties were observed with degeneration. The constitutive model fit well to samples oriented along the radial and circumferential directions (R(2)> or =0.97). The fibers supported the highest proportion of stress for circumferential loading at 60%. There was a 70% decrease in the matrix contribution to stress from the toe-region to the linear-region of both the nondegenerate and degenerate tissue. The shear fiber-matrix interaction (FMI) contribution increased by 80% with degeneration in the linear-region. Samples oriented along the radial and axial direction behaved similarly under uniaxial tension (modulus=0.32 MPa versus 0.37 MPa), suggesting that uniaxial testing in the axial direction is not appropriate for quantifying the mechanics of a fiber reinforcement in the annulus. In conclusion, the structurally motivated nonlinear anisotropic hyperelastic constitutive model helps to further understand the effect of microstructural changes with degeneration, suggesting that remodeling in the subcomponents (i.e., the collagen fiber, matrix and FMI) may minimize the overall effects on mechanical function of the bulk material with degeneration.


[Changes in the middle ear mucosa of the Wistar rat after experimental resection and obstruction of the eustachian tube].
Eustachian tube (ET) disfunction, alone or combined with other factors, is the main source of middle ear pathogenesis and can lead to other physiopathological events that originate disease (serous otitis media, adhesive otitis, cholesteatoma). In seven Wistar rats (study group), experimental mechanical obstruction of the left Eustachian tube was performed. Using an anterior cervical incision, the osteocartilaginous junction of the ET was severed and obliterated with a bit of muscle in order to prevent rechanneling. After a period of six months, the middle ear mucosa was removed for histological study. Comparisons were made of the experimental ear and the opposite ear, as well as the ears of three rats in the control group. We compared our findings with those of other authors and reviewed experimental animal models of serous otitis media and cholesteatoma that have been used to study the influence of ET in middle ear disease.


[Why controlled studies may lead to misleading and unconfirmed therapeutic concepts--a critical view of evidence-based medicine].
The concept of evidence-based medicine has gathered widespread support during recent years. While this concept has clear merits in compiling and qualifying up-to-date information for clinical decisions, it should be viewed with caution as the sole valid knowledge source for clinical decision-making. The limitations of such an approach are particularly striking when reviewing two key developments in modern cardiology, fibrinolysis and acute percutaneous intervention in acute myocardial infarction. In both cases, early studies and meta-analyses showed no benefit for these therapeutic interventions over earlier treatment. Only after further refinement (mainly in dosage, time window, concomitant heparin therapy for fibrinolysis, and the introduction of stents and IIb/IIIa inhibitors for acute intervention) did these therapies become universally acknowledged. It is therefore crucial to understand that especially for physicians actively participating in the development of a clinical field clinical decisions cannot be exclusively based on published evidence. Another important problem to consider is the time gap between the emergence of new therapies and the publication and reception by the medical audience, in particular in rapidly evolving fields as cardiology. While it is clear that clinical decision-making must be backed by solid knowledge of the published evidence, in particular the specialist involved in-depth in the field may use not yet proven therapeutic concepts and measures to the patient's advantage.


End-stage renal disease: a southern epidemic.
During the past decade, the annual incidence of patients entering long-term dialysis for end-stage renal disease (ESRD) has been increasing, while mortality from stroke and coronary artery heart disease has been decreasing. In the Southeast, hypertension is the most common cause of ESRD, followed closely by diabetes mellitus occurring most frequently in older minority patients, particularly blacks. The causes of the increase in ESRD are not known. Although control of any degree of hypertension with any antihypertensive drug will slow the progression of renal failure from any cause, captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been shown to slow progressive renal failure in patients with insulin-dependent diabetes mellitus to a greater degree than that expected from only its antihypertensive effect. This series of articles, originally presented at the 1993 annual meeting of the Southern Medical Association, reviews the epidemiology and pathophysiology of ESRD and offers a clinical approach to this serious problem.


Drugs for the perioperative control of hypertension: current issues and future directions.
The management of hypertension continues to pose important challenges. Recent developments have established the importance of more rigorous blood pressure control in the community. In the perioperative setting, hypertension has long been recognised as undesirable, although the adverse impact of high blood pressure on the acute risks of elective surgery may have been previously overstated.A number of agents and techniques are available to control blood pressure perioperatively. These include principally general and regional anaesthetics, alpha(2)-adrenoceptor agonists, peripheral alpha(1)- and beta-adrenoceptor antagonists, dihydropyridine calcium channel antagonists, dopamine D(1A)-receptor agonists (fenoldopam), and nitric oxide donors. Recent years have seen important developments in the receptor selectivity of new compounds and in pharmacokinetics, particularly esterase metabolism. The future study of genomics may enable us to identify patients at risk for hypertension-related adverse events and target therapies most effectively to these high-risk groups.


NHS Direct: the early years.
NHS Direct was developed as part of the government's drive to deliver quality care wherever and whenever needed. It enables nurses to carry out a clinical consultation and assessment over the telephone with the aid of computer-based clinical decision support systems. The service was preceded by a range of telephone-based services provided by nurses in a number of settings. However, many of these early services were not evidence-based, and their availability and delivery was limited. Although nurses working for NHS Direct are supported by decision-making systems, they act as autonomous practitioners and are able to use their clinical judgement in advising patients.


Predictive and prognostic significance of sodium levels in patients with NSCLC treated by erlotinib.
Hyponatremia is a well-known phenomenon in cancer patients. The aim of our retrospective study was to assess the relationship of natremia levels to predict treatment with erlotinib and also to assess the prognosis of patients with hyponatremia. We analyzed data of 544 patients with advanced-stage non-small cell lung cancer (NSCLC) treated with erlotinib. Hyponatremia was measured in 21.5 % of patients before treatment with erlotinib. We found a significant increase in the effectiveness of treatment with erlotinib in patients with normal levels of sodium to hyponatremic patients. Progression-free survival (PFS) and overall survival (OS) were also significantly higher in patients with normal natremia. Multivariate Cox model analysis demonstrated that natremia was an independent factor for PFS and OS. We reported hyponatremia not only as a prognostic marker in NSCLC patients but also as predictive marker of erlotinib treatment efficacy, being an independent factor at the present large retrospective study. Its possible effect in clinical practice is bigger thanks the simple possibility of testing of hyponatremia and the low cost of this biomarker.


Differential induction of macrophage recognition of carrier erythrocytes by treatment with band 3 cross-linkers.
Mouse native and hypotonically loaded erythrocytes were treated with two cross-linking reagents: bis(sulphosuccinimidyl)suberate (BS3)- and 3,3'-dithiobis-(sulphosuccinimidyl propionate) (DTSP), excluding clustering agents. Microscopic analyses revealed that band 3 cross-linked native and hypotonically loaded erythrocytes are more strongly recognized by peritoneal macrophages than native and loaded erythrocytes as a result of the cross-linking of band 3 protein in accordance with studies in vivo. Macrophage-recognition analyses of 51Cr-labelled erythrocytes also demonstrated increased recognition of cross-linked and cross-linked loaded erythrocytes. This shows that the only action of these two band 3 cross-linkers on mouse erythrocytes promotes recognition by macrophages without requiring the use of clustering agents. The extent of recognition of BS3 cross-linked and cross-linked loaded erythrocytes by macrophages is dependent on the presence or absence of homologous serum or immunoglobulins. In contrast, the presence of serum factors or IgG in the incubation medium did not seem to influence the recognition of DTSP-modified erythrocytes by macrophages. These results seem to indicate a different mechanism of recognition for the erythrocytes modified with either one or the other band 3 cross-linker. In summary, the unique use of both band 3 cross-linkers procedures can be used to target carrier erythrocytes conveying active compounds to macrophages, with possible therapeutical applications. Different mechanisms of induction of macrophage recognition by these band 3 cross-linkers could reveal differential actions on erythrocytes or the involvement of different factors in the recognition process.


Biological activity of acetylated phenolic compounds.
In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.


Analysis of adiabatic trapping phenomena for quasi-integrable area-preserving maps in the presence of time-dependent exciters.
In this paper, results concerning the phenomenon of adiabatic trapping into resonance for a class of quasi-integrable maps and Hamiltonians with a time-dependent exciter are presented and discussed in detail. The applicability of the results about trapping efficiency for Hamiltonian systems to the maps considered is proven by using perturbation theory. This makes possible to determine explicit scaling laws for the trapping properties. These findings represent a generalization of previous results obtained for the case of quasi-integrable maps with parametric modulation, as well as an extension of the work by Neishtadt et al. [Regul. Chaotic Dyn. 18, 686 (2013)10.1134/S1560354713060087] on a restricted class of quasi-integrable systems with time-dependent exciters.


Low linolenic and linoleic acid consumption are associated with chronic kidney disease in patients with type 2 diabetes.
This cross-sectional study aimed to assess the association of the fat content in the diet with Diabetic Kidney Disease (DKD) in patients with type 2 diabetes. Patients from the Diabetes research clinic at Hospital de Clínicas de Porto Alegre (Brazil) were consecutively recruited. The inclusion criterion was the diagnosis of type 2 diabetes. The exclusion criteria were as follows: body mass index >40 kg/m2, heart failure, gastroparesis, diabetic diarrhea, dietary counseling by a registered dietitian during the previous 12 months, and inability to perform the weighed diet records (WDR). The dietary fatty acids (saturated, monounsaturated and polyunsaturated) consumption was estimated by 3-day WDR. Compliance with the WDR technique was assessed by comparison of protein intake estimated from the 3-day WDR and from the 24-h urinary nitrogen output performed on the third day of the WDR period. The presence of DKD was defined as urinary albumin excretion (UAE) ≥ 30 mg / 24 h or/and glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Urinary albumin was measured twice and eGFR was estimated by using the CKD-EPI equation. A total of 366 patients were evaluated; of these, 33% (n = 121) had DKD. Multivariate analysis showed that the intake of linolenic acid was negatively associated with DKD (OR = 0.57; 95% CI 0.35-0.93; P = 0.024), adjusted for gender, smoking, cardiovascular disease, ACE inhibitors and/or angiotensin receptor blocker use, systolic blood pressure, fasting plasma glucose and HDL cholesterol. In a separate model, similar results were observed for linoleic acid, adjusting to the same co-variables (OR = 0.95; 95% CI 0.91-0.99; P = 0.006). The lower intake of polyunsaturated fatty acids, especially linolenic and linoleic acid, is associated with chronic kidney disease in patients with type 2 diabetes.


Contrasting patterns of synonymous and nonsynonymous sequence evolution in asexual and sexual freshwater snail lineages.
In asexual lineages, both synonymous and nonsynonymous sequence polymorphism may be reduced due to severe founder effects when asexual lineages originate. However, mildly deleterious (nonsynonymous) mutations may accumulate after asexual lineages are formed, because the efficiency of purifying selection is reduced even in the nonrecombining mitochondrial genome. Here we examine patterns of synonymous and nonsynonymous mitochondrial sequence polymorphism in asexual and sexual lineages of the freshwater snail Campeloma. Using clade-specific estimates, we found that synonymous sequence polymorphism was significantly reduced by 75% in asexuals relative to sexuals, whereas nonsynonymous sequence polymorphism did not differ significantly between sexuals and asexuals. Two asexual clades had high negative values for Tajima's D statistic. Coalescent simulations confirmed that various bottleneck scenarios can account for this result. We also used branch-specific estimates of the ratio of amino acid to silent substitutions, K(a)/K(s). Our study revealed that K(a)/K(s) ratios are six times higher in terminal branches of independent asexual lineages compared to sexuals. Coalescent-based reconstruction of gene networks for all sexual and asexual clades indicated that nonsynonymous mutations occurred at a higher frequency in recently derived asexual haplotypes. These findings suggest that patterns of synonymous and nonsynonymous nucleotide polymorphism in asexual snail lineages may be shaped by both severe founder effect and relaxed purifying selection.


Role of local IgA antitoxin-producing cells for intestinal protection against cholera toxin challenge.
We examined in mice, perorally immunized with cholera toxin (CT) or cholera B subunit (CTB), the association between protection against intestinal toxin challenge and frequency and function of gut mucosal IgA antitoxin-forming cells. The in vitro production of IgA antitoxin by isolated cells and the toxin-neutralizing ability of culture supernatants were determined. Repeated oral immunizations with CT gave rise to high numbers of IgA antitoxin 'spot-forming' cells (SFC) in the lamina propria as well as to protection against challenge with CT in ligated intestinal loops. In contrast, mice immunized with purified CTB, gave poor IgA antitoxin SFC responses in the lamina propria and little or no protection. When a small amount of CT was used to adjuvant the response to CTB, many IgA antitoxin SFC were found; however, protection in intestinal loops remained poor. This discrepancy was explained by the predominant localization of antitoxin SFC in the proximal small intestine following oral CTB/CT-adjuvant immunization, whereas relatively few SFC were found further down in the intestine where the loop-protection test was performed. Thus, when lamina propria plasma cells were isolated from challenged loops and cultured in vitro, they released only low titers of IgA antitoxin and CT-neutralizing antibodies in culture supernatants; this was in contrast to cells from optimally immunized mice which gave supernatants with high IgA antitoxin and toxin-neutralizing antibody titers. Increasing the dose of CT, added as adjuvant to the CTB, resulted in better protection and higher numbers of IgA antitoxin SFC in more distal parts of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)


Management of work-related common mental disorders in general practice: a cross-sectional study.
General practitioners (GPs) often manage individuals with work-related common mental disorders (CMD: depressive disorders, anxiety and alcohol abuse). However, little is known about the ways in which they proceed. The aim of this study is to analyze GPs' management and patterns of referral to other health professionals of patients with work-related CMD and associated factors. We used data from a cross-sectional study of 2027 working patients of 121 GPs in the Nord - Pas-de-Calais region in France (April - August 2014). Statistical analyses focused on patients with work-related CMD detected by the GP and examined the ways in which GPs managed these patients' symptoms. Associations between patient, work, GP and contextual characteristics and GPs' management were explored using modified Poisson regression models with robust variance. Among the 533 patients with work-related CMD in the study, GPs provided psychosocial support to 88.0%, prescribed psychotropic treatment to 82.4% and put 50.7% on sick leave. Referral rates to mental health specialists and occupational physicians were respectively 39.8 and 26.1%. Several factors including patients' characteristics (occupational and sociodemographic), GPs' characteristics and environmental data were associated with the type of management used by the GP. Our study emphasizes the major and often lonesome role of the GP in the management of patients with work-related CMDs. Better knowledge of the way GPs manage those patients could help GPs in their practice, improve patients care and be a starting point to implement a more collaborative care approach.


Systemic administration of recombinant methionyl human interleukin-2 (Ala 125) to cancer patients: clinical results.
Nineteen evaluable patients with advanced malignancy were treated with recombinant methionyl human interleukin-2 (Ala 125), 5 days per week by intravenous bolus. Patients were entered in five groups at starting doses ranging from 0.05 to 2.56 x 10(6) U/m2. Doses were escalated weekly as tolerated toward a potential maximal dose of 11.6 x 10(6) U/m2. Maximal tolerated dose was 3.84 x 10(6) U/m2. Dose-limiting toxicity included fatigue, rigors, nausea/vomiting, fever, and diarrhea. Other toxicities included hyperesthesias, arthralgias/myalgias, rash, fluid retention, balanitis, and mild confusion. Leukocytosis, including granulocytosis, eosinophilia, and mild lymphocytosis, was observed, as was rare mild thrombocytopenia. No partial or complete response occurred. T1/2 alpha averaged 13.4 min, with interleukin-2 detectable 2 h after doses of greater than or equal to 2.56 x 10(6) U/m2. Three patients developed anti-IL-2 antibodies without demonstrable clinical significance.


Dynamics of hydrogen-bonded OH stretches as revealed by single-mode infrared-ultraviolet laser double resonance spectroscopy on supersonically cooled clusters of phenol.
The hydrogen-bonded (H-bonded) OH stretching vibrations in the electronic ground state of jet-cooled phenol-H(2)O, phenol-methanol, and phenol-NH(3) clusters have been measured with high-resolution double resonance spectroscopy using single-mode IR and UV lasers. All the observed H-bonded OH bands are homogeneously broadened, and the corresponding bandwidths are obtained by curve fitting the observed spectra to Lorentzian functions. In comparison with the result of time-resolved experiments [Phys. Chem. Chem. Phys. 9, 1170 (2007)], it is found that there is a quantitative correlation between the bandwidth and the vibrational frequency shift upon the complex formation. It seems that the observed phenomena can be explained by considering the potential coupling between the intramolecular and intermolecular vibrational modes.


[Study on the antidiuretic efficacy and mechanism of indapamide in central diabetes insipidus].
To investigate the efficacy and antidiuretic mechanism of indapamide in central diabetes insipidus. We observed eight patients with central diabetes insipidus treated by indapamide (2.5-7.5 mg.d-1) or dihydro-chlorothiazide (50-70 mg.d-1) or carbamazepine (150-300 mg.d-1) for 8 days with randomized block design. The therapy was changed twice in sequence after 4 days without treatment. Urine output and indexes of water metabolism were also observed. The urine output was reduced on the 4th day and 8th day with each therapy. The serum potassium and chloride concentration was decreased and renin activity was increased on the 4th and 8th day with indapamide therapy. Indapamide has antidiuretic action on central diabetes insipidus. The action may result from the changes of hydroelectrolytes and renin-angiotensin-aldosterone system.


Immunohistochemical demonstration of estrophilin in mouse tissues using a biotinylated monoclonal antibody.
We have developed a direct avidin-biotin-peroxidase complex (ABC) immunohistochemical method for localization of estrophilin in mouse tissues. The method has been found especially useful for microscopic demonstration of the receptor in mouse liver, since the indirect alternative, autoradiography after injection of radiolabeled estrogens, is of no value in this organ. The ABC technique employs a biotinylated monoclonal antibody to human estrophilin (Abbot H222) which was previously shown to crossreact with the murine receptor. Cryostat-cut tissue sections which were briefly fixed were incubated with the modified antibody, and the estrophilin was revealed by subsequent exposure to ABC followed by H2O2/diaminobenzidine.


Rectal metastasis from breast cancer: an interval of 17 years.
Metastasis to gastrointestinal (GI) tract from breast cancer is rare. Commonly affected organ in GI tract is stomach, followed by colon and then rectum. The authors report a case of a 61-year-old woman who had a mastectomy for lobular carcinoma of the breast 17 years ago and was referred to colorectal clinic with increased frequency of stools. Colonoscopy showed a stricture in the rectum, but biopsy was inconclusive. As she was symptomatic, she had a Hartmann's resection 5 months after she initially presented to the clinic. Histopathology of the resected specimen showed it to be metastasis from lobular carcinoma of the breast. Awareness of potential long delays in the presentation of metastatic breast cancer especially lobular carcinoma helps in the earlier diagnosis and clinical management.


Companion cropping with potato onion enhances the disease resistance of tomato against Verticillium dahliae.
Intercropping could alleviate soil-borne diseases, however, few studies focused on the immunity of the host plant induced by the interspecific interactions. To test whether or not intercropping could enhance the disease resistance of host plant, we investigated the effect of companion cropping with potato onion on tomato Verticillium wilt caused by Verticillium dahliae (V. dahliae). To investigate the mechanisms, the root exudates were collected from tomato and potato onion which were grown together or separately, and were used to examine the antifungal activities against V. dahliae in vitro, respectively. Furthermore, RNA-seq was used to examine the expression pattern of genes related to disease resistance in tomato companied with potato onion compared to that in tomato grown alone, under the condition of infection with V. dahliae. The results showed that companion cropping with potato onion could alleviate the incidence and severity of tomato Verticillium wilt. The further studies revealed that the root exudates from tomato companied with potato onion significantly inhibited the mycelia growth and spore germination of V. dahliae. However, there were no significant effects on these two measurements for the root exudates from potato onion grown alone or from potato onion grown with tomato. RNA-seq data analysis showed the disease defense genes associated with pathogenesis-related proteins, biosynthesis of lignin, hormone metabolism and signal transduction were expressed much higher in the tomato companied with potato onion than those in the tomato grown alone, which indicated that these defense genes play important roles in tomato against V. dahliae infection, and meant that the disease resistance of tomato against V. dahliae was enhanced in the companion copping with potato onion. We proposed that companion cropping with potato onion could enhance the disease resistance of tomato against V. dahliae by regulating the expression of genes related to disease resistance response. This may be a potential mechanism for the management of soil-borne plant diseases in the intercropping system.


Stable recombinase-mediated cassette exchange in Arabidopsis using Agrobacterium tumefaciens.
Site-specific integration is an attractive method for the improvement of current transformation technologies aimed at the production of stable transgenic plants. Here, we present a Cre-based targeting strategy in Arabidopsis (Arabidopsis thaliana) using recombinase-mediated cassette exchange (RMCE) of transferred DNA (T-DNA) delivered by Agrobacterium tumefaciens. The rationale for effective RMCE is the precise exchange of a genomic and a replacement cassette both flanked by two heterospecific lox sites that are incompatible with each other to prevent unwanted cassette deletion. We designed a strategy in which the coding region of a loxP/lox5171-flanked bialaphos resistance (bar) gene is exchanged for a loxP/lox5171-flanked T-DNA replacement cassette containing the neomycin phosphotransferase (nptII) coding region via loxP/loxP and lox5171/lox5171 directed recombination. The bar gene is driven by the strong 35S promoter, which is located outside the target cassette. This placement ensures preferential selection of RMCE events and not random integration events by expression of nptII from this same promoter. Using root transformation, during which Cre was provided on a cotransformed T-DNA, 50 kanamycin-resistant calli were selected. Forty-four percent contained a correctly exchanged cassette based on PCR analysis, indicating the stringency of the selection system. This was confirmed for the offspring of five analyzed events by Southern-blot analysis. In four of the five analyzed RMCE events, there were no additional T-DNA insertions or they easily segregated, resulting in high-efficiency single-copy RMCE events. Our approach enables simple and efficient selection of targeting events using the advantages of Agrobacterium-mediated transformation.


Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance.
Insulin resistance (IR) precedes the onset of Type 2 diabetes, but its impact on preconditioning against myocardial ischemia-reperfusion injury is unexplored. We examined the effects of diazoxide and ischemic preconditioning (IPC; 5-min ischemia and 5-min reperfusion) on ischemia (30 min)-reperfusion (240 min) injury in young IR Zucker obese (ZO) and lean (ZL) rats. ZO hearts developed larger infarcts than ZL hearts (infarct size: 57.3 +/- 3% in ZO vs. 39.2 +/- 3.2% in ZL; P < 0.05) and also failed to respond to cardioprotection by IPC or diazoxide (47.2 +/- 4.3% and 52.5 +/- 5.8%, respectively; P = not significant). In contrast, IPC and diazoxide treatment reduced the infarct size in ZL hearts (12.7 +/- 2% and 16.3 +/- 6.7%, respectively; P < 0.05). The mitochondrial ATP-activated potassium channel (K(ATP)) antagonist 5-hydroxydecanoic acid inhibited IPC and diazoxide-induced preconditioning in ZL hearts, whereas it had no effect on ZO hearts. Diazoxide elicited reduced depolarization of isolated mitochondria from ZO hearts compared with ZL (73 +/- 9% in ZL vs. 39 +/- 9% in ZO; P < 0.05). Diazoxide also failed to enhance superoxide generation in isolated mitochondria from ZO compared with ZL hearts. Electron micrographs of ZO hearts revealed a decreased number of mitochondria accompanied by swelling, disorganized cristae, and vacuolation. Immunoblots of mitochondrial protein showed a modest increase in manganese superoxide dismutase in ZO hearts. Thus obesity accompanied by IR is associated with the inability to precondition against ischemic cardiac injury, which is mediated by enhanced mitochondrial oxidative stress and impaired activation of mitochondrial K(ATP).


N400 and P600 or the role of the ERP correlates in sentence comprehension: some applications to the Italian language.
In the present study, event-related brain potentials (ERPs) were applied to the study of language comprehension in the Italian language. The ERPs were recorded from 10 electrodes while the participants read (Experiment 1) or listened (Experiment 2) to sentences containing semantic or syntactic anomalies. Final words that were inconsistent with the sentence context elicited a negative wave at about 400 ms poststimulus that was more concentrated in the posterior sites of the scalp, whereas final words that were incongruous with the grammatical structure (subject-verb nonagreement) elicited a positive wave at about 600 ms poststimulus that was homogeneously distributed on the scalp. The authors found no differences based on the perceptual modality of the stimulus (visual or auditory), nor did they find different ERP correlates as a function of task relevance (explicit-implicit task induction). The available evidence indicated that the ERP response to semantic anomalies was at least partially distinct from the ERP response to syntactic anomalies, and that a syntactic parser is a plausible process included in sentence comprehension. The two semantic and syntactic effects appear as automatic processes of the decoding of the anomalies and also modality-independent processes. Cross-linguistic applications are considered in the general discussion.


Effect of diagnosis and treatment of clinical endometritis based on vaginal discharge score grading system in postpartum Holstein cows.
In this study, the prevalence, effectiveness of diagnosis, and treatment based on vaginal discharge score (VDS) of clinical endometritis in cattle were evaluated. To detect clinical endometritis and classify its severity, vaginoscopy was performed during 21 to 60 days postpartum in 164 Holstein cows consisting of 229 lactations. Groups were defined using the 4-point VDS scale. Study groups included the following: non-endometritis (VDS=0; no/clear mucus; NEM group; n=168); mild endometritis, no treatment (VDS=1; mucus containing flecks of white/off-white pus; NTR group; n=30); and severe endometritis, treated with PGF2α (VDS≥2; discharge containing <50% pus; and VDS=3; discharge containing >50% pus, and fluid or uterine horn asymmetry; TEM group; n=31). Cows treated with PGF2α that did not recover (VDS≥1, n=5) received intrauterine procaine penicillin and streptomycin. Prevalence of clinical endometritis (VDS≥1) was 26.6%. The NTR group required significantly more artificial inseminations per pregnancy than NEM and TEM groups (2.8 ± 1.8 vs 2.0 ± 1.3, 1.9 ± 0.8, P<0.05). In survival analysis, the proportion of non-pregnant cows was higher in the NTR group compared to the NEM (P=0.012) and TEM (P=0.076) groups. In the TEM group, calving to first artificial insemination interval tended to be higher in cows treated 41 to 60 days postpartum than cows treated 29 to 40 days postpartum (97.2 ± 27.1 vs 74.4 ± 19.7, P=0.084). Our study suggests that cows with VDS=1 may require treatment to recover fertility. Diagnosis and treatment of clinical endometritis based on a VDS grading system may improve dairy herd reproductive performance.


Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it's role in metabolic defects and neuronal apoptosis after TBI.
Metabolic defects and neuronal apoptosis initiated by traumatic brain injury (TBI) contribute to subsequent neurodegeneration. They are all regulated by mechanisms centered around mitochondrion. Type-1 cannabinoid receptor (CB1) is a G-protein coupled receptor (GPCR) enriched on neuronal plasma membrane. Recent evidences point to the substantial presence of CB1 receptors on neuronal mitochondrial outer membranes (mtCB1) and the activation of mtCB1 influences aerobic respiration via inhibiting mitochondrial cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/complex I pathway. The expression and role of neuronal mtCB1 under TBI are unknown. Using TBI models of cultured neurons, wild type and CB1 knockout mice, we found mtCB1 quickly upregulated after TBI. Activation of mtCB1 promoted metabolic defects accompanied with ATP shortage but protected neurons from apoptosis. Selective activation of plasma membrane CB1 showed no effects on neuronal metabolism and apoptosis. Activation of mtCB1 receptors inhibited mitochondrial cAMP/PKA/complex I and resulted in exacerbated metabolic defects accompanied with a higher ratio of ATP reduction to oxygen consumption decrease as well as neuronal apoptosis. Further research found the remarkable accumulation of protein kinase B (AKT) on neuronal mitochondria following TBI and the activation of mtCB1 upregulated mitochondrial AKT/complex V activity. Upregulation of mitochondrial AKT/complex V activity showed anti-apoptosis effects and alleviated ATP shortage in metabolic defects. Taken together, we have identified mtCB1 quickly upregulate after TBI and a dual role the mtCB1 might play in metabolic defects and neuronal apoptosis initiated by TBI: the inhibition of mitochondrial cAMP/PKA/complex I aggravates metabolic defects, energy insufficiency as well as neuronal apoptosis, but the coactivation of mitochondrial AKT/complex V mitigates energy insufficiency and neuronal apoptosis.


Cushing's syndrome: development of highly potent and selective CYP11B1 inhibitors of the (pyridylmethyl)pyridine type.
Potent and selective CYP11B1 inhibitors could be promising therapeutics for the treatment of Cushing's syndrome. Optimization of Ref 1 (5-((1H-imidazol-1-yl)methyl)-2-phenylpyridine) led to compound 44 (5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine) with a 50-fold improved IC50 value of 2 nM toward human CYP11B1 and an enhanced inhibition of the rat enzyme (IC50 = 2440 nM) compared to Ref 1 (IC50 > 10000 nM). Furthermore, selectivities over CYP11B2, CYP17, and CYP19 were observed, as well as satisfying metabolic stability not only in human and rat plasma but also in liver S9 fraction. Investigation of cytotoxicity and inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety criteria and can be considered for further in vivo evaluation in rats.


Contractile actin belt and mesh structures provide the opposite dependence of epithelial stiffness on the spontaneous curvature of constituent cells.
Actomyosin generates contractile forces within cells, which have a crucial role in determining the macroscopic mechanical properties of epithelial tissues. Importantly, actin cytoskeleton, which propagates actomyosin contractile forces, forms several characteristic structures in a 3D intracellular space, such as a circumferential actin belt lining adherence junctions and an actin mesh beneath the apical membrane. However, little is known about how epithelial mechanical property depends on the intracellular contractile structures. We performed computational simulations using a 3D vertex model, and demonstrated the longitudinal tensile test of an epithelial tube, whose inside and outside are defined as the apical and basal surfaces, respectively. As a result, these subcellular structures provide the contrary dependence of epithelial stiffness and fracture force on the spontaneous curvature of constituent cells; the epithelial stiffness increases with increasing the spontaneous curvature in the case of belt, meanwhile it decreases in the case of mesh. This qualitative difference emerges from the different anisotropic deformability of apical cell surfaces; while belt preserves isotropic apical cell shapes, mesh does not. Moreover, the difference in the anisotropic deformability determines the frequency of cell rearrangements, which in turn effectively decrease the tube stiffness. These results illustrate the importance of the intracellular contractile structures, which may be regulated to optimize mechanical functions of individual epithelial tissues.


State-of-the-art imaging of acute pancreatitis.
The purpose of this essay is to focus on the characteristic imaging features, as revealed by a variety of radiological modalities, which allow for an accurate diagnosis and staging of acute pancreatitis. In addition, emphasis will be made on the role of imaging in providing early prognostic information about the outcome of the disease.


Concordance of four methods of disability assessment using performance in the home as the criterion method.
To determine the concordance of 4 methods of disability assessment with the criterion method. Performance testing in the home was selected as the criterion. The task performance of 57 community-dwelling older women (>/=70 years) with knee osteoarthritis was examined through self report, proxy report, clinical judgment based on impairment measures, performance testing in an occupational therapy clinic, and performance testing in participants' homes. The 26 tasks represented 4 domains of daily living activities: 5 functional mobility, 3 personal care, 14 cognitively oriented instrumental activities of daily living (IADL), and 4 physically oriented IADL. In general, self reports and proxy reports had the highest concordance with in-home performance test results. Nonetheless, even for these methods, depending on task domain, the rate of discordance ranged from 31% to 54%, being least in personal care and greatest in the physically oriented IADL. Disability estimates based on self reports, proxy reports, clinical judgments, and hospital performance-based assessments are not interchangeable with in-home task performance.


Clinical and basic research on occipito-cervico-dorsal flaps: including a study of the anatomical territories of dorsal trunk vessels.
The authors have carried out a clinical study of all the patients who underwent reconstructions with occipito-cervico-dorsal flaps in their department between 1994 and 2003 and analyzed the outcomes of the surgery. The reconstructed areas ranged from the cheek to the anterior chest. Twenty-eight cases underwent reconstruction with microvascular augmented occipito-cervico-dorsal flaps, and four were reconstructed with single pedicle occipito-cervico-dorsal flaps. In five cases, distal partial necrosis was observed. The largest flap size was 43 x 23 cm (5 x 5-cm pedicle). In the microvascular augmented occipito-cervico-dorsal flaps, the circumflex scapular artery and veins were used in 28 cases, and dorsal intercostal perforators were used together with circumflex scapular artery and veins in five cases. The follow-up term was between 1 and 8 years. Neck scar contractures were released in all cases, and good results were obtained not only functionally but also aesthetically. In an anatomical study, the authors used 20 preserved cadavers and took angiograms of the dorsal region. Five cadavers were used to confirm the territory of each of the vessels that have close relations to the occipito-cervico-dorsal flap (the occipital artery, transverse cervical artery, circumflex scapular artery, and dorsal intercostal perforator artery). Each anatomical territory was clearly seen and its area identified.


Fasting produces antidepressant-like effects via activating mammalian target of rapamycin complex 1 signaling pathway in ovariectomized mice.
Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test. However, whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established. Therefore, in this study, we simulated perimenopausal depression via an ovariectomy in mice, and subjected them to a single 9-hour fasting 7 days later. We found that the ovariectomy increased the time spent immobile in the forced swimming test, inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefrontal cortex, and decreased the density of dendritic spines in the hippocampus. The 9-hour acute fasting alleviated the above-mentioned phenomena. Furthermore, all of the antidepressant-like effects of 9-hour fasting were reversed by an inhibitor of the mammalian target of rapamycin complex 1. Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting. These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus. Thus, fasting may be a potential treatment for depression.


Dissociative disorders: between neurosis and psychosis.
Dissociative disorders are a set of disorders defined by a disturbance affecting functions that are normally integrated with a prevalence of 2.4 percent in industrialised countries. These disorders are often poorly diagnosed or misdiagnosed because of sharing common clinical features with psychotic disorders, but requiring a very different trajectory of care. Repeated clinical situations in a crisis centre in Geneva provided us with a critical overview of current evidence of knowledge in clinical and etiopathological field about dissociative disorders. Because of their multiple expressions and the overlap with psychotic disorders, we focused on the clinical aspects using three different situations to better understand their specificity and to extend our thinking to the relevance of terms "neurosis" and "psychosis." Finally, we hope that this work might help physicians and psychiatrists to become more aware of this complex set of disorders while making a diagnosis.


Theory, targets and therapy in systemic lupus erythematosus.
The treatment of systemic lupus erythematosus (SLE) has been refined over the years, with the recognition that a fine balance lies between aggressive and prompt therapy and attendant complications brought upon by immunosuppressive therapy itself. However, there has been limited change to the repertoire of drugs available to treat this challenging disease. The current standard therapy for severe manifestations of SLE includes the use of high-dose corticosteroids and cytotoxic agents such as cyclophosphamide (CYC), which have been associated with an increased risk of serious and opportunistic infections. The need for safer, more targeted therapies has been recognized and now, with the exponential increase in the understanding of immunopathogenic mechanisms in SLE, the way has been paved for the development of biologic or targeted therapies in SLE. Although the potential immunosuppression, long-term safety issues and cost-effectiveness remain unclear. These targeted therapies may range from small molecules that specifically inhibit inflammatory processes at an intracellular, cell-cell or cell-matrix level to monoclonal antibodies, soluble receptors or natural antagonists that interfere with cytokine function, cellular activation and inflammatory gene transcription.


microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion.
Metastatic renal cancer manifests multiple signatures of gene expression. Deviation in expression of mature miRNAs has been linked to human cancers. Importance of miR-21 in renal cell carcinomas is proposed from profiling studies using tumor tissue samples. However, the role of miR-21 function in causing renal cancer cell proliferation and invasion has not yet been shown. Using cultured renal carcinoma cells, we demonstrate enhanced expression of mature miR-21 along with pre-and pri-miR-21 by increased transcription compared to normal proximal tubular epithelial cells. Overexpression of miR-21 Sponge to quench endogenous miR-21 levels inhibited proliferation, migration and invasion of renal cancer cells. In the absence of mutation in the PTEN tumor suppressor gene, PTEN protein levels are frequently downregulated in renal cancer. We show that miR-21 targets PTEN mRNA 3'untranslated region to decrease PTEN protein expression and augments Akt phosphorylation in renal cancer cells. Downregulation of PTEN as well as overexpression of constitutively active Akt kinase prevented miR-21 Sponge-induced inhibition of renal cancer cell proliferation and migration. Moreover, we show that miR-21 Sponge inhibited the inactivating phosphorylation of the tumor suppressor protein tuberin and attenuated TORC1 activation. Finally, we demonstrate that expression of constitutively active TORC1 attenuated miR-21 Sponge-mediated suppression of proliferation and migration of renal cancer cells. Our results uncover a layer of post-transcriptional regulation of PTEN by transcriptional activation of miR-21 to force the canonical oncogenic Akt/TORC1 signaling conduit to drive renal cancer cell proliferation and invasion.


Characterization of sol-gel Pb(Zr0.53Ti0.47O3) in thin film bulk acoustic resonators.
The behavior of {f111g}-textured Pb(Zr(0.53Ti0.47O3) (PZT) deposited by the sol-gel technique in thin film bulk acoustic resonators (TFBAR's) was investigated at a resonance frequency of about 1 GHz. The resonators were fabricated on Si wafers using deep silicon etching to create a membrane structure and using platinum as top and bottom electrodes. The best response of the resonators was observed at a bias voltage of -15 kV/cm with values of about 10% for the coupling constant and about 50 for the quality factor. This voltage corresponds to optimal values of piezoelectric constant d33 and dielectric constant measured as a function of the electric field. The influence of a bias voltage on the resonance frequency, antiresonance frequency, and coupling constant were observed. Both the resonance and antiresonance frequency show a hysteretic change with applied bias. This effect can be used to shift the whole band of a filter by applying a voltage. The TFBAR structure also allowed us to extract values for materials parameters of the PZT film. Dielectric, piezoelectric, and elastic properties of the f111g-textured PZT film are reported and compared to direct measurements and to literature values.


Birds of a Feather Flock Together: Category-Divergence Guidance for Domain Adaptive Segmentation.
Unsupervised domain adaptation (UDA) aims to enhance the generalization capability of a certain model from a source domain to a target domain. Present UDA models focus on alleviating the domain shift by minimizing the feature discrepancy between the source domain and the target domain but usually ignore the class confusion problem. In this work, we propose an Inter-class Separation and Intra-class Aggregation (ISIA) mechanism. It encourages the cross-domain representative consistency between the same categories and differentiation among diverse categories. In this way, the features belonging to the same categories are aligned together and the confusable categories are separated. By measuring the align complexity of each category, we design an Adaptive-weighted Instance Matching (AIM) strategy to further optimize the instance-level adaptation. Based on our proposed methods, we also raise a hierarchical unsupervised domain adaptation framework for cross-domain semantic segmentation task. Through performing the image-level, feature-level, category-level and instance-level alignment, our method achieves a stronger generalization performance of the model from the source domain to the target domain. In two typical cross-domain semantic segmentation tasks, i.e., GTA 5→ Cityscapes and SYNTHIA → Cityscapes, our method achieves the state-of-the-art segmentation accuracy. We also build two cross-domain semantic segmentation datasets based on the publicly available data, i.e., remote sensing building segmentation and road segmentation, for domain adaptive segmentation. Our code, models and datasets are available at https://github.com/HibiscusYB/BAFFT.


Should the Functional Residual Capacity be Ignored?
The functional residual capacity was given the least importance than the other lung volume parameters. Studies have revealed the restrictive pattern of lung disease in patients with liver cirrhosis. We aimed to analyze the importance of the functional residual capacity and other lung volumes of cirrhotic patients. Forty (40) patients with cirrhosis (Child's-B) were enrolled in this study. The vital capacity was measured by an instrument called V02 Max 22. The other lung volumes which were measured were derived parameters. The functional residual capacity was measured by the nitrogen wash-out method. The measured value of the functional residual capacity was below normal as compared to the reference value. The total lung capacity and the vital capacity were positively correlated with the functional residual capacity. The residual volume was found to be increased in twelve out of forty cirrhotic patients. The functional residual capacity can be determined by the compliance of the lung and the chest wall. The patients with a reduced functional residual capacity may be suffering from dyspnoea, probably due to the restrictive pattern of the lung disease. Hence, the reduced lung volumes of the subjects may be due to the abnormalities in the mechanics of ventilation.