Low Molecular Weight Cytokeratin Immunostaining for Extrafollicular Reticulum Cells is an Effective Means of Separating Salivary Gland Tumor-Associated Lymphoid Proliferation from True Lymph Node Involvement.
Tumor-associated lymphoid proliferation (TALP) is a well-recognized lymphocytic reaction that is commonly associated with certain salivary gland tumors. A salivary carcinoma with TALP may be confused for true lymph node involvement by that tumor, constituting a potential pitfall in tumor staging that may result in unnecessary therapeutic intervention or erroneous prognostication for patients. True lymph nodes harbor populations of extrafollicular reticulum cells (ERCs), which can be highlighted by low molecular weight cytokeratin immunohistochemistry. We sought to determine whether low molecular weight cytokeratin Cam5.2 immunostaining may be utilized to differentiate true lymph node involvement by salivary gland tumors from TALP. The surgical pathology archives of the University of Texas Southwestern Medical Center was searched for cases of salivary gland neoplasms exhibiting either TALP or true lymph node involvement. Hematoxylin and eosin-stained sections were examined. Cases were classified on the basis of a definitive lymph node capsule and subcapsular sinus, as seen on routine histologic evaluation. Low molecular weight cytokeratin Cam5.2 immunostaining was performed and evaluated on all cases. Twenty-three salivary gland carcinomas with TALP and 16 carcinomas involving a lymph node (14 carcinomas metastatic to regional lymph nodes and 2 carcinomas arising from benign lymph node inclusions) were identified. Numerous Cam5.2-positive ERCs were identified within the nodal tissue of all true lymph nodes involved by carcinoma (16 of 16 cases), while Cam5.2-positive ERCs were completely absent in all cases of salivary gland lesions with TALP (0 of 23 cases) (100% vs. 0%, p < .0001, Fisher's Exact). Utilization of low molecular weight cytokeratin Cam 5.2 immunostaining for ERCs is a highly useful tool for distinguishing true lymph node involvement by salivary gland carcinomas from TALP. This strategy may be useful in identifying genuine nodal metastasis in histologically ambiguous cases, and to avoid erroneously upstaging tumor with TALP as nodal metastasis with the resulting prognostic and therapeutic implications. Moreover, low molecular weight cytokeratin immunostaining may be useful in confirming the rare examples of salivary gland tumors arising from intranodal salivary gland inclusions.


Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma.
Burkitt lymphoma cells carrying either a rearranged or unrearranged c-myc oncogene were examined with the use of probes from the 5' exon and for the second and third exon of the oncogene. The results indicate that the normal c-myc gene on chromosome 8 and the 5' noncoding and 3' coding segments of the c-myc oncogene separated by the chromosomal translocation are under different transcriptional control in the lymphoma cells. Burkitt lymphoma cells carrying a translocated but unrearranged c-myc oncogene express normal c-myc transcripts. In contrast, lymphoma cells carrying a c-myc gene rearranged head to head with the immunoglobulin constant mu region gene express c-myc transcripts lacking the normal untranslated leader.


Evidence for onset of antipsychotic effects within the first 24 hours of treatment.
It is widely held that there is a delayed onset of antipsychotic action and that any early effects represent nonspecific behavioral effects. Recent research has shown that antipsychotic action begins within the first week. The authors tested the hypothesis that psychosis improves within the first 24 hours of antipsychotic treatment. In this multicenter, double-blind, placebo-controlled study, 311 patients with a diagnosis of schizophrenia spectrum disorder and an acute exacerbation were randomly assigned to receive 10 mg i.m. of olanzapine, 7.5 mg i.m. of haloperidol, or intramuscular placebo. Subjects were rated with structured rating scales (Positive and Negative Syndrome Scale and Clinical Global Impression) at baseline, 2 hours, and 24 hours. The olanzapine and haloperidol groups showed greater resolution of overall symptoms than the placebo group; for the olanzapine group, this effect was evident at 2 hours. A factor analysis showed that an independent change in psychosis (which included conceptual disorganization, hallucinatory behavior, unusual thought content) was evident within the first 24 hours for both drugs. This improvement in core psychosis was not mediated unidirectionally by changes in nonspecific behavioral effects or other psychopathology. These data suggest that the onset of antipsychotic action is early and that the magnitude of this action grows with time. This clinical reality calls into question some prevailing hypotheses regarding the mechanism of action of antipsychotics and suggests that antipsychotic action may be more proximally related to the blockade of dopamine transmission than was originally thought.


A meta-analysis of estimates of the AIDS incubation distribution.
Information from 12 studies is combined to estimate the AIDS incubation distribution with greater precision than is possible from a single study. The analysis uses a hierarchy of parametric models based on a four-parameter generalized F distribution. This general model contains four standard two-parameter distributions as special cases. The cases are the Weibull, gamma, log-logistic, lognormal distributions. These four special cases subsume three distinct asymptotic hazard behaviors. As time increases beyond the median of approximately 10 years, the hazard can increase to infinity (Weibull), can plateau at some constant level (gamma), or can decrease to zero (log-logistic and lognormal). The Weibull, gamma and 'log-logistic distributions' which represent the three distinct asymptotic hazard behaviors, all fit the data as well as the generalized F distribution at the 25 percent significance level. Hence, we conclude that incubation data is still too limited to ascertain the specific hazard assumption that should be utilized in studies of the AIDS epidemic. Accordingly, efforts to model the AIDS epidemic (e.g., back-calculation approaches) should allow the incubation distribution to take several forms to adequately represent HIV estimation uncertainty. It is recommended that, at a minimum, the specific Weibull, gamma and log-logistic distributions estimated in this meta-analysis should all be used in modeling the AIDS epidemic, to reflect this uncertainty.


Smoking and smoking cessation in relation to mortality in women.
Smoking is associated with an increased risk of total and cause-specific death, but the rate of mortality risk reduction after quitting compared with continuing to smoke is uncertain. There is inadequate or insufficient evidence to infer the presence or absence of a causal relationship between smoking and ovarian cancer and colorectal cancer. To assess the relationship between cigarette smoking and smoking cessation on total and cause-specific mortality in women. Prospective observational study of 104,519 female participants in the Nurses' Health Study with follow-up from 1980 to 2004. Hazard ratios (HRs) for total mortality, further categorized into vascular and respiratory diseases, lung cancer, other cancers, and other causes. A total of 12,483 deaths occurred in this cohort, 4485 (35.9%) among never smokers, 3602 (28.9%) among current smokers, and 4396 (35.2%) among past smokers. Compared with never smokers, current smokers had an increased risk of total mortality (HR, 2.81; 95% confidence interval [CI], 2.68-2.95) and all major cause-specific mortality. The HR for cancers classified by the 2004 surgeon general's report to be smoking-related was 7.25 (95% CI, 6.43-8.18) and 1.58 (95% CI, 1.45-1.73) for other cancers. Compared with never smokers, the HR for colorectal cancer was 1.63 (95% CI, 1.29-2.05) for current smokers and 1.23 (95% CI, 1.02-1.49) for former smokers. A significant association was not observed for ovarian cancer. Significant trends were observed for earlier age at initiation of smoking for total mortality (P = .003), respiratory disease mortality (P = .001), and all smoking-related cancer mortality (P = .001). The excess risk for all-cause mortality decreases to the level of a never smoker 20 years after quitting, with different time frames for risk reduction observed across outcomes. Approximately 64% of deaths among current smokers and 28% of deaths among former smokers were attributable to cigarette smoking. Most of the excess risk of vascular mortality due to smoking in women may be eliminated rapidly upon cessation and within 20 years for lung diseases. Postponing the age of smoking initiation reduces the risk of respiratory disease, lung cancer, and other smoking-related cancer deaths but has little effect on other cause-specific mortality. These data suggest that smoking is associated with an increased risk of colorectal cancer mortality but not ovarian cancer mortality.


The influence of circadian blood pressure changes on aortic distensibility and left ventricular diastolic function in hypertensive individuals.
Failure to decrease blood pressure (BP) normally during nighttime, which is called non-dipper, in hypertensive individuals is associated with higher cardiovascular morbidity and mortality. In addition, non-dipper BP leads to structural changes in the left ventricle; however, the influences of non-dipper BP on aortic elastic properties and left ventricular diastolic function have not been studied yet. In this study, we evaluated aortic elastic properties and left ventricular diastolic function of 22 subjects with non-dipper hypertension, and 15 subjects with dipper hypertension using transthoracic second harmonic standard and tissue Doppler echocardiography (Acuson Sequoia C256). None of the subjects had any systemic disease or coronary risk factor except hypertension. Age, gender, body mass index, lipids, and standard echocardiographic findings including left ventricular mass index were similar between the groups. Office BP recordings were similar between non-dipper and dipper groups (147.9+/-6.1/93.9+/-4.3 vs. 144.0+/-8.0/93.0+/-3.7). Daytime and 24-h ambulatory BP measurements were similar within the groups, but nighttime BPs were significantly greater in non-dipper group than those were in dipper group. Left ventricular diastolic parameters obtained by both standard and tissue Doppler did not differ between the non-dipper and dipper groups. However, aortic distensibility was found to be slightly lower (4.1+/-2.4 vs. 4.9+/-1.9, p=0.08), and aortic stiffness index (6.3+/-0.5 vs. 6.1+/-0.4, p=0.08) and elastic modulus (6.2+/-2.5 vs. 4.8+/-2.3, p=0.08; groups non-dipper and dipper respectively) higher in non-dipper group than in dipper group. However, these differences were not statistically significant. Left ventricular remodeling and diastolic function were similar in patients with non-dipper and dipper hypertension. However, aortic elastic properties were slightly impaired in non-dipper hypertensives than those were in dipper ones, but these differences did not reach statistically significance.


URIC ACID AND TISSUE REPAIR.
Uric acid, a metabolic product of purines, may exert a role in tissue healing. In this review we will explore its role as an alarm initiating the inflammatory process that is necessary for tissue repair, as a scavenger of oxygen free radicals, as a mobilizer of progenitor endothelial cells and as supporter of adaptive immune system.


Nutritional and Physical Prehabilitation in Elective Orthopedic Surgery: Rationale and Proposal for Implementation.
In the past, good food and exercise were not considered effective interventions to promote recovery in orthopedic surgery, and prolonged bed rest with not many calories has been deemed sufficient for the proper health restoration until the end of the nineteenth century. The advancement of scientific knowledge proved just the opposite, thus pushing health professionals to sustain the nutritional status and physical fitness of surgical patients. Nevertheless, the impoverishment of lifestyles and the lengthening of life expectancy have invariably contrasted the strength of constitution, giving rise to two of the most hazardous conditions for orthopedic patients: malnutrition and sarcopenia, often hiding nutrient deficits and poor body composition. These conditions are known to be negative prognostic factors in several areas of major surgery, including hip replacement, knee replacement, and spine surgery. Scoring systems to screen for malnutrition and physical inabilities exist, but disciplined management of the derived risks remains untested, potentially hindering the implementation of research findings into practice. A methodical approach of preoperative analysis, critical monitoring, and risk correction before surgery could lead to a substantial improvement of the prognosis while warranting the safety of patients and the efficiency of enhanced recovery after surgery pathways. The aim of this article is to discuss from a dietetic and exercise perspective the ideal nutritional and physical prehabilitation to lay the foundations for designing the appropriate integration of dietitians and physiotherapists in a preoperative enhanced recovery pathway. This methodical analysis could effectively calculate the patient's risks, detect the best choices for resolving the risk, underline the ignored aspects of perioperative care, and represent a concrete means to integrate novel discoveries.


An unusual precursor of 50S ribosomes in a mutant of Escherichia coli.
Escherichia coli strain 15-28 is a mutant with a defect in ribosome synthesis that leads to the accumulation of large amounts of ribonucleoprotein ("47S") particles during exponential growth. These particles are precursors to 50S ribosomes, but are distinct from precursors detected by pulse-labelling of the parent strain and also from ribosome precursors that accumulate during inhibition of growth by CoC12. Either ribosome assembly in the mutant differs from that in the wild-type strain, or 47S particles represent a hitherto unstudied stage in the synthesis of 50S ribosomes.


Acute and chronic paronychia.
Paronychia is an inflammation of the folds of tissue surrounding the nail of a toe or finger. Paronychia may be classified as either acute or chronic. The main factor associated with the development of acute paronychia is direct or indirect trauma to the cuticle or nail fold. This enables pathogens to inoculate the nail, resulting in infection. Treatment options for acute paronychia include warm compresses; topical antibiotics, with or without corticosteroids; oral antibiotics; or surgical incision and drainage for more severe cases. Chronic paronychia is a multifactorial inflammatory reaction of the proximal nail fold to irritants and allergens. The patient should avoid exposure to contact irritants; treatment of underlying inflammation and infection is recommended, using a combination of a broad-spectrum topical antifungal agent and a corticosteroid. Application of emollient lotions may be beneficial. Topical steroid creams are more effective than systemic antifungals in the treatment of chronic paronychia. In recalcitrant chronic paronychia, en bloc excision of the proximal nail fold is an option. Alternatively, an eponychial marsupialization, with or without nail removal, may be performed.


[Isolation and characteristics of endocytic vacuoles containing the influenza virus].
Endocytic vacuoles (receptosomes) containing influenza virus were isolated from the cytoplasm of Ehrlich ascitic carcinoma cells and characterized. In the sucrose density gradient, the virus-containing material was detected in two peaks with a buoyant density of 1.175-1.16 and 1.155-1.135 g/cm3 with which the activity of marker enzymes of cell plasma membranes was associated. The virus was present in receptosomes in morphologically and electrophoretically intact condition. Examinations for the lipid composition of endocytic vacuoles showed the presence in their membranes of large amounts of cholesterol and glycolipids, particularly asialo-GM1 which, according to some authors may enhance the fusion of viral and cell membranes.


Low Serum Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid are Risk Factors for Cardiogenic Syncope in Patients with Brugada Syndrome.
The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antiarrhythmic effects, possibly via modulation of the cardiac ion channels. Nevertheless, it is unknown whether low serum levels of n-3 PUFAs are risk factors for ventricular fibrillation in patients with Brugada syndrome (BrS). We retrospectively reviewed data from 62 men with BrS and evaluated their serum levels of EPA and DHA, and the risk factors for sudden cardiac death, including a history of cardiogenic syncope. Nineteen patients had a history of cardiogenic syncope, and their EPA and DHA levels were significantly lower than those of the patients without syncope. Multivariate logistic regression analysis revealed that low EPA and DHA levels were associated with the incidence of syncope. The receiver-operator characteristic curve showed the area under the curves of EPA and DHA for history of syncope were 0.84 and 0.72, respectively. In conclusion, low levels of EPA and DHA are risk factors for cardiogenic syncope in patients with BrS, which suggests that n-3 PUFAs play important roles in preventing ventricular fibrillation in BrS.


Population Screening of Gambling Behavior: Playing to Escape From Problems May Be a Key Characteristic of At-Risk Players.
The increase in gambling availability and the inclusion of gambling disorder as an addiction in DSM-5 highlight the importance of brief screening measures aiming to identify at-risk gamblers. The current study, using a brief telephone survey, assessed demographic characteristics and gambling behaviors in 2,118 adults. Questions were developed based on DSM-5 criteria for Gambling Disorder and common assessment tools. A 7% prevalence of as at-risk gamblers was identified. Male gender, low monthly income, high frequency of gambling behavior, large amounts of money spent, and gambling to escape from everyday problems or for amusement, specifically for men, were found to be the characteristics that can help in the early identification of at-risk gamblers. Gambling for financial gain and as a way to socialize, age, and employment status were not significant predictors of gambling severity. This study shows that the above characteristics can be assessed easily through phone screening of large populations, aiding in prevention practices to reduce the problematic use of gambling activities.


Sparassis cystidiosa sp. nov. from Thailand is described using morphological and molecular data.
Sparassis cystidiosa, collected recently from a primary montane cloud forest in northern Thailand is described as new. It is distinct from all others species in the genus because of the presence of hymenial cystidia, relatively large basidiospores and flabellae composed of six distinct layers of tissue. Analyses of a combined dataset of DNA sequences from three genes support its distinction and suggest that the S. cystidiosa lineage is the sister group of all other Sparassis.


Climate influences on the cost-effectiveness of vector-based interventions against malaria in elimination scenarios.
Despite the dependence of mosquito population dynamics on environmental conditions, the associated impact of climate and climate change on present and future malaria remains an area of ongoing debate and uncertainty. Here, we develop a novel integration of mosquito, transmission and economic modelling to assess whether the cost-effectiveness of indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) against Plasmodium falciparum transmission by Anopheles gambiae s.s. mosquitoes depends on climatic conditions in low endemicity scenarios. We find that although temperature and rainfall affect the cost-effectiveness of IRS and/or LLIN scale-up, whether this is sufficient to influence policy depends on local endemicity, existing interventions, host immune response to infection and the emergence rate of insecticide resistance. For the scenarios considered, IRS is found to be more cost-effective than LLINs for the same level of scale-up, and both are more cost-effective at lower mean precipitation and higher variability in precipitation and temperature. We also find that the dependence of peak transmission on mean temperature translates into optimal temperatures for vector-based intervention cost-effectiveness. Further cost-effectiveness analysis that accounts for country-specific epidemiological and environmental heterogeneities is required to assess optimal intervention scale-up for elimination and better understand future transmission trends under climate change.


Adjustment of rotation and saturation effects (AROSE) for CEST imaging.
Endogenous CEST signal usually has low specificity due to contaminations from the magnetization transfer contrast (MTC) and other labile protons with overlapping or close Larmor frequencies. We propose to improve CEST signal specificity with adjustment of rotation and saturation effects (AROSE). The AROSE approach measures the difference between CEST signals acquired with the same average irradiation power but largely different duty cycles, for example, a continuous wave or a high duty cycle pulse train versus a low duty cycle pulse train with a flip angle φ. Simulation, phantom, and in vivo rodent studies were performed to evaluate the characteristics of the AROSEφ signal. Simulation and experimental results show that AROSE2π is a low-pass filter that can suppress fast exchanging processes (e.g., >3000 s-1 ), whereas AROSEπ is a band-pass filter suppressing both fast and slow exchange (e.g., <30 s-1 ) rates. For other φ angles, the sensitivity and the exchange-rate filtering effect of AROSEφ falls between AROSEπ and AROSE2π . AROSE can also minimize MTC and improve the Larmor frequency selectivity of the CEST signal. The linewidth of the AROSE1.5π spectrum is about 60% to 65% when compared to the CEST spectrum measured by continuous wave. Depending on the needs of an application, the sensitivity, exchange-rate filtering, and Larmor frequency selectivity can be adjusted by varying the flip angle, duty cycle, and average irradiation power. Compared to conventional CEST signals, AROSE can minimize MTC and improve exchange rate filtering and Larmor frequency specificity.


Laser-light Visual Cueing Shoes with Foot Pressures and Inertial Sensing for Individuals with Parkinson's Disease.
Gait disorder is a core problem in individuals with Parkinson's disease (PD), including bradykinesia, shuffling steps, festinating gait, and freeze of gait (FOG). Laser-light visual cueing has been demonstrated to be efficient in the mediation of gaits and the reduction in number of FOG episodes. However, previous approaches commonly adopted independent controls of visual cueing on left and right sides which was prone to produce two cues while individual was not in normal walking. In this study, we developed laser-light visual shoes which produced interlaced visual cues for left and right feet in a manner of one-side cueing at a time, solving the aforementioned problem. With parallel measurement of foot inertial data and foot pressures in each shoe, our results showed that the proposed visual cueing made PD individuals in the on-medication condition walk with a longer stance and swing times, that is, they walked more carefully and stable. The proposed approach can also be used to study kinematic and kinetic characteristics of gaits in the off-medication condition to clarify the mediation of visual cueing on motor control of PD individuals.Clinical Relevance- This demonstrates the effect of laser-light visual cueing on gaits in individuals with Parkinson's disease.


Information filtering in complex weighted networks.
Many systems in nature, society, and technology can be described as networks, where the vertices are the system's elements, and edges between vertices indicate the interactions between the corresponding elements. Edges may be weighted if the interaction strength is measurable. However, the full network information is often redundant because tools and techniques from network analysis do not work or become very inefficient if the network is too dense, and some weights may just reflect measurement errors and need to be be discarded. Moreover, since weight distributions in many complex weighted networks are broad, most of the weight is concentrated among a small fraction of all edges. It is then crucial to properly detect relevant edges. Simple thresholding would leave only the largest weights, disrupting the multiscale structure of the system, which is at the basis of the structure of complex networks and ought to be kept. In this paper we propose a weight-filtering technique based on a global null model [Global Statistical Significance (GloSS) filter], keeping both the weight distribution and the full topological structure of the network. The method correctly quantifies the statistical significance of weights assigned independently to the edges from a given distribution. Applications to real networks reveal that the GloSS filter is indeed able to identify relevant connections between vertices.


Endothelial dysfunction and vascular disease - a 30th anniversary update.
The endothelium can evoke relaxations of the underlying vascular smooth muscle, by releasing vasodilator substances. The best-characterized endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) which activates soluble guanylyl cyclase in the vascular smooth muscle cells, with the production of cyclic guanosine monophosphate (cGMP) initiating relaxation. The endothelial cells also evoke hyperpolarization of the cell membrane of vascular smooth muscle (endothelium-dependent hyperpolarizations, EDH-mediated responses). As regards the latter, hydrogen peroxide (H2 O2 ) now appears to play a dominant role. Endothelium-dependent relaxations involve both pertussis toxin-sensitive Gi (e.g. responses to α2 -adrenergic agonists, serotonin, and thrombin) and pertussis toxin-insensitive Gq (e.g. adenosine diphosphate and bradykinin) coupling proteins. New stimulators (e.g. insulin, adiponectin) of the release of EDRFs have emerged. In recent years, evidence has also accumulated, confirming that the release of NO by the endothelial cell can chronically be upregulated (e.g. by oestrogens, exercise and dietary factors) and downregulated (e.g. oxidative stress, smoking, pollution and oxidized low-density lipoproteins) and that it is reduced with ageing and in the course of vascular disease (e.g. diabetes and hypertension). Arteries covered with regenerated endothelium (e.g. following angioplasty) selectively lose the pertussis toxin-sensitive pathway for NO release which favours vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. In addition to the release of NO (and EDH, in particular those due to H2 O2 ), endothelial cells also can evoke contraction of the underlying vascular smooth muscle cells by releasing endothelium-derived contracting factors. Recent evidence confirms that most endothelium-dependent acute increases in contractile force are due to the formation of vasoconstrictor prostanoids (endoperoxides and prostacyclin) which activate TP receptors of the vascular smooth muscle cells and that prostacyclin plays a key role in such responses. Endothelium-dependent contractions are exacerbated when the production of nitric oxide is impaired (e.g. by oxidative stress, ageing, spontaneous hypertension and diabetes). They contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive and diabetic patients. In addition, recent data confirm that the release of endothelin-1 can contribute to endothelial dysfunction and that the peptide appears to be an important contributor to vascular dysfunction. Finally, it has become clear that nitric oxide itself, under certain conditions (e.g. hypoxia), can cause biased activation of soluble guanylyl cyclase leading to the production of cyclic inosine monophosphate (cIMP) rather than cGMP and hence causes contraction rather than relaxation of the underlying vascular smooth muscle.


Analysis of the expression of chondroadherin in mouse ocular and non-ocular tissues.
Chondroadherin (Chad) is a unique member of the small leucine rich repeat proteoglycan gene family. It is expressed at high levels in certain zones of cartilage and also has been detected in bone, tendon, bone marrow, and chondrosarcoma cells. Recently, we demonstrated that Chad is expressed in human and mouse lens and that its expression is decreased in the absence of mimecan/osteoglycin. This finding prompted us to explore the expression of Chad in other ocular and non-ocular tissues. Reverse transcription-polymerase chain reaction amplification (RT-PCR), in situ hybridization (ISH), and immunohistochemistry (IHC) were used to determine the expression of Chad in human and mouse tissues. RT-PCR analysis showed strong expression of Chad in mouse brain, heart, lung, and embryo. Moderate expression was detected in mouse thymus, spleen, testis, and ovary, and very low expression in kidney and liver. Chad was highly expressed in human cornea, brain, and skeletal muscle, and moderately in human retina and lens. By ISH, Chad mRNA was detected in cornea, lens, and retina of postnatal day 21 mouse eyes. By IHC, immunostaining for Chad was seen in epithelial and endothelial layers of the cornea, as well as in lens, ciliary body, and retina of the adult mouse eye. Strong immunostaining was noted in retinal rod, cone, and plexiform layers. IHC analysis of tissue microarray demonstrated presence of Chad in brain (cerebellum), skeletal and cardiac muscles, lung, gastrointestinal tract, ovary, and cartilage. In most tissues, Chad expression was associated with either peripheral nerves and/or blood vessels. In the stomach and intestines, positive immunostaining was observed in Meissner's plexus and enteroendocrine cells. Intriguingly, positive immunostaining also was observed in Purkinje cells of the cerebellum and pancreatic islets. The present work establishes the expression and localization of Chad in several new locations including cornea, lens, ciliary body, retina, cerebellum, pancreatic islet, blood vessels, and peripheral nerves. The surprisingly broad expression pattern of Chad suggests potential roles for this protein in cell specific and/or tissues specific function(s). The results reported here are an essential prerequisite for future studies aimed at understanding the biological roles of Chad in health and disease.


Leadership in informal stormwater governance networks.
Recent transitions in the governance of urban stormwater, specifically developments that leverage the environmental and social benefits of green infrastructure (GI) including infiltration and neighborhood stabilization, often require capacities beyond those of any single municipal- or regional-scale organization. In many cities, transitions toward green stormwater infrastructure have been shepherded by networks of individuals spanning a diversity of organizations from governments to NGOs. These networks are often informal, that is, not established by legal mandate, governing authority, or formal agreement, and are often striking for their lack of formal hierarchy or formal leadership. Previous scholarship has revealed the importance of leadership in the development and efficacy of these multiorganizational, cross-sector environmental governance networks, but research has yet to empirically investigate and characterize informal network leaders within the context of GI for stormwater mitigation. To address this gap, we designed and administered a social network analysis (SNA) survey to individuals in a regional network of GI stormwater management professionals in and around Cleveland, Ohio USA. We collected network data on individual relationships, including collaboration and trust, and tested the impact of these relationships on peer-recognition of leaders in the GI network. Our findings suggest that network size, frequency of collaboration, and individual position within the network-specifically, betweenness centrality and openness-defined and likely supported leaders in the stormwater governance network. Leaders in this non-hierarchical, multi-institution context were more likely to be women and brokerage roles within the network benefitted women, not men, which contrasts with previous findings from research on single-organization and corporate networks. The implications of this research suggest that informal environmental governance networks, such as the GI network investigated, differ substantially from the generally more hierarchical networks of organizations. This finding is useful for municipalities and regional authorities grappling with complex environmental challenges, including transitions in strategies to manage excess stormwater for the protection of municipal drinking water sources and urban freshwater ecosystems.


[Nurses' perception regarding the implementation of computer-based clinical nursing documentation].
This qualitative, exploratory, descriptive study was performed with the objective of understanding the perception of the nurses working in medical-surgical units of a university hospital, regarding the strategies developed to perform a pilot test of the PROCEnf-USP electronic system, with the purpose of computerizing clinical nursing documentation. Eleven nurses of a theoretical-practical training program were interviewed and the obtained data were analyzed using the Content Analysis Technique. The following categories were discussed based on the references of participative management and planned changes: favorable aspects for the implementation; unfavorable aspects for the implementation; and expectations regarding the implementation. According to the nurses' perceptions, the preliminary use of the electronic system allowed them to show their potential and to propose improvements, encouraging them to become partners of the group manager in the dissemination to other nurses of the institution.


Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age.
In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen presenting cells (APC) and regulatory T cells (Treg) are important modifiers of T cell immunity but little is known about their distribution in bronchial mucosa at this age. Here the subset distribution of APC and the appearance of Foxp3(+) Treg and bronchus associated lymphoid tissue (BALT) were examined immunohistochemically in children less than 2 years of age with chronic asthma-like symptoms of the lower airways. Immunophenotyping was performed in situ on bronchial biopsy specimens obtained from 45 infants, 4-23 months of age, under investigation for airway disease. A well developed HLA-DR(+) network of APC was present in all samples, approximately 50% of the cells being CD68(+) macrophages and the remainder various subsets of dendritic cells. The density of HLA-DR(+) cells increased significantly with age but was not related to atopy, clinical symptoms or lung function. Comparing the density of APC subsets and clinical parameters, only the number of intraepithelial CD1a(+) dendritic cells was significantly increased in infants who had recently suffered a respiratory infection. BALT structures were identified in 22 children, with no relation to lung function, atopic status or human rhinovirus positivity. Plasmacytoid dendritic cells and Foxp3(+) Treg were located primarily within these isolated lymphoid follicles. A bronchial network of dendritic cells and macrophages develops quite rapidly after birth, apparently independent of clinical symptoms or atopy. The high frequency of BALT structures containing putative tolerogenic dendritic cells and Treg suggests that these lymphoid follicles play an important role in bronchial immune homeostasis during infancy.


Effect of hyperbaric oxygen therapy on HMGB1/NF-κB expression and prognosis of acute spinal cord injury: A randomized clinical trial.
Although there are reports of the beneficial effects of hyperbaric oxygen (HBO) therapy in experimental settings, there are few clinical trials of HBO therapy for acute spinal cord injury (SCI). We investigated the effect of HBO in acute SCI by measuring plasma high mobility group box 1 (HMGB1) and nuclear factor kappa-B (NF-κB) levels, and by monitoring changes in electromyogram F-persistence (the percentage of discernible F-waves) and F-chronodispersion (the difference between minimal and maximal latency). We enrolled 79 acute SCI patients and randomly divided them into control (conventional treatment) and the treatment (conventional treatment plus HBO therapy) groups. Plasma was collected before treatment and after treatment on 1st, 3rd, 7th, 10th and 30th day for the measurement of HMGB1 and NF-κB. Electromyogram F-waves were detected before therapy and after therapy on the 10th and 30th days. Clinical profiles and neurological outcomes were evaluated using American Spinal Injury Association (ASIA) and Frankel Grade scores. Compared to the control group, HBO therapy down-regulated HMGB1 and NF-κB expression in patients with acute SCI on days 3, 7, 10 and 30 (p < 0.05). F-wave chronodispersion decreased at days 10 and 30 (p < 0.01) following HBO. ASIA and Frankel Grade motor/pain scores in the treatment group were significantly improved on day 30 (p < 0.01). There was a positive correlation between plasma NF-κB at day 7 and F-wave dispersion at day 30 (r = 0.76, p = 0.00). In summary, HBO therapy regulated the inflammatory reaction in secondary SCI by decreasing plasma HMGB1/NF-κB levels and reducing the dispersion of electromyogram F-waves of the lower limbs, thereby promoting neurological function recovery.


Early toxicity and clinical outcomes after chimeric antigen receptor T-cell (CAR-T) therapy for lymphoma.
Chimeric antigen receptor T-cell (CAR-T) infusion is associated with early toxicity. Yet, whether early toxicity development holds ramifications for long-term outcomes is unknown. From a large cohort of consecutive adult patients treated with CAR-T therapies for relapsed or refractory lymphomas from 2016 to 2019, we assessed progression-free survival (PFS), by toxicity development (cytokine release syndrome (CRS), neurotoxicity, or cardiotoxicity]. We also assessed the relationship of toxicity development to objective disease response, and overall survival (OS). Multivariable regression was utilized to evaluate relationships between standard clinical and laboratory measures and disease outcomes. Differences in outcomes, by toxicity status, were also assessed via 30-day landmark analysis. Furthermore, we assessed the effects of early anti-CRS toxicity therapy use (at ≤grade 2 toxicity) on maximum toxicity grade observed, and long-term disease outcomes (PFS and OS). Overall, from 102 CAR-T-treated patients, 90 were identified as treated with single-agent therapy, of which 88.9% developed toxicity (80 CRS, 41 neurotoxicity, and 17 cardiotoxicity), including 28.9% with high-grade (≥3) events. The most common manifestations were hypotension at 96.6% and fever at 94.8%. Among patients with cardiac events, there was a non-significant trend toward a higher prevalence of concurrent or preceding high-grade (≥3) CRS. 50.0% required tocilizumab or corticosteroids. The median time to toxicity was 3 days; high grade CRS development was associated with cardiac and neurotoxicity. In multivariable regression, accounting for disease severity and traditional predictors of disease response, moderate (maximum grade 2) CRS development was associated with higher complete response at 1 year (HR: 2.34; p=0.07), and longer PFS (HR: 0.41; p=0.02, in landmark analysis), and OS (HR: 0.43; p=0.03). Among those with CRS, relative blood pressure (HR: 2.25; p=0.004), respectively, also associated with improved PFS. There was no difference in disease outcomes, or maximum toxicity grade (CRS, neurotoxicity, or cardiotoxicity) observed, based on the presence or absence of the use of early CRS-directed therapies. Among adult lymphoma patients, moderate toxicity manifest as grade 2 CRS after CAR-T infusion may associate with favorable clinical outcomes. Further studies are needed to confirm these findings.


[Transtheoretical model approach in eating behavior].
The study of eating behavior has been much interest, as this is an essential element for the success of dietary interventions. In view of the complexity of the subject and the countless influences to which it is subject, it is suggested that an in-depth exploration of eating behavior determinants enhances the impact of programs promoting healthy dietary practices. Increasingly more frequent, the adoption of inadequate diets in Brazil and elsewhere in the world leads to questions about the impact of dietary interventions traditionally applied to population groups. Many nutritional education strategies are currently described in the literature; however, motivating people to change their eating habits is still a major public health challenge. Applying the transtheoretical model seems to have a promising role for an enhanced understanding of changes in eating habits that are targeted by dietary interventions. Strategies that are tailored to each step in these changes, as identified by this theory, can motivate people more effectively to adopt healthier eating habits.


Climate change and European forests: what do we know, what are the uncertainties, and what are the implications for forest management?
The knowledge about potential climate change impacts on forests is continuously expanding and some changes in growth, drought induced mortality and species distribution have been observed. However despite a significant body of research, a knowledge and communication gap exists between scientists and non-scientists as to how climate change impact scenarios can be interpreted and what they imply for European forests. It is still challenging to advise forest decision makers on how best to plan for climate change as many uncertainties and unknowns remain and it is difficult to communicate these to practitioners and other decision makers while retaining emphasis on the importance of planning for adaptation. In this paper, recent developments in climate change observations and projections, observed and projected impacts on European forests and the associated uncertainties are reviewed and synthesised with a view to understanding the implications for forest management. Current impact assessments with simulation models contain several simplifications, which explain the discrepancy between results of many simulation studies and the rapidly increasing body of evidence about already observed changes in forest productivity and species distribution. In simulation models uncertainties tend to cascade onto one another; from estimating what future societies will be like and general circulation models (GCMs) at the global level, down to forest models and forest management at the local level. Individual climate change impact studies should not be uncritically used for decision-making without reflection on possible shortcomings in system understanding, model accuracy and other assumptions made. It is important for decision makers in forest management to realise that they have to take long-lasting management decisions while uncertainty about climate change impacts are still large. We discuss how to communicate about uncertainty - which is imperative for decision making - without diluting the overall message. Considering the range of possible trends and uncertainties in adaptive forest management requires expert knowledge and enhanced efforts for providing science-based decision support.


Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course.
Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder caused by mutations in the ABCC6 gene. Fragmentation of elastic fibres and deposition of proteoglycans result in a highly variable clinical picture. The altered proteoglycan metabolism suggests that enzymes from this pathway function as genetic co-factors in the severity of PXE. Therefore, we propose the XYLT genes encoding xylosyltransferase I (XT-I) as the chain-initiating enzyme in the biosynthesis of proteoglycans and the highly homologous XT-II as potential candidate genes. We screened all XYLT exons in 65 German PXE patients using denaturing high performance liquid chromatography and analysed the influence of the variations on clinical characteristics. We identified 22 variations in the XYLT genes. The missense variation p.A115S (XT-I) is associated with higher serum XT activity (p = 0.005). The amino acid substitution p.T801R (XT-II; c.2402C>G) occurs with significantly higher frequency in patients under 30 years of age at diagnosis (43% v 26%; p = 0.04); all PXE patients with this variation suffer from skin lesions compared to only 75% of the wild type patients (p = 0.002). c.166G>A, c.1569C>T, and c.2402C>G in the XYLT-II gene were found to be more frequent in patients with higher organ involvement (p = 0.04, p = 0.01, and p = 0.02, respectively). Here we show for the first time that variations in the XYLT-II gene are genetic co-factors in the severity of PXE. Furthermore, the higher XT activity in patients with the exchange p.A115S (XT-I) indicates that this polymorphism is a potential marker for increased remodelling of the extracellular matrix.


Possible role of pseudoephedrine and other over-the-counter cold medications in the deaths of very young children.
The Philadelphia Medical Examiners Office has reported a series of 15 deaths between February 1999 and June 2005 of infants and toddlers 16 months and younger in which drugs commonly found in over-the-counter (OTC) cold medications were present. A total of 10 different drugs were detected: pseudoephedrine, dextromethorphan, acetaminophen, brompheniramine, carbinoxamine, chlorpheniramine, ethanol, doxylamine and the anticonvulsants, phenobarbital, and phenytoin. The drugs were confirmed and quantified by gas chromatography (GC)-mass spectrometry, with the exception of ethanol, which was analyzed by headspace GC and of phenobarbital and phenytoin that were quantified by GC with a nitrogen phosphorus detector. The most predominant drug was pseudoephedrine, which was found in all of the cases (blood concentration, n=14, range=0.10-17.0 mg/L, mean=3.34 mg/L) and was the sole drug detected in three cases. Acetaminophen was detected in blood from each of the five cases with sufficient sample. Other drugs (with frequency of detection) were dextromethorphan (five cases), carbinoxamine (four cases), chlorpheniramine (two cases) and brompheniramine, doxylamine, and ethanol (one case each). In the majority of the cases, toxicity from drugs found in easily available OTC medications was listed either as the direct cause of death or as a contributory factor. The manner of death was determined to be natural in only two of the cases. This postmortem study supports previous evidence that the administration of OTC cold medications to infants may, under some circumstances, be an unsafe practice and in some cases may even be fatal. The treating physicians and the general public need to be made more aware of the dangers of using OTC cold medications to treat very young children so that these types of tragedies might be avoided.


Sodium channels in planar lipid bilayers. Channel gating kinetics of purified sodium channels modified by batrachotoxin.
Single channel currents of sodium channels purified from rat brain and reconstituted into planar lipid bilayers were recorded. The kinetics of channel gating were investigated in the presence of batrachotoxin to eliminate inactivation and an analysis was conducted on membranes with a single active channel at any given time. Channel opening is favored by depolarization and is strongly voltage dependent. Probability density analysis of dwell times in the closed and open states of the channel indicates the occurrence of one open state and several distinct closed states in the voltage (V) range-120 mV less than or equal to V less than or equal to +120 mV. For V less than or equal to 0, the transition rates between stages are exponentially dependent on the applied voltage, as described in mouse neuroblastoma cells (Huang, L. M., N. Moran, and G. Ehrenstein. 1984. Biophysical Journal. 45:313-322). In contrast, for V greater than or equal to 0, the transition rates are virtually voltage independent. Autocorrelation analysis (Labarca, P., J. Rice, D. Fredkin, and M. Montal. 1985. Biophysical Journal. 47:469-478) shows that there is no correlation in the durations of successive open or closing events. Several kinetic schemes that are consistent with the experimental data are considered. This approach may provide information about the mechanism underlying the voltage dependence of channel activation.


Characterization of recombinant glutamine synthetase from the hyperthermophilic archaeon Pyrococcus sp. strain KOD1.
The glnA gene encoding glutamine synthetase was cloned from the hyperthermophilic archaeon Pyrococcus sp. strain KOD1, and its nucleotide sequence was determined. The glnA gene was expressed in Escherichia coli ME8459 (glnA mutant strain), and the protein was purified to homogeneity and shown to be functional in a dodecameric from (637,000 Da), exhibiting both transferase and synthetase activities. However, kinetic studies indicated that the enzyme possessed low biosynthetic activity, suggesting that the reaction was biased towards glutamate production. The optimum temperature for both activities was 60 degrees C, which was lower than the optimal growth temperature of KOD1. Recombinant KOD1 GlnA exhibited different optimum pHs depending on the reaction employed (pH 7.8 for the synthetase reaction and pH 7.2 for the transferase reaction). Of the various nucleoside triphosphates tested, GTP as well as ATP was involved in the synthetase reaction.


Iron and holotransferrin induce cAMP-dependent differentiation of Schwann cells.
The differentiation of myelin-forming Schwann cells (SC) is completed with the appearance of myelin proteins MBP and P(0) and a concomitant downregulation of markers GFAP and p75NTR, which are expressed by immature and adult non-myelin-forming SC. We have previously demonstrated that holotransferrin (hTf) can prevent SC dedifferentiation in culture (Salis et al., 2002), while apotransferrin (aTf) cannot. As a consequence, we used pure cultured SC and submitted them to serum deprivation in order to promote dedifferentiation and evaluate the prodifferentiating ability of ferric ammonium citrate (FAC) through the expression of MBP, P(0), p75NTR and c-myc. The levels of cAMP, CREB and p-CREB were also measured. Results show that Fe(3+), either in its free form or as hTf, can prevent the dedifferentiation promoted by serum withdrawal. Both FAC and hTf were proven to promote differentiation, probably through the increase in cAMP levels and CREB phosphorylation, as well as levels of reactive oxygen species. This effect was inhibited by deferroxamine (Dfx, an iron chelator), H9 (a cAMP-PKA antagonist) and N-acetylcysteine (NAC, a powerful antioxidant).


Legumes and meat analogues consumption are associated with hip fracture risk independently of meat intake among Caucasian men and women: the Adventist Health Study-2.
In contrast to non-vegetarians, vegetarians consume more legumes and meat analogues as sources of protein to substitute for meat intake. The present study aimed to assess the association between foods with high protein content (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians) and hip fracture incidence, adjusted for selected lifestyle factors. A prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a comprehensive lifestyle and dietary questionnaire between 2002 and 2007. Every two years after enrolment, a short questionnaire on hospitalizations and selected disease outcomes including hip fractures was sent to these members. Respondents (n 33,208) to a baseline and a follow-up questionnaire. In a multivariable model, legumes intake of once daily or more reduced the risk of hip fracture by 64% (hazard ratio = 0·36, 95% CI 0·21, 0·61) compared with those with legumes intake of less than once weekly. Similarly, meat intake of four or more times weekly was associated with a 40% reduced risk of hip fracture (hazard ratio = 0·60, 95% CI 0·41, 0·87) compared with those whose meat intake was less than once weekly. Furthermore, consumption of meat analogues once daily or more was associated with a 49 % reduced risk of hip fracture (hazard ratio = 0·51, 95% CI 0·27, 0·98) compared with an intake of less than once weekly. Hip fracture incidence was inversely associated with legumes intake and, to a lesser extent, meat intake, after accounting for other food groups and important covariates. Similarly, a high intake of meat analogues was associated with a significantly reduced risk of hip fracture.


Evaluation of Temporomandibular Disorders before and after Orthognathic Surgery: Therapeutic Considerations on a Sample of 76 Patients.
Temporomandibular disorders may be associated with dental and facial malformations. The aim of this study is to record the prevalence of TMDs in patients scheduled for orthognathic surgery, reporting the development of TMDs and symptoms during the entire period of the treatment, and demonstrating the benefits of a team effort on this population. Assessment of temporomandibular status was performed using the RDC/TMD criteria at T0 (prior to orthodontic therapy), T1 (3 months after the surgery), and T2 post-therapeutic cycle (6 to 12 months postoperatively). A total of 76 participants were included in the study; all the patients underwent surgical treatment: 12 had bilateral sagittal split osteotomy, 6 with condylar position devices; 64 had Le Fort I + bilateral sagittal split osteotomy, and 15 with condylar position devices. Results were evaluated with a paired-sample t-test and segmentation analysis. Forty-seven patients were affected by TMDs. At T0, 25 patients experienced TMJ pain, 27 had muscular pain, 31 suffered headaches, 42 had disc dislocation with reduction, and 5 were affected by disc dislocation without reduction. Thirty-five patients had occlusal signs of parafunctions, 8 reported tinnitus, and 7 dizziness. At T1, TMJ pain changed from 33.3% to 4.44%, muscular pain changed from 35.5% to 11.1%, headaches improved from 40% to 6.67%, and disc dislocation from 55.2% to 17.7%. Segmentation analysis highlighted improvement after therapy; 57 patients were considered recovered, 14 improved, none were considered stable, whereas 5 patients demonstrated some worsening, 3 of whom had not presented disc dislocation before surgery. At T2, 71 patients were considered completely recovered or improved. Our data indicates beyond any doubt that both functional status and pain levels related to TMDs can be significantly improved with a multi-disciplinary approach. We concluded that surgeon's intervention need to be modified in the presence of presurgical TMDs.


Male reproductive assessment of the rubber accelerator N-oxydiethylene thiocarbamyl-N-oxydiethylene sulfenamide in rats.
The rubber accelerator N-oxydiethylene thiocarbamyl-N-oxydiethylene sulfenamide (OTOS) was evaluated to determine its potential to cause reproductive effects. No evidence of a compound-related effect on mating, fertility, gestation length, number of implants or live births, pup growth, and survival was observed using Sprague-Dawley rats. Furthermore, light and electron microscopy of the testes from the high-dose males failed to reveal any morphological changes compared to the controls. Groups of 12 male Sprague-Dawley rats were continuously administered diets containing 0, 60, 200, or 600 ppm OTOS for 12 weeks. Following 56 days of exposure, the males were subsequently cohoused nightly with two females for a maximum of 21 days. During this mating period, males continued to receive control and OTOS-containing diets; however, feeders were removed for nightly cohabitation. Although a 4 to 8% reduction in body weight was observed in the 600 ppm animals, statistical significance was reached only at the end of the first week of treatment. In the 60 and 200 ppm males body weights generally were slightly elevated compared to the control, with the 60 ppm body weights showing statistically significant differences during Weeks 5 to 7 of exposure.


A detailed evaluation of the anatomical variations of the profunda artery perforator flap using computed tomographic angiograms.
The profunda artery perforator flap is a new option for breast reconstruction in appropriate patients. While the basic anatomy is known, detailed profunda perforator anatomy has never fully been described and we present new data that will aid dissection. Fifty consecutive lower extremity computed tomography angiogram scans (100 legs) were retrospectively analyzed to acquire profunda artery perforator measurements. Patient medical records were then examined to ascertain patient information. Data were then analyzed using simple descriptive statistics and bivariate linear regressions with repeated measures. Bilateral thighs from 50 consecutive angiograms were included for a total of 100 thighs. Females comprised 30 (60 percent) of the patients and the cohort average age was 59.1 years old. All thighs had at least two perforators, with 85 percent having three or more. On average, perforators were located 6.2 cm below the gluteal crease, and were evenly distributed between the medial and lateral halves of the thigh. The average perforator diameter at origin off profunda was 2.7 mm. There was significantly greater diameter in vessels in the lateral thigh (p<0.001), in patients with higher Body Mass Index (BMI) (p<0.05), and in patients with decreased age (p<0.05). Males were more likely to have perforators that shared a common trunk off the profunda artery (p<0.05). At least two profunda perforators exist in each thigh with an average diameter suitable for microvascular transfer, although larger perforators are observed laterally and in younger patients with higher BMI.


[Clotting factor VIII in Sneddon syndrome].
Hyperactivity of coagulation factor VIII (fVIII) marks hypercoagulation. FVIII enhances activity of factor IX and their combination activates factor X, which is of primary importance in prothrombin transformation into thrombin, on the phospholipid membrane. The activity of fVIII was studied in 28 patients (26 women, 2 men, mean age 49.6 +/- 7.8 years) with Sneddon's syndrome (SS). SS manifests clinically similarly to primary antiphospholipid syndrome (PAS). The leading of them are ischemic disorders of cerebral circulation (IDCC) and advanced livedo present in all the examinees. Hyperactivity of fVIII was registered in 21 (75%) of 28 patients. Most of thrombosis-related symptoms occurred more frequently in patients with high than normal activity of fVIII: ischemic strokes (91% vs 57%, p > 0.05), repeated strokes (71% vs 0%, p = 0.0014), transient IDCC (76% vs 57%, p > 0.05), vascular dementia (43% vs 0%, p > 0.05), ischemic heart disease (43% vs 0%, p > 0.05), thickening of heart valves according to echocardiography (91% vs 57%, p > 0.05), peripheral venous thromboses (24% vs 0%, p > 0.05). In high fVIII activity cardiolipin antibodies occurred more rarely (24% vs 43%, p > 0.05) but lupus anticoagulant was seen more often (47% vs 14%, p > 0.05). High fVIII activity was in 8 of 12 aPL-negative patients. It is demonstrated that elevated fVIII activity is an essential mechanism of thrombosis development in SS. The cause of this enhanced activity is suggested to be special aPL in interaction with which fVIII becomes insensitive to inactivation with protein C. The activity of protein C was normal in all the cases.


Imaging characteristics of diffuse primary cutaneous B-cell lymphoma of the cranial vault with orbital and brain invasion.
We herein present the imaging findings in a case of diffuse primary cutaneous B-cell lymphoma of the cranial vault with orbital and brain invasion. MR imaging revealed first concomitant orbital and parenchymal invasion in a case of primary diffuse non-Hodgkin lymphoma of the cranial vault. Contrast-enhanced MR imaging revealed a diffuse mass in the scalp of the frontoparietal region bilaterally and invasion of the right orbit and left frontoparietal lobe. Histologic and immunopathologic examinations revealed diffuse primary cutaneous B-cell lymphoma.


Human cell hybrids: analysis of transformation and tumorigenicity.
Intraspecific human-human cell hybrids provide a stable model system with which to investigate the genetic control of transformed and tumorigenic phenotypes. Using this system it has been shown that these phenotypes are under separate genetic control. Furthermore, the tumorigenic phenotype can be complemented by fusion of different tumorigenic cells, resulting in nontumorigenic hybrids. This system also provides information on the control of differentiated function. Molecular cytogenetic techniques should reveal the nature of the chromosomal control of neoplastic transformation.


Patient-derived stem cell line UKMi005-A (hiPSC) harboring a non-synonymous heterozygous KCNJ5 gene variant.
A published heterozygous gain-of-function variant in the KCNJ5 gene (p.Trp101Cys) encoding the G-protein-activated inward-rectifier potassium channel 4 subunit of the IK,ACh channel is associated with human sinus node dysfunction (SND). Differentiated hiPSC-cardiomyocytes may serve as an in-vitro model to study SND and to develop pharmacological rescue strategies. Therefore, a mutant hiPSCs line from patient-derived peripheral blood mononuclear cells (PBMCs) were reprogrammed with CytoTune-iPS 2.0 Sendai Reprogramming Kit. The hiPSC line (KCNJ5 K8) showed a regular karyotype, a typical hiPSC morphology, expressed pluripotency-associated markers in immunofluorescence stainings and RT-qPCR analysis. The ability for differentiation into all three germ layers was shown.


Preparing military installations for pandemic influenza through tabletop exercises.
Effective Department of Defense (DoD) response to pandemic influenza requires robust and well-exercised plans at the installation level. This article describes proceedings and key findings from a half-day "train-the-trainer" pandemic influenza tabletop exercise for Tri-Service installation public health emergency officers (PHEOs) at the August 2008 Force Health Protection conference. Exercise participants were expected to facilitate the execution of a pandemic influenza exercise at their respective installations within 6 months of attendance. On a 6-month follow-up survey (N= 50), 68% indicated their installations had since created a new pandemic influenza plan or revised an existing one, whereas 44% indicated that their installation had since conducted a pandemic influenza exercise. Chief reported barriers to conducting installation-level pandemic influenza exercises included competing priorities, followed by time, personnel, and budget limitations. Relevant policy implications for installation-level pandemic influenza readiness include access to higher level plans, strategic utilization of assets to optimize surge capacity, and cross-training of personnel.


Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2.
Platelet-leukocyte interactions amplify inflammatory reactions, but the underlying mechanism is still unclear. CLEC5A and CLEC2 are spleen tyrosine kinase (Syk)-coupled C-type lectin receptors, abundantly expressed by leukocytes and platelets, respectively. Whereas CLEC5A is a pattern recognition receptor (PRR) to flaviviruses and bacteria, CLEC2 is the receptor for platelet-activating snake venom aggretin. Here we show that dengue virus (DV) activates platelets via CLEC2 to release extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles (MVs). DV-induced EXOs (DV-EXOs) and MVs (DV-MVs) further activate CLEC5A and TLR2 on neutrophils and macrophages, thereby induce neutrophil extracellular trap (NET) formation and proinflammatory cytokine release. Compared to stat1-/- mice, simultaneous blockade of CLEC5A and TLR2 effectively attenuates DV-induced inflammatory response and increases survival rate from 30 to 90%. The identification of critical roles of CLEC2 and CLEC5A/TLR2 in platelet-leukocyte interactions will support the development of novel strategies to treat acute viral infection in the future.


Tris(phosphino)borato silver(I) complexes as precursors for metallic silver aerosol-assisted chemical vapor deposition.
A series of light- and air-stable tris(phosphino)borato silver(I) complexes has been synthesized, structurally and spectroscopically characterized, and implemented in the growth of low resistivity metallic silver thin films by aerosol-assisted chemical vapor deposition (AACVD). Of the four complexes in the series, [RB(CH2PR'2) 3]AgPEt3 (R = Ph (1, 3), (n)Bu (2, 4); R' = Ph (1, 2), (i)Pr (3, 4), complexes 1 and 2 have been characterized by single-crystal X-ray diffraction. Complex 2 represents a significant improvement over previously available nonfluorinated Ag precursors, owing to ease of handling and efficient film deposition characteristics. Thermogravimetric analysis (TGA) shows that the thermolytic properties of these complexes can be significantly modified by altering the ligand structure. Polycrystalline cubic-phase Ag thin films were grown on glass, MgO(100), and 52100 steel substrates. Ag films of thicknesses 3 microm, grown at rates of 14-18 nm/min, exhibit low levels of extraneous element contamination by X-ray photoelectron spectroscopy (XPS). Atomic force microscopy (AFM) and scanning electron microscopy (SEM) indicate that film growth proceeds primarily via an island growth (Volmer-Weber) mechanism.


GSK-3β heterozygous knockout is cardioprotective in a knockin mouse model of familial dilated cardiomyopathy.
Glycogen synthase kinase-3β (GSK-3β) plays a central role in both cardiac physiology and pathology. Herein we want to clarify the role of GSK-3β in familial dilated cardiomyopathy. We generated a mouse model carrying a heterozygous knockout mutation of GSK-3β (GSK-3β(+/-) KO), together with a ΔK210 knockin mutation in cardiac troponin T (ΔK210 cTnT KI), which was proved to be one of the genetic causes of familial dilated cardiomyopathy (DCM). GSK-3β(+/-) KO prevented the slow and rapid deterioration in left ventricular systolic function accompanying heart failure (HF) in DCM mice with heterozygous and homozygous ΔK210 cTnT KI mutations, respectively. GSK-3β(+/-) KO also prevented cardiac enlargement, myocardial fibrosis, and cardiomyocyte apoptosis and markedly reduced the expression of cardiac β-myosin heavy chain isoform, indicative of HF, in DCM mice with homozygous ΔK210 cTnT KI mutation. GSK-3β(+/-) KO also extended the life span of these DCM mice. This study suggests that the inhibition of GSK-3β is cardioprotective in familial DCM associated with ΔK210 cTnT mutation.


Mutation-specific effects in germline transmission of pathogenic mtDNA variants.
Does germline selection (besides random genetic drift) play a role during the transmission of heteroplasmic pathogenic mitochondrial DNA (mtDNA) mutations in humans? We conclude that inheritance of mtDNA is mutation-specific and governed by a combination of random genetic drift and negative and/or positive selection. mtDNA inherits maternally through a genetic bottleneck, but the underlying mechanisms are largely unknown. Although random genetic drift is recognized as an important mechanism, selection mechanisms are thought to play a role as well. We determined the mtDNA mutation loads in 160 available oocytes, zygotes, and blastomeres of five carriers of the m.3243A>G mutation, one carrier of the m.8993T>G mutation, and one carrier of the m.14487T>C mutation. Mutation loads were determined in PGD samples using PCR assays and analysed mathematically to test for random sampling effects. In addition, a meta-analysis has been performed on mutation load transmission data in the literature to confirm the results of the PGD samples. By applying the Kimura distribution, which assumes random mechanisms, we found that mtDNA segregations patterns could be explained by variable bottleneck sizes among all our carriers (moment estimates ranging from 10 to 145). Marked differences in the bottleneck size would determine the probability that a carrier produces offspring with mutations markedly different than her own. We investigated whether bottleneck sizes might also be influenced by non-random mechanisms. We noted a consistent absence of high mutation loads in all our m.3243A>G carriers, indicating non-random events. To test this, we fitted a standard and a truncated Kimura distribution to the m.3243A>G segregation data. A Kimura distribution truncated at 76.5% heteroplasmy has a significantly better fit (P-value = 0.005) than the standard Kimura distribution. For the m.8993T>G mutation, we suspect a skewed mutation load distribution in the offspring. To test this hypothesis, we performed a meta-analysis on published blood mutation levels of offspring-mother (O-M) transmission for the m.3243A>G and m.8993T>G mutations. This analysis revealed some evidence that the O-M ratios for the m.8993T>G mutation are different from zero (P-value <0.001), while for the m.3243A>G mutation there was little evidence that the O-M ratios are non-zero. Lastly, for the m.14487T>G mutation, where the whole range of mutation loads was represented, we found no indications for selective events during its transmission. All data are included in the Results section of this article. The availability of human material for the mutations is scarce, requiring additional samples to confirm our findings. Our data show that non-random mechanisms are involved during mtDNA segregation. We aimed to provide the mechanisms underlying these selection events. One explanation for selection against high m.3243A>G mutation loads could be, as previously reported, a pronounced oxidative phosphorylation (OXPHOS) deficiency at high mutation loads, which prohibits oogenesis (e.g. progression through meiosis). No maximum mutation loads of the m.8993T>G mutation seem to exist, as the OXPHOS deficiency is less severe, even at levels close to 100%. In contrast, high mutation loads seem to be favoured, probably because they lead to an increased mitochondrial membrane potential (MMP), a hallmark on which healthy mitochondria are being selected. This hypothesis could provide a possible explanation for the skewed segregation pattern observed. Our findings are corroborated by the segregation pattern of the m.14487T>C mutation, which does not affect OXPHOS and MMP significantly, and its transmission is therefore predominantly determined by random genetic drift. Our conclusion is that mutation-specific selection mechanisms occur during mtDNA inheritance, which has implications for PGD and mitochondrial replacement therapy. This work has been funded by GROW-School of Oncology and Developmental Biology. The authors declare no competing interests.


Dental disease levels and reasons for emergency clinic attendance in patients seeking relief of pain in Auckland.
This study examined the reasons for attendance, duration of the problem, treatment expectations and oral health of patients seeking relief of pain at Auckland hospital dental departments and a private accident and emergency clinic. One-third of hospital-clinic participants and 15 percent of private-clinic participants had delayed treatment for more than 1 month. Sixty-three percent of hospital-clinic and 30 percent of private-clinic participants expected to receive an extraction. The hospital-clinic group had a mean of 5.0 (SD 3.9) decayed teeth, and the private clinic group a mean of 2.3 (SD 2.8) decayed teeth. Periodontal treatment needs were also significantly higher among participants attending the hospital clinics. Twenty-five percent of hospital-clinic participants had complex periodontal treatment needs. Further research is required to estimate the size of the population these groups represent and to investigate the reasons for these differences.


Predicting acute brain lesions on magnetic resonance imaging in acute carbon monoxide poisoning: a multicenter prospective observational study.
An acute brain lesion (ABL) identified by brain magnetic resonance imaging (MRI) after acute carbon monoxide (CO) poisoning is a strong prognostic factor for the development of delayed neuropsychiatric syndrome (DNS). This study aimed to identify predictors of ABLs on MRI in patients with acute CO poisoning. This was a multicenter prospective registry-based observational study conducted at two tertiary hospitals. A total of 1,034 patients were included. Multivariable logistic regression analysis showed that loss of consciousness (LOC) (adjusted odds ratio [aOR] 2.68, 95% Confidence Interval [CI]: 1.49-5.06), Glasgow Coma Scale (GCS) score < 9 (aOR 2.41, 95% CI: 1.49-3.91), troponin-I (TnI) (aOR 1.22, 95% CI: 1.08-1.41), CO exposure duration (aOR 1.09, 95% CI: 1.05-1.13), and white blood cell (WBC) (aOR 1.05, 95% CI: 1.01-1.09) were independent predictors of ABLs on MRI. LOC, GCS score, TnI, CO exposure duration, and WBC count can be useful predictors of ABLs on MRI in patients with acute CO poisoning, helping clinicians decide the need for an MRI scan or transfer the patient to an appropriate institution for MRI or hyperbaric oxygen therapy.


[Extra-oral digestion and the problem of parasitism in Parasitengona mites (Acariformes)].
An analysis of the extra-oral digestion in Parasitengona being a highly specialized group of Acariform mites is carried out from the viewpoint of functional morphology and ecology. The significance of the extra-oral digestion in the life strategy of these mites and their larval parasitism is also evaluated. The morphological pre-adaptations of this mode of feeding as well as its probable evolutionary consequences are demonstrated by an example of trombiculid mites (Trombiculidae). It is shown, in particular, that parasitism in general may be considered as a particular life scenario implying that the feeding preferences of the organism are evolutionary formed in a close association with other organisms, which provide a parasite with a feeding substrate mainly already prepared for utilization. Based on this assumption, all Parasitengona, including both larval and post-larval instars, irrespectively of the size of their potential victim, preferably should not be considered as parasites, but as micro-predators.


The Kinesio Taping Method for Myofascial Pain Control.
Many people continue suffering from myofascial pain syndrome (MPS) defined as a regional pain syndrome characterized by muscle pain caused by myofascial trigger points (MTrPs) clinically. Muscle spasm and block of blood circulation can be noticed in the taut bands. In the MTrP region, nociceptors can be sensitized by the peripheral inflammatory factors and contracture of fascia can also be induced. Traditional treatments of MPS include stretching therapy, thermal treatment, electrical stimulation, massage, manipulation, trigger points injection, acupuncture, and medicine. However, the pain syndrome may not be relieved even under multiple therapies. Recently, the Kinesio Taping (KT) method is popularly used in sports injuries, postoperative complications, and various pain problems, but little research is focused on MPS with KT method. In this paper, we review the research studies on the application to KT in treating MPS and other related issues. It appears that the KT application can elevate the subcutaneous space and then increase the blood circulation and lymph fluid drainage to reduce the chemical factors around the MTrP region. Therefore, it is suggested that KT method can be used as a regular treatment or added to the previous treatment for myofascial pain.


Risk factors for methicillin-resistant Staphylococcus aureus skin and soft tissue infection in MRSA-colonized patients discharged from a Veterans Affairs hospital.
Currently, limited studies have quantified the risk of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) for MRSA-colonized patients on discharge from hospital. Our retrospective, case-control study identified independent risk factors for the development of MRSA SSTIs among such patients detected by active MRSA nasal screening in an acute care hospital by PCR on admission, and bacteriological cultures on discharge. Cases were MRSA-colonized patients aged ⩾18 years who developed a MRSA SSTI post-discharge and controls were those who did not develop a MRSA SSTI post-discharge. Controls were matched to cases by length of follow-up (±10 days) for up to 18 months. Potential demographic and clinical risk factors for MRSA infection were identified using electronic queries and manual chart abstraction; data were compared by standard statistical tests and variables with P values ⩽0·05 in bivariable analysis were entered into a logistic regression model. Multivariable analysis demonstrated prior hospital admission within 12 months (P = 0·02), prior MRSA infection (P = 0·05), and previous myocardial infarction (P = 0·01) were independently predictive of a MRSA SSTI post-discharge. Identification of MRSA colonization upon admission and recognition of risk factors could help identify a high-risk population that could benefit from MRSA SSTI prevention strategies.


Rosacea and rhinophyma.
Rosacea is a common and chronic inflammatory cutaneous disease with unknown etiology. The pathophysiology of rosacea is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been detected yet. Recent molecular studies propose that an altered innate immune response is involved in the pathogenesis of the rosacea disease. Signs of rosacea are indicated by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. A wide range of drug options is available for the treatment of rosacea, including several topical ones (metronidazole, antibiotics, azelaic acid, benzoyl peroxide, sulfacetamide/sulfur, retinoids) and oral ones (mainly tetracyclines, metronidazole, macrolides, isotretinoin). This review highlights the recent clinical and pathophysiological developments concerning rosacea.


Grain splitting is a mechanism for grain coarsening in colloidal polycrystals.
In established theories of grain coarsening, grains disappear either by shrinking or by rotating as a rigid object to coalesce with an adjacent grain. Here we report a third mechanism for grain coarsening, in which a grain splits apart into two regions that rotate in opposite directions to match two adjacent grains' orientations. We experimentally observe both conventional grain rotation and grain splitting in two-dimensional colloidal polycrystals. We find that grain splitting occurs via independently rotating "granules" whose shapes are determined by the underlying triangular lattices of the two merging crystal grains. These granules are so small that existing continuum theories of grain boundary energy are inapplicable, so we introduce a hard sphere model for the free energy of a colloidal polycrystal. We find that, during splitting, the system overcomes a free energy barrier before ultimately reaching a lower free energy when splitting is complete. Using simulated splitting events and a simple scaling prediction, we find that the barrier to grain splitting decreases as grain size decreases. Consequently, grain splitting is likely to play an important role in polycrystals with small grains. This discovery suggests that mesoscale models of grain coarsening may offer better predictions in the nanocrystalline regime by including grain splitting.


Damage and recovery from drift of synthetic-auxin herbicide dicamba depends on concentration and varies among floral, vegetative, and lifetime traits in rapid cycling Brassica rapa.
Herbicides can drift from intended plants onto non-target species. It remains unclear how drift impacts plant functional traits that are important for fitness. To address this gap, we conducted an experiment where fast cycling Brassica rapa plants were exposed to one of three drift concentrations (0.5%, 1%, 10%) of synthetic-auxin dicamba. We evaluated damage to and capacity of floral and vegetative traits to recover as well as lifetime fitness by comparing treated plants to controls. Response to dicamba exposure was concentration-dependent across all traits but varied with trait type. At 0.5% dicamba, three out of five floral traits were affected, while at 1% dicamba, four floral traits and one out of two vegetative traits were negatively impacted. At 10% dicamba all floral and vegetative traits were stunted. Overall, floral traits were more responsive to all dicamba drift concentrations than vegetative traits and displayed a wide range of variation ranging from no response (e.g., pistil length) to up to 84% reduction (ovule number). However, despite floral traits were more affected across the dicamba drift concentrations they were also more likely to recover than the vegetative traits. There was also variation among lifetime traits; the onset of flowering was delayed, and reproductive fitness was negatively affected in a concentration-dependent manner, but the final biomass and total flower production were not affected. Altogether, we show substantial variation across plant traits in their response to dicamba and conclude that accounting for this variation is essential to understand the full impact of herbicide drift on plants and the ecological interactions these traits mediate.


Neurite Mistargeting and Inverse Order of Intraretinal Vascular Plexus Formation Precede Subretinal Vascularization in Vldlr Mutant Mice.
In the retina blood vessels are required to support a high metabolic rate, however, uncontrolled vascular growth can lead to impaired vision and blindness. Subretinal vascularization (SRV), one type of pathological vessel growth, occurs in retinal angiomatous proliferation and proliferative macular telangiectasia. In these diseases SRV originates from blood vessels within the retina. We use mice with a targeted disruption in the Vldl-receptor (Vldlr) gene as a model to study SRV with retinal origin. We find that Vldlr mRNA is strongly expressed in the neuroretina, and we observe both vascular and neuronal phenotypes in Vldlr-/- mice. Unexpectedly, horizontal cell (HC) neurites are mistargeted prior to SRV in this model, and the majority of vascular lesions are associated with mistargeted neurites. In Foxn4-/- mice, which lack HCs and display reduced amacrine cell (AC) numbers, we find severe defects in intraretinal capillary development. However, SRV is not suppressed in Foxn4-/-;Vldlr-/- mice, which reveals that mistargeted HC neurites are not required for vascular lesion formation. In the absence of VLDLR, the intraretinal capillary plexuses form in an inverse order compared to normal development, and subsequent to this early defect, vascular proliferation is increased. We conclude that SRV in the Vldlr-/- model is associated with mistargeted neurites and that SRV is preceded by altered retinal vascular development.


Production of lentiviral vectors for transducing cells from the central nervous system.
Efficient gene delivery in the central nervous system (CNS) is important in studying gene functions, modeling neurological diseases and developing therapeutic approaches. Lentiviral vectors are attractive tools in transduction of neurons and other cell types in CNS as they transduce both dividing and non-dividing cells, support sustained expression of transgenes, and have relatively large packaging capacity and low toxicity. Lentiviral vectors have been successfully used in transducing many neural cell types in vitro and in animals. Great efforts have been made to develop lentiviral vectors with improved biosafety and efficiency for gene delivery. The current third generation replication-defective and self-inactivating (SIN) lentiviral vectors are depicted in Figure 1. The required elements for vector packaging are split into four plasmids. In the lentiviral transfer plasmid, the U3 region in the 5' long terminal repeat (LTR) is replaced with a strong promoter from another virus. This modification allows the transcription of the vector sequence independent of HIV-1 Tat protein that is normally required for HIV gene expression. The packaging signal (Ψ) is essential for encapsidation and the Rev-responsive element (RRE) is required for producing high titer vectors. The central polypurine tract (cPPT) is important for nuclear import of the vector DNA, a feature required for transducing non-dividing cells. In the 3' LTR, the cis-regulatory sequences are completely removed from the U3 region. This deletion is copied to 5' LTR after reverse transcription, resulting in transcriptional inactivation of both LTRs. Plasmid pMDLg/pRRE contains HIV-1 gag/pol genes, which provide structural proteins and reverse transcriptase. pRSV-Rev encodes Rev which binds to the RRE for efficient RNA export from the nucleus. pCMV-G encodes the vesicular stomatitis virus glycoprotein (VSV-G) that replaces HIV-1 Env. VSV-G expands the tropism of the vectors and allows concentration via ultracentrifugation. All the genes encoding the accessory proteins, including Vif, Vpr, Vpu, and Nef are excluded in the packaging system. The production and manipulation of lentiviral vectors should be carried out according to NIH guidelines for research involving recombinant DNA (http://oba.od.nih.gov/oba/rac/Guidelines/NIH_Guidelines.pdf). An approval from individual Institutional Biological and Chemical Safety Committee may be required before using lentiviral vectors. Lentiviral vectors are commonly produced by cotransfection of 293T cells with lentiviral transfer plasmid and the helper plasmids encoding the proteins required for vector packaging. Many lentiviral transfer plasmids and helper plasmids can be obtained from Addgene, a non-profit plasmid repository (http://www.addgene.org/). Some stable packaging cell lines have been developed, but these systems provide less flexibility and their packaging efficiency generally declines over time. Commercially available transfection kits may support high efficiency of transfection, but they can be very expensive for large scale vector preparations. Calcium phosphate precipitation methods provide highly efficient transfection of 293T cells and thus provide a reliable and cost effective approach for lentiviral vector production. In this protocol, we produce lentiviral vectors by cotransfection of 293T cells with four plasmids based on the calcium phosphate precipitation principle, followed by purification and concentration with ultracentrifugation through a 20% sucrose cushion. The vector titers are determined by fluorescence- activated cell sorting (FACS) analysis or by real time qPCR. The production and titration of lentiviral vectors in this protocol can be finished with 9 days. We provide an example of transducing these vectors into murine neocortical cultures containing both neurons and astrocytes. We demonstrate that lentiviral vectors support high efficiency of transduction and cell type-specific gene expression in primary cultured cells from CNS.


Are there any effects of Sevoflurane and Desflurane anaesthesia on blood glucose levels in acute hyperglycemic diabetic rats?
The aim of this study was to investigate blood glucose level of desflurane and sevoflurane on blood glucose in diabetic rats undergoing acute hyperglycemia. In this study, 30 male Wistar albino rats were included. Diabetes was induced by a single IP injection of streptozotocin. After the effects of chronic diabetes encountered, diabetic rats were randomly assigned into diabetic control (group DC), diabetic hyperglycemia group (group DH), diabetic hyperglycemia group with desflurane (group DH-D), and diabetic hyperglycemia group with sevoflurane (group DH-S) groups. The normoglycemic groups received an IP injection of the same amount of saline. Hyperglycemic diabetic rats were anaesthetized by desflurane 6 % or sevoflurane 2 % at a dose, by which minimal alveolar concentration (MAC) for rats would be one. The drugs were given for 4 hours within 100 % oxygen at a rate of 6 L.min-1. One hour after cessation of inhalation anesthesia, blood glucose levels were determined at 1st, 4th and 24th hours. 24 hours after the anaesthesia. Serum glucose was detected to be significantly lower in Group C, when compared to Groups DC, DH, DH-D and DH-S (p = 0.002, p = 0.001, p = 0.002, p = 0.003, respectively). Blood glucose levels in the diabetic groups were similar at the end of 6 weeks period, after hyperglycemia and anaesthesia induction. We found out that sevoflurane and desflurane administrations in hyperglycemic rats were both related with insignificant blood glucose level increase at early post anaesthesia period and at post anaesthesia 24th hours. We still think that patients undergoing anaesthesia protocols with acute hyperglycemia need relatively longer follow up periods (Tab. 1, Ref. 28).


Fiber optic mechanical deformation sensors employing perpendicular photonic crystals.
Existing fiber optics (FOs)-based sensors, including mechanical deformation ones rely on structures embedded along the length of the FO. In this paper, we introduce and evaluate photonic crystals (PCs) embedded into FO cores acting as mechanical deformation sensors which are departing from this classical approach as the PCs are perpendicular to the length of the FO. Another noteworthy difference from classical FO-PC based sensors is that while classical ones rely on amplitude variations, the ones presented here use the phase variations of the electromagnetic components for assessing mechanical deformations. We start with a straightforward rectangular-lattice PC while also exploring a triangular-lattice PC. Light transmission simulations through the proposed FO-PC mechanical deformation sensors were performed using EM Explorer, and revealed their behaviors under small mechanical deformations. These simulations (of the rectangular-lattice and triangular-lattice PCs) show that these two FO-PC mechanical deformation sensors have roughly the same sensitivities while the triangular-lattice PC triggers at a lower threshold than the rectangular-lattice PC.


Broth versus Surface-Grown Cells: Differential Regulation of RsmY/Z Small RNAs in Pseudomonas aeruginosa by the Gac/HptB System.
Two-component systems are capable of profoundly affecting genetic regulation in bacteria by detecting environmental stimuli, allowing them to quickly adapt. In Pseudomonas aeruginosa, the small RNAs (sRNAs) RsmY and RsmZ are under the control of the GacS/A system. They have been described as ones of the major key players in the control of planktonic and surface-associated behaviors. Genetic regulation by these sRNAs is achieved by the titration of the negative post-transcriptional regulator RsmA which affects the expression of over 500 genes. There is increasing evidence pinpointing the importance of RsmY and RsmZ in the planktonic-sessile P. aeruginosa lifestyles switch control. Using swarming motility as a model, we show here that these sRNA are differentially regulated depending on the selected growth conditions (i.e., planktonic versus surface grown-cells). Also, we report that opposite to planktonically grown cells, rsmZ regulation does not implicate the response regulator GacA in swarming cells. Furthermore, we present data indicating that RsmY/Z expression influence swarming motility via the protein HptB which acts as a negative regulator of these sRNAs and that they do not strictly converge to RsmA as previously reported.


Ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry analysis of icariside II metabolites in rats.
The possible metabolic pathways of icariside II were proposed. An ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry method was used for analysing the faecal, bile, plasma and urine samples of rats administrated with icariside II. In all, 27 metabolites were identified in the biosamples. Of these, 20, including F1-F12, D3, D4, D6, D7-D9 and M3, M4, were, to our knowledge, reported for the first time. The results indicated that icariside II was metabolised via desugarisation, dehydrogenation, hydrogenation, hydroxylation, demethylation, glucuronidation, dehydration and glycosylation pathways in vivo. Specific hydrolysis of 7-O glucosides in the gut lumen and glucuronic acid conjugation in the liver were considered as the main physiologic processes of icariside II. This study revealed the possible metabolite profiles of icariside II in rats.


Birthing Stories and Techno-moral Change across Generations: Coping with Hospital Births and High-tech Medicalization in Rural South China, 1960s-2010s.
In the last 100 years, new biomedical technologies altered childbirth practices in China on virtually every level. This transformation was significantly accelerated after the launch of the Birth Planning Policy in 1979. At the turn of the millennium, the government enforced a policy of mandatory hospital births to bring the country closer to United Nations' Millennium Development Goals in terms of maternal and infant health, but these reforms were accompanied by a dramatic increase in cesarean rates. Drawing on oral history materials collected in a rural community in Guangdong province, this article shows how China's cesarean surge gave rise to complex generational frictions in women's techno-moral understandings of what should be the right way to give birth. These generational frictions show that the history of childbirth medicalization is not just a history of changing institutions, policies and technologies; it is also a history of changing technological selves and moral ideals.


Who should provide genetic education prior to gene testing? Computers and other methods for improving patient understanding.
As numerous new gene tests are introduced into clinical practice, patients have a growing need for accurate and comprehensive information about the risks and benefits of gene testing. However, in the changing healthcare environment, it is not clear who will provide such information because genetic counselors are scarce and their services are not widely utilized, and primary care providers lack time and expertise in genetics. Interactive computers may help fill the information gap. We review a variety of educational modalities for providing patient education and argue that interactive computers have potential advantages over other educational methods for providing information and promoting informed consent to genetic testing. Finally, some questions for further research are raised.


Serotonergic neurons mediate ectopic release of dopamine induced by L-DOPA in a rat model of Parkinson's disease.
Benefit and motor side effects of l-DOPA in Parkinson's disease have been related to dopamine transmission in the striatum. However, the putative involvement of serotonergic neurons in the dopaminergic effects of l-DOPA suggests that the striatum is not a preferential target of l-DOPA. By using microdialysis in a rat model of Parkinson's disease, we found that l-DOPA (3-100 mg/kg) increased dopamine extracellular levels monitored simultaneously in four brain regions receiving serotonergic innervation: striatum, substantia nigra, hippocampus, prefrontal cortex. The increase was regionally similar at the lowest dose and 2-3 times stronger in the striatum at higher doses. Citalopram, a serotonin reuptake blocker, or the destruction of serotonergic fibers by 5,7-dihydroxytryptamine impaired l-DOPA-induced dopamine release in all regions. These data demonstrate that l-DOPA induces an ectopic release of dopamine due to serotonergic neurons. The new pattern of dopamine transmission created by l-DOPA may contribute to the benefit and side effects of l-DOPA.


[Possibilities and status of heart surgery in dogs].
Before use of cardiovascular surgical techniques and procedures in humans, many experiments, e.g., hypothermic circulatory arrest and cardiopulmonary bypass using the heart-lung machine, have been performed in the dog. As a consequence experimental canine cardiovascular surgery is highly developed. This has not resulted in the routine performance of open heart surgery in veterinary medicine, probably because of the high costs. Cardiovascular surgery in the dog is generally limited to interventions not depending on hypothermic circulatory arrest or cardiopulmonary bypass. The clinical cardiovascular surgery in dogs can be divided into routine and more specialized interventions. The first category includes correction of peritoneopericardial diaphragmatic hernia, pericardial fenestration in dogs with pericardial effusion, treatment of persistent right aortic arch, and patent ductus closure. The specialized interventions include dilation of pulmonic and aortic stenoses and pacemaker implantation. The diagnosis and surgical treatment of such diseases is described. New developments in cardiovascular surgical treatment that can be expected include catheter techniques for occlusion of shunts and dilations using balloons, because the financial costs of these procedures are not prohibitive.