A Commercial Anti-TIF1γ ELISA Is Superior to Line and Dot Blot and Should Be Considered as Part of Routine Myositis-Specific Antibody Testing.
Anti-TIF1γ is an important autoantibody in the diagnosis of cancer-associated dermatomyositis and the most common autoantibody in juvenile onset dermatomyositis. Its reliable detection is important to instigate further investigations into underlying malignancy in adults. We previously showed that commercial assays using line and dot blots do not reliably detect anti-TIF1γ. We aimed to test a new commercial ELISA and compare with previously obtained protein immunoprecipitation. Radio-labelled immunoprecipitation had previously been used to determine the autoantibody status of patients with immune-mediated inflammatory myopathies and several healthy controls. ELISA was undertaken on healthy control and anti-TIF1γ sera and compared to previous immunoprecipitation data. A total of 110 serum samples were analysed: 42 myositis patients with anti- TIF1γ and 68 autoantibody negative healthy control sera. Anti-TIF1γ was detected by ELISA in 41 out of 42 of the anti-TIF1γ-positive samples by immunoprecipitation, and in none of the healthy controls, giving a sensitivity of 97.6% and specificity of 100%. The false negative rate was 2%. ELISA is an affordable and time-efficient method which is accurate in detecting anti-TIF1γ.


The neuroscience of early intervention: Moving beyond our appeals to fear.
This viewpoint is a continuation of the debate on the early intervention movement in psychiatry. The criticisms of Malhi and colleagues have generated some fundamental questions about the priorities of the early intervention movement and the need for further work. In particular, the summons sent to neuroscience need to be more specific in the near future. We may be doing well with what we have, but more directed efforts are needed to purposefully seek what we do not.


Considering Autonomous Exploration in Healthy Environments: Reflections from an Urban Wildscape.
Autonomous exploration should be considered in the creation of healthy environments since autonomy is an important developmental experience for children. For a group of boys in Raleigh, N.C., U.S. during the period 2002-2006, autonomous exploration was a meaningful experience. Results of a qualitative research project (n = 5) which highlight the importance of autonomous exploration are organized within a proposed framework for thick description. The framework creates verisimilitude by reporting on the context, social action and cultural context, and behavior and intentionality. The context of Raleigh and urban wildscapes furnished areas ripe for exploration. The social action and cultural context of attachment supported the autonomous exploration through scaffolded experiences of autonomy. The intentionality of the behavior was a desire to distinct themselves through a focus on individual development and the pursuit of extraordinary experiences. The ultimate outcomes of autonomous exploration for the boys were the development of long-term, intimate friendships and confidence in their decision-making ability. As cities become more health-focused, attention should be paid to preserve the rough edges of a city for children to explore.


A surgeon's risk of AIDS.
A probabilistic model is used to estimate the cumulative risk to surgeons from human immunodeficiency virus (HIV). Recent data suggest that the probability of infection following percutaneous inoculation is about 1 in 250 cases. Several studies suggest that the frequency of percutaneous injury in surgery is at least 1 in 40 cases, for some as high as 1 in 20 cases. Assuming that on the average a surgeon will perform 350 operations per year and will practice for 30 years, the cumulative risk of HIV infection will depend on the prevalence of HIV infection in the surgical population. For HIV prevalences of 1 in 100 to 1 in 10, the cumulative risk per surgeon ranges from 1 in 100 to 1 in 5, respectively. Based on these risk estimates, it is crucial to decrease the frequency of percutaneous injury. The case is made for substantial improvements in barrier protection and modification of surgical technique.


Haematological parameters in postpartum women and their babies in Poland - comparison of urban and rural areas.
Anaemia is a serious health problem in the contemporary world which aff ects 24.8% of the total human population. It is especially frequent among pregnant women and children. Anaemia is considered as a risk factor of an unfavourable outcome of pregnancy. More than a half of the cases of anaemia, especially among pregnant women, are caused by iron deficiency. The prevalence of anaemia worldwide is especially high among the rural population. It is estimated that the incidence of anaemia after delivery is 4-27%. Anaemia occurring in pregnant women is the cause of anaemia in newborns after birth. The objective of the study was analysis of the haematological parameters of postpartum women and newborns, with particular consideration of the comparison between urban and rural areas. The studies were conducted with the use of questionnaire forms based on the project undertaken in the USA: Pregnancy Risk Assessment Monitoring System (PRAMS). The survey was carried out on a single day, during the period 9-13 August 2010, in all hospitals in Poland where mothers were hospitalized with their newborns. The presented study was based on the replies concerning the results of whole blood count tests in mothers and their babies. The results of the study did not confirm any significant differences between Hct, Hb and RBC values between urban and rural mothers. In both cases, the Hct levels were at the lower limit of normal. Also, no differences with respect to the above-mentioned values were noted among the newborns, although the babies of urban mothers had a higher Hb level. The results of the studies indicate the lack of differences in the health of mothers and their newborn babies with respect to the urban or rural place of residence. Despite this, anaemia is associated with complications which are life-threatening for the mother and the baby; therefore, efforts should be undertaken in order to minimize this problem.


Residential long-term care capacity planning: the shortcomings of ratio-based forecasts.
This paper uses observations from two British Columbia studies to illustrate the shortcomings of widely used ratio-based approaches for residential long-term care capacity planning. It shows that capacity plans based on a fixed ratio of beds per population over age 75 may result in either excess capacity or long wait times for admission. It then investigates the use of linear regression models to obtain a "best" ratio by relating optimal plans derived by rigorous analytical methods to population characteristics and shows that no single ratio applies broadly. While the use of regression is promising, finding these "best" ratios is too analytically complex for general practice. The paper concludes by providing and evaluating an easy-to-use planning method, which we call the average flow model (AFM). The AFM combines demand forecasts with length-of-stay estimates to produce enhanced capacity plans. The AFM is transparent, easily implemented in a spreadsheet and well suited for "what if?" analyses.


Polymorphic Behavior and Phase Transition of Poly(1-Butene) and Its Copolymers.
The properties of semicrystalline polymeric materials depend remarkably on their structures, especially for those exhibiting a polymorphic behavior. This offers an efficient way to tailor their properties through crystal engineering. For control of the crystal structure, and therefore the physical and mechanical properties, a full understanding of the polymorph selection of polymers under varied conditions is essential. This has stimulated a mass of research work on the polymorphic crystallization and related phase transformation. Considering that the isotactic poly(1-butene) (iPBu) exhibits pronounced polymorphs and complicated transition between different phases, the study on its crystallization and phase transformation has attracted considerable attention during the past decades. This review provides the context of the recent progresses made on the crystallization and phase transition behavior of iPBu. We first review the crystal structures of known crystal forms and then their formation conditions and influencing factors. In addition, the inevitable form II to form I spontaneous transition mechanism and the transformation kinetics is reviewed based on the existing research works, aiming for it to be useful for its processing in different phases and the further technical development of new methods for accelerating or even bypass its form II to form I transformation.


[B-cell subpopulation, rosetting with mouse erythrocytes, in patients with rheumatoid arthritis].
Inactive peripheral B-cells rosetting with mouse erythrocytes (BMR+), as well as the stimulation with anti-mu sepharose beads of peripheral mononuclear cells, are diminished in patients with active rheumatoid arthritis (RA). These data provide further evidence for a B-cell activation in active RA.


Enantioselective protonation of alkenyl trifluoroacetates catalyzed by chiral tin methoxide.
Go catalytic! A catalytic enantioselective protonation of alkenyl trifluoroacetates was achieved by using an in situ generated chiral tin bromide methoxide as the chiral catalyst in the presence of methanol. Optically active ketones containing a tertiary stereogenic center at the α-position were obtained with enantioselectivities of up to 94 % ee.


Strongly correlated s-wave superconductivity in the N-type infinite-layer cuprate.
Quasiparticle tunneling spectra of the electron-doped ( n-type) infinite-layer cuprate Sr0.9La0.1CuO2 reveal characteristics that counter a number of common phenomena in the hole-doped ( p-type) cuprates. The optimally doped Sr0.9La0.1CuO2 with T(c) = 43 K exhibits a momentum-independent superconducting gap Delta = 13.0+/-1.0 meV that substantially exceeds the BCS value, and the spectral characteristics indicate insignificant quasiparticle damping by spin fluctuations and the absence of pseudogap. The response to quantum impurities in the Cu sites also differs fundamentally from that of the p-type cuprates with d(x(2)-y(2))-wave pairing symmetry.


Estero real virus: a new virus isolated from argasid ticks Ornithodoros tadaridae in Cuba.
Isolation and serologic identification of a virus isolated from argasid Ornithodoros tadaridae ticks collected in the province Sancti Spíritus in Cuba are described. The virus was named according to the isolation locality El Estero Real. The virus circulation in nature is discussed.


Real-time Functional Analysis of Inertial Microfluidic Devices via Spectral Domain Optical Coherence Tomography.
We report the application of spectral-domain optical coherence tomography (SD-OCT) technology that enables real-time functional analysis of sorting microparticles and cells in an inertial microfluidic device. We demonstrated high-speed, high-resolution acquisition of cross-sectional images at a frame rate of 350 Hz, with a lateral resolution of 3 μm and an axial resolution of 1 μm within the microfluidic channel filled with water. We analyzed the temporal sequence of cross-sectional SD-OCT images to determine the position and diameter of microspheres in a spiral microfluidic channel under various flow rates. We used microspheres with known diameters to validate the sub-micrometer precision of the particle size analysis based on a scattering model of spherical microparticles. An additional investigation of sorting live HT-29 cells in the spiral microfluidic channel indicated that the distribution of cells within in the microchannel has a close correspondence with the cells' size distribution. The label-free real-time imaging and analysis of microscale particles in flow offers robustness for practical applications with live cells and allows us to better understand the mechanisms of particle separations in microfluidic sorting systems.


Aroclor 1254 modulates gene expression of nuclear transcription factors: implications for albumin gene transcription and protein synthesis in rat hepatocyte cultures.
Human exposure to polychlorinated biphenyls (PCBs) may lead to increased albumin serum levels, but little is known about the underlying events. Certain PCBs are also ligands for the aryl hydrocarbon receptor (Ahr) and this receptor regulates transcriptional activation of many different genes, including CYP1A1. We tested our hypothesis that expression of certain nuclear transcription factors is altered upon treatment of rat hepatocyte cultures with Aroclor 1254 and we studied the gene expression of albumin and liver-enriched transcription factors simultaneously. We correlate albumin gene expression with protein synthesis and we used CYP1A1 gene expression and enzyme activity as a surrogate endpoint for aryl hydrocarbon receptor activation. We found mRNA transcripts of CCAAT/enhancer binding protein alpha and gamma, hepatic nuclear factor 1, and hepatic nuclear factor 4 to be increased up to 62-fold, whereas albumin gene expression and secretion was increased 3-fold. Noticeably, expression of c-fos, c-jun (AP-1), HNF-6, CCAAT/enhancer binding protein beta and delta, tissue-specific enhancer-1, Ah-receptor, and albumin D-site-binding protein was unchanged. We show coordinate albumin gene expression and protein secretion in primary rat hepatocyte cultures and propose a relationship between induction of certain liver-enriched transcription factors and of the albumin gene via an Ahr-mediated mechanism.


The next step in shallow coral reef monitoring: combining remote sensing and in situ approaches.
Most current coral reef management is supported by mapping and monitoring limited in record length and spatial extent. These deficiencies were addressed in a multidisciplinary study of cyclone impacts on Aboré Reef, New-Caledonia. Local knowledge, high thematic-resolution maps, and time-series satellite imagery complemented classical in situ monitoring methods. Field survey stations were selected from examination of pre- and post-cyclone images and their post-cyclone coral communities documented in terms of substrata, coral morphologies, live coral cover, and taxonomy. Time-series maps of hierarchically defined coral communities created at spatial scales documenting the variability among communities (29-45 classes) and suggesting the processes that affected them. The increased spatial coverage and repeatability of this approach significantly improved the recognition and interpretation of coral communities' spatio-temporal variability. It identified precise locations of impacted areas and those exhibiting coral recovery and resilience. The approach provides a comprehensive suite of information on which to base reef-scale conservation actions.


Myotonic dystrophy: an electrophysiological study of cognitive deficits.
Patients with Myotonic Dystrophy (MyD) frequently suffer from a dysfunction of the primary sensory pathways, as documented by abnormalities of short-latency evoked potentials. Impairment of intellectual functions has been less extensively investigated. Short-latency brainstem auditory evoked potentials (BAEPs) as well as long-latency auditory event-related potentials (ERPs) were recorded from 5 female and 6 male patients affected by MyD. A simple discrimination ("oddball") paradigm was used to record ERPs to tones from Fz, Cz, Pz. Both BAEPs and ERPs were significantly altered as compared to normals. BAEP abnormalities were detected in 9 patients and ERP components N2 and P3 were delayed or absent for all patients, who nonetheless correctly discriminated between tones. These data indicate that CNS dysfunction in MyD involves not only primary sensory systems but also neural mechanisms underlying cognitive events and ERP generation.


Quality of life assessment in patients with alopecia areata and androgenetic alopecia in the People's Republic of China.
In medical terms, alopecia is considered a relatively mild dermatological condition that nevertheless is a serious condition, but it causes major depression in many sufferers. Alopecia areata (AA) and androgenetic alopecia (AGA) are the main types of hair loss. This study assessed the quality of life (QoL) of Chinese patients with AA and AGA using the Dermatology Life Quality Index (DLQI) questionnaire. A total of 178 AA and AGA patients were enrolled in this study, and DLQI was used to evaluate the QoL of the patients. The DLQI used 10 items regarding symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment as dimensions of life. Each was scored on a 0-3 scale. The total DLQI score equaled 0-30; higher scores showed greater impact on QoL. The DLQI scores of the 178 patients ranged from 0 to 28, with a mean score of 6.3. Higher DLQI scores were reported by younger patients (P<0.05) and by those who had hair loss for a duration of >12 months (P<0.05). The DLQI score of AA patients was significantly higher than that of AGA patients (P<0.05). QoL was not affected by gender, marital status, educational level, past history of alopecia, family history of alopecia, or severity of alopecia. AA and AGA moderately affected the QoL of the patients. A higher DLQI score was significantly associated with younger age, hair loss for a duration of >12 months, and AA. Both AA and AGA moderately affected the QoL of the patients not only in physiological aspects but also in their emotional and social aspects. The bio-psycho-social aspects of disease need to be addressed in patients with AA and AGA, even though these conditions are not life-threatening.


Role of pi-conjugation in influencing the magnetic interactions in dinitrenes: a broken-symmetry approach.
In the present study, we investigated the magnetic interactions of some dinitrenes by employing the broken symmetry-unrestricted density functional theoretical (BS-UDFT) approach along with the use of three basis sets. The magnetic coupling parameter (J) has been calculated, and thereby the magnetic character of the molecule and the strength of magnetic interaction are explored for these molecules. The exchange coupling parameters for the corresponding unconjugated systems are also calculated to see the role of pi-conjugation. Our results suggest that a strong antiferromagnetic interaction exists in conjugated dinitrenes, and the strength of magnetic interaction decreases with increase in spacer length. For the unconjugated dinitrenes, the nature of magnetic interaction reduced appreciably and becomes weakly antiferromagnetic. The singlet-triplet energy gap for each system is also calculated. For the conjugated systems, it is observed that the singlet states are more stable than the triplet states, whereas for the unconjugated systems, the relative stability of the singlet state reduces to a considerable extent. This discrepancy of results for the conjugated and unconjugated dinitrenes can be attributed to the effect of pi-conjugation, and the results can be well explained by this effect.


Substance use disorders and psychiatric comorbidity in mid and later life: a review.
Globally, adults aged 65 years or older will increase from 516 million in 2009 to an estimated 1.53 billion in 2050. Due to substance use at earlier ages that may continue into later life, and ageing-related changes in medical conditions, older substance users are at risk for substance-related consequences. MEDLINE and PsychInfo databases were searched using keywords: alcohol use disorder, drug use disorder, drug misuse, substance use disorder, prescription drug abuse, and substance abuse. Using the related-articles link, additional articles were screened for inclusion. This review focused on original studies published between 2005 and 2013 to reflect recent trends in substance use disorders. Studies on psychiatric comorbidity were also reviewed to inform treatment needs for older adults with a substance use disorder. Among community non-institutionalized adults aged 50+ years, about 60% used alcohol, 3% used illicit drugs and 1-2% used nonmedical prescription drugs in the past year. Among adults aged 50+, about 5% of men and 1.4% of women had a past-year alcohol use disorder. Among alcohol users, about one in 14 users aged 50-64 had a past-year alcohol use disorder vs one in 30 elder users aged 65+. Among drug users aged 50+, approximately 10-12% had a drug use disorder. Similar to depressive and anxiety disorders, substance use disorders were among the common psychiatric disorders among older adults. Older drug users in methadone maintenance treatment exhibited multiple psychiatric or medical conditions. There have been increases in treatment admissions for illicit and prescription drug problems in the United States. Substance use in late life requires surveillance and research, including tracking substance use in the racial/ethnic populations and developing effective care models to address comorbid medical and mental health problems.


[Insights of young French surgical oncologists: motives and training].
In France, surgical oncology is not recognized as a unique specialty, but as a sub-specialization offered to surgeons in training. To date, their motives and training have not been studied. We set a dedicated online survey suggested to 102 surgeons applying for the specific national degree in surgical oncology. The answer rate was 60%. Responders were constituted of a majority of male (61%), their median age was 31 years. They were mainly residents (33%) and fellows working in university (25%) or non-university (28%) hospitals. Most responders have chosen their organ specialization at the beginning, and their oncologic sub-specialization at the middle of their residency, after a meeting with a senior surgeon. Regarding practical education, 85% used surgical videos, 62% mechanical training devices, 60% animal surgery, and 38% cadaver dissection. Regarding career expectations, 67% would like to work in a cancer centre, 51% in a university hospital, and 26% in a private institution. To explain these choices, 51% referred to research and 65% to teaching interests. This study outlines the role of mentorship and the lack of practical teaching outside the operating room during the training in surgical oncology in France.


Laser therapy for rhegmatogenous retinal detachment.
Traditional techniques for managing uncomplicated macula-sparing rhegmatogenous retinal detachments include scleral buckling and pneumatic retinopexy. Demarcation laser photocoagulation is associated with less morbidity than these techniques and may be equally as effective in stabilizing selected macula-sparing retinal detachments.


The impact of postoperative neurologic complications on recovery kinetics in cervical deformity surgery.
The objective of the study is to investigate which neurologic complications affect clinical outcomes the most following cervical deformity (CD) surgery. CD patients (C2-C7 Cobb >10°, CL >10°, cSVA >4 cm or chin-brow vertical angle >25°) >18 years with follow-up surgical and health-related quality of life (HRQL) data were included. Descriptive analyses assessed demographics. Neurologic complications assessed were C5 motor deficit, central neurodeficit, nerve root motor deficits, nerve sensory deficits, radiculopathy, and spinal cord deficits. Neurologic complications were classified as major or minor, then: intraoperative, before discharge, before 30 days, before 90 days, and after 90 days. HRQL outcomes were assessed at 3 months, 6 months, and 1 year. Integrated health state (IHS) for the neck disability index (NDI), EQ5D, and modified Japanese Orthopaedic Association (mJOA) were assessed using all follow-up time points. A subanalysis assessed IHS outcomes for patients with 2Y follow-up. 153 operative CD patients were included. Baseline characteristics: 61 years old, 63% female, body mass index 29.7, operative time 531.6 ± 275.5, estimated blood loss 924.2 ± 729.5, 49% posterior approach, 18% anterior approach, 33% combined. 18% of patients experienced a total of 28 neurologic complications in the postoperative period (15 major). There were 7 radiculopathy, 6 motor deficits, 6 sensory deficits, 5 C5 motor deficits, 2 central neurodeficits, and 2 spinal cord deficits. 11.2% of patients experienced neurologic complications before 30 days (7 major) and 15% before 90 days (12 major). 12% of neurocomplication patients went on to have revision surgery within 6 months and 18% within 2 years. Neurologic complication patients had worse mJOA IHS scores at 1Y but no significant differences between NDI and EQ5D (0.003 vs. 0.873, 0.458). When assessing individual complications, central neurologic deficits and spinal cord deficit patients had the worst outcomes at 1Y (2.6 and 1.8 times worse NDI scores, P = 0.04, no improvement in EQ5D, 8% decrease in EQ5D). Patients with sensory deficits had the best NDI and EQ5D outcomes at 1Y (31% decrease in NDI, 8% increase in EQ5D). In a subanalysis, neurologic patients trended toward worse NDI and mJOA IHS outcomes (P = 0.263, 0.163). 18% of patients undergoing CD surgery experienced a neurologic complication, with 15% within 3 months. Patients who experienced any neurologic complication had worse mJOA recovery kinetics by 1 year and trended toward worse recovery at 2 years. Of the neurologic complications, central neurologic deficits and spinal cord deficits were the most detrimental.


Medication compliance after renal transplantation.
Noncompliance is known to be an important cause of late graft failure after renal transplantation. We investigated prospectively the degree of compliance with immunosuppressive and antihypertensive drugs during the first year after renal transplantation by monthly pill counts. In addition, we examined whether noncompliance was related to a number of demographic and clinical variables or to the occurrence of rejections. The study population consisted of 127 patients who were involved in a randomized trial comparing cyclosporine monotherapy with azathioprine-prednisone treatment. Average compliance rates approximated 100%, although considerable variability within and between subjects was observed. Using an arbitrary limit to classify patients as compliers or noncompliers, the following frequencies of noncompliance were observed during the study year: cyclosporine, 23%; azathioprine, 13%; prednisone, 23%; atenolol, 36%; and nifedipine, 32%. Average compliance scores for all immunosuppressive drugs were superior to those of antihypertensive medication (P < 0.001). Except for a better compliance for prednisone in men as compared with women, we found no consistent relationship between compliance on the one hand and several demographic variables, graft function, or quality of life on the other hand. Patients who developed one or more acute rejection episodes showed a higher degree of undercompliance, especially for prednisone, than patients without rejections (P < 0.01). Following the occurrence of a rejection episode, compliance scores improved significantly. Keeping in mind the limitations of the pill count method, we conclude that noncompliance with immunosuppressive drugs is not a huge problem during the first year after renal transplantation. However, it is likely that noncompliance contributes to a certain number of acute rejection episodes.


A novel flucytosine-resistant yeast species, Candida pseudoaaseri, causes disease in a cancer patient.
Some members of the genus Candida are among the most common human fungal pathogens and cause serious diseases especially in immunocompromised people. A yeast was isolated from a blood culture from an immunocompromised cancer patient who suffered from acute pneumonia. The growth characteristics of the yeast on CHROMagar Candida were similar to those of Candida tropicalis, whereas the API ID 32C system identified the yeast as Candida silvicola. On the basis of the nucleotide divergence in the D1/D2 domain of the 26S nuclear rRNA (nrRNA) gene, as well as the internal transcribed spacer (ITS) domain of the nrRNA gene region, a new species, Candida pseudoaaseri sp. nov. with type strain VK065094 (CBS 11170(T)), which was found to be closely related to Candida aaseri, is proposed. While C. aaseri strains were susceptible to all tested antifungals, the new species is resistant to flucytosine and may also be distinguished from C. aaseri by its ability to assimilate l-rhamnose, whereas its colony morphology on CHROMagar Candida may be helpful for differentiation.


[Clinicopathological features of hybrid oncocytic/chromophobe renal cell tumor].
Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of hybrid oncocytic/chromophobe tumor (HOCT) of the kidney and its associations with renal oncocytoma (RO) and eosinophilic chromophobe renal cell carcinoma (eChRCC). Methods: A total of 8 HOCT cases were collected from 2008 to 2019 at the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of PLA Navy (3 cases), Qingdao, China for morphological studies, immunohistochemical staining and follow-up. The immunohistochemical results of HOCT were compared with those of 27 typical RO and 17 eChRCC. Results: Among the 8 patients, 3 were male and 5 were female. Their ages ranged from 39 to 75 years (median: 56 years). All cases were sporadic. Seven patients were asymptomatic and one suffered from lumbago. During a mean follow-up of 37 months in 7 patients, none of them developed tumor recurrence or metastasis. Seven cases were solitary and one was multiple. The tumor size ranged from 1.4 to 5.7 cm (mean, 3.6 cm). The cut surface of the tumors was dark red or yellowish. Histologically, the tumors were well-defined. Six cases were directly adjacent to the surrounding renal tissue, 2 cases had pseudocapsule, 3 cases showed entrapped renal tubules at the edge of tumor tissue, and one circumscribed with focal infiltrating borders. There were two types of histological morphology: one type (4 cases) was composed of mixed areas of otherwise typical RO and areas resembling chromophobe renal cell carcinoma; another type (4 cases) showed the morphological characteristics of both RO and eChRCC. Three second-type tumors showed nest-like, trabecular, and solid growth patterns with conspicuous edematous stroma. The cell border was conspicuous and the cytoplasm showed an eosinophilic appearance. The nuclei were small and round with clear perinuclear halo. One tumor showed a multi-nodular and solid growth pattern, and the cytoplasm was eosinophilic, hypochromatic or transparent. The nuclei were small and round, and some of them had obvious perinuclear halo. Immunohistochemically, the tumor cells in all 8 cases were positive for Ksp-cad but negative for vimentin. CD117 was diffusely positive in 6/8 cases. CK7 staining showed patchy positivity in 6/8 cases. S-100A1, cyclin D1 and claudin7 showed variable positivity in 4/8, 6/8 and 5/8 cases, respectively, but the range and intensity were narrower and weaker than those in RO and eChRCC. Conclusions: HOCT is a low-grade eosinophilic renal tumor with morphological characteristics resembling RO and eChRCC. The combined application of immunohistochemical stains of CK7, CD117, Ksp-cad, cyclin D1, claudin7 and S-100A1 may play an auxiliary role in the differentiation of the three tumors. HOCT has a good prognosis after surgical resection and can be regarded as a tumor with uncertain malignant potential.


Demixing by a Nematic Mean Field: Coarse-Grained Simulations of Liquid Crystalline Polymers.
Liquid crystalline polymers exhibit a particular richness of behaviors that stems from their rigidity and their macromolecular nature. On the one hand, the orientational interaction between liquid-crystalline motifs promotes their alignment, thereby leading to the emergence of nematic phases. On the other hand, the large number of configurations associated with polymer chains favors formation of isotropic phases, with chain stiffness becoming the factor that tips the balance. In this work, a soft coarse-grained model is introduced to explore the interplay of chain stiffness, molecular weight and orientational coupling, and their role on the isotropic-nematic transition in homopolymer melts. We also study the structure of polymer mixtures composed of stiff and flexible polymeric molecules. We consider the effects of blend composition, persistence length, molecular weight and orientational coupling strength on the melt structure at the nano- and mesoscopic levels. Conditions are found where the systems separate into two phases, one isotropic and the other nematic. We confirm the existence of non-equilibrium states that exhibit sought-after percolating nematic domains, which are of interest for applications in organic photovoltaic and electronic devices.


Increased bile acid excretion and reduction of serum cholesterol after crenotherapy with salt-rich mineral water.
The effect of a spring mineral water from Montecatini (Italy) on bile acid excretion, and lipid and apolipoprotein serum levels was evaluated. The study was conducted in subjects with serum total cholesterol (TC) level > 240 mg/dL and LDL cholesterol (LDL-C) > 170 mg/dL, over a 9-week period, with 3 weeks of dietary stabilization, 3 weeks of active treatment, and 3 weeks of tap-water treatment as a control period. Serum lipids and apolipoproteins, total and fractionated bile acid excretion, gallbladder motility, and safety parameters were evaluated. Active treatment with mineral water significantly reduced serum TC by 7.5%, LDL-C by 12.5%, TC/HDL-cholesterol ratio by 6.3%, and apolipoprotein B by 6.3%; total fecal bile acid excretion was increased by 98.9%, and gallbladder volume was reduced by 40%. The reduction in serum and LDL-cholesterol levels observed during the active treatment period ran parallel to the increased excretion of bile acids in the stools. We suggest that salt-rich spring water treatment reduces serum and LDL-cholesterol levels in subjects with mild hypercholesterolemia through a mechanism of increased excretion of fecal bile acid sterols.


Correlated divergence of female and male genitalia in replicated lineages with ongoing ecological speciation.
Divergence of genital traits among lineages has the potential to serve as a reproductive isolating barrier when copulation, insemination, and fertilization are inhibited by incompatibilities between female and male genitalia. Despite widespread evidence for genital trait diversity among closely related lineages and coevolution of female and male genitalia within lineages, few studies have investigated genital evolution during the early stages of speciation. We quantified genital variation in replicated population pairs of Poecilia mexicana with ongoing ecological speciation between sulfidic (H2 S containing) and nearby nonsulfidic habitats. These analyses revealed rapid and correlated divergence of female and male genitalia across evolutionarily independent population pairs exposed to divergent selection regimes. Both sexes exhibited convergent evolution of genital traits among populations inhabiting similar habitat types. Our results demonstrate that genital evolution can occur during the early stages of speciation-with-gene-flow, potentially as a result of variation in the intensity of sexual conflict among populations. Our results suggest genitalia may contribute to early stages of divergence and challenge the generality of previously suggested mechanisms of genital evolution in poeciliids.


Microscale phosphoproteome analysis of 10,000 cells from human cancer cell lines.
We developed a miniaturized LC-MS system with a high-recovery phosphopeptide enrichment protocol that allows phosphoproteome analysis of 10(4) cells. In the enrichment protocol, the key step is to add sodium deoxycholate and sodium lauroyl sarcosinate to the buffer solution for protein extraction and digestion and to omit any subsequent desalt/desurfactant step before phosphopeptide enrichment. The phosphopeptides enriched by hydroxy acid-modified metal oxide chromatography (HAMMOC) are directly injected onto a miniaturized LC column using a nitrogen-pressure-driven cell, instead of switching valve-type injectors. The miniaturized analytical column of 25 μm diameter provided a 3.6-fold improvement in sensitivity over the conventional 100 μm diameter column. Overall, our analytical system provided approximately 80-fold improvement on average in the LC-MS response, and we identified 1011 unique phosphorylated sites based on 995 unique phosphopeptides from a single analysis of 10(4) HeLa cells (approximately 1 μg of proteins). This is the most sensitive phosphoproteomics system that has so far been reported for proteome-wide analysis of in vivo phosphorylation in mammalian cells.


Dynamics of glutathione and ophthalmate traced with 2H-enriched body water in rats and humans.
We developed a LC-MS-MS assay of the (2)H labeling of free glutathione (GSH) and bound glutathione [GSSR; which includes all DTT-reducible forms, primarily glutathione disulfide (GSSG) and mixed disulfides with proteins] and ophthalmate (an index of GSH depletion) labeled from (2)H-enriched body water. In rats whose body water was 2.5% (2)H enriched for up to 31 days, GSH labeling follows a complex pattern because of different rates of labeling of its constitutive amino acids. In rats infused with [(13)C(2),(15)N-glycine]glutathione, the rate of appearance of plasma GSH was 2.1 micromol.min(-1).kg(-1), and the half-life of plasma GSH/GSSR was 6-8 min. In healthy humans whose body fluids were 0.5% (2)H enriched, the (2)H labeling of GSH/GSSR and ophthalmate can be precisely measured after 4 h, with GSH being more rapidly labeled than GSSR. Since plasma GSH/GSSR derives mostly from liver, this technique opens the way to 2) probe noninvasively the labeling pattern and redox status of the liver GSH system in humans and 2) assess the usefulness of ophthalmate as an index of GSH depletion.


[Reforms of medical / health studies: in the middle of the ford].
IN THE MIDDLE OF THE FORD Medical Education Reform: The main aim is learning of skills, attitudes and behavior of students and graduates which was very often neglected until then. Two problems remains ; first, what are the disponibility and motivation of medical faculties and teachers and second how the students will accept the new form of evaluation to access at post graduate level (specialization cycle).


Practical Guide to Trapping Peromyscus leucopus (Rodentia: Cricetidae) and Peromyscus maniculatus for Vector and Vector-Borne Pathogen Surveillance and Ecology.
Arthropods pests are most frequently associated with both plants and vertebrate animals. Ticks, in particular the blacklegged ticks Ixodes scapularis Say and Ixodes pacificus Cooley & Kohls (Acari: Ixodidae), are associated with wildlife hosts and are the primary vectors of Lyme disease, the most frequently reported vector-borne disease in the United States. Immature blacklegged ticks in the eastern United States frequently use small mammals from the genus Peromyscus as hosts. These mice are competent reservoirs for Borrelia burgdorferi, the causative agent of Lyme disease, as well as other tick-borne pathogens. To conduct surveillance on immature ticks and pathogen circulation in hosts, capture and handling of these small mammals is required. While protocols for rearing and pest surveillance on plants are common, there are very few protocols aimed at entomologists to conduct research on vertebrate-arthropod relationships. The goal of this manuscript is to provide a practical template for trapping Peromyscus spp. for vector and vector-borne pathogen surveillance and ecology for professionals that may not have a background in wildlife research. Important considerations are highlighted when targeting P. leucopus Rafinesque and P. maniculatus Wagner. Specifically, for tick and tick-borne disease-related projects, materials that may be required are suggested and references and other resources for researchers beginning a trapping study are provided.


Does hsa-miR-223-3p from platelet-derived extracellular vesicles regulate tissue factor expression in monocytic cells?
Extracellular vesicles (EVs) released from activated platelets contain microRNAs, the most abundant of which is hsa-miR-223-3p. Endogenous hsa-miR-223-3p suppresses the expression of tissue factor (TF), the initiator of the extrinsic coagulation pathway, in endothelial cells. Monocytes can be induced to express TF to enhance coagulation, but the role of hsa-miR-223-3p in regulating monocyte TF remains unknown. This study examined whether hsa-miR-223-3p from platelet-derived EVs (pdEVs) affects TF expression in monocytes. THP-1 cells, differentiated into a monocyte-like phenotype with 1α,25-dihydroxyvitaminD3, were transfected with hsa-miR-223-3p mimic or control microRNA. Alternatively, THP-1 cells were incubated with pdEVs from PAR1-agonist peptide activated-platelets, as platelet releasate, or pdEVs isolated by ultracentrifugation. Transfection with hsa-miR-223-3p mimic resulted in significant reductions in TF protein, determined by western blotting and flow cytometry and reduced procoagulant activity, measured by a TF-specific factor Xa generation assay, compared to cells transfected with control microRNA. This reduction was reversed by co-transfection with hsa-miR-223-3p inhibitor, AntagomiR-223. Incubation of THP-1 cells with pdEVs also decreased TF expression; however, this was not reversed by AntagomiR-223. Taken together, monocyte TF expression is downregulated by hsa-miR-223-3p, but when transferred via pdEVs the effect was not reversed with Antagomir-223, suggesting other pdEV components may contribute to TF regulation.Abbreviations: Tissue factor (TF), Factor VII (FVII), activated Factor VII (FVIIa), Factor X (FX), activated Factor X (FXa), extracellular vesicles (EVs), microvesicles (MVs), platelet-derived extracellular vesicles (pdEVs), protease-activated receptor 1 agonist peptide (PAR1-AP), lipopolysaccharide (LPS), P-selectin glycoprotein ligand-1 (PSGL-1), Tris-Buffered Saline Tween (TBST), room temperature (RT)[Figure: see text].


Interactive effects of catastrophizing and suppression on responses to acute pain: a test of an appraisal x emotion regulation model.
We examined whether people who tend to catastrophize about pain and who also attempt to regulate negative thoughts and feelings through suppression may represent a distinct subgroup of individuals highly susceptible to pain and distress. Ninety-seven healthy normal participants underwent a 4-min ischemic pain task followed by a 2-min recovery period. Self-reported pain and distress was recorded during the task and every 20 s during recovery. Participants completed the Pain Catastrophizing Scale and the White Bear Suppression Inventory. Repeated measures multiple regression analysis (using General Linear Model procedures) revealed significant 3-way interactions such that participants scoring high on the rumination and/or helplessness subscales of the Pain Catastrophizing Scale and who scored high on the predisposition to suppress unwanted thoughts and feelings reported the greatest pain and distress during recovery. Results suggest that pain catastrophizers who attempt to regulate their substantial pain intensity and distress with maladaptive emotion regulation strategies, such as suppression, may be especially prone to experience prolonged recovery from episodes of acute pain. Thus, emotion regulation factors may represent critical variables needed to understand the full impact of catastrophic appraisals on long-term adjustment to pain.


[Caveolar endocytosis and virus entry].
The endocytic function of caveolae has been controversial for a long time. However, a real-time-imaging analysis of Simian virus 40 (SV40) 's entry in cells has indicated the existence of caveolar endocytosis during virus entry. The caveolae engulfed SV40 virions begin budding from plasma membrane depending on dynamin. SV40 enclosed in caveolae vesicles move to the caveosome, then to the endoplasmic reticulum. In addition, it was demonstrated that human coronavirus-229E enters the cell through caveolae. This review examines the involvement of caveolae in endocytosis used by the viral entry system.


Compensatory Puffing With Lower Nicotine Concentration E-liquids Increases Carbonyl Exposure in E-cigarette Aerosols.
Article 20 of the European Tobacco Products Directive (EU-TPD) specifies that e-liquids should not contain nicotine in excess of 20 mg/mL, thus many vapers may be compelled to switch to lower concentrations and in so doing, may engage in more intensive puffing. This study aimed to establish whether more intensive puffing produces higher levels of carbonyl compounds in e-cigarette aerosols. Using the HPLC-UV diode array method, four carbonyl compounds (formaldehyde, acetaldehyde, acetone, and acrolein) were measured in liquids and aerosols from nicotine solutions of 24 and 6 mg/mL. Aerosols were generated using a smoking machine configured to replicate puffing topography data previously obtained from 12 experienced e-cigarette users. Carbonyl levels in aerosols from the puffing regimen of 6 mg/mL were significantly higher (p < .05 using independent samples t tests) compared with those of 24 mg/mL nicotine. For the 6 and 24 mg/mL nicotine aerosols respectively, means ± SD for formaldehyde levels were 3.41 ± 0.94, and 1.49 ± 0.30 µg per hour (µg/h) of e-cigarette use. Means ± SD for acetaldehyde levels were 2.17 ± 0.36 and 1.04 ± 0.13 µg/h. Means ± SD for acetone levels were 0.73 ± 0.20 and 0.28 ± 0.14 µg/h. Acrolein was not detected. Higher levels of carbonyls associated with more intensive puffing suggest that vapers switching to lower nicotine concentrations (either due to the EU-TPD implementation or personal choice), may increase their exposure to these compounds. Based on real human puffing topography data, this study suggests that limiting nicotine concentrations to 20 mg/mL may not result in the desired harm minimalization effect. More intensive puffing regimens associated with the use of low nicotine concentration e-liquids can lead to higher levels of carbonyl generation in the aerosol. Although in need of replication in a larger sample outside a laboratory, this study provides pragmatic empirical data on the potential risks of compensatory puffing behaviors in vapers, and can help to inform future regulatory decisions on nicotine e-liquid concentrations. The cap on nicotine concentration at 20 mg/mL set by the EU-TPD may therefore have the unintended consequence of encouraging use of lower nicotine concentration e-liquid, in turn increasing exposure to carbonyl compounds through compensatory puffing.


Body size and symbiotic status influence gonad development in Aiptasia pallida anemones.
Pale anemones (Aiptasia pallida) coexist with dinoflagellates (primarily Symbiodinium minutum) in a mutualistic relationship. The purpose of this study was to investigate the role of these symbionts in gonad development of anemone hosts. Symbiotic and aposymbiotic anemones were subjected to light cycles that induced gametogenesis. These anemones were then sampled weekly for nine weeks, and gonad development was analyzed histologically. Anemone size was measured as mean body column diameter, and oocytes or sperm follicles were counted for each anemone. Generalized linear models were used to evaluate the influence of body size and symbiotic status on whether gonads were present and on the number of oocytes or sperm follicles produced. Body size predicted whether gonads were present, with larger anemones being more likely than smaller anemones to develop gonads. Both body size and symbiotic status predicted gonad size, such that larger and symbiotic anemones produced more oocytes and sperm follicles than smaller and aposymbiotic anemones. Overall, only 22 % of aposymbiotic females produced oocytes, whereas 63 % of symbiotic females produced oocytes. Similarly, 6 % of aposymbiotic males produced sperm follicles, whereas 60 % of symbiotic males produced sperm follicles. Thus, while gonads were present in 62 % of symbiotic anemones, they were present in only 11 % of aposymbiotic anemones. These results indicate that dinoflagellate symbionts influence gonad development and thus sexual maturation in both female and male Aiptasia pallida anemones. This finding substantiates and expands our current understanding of the importance of symbionts in the development and physiology of cnidarian hosts.


A fluid dynamics multidimensional model of biofilm growth: stability, influence of environment and sensitivity.
In this article, we study in detail the fluid dynamics system proposed in Clarelli et al. (2013, J. Math. Biol., 66, 1387-1408) to model the formation of cyanobacteria biofilms. After analysing the linear stability of the unique non-trivial equilibrium of the system, we introduce in the model the influence of light and temperature, which are two important factors for the development of a cyanobacteria biofilm. Since the values of the coefficients we use for our simulations are estimated through information found in the literature, some sensitivity and robustness analyses on these parameters are performed. All these elements enable us to control and to validate the model we have already derived and to present some numerical simulations in the 2D and the 3D cases.


Dosimetric comparison of graphical optimization and inverse planning simulated annealing for brachytherapy of cervical cancer.
Graphical optimization (GO) and inverse planning simulated annealing (IPSA) are the main treatment planning optimization techniques used in patients undergoing 3D brachytherapy treatment. This study aims to compare the dosimetric difference of plans optimized by GO and IPSA in cervical cancer brachytherapy. 21 cervical cancer patients data sets consisted of computed tomography (CT) and magnetic resonance imaging (MRI), acquired with the Fletcher applicator in situ were transferred to the Oncentra brachytherapy planning system. For each patient, the treatment plan was initially optimized with GO to reach a maximal D90 tumor dose (6 Gy/fraction, 5 fractions), while keeping the dose to organs at risk (OARs) as low as possible. A second plan was then optimized with IPSA on the same CT images and data set (i.e., contours, catheters, and location of dwell points). Targets and OARs dose volume histograms and irradiation time were compared; data were analyzed with paired t-test; p value < 0.05 was considered statistically significant. The plans with both optimizations meet the clinical requirements. The mean D90 of the clinical target volume was comparable for GO and IPSA. Similar values (p > 0.05) of target V100, V150, V200, HI, and CI were registered for GO and IPSA optimizations. Bladder and rectum D1cc and D2cc obtained by GO resulted in larger values than those obtained by IPSA (p = 0.002). V75 for bladder and rectum were slightly higher for IPSA, but without statistical difference (p > 0.05). The irradiation time was comparable (p > 0.05). In 3D brachytherapy of cervical cancer, GO and IPSA optimizations do not present a significant difference in target dose coverage; nevertheless, IPSA may reduce the maximum dose to normal tissue when compared with GO.


Neurologic complications of transplantation.
Major neurologic morbidity, such as seizures and encephalopathy, complicates 20-30% of organ and stem cell transplantation procedures. The majority of these disorders occur in the early posttransplant period, but recipients remain at risk for opportunistic infections and other nervous system disorders for many years. These long-term risks may be increasing as acute survival increases, and a greater number of "sicker" patients are exposed to long-term immunosuppression. Drug neurotoxicity accounts for a significant proportion of complications, with posterior reversible leukoencephalopathy syndrome, primarily associated with calcineurin inhibitors (i.e., cyclosporine and tacrolimus), being prominent as a cause of seizures and neurologic deficits. A thorough evaluation of any patient who develops neurologic symptoms after transplantation is mandatory, since reversible and treatable conditions could be found, and important prognostic information can be obtained.


Mechanism of inhibition by methacholine of norepinephrine-stimulated ANP secretion.
We have previously reported that methacholine inhibits norepinephrine-stimulated immunoreactive atrial natriuretic peptide (ANP-IR) secretion by 65% in vitro. In the present study, we examined the mechanism by which methacholine inhibits norepinephrine-stimulated secretion using isolated, paced rat left atria superfused in vitro. Norepinephrine has beta- and alpha-adrenergic properties, both of which stimulate ANP secretion. Thus we separately examined the effect of 10 microM methacholine on ANP-IR secretion stimulated by the beta-adrenergic agonist isoproterenol (0.1 microM) and by the alpha-adrenergic agonist phenylephrine (10 microM). Methacholine lowered isoproterenol-stimulated ANP-IR secretion to base line but did not inhibit phenylephrine-stimulated ANP-IR secretion. Atria were superfused with 0.5 mM dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) to determine whether inhibition of isoproterenol-stimulated secretion by methacholine occurred by a reduction in adenylate cyclase activity or at a point distal to cAMP. Methacholine inhibited dibutyryl cAMP-stimulated ANP-IR secretion by 50%. This inhibition could not be reversed by 20 microM isobutylmethylxanthine. We conclude that 1) methacholine completely blocks isoproterenol-stimulated ANP-IR secretion; 2) inhibition appears to be primarily due to a decrease in adenylate cyclase activity; however, inhibition occurs at a point(s) distal to cAMP production; 3) methacholine does not inhibit phenylephrine-stimulated ANP-IR secretion; and 4) inhibition by methacholine of norepinephrine-stimulated ANP-IR secretion reflects a block in beta-adrenergic activity.


Association of Vitamin D3 Level with Breast Cancer Risk and Prognosis in African-American and Hispanic Women.
Background: This study investigated the association of vitamin D3 levels with breast cancer risk and progression in African-Americans and Hispanics. Methods: A total of 237 African-American (Cases = 119, Control = 118) and 423 Hispanic women (Cases = 124, Control = 299) were recruited in the study. Blood samples were collected at the time of breast cancer screening and prior to cancer treatment for 4 weeks on average for the cases. The serum 25-hydroxyvitamin D (25(OH)D3) was measured at a Quest-Diagnostics facility. Results: The results showed that 69.2% of African-Americans and 37.8% of Hispanics had 25(OH)D3 levels below 20 ng/mL. The 25(OH)D3 level below 20 ng/mL was significantly associated with breast cancer in both African-Americans (OR = 2.5, 95% CI = 1.3-4.8) and Hispanics (OR = 1.9, 95% CI = 1.1-3.0). However, the predicted probabilities of breast cancer in African-Americans were significantly higher than in Hispanics (p < 0.001). The 25(OH)D3 below 20 ng/mL was significantly associated with triple negative breast cancer (TNBC) in African-Americans (OR = 5.4, p = 0.02, 95% CI = 1.4-15), but not in Hispanics in our cohort of participants. Levels of 25(OH)D3 below 26 ng/mL predicts a decrease in disease-free survival, but it was not an independent predictor. Conclusions: Our data shows an association between 25(OH)D3 levels and the risk of breast cancer. Further studies on the relationship between 25(OH)D3 level and breast cancer risk are warranted.


Transdermal Delivery of Therapeutic Compounds With Nanotechnological Approaches in Psoriasis.
Psoriasis is a chronic, immune-mediated skin disorder involving hyperproliferation of the keratinocytes in the epidermis. As complex as its pathophysiology, the optimal treatment for psoriasis remains unsatisfactorily addressed. Though systemic administration of biological agents has made an impressive stride in moderate-to-severe psoriasis, a considerable portion of psoriatic conditions were left unresolved, mainly due to adverse effects from systemic drug administration or insufficient drug delivery across a highly packed stratum corneum via topical therapies. Along with the advances in nanotechnologies, the incorporation of nanomaterials as topical drug carriers opens an obvious prospect for the development of antipsoriatic topicals. Hence, this review aims to distinguish the benefits and weaknesses of individual nanostructures when applied as topical antipsoriatics in preclinical psoriatic models. In view of specific features of each nanostructure, we propose that a proper combination of distinctive nanomaterials according to the physicochemical properties of loaded drugs and clinical features of psoriatic patients is becoming a promising option that potentially drives the translation of nanomaterials from bench to bedside with improved transdermal drug delivery and consequently therapeutic effects.


[Development of monogeneans from the family Tetraonchidae under experimental conditions].
Experimental data on the development of the Tetraonchus borealis larvae and species of the genus Salmonchus are given for the first time. The experiments was carried out in field conditions, in the estuary of the Shegnanda river (Baikal Lake basin), during 25 days. It was established that temperatures from 15 to 22 degrees C are favorable for the culture of the Salmonchus eggs followed by the emergence of larvae at eighth or ninth day. At the same time, T. borealis larvae need in lower temperatures, from 15 to 17 degrees C for their development. Detailed descriptions of eggs and larvae of the Tetraonchidae species under are given.


Implications of methadone maintenance for theories of narcotic addiction.
Clinical success in rehabilitation of heroin addicts with maintenance treatment requires stability of the blood level in a pharmacologically effective range (optimally, 150 to 600 ng/mL)-a phenomenon that emphasizes the central importance of narcotic receptor occupation. It is postulated that the high rate of relapse of addicts after detoxification from heroin use is due to persistent derangement of the endogenous ligand-narcotic receptor system and that methadone in an adequate daily dose compensates for this defect. Some patients with long histories of heroin use and subsequent rehabilitation on a maintenance program do well when the treatment is terminated. The majority, unfortunately, experience a return of symptoms after maintenance is stopped. The treatment, therefore, is corrective but not curative for severely addicted persons. A major challenge for future research is to identify the specific defect in receptor function and to repair it. Meanwhile, methadone maintenance provides a safe and effective way to normalize the function of otherwise intractable narcotic addicts.


Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies.
The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau's function in microtubule assembly and stabilization and with regards to tau's interactions with other proteins, membranes, and DNA. We describe and analyze important posttranslational modifications: hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and truncation. We discuss how these post-translational modifications can alter tau's biological function and what is known about tau self-assembly, and we propose a mechanism of tau polymerization. We analyze the impact of natural mutations on tau that cause fronto-temporal dementia associated with chromosome 17 (FTDP-1 7). Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration.


Effects of transpositional muscle flaps transfected with vascular endothelial growth factor gene in the treatment of experimental osteomyelitis.
Based on the angiogenetic and stimulating effects of bone healing and formation of vascular endothelial growth factor (VEGF), the present study was designed to assess the efficacy of VEGF gene application in the management of experimentally induced osteomyelitis. Thirty-two male Sprague Dawley rats were divided into 4 groups, and osteomyelitis was induced in the left tibial bones. Group 1 (n=8) was designated as a control group, and, after the induction of osteomyelitis, no treatment was applied for a period of 4 weeks. Group 2 (n=8) received only antibiotic treatment for 4 weeks following induction of osteomyelitis. In Group 3 (n=8), proximally pedicled gastrocnemius muscle flap was transposed over the osteomyelitic region following induction of osteomyelitis and antibiotic treatment applied for a 4-week period. In Group 4 (n=8), VEGF gene-transfected gastrocnemius muscle flap was transposed over the osteomyelitic region following identical antibiotic regimen applied for a 4-week period. For each group, body temperature, white blood cell (WBC) count, and radiological and histological parameters were evaluated. Body temperature and WBC count remained high in the control group, but returned to normal in Groups 2, 3, and 4 after the third week of treatment. Statistical analysis of the total scores of radiological and histological results revealed significant differences between Groups 1 and 3, Groups 1 and 4, Groups 2 and 3, and Groups 2 and 4 (p<0.05). Regarding radiological parameters of abscess and sequester, and histological parameter of abscess, statistically significant differences were found between Group 4 and the other groups (p<0.05). The efficacy of the VEGF gene-transfected muscle flap in the management of experimental osteomyelitis was proven by the results of the present study.


The 3'-untranslated region of ADAMTS1 regulates its mRNA stability.
ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'-UTR may regulate the expression of ADAMTS1 mRNA.


Collecting Duct Nitric Oxide Synthase 1ß Activation Maintains Sodium Homeostasis During High Sodium Intake Through Suppression of Aldosterone and Renal Angiotensin II Pathways.
During high sodium intake, the renin-angiotensin-aldosterone system is downregulated and nitric oxide signaling is upregulated in order to remain in sodium balance. Recently, we showed that collecting duct nitric oxide synthase 1β is critical for fluid-electrolyte balance and subsequently blood pressure regulation during high sodium feeding. The current study tested the hypothesis that high sodium activation of the collecting duct nitric oxide synthase 1β pathway is critical for maintaining sodium homeostasis and for the downregulation of the renin-angiotensin-aldosterone system-epithelial sodium channel axis. Male control and collecting duct nitric oxide synthase 1β knockout (CDNOS1KO) mice were placed on low, normal, and high sodium diets for 1 week. In response to the high sodium diet, plasma sodium was significantly increased in control mice and to a significantly greater level in CDNOS1KO mice. CDNOS1KO mice did not suppress plasma aldosterone in response to the high sodium diet, which may be partially explained by increased adrenal AT1R expression. Plasma renin concentration was appropriately suppressed in both genotypes. Furthermore, CDNOS1KO mice had significantly higher intrarenal angiotensin II with high sodium diet, although intrarenal angiotensinogen levels and angiotensin-converting enzyme activity were similar between knockout mice and controls. In agreement with inappropriate renin-angiotensin-aldosterone system activation in the CDNOS1KO mice on a high sodium diet, epithelial sodium channel activity and sodium transporter abundance were significantly higher compared with controls. These data demonstrate that high sodium activation of collecting duct nitric oxide synthase 1β signaling induces suppression of systemic and intrarenal renin-angiotensin-aldosterone system, thereby modulating epithelial sodium channel and other sodium transporter abundance and activity to maintain sodium homeostasis.


Possibilities for developing texture-modified beef steaks suitable for older consumers using fruit-derived proteolytic enzymes.
Meat intakes in the older population are commonly reduced because the relatively tough texture of meat can impair mastication. Fruit-derived proteolytic enzymes have been reported to have beneficial effects on tenderness, by causing significant degradation of myofibrillar proteins and collagen. Three treatments including: papain, bromelain, and a 50:50 mixture of papain/bromelain, alongside one control were applied to beef M. semitendinosus steaks. Effects on Warner-Bratzler shear force, texture parameters, color, and cook loss were determined. Both enzymatic treatments that included papain significantly reduced Warner-Bratzler shear force values (p < .05) and increased cook loss. Beef steaks tenderized with papain and papain/bromelain offer potential for inclusion in older consumers' diets, but improvement in tenderization may be associated with a reduction in processing yield. Meat processors have a role to play in enhancing the availability of appropriate foodstuffs for older people, through developing targeted products that will meet the specialized nutritional and chemosensory needs of this cohort. Meat intakes in the older population are commonly reduced because the relatively tough texture of meat can impair mastication. In this study, beef steaks tenderized with papain and papain: bromelain (50:50) were demonstrated to produce more tender meat products, with a lower cook loss compared with tenderization with bromelain alone, which has relevance to the development of texture-optimized meat products that appeal to older adults with difficulty in mastication. This information could help meat processors to develop strategies for optimization of texture-modified beef products within their own businesses.


Use of a computerized closed-loop sodium nitroprusside titration system for antihypertensive treatment after open heart surgery.
This study evaluates the clinical applicability of administering sodium nitroprusside by a closed-loop titration system compared with a manually adjusted system. The mean arterial pressure (MAP) was registered every 10 and 30 sec during the first 150 min after open heart surgery in 20 patients (group 1: computer regulation) and in ten patients (group 2: manual regulation). The results (16,343 and 2,912 data points in groups 1 and 2, respectively), were then analyzed in four time frames and five pressure ranges to indicate clinical efficacy. Sixty percent of the measured MAP in both groups was within the desired +/- 10% during the first 10 min. Thereafter until the end of observation, the MAP was maintained within +/- 10% of the desired set-point 90% of the time in group 1 vs. 60% of the time in group 2. One percent and 11% of data points were +/- 20% from the set-point in groups 1 and 2, respectively (p less than .05, chi-square test). The computer-assisted therapy provided better control of MAP, was safe to use, and helped to reduce nursing demands.


Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.
The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy.


Animal facility design.
An animal facility is designed to provide the appropriate environmental conditions for the well-being of laboratory animals used in biomedical research. The design also must provide for the comfort, health, and safety of animal care technicians, research personnel, and veterinary staff who work in the facility. This chapter describes the functional areas of an animal facility and the engineering controls designed into animal facilities for restricting hazards and minimizing occupational risks of illness and injury to personnel.


Eye movements during scene recollection have a functional role, but they are not reinstatements of those produced during encoding.
Current debate in mental imagery research revolves around the perceptual and cognitive role of eye movements to "nothing" (Ferreira, Apel, & Henderson, 2008; Richardson, Altmann, Spivey, & Hoover, 2009). While it is established that eye movements are comparable when inspecting a scene (or hearing a scene description) as when visualizing it from memory (Johansson, Holsanova, & Holmqvist, 2006), the exact purpose of these eye movements remains elusive. Are eye movements during recall purely epiphenomenal or do they have a functional purpose? Here we address this question in four experiments where eye movements were prohibited either during the encoding or recall phases. Experiments 1 and 2 showed that maintaining central fixation during visual or auditory encoding, respectively, had no effect on how eye movements were executed during recall (but it did hinder memory retrieval). Thus, oculomotor events during recall are not reinstatements of those produced during encoding. When fixation was restricted during recall, Experiments 3 and 4 revealed that scene recollection was altered and impaired, irrespective of the modality of encoding. The functional role of eye movements during mental visualization is therefore apparent in this perturbation of visuospatial capabilities.


Synchronization and long-time memory in neural networks with inhibitory hubs and synaptic plasticity.
We investigate the dynamical role of inhibitory and highly connected nodes (hub) in synchronization and input processing of leaky-integrate-and-fire neural networks with short term synaptic plasticity. We take advantage of a heterogeneous mean-field approximation to encode the role of network structure and we tune the fraction of inhibitory neurons f_{I} and their connectivity level to investigate the cooperation between hub features and inhibition. We show that, depending on f_{I}, highly connected inhibitory nodes strongly drive the synchronization properties of the overall network through dynamical transitions from synchronous to asynchronous regimes. Furthermore, a metastable regime with long memory of external inputs emerges for a specific fraction of hub inhibitory neurons, underlining the role of inhibition and connectivity also for input processing in neural networks.


New Leucettidae de Laubenfels, 1936 (Porifera, Calcarea) from Western Australia.
This paper reports four new Leucettidae (Porifera, Calcarea) from Western Australia, with two representatives of Leucetta and two of Pericharax: L. foliata sp. nov., L. purpurea sp. nov., Pericharax crypta sp. nov., and P. vallii sp. nov. This is the first time tripods have been described within Pericharax. In addition, one species (L. foliata sp. nov.) has an external morphology not previously reported for Leucetta, and for the first time tetractines of the inhalant and exhalant canals have been distinguished. Leucettidae now comprises 28 species, eight of them occur in Western Australia, which means this Australian State has the highest species richness for this family in Australia. The WA coastline has been largely unexplored for Calcarea so it is likely that further collecting will yield additional species. Leucetta microraphis is the most widespread species of Leucettidae in Australia, occurring in all States except the Northern Territory and Tasmania. We highlight the importance of a revision of the Leucettidae using molecular and morphological characters to determine which morphological characters have a phylogenetic signal.


Features of the normal choriocapillaris with OCT-angiography: Density estimation and textural properties.
The main objective of our work is to perform an in depth analysis of the structural features of normal choriocapillaris imaged with OCT Angiography. Specifically, we provide an optimal radius for a circular Region of Interest (ROI) to obtain a stable estimate of the subfoveal choriocapillaris density and characterize its textural properties using Markov Random Fields. On each binarized image of the choriocapillaris OCT Angiography we performed simulated measurements of the subfoveal choriocapillaris densities with circular Regions of Interest (ROIs) of different radii and with small random displacements from the center of the Foveal Avascular Zone (FAZ). We then calculated the variability of the density measure with different ROI radii. We then characterized the textural features of choriocapillaris binary images by estimating the parameters of an Ising model. For each image we calculated the Optimal Radius (OR) as the minimum ROI radius required to obtain a standard deviation in the simulation below 0.01. The density measured with the individual OR was 0.52 ± 0.07 (mean ± STD). Similar density values (0.51 ± 0.07) were obtained using a fixed ROI radius of 450 μm. The Ising model yielded two parameter estimates (β = 0.34 ± 0.03; γ = 0.003 ± 0.012; mean ± STD), characterizing pixel clustering and white pixel density respectively. Using the estimated parameters to synthetize new random textures via simulation we obtained a good reproduction of the original choriocapillaris structural features and density. In conclusion, we developed an extensive characterization of the normal subfoveal choriocapillaris that might be used for flow analysis and applied to the investigation pathological alterations.


Phosphorylation of the adenosine triphosphatase in a deoxycholate-treated plasma membrane fraction from corn roots.
The ATP phosphohydrolase (ATPase) activity of a corn (Zea mays L., WF9 x Mo17) root plasma membrane fraction was enriched almost 2-fold by selective extraction with 0.1% (w/v) deoxycholate. The detergent treatment solubilized about 30% of the total membrane protein and some ATP hydrolyzing activity that was not K(+)-stimulated, but the major portion of the ATPase activity could be pelleted with membranes. The properties of the ATPase associated with the detergent-extracted plasma membrane fraction were similar to those for the ATPase of the untreated plasma membrane fraction with respect to substrate specificity, pH optimum, kinetics with MgATP, ion stimulation, and inhibitor sensitivity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed only minor differences in protein composition resulting from the detergent treatment.The plasma membrane fraction from corn roots contained an endogenous protein kinase activity. This was shown by the time course of phosphate incorporation and by the labeling of a number of protein bands on SDS-polyacrylamide gel electrophoresis. The deoxycholate treatment removed measurable protein kinase activity and allowed the demonstration of a rapidly turning over covalent phosphorylated intermediate associated with the detergent-extracted plasma membrane fraction. The phosphorylated intermediate was present as a 100,000 dalton polypeptide and may represent the catalytic subunit of the plasma membrane K(+)-ATPase.


Radiomics Analysis of Multi-Phase DCE-MRI in Predicting Tumor Response to Neoadjuvant Therapy in Breast Cancer.
To explore whether the pretreatment dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and radiomics signatures were associated with pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer. A retrospective review of 70 patients with breast invasive carcinomas proved by biopsy between June 2017 and October 2020 (26 patients were pathological complete response, and 44 patients were non-pathological complete response). Within the pre-contrast and five post-contrast dynamic series, a total of 1037 quantitative imaging features were extracted from in each phase. Additionally, the Δfeatures (the difference between the features before and after the comparison) were used for subsequent analysis. The least absolute shrinkage and selection operator (LASSO) regression method was used to select features related to pCR, and then use these features to train multiple machine learning classifiers to predict the probability of pCR for a given patient. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the predictive performances of the radiomics model for each of the five phases of time points. Among the five phases, each individual phase performed with AUCs ranging from 0.845 to 0.919 in predicting pCR. The best single phases performance was given by the 3rd phase (AUC = 0.919, sensitivity 0.885, specificity 0.864). 5 of the features have significant differences between pCR and non-pCR groups in each phase, most features reach their maximum or minimum in the 2nd or 3rd phase. The radiomic features extracted from each phase of pre-treatment DCE-MRI possess discriminatory power to predict tumor response.


Acute hemodynamic effects of angiotensin- converting enzyme inhibition after prolonged cardiac arrest with Bretschneider's solution.
Evidence as to how ACE inhibitors attenuate ischemia-reperfusion injury (IR) after cardioplegic arrest remains scarce. Twenty-four rabbit hearts were perfused on a Langendorff apparatus. Control hearts (n = 6) were arrested with pure histidine-tryptophan-ketoglutarate (HTK)-Bretschneider. Treatment groups received added to the cardioplegic solution (n = 6) captopril (100 μmol/l) and losartan (100 μmol/l) for selective AT1-receptor antagonism or BQ123 (100 nmol/l) for selective ETA-receptor antagonism. Pre-ischemic equilibration of 45 min was followed by 90 min of cardioplegic arrest and 30 min of reperfusion. Indices of myocardial contractility (LVP, dp/dt max, dp/dt min), coronary flow, heart rate, and O2 consumption were recorded before and after ischemic arrest. Tissue adenosine triphosphate (ATP) and malondialdehyde (MDA) contents were measured to evaluate energy content and oxidative stress, respectively. After selective cardiac arrest with Bretschneider, captopril-treated hearts showed improved hemodynamics compared to control and the other treatment groups. Oxygen consumption was significantly decreased during early reperfusion in captopril-treated hearts (34 ± 3 μmol/min/g/mmHg) compared to controls and losartan- and BQ123-treated hearts (controls: 77 ± 9 μmol/min/g/mmHg, p = 0.003; losartan: 54 ± 9 μmol/min/g/mmHg, p = 0.015; BQ123: 64 ± 13 μmol/min/g/mmHg, p = 0.046). The ATP content of the reperfused tissue was significantly elevated after captopril treatment compared to control group (24 ± 2 vs. 16 ± 2 μmol/g, p = 0.033), whereas the level of MDA was substantially decreased (0.58 ± 0.163 vs. 1.5 ± 0.28 μmol/g, p = 0.009). ACE inhibition leads to a significantly greater and faster recovery of myocardial contractility after prolonged cardiac arrest with Bretschneider solution. Due to decreased oxygen consumption, myocardial protection is enhanced. The association between ACE and ischemia cannot be clarified by selective blockade of angiotensin-II receptor type 1 (AT1-R) or ETa receptor (ETa-R).


Secondary nephrogenic diabetes insipidus as a complication of inherited renal diseases.
Nephrogenic diabetes insipidus (NDI) is a serious condition with large water losses in the urine and the risk of hypernatremic dehydration. Unrecognized, repeated episodes of hypernatremic dehydration can lead to permanent brain damage. Primary NDI is due to mutations in either AVPR2 or AQP2. NDI can also occur as a secondary complication, most commonly from obstructive uropathy or chronic lithium therapy. We observed NDI in patients with inherited tubulopathies and aimed to define the clinical and molecular phenotype. We reviewed the medical notes of 4 patients with clinical NDI and an underlying molecularly confirmed diagnosis of nephropathic cystinosis, Bartter syndrome, nephronophthisis and apparent mineralocorticoid excess, respectively. The patients all failed to concentrate their urine after administration of 1-desamino[8-D-arginine] vasopressin. None had an identifiable mutation in AVPR2 or AQP2, consistent with secondary NDI. Patients experienced repeated episodes of hypernatremic dehydration, and in 2 cases, NDI was initially thought to be the primary diagnosis, delaying recognition of the underlying problem. The recognition of this potential complication is important as it has direct implications for clinical management. The occurrence of NDI in association with these conditions provides clues for the etiology of aquaporin deficiency.


CiliateGEM: an open-project and a tool for predictions of ciliate metabolic variations and experimental condition design.
The study of cell metabolism is becoming central in several fields such as biotechnology, evolution/adaptation and human disease investigations. Here we present CiliateGEM, the first metabolic network reconstruction draft of the freshwater ciliate Tetrahymena thermophila. We also provide the tools and resources to simulate different growth conditions and to predict metabolic variations. CiliateGEM can be extended to other ciliates in order to set up a meta-model, i.e. a metabolic network reconstruction valid for all ciliates. Ciliates are complex unicellular eukaryotes of presumably monophyletic origin, with a phylogenetic position that is equal from plants and animals. These cells represent a new concept of unicellular system with a high degree of species, population biodiversity and cell complexity. Ciliates perform in a single cell all the functions of a pluricellular organism, including locomotion, feeding, digestion, and sexual processes. After generating the model, we performed an in-silico simulation with the presence and absence of glucose. The lack of this nutrient caused a 32.1% reduction rate in biomass synthesis. Despite the glucose starvation, the growth did not stop due to the use of alternative carbon sources such as amino acids. The future models obtained from CiliateGEM may represent a new approach to describe the metabolism of ciliates. This tool will be a useful resource for the ciliate research community in order to extend these species as model organisms in different research fields. An improved understanding of ciliate metabolism could be relevant to elucidate the basis of biological phenomena like genotype-phenotype relationships, population genetics, and cilia-related disease mechanisms.


Antiviral activity of hexapeptides derived from conserved regions of bacterial proteases against HCV NS3 protease.
The main cause of hepatitis C is hepatitis C virus or HCV and for the cure of hepatitis C, NS3/4A protease has been found an important and emerging target. A number of HCV NS3/4A protease inhibitors have been discovered which have shown subsequent reduction in reducing the viral load leading to this infection however they are still undergoing clinical trials for improvement. Bacterial proteases are of great pharmaceutical importance and have a key role in various biological processes and in life cycle of several pathogens. The current study was planned to explore hexapeptides derived from conserved regions of bacterial proteases for their potential in blocking the NS3 protease activity of HCV which would finally inhibit HCV multiplication. For this, a novel protease gene nprB was isolated from a thermophilic bacterium Streptomyces thermovulgaris and bioinformatics analyses were performed. PCR amplification and sequencing of nprB gene indicated an open reading frame of 178 aa (20191.18 Dalton).The peptide GGVHIN was the top ranked with minimum S-score of -17.21) followed by hexapeptides VDAHAN, GVGREA, GALNES and VHINSS with their S-scores of -14.73, -13.78, -10.72 and -10.70, respectively. A phylogram was also reconstructed to reveal evolutionary relationships of nprB with its various homologs. The provided data will serve as a background to further reveal pharmaceutical and biotechnological importance of this novel protease gene from S. thermovulgaris in future.


[Clipping for large paraclinoid internal carotid artery aneurysms by non-fluoroscopic occlusion via a micro-bone window frontolateral approach].
Objective: To evaluate the clinical value and outcomes of technical improvement of hybrid operatical clipping for large paraclinoid internal carotid artery aneurysms. Methods: A review was conducted on 18 cases of large paraclinoid internal carotid artery aneurysm which were clipped by balloon non-fluoroscopic occlusion of the parent artery via a micro-bone window frontolateral approach in hybrid operating room at Neurosurgery Department of Tianjin Medical University General Hospital from June 2014 to December 2017. There were 8 males and 10 females with age of (63±4) years. There were 6 cases of unruptured aneurysm and 12 cases of ruptured aneurysm of subarachnoid hemorrhage (6 cases of grade Ⅱ, 4 cases of grade Ⅲ and 2 cases of grade Ⅳ in Hunt-Hess classification). Frontolateral approach incision (average length of about 5 cm) and bone window about 3 cm×3 cm were performed. No incision of the neck was needed to expose the internal carotid artery for temporary occlusion. In the operation, the balloon was slowly pushed to the preset position of the internal carotid artery under non-fluoroscopy. The balloon was expanded to block the blood flow of internal carotid artery. Then aneurysm was clipped. The balloon was loosened and retraced to the guiding catheter after clipping. The clipping condition was examined by cerebral angiography. If there was residual aneurysm neck or stenosis of the parent artery, the balloon was pushed under non-fluoroscopy again to temporary occlusion and the clip was adjusted until the aneurysm neck was clamped satisfactorily. Results: Eighteen aneurysms were successfully clipped in hybrid operating room. Fourteen aneurysms showed complete occlusion of the aneurysm neck and no stenosis of the parent artery. Four cases showed residual aneurysm neck after clipping by intraoperative angiography, then aneurysms were clipped satisfy by adjusting the aneurysm clip. The patients were followed up for 3 months to 1 year. Ten patients recovered well (modifed Rankin score (mRS): 0), and 3 patients had no obvious disability (mRS: 1). Two patients with Hunt-Hess grade Ⅲ were slightly disabled (mRS: 2). 1 patients with Hunt-Hess grade Ⅲ were moderately disabled (mRS: 3). 1 patients with Hunt-Hess grade Ⅳ were severely disabled (mRS: 4). One elderly patients with Hunt-Hess grade Ⅳ were seriously disabled (mRS: 5). Conclusions: Application of balloon non-fluoroscopic occlusion clipping for large paraclinoid internal carotid artery aneurysm via a micro-bone window frontolateral approach is safe, effective and minimally invasive.


Screening of potential diagnostic markers and therapeutic targets against colorectal cancer.
To identify genes with aberrant promoter methylation for developing novel diagnostic markers and therapeutic targets against primary colorectal cancer (CRC). Two paired CRC and adjacent normal tissues were collected from two CRC patients. A Resi: MBD2b protein-sepharose-4B column was used to enrich the methylated DNA fragments. Difference in the average methylation level of each DNA methylation region between the tumor and control samples was determined by log2 fold change (FC) in each patient to screen the differentially methylated DNA regions. Genes with log2FC value ≥4 or ≤-4 were identified to be hypermethylated and hypomethylated, respectively. Then, the underlying functions of methylated genes were speculated by Gene Ontology database and pathway enrichment analyses. Furthermore, a protein-protein interaction network was built using Search Tool for the Retrieval of Interacting Genes/Proteins database, and the transcription factor binding sites were screened via the Encyclopedia of DNA Elements (ENCODE) database. Totally, 2,284 and 1,142 genes were predicted to have aberrant promoter hypermethylation or hypomethylation, respectively. MAP3K5, MAP3K8, MAPK14, and MAPK9 with promoter hypermethylation functioned via MAPK signaling pathway, focal adhesion, or Wnt signaling pathway, whereas MAP2K1, MAPK3, MAPK11, and MAPK7 with promoter hypomethylation functioned via TGF-beta signaling pathway, neurotrophin signaling pathway, and chemokine signaling pathway. CREBBP, PIK3R1, MAPK14, APP, ESR1, MAPK3, and HRAS were the seven hubs in the constructed protein-protein interaction network. RPL22, RPL36, RPLP2, RPS7, and RPS9 were commonly regulated by transcription factors, and YY1 and IRF4 were hypermethylated. MAPK14, MAPK3, HRAS, YY1, and IRF4 may be considered as potential biomarkers for early diagnosis and therapy of CRC.


Difficulties associated with the development and licensing of vaccines for protection against bio-warfare and bio-terrorism.
Today there is an increasing need to license vaccines for the protection of individuals against bio-warfare and bio-terrorism. While the need is apparent, the actual road to developing, producing and licensing such vaccines successfully is as yet undefined. Bio-defence vaccine candidates may come from several sources. They may come from vaccines that were previously licensed but are no longer in production, vaccines that are currently in an IND status, vaccines currently licensed in foreign countries, and newer vaccines currently under development. The issues that apply to the development and licensing of these vaccines can be defined by currently accepted standards for manufacture, and the requirement to demonstrate safety and efficacy to a level that gives the scientific and medical community, regulatory agencies, users and the public at large confidence. Requirements for manufacturing and demonstration of safety will be consistent with vaccines being developed for traditional purposes. However, demonstration of efficacy will be more difficult. Because field trials for these vaccines are generally not feasible and the conduct of human challenge studies is generally considered unethical, the demonstration of efficacy will need to be based on existing efficacy data, a thorough understanding of both the disease's pathogenesis and mechanism of protection, the ability to identify surrogate markers for efficacy, and the use of the proposed FDA "animal rule".


Traumatized women's infants are bigger than children of mothers without traumas.
Life history theory predicts that experiencing stress during the early period of life will result in accelerated growth and earlier maturation. Indeed, animal and some human studies documented a faster pace of growth in the offspring of stressed mothers. Recent advances in epigenetics suggest that the effects of early developmental stress might be passed across the generations. However, evidence for such intergenerational transmission is scarce, at least in humans. Here we report the results of the study investigating the association between childhood trauma in mothers and physical growth in their children during the first months of life. Anthropometric and psychological data were collected from 99 mothers and their exclusively breastfed children at the age of 5 months. The mothers completed the Early Life Stress Questionnaire to assess childhood trauma. The questionnaire includes questions about the most traumatic events that they had experienced before the age of 12 years. Infant growth was evaluated based on the anthropometric measurements of weight, length, and head circumference. Also, to control for the size of maternal investment, the composition of breast milk samples taken at the time of infant anthropometric measurements was investigated. The children of mothers with higher early life stress tended to have higher weight and bigger head circumference. The association between infant anthropometrics and early maternal stress was not affected by breast milk composition, suggesting that the effect of maternal stress on infant growth was independent of the size of maternal investment. Our results demonstrate that early maternal trauma may affect the pace of growth in the offspring and, in consequence, lead to a faster life history strategy. This effect might be explained via changes in offspring epigenetics.


[Subcutaneous cervical emphysema secondary to tooth extraction].
Cervical emphysema is rare and its diagnosis involves the ENT specialist. A case of cervical subcutaneous emphysema secondary to lower molar extraction is reported. The patient had no signs or symptoms other than cervical emphysema. Simple radiography and CT are recommended for early diagnosis. The etiopathogenic mechanisms of subcutaneous cervical emphysema are reviewed. Recent literature contains few cases of dental origin.


Leaf Age and Ethylene-induced Abscission.
Ethylene has been generally credited with promoting the abscission of the oldest leaves on a plant first. Vegetative cotton (Gossypium hirsutum L.) seedlings are an exception to this generalization. Under some conditions the younger, apical, unexpanded, or partially expanded leaves abscise before the less young, basal leaves or cotyledons. The degree or extent of apical leaf abscission increases with ethylene concentration and with plant age from 2 to 5 weeks. The response is promoted by auxin transport inhibitors. Usually the leaves which abscise first are those which have just unfolded and ones apical to the opened but unexpanded leaves. With plants with eight or nine leaves and macroscopic leaf buds, after the initial loss of unexpanded leaves, abscission tends to progress downward from the youngest remaining leaves and upward from the oldest leaves. The findings indicate that some characteristic(s) of apical leaves increases their sensitivity to ethylene. The characteristic may be differences in the abscission process between expanded and unexpanded leaves or differences in the hormone complement of the different leaves. Work is under way to modify this young leaf abscission response in an effort to determine its cause.


[Mechanical ileus caused by a Provox voice prosthesis -- an "iatrogenic" enteral complication in voice prosthesis rehabilitation of laryngectomees].
During the exchange of a defect Provox-I voice prosthesis followed by an insertion of a Provox-II voice prosthesis the esophageal part of the prosthesis often is pushed into the esophagus, as the enteral passage of the prosthesis was thought to be less traumatic for the voice shunt in comparison to a complete extraction of the stiff esophageal flange through the tracheostoma. This procedure is also recommended in the users video of the ATOS company. A laryngectomized patient, in whom the change of the voice prosthesis was carried out pushing the esophageal flange of the prosthesis into the esophagus, developed a mechanical ileus, as the voice prosthesis got stuck in Bauhin's valve. This resulted in the necessity of a laparatomy for removal of the voice prosthesis. During the replacement of the Provox voice prosthesis it is necessary in all cases that the esophageal remnant of the voice prosthesis either is pulled out of the tracheoesophageal shunt via the tracheostoma or removed with a guide-wire transorally.


FCS-activated blast T cells inhibit the in vitro response of memory CTL precursors to alloantigens by removal of factor(s) from MLC supernatant.
The inhibitory effect of spleen cells, precultured in the presence of FCS, was assayed on the memory cytolytic T lymphocytes (CTL) response to alloantigens. For this, we have used in vitro conditions in which both particulate alloantigen and MLC SN are required to allow the generation of CTL. It was shown that the CTL response was totally inhibited in the presence of 5 to 7 days precultured spleen cells. This inhibitory effect was partly due to removal, by those precultured cells, of relevant factor(s) contained in the MLC SN. After velocity sedimentation at unit gravity, it was shown that the T cells able to inhibit the cytolytic response and to remove MLC SN factor(s) are found in the fractions containing the large proliferating cells. It was further demonstrated that in the presence of inhibiting cells, a significant CTL response may be obtained after addition of concentrated MLC SN. However, in this way, this inhibitory effect was not totally circumvented, which suggests that the memory CTL response is also impaired by other mechanisms.