The ICF as a common language for rehabilitation goal-setting: comparing client and professional priorities.
Joint rehabilitation goals are an important component for effective teamwork in the rehabilitation field. The activities and participation domain of the ICF provides a common language for professionals when setting these goals. Involving clients in the formulation of rehabilitation goals is gaining momentum as part of a person-centred approach to rehabilitation. However, this is particularly difficult when clients have an acquired communication disability. The expressive communication difficulties negatively affect the consensus building process. As a result, obtaining information regarding rehabilitation goals from professionals and their clients warrants further investigation for this particular population. This comparative study investigated clients and their assigned rehabilitation professionals' perception of the importance of ICF activities and participation domains for inclusion in their rehabilitation program. Twelve clients in an acute rehabilitation centre and twenty of their corresponding rehabilitation professionals participated in an activity using the Talking Mats™ visual framework for goal setting. Each participant rated the importance of the nine activities and participation domains of the ICF for inclusion in their current rehabilitation program. The ICF domains which consistently appear as very important across these groups are mobility, self-care and communication. Domains which consistently appear in the lower third of the rankings include spare time, learning and thinking and domestic life. Results indicate however that no statistical significant differences exist in terms of the individual domains across each of the participant groups. Within group differences however indicated that amongst the speech-language therapists and physiotherapists there was a statistical significant difference between spare time activities and communication and mobility. Findings indicate that consensus is possible amongst professionals and clients even within an acute-rehabilitation setting. In addition, the Talking Mats™ visual framework appears to be a valid protocol for including clients with acquired communication disabilities in the process of obtaining consensus during goal-setting.


Interstitial lung disease in rheumatoid arthritis in the era of biologics.
Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.


Deviations From Age-Adjusted Normative Biometry Measures in Children Undergoing Cataract Surgery: Implications for Postoperative Target Refraction and IOL Power Selection.
To evaluate whether pediatric eyes that deviate from age-adjusted normative biometry parameters predict variation in myopic shift after cataract surgery. This is a single institution longitudinal cohort study combining prospectively collected biometry data from normal eyes of children <10 years old with biometry data from eyes undergoing cataract surgery. Refractive data from patients with a minimum of 5 visits over ≥5 years of follow-up were used to calculate myopic shift and rate of refractive growth. Cataractous eyes that deviated from the middle quartiles of the age-adjusted normative values for axial length and keratometry were studied for variation in myopic shift and rate of refractive growth to 5 years and last follow-up visit. Multivariable analysis was performed to determine the association between myopic shift and rate of refractive growth and factors of age, sex, laterality, keratometry, axial length, intraocular lens power, and follow-up length. Normative values were derived from 100 eyes; there were 162 eyes in the cataract group with a median follow-up of 9.6 years (interquartile range: 7.3-12.2 years). The mean myopic shift ranged from 5.5 D (interquartile range: 6.3-3.5 D) for 0- to 2-year-olds to 1.0 D (interquartile range: 1.5-0.6 D) for 8- to 10-year-olds. Multivariable analysis showed that more myopic shift was associated with younger age (P < .001), lower keratometry (P = .01), and male gender (P = .027); greater rate of refractive growth was only associated with lower keratometry measures (P = .001). Age-based tables for intraocular lens power selection are useful, and modest adjustments can be considered for eyes with lower keratometry values than expected for age.


Herpesviruses: latency and reactivation - viral strategies and host response.
Eight members of the Herpesviridae family commonly infect humans, and close to 100% of the adult population is infected with at least one of these. The five that cause the most health concerns are: herpes simplex virus (HSV) type 1 and 2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV). In addition, there are human herpes virus (HHV) types 6-8. The review starts by introducing possible viral strategies in general. The particular biology and host relationship of the various human herpesviruses, including their pathology, are examined subsequently. Factors that contribute to the maintenance of latency and reactivation of viral replication are discussed. There will be special reference to how these viruses exploit and contribute to pathology in the oral cavity. Reactivation does not necessarily imply clinical symptoms, as reflected in the asymptomatic shedding of EBV and CMV from oral mucosa. The immune response and the level of viral output are both important to the consequences experienced.


Methylenetetrahydrofolate reductase gene polymorphisms and neural tube defects epidemiology in the Slovak population.
Folate deficiency is a known factor contributing to the formation of neural tube defects (NTDs). Many folate metabolism gene variants have been investigated, but only a few substantial associations have been established, the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene being one of the most significant. We determine the MTHFR C677T and A1298C genotypes in 93 Slovak NTD patients and 290 control newborns with respect to sex and ethnicity. Furthermore, we summarize current data on the incidence and types of NTDs in Slovakia. The Slovak population frequencies of T allele and TT genotype of the C677T MTHFR gene polymorphism were 0.25 and 6.9%, respectively; similarly, those of the C allele and CC genotype of the A1298C polymorphism were 0.35 and 13.8%, respectively. No differences between the sexes and within ethnic groups were observed. In NTD patients, genotype analysis of the C677T polymorphism revealed 0.29 and 9.8% for T allele and TT genotype frequencies, respectively (p = 0.26; OR, 1.23; 95% CI, 0.84-1.81; resp. p = 0.36; OR, 1.46; 95% CI, 0.56-3.52) compared to the controls. The frequencies of C allele and CC genotype of A1298C polymorphism were 0.34 and 6.5%, respectively (p = 0.81; OR, 0.96; 95% CI, 0.66-1.38; resp. p = 0.06; OR, 0.44; 95% CI, 0.15-1.09). There were also no sex-related differences in genotypes distribution in NTD patients. No significant associations between the C677T and A1298C MTHFR gene polymorphisms and NTDs and no differences between the two main ethnic groups (white-Caucasians, Roma) were found in Slovakia. The total incidence of NTDs in Slovakia is, according to the official sources, 0.53/1000, and the incidence among liveborn newborns is 0.28/1000.


Triamcinolone Acetonide Suppresses Keloid Formation Through Enhancing Apoptosis in a Nude Mouse Model.
Current understanding of steroid treatments for keloids is in regards to modulation of inflammation, proliferation, and apoptosis, with no in vivo study on the latter. Using a nude mouse model, we investigated whether triamcinolone acetonide (TA) injections induce keloids regression through enhancing apoptosis. Thirty-six keloid specimens (1 × 1 cm) were harvested from 6 patients and separated into sets of 2 from the same patient: no treatment and intralesional TA injection (0.4 mg/mL/kg) at 8 weeks of postimplantation. One set was implanted in each of 18 randomly selected nude mice, which were separated into 3 groups based on time of keloid harvesting after treatment: group A, 2 weeks; group B, 8 weeks; and group C, 14 weeks. Each group had 1 set of specimen from each patient. Histological staining was performed with hematoxylin and eosin stain. Immunohistochemistry staining was performed for human-prolyl 4-hydroxylase (hPH4) and caspase 3 protein, along with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. All keloid specimens survived, with no noted overgrowth. Hematoxylin and eosin staining revealed dense extracellular matrix and viable fibroblasts, and hPH4 immunohistochemistry revealed strong expression, demonstrating keloid viability. Caspase 3 protein and TUNEL expressions were significantly increased in the treatment versus control groups, demonstrating that TA injections induced apoptosis. Triamcinolone acetonide intralesional injections significantly increased apoptosis in keloids, represented by increased caspase 3 protein and TUNEL expressions, supporting that steroids suppress keloids in part owing to enhancement of apoptosis.


LY83583: an agent that lowers intracellular levels of cyclic guanosine 3',5'-monophosphate.
A novel compound, LY83583 (6-anilino-5,8-quinolinedione), was found to lower basal levels of cyclic GMP (cGMP) in fragments of guinea-pig lung incubated in vitro. The lowering of cGMP was dose-related reaching a maximum of 72% at 5 X 10(-5) M. Basal levels of cyclic AMP (cAMP) were not lowered by LY83583. cGMP concentrations were also reduced in guinea-pig heart and cerebellum after incubation with LY83583. However, the drug did not alter the levels of this cyclic nucleotide in spleen. Exposure of lung fragments from sensitized guinea pigs to ovalbumin resulted in a marked increase in cGMP and cAMP. LY83583 prevented completely the accumulation of cGMP and attenuated the rise in cAMP. Similar results were obtained in rat cerebellum stimulated with kainic acid. The compound also blocked ovalbumin-induced release of slow reacting substance of anaphylaxis (leukotrienes) from guinea-pig lung. Subcutaneous administration of LY83583 to guinea pigs did not affect cGMP concentrations in vivo in lung, but the total amount of cGMP in spleen was reduced dramatically. This was accompanied by a marked splenomegaly. LY83585 did not inhibit lung guanylate cyclase. In fact, activity was increased in a cell-free preparation from guinea-pig lung. The mechanism by which LY83583 reduced concentrations of cGMP is presently unknown. Nevertheless, our studies suggest that LY83583 will be a valuable pharmacological tool to help elucidate the role of cGMP in biological events.


Substance use in childhood and adolescence and its associations with quality of life and behavioral strengths and difficulties.
Substance use in childhood and adolescence continues to be a current health concern. The aims of the present study were to identify trends in the use of alcohol, cigarettes, and cannabis in children and adolescents in the last 10 years and to assess associations between substance use and quality of life and behavioral strengths and difficulties. Substance use was examined in 1829 9- to 18-year-old German children and adolescents participating in the LIFE Child cohort study between 2011 and 2020. Quality of life was investigated using the KIDSCREEN-27 questionnaire. The Strength and Difficulties Questionnaire was used to assess behavioral strengths and difficulties. Associations were assessed using linear regression analyses. All effects were adjusted for age, gender, and family socio-economic status. 38.44% of participants reported drinking alcohol at least sometimes. Smoking (6.23%) and the use of cannabis (3.94%) were less frequent. While we observed no significant changes in smoking between 2011 and 2021, the consumption of cannabis and the frequent consumption of alcohol has increased in this time period. Cigarette and cannabis use were associated with additional symptoms of hyperactivity/inattention and reduced prosocial behavior. For all three substances, usage was associated with more conduct problems. We also found significant associations between substance use and a lower quality of life in the areas of physical wellbeing, psychological wellbeing, parent relation and autonomy, and school environment. One noteworthy finding was that cigarette consumption and frequent alcohol use were associated with higher quality of life in terms of social support/peer group relations. Some significant interactions between substance use and child age indicated that associations between substance use and quality of life or behavioral difficulties were stronger in younger than in older children. The results show that quality of life and behavioral difficulties are associated with substance use and should be considered when developing or implementing preventive measures to counter substance use. Furthermore, the findings indicate that substance use can be accompanied by improved peer relations. Therefore, the influence of peers, especially of peers who use these substances, should not be underestimated.


High-Throughput and Controllable Fabrication of Helical Microfibers by Hydrodynamically Focusing Flow.
Due to the unique spiral geometry, different functional helical fibers are fabricated to perform vital tasks, including cargo transportation, medical treatment, cell manipulation, and so on. Although microfluidic techniques are widely used to fabricate helical fibers, the problems of channel blockage and spinning instability have not been well solved, which limits the mass preparation and practical application of spiral microfibers. In addition, the spinning mechanism is simply limited to liquid rope coiling, which has little impact on the design of microfluidic devices. Here, new types of microfluidic devices, which were easy to make and exhibited excellent spiral spinning performance, were designed. It was found that adding a sleeve layer outside the inner core needle in a coaxial microfluidic device could effectively promote the stable formation of helical microfibers. This novel microchannel could fabricate helical microfibers of more than 100 m in length continuously at one time with almost no blockage or deformation, and the key parameters of the fibers could be precisely adjusted. Combined with micro-particle image velocimetry (micro-PIV) measurements, it was confirmed that the improvement in the spinning performances was mainly attributed to the emergence of a focusing flow in the presence of the sleeve layer. After loading magnetic nanoparticles, the helical microfibers exhibited excellent motion manipulation capabilities, which showed great potential for drug delivery, cargo transportation, clogging removal, etc. This new design not only realized the high-throughput fabrication of helical microfibers but also provided deeper insights into the underlying mechanisms of spiral generation and new ideas for the design of microfluidic devices.


GLS2 is protumorigenic in breast cancers.
Many types of cancers have a well-established dependence on glutamine metabolism to support survival and growth, a process linked to glutaminase 1 (GLS) isoforms. Conversely, GLS2 variants often have tumor-suppressing activity. Triple-negative (TN) breast cancer (testing negative for estrogen, progesterone, and Her2 receptors) has elevated GLS protein levels and reportedly depends on exogenous glutamine and GLS activity for survival. Despite having high GLS levels, we verified that several breast cancer cells (including TN cells) express endogenous GLS2, defying its role as a bona fide tumor suppressor. Moreover, ectopic GLS2 expression rescued cell proliferation, TCA anaplerosis, redox balance, and mitochondrial function after GLS inhibition by the small molecule currently in clinical trials CB-839 or GLS knockdown of GLS-dependent cell lines. In several cell lines, GLS2 knockdown decreased cell proliferation and glutamine-linked metabolic phenotypes. Strikingly, long-term treatment of TN cells with another GLS-exclusive inhibitor bis-2'-(5-phenylacetamide-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) selected for a drug-resistant population with increased endogenous GLS2 and restored proliferative capacity. GLS2 was linked to enhanced in vitro cell migration and invasion, mesenchymal markers (through the ERK-ZEB1-vimentin axis under certain conditions) and in vivo lung metastasis. Of concern, GLS2 amplification or overexpression is linked to an overall, disease-free and distant metastasis-free worse survival prognosis in breast cancer. Altogether, these data establish an unforeseen role of GLS2 in sustaining tumor proliferation and underlying metastasis in breast cancer and provide an initial framework for exploring GLS2 as a novel therapeutic target.


Increased risk of death among children with Lennox-Gastaut syndrome and infantile spasms.
The magnitude and causes of death among a cohort of children with epilepsy were determined. A follow-up study with a population-based cohort of 10-year-old children in the metropolitan Atlanta area with epilepsy was conducted. The National Death Index and linkage to State of Georgia death certificates were used to identify deaths. The authors estimated the expected numbers of deaths by applying mortality rates adjusted by age, race, and sex for the entire state of Georgia to the population for the follow-up period. Among the 688 children who were in the final epilepsy cohort, 64 deaths occurred; 20.6 deaths were expected (mortality ratio adjusted for age, race, and sex = 3.11). The mortality ratios for children with Lennox-Gastaut syndrome and infantile spasms were 13.92 and 11.91, respectively. Children and adolescents with epilepsy, especially those with Lennox-Gastaut syndrome or infantile spasms, have an increased risk of death.


Candida albicans expresses a focal adhesion kinase-like protein that undergoes increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and the EA.hy 926 human endothelial cell line.
The signaling pathways triggered by adherence of Candida albicans to the host cells or extracellular matrix are poorly understood. We provide here evidence in C. albicans yeasts of a p105 focal adhesion kinase (Fak)-like protein (that we termed CaFak), antigenically related to the vertebrate p125Fak, and its involvement in integrin-like-mediated fungus adhesion to vitronectin (VN) and EA.hy 926 human endothelial cell line. Biochemical analysis with different anti-chicken Fak antibodies identified CaFak as a 105-kDa protein and immunofluorescence and cytofluorimetric analysis on permeabilized cells specifically stain C. albicans yeasts; moreover, confocal microscopy evidences CaFak as a cytosolic protein that colocalizes on the membrane with the integrin-like VN receptors upon yeast adhesion to VN. The protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A strongly inhibited C. albicans yeast adhesion to VN and EA.hy 926 endothelial cells. Moreover, engagement of alpha v beta 3 and alpha v beta 5 integrin-like on C. albicans either by specific monoclonal antibodies or upon adhesion to VN or EA.hy 926 endothelial cells stimulates CaFak tyrosine phosphorylation that is blocked by PTK inhibitor. A role for CaFak in C. albicans yeast adhesion was also supported by the failure of VN to stimulate its tyrosine phosphorylation in a C. albicans mutant showing normal levels of CaFak and VNR-like integrins but displaying reduced adhesiveness to VN and EA.hy 926 endothelial cells. Our results suggest that C. albicans Fak-like protein is involved in the control of yeast cell adhesion to VN and endothelial cells.


Trabecular architecture of the mandibular condyle of the rat as revealed by vital staining.
The variability of the internal architecture of bone was studied in the mandibular condyle of young rats with the aid of vital staining capable of revealing bone trabeculae. The effect of season and age was observed in Spring- and Fall-born rats 28 and 56 days of age. There was no clear left-right asymmetry in the average direction of the condylar trabeculae, but their ranges of direction within the condyles exhibited such asymmetry. Both the average directions and the internal variability were different in the medial and the lateral sides of the condyles. There were also small but in most respects significant seasonal differences. These findings indicate that even the relatively small mandibular condyle of the rat is a very complex structure.


Flubromazolam: Detection in five post-mortem cases.
Flubromazolam is a potent triazole benzodiazepine with moderately long-lasting central nervous system-depressant effects relative to other benzodiazepines such as commonly prescribed diazepam. Flubromazolam has been studied in the living. However, there are no published reports including measured drug concentrations in post-mortem cases. We report five cases in which flubromazolam was detected in a systematic screen using high-resolution mass spectrometry and then quantified in femoral blood. In none of the five cases was the cause of death directly attributed to flubromazolam toxicity, as there was a variety of both sedative and stimulant drugs also present. However, it is important that the drug concentrations that were measured are made available for future post-mortem forensic interpretation.


Bilateral abortive cryptophthalmos associated with oculocutaneous albinism.
To document a case of bilateral abortive cryptophthalmos associated with oculocutaneous albinism. We describe a 13-year-old female patient with blond skin and hair who had anomalous face and eyes first noted at birth. The patient had fair hair and complexion, bilateral anomalous wedge of scalp hair, upper eyebrow and eyelid deformities, cup-shaped ears, broad based nose with depressed bridge and midline groove, iris transillumination and diffuse hypopigmentation and foveal hypoplasia in fundus examination. Based on the clinical and laboratory findings, the reported case represents tyrosinase-positive oculocutaneous albinism together with bilateral abortive cryptophthalmos. The oculocutaneous albinism can either be an entirely new criterion to the whole syndrome of cryptophthalmos, or, more probably, the condition can be due to a double affliction which is primarily related with consanguinity of the parents. The importance of ante-natal diagnosis and genetic counseling are emphasized in such cases where the two recessive genes for two different conditions coexist.


Design of a nonpolarizing beam splitter inside a glass cube.
The reflectance and transmittance of dielectric thin films at oblique angles of incidence have strong polarization effects. For some applications these effects are undesirable. A nonpolarizing beam splitter design concept is shown, which is based on the fact that in a quarter-wave stack at lambda(o) two effective indices that obey the Brewster condition affect only the spectral performance of the s state at lambda(o). This property is used as a design tool. The concept can be applied to a wide range of angles and transmittance values, with the use of effective quarter-wave layers of at least three different materials. A few examples are elaborated where these values are designed and optimized to give either T(p) = T(s) or T(p) + T(s) = constant, in the vicinity of lambda(o).


Infant mortality and economic status in metropolitan Ohio, total and cause-specific: 1979-81 and 1989-91.
"This paper presents the results of an ecological analysis of the relationship between infant mortality and economic status in a metropolitan aggregate comprised of six of the larger cities in Ohio covering the years 1979-81 and 1989-91.... Results of the analysis revealed, first of all, that there continues to be a clear and pronounced inverse association between the aggregate economic status of an area and the probability that a newborn infant will not survive the first year of life. There are, however, some noteworthy race-cause differences....Only one cause, Sudden Infant Death Syndrome, stood out as having a generally consistent and very strong inverse relationship with economic status."


[PICK1 is associated with central nervous system diseases].
PICK1 (protein interacting with C kinase 1) contains a PDZ (PSD-95/Dlg/ZO1) domain and a BAR (Bin/amphiphysin/Rvs) domain. Via the PDZ domain, PICK1 interacts directly with more than 40 proteins. Among these interacting proteins, some are important for physiological and pathophysiological processes of central nervous system. In this review, recent findings about how PICK1 is associated with central nervous system diseases are summarize.


Chemical communication in Chagas disease vectors. Source, identity, and potential function of volatiles released by the metasternal and Brindley's glands of Triatoma infestans adults.
Compounds from the metasternal and Brindley's glands of the blood-sucking bug, Triatoma infestans, were identified by solid phase microextraction (SPME) and gas chromatography-mass spectrometry. Volatile compounds released by adult bugs during copulation or after mechanical disturbance were also characterized. Six compounds were identified and found consistently in all samples from metasternal glands. The most abundant were 3-pentanone, 2-methylbutanol, 3-pentanol, and an unidentified compound. The metasternal gland blends did not differ qualitatively between sexes. Compounds found in Brindley's glands were short chain acids, alcohols, esters, and a ketone with no qualitative differences between sexes. Isobutyric acid was the main component of this blend, and two new confirmed compounds were described as products of these glands: 2-butanone and 2-methylbutyric acid. 3-Pentanone was collected from the headspace over 33% of the copulating pairs of T. infestans. Volatiles found in the headspace of disturbed T. infestans adults included short-chain fatty acids, alcohols, esters, and ketones, with no qualitative differences between sexes. Both types of glands apparently discharge their contents after disturbance. However, most of the volatiles released by bugs after disturbance came from Brindley's glands. The locomotor activity of fourth instars increased significantly after stimulation with the odors emitted by disturbed adults, as compared with larvae stimulated by the odor of undisturbed adults or by clean air. We also studied the directional behavioral response of fifth instars to the disturbance scent in a locomotion compensator. Larvae exposed to volatiles released by disturbed adults walked away from the direction of the odor. The results suggest that this blend or part of it functions as an alarm pheromone for T. infestans. We suggest that the metasternal glands of this species are involved both in the sexual and the alarm contexts, and that the Brindley's glands probably have both alarm and defensive roles.


BLUE-GREEN ALGAE FROM BERMUDA WATERS: ECOLOGICALLY SELECTED VARIATIONS OF A SINGLE SPECIES.
Three strains were isolated from Bermuda waters as unialgal cultures. Although identical in cell shape, cell size, and general growth features, marked differences in pigmentation, filament length, and sheath thickness were noted. These differences are explained as being due to differences in physical conditions of the areas of isolation of the 3 strains. It is concluded that the 3 strains are ecologically selected mutants of the single species, Schizothrix calcicola.


Mechanisms by which reactions catalyzed by chloroplast coupling factor 1 are inhibited: ATP synthesis and ATP-H2O oxygen exchange.
The ATP-H2O back-exchange reaction catalyzed by membrane-bound chloroplast coupling factor 1 (CF1) in the light is known to be extensive; each reacting ATP molecule nearly equilibrates its gamma-PO3 oxygens with H2O before it dissociates from the enzyme. Pi, ASi, ADP, and GDP, alternate substrates of photophosphorylation, each inhibit the exchange reaction. At all concentrations of these substrate/inhibitor molecules tested, the high extent of exchange per molecule of ATP that reacts remains the same, while the number of ATP molecules experiencing exchange decreases. Thus, these inhibitors appear to act in a competitive-type manner, decreasing ATP turnover, as opposed to modulating the rate constants responsible for the partitioning of E X ATP during the exchange reaction. This is consistent with the identity of CF1 catalytic sites for ATP-H2O back-exchange and ATP synthesis. Carbonyl cyanide m-chlorophenylhydrazone and NH4Cl (uncouplers of photophosphorylation) and phloridzin (an energy-transfer inhibitor) also lower the rate of ATP-H2O back-exchange; they too are found to act by decreasing the turnover of the ATP pool, not the extent of exchange per reacting ATP molecule. The extent of ATP-H2O forward oxygen exchange, which occurs during net ATP synthesis prior to product dissociation, is unaffected by uncouplers, whether catalyzed by native CF1 (ATPase latent) or the dithiothreitol/light-activated ATPase form. The mode of NH4Cl inhibition of the ATP synthesis reaction, therefore, is not through a change in the partitioning of the E X ATP complex.(ABSTRACT TRUNCATED AT 250 WORDS)


Curative resection for stage I rectal cancer: natural history, prognostic factors, and recurrence patterns.
Our goal was to evaluate the recurrence patterns and outcomes of a large group of patients with stage I rectal adenocarcinoma treated at a single institution with uniform surgical and pathological techniques. Medical records of 71 patients who had undergone potentially curative surgery were reviewed to determine clinical and histologically significant prognostic factors that could affect survival and recurrence patterns. The median follow-up for all patients was 81 months. Twenty patients had T1N0M0 cancers and 51 patients had T2N0M0 cancers. The median number of lymph nodes examined per surgical specimen was 32. There were no recurrences in the 20 patients with T1 lesions. All 7 recurrences (10%) occurred in patients with T2 lesions. Only 2 of these recurrences were local. In the T2 group, the 5- and 10-year disease-free survivals were 88% and 83%, respectively. The 5- and 10-year disease-free survival for all state I lesions was 91% and 88%, respectively. The overall recurrence rate of 10% does not justify adjuvant therapy for stage I rectal adenocarcinoma. Although the subset of patients with T2N0M0 distal one-third rectal cancers may be at risk for recurrence, additional prognostic factors are needed to evaluate these patients before adjuvant therapy can be recommended.


Using semifield studies to examine the effects of pesticides on mobile terrestrial invertebrates.
Many farmers rely on regular pesticide applications to avoid losses from arthropod pests and the diseases they vector. However, widespread and injudicious use of pesticides is detrimental to the environment, poses a health risk, and undermines biocontrol services. Researchers are increasingly required to develop techniques to quantify the trade-offs and risks associated with pesticides. Laboratory studies, though useful for assessing short-term impacts (e.g., mortality), cannot detect longer-term or indirect effects that can potentially be assessed using semifield studies. Here we review the range and scope of studies that have used semifield methods for regulatory testing and risk assessment of pesticides and for understanding the community-level effects of pesticide use in agricultural landscapes. We include studies on target and nontarget species, with an emphasis on quantifying effects when the target species is highly mobile. We suggest improvements in the design and analysis of semifield studies to more effectively assess effects on highly mobile species.


Effect of inducible costimulator blockade on the pathological and protective immune responses induced by the gastrointestinal helminth Trichinella spiralis.
Infections with gastrointestinal helminths elicit potent Th2 responses, which ultimately result in their expulsion. However, during expulsion of Trichinella spiralis this Th2 response also induces a severe enteropathy characterized by villus atrophy and crypt hyperplasia. Inducible costimulator (ICOS), a homologue of CD28, interacts with B7-related protein 1, and has been shown to be important in T-B cell interactions and antibody class switching. Significantly, ICOS appears to be involved in the induction of both Th1 and Th2 responses, but may be of heightened importance in Th2 responses. Here we employed a blocking antibody against ICOS to investigate the contribution of ICOS costimulation to the development of the protective and pathological immune responses induced during infection with T. spiralis. We show that, although blocking ICOS resulted in a decrease in TNF-alpha and the Th2 cytokines IL-4 and IL-5 and serum levels of total IgE, it did not affect the expulsion of the adult parasites. Surprisingly, levels of IL-9, IL-13 and IL-10 were elevated and protection against the larval muscle stage of the parasite was enhanced. Importantly, these findings may relate to the fact that ICOS blockade significantly ameliorated the enteropathy that usually accompanies expulsion of the adult parasite.


Mutational analysis of the RB1 gene in Moroccan patients with retinoblastoma.
Retinoblastoma (RB), the most common intraocular tumor occurring in infancy and early childhood, is most often related to mutations in the RB1 gene. In this study, we screened the RB1 germline mutations in 41 unrelated Moroccan patients with retinoblastoma, 25 heritable cases, and 16 sporadic unilateral cases. After complete ophthalmic examinations were performed and consent obtained, DNA was extracted from peripheral blood, and screening of RB1 mutations was performed with PCR direct sequencing of the promoter and the 27 coding exons of the RB1 gene. We identified ten germline mutations in 10/41 (24.39%) unrelated patients, among which three had not been previously reported. The mutation detection rate was 40% (10/25) in the heritable cases and 0% (0/16) in the sporadic unilateral cases. Of these mutations, six were nonsense, and three were frameshifts, all associated with severe phenotypes resulting in bilateral and multifocal tumors. One splice site mutation was found in a familial case associated with a low expressivity phenotype resulting in unilateral and unifocal tumors. Moreover, eight intronic variants were identified, three of which were novel. This first report of RB1 gene screening in Moroccan patients with retinoblastoma shows a comparable mutational spectrum to those reported previously, which has evident importance for managing patients with retinoblastoma and their families.


The role of interleukin-4 in the regulation of mouse primordial germ cell numbers.
Interleukin-4 (IL-4), a pleiotropic cytokine, stimulates a dose-dependent increase in the number of mouse primordial germ cells in culture. Results from bromodeoxyuridine incorporation assays suggest that IL-4 acts as a survival factor rather than as a mitogen for primordial germ cells in this system. Studies on the embryonic expression patterns of IL-4 and its receptors, using RT-PCR and ELISA, show that IL-4 and its receptors are present at the correct time and place to influence PGC numbers in vivo.


Respiration-independent Binding of SR to Bean Mitochondria.
Binding of Sr(2+) to bean mitochondria (Phaseolus vulgaris) shows a dissociation constant of 25 x 10(-6) and results in 40 to 50 nmoles of Sr(2+) bound per mg protein. The binding is partially inhibited by valinomycin plus K(+), 2, 4-dinitrophenol, as well as ruthenium red at a level of the 120 nmoles per mg protein. These compounds also partially inhibit active uptake of Sr(2+). Calcium and Mg(2+) also partially inhibit binding in the same magnitude as previously reported for inhibition of transport. Phosphate which is required for divalent cation transport is without effect on the binding of Sr(2+). The possible role of the observed binding sites in divalent cation transport is discussed.


Cat retinal ganglion cell receptive-field alterations after 6-hydroxydopamine induced dopaminergic amacrine cell lesions.
Optic tract single-unit recordings were used to study ganglion cell response functions of the intact cat eye after 6-hydroxydopamine (6-OHDA) lesioning of the dopaminergic amacrine cell (AC) population of the inner retina. The impairment of the dopaminergic AC was verified by high pressure-liquid chromatography (HPLC) with electrochemical detection of endogenous dopamine content and by [3H]dopamine high-affinity uptake; the dopaminergic ACs of the treated eyes demonstrated reduced endogenous dopamine content and reduced [3H]dopamine uptake compared with that of their matched controls. Normal appearing [3H]GABA and [3H]-glycine uptake in the treated retinas suggests the absence of any nonspecific action of the 6-OHDA on the neural retina. The impairment of the dopaminergic AC population was found to alter a number of response properties in off-center ganglion cells, but this impairment had only a modest effect on the on-center cells. An abnormally high proportion of the off-center ganglion cells in the 6-OHDA treated eyes possessed nonlinear, Y-type receptive fields. These cells also possessed shift-responses of greater than normal amplitude, altered intensity-response functions, reduced maintained activities, and more transient center responses. Of the on-center type cells, only the Y-type on-center cells were affected by 6-OHDA, possessing higher than normal maintained activities and altered intensity-response functions. The on-center X-cells were unaffected by 6-OHDA treatment. The dopaminergic AC of the photopically adapted cat retina therefore modulates a number of ganglion cell response properties and within the limits of this study is most prominent in off-center ganglion cell circuitry. When functioning normally, the dopaminergic AC of the cat's retina appears to make the receptive field of the off-center cell more sustained and may make its spatial summation characteristics more linear while adjusting the intensitive properties of neurons in both the on- and off-center pathways.


Clinical applications of serum tumor markers.
The pursuit of the ideal tumor marker has generated many tests for use in the diagnosis and management of cancer, several of which are now widely available. Tumor markers have five potential uses in patient care: They can be used for screening, for diagnosis, for establishing prognosis, for monitoring treatment, and for detecting relapse. The value of a marker in a given setting depends on two marker-related characteristics--sensitivity and specificity. The value of a marker in a particular malignancy also depends on the effectiveness of therapy for the malignancy. Tumor markers have been used to screen for occult cancer but have proved to be valuable only in selected cancers. As diagnostic tools, tumor markers have limitations: Nearly all markers can be elevated in benign disorders, and most markers are not elevated in the early stages of malignancy. Extreme marker elevation often indicates a poor prognosis and in some malignancies can indicate the need for more aggressive treatment. Tumor markers have their greatest value when used to monitor therapy in patients with widespread cancer. Nearly all markers show some correlation with the clinical course of disease, with marker elevation in any stage declining to normal after a curative intervention. Recurrent disease can be accompanied by increased marker levels, but markers can detect an occult recurrence in only a few diseases, thereby facilitating a second attempt at cure. Although it seems unlikely that an ideal tumor marker will be identified for every malignancy, several workable markers are already available. Increasing our knowledge about the capabilities and limitations of existing markers will enable us to use them judiciously in the treatment of cancer.


Introducing Upfront Money Can Decrease Discounting in Intertemporal Choices with Losses.
People generally tend to advance gains and postpone losses in intertemporal choice. Jiang et al. (2014) recently showed that adding upfront losses or gains to both smaller and sooner (SS) and larger and later (LL) rewards can decrease people's discounting. To account for this decrease, they proposed the salience hypothesis, which states that introducing upfront losses or gains makes the money dimension more salient than not, thus increasing people's preference for LL rewards. Considering that decreasing the discounting of delayed losses is imperative and that most previous studies have focused on intertemporal choices with gains, in the current paper we conducted two experiments and used hypothetical money outcomes to examine whether the effect of upfront money could be extended to intertemporal choices with losses. The results showed that when both SS and LL intertemporal losses were combined with an upfront loss or gain, people's discounting rate decreased and the preference for the SS option increased. This finding further supports the salience account.


High uptake of pre-exposure prophylaxis (PrEP) during early roll-out in Belgium: results from surveillance reports.
Background Since 1 June 2017, oral pre-exposure prophylaxis (PrEP) could be prescribed and reimbursed in Belgium as prophylactic medication for people who are at increased risk of HIV acquisition. The aim of this study was to determine the uptake of daily and event-driven PrEP in Belgium during the first 9 months of roll-out. Routine aggregated data on the number of reimbursement requests and the number of boxes of Truvada (Gilead Sciences, Cambridge, UK) delivered for PrEP through the Belgian pharmacies were obtained from the National Institute for Health and Disability Insurance. We also collected aggregated data from seven Aids Reference Centres (ARCs) currently providing most of the PrEP care in Belgium. From 1 June 2017 to 28 February 2018, 1352 requests for reimbursement were approved by the National Institute for Health and Disability Insurance. Almost 98% of those who bought at least one box of 30 tablets of emtricitabine 200mg/tenofovir disoproxil fumarate 300mg (FTC/TDF) in a Belgian pharmacy were male, and most (67%) were between 30 and 50 years of age. According to data obtained from ARCs, the proportion of those choosing event-driven PrEP initially ranged between 29% and 73%. The uptake of PrEP in Belgium since the start of the roll-out in June 2017 has been high, and almost entirely limited to men who have sex with men, of whom 43% initially prefer a non-daily regimen. A better understanding is needed as to why other populations, such as sub-Saharan African migrants, are not accessing PrEP, as well as the development of a more sustainable PrEP delivery model.


Quantitative Videofluoroscopic Analysis of Swallowing Physiology and Function in Individuals With Chronic Obstructive Pulmonary Disease.
Purpose Dysphagia is a serious extra pulmonary manifestation of chronic obstructive pulmonary disease (COPD). However, the nature of abnormalities in swallowing physiology in COPD has yet to be clearly established. We explored the frequency of swallowing measures outside the healthy reference range in adults with COPD. Method Participants were 28 adults aged 41-79 years (18 men, 20 women) with stable COPD. Disease severity was classified as GOLD (Global Initiative For Chronic Obstructive Lung Disease) Stages 1 (4%), 2 (25%), 3 (53%), and 4 (18%). Participants underwent a videofluoroscopy and swallowed 20% w/v thin barium in, followed by 20% w/v mildly, moderately, and extremely thick barium prepared with a xanthan gum thickener. Blinded duplicate ratings of swallowing safety, efficiency, kinematics, and timing were performed according to the ASPEKT method (Analysis of Swallowing Physiology: Events, Kinematics and Timing). Comparison data for healthy adults aged < 60 years were extracted from an existing data set. Chi-square and Fisher's exact tests compared the frequencies of measures falling < 1 SD/ > 1 SD from mean reference values (or < the first or > the third quartile for skewed parameters). Results Participants with COPD did not display greater frequencies of penetration-aspiration, but they were significantly more likely (p < .05) to display incomplete laryngeal vestibule closure (LVC), longer time-to-LVC, and shorter LVC duration. They also displayed significantly higher frequencies of short upper esophageal sphincter opening, reduced pharyngeal constriction, and pharyngeal residue. Conclusion This analysis reveals differences in swallowing physiology in patients with stable COPD characterized by impaired safety related to the mechanism, timing, and duration of LVC and by impaired swallowing efficiency with increased pharyngeal residue related to poor pharyngeal constriction.


Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: reverse docking, enzymatic assay, and X-ray crystallography validation.
Colonization of human stomach by the bacterium Helicobacter pylori is a major causative factor for gastrointestinal illnesses and gastric cancer. However, the discovery of anti-H. pylori agents is a difficult task due to lack of mature protein targets. Therefore, identifying new molecular targets for developing new drugs against H. pylori is obviously necessary. In this study, the in-house potential drug target database (PDTD, http://www.dddc.ac.cn/tarfisdock/) was searched by the reverse docking approach using an active natural product (compound 1) discovered by anti-H. pylori screening as a probe. Homology search revealed that, among the 15 candidates discovered by reverse docking, only diaminopimelate decarboxylase (DC) and peptide deformylase (PDF) have homologous proteins in the genome of H. pylori. Enzymatic assay demonstrated compound 1 and its derivative compound 2 are the potent inhibitors against H. pylori PDF (HpPDF) with IC50 values of 10.8 and 1.25 microM, respectively. X-ray crystal structures of HpPDF and the complexes of HpPDF with 1 and 2 were determined for the first time, indicating that these two inhibitors bind well with HpPDF binding pocket. All these results indicate that HpPDF is a potential target for screening new anti-H. pylori agents. In addition, compounds 1 and 2 were predicted to bind to HpPDF with relatively high selectivity, suggesting they can be used as leads for developing new anti-H. pylori agents. The results demonstrated that our strategy, reverse docking in conjunction with bioassay and structural biology, is effective and can be used as a complementary approach of functional genomics and chemical biology in target identification.


Micro-regional hypersensitivity variations to inhalant allergens in the city of Zagreb and Zagreb County.
Depending on the geographic and climatic region and vegetation, allergenic plants are characteristic for certain areas and the pollen concentrations of various plant species depend on the fenophase of each single species and most of all on the climatic and meteorological conditions of a certain area. It is precisely because of these specific characteristics that the hypersensitivity of patients to various types of pollen allergens differs according to the geographic regions. The aim of this paper is to determine the frequency of inhalation allergies in adult population (> 19 years of age) caused by single types of allergens according to the defined space units (micro-regions) with special emphasis on the rural and urban areas. A number of 2,192 patients have been tested for allergy skin prick tests over a period of four years. Every patient was asked to fill in the questionnaire which contained 29 questions. The results of skin prick testing show that out of a total of 2,192 patients 86.72% were sensitized to pollen, 36.45% to mites, 2.46% to spores of fungi and mould and 5.1% of patients to other allergens which include the allergens of cockroaches, feathers and animal hair (p < 0.001). The largest number of poly-sensitized persons allergic to pollen allergens was sensitized to allergens from the pollen of plants that belong to the botanical family of grass. There were 25.36% patients mono-sensitized to individual allergens. In the northern and western parts of the city and the county, the majority of persons were sensitized to the birch pollen allergens, and this is statistically much more than the share of patients with the place of residence in the southern and eastern parts of the city and the county. In the southern and eastern locations prevails the share of sensitized persons to ambrosia which is statistically much more than the share of patients with the place of residence in the northern and western part of the city and the county.


Discriminative Analysis of Schizophrenia Patients Using Topological Properties of Structural and Functional Brain Networks: A Multimodal Magnetic Resonance Imaging Study.
Interest in the application of machine learning (ML) techniques to multimodal magnetic resonance imaging (MRI) data for the diagnosis of schizophrenia (SZ) at the individual level is growing. However, a few studies have applied the features of structural and functional brain networks derived from multimodal MRI data to the discriminative analysis of SZ patients at different clinical stages. In this study, 205 normal controls (NCs), 61 first-episode drug-naive SZ (FESZ) patients, and 79 chronic SZ (CSZ) patients were recruited. We acquired their structural MRI, diffusion tensor imaging, and resting-state functional MRI data and constructed brain networks for each participant, including the gray matter network (GMN), white matter network (WMN), and functional brain network (FBN). We then calculated 3 nodal properties for each brain network, including degree centrality, nodal efficiency, and betweenness centrality. Two classifications (SZ vs. NC and FESZ vs. CSZ) were performed using five ML algorithms. We found that the SVM classifier with the input features of the combination of nodal properties of both the GMN and FBN achieved the best performance to discriminate SZ patients from NCs [accuracy, 81.2%; area under the receiver operating characteristic curve (AUC), 85.2%; p < 0.05]. Moreover, the SVM classifier with the input features of the combination of the nodal properties of both the GMN and WMN achieved the best performance to discriminate FESZ from CSZ patients (accuracy, 86.2%; AUC, 92.3%; p < 0.05). Furthermore, the brain areas in the subcortical/cerebellum network and the frontoparietal network showed significant importance in both classifications. Together, our findings provide new insights to understand the neuropathology of SZ and further highlight the potential advantages of multimodal network properties for identifying SZ patients at different clinical stages.


Supportive strut grafts for diaphyseal bone defects in revision hip arthroplasty.
Large femoral cortical strut allografts were used to provide structural support of the femur in 20 patients in whom uncemented, extensively porous-coated, press-fit revision femoral stems were applied. The mean followup was 4.7 years. Radiographic analysis of the patients who had revision surgery revealed that in all 20 patients, the cortical femoral strut allografts showed incorporation. Small areas of graft resorption were observed in only two patients. Seventeen of the uncemented femoral revision stems radiographically showed bone ingrowth. Three of the revision femoral stems were interpreted as being fixed only by fibrous ingrowth after early subsidence after surgery. There were no reoperations. Before surgery, all patients were unable to walk and had severe pain. At followup, all patients were ambulatory and had considerable improvement in pain relief and in their ability to walk. The mean Harris hip score after surgery was 75 (range, 57.5-92). Complications consisted of one peroneal nerve palsy, which resolved; one deep venous thrombosis; one gastrointestinal ulcer; and one case of pneumonia. Supportive cortical strut allografts represent an alternative to the use of circumferential bulk allografts and total femoral replacements in patients with large combined proximal and diaphyseal bone defects.


[Should all menopausal women have hormone replacement therapy for the prevention of coronary disease?].
A review of the biochemical changes which occur after menopause. Menopause is the onset of a chronic hypoestrogenism. The lack of estrogens which follows either a premature oophorectomy or menopause is a cause of risk factors and diseases at several levels, amongst which, due to its importance, is the cardiovascular system. Estrogens can favorably modify those risk factors and thus contribute to a sharp decrease in cardiovascular morbidity and mortality. For this reason, its use is legitimate for the primary and secondary prevention of coronary disease.


Cross-cultural translation and adaptation of Functional Assessment of Cancer Therapy - Multiple Myeloma tool - MM1 and LEU3 - for Portuguese.
To describe of the translation from English to Portuguese and adaption process of subitems of the Functional Assessment of Cancer Therapy - Multiple Myeloma. In the first phase, translations from English into Portuguese of two subitems of Functional Assessment of Cancer Therapy - Multiple Myeloma were performed. Subsequently, a consensus and back translation were conducted, and, finally, translation and back translations were reviewed by four independent bilingual experts. In the second phase, the translated subitems were applied, along with a questionnaire, to 10 native Portuguese speakers patients with multiple myeloma. There was a recognition of the translation process in its first version applied to 10 patients with multiple myeloma, whose reported no difficult to understand the translated and validated instrument. Patients also did not find the content irrelevant or offensive, and they did not suggested changes. The subitems of the Functional Assessment of Cancer Therapy - Multiple Myeloma were translated from English into Portuguese following the proposed methodology and there was not need of readjustments. This process allowed this instrument of quality of life, which is widely known to be beneficial in the management of patients with multiple myeloma, to be used among our population.


Prevention of liver fibrosis by triple helix-forming oligodeoxyribonucleotides targeted to the promoter region of type I collagen gene.
Hepatic fibrosis leading to cirrhosis remains a global health problem. The most common etiologies are alcoholism and viral infections. Liver fibrosis is associated with major changes in both quantity and composition of extracellular matix and leads to disorganization of the liver architecture and irreversible damage to the liver function. As of now there is no effective therapy to control fibrosis. The end product of fibrosis is abnormal synthesis and accumulation of type I collagen in the extracellular matrix, which is produced by activated stellate or Ito cells in the damaged liver. Therefore, inhibition of transcription of type I collagen should in principle inhibit its production and accumulation in liver. Normally, DNA exists in a duplex form. However, under some circumstances, DNA can assume triple helical (triplex) structures. Intermolecular triplexes, formed by the addition of a sequence-specific third strand to the major groove of the duplex DNA, have the potential to serve as selective gene regulators. Earlier, we demonstrated efficient triplex formation between the exogenously added triplex-forming oligodeoxyribonucleotides (TFOs) and a specific sequence in the promoter region of the COL1A1 gene. In this study we used a rat model of liver fibrosis, induced by dimethylnitrosamine, to test whether these TFOs prevent liver fibrosis. Our results indicate that both the 25-mer and 18-mer TFOs, specific for the upstream nucleotide sequence from -141 to -165 (relative to the transcription start site) in the 5' end of collagen gene promoter, effectively prevented accumulation of liver collagen and fibrosis. We also observed improvement in liver function tests. However, mutations in the TFO that eliminated formation of triplexes are ineffective in preventing fibrosis. We believe that these TFOs can be used as potential antifibrotic therapeutic molecules.


Spatiotemporal distribution and source apportionment of low molecular weight organic acids in wet precipitation at a coastal city, China.
To investigate the characteristics and sources of low molecular weight (LMW) organic acids in wet precipitation at a coastal city, Xiamen, a total of 313 rainwater samples were collected at seven different functional areas from September 2012 to August 2013. Spatiotemporal characteristics of LMW organic acids as well as pH and electrical conductivity were analyzed. Meanwhile, air mass clusters in different seasons and the positive matrix factorization (PMF) source apportion model were comprehensively used to identify the sources of organic acids. In conclusion, the volume-weighted mean (VWM) concentration of formic (3.20 μmol/L), acetic (1.84 μmol/L), lactic (0.44 μmol/L), and oxalic acid (0.53 μmol/L) were obtained, which jointly contributed to 4.33% of the total free acidity (TFA). At the same time, the highest wet deposition flux of LMW organic acids and contribution of that to TFA were achieved at the forest protection area during growing season in Xiamen. In addition, biogenic emissions (77.12%), sea salts (13.77%), regional agriculture activities (3.92%), soil emissions (2.56%), biomass burning (1.47%), and secondary aerosols (1.15%) were determined as the source of LMW organic acids. Besides, the dominancy of biomass burning via long-range transport in non-growing season (NGS) and the contribution of biogenic emission in growing season (GS) were recognized. Finally, the considerable influence of sea salts on the LMW organic acids (13.77%) in Xiamen was quantified, especially for oxalic acid.


Research progress of stem cells on glaucomatous optic nerve injury.
Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma.


Identification of a Prognostic 3-Gene Risk Prediction Model for Thyroid Cancer.
Objective: We aimed to screen the genes associated with thyroid cancer (THCA) prognosis, and construct a poly-gene risk prediction model for prognosis prediction and improvement. Methods: The HTSeq-Counts data of THCA were accessed from TCGA database, including 505 cancer samples and 57 normal tissue samples. "edgeR" package was utilized to perform differential analysis, and weighted gene co-expression network analysis (WGCNA) was applied to screen the differential co-expression genes associated with THCA tissue types. Univariant Cox regression analysis was further used for the selection of survival-related genes. Then, LASSO regression model was constructed to analyze the genes, and an optimal prognostic model was developed as well as evaluated by Kaplan-Meier and ROC curves. Results: Three thousand two hundred seven differentially expressed genes (DEGs) were obtained by differential analysis and 23 co-expression genes (|COR| > 0.5, P < 0.05) were gained after WGCNA analysis. In addition, eight genes significantly related to THCA survival were screened by univariant Cox regression analysis, and an optimal prognostic 3-gene risk prediction model was constructed after genes were analyzed by the LASSO regression model. Based on this model, patients were grouped into the high-risk group and low-risk group. Kaplan-Meier curve showed that patients in the low-risk group had much better survival than those in the high-risk group. Moreover, great accuracy of the 3-gene model was revealed by ROC curve and the remarkable correlation between the model and patients' prognosis was verified using the multivariant Cox regression analysis. Conclusion: The prognostic 3-gene model composed by GHR, GPR125, and ATP2C2 three genes can be used as an independent prognostic factor and has better prediction for the survival of THCA patients.


Synthesis, characterization, and alkoxide transfer reactivity of dimeric Tl2(OR)2 complexes.
Reaction of LiOCtBu2Ph with TlPF6 forms the dimeric Tl2(OCtBu2Ph)2 complex, a rare example of a homoleptic thallium alkoxide complex demonstrating formally two-coordinate metal centers. Characterization of Tl2(OCtBu2Ph)2 by 1H and 13C NMR spectroscopy and X-ray crystallography reveals the presence of two isomers differing by the mutual conformation of the alkoxide ligands, and by the planarity of the central Tl-O-Tl-O plane. Tl2(OCtBu2Ph)2 serves as a convenient precursor to the formation of old and new [M(OCtBu2Ph)n] complexes (M = Cr, Fe, Cu, Zn), including a rare example of T-shaped Zn(OCtBu2Ph)2(THF) complex, which could not be previously synthesized using more conventional LiOR/HOR precursors. The reaction of [Ru(cymene)Cl2]2 with Tl2(OCtBu2Ph)2 results in the formation of a ruthenium(ii) alkoxide complex. For ruthenium, the initial coordination of the alkoxide triggers C-H activation at the ortho-H of [OCtBu2Ph] which results in its bidentate coordination. In addition to Tl2(OCtBu2Ph)2, related Tl2(OCtBu2(3,5-Me2C6H3))2 was also synthesized, characterized, and shown to exhibit similar reactivity with iron and ruthenium precursors. Synthetic, structural, and spectroscopic characterizations are presented.


Rising Geographic Disparities in US Mortality.
The 21st century has been a period of rising inequality in both income and health. In this paper, we find that geographic inequality in mortality for midlife Americans increased by about 70 percent between 1992 and 2016. This was not simply because states like New York or California benefited from having a high fraction of college-educated residents who enjoyed the largest health gains during the last several decades. Nor was higher dispersion in mortality caused entirely by the increasing importance of "deaths of despair," or by rising spatial income inequality during the same period. Instead, over time, state-level mortality has become increasingly correlated with state-level income; in 1992 income explained only 3 percent of mortality inequality, but by 2016 state-level income explained 58 percent. These mortality patterns are consistent with the view that high-income states in 1992 were better able to enact public health strategies and adopt behaviors that, over the next quarter-century, resulted in pronounced relative declines in mortality. The substantial longevity gains in high-income states led to greater cross-state inequality in mortality.


Effect of vaginally administered DHA fatty acids on pregnancy outcome in high risk pregnancies for preterm delivery: a double blinded randomised controlled trial.
to verify whether vaginally intake of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, would improve length of gestation and newborn birth weight in high risk pregnancies for preterm delivery. this study was a randomized, double-blind, controlled, clinical trial, including women at high risk for preterm delivery. Of 74 eligible women, 31 refused to participate and 34 were enrolled and randomized with equal chance of selection, 22 were assigned to treatment group and 21 were assigned to the control group, and received placebo. One gram of DHA was administered vaginally once a day starting from 21 (1 week of gestation until 37 weeks + 0 day). The primary endpoint was to determine the length of the pregnancy and secondary endpoint the newborn weight. gestational age at delivery was 38.6 (SD, 1.05) weeks in the docosahexaenoic acid group and 37.6 (SD, 0.84) weeks in the placebo group (P =0.007). For women who completed the treatment and delivered at term there was a statistically difference of the weights in the two groups [3082.1 (SD, 293) gr cases vs 2699.3 (SD, 150) gr controls P <0.0001]. in high risk patients for preterm delivery, the vaginal administration of a DHA increases length of gestation and newborn birth weight.


Determinants of histone H4 N-terminal domain function during nucleosomal array oligomerization: roles of amino acid sequence, domain length, and charge density.
Mg(2+)-dependent oligomerization of nucleosomal arrays is correlated with higher order folding transitions that stabilize chromosome structure beyond the 30-nm diameter fiber. In the present studies, we have employed a novel mutagenesis-based approach to identify the macromolecular determinants that control H4 N-terminal domain (NTD) function during oligomerization. Core histones were engineered in which 1) the H2A, H2B, and H3 NTDs were swapped onto the H4 histone fold; 2) the length of the H4 NTD and the H2A NTD on the H4 histone fold, were increased; 3) the charge density of the NTDs on the H4 histone fold was increased or decreased; and 4) the H4 NTD was placed on the H2B histone fold. Model nucleosomal arrays were assembled from wild type and mutant core histone octamers, and Mg(2+)-dependent oligomerization was characterized. The results demonstrated that the H2B and H3 NTDs could replace the H4 NTD, as could the H2A NTD if it was duplicated to the length of the native H4 NTD. Arrays oligomerized at lower salt concentrations as the length of the NTD on the H4 histone fold was increased. Mutations that decreased the NTD charge density required more Mg(2+) to oligomerize, whereas mutants that increased the charge density required less salt. Finally, the H4 NTD functioned differently when attached to the H2B histone fold than the H4 histone fold. These studies have revealed new insights into the biochemical basis for H4 NTD effects on genome architecture as well as the protein chemistry that underlies the function of the intrinsically disordered H4 NTD.


Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas.
In this review we will describe eight commonly used rat brain tumor models and their application for the development of novel therapeutic and diagnostic modalities. The C6, 9L and T9 gliomas were induced by repeated injections of methylnitrosourea (MNU) to adult rats. The C6 glioma has been used extensively for a variety of studies, but since it arose in an outbred Wistar rat, it is not syngeneic to any inbred strain, and its potential to evoke an alloimmune response is a serious limitation. The 9L gliosarcoma has been used widely and has provided important information relating to brain tumor biology and therapy. The T9 glioma, although not generally recognized, was and probably still is the same as the 9L. Both of these tumors arose in Fischer rats and can be immunogenic in syngeneic hosts, a fact that must be taken into consideration when used in therapy studies, especially if survival is the endpoint. The RG2 and F98 gliomas were both chemically induced by administering ethylnitrosourea (ENU) to pregnant rats, the progeny of which developed brain tumors that subsequently were propagated in vitro and cloned. They are either weakly or non-immunogenic and have an invasive pattern of growth and uniform lethality, which make them particularly attractive models to test new therapeutic modalities. The CNS-1 glioma was induced by administering MNU to a Lewis rat. It has an infiltrative pattern of growth and is weakly immunogenic, which should make it useful in experimental neuro-oncology. Finally, the BT4C glioma was induced by administering ENU to a BD IX rat, following which brain cells were propagated in vitro until a tumorigenic clone was isolated. This tumor has been used for a variety of studies to evaluate new therapeutic modalities. The Avian Sarcoma Virus (ASV) induced tumors, and a continuous cell line derived from one of them designated RT-2, have been useful for studies in which de novo tumor induction is an important requirement. These tumors also are immunogenic and this limits their usefulness for therapy studies. It is essential to recognize the limitations of each of the models that have been described, and depending upon the nature of the study to be conducted, it is important that the appropriate model be selected.


The transcription factor RBP-J is essential for retinal cell differentiation and lamination.
The highly ordered vertebrate retina is composed of seven cell types derived from a common pool of retinal progenitor cells (RPCs), and is a good model for the studies of cell differentiation and interaction during neural development. Notch signaling plays a pivotal role in retinogenesis in mammals, but the full scope of the functions of Notch pathway, and the underlying molecular mechanisms, remain unclear. In this study, we conditionally knocked out RBP-J, the critical transcription factor downstream to all four Notch receptors, in RPCs of mouse retina at different developmental stages. Disruption of RBP-J at early retinogenesis resulted in accelerated RPCs differentiation, but only photoreceptors and ganglion cells were overrepresented, with other neuronal populations diminished. Similarly, deletion of RBP-J at early postnatal days also led to overproduction of photoreceptors, suggesting that RBP-J governed RPCs specification and differentiation through retinogenesis. In all the RBP-J deletion models, the retinal laminar structures were distorted by the formation of numerous rosette-like structures, reminiscent of beta-catenin deficient retina. Indeed, we found that these rosettes aligned with gaps in beta-catenin expression at the apical surface of the retina. By in vivo electroporation-mediated transfection, we demonstrated that lamination defects in RBP-J deficient retinae were rescued by overexpressing beta-catenin. Our data indicate that RBP-J-mediated canonical Notch signaling governs retinal cell specification and differentiation, and maintains retinal lamination through the expression of beta-catenin.


DRGs and MDs: now's the time to review medical staff policies.
The definition of "problem" physicians and the specification of economic cause for their removal from medical staffs may cause boards some problems in the future. To prevent potential conflicts between the medical staff and administration, the authors discuss the need to evaluate current policies and procedures, and the make sure that these strategies are articulated in medical staff bylaws.


[Turning over rough surface of aponeurosis of gastrocnemius with fascia lata graft for Achilles tendon rerupture].
To explore clinical effects of turning over rough surface of aponeurosis of gastrocnemius with fascia graft for Achilles tendon rerupture. From July 2013 to April 2017, 11 patients with Achilles tendon reruptures were repaired by turning over rough surface of aponeurosis of gastrocnemius with fascia graft, including 10 males and 1 female aged from 25 to 48 years old. The patients were all manifested weakness of plantar flexion strength injured foot, and positive of single heel rise test before operation. Postoperative complications was observed, and AOFAS score at 6 months after operation was applied to evaluate clinical efficacy. All patients were followed up for 6 to 11 months. All wound were healed at stage I without skin necrosis, wound infection, deep vein thrombosis and rerupture. The length of tendon defect ranged from 4 to 7 cm, the full weight-bearing time ranged from 8 to 11 weeks. Postoperative AOFAS score at 6 months was for 79 to 100, and 9 patients got excellent results, and 2 good. For patients with recurrent ruptures of Achilles tendon, turning over rough surface of aponeurosis of gastrocnemius with fascia graft has advantages of stable repair, less complications and good recovery of function.


Carcinoid syndrome caused by a serotonin-secreting pituitary tumour.
Neuroendocrine tumours are most frequently located in the gastrointestinal organ system or in the lungs, but they may occasionally be found in other organs. We describe a 56-year-old woman suffering from a carcinoid syndrome caused by a large serotonin-secreting pituitary tumour. She had suffered for years from episodes of palpitations, dyspnoea and flushing. Cardiac disease had been suspected, which delayed the diagnosis, until blood tests revealed elevated serotonin and chromogranin A in plasma. The somatostatin receptor (SSR) scintigraphy showed a single-positive focus in the region of the pituitary gland and MRI showed a corresponding intra- and suprasellar heterogeneous mass. After pre-treatment with octreotide leading to symptomatic improvement, the patient underwent trans-cranial surgery with removal of the tumour. This led to a clinical improvement and to a normalisation of SSR scintigraphy, as well as serotonin and chromogranin A levels. To our knowledge, this is the first reported case of a serotonin-secreting tumour with a primary location in the pituitary.


Biomarker discovery in rat plasma for estrogen receptor-alpha action.
To support in vivo screening efforts for estrogen receptor (ER) subtype selective therapeutic agents, we initiated work to discover surrogate markers (biomarkers) in blood plasma that would change in response to ER subtype-specific action. We used a proteomic approach employing strong anion exchange chromatography (SAX), PAGE, and MS to identify potential plasma markers for selective ER-alpha action. The methodology was used to compare blood from vehicle-treated rats to blood from rats treated with either 17beta-estradiol (an ER-alpha/ER-beta agonist) or compound 1 (17alpha-ethynyl-[3,2-c]pyrazolo-19-nor-4-androstene-17beta-ol, an ER-alpha-selective agonist). Blood samples were first fractionated by SAX to separate fractions containing dominant common plasma proteins from fractions enriched for less-abundant plasma proteins. 1-D PAGE analysis of fractions depleted of dominant plasma proteins revealed treatment-specific changes in protein profiles. Protein bands that changed reproducibly in response to ER-alpha action were excised from the gel, separated by capillary LC, and identified by microspray ESI-MS. Using this method, the plasma levels of two proteins, transthyretin and apolipoprotein E, were shown to decrease in response to ER-alpha agonism. The method lacked the sensitivity to identify the known, 1000-fold less-abundant, estrogenic marker prolactin (PRL). However, using a commercial RIA and immunoblots, we showed that PRL levels increase significantly in response to treatment with the ER-alpha selective agonist, compound 1.


Light-Induced Renormalization of the Dirac Quasiparticles in the Nodal-Line Semimetal ZrSiSe.
In nodal-line semimetals, linearly dispersing states form Dirac loops in the reciprocal space with a high degree of electron-hole symmetry and a reduced density of states near the Fermi level. The result is reduced electronic screening and enhanced correlations between Dirac quasiparticles. Here we investigate the electronic structure of ZrSiSe, by combining time- and angle-resolved photoelectron spectroscopy with ab initio density functional theory (DFT) complemented by an extended Hubbard model (DFT+U+V) and by time-dependent DFT+U+V. We show that electronic correlations are reduced on an ultrashort timescale by optical excitation of high-energy electrons-hole pairs, which transiently screen the Coulomb interaction. Our findings demonstrate an all-optical method for engineering the band structure of a quantum material.


Developmental Dysplasia of Hip: Perspectives in Genetic Screening.
Development dysplasia of the hip (DDH) is a complex developmental disorder despite being a relatively common condition mainly caused by incompatibility of the femoral head and the abnormal joint socket. Development dysplasia of the hip describes a wide spectrum of disorders ranging from minor acetabular dysplasia to irreducible dislocation of the hip. Modern medicine still suffers from lack of information about screening and precise genetic examination. Genome wide linkage and association studies have brought significant progress to DDH diagnosis. Association studies managed to identify many candidate (susceptible) genes, such as PAPPA2, COL2A1, HOXD9, GDF-5, and TGFB1, which play a considerable role in the pathogenesis of DDH. Early detection of DDH has a big chance to help in preventing further disability and improve the psychological health and quality of life in those children. This emphasizes the importance to establish a universal screening program along with the genetic counseling.


The morbidity of subthreshold pediatric bipolar disorder: A systematic literature review and meta-analysis.
The objective of this study was to evaluate the morbidity of subthreshold pediatric bipolar (BP) disorder. We performed a systematic literature search in November 2017 and included studies examining the morbidity of pediatric subthreshold BP. Extracted outcomes included functional impairment, severity of mood symptoms, psychiatric comorbidities, suicidal ideation and behaviors, and mental health treatment. We used meta-analysis to compute the pooled standardized mean difference (SMD) for continuous measures and the pooled risk ratio (RR) for binary measures between two paired groups: subthreshold pediatric BP vs controls and subthreshold pediatric BP vs pediatric BP-I. Eleven papers, consisting of seven datasets, were included. We compared subthreshold pediatric BP (N = 244) to non-BP controls (N = 1125) and subthreshold pediatric BP (N = 643) to pediatric BP-I (N = 942). Subthreshold pediatric BP was associated with greater functional impairment (SMD = 0.61, CI 0.25-0.97), greater severity of mood symptomatology (mania: SMD = 1.88, CI 1.38-2.38; depression: SMD = 0.66, CI 0.52-0.80), higher rates of disruptive behavior (RR = 1.75, CI 1.17-2.62), mood (RR = 1.78, CI 1.29-2.79) and substance use (RR = 2.27, CI 1.23-4.21) disorders, and higher rates of suicidal ideation and attempts (RR = 7.66, CI 1.71-34.33) compared to controls. Pediatric BP-I was associated with greater functional impairment, greater severity of manic symptoms, higher rates of suicidal ideation and attempts, and higher rates of mental health treatment compared to subthreshold pediatric BP. There were no differences between full and subthreshold cases in the severity of depressive symptoms or rates of comorbid disorders. Subthreshold pediatric BP disorder is an identifiable morbid condition associated with significant functional impairment including psychiatric comorbidities and high rates of suicidality.


Genetic and life-style determinants of peptic ulcer. A study of 3387 men aged 54 to 74 years: The Copenhagen Male Study.
In the Copenhagen Male Study men with the Lewis blood group phenotype Le(a+b-), non-secretors of ABH antigen, and men with the O or the A phenotype in the ABO blood group have been found to have a significantly higher lifetime prevalence of peptic ulcer than others. We investigated the importance of the association of these genetic markers, life-style factors, and social class with lifetime risk of peptic ulcer, testing specifically the hypothesis that the strength of the association of risk factors with peptic ulcer depends on genetic susceptibility. Three thousand three hundred and forty-six white men 55-74 years old were included for study. From a questionnaire validated during an interview information was obtained about life-style factors and peptic ulcer history (gastric or duodenal). Potential non-genetic risk factors examined were smoking history, alcohol consumption, physical activity level, consumption of tea and coffee, and use of sugar in tea or coffee. Three hundred and eighty-four men (11.5%) had a history of peptic ulcer; 120 (3.6%) had had an operation due to peptic ulcer. Non-genetic peptic ulcer risk factors identified were ever having been a smoker, use of sugar in tea or coffee, abstention from tea consumption, and low social class. On the basis of these and the genetic factors, it was possible to identify a low-risk group (n = 142) with a lifetime prevalence of 4.2%, several intermediate-risk groups, and a high-risk group (n = 55) with a prevalence of 29%; the odds ratio with 95% confidence limits (OR) was 9.3 (3.4-25.3). Corresponding values with regard to operation were 1.4% and 20.0%; OR = 17.5 (3.7-82.0). Several significant interactions were found; for example, the use of sugar was associated with peptic ulcer risk only when interacting with genetic risk groups. Considering the role of Helicobacter pylori, it is interesting that the factors identified in this study were able to identify groups with extremely different lifetime risks. This finding and also the finding of strong interactions between genetic and life-style factors and between genetic factors and social class for the risk of peptic ulcer may have both public-health and clinical implications.


Medial plantar neurapraxia (jogger's foot): report of 3 cases.
Entrapment of the medial plantar nerve in the longitudinal arch causes burning heel pain, aching in the arch, and deficient sensation in the sole of the foot behind the great toe. Long distance valgus running may cause such a disorder in a jogger and the condition usually responds to conservative measures which include a change in running posture of the foot, anti-inflammatory medications, and proper footwear. The name "jogger's foot" is selected for this clinical syndrome.


Competitive Deep-Belief Networks for Underwater Acoustic Target Recognition.
Underwater acoustic target recognition based on ship-radiated noise belongs to the small-sample-size recognition problems. A competitive deep-belief network is proposed to learn features with more discriminative information from labeled and unlabeled samples. The proposed model consists of four stages: (1) A standard restricted Boltzmann machine is pretrained using a large number of unlabeled data to initialize its parameters; (2) the hidden units are grouped according to categories, which provides an initial clustering model for competitive learning; (3) competitive training and back-propagation algorithms are used to update the parameters to accomplish the task of clustering; (4) by applying layer-wise training and supervised fine-tuning, a deep neural network is built to obtain features. Experimental results show that the proposed method can achieve classification accuracy of 90.89%, which is 8.95% higher than the accuracy obtained by the compared methods. In addition, the highest accuracy of our method is obtained with fewer features than other methods.


Rhodiola Crenulata ameliorates exhaustive exercise-induced fatigue in mice by suppressing mitophagy in skeletal muscle.
The aim of present study was to evaluate the potential effects of Rhodiola crenulata oral liquid (RCOL) on exhaustive exercise (EE)-induced fatigue in mice. Male Institute of Cancer Research mice from five treatment groups (n=10 per group) were orally administered with sterilized water for the Control and EE groups and/or RCOL at doses of 1.02, 3.03 and 6.06 ml/kg/day, once daily for 2 weeks. Anti-fatigue activity was subsequently evaluated by measuring the levels of creatine kinase (CK), lactic acid (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and total anti-oxidative capability (T-AOC). Histopathology was assessed using hematoxylin and eosin staining. Ultrastructures of mitochondria were observed by transmission electron microscopy. Energy supply capacity was assessed using citrate synthase (CS), succinate dehydrogenase (SDH), Na+-K+-ATPase, and liver and quadriceps glycogen content assays. Expression levels of mRNA and protein associated with mitophagy in the skeletal muscle were measured by reverse transcription-quantitative PCR and western blotting, respectively. RCOL was observed to markedly inhibit fatigue-induced oxidative stress by increasing the activities of SOD, CAT and T-AOC, whilst reducing the accumulation of LA, CK, LDH and MDA. Histological analysis of the quadriceps femoris tissue suggested increased numbers of muscle fibers in the RCOL groups compared with those in the EE group. RCOL administration was found to reverse EE-induced mitochondrial structural damage and alleviated defects inflicted onto the energy supply mechanism by increasing CS, SDH, Na+-K+-ATPase and glycogen levels. Additionally, RCOL reduced the protein expression of PTEN-induced kinase 1 (PINK1), Parkin, microtubule-associated proteins 1A/1B light chain 3, sequestosome 1 and ubiquitin, whilst lowering the gene expression of PINK1 and Parkin. Taken together, results from the present study clarified the anti-fatigue effect of RCOL, where the underlying mechanism may be associated with increased antioxidant activity, enhanced energy production and the inhibition of mitophagy by suppressing the PINK1/Parkin signaling pathway.


Radiofrequency ablation in an infant with recurrent supraventricular tachycardia and cyanosis.
We report an unusual presentation of supraventricular tachycardia, in an infant, with cyanosis. The child had atrial septal defect with hypoplastic right ventricle. Radiofrequency ablation was performed in view of drug resistant SVT.


Review about Psychological Barriers to Lifestyle Modification, Changes in Diet Habits, and Health-Related Quality of Life in Bariatric Endoscopy.
Obesity is an expanding disease responsible for significant deterioration in the Health-Related Quality of Life (HRQL) of those who suffer from it. Bariatric Endoscopy (BE) therapies have proven to be an effective treatment for this pathology. A multidisciplinary approach is essential for the successful therapeutic management of BE. This article addresses the multidisciplinary treatment of BE by considering the possible variables that can influence treatment. In particular, the variables that can facilitate or hinder changes in patients' habits are discussed. These include the neuropsychological, emotional, and social implications that may influence the formation of healthy habits necessary for improvement in a patient's quality of life; the individual and environmental psychological factors that influence the monitoring of nutritional and physical activity indications; and different psychological disorders such as depression, anxiety, or disorders related to eating. The main objective of BE treatment, except in certain special biological situations, must be to establish a long-term sustainable change in habits such that patients, once they reach a healthy weight, do not revert to the lifestyle that caused their obesity, as well as identifying and addressing major problems that may exist prior to, or arise during, treatment.


The role of the immunoproteasome in interferon-γ-mediated microglial activation.
Microglia regulate the brain microenvironment by sensing damage and neutralizing potentially harmful insults. Disruption of central nervous system (CNS) homeostasis results in transition of microglia to a reactive state characterized by morphological changes and production of cytokines to prevent further damage to CNS tissue. Immunoproteasome levels are elevated in activated microglia in models of stroke, infection and traumatic brain injury, though the exact role of the immunoproteasome in neuropathology remains poorly defined. Using gene expression analysis and native gel electrophoresis we characterize the expression and assembly of the immunoproteasome in microglia following interferon-gamma exposure. Transcriptome analysis suggests that the immunoproteasome regulates multiple features of microglial activation including nitric oxide production and phagocytosis. We show that inhibiting the immunoproteasome attenuates expression of pro-inflammatory cytokines and suppresses interferon-gamma-dependent priming of microglia. These results imply that targeting immunoproteasome function following CNS injury may attenuate select microglial activity to improve the pathophysiology of neurodegenerative conditions or the progress of inflammation-mediated secondary injury following neurotrauma.


Analysis of Non-Small Bowel Lesions Detected by Capsule Endoscopy in Patients with Potential Small Bowel Bleeding.
Gastrointestinal (GI) bleeding cases in whom source cannot be identified after conventional upper and lower GI endoscopy are defined as potential small bowel bleeding. We aimed to search for lesions in the reach of conventional endoscopy in patients to whom video capsule endoscopy (VCE) had been applied for potential small bowel bleeding. 114 patients who had VCE evaluation for potential small bowel bleeding between January 2009 and August 2015 were retrospectively evaluated. Mean age of the patients was 55 ± 17 years. Female/male ratio is 39/75. In 58 patients (50.9%) bleeding lesion could be determined. Among these 58 patients 8 patients' lesions were in the reach of conventional endoscopes. Overall these 8 patients comprised 7% of patients in whom VCE was performed for potential small bowel bleeding. Among these 8 patients 5 had colonic lesions (4 angiodysplasia, 1 ulcerated polypoid cecal lesion), 2 had gastric lesions (1 GAVE, 1 anastomotic bleeding), and 1 patient had a bleeding lesion in the duodenal bulbus. Although capsule endoscopy is usually performed for potential small bowel bleeding gastroenterologists should always keep in mind that these patients may be suffering from bleeding from non-small bowel segments and should carefully review images captured from non-small bowel areas.


Stasis-induced thrombosis of rat microvascular anastomosis.
The rate of stasis-induced thrombosis in the rat femoral artery at varying times following microvascular anastomosis, was evaluated by direct inspection as well as by light and electron microscopy. The rate of thrombosis decreased with increasing postoperative time intervals. This decrease appears to coincide with histologic evidence of growth of the neo-intima at the anastomosis site.


Phonological assessment and analysis tools for Tagalog: Preliminary development.
Information and assessment tools concerning Tagalog phonological development are minimally available. The current study thus sets out to develop elicitation and analysis tools for Tagalog. A picture elicitation task was designed with a warm-up, screener and two extension lists, one with more complex and one with simpler words. A nonlinear phonological analysis form was adapted from English (Bernhardt & Stemberger, 2000) to capture key characteristics of Tagalog. The tools were piloted on a primarily Tagalog-speaking 4-year-old boy living in a Canadian-English-speaking environment. The data provided initial guidance for revision of the elicitation tool (available at phonodevelopment.sites.olt.ubc.ca). The analysis provides preliminary observations about possible expectations for primarily Tagalog-speaking 4-year-olds in English-speaking environments: Lack of mastery for tap/trill 'r', and minor mismatches for vowels, /l/, /h/ and word stress. Further research is required in order to develop the tool into a norm-referenced instrument for Tagalog in both monolingual and multilingual environments.


Bilateral dysplasia epiphysealis hemimelica: a case report.
Dysplasia epiphysealis hemimelica is a rare disorder of cartilage growth. Classically, the disease involves a single limb and is isolated to the medial or lateral half of that limb. A patient is described who presented with classic findings of this disease but involvement of both ankles.


Expressive Suppression of Emotions and Overeating in Individuals with Overweight and Obesity.
Emotions have a considerable impact on eating behaviour; however, research addressing emotion regulation in obesity is rare. The present study is the first to investigate the association between emotional suppression and overeating in individuals with overweight. In total, 314 participants including 190 individuals with obesity filled in a cross-sectional online survey, which assessed emotional suppression, eating behaviour and psychopathology. A hierarchical linear regression analysis was conducted to identify factors associated with overeating. Individuals with obesity reported more frequent overeating compared with individuals without obesity. The habitual use of emotional suppression was associated with more overeating; however, this link was moderated by increased body mass index (BMI). The results suggest that suppression of emotional expression contributes to overeating and is maladaptive especially in individuals with obesity. Further research should longitudinally investigate the predictive value of emotional suppression on overweight, as the training of emotion regulation could contribute to treating obesity. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.


Template-Free Synthesis of an Interlocked Covalent Organic Molecular Cage.
An interlocked covalent organic molecular cage with a trigonal-prismatic structure based on anthracene units and imine bonds was synthesized by a template-free and one-pot reaction in a relatively good yield. By comparing the single-crystal structures of the interlocked cage and two additional monomeric cages as reference compounds, a cause of weak supramolecular interaction-induced synthesis was proposed; π···π interactions induce the triphenylbenzene units as the core and anthracenes as side parts close to each other, which provides a possibility of the preorganization for the formation of the interlocked structure.


Sepsis in the intensive care unit: etiologies, prognostic factors and mortality.
Sepsis is the main cause of death in patients treated in intensive care units (ICU). The aim of this study was to evaluate etiology, prognostic factors and mortality of septic patients treated in ICU of Passo Fundo, Brazil. Out of 971 consecutive patients prospectively evaluated from August 2005 to February 2006, 560 were selected due to presence of systemic inflammatory response syndrome (SIRS) and followed for 28 days or until discharge or death. Patients were categorized according with the etiology of SIRS and further classified as having SIRS, sepsis, severe sepsis and septic shock. Prognosis was assessed by means of Apache II and SOFA. Mortality was compared in different etiologies of sepsis, APACHE II and SOFA scores, parameters. Of the 971 patients admitted to the ICU, 560 developed SIRS (58%). The most frequent cause of internation was neurological disease (28.9%), the most frequent site of infection was the respiratory tract (71.6%), and the most prevalent pathogens were gram-negative bacilli (53.2%). Mean APACHE II score was 18 ± 9, and mean SOFA score was 5 ± 4. Median ICU stay was 6 (3-11) days and overall mortality rate was 31.1%: 6.1% for non-infectious SIRS, 10.1% for sepsis, 22.6% for severe sepsis, and 64.8% for septic shock. Sepsis is an important health problem that leads to an extremely high mortality rate in the ICU of Passo Fundo, Brazil.


The compact Erlangen Active Simulator for Interventional Endoscopy: a prospective comparison in structured team-training courses on "endoscopic hemostasis" for doctors and nurses to the "Endo-Trainer" model.
In 1997 Hochberger and Neumann presented the "Erlangen Biosimulation Model" (commercialized as the "Erlangen Endo-Trainer") at various national and international meetings. The new compactEASIE is a simplified version of the original "Biosimulation Model" (Endo-Trainer) and is specially designed for easy handling. CompactEASIE is reduced in its features, focusing exclusively on flexible endoscopy training. The acceptance of training in endoscopic hemostasis is accepted by workshop participants, as evaluated by a questionnaire on both models. Eleven structured courses on endoscopic hemostasis for doctors and nurses organized by the same endoscopists from 3/1998 to 5/1999 were evaluated using one of both models. The questionnaires were filled in by 207/291 trainees (71%). The Endo-Trainer was used in 4 (n = 103) and the compactEASIE in 7 courses (n = 104). Both simulators were equipped with identical types of specially prepared pig-organ packages consisting of esophagus, stomach and duodenum, including artificial sewn-in vessels, polyps and varices. Blood perfusion was done with a roller pump connected to the sewn-in vessels and blood surrogate. All workshops were identical concerning the course structure: a 30-min theoretical introduction on ulcer bleeding was followed by 2 h of practical training in injection techniques and hemoclip application. The second part of variceal therapy consisted of a 30-min theoretical introduction prior to 2 h of practical training on sclerotherapy, band ligation and cyanoacrylate application. Finally, a questionnaire on the trainees' pre-experience and their rating of the different workshop sections was handed out to each participant. Previous endoscopic experience was comparable in both groups. The training in both simulators was highly accepted by the trainees (compactEASIE 95% excellent and good versus EASIE (Endo-Trainer) 97%) and did not show any significant difference (P = 0.493). Even in the assessment of the single techniques, no statistical difference was observed. Furthermore, the assessments of the closeness to reality and the endoscopic environment in both simulators were identical. Both simulators (Endo-Trainer, compactEASIE) are excellent educational tools for interventional endoscopy with a high level of acceptance. The easy-to-handle, "lightweight" compactEASIE is a significant, progress tool for the future.