Differential redundancy gain in onset detection versus offset detection.
In a visual simple reaction time paradigm with attention divided between the left and right visual fields, redundancy gain refers to the finding of faster responses to stimuli presented in both fields than to single stimuli. The present study investigated whether the effects of low-level perceptual processing affect the redundancy gain by comparing the detection of onsets versus offsets. In different blocks, participants responded to left and right visual field stimuli that either appeared (onset) or disappeared (offset), with a single stimulus change in some trials and two redundant stimulus changes in others. With onset stimuli, the results replicated previous redundancy gain effects. In contrast, there was much less redundancy gain when participants responded to stimulus offsets. This finding suggests that redundancy gain is sensitive to low-level perceptual characteristics, such as onset versus offset presentation of stimuli.


Using preoperative ultrasound vascularity characteristics to estimate medullary thyroid cancer.
The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as "ultrasound-high suspicious" (h-MTC) and "ultrasound-low suspicious" (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P < 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (87.1% vs. 32.3%, P < 0.001)) and CHEN IV patterns (penetrating vascularity) (100% vs. 25.8%, P < 0.001) were found in l-MTC than benign nodules. Vascularity features can help differentiate l-MTC from benign nodules; moreover, we report a novel sonographic vascularity pattern of l-MTC disease, penetrating branching vascularity. The utilization of vascularity features will help to identify MTC among nodules with low-intermediate suspicion by ultrasound risk classification to ensure appropriate clinical management.


New, fast and cheap prediction tests for BRCA1 gene mutations identification in clinical samples.
Despite significant progress in cancer therapy, cancer is still the second cause of mortality in the world. The necessity to make quick therapeutic decisions forces the development of procedures allowing to obtain a reliable result in a quick and unambiguous manner. Currently, detecting predictive mutations, including BRCA1, is the basis for effectively treating advanced breast cancer. Here, we present new insight on gene mutation detection. We propose a cheap BRCA1 mutation detection tests based on the surface plasmon resonance (SPR) or quartz crystal microbalance with energy dissipation (QCM-D) response changes recorded during a hybridization process of an oligonucleotide molecular probe with DNA fragments, with and without the BRCA1 mutation. The changes in the morphology of the formed DNA layer caused by the presence of the mutation were confirmed by atomic force microscopy. The unique property of the developed SPR and QCM tests is really short time of analysis: ca. 6 min for SPR and ca. 25 min for QCM. The proposed tests have been verified on 22 different DNA extracted from blood leukocytes collected from cancer patients: 17 samples from patients with various BRCA1 gene mutation variants including deletion, insertion and missense single-nucleotide and 5 samples from patients without any BRCA1 mutation. Our test is a response to the need of medical diagnostics for a quick, unambiguous test to identify mutations of the BRCA1 gene, including missense single-nucleotide (SNPs).


Dysphagia in Dementia: Influence of Dementia Severity and Food Texture on the Prevalence of Aspiration and Latency to Swallow in Hospitalized Geriatric Patients.
To evaluate influences of disease severity and food texture on prevalence and type of dysphagia in hospitalized geriatric patients. We screened for dysphagia in 161 geriatric inpatients with different forms of dementia and 30 control patients. Signs of aspiration were registered with 3 different food consistencies (water, apple puree, and slice of an apple) and the latency until the first swallow was documented. Geriatric department of an academic teaching hospital in Hamburg, Germany. Compared with the controls, patients with dementia more often showed signs of aspiration. In the patients with dementia, signs of aspiration occurred more frequently with water (35.6%) than with a slice of an apple (15.1%) or apple puree (6.3%). We observed an inverse relationship between Mini-Mental State Examination score level and the suspected rate of aspiration, as well as with the length of latency until the first swallow of puree. The prevalence of dysphagia is high in patients with dementia, especially in patients with moderate to severe cognitive impairment. The relationships observed in this study encourage screening for dysphagia and adapting meal consistencies to prevent aspiration in patients with dementia.


Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates.
Secretion systems require high-fidelity mechanisms to discriminate substrates among the vast cytoplasmic pool of proteins. Factors mediating substrate recognition by the type VI secretion system (T6SS) of Gram-negative bacteria, a widespread pathway that translocates effector proteins into target bacterial cells, have not been defined. We report that haemolysin coregulated protein (Hcp), a ring-shaped hexamer secreted by all characterized T6SSs, binds specifically to cognate effector molecules. Electron microscopy analysis of an Hcp-effector complex from Pseudomonas aeruginosa revealed the effector bound to the inner surface of Hcp. Further studies demonstrated that interaction with the Hcp pore is a general requirement for secretion of diverse effectors encompassing several enzymatic classes. Though previous models depict Hcp as a static conduit, our data indicate it is a chaperone and receptor of substrates. These unique functions of a secreted protein highlight fundamental differences between the export mechanism of T6 and other characterized secretory pathways.


High-Protein Nutritious Flatbreads and an Option for Gluten-Sensitive Individuals.
Whole grain quinoa and wheat, high-protein vegetable flatbreads were evaluated by tasters and a physical analysis was conducted. The objective was to produce nutritious, tasty gluten-free (quinoa) as well as gluten-containing (wheat) flatbreads. Flatbreads were Quinoa Peanut Oilcake Broccoli (QPCBROC), Wheat Peanut Oilcake Broccoli (WPCBROC), Quinoa Peanut Oilcake Beets (QPCBEET) and Wheat Peanut Oilcake Beets (WPCBEET). Peanut Oilcake would increase protein and add value to this farm byproduct. Bile acid binding broccoli and beets with cholesterol-lowering potential were used. Tasters preferred QPCBROC flatbreads for all sensory parameters. Acceptance of flatbreads was QPCBROC (83%), WPCBROC (70%), QPCBEET (78%) and WPCBEET (69%); these values were statistically similar. The objective of ≥25% protein content was exceeded by 5-8% and that of ≥70% acceptance was adequately achieved. These flatbreads were low in fat (5-6%) and contained essential minerals (4%) with only ≤1% added salt. Porosity and expansion data suggest that these flatbreads would take up relatively little shelf space. These flatbreads require only three ingredients and can be made in a household kitchen or by commercial production. These flatbreads offer a nutritious, tasty choice for all, and quinoa flatbreads offer an option for gluten-sensitive individuals.


[Intracranial vascular malformations].
Intracranial vascular malformations range from incidental asymptomatic vascular alterations up to life-threatening vascular disorders. Arteriovenous malformations and dural arteriovenous fistulas are cerebral vascular malformations with arteriovenous shunting of blood. In the majority of cases they are accompanied by an elevated risk of intracerebral hemorrhage and can cause severe symptoms. They can be treated conservatively or interventionally via microneurosurgery, endovascular embolization and radiation therapy. Cavernous malformations, developmental venous anomalies (DVA) and capillary telangiectasia are cerebral vascular malformations without arteriovenous shunting. Cavernous malformations are rarely symptomatic in the form of cerebral hemorrhage, headache or seizures and in such cases an operative treatment can be indicated. The DVA and capillary telangiectasia are usually asymptomatic and do not require treatment.


Substrate inhibition in a human variant of hypoxanthine-guanine phosphoribosyltransferase.
Hypoxanthine-guanine phosphoribosyltransferase from a young man with purine overproduction and decreased purine salvage in fibroblast cultures was found to have low activity at concentrations of purine substrates at which the enzyme from normal individuals showed near maximal activity. The low enzyme activity was not associated with changes in the values of the Km(app) and Vmax(app) for any of the enzyme substrates. However, the enzyme activity was susceptible to substrate inhibition by hypoxanthine and guanine. The values obtained for the true Km, true Vmax, and true Ki for hypoxanthine were 26 +/- 10 microM, 1761 +/- 382 microunits/mg of protein, and 80 +/- 20 microM, respectively. The pattern of the substrate inhibition, as seen on a plot of 1/v versus hypoxanthine concentration, was characteristic of that associated with the formation of a dead-end complex between the inhibitory substrate and an enzyme form with which it normally does not react. The nature of this enzyme form and that of the dead-end complex was determined from double inhibition experiments, which indicated that hypoxanthine interacted with an enzyme-PPi intermediate to form an enzyme-hypoxanthine-PPi dead-end complex. The trapping of the enzyme in this inactive form explains the low activity at high purine base concentrations. Further information as to the nature of the reaction mechanism was obtained from plots of the reciprocal of enzyme activity versus the reciprocal of PP-ribose-P concentration at different fixed hypoxanthine concentrations. A pattern characteristic of uncompetitive substrate inhibition was obtained. This is indicative of an ordered sequential binding of substrates on the enzyme; PP-ribose-P binding before hypoxanthine. Thus, the variant enzyme showed an ordered sequential reaction mechanism, with the inhibitory substrate forming a dead-end complex with an enzyme-PPi intermediate.


Predicting blood pressure from physiological index data using the SVR algorithm.
Blood pressure diseases have increasingly been identified as among the main factors threatening human health. How to accurately and conveniently measure blood pressure is the key to the implementation of effective prevention and control measures for blood pressure diseases. Traditional blood pressure measurement methods exhibit many inherent disadvantages, for example, the time needed for each measurement is difficult to determine, continuous measurement causes discomfort, and the measurement process is relatively cumbersome. Wearable devices that enable continuous measurement of blood pressure provide new opportunities and hopes. Although machine learning methods for blood pressure prediction have been studied, the accuracy of the results does not satisfy the needs of practical applications. This paper proposes an efficient blood pressure prediction method based on the support vector machine regression (SVR) algorithm to solve the key gap between the need for continuous measurement for prophylaxis and the lack of an effective method for continuous measurement. The results of the algorithm were compared with those obtained from two classical machine learning algorithms, i.e., linear regression (LinearR), back propagation neural network (BP), with respect to six evaluation indexes (accuracy, pass rate, mean absolute percentage error (MAPE), mean absolute error (MAE), R-squared coefficient of determination (R2) and Spearman's rank correlation coefficient). The experimental results showed that the SVR model can accurately and effectively predict blood pressure. The multi-feature joint training and predicting techniques in machine learning can potentially complement and greatly improve the accuracy of traditional blood pressure measurement, resulting in better disease classification and more accurate clinical judgements.


Homogeneous liquid-liquid extraction for preconcentration of polycyclic aromatic hydrocarbons using a water/methanol/chloroform ternary component system.
A fast and effective preconcentration method for the extraction of polycyclic aromatic hydrocarbons (PAHs) was developed using a homogeneous liquid-liquid extraction based on phase separation phenomenon in a ternary solvent (water/methanol/chloroform) system. The phase separation phenomenon occurred by salt addition. After centrifugation, the extracting solvent was sedimented in the bottom of the conical test tube. The PAHs were transferred into the sedimented phase during the phase separation step. The extracted PAHs were determined using gas chromatography-flame ionization detection. Several factors influencing the extraction efficiency were investigated and optimized. Optimal results were obtained at the following conditions: volume of the consolute solvent (methanol), 1.2 mL; volume of the extracting solvent (chloroform), 60 muL; volume of the sample, 2.5 mL; concentration of NaCl, 15% (w/v). Under the optimum conditions, the enrichment factors of 225-257, the extraction percent of 90-100%, the dynamic linear range of 0.1-400 microg L(-1), and the limits of detection of 0.02-0.18 microg L(-1) were obtained for the PAHs. Using internal standard, the relative standard deviations for 100 microg L(-1) of the PAHs in the water samples were obtained in the range of 4.2-10.3% (n=5). Finally, the proposed method was successfully applied for the extraction and determination of the PAHs in waste water samples.


Gastric intestinal metaplasia assessment between linked color imaging based on endoscopy and pathology.
Cumulative evidence suggests that linked color imaging (LCI) can be used to identify gastric intestinal metaplasia (GIM). We aimed to develop endoscopic grading for GIM (EGGIM) with LCI. Two hundred and seventy-seven patients who underwent high-resolution white-light gastroscopy followed by LCI for EGGIM estimation were included. LCI was performed for the entire mucosa, and images of five areas each were recorded from the lesser and greater curvatures of the antrum and corpus, and for the incisura. For each area, scores of 0 (no GIM), 1 (focal GIM, ≤30% of the area), and 2 (extensive GIM, >30% of the area) were attributed for 10 points. If GIM was suspected based on endoscopy findings, targeted biopsies were performed; if GIM was not evident, random biopsies were performed according to the Sydney system to estimate the operative link on GIM (OLGIM). GIM was staged as OLGIM 0, I, II, III, and IV in 136, 70, 37, 28, and 6 patients, respectively. For OLGIM III/IV diagnosis, the area under the receiver operating curve was 0.949 (95% CI 0.916-0.972). EGGIM of 4, with sensitivity and specificity of 94.12% (95% CI 80.3%-99.3%) and 86.42% (95% CI 81.5%-90.5%), respectively, was determined the best cut-off value for identifying OLGIM III/IV patients. Our findings demonstrated the ability of EGGIM for diagnosing the extent of intestinal metaplasia and showed that EGGIM is related to OLGIM staging. EGGIM of 4 was the best cut-off value for identifying OLGIM III/IV patients.


Annual variation in Finch numbers, foraging and food supply on Isla Daphne Major, Galápagos.
(1) We report some effects of an annually variable and unpredictable rainfall upon Darwin's Finches on the Galápagos. Finch numbers, foraging and food supply were studied on I. Daphne Major in December of 1973 and 1977, and compared. 1973 was the second of two successive wet years and 1977 was a drought year. (2) Seed numbers and biomass were approximately one order of magnitude lower in the drought year than in the wet year. Small and soft seeds were absolutely and relatively rarer in the drought year than in the wet year. (3) Similarly finch numbers and biomass were approximately one order of magnitude lower in the drought year than in the wet year. Numbers of G. scandens declined less than did number of G. fortis. Both species exhibited unabalaced sex ratios, in favour of males, in the dry year in contrast to balanced sex ratios in the wet year. Male scandens were heavier on average in the wet year, but male fortis were heavier in the dry year. (4) The foraging of scandens, a cactus (Opuntia) specialist, was similar in the two years. The foraging of fortis in the dry year differed from foraging in the wet year in three important respects: fortis devoted a disproportionate amount of time to feeding on small seeds while tending to avoid seeds of Opuntia, they fed more on floral and extra-floral parts of Opuntia and they fed on Tribulus cistoides, a large and hard fruit which was absent from their diet in the wet year. As a consequence of feeding more on Opuntia, fortis foraging was more similar to scandens foraging in the dry year than in the wet year. (5) The results are discussed in relation to expectations from competition theory. The decline in numbers in relation to a decline in food supply was expected, but a convergence in diets was not. The convergence is attributed to the recent renewal of a single resource, Opuntia flowers, against a background of general resource scarcity. Diet overlap and limitation of numbers by food provide indirect evidence of interspecific competition; scandens, with an included niche, was competitively superior to fortis.


Aboriginal and Torres Strait Islander worldviews and cultural safety transforming sexual assault service provision for children and young people.
Child Sexual Assault (CSA) in Aboriginal and Torres Strait Islander communities is a complex issue that cannot be understood in isolation from the ongoing impacts of colonial invasion, genocide, assimilation, institutionalised racism and severe socio-economic deprivation. Service responses to CSA are often experienced as racist, culturally, financially and/or geographically inaccessible. A two-day forum, National Yarn Up: Sharing the Wisdoms and Challenges of Young People and Sexual Abuse, was convened by sexual assault services to identify the main practice and policy concerns regarding working with Aboriginal and Torres Strait Islander children and young people (C&YP), families and communities in the context of CSA. The forum also aimed to explore how services can become more accountable and better engaged with the communities they are designed to support. The forum was attended by eighty invited Aboriginal and Torres Strait Islander and non-Aboriginal youth sexual assault managers and workers representing both "victim" and "those who sexually harm others" services. In keeping with Aboriginal Community-Based Research methods forum participants largely directed discussions and contributed to the analysis of key themes and recommendations reported in this article. The need for sexual assault services to prioritise cultural safety by meaningfully integrating Aboriginal and Torres Strait Islander Worldviews emerged as a key recommendation. It was also identified that collaboration between "victims" and "those who sexually harm" services are essential given Aboriginal and Torres Strait Islander C&YP who sexually harm others may have also been victims of sexual assault or physical violence and intergenerational trauma. By working with the whole family and community, a collaborative approach is more likely than the current service model to develop cultural safety and thus increase the accessibility of sexual assault services.


Phosphorylation of myosin II regulatory light chain controls its accumulation, not that of actin, at the contractile ring in HeLa cells.
During cytokinesis in eukaryotic cells, an actomyosin-based contractile ring (CR) is assembled along the equator of the cell. Myosin II ATPase activity is stimulated by the phosphorylation of the myosin II regulatory light chain (MRLC) in vitro, and phosphorylated MRLC localizes at the CR in various types of cells. Previous studies have determined that phosphorylated MRLC plays an important role in CR furrowing. However, the role of phosphorylated MRLC in CR assembly remains unknown. Here, we have used confocal microscopy to observe dividing HeLa cells expressing fluorescent protein-tagged MRLC mutants and actin during CR assembly near the cortex. Di-phosphomimic MRLC accumulated at the cell equator earlier than non-phosphorylatable MRLC and actin. Interestingly, perturbation of myosin II activity by non-phosphorylatable MRLC expression or treatment with blebbistatin, a myosin II inhibitor, did not alter the time of actin accumulation at the cell equator. Furthermore, inhibition of actin polymerization by treatment with latrunculin A had no effect on MRLC accumulation at the cell equator. Taken together, these data suggest that phosphorylated MRLC temporally controls its own accumulation, but not that of actin, in cultured mammalian cells.


The supracondylar approach to the jugular tubercle and hypoglossal canal.
Circumscribed lesions of the hypoglossal canal and of the jugular tubercle still remain a surgical challenge. So far, transpetrosal, transcondylar suboccipital, and extreme lateral approaches have been used to access this region. These surgical procedures bear a high risk for neurological deficits. Therefore, we introduce a new minimally invasive extradural approach to the hypoglossal canal that also allows access to the lateral aspects of the jugular tubercle. After a paramedian retromastoid skin incision, a basal suboccipital craniectomy lateral to the foramen magnum toward the jugular tubercle is performed. With this approach the occipital condyle and the lateral osseous circumference of the foramen magnum are preserved. Drilling extradurally, the dorsal parts of the jugular tubercle are removed. The exposure is extended downward to the posterior margins of the hypoglossal canal and laterally to the jugular bulb, enabling a minimally invasive exposure of the hypoglossal canal, the lateral aspects of the jugular tubercle, and medial aspects of the jugular bulb. Using this supracondylar approach, surgical interventions were performed in three patients suffering from a hypoglossal neurinoma, a cholesterol granuloma extending into the jugular tubercle, and a cyst of the hypoglossal canal, respectively. No additional postoperative neurological deficits were seen. The supracondylar approach seems to be useful to gain access to benign lesions of the hypoglossal canal and of the jugular tubercle to decompress tumors or cysts. In contrast to previously reported techniques this approach has a low risk of morbidity. The surgical field, however, is restricted laterally by the jugular bulb, medially and basally by the residual occipital condyle and dorsally by the dura. Therefore, this approach is useful to remove small lesions or to perform extended biopsies. Radical removal of large tumors seems to be problematic using this approach.


Tolerability and safety of rituximab (MabThera).
Rituximab, a human/mouse chimeric anti-CD20 antibody, has become part of standard therapy for patients with CD20-expressing B-cell lymphoma, and is currently under investigation for other indications including autoimmune diseases, in particular rheumatoid arthritis (RA). Its characteristic tolerability profile was established soon after clinical testing began and compares favourably with chemotherapy. The majority of patients experience mild to moderate infusion-related reactions (IRRs) during the first administration of rituximab, but the incidence decreases markedly with subsequent infusions. Current data suggest that the type of adverse events in patients with RA are similar to those in lymphoma, but that adverse events related to the rituximab infusions are less severe and less frequent. Rituximab induces a rapid depletion of normal CD20-expressing B-cells in the peripheral blood, and levels remain low or undetectable for 2-6 months before returning to pretreatment levels, generally within 12 months. Serum immunoglobulin levels remain largely stable, although a reduction in IgM has been described. T-cells are unaffected by rituximab and consequently opportunistic infections rarely occur in association with rituximab therapy. When used in combination with a variety of chemotherapeutic regimens, rituximab does not add to the toxicity of chemotherapy, with the exception of a higher rate of neutropenia. However, this does not translate into a higher infection rate. Over 540,000 patients worldwide have now received rituximab and serious adverse reactions have occurred in a small minority of patients, but for the great majority of patients, rituximab is safe and well tolerated.


Impact of intravenous infusion time on AAV8 vector pharmacokinetics, safety, and liver transduction in cynomolgus macaques.
Systemically delivered adeno-associated viral (AAV) vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system. The dose of AAV8 vector in terms of genome copies per kilogram body weight and its concentration were fixed, while the rate of infusion varied to deliver the entire dose over different time periods, including 1, 10, or 90 minutes. Analyses during the in-life phase of the experiment included sequential evaluation of whole blood for vector genomes and appearance of proinflammatory cytokines. Liver tissues were analyzed at the time of necropsy for enhanced green fluorescent protein (eGFP) expression and vector genomes. The data were remarkable with a relative absence of any statistically significant effect of infusion time on vector transduction, safety, and clearance. However, some interesting and unexpected trends did emerge.


β1 and β3 subunits amplify mechanosensitivity of the cardiac voltage-gated sodium channel Nav1.5.
In cardiomyocytes, electrical activity is coupled to cellular contraction, thus exposing all proteins expressed in the sarcolemma to mechanical stress. The voltage-gated sodium channel Nav1.5 is the main contributor to the rising phase of the action potential in the heart. There is growing evidence that gating and kinetics of Nav1.5 are modulated by mechanical forces and pathogenic variants that affect mechanosensitivity have been linked to arrhythmias. Recently, the sodium channel β1 subunit has been described to stabilise gating against mechanical stress of Nav1.7 expressed in neurons. Here, we tested the effect of β1 and β3 subunits on mechanosensitivity of the cardiac Nav1.5. β1 amplifies stress-induced shifts of V1/2 of steady-state fast inactivation to hyperpolarised potentials (ΔV1/2: 6.2 mV without and 10.7 mV with β1 co-expression). β3, on the other hand, almost doubles stress-induced speeding of time to sodium current transient peak (Δtime to peak at - 30 mV: 0.19 ms without and 0.37 ms with β3 co-expression). Our findings may indicate that in cardiomyocytes, the interdependence of electrical activity and contraction is used as a means of fine tuning cardiac sodium channel function, allowing quicker but more strongly inactivating sodium currents under conditions of increased mechanical stress. This regulation may help to shorten action potential duration during tachycardia, to prevent re-entry phenomena and thus arrhythmias.


In situ hybridization analysis of preprotachykinin-A mRNA levels in young and old rats.
The present study examined the effects of ageing on preprotachykinin-A (PPT-A) mRNA levels in discrete regions of the rat brain. Semiquantitative analysis of silver grains revealed a 16% statistically significant decrease in PPT-A mRNA in the shell of the nucleus accumbens (AcbSh), a 27.6% statistically significant lower level of PPT-A mRNA in the olfactory tubercle (Tu), a 19.2% and 31. 5% statistically significant decrease in PPT-A mRNA in the dorsal and ventral caudate-putamen (d-CPu) (v-CPu), respectively, a 30% statistically significant lower expression of PPT-A mRNA in the bed nucleus of the stria terminalis (BNST), a 33.7% statistically significant decrease in PPT-A mRNA in the habenula (Hb) and a 30% statistically significant decrease of PPT-A mRNA levels in the postero-dorsal part of the medial amygdala (MePD). No changes in PPT-A mRNA levels were found in the nucleus accumbens, core (AcbC), in the islands of Calleja (Icj), and in the medial preoptic area (mPOA). These results show that ageing of the central nervous system (CNS) is associated with widespread changes in tachykinin gene expression, suggesting that alteration in the tachykinergic system may have implications in the physio-pathology of the elderly.


Long noncoding RNA 01534 maintains cancer stemness by downregulating endoplasmic reticulum stress response in colorectal cancer.
Studies have shown that cancer stemness and the endoplasmic reticulum (ER) stress response are inversely regulated in colorectal cancer (CRC), but the mechanism has not been fully clarified. Long noncoding RNAs (lncRNAs) play key roles in cancer progression and metastasis. In this study we investigated lncRNA 01534 (LINC01534) as a possible modulator between cancer stemness and ER stress response. In vitro experiments using CRC cell lines were performed to explore a possible role of LINC01534. The expression of LINC01534 in clinical CRC samples was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization. Silencing LINC01534 led to suppression of cell proliferation, invasiveness, and cell cycle progression at the G2-M phase, and promoted apoptosis. Moreover, we found that silencing LINC01534 suppressed cancer stemness, while it activated the ER stress response, especially through the PERK/eIF2α signaling pathway. In situ hybridization revealed LINC01534 was expressed in tumor cells and upregulated in CRC tissues compared with normal epithelium. A survival survey indicated that high LINC01534 expression was significantly associated with shorter overall survival in 187 CRC patients. This is the first report on LINC01534 in human cancer. Our findings suggest that LINC01534 may be an important modulator of the maintenance of cancer stemness and suppression of the ER stress response, and that it could be a novel prognostic factor in CRC.


Investigation of the Relationship Between Spiritual Coping Styles and Hope Levels in Mothers with Disabled Children in Turkey.
The birth of a child is a process in which family life and daily routines undergo significant changes and adjustments. This study aims to investigate the relationship between spiritual coping styles and hope levels in mothers with disabled children. The study was conducted between January and April 2022 with mothers whose children were enrolled in a rehabilitation center of a district located in eastern Turkey. The target population of the study was 110 mothers who had children enrolled in the rehabilitation center. The sample of the study was 102 mothers who agreed to participate in the study. Data were collected through the Personal Information Form, the Trait Hope Scale, and the Maternal Spiritual Coping Scale. Spiritual coping mean scores were high in mothers who had a female disabled child, did not have any other disabled children, received support from the state for their child's care, did not ignore their other children's care due to the special condition of the disabled child and did not feel guilty, and were worried about their children's future. The difference between the mean scores was statistically significant (p < 0.05). Hope mean scores were found to be high in women who had children with physical and hearing disability, were illiterate, had a low economic condition, and received psychological support for the condition of their children. The difference between the mean scores was statistically significant (p < 0.05). A positive relationship was found between maternal spiritual coping levels and hope levels. In-line with this result, it is recommended to organize programs to help mothers to accept their children's condition and cope with their situation.


Characterization and associated risk factors of Pneumocystis jirovecii pneumonia in patients with AIRD: a retrospective study.
To explore clinical features of autoimmune inflammatory rheumatic disease (AIRD) patients with Pneumocystis jirovecii pneumonia (PJP) and identify potential risk factors and prognostic factors. AIRD patients who had respiratory symptoms and underwent P. jirovecii detection were identified from the database in our department from November 2018 to October 2020. These patients were categorized into PJP and non-PJP groups according to the diagnostic criteria of PJP. Univariate and multivariate analyses were conducted. A total of 173 patients were enrolled and 46 of them had laboratory-confirmed PJP. Glucocorticoid increased the risk of PJP in a dose-dependent manner. In addition, shorter duration of immunosuppressive therapy (IST), combination therapy with CSA and chronic pulmonary comorbidities were also strongly associated with a higher risk of PJP. Combination of IgM and IgA could well identify AIRD patients with PJP from other AIRD patients with respiratory symptoms, with the optimal cut-off value of -0.96 g/l. Seven of 46 AIRD patients with PJP died (15.2%). A higher level of serum LDH, dyspnoea and ARDS, and the presence of extensive ground glass opacity (GGO) in radiologic examinations were more common in deceased patients. AIRD patients with high-dose glucocorticoid treatment, recent initiation of IST, combination therapy with CSA and history of chronic pulmonary diseases had a greater risk of PJP infection. PJP patients with a higher level of serum LDH, dyspnoea, moderate and severe ARDS, and the presence of extensive GGO in radiologic examinations had poorer prognosis. Chinese Clinical Trial Register; https://www.chictr.org.cn/; ChiCTR2100044095.


Pharmacodynamics, pharmacokinetics, safety, and tolerability of a ready-to-use, room temperature, liquid stable glucagon administered via an autoinjector pen to youth with type 1 diabetes.
Prompt and reliable management of hypoglycemia in youth with diabetes is important to prevent serious medical complications. To determine efficacy, pharmacodynamics (PD), pharmacokinetics (PK), safety, and tolerability of a ready-to-use, liquid stable glucagon formulation administered subcutaneously via an autoinjector pen to youth with type 1 diabetes (T1D). After plasma glucose concentration was < 80 mg/dL (< 4.4 mmol/L) after insulin, participants aged 2 to < 12 years with T1D were administered 0.5 mg of glucagon; participants aged 12 to < 18 years instead received 1 mg of glucagon. Then, adolescents were challenged with 0.5 mg after a 7- to 28-day washout period. Primary endpoint was mean plasma glucose concentration at 30 min after glucagon. Plasma glucose concentrations significantly (p < 0.001) increased from baseline to 30 min after glucagon, with mean change in plasma glucose concentration between baseline and 30 min for each age cohort as follows: 2 to < 6 years (n = 7; 81.4 mg/dL [4.5 mmol/L]); 6 to < 12 years (13; 84.2 mg/dL [4.7 mmol/L]); 12 to < 18 years (11; dose, 1 mg; 54.0 mg/dL [3.0 mmol/L]); and 12 to < 18 years (11; 0.5 mg; 52.4 mg/dL [2.9 mmol/L]). Among age cohorts, no clinically relevant differences were observed for PD and PK parameters. Common adverse events were nausea, vomiting, and hypoglycemia. Age-appropriate dosing of this glucagon formulation was effective at 30 min in reversing plasma glucose concentrations from < 80 mg/dL in youth with T1D.


Upward social comparison sensitivity on teachers' emotional exhaustion: A moderated moderation model of self-esteem and gender.
Drawing on conservation of resources theory, this study aims to extend the work on individual differences in the relationship between upward social comparison sensitivity and emotional exhaustion in a sample of teachers by examining the interaction effects of self-esteem and gender differences. A total of 681 teachers completed a self-reported questionnaire including the Upward Social Comparison Sensitivity Scale, the Self-Esteem Scale, and the Maslach Burnout Inventory-Educators Survey (MBI-ES) subscale. The results based on a moderated moderation model indicated that: (1) Upward social comparison sensitivity was positively correlated with emotional exhaustion; (2) self-esteem moderated the relationship between upward social comparative sensitivity and emotional exhaustion; and (3) there was a significant gender difference in self-esteem that moderated the relationship between upward social comparison sensitivity and emotional exhaustion. These findings contribute to the understanding of how upward social comparison sensitivity predicts teachers' emotional exhaustion and provide practical insights for prevention and intervention programs to protect teachers' mental health in school settings.


Using vacuum-assisted ureteral access sheath in the treatment of complex steinstrasse.
Steinstrasse is an iatrogenic condition resulting from upper urinary tract lithotripsy. Uncomplicated steinstrasse can be managed expectantly. Complex steinstrasse can pose a therapeutic challenge. The vacuum-assisted ureteral access sheath (vaUAS) is similar to a conventional ureteral access sheath but has a side branch that can be connected to vacuum apparatus. This device seemed to be useful in the management of complex steinstrasse. 35 patients with complex steinstrasse, defined as steinstrasse containing ≥ 4 stones or with an aggregate length of ≥ 1.5 cm, were treated in four tertiary medical centers using the vaUAS in this prospective and non-randomized study. The vaUAS was inserted into the ureter over a guidewire until the tip of the vaUAS was in contact with the lowermost stone fragment. A 7 Fr./8.4 Fr. semirigid ureteroscope and a holmium laser were used to pulverize the obstructing stone. All the stone fragments were aspirated either in the space between the scope and the sheath, or through the channel of the sheath by withdrawing the scope to the proximal of the aspiration port. All patients were steinstrasse-free at end of the procedure, as assessed visually and by KUB. At the 3-month follow-up, 94.3% of patients were stone-free with or without a supplementary procedure. There were no perioperative complications. Five patients experienced postoperative fever and/or significant hematuria, and one patient had transient sepsis, a grade I and IV Clavien complication, respectively. vaUAS can be an effective adjunctive device in the management of complex steinstrasse.


Research progress in allele-specific expression and its regulatory mechanisms.
Although the majority of genes are expressed equally from both alleles, some genes are differentially expressed. Organisms possess characteristics to preferentially express a particular allele under regulatory factors, which is termed allele-specific expression (ASE). It is one of the important genetic factors that lead to phenotypic variation and can be used to identify the variance of gene regulation factors. ASE indicates mechanisms such as DNA methylation, histone modifications, and non-coding RNAs function. Here, we review a broad survey of progress in ASE studies, and what this simple yet very effective approach can offer in functional genomics, and possible implications toward our better understanding of the underlying mechanisms of complex traits.


Navigating ethical discharge planning: A case study in older adult rehabilitation.
Ethical issues are becoming more complex as individuals live longer with increased disability and medical needs. This article elucidates common ethical issues encountered in discharge planning with older adults. We conducted normative ethical analysis of a clinical case using methods of philosophical inquiry, including thick description, reflexivity, conceptual clarification and examination of competing arguments for internal consistency. The analysis demonstrates how health-care teams struggle to balance protection from harm while honouring informed choices. We argue that ethical discharge planning requires judicious identification of client values, even if these conflict with team determinations of best interests. Dialogue is needed to identify risks, help clients determine their personal level of acceptable risk and determine provisions to minimise risks.


Determination of T-2 toxin, HT-2 toxin, and three other type A trichothecenes in layer feed by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS)--comparison of two sample preparation methods.
A sensitive method for the simultaneous determination of T-2 toxin, HT-2 toxin, neosolaniol, T-2 triol, and T-2 tetraol in layer feed using high-performance liquid chromatography coupled to triple quadrupole mass spectrometry in the positive ionization mode (LC-ESI-MS/MS) is described. Two fast and easy clean-up methods-with BondElut Mycotoxin and MycoSep 227 columns, respectively-were tested. The separation of the toxins was conducted on a Pursuit XRs Ultra 2.8 HPLC column using 0.13 mM ammonium acetate as eluent A and methanol as eluent B. Detection of the mycotoxins was carried out in the multiple reaction monitoring (MRM) mode using ammonium adducts as precursor ions. Quantification of all analytes was performed with d3-T-2 toxin as an internal standard. The clean-up method with MycoSep 227 columns gave slightly better results for layer feed compared to the method using BondElut Mycotoxin columns (MycoSep 227: recovery between 50 and 63%, BondElut Mycotoxin: recovery between 32 and 67%) and was therefore chosen as the final method. The limits of detection ranged between 0.9 and 7.5 ng/g depending on the mycotoxin. The method was developed for the analysis of layer feed used at carry-over experiments with T-2 toxin in laying hens. For carry-over experiments, it is necessary that the method includes not only T-2 toxin but also the potential metabolites in animal tissues HT-2 toxin, neosolaniol, T-2 triol, and T-2 tetraol which could naturally occur in cereals used as feed stuff as well.


Construction of C(aryl)-C(alkynyl) bond from copper-mediated arene-alkyne and aryl iodide-alkyne cross-coupling reactions: a common aryl-Cu(III) intermediate in arene C-H activation and Castro-Stephens reaction.
Both copper(II)-mediated oxidative C-H bond activation and oxidative addition of copper(I) into a C-I bond produced an identical and structurally well-defined aryl-Cu(III) intermediate. The cross-coupling reaction of an aryl-Cu(III) intermediate with both terminal alkynes at an elevated temperature and alkynyllithium reagents under mild conditions led effectively to the formation of a C(aryl)-C(alkynyl) bond. An alternative mechanism has been proposed for the Castro-Stephens reaction.


Increased hydraulic risk in assemblages of woody plant species predicts spatial patterns of drought-induced mortality.
Predicting drought-induced mortality (DIM) of woody plants remains a key research challenge under climate change. Here, we integrate information on the edaphoclimatic niches, phylogeny and hydraulic traits of species to model the hydraulic risk of woody plants globally. We combine these models with species distribution records to estimate the hydraulic risk faced by local woody plant species assemblages. Thus, we produce global maps of hydraulic risk and test for its relationship with observed DIM. Our results show that local assemblages modelled as having higher hydraulic risk present a higher probability of DIM. Metrics characterizing this hydraulic risk improve DIM predictions globally, relative to models accounting only for edaphoclimatic predictors or broad functional groupings. The methodology we present here allows mapping of functional trait distributions and elucidation of global macro-evolutionary and biogeographical patterns, improving our ability to predict potential global change impacts on vegetation.


Molecular size of myelin basic protein immunoactivity in spinal fluid.
The molecular size of myelin basic protein (MBP) immunoactivity in spinal fluid from patients with multiple sclerosis, acute stroke or who had gone through neurosurgery was determined by gel filtration. Gel filtration fractions were analysed for MBP by radioimmunoassay. Spinal fluid from all patients demonstrated a broad range of MBP immunoactivity. The neurosurgery and stroke cases had high MBP immunoactivity in the higher molecular range, around 67 000 daltons. The spinal fluid from MS patients had increased levels of low molecular size MBP immunoactivity, around 10-13 000 daltons. The results suggest that different forms of demyelinating processes give rise to various kinds of MBP fragments and/or different proteolytic activity on MBP within the spinal fluid space.


When should women be recruited to intrapartum research projects? A retrospective review.
To review and describe the impact of varied recruitment processes in two intrapartum studies. Retrospective review of one prospective cohort study and one pilot randomized controlled trial. Australian tertiary referral hospital. Women with term, cephalic singleton pregnancies. Recruitment processes in one observational and one interventional study examining the management of occipitoposterior position in labor were reviewed. Data concerning recruitment and serial attrition for these studies were collected. The value of allowing consent in early labor in addition to consent in the antenatal period was assessed. Relative proportions of women participating compared with the numbers approached and recruited. One in 48 women approached about the observational study agreed to participate and then had a fetus in occipitoposterior position. One in 33 women in the intervention study were eventually randomized. Women approached in early labor were more likely to agree to participate (77% vs. 58%; p < 0.0001), more likely to have an ultrasound scan during labor (40% vs. 15%; p < 0.0001) and more likely to be randomized to intervention (4% vs. 1.5%; p = 0.02). Intrapartum research is associated with low rates of recruitment and these rates may be improved by asking women to provide informed consent during labor rather than the antenatal period. It is important to consider ways to facilitate randomized controlled trials involving women in labor to advance evidence-based care in this environment. This should include prospective research that seeks to define the best approach to patient recruitment.


Novel Agglomeration Strategy for Elemental Sulfur Produced during Biological Gas Desulfurization.
This article presents a novel crystal agglomeration strategy for elemental sulfur (S) produced during biological desulfurization (BD). A key element is the nucleophilic dissolution of S by sulfide (HS-) to polysulfides (S x 2-), which was enhanced by a sulfide-rich, anoxic reactor. This study demonstrates that with enhanced S x 2- formation, crystal agglomerates are formed with a uniform size (14.7 ± 3.1 μm). In contrast, with minimal S x 2- formation, particle size fluctuates markedly (5.6 ± 5.9 μm) due to the presence of agglomerates and single crystals. Microscopic analysis showed that the uniformly sized agglomerates had an irregular structure, whereas the loose particles and agglomerates were more defined and bipyramidal. The irregular agglomerates are explained by dissolution of S by (poly)sulfides, which likely changed the crystal surface structure and disrupted crystal growth. Furthermore, S from S x 2- appeared to form at least 5× faster than from HS- based on the average S x 2- chain length of x ≈ 5, thereby stimulating particle agglomeration. In addition, microscopy suggested that S crystal growth proceeded via amorphous S globules. Our findings imply that the crystallization product is controlled by the balance between dissolution and formation of S. This new insight has a strong potential to prevent poor S settleability in BD.


Biomechanical properties of lightweight versus heavyweight meshes for laparoscopic inguinal hernia repair and their impact on recurrence rates.
Laparoscopic inguinal hernia repair can be performed using light- or heavyweight meshes. Apart from the size of the mesh, its friction coefficient (mu(0)) and flexural stiffness are of crucial importance to avoidance of hernia recurrence. In the current biomechanical study, tensile tests were performed to determine the ultimate tensile strength and modulus of elasticity of six lightweight meshes and six heavyweight meshes for laparoscopic inguinal hernia repair. To determine their friction coefficient (mu(0)), the meshes were placed between a resected peritoneum and groin muscles during an autopsy. Meshes measuring 15 x 10 cm in size then were used in a hernia model with an opening size of 1.5, 3, or 5 cm. The ultimate tensile strength and modulus of elasticity were significantly lower in the lightweight mesh group than in the heavyweight mesh group. The mean friction coefficient (mu(0)) of the meshes was 0.4. Given an opening of 1.5 cm, all meshes remained adequately stable. At opening sizes of 3 and 5 cm, the lightweight meshes flexed on the average by 3.16 +/- 0.4 mm and 10.40 +/- 2.5 mm, respectively. Heavyweight meshes, on the other hand, were significantly less flexible. Their mean flexure was, respectively, 0.34 +/- 0.2 mm and 3.97 +/- 0.7 mm (p < 0.001). Stable meshes are characterized by a small degree of flexure and do not slide into the gap even when subjected to repetitive loads. Therefore, in terms of hernia recurrence, meshes with greater flexural stiffness or well-fixed lightweight meshes that adequately overlap the hernia defect can be used for laparoscopic treatment of large inguinal hernias.


A g-C3N4/nanocarbon/ZnIn2S4 nanocomposite: an artificial Z-scheme visible-light photocatalytic system using nanocarbon as the electron mediator.
A g-C3N4/nanocarbon/ZnIn2S4 (CN/C/ZIS) nanocomposite with enhanced photocatalytic H2 production performance has been successfully synthesized. Based on the experimental results, for the first time, it has been demonstrated that nanocarbon could be integrated into a Z-scheme photocatalytic system and acted as an excellent solid electron mediator.


Wheat cultivar-specific proteins in grain revealed by 2-DE and their application to cultivar identification of flour.
Wheat flour proteins were studied to identify the cultivar-specific proteins and use them to identify cultivars in flours. Proteins extracted from flours of Japanese wheat (cultivars Hokushin, Horoshirikomugi, Kitanokaori and Kachikei 33) and Canadian wheat (Canada Western Red Spring Wheat No. 1; 1CW) were analyzed by 2-DE with IEF gels over three pH ranges: pH 4-7, pH 5-8, and pH 6-11. This system enabled detection of more than 1600 protein spots. We recognized that among 50 protein spots showing cultivar-dependent qualitative changes, 25 proteins were wheat cultivar specific. These 50 protein spots were analyzed by N-terminal Edman degradation microsequencing and MALDI-TOF-MS; 21 protein spots were storage proteins, such as gliadin and low-molecular mass glutenin subunit. Five protein spots were identified as dehydroascorbate reductase (Triticum aestivum), triticin precursor (T. aestivum), alpha-amylase inhibitor (Oryza sativa), DNA-binding with one finger (Dof) zinc family protein (O. sativa), and nonphototropic hypocotyl 1 (NPH1) protein (Avena sativa). The other protein spots appeared to be hypothetical proteins (O. sativa or Arabidopsis thaliana) or functional unknown proteins. These specific proteins can be used as markers to identify wheat cultivars in blended flour composed of two or three flours.


Recovery of low thymic hormone levels in cancer patients by lysine-arginine combination.
Thymic hormones are required for maturation and maintenance of the immune efficiency. It has been previously demonstrated that with advancing age there occurs a progressive reduction of the plasma level of one of the best known thymic peptides, i.e. thymulin, and that the administration of an amino acid combination (lysine-arginine, as present in the commercial preparation Lysargin, Baldacci, Italy) to elderly individuals is able to increase the synthesis and/or release of thymulin to values comparable to those recorded in young subjects. In the present paper we report evidence that cancer patients show much lower thymulin values than those recorded in healthy age-matched individuals and that the oral administration of the amino acid preparation is able to significantly increase thymulin levels even over the values of age-matched controls and to increase the number of peripheral T-cell subsets. It is suggested that such an effect is mediated through the known secretagogue activity of the amino acids on the pituitary release of growth hormone, which has a modulating effect on the thymic endocrine activity.


"I'm Going to Shut Down All of Your Tricks": Depictions of Treatment Professionals in Addiction Entertainment.
Previous research on addiction themed reality television shows has focused on the depiction of addiction and treatment and has concluded that these shows reinforce stigma. Existing research has not investigated the depiction of treatment professionals in these series. This study fills the gap in existing research by analyzing the representations of treatment professionals in reality television shows, including the ways that the shows are edited, the statements made by treatment professionals, and interactions between treatment professionals and laypersons. The data for this study was drawn from two popular reality shows Intervention and Celebrity Rehab with Dr. Drew. Using a total of 117 episodes, a qualitative content analysis of the representations of treatment professionals in the two series was conducted. The data reveal the ways that depictions of treatment professionals are carefully controlled compared to those of people with substance use issues. In addition, treatment professionals are granted opportunities to interpret, explain, and diagnose the behaviors and experiences of people with substance use problem. Finally, when confronted with resistance treatment professionals assert their authority and demand compliance with their orders. In strategically presenting treatment professionals in sharp contrast to people with substance use problems, these portrayals of treatment professionals actually reinforce rather than contradict the stigma of addiction.


Effect of nanoparticle loading and magnetic field application on the thermodynamic, optical, and rheological behavior of thermoresponsive polymer solutions.
Although processing via external stimuli is a promising technique to tune the structure and properties of polymeric materials, the impact of magnetic fields on phase transitions in thermoresponsive polymer solutions is not well-understood. As nanoparticle (NP) addition is also known to impact these thermodynamic and optical properties, synergistic effects from combining magnetic fields with NP incorporation provide a novel route for tuning material properties. Here, the thermodynamic, optical, and rheological properties of aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions are examined in the presence of hydrophilic silica NPs and magnetic fields, individually and jointly, via Fourier-transform infrared spectroscopy (FTIR), magneto-turbidimetry, differential scanning calorimetry (DSC), and magneto-rheology. While NPs and magnetic fields both reduce the phase separation energy barrier and lower optical transition temperatures by altering hydrogen bonding (H-bonding), infrared spectra demonstrate that the mechanism by which these changes occur is distinct. Magnetic fields primarily alter solvent polarization while NPs provide PNIPAM-NP H-bonding sites. Combining NP addition with field application uniquely alters the solution environment and results in field-dependent rheological behavior that is unseen in polymer-only solutions. These investigations provide fundamental understanding on the interplay of magnetic fields and NP addition on PNIPAM thermoresponsivity which can be harnessed for increasingly complex stimuli-responsive materials.


Decaffeination and improvement of taste, flavor and health safety of coffee and tea using mid-infrared wavelength rays.
Coffee (Coffea arabica) and tea (Camellia sinensis) are beverages consumed widely across the globe. Flavor enhancement of beverages is the prime interest for consumers and industry, but it is still a major challenge for researchers. In this work, we aimed to enhance the sensory characteristics and lower the caffeine content of tea and coffee by applying 2-6 μm mid-infrared wavelengths emitted through our recently invented Mid-Infrared Generating Atomizer (MIRGA) without creating any adverse effects. Two methods were followed: Direct MIRGA spraying over the packaged coffee or tea powder packets, and direct MIRGA spraying over the liquid coffee or tea. Controls were maintained in both methods. The treated samples were subjected to organoleptic tests by an expert panel and consumers. This study is supported by comprehensive field trials, including sensory attributes evaluation and laboratory analyses. In coffee, spraying resulted in 8% decaffeination and increase in theobromine and theophylline by 40% and 10-20%, respectively. In tea, caffeine and theobromine increased by 20-25% and 30%, respectively in addition to a 0.6-1.2% increase in thearubigins. A 20-30% lower amount of sprayed coffee or tea powder was required to prepare beverages with regular sensory characteristics. We have proven that the MIRGA technology applied to the products reduced the caffeine content in coffee, rendered them safe to consume, improved the taste and flavor, and induced health benefits. In addition, as the MIRGA platform contributed toward improving the product characteristics, it can also positively impact their price and affordability. Applications of MIRGA technique and its benefits can be potentially scaled up and utilized for a variety of products used in daily life.


Workplace bullying and general health status among the nursing staff of Greek public hospitals.
The arduous emotional and physical nurses' work, the gradual nursing staff cutbacks and the lack of recognition that nurses feel regarding their skills and overall capabilities are some of the factors that act of bullying between nursing staff and management, between nurses and patients/families or even among nurses themselves. Workplace bullying has physical and psychological effects on worker-victims and, by extension, patients themselves. The purpose of this study was to investigate the relationship between the phenomenon of workplace bullying and general health status among the nursing staff of Greek public hospitals. A cross-sectional study was conducted on a convenience sample of 841 members of the nursing staff working in five major hospitals of the 1st Regional Health Authority of Attica, located in Athens. The response rate was 84.1 %. The respondents completed the Negative Acts Questionnaire (NAQ) and the General Health Questionnaire (GHQ-12) and also their demographic characteristics. The appropriate permissions were obtained by the Hospitals' Ethics Committees and the questionnaire's authors. Data were collected from March to July 2013. Data analysis was performed with IBM SPSS 21.0 and included t test, χ (2) test and regression analysis. The two-tailed significance level was set ≤0.05. 30.2 % of the respondents reported that they had been psychologically harassed in their workplaces during the preceding 6 months. Statistical analysis revealed that relative to other respondents, respondents who had received support from their families and friends enjoyed better health but respondents who perceived their work environments more negatively because of work-related bullying suffered from worse general health. Workplace bullying among nursing staff is a major concern in Greece. Support systems play a crucial role in addressing the negative effects of bullying and they should be taken into account when designing prevention and troubleshooting policies about bullying.


Searching for unpublished data for Cochrane reviews: cross sectional study.
To describe the experiences of authors of Cochrane reviews in searching for, getting access to, and using unpublished data. Cross sectional study. Cochrane reviews. 2184 corresponding authors of Cochrane reviews as of May 2012. Frequencies of responses to open ended and closed questions in an online survey. Of 5915 authors contacted by email, 2184 replied (36.9% response rate). Of those, 1656 (75.8%) had searched for unpublished data. In 913 cases (55.1% of 1656), new data were obtained and we received details about these data for 794 data sources. The most common data source was "trialists/investigators," accounting for 73.9% (n=587) of the 794 data sources. Most of the data were used in the review (82.0%, 651/794) and in 53.4% (424/794) of cases data were provided in less than a month. Summary data were most common, provided by 50.8% (403/794) of the data sources, whereas 20.5% (163/794) provided individual patient data. In only 6.3% (50/794) of cases were data reported to have been obtained from the manufacturers, and this group waited longer and had to make more contacts to get the data. The data from manufacturers were less likely to be for individual patients and less likely to be used in the review. Data from regulatory agencies accounted for 3.0% (24/794) of the obtained data. Most authors of Cochrane reviews who searched for unpublished data received useful information, primarily from trialists. Our response rate was low and the authors who did not respond were probably less likely to have searched for unpublished data. Manufacturers and regulatory agencies were uncommon sources of unpublished data.


Glatiramer acetate induces pro-apoptotic mechanisms involving Bcl-2, Bax and Cyt-c in peripheral lymphocytes from multiple sclerosis patients.
Apoptotic deletion of autoreactive T-cells is defective in patients with multiple sclerosis (MS). Glatiramer acetate (GA) treatment seems to restore apoptosis of detrimental T-cells. We analyzed the mitochondria membrane pro- (Bax) and anti-apoptotic (Bcl- 2) and cytosolic pro-apoptotic (Cyt-c, APAF-1) proteins expression in peripheral lymphocytes from relapsing-remitting (RR) MS patients during GA treatment. Blood samples were collected from 8 healthy controls (HCs) and from 8 RR MS patients prior to and every three months during the 9 months of GA treatment. Peripheral blood mononuclear cells (PBMNCs) Bcl-2, Bax, Cyt-c and APAF-1 were quantified by western blot followed by densitometric scanning and Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios were calculated. T-cells were in vitro tested for oxygen consumption by a respirometric analysis. Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios in untreated MS patients were significantly (p < 0.05) lower than in HCs. Bax/Bcl-2 ratio increased (p = 0.03) and Cyt-c/Bcl-2 ratio showed a trend to increase during the 9 months of GA treatment in MS patients. A reduction of 58% and 59% in oxygen consumption by PBMNCs was evident after GA treatment in vitro or when GA treated patients' cells were compared with those from HCs, respectively. Our findings suggest that GA exerts a regulatory effect on peripheral T lymphocytes through pro-apoptosis mechanisms involving mitochondria and cytosolic proteins.


AGXT2: An unnegligible aminotransferase in cardiovascular and urinary systems.
Cardiovascular diseases (CVDs) and renal impairment interact in a complex and interdependent manner, which makes clarification of possible pathogenesis between CVDs and renal diseases very challenging and important. There is increasing evidence showing that both asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) play a crucial role in the development of CVDs as well as in the prediction of cardiovascular events. Also, the plasma levels of ADMA and SDMA were reported to be significantly associated with renal function. Alanine-glyoxylate aminotransferase 2 (AGXT2) is reported to be involved in ADMA and SDMA metabolism, thus deficiency in the expression or activity of AGXT2 may play a part in the progression of cardiovascular or renal diseases through affecting ADMA/SDMA levels. Here, we focused our attention on AGXT2 and discussed its potential impact on CVDs and renal diseases. Meanwhile, the review also summarized the functions and recent advances of AGXT2, as well as the clinical association studies of AGXT2 in cardiovascular and urinary systems, which might arouse the interest of researchers in these fields.


Ligneous conjunctivitis. A clinicopathologic study of 17 cases.
Seventeen cases of ligneous conjunctivitis were studied. Most of the patients were children; however, two elderly individuals were involved (range, birth to 85 years). The most common site was the tarsal conjunctiva, where firm sessile or pedunculated membranous lesions were seen. However, corneal involvement, as well as similar and recurrent lesions, were also present in the larynx, vocal cords, trachea, nose, vagina, cervix, and gingiva. Many recurrences (up to 10 times) rapidly followed simple surgical excision in all patients. Histopathologically, the lesions were characterized by subepithelial, eosinophilic, amorphous material admixed with acute and chronic inflammatory cells. The finding of amorphous material containing fibrin, immunoglobulins, and albumin suggested leakage from hyperpermeable blood vessels. Electron microscopic studies of the lesions disclosed few abnormal blood vessels with wide gaps between endothelial cells that were surrounded by a thick multilaminar basement membrane. The duration of the disease ranged from 4 months to 44 years. After several recurrences, spontaneous resolution occurred in six patients.


Rights as Relationships: Collaborating with Faith Healers in Community Mental Health in Ghana.
This paper explores the ways in which mental health workers think through the ethics of working with traditional and faith healers in Ghana. Despite reforms along the lines advocated by global mental health, including rights-based legislation and the expansion of community-based mental health care, such healers remain popular resources for treatment and mechanical restraint and other forms of coercion commonplace. As recommended in global mental health policy, mental health workers are urged to form collaborations with healers to prevent human rights abuses and promote psychiatric alternatives for treatment. However, precisely how such collaborations might be established is seldom described. This paper draws on ethnographic research to investigate how mental health workers approach working with healers and the moral imagination which informs their relationship. Through an analysis of trainee mental health workers' encounters with a Prophet and his patients, the paper reveals how mental health workers attempt to negotiate the tensions between their professional duty of care, their Christian faith, and the authority of healers. I argue that, rather than enforcing legal prohibitions, mental health workers seek to avoid confrontation and manouver within existing hierarchies, thereby preserving sentiments of obligation and reciprocity within a shared moral landscape and established forms of sociality.


In vitro metabolism of chlorpheniramine in the rabbit.
The in vitro metabolism of 3-(p-chlorophenyl)-3-(2-pyridyl)-N, N-dimethylpropylamine (chlorpheniramine, I) by rabbit liver microsomes was examined. The metabolites, tentatively identified by gas-liquid chromatography-mass spectrometry, included the mono- and didemethyl metabolites, the aldehyde that results from deamination, and further metabolites of this aldehyde including its intramolecular cyclization product, an indolizine, and its reduction product, the alcohol. Inhibition of metabolism of I by N2, CO, SKF-525A, 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), or deletion of NADPH implies some involvement of cytochrome P-450 in the metabolic reactions. Quantitation of metabolism in these studies accounted for only 69% of the dose, so that binding and/or other undetected metabolic pathways were operative.


Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages.
For the discovery of new pentacyclic triterpenes as a potential anti-inflammatory agent, microbial transformation of uvaol by Penicilium griseofulvum CICC 40293 and Streptomyces griseus ATCC 13273 was investigated. Stereoselective hydroxylation and epoxidation reactions were observed in the biotransformation. Moreover, six new metabolites were isolated and structurally elucidated by HR-ESI-MS and NMR spectrum. All the compounds were evaluated upon the inhibitory effects of nitric oxide (NO) release in RAW 264.7 cells induced by lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1). Among them, compound 3 (13, 28-epoxy-3β, 7β, 21β-trihydroxy-urs-11-ene) with the unique epoxy structure and compound 5 (3β, 21β, 24, 28-tetrahydroxy-urs-12-en-30-oic acid), exhibited a considerable inhibitory effect on both models while compound 2 (urs-12-ene-3β, 7β, 21β, 28-tetraol) showed a significant bias in the LPS-induced inflammatory response with IC50 value of 2.22 μM. Therefore, this study could provide some insights on the discovery of the pentacyclic triterpene leads for the treatment of either DAMPs or PAMPs triggered inflammation.


Cell surface characteristics and DNA content of macrophages in murine bone marrow cultures. A study using simultaneous scanning electron microscopy and fluorescence microscopy.
An instrument combining scanning electron microscopy (SEM) and light microscopy (LM) was used to study the cell surface characteristics and DNA content of macrophages in murine bone marrow cultures. After a quantitative Feulgen DNA staining, the DNA content of the individual macrophages was measured and their cell surface morphology was studied immediately thereafter with the SEM part of the instrument. The cells were divided into six groups according to the number of microvilli and/or microridges present on their surface. A proportion of macrophages showed a DNA content more than occurs in diploid cells, which could indicate a future division. No special surface morphology could be detected in this cell type.


Moiré Superstructure and Dimensional Crossover of 2D Electronic States on Nanoscale Lead Quantum Films.
We investigate using scanning tunneling microscopy and spectroscopy electronic aspects of Moiré superstructures in nanoscale Pb quantum films grown on IrTe2, which is a unique layered material with charge-order transitions into stripe phases. Pb ultrathin films exhibit a Moiré superstructure due to the lattice mismatch of Pb and IrTe2, which produces strong lateral electronic modulation of hexagonal symmetry and discreet subbands. Moreover, strongly anisotropic or 1D electronic states are formed in Pb films as modulated by the stripe charge order. Present results indicate the controllability of lateral electronic structures of various ultrathin films by extra interfacial potentials due not only to Moiré superstructures but also to novel electronic orderings of substrates.


Predictors of adverse maternal and perinatal outcomes in a refugee population from an active conflict country, Syria.
To elucidate predictors of adverse maternal and perinatal outcomes in refugees emigrating from an active conflict region (Syria). This study included Syrian pregnant women who gave birth in Etlik Zübeyde Hanım Training and Research Hospital between 2013 and 2016. Adverse perinatal outcomes were defined as preterm labor, premature rupture of membranes, early membrane rupture, intrauterine growth retardation, hypertension, perinatal excites, and erythrocyte-transfused cases. Factors associated with those adverse outcomes were assessed using multiple logistic regression analysis. Having an active smoking habit [odds ratio (OR): 2.647, 95% confidence interval (CI): 1.767-3.965; p<0.001], obesity (OR: 2.272, 95% CI: 1.396-3.699; p=0.001), and adolescent age (OR: 1.732, 95% CI: 1.204-2.491; p=0.003) were found to be the most important predictors of adverse maternal and perinatal outcomes. Eighty of 129 (62%) smokers, 45 of 81 (55.65%) obese individuals, and 91 of 169 adolescents (53.8%) had adverse maternal and perinatal outcomes. Prevention strategies for obesity, smoking, and adolescent pregnancies should be implemented primarily to reduce maternal and antenatal adverse outcomes. Pregnant women with these risk factors in a refugee community emigrating from a conflict-zone nation should be followed up closely.


INTRAVITREAL CONBERCEPT (KH902) FOR SURGICAL TREATMENT OF SEVERE PROLIFERATIVE DIABETIC RETINOPATHY.
To evaluate the role, safety, and effectiveness of intravitreal conbercept (KH902) injections as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy. A randomized controlled trial was performed on 36 eyes of 36 patients affected by vitreous hemorrhage and tractional retinal detachment, which occurred as a consequence of active proliferative diabetic retinopathy. The patients were randomly assigned to two groups. The patients in one of the groups received an intravitreal injection of conbercept in the inferior temporal sector 4 mm from the sclerocorneal limbus with a sterile technique 1 week before vitrectomy. In the group without conbercept, intraoperative bleeding occurred in 14 patients (77.8%), and in five of these cases, bleeding was significant. The use of endodiathermy was necessary in 8 patients (44.4%). In 3 patients (16.6%), iatrogenic retinal breaks occurred, and in 1 patient (5.5%), a relaxing retinotomy was performed. Endotamponade with silicone oil was performed in 12 patients (66.6%). In the group treated with conbercept, intraoperative bleeding occurred in 2 cases (11.1%). The use of endodiathermy was necessary in 1 patient (5.5%). No patients experienced iatrogenic breaks or relaxing retinotomy during the surgery. Endotamponade with silicone oil was performed in 2 patients (11.1%). Preoperative intravitreal injection of conbercept could reduce the chances of intraoperative bleeding, which are beneficial in the management of proliferative diabetic retinopathy.


S100 beta stimulates calcium fluxes in glial and neuronal cells.
The glial-derived protein S100 beta can act as a mitogen or a neurotrophic factor, stimulating proliferation of glial cells or differentiation of immature neurons. We report here that dimeric S100 beta evokes increases in intracellular free calcium concentrations ([Ca2+]i) in both glial cells and neuronal cells. The [Ca2+]i increase exhibited a rapid transient component which was not affected by removal of extracellular calcium and a sustained component which appeared to require influx of extracellular calcium through Ni(2+)-sensitive channels. S100 beta also stimulated hydrolysis of phosphoinositides, suggesting a mobilization of calcium from intracellular stores. These data suggest that although the final biological responses of neuronal and glial cells to S100 beta are different, transduction of the S100 beta signal in both cell types involves changes in [Ca2+]i.


Yeast artificial chromosomes: tools for mapping and analysis of complex genomes.
Libraries of yeast artificial chromosomes (YACs) are representative of complex genomes, and typical YACs contain single fragments of DNA that are up to a megabase or more in size, are stable during growth, and are faithful to genomic DNA. Such YACs may permit (1) the use of complete gene units for a number of research and medical purposes; and (2) the assembly of chromosome-sized contigs in a single map that unifies genetic and physical data.


Growth charts for Brazilian children with Down syndrome: Birth to 20 years of age.
The growth of youth with Down syndrome (DS) differs from that of youth without DS, and growth charts specific to DS have been developed. However, little is known about the growth of Brazilian youth with DS. The objective of this study was to construct growth charts for Brazilian youth with DS and compare the growth data with the Child Growth Standards of the World Health Organization (WHO) and charts for children with DS from other studies. Mixed longitudinal and cross-sectional data were collected at University of Campinas, 48 specialized centers for people with intellectual disabilities, and two foundations for people with DS between 2012 and 2015. A total of 10,516 growth measurements from birth to 20 years of age were available from 938 youth with DS (53.7% boys) born between 1980 and 2013. The Lambda Mu Sigma method was applied to construct the curves using generalized additive models for location, scale, and shape. Length/height-for-age, weight-for-age, and head circumference-for-age percentile curves were generated for Brazilian boys and girls from birth to 20 years of age. Differences in growth of Brazilian youth ranged from -0.8 to -3.2 z-scores compared to WHO standards, and -1.9 to +1.3 compared to children with DS in other studies. These specific growth charts may guide clinicians and families in monitoring the growth of Brazilian children and adolescents with DS.


The effects of genetic screening and assortative mating on lethal recessive-allele frequencies and homozygote incidence.
The widespread use of genetic screening, along with mating and reproductive patterns reflecting that information, can significantly alter the genetic structure of populations. Both allele frequencies and mortality could be significantly reduced if carriers of lethal recessive alleles were withdrawn from the mating pool. But schemes to mask deleterious alleles in heterozygous condition could significantly increase the deleterious-allele frequencies while resulting in only a slight reduction in mortality. The immediate and equilibrium consequences of such mating strategies may be quite disparate.


Relationships among pulmonary function, anxiety and depression in mild asthma: An exploratory study.
In a secondary analysis of data from a prior study, we calculated the relationships among depression (PHQ-8), anxiety (GAD-7), and measures of asthma in 69 steroid-naïve patients with mild and moderate symptomatic asthma. Average levels of pulmonary function, depression and anxiety tended to be in the normal range, and asthma tended to be well controlled (Asthma Control Test). Nevertheless, PHQ-8 scores were significantly correlated with forced oscillation (FO) measures of airway reactance (AX) and resistance at a low frequency of stimulation (Rrs5 Hz). GAD-7 scores also were significantly related to Rrs5 Hz. Exploratory analyses in Supplementary data provide no evidence for vagal mediation of the association. Further research is necessary to discover mechanisms for the associations found here. Future studies might examine the utility of assessing and treating mild anxiety and depression in mild to moderate asthma.


[Structure and aggregation of histones. I. Influence of the ionic composition of the medium on the structure and effectiveness of the intermolecular relationships of histone F2a (H2A+H4)].
The investigation of fluorescence and light-scattering change of histone F2a, ribonuclease, tyrosine, N-acetyltirosinamide, methyl ether tyrosine by the concentration increasing of NaCl, MgCl2, Na2SO4 in the surrounding medium was carried out. In the case of used salts the changes of tertiary structure and histones aggregations depend on the anion type, which is presented in the environment. The tertiary structure of histones formed in the presence of salt is stabilized by weak (hydrophobic and hydrogenic) interactions.


Percutaneous cerclage wiring and minimally invasive plate osteosynthesis (MIPO): a percutaneous reduction technique in the treatment of Vancouver type B1 periprosthetic femoral shaft fractures.
Periprosthetic femoral fractures (PPFs) associated at or near a well-fixed femoral prostheses (Vancouver type-B1) present a clinical challenge due to the quality of the bone stock and instability of the fracture. The purpose of this study was to present a novel reduction technique and analyze clinical and radiographic outcome in patients with Vancouver type-B1 fractures treated with percutaneous cerclage wiring for fracture reduction and maintenance of reduction with minimally invasive plate osteosynthesis (MIPO) utilizing a locking compression plate (LCP). Between March 2007 and December 2008, ten consecutive patients with spiral, oblique or wedge Vancouver type-B1 were treated with closed percutaneous cerclage wiring using a new cerclage passer instrument (Synthes) through small 2-3 cm incisions for reduction and maintenance of reduction. Internal fixation with MIPO was obtained utilizing a long LCP Synthes bridging the fracture. The reduction time, fixation time and operative time were recorded. The rehabilitation protocol consisted of partial weight bearing as tolerated. Clinical and radiographic outcomes included evidence of union, return to pre-injury mobility, and surgical complications were recorded. There were three men and seven women with an average age of 74 years (range 47-84 years) at the time the fracture occured. The average follow-up was 13.2 months. One patient died 2 months after surgery due to cardiovascular problems and was excluded. The average reduction time with percutaneous cerclage wiring was 24.4 min (range 7-45 min). The average fixation time was 79 min (range 53-100 min). The average operative time was 103 min (range 75-140 min). Blood loss was minimal and only two patients needed a blood transfusion. All fractures healed with a mean time to union of 18 weeks (range 16-20 weeks). There was one implant which bent 10° in the post-operative period but went on to heal uneventfully within 16 weeks. There was no evidence of loosening of any implants. Seven patients returned to their previous level of mobility. Two patients required a walker. There were no implant failures, wound complications or infections. Percutaneous reduction of spiral, oblique or wedge-type B1 PPFs with percutaneous cerclage wiring combined with minimally invasive locking plate osteosynthesis provided satisfactory reduction, adequate stability and healing in nine patients. Our early results suggest that this reduction technique and fixation may be a useful solution for this growing challenge in orthopaedics. The authors caution that this technique must be done carefully to avoid serious complications, e.g., vascular injury.


Involvement of histone methylation in the regulation of neuronal death.
Neuronal death occurs in various physiological and pathological processes, and apoptosis, necrosis, and ferroptosis are three major forms of neuronal death. Neuronal apoptosis, necrosis, and ferroptosis are widely identified to involve the progress of stroke, Parkinson's disease, and Alzheimer's disease. A growing body of evidence has pointed out that neuronal death is tightly associated with expression of related genes and alteration of signaling molecules. In addition, recently, epigenetics has been increasingly focused on as a vital regulatory mechanism for neuronal apoptosis, necrosis, and ferroptosis, providing a new direction for treating nervous system diseases. Moreover, growing researches suggest that histone methylation or demethylation is involved in the processes of neuronal apoptosis, necrosis, and ferroptosis. These researches may imply that studying the potential roles of histone methylation is essential for treating the nervous system diseases. Here, we review potential roles of histone methylation and demethylation in neuronal death, which may give us a new direction in treating the nervous system diseases.


Tricuspid Regurgitation Velocity and Mean Pressure Gradient for the Prediction of Pulmonary Hypertension According to the New Hemodynamic Definition.
The hemodynamic definition of PH has recently been revised with unchanged threshold of peak tricuspid regurgitation velocity (TRV). The aim of this study was to evaluate the predictive accuracy of peak TRV for PH based on the new (>20 mmHg) and the old (>25 mmHg) cut-off value for mean pulmonary artery pressure (mPAP) and to compare it with the mean right ventricular-right atrial (RV-RA) pressure gradient. Patients with advanced heart failure were screened from 2016 to 2021. The exclusion criteria were absent right heart catheterization (RHC) results, chronic obstructive pulmonary disease, any septal defect, inadequate acoustic window or undetectable TR. The mean RV-RA gradient was calculated from the velocity-time integral of TR. The study included 41 patients; 34 (82.9%) had mPAP > 20 mmHg and 24 (58.5%) had mPAP > 25 mmHg. The AUC for the prediction of PH with mPAP > 20 mmHg was 0.855 for peak TRV and mean RV-RA gradient was 0.811. AUC for the prediction of PH defined as mPAP > 25 mmHg for peak TRV was 0.860 and for mean RV-RA gradient was 0.830. A cutoff value of 2.4 m/s for peak TRV had 65% sensitivity and 100% positive predictive value for predicting PH according to the new definition. Peak TRV performed better than mean RV-RA pressure gradient in predicting PH irrespective of hemodynamic definitions. Peak TRV performed similarly with the two definitions of PH, but a lower cutoff value had higher sensitivity and equal positive predictive value for PH.


Coronary sinus anatomical features: Description and procedural implications during coronary sinus Reducer implantation.
We hypothesized that some coronary sinus (CS) anatomies allow a more straightforward CS Reducer (CSR) implantation. Recent decades have seen a rise in patients with chronic angina. When complete revascularization and maximal medical therapy fail to reduce symptoms, CSR has become a new therapeutic option. We identified a classical C-shape-a near horizontal course of the proximal portion of a circular CS-in a retrospective analysis of 47 CSR implantations and compared the procedural time, fluoroscopic time, contrast use, presence of valves or bifurcations and procedural complications with the non-C-shape CS anatomy. We found a significant difference in procedural (20.0 [19.0-24.7] min vs. 24.5 [20.7-51.0] min; p = .028 and fluoroscopic time (9.5 [7.5-14.5] min vs. 11.0 [7.9-30.0] min; p = .016). There was no significant difference in contrast use. The presence of bifurcations or valves along the CS course did not influence the procedural timings. This study is the first systematic evaluation of CS anatomy and its procedural implications. We identified a favorable C-shape anatomy which allows for a more straightforward implantation. Operators should be aware of the different implications of CS anatomy, their influence on guiding catheter stability and overall procedure complexity.


Fluid Dynamics-Derived Parameters in Coronary Vessels.
Continued development in the field of cardiovascular modeling over the past few years has contributed to the production of precise three-dimensional models of main coronary arteries. Computational fluid dynamic-derived parameters such as smartFFR, a CT-FFR surrogate, and endothelial shear stress (ESS) can be assessed from non-invasive imaging techniques like computed tomography coronary angiography using novel 3D reconstruction methods and can be used to investigate the functional significance of an artery. The investigation of the different flow conditions for the calculation (steady state vs. transient) of the ESS presents that while there is a difference in the final values, it is not statistically significant. ESS in the whole vessel is higher compared to the lesion-specific segments and smartFFR calculated in lesion segment does not reflect accurately the flow capability of the vessel. Higher ESS is present in vessels with <0.85 smartFFR and both parameters are present higher values in vessels with abnormal PET myocardial perfusion imaging.


Three novel BRCA1/BRCA2 mutations in breast/ovarian cancer families in Croatia.
BRCA1 and BRCA2 genes from 167 candidates (145 families) were scanned for mutations. We identified 14 pathogenic point mutations in 17 candidates, 9 in BRCA1 and 5 in BRCA2. Of those, 11 have been previously described and 3 were novel (c.5335C>T in BRCA1 and c.4139_4140dupTT and c.8175G>A in BRCA2). No large deletions or duplications involving BRCA1 and BRCA2 genes were identified. No founder mutations were detected for the Croatian population. Croatia shares most of the mutations with neighboring Slovenia and also with Germany, Austria and Poland. Two common sequence variants in BRCA1, c.2077G>A and c.4956G>A, were found more frequently in mutation carriers compared to healthy controls. No difference in BRCA2 variants was detected between the groups. Haplotype inference showed no difference in haplotype distributions between deleterious mutation carriers and non-carriers in neither BRCA1 nor BRCA2. In silico analyses identified one BRCA1 sequence variant (c.4039A>G) and two BRCA2 variants (c.5986G>A and c.6884G>C) as harmful with high probability, and inconclusive results were obtained for our novel BRCA2 variant c.3864_3866delTAA. Combination of QMPSF and HRMA methods provides high detection rate and complete coverage of BRCA1/2 genes. Benefit of BRCA1/2 mutation testing is clear, since we detected mutations in young unaffected women, who will be closely monitored for breast and ovarian cancer.


Age-related vulnerabilities of older adults with colon adenomas: evidence from Project Prevent.
This report addresses the interface between cancer and aging in the context of colorectal carcinoma (CRC), the second leading cause of cancer death in the U.S. overall and the first leading cause among individuals age > or = 75 years. Because polyp risk increases with age, interventions to prevent recurrent polyps among older adults likely would reduce CRC morbidity and mortality. Data for this study derive from Project Prevent, a multisite, randomized controlled trial designed to reduce behavioral risk factors for CRC among 1247 adults who underwent the removal of > or = 1 adenomatous colon polyps. Middle-aged and older patients were compared on key cognitive-behavioral mechanisms associated with CRC risk and established age-related factors associated with adverse health outcomes. Relations between cognitive-behavioral mechanisms and age-related vulnerability factors identified subgroups of older polyp patients that may have an enhanced risk for CRC. Compared with middle-aged patients, older patients were less concerned about developing CRC, less motivated to reduce their risk, and less confident that their behavior change efforts would succeed. As expected, they also reported more age-related physical, social, and economic vulnerabilities, as expected. Evidence for enhanced CRC risk was found for older patients with multiple comorbid conditions, low social support for change, and perceptions of income inadequacy. The presence of age-related vulnerability factors may enhance the risk of CRC among older cancer patients by creating barriers to behavioral change. Efforts to reduce the cancer burden in older populations will require attention beyond early detection and surveillance to interventions that account for the unique physical and psychosocial characteristics of older adults.


Phorbol 12-myristate 13-acetate and serum synergize to promote rapamycin-insensitive cell proliferation via protein kinase C-eta.
Previously, we have shown that PKC-eta (protein kinase C-eta) positively regulates glioblastoma proliferation and confers resistance to irradiation-induced apoptosis. In this study, we investigated the efficacy of rapamycin in inhibiting cell proliferation in two glioblastoma cell lines U-251MG (PKC-eta expressing) and U-1242MG (PKC-eta deficient) following PKC-eta activation. In U-251MG cells, rapamycin (10 nM) treatment was less effective as an antiproliferative agent when cells were concurrently stimulated with 10% serum and phorbol 12-myristate 13-acetate (PMA, 100 nM), a potent activator of PKC isozymes. Rapamycin-insensitive growth was owing to PKC-eta, as U-1242MG and U-251MG cells infected with a kinase-dead form of PKC-eta (U-251kr) were susceptible to rapamycin-induced inhibition of cell proliferation. Furthermore, U-251MG cells transfected with PKC-eta antisense oligonucleotides were sensitive to rapamycin. PKC-eta-expressing cells stimulated with PMA maintained p70S6K phosphorylation on Thr389 and phosphorylation of rpS6 (ser235/36), suggesting p70S6K kinase activity was still intact. Inhibition of p70S6K expression with small interfering RNA oligonucleotides inhibited cell proliferation greater than 50% in the presence of a combination of PMA and serum. Additionally, p70S6K co-precipitated with PKC-eta, suggesting a physical interaction between PKC-eta and p70S6K regulates the observed phosphorylation. Taken together, these data demonstrate that rapamycin-insensitive glioblastoma proliferation involves PKC-eta signaling.


Association of RBP4 genetic variants with childhood obesity and cardiovascular risk factors.
Recent data suggest that retinol-binding protein 4 (RBP4) gene variants could be associated with a risk of obesity and its co-morbidities, such as metabolic syndrome, which increases the risk of developing type 2 diabetes mellitus and cardiovascular disease. The present study examined the potential association of RBP4 single nucleotide polymorphisms (SNPs) with childhood obesity and its metabolic complications. Four RBP4 SNPs, rs3758538 (3944A>C), rs3758539 (4406G>A), rs12265684 (12177G>C) and rs34571439 (14684T>G), were genotyped in a population of 180 Spanish Caucasian children (97 obese and 83 normal-weight children). Association of RBP4 SNPs with obesity, metabolic risk factors (blood pressure, triglycerides, high-density lipoprotein cholesterol, insulin resistance) and markers of vascular inflammation, such as high-sensitive C-reactive protein (hs-CRP), was tested. We found SNP rs3758538 to be associated with obesity (p = 0.007). Specifically, each copy of the minor allele C was associated with an increased risk of obesity, by more than twofold, in respect of being homozygous for the major allele A (odds ratio = 2.4; 95% confidence interval = 1.2-4.8). The rs3758538 and rs34571439 RBP4 SNPs correlated with plasma RBP4 levels. The SNPs rs12265684 and rs34571439 correlated with plasma triglyceride levels. The rs34571439 was also associated to hs-CRP levels. Marginal association of RBP4 SNPs with plasma high-density lipoprotein levels (rs34571439), blood pressure (rs12265684) and insulin resistance (rs3758539) was also observed. These findings suggest that childhood obesity may be associated with variations in RBP4 gene. The presence of selective SNPs in the RBP4 gene may account for metabolic complications.


A randomized evaluation of intravenous dexamethasone versus oral acetaminophen codeine in pediatric adenotonsillectomy: emergence agitation and analgesia.
Adenotonsillectomy is the most frequently performed ambulatory surgical procedure in children. Post operative agitation and inadequate pain control, for children undergoing adenotonsillectomy, can be a challenge. The aim of this study was to assess the effect of intravenous dexamethasone and oral acetaminophen codeine on emergence agitation and pain after adenotonsillectomy in children. One hundred and five pediatric patients (3-7 years old), scheduled to undergo adenotonsillectomy under general anesthesia, were enrolled in the study. Thirty minutes before induction, patients were randomized to three groups. Group 1 received 0.2 mg/kg of intravenous dexamethasone and 0.25 ml/kg of oral placebo syrup. Group 2 received 20 mg/kg of oral acetaminophen codeine syrup and 0.05 ml/kg of intravenous saline. Group 3 received 0.25 ml/kg of oral placebo syrup and 0.05 ml/kg of intravenous saline. Emergence agitation and postoperative pain were assessed, recorded and compared. Agitation was less frequent in dexamethasone and acetaminophen codeine groups in comparison with placebo group, but there were not significant differences between the two groups. The pain frequencies in the three groups were not significantly different. The results of this study suggest that the administration of intravenous dexamethasone (0.2 mg/kg) and oral acetaminophen codeine (20 mg/kg) thirty minutes before anesthesia can significantly decrease the incidence and severity of agitation but does not have an effect on postoperative pain.


Reversing the emotional Stroop effect reveals that it is not what it seems: the role of fast and slow components.
The relative contributions of slow and fast (online) components in a modified emotional Stroop task were evaluated. The slow component, neglected in previous research, was shown to lead to the prediction of a reversed emotional intrusion effect using pseudorandomly mixed negative and neutral stimuli. This prediction was supported in Experiments 1 and 2. In Experiments 3 and 4, a new paradigm was developed that allowed a more direct observation of the nature of disruptive effects from negative stimuli. The results provided a clear demonstration of the presence of the slow component. The fast component, which has generally been assumed to be the source of the interference, was shown, in fact, to have little or no role in the disruption.