Gender Inequality Prevents Abused Women from Seeking Care Despite Protection Given in Gender-Based Violence Legislation: A Qualitative Study from Rwanda.
Despite its burden on a person's life, Intimate Partner Violence (IPV) is known to be poorly recognised and managed in most countries and communities. This study aimed to explore health care professionals' experiences of the health care seeking processes of women exposed to intimate partner violence in Rwanda. Six focus group discussions were conducted in three district hospitals and three mental health units in Rwanda. A sample of 43 health care professionals with various professions and length of work experience, who regularly took care of patients subjected to IPV, was selected for focus group discussions. The analysis was performed using qualitative content analysis. The theme "Gendered norms and values defeat the violence legislation in women's health care seeking when women are abused" expressed the health care professionals' experiences of the double-faced situation which women exposed to IPV met in their help seeking process. Positive initiatives to protect women were identified, but the potential for abused women to seek help and support was reduced because of poverty, gender inequality with prevailing strong norms of male superiority, and the tendency to keep abuse as a private family matter. Legislative measures have been instituted to protect women from abuse. Still many Rwandan women do not benefit from these efforts. The role of the health care services needs to be reinforced as an important and available resource for help and support for abused women but further legislative changes are also needed. Initiatives to further improve gender equality, and institutionalised collaboration between different sectors in society would contribute to protecting women from IPV.


Theta oscillations modulate attentional search performance periodically.
Visual search--finding a target element among similar-looking distractors--is one of the prevailing experimental methods to study attention. Current theories of visual search postulate an early stage of feature extraction interacting with an attentional process that selects candidate targets for further analysis; in difficult search situations, this selection is iterated until the target is found. Although such theories predict an intrinsic periodicity in the neuronal substrates of attentional search, this prediction has not been extensively tested in human electrophysiology. Here, using EEG and TMS, we study attentional periodicities in visual search. EEG measurements indicated that successful and unsuccessful search trials were associated with different amounts of poststimulus oscillatory amplitude and phase-locking at ∼6 Hz and opposite prestimulus oscillatory phase at ∼6 Hz. A trial-by-trial comparison of pre- and poststimulus ∼6 Hz EEG phases revealed that the functional interplay between prestimulus brain states, poststimulus oscillations, and successful search performance was mediated by a partial phase reset of ongoing oscillations. Independently, TMS applied over occipital cortex at various intervals after search onset demonstrated a periodic pattern of interference at ∼6 Hz. The converging evidence from independent TMS and EEG measurements demonstrates that attentional search is modulated periodically by brain oscillations. This periodicity is naturally compatible with a sequential exploration by attention, although a parallel but rhythmically modulated attention spotlight cannot be entirely ruled out.


Population coding of interaural time differences in gerbils and barn owls.
Interaural time differences (ITDs) are the primary cue for the localization of low-frequency sound sources in the azimuthal plane. For decades, it was assumed that the coding of ITDs in the mammalian brain was similar to that in the avian brain, where information is sparsely distributed across individual neurons, but recent studies have suggested otherwise. In this study, we characterized the representation of ITDs in adult male and female gerbils. First, we performed behavioral experiments to determine the acuity with which gerbils can use ITDs to localize sounds. Next, we used different decoders to infer ITDs from the activity of a population of neurons in central nucleus of the inferior colliculus. These results show that ITDs are not represented in a distributed manner, but rather in the summed activity of the entire population. To contrast these results with those from a population where the representation of ITDs is known to be sparsely distributed, we performed the same analysis on activity from the external nucleus of the inferior colliculus of adult male and female barn owls. Together, our results support the idea that, unlike the avian brain, the mammalian brain represents ITDs in the overall activity of a homogenous population of neurons within each hemisphere.


KIR genotypic diversity in Portuguese and analysis of KIR gene allocation after allogeneic hematopoietic stem cell transplantation.
The diversity of killer-cell immunoglobulin-like receptors (KIR) genes was evaluated in Portuguese and the observed genotypic profiles were found related to the ones reported in European populations. The KIR repertoire after hematopoietic stem cell transplantation is determined by these gene frequencies and the KIR group B motifs are the less common. We estimated donor-KIR/recipient-ligand interactions in transplants with related donors and unrelated donors found in a local registry or from abroad. A large fraction of transplants had all three ligands of inhibitory receptors, and therefore, in theory were not prone to natural killer cell (NK) mediated alloreactivity. Furthermore, the distribution of KIR alloreactive interactions was found independent of the donor-recipient genetic proximity, probably because of different gene segregation and comparable KIR frequencies in the donor pools.


SU-E-T-596: Choroidal Metastases Irradiation with Volumetric Modulated Arc Radiotherapy.
Intraocular metastases are present in up to 10% of patients with systemic malignancies. With tumor cells spreading hematogenously, the posterior choroid is frequently involved because of its rich vasculature. We treated a woman who developed bilateral choroidal metastases from breast cancer. For the patient, we designed three radiotherapy techniques. The study was to find the dosimetric differences between them. For the patient with bilateral choroidal metastases, three-dimensional conformal radiotherapy (3D-CRT), inverse intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (V-MAT) plans were designed. The prescription dose was 60 Gy in 30 fractions. The dose distribution in the target, the dose to the organs at risk, total MU and delivery time were compared. In 3D-CRT, IMRT and V-MAT plans, the volume of target in 100% prescription dose were 92.5%, 93.3% and 92.0% respectively. V-MAT plan showed the best conformity and homogeneity in target. IMRT plan showed a better homogeneity than 3D-CRT plan. In 3D- CRT, IMRT and V-MAT plans, the max doses on left lens were 975.3 cGy, 739.9cGy, 870.2 cGy respectively. The max doses on right lens were 929.9 cGy, 802.9 cGy and 889.0 cGy respectively. V-MAT plan showed the lowest value for the max dose on left optic nerve and the lower value for the right one compared to 3D-CRT plan. The MUs were 386, 973, 709 and the delivery times were 10 min, 14min and 1.6 min respectively in 3D-CRT, IMRT and V-MAT. V-MAT could significantly reduce the delivery time. V-MAT plan showed the best conformity and homogeneity in target. IMRT showed the lowest value in the max doses to lenses though the delivery time was longest. Overall, V-MAT showed a similar or better dose distribution, and most importantly, improved treatment delivery efficiency. With the results, V-MAT technology could be expected to choroidal metastases.


Can early myocardial infarction-related deaths be diagnosed using postmortem urotensin receptor expression levels?
Myocardial infarction (MI) is one of the most prevalent causes of sudden adult death. It is difficult to diagnose early MI postmortem because there are no typical or characteristic changes in morphology. In this study, changes in the level of the mRNA for the urotensin receptor (UR) were investigated postmortem to determine the suitability of UR as a biomarker for diagnosis of early MI after death. An MI rat model was developed by injecting rats with isoproterenol (ISO) (lethal dose 850 mg/kg) or normal saline (control group). The hearts of rats in the control and ISO-induced MI groups were harvested at 0, 1, 3, 6, 12, 24, 48, and 72 h (h) postmortem. The hearts were then immediately submerged in 1 mL of RNA stabilization solution and stored at 4 °C for <1 week before RNA extraction. Relative UR expression analysis was performed using the StepOne Plus Real Time PCR System with cDNA synthesized from rat heart. Postmortem UR mRNA expression was higher in the ISO-induced MI group than in the control group, at both 4 and 20 °C, at all of the time points examined except 72 h postmortem (p < 0.0001). The largest increases were observed at ambient temperature and 6 h postmortem. Based on our findings, increased postmortem UR expression could serve as a biomarker to aid diagnosis of early MI.


Accurate and exact CNV identification from targeted high-throughput sequence data.
Massively parallel sequencing of barcoded DNA samples significantly increases screening efficiency for clinically important genes. Short read aligners are well suited to single nucleotide and indel detection. However, methods for CNV detection from targeted enrichment are lacking. We present a method combining coverage with map information for the identification of deletions and duplications in targeted sequence data. Sequencing data is first scanned for gains and losses using a comparison of normalized coverage data between samples. CNV calls are confirmed by testing for a signature of sequences that span the CNV breakpoint. With our method, CNVs can be identified regardless of whether breakpoints are within regions targeted for sequencing. For CNVs where at least one breakpoint is within targeted sequence, exact CNV breakpoints can be identified. In a test data set of 96 subjects sequenced across ~1 Mb genomic sequence using multiplexing technology, our method detected mutations as small as 31 bp, predicted quantitative copy count, and had a low false-positive rate. Application of this method allows for identification of gains and losses in targeted sequence data, providing comprehensive mutation screening when combined with a short read aligner.


Applications of Nanoflowers in Biomedicine.
Nanotechnology has opened new windows for biomedical researches and treatment of diseases. Nanostructures with flower-like shapes (nanoflowers) which have exclusive morphology and properties have been interesting for many researchers. In this review, various applications of nanoflowers in biomedical researches and patents from various aspects have been investigated and reviewed. Nanoflowers attracted serious attentions in whole biomedical fields such as cardiovascular diseases, microbiology, sensors and biosensors, biochemical and cellular studies, cancer therapy, healthcare, etc. The competitive power of nanoflowers against other in use technologies provides successful achievements in the progress of mentioned biomedical studies. The use of nanoflowers in biomedicine leads to improving accuracy, reducing time to achieve the results, reducing costs, creating optimal treatment conditions as well as avoiding side effects of the treatment of specific diseases, and increasing functional strength.


Common Cancer Types and Risk of Stroke and Bleeding in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Study in England.
Background The association between cancer and stroke or bleeding outcomes in atrial fibrillation is unclear. We sought to examine how certain types of cancer influence the balance between stroke and bleeding risk in patients with nonvalvular atrial fibrillation (NVAF). Methods and Results We estimated stroke and bleeding risk among adult patients with NVAF and certain types of cancer (breast, prostate, colorectal, lung, and hematological cancer) from 2009 to 2019 based on data from the UK Clinical Practice Research Datalink GOLD and Aurum databases. The control group included patients with NVAF only. Of 177 065 patients with NVAF, 11379 (6.4%) had cancer (1691 breast, 3955 prostate, 1666 colorectal, 2491 hematological, and 1576 lung). Compared with patients without cancer, stroke risk was higher in patients with breast cancer (adjusted hazard ratio [aHR], 1.20 [95% CI, 1.07-1.35) and with prostate cancer (aHR, 1.11 [95% CI, 1.01-1.12) if diagnosed within 6 months before NVAF. The risk of bleeding was increased in subjects with hematological cancer (aHR, 1.55 [95% CI, 1.40-1.71]), lung cancer (aHR, 1.49 [95% CI, 1.25, 1.77]), prostate cancer (aHR, 1.38 [95% CI, 1.28-1.49]), and colorectal cancer (aHR, 1.36 [95% CI, 1.21-1.53]), but not for subjects with breast cancer. The more recent the cancer diagnosis before NVAF diagnosis (within 6 months), the higher the risk of bleeding. Conclusions Breast and prostate cancer are associated with increased stroke risk, whereas in some cancer types, the risk of bleeding seemed to exceed stroke risk. In these patients, prescribing of oral anticoagulant should be carefully evaluated to balance bleeding and stroke risk.


ARbis Pictus: A Study of Vocabulary Learning with Augmented Reality.
We conducted a fundamental user study to assess potential benefits of AR technology for immersive vocabulary learning. With the idea that AR systems will soon be able to label real-world objects in any language in real time, our within-subjects lab-based study explores the effect of such an AR vocabulary prompter on participants learning nouns in an unfamiliar foreign language, compared to a traditional flashcard-based learning approach. Our results show that the immersive AR experience of learning with virtual labels on real-world objects is both more effective and more enjoyable for the majority of participants, compared to flashcards. Specifically, when participants learned through augmented reality, they scored significantly better on both same-day and 4-day delayed productive recall tests than when they learned using the flashcard method. We believe this result is an indication of the strong potential for language learning in augmented reality, particularly because of the improvement shown in sustained recall compared to the traditional approach.


Specific MRI Abnormalities Reveal Severe Perrault Syndrome due to CLPP Defects.
In establishing a genetic diagnosis in heterogeneous neurological disease, clinical characterization and whole exome sequencing (WES) go hand-in-hand. Clinical data are essential, not only to guide WES variant selection and define the clinical severity of a genetic defect but also to identify other patients with defects in the same gene. In an infant patient with sensorineural hearing loss, psychomotor retardation, and epilepsy, WES resulted in identification of a novel homozygous CLPP frameshift mutation (c.21delA). Based on the gene defect and clinical symptoms, the diagnosis Perrault syndrome type 3 (PRLTS3) was established. The patient's brain-MRI revealed specific abnormalities of the subcortical and deep cerebral white matter and the middle blade of the corpus callosum, which was used to identify similar patients in the Amsterdam brain-MRI database, containing over 3000 unclassified leukoencephalopathy cases. In three unrelated patients with similar MRI abnormalities the CLPP gene was sequenced, and in two of them novel missense mutations were identified together with a large deletion that covered part of the CLPP gene on the other allele. The severe neurological and MRI abnormalities in these young patients were due to the drastic impact of the CLPP mutations, correlating with the variation in clinical manifestations among previously reported patients. Our data show that similarity in brain-MRI patterns can be used to identify novel PRLTS3 patients, especially during early disease stages, when only part of the disease manifestations are present. This seems especially applicable to the severely affected cases in which CLPP function is drastically affected and MRI abnormalities are pronounced.


Adsorption of the protein bovine serum albumin in a planar poly(acrylic acid) brush layer as measured by optical reflectometry.
The adsorption of bovine serum albumin (BSA) in a planar poly(acrylic acid) (PAA) brush layer has been studied by fixed-angle optical reflectometry. The influence of polymer length, grafting density, and salt concentration is studied as a function of pH. The results are compared with predictions of an analytical polyelectrolyte brush model, which incorporates charge regulation and excluded volume interactions. A maximum in adsorption is found near the point of zero charge (pzc) of the protein. At the maximum, BSA accumulates in a PAA brush to at least 30 vol %. Substantial adsorption continues above the pzc, that is, in the pH range where a net negatively charged protein adsorbs into a negatively charged brush layer, up to a critical pH value. This critical pH value decreases with increasing ionic strength. The adsorbed amount increases strongly with both increasing PAA chain length and increasing grafting density. Experimental data compare well with the analytical model without having to include a nonhomogeneous charge distribution on the protein surface. Instead, charge regulation, which implies that the protein adjusts its charge due to the negative electrostatic potential in the brush, plays an important role in the interpretation of the adsorbed amounts. Together with nonelectrostatic interactions, it explains the significant protein adsorption above the pzc.


The impact of workplace risk factors on long-term musculoskeletal sickness absence: a registry-based 5-year follow-up from the Oslo health study.
To determine the influence of work-related risk factors by gender on long-term sickness absence with musculoskeletal diagnoses (LSM). Data from the Oslo Health Study were linked to the historical event database of Statistics Norway. Eight thousand three hundred thirty-three participants were followed from 2001 through 2005. Generalized linear models were used to compute risk differences for LSM. In total, 12.6% of the women and 8.8% of the men experienced at least one LSM. Statistically, significant LSM risk increases between 0.039 and 0.086 in association with work environment were found for heavy physical work, low job control (men only), low support from superior (women only), and having shift/night work (men only). Women exhibited a higher LSM risk, but the associations with job exposures were stronger for men. This should be addressed when occupational health services give advice on preventive measures.


Ten-Step Surgical Approach to Management of Pathology of the Ischiorectal Fossa-A Review of the Literature and Application in a Rare Pelvic Schwannoma.
Objective: The ischiorectal fossa is a key anatomical location with boundaries and internal structures owing distinct contributions to function and quality of life. Methods: We highlight the importance of management of pathology in this deep anatomically complex location. Results: We present a ten-step multidisciplinary surgical approach; achieving en bloc radical excision with primary closure and reassuring outcomes. Schwannomas are benign slow-growing nerve sheath tumors. Conclusions: Pelvic schwannomas are rare with only 3 reported cases of the pudendal nerve. We also offer an overview of this rare pathology whilst acknowledging a paucity of recommendations regarding management of disease of the ischiorectal fossa.


Social Network Centrality and Leadership Status: Links with Problem Behaviors and Tests of Gender Differences.
Seventh-grade students (N = 324) completed social cognitive maps to identify peer groups and peer group leaders, sociometric nominations to describe their peers' behaviors, and questionnaires to assess their own behaviors. Peer group members resembled one another in levels of direct and indirect aggression and substance use; girls' cliques were more behaviorally homogenous than were boys' cliques. On average, leaders (especially if they were boys) were perceived as engaging in more problem behaviors than were nonleaders. In girls' cliques, peripheral group members were more similar to their group leader on indirect aggression than were girls who were more central to the clique. Peer leaders perceived themselves as being more able to influence peers but did not differ from nonleaders in their perceived susceptibility to peer influence. The findings contribute to our understanding of processes through which influence may occur in adolescent peer groups.


Comparison of algal and fish sources on the oxidative stability of poultry meat and its enrichment with omega-3 polyunsaturated fatty acids.
Human consumption of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) is below recommendations, and enriching chicken meat (by incorporating LC n-3 PUFA into broiler diets) is a viable means of increasing consumption. Fish oil is the most common LC n-3 PUFA supplement used but is unsustainable and reduces the oxidative stability of the mat. The objective of this experiment was to compare fresh fish oil (FFO) with fish oil encapsulated (EFO) in a gelatin matrix (to maintain its oxidative stability) and algal biomass at a low (LAG, 11), medium (MAG, 22), or high (HAG, 33 g/kg of diet) level of inclusion. The C22:6n-3 contents of the FFO, EFO, and MAG diets were equal. A control (CON) diet using blended vegetable oil was also made. As-hatched 1-d-old Ross 308 broilers (144) were reared (21 d) on a common starter diet then allocated to treatment pens (4 pens per treatment, 6 birds per pen) and fed treatment diets for 21 d before being slaughtered. Breast and leg meat was analyzed (per pen) for fatty acids, and cooked samples (2 pens per treatment) were analyzed for volatile aldehydes. Concentrations (mg/100 g of meat) of C20:5n-3, C22:5n-3, and C22:6n-3 were (respectively) CON: 4, 15, 24; FFO: 31, 46, 129; EFO: 18, 27, 122; LAG: 9, 19, 111; MAG: 6, 16, 147; and HAG: 9, 14, 187 (SEM: 2.4, 3.6, 13.1) in breast meat and CON: 4, 12, 9; FFO: 58, 56, 132; EFO: 63, 49, 153; LAG: 13, 14, 101; MAG: 11, 15, 102; HAG: 37, 37, 203 (SEM: 7.8, 6.7, 14.4) in leg meat. Cooked EFO and HAG leg meat was more oxidized (5.2 mg of hexanal/kg of meat) than the other meats (mean 2.2 mg/kg, SEM 0.63). It is concluded that algal biomass is as effective as fish oil at enriching broiler diets with C22:6 LC n-3 PUFA, and at equal C22:6n-3 contents, there is no significant difference between these 2 supplements on the oxidative stability of the meat that is produced.


Influence of Classroom and School Climate on Teacher Perceptions of Student Problem Behavior.
Reducing student problem behavior remains a leading concern for school staff, as disruptive and aggressive behavior interferes with student achievement and the school climate. However, the multi-systemic nature of schools makes it difficult for researchers and practitioners to identify factors influencing to students' behavior. The current study examined student problem behavior through an ecological lens by taking into account individual (e.g., gender, ethnicity, prosocial behavior), classroom (e.g., class size, average classroom behavior), and school-level factors (e.g., location, school climate). Using data from 37 elementary schools, 467 classrooms, and 8,750 students, a series of hierarchical linear models was tested. Multilevel analyses revealed that while individual student characteristics had the largest influence on problem behavior, average prosocial behavior and concentration problems of students within the classroom, as well as teacher perceptions of the school climate significantly related to how students behaved. These findings support the use of classroom-based intervention programs to reduce student problem behavior.


Inhibition of erbB receptor (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer.
It has been proposed that binding of ligand to the estrogen receptor (ER) releases its association with transcriptional corepressors, allowing the ER to recruit coactivators, which possess histone acetylase activity, and induce transcription of gene promoters containing estrogen response elements. It has also been proposed that the antiestrogen tamoxifen recruits transcriptional corepressors to the AF-2 region of the hormone-binding domain of the ER, thus blocking ER-mediated transcription. The ER cross-talks with a number of mitogenic signaling pathways and second messengers, like the epidermal growth factor receptor, the insulin-like growth factor-I receptor, mitogen-activated protein (MAP) kinase, phosphatidylinositol-3 kinase/Akt, dopamine, and cyclic AMP. Some of these molecules may: (a) support ligand-independent ER transcription; (b) increase the association of ER with coactivators of transcription; and/or (c) reduce the antiestrogen-induced association of ER with corepressors. These events either alone or in combination may result in hormone independence and/or antiestrogen resistance. We have examined whether signaling by HER2/neu (erbB-2) receptor tyrosine kinase, which can induce antiestrogen resistance, can also disrupt the tamoxifen-induced interaction of ER with transcriptional corepressors. Notably, tamoxifen-induced association of ER with the transcriptional corepressors N-CoR or SMRT was reduced in HER2-overexpressing breast tumor cells but not in cells with low HER2 levels. Small molecule inhibitors of the HER2 kinase or MAP extracellular signal-regulated kinase 1/2 or dominant-negative MAP extracellular signal-regulated kinase 1/2 constructs restored the inhibitory effect of tamoxifen on both ER-mediated transcription and tumor cell proliferation. Treatment with both tamoxifen and the small molecule HER1/2 kinase inhibitor AG1478 reduced mitogen-activated protein kinase activity and markedly reduced growth of established MCF-7/HER2 xenografts in athymic nude mice. Similar results have been obtained with ZD1839 ("Iressa"), an epidermal growth factor receptor (HER1) tyrosine kinase inhibitor. Taken together, these data suggest that exogenous inhibitors of the HER-signaling network and other mitogenic pathways can abrogate or delay the emergence of antiestrogen resistance, thus providing an evaluable therapeutic strategy in human breast carcinoma.


Oocyte vitrification for fertility preservation in women with endometriosis: an observational study.
To describe the outcome of fertility preservation (FP) using vitrified oocytes in patients with endometriosis and to determine the impact of ovarian surgery. Retrospective observational study. University-affiliated private in vitro fertilization (IVF) center. Four hundred and eighty-five women with endometriosis who underwent FP from January 2007 to July 2018. Vitrification of metaphase II (MII) oocytes for future use. Oocyte survival rate and cumulative live-birth rate (CLBR). Mean age at vitrification was 35.7 ± 3.7 years. The women undergoing operations were younger than the nonsurgical patients (33.4 ± 3.6 years vs. 36.7 ± 3.7 years). The survival rate and CLBR were 83.2% and 46.4%, respectively. The number of vitrified oocytes per cycle (6.2 ± 5.8) was higher for the nonsurgical patients compared with the unilateral (5.0 ± 4.5) or bilateral (4.5 ± 4.4) surgery groups, but was comparable among the surgical patients. The effect of age (adjusted odds ratio [OR] 0.904; 95% CI, 0.858-0.952), number of oocytes (adjusted OR 1.050; 95% CI, 1.025-1.091), and survival (adjusted OR 1.011; 95% CI, 1.001-1.020) on the CLBR was confirmed. However, the effect of surgery was not observed (adjusted OR 1.142; 95% CI, 0.778-1.677). Nonetheless, the ovarian response (vitrified oocytes = 8.6 ± 6.9 vs. 5.1 ± 4.8) and CLBR (72.5% vs. 52.8%) were higher in young (≤35 years) nonsurgical patient versus the surgical patients; older women showed similar outcomes. Fertility preservation gives patients with endometriosis a valid treatment option to help them increase their reproductive chances. We suggest performing surgery after ovarian stimulation for FP in young women. In older women, an individualized treatment should be considered.


Evidence against a role of physiological concentrations of estrogen in post-myocardial infarction remodeling.
The purpose of this study was to examine whether endogenous estrogen deficiency induced by ovariectomy affects chronic left ventricular dysfunction post-myocardial infarction (MI). Epidemiologic findings suggest that mortality of postmenopausal women is increased after MI, but the underlying mechanisms are unknown. Rats were either not ovariectomized (non-OVX), ovariectomized (OVX) or ovariectomized and treated with subcutaneous 17-beta-estradiol (E2) pellets (OVX + E2). Two weeks later, animals were sham-operated (Sham) or left coronary artery ligated (MI). Eight weeks later, in vivo echocardiographic and hemodynamic measurements were performed. Thereafter, hearts were isolated and perfused isovolumically. Mean infarct size was similar among the three MI groups. Ovariectomy decreased serum E2 levels (11 +/- 4 vs. 49 +/- 11 pg/ml in non-OVX, p < 0.01) and increased body weight. These changes were reversed by E2 replacement. The degree of cardiac hypertrophy was similar for all groups post-MI. Left ventricular diameters were increased post-MI (8.9 +/- 0.4 in non-OVX + MI vs. 6.7 +/- 0.2 mm in non-OVX + Sham hearts, p < 0.0001), but OVX or OVX + E2 replacement did not alter left ventricular diameters in post-MI and Sham hearts. Left ventricular fractional shortening was severely impaired post-MI (19 +/- 2% vs. 50 +/- 3 in non-OVX + Sham hearts, p < 0.0001) with no influence of hormonal status. Left ventricular end-diastolic pressure, measured in vivo, was increased in all MI groups without significant differences between groups. Pressure-volume curves, obtained in perfused hearts, demonstrated a right and downward shift with reduced maximum left ventricular developed pressure post-MI (75 +/- 6 vs. 108 +/- 3 mm Hg in non-OVX + Sham hearts, p < 0.001) and were also unaffected by either OVX or E2 replacement. Chronic endogenous estrogen deficiency does not have major effects on the development of cardiac hypertrophy, dysfunction and dilation post-MI.


The Levels of Lactate, Troponin, and N-Terminal Pro-B-Type Natriuretic Peptide Are Predictors of Mortality in Patients with Sepsis and Septic Shock: A Retrospective Cohort Study.
BACKGROUND Serum lactate, troponin, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been proposed to be useful prognostic indicators in patients with sepsis and septic shock. This study aimed to evaluate the predictive ability of these biomarkers and assess how their prognostic utility may be improved by using them in combination. MATERIAL AND METHODS A retrospective review of the medical records of 1242 patients with sepsis and septic shock who were admitted to the Richmond University Medical Center between June 1, 2018, and June 1, 2019, was carried out; 427 patients met the study criteria and were included in the study. The primary outcome measures included 30-day mortality, APACHE II scores, length of hospital stay, and admission to the Medical Intensive Care Unit (MICU). RESULTS High levels of lactate (>4 mmol/L), troponin (>0.45 ng/mL), and NT-proBNP (>8000 pg/mL) were independent predictors of 30-day mortality, with an adjusted odds ratio of mortality being 3.19 times, 2.13 times, and 2.5 times higher, respectively, compared with corresponding reference groups, at 95% confidence intervals. Elevated levels of lactate, troponin, and NT-proBNP were associated with 9.12 points, 7.70 points, and 8.88 points in higher APACHE II scores, respectively. Only elevated troponin levels were predictive of a longer length of hospital stay. In contrast, elevated lactate and troponin were associated with an increased chance of admission to the MICU. CONCLUSIONS Elevated levels of serum lactate, troponin, and NT-proBNP are independent predictors of mortality and higher APACHE II scores in patients with sepsis and septic shock.


Innate sensing of foamy viruses by human hematopoietic cells.
Foamy viruses (FV) are nonpathogenic retroviruses that have cospeciated with primates for millions of years. FV can be transmitted through severe bites from monkeys to humans. Viral loads remain generally low in infected humans, and no secondary transmission has been reported. Very little is known about the ability of FV to trigger an innate immune response in human cells. A few previous reports suggested that FV do not induce type I interferon (IFN) in nonhematopoietic cells. Here, we examined how human hematopoietic cells sense FV particles and FV-infected cells. We show that peripheral blood mononuclear cells (PBMCs), plasmacytoid dendritic cells (pDCs), and the pDC-like cell line Gen2.2 detect FV, produce high levels of type I IFN, and express the IFN-stimulated gene MxA. Fewer than 20 FV-infected cells are sufficient to trigger an IFN response. Both prototypic and primary viruses stimulated IFN release. Donor cells expressing a replication-defective virus, carrying a mutated reverse transcriptase, induced IFN production by target cells as potently as wild-type virus. In contrast, an FV strain with env deleted, which does not produce viral particles, was inactive. IFN production was blocked by an inhibitor of endosomal acidification (bafilomycin A1) and by an endosomal Toll-like receptor (TLR) antagonist (A151). Silencing experiments in Gen2.2 further demonstrated that TLR7 is involved in FV recognition. Therefore, FV are potent inducers of type I IFN by pDCs and by PBMCs. This previously underestimated activation of the innate immune response may be involved in the control of viral replication in humans.


Fusion moves for Markov random field optimization.
The efficient application of graph cuts to Markov Random Fields (MRFs) with multiple discrete or continuous labels remains an open question. In this paper, we demonstrate one possible way of achieving this by using graph cuts to combine pairs of suboptimal labelings or solutions. We call this combination process the fusion move. By employing recently developed graph-cut-based algorithms (so-called QPBO-graph cut), the fusion move can efficiently combine two proposal labelings in a theoretically sound way, which is in practice often globally optimal. We demonstrate that fusion moves generalize many previous graph-cut approaches, which allows them to be used as building blocks within a broader variety of optimization schemes than were considered before. In particular, we propose new optimization schemes for computer vision MRFs with applications to image restoration, stereo, and optical flow, among others. Within these schemes the fusion moves are used 1) for the parallelization of MRF optimization into several threads, 2) for fast MRF optimization by combining cheap-to-compute solutions, and 3) for the optimization of highly nonconvex continuous-labeled MRFs with 2D labels. Our final example is a nonvision MRF concerned with cartographic label placement, where fusion moves can be used to improve the performance of a standard inference method (loopy belief propagation).


Hsp70 is an independent stress marker among frequent users of mobile phones.
The aim of this study was to measure the serum concentrations of heat shock protein (HSP) 70 and C-reactive protein (CRP) and the expression levels of the hsp70 gene among frequent users of mobile phones (FUMPs). We enrolled 120 employees of information technology (IT)/IT enabled service companies (FUMPs; IT professionals) and 102 infrequent users of mobile phones (IFUMPs; people from non-IT professions) as controls. The serum concentrations of HSP70 and CRP were measured by enzyme-linked immunosorbant assay and hsp70 gene expression by reverse transcription polymerase chain reaction. Significantly higher concentrations of serum HSP70 (P < 0.00012) and CRP (P < 0.04) were observed among FUMPs than IFUMPs. A higher level of hsp70 gene expression (fold induction) was observed among FUMPs than IFUMPs (P < 7.06 × 10-13). In contrast to the duration of exposure-dependent increase of serum concentration of CRP, the serum HSP70 concentration was found to be independent of the duration of exposure to mobile phones. Thus, the study convincingly demonstrated the role of serum HSP and CRP as systemic inflammatory biomarkers for mobile phone-induced radiation.


Adapting Methodology Used on Captive Subjects for Estimating Gut Passage Time in Wild Monkeys.
Gut passage time of food has consequences for primate digestive strategies, which subsequently affect seed dispersal. Seed dispersal models are critical in understanding plant population and community dynamics through estimation of seed dispersal distances, combining movement data with gut passage times. Thus, developing methods to collect in situ data on gut passage time are of great importance. Here we present a first attempt to develop an in situ study of gut passage time in an arboreal forest guenon, the samango monkey (Cercopithecus albogularis schwarzi) in the Soutpansberg Mountains, South Africa. Cercopithecus spp. consume large proportions of fruit and are important seed dispersers. However, previous studies on gut passage times have been conducted only on captive Cercopithecusspp. subjects, where movement is restricted, and diets are generally dissimilar to those observed in the wild. Using artificial digestive markers, we targeted provisioning of a male and a female samango monkey 4 times over 3 and 4 days, respectively. We followed the focal subjects from dawn until dusk following each feeding event, collecting faecal samples and recording the date and time of deposition and the number of markers found in each faecal sample. We recovered 6.61 ± 4 and 13 ± 9% of markers from the male and the female, respectively, and were able to estimate a gut passage window of 16.63-25.12 h from 3 of the 8 trials. We discuss methodological issues to help future researchers to develop in situ studies on gut passage times.


Risk factors associated with incident sexually transmitted infections in HIV-positive patients in the Australian HIV Observational Database: a prospective cohort study.
We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0-13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30-39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2-0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6-3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1-0.6; P < 0.001). In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30-39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.


Transcriptional profiling of stellate ganglia from normotensive and spontaneously hypertensive rat strains.
The course of hypertension remains poorly understood, although impairment of the sympathetic nervous systems is thought to play a role in its aetiology. In this study, RNA-sequencing (RNAseq) was used to identify transcriptomal differences in the sympathetic stellate ganglia between 16-week-old normotensive Wistar rats and spontaneously hypertensive rats (SHR). Sequencing quality was assessed by FastQC and quasi-mapping rate by Salmon. Differential expression results were confirmed by real time reverse transcriptase Quantitative Polymerase Chain Reaction (qRT-PCR). RNAseq analysis was found to be predictive and representative of transcriptomal changes when compared to qRT-PCR by correlation analysis. Whether these changes underpin physiological sympathetic phenotypes associated with hypertension remains to be established, however this dataset identifies lead transcripts as a priori targets for further investigation.


Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy.
Cardiac pathology is emerging as a prominent systemic feature of spinal muscular atrophy (SMA), but little is known about the underlying molecular pathways. Using quantitative proteomics analysis, we demonstrate widespread molecular defects in heart tissue from the Taiwanese mouse model of severe SMA. We identify increased levels of lamin A/C as a robust molecular phenotype in the heart of SMA mice and show that lamin A/C dysregulation is also apparent in SMA patient fibroblast cells and other tissues from SMA mice. Lamin A/C expression was regulated in vitro by knockdown of the E1 ubiquitination factor ubiquitin-like modifier activating enzyme 1, a key downstream mediator of SMN-dependent disease pathways, converging on β-catenin signaling. Increased levels of lamin A are known to increase the rigidity of nuclei, inevitably disrupting contractile activity in cardiomyocytes. The increased lamin A/C levels in the hearts of SMA mice therefore provide a likely mechanism explaining morphological and functional cardiac defects, leading to blood pooling. Therapeutic strategies directed at lamin A/C may therefore offer a new approach to target cardiac pathology in SMA.


Understanding alkali metal cation affinities of multi-layer guanine quadruplex DNA.
To gain better understanding of the stabilizing interactions between metal ions and DNA quadruplexes, dispersion-corrected density functional theory (DFT-D) based calculations were performed on double-, triple- and four-layer guanine tetrads interacting with alkali metal cations. All computations were performed in aqueous solution that mimics artificial supramolecular conditions where guanine bases assemble into stacked quartets as well as biological environments in which telomeric quadruplexes are formed. To facilitate the computations on these significant larger systems, optimization of the DFT description was performed first by evaluating the performance of partial reduced basis sets. Analysis of the stabilizing interactions between alkali cations and the DNA bases in double and triple-layer guanine quadruplex DNA reproduced the experimental affinity trend of the order Li+< Rb+ < Na+ < K+. The desolvation and the size of alkali metal cations are thought to be responsible for the order of affinity. Nevertheless, for the alkali metal cation species individually, the magnitude of the bond energy stays equal for binding as first, second or third cation in double, triple and four-layer guanine quadruplexes, respectively. This is the result of an interplay between a decreasingly stabilizing interaction energy and increasingly stabilizing solvation effects, along the consecutive binding events. This diminished interaction energy is the result of destabilizing electrostatic repulsion between the hosted alkali metal cations. This work emphasizes the stabilizing effect of aqueous solvent on large highly charged biomolecules.


When condition trumps location: seed consumption by fruit-eating birds removes pathogens and predator attractants.
Seed ingestion by frugivorous vertebrates commonly benefits plants by moving seeds to locations with fewer predators and pathogens than under the parent. For plants with high local population densities, however, movement from the parent plant is unlikely to result in 'escape' from predators and pathogens. Changes to seed condition caused by gut passage may also provide benefits, yet are rarely evaluated as an alternative. Here, we use a common bird-dispersed chilli pepper (Capsicum chacoense) to conduct the first experimental comparison of escape-related benefits to condition-related benefits of animal-mediated seed dispersal. Within chilli populations, seeds dispersed far from parent plants gained no advantage from escape alone, but seed consumption by birds increased seed survival by 370% - regardless of dispersal distance - due to removal during gut passage of fungal pathogens and chemical attractants to granivores. These results call into question the pre-eminence of escape as the primary advantage of dispersal within populations and document two overlooked mechanisms by which frugivores can benefit fruiting plants.


Non-viral delivery of the gene for glial cell line-derived neurotrophic factor to mesenchymal stem cells in vitro via a collagen scaffold.
Recent advances in tissue engineering that combine an extracellular matrix-like scaffold with therapeutic molecules, cells, DNA encoding therapeutic proteins, or a combination of the three hold promise for treating defects in the brain resulting from a penetrating injury or tumor resection. The purpose of this study was to investigate a porous sponge-like collagen scaffold for non-viral delivery of a plasmid encoding for glial cell line-derived neurotrophic factor (pGDNF) to rat marrow stromal stem cells (also referred to as mesenchymal stem cells, MSCs). The effects of the following parameters on GDNF synthesis in the three-dimensional (3D) constructs were evaluated and compared with results in monolayer culture: initial plasmid load (2-50 microg pGDNF), ratio of a lipid transfection reagent to plasmid (5:10), culture environment during the transfection (static and dynamic), and cell density. The level of gene expression in the collagen scaffolds achieved therapeutic levels that had previously been found to support survival of dopaminergic and trigeminal neurons in vitro. For the highest loading of plasmid (50 microg), the level of GDNF protein remained six to seven times above the control level after 2 weeks, a significant difference. Cell density in the scaffold was of importance for an early increase in GDNF production, with accumulated GDNF being approximately 60% greater after 9 days of culture when scaffolds were initially seeded with 2 million rat MSCs compared to 500,000 cells. Application of orbital shaking during the 4 h of transfection had a positive effect on the production of GDNF on 3D constructs but not of the same magnitude as reported in monolayer studies. Overall, these results demonstrate that the combination of tissue engineering and non-viral transfection of MSCs for the over-expression of GDNF is a promising approach for the long-term production of GDNF and probably for neurotrophic factors in general.


Serum Albumin Is an Independent Predictor of Clinical Outcomes in Critically Ill Children.
Serum albumin is a strong biomarker of disease severity and prognosis in adult patients. In contrast, its value as predictor of outcome in critically ill children has not been established. We aimed to determine whether admission hypoalbuminemia is associated with outcome in a general pediatric population of critically ill patients, taking into account the inflammatory response, disease severity, and nutritional status of the patient. Analysis of prospectively collected database. PICU of a teaching hospital. Two hundred seventy-one patients consecutively admitted. Neonates, patients with chronic liver or kidney disease, inborn errors of metabolism, those who received prior administration of albumin solution, and readmissions were excluded. Outcome variables were 60-day mortality, probability of ICU discharge at 60 days, and ventilator-free days. Potential exposure variables for the outcome were sex, age, nutritional status, albumin, C-reactive protein and serum lactate at admission, and Pediatric Index of Mortality 2 score. Admission hypoalbuminemia was present in 64.2% of patients. After adjustment for confounding factors, only serum lactate, Pediatric Index of Mortality 2 score, and serum albumin were associated with higher mortality: the increase of 1.0 g/dL in serum albumin at admission resulted in a 73% reduction in the hazard of death (hazard ratio, 0.27; 95% CI, 0.14-0.51; p < 0.001). The increase of 1 g/dL in serum albumin was also independently associated with a 33% rise in the probability of ICU discharge (subhazard ratio, 1.33; 95% CI, 1.07-1.64; p = 0.008) and increased ventilator-free-days (odds ratio, 1.86; 95% CI, 0.56-3.16; p = 0.005). Hypoalbuminemia at admission to a PICU is associated with higher 60-day mortality, longer duration of mechanical ventilation, and lower probability of ICU discharge. These associations are independent of the magnitude of inflammatory response, clinical severity, and nutritional status.


B7-H1-dependent sex-related differences in tumor immunity and immunotherapy responses.
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are immunopathogenic in cancers by impeding tumor-specific immunity. B7-homologue 1 (B7-H1) (CD274) is a cosignaling molecule with pleiotropic effects, including hindering antitumor immunity. In this study, we demonstrate sex-dependent, B7-H1-dependent differences in tumor immunity and response to immunotherapy in a hormone-independent cancer, murine B16 melanoma. Antitumor immunity was better in B7-H1(-/-) females versus males as a result of reduced regulatory T cell function in the B7-H1(-/-) females, and clinical response following B7-H1 blockade as tumor immunotherapy was significantly better in wild-type females than in males, owing to greater B7-H1 blockade-mediated reduction of Treg function in females. Wild-type female Tregs expressed significantly lower B7-H1 versus males but were insensitive to estrogen in vitro. Female B7-H1(-/-) Tregs were exquisitely sensitive to estrogen-mediated functional reduction in vitro, suggesting that B7-H1 effects occur before terminal Treg differentiation. Immune differences were independent of known B7-H1 ligands. Sex-dependent immune differences are seldom considered in designing immune therapy or interpreting immunotherapy treatment results. Our data demonstrate that sex is an important variable in tumor immunopathogenesis and immunotherapy responses through differential Treg function and B7-H1 signaling.


Looking into Enteric Virome in Patients with IBD: Defining Guilty or Innocence?
Although there is some evidence suggesting that certain viruses may be involved in the onset of inflammatory bowel disease (IBD), data regarding viral prevalence and viral load in blood and mucosa of patients with IBD are scarce. The main aim of this study is to evaluate the prevalence and viral load of common Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 6 in blood and mucosa of adult patients with endoscopic active IBD. From January to December 2014, ulcerative colitis and Crohn's disease patients with active endoscopic disease were consecutively enrolled. Subjects undergoing colonoscopy for colorectal cancer screening served as healthy controls (HCs). Paired blood and mucosal samples from each patient and HC were collected for EBV, CMV, and human herpes virus 6 quantitative real time polymerase chain reaction assessment of the viral load. One hundred forty-five subjects were included; 95 IBD patients with active endoscopic disease (43 ulcerative colitis and 52 Crohn's disease) and 50 healthy subjects. CMV and EBV DNA were detected more frequently in the mucosa of patients with IBD compared with HCs (CMV P = 0.017; EBV P < 0.001), irrespective of IBD type. The frequency of human herpes virus 6 DNA detection both in the blood and in the mucosa did not differ between patients with IBD and HCs. EBV median viral load was similar in the inflamed and noninflamed mucosa was not affected by the use of immunomodulators and/or anti-tumor necrosis factor alpha agents, and did not correlate with endoscopic disease activity. EBV, and to a lesser extent CMV, were more prevalent in patients with IBD than in HCs. Mucosal viral load was not influenced by the therapeutic regimen, did not differ between inflamed and noninflamed mucosa, and did not seem to be influenced by the endoscopic activity of the disease, suggesting that EBV may be more involved in the onset of IBD than in its severity and clinical evolution.


Progressive resistance training improves overall physical activity levels in patients with early osteoarthritis of the knee: a randomized controlled trial.
Prescription of resistance training (RT) exercises is an essential aspect of management for knee osteoarthritis (OA). However, whether patients with knee OA who are randomly assigned to receive RT simply substitute RT for other modes of physical activity remains unclear. The aim of this study was to determine the effect of a structured RT intervention on overall levels of moderate- and vigorous-intensity physical activity (MVPA) in patients with early-onset knee OA. The study compared patients with early-onset OA who participated in an RT program, those who participated in a self-management (SM) program, and those who participated in both RT and SM. Because participants randomly assigned to receive the RT intervention may simply switch activity modes, resulting in little net effect, we assessed total MVPA in addition to tracking changes in strength (force-generating capacity). This study was a randomized controlled trial comparing the effectiveness of SM alone, RT alone, and combined RT+SM on MVPA in patients with early OA of the knee. The study was conducted on a university campus, with patient recruitment from the local community. The participants in this study were 171 patients (74% women, 26% men) with knee OA. They had a mean age of 55.1 (SD=7.1) years, a mean body mass index of 27.6 (SD=4.2) kg/m(2), and radiographic status of grade II OA (and no higher) in at least one knee, as defined by the Kellgren and Lawrence classification. They wore an accelerometer while awake (X=14.2 [SD=2.2] hours) for 5 to 7 contiguous days (X=6.8 [SD=0.5] days) at baseline and at 3 and 9 months of intervention. The participants engaged in MVPA a mean of 26.2 (SD=19.3) minutes per day at baseline. Both groups significantly increased their MVPA from baseline to 3 months (RT group by 18% [effect size (d)=0.26]; SM group by 22% [effect size (d)=0.25]), but only the RT group sustained those changes at 9 months (RT group maintained a 10% increase [effect size (d)=0.15]; SM group maintained a 2% increase [effect size (d)=0.03]). A significant group x time interaction for MVPA indicated that the RT group maintained higher MVPA levels than the SM group. Lack of direct measures of energy expenditure and physical function was a limitation of the study. Patients with early-onset OA of the knee can engage in an RT program without sacrificing their overall MVPA levels. These results support the value of RT for management of knee OA.


Jejunal feeding is followed by a greater rise in plasma cholecystokinin, peptide YY, glucagon-like peptide 1, and glucagon-like peptide 2 concentrations compared with gastric feeding in vivo in humans: a randomized trial.
Jejunal feeding is preferred instead of gastric feeding in patients who are intolerant to gastric feeding or at risk of aspiration. However, the impact of gastric feeding compared with that of jejunal feeding on postprandial circulating plasma glucose and amino acid concentrations and the associated endocrine response in vivo in humans remains largely unexplored. We compared the impact of administering enteral nutrition as either gastric feeding or jejunal feeding on endocrine responses in vivo in humans. In a randomized, crossover study design, 12 healthy young men (mean ± SD age: 21 ± 2 y) received continuous enteral nutrition that contained noncoagulating proteins for 12 h via a nasogastric tube or a nasojejunal tube placed 30-40 cm distal to the ligament of Treitz. Blood samples were collected during the 12-h postprandial period to assess the rise in plasma glucose, amino acid, and gastrointestinal hormone concentrations. No differences were observed in the postprandial rise in circulating plasma amino acid and glucose concentrations between regimens. Jejunal feeding resulted in higher peak plasma insulin concentrations than did gastric feeding (392 ± 53 compared with 326 ± 54 pmol/L, respectively; P < 0.05). The postprandial rise in plasma cholecystokinin, peptide YY (PYY), glucagon-like peptide 1 (GLP-1), and glucagon-like peptide 2 (GLP-2) concentrations was greater after jejunal feeding than after gastric feeding, with higher peak concentrations and a greater postprandial incremental AUC for GLP-1 and cholecystokinin (all P < 0.05). Plasma ghrelin concentrations did not differ between regimens. Enteral nutrition with gastric or jejunal feeding in healthy young men results in similar postprandial plasma amino acid and glucose concentrations. However, the endocrine response differs substantially, with higher peak plasma cholecystokinin, PYY, GLP-1, and GLP-2 concentrations being attained after jejunal feeding. This effect may result in an improved anabolic response, greater insulin sensitivity, and an improved intestinotropic effect. Nevertheless, it may also lead to delayed gastric emptying. This trial was registered at trialregister.nl as NTR2801.


Does gender affect asthma control in adult asthmatics?
Several studies have shown gender differences in prevalence of asthma but there is little information about asthma control. In this study, we aimed to evaluate the effect of gender on asthma control in adult asthmatics. Medical records of 242 patients older than 18 years of age who regularly visited the allergy unit were evaluated. Standardized asthma questionnaires like the asthma control test (ACT) were performed. ACT scores, clinical characteristics, and demographic data such as smoking status, education, duration and severity of asthma, atopic status, family history of asthma, analgesic hypersensitivity, number of emergency visits, and hospitalization in the previous year were compared based on gender. In this study, 77.3% of the patients were female. Mean age, body mass index, and duration of asthma were 39.0 ± 0.7, 27.3 ± 0.3, and 6.6 ± 0.4 years, respectively. Of the total, 14.9% of the patients were smokers. Also, 55.8% of them were graduated from middle school, 22.7% from high school, and 14% from university. Atopy rate was 57%. Analgesic hypersensitivity was found in 18.6% of them. There was 30.2% family history of asthma. The asthma severity was mild in 45.5%, moderate in 40.9%, and severe in 13.6% of the patients. One-third of the patients were admitted to emergency room; 1/10th were hospitalized due to asthma in the previous year. ACT scores indicated complete control in 67.8%, partial control in 17.8%, and uncontrolled asthma in 14.5%. Comparing the results of males with females having asthma, there was no statistically significant difference between the two gender according to ACT scores and clinical characteristics. Finally, the results conclude that there was no effect of gender on asthma control assessed with standardized questionnaire in adult asthmatics.


Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex.
Newly generated neurons are continuously added to the olfactory epithelium and olfactory bulbs of adult mammals. Studies also report newly generated neurons in the piriform cortex, the primary cortical projection site of the olfactory bulbs. The current study used BrdU-injection paradigms, and in vivo and in vitro DiI tracing methods to address three fundamental issues of these cells: their origin, migratory route and fate. The results show that 1 day after a BrdU-injection, BrdU/DCX double-labeled cells appear deep to the ventricular subependyma, within the white matter. Such cells appear further ventral and caudal in the ensuing days, first appearing in the rostral piriform cortex of mice at 2 days after the BrdU-injection, and at 4 days in the rat. In the caudal piriform cortex, BrdU/DCX labeled cells first appear at 4 days after the injection in mice and 7 days in rats. The time it takes for these cells to appear in the piriform cortex and the temporal distribution pattern suggest that they migrate from outside this region. DiI tracing methods confirmed a migratory route to the piriform cortex from the ventricular subependyma. The presence of BrdU/NeuN labeled cells as early as 7 days after a BrdU injection in mice and 10 days in the rat and lasting as long as 41 days indicates that some of these cells have extended survival durations in the adult piriform cortex.


Blast2GO goes grid: developing a grid-enabled prototype for functional genomics analysis.
The vast amount in complexity of data generated in Genomic Research implies that new dedicated and powerful computational tools need to be developed to meet their analysis requirements. Blast2GO (B2G) is a bioinformatics tool for Gene Ontology-based DNA or protein sequence annotation and function-based data mining. The application has been developed with the aim of affering an easy-to-use tool for functional genomics research. Typical B2G users are middle size genomics labs carrying out sequencing, ETS and microarray projects, handling datasets up to several thousand sequences. In the current version of B2G. The power and analytical potential of both annotation and function data-mining is somehow restricted to the computational power behind each particular installation. In order to be able to offer the possibility of an enhanced computational capacity within this bioinformatics application, a Grid component is being developed. A prototype has been conceived for the particular problem of speeding up the Blast searches to obtain fast results for large datasets. Many efforts have been done in the literature concerning the speeding up of Blast searches, but few of them deal with the use of large heterogeneous production Grid Infrastructures. These are the infrastructures that could reach the largest number of resources and the best load balancing for data access. The Grid Service under development will analyse requests based on the number of sequences, splitting them accordingly to the available resources. Lower-level computation will be performed through MPIBLAST. The software architecture is based on the WSRF standard.


Inhibition of NMDA-gated ion channels by bis(7)-tacrine: whole-cell and single-channel studies.
Bis(7)-tacrine is a novel dimeric acetylcholinesterase inhibitor derived from tacrine, and has been proposed as a promising agent to treat Alzheimer's disease. We have recently reported that bis(7)-tacrine prevents glutamate-induced neuronal apoptosis by antagonizing NMDA receptors. The purpose of this study was to characterize bis(7)-tacrine inhibition of NMDA-activated current by using patch-clamp recording techniques. In cultured rat hippocampal neurons, bis(7)-tacrine inhibited NMDA-activated whole-cell current in a concentration-dependent manner with an IC(50) of 0.66+/-0.07 microM. Bis(7)-tacrine produced a gradual decline of NMDA-activated current to a steady-state, but this was not an indication of use-dependence. Also, the slow onset of inhibition by bis(7)-tacrine was not apparently due to an action at an intracellular site. Bis(7)-tacrine, 0.5 microM, decreased the maximal response to NMDA by 40% without changing its EC(50). Bis(7)-tacrine inhibition of NMDA-activated current was not voltage-dependent, and was independent of glycine concentration. Results of single-channel experiments obtained from cells expressing NR1 and NR2A subunits revealed that bis(7)-tacrine decreased the open probability and frequency of channel opening, but did not significantly alter the mean open time or introduce rapid closures. These results suggest that bis(7)-tacrine can inhibit NMDA receptor function in a manner that is slow in onset and offset and noncompetitive with respect to both NMDA and glycine. The noncompetitive inhibition of NMDA receptors by bis(7)-tacrine could contribute to its protective effect against glutamate-induced neurotoxicity.


Tuning thermoresponsive behavior of diblock copolymers and their gold core hybrids: part 1. Importance of placement of amphiphilic end groups on the diblock copolymers.
We report the effects of use and placement of amphiphilic end groups as a valuable tool to achieve significant changes in the thermoresponsive properties of diblock copolymers without the need to resort to compositional changes. We prepared diblock copolymers of di(ethylene glycol) methyl ether methacrylate and oligo(ethylene glycol) methyl ether acrylate with phenyl dithioester and carboxylic acid chain ends and compared the effects of placement of these amphiphilic chain ends on the cloud points of the copolymers. All the copolymers were high molecular weight (greater than 20 kDa) with a polydispersity between 1.1 and 1.2, and the cloud points were measured by UV-vis spectrophotometry and reported as the temperature at 50% normalized transmission. The thermoresponse showed a significant dependency on end group placement, reaching as much as a 28°C difference in measured cloud point simply by exchanging end group placement rather than compositional changes. The effect is attributed to changes in the solvation and mobility from chain end placement affecting the degree of association of the chains. The underlying effect is due to the hydrophilic/hydrophobic balance in combination with the use of amphiphilic chain end placement that can be applied to copolymers with different blocks at the chain ends. This work shows that substantial changes in thermo-response properties can be achieved by re-arranging monomer components rather than changing monomer composition. This may have value in biomedical materials where the range of acceptable monomers is limited.


How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel.
For many recessive genetic syndromes, carrier frequencies have been assessed through screening studies in founder populations but remain unclear in heterogeneous populations. One such syndrome is Fanconi Anemia (FA). FA is a model disease in cancer research, yet there are no contemporary data on carrier frequency or prevalence in the general United States (US) population or elsewhere. We inferred carrier frequency from birth incidence using the Hardy-Weinberg law. We estimated prevalence using birth incidence and survival data. We defined "plausible ranges" to incorporate uncertainty about completeness of case ascertainment. We made estimates for the US and Israel using demographic data from the Fanconi Anemia Research Fund and Israeli Fanconi Anemia Registry. In the US, a plausible range for the carrier frequency is 1:156-1:209 [midpoint 1:181]; we estimate that 550-975 persons were living with FA in 2010. For Israel, a plausible range for the carrier frequency is 1:66-1:128 [midpoint 1:93] in line with founder screening studies; we estimate that 40-135 Israelis were living with FA in 2008. The estimated US FA carrier frequency of 1:181 is significantly higher than the historical estimate of 1:300; hence, the gap may be narrower than previously recognized between the US carrier frequency and higher carrier frequencies of around 1:100 in several founder groups including Ashkenazi Jews. Assessment of cancer risks in heterozygous carriers merits further study. Clinical trials in FA will require co-ordination and innovative design because the number of living US patients is probably less than 1,000.


Using silver yoga exercises to promote physical and mental health of elders with dementia in long-term care facilities.
This study aimed to test the effects of yoga exercises on the physical and mental health of elderly people with dementia living in long-term care facilities. A quasi-experimental, pretest-post-test design was used. A convenience sample of 68 residents in long-term care facilities in southern Taiwan, aged 60 years and above with mild to moderate dementia, was selected. An experimental group of 33 elders participated in a 12-week yoga training program of three 55-minute sessions a week; a control group of 35 elders maintained their usual daily activities. Data were collected before and after completing the 12-week study. Measurements included body composition, cardiopulmonary functions, body flexibility, muscle strength and endurance, balance, joints motion, depression, and problem behaviors. The yoga-trained participants had better physical and mental health than those who did not participate, including lowered blood pressure, reduced respiration rate, strengthened cardiopulmonary fitness, enhanced body flexibility, improved muscle strength and endurance, improved balance, and increased joints motion (all p values < 0.05). In addition, the depression state (p < 0.001) and problem behaviors (p < 0.001) of these demented elders were significantly reduced. Yoga exercise has positive benefits for both the physical and mental health of elders with dementia living in long-term care facilities. It is recommended that yoga be included as one of the routine activities in these long-term care facilities.


[TRIGLYCERIDE LEVELS AS A RISK FACTOR DURING PREGNANCY; BIOLOGICAL MODELING; SYSTEMATIC REVIEW].
introduction: Some of the diseases that can appear in pregnancy (gestational diabetes, hypertension and preeclampsia) are being associated with an increased risk of heart throughout life diseases. This should be present in future assessments of the health of women. One of the most important biomarkers in cardiovascular diseases is the triglyceride level, and that undergoes a significant change during pregnancy. the objective of this review is to analyze the studies that have investigated triglyceride levels during pregnancy as a risk factor for cardiovascular disease in the last weeks of pregnancy and childbirth. a systematic search was made and 14 specific articles on the subject were selected following the PRISMA guidelines. in normal pregnancy decreased the level of lipids in the first weeks, followed by a gradual increase. Especially high from the 12th week of gestation. This increase in plasma levels of circulating lipids occurs linearly, reaching a peak a few days before delivery. This increase results because of the increased estrogen levels and insulin resistance. It has also been associated with prolactin levels. through this review, it has been able to demonstrate the relationship of elevated triglycerides some pathologies or more frequent changes in risk pregnancies, in which a significantly higher elevation occurs compared to normal pregnancies. It is in this context that the biological modeling may be particularly important, facilitating the creation of models and percentile curves applicable to the population, and allow monitoring of changes in triglycerides, which end up pointing situations passing be predictors of a potentially pathological situation. Thus, appropriate interventions would be carried rafter more briefly, and see so favored adequate primary prevention.


A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis.
Relationships between genetic alterations, such as co-occurrence or mutual exclusivity, are often observed in cancer, where their understanding may provide new insights into etiology and clinical management. In this study, we combined statistical analyses and computational modeling to explain patterns of genetic alterations seen in 178 patients with bladder tumors (either muscle-invasive or non-muscle-invasive). A statistical analysis on frequently altered genes identified pair associations, including co-occurrence or mutual exclusivity. Focusing on genetic alterations of protein-coding genes involved in growth factor receptor signaling, cell cycle, and apoptosis entry, we complemented this analysis with a literature search to focus on nine pairs of genetic alterations of our dataset, with subsequent verification in three other datasets available publicly. To understand the reasons and contexts of these patterns of associations while accounting for the dynamics of associated signaling pathways, we built a logical model. This model was validated first on published mutant mice data, then used to study patterns and to draw conclusions on counter-intuitive observations, allowing one to formulate predictions about conditions where combining genetic alterations benefits tumorigenesis. For example, while CDKN2A homozygous deletions occur in a context of FGFR3-activating mutations, our model suggests that additional PIK3CA mutation or p21CIP deletion would greatly favor invasiveness. Furthermore, the model sheds light on the temporal orders of gene alterations, for example, showing how mutual exclusivity of FGFR3 and TP53 mutations is interpretable if FGFR3 is mutated first. Overall, our work shows how to predict combinations of the major gene alterations leading to invasiveness through two main progression pathways in bladder cancer.


Structural and orientational constraints of bacteriorhodopsin in purple membranes determined by oriented-sample solid-state NMR spectroscopy.
We report for the first time, oriented-sample solid-state NMR experiments, specifically polarization inversion spin exchange at the magic angle (PISEMA) and 1H-15N heteronuclear chemical shift correlation (HETCOR), applied to an integral seven-transmembrane protein, bacteriorhodopsin (bR), in natural membranes. The spectra of [15N]Met-bR revealed clearly distinguishable signals from the helical and loop regions. By deconvolution of the helix resonances, it was possible to establish constraints for some helix tilt angles. It was estimated that the extracellular section of helix B has a tilt of less than 5 degrees from the membrane normal, while the tilt of helix A was estimated to be 18-22 degrees , both of which are in agreement with most crystal structures. Comparison of the experimental PISEMA spectrum with simulated spectra based on crystal structures showed that PISEMA and HETCOR experiments are extremely sensitive to the polytopic protein structure, and the solid-state NMR spectra for membrane-embedded bR matched most favorably with the recent 1FBB electron crystallography structure. These results suggest that this approach has the potential to yield structural and orientational constraints for large integral polytopic proteins whilst intercalated and functionally competent in a natural membrane.


An integrative framework for the appraisal of coloration in nature.
The world in color presents a dazzling dimension of phenotypic variation. Biological interest in this variation has burgeoned, due to both increased means for quantifying spectral information and heightened appreciation for how animals view the world differently than humans. Effective study of color traits is challenged by how to best quantify visual perception in nonhuman species. This requires consideration of at least visual physiology but ultimately also the neural processes underlying perception. Our knowledge of color perception is founded largely on the principles gained from human psychophysics that have proven generalizable based on comparative studies in select animal models. Appreciation of these principles, their empirical foundation, and the reasonable limits to their applicability is crucial to reaching informed conclusions in color research. In this article, we seek a common intellectual basis for the study of color in nature. We first discuss the key perceptual principles, namely, retinal photoreception, sensory channels, opponent processing, color constancy, and receptor noise. We then draw on this basis to inform an analytical framework driven by the research question in relation to identifiable viewers and visual tasks of interest. Consideration of the limits to perceptual inference guides two primary decisions: first, whether a sensory-based approach is necessary and justified and, second, whether the visual task refers to perceptual distance or discriminability. We outline informed approaches in each situation and discuss key challenges for future progress, focusing particularly on how animals perceive color. Given that animal behavior serves as both the basic unit of psychophysics and the ultimate driver of color ecology/evolution, behavioral data are critical to reconciling knowledge across the schools of color research.


Drug treatment for spinal muscular atrophy type I.
Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a point mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. By definition, children with SMA type I are never able to sit without support and usually die or become ventilator dependent before the age of two years. There have until very recently been no drug treatments to influence the course of SMA. We undertook this updated review to evaluate new evidence on emerging treatments for SMA type I. The review was first published in 2009 and previously updated in 2011. To assess the efficacy and safety of any drug therapy designed to slow or arrest progression of spinal muscular atrophy (SMA) type I. We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. We also searched two trials registries to identify unpublished trials (October 2018). We sought all randomised controlled trials (RCTs) or quasi-RCTs that examined the efficacy of drug treatment for SMA type I. Included participants had to fulfil clinical criteria and have a genetically confirmed deletion or mutation of the SMN1 gene (5q11.2-13.2). The primary outcome measure was age at death or full-time ventilation. Secondary outcome measures were acquisition of motor milestones, i.e. head control, rolling, sitting or standing, motor milestone response on disability scores within one year after the onset of treatment, and adverse events and serious adverse events attributable to treatment during the trial period. Treatment strategies involving SMN1 gene replacement with viral vectors are out of the scope of this review. We followed standard Cochrane methodology. We identified two RCTs: one trial of intrathecal nusinersen in comparison to a sham (control) procedure in 121 randomised infants with SMA type I, which was newly included at this update, and one small trial comparing riluzole treatment to placebo in 10 children with SMA type I. The RCT of intrathecally-injected nusinersen was stopped early for efficacy (based on a predefined Hammersmith Infant Neurological Examination-Section 2 (HINE-2) response). At the interim analyses after 183 days of treatment, 41% (21/51) of nusinersen-treated infants showed a predefined improvement on HINE-2, compared to 0% (0/27) of participants in the control group. This trial was largely at low risk of bias. Final analyses (ranging from 6 months to 13 months of treatment), showed that fewer participants died or required full-time ventilation (defined as more than 16 hours daily for 21 days or more) in the nusinersen-treated group than the control group (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.32 to 0.89; N = 121; a 47% lower risk; moderate-certainty evidence). A proportion of infants in the nusinersen group and none of 37 infants in the control group achieved motor milestones: 37/73 nusinersen-treated infants (51%) achieved a motor milestone response on HINE-2 (risk ratio (RR) 38.51, 95% CI 2.43 to 610.14; N = 110; moderate-certainty evidence); 16/73 achieved head control (RR 16.95, 95% CI 1.04 to 274.84; moderate-certainty evidence); 6/73 achieved independent sitting (RR 6.68, 95% CI 0.39 to 115.38; moderate-certainty evidence); 7/73 achieved rolling over (RR 7.70, 95% CI 0.45 to 131.29); and 1/73 achieved standing (RR 1.54, 95% CI 0.06 to 36.92; moderate-certainty evidence). Seventy-one per cent of nusinersen-treated infants versus 3% of infants in the control group were responders on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) measure of motor disability (RR 26.36, 95% CI 3.79 to 183.18; N = 110; moderate-certainty evidence). Adverse events and serious adverse events occurred in the majority of infants but were no more frequent in the nusinersen-treated group than the control group (RR 0.99, 95% CI 0.92 to 1.05 and RR 0.70, 95% CI 0.55 to 0.89, respectively; N = 121; moderate-certainty evidence). In the riluzole trial, three of seven children treated with riluzole were still alive at the ages of 30, 48, and 64 months, whereas all three children in the placebo group died. None of the children in the riluzole or placebo group developed the ability to sit, which was the only milestone reported. There were no adverse effects. The certainty of the evidence for all measured outcomes from this study was very low, because the study was too small to detect or rule out an effect, and had serious limitations, including baseline differences. This trial was stopped prematurely because the pharmaceutical company withdrew funding. Various trials and studies investigating treatment strategies other than nusinersen, such as SMN2 augmentation by small molecules, are ongoing. Based on the very limited evidence currently available regarding drug treatments for SMA type 1, intrathecal nusinersen probably prolongs ventilation-free and overall survival in infants with SMA type I. It is also probable that a greater proportion of infants treated with nusinersen than with a sham procedure achieve motor milestones and can be classed as responders to treatment on clinical assessments (HINE-2 and CHOP INTEND). The proportion of children experiencing adverse events and serious adverse events on nusinersen is no higher with nusinersen treatment than with a sham procedure, based on evidence of moderate certainty. It is uncertain whether riluzole has any effect in patients with SMA type I, based on the limited available evidence. Future trials could provide more high-certainty, longer-term evidence to confirm this result, or focus on comparing new treatments to nusinersen or evaluate them as an add-on therapy to nusinersen.


Who are we feeding? Asymmetric individual use of surplus food resources in an insular population of the endangered Egyptian vulture Neophron percnopterus.
Supplementary feeding stations, or "vulture restaurants", are common conservation management tools. While a number of studies have investigated the consequences of surplus food on the population dynamics of scavengers, relatively little is known about the effects of such practices at the individual level. Within the long-term monitored breeding population of Canarian Egyptian vultures (Neophron percnopterus majorensis) we investigated individual bird's patterns of use of a supplementary feeding station at Fuerteventura (Canary Islands), over the course of breeding (2001, 2002; 2004-2011) and non-breeding seasons (2000-2010). Our results show that during the breeding season the individual use of the supplementary feeding station was inversely related to the distance to the breeding territory, which suggests the existence of central-place foraging constraints. In addition, larger birds of poor body-condition and individuals that ultimately failed to fledge young were detected more frequently at the feeding station. During the non-breeding season, and because most breeding birds abandoned the breeding territories, the overall abundance of Egyptian vultures at the feeding station grew. Moreover, the only variable increasing the probability of presence of individuals was poor body condition so that birds with lower wing residual visited the feeding station more frequently. Supplementary feeding may benefit individuals who would otherwise have been subject to selective pressures. From our results it follows that this conservation strategy must be used with caution because it can have consequences on an individual level and thus potentially affect the viability of endangered populations.


Impact of decreasing the proportion of higher energy foods and reducing portion sizes on food purchased in worksite cafeterias: A stepped-wedge randomised controlled trial.
Overconsumption of energy from food is a major contributor to the high rates of overweight and obesity in many populations. There is growing evidence that interventions that target the food environment may be effective at reducing energy intake. The current study aimed to estimate the effect of decreasing the proportion of higher energy (kcal) foods, with and without reducing portion size, on energy purchased in worksite cafeterias. This stepped-wedge randomised controlled trial (RCT) evaluated 2 interventions: (i) availability: replacing higher energy products with lower energy products; and (ii) size: reducing the portion size of higher energy products. A total of 19 cafeterias were randomised to the order in which they introduced the 2 interventions. Availability was implemented first and maintained. Size was added to the availability intervention. Intervention categories included main meals, sides, cold drinks, snacks, and desserts. The study setting was worksite cafeterias located in distribution centres for a major United Kingdom supermarket and lasted for 25 weeks (May to November 2019). These cafeterias were used by 20,327 employees, mainly (96%) in manual occupations. The primary outcome was total energy (kcal) purchased from intervention categories per day. The secondary outcomes were energy (kcal) purchased from nonintervention categories per day, total energy purchased per day, and revenue. Regression models showed an overall reduction in energy purchased from intervention categories of -4.8% (95% CI -7.0% to -2.7%), p < 0.001 during the availability intervention period and a reduction of -11.5% (95% CI -13.7% to -9.3%), p < 0.001 during the availability plus size intervention period, relative to the baseline. There was a reduction in energy purchased of -6.6% (95% CI -7.9% to -5.4%), p < 0.001 during the availability plus size period, relative to availability alone. Study limitations include using energy purchased as the primary outcome (and not energy consumed) and the availability only of transaction-level sales data per site (and not individual-level data). Decreasing the proportion of higher energy foods in cafeterias reduced the energy purchased. Decreasing portion sizes reduced this further. These interventions, particularly in combination, may be effective as part of broader strategies to reduce overconsumption of energy from food in out-of-home settings. ISRCTN registry ISRCTN87225572.


Promotion of testa rupture during garden cress germination involves seed compartment-specific expression and activity of pectin methylesterases.
Pectin methylesterase (PME) controls the methylesterification status of pectins and thereby determines the biophysical properties of plant cell walls, which are important for tissue growth and weakening processes. We demonstrate here that tissue-specific and spatiotemporal alterations in cell wall pectin methylesterification occur during the germination of garden cress (Lepidium sativum). These cell wall changes are associated with characteristic expression patterns of PME genes and resultant enzyme activities in the key seed compartments CAP (micropylar endosperm) and RAD (radicle plus lower hypocotyl). Transcriptome and quantitative real-time reverse transcription-polymerase chain reaction analysis as well as PME enzyme activity measurements of separated seed compartments, including CAP and RAD, revealed distinct phases during germination. These were associated with hormonal and compartment-specific regulation of PME group 1, PME group 2, and PME inhibitor transcript expression and total PME activity. The regulatory patterns indicated a role for PME activity in testa rupture (TR). Consistent with a role for cell wall pectin methylesterification in TR, treatment of seeds with PME resulted in enhanced testa permeability and promoted TR. Mathematical modeling of transcript expression changes in germinating garden cress and Arabidopsis (Arabidopsis thaliana) seeds suggested that group 2 PMEs make a major contribution to the overall PME activity rather than acting as PME inhibitors. It is concluded that regulated changes in the degree of pectin methylesterification through CAP- and RAD-specific PME and PME inhibitor expression play a crucial role during Brassicaceae seed germination.


Experimental and computational determination of blend time in USP Dissolution Testing Apparatus II.
Blend time, the time to achieve a predefined level of homogeneity of a tracer in a mixing vessel, is an important parameter to evaluate the mixing efficiency of mixing devices. In this work, the blend time required to homogenize the liquid content of a USP Dissolution Testing Apparatus II under a number of operating conditions was obtained using two different experimental methods (tracer detection via colorimetric and conductivity measurements), a computational approach (computational fluid dynamics (CFD)), and a semi-theoretical analysis of the phenomenon. Under the standard geometric and operating conditions in which the USP Apparatus II is typically used (N = 50 rpm) the experimental blend time to achieve a 92.74% uniformity level was found to be between 27.5 and 33.3 s, depending on the location of the injection point and monitoring point for the tracer. These values were in close agreement with those obtained from CFD simulations. Changing the impeller vertical position (+/-2 mm) had only a limited effect. The CFD predictions also indicated that blend time is inversely proportional to the agitation speed. This conclusion is in agreement with previous reports and equations for blend time in mixing vessels. The blend times obtained in this work appear to be some two orders of magnitude smaller than the time usually required for appreciable tablet dissolution during the typical dissolution test, implying that the liquid contents of the USP Apparatus II can be considered to be relatively well mixed during the typical dissolution test.


Stimulation of the antigen receptor on WEHI-231 B lymphoma cells results in a voltage-independent increase in cytoplasmic calcium.
WEHI-231, a lymphoma-derived murine B cell line, responded to anti-IgM antibodies by increasing the concentration of free calcium in the cytoplasm from 140 nM to 590 nM within 15 sec. This is very similar to the response observed previously in normal B cells (Pozzan et al., 1982, J. Cell Biol. 94:335). Only antibodies specific for mIgM stimulated this response; control antibodies had no effect. In addition, anti-IgM did not stimulate a response by a mutant with a greatly decreased amount of membrane IgM. The relationship of this increase in cytoplasmic calcium to the plasma membrane potential was examined. Anti-IgM did not cause a rapid depolarization of the cells, suggesting that a voltage-dependent calcium channel was not responsible for the calcium increase. Furthermore, experimental depolarization of WEHI-231 cells did not cause a calcium influx, and the calcium increase caused by anti-IgM was not greatly affected by previous depolarization or by prevention of depolarization. These experiments argue strongly that the increase in cytoplasmic calcium was not mediated by a depolarization-activated calcium channel, such as the one found in cardiac muscle and in some neurons. Indeed, a significant portion of the initial increase in cytoplasmic calcium was due to the release of calcium from internal stores, suggesting the involvement of a soluble mediator. Examination of these internal storage sites in permeabilized cells revealed that inositol 1,4,5-trisphosphate could induce the release of calcium. These results are consistent with the hypothesis that the calcium increase in B cells stimulated by anti-IgM is caused by breakdown of phosphatidylinositol 4,5-bisphosphate, generating diacylglycerol and inositol trisphosphate, with the latter compound mediating calcium mobilization.


Characterization of air-liquid interface culture of A549 alveolar epithelial cells.
Alveolar epithelia play an essential role in maintaining the integrity and homeostasis of lungs, in which alveolar epithelial type II cells (AECII) are a cell type with stem cell potential for epithelial injury repair and regeneration. However, mechanisms behind the physiological and pathological roles of alveolar epithelia in human lungs remain largely unknown, partially owing to the difficulty of isolation and culture of primary human AECII cells. In the present study, we aimed to characterize alveolar epithelia generated from A549 lung adenocarcinoma cells that were cultured in an air-liquid interface (ALI) state. Morphological analysis demonstrated that A549 cells could reconstitute epithelial layers in ALI cultures as evaluated by histochemistry staining and electronic microscopy. Immunofluorescent staining further revealed an expression of alveolar epithelial type I cell (AECI) markers aquaporin-5 protein (AQP-5), and AECII cell marker surfactant protein C (SPC) in subpopulations of ALI cultured cells. Importantly, molecular analysis further revealed the expression of AQP-5, SPC, thyroid transcription factor-1, zonula occludens-1 and Mucin 5B in A549 ALI cultures as determined by both immunoblotting and quantitative RT-PCR assay. These results suggest that the ALI culture of A549 cells can partially mimic the property of alveolar epithelia, which may be a feasible and alternative model for investigating roles and mechanisms of alveolar epithelia in vitro.


Critical care: Are we customer friendly?
Assessing and enhancing family satisfaction are imperative for the provision of comprehensive intensive care. There is a paucity of Indian data exploring family's perception of Intensive Care Unit (ICU) patients. We wanted to explore family satisfaction and whether it differed in families of patients admitted under intensivists and nonintensivists in our semi-open ICU. We surveyed family members of 200 consecutive patients, between March and September 2009 who were in ICU for >3 days. An internationally validated family satisfaction survey was adapted and was administered to a family member, on day 4 of the patient's stay. The survey consisted of 15 questions in five categories - patient care, medical counseling, staff interaction, visiting hours, and facilities and was set to a Likert scale of 1-4. Mean, median, and proportions were computed to describe answers for each question and category. A total of 515 patients were admitted during the study period, of which 200 patients stayed in the ICU >3 days. One family member each of the 200 patients completed the survey with 100% response rate. Families reported the greatest satisfaction with patient care (94.5%) and least satisfaction with visiting hours (60.5%). Chi-square tests performed for each of the five categories revealed no significant difference between satisfaction scores of intensivists and nonintensivists' patients. Family members of ICU patients were satisfied with current care and communication, irrespective of whether they were admitted under intensivists or nonintensivists. Family members preferred open visiting hours policy than a time limited one.


To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis: a position paper of ESGBOR, the ESCMID study group for Lyme borreliosis.
Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato. The most frequent clinical manifestations are erythema migrans and Lyme neuroborreliosis. Currently, a large volume of diagnostic testing for LB is reported, whereas the incidence of clinically relevant disease manifestations is low. This indicates overuse of diagnostic testing for LB with implications for patient care and cost-effective health management. The recommendations provided in this review are intended to support both the clinical diagnosis and initiatives for a more rational use of laboratory testing in patients with clinically suspected LB. This is a narrative review combining various aspects of the clinical and laboratory diagnosis with an educational purpose. The literature search was based on existing systematic reviews, national and international guidelines and supplemented with specific citations. The main recommendations according to current European case definitions for LB are as follows. Typical erythema migrans should be diagnosed clinically and does not require laboratory testing. The diagnosis of Lyme neuroborreliosis requires laboratory investigation of the spinal fluid including intrathecal antibody production, and the remaining disease manifestations require testing for serum antibodies to B. burgdorferi. Testing individuals with non-specific subjective symptoms is not recommended, because of a low positive predictive value.


We know very little about the subjective effects of drugs in females.
Pharmaceutical companies assessing the nervous system effects of candidate therapeutics often use a behavioral assay in rodents that assesses the drug's subjective (internal stimulus) effects. Variants of this so-called "drug discrimination task" have also been widely used by basic scientist for more than 50 years to study the receptor actions of a host of ligands related to disease states and neuropathologies. Notably, most published research with this task has used male rats or mice. This situation is unfortunate and severely limits the utility of the research, given the well-documented differences between women and men on drug efficacy and safety, as well as known sex differences in the neural and behavioral effects of drugs. In this Viewpoint, we highlight the need for basic researchers, as well as pharmaceutical scientists, to include females in drug discrimination studies in a manner that allows detection and interpretation of potential sex differences.