Parallel Processing of Two Mechanosensory Modalities by a Single Neuron in C. elegans.
Neurons convert synaptic or sensory inputs into cellular outputs. It is not well understood how a single neuron senses, processes multiple stimuli, and generates distinct neuronal outcomes. Here, we describe the mechanism by which the C. elegans PVD neurons sense two mechanical stimuli: external touch and proprioceptive body movement. These two stimuli are detected by distinct mechanosensitive DEG/ENaC/ASIC channels, which trigger distinct cellular outputs linked to mechanonociception and proprioception. Mechanonociception depends on DEGT-1 and activates PVD's downstream command interneurons through its axon, while proprioception depends on DEL-1, UNC-8, and MEC-10 to induce local dendritic Ca2+ increase and dendritic release of a neuropeptide NLP-12. NLP-12 directly modulates neuromuscular junction activity through the cholecystokinin receptor homolog on motor axons, setting muscle tone and movement vigor. Thus, the same neuron simultaneously uses both its axon and dendrites as output apparatus to drive distinct sensorimotor outcomes.


Exploiting SERS sensitivity to monitor DNA aggregation properties.
In the last decades, DNA has been considered far more than the system carrying the essential genetic instructions. Indeed, because of the remarkable properties of the base-pairing specificity and thermoreversibility of the interactions, DNA plays a central role in the design of innovative architectures at the nanoscale. Here, combining complementary DNA strands with a custom-made solution of silver nanoparticles, we realize plasmonic aggregates to exploit the sensitivity of Surface Enhanced Raman Spectroscopy (SERS) for the identification/detection of the distinctive features of DNA hybridization, both in solution and on dried samples. Moreover, SERS allows monitoring the DNA aggregation process by following the temperature variation of a specific spectroscopic marker associated with the Watson-Crick hydrogen bond formation. This temperature-dependent behavior enables us to precisely reconstruct the melting profile of the selected DNA sequences by spectroscopic measurements only.


Towering tribute to botany.
One of the world's greatest plant collections has won a top heritage award at a time when it is highlighting with a tree-top walkway the need to study the forest canopy which is one of the most crucial but least understood habitats.


Subphrenic abscess: a pulmonary presentation.
A patient with subphrenic abscess can present with pulmonary or abdominal symptoms because of the location of the abscess adjacent to the diaphragm. This thoracoabdominal clinical complex has been described previously and, if chest symptoms predominate, may obscure the diagnosis of subphrenic abscess. The case of a patient with occult abdominal pathology who presented with respiratory complaints is discussed.


Detection of citrinin in ochratoxin A-containing products by a new HPLC method.
A new method for citrinin was developed and validated, which is based on solid phase extraction with polyamide columns and HPLC with fluorescence detection. Sufficient skill with the method given, precise results, i.e. variation coefficients <10%, will be achieved. The mean recovery rates were in the range 74 - 90%. The detection limits of the method determined according to DIN 32645, at good precision, were 1 µg/kg for wheat, rye, barley, maize, and oats. The analysis of several samples containing ochratoxin A (OTA) showed that citrinin is present in brans, wheatings and shorts containing a higher ratio of the outer layers of the grain kernel; both OTA and citrinin were found in in cocoa shells and raisins. Citrinin was detected in 14 OTA-containing samples (1-8 µg/kg). Furthermore, it was demonstrated that citrinin also can be determined in red mold rice according to the new method.


Fast and accurate metagenotyping of the human gut microbiome with GT-Pro.
Single nucleotide polymorphisms (SNPs) in metagenomics are used to quantify population structure, track strains and identify genetic determinants of microbial phenotypes. However, existing alignment-based approaches for metagenomic SNP detection require high-performance computing and enough read coverage to distinguish SNPs from sequencing errors. To address these issues, we developed the GenoTyper for Prokaryotes (GT-Pro), a suite of methods to catalog SNPs from genomes and use unique k-mers to rapidly genotype these SNPs from metagenomes. Compared to methods that use read alignment, GT-Pro is more accurate and two orders of magnitude faster. Using high-quality genomes, we constructed a catalog of 104 million SNPs in 909 human gut species and used unique k-mers targeting this catalog to characterize the global population structure of gut microbes from 7,459 samples. GT-Pro enables fast and memory-efficient metagenotyping of millions of SNPs on a personal computer.


Control of fecundity through abortion in Epilobium montanum L.
Plants of the inbreeding perennial herb Epilobium montanum L. were defoliated at two stages in development and the formation and abortion of flower buds, flowers, copsules and ovules was compared with control plants. A comparison was also made of the effects of self- and cross-pollination on fecundily. Defoliation reduced the number of flower buds formed but its greatest effect was to increase the abortion of flower buds. Defoliation also caused earlier abortions which were generally lower on the racemes of the treated than on the control plants. The abortion of flowers and capsules was much less significant. The number of ovules formed per capsule decreased with height on the raceme and the abortion rate of ovules was increased by defoliation. The pattern of ovule abortion within the capsules differed between cross- and self-pollinated plants but the number of seeds ripened was not affected. The overall survivorship of ovules to mature seeds was 89.3% which compares with the average of 85% found by Wiens for inbreeding annuals. The findings suggest that such high values of ovule survivorship may be characteristics of normally inbreeding species irrespective of whether they are annuals or perennials.


Safety and efficacy of neoadjuvant chemotherapy containing bevacizumab and interval debulking surgery for advanced epithelial ovarian cancer: A feasibility study.
The optimum treatment strategy for patients with unresectable advanced epithelial ovarian cancer is controversial. This study examined bevacizumab combined with neoadjuvant chemotherapy (NAC; paclitaxel plus carboplatin), followed by interval debulking surgery (IDS), for these patients. In a prospective nonrandomized study, newly diagnosed patients received four cycles of NAC (three cycles combined with bevacizumab), followed by IDS. The primary endpoint was the complete resection rate at IDS. Secondary endpoints were the NAC response rate, adverse events during NAC, and perioperative complications. Twenty-three patients were enrolled. The complete resection rate at IDS was 60.9% (95% confidence intervals [CI]: 38.5% to 80.3%). The NAC response rate was 86.9% (95% CI: 66.4% to 97.2%). Adverse events ≥ grade 3 during NAC were neutropenia (78.3%), anemia (52.2%), hypertension (17.4%), and proteinuria (8.7%). There was no thromboembolism or gastrointestinal perforation. Grade 2 complications of IDS included lymphatic complications (13.6%), infections (9.1%), ileus (4.5%), and wound dehiscence (4.5%). There were no thromboembolic complications, fistula/abscess, or perforation/anastomotic leak, and no complications ≥ grade 3. In Japanese patients with advanced ovarian cancer, bevacizumab + NAC followed by IDS is an acceptable strategy. Further investigation of its prognostic effect is warranted.


Immunoadolescence: Neuroimmune development and adolescent behavior.
The brain is increasingly appreciated to be a constantly rewired organ that yields age-specific behaviors and responses to the environment. Adolescence in particular is a unique period characterized by continued brain maturation, superimposed with transient needs of the organism to traverse a leap from parental dependence to independence. Here we describe how these needs require immune maturation, as well as brain maturation. Our immune system, which protects us from pathogens and regulates inflammation, is in constant communication with our nervous system. Together, neuro-immune signaling regulates our behavioral responses to the environment, making this interaction a likely substrate for adolescent development. We review here the identified as well as understudied components of neuro-immune interactions during adolescence. Synaptic pruning, neurite outgrowth, and neurotransmitter release during adolescence all regulate-and are regulated by-immune signals, which occur via blood-brain barrier dynamics and glial activity. We discuss these processes, as well as how immune signaling during this transitional period of development confers differential effects on behavior and vulnerability to mental illness.


Does the choice of suture material matter in anterior and posterior colporrhaphy?
The optimal suture material in traditional prolapse surgery is still controversial. Our aim was to investigate the effect of using sutures with rapid (RA) or slow (SA) absorption, on symptomatic recurrence after anterior and posterior colporrhaphy. A population-based longitudinal cohort study with data from the Swedish National Quality Register for Gynecological Surgery. A total of 1,107 women who underwent primary anterior colporrhaphy and 577 women who underwent primary posterior colporrhaphy between September 2012 and September 2013 were included. Two groups in each cohort were created based on which suture material was used. Pre- and postoperative prolapse-related symptoms and patient satisfaction were assessed. We found a significantly lower rate of symptomatic recurrence 1 year after anterior colporrhaphy in the SA suture group compared with the RA suture group, 50 out of 230 (22 %) vs 152 out of 501 (30 %), odds ratio 1.6 (CI 1.1-2.3; p = 0.01). The SA group also had a significantly higher patient satisfaction rate, 83 % vs 75 %, odds ratio 1.6 (CI 1.04-2.4), (p = 0.03). Urgency improved significantly more in the RA suture group (p < 0.001). In the posterior colporrhaphy cohort there was no significant difference between the suture materials. This study indicates that the use of slowly absorbable sutures decreases the odds of having a symptomatic recurrence after an anterior colporrhaphy compared with the use of rapidly absorbable sutures. However, the use of RA sutures may result in less urgency 1 year postoperatively. In posterior colporrhaphy the choice of suture material does not affect postoperative symptoms.


A genetic variant in pre-miR-27a is associated with a reduced breast cancer risk in younger Chinese population.
Accumulating evidence has indicated that single nucleotide polymorphisms (SNPs) in miRNA precursors may have an effect on miRNA expression levels. Recently, an important A to G transition SNP in pre-mir-27a (rs895819) was identified. Previous studies have investigated the role of rs895819 in cancer risk, but the results remain contradictory, rather than conclusive. The present study aimed to evaluate the association of rs895819 with sporadic breast cancer susceptibility, clinicopathological characteristics and prognosis. We first analyzed the influence of rs895819 on the miR-27a expression level and determined that miR-27a expression was significantly lower in samples with the AG/GG genotype compared to samples with the AA genotype (p=0.022). Further investigation revealed that subjects with the G allele exhibited a significantly decreased risk of breast cancer relative to subjects carrying the A allele among the younger population (adjusted OR=0.628, 95% confidence interval 0.410-0.961; p=0.032). Moreover, significant associations between the presence of rs895819 and the histological grade and estrogen status of breast cancers were observed among the older group. However, the SNP did not influence the survival rate of patients with breast cancer. In conclusion, our results suggest that the SNP rs895819 may serve as a risk factor for breast cancer in younger Chinese populations; however, larger population-based studies are needed to validate these findings.


Within-subject effects of environmental and social stressors on pre- and post-partum obesity-related biobehavioral responses in low-income Hispanic women: protocol of an intensive longitudinal study.
Disproportionately high rates of maternal overweight and obesity among the Hispanic population before, during, and after pregnancy pose serious health concerns for both mothers (e.g., preeclampsia, gestational diabetes, weight retention) and children (e.g., elevated lifelong obesity risk). A growing body of evidence implicates environmental exposures (e.g., air pollution, metals) and social stressors (e.g., poverty, violence) in contributing to obesity-related biobehavioral processes, such as physical activity, dietary intake, perceived stress, and cortisol regulation. However, current understanding of the role of environmental exposures and social stressors on obesity-related biobehavioral processes is limited by infrequent, inter-individual measurement, and lack of personal exposure monitoring. The "Maternal and Developmental Risks from Environmental and Social Stressors" (MADRES) real-time and personal sampling study examines the within-subject day-level effects of environmental and social stressors on maternal pre- and post-partum obesity-related biobehavioral responses. Among a cohort of 65 low-income, Hispanic women in urban Los Angeles, this study uses innovative personal, real-time data capture strategies (e.g., ecological momentary assessment [EMA], personal exposure monitoring, geolocation monitoring, accelerometry) to repeatedly assess obesity-related processes during the 1st and 3rd trimester, and at 4-6 months postpartum. Day-level effects of environmental exposures and social stressors on women's physical activity, diet, perceived stress and salivary cortisol measured across repeated days will be tested using multilevel modeling. Hispanic women of childbearing age bear a disproportionately high burden of obesity, and this population is also unduly exposed to numerous obesogenic settings. By using innovative real-time data capture strategies, the current study will uncover the daily impacts of environmental and social stressor exposures on women's obesity-related biobehavioral responses, which over time can lead to excessive gestational weight gain, postpartum weight retention and can pose serious consequences for both mother and child. Findings from the real-time and personal sampling study will identify key mechanistic targets for policy, clinical, and programmatic interventions, with the potential for broad-reaching public health impacts.


Platelet reactivity testing in peripheral artery disease.
Oral antiplatelet therapy is routinely used to prevent adverse cardiovascular events in patients with peripheral artery disease (PAD). Several laboratory tests are available to quantify the degree of platelet inhibition following antiplatelet therapy. This article aims to provide a review of the literature surrounding platelet functional testing in patients with PAD receiving oral P2Y12 inhibitors and to offer guidance to clinicians for the use and interpretation of these tests. A literature search of PubMed and the Web of Science Core Collection database was conducted. All studies that performed platelet function testing and reported clinical outcomes in patients with PAD were included. Evaluation of the data suggests that, among the available testing strategies, the VerifyNow platelet reactivity unit (PRU) test is the most widely used. Despite numerous investigations attempting to define a laboratory threshold indicating suboptimal response to antiplatelet therapy, controversy exists about which PRU value best correlates with cardiovascular outcomes (ie, mortality, stent thrombosis, etc). In the PAD literature, the most commonly used PRU thresholds are 208 or higher and 235 or higher. Nonetheless, adjusting antiplatelet regimens based on suboptimal P2Y12 reactivity values has yet to be proven useful in reducing the incidence of adverse cardiovascular outcomes. This review examines platelet function testing in patients with PAD and discusses the interpretation and application of these tests when monitoring the safety and efficacy of P2Y12 inhibitors. Although platelet functional tests may be simple to use, clinical trials thus far have failed to show benefit from therapy adjustments based on test results. Clinicians should be cautioned against relying on this test result alone and should instead consider a combination of laboratory, clinical, and patient-specific factors when adjusting P2Y12 inhibitor therapy in clinical practice.


A newly discovered Fc receptor that explains IgG-isotype disparities in effector responses.
The known IgG FcRs primarily mediate inflammation by interacting with IgG1, even though IgG2 isotypes tend to be more pathogenic. A novel FcgammaR that binds IgG2 but not IgG1 has just been identified, potentially explaining differences in biological activity that are seen with various IgG isotypes.


A Wench's Guide to Surviving a 'Global' Pandemic Crisis: Feminist Publishing in a Time of COVID-19.
It has been quite a year so far(!) and as the wenches we are, we have been taking our time to collect our thoughts and reflections before sharing them at the start of this issue of the journal. In this editorial we think through the COVID-19 pandemic and its devastating effects on the world, on our lives and on our editorial processes. We renew our commitment to improving our operations as a journal and its health along with our own as we deploy wench tactics to restore, sustain and slow down to negotiate this new reality, this new world. We conclude with an introduction to the fascinating contents of this issue along with a collaborative statement of values on open access as part of a collective of intersectional feminist and social justice editors. Through all of the pain and suffering we focus our gaze on hope: hope that we can come through this global crisis together engaging in critical conversations about how we can be better and do better as editors, academics and individuals for ourselves, our colleagues and our journal.


PEG superoxide dismutase derivatives: anti-inflammatory activity in carrageenan pelurisy in rats.
Two derivatives of superoxide dismutase (SOD) with monomethoxypolyethyleneglycol, having different molecular weights (46,000 and 121,000 D) and different plasma half-lives are tested in carrageenan pleurisy in rats after single i.v. injection. The compounds were prepared following an original method where the polymer is activated by trichlorophenylchloroformate to give a phenylcarbonate which is reactive towards the protein amino groups. The anti-inflammatory activity of derivatives results correlated to their kinetics, lasting longer for the derivative with the longest half-life (SOD-PEG 18). SOD activity, in plasma of rats treated with SOD-PEG 18, is still present 24 hour after carrageenan, in agreement with the prolonged anti-inflammatory activity. Moreover SOD-PEG 18 diffuses well in pleural exudate, as it is evidentiated from the increase with time of exudate/plasma concentration ratio.


Wildlife Conservation and Private Protected Areas: The Discrepancy Between Land Trust Mission Statements and Their Perceptions.
In 2010, land trusts in the U.S. had protected nearly 50 million acres of land, with much of it providing habitat for wildlife. However, the extent to which land trusts explicitly focus on wildlife conservation remains largely unknown. We used content analysis to assess land trust involvement in wildlife and habitat conservation, as reflected in their mission statements, and compared these findings with an organizational survey of land trusts. In our sample of 1358 mission statements, we found that only 17 % of land trusts mentioned "wildlife," "animal," or types of wildlife, and 35 % mentioned "habitat" or types. Mission statements contrasted sharply with results from a land trust survey, in which land trusts cited wildlife habitat as the most common and significant outcome of their protection efforts. Moreover, 77 % of land trusts reported that at least half of their acreage protected wildlife habitat, though these benefits are likely assumed. Importantly, mission statement content was not associated with the percentage of land reported to benefit wildlife. These inconsistencies suggest that benefits to wildlife habitat of protected land are recognized but may not be purposeful and strategic and, thus, potentially less useful in contributing toward regional wildlife conservation goals. We outline the implications of this disconnect, notably the potential omission of wildlife habitat in prioritization schema for land acquisition and potential missed opportunities to build community support for land trusts among wildlife enthusiasts and to develop partnerships with wildlife conservation organizations.


Infectious complications in patients with myelodysplastic syndromes: A review of the literature with emphasis on patients treated with 5-azacitidine.
Myelodysplastic Syndromes are oligo-clonal stem cell disorders that are associated with cytopenias in the peripheral blood. Major causes for morbidity and mortality in myelodysplastic syndromes (MDS) patients are infections mostly due to bacteria or fungi. Beside leucopenia per se in affected patients, function of white blood cells particularly that of neutrophils seems to be impaired. Here we summarize the available data on infections in MDS patients in general and particularly those treated with 5-azacitidine.


Immunohistochemical examination of tumor-suppressor gene p53 product and pyrimidine dimer in solar keratosis.
In order to find biomarkers to measure the effects of UV irradiation, we examined the accumulation of p53 protein and pyrimidine dimers in 18 solar keratosis specimens. Frozen or AMeX-fixed solar keratosis specimens were immunohistochemically stained by anti-p53 mouse monoclonal antibody, pAb1801 and polyclonal anti-(pyrimidine dimer) antibody. Nuclear accumulation of p53 protein was found in 5/18 (28%) solar keratosis lesions. The percentage of cases showing nuclear p53 protein varied according to the histological type; in the bowenoid type it was 4/7 (57%); in the atrophic type it was 1/7 (14%). Nuclear pyrimidine dimers were not stained in solar keratosis, although the skin of UV-irradiated nude mice was positive. Accumulation of p53 protein is a good marker for early precancerous change caused by UV exposure.


["DIabetes Versorgungs-Evaluation" (DIVE)--a national quality assurance initiative at physicians providing care for patients with diabetes].
Due to the variety of affected organ systems, necessitating a multidisciplinary and interconnected approach in deciding on individual diagnostic and therapeutic strategies, a structured documentation of data for patients suffering from diabetes mellitus is steadily gaining importance. Towards this purpose, multiple quality initiatives (e. g. SWEET, QS-DPV, EUBIROD etc.) as well as several software systems (e. g. [DPV2] DIAMAX, DPV, EMIL, Qmax etc.) have been developed to capture patient-related data. This is further complicated by the necessity to exchange data with a large variety of doctor's office administration systems. To address this complex of issues, DiabetesDE in cooperation with several societies, doctor's associations and prospective end users launched a national register platform. DIVE (Diabetes Care Evaluation) is aimed at establishing a national diabetes register to centrally capture data from diabetes patients being treated by diabetology specialists in Germany, thus making them available for quality assurance and health services research. Since September 2011, 142 so far participating doctors have documented data for 84,774 patients. Compared to patients treated by general practitioners, persons under specialist care show a more advanced clinical picture with substantial co-morbidity. DIVE provides a national platform which will address essential fields of activity with regard to the development of a national diabetes strategy--epidemiology, diabetes registry, health care research, quality assurance--based on usual office administration systems, thus contributing to the improvement of care and treatment for patients suffering from diabetes.


[Transcription of the prune gene during a position effect of the mosaic type in Drosophila melanogaster].
Analysis of transcription of the gene prune being undergone position effect variegation in the inversion In(1LR)pn2a is presented. Using Northern hydridization with following densitometric analysis of blots it was shown that the quantity of the prune mRNA is decreased 1.8 +/- 0.4 times in comparison with normal. Transcripts differing from wild type sizes are not detected. On the basis of the results obtained of inactivation propagation in the case of the position effect.


Unilateral stenosis of the vertebral artery--secondary finding with no prognostic relevance?
The outcome of 142 patients suffering from ischemic cerebral circulation disorders was followed up over a period of 33 months on average. The spontaneous course of 25 patients with unilateral, hemodynamically ineffective stenoses of the vertebral artery was compared with that of 107 patients without vertebral artery stenoses. Within the first 12 months, novel clinically manifest cerebrovascular events were observed in 16.0% of patients without vertebral artery stenosis (deaths 5.0%), but in only 4.3% of the patients with vertebral artery stenosis (no deaths). Within 30 months, only 2 of the 13 patients with vertebral artery stenosis had suffered a new cerebrovascular attack. At the end of the observation period, 39.3% of the patients without vertebral artery stenosis and 48.0% of the patients with vertebral artery stenosis were significantly disabled in their social life or had died. An additional unilateral hemodynamically irrelevant vertebral artery stenosis did not influence the rate of reinfarction or the remission of neurological deficits, independently of age, the degree of the circulatory disorder, the vascular territory involved, the presence of an organic psychosyndrome, or of additional stenoses in the carotid arteries. Consequently, a vertebral artery stenosis narrowing the vessel diameter to less than 1/3 is without prognostic relevance.


Prognosis of elderly non-valvular atrial fibrillation patients stratified by B-type natriuretic peptide: ELDERCARE-AF subanalysis.
B-type natriuretic peptide (BNP) is a risk factor for stroke and cardiac death in patients with atrial fibrillation. We hypothesized the prognostic outcomes of very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment would vary according to BNP stratification. In this subanalysis of the ELDERCARE-AF trial, patients were stratified by BNP levels at enrollment, and clinical outcomes compared among BNP subgroups. Hazard ratios were adjusted for age, atrial fibrillation type, body mass index, creatine clearance, congestive heart failure, and D-dimer. BNP levels were measured using chemiluminescence enzyme immunoassays. In total, 984 patients (average age: 86.6 years) not considered eligible for oral anticoagulant therapy at approved doses for stroke prevention were included. The BNP levels at enrollment were <200 (low), 200 to <400 (moderate), and ≥400 (high) pg/mL in 428, 300, and 256 patients, respectively. The number (%) of patients with stroke or systemic embolism (SSE) was 7 (1.2%), 24 (5.9%), and 28 (8.6%) in the low, moderate, and high BNP subgroups, respectively (adjusted hazard ratio 3.82, P = .0025 for low vs moderate BNP and 4.76, P = .0007 for low vs high BNP). There was no significant difference in major bleeding incidence between the BNP subgroups. Edoxaban 15 mg was associated with a consistent reduction in SSE vs placebo in all BNP subgroups. Stratification by BNP level was associated with the incidence of SSE for very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment, and the effect of edoxaban 15 mg was consistent across BNP levels.


A macroscopic investigation of the nerves to the eye and ocular annexes in the Van cat.
The orbital nerves were examined grossly in eight adult Van cats from either sex. The optic nerve, in a sigmoid curl, reached the eyeball after coursing between the retractor bulbi and medial rectus muscles. The oculomotor nerve gave off dorsal and ventral branches between the retractor bulbi and lateral rectus muscles. The ciliary ganglion was located on the lateral subbranch of the ventral branch of this nerve in all materials. There were short ciliary nerves originated from the ciliary ganglion in all the materials observed. The lacrimal nerve was a branch of the maxillary nerve.


Expression, purification, and characterisation of human soluble Epoxide Hydrolase (hsEH) and of its functional C-terminal domain.
The human soluble Epoxide Hydrolase (hsEH) is an enzyme involved in the hydrolysis of endogenous anti-inflammatory and cardio-protective signalling mediators known as epoxyeicosatrienoic acids (EETs). EETs' conversion into the corresponding diols by hsEH generates non-bioactive molecules, thereby the enzyme inhibition would be expected to enhance the EETs bioavailability, and their beneficial properties. Numerous inhibitors have been developed to target the enzyme, some of which are showing promising antihypertensive and anti-inflammatory properties in vivo. Thus far, the preparation of the recombinant enzyme for enzymatic and structural in vitro studies has been performed mainly using a baculovirus expression system. More recently, it was reported that the enzyme could be exogenously expressed and isolated from E. coli, although limited amounts of active protein were obtained. We herein describe two novel methods to yield pure recombinant enzyme. The first describes the expression and purification of the full-length enzyme from eukaryotic cells HEK293-F, whilst the second concerns the C-terminal domain of hsEH obtained from the cost-effective and rapid E. coli prokaryotic system. The two methods successfully generated satisfactory amounts of functional enzyme, with virtually identical enzymatic activity. Overall, the protocols described in this paper can be employed for the recombinant expression and purification of active hsEH, to be used in future biomedical investigations and for high-throughput screening of inhibitors for potential use in the treatment of cardiovascular disease.


Early in vivo discrimination of vulnerable atherosclerotic plaques that disrupt: A serial MRI study.
MRI has been validated as a suitable imaging modality for in vivo, non-invasive detection of atherosclerosis and has provided quantitative predictors of high-risk plaque. Here, we apply serial MRI to monitor the natural progression of plaques over a 3-month period in a rabbit model of atherothrombosis to determine differences over time between plaques that ultimately disrupt to form a luminal mural thrombus and plaques that remain stable. Atherosclerotic plaques were induced in 12 male New Zealand White (NZW) rabbits by aortic endothelial injury and a 1% cholesterol diet. The rabbits were imaged 5 times: at baseline, 1, 2, and 3 months, and 48hr after pharmacological triggering for plaque disruption. Starting at 2 months, plaques that disrupted after triggering exhibited a higher remodeling ratio (RR, 1.05 ± 0.11 vs 0.97 ± 0.10, p = 0.0002) and a larger vessel wall area (VWA, 6.99 ± 1.54 mm(2) vs 6.30 ± 1.37 mm(2), p = 0.0072) than the stable non-disrupted plaques. The same trends were observed at 3 months: plaques that disrupted had a higher RR (1.04 ± 0.02 vs 0.99 ± 0.01, p = 0.0209), VWA (8.19 ± 2.69 mm(2) vs 6.81 ± 1.60 mm(2), p = 0.0001), and increased gadolinium uptake (75.51 ± 13.77% for disrupted vs 31.02 ± 6.45% for non-disrupted, p = 0.0022). MR images of plaques that disrupted revealed larger VWAs, RRs, and increased gadolinium uptake at 2 months and continued progression of these vulnerable features between 2 and 3 months. Non-disrupted plaques had an independent history without these hallmarks of vulnerability. Our results show that MRI can provide early detection of plaques at a higher-risk for luminal thrombosis.


Interindividual differences in the susceptibility of the cortisol system: an important factor for the degree of hypercortisolism in stress situations?
Whereas in psychophysiological research, the specificity of the individual responses has been assumed to be an important trait variable influencing the investigated parameters in stress experiments or in psychopathological states, in psychoneuroendocrinology, the individual differences in the susceptibility of the investigated neuroendocrine axes have been widely neglected. The present study on the cortisol response of 12 healthy young men to 5 different stress tests is considered to be an initial orientation step into this field. All five stress tests (quiz, arithmetic tasks, stress film, cold pressor test, and physical exercise test) could be proven to be effective stimuli regarding the cortisol system. There was, however, a broad spectrum of cortisol responses among the 12 subjects, with a continuum between complete reactors and nonreactors. This did not correlate with the subjective judgment of stress at all. Although the data showed a tendency toward an augmented dispersion of the response frequencies in comparison with random variation, the limited sample size of subjects and stress tests did not allow a statistically significant proof of a stimulus-independent, individual response specificity. Further experimental clarification seems to be necessary to avoid misinterpretations of neuroendocrine data in psychiatric disorders due to neglect of this variable.


Developing drug prototypes: pharmacology replaces safety and tolerability?
New medicines are designed to bind to receptors or enzymes and are tested in animal cells, tissues and whole organisms in a highly scientific process. Subsequently they are often administered to human subjects with tolerability as the primary objective. The process of development is considered to be linear and consecutive and passes through the famous four phases of development (Phase I-Phase IV). This is efficient for those projects for which the uncertainty about the development is low. There is, however, an increasing number of new prototypical compounds resulting from the increased biological knowledge with a high level of uncertainty. For these prototypical drugs development has to proceed in a much more adaptive manner, using tailor-made objectives, the development of special methodology and a cyclical rather than a linear type of project management.


Data mining based approach to study the effect of consumption of caffeinated coffee on the generation of the steady-state visual evoked potential signals.
The steady-state visual evoked potentials (SSVEP), are elicited at the parieto-occipital region of the cortex when a light source (3.5-75 Hz), flickering at a constant frequency, stimulates the retinal cells. In the last few decades, researchers have reported that caffeine enhances the vigilance and the executive control of visual attention. However, no study has investigated the effect of caffeinated coffee on the SSVEP response, which is used for controlling the brain-computer interface (BCI) devices for rehabilitative applications. The current work proposes a data mining-based approach to gain insight into the alterations in the SSVEP signals after the consumption of caffeinated coffee. Recurrence quantification analysis (RQA) of the electroencephalogram (EEG) signals was employed for this purpose. The EEG signals were acquired at seven frequencies of photic stimuli. The stimuli frequencies were chosen such that they were distributed throughout the EEG frequency bands. The prominent SSVEP signals were identified using the Canonical Correlation Analysis (CCA) method. Several statistical features were extracted from the recurrence plot of the SSVEP signals. Statistical analyses using the t-test and decision tree-based methods helped to select the most relevant features, which were then classified using Automated Neural Network (ANN). The relevant features could be classified with a maximum accuracy of 97%. This supports our hypothesis that the consumption of caffeinated coffee can alter the SSVEP response. In conclusion, utmost care should be taken in selecting the features for designing BCI devices.


[Is transition from pure laparoscopic to robotic-assisted radical prostatectomy associated with increase of surgical procedures for urinary incontinence and erectile dysfunction?]
To study the impact of changing the technique of radical prostatectomy [pure laparoscopic radical (PR-Lap) to robot-assisted radical prostatectomy (RP-Rob)] on the rate of secondary procedures for urinary incontinence (UI) and erectile dysfunction (ED). Retrospective study evaluating the number and type of surgical procedures for post-RP UI and DE between 2008 and 2015, according to the technique of (RP-Lap or RP-Rob). Between 2008 et 2015, 2046 RP were performed in our department including 372 RP-Lap and 1674 RP-Rob. Among these patients, 84 (4%) had a surgical procedure for post-RP UI (18 AMS800, 9 balloons Pro-Act, and 57 male slings) and 15 (0.7%) had implantation of penile prosthesis for post-RP ED; 16 (0.7%) patients had both procedures. The mean delay between RP and UI surgery decrease from 3.2 years in 2008 to 1 year in 2015 and remain stable for penile prosthesis implantation (mean delay: 3.4 years). The overall rates of secondary procedures for UI and DE remained stable and below 5% and 1.7%, respectively, even during the transition period. For each year of PR studied, the rates of secondary procedure were higher in the RP-Lap group. Changing the technique of RP from RP-Lap to PR-Rob has a favorable impact on the rate of secondary procedures for UI and ED from the outset.


Cardiovascular gene therapy with vascular endothelial growth factors.
Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) is a promising approach for the treatment of ischemic myocardium and peripheral skeletal muscles. Preclinical studies in large animals have clearly demonstrated safety and efficacy of VEGF gene therapy in clinically relevant disease models. However, first clinical trials with intravascular delivery of VEGF vector constructs have only resulted in limited benefits to the patients. Second generation VEGF-based gene therapy trials are based on direct intramyocardial and intraskeletal muscle injections in order to achieve better transfection efficiency and more targeted effects. Phase I/II studies are currently ongoing to test safety, feasibility and efficacy of these improved approaches in patients with severe cardiovascular diseases.


Prevention of Postoperative Surgical Site Infection Following Cesarean Delivery.
Cesarean delivery is the most common major surgical procedure performed among birthing persons in the United States, and surgical-site infection is a significant complication. Several significant advances in preventive measures have been shown to reduce infection risk, while others remain plausible but not yet proven in clinical trials.


Current status and challenges of Pediatric heart transplantation in Japan.
It has been about 10 years since the revised Japanese Organ Transplant Law came into action. Organ donation from brain dead donors has increased in the past decade, but the number of recipients waiting for transplant is increasing more rapidly. Implantable continuous flow ventricular assist device, such as Jarvik 2000 and HeartWare, available from 2011, and Berlin heart EXCOR, available from 2015, has changed the scene for children with severe heart failure. About 80% of the patients who received heart transplantation (HTx) were supported by one of these devices, and average waiting time is 688±502 days. Despite small number of patients transplanted in Japan, patient survival at 10 years was 97.5%, which is superior to that of the International Registry of Heart and Lung Transplantation. Immunosuppression regimen included calcineurin inhibitor (mostly tacrolimus), mycophenolate mofetil, and steroid at the time of HTx. Major complications after HTx include rejection, infection, renal failure, cardiac allograft vasculopathy, and post-transplant lymphoproliferative disorders. Reasons for survival of Japanese pediatric HTx includes selections: limited number of patients with congenital heart disease, low donor risks, and good compliance. Further effort is required to achieve self-sufficiency of organ donors and transplantation, and reduce morbidity and mortality after HTx.


Lack of association between the CXCL12 rs501120 polymorphism and cardiovascular disease in Spanish patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis. CXCL12 is a strong chemotactic signal for lymphocytes. Because previous genome-wide association studies demonstrated an association between CXCL12 rs501120 and coronary artery disease, in the present study we assessed the potential association of this polymorphism with the risk of cardiovascular (CV) disease in 1,321 Spanish patients with RA. A subgroup of patients without CV events was also studied to determine the presence of subclinical atherosclerosis by ultrasonography (brachial flow-mediated endothelium-dependent vasodilatation and carotid intima-media wall thickness). However, no significant differences in genotypic and allelic frequencies between RA patients with and without CV events were observed, as was also the case when values of surrogate markers of atherosclerosis were assessed according to CXCL12 rs501120 genotype frequencies. In conclusion, our results do not confirm an association of the CXCL12 rs501120 polymorphism with atherosclerosis or with CV disease in RA.


Chinese-English bilinguals are more sensitive to environmental sound perception than Spanish-English bilinguals through top-down cognitive mechanism.
Sensitive perception to environmental sound is important for an individual's daily life since it helps in responding to the environment quickly and avoiding potential risks. It remains unclear, however, whether and how bilingual experiences with different native language backgrounds influence brain responses reflecting environmental sound perception. The present study compared Chinese-English bilinguals, Spanish-English bilinguals, and English monolinguals on their brain response to environmental sound perception and further examined its processing mechanism. The present study did not find the differences between English monolinguals and two bilingual groups on the environmental sound perception. However, we found that compared with Spanish-English bilinguals, Chinese-English bilinguals showed significantly larger mismatch negativity (MMN), indicating that Chinese-English bilinguals were more sensitive to the environmental sounds than that of Spanish-English bilinguals. Further, compared with Spanish-English bilinguals, Chinese-English bilinguals showed significantly larger theta oscillation. In addition, the theta oscillation is significantly correlated with MMN for Chinese-English bilinguals. The results indicated that the advantage of Chinese-English bilingual experience on environmental sound perception may be due to the enhanced top-down cognitive ability. In summary, these findings suggest that compared with the Spanish-English bilinguals, Chinese-English bilinguals showed an advantage in environmental sound perception via enhanced top-down cognitive modulation.


Life-long overexpression of S100beta in Down's syndrome: implications for Alzheimer pathogenesis.
Chronic overexpression of the neurite growth-promoting factor S100beta has been implicated in the pathogenesis of neuritic plaques in Alzheimer's disease. Such plaques are virtually universal in middle-aged Down's syndrome, making Down's a natural model of Alzheimer's disease. We determined numbers of astrocytes overexpressing S100beta, and of neurons overexpressing beta-amyloid precursor protein (beta-APP), and assayed for neurofibrillary tangles in neocortex of 20 Down's syndrome patients (17 weeks gestation to 68 years). Compared to controls, there were twice as many S100beta-immunoreactive (S100beta+) astrocytes in Down's patients at all ages: fetal, young, and adult (p = 0.01, or better, in each age group). These were activated (i.e., enlarged), and intensely immunoreactive, even in the fetal group. There were no neurofibrillary changes in fetal or young Down's patients. The numbers of S100beta+ astrocytes in young and adult Down's patients correlated with the numbers of neurons overexpressing beta-APP (p < 0.05). Our findings are consistent with the idea that conditions--including Down's syndrome--that promote chronic overexpression of S100beta may confer increased risk for later development of Alzheimer's disease.


Post-stroke restless leg syndrome and periodic limb movements in sleep.
Primary restless leg syndrome (RLS) and periodic limb movements in sleep (PLMS) frequently co-exist, obscuring the boundaries between the two conditions. In such instances, a study of secondary cases with focal lesions such as post-stroke RLS and PLMS (psRLS and psPLMS, respectively) can be helpful in identifying characteristics of the individual conditions. Patients who had suffered strokes and who subsequently developed psRLS or psPLMS were recruited. To determine the overall features of psRLS/PLMS, historical cases were selected from the literature. All cases with either psRLS or psPLMS alone were further analyzed to elucidate the distinctive pathomechanisms of the two conditions. Six patients with either psRLS or psPLMS were recruited from our hospital; two patients had both conditions contemporaneously. The literature contains details on 30 cases of psRLS or psPLMS. The causative lesion was most frequently located in the pons. We found that psRLS was more often bilateral, and usually detected later in time. Lesions in both the pontine base and tegmentum (together) were associated with unilateral psPLMS, whereas lesions in the corona radiata and adjacent basal ganglia were associated with bilateral RLS. Lesions confined to the corona radiata resulted in either unilateral or bilateral RLS. The observed differences in the clinical and radiological features of psRLS and psPLMS suggest that the pathophysiologies of the two conditions are distinct. Further research is needed to understand the pathophysiologies of primary RLS and PLMS.


The cranial sartorius muscle undergoes true hypertrophy in dogs with golden retriever muscular dystrophy.
The degree of atrophy or hypertrophy of selected pelvic limb muscles was determined in the canine homologue of Duchenne muscular dystrophy. While most muscles were atrophied, the caudal and cranial sartorius were hypertrophied. Cranial sartorius weights were corrected for body weight and endomysial space to determine true muscle weights (g/kg; mean+/-SD) in three golden retriever muscular dystrophy age groups, 4-10 (Group 1; n=15), 13-26 (Group 2; n=4), and 33-66 (Group 3; n=4) months and grouped normal dogs (6-20 months; n=12). Group 1 golden retriever muscular dystrophy weights (2.2063+/-0.6884) were greater than those of normal dogs (1.2699+/-0.1966), indicating that young golden retriever muscular dystrophy dogs have true cranial sartorius muscle hypertrophy. Values of Group 2 (1.3758+/-0.5078) and Group 3 (0.5720+/-0.2423) golden retriever muscular dystrophy dogs were less than those of Group 1, suggesting that the cranial sartorius muscle atrophies over time. Given that cranial sartorius muscle weight correlated with tarsal joint angle in affected dogs (r=-0.817), the hypertrophied muscle may play a role analogous to iliotibial band tightness in Duchenne muscular dystrophy.


Genome sequence of Rhizomucor pusillus FCH 5.7, a thermophilic zygomycete involved in plant biomass degradation harbouring putative GH9 endoglucanases.
We report here the annotated draft genome sequence of the thermophilic zygomycete Rhizomucor pusillus strain FCH 5.7, isolated from compost soil in Vietnam. The genome assembly contains 25.59 Mb with an overall GC content of 44.95%, and comprises 10,898 protein coding genes. Genes encoding putative cellulose-, xylan- and chitin-degrading proteins were identified, including two putative endoglucanases (EC 184.108.40.206) from glycoside hydrolase family 9, which have so far been mostly assigned to bacteria and plants.


Occurrence of the Seven Most Common Serotypes of Shiga Toxin-Producing Escherichia coli in Beef Cuts Produced in Meat Processing Plants in the State of São Paulo, Brazil.
Healthy cattle are considered the main reservoir of Shiga toxin-producing Escherichia coli (STEC) strains, so in some places in the world, products derived from beef are the most common source for disease outbreaks caused by these bacteria. Therefore, to guarantee that the beef produced by our slaughterhouses is safe, there is a need for continuous monitoring of these bacteria. In this study, 215 beef cuts were evaluated, including chilled vacuum-packed striploins (151 samples), rib eyes (30 samples), and knuckles (34 samples), from March to June 2018. These meat samples were collected from the slaughter of unconfined cattle, being arbitrarily collected from eight meat processing companies in São Paulo state, Brazil. Each sample was examined for the presence of STEC toxin type (stx1 and/or stx2 genes) and also the attaching and effacing E. coli (eae) gene, determined by a multiplex PCR assay. We show that the major seven STEC strains (O serogroups O26, O45, O103, O111, O121, O145, and O157) are not detected in any of the analyzed beef cut samples; however, three of them presented the virulence eae gene. Therefore, the absence of STEC strains in the beef samples may be an indication of the low prevalence of this pathogen in the cattle herd on the farm, associated with good hygiene and handling practices adopted by the meat industry.


[Dynamics of protein concentration in the neurons of a chronic "mirror" epileptiform focus].
Protein content in the neurons of layers III and V in the rat brain anterior-parietal cortex and the lateral thalamic nucleus was studied 11 and 63 days after cobalt implantation. In the course of the experiment, protein content increased by 44--49% in the neurons of layer III and decreased by 24--32% in the thalamic neurons. In small and large pyramids of layer V, protein content decreased by 21--28%, 11 days after cobalt implantation, and approached normal content by the 63rd day. It was concluded that according to morpho-functional characteristic of certain neuronal types (associative, in layer III, predominantly efferent, in layer V and associative neurons in subcortical formations of the lateral thalamic nucleus) their protein changes in response to convulsive activity were different.


A method for the accurate determination of the specificity of monoclonal antibodies reactive with porcine immunoglobulins.
Monoclonal antibodies against porcine IgG were produced by fusion and characterized. The supernatants of microtiter wells containing fusion hybrids were first screened with an ELISA using semi-purified porcine IgG as antigen. Hybrids reactive in ELISA were cloned by limiting dilution. Further characterization of the specificity of the monoclonal antibodies was done by a combination of two methods: SDS-PAGE electroimmunoblotting and convection blotting of immunoelectrophoretic patterns (IEP-immunoblotting). Using these techniques, we identified monoclonal antibodies specific for porcine Ig gamma chains.


Short term increase in low birth weight babies after Fukushima.
An analysis of low birth weight (LBW) births in ten contaminated prefectures of Japan, 1995-2018, finds a statistically significant increase in the LBW proportion in 2012-2013, but no increase after 2013. In the rest of Japan (37 prefectures), no increase in LBW births was found after the Fukushima accident.


Optimized protocol for the large scale production of HIV pseudovirions by transient transfection of HEK293T cells with linear fully deacylated polyethylenimine.
HIV vaccine strategies which employ pseudovirions (PVs) as the source of antigen require large amounts of particles. These are typically generated by transient transfection of mammalian cells and purification of the released PVs from the culture supernatant. Since efficiency and cost of transfection are key issues, in this report the transfection efficiencies, achieved by employing a panel of high-molecular-weight linear polyethylenimines (PEIs) and small cross-linked PEIs, were analyzed and compared to those obtained by transfections with calcium phosphate or the commercial reagent Polyfect. High efficiencies were obtained using several of the modified PEIs, and the transfections with these inexpensive reagents were very robust. The observed efficiencies (as quantitated by amounts of expressed gene product) were two to four fold superior to calcium phosphate transfection and approximately equal to that achieved using Polyfect which is, however, prohibitively expensive for large scale applications. An optimized and rapid protocol for the large scale production and purification of HIV-PVs from 293T cells growing in so-called cell stacks and transfected with the best reagent identified, PEI87, is described here. The generated PVs, obtained with a yield in the range of 0.4mg virion-associated HIV-CA/liter culture supernatant, exhibited only very minimal contamination with non-viral proteins and were thus suitable for vaccination applications.


A European workshop to investigate technical problems of using HLA monoclonal antibodies in microcytotoxicity assays.
Various methods for controlling carryover from monoclonal antibodies (MCA) used in the microcytotoxicity assay to detect HLA antigens were investigated by 45 European laboratories. Carryover was demonstrated in most laboratories when using standard techniques (i.e. as for allo-antisera). Taking into consideration factors such as technical ease, time, accuracy and reagent availability, nearly half the participants selected the "no-touch" technique for adding cells and complement as being the best method for controlling carryover in their laboratory. (This method allows the needle of the Hamilton syringe to touch the oil but not the antibody in each well). Most participants (75%) thought that at least one diluent well was still necessary between each MCA well, even when using their preferred technique.


The complex nature of the mechanism of toxicity of antibiotic dithiacyclohexadiene polyines (thiarubrines) from the asteraceae.
Thiarubrine A, a dithiacyclohexadiene polyine from the roots of Chaenactis douglasii, and a related dithiacyclohexadiene from Rudbeckia hirta exhibit strong light-independent antibacterial and antifungal activity. This activity is enhanced by exposure to visible light. Visible light also converts the compounds to the corresponding thiophenes. These are antibiotic only when irradiated with UV-A. Dithiacyclohexadienes are the first polyines to exhibit such complex mechanisms of toxicity towards microorganisms.


Assessment of the value of confirming responses in clinical trials in oncology.
The requirement for a second assessment to confirm initial tumour response is required by all response guidelines. Its rationale, however, is not clear. We have conducted this study to compare validity of response rate assessment determined with and without secondary confirmation. Using specified criteria, nine trials of one single cytotoxic drug including 416 patients were selected from a pharmaceutical database. Objective response rates were determined by a single determination and by two separate determinations. 81 responses (19.5%, [15.8-23.6%]) were scored by the confirmation method and 97 responses (23.3% [19.3-27.7%]) by the no-confirmation method. The Kappa (kappa) coefficient of 0.89 indicates good agreement between both methods. This is the first study that systematically compares response rates calculated with and without performing response confirmation. Results show good agreement between both methods. We suggest that assessing response without confirmation may be the preferred method. These results should be confirmed by additional studies in a variety of cancer settings.


Weight stigma and media: An examination of the effect of advertising campaigns on weight bias, internalized weight bias, self-esteem, body image, and affect.
While some media perpetuate weight stigma and an ideal of thinness, certain advertising campaigns, such as Aerie Real and Dove Real Beauty, have attempted to promote body acceptance. The current study evaluated the influence of exposure to these campaigns on weight bias, internalized weight bias (IWB), self-esteem, body image, and affect relative to exposure to a campaign perpetuating the thin ideal and a documentary on weight stigma. 475 female participants were randomized to one of five conditions: Aerie, Dove, Victoria's Secret, an HBO documentary, or control (i.e., neutral video clip). Participants completed measures of weight bias, IWB, self-esteem, body image, and affect one week prior to and immediately after watching the assigned video clip. Results showed positive effects of the Aerie and Dove campaigns on women. While global measures of weight bias and IWB were unchanged, women who viewed the Dove and Aerie campaigns reported significantly improved self-esteem and positive affect. Further, women found the campaigns to have positive, uplifting, and empowering messages. Aerie's and Dove's acceptance-promoting advertising campaigns positively influenced self-esteem and mood, and they are potential tools for weight bias reduction. Advertisements and media have the potential to impact weight-based attitudes in society.


Hierarchical porous bimetal-sulfide bi-functional nanocatalysts for hydrogen production by overall water electrolysis.
Electrocatalytic water splitting using bi-functional catalysts is one of the most promising approaches for clean hydrogen fuel production. To address shortcomings of the existing catalysts, here we develop a new bi-functional catalysts cobalt-based nano-architecture with ordered, Ni-doped two-dimensional (2D) defect-rich nanosheets. Innovative combination of doping, annealing, and sulfidation is developed to fabricate the hierarchical porous metal sulfide (denoted as Ni-Co-S) nanosheets arrays (HPNA) directly on conductive carbon cloth (CC). Owing to the unique architecture with the specific surface area and porous structure, short ion diffusion paths, the Ni-Co-S HPNA exhibits excellent electrocatalytic activitiy for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline solution, featuring low overpotentials of 110 and 270 mV at a current density of 10 mA cm-2, respectively. The excellent catalytic performance is attributed to the unique porous structure, abundant active sites and efficient mass transport. More importantly, when the Ni-Co-S HPNA serves as both the anode and cathode, it achieves a 1.62 V at 10 mA cm-2 and remains stable over 12 h of the overall water splitting process. This work opens new avenues for rational design of high-efficiency and stable bifunctional electrocatalysts for water electrolysis and a broader range of clean energy and sustainable chemistry applications.


CVID enteropathy- a rare cause of chronic diarrhea in a child.
Common variable immunodeficiency (CVID) is a rare primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections especially in respiratory and gastrointestinal systems. The authors present here a case of CVID with uncommon gastrointestinal manifestation in the form of CVID enteropathy. Based upon the clinical presentation and histopatholic findings the patient was diagnosed as CVID enteropathy and treated with intravenous antibiotics and 3-4 wkly intravenous immunoglobulin infusion and he had responded poorly to gastrointestinal symptoms but the frequency of respiratory and skin infection reduced. CVID has heterogenous gastrointestinal manifestations; among them the CVID enteropathy is an uncommon presentation which responds poorly to the mainstay therapy of intravenous immunoglobulin infusion and represents a diagnostic as well as therapeutic challenge for treating physician.


Prospective multicenter evaluation of the pulmonary embolism rule-out criteria.
Over-investigation of low-risk patients with suspected pulmonary embolism (PE) represents a growing problem. The combination of gestalt estimate of low suspicion for PE, together with the PE rule-out criteria [PERC(-): age < 50 years, pulse < 100 beats min(-1), SaO(2) >or= 95%, no hemoptysis, no estrogen use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative testing for PE. We hypothesized that low suspicion and PERC(-) would predict a post-test probability of VTE(+) or death below 2.0%. We enrolled outpatients with suspected PE in 13 emergency departments. Clinicians completed a 72-field, web-based data form at the time of test order. Low suspicion required a gestalt pretest probability estimate of <15%. The main outcome was the composite of image-proven VTE(+) or death from any cause within 45 days. We enrolled 8138 patients, 85% of whom had a chief complaint of either dyspnea or chest pain. Clinicians reported a low suspicion for PE, together with PERC(-), in 1666 patients (20%). At initial testing and within 45 days, 561 patients (6.9%, 95% confidence interval 6.5-7.6) were VTE(+), and 56 others died. Among the low suspicion and PERC(-) patients, 15 were VTE(+) and one other patient died, yielding a false-negative rate of 16/1666 (1.0%, 0.6-1.6%). As a diagnostic test, low suspicion and PERC(-) had a sensitivity of 97.4% (95.8-98.5%) and a specificity of 21.9% (21.0-22.9%). The combination of gestalt estimate of low suspicion for PE and PERC(-) reduces the probability of VTE to below 2% in about 20% of outpatients with suspected PE.


A heat-stable protein inhibitor of cyclic 3',5'-nucleotide phosphodiesterase.
A heat-stable, non-dialyzable inhibitory factor of cyclic nucleotide phosphodieterase was detected in and partially purified from bovine retina. The factor appears to be a protein, since the inhibitory activity was abolished by trypsin digestion but not by DNAase or RNAase treatment. The protein inhibitor from bovine retina effectively inhibits the Ca2+-independent phosphodiesterase from several sources, including bovine retina, bovine rod outer segment, and a human lymphoblastic leukemia cell line, indicating lack of tissue and species specificity.


Increased bleeding risk with enoxaparin venothromboembolism prophylaxis compared with heparin in patients undergoing bariatric surgery.
Perioperative venothromboembolism (VTE) chemoprophylaxis is an established tenant of bariatric surgery; however, there is little comparative data to guide medication choice. The objective of this study was to determine if a change in VTE prophylaxis from heparin to enoxaparin was associated with differing rates of postoperative bleeding and VTE occurrence after bariatric surgery. This retrospective cohort study included patients 18 years or older who underwent primary bariatric surgery (sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB)) at a single institution between March 2012 and December 2021. Subcutaneous unfractionated heparin was utilized for VTE prophylaxis from March 2012 through February 2018 and then enoxaparin was used from March 2018 through December 2021. Postoperative bleeding was defined as requiring a blood transfusion or reoperation for bleeding within 30 days of surgery. Chi-square test was used to test for differences between groups. There were 2159 patients who underwent bariatric surgery with 1324 (61.3%) patients in the heparin group and 835 (38.7%) in the enoxaparin group. Overall, 1,503 (69.6%) patients underwent SG and 656 (30.4%) RYGB. There was no difference in the ratio of SG to RYGB between the heparin and enoxaparin groups. Most patients were female (n = 1709, 79.2%) with a median age of 43.2 years (interquartile range (IQR): 35.6-52.2), and median BMI of 44.9 (IQR: 40.9-50.5). Overall postoperative bleeding occurred more frequently in the enoxaparin group (n = 26, 3.1%) compared with the heparin group (n = 12, 0.9%) (p < 0.01). Additionally, reoperation for bleeding was more frequent with enoxaparin (enoxaparin 0.8% vs. heparin 0.2%, p = 0.04). There was no difference in VTE occurrence between the two groups (heparin: n = 14, 1.1%, enoxaparin: n = 7, 0.8% (p = 0.61)). An institutional change from heparin to enoxaparin for bariatric surgery perioperative VTE prophylaxis was associated with a significant increase in postoperative bleeding, with no difference in VTE complications.


Fos cooperation with PTEN loss elicits keratoacanthoma not carcinoma, owing to p53/p21 WAF-induced differentiation triggered by GSK3beta inactivation and reduced AKT activity.
To investigate gene synergism in multistage skin carcinogenesis, the RU486-inducible cre/lox system was employed to ablate Pten function (K14.cre/Delta5Pten flx) in mouse epidermis expressing activated Fos (HK1.Fos). RU486-treated HK1.Fos/Delta5Pten flx mice exhibited hyperplasia, hyperkeratosis and tumours that progressed to highly differentiated keratoacanthomas, rather than to carcinomas, owing to re-expression of high p53 and p21 WAF levels. Despite elevated MAP kinase activity, cyclin D1 and cyclin E2 overexpression, and increased AKT activity that produced areas of highly proliferative papillomatous keratinocytes, increasing levels of GSK3beta inactivation induced a novel p53/p21 WAF expression profile, which subsequently halted proliferation and accelerated differentiation to give the hallmark keratosis of keratoacanthomas. A pivotal facet to this GSK3beta-triggered mechanism centred on increasing p53 expression in basal layer keratinocytes. This increase in expression reduced activated AKT expression and released inhibition of p21 WAF, which accelerated keratinocyte differentiation, as indicated by unique basal layer expression of differentiation-specific keratin K1 alongside premature filaggrin and loricrin expression. Thus, Fos synergism with Pten loss elicited a benign tumour context where GSK3beta-induced p53/p21 WAF expression continually switched AKT-associated proliferation into differentiation, preventing further progression. This putative compensatory mechanism required the critical availability of normal p53 and/or p21 WAF, otherwise deregulated Fos, Akt and Gsk3beta associate with malignant progression.


Treatment Options in Oligometastatic Disease in Prostate Cancer: Thinking Outside the Box.
Due to its relatively indolent disease course, the sensitivity of PSA testing, and the emergence of novel PET imaging, metastatic prostate cancer is particularly likely to present with a limited volume of disease. Patients with up to five metastatic lesions should be considered for an oligometastatic treatment approach. Systemic therapy remains the cornerstone of treatment for these patients. The optimal type and duration are unknown; however, the addition of a second agent to ADT appears to be beneficial. Multiple recent studies have found significant benefits to the integration of systemic therapy and local metastasis-directed therapies (MDT), including radiation and surgery, to the prostate and metastatic sites. MDT may also be used in select patients wishing to delay the initiation of systemic therapy. For patients with isolated regional nodal recurrences, whole pelvic radiotherapy or extensive lymphadenectomy is preferred, in combination with ADT.


Impact of social media education on antimicrobial stewardship awareness among pharmacy, medical and nursing students and residents.
Antimicrobial resistance has always been an important issue as antimicrobial therapies are becoming less effective due to incorrect use and overuse. Our objective was to evaluate the impact of social media education on spreading antimicrobial stewardship awareness among healthcare students and residents. A prospective interventional study was conducted over 5 months, from November 2021 until March 2022. Weekly educational posts on infectious diseases were posted along with pre- and post- quizzes on a designated Facebook page. The primary endpoint of change in knowledge score was assessed using the independent t-test. Expected average pre-training is 2.5 over 5, and the expected average post-training is a minimum of 3.5 over 5 (common standard deviation of 1) for a minimum of 20% improvement that produces an effect size d = 1. Expecting a larger number of respondents on the pre-test than post-test, the ratio N1/N2 was set to 1.5. With the desired power set to 80% and alpha at 5%, sample size was determined as a minimum of 22 (N1) and 14 (N2). All analyses were carried at the 0.05 significance level. In the entry questionnaire, 85.6% (107/125) of participants believed that antibiotics are overused, 26.4% (33/125) confirmed that they overuse antibiotics, and 88.8% (111/125) confirmed the importance of having an antimicrobial stewardship program. 76.8% (96/125) of the participants regularly use social media for educational purposes and only 2.4% sometimes refer to social media as an educational tool. Improvement in knowledge was noted in all pre and post - quizzes except for two quizzes (prostatitis and acute cystitis - 18.4% and 13.2% improvement respectively). In total, there was a significant 36.2% improvement between all pre and post quizzes [min 13.2% and max 52.8% across all quizzes]. This intervention demonstrated the importance of social media as a valuable tool to enhance antimicrobial stewardship knowledge among pharmacy, medical and nursing students and residents. Future studies are needed to examine the impact of social media education on behaviors in practice.


Efficient allocation of attentional sensitivity gain in visual cortex reduces foveal sensitivity in visual search.
The human visual system has a high-resolution fovea and a low-resolution periphery. When actively searching for a target, humans perform a covert search during each fixation, and then shift fixation (the fovea) to probable target locations. Previous studies of covert search under carefully controlled conditions provide strong evidence that for simple and small search displays, humans process all potential target locations with the same efficiency that they process those locations when individually cued on each trial. Here, we extend these studies to the case of large displays, in which the target can appear anywhere within the display. These more natural conditions reveal an attentional effect in which sensitivity in the fovea and parafovea is greatly diminished. We show that this "foveal neglect" is the expected consequence of efficiently allocating a fixed total attentional sensitivity gain across the retinotopic map in the visual cortex. We present a formal theory that explains our findings and the previous findings.


The Insula: An Underestimated Brain Area in Clinical Neuroscience, Psychiatry, and Neurology.
Supported by recent human neuroimaging studies, the insula is re-emerging as an important brain area not only in the physiological understanding of the brain, but also in pathological contexts in clinical research. In this opinion article, we briefly introduce the anatomical and histological features of the human insula. We then summarize the physiological functions of the insula and underscore its pathological roles in psychiatric and neurological disorders that have long been underestimated. We finally propose possible strategies through which the role of the insula may be further understood for both basic and clinical neuroscience.


Sr2+-dependent asynchronous evoked transmission at rat striatal inhibitory synapses in vitro.
1. At striatal inhibitory synapses in cell culture, replacement of extracellular Ca2+ with Sr2+ desynchronized inhibitory postynaptic currents (IPSCs), reducing their peak amplitude and producing a succession of late, asynchronous synaptic events (late release). In the averaged IPSC waveform this resulted in an increase in both the fast and the slow decay time constant as well as in the time to peak. 2. Rapid removal of extracellular Sr2+ during late release was without effect on the time course of the averaged IPSC. Thus, late release is not dependent on continuous Sr2+ influx, but must be related to the way in which Sr2+, as opposed to Ca2+, interacts with constituents of the intracellular space. 3. After application of the membrane-permeant acetoxymethyl ester (AM) form of the Ca2+-chelator BAPTA, Sr2+-induced late release was greatly reduced and the kinetics of the Sr2+-dependent IPSC approached those of the Ca2+-dependent response. EGTA AM had a similar but less pronounced effect. 4. Using rapid solution exchange, we stimulated synapses first in Sr2+- or Ca2+- and 100-300 ms afterwards in Ca2+-containing solution. Paired-pulse facilitation of late release was the same whether the conditioning pulse induced a presynaptic influx of Sr2+ or of Ca2+. 5. It is concluded that Sr2+-mediated asynchrony is probably due to a less efficient intraterminal buffering of Sr2+ as opposed to Ca2+, allowing for Sr2+ ions to activate release in an area less confined to the immediate vicinity of the presynaptic Ca2+ channel. This hypothesis explains both the action of endogenous buffers and the apparent lack of specific facilitatory interaction between Ca2+-mediated and Sr2+-induced late release.


Mathematical Foundations of Adaptive Isogeometric Analysis.
This paper reviews the state of the art and discusses recent developments in the field of adaptive isogeometric analysis, with special focus on the mathematical theory. This includes an overview of available spline technologies for the local resolution of possible singularities as well as the state-of-the-art formulation of convergence and quasi-optimality of adaptive algorithms for both the finite element method and the boundary element method in the frame of isogeometric analysis.


Crystal structure of metagenome-derived LC11-RNase H1 in complex with RNA/DNA hybrid.
LC11-RNase H1 is a Sulfolobus tokodaii RNase H1 (Sto-RNase H1) homologue isolated by metagenomic approach. In this study, the crystal structure of LC11-RNase H1 in complex with an RNA/DNA substrate was determined. Unlike Bacillus halodurans RNase H1 without hybrid binding domain (HBD) (Bh-RNase HC) and human RNase H1 without HBD (Hs-RNase HC), LC11-RNase H1 interacts with four non-consecutive 2'-OH groups of the RNA strand. The lack of interactions with four consecutive 2'-OH groups leads to a dramatic decrease in the ability of LC11-RNase H1 to cleave the DNA-RNA-DNA/DNA substrate containing four ribonucleotides as compared to those to cleave the substrates containing five and six ribonucleotides. The interaction of LC11-RNase H1 with the DNA strand is also different from those of Bh-RNase HC and Hs-RNase HC. Beside the common phosphate-binding pocket, LC11-RNase H1 has a unique DNA-binding channel. Furthermore, the active-site residues of LC11-RNase H1 are located farther away from the scissile phosphate group than those of Bh-RNase HC and Hs-RNase HC. Modeling of Sto-RNase H1 in complex with the 14bp RNA/DNA substrate, together with the structure-based mutational analyses, suggest that the ability of Sto-RNase H1 to cleave double-stranded RNA is dependent on the local conformation of the basic residues located at the DNA binding site.


Risk of hematological malignancy in blood donors: A nationwide cohort study.
There has been a concern that blood donations can increase the risk of hematological malignancies. We investigated if blood donations increase the risk of developing hematological malignancies, specifically acute lymphoblastic leukemia, acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia, Hodgkin lymphoma, and myeloma, as well other non-Hodgkin lymphoma. In total, the study included 1,021,433 Swedish blood donors, with 19.5 million person-years of follow-up. Two sets of analysis were performed. In the first cohort analysis, standardized incidence ratios (SIRs) were calculated, comparing the incidence of the different types of hematological cancers in blood donors to that of the general population. In the second analysis, a nested case-control study was conducted, investigating the association between number of donations and the risk of each type of malignancy. Apart from a modestly elevated risk of CLL (SIR, 1.07; 95% confidence interval [CI], 1.01-1.15) and a modestly decreased risk of AML (SIR, 0.85; 95% CI, 0.77-0.83), the risk of hematological malignancies did not differ between blood donors and the general population. In the nested case-control study there were no convincing associations between number of prior whole blood donations and site-specific malignancy risk. There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses.


Relevance of Helicobacter pylori vacA 3'-end Region Polymorphism to Gastric Cancer.
Helicobacter pylori vacA genotypes play an important role in the pathogenesis of severe gastrointestinal disease. We identified a novel polymorphic site in the 3'-end region of H. pylori vacA gene, denoted by c1/-c2 (c1: with deletion of 15 bp), and examined associations of this and the previous four sites as well as cagA status with gastroduodenal diseases, in a total of 217 Iranian H. pylori isolates. Histopathologic evaluations were performed and patients with gastric cancer (GC) were further classified based on the anatomic site of tumor, including cardia and noncardia GC, and the histopathologic type of tumor, including intestinal- and diffuse-type GC. The vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with an increased risk of GC, the odds ratio (95% confidence interval) was 4.29 (2.03-9.08), 6.11 (2.63-14.19), 3.18 (1.49-6.76), 15.13 (5.86-39.01), and 2.59 (1.09-6.12), respectively. The vacA c1 genotype had an increased age- and sex-adjusted risk for GC by the multiple logistic regression analysis; the OR was 38.32 (95% CI, 6.60-222.29). This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. No significant correlation was found between s1, whether independently or in combination, and the risk of GC or peptic ulcer disease (PUD). The vacA i1 and cagA genotypes were linked to an increased risk of PUD; the OR (95% CI) was 2.80 (1.45-5.40) and 2.62 (1.23-5.61), respectively. The presence of both the vacA i1 and cagA genotypes further increased the risk of PUD; the OR was 5.20 (95% CI, 1.92-14.03). The H. pylori vacA c1 genotype might therefore be one of the strongest risk predictors of GC in male patients aged ≥55 in Iran.


Novel pirfenidone analogues: synthesis of pyridin-2-ones for the treatment of pulmonary fibrosis.
A new series of polysubstituted 1-aryl-2-oxo-1,2-dihydropyridine-3-carbonitriles and pyrazolo[3,4-b]pyridine-5-carbonitriles and pyrido[2,3-d]pyrimidine-6-carbonitriles have been synthesized and tested for their antifibrotic activity. Among the tested compounds, compounds IIc and IVb exhibited higher antifibrotic activity than the standard pirfenidone PD with a reduction of the hydroxyproline level to 50 and 140 micromol/lung, respectively. However, bicyclic pyridone VIIIb displayed a high mortality rate. Detailed syntheses, spectroscopic and biological data are reported.


Explaining lower rates of sexual abuse in China.
Accumulating research suggests that rates of child sexual abuse are comparatively low in China. This commentary is an effort to evaluate whether it reflects a true lower prevalence or alternatively the effect of inhibited disclosure by victims. We conclude that while some estimates have almost certainly been affected by inhibited disclosure, the overall magnitude of the contrast between Chinese and international rates, particularly for girls, and its consistency with other indicators do suggest a true lower prevalence, although the evidence is equivocal. We discuss some factors that could account for such lower rates including Confucian family values, definitions of masculinity and a collectivist culture that may be protective.


Ability of in vitro (corneal injury--eye organ--and chorioallantoic membrane) tests to represent histopathological features of acute eye inflammation.
The spontaneous removal of substances from the eye in vivo and histopathological responses to mild or moderate irritants were examined to define the main features that may be reflected in a valid in vitro test for irritant potential. Solutions or fine particulate suspensions applied to the rabbit eye are quickly removed from the central corneal surface by the blink reflex, gravity and drainage. The histological changes in the first 24 hours of mild-to-moderate irritation show some thinning of, but no severe irreversible damage to, the corneal epithelium. Other changes are oedema, congestion, some leucocyte infiltration and variable degeneration and desquamation of the conjunctival epithelium. In vitro cell-culture cytotoxicity tests are a useful screen for direct cytotoxic damage to epithelial cells but there are anomalies between the results of such tests and in vivo eye responses. Test systems using inhibition of DNA synthesis in cultured fibroblasts and histamine release from mast cells have shown poor correlation between in vitro and in vivo test results. The in vitro corneal injury (eye organ) test of Burton et al. (Fd Cosmet. Toxicol. 1981, 19,471) predicts very effectively the activity of moderate-to-severe irritants, and that of mild irritants when the contact time is modified or fluorescein or histology are used. This method demonstrates the response of a specialized tissue of the eye and facilitates the examination of powders, acids and alkalies, for which cell systems are not suitable. So far the chorioallantoic membrane of the egg has not been found to predict for pure chemicals the activities demonstrated in in vivo or in vitro tests on the eye; the main change seen in the egg membrane is necrosis, with little evidence of inflammation.


On the orientation of stripes in fish skin patterning.
This paper is focused on the study of the stripes orientation in the fish skin patterns. Based on microscopic observations of the pigment cells behavior at the embryonic stage, the key aspects of the pigmentation process are implemented in an experimental reaction-diffusion system. The experiment consists of a photosensitive Turing pattern of stripes growing directionally in one direction with controlled velocity. Different growth velocities of the system rearrange the stripes in the same three possible orientations observed in the skin of the colored fishes: parallel, oblique, and perpendicular. Our results suggest that the spreading velocity of the pigment cells in the fish dermis selects the orientation in the patterning processes.


Wheel running, food intake, and body weight in male rats.
The acquisition of wheel running, its effects on food intake and body weight, and the effects of wheel deprivation, were examined in male rats. Running increased during the first 15 days of access, then plateaued. When wheels were unlocked after 10 days of deprivation, running was reduced, but quickly recovered to original levels. Animals first given wheel access 49 days into the study ran little, with no increase over days. Food intake dropped each time with wheel access, but recovered to control levels over 10-14 days. Wheel deprivation resulted in a temporary hyperphagia. With wheel access, weight initially dropped and was then maintained at a reduced percentage of homecage-housed animals. In male rats wheel access appears to have temporary effects on food intake, and long term effects on weight. Marked differences in the activity of same-age rats suggest that wheel running is in part a function of housing history.


Development and evaluation of the psychometric properties of a digital questionnaire for the self-management of health and well-being in the postpartum period.
Despite the fact that the Global Strategy for Women's, Children's and Adolescents' Health (2016-2030) recognises the special importance of care for women during the postpartum period, thus highlighting the need to identify and measure any condition that may affect the welfare of pregnant women in any way, this is one of the most neglected stages in the health system. Given the absence in our area of global, efficient instruments, the objective of this study was to design a complete, specific measurement tool with good metric qualities in digital format for the evaluation of self-reported health and well-being during the puerperium, to conform to what was proposed by the ICHOM. A cross-sectional study was carried out to evaluate the psychometric characteristics of a digital measurement tool. The development of the tool was carried out in 4 steps, following the recommendations of the International Test Commission. It was tested on 280 puerperas attending primary healthcare appointments in the Basque Healthcare System (Osakidetza), and they did the newly created survey, answering all the questions that had been selected as the gold standard. The average age of the women was 34.93 (SD = 4.80). The analysis of the psychometric characteristics was based on mixed procedures of expert judgment (a focus group of healthcare professionals, an item evaluation questionnaire and interviews with users) and quantitative evaluations (EFA, CFA, and correlation with gold standard, ordinal alpha and McDonald's omega). The final version of the tool comprised 99 items that evaluate functional state, incontinence, sexuality, breastfeeding, adaptation to the role of mother and mental health, and all of these questions can be used globally or partially. It was found that the scores were valid and reliable, which gives metric guarantees for using the tool in our area. The use of this comprehensive concise tool with good psychometric properties will allow women to take stock of their situation, assess if they have the necessary resources, in psychological and social terms, and work together with midwives and other healthcare professionals on the most deficient areas.


Prenatal diagnosis of Potocki-Lupski syndrome in a fetus with hypoplastic left heart and aberrant right subclavian artery.
Potocki-Lupski syndrome (PTLS) is a rare genetic disorder associated with neurodevelopmental delay and heart defects. We report the first case of prenatal diagnosis of PTLS in a fetus with hypoplastic left heart and aberrant right subclavian artery. Detection of a fetal heart defect should be followed by chromosomal and genetic studies in order to rule out fetal aneuploidy and/or associated genetic syndromes with significant implications for the treatment of children with PTLS.


nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks.
Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2. A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene co-regulatory network was built using host-responsive miRNAs and it's associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth. Supplementary information accompanies this paper at 10.1186/s41544-020-00057-y.


Partial denitrification-anammox (PdNA) application in mainstream IFAS configuration using raw fermentate as carbon source.
This research examined the feasibility of raw fermentate for mainstream partial denitrification-anammox (PdNA) in a pre-anoxic integrated fixed-film activated sludge (IFAS) process. Fermentate quality sampled from a full-scale facility was highly dynamic, with 360-940 mg VFA-COD/L and VFA/soluble COD ratios ranging from 24% to 48%. This study showed that PdNA selection could be achieved even when using low quality fermentate. Nitrate residual was identified as the main factor driving the PdN efficiency, while management of nitrate conversion rates was required to maximize overall PdNA rates. AnAOB limitation was never observed in the IFAS system. Overall, this study showed PdN efficiencies up to 38% and PdNA rates up to 1.2 ± 0.7 g TIN/m2 /d with further potential for improvements. As a result of both PdNA and full denitrification, this concept showed the potential to save 48-89% methanol and decrease the carbon footprint of water resource recovery facilities (WRRF) by 9-15%. PRACTITIONER POINTS: Application of PdNA with variable quality fermentate is feasible when the nitrate residual concentration is increased to enhance PdN selection. To maximize nitrogen removed through PdNA, nitrate conversion rates need enhancement through optimization of upstream aeration and PdN control setpoints. The IFAS PdNA process was never anammox limited; success depended on the degree of PdN achieved to make nitrite available. Application of PdNA with fermentate can yield 48-89% savings in methanol or other carbon compared with conventional nitrification and denitrification. Integrating PdNA upstream from polishing aeration and anoxic zones guarantees that stringent limits can be met (<5 mg N/L).


Collagen IV trafficking: The inside-out and beyond story.
Collagen IV networks endow basement membranes (BMs) with remarkable tensile strength and function as morphoregulatory substrata for diverse tissue-specific developmental events. A complex repertoire of intracellular and extracellular molecular interactions are required for collagen IV secretion and supramolecular assembly into BMs. These include intracellular chaperones such as Heat shock protein 47 (Hsp47) and the chaperone-binding trafficking protein Transport and Golgi organization protein 1 (Tango1). Mutations in these proteins lead to compromised collagen IV protomer stability and secretion, leading to defective BM assembly and function. In addition to intracellular chaperones, a role for extracellular chaperones orchestrating the transport, supramolecular assembly, and architecture of collagen IV in BM is emerging. We present evidence derived from evolutionarily distant model organisms that supports an extracellular collagen IV chaperone-like activity for the matricellular protein SPARC (Secreted Protein, Acidic, Rich in Cysteine). Loss of SPARC disrupts BM homeostasis and compromises tissue biomechanics and physiological function. Thus, the combined contributions of intracellular and extracellular collagen IV-associated chaperones and chaperone-like proteins are critical to ensure proper secretion and stereotypic assembly of collagen IV networks in BMs.


Anesthetic management of a patient with Freeman-Sheldon syndrome: case report.
The Freeman-Sheldon syndrome (FSS) is a rare congenital myopathy and dysplasia. The musculoskeletal and soft-tissue manifestations of FSS often require orthopedic and plastic reconstructive surgery. We report a case of a 7-year-old girl with FSS operated for lower limb malformation during spinal anesthesia.


The Emerging Role of Continuous Glucose Monitoring in the Management of Diabetic Peripheral Neuropathy: A Narrative Review.
The aim of this narrative review is to present data on the role of continuous glucose monitoring (CGM) in the management of peripheral diabetic neuropathy (DPN) among individuals with type 1 and type 2 diabetes mellitus. Adequate glycaemic control is crucial to prevent the development or progression of DPN. CGM systems are valuable tools for improving glycaemic control and reducing glycaemic variability (GV). Chronic hyperglycaemia is known to be a risk factor for the development of diabetic microvascular complications, including DPN. In addition, there is now evidence that GV, evaluated by mean amplitude of glycaemic excursions, may be a novel factor in the pathogenesis of diabetic complications. Increased GV appears to be an independent risk factor for DPN and correlates with painful neuropathy. Similarly, time-in-range correlates positively with peripheral nerve function and negatively with sudomotor dysfunction. However, relevant studies are rather limited in scope, and the vast majority are cross-sectional and use different methodologies for the assessment of DPN. Therefore, the causal relationship between CGM-derived data and the development of DPN cannot be firmly established at the present time. It also remains to be elucidated whether CGM measures can be considered the new therapeutic targets for DPN management.


Variations in the recombination rate of Drosophila melanogaster induced by balloon flight.
Drosophila males, heterozygous for b, pr, cn and en genes, were submitted to balloon flights, ceiling time ranging from about 8 hours (flights performed in France) to 22 hours (transmediterranean flight). Effects on recombination were investigated on progeny after breeding with females homozygous for the same genes. The transmediterranean flight and one flight performed in France resulted in a significantly higher recombination rate.


Controlling Diels-Alder reactions in catalytic pyrolysis of sawdust and polypropylene by coupling CO2 atmosphere and Fe-modified zeolite for enhanced light aromatics production.
Producing value-added light aromatics (BTEX) from solid waste streams holds excellent promise for resource recovery. Here we present a thermochemical conversion approach that enhanced BTEX production by coupling CO2 atmosphere and Fe-modified HZSM-5 zeolite to facilitate the Diels-Alder reactions in catalytic pyrolysis of sawdust and polypropylene. The Diels-Alder reactions between sawdust-derived furans and polypropylene-derived olefins could be controlled by tuning CO2 concentration and Fe loading amount. Sufficient CO2 (≥50%) with moderate Fe loading (10 wt%) were observed to produce more BTEX and fewer heavy fractions (C9+aromatics). To deepen the mechanistic understanding, quantification of polycyclic aromatic hydrocarbons (PAHs) and catalyst coke was further conducted. The co-use of CO2 atmosphere and Fe modification suppressed the appearance of low-, medium-, and high-membered ring PAHs by over 40%, decreased pyrolysis oil toxicity from 42.1 to 12.8 μg/goil TEQ, and transformed coke from "hard" to "soft". Based on the characterization of CO2 adsorption behavior, it was deduced that the introduced CO2 was activated by loaded Fe and reacted in situ with H2 generated during aromatization to expedite H-transfer. Meanwhile, BTEX recondensation was prevented through the Boudouard reactions of CO2 and water-gas reactions between the resulting water and carbon deposits. These synergistically enhanced the production of BTEX and suppressed the formation of heavy species, including PAHs and catalyst coke.


Erratum to: Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci.
[This corrects the article DOI: 10.1186/s13148-015-0143-8.].


preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?
Tellurium compounds have been described as potential leishmanicides, bearing promising leishmanicidal and antimalarial effects. Therefore, the present study investigated the pharmacological potential of the organotellurane compound RF07 through preADMET parameters, such as absorption, distribution, metabolism and excretion. After studying the pharmacokinetic properties of RF07, studies were carried out on dogs naturally infected with visceral leishmaniasis after the administration of RF07, in order to assess pathophysiological parameters. Thus, dogs were divided into 4 groups with administration of daily intraperitoneal injections for 3 weeks (containing RF07 or placebo). During the trial, hematological parameters, renal and hepatic toxicity were evaluated. Serum urea, creatinine, alkaline phosphatase, transaminases (GOT and GPT), as well as hemogram results, were evaluated before the first administration and during the second and third weeks after the start of the treatment. In dogs with VL, RF07 improved liver damage, regulated GPT levels and significantly decreased leukocyte count, promoting its regularization. These phenomena occurred at the end of the third week of treatment. The administration of RF07 promoted a significant decrease in the average levels of GOT and GPT after the third week of treatment and did not significantly alter the hematological parameters. The application of RF07 in the treatment of visceral leishmaniasis suggests that it is an alternative to the disease, since the reversal of clinical signs in dogs with VL requires the use of 0.6 mg/kg.