Loss- and gain-of-function analysis of the lipid raft proteins Reggie/Flotillin in Drosophila: they are posttranslationally regulated, and misexpression interferes with wing and eye development.
Reggie/Flotillin proteins are upregulated after optic nerve dissection and evolutionary highly conserved components of lipid rafts. Whereas many biochemical and cell culture studies suggest an involvement in the assembly of multiprotein complexes at cell contact sites, not much is known about their biological in vivo functions. We therefore set out to study the expression pattern and the effects of loss- and gain-of-function in the Drosophila melanogaster model system. We found that in flies these proteins are mainly expressed in axons at the root of fiber tracts, in places where strong fasciculation is required, e.g. at the neck of the peduncle of the mushroom bodies and in the optic chiasms. Despite their evolutionary conservation which implies fundamental and important functions, a P-element-induced null mutant (KG00210) of reggie1/flotillin2 (reggie1/flo2) in D. melanogaster shows no apparent phenotypic defects. This was even more surprising as we show that in this reggie1/flo2 null mutant the paralogous Reggie2/Flo1 protein is unstable and degraded, while the transcript is still present. The requirement of Reggie1/Flo2 for Reggie2/Flo1 stabilization is confirmed by misexpression experiments. Reggie2/Flo1 can only be misexpressed when Reggie1/Flo2 is provided as well. Conversely, Reggie1/Flo2 immunoreactivity can be detected, when its transgene is misexpressed alone. Using appropriate Gal4 driver lines, misexpression of Reggie1/Flo2 alone or together with Reggie2/Flo1 in the eye imaginal disc results in a specific and severe mislocalization of cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) (while DE-Cadherin is unaffected) and in differentiation defects pointing to impaired signaling. In the wing imaginal disc, global overexpression of Reggie/Flotillin proteins leads to a significant extension of the Wingless signal and severely disrupts normal wing development. Our data support the notion that Reggie/Flotillin proteins are implicated in signaling processes at cellular contact sites.


Rho-kinase (ROCK) in sea urchin sperm: its role in regulating the intracellular pH during the acrosome reaction.
Sperm must undergo the acrosome reaction (AR) in order to fertilize the egg. In sea urchins, this reaction is triggered by the egg jelly (EJ) which, upon binding to its sperm receptor, induces increases in the ion permeability of the plasma membrane and changes in protein phosphorylation. Here, we demonstrated that the sperm expresses ROCK (approximately 135kDa), which is a serine/threonine protein kinase. ROCK localized, as RhoGTPase (Rho), in the acrosomal region, midpiece and flagellum. H-1152, a ROCK antagonist, inhibited the two cellular processes defining the AR: the acrosomal exocytosis and the actin polymerization. The ionophores nigericin and A23187 reversed the AR inhibition induced by H-1152, suggesting that ROCK functions at the level of the EJ-induced ion fluxes. Accordingly, H-1152 blocked 70% the intracellular alkalinization induced by EJ. These results indicate that EJ activates a Na+-H+ exchanger (NHE) in the sperm through a Rho/ROCK-dependent signaling pathway that culminates in the AR.


Perioperative management in cardiovascular surgery.
Cardio-surgical patient care requires a comprehensive and multidisciplinary approach to develop strategies to improve patient safety and outcomes. In the preoperative period, prophylaxis for frequent postoperative complications, such as de novo atrial fibrillation or bleeding, and prehabilitation based on exercise training, respiratory physiotherapy and nutritional and cognitive therapy, especially in fragile patients, stand out. There have been great advances, during the intraoperative phase, such as minimally invasive surgery, improved myocardial preservation, enhanced systemic perfusion and brain protection during extracorporeal circulation, or implementation of Safe Surgery protocols. Postoperative care should include goal-directed hemodynamic theraphy, a correct approach to coagulation disorders, and a multimodal analgesic protocol to facilitate early extubation and mobilization. Finally, optimal management of postoperative complications is key, including arrhythmias, vasoplegia, bleeding, and myocardial stunning that can lead to low cardiac output syndrome or, in extreme cases, cardiogenic shock. This global approach and the high degree of complexity require highly specialised units where intensive care specialists add value and are key to obtain more effective and efficient clinical results.


Outcome After Protontherapy for Progression or Recurrence of Surgically Treated Meningioma.
To assess the outcome after meningioma surgery and protontherapy (PT). We processed the French Système National des Données de Santé database to retrieve appropriate cases of meningiomas operated and irradiated between 2008 and 2017. Survival methods were implemented. One hundred ninety-three patients who received PT after meningioma surgery over a 10-year period were identified. Of the 193 patients, 75.6% were female. Median age at surgery was 50 years (interquartile range [IQR] 41-62). The median number of PT fractions was 31 (IQR 30-39) given over a median duration of 52 days (IQR 44-69). Fourteen patients (7.3%) also received photon radiotherapy and six patients (3.1%) stereotactic radiosurgery. Median follow-up was 4.4 years (IQR 3.86-4.71). Five-year progression-free survival (PFS) rate was 69% (95% confidence interval [CI] 62.1-76.6). For benign, atypical, and malignant meningioma, 5-year PFS rates were 71.5% (95% CI 64.4-79.4), 55.6% (95% CI 32.5-95), and 35.6% (95% CI 12.8-98.9), respectively (p<0.01). In the adjusted regression, tumour location (hazard ratio [HR]=0.1, 95% CI 0.05-0.22, p<0.001), aggressive meningioma (HR=2.26, 95% CI 1.1-4.66, p=0.027), and the need of cerebrospinal fluid (CSF) insertion for hydrocephalus (HR=3.51, 95% CI 1.32-9.31, p=0.012) remained significantly associated to the PFS. All grades considered, 5-year overall survival (OS) rates was 89.7% (95% CI 84.6-95.1). For benign, atypical, and malignant meningioma, 5-year OS rates were 93% (95% CI 88.7-97.4), 76.4% (95% CI 51.4-100), and 44.4% (95% CI 16.7-100), respectively (p<0.01). In the multivariable regression, an older age above 70 years (HR=5.95, 95% CI 2.09-16.89, p<0.001) associated to a high level of comorbidities (HR=5.31, 95% CI 1.43-19.78, p=0.013) and a malignant meningioma (HR=5.68, 95% CI 1.54-20.94, p=0.009) remained significantly associated to a reduced OS. Five-year PFS and OS after meningioma surgery and PT is favourable but impaired for older patients with high level of morbidities, tumour of the convexity, malignant histopathology and for those requiring CSF shunting. Further inclusion and prolonged follow-up is required to assess other predictors such as sex, tumour volume, or given dose.


Hepatic triglyceride lipase plays an essential role in changing the lipid metabolism in genotype 1b hepatitis C virus replicon cells and hepatitis C patients.
Recently, several studies have shown the existence of associations between lipoprotein profiles and hepatitis C virus (HCV), although only a limited amount of information is available about the mechanisms underlying the changes in the lipoprotein profiles associated with HCV. In this study, we investigated the association between lipoprotein profile, classified according to the particle size, and lipoprotein metabolism. We used four kinds of cells for this experiment; full-length genome HCV RNA replicon cells (OR6), sub-genomic HCV RNA replicon cells (sO), and OR6c cells and sOc cells, which were the same cell lines treated with interferon-α. The triglyceride (TG) levels in the lipoprotein subclasses of the culture medium were measured by high-performance liquid chromatography. The mRNA expression levels of several molecules associated with lipoprotein metabolism were measured in the OR6, OR6c, sO and sOc cells. To confirm some of the results obtained using the in vitro system, liver biopsy samples obtained from the patients were also examined. The content of TG in the large low-density lipoprotein (LDL) and medium LDL in the culture medium was increased only in the OR6 cells. The hepatic triglyceride lipase (HTGL) mRNA expression levels were lower in the OR6 cells than in the OR6c cells (P < 0.01). Examination of the HTGL expression levels in the patients' livers revealed a decrease in HTGL expression in the chronic hepatitis C liver as compared with that in the chronic hepatitis B or non-alcoholic steatohepatitis liver (P < 0.01). We showed that HCV inhibits HTGL production in hepatocytes, inducing a change of the lipoprotein profile.


Down-regulation of EGFL8: a novel biomarker for advanced gastric cancer.
Recently, we have reported an important role of epidermal growth factor-like domain 8 (EGFL8) in the progression of colorectal cancer (CRC) and documented EGFL8 to be a novel prognostic biomarker for this malignancy. However, the function of EGFL8 in the other human gastroenterological malignancies such as gastric cancer remains largely unknown. EGFL8 expression in 53 cases of gastric cancer and the corresponding normal tissues were determined by quantitative real-time PCR and the EGFL8 down-regulation score for each patient was calculated. Subsequently, the correlations between EGFL8 down-regulation score and the clinicopathological features of gastric cancer were evaluated. EGFL8 expression was significantly lower in the gastric cancer tissues than the corresponding normal tissues (p=0.0001) and the down-regulation of EGFL8 was evident in 73.6% (39/53) of the gastric carcinomas. More importantly, EGFL8 down-regulation was correlated significantly with peritoneal dissemination (p=0.037) and high TNM stage (p=0.025) of gastric cancer. The down-regulation of EGFL8 might be a novel biomarker for advanced gastric cancer.


Positron-emission tomography CT to identify local recurrence in stage I lung cancer patients 1 year after stereotactic body radiation therapy.
To evaluate the diagnostic value of positron-emission tomography/computed tomography (PET/CT) in stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT), who have suspicious or unclear local recurrence findings in CT 1 year after treatment. A group of 29 patients with unclear or suspicious CT findings 1 year after SBRT were examined with PET/CT. The ability of standard uptake values (SUVmax, SUVmean and posttherapeutic reduction in SUV) to detect local failure and identify patients at a high risk of disease-specific death was evaluated using logrank statistics. Histology and clinical follow-up were the gold standards for local recurrence. SUVmean greater than 3.44 (p = 0.001); SUVmax greater than 5.48 (p = 0.009) or a relative reduction in SUVmean or SUVmax of less than 43 (p = 0.030) or 52 % (p = 0.025), respectively, was indicative of local recurrence. These parameters also correlated with an increased risk of disease-specific death: SUVmean greater than 2.81 (p = 0.023); SUVmax greater than 3.45 (p = 0.007) or a relative reduction in SUVmean or SUVmax of less than 32 (p = 0.015) or 52 % (p = 0.013), respectively, was indicative of an increased risk of disease-specific death. PET/CT performed 1 year after SBRT can reliably identify local recurrence and therefore help to clarify unclear CT findings. As posttherapeutic glucose metabolism also correlates with disease-specific survival, PET/CT may help to stratify lung cancer patients for additional treatment 1 year after SBRT.


The meanings of 'function' in biology and the problematic case of de novo gene emergence.
The word function has many different meanings in molecular biology. Here we explore the use of this word (and derivatives like functional) in research papers about de novo gene birth. Based on an analysis of 20 abstracts we propose a simple lexicon that, we believe, will help scientists and philosophers discuss the meaning of function more clearly.


Endothelial-Cell-Derived Human Secretory Leukocyte Protease Inhibitor (SLPI) Protects Cardiomyocytes against Ischemia/Reperfusion Injury.
Vascular endothelial cell (EC)-derived factors play an important role in endothelial-cardiomyocyte crosstalk and could save cardiomyocytes (CMs) from injury. The manipulation of endothelial cells to secrete protective factors could enhance cardioprotection. Secretory leukocyte protease inhibitor (SLPI) has been known to protect the heart. The goal of this study was to evaluate the in vitro paracrine protective effect and mechanisms of EC-derived human SLPI on cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Stable endothelial cells overexpressing human SLPI were generated from an endothelial cell line (EA.hy926). The cytoprotective effect was determined by cell survival assay. The results showed that endothelial-derived recombinant human SLPI (rhSLPI) reduced simulated ischemia/reperfusion (I/R)-(81.75% ± 1.42% vs. 60.27% ± 2.52%, p < 0.05) and hypoxia/reoxygenation (H/R)-induced EC injury (83.57% ± 1.78% vs. 63.07% ± 1.93%, p < 0.05). Moreover, co-culture of ECs overexpressing rhSLPI with CMs at ratios 1:1 and 1:3 or treatment with conditioned medium enhanced cell viability by 10.51-16.7% (co-culture) and 15.25-20.45% (conditioned medium) by reducing intracellular reactive oxygen species (ROS) production, the Bax/Bcl-2 expression ratio, caspase-3, and caspase-8, and in preconditioned CMs by activation of p38 MAPK and Akt survival kinase. In conclusion, this study showed for the first time that EC-derived rhSLPI provided cardio-vasculoprotective effects against I/R injury as a possible alternative therapeutic strategy for cardioprotection.


Voice Quality in Cochlear Implant Recipients: An Observational Cross Sectional Study.
Children with hearing loss are more likely to suffer from voice and speech disorders than with normal hearing due to their poor and less robust auditory feedback mechanisms. Prelingually deaf children are not able to supervise their own voice due to lack of auditory feedback. Cochlear implanted children achieve better hearing and consequently enhanced speech intelligibility. Various parameters of voice improve with continous usage of cochlear implant. However all the vocal parameters do not show similar degree of change. Previous studies have assessed the voice quality of cochlear implantees and have given inconsistent results. The aim of the study is to compare the voice quality of cochlear implant children with normal subjects using objective and subjective methods. The study was undertaken after obtaining clearance from the Institutional Ethics committee. Written informed consent for carrying out voice analysis was taken from the parents. The voice analysis of 42 normal and 42 cochlear implant children were done using the Dr Voice software by Tiger Inc. All the children were age and sex matched. The parameters assessed were fundamental frequency, maximum phonation time, jitter%, shimmer% and harmonics to noise ratio. The findings of both the group were compared. The cochlear implanted children showed significant deviation of all the measured parameters as compared to the normal children. The voice quality of the implanted children is poor and deviant from the normal. Even after continuous usage of cochlear implant for 1 year the voice quality of these children did not reach to the levels of their normal hearing peers.


Differentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progression.
Epidemiological studies have implicated androgens in the etiology and progression of epithelial ovarian cancer. We previously reported that some androgen responses were dysregulated in malignant ovarian epithelial cells relative to control, non-malignant ovarian surface epithelial (OSE) cells. Moreover, dysregulated androgen responses were observed in OSE cells derived from patients with germline BRCA-1 or -2 mutations (OSEb), which account for the majority of familial ovarian cancer predisposition, and such altered responses may be involved in ovarian carcinogenesis or progression. In the present study, gene expression profiling using cDNA microarrays identified 17 genes differentially expressed in response to continuous androgen exposure in OSEb cells and ovarian cancer cells as compared to OSE cells derived from control patients. A subset of these differentially affected genes was selected and verified by quantitative real-time reverse transcription-polymerase chain reaction. Six of the gene products mapped to the OPHID protein-protein interaction database, and five were networked within two interacting partners. Basic leucine zipper transcription factor 2 (BACH2) and acetylcholinesterase (ACHE), which were upregulated by androgen in OSEb cells relative to OSE cells, were further investigated using an ovarian cancer tissue microarray from a separate set of 149 clinical samples. Both cytoplasmic ACHE and BACH2 immunostaining were significantly increased in ovarian cancer relative to benign cases. High levels of cytoplasmic ACHE staining correlated with decreased survival, whereas nuclear BACH2 staining correlated with decreased time to disease recurrence. The finding that products of genes differentially responsive to androgen in OSEb cells may predict survival and disease progression supports a role for altered androgen effects in ovarian cancer. In addition to BACH2 and ACHE, this study highlights a set of potentially functionally related genes for further investigation in ovarian cancer.


Short- and Long-Term Recovery after Moderate/Severe AKI in Patients with and without COVID-19.
Severe AKI is strongly associated with poor outcomes in coronavirus disease 2019 (COVID-19), but data on renal recovery are lacking. We retrospectively analyzed these associations in 3299 hospitalized patients (1338 with COVID-19 and 1961 with acute respiratory illness but who tested negative for COVID-19). Uni- and multivariable analyses were used to study mortality and recovery after Kidney Disease Improving Global Outcomes Stages 2 and 3 AKI (AKI-2/3), and Machine Learning was used to predict AKI and recovery using admission data. Long-term renal function and other outcomes were studied in a subgroup of AKI-2/3 survivors. Among the 172 COVID-19-negative patients with AKI-2/3, 74% had partial and 44% complete renal recovery, whereas 12% died. Among 255 COVID-19 positive patients with AKI-2/3, lower recovery and higher mortality were noted (51% partial renal recovery, 25% complete renal recovery, 24% died). On multivariable analysis, intensive care unit admission and acute respiratory distress syndrome were associated with nonrecovery, and recovery was significantly associated with survival in COVID-19-positive patients. With Machine Learning, we were able to predict recovery from COVID-19-associated AKI-2/3 with an average precision of 0.62, and the strongest predictors of recovery were initial arterial partial pressure of oxygen and carbon dioxide, serum creatinine, potassium, lymphocyte count, and creatine phosphokinase. At 12-month follow-up, among 52 survivors with AKI-2/3, 26% COVID-19-positive and 24% COVID-19-negative patients had incident or progressive CKD. Recovery from COVID-19-associated moderate/severe AKI can be predicted using admission data and is associated with severity of respiratory disease and in-hospital death. The risk of CKD might be similar between COVID-19-positive and -negative patients.


Developing PM2.5 and PM10 prediction models on a national and regional scale using open-source remote sensing data.
Clean air is the precursor to a healthy life. Air quality is an issue that has been getting under its well-deserved spotlight in the last few years. From a remote sensing point of view, the first Copernicus mission with the main purpose of monitoring the atmosphere and tracking air pollutants, the Sentinel-5P TROPOMI mission, has been widely used worldwide. Particulate matter of a diameter smaller than 2.5 and 10 μm (PM2.5 and PM10) significantly determines air quality. Still, there are no available satellite sensors that allow us to track them remotely with high accuracy, but only using ground stations. This research aims to estimate PM2.5 and PM10 using Sentinel-5P and other open-source remote sensing data available on the Google Earth Engine (GEE) platform for heating (December 2021, January, and February 2022) and non-heating seasons (June, July, and August 2021) on the territory of the Republic of Croatia. Ground stations of the National Network for Continuous Air Quality Monitoring were used as a starting point and as ground truth data. Raw hourly data were matched to remote sensing data, and seasonal models were trained at the national and regional scale using machine learning. The proposed approach uses a random forest algorithm with a percentage split of 70% and gives moderate to high accuracy regarding the temporal frame of the data. The mapping gives us visual insight between the ground and remote sensing data and shows the seasonal variations of PM2.5 and PM10. The results showed that the proposed approach and models could efficiently estimate air quality.


Expression and Clinical Significance of circRNA Changes in Stored Erythrocytes During Platelet Transfusion in Acute Lymphoblastic Leukemia.
This study was to store the expression and clinical significance of circRNA changes in red blood cells during platelet transfusion in acute lymphoblastic leukemia (ALL). Sixty patients with ALL who underwent platelet transfusion were enrolled. Post-transfusion symptoms, platelet count (PLT), 24-hour corrected platelet increase index (CCI), and 24-hour platelet recovery rate (PPR) were collected, and their correlation with age, gender, bleeding, infection, splenomegaly, antibiotic use and infusion times were analyzed. High-throughput sequencing was used to detect the expression levels of circRNAs in suspended red blood cells of the blood samples. Then, the circRNA expression profiles were constructed, the differentially expressed circRNAs were screened, and the circRNAs related to platelet transfusion in AML were mined. PLT values of 60 ALL patients after platelet transfusion were significantly increased. Thirty-five patients were effective and 25 were ineffective after platelet transfusion, and the total effective rate was 58.33%. Patients with hemorrhage and splenomegaly, or antibiotic use, or increased blood transfusion frequency will show reduced efficacy of platelet transfusion. A total of 2,358 circRNAs were obtained from all samples, most of which were distributed in 200 - 3,000 nt. circRNAs can be divided into exonic circRNAs (58.74%), sense overlapping circRNAs (21.76%), intronic circRNAs (17.60%), antisense circRNAs (0.93%), and intergenic circRNAs (0.98%). A total of 257 differentially expressed circRNAs were obtained by volcano plot analysis, of which 126 were up-regulated and 131 were down-regulated. Differentially up-regulated and down-regulated circRNAs were mainly enriched in dif-ferent cellular processes. ALL is improved after platelet transfusion. By constructing circRNA expression profiles and screening differentially expressed circRNAs, 257 circRNAs that may be related to ALL platelet transfusion were mined.


Polarization characteristics of Spectralon illuminated by coherent light.
The Multiangle Imaging Spectroradiometer makes use of an onboard calibration system that includes two Spectralon panels that are used to reflect sunlight into the cameras. During preflight testing, these panels were quantified in terms of their bidirectional reflectance distribution function, which was measured as a function of the source-incident and detector view angles and at laser wavelengths of 442.0, 632.8, and 859.9 nm. Principal plane measurements are presented in which polarizations of the source and detector are analyzed. These data are unique and valuable in modeling Spectralon reflectance properties and for experiments in which polarization sensitivities are important.


Effects of oxidative stress on the production of carotenoid pigments byPhaffia rhodozyma (Xanthophyllomyces dendrorhous).
The resistance to killing by free radicals of two mutants ofPhaffia rhodozyma was determined. Mutant 5-7 did not produce astaxanthin but produced beta-carotene, while mutant 3-4 did not produce any carotenoid pigments. The resistance of mutant 5-7 was the same as that of the wild type but mutant 3-4 was rapidly killed. Carotenoid pigments increased the resistance to killing by free radicals. We investigated the effects of free radicals, generated by H(2)O(2) and Fe(2+) added to the medium, on wild-type cells and mutants ofP. rhodozyma. Unpigmented mutants of basidiomycetous yeasts (Rhodotorula spp. and others) are more susceptible to killing by UV-irradiation than the pigmented, wild-type strains. Therefore, we investigated the effect of free radicals on a similar basidiomycetous yeast,P. rhodozyma, a species of economic importance, in the biological production of astaxanthin.


[Free small intestine transplantation in plastic reconstruction of the oral cavity, pharynx and cervical esophagus. Report of experiences following 3 years of use].
Between August 1984 and August 1987 77 free intestinal grafts were transplanted in our Department of otorhinolaryngology using microvascular anastomoses. These reconstructions were necessary after tumour resections in the oral cavity, in the pharynx, and the cervical oesophagus. Patients, operative technique, perioperative treatment, and complications are described. The definition of oncologic results is still problematic. Only trends have been discovered. In conclusion, complications, functional results, and the advantages of free intestinal grafts are discussed.


[Preterm labor and IUGR rates in patients with cardiac anomalies in the material of the Pregnancy Pathology Unit at the Jagiellonian University OB/GYN Department between 1986-1999].
Advance in medicine in general caused more and more women with cardiac defects reach reproductive age. Analysis of kind and advance of cardiac disease influence on preterm labour and IUGR rates. A prospective study on 232 pregnant patients with cardiac malformations, who were hospitalised in Pathology of Pregnancy Unit of OB./ GYN Jagiellonian University Clinic was performed between 1986-1999. Acquired data were compared with results obtained from control group of 424 pregnant patients with physiological course of pregnancy. Results prove of shorter pregnancy duration in patients with higher NYHA classes. Preterm labour rate in patients of NYHA III and IV equals to 31.15% and is 3 times higher than in control group. Patients of NYHA I and II revealed comparable gestational age with control group. Worse obstetric outcome is characteristic for 3rd and 4th NYHA classes. Intrauterine growth retardation in patients with cardiac malformations occurs after 34 week of pregnancy.


Benefit-risk assessment of levetiracetam in the treatment of partial seizures.
Levetiracetam is a novel antiepileptic drug that has been demonstrated as being effective in the management of partial seizures. It is rapidly and completely absorbed after oral administration and it is predominantly eliminated as unchanged drug in the urine. Its metabolism is independent of the cytochrome P450 enzyme system, nor does it induce cytochrome P450 enzymes. As a result of its pharmacokinetic features, levetiracetam has not been demonstrated to interact with other drugs in either direction. In double-blind, placebo-controlled trials, all the levetiracetam dosages tested were effective, including 1000 mg/day, 2000 mg/day and 3000 mg/day. The ineffective dose is not known. Efficacy seemed to be maintained in long-term studies, with no evidence of tolerance. In major double-blind, placebo-controlled trials discontinuation rates because of adverse events were 6.9-10.9% for levetiracetam-treated patients (all doses) compared with 5.3-8.6% for placebo-treated patients. The most common adverse events that differed between treatment groups and placebo control groups were somnolence, asthenia, dizziness and, in the US study, infection. Since levetiracetam was marketed, behavioural effects have been reported, namely irritability, agitation, anger and aggressive behaviour. These adverse effects are more likely in learning disabled individuals, those with prior psychiatric history and those with symptomatic generalised epilepsy. Overall, the risk has been estimated at 12-15%. Laboratory parameters overall seem to be not significantly affected by levetiracetam, although slight trends to lower white and red blood cell counts were detected in the studies. No organ toxicity has been described so far, with patient exposures exceeding 500,000. In summary, levetiracetam exhibits a very favourable safety profile in patients with partial onset seizures. Whereas somnolence, asthenia and dizziness were the most prominent adverse effects in clinical trials, behavioural adverse effects have generally been the most common reason for drug discontinuation in clinical practice.


Prenatal application of somatic gene therapy.
Somatic gene therapy in the fetus or neonate represents an exciting new approach for the management of some congenital or inherited diseases. It is likely that clinical trials of these methods will take place in the future. In contrast, despite the potential for manipulation of embryos and inherited genetic material, the clinical applicability of these methods is uncertain.


Retrospective analysis of children with uveitis treated with infliximab.
Tumor necrosis factor-alpha (TNF-alpha) antagonists have been successfully used in refractory cases of pediatric uveitis.(1-7) We report our experience with the monoclonal anti-TNF-alpha antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy.


Expression and Purification of FGFR1-Fc Fusion Protein and Its Effects on Human Lung Squamous Carcinoma.
Molecular-targeted therapies for lung squamous cell carcinoma (LSCC) are limited mainly because targetable oncogenic aberrations are absent in LSCC. Recent genomic analyses have revealed that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in LSCC progression via cancer cell proliferation and angiogenesis. In the present study, we designed, expressed, and purified a fibroblast growth factor receptor fragment (FGFR1-Fc) fusion protein using NS/0 cells. In FGF2-FGFR1 overexpressed NCI-H1703 cells, the FGFR1-Fc fusion protein effectively inhibited proliferation and invasion and arrested the cell cycle at the G0-G1 phase. In NCI-H1703 cells treated with the FGFR1-Fc fusion protein, the phosphorylation levels of FGFR1, FRS2, ERK, and AKT were significantly reduced. Using an siRNA assay, we demonstrated that FGF2-FGFR1 is the major anti-tumor target of FGFR1-Fc fusion the FGFR1-Fc fusion protein, which also significantly inhibited proliferation and invasion by NCI-H1703 cells via the FGF2-FGFR1 signaling pathway. In addition, the FGFR1-Fc fusion protein significantly inhibited angiogenesis in an embryonic chorioallantoic membrane model. The FGFR1-Fc fusion protein may be an effective therapeutic candidate for LSCC.


Prevalence of metal levels above the reference values in a municipality affected by the collapse of a mining tailings dam: Brumadinho Health Project.
To describe the prevalence of levels of arsenic, cadmium, mercury, lead and manganese above the reference values (RV) in the population of Brumadinho, after the rupture of the mining tailings dam and to verify the factors associated with these levels. Baseline study of a prospective cohort, in a representative sample of 3,080 residents (aged 12 and over) in Brumadinho, Minas Gerais. Exploratory variables (age, sex, skin color, household income, smoking and place of residence) were collected using a questionnaire and the levels of As, Cd and Hg in urine and Pb and Mn in blood were evaluated using the technique of inductively coupled plasma mass spectrometry. The distribution of prevalence of levels above the reference for metals was made, according to the exploratory variables. Multiple logistic regression analyzes were used to investigate the association between altered levels of metals and characteristics evaluated. Concentrations above RV were found in 38.08% of the population for Mn, 33.37% for As, 5.04% for Pb, 0.76% for Hg and 0.17% for Cd. There was a significant association between age group and levels of Mn and Pb; and between place of residence and As level. The results show a high prevalence of levels above the reference for Mn, As and Pb, with small differences in relation to the other variables, suggesting that it is an exposure distributed throughout the municipality.


Solid-state random microlasers fabricated via femtosecond laser writing.
Here we demonstrate resonant random lasing in Rhodamine B-doped polymeric microstructures fabricated by means of femtosecond laser writing via two-photon polymerization. To the best of our knowledge, this is the first demonstration of random lasing action in on-chip microdevices. Their feedback mechanism relies on diffuse reflections at the structure sidewall surfaces, which is known as spatially localized feedback since the scattering centers lie over the edges of the gain medium. By exciting the structures with a pulsed laser at 532 nm, a multimode emission with randomly distributed narrow peaks was observed, in accordance with the random nature of the feedback mechanism. Interestingly, their lasing threshold was found to be on the order of tens of nanojoules, which is comparable to what had been achieved for usual microcavities, thereby demonstrating the potentiality of these devices as solid-state lasers for integrated optics applications.


Feasibility and utility of transcutaneous spinal cord stimulation combined with walking-based therapy for people with motor incomplete spinal cord injury.
Prospective case series. To evaluate the feasibility and preliminary efficacy of combining transcutaneous spinal cord stimulation (TSCS) with walking-based physical therapy. Hospital-based outpatient center in Maryland, United States. Ten individuals with chronic (>1 year) motor incomplete spinal cord injury (iSCI) completed 23 sessions of 2-h therapy over 8 weeks. TSCS was delivered for the first 30 min of each session using a clinically available device with adjustable current. To assess feasibility of the intervention, we tracked pain, adverse events, and participant retention. Preliminary efficacy was assessed by evaluating changes in walking speed, endurance, and quality following the intervention with select functional outcome measures (10-m walk test (10MWT), 6-min walk test (6MWT), timed up and go, and walking index for spinal cord injury II). We found that the combined intervention was feasible in an outpatient clinical setting. Participants tolerated the TSCS well, with no reports of significant adverse events or other issues (e.g., skin irritation or pain that disrupted training). None of the participants elected to discontinue the study. Participants also showed significant improvements in each measure of walking function following the intervention. Changes in walking speed, as measured by the 10MWT (0.56 ± 0.29 m/s to 0.72 ± 0.36 m/s), exceeded the minimal clinically important difference for individuals with iSCI. Changes in walking quality and endurance, as measured by the 6MWT (149.88 ± 99.87 m to 194.53 ± 106.56 m), exceeded the minimal detectable change for individuals with iSCI. These results indicate that TSCS is clinically feasible and may be useful as an adjunct to walking-based therapy for adults with iSCI.


Accuracy and efficiency of germline variant calling pipelines for human genome data.
Advances in next-generation sequencing technology have enabled whole genome sequencing (WGS) to be widely used for identification of causal variants in a spectrum of genetic-related disorders, and provided new insight into how genetic polymorphisms affect disease phenotypes. The development of different bioinformatics pipelines has continuously improved the variant analysis of WGS data. However, there is a necessity for a systematic performance comparison of these pipelines to provide guidance on the application of WGS-based scientific and clinical genomics. In this study, we evaluated the performance of three variant calling pipelines (GATK, DRAGEN and DeepVariant) using the Genome in a Bottle Consortium, "synthetic-diploid" and simulated WGS datasets. DRAGEN and DeepVariant show better accuracy in SNP and indel calling, with no significant differences in their F1-score. DRAGEN platform offers accuracy, flexibility and a highly-efficient execution speed, and therefore superior performance in the analysis of WGS data on a large scale. The combination of DRAGEN and DeepVariant also suggests a good balance of accuracy and efficiency as an alternative solution for germline variant detection in further applications. Our results facilitate the standardization of benchmarking analysis of bioinformatics pipelines for reliable variant detection, which is critical in genetics-based medical research and clinical applications.


Assessment of socio-relational self-efficacy in breast cancer patients: Italian validation of the social relationship coping efficacy scale (SRCE-I).
Social relationship coping efficacy (SRCE) represents the ability to maintain or enhance social relationships in the context of serious illness. The purpose of the current study was to confirm the factor structure, psychometric properties, and utility of the Italian version of the SRCE scale. 181 breast cancer patients completed the SRCE-Italian (SRCE-I), the Cancer Behavior Inventory-Brief/Italian (CBI-B/I), quality of life (QOL) measures (EORTC QLQ-C30; EORTC QLQ-BR23), and the Hospital Anxiety and Depression Scale (HADS). The SRCE-I was internally consistent (Cronbach alpha = .95) and factor analysis confirmed that the SRCE-I was a unidimensional construct. In terms of validity, the SRCE-I was correlated with QOL (EORTC QLQ-30, Social Functioning, r = .33, Emotional Functioning, r = .57, and Global Health/Quality of Life; r = .54) and scales of the EORTC QLQ-BR23 (e.g., Future Perspective, r = .38; Breast Symptoms, -.31). SRCE-I was also correlated negatively with the HADS (r = -.72) and positively with the CBI-B/I (r = .79), a measure of coping efficacy (all ps < .001). Mediation analyses confirmed the utility of the SRCE-I scale as a mediating mechanism in enhancing social functioning and QOL. The SRCE-I is a structurally sound, reliable, and valid measure that assesses the ability to maintain or enhance social support and mitigate the loss of social support. The SRCE-I can be used as a screening measure to assess low efficacy for maintaining social support or as a measure to detect the change in efficacy for enhancing social support in interventions to improve the QOL of patients.


A tissue-specific endothelial cell molecule involved in lymphocyte homing.
An endothelial cell surface molecule that is selectively expressed in mucosal organs is required for lymphocyte homing to mucosal lymphoid tissues. This 'vascular addressin' appears to function as a tissue-specific marker or address signal for recognition by lymphocytes circulating in the blood.


[Advanced life support under special circumstances: part 1].
Based on the 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations of the International Liaison Committee on Resuscitation (ILCOR), guidelines were published for managing basic and advanced life-saving procedures in the event of cardiac arrest. The fact that special circumstances sometimes must be considered in patient treatment resulted in a separate chapter. This first part of a two-part article reviews essential information as well as necessary modifications of the standard advanced life support algorithm in cases of life-threatening drowning, asthma, anaphylaxis, and poisoning. The second part will deal with electrolyte disorders, hypothermia, electrical emergencies, trauma, cardiac arrest during pregnancy, and cardiac surgery.


Histopathologic and Clinical Features in Patients with Diabetes and Kidney Disease.
The discovery of nondiabetic kidney disease (NDKD) in an individual patient with diabetes may have significant treatment implications. Extensive histopathologic data in this population are lacking, but they may provide insights into the complex pathogenesis of diabetic nephropathy (DN) and reveal specific phenotypes for the development of targeted therapies. This study seeks to elucidate the clinical and laboratory parameters associated with the spectrum of kidney histopathologic features in patients with diabetes. This study is a retrospective analysis of 399 kidney biopsies assessed from 2014 to 2016 at the University of Washington among patients with diabetes. More comprehensive clinical data were evaluated in a subset of 79 participants. Of the 399 biopsies reviewed, 192 (48%) had a primary diagnosis of DN (including 26 with an additional diagnosis), and 207 (52%) had a primary diagnosis of NDKD (including 67 who also had DN). Retinopathy (sensitivity: 0.86; specificity: 0.81; OR, 27.1; 95% CI, 6.8 to 107.7) and higher levels of proteinuria (7.6 versus 4.1 g/d; P=0.004) were associated with DN, whereas a physician description of AKI was associated with a lower risk of DN (OR, 0.13; 95% CI, 0.04 to 0.38). The four most prevalent diagnoses in participants with NDKD were FSGS in 39, nephrosclerosis in 29, IgA nephropathy in 27, and acute tubular injury in 21. Among patients with diabetes who undergo kidney biopsy in the Pacific Northwest, approximately half have DN, and half have NDKD. Retinopathy and more severe proteinuria were associated with DN, and AKI was a more common descriptor in NDKD.Podcast: This article contains a podcast at https://www.asnonline.org/media/podcast/K360/2020_11_25_KID0003962020.mp3.


Binding of reactive metabolites of CCl4 to specific microsomal proteins.
The covalent binding of [14C]carbon tetrachloride to microsomal proteins in rat liver microsomes under anaerobic conditions was investigated by SDS-polyacrylamide slab gel electrophoresis and fluorography. Most of the labeled proteins were observed in the molecular weight range of 52-61 kDa, indicating that cytochrome P-450 forms (EC 18.104.22.168) were labeled. Protein bands at the position of the NADPH-cytochrome P-450 reductase (78 kDa) (EC 184.108.40.206) and NADH-cytochrome b5 reductase (33 kDa) (EC 18.104.22.168) also showed radioactivity. The fluorographic pattern of the protein labeling was cytochrome P-450-dependent, as was demonstrated by CO and metyrapone inhibition as well as by pretreatment of rats with inducing drugs such as 3-methylcholanthrene, benzo(a)pyrene, phenobarbitone and Aroclor 1254. Immuno-precipitation with a purified anti-P-450 immunoglobulin against cytochrome P-450 PB-B (52 kDa) of rat liver indicated that this protein contained about 10-20% of the total bound radioactivity in an average ratio of 0.8 mol [14C]CCl4-metabolite/mol cytochrome P-450 PB-B.


Square wave anodic stripping voltammetric determination of Pb2+ using acetylene black paste electrode based on the inducing adsorption ability of I-.
Herein, a sensitive and simplified electrochemical method was proposed for the determination of trace levels of Pb2+ by anodic stripping voltammetry (ASV) based on the inducing adsorption ability of I- toward Pb2+. In the presence of low concentration of I-, Pb2+ was induced to accumulate onto the acetylene black (AB) paste electrode surface, and then reduced at -0.90 V. During the following square wave sweep from -0.90 to -0.30 V, the reduced Pb was oxidized, resulting in a sensitive and well-shaped stripping peak at -0.56 V. Further studies indicate that low concentration of I- significantly enhances the sensitivity of determination of Pb2+. After all the experimental parameters were optimized, a novel and sensitive method was developed for the electrochemical determination of Pb2+. The linear range is found to be from 2.0 x 10(-8) to 4.0 x 10(-6) mol L(-1), and the lowest detectable concentration is estimated to be 6.0 x 10(-9)mol L(-1). This newly proposed method was finally demonstrated with water samples. Otherwise, the anodic stripping responses of Pb2+ on AB paste electrode and graphite paste electrode were compared.


Evaluation of PEG-b-polycarbonates self-assemblies containing azobenzene or coumarin moieties as nanocarriers using paclitaxel as a model hydrophobic drug.
The work assesses the performance of nanocarriers from amphiphilic block copolymers with functional azobenzene or coumarin moieties for delivery of paclitaxel. Placlitaxel was encapsulated by the nanoprecipitation method. Characterisations were performed by DLS, TEM, Zeta potential and HPLC. Cell viability was investigated in HeLa and Huh-5-2-cell lines. Coumarin-containing polymeric micelles (Dh = 26 ± 2 nm, PDI = 0.28, ζ = ‒22.9 ± 3.6 mV) with 11.2 ± 0.5%w/w drug loading showed enhanced cytotoxicity in HeLa cells (IC50 < 0.02 nM) compared to free paclitaxel (IC50 = 0.17 ± 0.02 nM). Azobenzene-containing polymeric vesicles (Dh = 390 ± 20 nm, PDI = 0.24, ζ = ‒33.2 ± 5.0 mV) with a 6.8 ± 0.4%w/w drug loading showed increased cytotoxicity under 530 nm light (IC50 = 0.0114 ± 0.00033 nM) in HeLa cells due to a stimulated delivery of paclitaxel. Effectivity of these block copolymers as paclitaxel nanovectors and light stimulated release has been demonstrated.


Combined treatment of nerve growth factor and transcranical direct current stimulations to improve outcome in children with vegetative state after out-of-hospital cardiac arrest.
Out-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA. Transcranial Direct Current Stimulation (tDCS) has been reported to be neuroprotective in many neurological diseases, such as motor deficit and cognitive impairment. Children with the diagnosis of chronic vegetative state after OHCA were enrolled. These patients underwent a combined treatment of intranasal administration of human recombinant NGF (hr-NGF), at a total dose of 50 gamma/kg, and tDCS, in which current intensity was increased from zero to 2 mA from the first 5 s of stimulation and maintained constant for 20 min. The treatment schedule was performed twice, at one month distance each. Neuroradiogical evaluation with Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Power Spectral Density of the brain (PSD) was determined before the treatment and one month after the end. Neurological assessment was deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. Three children with a chronic vegetative state secondary to OHCA were treated. The combined treatment with hr-NGF and tDCS improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary finger movements, improved facial mimicry and reaction to painful stimuli. No side effects were reported. These promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from OHCA and in patients with better baseline neurological conditions, in order to explore more thoroughly the benefits of this new approach on neuronal function recovery after OHCA.


Inhibition of associative long-term depression by activation of beta-adrenergic receptors in rat hippocampal CA1 synapses.
The aim of this study was to investigate the role of beta-adrenergic receptors in modulating associative long-term depression (LTD) at CA1 synapses in rat hippocampal slices. Standard extracellular electrophysiological techniques were employed to record field excitatory post-synaptic potential (fEPSP) activity and to induce associative LTD. Two independent Schaffer collateral pathways were elicited in hippocampal CA1 areas. In one (weak) pathway, the stimulating intensity was adjusted to elicit small fEPSP activity (20-30% of the maximum response). In contrast, 80-90% of the maximum response was evoked in the other (strong) pathway. Associative LTD of weak pathway could be induced by paired stimulation of weak and the strong pathways, repeated 100 times at 0.167 Hz. The associative LTD of weak pathway was NMDA receptor- and phosphatase 2B dependent, because bath application of 50 microM D, L-AP5 or 10 microM cypermethrin blocked its induction. Bath application of 1 microM isoproterenol inhibited associative LTD, and this effect was blocked by timolol, suggesting the involvement of beta-adrenergic receptors. The inhibitory effect of beta-adrenergic receptors on LTD induction was blocked in slices pretreated with inhibitors of protein kinase A and mitogen-activated protein kinase, suggesting that these signal cascades are downstream effectors following activation of beta-adrenergic receptors. Nevertheless, bath application of timolol or cypermethrin alone did not have significant effect on associative LTD induction, suggesting neither endogenous function of beta-adrenergic receptor nor endogenous PKA activity does have a role in associative LTD induction.


Dynamic Stiffening Hydrogel with Instructive Stiffening Timing Modulates Stem Cell Fate In Vitro and Enhances Bone Remodeling In Vivo.
Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through 3D and spatiotemporal changes in vivo. The matrix stiffness is a crucial factor during bone tissue development. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment. Here, a dynamic and controllable stiffening 3D biomimetic model is created to regulate the osteogenic differentiation of MSCs with a dual-functional gelatin macromer that can generate a double-network hydrogel by sequential enzymatic and light-triggered crosslinking reactions. The findings show that these dynamic hydrogels allowed cells to spread and expand prior to the secondary crosslinking and to sense high stiffness after stiffening. The MSCs in the dynamic hydrogels, especially the hydrogel stiffened at the late period, present significantly elevated osteogenic ECM secretion, gene expression, and nuclear localization of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). In vivo evaluation of animal experiments further indicates that the enhancement of dynamic stiffening on osteogenesis of MSCs substantially promotes bone remodeling. Consequently, this work reveals that the 3D dynamic stiffening microenvironment as a critical biophysical cue not only mediates the stem cell fate in vitro, but also augments bone restoration in vivo.


A study of electron and thermal transport in layered titanium disulphide single crystals.
We present a detailed study of thermal and electrical transport behavior of single crystal titanium disulphide flakes, which belong to the two dimensional, transition metal dichalcogenide class of materials. In-plane Seebeck effect measurements revealed a typical metal-like linear temperature dependence in the range of 85-285 K. Electrical transport measurements with in-plane current geometry exhibited a nearly T 2 dependence of resistivity in the range of 42-300 K. However, transport measurements along the out-of-plane current geometry showed a transition in temperature dependence of resistivity from T 2 to T 5 beyond 200 K. Interestingly, Au ion-irradiated TiS2 samples showed a similar T 5 dependence of resistivity beyond 200 K, even in the current-in-plane geometry. Micro-Raman measurements were performed to study the phonon modes in both pristine and ion-irradiated TiS2 crystals.


Clinical correlates of acute right ventricular infarction in acute inferior myocardial infarction.
Right ventricular infarction was diagnosed on the basis of ST-segment elevation greater than or equal to 1 mm in at least one right precordial lead (V3R-V6R) in 20 of 50 patients with first acute inferior myocardial infarction. Seventy five percent of these had ST elevation in 2 or more right precordial leads. Giddiness and hiccups were more common amongst such patients (P less than 0.05). Signs of right ventricular dysfunction-raised jugular venous pressure (65%), Kussmaull's sign (45%), hypotension (without cardiogenic shock, 40%) and right-sided third sound (25%) in the absence of clinical left ventricular failure, were noted in 65% of such patients. Eleven patients had 2 or more of the above signs. ST elevation in 2 or more right precordial leads was found in 10 of these 11 patients. A more complicated course in the hospital characterised by bradyarrhythmias, hypotension and cardiogenic shock, combined with a greater mortality was seen in such patients. We conclude that the bedside diagnosis of haemodynamically significant right ventricular infarction can be made on the basis of a combination of clinical signs and ST elevation in 2 or more right precordial leads, even in units not equipped for bedside haemodynamic monitoring, echocardiography and radionuclide studies. This should lead to a better identification and management of such patients.


Adsorption of Acylhydroperoxy-Derivatives of Phospholipids from Biomembranes by Blood Plasma Lipoproteins.
It has been established that acylhydroperoxy derivatives of phospholipids from oxidized rat liver mitochondria are captured predominantly by LDL particles but not by HDL during co-incubation with blood plasma lipoproteins, which refutes the previously suggested hypothesis about the involvement of HDL in the reverse transport of oxidized phospholipids and confirms the possibility of different mechanisms of lipohydroperoxide accumulation in LDL during oxidative stress.


Characterization of the novel HLA-DPA1*01:03:16 allele by sequencing-based typing.
HLA-DPA1*01:03:16 differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in codon 171 in exon 3.


Simultaneous adsorption of As(III) and Cd(II) by ferrihydrite-modified biochar in aqueous solution and their mutual effects.
A simply synthetic ferrihydrite-modified biochar (Fh@BC) was applied to simultaneously remove As(III) and Cd(II) from the aqueous solution, and then to explore the mutual effects between As(III) and Cd(II) and the corresponding mechanisms. The Langmuir maximum adsorption capacities of As(III) and Cd(II) in the single adsorbate solution were 18.38 and 18.18 mg g-1, respectively. It demonstrated that Fh@BC was a potential absorbent material for simultaneous removal of As(III) and Cd(II) in aqueous solution. According to the XRF, SEM-EDS, FTIR, XRD, and XPS analysis, the mechanisms of simultaneous removal of As(III) and Cd(II) by Fh@BC could be attributable to the cation exchange, complexation with R-OH and Fe-OH, and oxidation. Moreover, the mutual effect experiment indicated that Cd(II) and As(III) adsorption on Fh@BC in the binary solution exhibited competition, facilitation and synergy, depending on their ratios and added sequences. The mechanisms of facilitation and synergy between Cd(II) and As(III) might include the electrostatic interaction and the formation of both type A or type B ternary surface complexes on the Fh@BC.


Pulmonary scedosporiosis mimicking aspergilloma in an immunocompetent host: a case report and review of the literature.
A case of localized lung scedosporiosis is reported here that mimicked aspergilloma in an immunocompetent host. Through this case the importance of considering Scedosporium spp. in differential diagnosis of locally invasive lung infections and fungal ball is highlighted. As it is difficult to differentiate Scedosporium from Aspergillus on clinical grounds, microscopy, radiology and histopathology, this case is further emphasizing the significance of the definitive etiological characterization of Scedosporium through culture or molecular diagnostic tools. Accurate identification of Scedosporium, surgical resection and high-dose voriconazole has been associated with favorable outcome in most reported cases of scedosporiosis.


Physiological plasticity of metabolic rates in the invasive honey bee and an endemic Australian bee species.
Seasonal variation in metabolic rate and evaporative water loss as a function of ambient temperature were compared in two species of bees. The endemic blue-banded bee, Amegilla chlorocyanea, is a solitary species that is an important pollinator in the south-west Australian biodiversity hotspot. Responses were compared with the European honeybee, Apis mellifera, naturalised in Western Australia almost 200 years ago. Metabolic rate increased exponentially with temperature to a peak in both species, and then declined rapidly, with unique scaling exponents and peaks for all species-by-season comparisons. Early in the austral summer, Apis was less thermally tolerant than Amegilla, but the positions reversed later in the foraging season. There were also significant exponential increases in evaporative water loss with increasing temperature, and both season and species contributed to significantly different responses. Apis maintained relatively consistent thermal performance of metabolic rate between seasons, but at the expense of increased rates of evaporative water loss later in summer. In contrast, Amegilla had dramatically increased metabolic requirements later in summer, but maintained consistent thermal performance of evaporative water loss. Although both species acclimated to higher thermal tolerance, the physiological strategies underpinning the acclimation differed. These findings may have important implications for understanding the responses of these and other pollinators to changing environments and for their conservation management.


The prediction philosophy in statistics.
Estimation and hypothesis testing have been popular in applied statistical analysis. More recently, emphasis has been placed on prediction. Traditional questions of estimation and hypothesis testing are being reframed as problems of prediction, and as such, the methods and approaches have shifted. The reporting of P values is de-emphasized from the prediction philosophy perspective, and incremental predictive accuracy has become the metric of choice. Ties to individual patient decision making and outcomes research are presented.


SNAPs, a family of NSF attachment proteins involved in intracellular membrane fusion in animals and yeast.
Three new and likely related components of the cellular fusion machinery have been purified from bovine brain cytosol, termed alpha-SNAP (35 kd), beta-SNAP (36 kd), and gamma-SNAP (39 kd). Transport between cisternae of the Golgi complex measured in vitro requires SNAP activity during the membrane fusion stage, and each SNAP is capable of binding the general cellular fusion protein NSF to Golgi membranes. The SNAP-NSF-membrane complex may be an early stage in the assembly of a proposed multisubunit "fusion machine" on the target membrane. SNAP transport factor activity is also found in yeast. Yeast cytosol prepared from a secretion mutant defective in export from the endoplasmic reticulum (sec17) lacks SNAP activity, which can be restored in vitro by the addition of pure alpha-SNAP, but not beta- or gamma-SNAPs. These data suggest that the mechanism of action of SNAPs in membrane fusion is conserved in evolution.


Improving our ability to diagnose infections associated with central venous catheters: value of Gram's staining and culture of entry site swabs.
We prospectively studied 45 central venous catheters to determine whether Gram's staining and culture of skin swabs from the entry site could be used to predict catheter-related infection. Data were collected from insertion site swabs, intracutaneous and intravascular catheter segments, and blood cultures. Surveillance site cultures at the time of dressing changes showed that bacterial growth, once established, persisted until removal of the catheter but that the time of onset of infection was not predictable. Gram's staining alone and Gram's staining combined with culture were tested for their ability to predict catheter colonization and catheter-related infection. Bacteria seen with Gram's staining invariably denoted catheter colonization. When bacteria were not seen with Gram's staining, positive results of culture did not change the pretest probabilities of colonization or infection; however, negative results of culture reduced the probability of colonization to low levels (likelihood ratio less than 0.06). We conclude that Gram's staining and culture of skin swabs from the entry site provide, without line removal, a simple, inexpensive and practical test for the diagnosis of catheter-related infection.


Comparison of the mechanical destructive force in the small intestine of dog and human.
The purpose of this study was to evaluate the destructive force that oral solid dosage forms receive in the small intestine of dogs and humans. Information on the mechanical destructive forces of the gastrointestinal tract (GI) helps formulation design research in the following way: (1) to improve the predictability of the dissolution test since in vivo drug release is affected by not only agitation intensity but also mechanical stress; (2) to design safe and robust products by avoiding dose-dumping or unintended drug release at an inadequate site; (3) to better understand the species difference in bioavailability by comparing the destructive forces against dosage forms in the GI of dogs with those of humans. "Destructive force Dependent Release System" (DDRS) was developed to measure the mechanical destructive forces of the GI tract by using highly hydrophobic Teflon powder. In a DDRS, a marker drug contained in the core tablet is released only when the DDRS receives a force larger than its pre-determined crushing strength. DDRS-Small Intestine (DDRS-SI), a modified DDRS, was prepared for targeting the small intestine. DDRS-SI was encapsulated in starch capsules (Capill) and then the capsules were coated with an enteric film (DDRS-SI-Ecap). The capsules were administered to six dogs and nine human volunteers. Both dogs and human volunteers crushed a DDRS-SI having a crushing strength of 1.2 N. Therefore, these controlled-release formulations should withstand a destructive force of 1.2 N when they pass through the small intestine.


Effect of fertilization treatments on yield parameters and mucilage and fat contents in roots of moghat (Glossostemon bruguiri Desf.).
Moghat plants, Glossostemon bruguieri, Desf., received three levels of both N and K fertilizers, either alone or in combination, with a basic dose of P for all the treatments. The results with one and two year old plants revealed the importance of potassium for higher yield of roots, reflected in greater length and diameter. The lower level K1 was enough to attain that goal and the N1K1 treatment was the best in this regard. On the other hand, N fertilization rather favoured the vegetative growth and seed yield. Both N and K fertilization decreased the mucilage content of the roots, but increased their fat content. The root yield after two years increased by 72% compared with one year old plants. That increment was rather dependent on the root diameter than its elongation. The mucilage content was doubled, while the fat content decreased.


Systolic and diastolic heart failure are associated with different plasma levels of B-type natriuretic peptide.
Previous studies have found that plasma B-type natriuretic peptide (BNP) is elevated during left ventricular systolic or diastolic dysfunction. It is unclear whether the ventricular systolic and diastolic function is associated with different levels of plasma BNP. Plasma BNP was measured in 149 heart failure patients by a rapid point-of-care assay. The patients were divided into left ventricular diastolic dysfunction (n = 48), left ventricular systolic dysfunction (n = 62) and right ventricular systolic dysfunction group (n = 39). The mean BNP level in the left ventricular diastolic dysfunction, left ventricular systolic dysfunction and right ventricular systolic dysfunction was 115 +/- 80 pg/ml, 516 +/- 445 pg/ml and 345 +/- 184 pg/ml, respectively (p < 0.05). We concluded that ventricular systolic and diastolic dysfunction increases plasma BNP levels to a different extent. Left and right ventricular systolic dysfunction is associated with a higher level of plasma BNP than left ventricular diastolic dysfunction.


A systematic review of radiomics in pancreatitis: applying the evidence level rating tool for promoting clinical transferability.
Multiple tools have been applied to radiomics evaluation, while evidence rating tools for this field are still lacking. This study aims to assess the quality of pancreatitis radiomics research and test the feasibility of the evidence level rating tool. Thirty studies were included after a systematic search of pancreatitis radiomics studies until February 28, 2022, via five databases. Twenty-four studies employed radiomics for diagnostic purposes. The mean ± standard deviation of the adherence rate was 38.3 ± 13.3%, 61.3 ± 11.9%, and 37.1 ± 27.2% for the Radiomics Quality Score (RQS), the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, and the Image Biomarker Standardization Initiative (IBSI) guideline for preprocessing steps, respectively. The median (range) of RQS was 7.0 (- 3.0 to 18.0). The risk of bias and application concerns were mainly related to the index test according to the modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The meta-analysis on differential diagnosis of autoimmune pancreatitis versus pancreatic cancer by CT and mass-forming pancreatitis versus pancreatic cancer by MRI showed diagnostic odds ratios (95% confidence intervals) of, respectively, 189.63 (79.65-451.48) and 135.70 (36.17-509.13), both rated as weak evidence mainly due to the insufficient sample size. More research on prognosis of acute pancreatitis is encouraged. The current pancreatitis radiomics studies have insufficient quality and share common scientific disadvantages. The evidence level rating is feasible and necessary for bringing the field of radiomics from preclinical research area to clinical stage.


Chronic urticaria and Helicobacter pylori.
Helicobacter pylori (HP) have recently emerged as a novel eliciting factor for chronic urticaria (CU). The possible association between HP and CU has enormous potential, as eradicating HP could cure CU. We conducted a study to assess the prevalence of HP infection and effect of bacterium eradication on skin lesions in patients of chronic idiopathic urticaria (CIU). Four hundred sixty patients of CU attending the allergy clinic, SMS hospital, Jaipur during the period February 6, 2004, to February 6, 2006, were screened for possible eliciting factors. Patients with CIU were enrolled and others were excluded. Sixty-eight patients of CIU and similar number of age and sex matched controls, attending the allergy clinic, SMS Hospital, Jaipur were enrolled in the study. All patients underwent endoscopy with antral biopsy for urease and histopathology to identify HP-associated gastritis. Infected patients were given HP eradication therapy. Eradication of bacterium was confirmed by fecal antigen assay. Subjective response to treatment was judged using chronic urticaria quality-of-life questionnaire (CU-Q 2 oL) while objective response to treatment was judged by need for 'rescue medication' (antihistaminics). Data were analyzed using Chi square and paired 't' test for their level of significance. HP associated gastritis was present in 48 (70.58%) patients, out of which 39 (81.25%) patients responded to eradication therapy. Ten (50.00%) patients without HP associated gastritis showed response to symptomatic therapy. Overall 49 (72.05%) patients responded and 19 (27.94%) showed no response. The value of chi2 was 28.571 (P = 0.003), which showed significant association between presence of HP and response to eradication regimen. The response of HP eradication therapy in infected patients of CIU is significant. HP should be included in diagnostic workup of patients with CIU.


Comb-like amphiphilic polypeptide-based copolymer nanomicelles for co-delivery of doxorubicin and P-gp siRNA into MCF-7 cells.
A comb-like amphiphilic copolymer methoxypolyethylene glycol-graft-poly(L-lysine)-block-poly(L-phenylalanine) (mPEG-g-PLL-b-Phe) was successfully synthesized. To synthesize mPEG-g-PLL-b-Phe, diblock copolymer PLL-b-Phe was first synthesized by successive ring-opening polymerization of α-amino acid N-carboxyanhydrides followed by the removal of benzyloxycarbonyl protecting groups, and then mPEG was grafted onto PLL-b-Phe by reductive amination via Schiff's base formation. The chemical structures of the copolymers were identified by (1)H NMR. mPEG-g-PLL-b-Phe copolymer had a critical micelle concentration of 6.0mg/L and could self-assemble in an aqueous solution into multicompartment nanomicelles with a mean diameter of approximately 78 nm. The nanomicelles could encapsulate doxorubicin (DOX) through hydrophobic and π-π stacking interactions between DOX molecules and Phe blocks and simultaneously complex P-gp siRNA with cationic PLL blocks via electrostatic interactions. The DOX/P-gp siRNA-loaded nanomicelles showed spherical morphology, possessed narrow particle size distribution and had a mean particle size of 120 nm. The DOX/P-gp siRNA-loaded nanomicelles exhibited pH-responsive release behaviors and displayed accelerated release under acidic conditions. The DOX/P-gp siRNA-loaded nanomicelles were efficiently internalized into MCF-7 cells, and DOX released could successfully reach nuclei. In vitro cytotoxicity assay demonstrated that the DOX/P-gp siRNA-loaded nanomicelles showed a much higher cytotoxicity in MCF-7 cells than DOX-loaded nanomicelles due to their synergistic killing effect and that the blank nanomicelles had good biocompatibility. Thus, the novel comb-like mPEG-g-PLL-b-Phe nanomicelles could be a promising vehicle for co-delivery of chemotherapeutic drug and genetic material.


Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects.
Selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective mitogen-activated protein kinase 1/2 inhibitor with a short half-life, has shown activity across various tumor types. Before initiation of Phase III trials, the site, scale, and color (hypromellose shell from white [Phase II] to blue [Phase III]) of the selumetinib 25mg capsule manufacture was changed. We present 2 crossover trials evaluating Phase III capsules in healthy subjects. The relative bioavailability trial was a Phase I, open-label, randomized, 3-treatment, 4-period, 6-sequence crossover trial in healthy male subjects (aged 18-55 years). Subjects received selumetinib 75mg (3 × 25 mg) Phase II or Phase III capsules, or a 35mg oral solution, during 4 dosing periods in 1 of 6 randomized treatment sequences. The food effect trial was a Phase I, open-label, randomized, 2-period crossover trial in healthy male subjects (aged 18-45 years). Subjects were randomized to 1 of 2 sequences to receive selumetinib 75mg (3 × 25 mg) Phase III capsules. In sequence 1, subjects received selumetinib after 10 hours of fasting. Following a washout period, selumetinib was administered after a high-fat meal. In sequence 2, subjects received selumetinib in the fed state, before the fasted state. Pharmacokinetic parameters were determined from serial blood sampling. Twenty-seven subjects were randomized to the relative bioavailability trial; 26 completed all dosing periods. Mean selumetinib AUC was unchanged (geometric least squares mean ratio [GLSMR], 90.01% [90% CI, 81.74-99.11]). Cmax was 18% lower with the Phase III capsules (GLSMR, 81.97% [90% CI, 69.01-97.36]). A post hoc exploratory statistical analysis excluding outlying observations with later Tmax showed that Phase II and III capsules produced similar exposure in terms of Cmax and AUC. High intrasubject variability for Cmax attributed to the pharmacokinetic sampling schedule was judged to have impacted on the estimated GLSMR. In the food effect trial, 34 subjects completed both study periods. A high-fat meal reduced selumetinib Cmax compared with the fasted state (GLSMR, 49.76% [90% CI, 43.82-56.51]); AUC was minimally changed (GLSMR, 84.08% [90% CI, 80.72-87.59]). Median Tmax was prolonged by 1.49 hours. No deaths or serious adverse events were reported. Selumetinib 75mg (3 × 25 mg) Phase III capsules are being used in ongoing pivotal Phase III trials and should be administered in the fasted state. Based on findings from the relative bioavailability trial, pharmacokinetic sampling frequency was increased for healthy subject trials, including the food effect trial. ClinicalTrials.gov identifiers: NCT01635023 (relative bioavailability) and NCT01974349 (food effect).


Symptomatic intracranial tumors in pregnancy: an updated management algorithm. Illustrative case.
Intracranial tumors are infrequently encountered during pregnancy, and their diagnosis and management require a multidisciplinary approach to ensure the best possible outcomes for the mother and fetus. The pathophysiology and manifestations of these tumors are influenced by hormonal changes, hemodynamic modifications, and alterations in immunological tolerance that occur during pregnancy. Despite the complexity of this condition, no standardized guidelines exist. This study aims to highlight the key points of this presentation, along with the discussion of a possible management algorithm. The authors report the case of a 35-year-old woman who presented during the third trimester of pregnancy with severe signs of increased intracranial pressure (ICP) due to a posterior cranial fossa mass. The decision was made to stabilize the patient by placing an external ventricular drain to temporize her increased ICPs until the baby could be safely delivered via cesarean section. The mass was resected via suboccipital craniectomy 1 week postpartum. In considering treatment modalities and their timing in patients presenting with intracranial tumors during pregnancy, each patient should be managed on the basis of an individual treatment algorithm. Symptoms, prognosis, and gestational age should be taken into account to optimize the surgical and perioperative outcomes of both the mother and fetus.


Radiotherapy of internal mammary lymph nodes in breast cancer. Principle considerations on the basis of dosimetric data.
Radiotherapy of internal mammary lymph nodes (IMN) in breast cancer is discussed controversially due to its potential toxicity and debatable efficacy. Aim of the present study was to assess the cardiac and lung dose in 3-D planned radiotherapy and to discuss these results with regard to arguments pro and contra IMN irradiation. 32 patients underwent 3-D planning (Helax TMS) for irradiation of breast and IMN in three different techniques either using separate IMN fields (A, B) or a wide tangent (C). For each technique the respective doses to the heart (including the base of the aorta and the ostium of the coronary arteries) and lung were analyzed in dose volume histograms. The mean dose to the heart (left side irradiation) was 6.4 Gy (A), 8.1 Gy (B) and 3.8 Gy (C). The mean dose to the lung was 11.7 Gy (A), 15.4 Gy (B) and 10.2 Gy (C). The 10-Gy isodose comprised 19.5% (A), 32.9% (B) and 5.6% (C) of the heart (left breast). The respective values for the 20-Gy isodose were 7.8, 11.5 and 4.4%. The irradiated volumes of the lung were 37.7% (A), 52.7% (B) and 20% (C) in the 10-Gy isodose. The 20-Gy isodose comprised 16.7% (A), 28.3% (B) and 17.8% (C). Whether radiotherapy of the IMN may improve treatment results in breast cancer is currently unresolved. However, the present data indicate that relevant cardiovascular side effects are unlikely to occur. Thus, the indication should be considered on the basis of individual risk factors.


Rational design and development of a universal baby spinach-based sensing platform for the detection of biomolecules.
Here, we designed and developed a Universal Baby Spinach-based Probe (UBSP) for biomolecule detection by introducing a DNA repressor containing a target recognition element. By employing different interaction modes between targets and repressors, we applied the UBSP to detect diverse classes of analytes, including microRNA, proteins, and heavy metal ions.


How Farm Animals React and Perceive Stressful Situations Such As Handling, Restraint, and Transport.
An animal that has been carefully acclimated to handling may willingly re-enter a restrainer. Another animal may have an intense agitated behavioral reaction or refuse to re-enter the handling facility. Physiological measures of stress such as cortisol may be very low in the animal that re-enters willingly and higher in animals that actively resist restraint. Carefully acclimating young animals to handling and restraint can help improve both productivity and welfare by reducing fear stress. Some of the topics covered in this review are: How an animal perceives handling and restraint, the detrimental effects of a sudden novel event, descriptions of temperament and aversion tests and the importance of good stockmanship.


Australian medical students' and junior doctors' perceptions of gender discrepancies in obstetrics and gynaecology.
There is currently a gender imbalance 85:15 female/male in the intake into specialist training for the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). To determine the views and perceptions of Australian medical students, and junior doctors in the first five years of practice, toward obstetrics and gynaecology (O&G) as a career, including whether there are any perceived barriers to the pursuit of such a career. A semi-structured questionnaire was developed with members of the RANZCOG Gender Equity and Diversity Working Group There were two separate studies: the first involved telephone interviews of medical students across three campuses of a medical school in North Queensland. The second study surveyed junior doctors in Queensland who are members of the Australian Medical Association. Responses were analysed and compared using quantitative and qualitative methods. Both studies found that experiences with O&G as a medical student influenced the decision to pursue O&G as a career. Exclusion from clinical scenarios and difficulty establishing good relationship with midwives within busy birthing suites were some reasons deterring male students from O&G. In addition, students felt poorly informed about the specialty in their preclinical years, affecting their early decisions in choice of specialty. Post-rotation, more female than male students reported positive experiences and were considering O&G as a career. Both groups see medical student experience as critical in attitudes toward the specialty as a possible career. This experience plays a significant role in encouraging female students toward a career in O&G and discouraging male students. More exposure to the specialty in the preclinical years, and attention to improving clinical rotations for all students, is required.


Botulinum ADP-ribosyltransferase activity as affected by detergents and phospholipids.
GTP-binding proteins with Mr values of 22,000 and 25,000 in bovine brain cytosol were ADP-ribosylated by an exoenzyme (termed C3) purified from Clostridium botulinum type C. The rate of C3-catalyzed ADP-ribosylation of the partially purified substrates was extremely low by itself, but was increased enormously when a protein factor(s) obtained from the cytosol was simultaneously added. The rate of the C3-catalyzed reaction was also stimulated by the addition of certain types of detergents or phospholipids even in the absence of the protein factors. The ADP-ribosylation appeared to be enhanced to an extent more than the additive effect of either the protein factors or the detergents (and phospholipids). Thus, ADP-ribosylation catalyzed by botulinum C3 enzyme was affected not only by cytoplasmic protein factors but also by detergents or phospholipids in manners different from each other.


The induction of differentiation in teratocarcinoma stem cells by retinoic acid.
Embryonal carcinoma cells, the stem cells of teratocarcinomas, usually undergo extensive differentiation in vivo and in vitro to a wide variety of cell types. There exist, however, several embryonal carcinoma cell lines that have almost completely lost the capacity to differentiate, so that the cells are propagated primarily as the stem cells. Using one such cell line, F9, we have found that retinoic acid at concentrations as low as 10(-9) M induces multiple phenotypic changes in the cultures in vitro. These changes include morphological alteration at the resolution of the light microscope, elevated levels of plasminogen activator production, sensitivity to cyclic AMP compounds and increased synthesis of collagen-like proteins. The nature of these changes, as well as their independence of the continued presence of retinoic acid, are consistent with the proposition that retinoic acid induces differentiation of embryonal carcinoma cells into endoderm.


Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2.
Phaeochromocytomas in patients with multiple endocrine neoplasia type 2 (MEN 2) produce adrenaline, whereas those with von Hippel-Lindau (VHL) syndrome do not. This study assessed whether these distinctions relate to differences in expression of the transporters responsible for uptake and storage of catecholamines - the noradrenaline transporter and the vesicular monoamine transporters (VMAT 1 and VMAT 2). Tumour tissue and plasma samples were obtained from 31 patients with hereditary phaeochromocytoma - 18 with VHL syndrome and 13 with MEN 2. We used quantitative PCR, Western blotting, electron microscopy, immunohistochemistry and measurements of plasma and tumour catecholamines to assess differences in expression of the transporters in noradrenaline-producing vs adrenaline-producing hereditary tumours. These differences were compared with those in a further group of 26 patients with non-syndromic phaeochromocytoma. Adrenaline-producing phaeochromocytomas in MEN 2 patients expressed more noradrenaline transporter mRNA and protein than noradrenaline-producing tumours in VHL patients. In contrast, there was greater expression of VMAT 1 in VHL than MEN 2 tumours, while expression of VMAT 2 did not differ significantly. These differences were associated with larger numbers of storage vesicles and higher tissue contents of catecholamines in MEN 2 than in VHL tumours. Differences in expression of the noradrenaline transporter were weaker, and those of VMAT 1 and VMAT 2 stronger, in noradrenaline and adrenaline-producing non-syndromic than in hereditary tumours. The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines.


Draft Genome Sequence of the Multidrug-Resistant Strain Stenotrophomonas maltophilia N0320, Isolated from a Commercial Nanoparticle Product.
Stenotrophomonas maltophilia is an emerging opportunistic pathogen that is frequently associated with hospital infections. We report the 4.8-Mbp draft genome sequence of the oxidase-positive S. maltophilia strain N0320, an isolate from a commercial hydroxyapatite nanoparticle product.


Revalorization of sunflower stalks as novel sources of cellulose nanofibrils and nanocrystals and their effect on wheat gluten bionanocomposite properties.
Novel gluten based bionanocomposites reinforced with cellulose nanofibrils (CNF) and cellulose nanocrystals (CNC) extracted from sunflower stalks by respectively a steam explosion treatment and a hydrolysis procedure, were prepared by casting/evaporation. The extracted cellulose nanomaterials, both CNC and CNF, were embedded in gluten matrix and their effect was investigated. Morphological investigations highlighted that gluten based bionanocomposites showed a homogenous morphology, the absence of visible cellulose nanoreinforcements, and the presence of holes for Gluten_CNF nanocomposites. Gluten_CNF showed a reduction of water vapour permeability coefficients but the values are higher respect to gluten reinforced with CNC. This behaviour could be related to the ability of CNC to increase the tortuous path of gas molecules. Moreover, the results from thermal, mechanical and barrier properties confirmed the strong interactions obtained between CNC and gluten matrix during the process. The study suggested the possibility to re-valorise agricultural wastes with potential applications as reinforcement in polymer matrix bionanocomposites.


Effect of glycerol and dihydroxyacetone on hepatic lipogenesis.
Glycerol is a dietary component which is metabolized primarily by the liver and kidney where it is used mainly for glucose synthesis. The metabolism of glycerol is very similar to that of dihydroxyacetone which can be considered its more oxidized counterpart. The effects of these substrates on hepatic lipogenesis and gluconeogenesis were examined. In isolated hepatocytes, 10 mM dihydroxyacetone caused a large increase in glucose output and stimulated lipogenesis without affecting the lactate/pyruvate ratio or the total ATP content of the cells. (As compared to dihydroxyacetone, 10 mM glycerol was less effective as a gluconeogenic substrate, increased the lactate/pyruvate ratio, caused a slight decrease in the total ATP content, and inhibited lipogenesis by at least 40% depending on the type of diet fed to the rats.) The fall in ATP levels was very small and did not correlate with the changes in fatty acid synthesis. The immediate cause of the inhibition of lipogenesis, brought about by glycerol in hepatocytes from sucrose fed rats, seemed to be a large decrease in pyruvate levels. This did not result from impairment of glycolysis but from a rise in the cytosolic NADH/NAD ratio.


Characteristic magnetic resonance features of focal autoimmune pancreatitis useful for differentiation from pancreatic cancer.
To identify characteristic magnetic resonance (MR) features of focal autoimmune pancreatitis (f-AIP) useful for differentiation from pancreatic cancer (PC). We retrospectively analyzed MR imaging findings of 20 f-AIP lesions and 40 PC lesions smaller than 40 mm in diameter. On fat-suppressed T2-weighted images and dynamic contrast-enhanced fat-suppressed T1-weighted images (DCE-T1WI), we classified MR features of internal signal intensity for each lesion into homogeneous, speckled, or target type. We assessed the sensitivity, specificity, and accuracy of these findings in the diagnosis of f-AIP. We also investigated the incidence of previously reported findings for differentiation between f-AIP and PC. Speckled enhancement within a hypointense or isointense lesion on pancreatic phase DCE-T1WI (speckled type) was observed more frequently in f-AIP than in PC, with high sensitivity, high specificity, and high accuracy. Hypointensity to hyperintensity surrounding a less enhanced focal area on DCE-T1WIs (target type) and upper stream main pancreatic duct dilatation were observed more frequently in PC than in f-AIP. Speckled enhancement inside an f-AIP lesion on pancreatic phase DCE-T1WI was useful for differentiation from PC.


Atomic force microscopy for protein nanotechnology.
This chapter introduces atomic force microscopy (AFM) as an important tool for protein nanotechnology. A short review of AFM-based imaging, mapping, and spectroscopy of protein samples is given. AFM imaging of β-lactoglobulin nanofibrils in air is demonstrated. Basic concepts of AFM are described. Protocols for β-lactoglobulin nanofibrils and multiwall carbon nanotubes (MWCNT) samples preparation are defined. The operation of the microscope is described using MWCNT and the NanoScope E instrument in contact mode as an example. Nanostructure manipulation based on AFM nano-sweeping is demonstrated.


29Si NMR Chemical Shifts in Crystalline and Amorphous Silicon Nitrides.
We investigate 29Si nuclear magnetic resonance (NMR) chemical shifts, δiso, of silicon nitride. Our goal is to relate the local structure to the NMR signal and, thus, provide the means to extract more information from the experimental 29Si NMR spectra in this family of compounds. We apply structural modeling and the gauge-included projector augmented wave (GIPAW) method within density functional theory (DFT) calculations. Our models comprise known and hypothetical crystalline Si₃N₄, as well as amorphous Si₃N₄ structures. We find good agreement with available experimental 29Si NMR data for tetrahedral Si[4] and octahedral Si[6] in crystalline Si₃N₄, predict the chemical shift of a trigonal-bipyramidal Si[5] to be about -120 ppm, and quantify the impact of Si-N bond lengths on 29Si δiso. We show through computations that experimental 29Si NMR data indicates that silicon dicarbodiimide, Si(NCN)₂ exhibits bent Si-N-C units with angles of about 143° in its structure. A detailed investigation of amorphous silicon nitride shows that an observed peak asymmetry relates to the proximity of a fifth N neighbor in non-bonding distance between 2.5 and 2.8 Å to Si. We reveal the impact of both Si-N(H)-Si bond angle and Si-N bond length on 29Si δiso in hydrogenated silicon nitride structure, silicon diimide Si(NH)₂.


Quality of life of mothers at the sixth week and sixth month post partum and type of infant feeding.
there is little scientific evidence on the relationship between maternal quality of life and type of infant feeding. The purpose of this study was to determine if there were differences in mother's quality of life by type of infant feeding. longitudinal prospective study with 364 women who gave birth at a public hospital at Madrid, Spain, between February and October 2013. To be included, the participants had to be a healthy primigravida aged 18-45 years who gave birth to a healthy newborn with a gestational age between 36 and 42 completed weeks, regardless of birth type. The hospital interviews were performed between 36 and 48 hours post partum in women who had case of vaginal/instrumental births and 60-72 hours post partum for women who had a caesarean birth. Telephone interviews were conducted at the sixth week and sixth month post partum, and included the SF-36 to measure quality of life. SF-36 scores were compared between breast feeding and artificial milk feeding. We also analysed the longitudinal change in SF-36 scores in both groups. at the sixth week post partum, regardless of the infant feeding modality, an increased mental health score was recorded for mothers who reported that their children ate and slept well and for those who did not go to the emergency hospital service because of concern over their baby's health. No significant differences in quality of life were found between the two groups at six months post partum. Between the sixth week and sixth month post partum, quality of life improved significantly in both groups. at the sixth week post partum, the proportion of children who ate and slept well and did not have to attend in an emergency hospital service was higher in the breast feeding group. This observation was associated with greater maternal quality of life. This positive indirect relationship between breast feeding and quality of life should be considered an additional maternal health benefit in the short term.


Evoked otoacoustic emissions as cochlear Bragg reflections.
The reflection of cochlear waves is mathematically described for various assumptions about the dependence of the echo-generating mechanism on place and frequency, without requiring knowledge of the physical details of the mechanism. Any 'wave-related' reflections, caused by intrinsic features of the resonance or active-feedback mechanism, cannot explain long group delays in an approximately shift-similar basilar membrane (BM). Only 'BM related' scattering due to inhomogenities is a possible explanation then. Reflection at a fixed point of the BM could cause only narrow-band evoked otoacoustic emissions (EOAEs). Long group delays in a wider frequency band can be obtained by assuming Bragg reflection at an approximately periodic inhomogenity of BM parameters, possibly due to spatial variations of active undamping. This explains the long delays, about inversely proportional to frequency, the decreasing instantaneous frequency, the often found multi-packet or modulated structure of echoes (vanishing at higher SPL), the spectra of simultaneous and delayed EOAEs and their relation to the threshold of hearing. These phenomena do not necessarily require multiple reflection due to middle/inner-ear mismatch.


New species and records of ptyctimous mites (Acari, Oribatida) from Cuba.
An annotated checklist of identified oribatid mites from Cuba, including 16 species, 9 genera and 4 families, is provided. Three new species, Prototritia triangularibus Niedbała sp. nov. (Protoplophoridae), Hoplophthiracarus vinalesensis Niedbała sp. nov. and Protophthiracarus paratripartitus Niedbała sp. nov. (both Steganacaridae), are described from leaf litter. Three species of the subgenus Atropacarus (Hoplophorella)-A. (H.) andrei (Balogh, 1958), A. (H.) brachys Niedbała, 2004 and A. (H.) stilifer (Hammer, 1961)-are recorded in the Cuban mite fauna for the first time.


Chemical composition, antioxidant activity and in vitro antibacterial activity of Achillea wilhelmsii C. Koch essential oil on methicillin-susceptible and methicillin-resistant Staphylococcus aureus spp.
The present study investigated the chemical composition of the essential oil (EO) from aerial parts (flowering stage) of Achillea wilhelmsii C. Koch by GC-MS. In addition, the antioxidant activity of the EO as well as its antimicrobial activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MRSA) strains was tested. Antioxidant activity was measured by the ability of the EO to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals while the antimicrobial activity was assessed by the disc-diffusion method. In total, 52 compounds were recognized, accounting for 97.33 % of the EO. The main compounds in the EO were carvacrol (22.49 %), dihydrocarvone (13.23 %), linalool (12 %), 1,8-cineol (11.42 %), camphene (8.31 %), thymol (5.28 %), camphor (3.71 %), pulegone (2.82 %) α-terpineol (2.11 %), bornyl acetate (1.14 %), and farganol (1.01 %). The EC50 value of the EO was 0.01 and 0.08 mg/mL for the antioxidant and DPPH-scavenging ability, respectively. A. wilhelmsii EO affected methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA, but the impact was more effective on MSSA.


Leveraging polymer modeling to reconstruct chromatin connectivity from live images.
Chromosomal dynamics plays a central role in a number of critical biological processes, such as transcriptional regulation, genetic recombination, and DNA replication. However, visualization of chromatin is generally limited to live imaging of a few fluorescently labeled chromosomal loci or high-resolution reconstruction of multiple loci from a single time frame. To aid in mapping the underlying chromosomal structure based on parsimonious experimental measurements, we present an exact analytical expression for the evolution of the polymer configuration based on a flexible-polymer model, and we propose an algorithm that tracks the polymer configuration from live images of chromatin marked with several fluorescent marks. Our theory identifies the resolution of microscopy needed to achieve high-accuracy tracking for a given spacing of markers, establishing the statistical confidence in the assignment of genome identity to the visualized marks. We then leverage experimental data of locus-tracking measurements to demonstrate the validity of our modeling approach and to establish a basis for the design of experiments with a desired resolution. Altogether, this work provides a computational approach founded on polymer physics that vastly improves the interpretation of in vivo measurements of biopolymer dynamics.