A Novel Necroptosis-Related miRNA Signature for Predicting the Prognosis of Breast Cancer Metastasis.
Necroptosis was recently identified as a form of programmed cell death that plays an essential role in breast cancer metastasis. MicroRNAs (miRNAs) have long been recognized to affect cell death and tumor growth. In this study, we aimed to screen for necroptosis-associated miRNAs that predict breast cancer metastasis. This study used The Cancer Genome Atlas (TCGA) public database to obtain miRNA expression data and associated clinical data from breast cancer patients and then retrieved miRNA data related to necrosis and apoptosis. Next, using Cox regression model analysis (univariate or multivariate) as well as a comparison analysis (differential analysis), a prognostic multi-miRNA molecular marker was established. Finally, prognosis-related miRNAs were utilized to identify target genes, and the functions of the target genes were analyzed for enrichment to investigate the probable mechanisms of the miRNAs. Ten miRNAs were screened through differential analysis to build models: hsa-miR-148a-3p, hsa-miR-223-3p, hsa-miR-331-3p, has-miR-181a-5p, hsa-miR-181b-5p, hsa-miR-181c-5p, hsa-miR-181d-5p, hsa-miR-200a-5p, hsa-miR-141-3p, and hsa-miR-425-5p. The multivariate Cox regression model was an independent prognostic factor (univariate Cox regression results: HR = 3.2642, 95%CI = 1.5773 - 6.7554, P = 0.0014; multivariate Cox regression results: HR = 3.1578, 95%CI = 1.5083 - 6, P = 0.0023). The survival curve of the risk score also revealed that patients with a high risk score had a poor prognosis (P = 2e - 04). The receiver operating characteristic (ROC) curve showed that the model has a certain prediction ability. Batch survival analysis of the miRNAs in the model was conducted and showed that hsa-miR-331-3p (P = 0.0182) was strongly associated with prognosis. Twenty-three predicted target genes were obtained, and Gene Ontology (GO) enrichment analysis showed that these target genes were strongly enriched in transcriptional initiation and cell membrane trafficking. Our research identified a novel miRNA marker for predicting breast cancer patient prognosis and lays the groundwork for future research on necroptosis-related genes.


Longitudinal Trends in Vaccine Hesitancy in a Cohort of Mothers Surveyed in Washington State, 2013-2015.
Parents who refuse or delay vaccines because of vaccine hesitancy place children at increased risk for vaccine-preventable disease. How parental vaccine hesitancy changes as their children age is not known. In 2015, we conducted a follow-up survey of 237 mothers enrolled in a 2-arm clinic-level cluster randomized trial (n = 488) in Washington State that was completed in 2013. We surveyed mothers at their baby's birth, age 6 months, and age 24 months using a validated measure of vaccine hesitancy. Both mean hesitancy scores (mean 4.1-point reduction; 95% CI, 2.5-5.6; P = .01) and the proportion of mothers who were vaccine hesitant (9.7% at baseline vs 5.9% at 24 months; P = .01) decreased significantly from child's birth to age 24 months. Changes from baseline were similar for first-time mothers and experienced mothers. Individual item analysis suggested that the decrease may have been driven by increases in maternal confidence about the safety and efficacy of vaccines. Our results suggest that hesitancy is a dynamic measure that may peak around childbirth and may remit as experience with vaccines accumulates.


Effects of load and speed on lumbar vertebral kinematics during lifting motions.
This experimental study investigated the effects of load magnitude and movement speed on lumbar vertebral kinematics during lifting task performance. Ten participants performed sagittally symmetric lifting movements with systematically varied load using either a normal or a faster-than-normal speed. Skin-surface markers were strategically placed over the participants' spinous processes and other landmarks representing major body joints and were recorded during the movements by a motion capture system. The center of rotation (COR) locations and segmental movement profiles for lumbar vertebrae L2 to L5 were derived and analyzed. Results suggested that (a) the COR locations and vertebral angular displacement were not significantly affected by the speed or load variation; (b) a faster speed tended to shorten the time to complete the acceleration for all the lumbar vertebrae considered; and (c) the load increase incurred a tendency for the L5 to complete the primary displacement in a briefer time while enduring greater peak acceleration and velocity. The findings lead to a better understanding of the relation between lifting dynamics and spinal motion. Potential applications of this research include the development of more accurate biomechanical models and software tools for depicting spinal motions and quantifying low-back stress.


Bovine colostrum enriched with lyophilized bovine colostrum stimulates intestinal epithelium renewal of Holstein calves in the first days of life.
Consumption of a second meal of colostrum with high quality could contribute to the intestinal epithelium development, especially if there is poor supply of colostrum just after birth. The effect of a second colostrum meal was evaluated on histomorphometry of the intestinal mucosa of newborn Holstein calves fed with high- and low-quality first colostrum. Seventy-two calves were fed with a first colostrum meal with high (HFM, close to 100 mg/ml) or low (LFM, close to 30 mg/ml) IgG concentration. At 12 hr of life, three treatments of second colostrum feeding were applied to the calves either fed high or low first colostrum: calves fed with low (LOW-close to 30 mg/ml) or high (HIGH-close to 100 mg/ml) IgG concentration; and colostrum enriched with lyophilized bovine colostrum with high IgG concentration (ENRICHED-higher than 120 mg/ml), resulting in six groups. Intestinal samples were collected after 24 and 72 hr of life. In the distal jejunum and ileum, LOW showed higher villus height than ENRICHED (p < .05). In the distal jejunum, greater villus perimeter was observed in the LOW compared to ENRICHED at 24 hr (p < .05). In ileum, LFM showed higher villus perimeter compared to HFM (p < .05). LOW showed the highest villus height-to-crypt depth ratio in the medium and distal jejunum and ileum, p < .05. ENRICHED and HFM showed decreased muscle layer thickness in the proximal and distal jejunum respectively (p < .05). The results reveal that the high concentration of total solids, crude protein, IgG and IGF-I of colostrum with high quality worsened the absorptive area, but may have stimulated the activity of cell division in intestinal crypts. Considering the present results, bovine colostrum enriched with lyophilized bovine colostrum stimulates intestinal epithelium renewal of Holstein calves in the first days of life.


[Genetic characterization of rye samples with regard to leaf rust resistance].
The genetic control of leaf rust resistance has been investigated by test crosses and the test-clone method in the rye samples Malysh 72-2, Chulpan 3, Immunnaya 4, Yaroslavna 3, Lovashpatonae 2, Gotor 2, Talovskaya 12-2, Braunrostresisten 2, Orlovskaya 9-2, 3098/18, and 4001/10. It has been found that this trait is controlled by a set of nonidentical oligogenes. Dominant gene Lr6 controls leaf rust resistance in Chulpan 3 and Immunnaya 4; Lr5, in Malysh 72-2; and Lr-c, in Yaroslavna 3. Test crosses have shown that genes Lr-a and Lr-b differ from the genes determining the resistance in Gotor 2 and Braunrostresisten 2. In German samples 3098/18 and 4001/10, the resistance to the Petersburg population of the pathogen is controlled by nonallelic genes Lr-a and Lr-b. It has been found that gene Lr-b is not identical to the resistance gene of Lovashpatonae 2, and Lr-a is not identical to Lr-c. In all samples, resistance to the leaf rust population is controlled by dominant genes from the stage of seedlings till maturity. Highly efficient Lr genes are present in the samples Malysh 72-2, Chulpan 3, Immunnaya 4, Yaroslavna 3, Lovashpatonae 2, Gotor 2, Talovskaya 12-2, 3098/18, and 4001/10. In addition to the oligogenes, most samples possess genes efficiently controlling particular clones of the pathogen.


The role of LigaSure™ and Harmonic Scalpel in the preservation of recurrent laryngeal nerve during thyroidectomy.
Transient or permanent damage to the recurrent laryngeal nerve (RLN) during thyroidectomy is of paramount importance for patient quality of life. The aim of this study is to systematically review the literature concerning the role of the most popular energy-based vessel-sealing devices (LigaSure™ (LS) and Harmonic Scalpel (HS)) in preservation of the RLN during thyroidectomy. The safety and inferiority or superiority of LS and HS compared with conventional haemostatic techniques are highlighted. A systematic search of the literature was performed. Clinical trials, prospective and retrospective studies that significantly compared the use of LS and HS with conventional haemostasis regarding the postoperative incidence of RLN palsy were included. The search resulted in 43 studies, including 17,953 patients treated using energy-based devices or conventional haemostatic methods. Concerning the incidence of RLN palsy, 40 studies showed no significant difference between the energy-based device and conventional groups, whereas two studies demonstrated a significant superiority in performance for LS and HS compared with conventional haemostasis. Only one study exhibited significant inferiority of LS and HS compared with conventional methods. No statistical relationship was observed between energy-based devices and conventional techniques regarding permanent damage to the RLN. The performance of both LS and HS shows no inferiority compared with conventional haemostatic techniques, regarding damage to the laryngeal nerve. Further well-designed studies are needed to investigate their potential benefit in preservation of the RLN.


Comparison of Cognitive Functions Between Obstructive Sleep Apnea Syndrome and Simple Snoring Patients: OSAS May Be a Modifiable Risk Factor for Cognitive Decline.
By comparing neurocognitive test results from patients with obstructive sleep apnea syndrome (OSAS) and those from patients with simple snoring, we aimed to establish whether OSAS negatively influences cognition. Patients with mild-to-severe OSAS (n = 29) and nonhypoxic simple-snoring patients (n = 30) were admitted to the study. All participants in both groups were evaluated with polysomnography and neurocognitive tests, including the Stroop Test, Rey Auditory Verbal Learning Test, Judgment of Line Orientation, Trail-Making Test, and Symbol Digit Modalities Test (SDMT). Significant differences were identified between the groups for test scores on the Rey 1, SDMT, and Stroop tests. We propose that accurate OSAS diagnosis and treatment might help to prevent cognitive decline.


Identification and characterization of functional residues in a Na+/H+ antiporter (NhaA) from Escherichia coli by random mutagenesis.
Forty-one mutants were isolated by means of random PCR mutagenesis of the Escherichia coli Na+/H+ antiporter (nhaA), which could not support the growth of a nhaAnhaB mutant (HIT delta AB-) on plates containing 0.15 M LiCl (pH 7.5) or 0.65 M NaCl (pH 8.0). Most of the mutants were sensitive to both NaCl and LiCl, or to LiCl alone. DNA sequencing revealed that twelve of the mutants had single amino acid substitutions. All the mutations, except for H225P, were of the conserved residues of NhaA homologues and located in the putative transmembrane helices. The Na+/H+ and Li+/H+ antiporter activities of the mutant NhaA were measured with everted membrane vesicles: eight of the mutants lost both antiporter activities completely under all pH conditions examined. Although both D133A and L138P retained low Li+/H+ antiporter activity, D133A lost Na+/H+ antiporter activity, while L138P retained normal Na+/H+ antiporter activity at pH 7.0 and 8.0. Interestingly, at pH 8.5, L138P no longer showed any Li+/H+ antiporter activity. H225P retained relatively high antiporter activities, although their pH dependence was altered. These observations supported the previous indication that His-225 is part of the pH sensor [Gerchman, Y. et al. (1993) Proc. Natl. Acad. Sci. USA 90, 1212-1216]. L73R exhibited about 20% each of the activities only at pH 8.0, and showed a similar pH dependence to H225P in both Na+/H+ and Li+/H+ antiport. Therefore, in addition to His-225, Leu-73, and/or its vicinity may also contribute to the pH sensing.


Composting winery waste: sludges and grape stalks.
The composting of winery waste is an alternative to the traditional disposal of residues, and also involves a commitment to reducing the production of waste products. We studied two residues (sludge and grape stalks), mixed in two proportions (1:1 and 1:2 sludge and grape stalks (v/v)), and we also examined the effects of grinding the grape stalks. Our results showed that composting the assayed materials was possible. Best results were obtained in the compost heap in which the residues were mixed in the proportion 1:2, and where the grape stalks had been previously ground. Optimum results required a moisture around 55% and a maximum temperature around 65 degrees C and an oxygen concentration not lower than 5-10%. The resulting compost had a high agronomic value and is particularly suitable for the soils of the vineyards which have a very low organic matter content. The compost can be reintroduced into the production system, thereby closing the residual material cycle.


Leaf biochemistry of Lycopersicon esculentum Mill. at different stages of plant development as affected by mercury treatment.
The effect of mercury (Hg) on the biochemical parameters of Lycopersicon esculentum Mill leaf was studied. Application of mercuric chloride in varying concentrations (0.5, 1.0, 1.5 and 2.0 mM HgCl2 kg(-1) sand) caused significant reduction that went up to 89% and 72% chlorophyll a and chlorophyll b contents respectively (at flowering stage), 69% in carotenoid content, 64% in total soluble protein content and 91% in nitrate reductase activity (all at post-flowering stage). The amounts of nitrate and proline increased maximally (151% and 143% respectively) at the flowering stage, whereas total soluble sugar enhanced by 57% at the post-flowering stage. Changes observed in most of the parameters, were concentration dependent. Such studies seem to be able to discover suitable bioindicators of heavy metal pollution.


Serum gamma glutamyl transferase activity in horses with right or left dorsal displacements of the large colon.
The purpose of this study was to test the hypothesis that horses with right dorsal displacement of the large colon (RDDLC) have elevations in serum gamma glutamyl transferase (GGT) activity when compared with horses with left dorsal displacement of the large colon (LDDLC). Medical records from 37 horses with RDDLC and 48 horses with LDDLC were reviewed. Horses were included for study if the RDDLC or LDDLC was confirmed by exploratory laparotomy or postmortem examination and if a serum GGT measurement was obtained within 24 hours before surgery. The proportion of horses with GGT activity within or above the reference range was determined. Of 37 horses, 18 (49%; exact binomial 95% confidence interval, 32-66%) with RDDLC and, of 48 horses, 1 (2%; 95% CI, 0-11%) with LDDLC had GGT above the reference range. Horses with RDDLC had higher serum GGT than did horses with LDDLC. Of 37 horses, 36 (97%) with RDDLC were discharged with a good prognosis and none returned as a result of hepatic disease. Evaluation of surgical and postmortem examinations revealed that positioning of the colon in horses with RDDLC results in compression of the bile duct, which can cause extrahepatic bile duct obstruction and a subsequent elevation in serum GGT activity.


Commentary on: The actin bundling activity of ITPKA mainly accounts for its migration-promoting effect in lung cancer cells.
1,4,5-triphosphate 3-kinase A (ITPKA) was first described and characterized by Irvine et al. in 1986 and cloned by Takazawa et al. in 1990. It is one of the components of the Ca2+ and calmodulin signaling pathway and a substrate for cAMP-dependent kinase (PKA) and protein kinase C (PKC), and is mainly involved in the regulation of intracellular inositol polyphosphate signaling molecules. Through a series of studies, Sabine's team has found that ITPKA expression was up-regulated in a variety of cancer cells, and silencing ITPKA inhibited while overexpressing ITPKA promoted cancer cell migration in vitro and metastasis in vivo. The latest research from Sabine's team has demonstrated that in H1299 lung cancer cells, the mechanism by which ITPKA promoted migration and invasion was predominantly depending on the ability of binding to F-actin, which will induce cancer cells to form a tight flexible actin networks. Small molecule compounds targeting the IP3 kinase activity of ITPKA protein may only inhibit the migration and invasion of cancer cells caused by the enhanced ITPKA kinase activity under ATP stimulation, but not the cytoskeletal remodeling caused by the binding of ITPKA protein to F-actin and the driven migration and invasion of cancer cells. Therefore, targeted therapeutic strategy focusing on blocking the binding of ITPKA to F-actin is indispensable when designing the inhibitors targeting ITPKA protein.


Use of new T-cell-based cell lines expressing two luciferase reporters for accurately evaluating susceptibility to anti-human immunodeficiency virus type 1 drugs.
Two new T-cell-based reporter cell lines were established to measure human immunodeficiency virus type 1 (HIV-1) infectivity. One cell line naturally expresses CD4 and CXCR4, making it susceptible to X4-tropic viruses, and the other cell line, in which a CCR5 expression vector was introduced, is susceptible to both X4- and R5-tropic viruses. Reporter cells were constructed by transfecting the human T-cell line HPB-Ma, which demonstrates high susceptibility to HIV-1, with genomes expressing two different luciferase reporters, HIV-1 long terminal repeat-driven firefly luciferase and cytomegalovirus promoter-driven renilla luciferase. Upon HIV infection, the cells expressed firefly luciferase at levels that were highly correlated (r2=0.91 to 0.98) with the production of the capsid antigen p24. The cells also constitutively expressed renilla luciferase, which was used to monitor cell numbers and viability. The reliability of the cell lines for two in vitro applications, drug resistance phenotyping and drug screening, was confirmed. As HIV-1 efficiently replicated in these cells, they could be used for multiple-round replication assays as an alternative method to a single-cycle replication protocol. Coefficients of variation for drug susceptibility evaluated with the cell lines ranged from 17 to 41%. The new cell lines were beneficial for evaluating antiretroviral drug resistance. Firefly luciferase gave a wider dynamic range for evaluating virus infectivity, and the introduction of renilla luciferase improved assay reproducibility. The cell lines were also beneficial for screening new antiretroviral agents, as false inhibition caused by the cytotoxicity of test compounds was easily detected by monitoring renilla luciferase activity.


HOW TO OPTIMALLY SEQUENCE AVAILABLE THERAPY LINES IN ADVANCED PROSTATE CANCER.
Optimal sequencing of available therapy lines in patients with advanced prostate cancer often poses quite a challenge. The guidelines are sometimes equivocal and clinical trial data are not always applicable to a particular patient. There is a difference in availability of therapy options throughout the world. In decision making, a patient as a whole should be taken into consideration, not just the stage and biology of the disease, but also patient's age, performance status, comorbidities, previous therapy lines, drug's safety profile and patient's preferences. This review article will show certain therapeutic options in the treatment of advanced hormone-sensitive prostate cancer and castration resistant prostate cancer: non- metastatic and metastatic. An attempt will be made to clarify the optimal sequencing.


Ferromagnetic resonance of NiCoFe2O4 nanoparticles and microwave absorption properties of flexible NiCoFe2O4-carbon black/poly(vinyl alcohol) composites.
The effect of cationic disorder and particle morphology on the ferromagnetic resonance (FMR) of NiCoFe2O4 nanoparticles (NPs) and the electromagnetic shielding effectiveness of flexible composites (wherein the nanoparticles are used as fillers) has been presented. Upon annealing at 1000 °C, spherical, ∼25 nm, single crystalline (as-prepared) NPs are transformed into octahedral, ∼200 nm, polycrystalline (annealed) NPs and change the cationic distribution significantly. The effect of shape, size and cationic distribution on the resonance properties has been discussed using the randomly-oriented anisotropic-axis model. The temperature dependent evolution of FMR spectra has been found to be consistent with a Bloch spin-relaxation model. Analysis of the FMR spectra reveals that NiCoFe2O4 nanoparticles have a large internal magnetic field along with broad FMR linewidths of ∼2-3 kOe, signifying high magnetic losses that are essential for the absorption of electromagnetic (EM) waves. Next, NiCoFe2O4-carbon black (NCF-CB) hybrids grafted in a PVA matrix, as flexible composite films with a thickness of ∼1.5 mm, are assessed for EM wave absorption properties in the range of 8-18 GHz. As compared to annealed-NCF-CB/PVA (21 dB, ∼99.5%), the as-prepared-NCF-CB/PVA composite film exhibits significantly large SE of 27 dB (∼99.9% attenuation of the EM wave), with a dominant contribution from absorption (SEA ∼ 21 dB). The electrical conductivity, the electric modulus, and Cole-Cole plots reveal that the dielectric losses in the as-prepared-NCF-CB/PVA have significant contributions from cationic disorder and particle size, as compared to the annealed-NCF-CB/PVA composites. Cationic disorder increases the d-d electron transition probability between adjacent ionic pairs such as Co2+/Fe3+ and a reduced particle size creates large interfacial polarization in the as-prepared NCF/CB hybrids. Considerably large values of the Landes g-factor, magnetic anisotropy and better impedance matching indicate a dominant magnetic loss contribution in ap-NCF (g = 4.5) as compared to an-NCF (g = 2.5) at 300 K.


Alcoholism risk reduction in France: a modernised approach related to alcohol misuse disorders.
During many years in France, risk reduction strategies for substance abuse concerned prevention strategies in the general population or interventions near users of illicit substances. In this spirit, the reduction of consumption only concerned opiate addicts. With regard to alcohol, the prevention messages relative to controlled consumption were difficult to transmit because of the importance of this product in the culture of the country. In addition, methods of treatment of alcoholism rested on the dogma of abstinence. Several factors have recently led to an evolution in the treatment of alcohol use disorders integrating the reduction of consumption in strategies. Strategies for reducing consumption should aim for consumption below recommended thresholds (two drinks per day for women, three for the men) or, at least, in that direction. It must also be supported by pharmacotherapy and psychotherapy, which offer possibilities. Failure to manage reduction will allow the goals to be revisited and to reconsider abstinence. Finally this evolution or revolution is a new paradigm carried in particular by a pragmatic approach of the disease and new treatments. The aims of this article are to give elements of comprehension relating to the evolution of the practices in France in prevention and treatment of alcohol use disorders and in particular with regard to the reduction of consumption.


Presbyopia and ocular motor balance.
Presbyopic case analysis generally involves determining the need for base-in prism. Common methods for prescribing prism, and components of convergence and the paradoxical lack of symptoms at near in presbyopic patients, and clinical measurement of fixation disparity are discussed in this context. Prism and vision therapy are treatment choices.


Catecholamine-secreting paraganglioma. The problem of classification.
Sudden catecholamine release, associated congestive heart failure, acute injury changes on ECG, and elevation of cardiac enzyme levels were observed after biopsy of a mediastinal mass. Five months later, a normal ECG and coronary arteriogram were recorded. Initial severe avoid unexpected catecholamine release, we recommend that all paragangliomas be evaluated for catecholaime production.


Impact of Sterilization on the Colloidal Stability of Ligand-Free Gold Nanoparticles for Biomedical Applications.
Sterilization is a major prerequisite for the utilization of nanoparticle colloids in biomedicine, a process well examined for particles derived from chemical synthesis although highly underexplored for electrostatically stabilized ligand-free gold nanoparticles (AuNPs). Hence, in this work, we comprehensively examined and compared the physicochemical characteristics of laser-generated ligand-free colloidal AuNPs exposed to steam sterilization and sterile filtration as a function of particle size and mass concentration and obtained physicochemical insight into particle growth processes. These particles exhibit long-term colloidal stability (up to 3 months) derived from electrostatic stabilization without using any ligands or surfactants. We show that particle growth attributed to cluster-based ripening occurs in smaller AuNPs (∼5 nm) following autoclaving, while larger particles (∼10 and ∼30 nm) remain stable. Sterile filtration, as an alternative effective sterilizing approach, has no substantial impact on the colloidal stability of AuNPs, regardless of particle size, although a mass loss of 5-10% is observed. Finally, we evaluated the impact of the sterilization procedures on potential particle functionality in proton therapy, using the formation of reactive oxygen species (ROS) as a readout. In particular, 5 nm AuNPs exhibit a significant loss in activity upon autoclaving, probably dedicated to specific surface area reduction and surface restructuring during particle growth. The filtered analog enhanced the ROS release by up to a factor of ∼2.0, at 30 ppm gold concentration. Our findings highlight the need for carefully adapting the sterilization procedure of ligand-free NPs to the desired biomedical application with special emphasis on particle size and concentration.


Mini-invasive anterior approach in total hip arthroplasty: short-term follow-up.
To evaluate short-term follow-up of patients treated with total hip arthroplasty through minimally invasive anterior approach. Twenty-four patients, surgically treated with this approach from January 2010 to December 2010. We measured the blood loss, the number of transfusions, the time of surgery, the length of hospital stay and intra and postoperative complications. All patients were clinically evaluated by Womac and Harris Hip Score 12 months after surgery. Radiographic views were performed postoperatively and at 1, 3 and 12 months after surgery in order to evaluate component positioning. The mean value of total blood loss was 1050 ml, the number of transfusions after surgery was on average 0.85. The mean time of surgery was 111 minutes. The mean hospital stay was 6.5 days. The radiographic views showed a correct component placement. We didn't encounter any complication and the mean score of Womac and Harris Hip Score was satisfactory in all cases. Minimally invasive anterior approach provides good short-term results. However, long-term studies are needed to confirm this evaluation.


Use of artificial intelligence in discerning the need for prostate biopsy and readiness for clinical practice: a systematic review protocol.
Variability and inaccuracies in the diagnosis of prostate cancer, and the risk of complications from invasive tests, have been extensively reported in the research literature. To address this, the use of artificial intelligence (AI) has been attracting increased interest in recent years to improve the diagnostic accuracy and objectivity. Although AI literature has reported promising results, further research is needed on the identification of evidence gaps that limit the potential adoption in prostate cancer screening practice. A systematic electronic search strategy will be used to identify peer-reviewed articles published from inception to the date of searches and indexed in CINAHL, IEEE Xplore, MEDLINE, Scopus, and Web of Science Core Collection databases. Registries including Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) will be searched for unpublished studies, and experts were invited to provide suitable references. The research and reporting will be based on Cochrane recommendations and PRISMA guidelines, respectively. The screening and quality assessment of the articles will be conducted by two of the authors independently, and conflicts will be resolved by a third author. This systematic review will summarise the use of AI techniques to predict the need for prostate biopsy based on clinical and demographic indicators, including its diagnostic accuracy and readiness for adoption in clinical practice. PROSPERO CRD42022336540.


Targeting PCNA with Peptide Mimetics for Therapeutic Purposes.
Proliferating cell nuclear antigen (PCNA) is an excellent inhibition target to shut down highly proliferative cells and thereby develop a broad-spectrum cancer therapeutic. It interacts with a wide variety of proteins through a conserved motif referred to as the PCNA-interacting protein (PIP) box. There is large sequence diversity between high-affinity PCNA binding partners, but with conservation of the binding structure-a well-defined 310 -helix. Herein, all current PIP-box peptides crystallised with human PCNA are collated to reveal common trends between binding structure and affinity. Key intra- and intermolecular hydrogen-bonding networks that stabilise the 310 -helix of PIP-box partners are highlighted and related back to the canonical PIP-box motif. High correlation with the canonical PIP-box sequence does not directly afford high affinity. Instead, we summarise key interactions that stabilise the binding structure that leads to enhanced PCNA binding affinity. These interactions also implicate the "non-conserved" residues within the PIP-box that have previously been overlooked. Such insights will allow a more directed approach to develop therapeutic PCNA inhibitors.


Clear and present danger: in childhood meningitis. The importance of Hib immunisation in infancy and high-risk groups.
The incidence of Haemophilus influenzae type b (Hib) invasive disease has declined significantly in the United Kingdom since the introduction of routine Hib immunisation. However life-threatening Hib infections such as meningitis and epiglottitis may still occur, especially in the unimmunised and immigrant children. A case of Hib meningitis is a reminder that the threat of invasive Hib disease has not been totally eliminated. Early diagnosis and treatment of bacterial meningitis (including Hib meningitis) is essential to prevent death and serious neurological sequelae. Health visitors play a vital role in encouraging parents to have their children immunised without any avoidable delays and in providing reliable information as necessary to back up this advice. Enquiring about immunisation status of all children new to a practice and addressing any omissions, should be routine; immigrant children (and their parents) may be particularly vulnerable and more likely to be inadequately immunised.


To offer or request? Disclosing variants of uncertain significance in prenatal testing.
The use of genomic testing in pregnancy is increasing, giving rise to questions over how the information that is generated should be offered and returned in clinical practice. While these tests provide important information for prenatal decision-making, they can also generate information of uncertain significance. This paper critically examines three models for approaching the disclosure of variants of uncertain significance (VUS), which can arise from forms of genomic testing such as prenatal chromosomal microarray analysis (CMA). Contrary to prevailing arguments, we argue that respect for reproductive autonomy does not justify adopting a model on which an offer to disclose VUS is a routine part of genetic counselling. Instead, we contend that a commitment both to solidarity between healthcare providers and pregnant women and to the acceptance of a novel principle of caution under normative uncertainty means that we should instead adopt a model of VUS disclosure that imposes a strong presumption against offering to disclose VUS. The upshot of this is that it should be standard practice to only offer to disclose VUS when this is requested by the woman undergoing CMA. We defend our position against claims that arise from an alleged right to such information and that a presumption against an offer will lead to inequity.


A Predictable Approach for Osteotomy in Rhinoplasty: A New Concept of Open External Osteotomy.
Nasal osteotomies are a cornerstone step for closing an open roof deformity after dorsal hump surgery. Notwithstanding, the optimal method of nasal osteotomy remains controversial, as evidenced by the variety of approaches with no consensus between authors. Moreover, the election of the technique responds to surgeon's preference. We proposed a new way to perform both medial and lateral osteotomies under direct vision. Direct vision of nasal osteotomies provides more predictable control and precision than blind procedures, making this procedure more reliable and easier for both novel and experienced surgeons. Other advantages include conservation of nasal muscle, angular vasculature, and periosteum, which allow less postoperative ecchymosis and edema and less risk of synechia and lacrimal sac injury.


Rat tyrosine hydroxylase promoter directs tetracycline-inducible foreign gene expression in dopaminergic cell types.
A prerequisite for creating animal models in which gene expression is spatially and temporally controlled is the development of promoters to target genetic switches to specific populations of cells. Here we used the dopaminergic biosynthetic enzyme, tyrosine hydroxylase (TH) to test various combinations of tetracycline (Tet) system elements to determine the optimal configuration for inducible, tissue-specific expression. The present study shows that the degree of expression and level of leakiness associated with the Tet transactivators rtTA, rtTA2S-M2, tTS/rtTA or tTS/rtTA2S-M2 was dependent upon both the promoter and cell type utilized. Specifically, CMV-driven tTS/rtTA2S-M2 exhibited the highest level of inducibility in HEK cells (approximately 1000-fold) versus the dopaminergic cell line, MN9D (approximately 70-fold). In contrast, TH-driven rtTA2S-M2 yielded the highest level of expression with the least background in dopaminergic cell types versus HEK cells. Moreover, the TH promoter could be combined with the bi-directional Tet response system, BiTetO, allowing for the co-expression and regulation of two genes in the same cell. To further test the feasibility of this system we replaced the reporter gene with human Bcl-2. Consistent with previous studies, induction of Bcl-2 expression in dopaminergic cell types attenuated cell death due to the neurotoxin, MPP+. Taken together, these data suggest that targeted, inducible gene expression can be achieved in dopaminergic cell types.


HPLC isolation and mass spectrometric characterization of two isomers of thymine glycols in oligodeoxynucleotides.
Thymine glycol, or 5,6-dihydroxy-5,6-dihydrothymine, is the major oxidation product of thymine. Herein we report the isolation of both the (5S, 6R) and (5R, 6S) isomers of cis thymine glycols from several synthetic oligodeoxynucleotides (ODNs) upon oxidation with osmium tetraoxide. Our results show that tandem mass spectrometry can determine the sites of thymine glycol in ODNs by producing characteristic fragment ions, [a - 143] and its complementary w ions at the modification site. We further demonstrate that the [M + H]+ and [M + Na]+ ions of the two cis stereoisomers of thymine glycol in the dinucleotides, which are extricated from the ODNs by nuclease P1, gave distinctive product-ion spectra.


[The biological specificity and superiority of human milk. Scientific basis, guarantees and safety controls].
Scientific knowledge has demonstrated that breastfeeding is the ideal method of feeding and nurturing infants and has recognised breastfeeding as primary in achieving optimal infant health, growth and development. Human milk is species-specific and offers a superior method of feeding. All other options differ markedly from it. Milk formulas are designed to mimic human milk as much as possible, but important compositional differences between human milk and formulas remain, and it is unlikely that this situation will change very soon, if ever. Thus, the breastfed infant remains the reference model against which all alternative feeding methods are measured, with regard to health, growth and development. Human milk has a dynamic nature and varies with time postpartum, but the variations of its composition with time of lactation match the changing needs of the growing infant. The role of the pediatrician is essential in promoting, protecting and supporting breastfeeding in the hospital, medical schools, individual practices and in the community. The purpose of this review is to describe and provide insight into the nutritional benefits, the contributions to host defence and the social and psychological benefits of maternal-infant bonding obtained by breastfeeding. This paper also summarises other substantial advantages obtained when infants are fed at the breast and describes the rare situations and medical reasons when human milk is not recommended, when alternative options should be considered, or when breastfeeding must be closely monitored. Early identification of those infants fed at the breast who have inadequate intakes is important, also to preserve breastfeeding.


Usefulness of chromosome 19 RFLP haplotypes in the diagnosis of myotonic dystrophy.
Three DNA probes (APOC2, PSC11, and LDR152) detecting RFLP polymorphisms were used to test the usefulness of the RFLP approach in myotonic dystrophy (MD) families from the isolated Finnish population. The informativeness of these polymorphisms did not differ from that reported in more mixed populations: in the 13 families of the study most of the 79 meiotic events studied were informative. One known recombinant is included in the study. The highest lod score obtained in the multilocus linkage analysis was z = 5.941 at recombination fraction theta = 0.02. The RFLP results significantly facilitated genetic counseling in problematic cases among the families studied. Although evidence could be found for linkage disequilibrium of the RFLP haplotypes formed in Finnish MD patients, our results do not exclude the possible existence of more than one ancient MD mutation in this population.


Mechanism Underlying the Effectiveness of Deferiprone in Alleviating Parkinson's Disease Symptoms.
Elevation in iron content as well as severe depletion of dopamine (DA) as a result of iron-induced loss of dopaminergic neurons has been recognized to accompany the progression of Parkinson's disease (PD). To better understand the mechanism of the mitigating effect of the iron chelator deferiprone (DFP) on PD, the interplay between iron and DFP was investigated both in the absence and presence of DA. The results show that DFP was extremely efficient in scavenging both aqueous iron and iron that was loosely bound to DA with the entrapment of iron in Fe-DFP complexed form critical to halting the iron catalyzed degradation of DA and associated generation of toxic metabolites. The DFP related scavenging of dopamine semiquinone (DA•-) and superoxide (O2•-) may also contribute to its positive effects in the treatment of PD.


The -308 promoter polymorphism in the tumour necrosis factor gene in patients with lichen planus.
The close chromosomal proximity of major histocompatibility complex and tumour necrosis factor genes may suggest the involvement of the latter in the pathogenesis of immunological diseases associated with HLA antigenes. The major histocompatibility complex antigens may play a certain role in the pathogenesis of lichen planus. Therefore we examined the -308 promoter polymorphism of tumour necrosis factor gene in patients with lichen planus. Sixty-six patients and 66 age- and sex-matched controls participated in the study. Genomic DNA from patients and controls was typed for tumour necrosis factor (-308) polymorphism using an allele-specific polymerase chain reaction. We did not find any correlation between genotype distribution, allele frequency and lichen planus. In our study we failed to observe any association between a genotype and mean level of tumour necrosis factor in plasma of our patients.


Superconducting aluminum heat switch with 3 nΩ equivalent resistance.
Superconducting heat switches with extremely low normal state resistances are needed for constructing continuous nuclear demagnetization refrigerators with high cooling power. Aluminum is a suitable superconductor for the heat switch because of its high Debye temperature and its commercial availability in high purity. We have constructed a high quality Al heat switch whose design is significantly different than that of previous heat switches. In order to join the Al to Cu with low contact resistance, we plasma etched the Al to remove its oxide layer and then immediately deposited Au without breaking the vacuum of the e-beam evaporator. In the normal state of the heat switch, we measured a thermal conductance of 8T W/K2, which is equivalent to an electrical resistance of 3 nΩ according to the Wiedemann-Franz law. In the superconducting state, we measured a thermal conductance that is 2 × 106 times lower than that of the normal state at 50 mK.


Single-cell analysis by a scanning thermal lens microscope with a microchip: direct monitoring of cytochrome c distribution during apoptosis process.
We developed a microsystem for cell experiments consisting of a scanning thermal lens microscope detection system and a cell culture microchip. The microchip system was good for liquid control in microspace, and this results in secure cell stimulation and coincident in vivo observation of the cell responses. The system could detect nonfluorescent biological substances with extremely high sensitivity without any labeling materials and had a high spatial resolution of approximately 1 microm. This system was applied to monitoring of cytochrome c distribution in a neuroblastoma-glioma hybrid cell cultured in the microflask (1 mm x 10 mm x 0.1 mm; 1 microL) fabricated in a glass microchip. Cytochrome c release from mitochondria to cytosol during the apoptosis process was successfully monitored with this system. The cytochrome c detected with this system was estimated to be approximately 10 zmol. We concluded that the system was suitable for measuring the distribution of chemical substances in a single cell because the microchip is good for liquid handling in microspace and the thermal lens microscope has high sensitivity and spatial resolution.


Physical Fitness and Frailty Syndrome in Institutionalized Older Women.
Associations between frailty and physical-functional fitness (PFF) indicators in frail women over 65 years of age remain largely unexplored. This study analyzed the relationship between frailty syndrome (FS) and PFF indicators and assessed how the latter might predict the former. Participants were 119 elderly women (81.96 ± 7.89 years) recruited from four social and healthcare centers. PFF was assessed through muscle strength tests of upper and lower limbs, endurance, agility-dynamic balance, flexibility, and body composition. The following FS indicators were assessed: weight loss, exhaustion, weakness, slowness, and low physical activity level. Significant correlations were found between FS and endurance, agility-dynamic balance, upper and lower limbs muscle strength tests. Comparitive analyses also revealed that, among FS groups, the frail subgroup performed significantly poorer on all PFF measures except body composition. Additionally, a receiving operating characteristics curve analysis revealed good diagnostic accuracy for predicting FS using the agility-dynamic balance test (Area Under Curve [AUC] = .82, 95% CI [0.74, 0.90]; sensitivity and specificity were 70.4% and 84.8% for the cutoff = 16.22 seconds). Accurately, the risk of frail condition (not pre-frail) increases about 2.12% per second spent in this test. Thus, the agility-dynamic balance test is a promising tool for screening institutionalized older people for risk of FS.


Invitation to a shared community ministry.
Health care reform presents new challenges as community clergy, health care chaplains, and parish nurses seek to provide spiritual care. This contribution describes both the advantages and barriers to a shared community ministry. Collaboration among these professionals can provide an important continuum of spiritual care. Health care chaplains can serve as a vital link between patients and their other spiritual caregivers. They should welcome community clergy as part of the healing team and offer resources such as residency programs and seminars. Parish nurses can expand the health ministry of the church and help community clergy and chaplains provide spiritual support. The skills and gifts of each can weave a shared community ministry to provide a holistic approach to the spiritual needs of congregants.


Electron affinity of (7)Li calculated with the inclusion of nuclear motion and relativistic corrections.
Explicitly correlated Gaussian functions have been used to perform very accurate variational calculations for the ground states of (7)Li and (7)Li(-). The nuclear motion has been explicitly included in the calculations (i.e., they have been done without assuming the Born-Oppenheimer (BO) approximation). An approach based on the analytical energy gradient calculated with respect to the Gaussian exponential parameters was employed. This led to a noticeable improvement of the previously determined variational upper bound to the nonrelativistic energy of Li(-). The Li energy obtained in the calculations matches those of the most accurate results obtained with Hylleraas functions. The finite-mass (non-BO) wave functions were used to calculate the alpha(2) relativistic corrections (alpha=1c). With those corrections and the alpha(3) and alpha(4) corrections taken from Pachucki and Komasa [J. Chem. Phys. 125, 204304 (2006)], the electron affinity (EA) of (7)Li was determined. It agrees very well with the most recent experimental EA.


Investigation on the Influence of Synovial Fluid and Vitreous Humour on Avulsion Wounds Healing in Rabbits.
In the present study, we investigated the efficacy of vitreous humour and synovial fluid on avulsion wound healing in a rabbit's model. The vitreous humour is a fluid that resembles gel consisting of approximately 98-99% water, little hyaluronic acid, glucose, collagen, anions, cations and ions. It is in the posterior eye chamber for the comparison with synovial fluid that consisted of hyaluronin, lubricin, proteinase, prostaglandins and collagenase. In this study, both synovial fluid and vitreous humour were collected from rabbits by aspiration of vitreous humour from the eye (postmortem) and arthrocentesis procedure was applied for collection of synovial fluid. Twelve adult rabbits were used in this study, they divided into three groups each group consisted of four animals wounded experimentally (an avulsion wound). Our results showed the influence of vitreous humour (group B) on healing of the wound is better than the synovial fluid (group C) in the clinical evaluation of shrinkage of the wound. The histo-pathologically changes also revealed that in the vitreous humour treated group (group B), the wound healing process proceeded better than other groups (control and synovial fluid groups). In conclusion, the histopathological and clinical observations demonstrated that application of vitreous humour on wound might be pivotal in improving the healing of avulsion wounds and establish a new tissue in rabbits.


The association between serum apolipoprotein B and fractional exhaled nitric oxide in bronchial asthma patients.
Asthma and lipid metabolism are associated with systemic inflammation. However, the studies about the relationship between lipid profile, fractional exhaled nitric acid (FeNO) and pulmonary function test (PFT) results are currently lacking. We enrolled asthma patients who had serum lipid profiles including apolipoprotein levels from March 1, 2019 to December 31, 2019. We classified the asthma patients into two groups according to the diagnosis method: (I) patients who were diagnosed based on clinical symptoms/signs and PFT results and (II) patients diagnosed with clinical symptoms/signs. Clinical characteristics including age, underlying diseases, smoking status, allergy test results and treatment agents were compared between the two groups. The associations between blood cholesterol levels including apolipoprotein and pulmonary functions were analyzed. Moreover, patients were divided into two groups according to the median value of apolipoprotein B (Apo B), and lung function test results were compared between the patients who had high and low Apo B levels. Among the 167 patients, 93 (55.7%) were PFT-proven asthma patients. In PFT-proven asthma patients, the levels of total cholesterol (TC) (r =0.37, P=0.03), low-density lipoprotein (LDL) (r =0.46, P=0.01) and Apo B (r =0.38, P=0.02) showed a significant correlation with FeNO, which had no statistical significance in physician-diagnosed asthma group. In multivariate regression analysis, log (FeNO) showed a significant correlation with Apo B (P<0.01) after adjustment for presence of PFT-proven asthma (P=0.01) and current smoking (P=0.01). Patients with high Apo B levels had a lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (69.8 vs. 74.9, P=0.02) and lower post-BD FEV1 (%) (77.5 vs. 85.0, P=0.04) compared with those showing low Apo B levels. The levels of Apo B and FeNO had positive correlations and high Apo B levels were associated with severe airflow obstruction and low FEV1 (%). Apo B could reflect the uncontrolled status of bronchial asthma and poor lung function.


Three-Dimensional Porous Si@SiOx/Ag/CN Anode Derived from Deposition Silicon Waste toward High-Performance Li-Ion Batteries.
The application of photovoltaic (PV) solid waste to the field of lithium-ion batteries is deemed to be an effective solution for waste disposal, which can not only solve the problem of environmental pollution but also avoid the loss of secondary resources. Herein, based on the volatile deposited waste produced by electron beam refining polysilicon, a simple and environmentally friendly method was designed to synthesize P-Si@SiOx/Ag/CN as an anode material for lithium-ion batteries. Remarkably, the presence of silver and the formation of a carbon-nitrogen network can enhance the electrical conductivity of the composite and boost the transport efficiency of lithium ions. Furthermore, the porous Si@SiOx structure is generated by silver-assisted chemical etching (Ag-ACE), and the carbon-nitrogen grid architecture is formed after lyophilization with NaCl as a template, which can jointly provide sufficient buffer space for the volume change of silicon during lithiation/delithiation. Benefitting from these advantages, the P-Si@SiOx/Ag/CN anode exhibits outstanding cycling performance with 759 mA h g-1 over 300 cycles at 0.5 A g-1. Meanwhile, the lithium-ion batteries employing the P-Si@SiOx/Ag/CN anodes present a superior rate capability of 950 mA h g-1 at 2 A g-1 and retain a high reversible specific capacity of 956 mA h g-1 at 1 A g-1 after 50 cycles. This work opens up a new economic strategy for the fabrication of high-performance silicon anodes and affords a promising avenue for the recycling of PV silicon waste.


Parthenolide, a natural inhibitor of Nuclear Factor-kappaB, inhibits lung colonization of murine osteosarcoma cells.
The transcription factor nuclear factor-kappaB (NF-kappaB) regulates the expression of several genes important for tumor metastasis and is constitutively active in the highly metastatic murine osteosarcoma cell line LM8. Parthenolide, a sesquiterpene lactone, was reported to inhibit the DNA binding of NF-kappaB. The purpose of this study is to investigate the usefulness of parthenolide as target for antimetastatic therapies. We examined the effect of parthenolide on metastasis-associated phenotypes in vitro and in murine experimental lung metastasis models by s.c. and i.v. inoculation of LM8 cells. We found that parthenolide strongly induced apoptosis and inhibited cell proliferation and the expression of vascular endothelial growth factor in vitro. In the in vivo metastasis models, parthenolide treatment suppressed lung metastasis when treatment was initiated concurrently with s.c. or i.v. inoculation of tumor cells, whereas lung metastasis was not reduced when parthenolide was given after the homing of tumor cells. The growth of s.c. tumors that developed at the inoculation site was not suppressed by parthenolide. We also found that the genetic inhibition of NF-kappaB activity by expressing mutant IkappaBalpha suppressed lung metastasis in vivo but not s.c. tumor growth. This supports our notion that the metastasis-preventing effect of parthenolide is mediated at least in part by inhibition of NF-kappaB activity. These findings suggested that NF-kappaB is a potential molecular target for designing specific prophylactic interventions against distant metastasis and that parthenolide is a hopeful candidate for an antimetastatic drug.


Determinants of the community living arrangements of older unmarried women.
Data from the nationally representative 1976 Survey of Income and Education provide the opportunity to examine the joint effects of age, marital status, personal income, and the need for functional assistance on living arrangements of older unmarried white women. A particular interest in this research is testing the hypothesis that the effects of income and functional health are interactive. This hypothesis implies that the effect of functional disability on living arrangements is contingent on level of personal income. Log-linear model analyses indicate that, although the main effects of all independent variables except marital status are significant, none of the interaction effects are significant. Odds calculated under the best-fitting model show that an unimpaired older woman has seven times the chance of living alone as one who requires frequent assistance, whereas those in the lowest income group have only a quarter of the likelihood of living alone as someone in the highest income group.


Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6-dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: relation to vascular effects.
A number of antitumor agents are known to cause selective reduction in tumor blood flow, leading in some cases to tumor necrosis and growth delay. These agents include flavone acetic acid (FAA), an antitumor agent with high experimental but no clinical antitumor activity, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a highly active analogue of FAA, endotoxin, vinblastine, and colchicine. We find here that plasma concentrations of serotonin (5-hydroxytryptamine) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) are increased following administration of these agents. Mice were injected with each at the maximum tolerated dose and, at various times later, blood samples were taken, cells and platelets removed by centrifugation, and serotonin and 5-HIAA concentrations were measured by high performance liquid chromatography. FAA and DMXAA induced six- and sevenfold increases in serotonin and 5-HIAA, respectively, with maximal levels 4 h after drug administration. 8-Methylxanthenone-4-acetic acid, an inactive analogue of DMXAA, failed to increase serotonin and caused only a small increase in 5-HIAA. Endotoxin, vinblastine, and colchicine each caused increases in serotonin and 5-HIAA between 2 and 6 h after drug administration. The mitotic poison paclitaxel, despite inducing growth delays of Colon 38 tumors, did not induce tumor necrosis and caused no increase in serotonin or 5-HIAA up to 6 h. The effect of the presence of subcutaneous Colon 38 tumors was tested and found not to affect the induction of increases in serotonin and 5-HIAA by DMXAA and colchicine. We suggest that the increases in plasma serotonin and its metabolite are a result of drug-induced vascular effects in host tissues, and that measurement of these compounds provides a potential means of monitoring drugs exerting vascular effects.


Ultrasonic method for monitoring the clotting process during whole blood coagulation.
The purpose of this work was to develop a multichannel ultrasonic measurement method for monitoring a spatially non-uniform blood clotting process. This novel method is based on simultaneous multi-channel measurements of ultrasound propagation velocities in different horizontal cross-sections of clotting blood. The most common method used for determining blood-clotting time is the capillary tube method. For this purpose ultrasonic methods based on measurements of the velocities of ultrasound waves in clotting blood are also used. Measurement results essentially depend on the propagation path of the ultrasonic wave in a blood sample. The ultrasound velocity changes as fresh blood transforms into clot plus serum. The objective of this work was to develop a measurement method that allows one to measure ultrasound velocity and its evolution in time and space in an evolving clot while avoiding the influence of serum. To achieve this objective, a novel method has been proposed that is based on ultrasound propagation velocity measurements in different horizontal cross-sections of clotting blood using a pulse-echo mode. Such a technique enables researchers to monitor the clotting process and a clot's spatial structure, which are different in different layers due to the influence of gravity. The four-channel measurement chamber utilizing this method has been designed and manufactured. For the generation and reception of ultrasonic waves of high frequency, wide band (3-20MHz at -6dB) ultrasonic transducers were developed. To verify that the multi-channel measurement system was operational, a special procedure based on monitoring of a polymerisation process in the acrylamide solution was proposed. Performance of the developed method was investigated by measuring clotting blood (sample volumes of less than 0.6ml) at the frequency of 12MHz. The results revealed that a clot structure indeed varies within a blood sample due to the influence of gravity; clotting times are different in different horizontal layers of the clot and range from 9 to 15min, defined by the standard capillary method. Clotting times are determined precisely from abrupt increases in ultrasound velocity. Uncertainty of the ultrasound velocity measurements was less than ±0.05m/s. The experiments were performed at 36.90±0.01°C. The proposed method may be exploited for monitoring polymerisation reactions in the chemistry field, as well.


Pancreatic acinar cell carcinoma extending into the common bile and main pancreatic ducts.
Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was found to have a mass lesion measuring approximately 4 cm in diameter in the pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed defect of the lower common bile duct (CBD) due to obstruction by the tumor cast. Histopathologically, the pancreatic head tumor invaded the main pancreatic duct (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous capsule and had extensive central necrosis with solid areas in the tumor periphery, and invaded with extension into the MPD in a form of tumor cast. The tumor cells resembled acinar cells in solid growths. Two resected cases of ACC with unusual tumor extension into the CBD and the MPD, respectively, are reported.


Metabolic alterations of lutein, β-carotene and chlorophyll a during germination of two soybean sprout varieties.
The metabolic changes of lutein, β-carotene and chlorophyll a during germination of the soybean (Glycine max (L.) Merr.) sprout varieties, 'Pungsannamulkong' and 'Bosug', have been studied. Seeds were germinated at 20 °C with 80% humidity in the darkness and sampled at 2 day intervals for 10 days. Partial least squares (PLS) scores plot showed that the responses of three metabolites during germination were linearly linked with each other except for day 2 in both varieties. PLS loading plots indicated that lutein content in whole sprout and cotyledon was closely associated with germination in 'Pungsannamulkong' while the chlorophyll a content in whole sprouts was highly linked with germination in 'Bosug'. Heatmap analyses revealed that lutein and β-carotene levels, but not those of chlorophyll a, accumulated in whole soybean sprouts and cotyledon. While hypocotyls did not accumulate lipophilic pigments during germination, the accumulation of lutein and β-carotene in the cotyledons was greater in 'Pungsannamulkong' than in 'Bosug' sprouts. In addition, the contents of lutein, β-carotene and chlorophyll a increased from those in the seeds. Overall, the metabolic changes of lutein, β-carotene and chlorophyll a during germination are affected not only by variety but also by organ type.


Engineering bone-forming biohybrid sheets through the integration of melt electrowritten membranes and cartilaginous microspheroids.
Bone fractures are one of the most common traumatic large-organ injuries and although many fractures can heal on their own, 2-12% of fractures are slow healing or do not heal (non-unions). Autologous grafts are currently used for treatment of non-unions but are associated with limited healthy bone tissue. Tissue engineered cell-based products have promise for an alternative treatment method. It was previously demonstrated that cartilaginous microspheroids of periosteum-derived cells could be assembled into scaffold-free constructs and heal murine critically-sized long bone defects (non-unions). However, the handleability of such scaffold-free implants can be compromised when scaling-up. In this work, cartilaginous spheroids were combined with melt electrowritten (MEW) meshes to create an engineered cell-based implant, able to induce in vivo bone formation. MEW polycaprolactone meshes were tailored to contain pores (116 ± 28 µm) of a size that captured microspheroids (180 ± 15 µm). Periosteum-derived microspheroids pre-cultured for 4 days, were seeded on MEW meshes and gene expression analysis demonstrated up-regulation of chondrogenic (SOX9, COL2) and prehypertrophic (VEGF) gene markers after 14 days, creating a biohybrid sheet. When implanted subcutaneously (4 weeks), the biohybrid sheets mineralized (23 ± 3% MV/TV) and formed bone and bone marrow. Bone formation was also observed when implanted in a murine critically-sized long bone defect, though a high variation between samples was detected. The high versatility of this biofabrication approach lies in the possibility to tailor the scaffolds to shape and dimensions corresponding to the large bone defects and the individual patient using robust bone forming building blocks. These strategies are instrumental in the development of personalized regenerative therapies with predictive clinical outcomes. STATEMENT OF SIGNIFICANCE: Successful treatments for healing of large long bone defects are still limited and 2-12% of fractures do not heal properly. We combined a novel biofabrication technique: melt electrowriting (MEW), with robust biology: bone forming cartilaginous spheroids to create biohybrid sheets able to form bone upon implantation. MEW enabled the fabrication of scaffolds with micrometer-sized fibers in defined patterns which allowed the capturing of and merging with cartilaginous spheroids which had the potency to mature into bone via the developmental process of endochondral ossification. The present study contributes to the rapidly growing field of "Biofabrication with Spheroid and Organoid Materials'' and demonstrates design considerations that are of great importance for biofabrication of functional tissues through the assembly of cellular spheroids.


Influence of patient related factors on number of mesenchymal stromal cells reached after in vitro culture expansion for clinical treatment.
Number of stromal cells injected in patients with ischaemic heart disease (IHD) may be of importance for the treatment efficacy, which in turn may be influenced by various patient-related factors. In this study, we investigate whether patient-related factors influence the number of autologous stromal cells reached after in vitro culture expansion for clinical therapy. Culture expansion data from 111 patients with IHD treated with autologous stromal cells in three clinical trials were used. We correlated the final cell count after two passages of cultivation with different patient factors. There was a significant relation between body mass index (BMI) and the number of adipose derived stromal cells (ASCs) reached after culture expansion and for all patients included into the three studies (r = 0.375, p = .019 and r = 0.200, p = .036, respectively). Moreover, there was a significantly higher number of ASCs reached in patients with hypertension compared to those without hypertension and for all patients overall (68.8 ± 39.6 × 106 vs. 39.1 ± 23.6 × 106, p = .020 and 62.0 ± 55.0 × 106 vs. 29.0 ± 19.3 × 106, p < .001, respectively). The same tendency was seen with bone marrow derived mesenchymal stromal cells (MSCs) in patients with hypertension compared to those without hypertension (58.4 ± 61.8 × 106 vs. 22.6 ± 13.3 × 106, p < .001) and in males compared to females (56.4 ± 61.5 × 106 vs. 30.9 ± 27.9 × 106, p = .041). Moreover, a significant negative correlation between left ventricular ejection fraction and number of MSCs was found (r = -0.287, p = .017). Patient related factors such as BMI, hypertension and gender may influence the number of MSCs reached after in vitro culture expansion.


Nicotinamide enhances myelin production after demyelination through reduction of astrogliosis and microgliosis.
Caloric restriction is the chronic reduction of total caloric intake without malnutrition and has attracted a lot of attention as, among multiple other effects, it attenuates demyelination and stimulates remyelination. In this study we have evaluated the effect of nicotinamide (NAM), a well-known caloric restriction mimetic, on myelin production upon demyelinating conditions. NAM is the derivative of nicotinic acid (vitamin B3) and a precursor of nicotinamide adenine dinucleotide (NAD+), a ubiquitous metabolic cofactor. Here, we use cortical slices ex vivo subjected to demyelination or cultured upon normal conditions, a lysolecithin (LPC)-induced focal demyelination mouse model as well as primary glial cultures. Our data show that NAM enhances both myelination and remyelination ex vivo, while it also induces myelin production after LPC-induced focal demyelination ex vivo and in vivo. The increased myelin production is accompanied by reduction in both astrogliosis and microgliosis in vivo. There is no direct effect of NAM on the oligodendrocyte lineage, as no differences are observed in oligodendrocyte precursor cell proliferation or differentiation or in the number of mature oligodendrocytes. On the other hand, NAM affects both microglia and astrocytes as it decreases the population of M1-activated microglia, while reducing the pro-inflammatory phenotype of astrocytes as assayed by the reduction of TNF-α. Overall, we show that the increased myelin production that follows NAM treatment in vivo is accompanied by a decrease in both astrocyte and microglia accumulation at the lesion site. Our data indicate that NAM influences astrocytes and microglia directly, in favor of the remyelination process by promoting a less inflammatory environment.


Prosthetic joint infections due to methicillin-resistant and methicillin-susceptible staphylococci treated with open debridement and retention of the prosthesis.
To compare the specific characteristics, the outcome and the predictors of failure of prosthetic joint infections (PJI) due to methicillin-resistant (MRS) and methicillin- susceptible staphylococci (MSS) treated with open debridement and retention of the implant. PJI due to MRS or MRS prospectively registered in a database from 1999 to 2009 were retrospectively reviewed. During the study period, 96 patients met the inclusion criteria of the study. The mean follow-up period was 3.9 years and at least 2 years in all patients. The failure rate was 25%. The only variable significantly associated with failure in the global cohort was polymicrobial infection (59.3% vs. 40.7%, p=0.036). Thirty-four (35.4%) patients had an infection due to MRS and 62 (63.6%) due to MSS. Among MSS infections, 95.2% corresponded to primary arthroplasties while 29.4% of PJI due to MRS were after revision arthroplasties (p=0.001). CRP was significantly higher in PJI due to MSS (5.2 mg/dl vs 9.1 mg/dL, p=0.02).The failure rate (20% vs 27%, p=0.62) was very similar in MSS and MRS groups. PJI due to MRS were mainly coagulase-negative staphylococci, more frequent after revision arthroplasties, had a lower inflammatory response, and had a similar failure rate than MSS infections.


The impact of COVID-19 on memory: Recognition for masked and unmasked faces.
Considering the current state of the worldwide pandemic, it is still common to encounter people wearing face protection masks. Although a safety measure against COVID-19, face masks might be compromising our capacity for face recognition. We conducted an online study where 140 participants observed masked and unmasked faces in a within-subjects design and then performed a recognition memory task. The best performance was found when there were no masks either at study and test phase, i.e., at the congruent unmasked condition. The worst performance was found for faces encoded with a mask but tested without it (i.e., masked-unmasked incongruent condition), which can be explained by the disruption in holistic face processing and the violation of the encoding specificity principle. Interestingly, considering the unmasked-masked incongruent condition, performance was probably affected by the violation of the encoding specificity principle but protected by holistic processing that occurred during encoding.


Trends of Serum Electrolyte Changes in Crush syndrome patients of Bam Earthquake; a Cross sectional Study.
Electrolyte imbalances are very common among crushed earthquake victims but there is not enough data regarding their trend of changes. The present study was designed to evaluate the trend of changes in sodium, calcium, and phosphorus ions among crush syndrome patients. In this retrospective cross-sectional study, using the database of Bam earthquake victims, which was developed by Iranian Society of Nephrology following Bam earthquake, Iran, 2003, the 10-day trend of sodium, calcium, and phosphorus ions changes in > 15 years old crush syndrome patients was evaluated. 118 patients with the mean age of 25.6 ± 6.9 years were studied (57.3 male). On the first day of admission, 52.5% (95% CI: 42.7 - 62.3) of the patients had hyponatremia, which reached 43.9% (95% CI: 28.5 - 59.3) on day 10. 100.0% of patients were hypocalcemic on admission and serum calcium level did not change dramatically during the 10 days of hospitalization. The prevalence of hyperphosphatemia on the first day was 90.5% (95% CI: 81.5 - 99.5) and on the 10th day of hospitalization 66.7% (95% CI: 48.5 - 84.8) of the patients were still affected. The results of the present study shows the 52.5% prevalence of hyponatremia, 100% hypocalcemia, and 90.5% hyperphosphatemia among crush syndrome patients of Bam earthquake victims on the first day of admission. Evaluation of 10-day trend shows a slow decreasing pattern of these imbalances as after 10 days, 43.9% still remain hyponatremic, 92.3% hypocalcemic, and 66.7% hypophosphatemic.


Novel domain combinations in proteins encoded by chimeric transcripts.
Chimeric RNA transcripts are generated by different mechanisms including pre-mRNA trans-splicing, chromosomal translocations and/or gene fusions. It was shown recently that at least some of chimeric transcripts can be translated into functional chimeric proteins. To gain a better understanding of the design principles underlying chimeric proteins, we have analyzed 7,424 chimeric RNAs from humans. We focused on the specific domains present in these proteins, comparing their permutations with those of known human proteins. Our method uses genomic alignments of the chimeras, identification of the gene-gene junction sites and prediction of the protein domains. We found that chimeras contain complete protein domains significantly more often than in random data sets. Specifically, we show that eight different types of domains are over-represented among all chimeras as well as in those chimeras confirmed by RNA-seq experiments. Moreover, we discovered that some chimeras potentially encode proteins with novel and unique domain combinations. Given the observed prevalence of entire protein domains in chimeras, we predict that certain putative chimeras that lack activation domains may actively compete with their parental proteins, thereby exerting dominant negative effects. More generally, the production of chimeric transcripts enables a combinatorial increase in the number of protein products available, which may disturb the function of parental genes and influence their protein-protein interaction network. our scripts are available upon request.


Selective infections of olfactory and respiratory epithelium by vesicular stomatitis and Sendai viruses.
Following intranasal instillation of vesicular stomatitis virus (VSV) in mice there was an extensive infection of the olfactory epithelium in contrast to a minimal involvement of the respiratory epithelium. Sendai virus (SV), on the other hand, caused an extensive infection of the respiratory epithelium and only minimal infection of the olfactory mucous membrane. VSV budded from basolateral surfaces of supporting cells and olfactory neurons, but not from their apical surfaces or the ciliated bulbous endings of the olfactory neuron dendrites. This asymmetric release of VSV favoured neuroinvasion. The virus spread along the olfactory nerves to the glomeruli in the olfactory bulbs after which it propagated transneuronally into the rest of the brain. SV budded only from the apical surface of respiratory epithelial cells, was released into the air passages, and there were no signs of invasion into the olfactory bulbs. Inoculation of the olfactory mucous membrane is a useful procedure for studies on selectivity of attack on peripheral neurons by viruses and on mechanisms of virus invasion of the nervous system in vivo.


Biosynthesis of heparin. Different molecular forms of O-sulfotransferases.
O-Sulfotransferases involved in heparin biosynthesis were purified > or = 10,000-fold from detergent extracts of mouse mastocytoma tissue by sequential chromatographies on DEAE-Sephacel, heparin-agarose, blue Sepharose, and 3',5'-ADP-Sepharose. The resultant preparation catalyzed the transfer of 35S from 3'-phosphoadenosyl-5'-phospho-[35S]sulfate into N,O-desulfated, re-N-sulfated heparin. Anion-exchange high performance liquid chromatography of disaccharides obtained by deaminative cleavage of the 35S-labeled polysaccharide product revealed O-35S-sulfation at C-2 of L-iduronic acid and at C-6 of D-glucosamine units. SDS-polyacrylamide gel electrophoresis of semipurified enzyme followed by extraction of gel segments and renaturation of proteins consistently showed two distinct fractions of O-sulfotransferase activity, corresponding to proteins of approximately 20 and approximately 60 kDa. The approximately 60-kDa enzyme(s) catalyzed both the 2-O- and 6-O-sulfotransferase reactions, whereas the approximately 20-kDa fraction promoted iduronosyl 2-O-sulfation only. These results are discussed in relation to previous findings, indicating that some of the enzymes involved in heparin biosynthesis catalyze more than one reaction.


Evidence for hydrogen bond formation to the PsaB chlorophyll of P700 in photosystem I mutants of Synechocystis sp. PCC 6803.
P700, the primary electron donor of photosystem I, is an asymmetric dimer made of one molecule of chlorophyll a' (P(A)) and one of chlorophyll a (P(B)) that are bound to the homologous PsaA and PsaB polypeptides. While the carbonyl groups of P(A) are involved in hydrogen-bonding interactions with several surrounding amino acid side chains and a water molecule, P(B) does not engage hydrogen bonds with the protein. Notably, the residue Thr A739 is donating a strong hydrogen bond to the 9-keto C=O group of P(A) and the homologous residue Tyr B718 is free from interaction with P(B). Light-induced FTIR difference spectroscopy of the photooxidation of P700 has been combined with a site-directed mutagenesis attempt to introduce hydrogen bonds to the carbonyl groups of P(B) in Synechocystis sp. PCC 6803. The FTIR study of the Y(B718)T mutant provides evidence that the 9-keto C=O group of P(B) and P(B)(+) engages a relatively strong hydrogen-bonding interaction with the surroundings in a significant fraction (40 +/-10%) of the reaction centers. Additional mutations on the two PsaB residues homologous to those involved in the main interactions between the PsaA polypeptide and the 10a-carbomethoxy groups of P(A) affect only marginally the vibrational frequency of the 10a-ester C=O group of P(B). The FTIR data on single, double, and triple mutants at these PsaB sites indicate a plasticity of the interactions of the carbonyl groups of P(B) with the surrounding protein. However, these mutations do not perturb the hydrogen-bonding interactions assumed by the 9-keto and 10a-ester C=O groups of P(A) and P(A)(+) with the protein and have only a limited effect on the relative charge distribution between P(A)(+) and P(B)(+).


Exercise during pregnancy: a comparative review of guidelines.
Exercise during pregnancy may be beneficial provided that there are no contraindications. The aim of this study was to summarize and compare recommendations regarding exercise in pregnancy. Thus, a comparative descriptive review was conducted and included guidelines by the American College of Obstetricians and Gynecologists, the Society of Obstetricians and Gynaecologists of Canada and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists. All compared guidelines recommend that pregnant women without contraindications should undertake physical activities regularly, however, the type of workout performed should be adjusted based on the previous exercise experience and the physical condition of each pregnant woman. A variation among the reviewed guidelines was identified on appropriate and inappropriate activities and on indications to interrupt exercise. To summarize, the adoption of an international up-to-date consensus regarding appropriate exercise during pregnancy may be beneficial in ensuring the safety of the pregnant women while promoting their physical and mental health.


Evaluation of Cognitive Behavioral Therapy on Improving Pain, Fear Avoidance, and Self-Efficacy in Patients with Chronic Low Back Pain: A Systematic Review and Meta-Analysis.
Cognitive-behavioral therapy (CBT) is commonly adopted in pain management programs for patients with chronic low back pain (CLBP). However, the benefits of CBT are still unclear. This review investigated the effectiveness of CBT on pain, disability, fear avoidance, and self-efficacy in patients with CLBP. Databases including PubMed, EMBASE, Web of Science, Cochrane Library, and PsycINFO were searched. RCTs examining the effects of CBT in adults with CLBP were included. The data about the outcome of pain, disability, fear avoidance, and self-efficacy were retained. Subgroup analysis about the effects of CBT on posttreatment was conducted according to CBT versus control groups (waiting list/usual care, active therapy) and concurrent CBT versus CBT alone. A random-effects model was used, and statistical heterogeneity was explored. 22 articles were included. The results indicated that CBT was superior to other therapies in improving disability (SMD -0.44, 95% CI -0.71 to -0.17, P < 0.05), pain (SMD -0.32, 95% CI -0.57 to -0.06, P < 0.05), fear avoidance (SMD -1.24, 95% CI -2.25 to -0.23, P < 0.05), and self-efficacy (SMD 0.27, 95% CI 0.15 to 0.40, P < 0.05) after intervention. No different effect was observed between CBT and other therapies in all the follow-up terms. Subgroup analysis suggested that CBT in conjunction with other interventions was in favor of other interventions alone to reduce pain and disability (P < 0.05). CBT is beneficial in patients with CLBP for improving pain, disability, fear avoidance, and self-efficacy in CLBP patients. Further study is recommended to investigate the long-term benefits of CBT. This meta-analysis is registered with Prospero (registration number CRD42021224837).


[Clinical observation on 80 cases with duodenal bulbar ulcer treated with kuiyangqing pill].
80 patients with duodenal bulbar ulcer were divided into two groups: one was the group of ulcer with Excess-Heat Syndrome (EHS); the other was that with Deficiency-Cold Syndrome (DCS). Both groups of patients were treated with Kuiyangqing Pill (KYQP) for observation, 32 cases treated with bismuth aluminate tablets as control. The therapeutical effect of EHS was better than that of the control. The recovery rate was 91.5%. The effective rate was 97.9% (P < 0.05). While the curative effect of DCS group was not so good as that of the control.


IAP-Mediated Protein Ubiquitination in Regulating Cell Signaling.
Over the last decade, the E3-ubiquitine ligases from IAP (Inhibitor of Apoptosis) family have emerged as potent regulators of immune response. In immune cells, they control signaling pathways driving differentiation and inflammation in response to stimulation of tumor necrosis factor receptor (TNFR) family, pattern-recognition receptors (PRRs), and some cytokine receptors. They are able to control the activity, the cellular fate, or the stability of actors of signaling pathways, acting at different levels from components of receptor-associated multiprotein complexes to signaling effectors and transcription factors, as well as cytoskeleton regulators. Much less is known about ubiquitination substrates involved in non-immune signaling pathways. This review aimed to present IAP ubiquitination substrates and the role of IAP-mediated ubiquitination in regulating signaling pathways.


TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator.
Hypoxia induces the epithelial-mesenchymal transition, EMT, to promote cancer metastasis. In addition to transcriptional regulation mediated by hypoxia-inducible factors, HIFs, other epigenetic mechanisms of gene regulation, such as histone modifications and DNA methylation, are utilized under hypoxia. However, whether DNA demethylation mediated by TET1, a DNA dioxygenase converting 5-methylcytosine, 5mC, into 5-hydroxymethylcytosine, 5hmC, plays a role in hypoxia-induced EMT is largely unknown. We show that TET1 regulates hypoxia-responsive gene expression. Hypoxia/HIF-2α regulates the expression of TET1. Knockdown of TET1 mitigates hypoxia-induced EMT. RNA sequencing and 5hmC sequencing identified the set of TET1-regulated genes. Cholesterol metabolic process genes are among the genes that showed high prevalence and statistical significance. We characterize one of the genes, INSIG1 (insulin induced gene 1), to confirm its expression and the 5hmC levels in its promoter. Knockdown of INSIG1 also mitigates hypoxia-induced EMT. Finally, TET1 is shown to be a transcriptional co-activator that interacts with HIF-1α and HIF-2α to enhance their transactivation activity independent of its enzymatic activity. TET1 acts as a co-activator to further enhance the expression of INSIG1 together with HIF-2α. We define the domain in HIF-1α that interacts with TET1 and map the domain in TET1 that confers transactivation to a 200 amino acid region that contains a CXXC domain. The TET1 catalytically inactive mutant is capable of rescuing hypoxia-induced EMT in TET1 knockdown cells. These findings demonstrate that TET1 serves as a transcription co-activator to regulate hypoxia-responsive gene expression and EMT, in addition to its role in demethylating 5mC.


Nanoparticle impregnated self-supporting protein gel for enhanced reduction in oxidative stress: A molecular dynamics insight for lactoferrin-polyphenol interaction.
In the present work, lactoferrin (Lf) based nanoparticle incorporated self-supporting gel encapsulating a flavonoid, quercetin (Q), was developed. The complex formation between Lf and Q was assessed using molecular docking and dynamics simulation that lactoferrin and quercetin showed strong interaction and binding supporting hydrophobic interaction. The microscopic, spectroscopic, and x-ray techniques were used to characterize the gel extensively. In vitro drug release was studied to understand the release pattern of quercetin from the protein gel. The viscosity of the gel and its rheological characteristics were determined using a Brookfield viscometer. Ex vivo skin permeation studies using vertical diffusion cells were carried out to understand its skin permeation properties. The gel showed strong anti-oxidant activity using the DPPH scavenging assay. The enhanced effect of the Lf-Q complex on antioxidant enzyme activity (superoxide dismutase, catalase, and malondialdehyde), was supported by molecular dynamics, surface hydrophobicity, and in vitro studies. To investigate the effect of the gel on angiogenesis, the chorioallantoic membrane assay was performed and its compatibility with erythrocytes was also assessed. Suitability for topical administration was assessed using skin irritation studies performed on Sprague Dawley rats. The overall results suggest that the developed NiPG is suitable for cutaneous localization of quercetin with enhanced antioxidant activity.


Neuromyelitis optica in the elderly.
Blindness and quadriparesis developed in an elderly woman whose symptoms began at the age of 69 years. Postmortem examination revealed extensive demyelinative lesions in the optic nerves and spinal cord. The clinical and pathologic findings were consistent with the diagnosis of neuromyelitis optica ( NMO ). This case serves to document that NMO and presumably typical multiple sclerosis can occur initially at an advanced age.


Pediatric herpes simplex masquerading as varicella-zoster.
A three-year-old girl developed a generalized cutaneous Herpes simplex infection and a dendritic corneal ulcer. The clinical appearance of the lesions led to the diagnosis of varicella by a pediatrician and of Herpes zoster corneal ulcer by an ophthalmologist, who prescribed topical adrenocorticosteroids. An enzyme-linked immunosorbent assay and cultures were positive for the Herpes simplex virus. Topical antiviral treatment was applied, and the lesions healed without significant sequelae.


Osteolytic Skull Lesions-Our Experience.
To present an overview of varied clinical presentations, investigations and treatment options for Osteolytic skull lesions. It is a prospective study. We conducted this study from January 2013 to December 2015 in the Department of Neurosurgery, Nil Ratan Sircar Medical College and Hospital, Kolkata. During this period, 14 patients presented with osteolytic skull lesions through the outpatient department. All patients were thoroughly investigated with appropriate hematological and radiological investigations and treated following admission, and surgery was performed in the Neurosurgery Department. All were followed regularly in OPD. Total 14 patients were included in the study. Amongst these 7 were male and 7 female. Age group of patients ranged from 5 to 72 years. Of 14 cases, three cases had dermoid cyst, four cases had metastasis, and one each case had epidermoid cyst, intradiploic meningioma, benign cystic lesion, tuberculosis, histiocytosis X, hemangioma, and osteomyelitis. All underwent diagnostic/therapeutic procedures and referred for Radio or chemotherapy where indicated. All scalp/skull lesions need careful clinical correlation, appropriate radiological investigations to establish diagnosis and subject them to suitable treatment.


Comparison of normal and dusty day impacts on fractional exhaled nitric oxide and lung function in healthy children in Ahvaz, Iran.
Children are the vulnerable group at risk of adverse health effects related to air pollution due to dust storm in Ahvaz. The purpose of this study was to compare the values of fractional exhaled nitric oxide (FENO) and lung functions as parameters of adverse health effects of particulate matter (PM) in dusty and normal (non-dusty) days in elementary schoolchildren. The study was conducted among elementary school students in Ahvaz. The healthy elementary schoolchildren (N = 105) were selected from different districts for FENO and lung function sampling during the dusty and normal days. The values of PM10 and PM2.5 during dusty days were higher than during normal days. Mean values of FENO during the normal and dusty days were 14.23 and 20.3 ppb, respectively, and the difference between these values was statistically significant (p < 0.05). Lung function results showed a statistically significant difference between the mean values of forced vital capacity during the dusty and normal days (p < 0.05). The results revealed a significant difference both in the values of inflammatory biomarker and in the lung function tests in dusty and normal days. Based on our results, fractional exhaled nitric oxide could be a useful short-term biomarker of particulate pollution effect coupled with spirometry.


Cross species association examination of UCN3 and CRHR2 as potential pharmacological targets for antiobesity drugs.
Obesity now constitutes a leading global public health problem. Studies have shown that insulin resistance affiliated with obesity is associated with intramyocellular lipid (IMCL) accumulation. Therefore, identification of genes associated with the phenotype would provide a clear target for pharmaceutical intervention and care for the condition. We hypothesized that urocortin 3 (UCN3) and corticotropin-releasing hormone receptor 2 (CRHR2) are associated with IMCL and subcutaneous fat depth (SFD), because the corticotropin-releasing hormone family of peptides are capable of strong anorectic and thermogenic effects. We annotated both bovine UCN3 and CRHR2 genes and identified 12 genetic mutations in the former gene and 5 genetic markers in the promoter region of the latter gene. Genotyping of these 17 markers on Wagyu times Limousin F(2) progeny revealed significant associations between promoter polymorphisms and SFD (P = 0.0203-0.0685) and between missense mutations of exon 2 and IMCL (P = 0.0055-0.0369) in the bovine UCN3 gene. The SFD associated promoter SNPs caused a gain/loss of 12 potential transcription regulatory binding sites, while the IMCL associated coding SNPs affected the secondary structure of UCN3 mRNA. However, none of five polymorphisms in CRHR2 gene clearly co-segregated with either trait in the population (P>0.6000). Because UCN3 is located on human chromosome 10p15.1 where quantitative trait loci for obesity have been reported, our cross species study provides further evidence that it could be proposed as a potential target for developing antiobesity drugs. None of the markers in CRHR2 was associated with obesity-type traits in cattle, which is consistent with findings in human. Therefore, CRHR2 does not lend itself to the development of antiobesity drugs.


Homeostatic feelings - a novel explanation of vein symptoms derived from an experimental patient study.
Background: Vein symptoms (VS) entail diffuse leg discomfort and pain coinciding with a perception of weighty or swollen legs. Their traditional classification as a form of venous disease may be inaccurate as they occur in patients with no or any venous disorder. We hypothesized that VS would emerge from a primordially standing associated perturbation in the lower limbs which is not necessarily connected with a venous disorder. Patients and methods: Patients were sorted into groups according to the CEAP classification, VS only (C0s), primary varicose veins (C2p), varicose veins plus oedema (C2p and C3), and venous dermatopathy (C4). Patients completed questionnaires before and one week after they were exposed to a test of stationary standing. Results: Patients (N = 127) in the four groups differed by sex, age and body weight. The VS experienced in the preceding week scored the same in all groups at 3.1 on a numeric rating scale (range 0-10; SD 1.6). During standing, lower leg volume increased and symptoms emerged to the same extent across patient groups and were reduced similarly by compression (volume by 1.7 %, symptoms by 41.7 %). The emergence of symptoms was neither correlated with leg volume increase per se, nor with limiting this increase by compression. Symptoms recorded at baseline correlated with the symptoms provoked by the stress test with bare legs while the symptoms reported at follow-up, when stockings were worn regularly, correlated with the stress test with compression. Conclusions: VS, in terms of neuropsychology, reflect a homeostatic disturbance experienced in the presence and absence of venous disease. Thus, VS are not distinctive for the presence of venous disease insofar as they may reflect dynamic homeostatic feelings resulting from a standing-related disequilibrium in the legs' internal environment.


Synthesis and anthelmintic activity of 3-substituted 5-methylthio-isoxazoles.
Isoxazole derivatives have been shown to possess antiparasitic activity. In the present study, 3-substituted 5-methylthio-isoxazoles were synthesized and tested for anthelmintic activity, along with some other isoxazoles which have been reported but not tested earlier. Nine compounds (2a, 2b, 2e, 2g, 2u, 3a, 3b, 3e and 3f) showed activity against both A. ceylanicum and N. dubius in vitro. Twelve compounds (2a, 2b, 2d, 2e, 2f, 2h, 2l, 2n, 2o, 2u, 3d and 3e) showed activity against N. dubius in vivo, a parasite of veterinary importance.


[The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities].
The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.