Periparturient transmission of Cryptosporidium xiaoi from ewes to lambs.
The mechanism for the maintenance of Cryptosporidium infection in sheep between yearly lambing periods is not clear. Previously, periparturient shedding of oocysts as the result of stress from lambing was suspected to be a mechanism for the initiation of Cryptosporidium infection in lambs, but this has never been verified by genotyping studies. In this study, fecal specimens from four age groups of sheep in Inner Mongolia, China were examined for Cryptosporidium spp. by PCR-restricted fragment length polymorphism and sequence analyses of the small subunit (SSU) rRNA gene, including 59 ewes 1 week before parturition, 154 ewes at parturition, 87 lambs of 3-4 weeks, and 75 lambs of 15-16 weeks. The Cryptosporidium infection rate in ewes at parturition (7.8%) was significantly higher than at 1 week before parturition (1.7%). Higher infection rates were found in lambs (18.4% and 26.7% for 3-4-week-old and 15-16-week-old lambs, respectively). Most (10/13) Cryptosporidium-positive ewes were shedding Cryptosporidium xiaoi, which was also the dominant species (15/16) in neonatal lambs of 3-4 weeks in age (15/16). The less common species in ewes, Cryptosporidium ubiquitum, was not found in lambs of 3-4 weeks but was the dominant species (14/20) in lambs of 15-16 weeks. The major zoonotic Cryptosporidium species, C. parvum (of the IIaA15G2R1 subtype), was only found in one lamb. These data support the occurrence of periparturient transmission of Cryptosporidium spp., especially C. xiaoi, from ewes to lambs.


Redo ileocolic resection in Crohn's disease - does time passed since previous surgery matter?
Surgical resection for Crohn's disease (CD) remains noncurative, therefore recurrence is a significant problem. Although numerous factors affecting surgical outcomes in redo ileocolic resection have been previously described, no study has considered the relation between the interval of time from initial ileocolic resection to the redo procedure and its effect on surgical outcomes. The aim of this study was to explore this relationship. A retrospective review of all adult patients undergoing redo ileocolic resection for CD between 2011 to 2020 was conducted. Patients were divided into two groups based on time from initial ileocolic resection. Patients operated within 10 years of their initial surgery (≤10 years) were assigned to the early group, while patients operated >10 years after initial surgery were allocated to the late group. Primary outcome was the 30-day postoperative major complication rate. Fifty-eight patients underwent redo ileocolic resection, 24 in the early group and 34 in the late group. Apart from older median age in the late group (56 vs. 46.5 years, p = 0.026), the groups were similar for patient factors, disease site and behaviour, use of immune-suppressing medication and procedural factors. Significant differences in 30-day postoperative morbidity included longer length of stay (6 vs. 5 days, p = 0.035), a higher major complication rate (23.5% vs. 4.1%, p = 0.04) and higher readmission rate (26.4% vs. 4.1%, p = 0.035) in the late group. The overall complication rate remained nonsignificant (37.5% vs. 61.8%, p = 0.1). Redo ileocolic resection, when performed >10 years from the initial ileocolic resection, may be associated with increased morbidity, specifically higher rates of major postoperative complications, a longer length of stay and more readmissions.


A randomized multicenter trial of cyclophosphamide, Novantrone and 5-fluorouracil (CNF) versus cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) in patients with metastatic breast cancer.
As of August 1984, 115 women with advanced breast cancer have been randomized to receive a combination of either cyclophosphamide, Novantrone (mitoxantrone) and 5-fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin) and 5-fluorouracil (CAF). Seventy-one percent of all patients were post-menopausal and 44% of CNF patients and 57% of CAF patients were estrogen receptor (ER) negative. Slightly over 30% of all patients had received hormonal therapy or chemotherapy in an adjuvant setting. Hematologic toxicity was similar in regard to platelet counts but slightly lower nadirs were experienced with CNF therapy than with CAF. However, there were fewer dosage decreases with CNF. Significantly less nausea and vomiting were observed with the CNF regimen compared to CAF. Moreover, alopecia was reduced appreciably in patients who received CNF. The response rate to CNF for the first 38 eligible and evaluable patients was 42%, and for 53 eligible and evaluable patients who received CAF the response rate was 45%, a non-significant difference. Median response durations were similar also, 140 days for CNF and 168 days for the CAF regimen. Time to treatment failure was similar for both regimens. CNF is an effective regimen for patients with advanced breast cancer, with less toxicity than CAF.


P53 in breast carcinomas: association between presence of mutation and immunohistochemical expression using a semiquantitative approach.
The aim of this study was to evaluate the concordance between the presence of p53 mutations in breast carcinomas expressing the protein by immunohistochemistry. A series of 60 breast carcinomas was evaluated by immunohistochemistry using monoclonal antibodies against p53 protein (DO 7 and PAb 1801). Twenty cases classified as being positive for p53 according to the current approach (if 5% or more of neoplastic cells contained reaction product in the nucleus) were used for molecular studies. These cases were re-assessed semi-quantitatively using a scoring system based on intensity and percentage of stained cells. DNA was phenol-chloroform extracted from microdissected normal and tumour cells obtained from formalin-fixed, paraffin-embedded tissue sections. Mutations in the p53 gene were analysed by SSCP (single strand conformational polymorphism) with primers covering exons 2-3 to 11. Ten out of the 20 p53-positive cases presented mutations detected by SSCP analysis. Mutations have been found in several exons ranging from exon 4 to exon 10. We observed a positive relationship between the presence of mutations and immunohistochemical evaluation of p53 protein expression using a semiquantitative scoring system. All cases with more than 2/3 stained tumour cells and strong intensity of staining exhibited p53 mutations. At variance, no p53 mutations were found in cases with less than 1/3 stained tumour cells and moderate intensity of staining. Therefore, only the identification of positivity for p53 detected by immunohistochemistry did not always reflect the detection of p53 mutations in breast cancer, however the use of a semi-quantitative approach seems to be useful as an indicator of the presence of mutation.


Lysophosphatidylcholine stabilizes small unilamellar phosphatidylcholine vesicles. Phosphorus-31 NMR evidence for the "wedge" effect.
Sonication of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-sn-glycero-3-phosphocholine (lysoPC, up to approximately 30 mol %) produces small unilamellar vesicles (SUV, 250-265 A diameter). Phosphorus-31 NMR of the POPC/lysoPC vesicles gives rise to four distinct peaks for POPC and lysoPC in the outer and in the inner bilayer leaflet which can be used to localize and quantify the phospholipids in both vesicle shells. Addition of paramagnetic ions (3 mM Pr3+) enhances outside/inside chemical shift differences and allows monitoring of membrane integrity by the absence of Pr3+ in the vesicle interior. 31P NMR shows that lysoPC in these highly curved POPC/lysoPC vesicles prefers the outer bilayer leaflet. LysoPC incorporation into POPC SUV furthermore causes a substantial and concentration-dependent decrease in spin-spin relaxations (T*2) of the outside POPC phosphorus signals from 55 ms for pure POPC vesicles (v1/2, 5.8 Hz) to 29.5 ms (v1/2, 10.8 Hz) for POPC/lysoPC vesicles containing 25 mol % lysoPC. Our findings are consistent with the idea of a cone-shaped lysoPC molecule which, for geometric reasons, is preferentially accommodated in the outer bilayer leaflet. LysoPC incorporation into POPC SUV restricts POPC headgroup motion and tightens phospholipid packing, but only in the outer bilayer shell.


Study on the regulation mechanism of cadmium adsorption system mediated by extraneous dissolved organic matter.
Adsorption of biochar on heavy metals is one of the hot spots in the application of biochar. However, the mediation of existing extraneous substances in the environment, such as dissolved organic matter (DOM), could regulate and affect the heavy metals adsorption process on biochar. In our study, we mainly focus on the regulation mechanism of modified biochar on the adsorption process of cadmium mediated by exogenous DOM. The modification significantly changed the functional groups composition on biochar, thus improving the adsorption capacity of cadmium on biochar. In the adsorption system concerned, the combination was formed between DOM and cadmium to a certain extent. The combination had a certain correlation with the influence on the adsorption capacity of cadmium onto biochar in the system.


Comparing transmembrane protein structures with ATOLL.
The 3D structure of transmembrane helices plays a key role in the function of membrane proteins. While visual inspection can usually discern the distinctive features of a helix bundle, simply translating them into a 2D diagram can be difficult. ATOLL (Aligned Transmembrane dOmains Layout fLattening) projects the helix bundle onto the lipid bilayer plane, thereby facilitating the comparison of different structures of the same membrane protein or structures of different membrane proteins. ATOLL is a program written in Python3. The source code is freely available on the web at https://github.com/LIT-CCM-lab/ATOLL. ATOLL is implemented into a web server (https://atoll.drugdesign.unistra.fr/). Supplementary data are available at Bioinformatics online.


Advances in three-dimensional bioprinted stem cell-based tissue engineering for cardiovascular regeneration.
Three-dimensional (3D) bioprinting of cellular or biological components are an emerging field to develop tissue structures that mimic the spatial, mechanochemical and temporal characteristics of cardiovascular tissues. 3D multi-cellular and multi-domain organotypic biological constructs can better recapitulate in vivo physiology and can be utilized in a variety of applications. Such applications include in vitro cellular studies, high-throughput drug screening, disease modeling, biocompatibility analysis, drug testing and regenerative medicine. A major challenge of 3D bioprinting strategies is the inability of matrix molecules to reconstitute the complexity of the extracellular matrix and the intrinsic cellular morphologies and functions. An important factor is the inclusion of a vascular network to facilitate oxygen and nutrient perfusion in scalable and patterned 3D bioprinted tissues to promote cell viability and functionality. In this review, we summarize the new generation of 3D bioprinting techniques, the kinds of bioinks and printing materials employed for 3D bioprinting, along with the current state-of-the-art in engineered cardiovascular tissue models. We also highlight the translational applications of 3D bioprinting in engineering the myocardium cardiac valves, and vascular grafts. Finally, we discuss current challenges and perspectives of designing effective 3D bioprinted constructs with native vasculature, architecture and functionality for clinical translation and cardiovascular regeneration.


Synthesis and antimycobacterial evaluation of various 7-substituted ciprofloxacin derivatives.
Tuberculosis continues to be a major cause of morbidity and mortality all over the world. Various 7-substituted ciprofloxacin derivatives were synthesized and evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis and for inhibition of the supercoiling activity of DNA gyrase from Mycobacterium smegmatis. Preliminary results indicated that most of the compounds demonstrated better in vitro antimycobacterial activity against M. tuberculosis than ciprofloxacin. Compound 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[N4-[1'-(5-methylisatinyl-beta-semicarbazo)]methyl]N1-piperazinyl]-3-quinoline carboxylic acid (3h) decreased the bacterial load in spleen tissue with 0.76-log10 protections and was considered to be moderately active in reducing bacterial count in spleen. The results demonstrated the potential and importance of developing new quinolone derivatives against mycobacterial infections.


Minimally invasive microsurgical resection of primary, intradural spinal tumours using a tubular retraction system.
This is a retrospective review of prospectively collected data. Primary, intradural spinal tumours have traditionally been microsurgically resected following macrosurgical laminectomy or laminoplasty. We hypothesize that approach-related morbidity can be reduced with less-invasive approaches; we have therefore implemented a minimally invasive approach, with the assistance of a tubular retraction system, for microsurgical resection of primary intradural spinal tumours. From January 2007 to December 2009, 54 patients underwent surgery for a spinal intradural tumour. Of these, nine patients who underwent minimally invasive posterior unilateral transmuscular surgery using a tubular retraction system were included in this study. Resection grade and surgery-related complications were retrospectively reviewed. All tumours were totally resected (verified by postoperative magnetic resonance imaging). There were no post-operative complications. Eight of the nine patients were mobilized on the day of surgery or on post-operative day 1. One patient was mobilized on post-operative day 2. Selected primary, intradural spinal tumours can be safely and successfully resected using a minimally invasive posterior unilateral transmuscular approach with the assistance of a tubular retraction system.


Increased Risk of Bacterial Infections among the Obese with Chronic Diseases.
It has been well understood that cigarette smokers have an increased risk of infections; however, the association between obesity and infections has not been well explored in general population. The analysis was based on data from the Canadian Community Health Survey - Healthy Aging (2008-2009), and included a total of 30 763 Canadians aged 45 years or older. Information on demographic data, body mass index (BMI), smoking status, chronic condition(s) and antibiotics use during the past month were collected. Logistic regression analysis was used to determine the associations of obesity and smoking with antibiotics use and adjusted for potential confounders. Overall, 6.6% used antibiotics in the previous month. Compared with those of normal weight, overweight and obese individuals were more likely to use antibiotics after adjustment for confounders, with odds ratios (ORs) of 1.28 (95% CI: 1.08, 1.50) and 1.25 (95% CI: 1.04, 1.50), respectively. When stratified by presence/absence of chronic condition(s), the associations were only significant among those with chronic condition(s) and the adjusted ORs were 1.30 (95% CI: 1.09, 1.55) for the overweight and 1.43 (95% CI: 1.18, 1.73) for the obese. Current smokers had an increased risk of antibiotics use when compared with non-smokers. The adjusted OR for smoking was similar for people with or without chronic condition(s), but was significant only for those with chronic condition(s) (OR 1.41, 95% CI: 1.16, 1.73). Overweight and obese Canadians aged 45 years or more, especially in those with chronic condition(s), had an increased risk of bacterial infections than their normal weight counterparts. The reasons for the modifying effect of chronic condition(s) on the association between body weight and infections were discussed.


It's All in the PAN: Crosstalk, Plasticity, Redundancies, Switches, and Interconnectedness Encompassed by PANoptosis Underlying the Totality of Cell Death-Associated Biological Effects.
The innate immune system provides the first line of defense against cellular perturbations. Innate immune activation elicits inflammatory programmed cell death in response to microbial infections or alterations in cellular homeostasis. Among the most well-characterized programmed cell death pathways are pyroptosis, apoptosis, and necroptosis. While these pathways have historically been defined as segregated and independent processes, mounting evidence shows significant crosstalk among them. These molecular interactions have been described as 'crosstalk', 'plasticity', 'redundancies', 'molecular switches', and more. Here, we discuss the key components of cell death pathways and note several examples of crosstalk. We then explain how the diverse descriptions of crosstalk throughout the literature can be interpreted through the lens of an integrated inflammatory cell death concept, PANoptosis. The totality of biological effects in PANoptosis cannot be individually accounted for by pyroptosis, apoptosis, or necroptosis alone. We also discuss PANoptosomes, which are multifaceted macromolecular complexes that regulate PANoptosis. We consider the evidence for PANoptosis, which has been mechanistically characterized during influenza A virus, herpes simplex virus 1, Francisella novicida, and Yersinia infections, as well as in response to altered cellular homeostasis, in inflammatory diseases, and in cancers. We further discuss the role of IRF1 as an upstream regulator of PANoptosis and conclude by reexamining historical studies which lend credence to the PANoptosis concept. Cell death has been shown to play a critical role in infections, inflammatory diseases, neurodegenerative diseases, cancers, and more; therefore, having a holistic understanding of cell death is important for identifying new therapeutic strategies.


Psychometric assessment of the Neonatal Abstinence Scoring System and the MOTHER NAS Scale.
The present study examined the psychometric characteristics of the Neonatal Abstinence Scoring System (NASS; "Finnegan Scale") and the MOTHER NAS Scale (MNS). Secondary analysis of data from 131 neonates from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a randomized trial in opioid-dependent pregnant women administered buprenorphine or methadone. Both the NASS and MNS demonstrated poor psychometric properties, with internal consistency (Cronbach's αs) failing to exceed .62 at first administration, peak NAS score, and NAS treatment initiation. Findings support the need for development of a NAS measure based on sound psychometric principles. This study found that two frequently used measures of neonatal abstinence syndrome suffer inadequacies in regard to their basic measurement characteristics. (Am J Addict 2016;25:370-373).


Phosphoinositide 3-kinase contributes to diabetes-induced abnormal vascular reactivity in rat perfused mesenteric bed.
Phosphatidylinositol 3-kinase (PI3K) is a signaling enzyme that plays key roles in vascular growth, proliferation, and cellular apoptosis and is implicated in modulating vascular smooth muscle contractility. The aim of this study was to determine whether PI3K contributes to development of diabetes-induced abnormal vascular reactivity to selected vasoactive agonists. The effect of 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a selective PI3K inhibitor, on isolated perfused mesenteric vascular bed from streptozotocin (STZ)-diabetic rats was investigated. Changes in perfusion pressure, which reflected peripheral resistance, were measured using isolated perfused mesenteric vascular beds. Our results showed that STZ treatment produced an increase in the vasoconstrictor response to norepinephrine (NE), angiotensin II (Ang II) and endothelin-1 (ET-1), and an attenuated vasodilator response to carbachol and histamine in the isolated perfused mesenteric vascular bed from STZ-diabetic animals. Chronic inhibition of PI3K with LY294002 resulted in prevention of diabetes-induced abnormal vascular reactivity to the vasoactive agonists. However, the high blood glucose levels were not normalized. Results of this study indicate that selective inhibition of PI3K can attenuate the development of diabetes-induced abnormal vascular responsiveness in the isolated perfused mesenteric vascular bed.


Aggregative protein-polyelectrolyte complex for high-concentration formulation of protein drugs.
Aggregative protein-polyelectrolyte complex (PPC) has been proposed as a concentrated state of protein with a great potential for biopharmaceutical application. In this review article, we introduce a unique concentration method of protein formulation using PPC for a dozen types of pharmaceutical antibodies, hormones, and enzymes. Aggregative PPC can be obtained only by mixing poly(amino acid)s with proteins under low salt concentration conditions at an ambient temperature. The aggregative PPC is in a stabilized state against shaking, heating, and oxidation. More importantly, the aggregative PPC can be fully redissolved by the addition of physiological saline without denaturation and activity loss for many proteins. In addition, the general toxicity and pharmacokinetic profiles of the aggregative PPC are identical to those of the control antibody formulation. Thus, the protein formulation produced by aggregative PPC would be applicable for biomedical use as a kind of concentrated-state protein.


A direct method to access various functional arylalkoxysilanes by Rh-catalysed intermolecular C-H silylation of alkoxysilanes.
Efficient protocols for intermolecular C-H silylations of unactivated arenes and heteroarenes with HMe2SiOEt are disclosed. The silylations are catalysed by a Rh-complex (0.5 mol%) derived from commercially available [Rh(coe)2Cl]2 and (S,S)-Ph-BPE in the presence of cyclohexene at 100 °C, furnishing desired arylethoxydimethylsilanes up to 99% yield. The regioselectivity is mainly affected by the steric bulk of the substituents in arenes and by electronic effects as an ancillary factor. Mechanistic study revealed that the mono-hydrido dimeric Rh-complex, [Rh2(Ph-BPE)2(μ-H)(μ-Cl)], is an active catalytic intermediate, which further suppresses the formation of redistribution byproducts in the silylation. Preliminary results show that the current protocol can be extended to double C-H silylations affording bis-silylated arenes and is applicable to the silylation of HMeSi(OEt)2 to deliver the corresponding (aryl)SiMe(OEt)2.


Reference gene selection for miRNA and mRNA normalization in potato in response to potato virus Y.
This was the first report on evaluating candidate reference genes for quantifying the expression profiles of both coding (e.g., mRNA) and non-coding (e.g., miRNA) genes in potato response to potato virus Y (PVY) inoculation. The reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) method was employed to quantify the expression profiles of eight selected candidate reference genes; their expression stability was analyzed by four statistical algorithms, i.e., geNorm, BestKeeper, NormFinder and RefFinder. The most stable reference genes were sEF1a, sTUBb and seIF5 with a high stability. The least stable ones were sPP2A, sSUI1 and sGAPDH. The same reference gene allows for normalization of both miRNA and mRNA levels from a single RNA sample using cDNAs synthesized in a single RT reaction, in which a stem-loop primer was used for miRNAs and the oligo (dT) for mRNAs.


Effect of ascorbic acid on human natural killer cells.
Ascorbic acid (vitamin C) was found to inhibit human natural killer cell (NK cell) activity in a dose-dependent manner. Neither effector/target cell binding nor interferon (IFN)- or interleukin-2 (IL-2)-induced increases of NK activity were affected by vitamin C. Lymphocytes incubated for 1 h at 4 degrees C with vitamin C showed a normal NK activity, whereas lymphocytes incubated for 1 h at 37 degrees C with vitamin C exhibited low NK activity. Our findings suggest that vitamin C influences NK cells, probably by acting as a radical scavenger which inactivates killing factors of NK cells.


Differences Among Native Hawaiian, Asian, and White Patients with Progressive Supranuclear Palsy.
Most studies of progressive supranuclear palsy (PSP) have been conducted in White populations. The objective of this study was to identify whether differences exist for patients with PSP among Whites, East Asians (EAs), and Native Hawaiians/Pacific Islanders (NHPIs) in Hawaii. We conducted a single-center, retrospective study of patients meeting Movement Disorder Society probable PSP criteria (2006-2021). Data variables included age of onset and diagnosis, comorbidities, and survival rate. Variables were compared across groups using Fisher's exact test, Kruskal-Wallis rank sum test, and log-rank tests. A total of 94 (59 EAs, 9 NHPIs, 16 Whites, and 10 Others) patients were identified. Mean age ± standard deviation (in years) of symptom onset/diagnosis were both youngest in NHPIs (64.0 ± 7.2/66.3 ± 8.0) followed by Whites (70.8 ± 7.6/73.9 ± 7.8), then EAs (75.9 ± 8.2/79.2 ± 8.3) (P < 0.001). Median survival from diagnosis was significantly lower (P < 0.05) in NHPIs (2 years) compared with EAs (4 years) and Whites (6 years). There may be racial disparities for PSP, and studies are needed to identify genetic, environmental, and socioeconomic contributions. © 2023 International Parkinson and Movement Disorder Society.


Psychophysiological and Psychosocial Profile of Patients Attending Drug Addiction Centers.
Drug treatment centres provide the highest level of rehab services for patients diagnosed with drug addictions. Most inpatient drug rehab programs focus on medical detox and mental health interventions. However, how to optimize the later remains a challenge. The aim of this study was to examine the psychophysiological and psychosocial profile of patients attending drug addiction centres in comparation with the general population. A total of 105 inpatient drug rehab patients and 50 participants from the general population were compared based on standardized psychophysiological and psychosocial measures. Results of this study suggest that patients attending drug addiction centers differ from general population in several different psychophysiological and psychosocial factors. Patients reported significantly lower levels of physical activity and increased sympathetic responsiveness, and significantly higher levels in loneliness, psychologically inflexibility and neuroticism. The results of this study highlight the importance of address healthy lifestyle behaviors such as sport practice and psychological variables such as loneliness, psychological (in)flexibility and neuroticism to improve current programs aim to prevent or reduce problematic drug consumptions.


Vitamin D nuclear binding to neurons of the septal, substriatal and amygdaloid area in the Siberian hamster (Phodopus sungorus) brain.
Autoradiographic experiments were performed on brains of Siberian hamsters (Phodopus sungorus) injected with tritiated 1,25-dihydroxycholecalciferol. Nuclear labeling was prevented in the presence of excess unlabeled hormone. Strong nuclear concentration of radioactivity was observed in neurons of the nucleus basalis of Meynert, the medial septal nucleus, the nucleus of the diagonal band of Broca and the central amygdaloid group. The latter has been defined as consisting of the central nucleus of the amygdala, its extension into the sublenticular part of the substantia innominata of Reichert, and the lateral division of the bed nucleus of the stria terminalis. All these structures have been reported to be involved in memory and other cognitive processes, and to be affected by age-dependent neurodegenerative disorders such as Alzheimer's disease. Corresponding localization of 1,25-dihydroxycholecalciferol receptor sites in these select basal forebrain nuclei of the Siberian hamster may implicate vitamin D (soltriol), the steroid hormone of sunlight, in memory processing.


ROS scavenging of SOD/CAT mimics probed by EPR and reduction of lipid peroxidation in S. cerevisiae and mouse liver, under severe hydroxyl radical stress condition.
The interaction between CuII, FeIII and MnII complexes, derived from the ligands 1-[bis(pyridine-2-ylmethyl)amino]-3-chloropropan-2-ol (hpclnol) and bis(pyridine-2-ylmethyl)amine (bpma), and the free radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) and reactive oxygen species (ROS), was investigated by colorimetric and EPR (Electron Paramagnetic Resonance) techniques. A comparison between these results and those reported to [Mn(salen)Cl] or EUK-8 was also addressed. EPR studies allowed us the identification of intermediates species such as superoxide‑copper(I) and superoxide‑copper(II), a mixed-valence FeIIIFeII species and a 16-line feature attributed to MnIII-oxo-MnIV species. The biomarker malondialdehyde (MDA) was determined by TBARS assay in S. cerevisiae cells, and the determination of the IC50 indicate that the antioxidant activity shown dependence on the metal center (CuII ≈ FeIII > MnII ≈ [Mn(salen)Cl]. The lipid peroxidation attenuation was also investigated in liver homogenates obtained from Swiss mice and the IC50 values were in the nanomolar concentrations. We demonstrated here that all the complexes interact with the free radical DPPH and with ROS (H2O2, O2•- and hydroxyl radical), enhancing the cellular protection against oxidative stress generated by hydroxyl radical, employing two experimental model systems, S. cerevisiae (in vivo) and mouse liver (ex vivo).


Production of monoclonal antibodies against Legionella pneumophila serogroup 1.
Four monoclonal antibodies to Legionella pneumophila Philadelphia 1 were produced by the fusion of immunized BALB/c lymphocytes to a murine myeloma cell line. Two (Lp1-1 and Lp1-3) of the four monoclonal antibodies reacted with 14 L. pneumophila serogroup 1 strains, and the other (Lp1-2 and Lp1-4) reacted with only three out of 20 strains tested. These four monoclonal antibodies did not bind to any strains of L. pneumophila serogroup 2-7 and other Legionella species. In addition, it has been shown that these monoclonal antibodies may be useful not only for subserotyping of L. pneumophila but also for retrospective diagnosis using immunopathological methods.


Antidepressant-like effect of asiaticoside in mice.
In the present study, the potential antidepressant properties of asiaticoside were investigated in male mice in three tests -- splash test in the unpredictable chronic mild stress (CMS) model, tail suspension test (TST), forced swimming test (FST) -- with clomipramine being a positive control. In the splash test, asiaticoside (10 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly augmented the frequency of grooming behavior in stressed mice. In the tail suspension test, asiaticoside (10, 20 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly decreased immobility time. In the forced swimming test, asiaticoside (10, 20 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly decreased immobility time. These results suggest that asiaticoside may have antidepressant-like action.


Regional brain superoxide dismutase activity is altered differently by heat in warm and cool mice.
The significant regional variation in brain superoxide dismutase (SOD) activity was similar in mice from both warm and cool cohorts. Mice in the cool cohort generally had higher SOD activity, which varied significantly with body temperature in striatum and in preoptic area of the hypothalamus. Changes in SOD activity following heating were revealed only when warm and cool cohorts were analysed separately. SOD activity decreased significantly in striatum, hypothalamus, and hippocampus of the cool cohort only. The decline was to levels consistent with those of the warm cohort. Body temperature of cool mice increased more than that of warm mice following each increment of heating so resultant body temperatures became similar. The role of SOD as part of a differential defense against heat stress in warm and cool mice is presented.


Serial volumetric (three-dimensional) intravascular ultrasound analysis of restenosis after directional coronary atherectomy.
We report the use of three-dimensional (volumetric) intravascular ultrasound (IVUS) analysis to assess serial changes after directional coronary atherectomy (DCA). Recent serial planar IVUS studies have described a decrease in external elastic membrane (EEM) area following catheter-based intervention as an important mechanism of late lumen renarrowing. Thirty-one patients with de novo native coronary lesions treated with DCA in the Serial Ultrasound Restenosis (SURE) Trial and in Optimal Atherectomy Restenosis Study (OARS) were enrolled in this study. Serial IVUS was performed before and after intervention and at 6 months' follow-up. In a subgroup of 18 patients from the SURE trial, IVUS was also performed at 24 h and at 1 month postintervention. Segments, 20-mm-long (200 image slices), were analyzed using a previously validated three-dimensional, computerized, automated edge-detection algorithm. The EEM, lumen, and plaque+media (P+M = EEM-lumen) volumes were calculated. At follow-up, lumen volume was smaller than at postintervention (159+/-69 mm3 vs. 179+/-49 mm3, p = 0.0003). From postintervention to follow-up, there was a decrease in EEM volume (377+/-107 to 352+/-125 mm3, p < 0.0001), but no change in P+M volume (p = 0.52). The delta lumen volume correlated strongly with deltaEEM volume (r = 0.842, p < 0.0001), but not with deltaP+M volume. In the 18 patients from the SURE Trial, the decrease in lumen and EEM volumes occurred late, between 1 month and 6 months of follow-up. Volumetric IVUS analysis demonstrated that late lumen volume loss following DCA was a result of a decrease in EEM volume. This was a late event, occurring between 1 and 6 months' postintervention.


Genomic diversity and phylogeography of norovirus in China.
Little is known about the phylogeography of norovirus (NoV) in China. In norovirus, a clear understanding for the characteristics of tree topology, migration patterns and its demographic dynamics in viral circulation are needed to identify its prevalence trends, which can help us better prepare for its epidemics as well as develop useful control strategies. The aim of this study was to explore the genetic diversity, temporal distribution, demographic dynamics and migration patterns of NoV that circulated in China. Our analysis showed that two major genogroups, GI and GII, were identified in China, in which GII.3, GII.4 and GII.17 accounted for the majority with a total proportion around 70%. Our demography inference suggested that during the long-term migration process, NoV evolved into multiple lineages and then experienced a selective sweep, which reduced its genetic diversity. The phylogeography results suggested that the norovirus may have originated form the South China (Hong Kong and Guangdong), followed by multicenter direction outbreaks across the country. From these analyses, we indicate that domestic poultry trade and frequent communications of people from different regions have all contributed to the spread of the NoV in China. Together with recent advances in phylogeographic inference, our researches also provide powerful illustrations of how coalescent-based methods can extract adequate information in molecular epidemiology.


Evaluation of confocal laser endomicroscopy as an aid to differentiate primary flat lesions of the larynx: A prospective clinical study.
In this trial, the ability of confocal laser endomicroscopy (CLE), a new imaging modality with a cellular resolution, to further differentiate primary flat lesions of the larynx was evaluated. First, an optical coherence tomography was used to filter out normal tissue and carcinoma. All other lesions (30 lesions in 19 patients) were investigated with CLE. The suspected diagnosis was compared to histopathology. Optical coherence tomography identified all noninvasive lesions. CLE provided further information with cellular resolution. In 2 of 30 cases, low image quality prevented classification. In laryngeal lesions (27 of 30), moderate to high-grade dysplasia was correctly suspected in 10 of 10 cases (100%). Hyperplasia was overrated as dysplasia in 7 of 15 cases (46.7%). Sensitivity was 100% and specificity was 40%. When used in conjunction with optical coherence tomography, CLE seems helpful for discrimination of noninvasive lesions, although it tends to overrate the severity of the changes. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1695-E1704, 2016.


Seroepidemiology of bovine anaplasmosis and babesiosis in Venezuela.
The serological prevalence of bovine anaplasmosis and babesiosis in the Centro-Occidental region of Venezuela was determined using the indirect fluorescent antibody (IFA) and latex agglutination (LAT) tests. Anaplasma marginale IFA and LAT prevalence rates were 57.7 and 48.6% respectively for cattle of all ages and breeds. The respective prevalence of IFA activity to B. bigemina and B. bovis was 78.2 and 38.8%. The LAT test specific only for Babesia spp. revealed that 61.4% of the animals tested were serologically positive for Babesia parasites. Anaplasma marginale and B. bigemina organisms were detected in peripheral blood smears of 21.1 and 7.5% respectively of cattle surveyed. A longitudinal survey of antibody activity and incidence of parasitaemia for Anaplasma and Babesia infections was conducted in two groups of calves from their birth to seven months of age. The animals generally experienced infections between three and four months of age the period subsequent to decline in colostral antibody levels. Seroepidemiological data are considered in the formulation of proposed vaccination regimens for anaplasmosis and babesiosis.


Translocation (12;13) in a case of infantile fibrosarcoma.
Cytogenetic analysis of an infantile fibrosarcoma showed the presence of a t(12;13) and numerical changes of chromosomes 15 and 20. Until now only non-random gain or loss of total chromosomes as well as one case with a deletion at 17p have been reported for this kind of tumor. This report represents the first cytogenetic description of an aggressive infantile fibrosarcoma with a translocation.


Is it ethical to prevent secondary use of stored biological samples and data derived from consenting research participants? The case of Malawi.
This paper discusses the contentious issue of reuse of stored biological samples and data obtained from research participants in past clinical research to answer future ethical and scientifically valid research questions. Many countries have regulations and guidelines that guide the use and exportation of stored biological samples and data. However, there are variations in regulations and guidelines governing the reuse of stored biological samples and data in Sub-Saharan Africa including Malawi. The current research ethics regulations and guidelines in Malawi do not allow indefinite storage and reuse of biological samples and data for future unspecified research. This comes even though the country has managed to answer pertinent research questions using stored biological samples and data. We acknowledge the limited technical expertise and equipment unavailable in Malawi that necessitates exportation of biological samples and data and the genuine concern raised by the regulatory authorities about the possible exploitation of biological samples and data by researchers. We also acknowledge that Malawi does not have bio-banks for storing biological samples and data for future research purposes. This creates room for possible exploitation of biological samples and data collected from research participants in primary research projects in Malawi. However, research ethics committees require completion and approval of material transfer agreements and data transfer agreements for biological samples and data collected for research purposes respectively and this requirement may partly address the concern raised by the regulatory authorities. Our concern though is that there is no such requirement for biological samples and data collected from patients for clinical or diagnostic purposes. In conclusion, we propose developing a medical data and material transfer agreement for biological samples and data collected from patients for clinical or diagnostic purposes in both public and private health facilities that may end up in research centers outside Malawi. We also propose revision of the current research ethics regulations and guidelines in Malawi in order to allow secondary use of biological samples and data collected from primary research projects as a way of maximizing the use of collected samples and data. Finally, we call for consultation of all stakeholders within the Malawi research community when regulatory authorities are developing policies that govern research in Malawi.


Author Correction: A large-scale test of the link between intergroup contact and support for social change.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Trends and variation in the use of radiotherapy in non-metastatic prostate cancer: A 12-year nationwide overview from the Netherlands.
This population-based study describes nationwide trends and variation in the use of primary radiotherapy for non-metastatic prostate cancer in The Netherlands in 2008-2019. Prostate cancer patients were selected from the Netherlands Cancer Registry (N = 103,059). Treatment trends were studied over time by prognostic risk groups. Multilevel analyses were applied to identify variables associated with external beam radiotherapy (EBRT) and brachy-monotherapy versus no active treatment in low-risk disease, and EBRT versus radical prostatectomy in intermediate and high-risk disease. EBRT use remained stable (5-6%) in low-risk prostate cancer and increased from 21% to 32% in intermediate-risk, 37% to 45% in high-risk localized and 50% to 57% in high-risk locally advanced disease. Brachy-monotherapy decreased from 19% to 6% and from 15% to 10% in low and intermediate-risk disease, respectively, coinciding an increase of no active treatment from 55% to 73% in low-risk disease. Use of EBRT or brachy-monotherapy versus no active treatment in low-risk disease differed by region, T-stage and patient characteristics. Hospital characteristics were not associated with treatment in low-risk disease, except for availability of brachy-monotherapy in 2008-2013. Age, number of comorbidities, travel time for EBRT, prognostic risk group, and hospital characteristics were associated with EBRT versus prostatectomy in intermediate and high-risk disease. Intermediate/high-risk PCa was increasingly managed with EBRT, while brachy-monotherapy in low/intermediate-risk PCa decreased. In low-risk PCa, the no active treatment-approach increased. Variation in treatment suggests treatment decision related to patient/disease characteristics. In intermediate/high-risk disease, variation seems furthermore related to the treatment modalities available in the diagnosing hospitals.


Dietary-Induced Obesity, Hepatic Cytochrome P450, and Lidocaine Metabolism: Comparative Effects of High-Fat Diets in Mice and Rats and Reversibility of Effects With Normalization of Diet.
The effects of a high-fat diet on mRNA and protein of cytochrome P450 (CYP) enzymes in rats and mice and its impact on lidocaine deethylation to its main active metabolite, monoethylglycinexylidide (MEGX), in rats were investigated. The effect of a change in diet from high-fat to standard diet was also evaluated. Plasma biochemistry, mRNA, protein expression for selected CYP, and the activity of lidocaine deethylation were determined. The high-fat diet curtailed the activity and the expression of the majority of CYPs (CYP1A2, CYP3A1, CYP2C11, CYP2C12, and CYP2D1), mRNA levels (Cyp1a2 and Cyp3a2), and MEGX maximal formation rate (Vmax). Mice showed complementary results in their protein expressions of cyp3a and 1a2. Switching the diet back to standard chow in rats for 4 weeks reverted the expression levels of mRNA and protein back to normal levels as well as the maximum formation rates of MEGX. Female and male rodents showed similar patterns in CYP expression and lidocaine metabolism in response to the diets, although MEGX formation was faster in male rats. In conclusion, diet-induced obesity caused general decreases in CYP isoforms not only in rats but also in mice. The effects were shown to be reversible in rats by normalizing the diet.


American Society for Metabolic and Bariatric Surgery position statement on long-term survival benefit after metabolic and bariatric surgery.
The following position statement has been issued by the American Society for Metabolic and Bariatric Surgery in response to numerous inquiries made to the Society by patients, physicians, society members, hospitals, health insurance payors, the media, and others regarding the benefit of metabolic and bariatric surgery on long-term survival. An overview of the current available published peer-reviewed scientific evidence is presented.


Epidermoid cysts of the fourth ventricle.
Epidermoid tumors located in the fourth ventricle are exceedingly rare. Seven cases of this pathological condition were observed during a 10-year period. Patients were mostly middle-aged men, with a clinical history of relatively short duration (5 months). Clinical symptoms consisted of vertigo and ataxia, followed by incoordination, dysmetria, and tremor at a later stage. Computed tomography scanning represented the main diagnostic technique for these lesions, and typically showed a highly hypodense, round-shaped area within the fourth ventricle, occasionally accompanied by hydrocephaly. Subtotal surgical removal of the cysts produced excellent results in 86% of the cases. The implications of these findings are discussed.


Urinary tract dysfunctions in tethered spinal cord syndrome: improvement after surgical untethering.
We reviewed 55 patients with urinary tract dysfunction owing to the tethered spinal cord syndrome, a form of spina bifida occulta with or without mild myelodysplasia, to evaluate the effects of neurosurgical treatment. Of the patients 24 underwent laminectomy with release of a tethered spinal cord and 31 were followed without the operation. Median followup was approximately 5 years. Urological findings at the most recent examination were compared between the 2 groups. In the operated group 5 patients, including 2 with myelodysplasia, apparently were cured of urinary tract dysfunction and 6, including 2 with myelodysplasia, had somewhat satisfactory results, whereas in the unoperated group only 4 patients had satisfactory results and the remainder were unaffected. Urinary tract dysfunction in some patients with spina bifida occulta may be relieved by surgical release of a tethered spinal cord.


Patients hospitalised with heart failure across different waves of the COVID-19 pandemic show consistent clinical characteristics and outcomes.
During the first wave of the COVID-19 pandemic, admissions for cardiovascular disease, including Heart Failure (HF), were reduced. Patients hospitalised for HF were sicker and with increased in-hospital mortality. So far, whether following waves had a different impact on HF patients is unknown. All consecutive patients hospitalised for acute heart failure during three different COVID-19 related national lockdowns were analysed. The lockdown periods were defined according to Government guidelines as 23/3/2020 to 4/7/2020 (First Lockdown), 4/11/2020 to 2/12/2020 (Second Lockdown) and 5/1/2021 to 28/2/2021 (Third Lockdown). Overall, 184 patients hospitalised for HF were included in the study, 95 during the 1st lockdown, 30 during the 2nd lockdown and 59 during the 3rd lockdown. Across the three groups had comparable clinical characteristics, comorbidities and cardiovascular risk factors. Specialist in-hospital care was uninterrupted during the pandemic showing comparable mortality rates (p = 0.10). Although medical therapy for HF was comparable between the three lockdowns, a significantly higher proportion of patients received Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in the second and third lockdowns (p < 0.001). Although public health approaches changed throughout the pandemic, the clinical characteristics and outcomes of HF patients were consistent across different waves. For patients hospitalised in the subsequent waves, a more rapid optimization of medical therapy was observed during hospitalization. Particular attention should be devoted to prevent collateral cardiovascular damage during public health emergencies.


The use of Cole-Cole plots to compare two multifrequency bioimpedance instruments.
Two commercially available multifrequency bioimpedance spectrometers (Xitron 4000B and SEAC SFB3) were compared by performing measurements on a set of electronic circuits and by studying 14 healthy volunteers. Output data were plotted as reactance versus resistance and fitted with a semi-circle using a least squares fitting program. In tests with six electronic circuits both instruments produced impedance loci that were well described by semicircular Cole-Cole plots, though there were some minor discrepancies using the Xitron instrument at frequencies above 150 kHz. When tested on the volunteers the SEAC instrument gave very good fits (RMSE = 1.5 Omega) to a semi-circle from 5-600 kHz on all volunteers. The Xitron instrument gave excellent fits to the semi-circle between 5 and 55 kHz (RMSE = 0.7 Omega) but above 55 kHz the phase measurements stayed constant or even increased, confirming the anomalous behaviour reported by other authors. The conclusions to be drawn are that the semicircular plots predicted by the Cole-Cole theory give a very good description of multifrequency impedance data recorded by the SEAC SFB3 instrument, on human subjects, for frequencies between 5 and 600 kHz. The Xitron 4000B is not able to reproduce the theoretically expected results in humans above 55 kHz.


A hemodynamic, metabolic and histopathological study of a heterotopic auxiliary swine liver graft with portal vein arterialization.
Auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA) is a model that has been hardly studied, despite its therapeutic potential. Hemodynamic and biochemical characterization was carried out during graft implantation, in a pig-to-pig model (n=15 AHLT-PVA). Furthermore a histopathological study was performed to establish microscopic alterations due to PVA. Reperfusion of the arterialized graft produced an increase in heart rate (HR) vs. baseline (P=.004) and vs. inferior vena cava clamping phase (P=.004); and a decrease in systemic vascular resistance vs. cava clamping phase (P=.021). At the end of implantation, cardiac output remained elevated (P=.001), likewise HR remained increased vs. baseline phase (P=.002). Mean arterial pressure decreased with cava clamping, but was not affected by the reperfusion of the graft, nor the skin closure. The histopathological study at 3, 10, and 21 days post-PVA revealed that functional liver structure was maintained although it is common to find foci of perilobular necrosis on day 3 (P=.049), and perilobular connective tissue proliferation at day 10 (P=.007), vs. native liver. The described arterialized liver graft model minimizes the number of vascular anastomoses vs. previously described models. It is hemodynamically and metabolically well tolerated and the double arterial vascularization of the graft does not cause significant changes in liver histology.


Motor performance deteriorates with simultaneously performed cognitive tasks in geriatric patients.
To investigate whether simultaneous cognitive tasks influence maximal motor performance in frail geriatric patients with a history of injurious falls and different levels of cognitive function. Experimental 3-group design. Geriatric rehabilitation hospital. Twenty-two healthy, young adults (mean age +/- standard deviation, 27.7 +/- 9y) and 23 geriatric patients (mean age, 80.9 +/- 5.4y) with a history of injurious falls with (Mini-Mental State Examination [MMSE] score, 20.5 +/- 1.6) and without (MMSE score, 28.1 +/- 1.2) cognitive impairment. Not applicable. Motor performance: peak and integral of maximal isometric strength of leg extensors. Cognition: semiautomated calculation steps (serial 2 forward) and nonautomated calculation steps derived from the MMSE (serial 7 retro). Motor and cognitive performances were examined as single and dual tasks. In frail geriatric patients, especially in patients with cognitive impairment, maximal motor performance decreased significantly during all dual tasks. Cognitive performance was reduced, depending on the task and group. In frail or cognitively impaired geriatric patients, additional tasks can substantially decrease maximal motor performance. Insufficient resources on dual tasking may thus be a link in connecting the high incidence of falls with frailty and cognitive impairment in geriatric patients with a history of injurious falls.


Coccidioides immitis endospores: phagocytosis by human cells.
Phagocytosis of killed endospores by glass adherent peripheral human mononuclear cells was studied. Phagocytosis continued through 30 minutes of incubation. No difference in rates of ingestion could be detected when cells from coccidioidin-reactive and nonreactive subjects were compared although both groups ingested endospores more avidly than latex particles.


A cross-sectional study of the prevalence of lameness and digital dermatitis in dairy cattle herds in Egypt.
Lameness is a significant problem for the dairy industry worldwide. No previous studies have evaluated the prevalence of lameness or digital dermatitis (DD) in dairy cattle herds in Egypt. A total of 16,098 dairy cows from 55 dairy herds in 11 Egyptian governorates underwent visual locomotion scoring using a 4-point scoring system. Cows that had a lameness score ≥ 2 were considered clinically lame. Following manure removal with water and using a flashlight, the cows' hind feet were examined in the milking parlour to identify DD lesions and classify with M-score. Furthermore, each cow was assigned a hock score (a 3-point scale) and a hygiene score (a 4-point scale). The cow-, within-and between-herd prevalence of lameness and DD and associated 95% confidence intervals (CI) were calculated. The prevalence of hock lesions and poor cow hygiene was also calculated. Of the examined cows, 6,883 were found to be clinically lame (42.8%, 95% CI = 42.0-43.5%). The average within-herd prevalence of lameness was 43.1% (95% CI = 35.9-50.3%). None of the dairy herds recruited into the study were found to be free from clinical lameness. The average within-herd prevalence of DD was 6.4% (95% CI = 4.9-8.0%). The herd-level prevalence of DD was 92.7% (95% CI = 85.9-99.6%). Active DD lesions (M1, M2, M4.1) were identified in 464 cows (2.9%) while inactive lesions (M3, M4) were identified in 559 cows (3.5%). The within-herd prevalence of hock lesions (score 2 or 3) was 12.6% (95% CI = 4.03-21.1%) while a severe hock lesion had within-herd prevalence of 0.31% (95% CI = 0.12-0.51%). Cow-level prevalence of hock lesions was 6.2% (n = 847, 95% CI = 5.8-6.2%). The majority of examined cows had a hygiene score of 4 (n = 10,814, prevalence = 70.3%, 95% CI = 69.5-71%). The prevalence of lameness was higher than prevalence estimates reported for other countries which could be due to differing management and/or environmental factors. DD was identified at lower prevalence in most herds but with high herd-level prevalence. Poor cow hygiene was notable in most herds. Measures to reduce the prevalence of lameness and to improve cow hygiene in dairy cattle herds in Egypt are therefore needed.


Real-time imaging of lymphocytes in vivo.
New preparations, fluorescent probes and imaging techniques are providing the means to observe the behavior of cells in the tissue environment of lymphoid organs. In particular, when combined with two-photon laser microscopy, intravital imaging of surgically exposed lymph nodes provides a unique view of lymphocyte migration and antigen presentation as it occurs within the living animal. The view is emerging that lymphocytes migrate randomly within lymphoid organs, and that lymphocyte contact with antigen-presenting cells may be a stochastic process rather than one guided by chemokine gradients.


Autonomic dysfunction is associated with cardiac remodelling in heart failure patients.
Orthostatic hypotension (OH) is a cardinal sign of autonomic dysfunction and a common co-morbidity in heart failure (HF). The role of autonomic dysfunction in the development of structural cardiac anomalies in HF patients has not been sufficiently explored. We aimed to assess relations between orthostatic blood pressure (BP) responses during active standing and echocardiographic changes in a series of patients admitted for HF. One hundred and forty-nine patients hospitalized for HF [mean age: 74 years; 30% women; ejection fraction (LVEF) 40 ± 16%] were examined with conventional echocardiograms and active-standing test. Associations of cardiac remodelling parameters with the difference between supine and standing (after 3 min) systolic/diastolic BP were examined. Systolic BP decreased (-1.1 ± 15 mmHg), whereas diastolic BP increased (+1.0 ± 9.5 mmHg) after 3 min of active standing. A total of 34 patients (23%) met conventional OH criteria; i.e. systolic/diastolic BP decreases by ≥20/10 mmHg. In the multivariable linear regression analysis, adjusted for traditional cardiovascular risk factors and LVEF, a decrease in systolic BP upon standing was associated with greater left atrial volume [β per -10 mmHg: 2.37, standard error (SE) = 1.16, P = 0.043], and greater left ventricular mass (β per -10 mmHg: 5.67, SE = 2.24, P = 0.012), but not with other echocardiographic parameters. No significant associations were observed between signs of cardiac remodelling and decrease in diastolic BP. Orthostatic decrease in systolic BP among older HF patients is associated with structural cardiac changes such as increased left atrial volume and left ventricular mass, independently of traditional risk factors and left ventricular dysfunction.


Affective state estimation based on Russell's model and physiological measurements.
Affective states are psycho-physiological constructs connecting mental and physiological processes. They can be represented in terms of arousal and valence according to the Russel's model and can be extracted from physiological changes in human body. However, a well-established optimal feature set and a classification method effective in terms of accuracy and estimation time are not present in the literature. This paper aims at defining a reliable and efficient approach for real-time affective state estimation. To obtain this, the optimal physiological feature set and the most effective machine learning algorithm, to cope with binary as well as multi-class classification problems, were identified. ReliefF feature selection algorithm was implemented to define a reduced optimal feature set. Supervised learning algorithms, such as K-Nearest Neighbors (KNN), cubic and gaussian Support Vector Machine, and Linear Discriminant Analysis, were implemented to compare their effectiveness in affective state estimation. The developed approach was tested on physiological signals acquired on 20 healthy volunteers during the administration of images, belonging to the International Affective Picture System, conceived for inducing different affective states. ReliefF algorithm reduced the number of physiological features from 23 to 13. The performances of machine learning algorithms were compared and the experimental results showed that both accuracy and estimation time benefited from the optimal feature set use. Furthermore, the KNN algorithm resulted to be the most suitable for affective state estimation. The results of the assessment of arousal and valence states on 20 participants indicate that KNN classifier, adopted with the 13 identified optimal features, is the most effective approach for real-time affective state estimation.


Differences in EBV receptor concentration between in vitro EBV-converted lymphoma sublines reflect biological differences between the converting viral substrains.
We have compared the EBV-receptor concentration of two originally EBV-negative human B-cell lymphoma lines, after in vitro conversion with the transforming B95-8 or the cytopathic P3HR-1 EB-viral substrain, respectively, into permanent EBV-carrying sublines. Receptors were measured by the quantitative EBV-absorption bioassay of Sairenji and Hinuma (1973). EBV receptor concentration of all P3HR-1 virus-converted sublines was significantly reduced, in comparison with the B95-8 virus-converted sublines. This suggests that cells with a low receptor concentration are more likely to survive the initial infection with the P3HR-1 viral harvest. The results further confirm the biological differences between the two EBV substrains.


Structural organization of pulmonary arteries in the rat lung.
The structure of the normal pulmonary arteries in the rat was studied with light and electron microscopy after use of a newly devised technique of perfusion fixation and tissue preparation. We distinguished two main types of artery in the rat lung on the basis of the structure of the media, an elastic artery and a muscular artery. The elastic artery was characterized by an abundance of extracellular matrix in the media and by an oblique arrangement of smooth muscle cells to connect neighboring elastic laminae. It was subdivided into two segments, a classical elastic and a transitional elastic segment. The muscular artery was distinguished by a paucity of extracellular matrix in the media and by a circumferential arrangement of smooth muscle cells (or pericytes) enclosing the lumina, and was subdivided into four segments, a thick muscular, an ordinary muscular, a partially muscular and a nonmuscular segment. The smooth muscle cells in the muscular artery contained well-developed microfilament bundles compared with those in the elastic artery. Structural differences in smooth muscle cells and in extracellular matrix in the media between the elastic and muscular arteries may reflect the functional heterogeneity of pulmonary arteries in response to hypoxic pulmonary vasoconstriction and to vasoactive substances such as endothelium-derived relaxing and hyperpolarizing factors, and endothelin.


Wind energy conversion technologies and engineering approaches to enhancing wind power generation: A review.
Nowadays, engineers are toiling away to achieve the maximum possible wind energy harvesting with low costs through enhancing the performances of WECSs in efforts to realize the wind power future forecasts. In fact, achieving this is basically not an easy task due to the intricacies that partly stem from the stochastic nature of wind energy. Further, the efforts in this regard can also be impacted by the ongoing trends in various wind energy conversion-related technologies, and engineering approaches. Hence, the wind power optimization is determined depending on the types of WECS technologies, output power smoothing, and design development approaches that be employed. Currently, the variable speed operations-based WECS technologies are generally opted in wind farm applications. Meanwhile, power management system is the heart of a WECS, where smoothing output power with reducing costs could be implemented. On the other hand, the automated control strategies were reported in literatures to better optimize WECSs' performances particularly in terms of costs compared to ESS devices. On this basis, MBPC and hybrid control algorithms were commonly presented as the current state-of-the-art for systems modeling, whereas MBD was preferred to be an efficient and cost-saving approach for advanced development of automated control systems. This study aims to conduct comparative analyses on WECS technologies (with different generators, and PECs) based on their energy harvesting capability, cost-effectiveness, and advances in designs. Assessments of the approaches and strategies for smoothing power production are also presented. Finally, the study concludes that trends in PECs, automated control strategies and MBD are the most compelling.


Design of a dual pH and temperature responsive hydrogel based on esterified cellulose nanocrystals for potential drug release.
In this study, new stimuli - responsive hybrid hydrogels were achieved via succinylated cellulose nanocrystals (Su-CNC). The innovation was concerned with the inclusion of Su-CNC, at different degree of substitution (DS), into hydrogel network to render it pH and thermo-responsive characters through free radical polymerization reaction with poly(N-isopropylacrylamide) (PNIPAm). The prepared hydrogel was also examined for the in vitro release of Famotidine at different pH values. As clearly evident from the results, all the hydrogels prepared with different DS of Su-CNC, which were nominated as Su-CNC / PNIPAm (1-3), showed a high response to temperature change since their swelling behavior and hydrophilicity were decreased at 35 °C and upwards. This led to the more hydrophobicity character and thus the hydrogel shrinkage occurred. On the other hand, at pH 6, the hydrogels exhibited a significant Equilibrium Swelling Ratio (ESR) attaining 18.1, 17.3 and 16.8 (g/g) for Su-CNC / PNIPAm (1-3), respectively. However, Su-CNC / PNIPAm 2 hydrogel showed a significant response to the pH change from 8 to 2 which was advised to be selected as a potential pH responsive hydrogel for the in vitro Famotidine release.


An immunological basis for chronic histiocytic intervillositis in recurrent fetal loss.
Chronic histiocytic intervillositis (CHIV) is a rare type of placental pathology that is associated with reproductive loss at all gestational ages. The aim of the study was to investigate the relationship between the severity of CHIV and the outcome of pregnancy and to compare the immune response between CHIV patients and controls to explore an immunological origin of CHIV. Microscopic slides were reviewed and scored according to a previously published grading system in 30 pregnancies of 22 CHIV patients. Partner-specific mixed lymphocyte reactions, cytotoxic T-lymphocyte precursor frequencies (CTLpf), and anti-HLA antibodies were determined in four patients and seven controls. Higher CHIV scores are associated with worse pregnancy outcome. CHIV patients demonstrated a higher CTLpf against their partner compared to non-complicated pregnancies (P = 0.03). The CTLpf was extremely high in 75% of the patients. Antipaternal HLA antibodies were only present in 75% of the CHIV patients compared to none of the controls (P = 0.02). CHIV scores seem to be associated with the severity of adverse pregnancy outcome. High antipaternal cellular (T-cell) and humoral (B-cell) response to partner-specific CTLpf and the presence of anti-HLA antibodies directed to the partner suggest an immunologic origin of CHIV.


The identification of a novel Pleurotus ostreatus dsRNA virus and determination of the distribution of viruses in mushroom spores.
Double-stranded RNAs and virus particles were identified in Pleurotus ostreatus strain Shin-Nong in Korea. Isometric virus particles with a diameter of 33 nm were purified, which are similar to other Pleurotus viruses reported previously. This strain contains 5 dsRNAs, 8.0, 2.5, 2.4, 2.0, and 1.8 kb in size. The virus particles contain 2 dsRNAs, designated RNA-1 (2.5 kb), and RNA-2 (2.4 kb) which is a typical pattern of Partitiviridae. A non-encapsidated dsRNA of about 8.0 kb also was identified. Partial cDNA from RNA-1 was cloned, and sequence analysis revealed that this gene codes for RdRp. The comparison of the sequence from partial cDNA clone showed 35% amino acid homology with the C-terminal end of the RdRp gene of Helicobasidum mompa virus and Rosalinia necatrix virus. Specific primers designed from the partial sequences successfully amplified RT-PCR product from the infected mycelium and a single spore culture. We used these primers to determine the pattern of distribution of viruses in spores. Of the 96 different single spore cultures generated from Shin-Nong strain, a specific RT-PCR product was identified in 25 cultures, indicating that about 26% of basidiospores contain viruses.


[The resonance nature of the dependence of epithelial lesions of the small intestine in mice on the interval between injections of an S-phase-specific agent--hydroxyurea].
The dependence of the injury of murine small intestinal epithelium on the interval between multiple regular injections of hydroxyurea (HU) was investigated. Mice were injected 8 times with HU (5 mg per injection) in different experimental groups of animals, and the interval between injections varied from 6 to 19 hours. With the intervals between the injections close to 8 or 16.5 hours the resonance decrease of the injury was observed whereas the intervals of 6, 12 and 19 hours corresponded to maximum injury.


Comparison of tumor-informed and tumor-naïve sequencing assays for ctDNA detection in breast cancer.
Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here, we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor-informed and tumor-naïve assays designed to detect structural variants (SVs), single nucleotide variants (SNVs), and/or somatic copy-number aberrations, by multiplex PCR, hybrid capture, and different depths of whole-genome sequencing. Our results demonstrate that the ctDNA dynamics and allele fractions (AFs) were highly concordant when analyzing the same patient samples using different assays. Tumor-informed assays showed the highest sensitivity for detection of ctDNA at low concentrations. Hybrid capture sequencing targeting between 1,347 and 7,491 tumor-identified mutations at high depth was the most sensitive assay, detecting ctDNA down to an AF of 0.00024% (2.4 parts per million, ppm). Multiplex PCR targeting 21-47 tumor-identified SVs per patient detected ctDNA down to 0.00047% AF (4.7 ppm) and has potential as a clinical assay.


Estimation and interrater reliability of pupillography by digital mobile app: Digital movil pupillography app validity.
The examination of pupillary light reflexes is widely employed to evaluate the autonomic system's balance, ocular, and neurological conditions, typically evaluated by qualitative observation. To describe and evaluate the inter-rater reliability and agreement of pupillometric values obtained with a novel semi-automatic mobile pupillography app. Two examiners and two graders perform the measurements with an android app which corrects the device-face distance, measure the maximum contraction of the pupil, and calculates its slope, in a hospital room setting with three levels of environmental light intensity: <100, 101 to 200, and 201 to 300 lux, at 200, 400, 600, 900, 1200, and 1500 milliseconds. Sixty healthy individuals, aged 18 to 45, were included; 85% had brown eyes. The reliability of the pupil/iris ratio had Ri = 70% to 88%, and bland Altman graphics show a uniform agreement. The pupillography curves show a similar slope at different light intensities, during the contraction phase. There were very good repeatability and inter-rater reproducibility of the measurements at average levels of illumination in examination rooms, even in dark-eyed people. This app provides a highly promising approach to pupillary measurements in clinical practice.


Epidermoid cyst appearing as a malignancy-mimicking subcutaneous lesion on ultrasonography.
It is challenging to diagnose epidermoid cysts on ultrasonography; except in typical, benign-appearing cases. The purpose of this study was to include epidermoid cysts in the differential diagnosis of diverse subcutaneous lesions, especially malignancy-mimicking lesions, as seen on ultrasonography. We reviewed 19 cases of pathologically confirmed epidermoid cysts in 19 patients (male, 8; female, 11). Three radiologists, who were blinded to the pathology data, classified (by consensus) these epidermoid cysts as benign or malignancy-mimicking lesions, according to generally accepted ultrasonographic criteria, including the margin, shape, echotexture, and transitional zone with surrounding tissue, and also including the growth pattern and adjacent tissue change. The ultrasonographic data were then correlated with the pathology results regarding the ruptured or unruptured status of the cysts. Epidermoid cysts have been noted as showing a wide-spectrum of findings on ultrasonography. Twelve of our cases showed benign ultrasonographic features: six cases had typical, benign ultrasonographic features with unruptured status; two cases with ruptured status did not have clear ultrasonographic features, although we decided by consensus that there were benign ultrasonographic features; and four cases with unruptured status had peculiar internal echogenicities, described as "internal rod-like contents", that could be considered to be a variation of the typical ultrasonographic finding of epidermoid cysts. Seven cases showed malignancy-mimicking ultrasonographic features; all seven of these had ruptured status. The diagnosis of ruptured epidermoid cysts should be included in the differential diagnosis of malignancy-mimicking subcutaneous lesions. The internal rod-like contents can be regarded as another typical ultrasonographic finding of epidermoid cysts.


Effects of taurolidine and octreotide on tumor growth and lipid peroxidation after staging-laparoscopy in ductal pancreatic cancer.
Irrigation with taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n = 20) with subsequent laparoscopic irrigation with taurolidine (gr. 2, n = 20) or octreotide (gr. 3, n = 20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group (P<0.05). Carcinomas were smaller after saline (6+/-23 mm(2)) than after octreotide irrigation (70+/-120 mm(2), P<0.05). In conclusion this study showed that laparoscopic irrigation with taurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.


Amplification of gene expression using both 5'- and 3'-untranslated regions of GLUT1 glucose transporter mRNA.
Cis-regulatory elements located at either the 5'- or 3'-untranslated region (UTR) of the GLUT1 glucose transporter mRNA increase the expression of luciferase reporter genes. The aim of the present study was to investigate the possible cooperative effects of 5'- and 3'-UTRs of the GLUT1 mRNA on the expression of a luciferase reporter gene in cultured brain endothelial cells. Luciferase reporter genes containing control elements in nucleotides (nt) 1-171 of GLUT1 5'-UTR, or nt 2100-2300 of GLUT1 3'-UTR produced a 10- and 6-fold increase in the expression of the luciferase reporter gene compared to the control vector containing no GLUT1 regulatory sequences, respectively. The insertion of both GLUT1 mRNA cis-regulatory elements increased 59-fold the activity of luciferase compared to controls. Data presented here demonstrate that cis-regulatory elements located at both the 5'- and 3'-UTR of GLUT1 mRNA increase expression of a reporter gene in an independent manner.


Systematic review of mRNA expression in human oocytes: understanding the molecular mechanisms underlying oocyte competence.
The biggest cell in the human body, the oocyte, encloses almost the complete machinery to start life. Despite all the research performed to date, defining oocyte quality is still a major goal of reproductive science. It is the consensus that mature oocytes are transcriptionally silent although, during their growth, the cell goes through stages of active transcription and translation, which will endow the oocyte with the competence to undergo nuclear maturation, and the oocyte and embryo to initiate timely translation before the embryonic genome is fully activated (cytoplasmic maturation). A systematic search was conducted across three electronic databases and the literature was critically appraised using the KMET score system. The aim was to identify quantitative differences in transcriptome of human oocytes that may link to patient demographics that could affect oocyte competence. Data was analysed following the principles of thematic analysis. Differences in the transcriptome were identified with respect to age or pathological conditions and affected chromosome mis segregation, perturbations of the nuclear envelope, premature maturation, and alterations in metabolic pathways-amongst others-in human oocytes.


STALing B cell responses with CD22.
Suppressing unwanted humoral immune responses without compromising the host's ability to respond to foreign pathogens is a primary goal for therapies aimed at ameliorating harmful autoantibody production. Global suppression of the immune system via lymphocyte depletion and/or immunosuppressive drugs can have off-target effects, a limitation to conventional therapies. In this issue of the JCI, Macauley and colleagues utilize a novel platform to inhibit antigen-specific antibody production that preserves the immune system's ability to respond to unrelated antigens.


Clonal hematopoiesis of indeterminate potential and outcomes after heart transplantation: A multicenter study.
Cardiac allograft vasculopathy (CAV) is a leading cause of late graft failure and mortality after heart transplantation (HT). Sharing some features with atherosclerosis, CAV results in diffuse narrowing of the epicardial coronaries and microvasculature, with consequent graft ischemia. Recently, clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a risk factor for cardiovascular disease and mortality. We aimed to investigate the relationship between CHIP and posttransplant outcomes, including CAV. We analyzed 479 HT recipients with stored DNA samples at 2 high-volume transplant centers, Vanderbilt University Medical Center and Columbia University Irving Medical Center. We explored the association between the presence of CHIP mutations with CAV and mortality after HT. In this case-control analysis, carriers of CHIP mutations were not at increased risk of CAV or mortality after HT. In a large multicenter genomics study of the heart transplant population, the presence of CHIP mutations was not associated with an increased risk of CAV or posttransplant mortality.


Benign mediastinal teratoma causing pericardial tamponade and pleural effusion.
Mediastinal teratomas are known to adhere to and penetrate the pericardium, but perforation and tamponade are uncommon. We present a patient who developed a life-threatening pericardial tamponade and pleural effusion, whose life was saved by timely surgery. We believe this to be the third successfully treated patient and the first to be reported from Great Britain.


Nitration of cAMP-Response Element Binding Protein Participates in Myocardial Infarction-Induced Myocardial Fibrosis via Accelerating Transcription of Col1a2 and Cxcl12.
Aims: Myocardial fibrosis after myocardial infarction (MI) leads to heart failure. Nitration of protein can alter its function. cAMP-response element binding protein (CREB) is a key transcription factor involved in fibrosis. However, little is known about the role of nitrated CREB in MI-induced myocardial fibrosis. Meanwhile, downstream genes of transcription factor CREB in myocardial fibrosis have not been identified. This study aims to verify the hypothesis that nitrated CREB promotes MI-induced myocardial fibrosis via regulating the transcription of Col1a2 and Cxcl12. Results: Our study showed that (1) the level of nitrative stress was elevated and nitrated CREB was higher in the myocardium after MI. Tyr182, 307, and 336 were the nitration sites of CREB; (2) with the administration of peroxynitrite (ONOO-) scavengers, CREB phosphorylation, nuclear translocation, and binding activity to TORC2 (transducers of regulated CREB-2) were attenuated; (3) the expressions of extracellular matrix (ECM) proteins were upregulated and downregulated in accordance with the expression alteration of CREB both in vitro and in vivo; (4) CREB accelerated transcription of Col1a2 and Cxcl12 after MI directly. With the administration of ONOO- scavengers, ECM protein expressions were attenuated; meanwhile, the messenger RNA (mRNA) levels of Col1a2 and Cxcl12 were alleviated as well. Innovation and Conclusion: Nitration of transcription factor CREB participates in MI-induced myocardial fibrosis through enhancing its phosphorylation, nuclear translocation, and binding activity to TORCs, among which CREB transcripts Col1a2 and Cxcl12 directly. These data indicated that nitrated CREB might be a potential therapeutic target against MI-induced myocardial fibrosis. Antioxid. Redox Signal. 38, 709-730.


Characteristics and outcomes of autoimmune hemolytic anemia after pediatric allogeneic stem cell transplant.
Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplant (HSCT) is a rare but complex and serious complication. Detailed descriptions of cases and management strategies are needed due to lack of prospective trials. Describe the incidence, clinical characteristics, and management of AIHA after HSCT in a pediatric cohort. This is a retrospective cohort study of 33 pediatric patients with AIHA after HSCT at an academic tertiary care center from 2003 to 2019. The overall incidence of AIHA after allogeneic HSCT was 3.8% (33/868). AIHA was significantly more common after transplant for nonmalignant versus malignant diagnoses (7.0% [26/370] vs. 1.4% [7/498], p < .0001). AIHA developed at a median of 4.7 months (range 1.0-29.7) after transplant. Sixteen of 33 patients (48.5%) required new AIHA-directed pharmacologic therapy; 17 (51.5%) were managed on their current immunosuppression and supportive care. Patients managed without additional therapy were significantly older, more likely to have a malignant diagnosis, and tended to develop AIHA at an earlier time point after transplant. Patients received a median of two red blood cell transfusions within the first 2 weeks of diagnosis and a median of one AIHA-directed medication (range one to four), most commonly corticosteroids and rituximab. AIHA after HSCT is rare but occurs more commonly in patients transplanted for nonmalignant diagnoses. While some pediatric patients who develop AIHA after transplant can be managed on current immunosuppression and supportive care, many require AIHA-directed therapy including second-line medications.


Relevance of a new rat model of osteoblastic metastases from prostate carcinoma for preclinical studies using zoledronic acid.
Animal models that mimic osteoblastic metastases associated with prostate carcinoma are required to improve the therapeutic options in humans. A new model was then developed and characterized in immunocompetent rats. The bisphosphonate zoledronic acid (ZOL) was tested to validate this model as a therapeutic application. Rat AT6-1 prostate tumor cells were characterized in vitro at the transcriptional (bone and epithelial markers) and functional (induction of mineralized nodules) levels. The bone lesions induced after their direct injection into the femur bone marrow were characterized by radiography, microscanner and histology analyses. ZOL effects were studied in vivo on bone lesion development and in vitro on AT6-1 cell proliferation, apoptosis and cell cycle analysis. Apart from epithelial markers, AT6-1 cells express an osteoblast phenotype as they express osteoblastic markers and are able to induce mineralized nodule formation in vitro. A disorganization of the trabecular bone at the growth zone level was observed in vivo after intraosseous AT6-1 cell injection as well as cortical erosion. The tumor itself is associated with bone formation as revealed by SEM analysis and polarized light microscopy. ZOL prevents the development of such osteoblastic lesions, related to a direct inhibitory effect on tumor cell proliferation independent of caspase 3 activation, but associated with cell cycle arrest. A new rat model of osteoblastic bone metastases was validated in immunocompetent rats and used to show the relevance of using ZOL in such lesions, as this compound shows bifunctional effects on both bone remodelling and tumor cell proliferation.


A single dose of meropenem is superior to ciprofloxacin in preventing infections after transrectal ultrasound-guided prostate biopsies in the era of quinolone resistance.
To evaluate the efficacy of meropenem single dose before transrectal prostate biopsy, instead of ciprofloxacin in the era of fluoroquinolones resistance. This prospective study included patients with indications for prostatic biopsy from January to December 2014. Those with known resistance in fluoroquinolones or meropenem or with decreased creatinine clearance were excluded. Patients were randomized into two groups, and statistical analysis was carried out. Group A received a 3-day course of ciprofloxacin 500 bid per os starting the day before biopsy. Group B received 1 g meropenem intravenously 1 h prior to the procedure. Patients were followed up for 15 days, and those with lower urinary tract symptoms (LUTS) and fever were called for hospitalization. Urine and blood cultures were obtained. A total of 110 patients, 52-75 years old (mean 67.5, median 66) participated in the study, allocated in Groups A and B. After the procedure, 18 patients (32.7 %) of Group A reported macroscopic hematuria, while 10 (18.2 %) reported rectal blood loss. Nine patients (16.3 %) presented because of fever and LUTS. One of them developed septic shock and died in the ICU. Cultures revealed multi-resistant E. coli with high sensitivity to meropenem, and patients were treated accordingly. In Group B, 20 (36.3 %) patients presented with macroscopic hematuria and 9 (16.3 %) with rectal blood loss. One patient returned to hospital with LUTS and fever. Cultures revealed Klebsiella pneumoniae sensitive to colimycine. A single dose of meropenem prior to prostate biopsy is a safe and effective way to avoid the possible infectious complications in high-risk patients.


A novel hepatic lectin of zebrafish Danio rerio is involved in innate immune defense.
ASGPR (asialoglycoprotein receptor, also known as hepatic lectin) was the first identified animal lectin, which participated in a variety of physiological processes. Yet its detailed immune functions are not well studied in lower vertebrates. After reporting a zebrafish hepatic lectin (Zhl), we identified a novel hepatic lectin (zebrafish hepatic lectin-like, Zhl-l) in zebrafish. The zhl-l was mainly expressed in liver in a tissue specific manner. And challenge with LPS/LTA induced a significant change of zhl-l expression. What's more, recombinant C-type lectin domain (rCTLD) of Zhl-l had the activity of agglutinating and binding to both Gram-negative and Gram-positive bacteria. It promoted the phagocytosis of bacteria by carp macrophages. Moreover, rCTLD could bind to insoluble lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN) independent of Ca2+, which was inhibited by galactose. Interestingly, Zhl-l was located in the membrane, and its overexpression could upregulate the production of pre-inflammatory cytokines. Taken together, these results indicated that Zhl-l played a role in immune defense, and would provide further information to understand functions of C-type lectin family and the innate immunity in vertebrates.


A Simulation Model of the Mass Rearing of Tetranychus urticae Koch (Acari: Tetranychidae) on Beans.
The supply of predatory mites as natural enemies is a key component to guarantee the success of biological pest control programs as alternatives to chemical control in commercial crops. To meet the demand for a supply of biologicals, the mass rearing of natural enemies is an option, and the first step must be to develop a standardized system that maximizes the production of prey. One choice for this first step is to use simulation models that can evaluate scenarios that are difficult or complex to address experimentally. In this work, a model was developed to evaluate the current management conditions for the mass rearing of the pest mite Tetranychus urticae Koch. Our aim was to identify alternative scenarios to maximize mite production through mass rearing that could be evaluated in real systems. We assumed that populations of T. urticae were regulated by the conditions of supply-demand theory and modeled the age structure, temperature effects, and individual phenology of T. urticae. The supply-demand theory of resources was used to regulate populations, which involved structured ages and temperature effects for the different stages in the development of individuals. We used the functional response and the paradigm of metabolic pool models to describe resource acquisition and allocation. We demonstrated that 7- to 14-day-old plants infested with 45 or 62 T. urticae/plant could reach 25,000 individuals/plant, being 50% of these preys at the preferred stages by the predator Phytoseiulus persimilis Athias-Henriot. Our theoretical model requires validation in experimental/real systems of mass rearing to better verify the validity of all of the parameters and predictions before commercial implementation.


In vitro RNA synthesis in nuclei from herpes simplex virus infected cells: effects of ultraviolet-irradiated, defective and bromodeoxyuridine-resistant virus preparations.
Transcription of virus DNA was detectable in vitro in nuclei isolated from cells infected with wild type and bromodeoxyuridine (BUdR)-resistant herpes simplex virus type 1 but was suppressed in nuclei of cells infected with ultraviolet irradiated or defective virus or cells treated with BUdR during infection.


Downregulation of Wnt signaling by increased expression of Dickkopf-1 and -2 is a prerequisite for late-stage osteoblast differentiation of KS483 cells.
We examined the role of Wnt/beta-catenin signaling in successive stages of osteoblast differentiation. It has been shown that Wnt signaling in mature osteoblasts needs to be downregulated to enable the formation of a mineralized matrix. Using RNA interference, we showed that this is, at least in part, accomplished by upregulation of the Wnt antagonists Dickkopf-1 and -2. The role of Wnt signaling in the initiation of osteoblast differentiation has been well studied. However, the role during late-stage differentiation is less clear. We have examined the role of Wnt/beta-catenin signaling in successive stages of osteoblast differentiation. We treated murine bone marrow and mesenchymal stem cell-like KS483 cells with either LiCl or Wnt3A during several stages of osteoblast differentiation. In addition, we generated stable KS483 cell lines silencing either the Wnt antagonist Dkk-1 or -2 Activation of Wnt signaling by LiCl inhibits the formation of a mineralized bone matrix in both cell types. Whereas undifferentiated KS483 cells respond to Wnt3A by inducing nuclear beta-catenin translocation, differentiated cells do not. This is at least in part accomplished by upregulated expression of Dkk-1 and -2 during osteoblast differentiation. Using RNA interference, we showed that Dkk-1 plays a crucial role in blunting the BMP-induced alkaline phosphatase (ALP) response and in the transition of an ALP+ osteoblast in a mineralizing cell. In contrast, Dkk-2 plays a role in osteoblast proliferation and the initiation of osteoblast differentiation. Our data suggest that Wnt signaling in maturing osteoblasts needs to be downregulated to enable the formation of a mineralized bone matrix. Furthermore, they suggest that Dkk-1 and Dkk-2 may have distinct functions in osteoblast differentiation.


Soluble form of Fas and Fas ligand in serum and bronchoalveolar lavage fluid of individuals infected with human T-lymphotropic virus type 1.
Human T-lymphotropic virus type 1 (HTLV-1) carriers are known to develop pulmonary complications characterized by T-lymphocytic alveolitis. The aim of this study was to determine the profile and role of soluble Fas (sFas) and sFas ligand (sFasL) in the lung of asymptomatic HTLV-1 carriers. We measured sFas and sFasL levels in serum and bronchoalveolar lavage fluid (BALF) of 16 seropositive asymptomatic HTLV-1 carriers and 32 healthy subjects. The serum levels of both sFas and sFasL were significantly higher in HTLV-1 carriers than in the control. In BALF, the percentage of lymphocytes and CD4 positive T-cells, and the levels of sFasL were also significantly higher in asymptomatic carriers than the control, but there were no significant differences in sFas levels between the two groups. There was a significant correlation between BALF sFasL levels and serum sFasL levels and percentage of CD4 positive T-cells in BALF. Our results suggest that the increased levels of sFasL in the lung of asymptomatic HTLV-1 carriers are associated with accumulation of CD4 positive T-cells, and that resistance to apoptosis in HTLV-1 infected T-cells and overproduction of sFasL could contribute to T-lymphocytic alveolitis by down-regulating Fas-FasL mediated apoptosis.


Initial phase performance in a 30-s verbal fluency task as being reflective of aging effect.
The purpose of the present study was to investigate if performance in a 30-s verbal semantic fluency task (i.e. animal naming) across five elderly aged groups (60-64; 65-69; 70-74; 75-79; 80-84 years) would be reflective of aging effect. We analyzed differences in performance across 5-s phases and the moment of first word production in these five age groups. The following results were obtained: (i) with increasing age, the total number of words produced gradually declined (P < 0.001); (ii) there were significant differences in performance among the age groups in three phases (0-5, 6-10, 16-20 s) (P < 0.05); and (iii) the first word production within the first 5-s phase was significantly delayed in the 75-79 years and 80-84 years age groups compared with the rest of the age groups. Performance in the initial 5-s phase might be sensitive to cognitive degeneration in normal older adults.


Exploring adaptation responses of maize to climate change scenarios in southern central Rift Valley of Ethiopia.
In this study, we assessed responses of adaptation options to possible climate change scenarios on maize growth and yield by using projections of 20 coupled ensemble climate models under two representative concentration pathways (RCPs) 4.5 and 8.5 by means of a DSSAT model. Growth and yield simulations were made across present and future climate conditions using the hybrid maize variety (Shone). Subsequently, simulated yields were compared with farmer' average and on-farm trial yields. Results showed that on-farm trial yield (5.1-7.3 t ha-1) lay in between farmers' average yield (2.9-5 t ha-1) and water-limited potential yield (6.3-10.6 t ha-1). Maize yields achieved in farmers' fields are projected to decline towards mid-century and further towards the end of the century regardless of the adaptation options compared with baseline in low potential clusters. Results of a combination of adaptation options including February planting, use of 64 kg ha-1 N and conservation tillage provided yield advantage of 5.8% over the 30 cm till under medium GHGs emission scenario during mid-century period at Shamana. Mulching with 5 t ha-1 was projected to produce a 4-5% yield advantage in the Hawassa cluster during the mid-century period regardless of changes in tillage or planting window. Under a high GHGs emission scenario, over 13.4% yield advantage was projected in the Bilate cluster due to conservation tillage and June planting during the mid-century period. In the Dilla cluster, the use of 10 t ha-1 mulch, conservation tillage and early planting (February) would result in a 1.8% yield advantage compared with the control either in medium or high GHGs emission scenarios. Thus, the most promising and least risky practices among simulated strategies were the use of nitrogen and mulching in combination with tillage or planting date adjustment. However, adaptation options remained least promising and highly risky if not integrated with mulching or nitrogen use. Hence, the negative impacts of future climate change and subsequent yield gaps would be reduced by optimizing the application of nitrogen, mulch and their interaction with planting date and tillage in high and low potential areas of maize production.


A New Preoperative Prognostic System Combining CRP and CA199 For Patients with Intrahepatic Cholangiocarcinoma.
In this study, we aimed at investigating the preoperatively available prognostic factors for intrahepatic cholangiocarcinoma (ICC) patients and proposing a new preoperative prognostic scoring system for ICC. A total of 246 consecutive ICC patients who underwent curative hepatectomy were enrolled retrospectively and were randomly divided into training (n=164) and validation cohorts (n=82) at a ratio of 2:1. The prognostic factors were investigated in both cohorts using multivariate Cox's proportional hazards regression model. Multivariate analyses identified that two preoperative factors (serum C-reactive protein (CRP) levels >4.1 mg/l (hazard ratio (HR): 2.75, 95% CI: 1.65-4.73, P<0.001) and carbohydrate antigen 19-9 (CA19-9) levels >300 mg/ml (HR: 3.76, 95% CI: 2.18-6.49)) were independent prognostic factors for postoperative survival in the training cohort. The results were further confirmed in the validation cohort. On the basis of these data, a preoperative prognostic score (PPS) was established by allocating 0 or 1 point to the two factors, respectively. Then, both in the training and validation cohorts, the PPS showed the power to stratify patients into three distinct groups (groups with scores 2, 1, and 0) with significant difference in the risk of postoperative death. A new preoperative scoring system consisting of preoperative CRP and CA19-9 levels could effectively predict postoperative survival of ICC patients.