Plant antimutagenic agents, 4. Isolation and structure elucidation of maesol, an inactive constituent of Maesa spp.
Maesol, a novel dimeric phenol, was isolated from seeds of Maesa montana and Maesa indica. Maesol was shown to have the formula C28H42O4 with structure 1, a dimeric, symmetrical 1,12-bis(3,3'-dihydroxy-4,4'-dimethyl-5,5'-dimethoxyphenyl)dodecane. It is the first compound with such structure to be isolated from plant material. Structure elucidation was based largely on 1H- and 13C-nmr techniques and comparison with a known synthetic isomeric dimer 3. Although crude extracts showed strong inhibition of 2-aminoanthracene activity against Salmonella typhimurium (T-98), the pure compound was inactive when tested for inhibition of the mutagenic activity of several mutagens.


Clinical risk factors for new-onset atrial fibrillation in acute myocardial infarction: A systematic review and meta-analysis.
New-onset atrial fibrillation (NOAF) remains common arrhythmia in acute myocardial infarction (AMI), and is closely associated with increased subsequent cardiovascular mortality. Our meta-analysis aims to summarize more clinical risk factors for NOAF.Comprehensive systematic search of MEDLINE, EMBASE, and the Cochrane Library were carried out to find relevant studies inception to December 2017. Pooled mean difference (MD) and 95% confidence interval (CI) were calculated to evaluate the value of clinical risk factors in the prediction of NOAF after AMI.Eleven studies containing 9570 patients were included in the meta-analysis. Overall, older age and increased heart rate (HR) levels had a significant positive association with NOAF in patients with AMI. The MD in age between the patients with, and those without NOAF, was 8.22 units (95% confidence interval [CI]: 7.44-9.01), test for overall effect z score = 20.51 (P < .00001, I = 0%). Moreover, the MD in a subgroup analysis for HR levels between the patients with, and those without NOAF was 4.34 units (95% Cl: 2.56-6.11), test for overall effect z score = 4.78 (P < .00001, I = 31%).In patient with AMI, our meta-analysis demonstrated that older age and increased HR levels on admission are related to greater risk of NOAF.


The Florey Lecture, 1990. How is the cell division cycle regulated?
It is argued in this lecture that in most eukaryotic cells onset of mitosis is coupled to attainment of a critical cell mass and to completion of the previous S-phase. In fission yeast these controls operate through a regulatory gene network that activates the p34cdc2 protein kinase at mitosis. This is brought about by dephosphorylation of a tyrosine residue located in the ATP binding site of the kinase. The p34cdc2 protein kinase is also important for regulating the onset of mitosis in vertebrate cells suggesting that there is a universal control regulating mitosis in all eukaryotic cells.


Antibiotic Resistance of Pseudomonas aeruginosa in Pneumonia at a Single University Hospital Center in Germany over a 10-Year Period.
Pseudomonas aeruginosa is a common cause of community-acquired and nosocomial-acquired pneumonia. The development of resistance of P. aeruginosa to antibiotics is increasing globally due to the overuse of antibiotics. This article examines, retrospectively, the antibiotic resistance in patients with community-acquired versus nosocomial-acquired pneumonia caused by P. aeruginosa or multidrug-resistant (MDR) P. aeruginosa. Data from patients with community-acquired and nosocomial-acquired pneumonia caused by P. aeruginosa and MDR P. aeruginosa were collected from the hospital charts at the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, between January 2004 and August 2014. An antibiogram was created from all study patients with community-acquired and nosocomial-acquired pneumonia caused by P. aeruginosa or MDR P. aeruginosa. A total of 168 patients with mean age 68.1 ± 12.8 (113 [67.3% males and 55 [32.7%] females) were identified; 91 (54.2%) had community-acquired and 77 (45.8%) had nosocomial-acquired pneumonia caused by P. aeruginosa. Patients with community-acquired versus nosocomial-acquired pneumonia had a mean age of 66.4 ± 13.8 vs. 70.1 ± 11.4 years [59 vs. 54 (64.8% vs. 70.1%) males and 32 vs. 23 (35.2% vs. 29.9%) females]. They included 41 (24.4%) patients with pneumonia due to MDR P. aeruginosa: 27 (65.9%) community-acquired and 14 (34.1%) nosocomial-acquired cases. P. aeruginosa and MDR P. aeruginosa showed a very high resistance to fosfomycin (community-acquired vs. nosocomial-acquired) (81.0% vs. 84.2%; 0 vs. 85.7%). A similar resistance pattern was seen with ciprofloxacin (35.2% vs. 24.0%; 70.4% vs. 61.5%), levofloxacin (34.6% vs. 24.5%; 66.7% vs. 64.3%), ceftazidime (15.9% vs. 30.9; 33.3% vs. 61.5%), piperacillin (24.2% vs. 29.9%; 44.4% vs. 57.1%), imipenem (28.6% vs. 27.3%; 55.6% vs. 50.0%), piperacillin and tazobactam (23.1% vs. 28.6%; 44.4% vs. 50.0%), tobramycin (28.0% vs. 17.2%; 52.0% vs. 27.3%), gentamicin (26.4% vs. 18.2%; 44.4% vs. 21.4%), and meropenem (20.2% vs. 20.3%; 42.3% vs. 50.0%). An elevated resistance of P. aeruginosa and MDR P. aeruginosa was found for cefepime (11.1% vs. 23.3%; 25.9% vs. 50.0%), and amikacin (10.2% vs. 9.1%; 27.3% vs. 9.1%). Neither pathogen was resistant to colistin (P = 0.574). While P. aeruginosa and MDR P. aeruginosa were resistant to a variety of commonly used antibiotics, they were not resistant to colistin in the few isolates recovered from patients with pneumonia.


Unraveling the Genetic Basis of Key Agronomic Traits of Wrinkled Vining Pea (Pisum sativum L.) for Sustainable Production.
Estimating the allelic variation and exploring the genetic basis of quantitatively inherited complex traits are the two foremost breeding scenarios for sustainable crop production. The current study utilized 188 wrinkled vining pea genotypes comprising historical varieties and breeding lines to evaluate the existing genetic diversity and to detect molecular markers associated with traits relevant to vining pea production, such as wrinkled vining pea yield (YTM100), plant height (PH), earliness (ERL), adult plant resistance to downy mildew (DM), pod length (PDL), numbers of pods per plant (PDP), number of peas per pod (PPD), and percent of small wrinkled vining peas (PSP). Marker-trait associations (MTAs) were conducted using 6902 quality single nucleotide polymorphism (SNP) markers generated from the diversity arrays technology sequencing (DArTseq) and Genotyping-by-sequencing (GBS) sequencing methods. The best linear unbiased prediction (BLUP) values were estimated from the two-decades-long (1999-2020) unbalanced phenotypic data sets recorded from two private breeding programs, the Findus and the Birds eye, now owned by Nomad Foods. Analysis of variance revealed a highly significant variation between genotypes and genotype-by-environment interactions for the ten traits. The genetic diversity and population structure analyses estimated an intermediate level of genetic variation with two optimal sub-groups within the current panel. A total of 48 significant (P < 0.0001) MTAs were identified for eight different traits, including five for wrinkled vining pea yield on chr2LG1, chr4LG4, chr7LG7, and scaffolds (two), and six for adult plant resistance to downy mildew on chr1LG6, chr3LG5 (two), chr6LG2, and chr7LG7 (two). We reported several novel MTAs for different crucial traits with agronomic importance in wrinkled vining pea production for the first time, and these candidate markers could be easily validated and integrated into the active breeding programs for marker-assisted selection.


Effect of gold on stimulation of reproductive function in immature female albino rats.
Significant increase in ovarian and uterine weight and stimulation of ovarian delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activity and elevation of serum estradiol level were observed following gold chloride (0.2 mg/kg body weight/day), s.c. administration in immature female albino rats. Moreover, normal cyclic changes of estrus were found in vaginal smears of these rats whereas the rats of other groups showed diestrus phase throughout the period of experiment. Histological study of ovary also showed Graafian follicle with ovum in rats treated with 0.2 mg/kg/day of gold proving stimulation of reproductive function, which was not found in the ovarian histological study of other groups including controls. Thus, the results suggest a significant stimulatory effect of gold chloride on female reproductive activity in immature rats. Further, since the above-mentioned changes were evident at a specific dose of gold chloride, the data may have some clinical implications on stimulation and enhancement of fertility in immature female rats.


Characterizing Websites That Provide Information About Complementary and Integrative Health: Systematic Search and Evaluation of Five Domains.
In recent years, there has been an increase in the utilization of complementary and integrative health (CIH) care, and an increase in information-seeking behavior focused on CIH. Thus, understanding the quality of CIH information that is available on the internet is imperative. Although there have been a limited number of studies evaluating the quality of websites providing information about specific CIH-related topics, a broad evaluation of CIH websites has not been conducted. This study was designed to fill that gap. We set out to assess website quality in 5 CIH domains: (1) acupuncture, (2) homeopathy, (3) massage, (4) reiki, and (5) yoga. This study aimed to 1) characterize the websites by type and quality; 2) evaluate website characteristics which may affect readers' perceptions, specifically message content, structural features, and presentation style, and 3) investigate the extent to which harms, benefits and purposes of use are stated on websites. This study employed a systematic search strategy to identify websites in each of the target domains to be evaluated. The websites were then classified by type, and a set of checklists focusing on quality, message content, structural features, and presentation style was used to evaluate the websites. Lastly, we performed content analysis to identify harms, benefits, and perceived purposes of use. There were similarities across domains regarding their overall quality and their message content. Across all domains, a high proportion of websites received strong scores in terms of ownership, currency, interactivity and navigability. Scores were more variable concerning authorship, balanced presentation of information and the use of sources of information. However, there were differences regarding their structural features and presentation style. Acupuncture and reiki sites tended to include more external links, and yoga, fewer. There was variation across domains in the extent to which the websites contained domain-specific terminology. Websites tended to provide an extensive list of potential benefits, while reporting of harms was scarce. This is the first study to perform a multidimensional assessment of websites in multiple CIH domains. This review showed that while there are similarities among websites of different CIH domains, there are also differences. The diverse distribution of website types suggests that, regardless of CIH domain, the public encounters information through many different types of media, and it would be useful to consider how the presentation of this content may differ depending on the medium. The characteristics for which variability exist are areas that warrant greater attention from researchers, policy makers, clinicians and patients. There is also a need to better understand how individuals may interact with CIH websites, and to develop tools to assist people to interpret the CIH-related information that they encounter.


Identification of stage-specific polypeptides synthesized during murine preimplantation development.
[35S]Methionine-labeled extracts of mouse ova and preimplantation embryos were analyzed by two dimensional polyacrylamide gel electrophoresis. Of the 400-600 molecular species that have been resolved as distinct spots on autoradiograms of gels for every stage of development from unfertilized eggs to early blastocysts, particular attention has been paid to the identification of 36 of these proteins, each of which is expressed only for a portion of the period under investigation. These molecules are referred to as stage-specific polypeptides and they are biochemical markers of early embryonic development and differentiation.


Triterpenoid Components from Oak Heartwood (Quercus robur) and Their Potential Health Benefits.
For centuries oak wood (Quercus robur) has been used in aging of wines and spirits, which is based on pleasant flavors given to beverages by phenolics transferred to the liquid during the maturation process. Other metabolites, such as triterpenoids, can also be released. Searching for extractable triterpenoids in oak heartwood, 12 new, 1-12, and five known, 13-17, oleanane types were isolated and characterized. Their cytotoxicities were tested against cancer cells (PC3 and MCF-7) and lymphocytes. Breast cancer cells (MCF-7) were the most affected by triterpenoids, with roburgenic acid, 4, being the most active compound (IC50 = 19.7 μM). Selectivity was observed for compounds 1-3, 8, 9, and 16, exhibiting an IC50 > 200 μM against lymphocytes, while active against cancer cells. A galloyl unit attached to the triterpenoid moiety was established as the key feature for such effect. These results highlight the occurrence of triterpenoids in oak heartwood and their relevance for chemoprevention of breast cancer.


Improve optical properties by modifying Ag nanoparticles on a razor clam SERS substrate.
Irregular substrates are inappropriate for enhancing surface enhanced Raman scattering (SERS) due to their poor performances in terms of uniformity, enhancement performance, and polarization characteristics. However, in this work, we purposely employed a natural biological razor clam material with messy and irregular structures to improve the SERS. The rough surface was achieved by magnetron sputtering Ag nanoislands on the prism layer of the razor clams, and the Ag nanoparticles were treated using the method of oil-water interface self-assembly to form relatively uniform structures. Compared to the substrate without Ag nanoparticles, the presented substrate has better reproducibility, polarization-independence, and higher SERS intensity, and the detect limitation of R6G can be decreased from 10-12 M to 10-18 M. The ultrasensitive detection of thiram gives our structures potential for high sensitivity biosensors.


Cervical conization with frozen section before planned hysterectomy.
To report our institutional experience with the accuracy and usefulness of cervical conization with frozen section before planned hysterectomy. One hundred fifty-nine patients who planned to have hysterectomies for or with a concomitant diagnosis of cervical intraepithelial neoplasia (CIN) underwent preliminary cone biopsies with frozen section. The frozen and permanent pathologic diagnoses were compared retrospectively. Detailed analysis was directed at the indications for cone biopsy and the patients who were found to have invasive cancer. Among 108 patients with negative specimens or CIN, the frozen section was accurate within one degree of CIN in 106. Cone biopsy for a positive endocervical curettage, unsatisfactory colposcopy, or discrepant cytology did not contribute to the diagnosis of invasive cancer but did lead to an ultimate diagnosis of CIN III. One of 12 women with a frozen-section diagnosis of microinvasion had deeper invasion on permanent sections. Frozen-section evaluation of a cone biopsy carries a degree of accuracy that enables the surgeon to make an immediate decision about definitive therapy. Exact indications, use during pregnancy, and accuracy for the diagnosis of microinvasion require further study.


Whipple's disease presenting with neurological symptoms in an immunosuppressed patient.
We report an unusual case of Whipple's disease, which remained undiagnosed for several years in a patient being treated with immunosuppressive therapy for many years. The patient presented with a purpuric rash, neurological symptoms, lymphadenopathy and gastrointestinal symptoms. The diagnosis was made by endoscopic biopsy of the duodenum with periodic acid Schiff staining, as well as PCR testing on blood and cerebrospinal fluid. The patient was successfully treated with intravenous ceftriaxone, followed by oral co-trimoxazole for 1 year.


Relation between intima-media thickness and bone mineral density in postmenopausal women: a cross-sectional study.
Controversy exists regarding the relationship between atherosclerosis and osteoporosis. The aim of this study was to determine the relationship between intima-media thickness (IMT) of the common carotid artery (CCA), presence of calcified atherosclerotic plaques and bone mineral density (BMD) evaluated by dual energy X-ray absorptiometry (DXA), in postmenopausal women. Cross-sectional study at Second Internal Medicine Clinic, Cluj-Napoca, Romania. We studied the IMT (left and right CCA and mean IMT) and T-score (lumbar spine L2-L4, femoral neck and total hip) in 100 postmenopausal women (mean age 64.5 years). The presence of calcified atherosclerotic plaque and osteoporotic vertebral fractures was also noted. IMT in the left and right CCA and mean IMT were significantly associated with T-score measured for the lumbar spine L2-L4, femoral neck and total hip, with lower T-score, in the osteoporotic group than in the normal and osteopenic groups (P < 0.05). IMT had a significantly negative correlation with the lumbar spine T-score and femoral neck T-score; and mean IMT with lowest T-score. Mean IMT (P < 0.001), high blood pressure (P = 0.005) and osteoporotic vertebral fractures (P = 0.048) showed statistical significance regarding the likelihood of developing atherosclerotic plaque. In women referred for routine osteoporosis screening, the relationship between CCA, atherosclerosis and osteoporosis can be demonstrated using either cortical or trabecular BMD. Vertebral fractures may be considered to be a likelihood factor for atherosclerotic plaque development.


Mutation Spectrum in the CACNA1A Gene in 49 Patients with Episodic Ataxia.
Episodic ataxia is an autosomal dominant ion channel disorder characterized by episodes of imbalance and incoordination. The disease is genetically heterogeneous and is classified as episodic ataxia type 2 (EA2) when it is caused by a mutation in the CACNA1A gene, encoding the α1A subunit of the P/Q-type voltage-gated calcium channel Cav2.1. The vast majority of EA2 disease-causing variants are loss-of-function (LoF) point changes leading to decreased channel currents. CACNA1A exonic deletions have also been reported in EA2 using quantitative approaches. We performed a mutational screening of the CACNA1A gene, including the promoter and 3'UTR regions, in 49 unrelated patients diagnosed with episodic ataxia. When pathogenic variants were not found by sequencing, we performed a copy number variant (CNV) analysis to screen for duplications or deletions. Overall, sequencing screening allowed identification of six different point variants (three nonsense and three missense changes) and two coding indels, one of them found in two unrelated patients. Additionally, CNV analysis identified a deletion in a patient spanning exon 35 as a result of a recombination event between flanking intronic Alu sequences. This study allowed identification of potentially pathogenic alterations in our sample, five of them novel, which cover 20% of the patients (10/49). Our data suggest that most of these variants are disease-causing, although functional studies are required.


Cellular junctions in a spectrum of human malignant tumors.
Cellular junctions in tumors are often considered a hallmark of epithelial differentiation. However, junctions are also seen in tumors having a different differentiation. This observation prompted us to study cellular junctions in malignant nonepithelial tumors. We found a variety of cellular junctions in such tumors, although the majority were poorly formed. This observation is of importance for diagnostic purposes. We have also tried to clarify the nomenclature of cellular junctions as applied in tumor diagnosis by proposing a systematic categorization of terms in everyday use by pathologists and by referring more extensively to the term paired subplasmalemmal densities (PSD) for non-well-formed junctions.


High-frequency oscillatory ventilation in term and near-term infants with acute respiratory failure: early rescue use.
This study describes a high-frequency oscillatory ventilation (HFOV) protocol for term and near-term infants with acute respiratory failure (ARF) and reports results of its prospective application. Neonates, with gestational age >or= 34 weeks, were managed with HFOV, if required, on conventional ventilation (CV), a fraction of inspired oxygen (F IO(2)) 0.5, and a mean airway pressure > 10 cm H (2)O to maintain adequate oxygenation or a peak inspiratory pressure > 24 cm H (2)O to maintain tidal volume between 5 and 7 mL/kg of body weight. Seventy-seven infants (gestational age, 37 +/- 2,3 weeks), received HFOV after a mean duration of CV of 7.5 +/- 9.7 hours. Arterial blood gases, oxygenation index (OI), and alveolar-arterial difference in partial pressure of oxygen (P AO(2) - Pa O(2)) were recorded prospectively before and during HFOV. There were a rapid and sustained decreases in mean airway pressure (MAP), F IO(2), OI, and P AO(2) - Pa O(2) during HFOV ( P <or= 0.01). Seventy infants (91%) were weaned successfully from HFOV. Seven infants (P AO(2) - Pa O(2) prior to HFOV, 601 +/- 89 mm Hg) were classified as having experienced treatment failure and died from their underlying disease. Treatment failure was associated with lack of improvement in P AO(2) - Pa O(2) at 1 hour of HFOV ( P < 0.01). Early rescue intervention with HFOV is an effective protocol for term and near-term infants with ARF. Failure to improve P AO(2) - Pa O(2) rapidly on HFOV is associated with HFOV failure. Randomized controlled trials are needed to identify benefits of HFOV versus conventional modes of mechanical ventilation.


Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy.
Chagas disease cardiomyopathy is a parasite-driven inflammatory disease to which there are no effective treatments. Here we evaluated the therapeutic potential of N,N-dimethylsphingosine(DMS), which blocks the production of sphingosine-1-phosphate(S1P), a mediator of cellular events during inflammatory responses, in a model of chronic Chagas disease cardiomyopathy. DMS-treated, Trypanosoma cruzi-infected mice had a marked reduction of cardiac inflammation, fibrosis and galectin-3 expression when compared to controls. Serum concentrations of galectin-3, IFNγ and TNFα, as well as cardiac gene expression of inflammatory mediators were reduced after DMS treatment. The gene expression of M1 marker, iNOS, was decreased, while the M2 marker, arginase1, was increased. DMS-treated mice showed an improvement in exercise capacity. Moreover, DMS caused a reduction in parasite load in vivo. DMS inhibited the activation of lymphocytes, and reduced cytokines and NO production in activated macrophage cultures in vitro, while increasing IL-1β production. Analysis by qRT-PCR array showed that DMS treatment modulated inflammasome activation induced by T. cruzi on macrophages. Altogether, our results demonstrate that DMS, through anti-parasitic and immunomodulatory actions, can be beneficial in the treatment of chronic phase of T. cruzi infection and suggest that S1P-activated processes as possible therapeutic targets for the treatment of Chagas disease cardiomyopathy.


Enhanced expression of Gi-protein precedes the development of blood pressure in spontaneously hypertensive rats.
In the present studies we have investigated if the increased expression of Gi alpha proteins reported earlier in heart and aorta from SHR (spontaneously hypertensive rats) is the cause or effect of hypertension. The SHRs at various ages of the development of blood pressure (3-5 days, 2 weeks, 4 weeks and 8 weeks) and their age-matched WKY were used for these studies. The expression of Gi alpha-2 and Gi alpha-3 (inhibitory guanine nucleotide regulatory protein and Gs alpha (stimulatory guanine nucleotide regulatory protein) at protein and mRNA level was determined by immunoblotting and Northern blotting technique using specific antibodies and cDNA probes. The SHR at early ages up to 2 weeks did not show any increase in blood pressure, however it started to go up from 4 weeks. The levels of Gi alpha 2 and Gi alpha 3 at protein and mRNA in heart from SHR were not different in 3-5 days old SHR as compared to WKY (Wistar-Kyoto rats), however, the expression of Gi alpha-2 and Gi alpha-3 protein and mRNA was significantly increased in 2 weeks and older SHR. The mRNA level of the catalytic subunit type V enzyme was significantly decreased in SHR 2 weeks and later ages as compared to their age-matched WKY. On the other hand, the expression of Gs alpha was not different in SHR as compared to WKY at all the ages studied. In addition, the oxotremorine and C-ANF4-23 (a ring deleted analog of atrial natriuretic factor) mediated inhibitions of adenylyl cyclase in hearts and aorta were also significantly enhanced in 2 weeks and older SHRs as compared to WKY rats, whereas, at younger age of SHR (3-5 days old), no change in the percent inhibition of adenylyl cyclase by C-ANF4-23 was observed and oxotremorine was unable to inhibit adenylyl cyclase activity. Furthermore, the basal enzyme activity and the stimulatory responses of isoproterenol, NECA (N-ethylcarboxamideadenosine), glucagon and forskolin on adenylyl cyclase were significantly decreased at all ages of SHR as compared to WKY. These results suggest that the increased expression of genes for Gi alpha-2 and Gi alpha-3, decreased expression of type V enzyme mRNA and decreased cAMP levels precedes the development of blood pressure and may participate in the pathogenesis of hypertension.


The Role of Inflammatory Processes in Occurrence of Left Ventricular Failure in Patients with Chronic Kidney Disease.
Recently, the relationship between increased level of inflammatory mediators and occurrence of left ventricular failure in patients with kidney disease has been suggested. The present study attempted to assess relationship between inflammatory mediators and occurrence of left ventricular failure in patients with chronic kidney disease. This cross-sectional study was performed at Noor and Hazrat Aliasghar hospital in Isfahan between September 2012 to September 2013 on patients aged >19 years that referred for following their chronic kidney disease. Serum level of inflammatory parameters including C-reactive protein (CRP) and Interleukin-6 (IL-6) was measured using spectrophotometer. All patients were also assessed using M-mode echocardiography to determine left ventricular ejection fraction (LVEF). The group with significant reduced LVEF showed lower GFR when compared to the normal LVEF group (40.73 ± 20.61% versus 44.43 ± 17.98%, P = 0.032). Comparing GFR across the three groups with normal LVEF (>55%), with mild LV dysfunction (LVEF: 45 - 55) those with significant LV dysfunction (LVEF < 45%) showed significantly lower GFR level in latter group compared with normal LVEF and mild LV dysfunction group (P = 0.026). Although the level of serum CRP was significantly higher in patients with significant left ventricular failure than other groups (P = 0.018). Inflammatory processes can potentially affect left ventricular function in patients with chronic kidney disease. In this regard, increased level of CRP may be a main factor for predicting severity of left ventricular failure in these patients.


Home-based exercise during preoperative therapy for pancreatic cancer.
Exercise concurrent with neoadjuvant chemotherapy and/or chemoradiation for pancreatic adenocarcinoma (PDAC) may mitigate the decline in function that may occur as a result of the disease or its treatment in the preoperative period. The primary objective of this single-arm prospective trial was to determine adherence to a home-based exercise program administered during preoperative therapy. Twenty patients from a quaternary cancer center with potentially resectable PDAC were enrolled. Patients were prescribed a minimum of 120 min of moderate-intensity exercise weekly: at least 60 min of aerobic exercise and 60 min of resistance exercise. Self-reported exercise was recorded in daily logs. Functional and survey measures were collected upon enrollment, following preoperative therapy, and 1 month after surgery. Fifteen out of 20 patients participated in the program. They reported a mean (standard deviation (SD)) of 98.6 (69.8) min of aerobic exercise weekly and 57.4 (36.0) min of strengthening exercise weekly over a median of 17 weeks (range, 5-35 weeks) of preoperative therapy, for a mean (SD) of 156.0 (64.5) min of total exercise weekly. Eighty percent reported a mean of least 120 min of total exercise weekly during preoperative therapy. Patients with low baseline physical activity based on the International Physical Activity Questionnaire significantly increased their preoperative physical activity (p = .01). There were no adverse events associated with the exercise program. Patients with PDAC will participate in a home-based exercise program of aerobic and strengthening exercise and will increase physical activity, concurrent with preoperative chemotherapy and/or chemoradiation.


Chronic coronary occlusions: age, morphology and chance of reopening.
In chronic coronary occlusions the chance of successful reopening by angioplasty can be judged from the age of the occlusion. Often, however, time since occlusion cannot be accurately assessed. Therefore we determined whether the chance of reopening can be predicted from angiographic morphology. In cineangiograms from 60 consecutive patients with chronic coronary occlusions morphological details in at least two projections were evaluated in relation to the rate of success and the estimated age of occlusion. Morphological features associated with a higher rate of success (type A) were a clearcut proximal stump, absence of side branches at the site of occlusion, absence of bridging collaterals, and only slight filling of the distal part of the vessel. Features associated with a low success rate (type B) were absence of proximal stump, side branches at the site of occlusion, bridging collaterals, and rapid high-contrast filling of the distal part of the vessel. 48/60 (80%) of occlusions could be classified as type A or type B. The success rate was 17/21 (81%) in type A versus 5/27 (18.5%) in type B (P < 0.0002). The estimated age of type B occlusions was higher than that of type A medians 8 and 4 months (P < 0.002). Thus in chronic coronary occlusions the likelihood of successful reopening can be judged in many patients from morphological features.


Relationship between heart rate turbulence and heart rate, heart rate variability, and number of ventricular premature beats in coronary patients.
Heart rate variability (HRV) illustrates regulation of the heart by the autonomic nervous system whereas heart rate turbulence (HRT) is believed to reflect baroreflex sensitivity. The aim of this study was to determine the association between HRT and HRV parameters and the relationship between HRT parameters and heart rate and number of ventricular premature beats (VPBs) used to calculate HRT parameters. In 146 patients (117 males and 29 females; mean age 62 years) with coronary artery disease, a 24-hour ECG Holter monitoring was performed to calculate mean heart rate (RR interval), number of VPBs, time- and frequency-domain HRV parameters and two HRT parameters: turbulence onset (TO) and turbulence slope (TS). Univariate and multivariate regression analyses were performed to evaluate the association between tested parameters. Significant correlation between TS and mean RR interval was observed (r = 0.42; p < 0.001), while no association for TO vs. RR interval was found. TS values were significantly higher in patients with less than 10 VPBs/24 hours than in patients with more frequent VPBs. Significant associations between HRT and HRV parameters were found with TS showing stronger correlation with HRV parameters than TO (r value ranging from 0.35 to 0.62 for TS vs. -0.16 to -0.38 for TO). HRT parameters correlate strongly with HRV parameters indicating that HRT should be considered as a reflection of both baroreceptors response and overall autonomic tone. Heart rate dependence of turbulence slope indicates the need to adjust this parameter for heart rate.


[Comparison of Quality of Life of Patients with Papillary Thyroid Microcarcinoma Treated by Different Modalities].
Objective To compare the health-related quality of life(HRQoL)of patients with papillary thyroid microcarcinoma(PTMC)treated by different modalities. Methods The PTMC patients after treatment who came to our department for follow-up from October to December in 2019 were enrolled and assigned into three groups according to treatment modalities:radiofrequency ablation(RFA)group(n=80), hemithyroidectomy(HT)group(n=34), and total thyroidectomy(TT)group(n=35).All patients completed three scales:short form 36-item health survey(SF-36), thyroid cancer-specific health-related quality of life questionnaire(THYCA-QoL), and fear of progression questionnaire-short form(FoP-Q-SF).Multivariate linear regression analysis was employed to adjust for confounders and the quality of life scores were compared among the three treatment modalities. Results In the SF-36, physical component summary(PCS)(P=0.006, P=0.033)and role-physical(RP)(P=0.003, P=0.001)scores of patients in the RFA and HT groups were significantly higher than those in the TT group, whereas PCS(P=1.000)and RP(P=1.000)showed no significant difference between the RFA group and the HT group.In addition, the mental component summary(MCS)score in RFA group was higher than that in TT group(P=0.034).The THYCA-QoL demonstrated that the patients in TT group complained more about scar than the patients in HT(P=0.003)and RFA(P<0.001)groups, and the patients in the RFA group complained less about weight gain than those in the HT(P=0.028)and TT(P<0.001)groups.In the FoP-Q-SF, the scores of the quality of life of patients concerned about disease progression had no significant difference among the three groups(P> 0.05).Conclusion Compared with traditional open surgery, ultrasound-guided RFA has unique advantages in improving patients' quality of life and can be used as an alternative to open surgery for PTMC.


A novel splice variant of human XRN2 gene is mainly expressed in blood leukocyte.
The XRN2 gene (XRN2a) is the human homologue of the Saccharomyces cerevisiae RAT1 gene, which encodes a nuclear 5'-->3' exoribonuclease, and is essential for RNA metabolism and cell viability. Xrn2p/Rat1p, product of XRN2/RAT1 gene, functions in the mRNA degradation and processing of rRNAs and small nucleolar RNAs (snoRNAs) in the nucleus. Here we describe the cloning and characterization of a novel splice variant of the human XRN2 gene (XRN2b). The 3271-bp cDNA encodes a putative protein with 907 amino acid residues, which shares high homology with mouse DHM1 protein. RT-PCR analysis showed that XRN2b was mainly expressed in blood leukocyte tissue, while XRN2a was detected in several human tissues and in human tumor tissues.


Objective threshold estimation and measurement of the residual background noise in auditory evoked potentials of goldfish.
A survey of papers using auditory evoked potentials (AEPs) published over the last 10 years (Table I) demonstrates that most AEP studies in animals have used subjective methods for auditory threshold determination. Subjective methods greatly reduce the value of statistical hypothesis testing and jeopardize tests of hypothetical experimental group differences in hearing sensitivity. Correspondingly, many attempts have been made to develop objective threshold determination methods, but these have not been used widely. Further, they seldom include an appreciation of the effects of residual noise in the AEP. In this study, AEPs evoked by tonal and noise stimuli in goldfish (Carassius auratus) were recorded and the residual background noise was measured and analyzed in detail. High variability was found in residual noise, but can be effectively controlled with a simple modification of averaging routines. Considerable interobserver disagreements were found using subjective threshold estimation. An objective method of threshold determination was developed based on comparison between AEP amplitude and controlled residual noise, using a signal detection theory approach to set specific threshold criteria. The usefulness of AEP in hypothesis testing for auditory function requires more control over residual background noise amplitudes and the use of objective threshold determination techniques.


Overexpression of NR4A2 alleviates renal and myocardial injury in diabetes nephropathy rats through the HDAC11/SPRY1 pathway.
Diabetic nephropathy (DN) remains the most prevalent cause of end-stage renal disease. Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a nuclear receptor with unique physiological characteristics. This study explored the molecular mechanism of NR4A2 in renal and cardiac functions of DN rats. A rat model of DN was established by intraperitoneal injection of streptozocin. NR4A2, histone deacetylase 11 (HDAC11), and sprouty 1 (SPRY1) expressions were detected. The fasting blood glucose (FBG), urinary albumin (UAlb), serum creatinine (Cr), and blood urea nitrogen (BUN) were determined. The pathological injury of renal and myocardial tissues was evaluated. The mitral early to late diastolic flow velocity ratio (E/A ratio), left ventricular ejection fraction (LVEF), left ventricular systolic function (LVSF), left ventricular internal dimension systole (LVIDs), and left ventricular internal diameter diastole (LVIDd) were tested, and the levels of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were examined. The enrichment of NR4A2 in HDAC11 promoter and enrichment of H3K27 acetylation in SPRY1 promoter were measured. NR4A2 and SPRY1 were downregulated while HDAC11 was upregulated in renal and myocardial tissues of DN rats. NR4A2 overexpression reduced FBG, UAlb, Cr, and BUN, alleviated pathological injury of renal and myocardial tissues, elevated the E/A ratio, LVEF, and LVFS, but reduced LVIDs, and decreased serum cTnI and CK-MB. NR4A2 depressed HDAC11 expression by binding to the HDAC11 promoter. HDAC11 repressed SPRY1 transcription by suppressing the H3K27ac level. HDAC11 overexpression or SPRY1 inhibition reversed the alleviating effect of NR4A2 overexpression on DN rats. NR4A2 was poorly expressed in DN rats. NR4A2 overexpression suppressed HDAC11 expression by binding to the HDAC11 promoter and enhanced SPRY1 transcription by enhancing H3K27 acetylation, thereby alleviating the renal and myocardial injury of DN rats.


The effects of statin therapy on brain tumors, particularly glioma: a review.
Brain tumors account for less than 2% of all malignancies. However, they are associated with the highest morbidity and mortality rates among all solid tumors. The most common malignant primary brain tumors are glioma or glioblastoma (GBM), which have a median survival time of about 14 months, often suffer from recurrence after a few months following treatment, and pose a therapeutic challenge. Despite recent therapeutic advances, the prognosis for glioma patients is poor when treated with modern therapies, including chemotherapy, surgery, radiation, or a combination of these. Therefore, discovering a new target to treat brain tumors, particularly glioma, might be advantageous in raising progression-free survival and overall survival (OS) rates. Statins, also known as competitive HMG-CoA reductase inhibitors, are effective medications for reducing cholesterol and cardiovascular risk. The use of statins prior to and during other cancer treatments appears to enhance patient outcomes according to preclinical studies. After surgical resection followed by concurrent radiation and treatment, OS for patients with GBM is only about a year. Statins have recently emerged as potential adjuvant medications for treating GBM due to their ability to inhibit cell growth, survival, migration, metastasis, inflammation, angiogenesis, and increase apoptosis in-vitro and in-vivo studies. Whether statins enhance clinical outcomes, such as patient survival in GBM, is still debatable. This study aimed to explore the effects of statin therapy in the context of cancer treatment, with a particular focus on GBM.


The 36th Harry G. Armstrong Lecture. The limits of human performance: a point of view.
The author describes his experience over the past 20 years in the Pentagon environment advocating greater understanding of the importance of human performance and its limits by military technologist. The human performance research community is a key player in the effort to reverse the present marginalization of the human in a technology-dominated world. The author suggests specific initiatives the community could take to strengthen this effort and reposition itself for a greater leadership role in science and technology of the 21st century.


[A case of multiple bone and joint tuberculosis which had been misdiagnosed as the rheumatoid arthritis and treated with prednisolone for eleven months].
A 34-year-old man had a multiple arthralgia for about eleven months. The swelling of his right wrist and foot had appeared in the dorsal side, and he had been misdiagnosed as the rheumatoid arthritis. He was treated with prednisolone in the dosages of 2.5 mg per day for one month, and 10 mg per day for ten months. When he admitted to our hospital, the bone X-ray examinations of the wrist and foot revealed the marked atrophy and destruction of the carpal and tarsal bones. The aspiration fluid from the swelling around his wrist and foot was positive for acid-fast bacilli on smear and Mycobacterium tuberculosis was found on culture. He was treated with isoniazid, rifampicin, ethambutol and pyrazinamide, however, these medication was not adequately effective to his complications of tuberculous arthritis. Curettage, irrigation and synovectomy of his right carpal and tarsal bone were performed in order to control his bone and joint infection. He recovered from his arthritis and tenosynovitis after these operations. The clinical practitioners should not omit tuberculosis from the differential diagnosis of persistent osteoarthralgia.


The interactions of aerosol and planetary boundary layer over a large city in the Mongolian Plateau.
The interactions of aerosol and planetary boundary layer (PBL) play a crucial role in deteriorating the air quality in vast urban agglomeration areas in eastern China. However, there remains a lacking of report regarding their performance in the hazy events in Mongolian Plateau cities in northern China. In this study, half-month (01-16 January 2020) physical and material datasets of the PBL measured by multi instrumentations mounted in downtown Hohhot, a largest Mongolian Plateau city, are statistically analyzed. Results demonstrate that the aerosol-PBL feedback is of particular importance in promoting the hazy outbreak and the statistical relationship follows PBLH = -76.14 × ln(PM2.5) + 820.61. The non-linear fitting implies that there exists a potential threshold of 76.14 μg m-3 for PM2.5, below which the PBLH decrease rapidly along with the increasing of air pollutants, defined as strong aerosol-PBL interaction phase, while beyond which there is minimal decrease for PBLH even when PM reaches to a high value, i.e., the hazy accumulation phase. Using a large-eddy simulation model named as Dutch Atmospheric Large-Eddy Simulation (DALES) initialized with the synergetical observations in a representative hazy process in 11 January 2020, we found that the DALES is effective to capture the diurnal PBLH in this region. The existence of atmospheric aerosols is essential for lowering PBLH by 51.4 % from 1090 m of clean scenario to 530 m of polluted condition, postponing the development time, and advancing the afternoon lapse time. The enhancement of aerosol absorption ability strengthens the aerosol heating rate, thereby weakening the sensible heat flux, and inhibiting the development of PBLH. While opposite elevation on PBLH is found for the scattering aerosols. These findings highlight the importance of aerosol-PBL interaction in motivating the hazy episodes in Mongolian Plateau cities, which provide scientific references for the local policy-making towards pollution reductions in future.


Long-term acclimation to reciprocal light conditions suggests depth-related selection in the marine foundation species Posidonia oceanica.
Phenotypic differences among populations of the same species reflect selective responses to ecological gradients produced by variations in abiotic and biotic factors. Moreover, they can also originate from genetic differences among populations, due to a reduced gene flow. In this study, we examined the extent of differences in photo-acclimative traits of Posidonia oceanica (L.) Delile clones collected above and below the summer thermocline (i.e., -5 and -25 m) in a continuous population extending along the water depth gradient. During a reciprocal light exposure and subsequent recovery in mesocosms, we assessed degree of phenotypic plasticity and local adaptation of plants collected at different depths, by measuring changes in several traits, such as gene expression of target genes, photo-physiological features, and other fitness-related traits (i.e., plant morphology, growth, and mortality rates). Samples were also genotyped, using microsatellite markers, in order to evaluate the genetic divergence among plants of the two depths. Measures collected during the study have shown a various degree of phenotypic changes among traits and experimental groups, the amount of phenotypic changes observed was also dependent on the type of light environments considered. Overall plants collected at different depths seem to be able to acclimate to reciprocal light conditions in the experimental time frame, through morphological changes and phenotypic buffering, supported by the plastic regulation of a reduced number of genes. Multivariate analyses indicated that plants cluster better on the base of their depth origin rather than the experimental light conditions applied. The two groups were genetically distinct, but the patterns of phenotypic divergence observed during the experiment support the hypothesis that ecological selection can play a role in the adaptive divergence of P. oceanica clones along the depth gradient.


Formation of 2,5-dimethyl-4-hydroxy-3(2H)-furanone through methylglyoxal: a Maillard reaction intermediate.
The caramel-like aroma compound, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) was quantified and verified by HPLC and GC-MS in the Maillard reaction based on methylglyoxal (MG). The reaction was performed in the 0.5 M phosphate buffer by heating MG with or without either glycine or cysteine at 120 degrees C for 1 h. MG alone or MG with cysteine could produce increased level of DMHF with pH increased, whereas MG with glycine had contrary trend. Experiments using a 1:1 mixture of [(13)C6]glucose and [(12)C6]glucose indicate that in the presence of glycine or cysteine, glucose skeleton kept intact during DMHF formation since a 1:1 mixture of [(13)C6]DMHF and [(12)C6]DMHF was formed. Acetylformoin was detected in the glucose with amino acid reaction system as a precursor of DMHF, while in the MG reaction systems, acetylformoin could not be identified. It is suggested different pathways of DMHF formation via MG and glucose.


The PD-1/PD-L1 pathway is induced during Borrelia burgdorferi infection and inhibits T cell joint infiltration without compromising bacterial clearance.
The Lyme disease bacterial pathogen, Borrelia burgdorferi, establishes a long-term infection inside its mammalian hosts. Despite the continued presence of the bacteria in animal models of disease, inflammation is transitory and resolves spontaneously. T cells with limited effector functions and the inability to become activated by antigen, termed exhausted T cells, are present in many long-term infections. These exhausted T cells mediate a balance between pathogen clearance and preventing tissue damage resulting from excess inflammation. Exhausted T cells express a variety of immunoinhibitory molecules, including the molecule PD-1. Following B. burgdorferi infection, we found that PD-1 and its ligand PD-L1 are significantly upregulated on CD4+ T cells and antigen presenting cell subsets, respectively. Using mice deficient in PD-1, we found that the PD-1/PD-L1 pathway did not impact bacterial clearance but did impact T cell expansion and accumulation in the ankle joint and popliteal lymph nodes without affecting B cell populations or antibody production, suggesting that the PD-1/PD-L1 pathway may play a role in shaping the T cell populations present in affected tissues.


Leptin downregulates aggrecan through the p38-ADAMST pathway in human nucleus pulposus cells.
The mechanistic basis of obesity-associated intervertebral disc degeneration (IDD) is unclear. Aberrant expression of aggrecan and its degrading enzymes ADAMTS-4 and ADAMTS-5 is implicated in the development of IDD. Here, we investigated the effect of leptin, a hormone with increased circulating levels in obesity, on the expression of aggrecan and ADAMTSs in primary human nucleus pulposus (NP) cells. Real-time PCR and Western blots showed that leptin increased the mRNA and protein expression of ADAMTS-4 and ADAMTS-5 and reduced the level of aggrecan in NP cells, accompanied by a prominent induction of p38 phosphorylation. Treatment of NP cells with SB203580 (a p38 inhibitor) abolished the regulation of aggrecan and ADAMTSs by leptin. Knockdown of ADAMTS-4 and ADAMTS-5 by siRNAs also attenuated the degradation of aggrecan in leptin-stimulated NP cells. To conclude, we demonstrated that leptin induces p38 to upregulate ADAMTSs and thereby promoting aggrecan degradation in human NP cells. These results provide a novel mechanistic insight into the molecular pathogenesis of obesity-associated IDD.


Expression of cholesterol synthesis and steroidogenic markers in females of the Chinese brown frog (Rana dybowskii) during prespawning and prehibernation.
The oviduct of the Chinese brown frog (Rana dybowskii) expands in prehibernation rather than in prespawning, which is one of the physiological phenomena that occur in the preparation for hibernation. Steroid hormones are known to regulate oviductal development. Cholesterol synthesis and steroidogenesis may play an important role in the expansion of the oviduct before hibernation. In this study, we investigated the expression patterns of the markers that are involved in the de novo steroid synthesis pathway in the oviduct of R. dybowskii during prespawning and prehibernation. According to histological analysis, the oviduct of R. dybowskii contains epithelial cells, glandular cells, and tubule lumens. During prehibernation, oviductal pipe diameter and weight were significantly larger than during prespawning. 3-Hydroxy-3-methylglutaryl CoA reductase (HMGCR), low-density lipoprotein receptor (LDLR), steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic factor 1 (SF-1) were detected in epithelial cells in prehibernation and glandular cells during prespawning. HMGCR, LDLR, StAR, and P450scc protein expression levels were higher in prehibernation than during prespawning, but the SF-1 protein expression level did not significantly differ. HMGCR, LDLR, StAR, P450scc (CYP11A1), and SF-1 (NR5A1) mRNA expression levels were significantly higher in prehibernation compared with prespawning. The transcriptome results showed that the steroid synthesis pathway was highly expressed during prehibernation. Existing results indicate that the oviduct is able to synthesize steroid hormones using cholesterol, and that steroid hormones may affect the oviductal functions of R. dybowskii.


[An interesting case of defective HLA phenotype].
In a 27 years old man whose parents had HLA phenotypes A 9/B 7, Bw 16 and Al/B 17, B 18 only HLA-B 18 could be reliably identified in lymphocytes by means of microlymphocytotoxic tests. It is probable that HLA-Bw 16 was also present in the lymphocytes of this test person. Even by applying the neutralisation test, the HLA antigens A 1 and a 9 could not be detected in the test person's serum. The cause for the existence of the defective HLA phenotype is discussed.


Is celiac disease an autoimmune disorder?
Celiac disease, which results from an immune reaction to ingested cereal gluten proteins, has several autoimmune features. In particular, celiac disease patients produce highly disease specific IgA and IgG autoantibodies to tissue transglutaminase when they are on a gluten-containing diet, and they have small intestinal intraepithelial lymphocytes which can mediate direct cytotoxicity of enterocytes expressing MIC molecules in an antigen non-specific manner. Similar to typical autoimmune disorders, celiac disease has a multifactorial aetiology with complex genetics, and several autoimmune diseases are commonly presented by patients with celiac disease. Much has been learned about the immunology of celiac disease in recent years, and there is overwhelming evidence that the immune response to gluten is central to the pathogenesis. In light of this, the many autoimmune phenomena associated with celiac disease are thought-provoking, and they challenge us to rethink the boundaries between autoimmunity and immunopathology.


Incidental carcinoma of the prostate: an improved modality for early detection.
In a prospective study 140 unselected patients with clinical evidence of benign adenoma of the prostate were resected via a transurethral approach. Pathohistological analysis was done according to selective criteria for tissue sampling. 16 incidental carcinomas (T0; 11.4%) were detected. In a retrospective analysis 244 patients were operated on by the same method compared with 326 patients with conventional transurethral resection. T0 tumors were found in 11.5 versus 5.2% of the patients. The increase in the incidence of T0 tumors was significant (p less than 0.004). We recommend this modality as a simple method to optimize early detection of T0 tumors in the transurethral resection specimens.


Yeast to Study Human Purine Metabolism Diseases.
Purine nucleotides are involved in a multitude of cellular processes, and the dysfunction of purine metabolism has drastic physiological and pathological consequences. Accordingly, several genetic disorders associated with defective purine metabolism have been reported. The etiology of these diseases is poorly understood and simple model organisms, such as yeast, have proved valuable to provide a more comprehensive view of the metabolic consequences caused by the identified mutations. In this review, we present results obtained with the yeast Saccharomyces cerevisiae to exemplify how a eukaryotic unicellular organism can offer highly relevant information for identifying the molecular basis of complex human diseases. Overall, purine metabolism illustrates a remarkable conservation of genes, functions and phenotypes between humans and yeast.


ScatterJ: An ImageJ plugin for the evaluation of analytical microscopy datasets.
We present ScatterJ, an ImageJ plugin that allows for extracting qualitative as well as quantitative information from analytical microscopy datasets. A large variety of analytical microscopy methods are used to obtain spatially resolved chemical information. The resulting datasets are often large and complex, and can contain information that is not obvious or directly accessible. ScatterJ extends and complements existing methods to extract information on correlation and colocalization from pairs of species-specific or element-specific maps. We demonstrate the possibilities to extract information using example datasets from biogeochemical studies, although the plugin is not restricted to this type of research. The information that we could extract from our existing data helped to further our understanding of biogeochemical processes such as mineral formation or heavy metal sorption. ScatterJ can be used for a variety of different two-dimensional (2D) and three-dimensional (3D) datasets such as energy-dispersive X-ray spectroscopy maps, 3D confocal laser scanning microscopy maps, and 2D scanning transmission X-ray microscopy maps.


Nerve function restoration following targeted muscle reinnervation after varying delayed periods.
Targeted muscle reinnervation has been proposed for reconstruction of neuromuscular function in amputees. However, it is unknown whether performing delayed targeted muscle reinnervation after nerve injury will affect restoration of function. In this rat nerve injury study, the median and musculocutaneous nerves of the forelimb were transected. The proximal median nerve stump was sutured to the distal musculocutaneous nerve stump immediately and 2 and 4 weeks after surgery to reinnervate the biceps brachii. After targeted muscle reinnervation, intramuscular myoelectric signals from the biceps brachii were recorded. Signal amplitude gradually increased with time. Biceps brachii myoelectric signals and muscle fiber morphology and grooming behavior did not significantly differ among rats subjected to delayed target muscle innervation for different periods. Targeted muscle reinnervation delayed for 4 weeks can acquire the same nerve function restoration effect as that of immediate reinnervation.


The rationale for adopting current international breastfeeding guidelines in South Africa.
Current international breastfeeding guidelines recommend exclusive breastfeeding for 6 months, followed by the appropriate and adequate introduction of complementary foods at 6 months, with continued breastfeeding for 2 years and beyond. This guideline is based on evidence to support exclusive and extended breastfeeding as the optimal method of feeding infants and young children. Not only do these breastfeeding practices meet the nutrition needs of infants and children for optimal growth and development, but they also offer a host of other health and socio-economic benefits at all levels of society. The poor breastfeeding rates and increase in infant and child morbidity and mortality in South Africa have led to increased prioritized attention towards the promotion, protection and support of breastfeeding. In 2000, the National Department of Health formally adopted the international breastfeeding guidelines for exclusive and extended breastfeeding practices. Therefore, it remains a priority to implement these guidelines in all current and future breastfeeding programmes and interventions, including the South African paediatric food-based dietary guidelines.


In vitro assessment of physiological traits and ROS detoxification pathways involved in tolerance of Damask rose genotypes under salt stress.
Rosa damascena is one of the most important medicinal and ornamental plants in Iran which is tolerant of salinity to some extent. However, the selection of genotypes that are more tolerant to salinity will influence on Damask cultivation in salt stress-affected regions. For this purpose, a factorial experiment in a completely randomized design with three replicates was performed under in vitro conditions on four Damask rose genotypes (Atashi, Bi-Khar, Chahar-Fasl and Kashan) at 5 concentrations of NaCl (0, 25, 50, 75, and 100 mM), and the physico-chemical traits were measured 14 and 28 days after treatment.The results showed that Atashi genotype with high levels of Chl a, Chl b, total Chl content, carotenoids, relative leaf water content, proline, total soluble protein, TPC, TFC, TAA, and the highest increase in the activity of antioxidant enzymes such as GPX, APX, CAT, SOD, and POD as well as the lowest amount of hydrogen peroxide showed a better protection mechanism against oxidative damage than the other three genotypes (Bi-Khar, Chahar-Fasl and Kashan) in the 14th and 28th days by maintaining the constructive and induced activities of antioxidant enzymes, it was shown that Bi-Khar genotype had moderate tolerance and Kashan and Chahar-Fasl genotypes had low tolerance to salinity stress. In vitro selection methods can be used effectively for salt tolerant screening of Damask rose genotypes, although the same experiment should be conducted in open filed cultures to verify the in vitro experimental results.


Relationship of ultrasonographic findings with synovial angiogenesis modulators in different forms of knee arthritides.
Angiogenesis is controlled by a variety of angiogenesis stimulators and inhibitors. The increased power Doppler (PD) signals determined by ultrasonography is an indirect marker of synovial vascularity in arthritis. We aimed to investigate relationship between ultrasonographic findings and synovial angiogenesis modulators. Thirteen Behcet's disease (BD), 15 spondyloarthropathy, 21 rheumatoid arthritis (RA), and 15 osteoarthritis (OA) patients with knee arthritis were included. Cumulative effusion, synovial hypertrophy, and PD signal scores were calculated in arthritic joints. In synovial fluid samples, angiogenesis inhibitors (angiostatin, thrombospondin-1, and endostatin) and stimulators [bFGF (basic fibroblast growth factor), angiopoietin-1] were studied. The comparisons between groups were made by Kruskal-Wallis test, and correlation analysis was calculated with Pearson and Spearman tests. Effusion scores were significantly higher in inflammatory arthritis than in OA. Synovial hypertrophy scores were higher in RA and spondylarthritis than in OA and BD. PD scores were not different between the groups. Synovial angiostatin and bFGF levels were significantly higher in patients with inflammatory arthritis than in OA. Cumulative effusion scores were positively correlated with angiopoietin-1, angiostatin, and bFGF and negatively correlated with thrombospondin-1 levels. Synovial hypertrophy scores were positively correlated with angiostatin and bFGF levels and negatively correlated with thrombospondin-1. No correlation was found between PD scores and modulators of angiogenesis. In large joints like knee, detecting PD signals alone was not sufficient to assess the angiogenesis. However, cumulative activity scores were positively correlated with angiogenesis stimulators. Therefore, when investigating the angiogenesis, PD technique should be added to gray-scale examinations.


Wearable Motion Capture: Reconstructing and Predicting 3D Human Poses From Wearable Sensors.
Reconstructing and predicting 3D human walking poses in unconstrained measurement environments have the potential to use for health monitoring systems for people with movement disabilities by assessing progression after treatments and providing information for assistive device controls. The latest pose estimation algorithms utilize motion capture systems, which capture data from IMU sensors and third-person view cameras. However, third-person views are not always possible for outpatients alone. Thus, we propose the wearable motion capture problem of reconstructing and predicting 3D human poses from the wearable IMU sensors and wearable cameras, which aids clinicians' diagnoses on patients out of clinics. To solve this problem, we introduce a novel Attention-Oriented Recurrent Neural Network (AttRNet) that contains a sensor-wise attention-oriented recurrent encoder, a reconstruction module, and a dynamic temporal attention-oriented recurrent decoder, to reconstruct the 3D human pose over time and predict the 3D human poses at the following time steps. To evaluate our approach, we collected a new WearableMotionCapture dataset using wearable IMUs and wearable video cameras, along with the musculoskeletal joint angle ground truth. The proposed AttRNet shows high accuracy on the new lower-limb WearableMotionCapture dataset, and it also outperforms the state-of-the-art methods on two public full-body pose datasets: DIP-IMU and TotalCaputre.


Murine multicolor banding.
Multicolor banding approach, first introduced for human chromosomes only, was established as an optimal approach for karyotyping of murine chromosomes. Here we present the established mcb probe sets for all murine autosomes and the X-chromosome and review their potential application.


[Rhabdomyolysis caused by thiazid-induced hypokalaemia].
This case report presents a 38-year-old woman who developed rhabdomyolysis following severe hypokalaemia due to a thiazid diuretic. Rhabdomyolysis is a severe condition with an incidence of 28% in hypokalaemic patients. It should be considered to measure concentrations of S-myoglobin and S-creatine kinase in severe cases of hypokalaemia. Thiazid diuretics can cause severe hypokalaemia with life-threatening complications and monitoring of S-potassium is advised during therapy.


Predicting quality of work life on nurses' intention to leave.
The purpose of this study was to explore the relationship between quality of work life (QWL) and nurses' intention to leave their organization (ITLorg). A descriptive cross-sectional survey design was conducted using purposive sampling of 1,283 nurses at seven hospitals in Taiwan. Data were collected from March to June 2012. Three questionnaires, including the Chinese version of the Quality of Nursing Work Life scale (C-QNWL), a questionnaire of intention to leave the organization, and a demographic questionnaire, with two informed consent forms were delivered to the nurses at their workplaces. Descriptive data, Pearson's correlations, and the ordinal regression model were analyzed. Over half (52.5%) of nurses had ITLorg. Seven QWL dimensions were significantly negatively correlated with ITLorg (r = -0.17 to -0.37, p < .01). Significant predictors (p < .05) of ITLorg (the pseudo R(2) = 0.282) were being single, having a diploma or lower educational level, working in a nonteaching hospital. Four of the QWL dimensions--supportive milieu with job security and professional recognition, work arrangement and workload, work or home life balance, and nursing staffing and patient care--were also predictors of ITLorg. Three QWL dimensions were not predictors of ITLorg. This study showed that individual-related variables (being single, having a diploma or lower educational level), a work-related variable (working at a nonteaching hospital), and the four QWL dimensions play a significant role in nurses' ITLorg. After the QWL dimensions were added to the regression, the variance explained by the model more than doubled. To reduce nurses' ITLorg, nursing administrators may offer more focused interventions to improve the supportive milieu with job security and professional recognition, work arrangement and workload, work or home life balance, and nursing staffing and patient care.


[Abnormalities of cardiovascular baroreflex control in renal failure and cardiac insufficiency. Experimental study and brief critical review of the literature].
We attempted to determine the relevance and relative prevalence of autonomic dysfunction in 7 patients with end-stage renal disease (ESRD) but no heart disease, 8 patients with left ventricular dysfunction (LVD) with no renal disease and 8 patients with ESRD + LVD. In each group, the assessment of autonomic function and location of the lesion was performed by using the baroreflex sensitivity tests, based upon heart rate (ie Valsalva, deep breathing, lying to standing) to study the parasympathetic system as well as based upon blood arterial pressure (ie standing and sustained handgrip) to evaluate the sympathetic system. The same tests were performed in 7 healthy volunteers enrolled as control group. Separate studies were performed on the efferent parasympathetic arc (atropine test) and the efferent sympathetic arc (cold pressor test). There was evidence of parasympathetic damage in 100% of ESRD patients, in 87.5% of ESRD + LVD patients, and in 62.5% of LVD. Only 1 of ESRD patients showed defective response to atropine whereas the remaining had a normal response, suggesting an afferent lesion alone. No abnormalities were found in the response to cold pressor test, thereby suggesting a lack of involvement of the efferent sympathetic arc. The response to handgrip was higher in LVD patients.(ABSTRACT TRUNCATED AT 250 WORDS)


The expression pattern and potential functions of PHB in the spermiogenesis of Phascolosoma esculenta.
Prohibitin (PHB) is a ubiquitous, evolutionarily conserved protein that is mainly localized in the inner mitochondrial membrane and exerts various mitochondrial functions. Here, we first cloned the phb gene from P. esculenta. The Pe-PHB protein has high homology and a similar protein structure to that of other animals, and it can be divided into the N-terminal hydrophobic/transmembrane domain, SPFH domain, and C-terminal coiled-coil domain. The Pe-phb gene is widely expressed, and the gene expression of phb is highest in coelomic fluid where spermiogenesis occurs, indicating a specific function in the coelom. We further observed continuous expression of the phb gene and localization of PHB proteins in mitochondria during spermiogenesis, indicating that PHB, as a mitochondrial component, may play a role during this process via its mitochondrial function. In addition, ubiquitination of mitochondria was detected, and the PHB signal was co-localized with the poly-ubiquitin signal during spermiogenesis. Mature sperm also showed ubiquitination of mitochondria and PHB. Therefore, PHB may be a substrate of poly-ubiquitin to regulate the ubiquitination of mitochondria and even subsequent elimination during P. esculenta spermiogenesis, and it has a potential role in guaranteeing the maternal inheritance of mitochondria. Taken together, these results support the hypothesis that PHB participates in the spermiogenesis of P. esculenta by maintaining the normal function of mitochondria and regulating the degradation of mitochondria.


Hydrolysis of phospholipids by a lysosomal enzyme.
The phospholipid-hydrolyzing activity of rat liver lysosomes has been studied. These lysosomes contain a phospholipase that cleaves both fatty acid ester linkages of lecithin and of phosphatidyl ethanolamine and releases free fatty acids from both positional isomers of lysolecithin. The enzyme does not require calcium for maximum activity, and is inhibited by diethyl ether and sodium deoxycholate. Mercuric ions and cetyltrimethyl ammonium bromide also inhibit the hydrolysis. Compared with lipase activity, this enzyme is relatively stable to heat. The specific activity of the hydrolysis of lecithin by the lysosomal enzyme is considerably higher than those reported for mitochondrial and microsomal phospholipases. The enzyme resembles other hydrolases of the lysosome in that it has an acid pH optimum (pH 4.5). This enzymic activity is present in both the lysosomal soluble enzyme fraction and in the lysosomal membrane fraction. The enzyme may participate in the intracellular digestion of mitochondria that is carried out by the intact lysosome in vivo. Localized inflammation and changes in vascular permeability following tissue damage could be catalyzed by this phospholipase.


Target selection by gaze pointing and manual confirmation: performance improved by locking the gaze cursor.
Eye movement-based human-computer interactions are emerging in diverse scenarios. When selecting targets on a user interface, the method of combining fast gaze pointing with reliable manual action is becoming increasingly popular. However, this method suffers from noise in gaze pointing caused by eye jitters and users' habitual early move-away of gaze before manual actions. Here we propose a novel solution to mitigate these problems by locking the gaze cursor at the target for imminent manual selection. We compared this gaze-lock cursor with a conventional gaze cursor in a typing task with varying key sizes and key gaps. Results show that typing performance was significantly better with larger key size and gap. More importantly, the gaze-lock cursor significantly increased speed and decreased errors when compared to a conventional gaze cursor. Our findings demonstrate that the gaze-lock cursor is a promising tool for gaze interactions involving frequent target selections. Practitioner summary: Target selection by gaze pointing and manual confirmation suffers from eye jitters and users' habitual early move-away of gaze before manual actions. The performance of this method can be improved by applying the gaze-lock cursor we proposed, increasing target size or increasing the target gap. Abbreviations: WTC: warping to target center; ALCM: automatic lock of cursor movement; LCD: liquid crystal display; EWMA: exponential weighted moving average; ER: error rate; ET: execution time; ED: edit distance; CV: coefficients of variation; ANOVA: analysis of variance; GUIs: general user interfaces.


[Structure kinetic model of Maackia amurensis cells in suspension culture].
A structure kinetic model was established for describing the relationship among cell growth, genistein formation and substrate utilization in suspension culture of Maackia amurensis. In this model, sucrose uptake, structure components production, intermediate matter changes, cell respiration loss and secondary metabolite (genistein) production were all predicted. The parameter sensitivity test was indicated that intermediate matter self-catalysis rate constant (k(b1)), structure component synthesis rate constant (k(b2)) and secondary metabolite synthesis rate constant (k(p)) were the most sensitive parameters for this model. If k(b1), k(b2) or k(p) are changed by 10%, the range of the aim function value would be changed by 12.8%, 4.61% and 2.54%, respectively. Adjustment of the other parameters only aroused a change of less than 0.5% in the aim function value. The predicted values were in good agreement with those obtained experimentally.


A machine-learned analysis suggests non-redundant diagnostic information in olfactory subtests.
The functional performance of the human sense of smell can be approached via assessment of the olfactory threshold, the ability to discriminate odors or the ability to identify odors. Contemporary clinical test batteries include all or a selection of these components, with some dissent about the required number and choice. Olfactory thresholds, odor discrimination and odor identification scores were available from 10,714 subjects (3662 with anomia, 4299 with hyposmia, and 2752 with normal olfactory function). To assess, whether the olfactory subtests confer the same information or each subtest confers at least partly non-redundant information relevant to the olfactory diagnosis, we compared the diagnostic accuracy of supervised machine learning algorithms trained with the complete information from all three subtests with that obtained when performing the training with the information of only two or one subtests. The training of machine-learned algorithms with the full information about olfactory thresholds, odor discrimination and odor identification from 2/3 of the cases, resulted in a balanced olfactory diagnostic accuracy of 98% or better in the 1/3 remaining cases. The most pronounced decrease in the balanced accuracy, to approximately 85%, was observed when omitting olfactory thresholds from the training, whereas omitting odor discrimination or identification was associated with smaller decreases (balanced accuracies approximately 90%). Results support partly non-redundant contributions of each olfactory subtest to the clinical olfactory diagnosis. Olfactory thresholds provided the largest amount of non-redundant information to the olfactory diagnosis.


Association between Physical Activity and Insomnia among Saudi Female College Students.
[Purpose] Insomnia is quite common and it can affect the quality of life of an individual. Students undergo stress due to various academic demands leading to sleeplessness and daytime sleepiness. This study was conducted to investigate the association between physical activity and insomnia among female Saudi students. [Subjects] 62 female students with a mean age of 21 ± 1.5 years took part in a motivational program to increase the number of steps taken per day for three weeks. [Methods] After obtaining subject's informed consent all the subjects were assessed for insomnia using the insomnia severity index (ISI), They were then given pedometers to calculate the number of steps they took per day. A physical activity log was kept for three weeks. Pre- and post -intervention ISI scores were calculated and correlated with the 3-week physical activity log. [Results] 50% of the subjects had no clinically significant insomnia (NCSI), 42% had sub threshold (STI), and 8% had moderate clinical (MCI) insomnia. There was a moderate negative correlation between physical activity and ISI scores after the 3-week motivation program. [Conclusion] Prevalence of insomnia was common among female Saudi students and increase in physical activity appears to improve the sleep pattern.


Prenylated 2-arylbenzofurans from Artocarpus petelotii.
Further phytochemical investigation on the root barks of Artocarpus petelotii Gagnep afforded two new prenylated 2-arylbenzofurans, artopetelins L and M (1 and 2), as well as a known compound, lakoochin B (3). Their structures were identified by spectroscopic methods. Artopetelins B-E (5-8), four 2-arylbenzofurans previously isolated from this plant, and lakoochin B (3) were potent against HepG2 (IC(50) = 14.4-44.4 microM) and MCF-7 (IC(50) = 29.7-59.1 microM).


FAIR Island: real-world examples of place-based open science.
The relationship between people, place, and data presents challenges and opportunities for science and society. While there has been general enthusiasm for and work toward Findable, Accessible, Interoperable, and Reusable (FAIR) data for open science, only more recently have these data-centric principles been extended into dimensions important to people and place-notably, the CARE Principles for Indigenous Data Governance, which affect collective benefit, authority to control, responsibility, and ethics. The FAIR Island project seeks to translate these ideals into practice, leveraging the institutional infrastructure provided by scientific field stations. Starting with field stations in French Polynesia as key use cases that are exceptionally well connected to international research networks, FAIR Island builds interoperability between different components of critical research infrastructure, helping connect these to societal benefit areas. The goal is not only to increase reuse of scientific data and the awareness of work happening at the field stations but more generally to accelerate place-based research for sustainable development. FAIR Island works reflexively, aiming to scale horizontally through networks of field stations and to serve as a model for other sites of intensive long-term scientific study.


Single-Molecule Spin Switch Based on Voltage-Triggered Distortion of the Coordination Sphere.
Here, we report on a new single-molecule-switching concept based on the coordination-sphere-dependent spin state of Fe(II) species. The perpendicular arrangement of two terpyridine (tpy) ligands within heteroleptic complexes is distorted by the applied electric field. Whereas one ligand fixes the complex in the junction, the second one exhibits an intrinsic dipole moment which senses the E field and causes the distortion of the Fe(II) coordination sphere triggering the alteration of its spin state. A series of complexes with different dipole moments have been synthesized and their transport features were investigated via mechanically controlled break-junctions. Statistical analyses support the hypothesized switching mechanism with increasing numbers of junctions displaying voltage-dependent bistabilities upon increasing the Fe(II) complexes' intrinsic dipole moments. A constant threshold value of the E field required for switching corroborates the mechanism.


Characterization of ESBL-producing Escherichia spp. and report of an mcr-1 colistin-resistance Escherichia fergusonni strain from minced meat in Pamplona, Colombia.
Foods of animal origin are increasingly considered a source of extended spectrum β-lactamase (ESBL) producing bacteria which can disseminate throughout the food chain and become a health concern for humans. This work aimed to evaluate the occurrence of ESBL-producing Escherichia coli in 100 retail minced meat samples taken in markets in Pamplona, Colombia. A total of 19 ESBL-producing isolates were obtained, 18 identified as E. coli and one as E. fergusonii. Fifteen isolates (78.9 %) carried blaCTX-M and blaTEM genes, one (5.2 %) blaSHV and blaTEM genes, one isolate (5.2 %) carried blaCTX-M and one (5.2 %) blaSHV alone. The majority of CTX-M-positive E. coli isolates carried the blaCTX-M-15 gene (13 isolates), being the blaCTX-M-9, blaCTX-M-2, and blaCTX-M-8 (one isolate each) also detected. Two SHV-positive isolates presented the blaSHV-5 and blaSHV-12 allele. The isolate identified as E. fergusonii was positive for blaCTX-M-65 gene and mcr-1 gene. Sixteen isolates (84.2 %) belonged to phylogroups A and B1 and grouped together in the phylogenetic tree obtained by MLST; phylogroups E and F were also detected. Transfer of ESBL resistance was demonstrated for the E. fergusonii isolate. Whole genome sequencing of this isolate revealed the presence of plasmids carrying additional resistance genes. This investigation showed the high prevalence of ESBL-producing E. coli in retail samples of minced meat. Also, the isolation of a strain of E. fergusonii is an additional concern, as some resistance genes are located in mobile elements, which can be transmitted to other bacteria. These evidences support the increasing public health concern considering the spreading of resistance genes through the food chain.


Conservation priorities of useful plants from different techniques of collection and analysis of ethnobotanical data.
This study analyzes three methods of data analysis to verify which one would be more appropriate to get information aiming the conservation, selecting the use value (VU) inventory in situ and conservation property index (IPC). It was developed in in Northeast Brazil, via interviewed householders (46 informants). The VU was calculated considering only the effective use of plants; the inventory in situ was made through the frequency of species occurrence in homes; and the IPC combining ethnobotanical and phytossociological data. It was observed a similar cast of the indicated species by VU and inventory in situ, being different from the IPC cast. As this study sought to analyze the best technique for species identification which were needing conservationist actions, and obtained different results among the chosen methods. It has been suggested the use of methods that unite in their analysis both ethnobotanical and ecological aspects, like in the plants list from the priority index of conservation, which demonstrated to be more efficient to identify rare species in the local vegetation. The VU and the inventory in situ are more efficient to identify the most known and used species in the communities, however without analyzing these plants in the local vegetation.


Recapitulation of cell signaling events associated with astrogliosis using the brain slice preparation.
Astroglial activation constitutes a dominant response to all types of injuries of the CNS. Despite the ubiquitous nature of this cellular reaction to neural injury, a little is known concerning the signaling mechanisms that initiate it. Recently, we demonstrated that astrocytic hypertrophy and enhanced expression of glial fibrillary acidic protein resulting from toxicant-induced neurodegeneration are linked to activation of the janus kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) pathway. These observations implicate ligands at the gp130 receptor as potential upstream effectors of astrogliosis. Here we used the brain slice preparation to examine potential activators of the JAK-STAT3 pathway. Following incubation of freshly cut striatal slices in phosphate-free oxygenated buffer for up to 75 min, we found that slicing the striatum itself was a sufficient stimulus to initiate a rapid activation of the JAK-STAT3 pathway as assessed with immunoblots of pSTAT3((tyr705)) using phospho-state specific antibodies. The mRNA for the gp130 cytokines, leukemia inhibitory factor, interleukin-6 and oncostatin M or the beta-chemokine, monocyte chemoattractive protein (CCl2) also were up-regulated in the slice. Moreover, we could enhance the activation of STAT3((tyr705)) by adding exogenous cytokines to the slice and we could inhibit phosphorylation of STAT3((tyr705)) by addition of tyrosine kinase inhibitors (Lav A and AG490) or neutralizing antibodies directed against leukemia inhibitory factor or oncostatin M. These data suggest that STAT3 activation is an early event in slice-induced glial activation and establishes the brain slice preparation method as a reliable model to examine the signaling mechanisms that underlie glial activation.


[The staged approach--an overview on a strategy to reduce spinal cord injury in thoracoabdominal aortic aneurysm repair].
The spinal cord is particularly susceptible to ischaemic injury following repair of extensive descending thoracic and thoracoabdominal aortic aneurysms (TAAA). For the past decade, the Mount Sinai group in New York has intensively studied the anatomy of the extensive vascular network surrounding the spinal cord, as well as its dynamic morphology in response to decreased blood pressure and flow. Along with clinical data, experimental findings gave rise to the Collateral Network Concept, by which spinal cord injury in open TAAA repair can be significantly reduced. With the more recent widespread use of endovascular repair, strategies to prevent ischaemic spinal cord damage after extensive segmental artery sacrifice/occlusion are still evolving. The hypothesis that dividing extensive aneurysm repair into two steps may mitigate the impact of diminished blood flow to the collateral network has led to a recently conducted series of staged repair experiments. By exploiting the resources of the collateral network, spinal cord injury could be minimised in staged open, as well as in staged hybrid repair and seems equally adoptable for endovascular procedures. The contribution presented herein provides an overview of clinical and experimental studies on the staged approach. Furthermore, it briefly assesses the anatomic rationale for the collateral network concept.


Influence of dietary calcium stress on lethality of avian influenza viruses for laying chickens.
The effect of calcium stress was studied in an attempt to reproduce lethal infections in laying chickens with A/Chicken/Alabama/75 (H4N8) influenza virus and with two nonpathogenic H5N2 influenza viruses from the 1983-84 outbreak in the eastern United States. Hens were fed calcium-deficient or standard diets for 7 to 14 days; then the calcium-deficient feed was replaced with standard feed supplemented with ad libitum oyster shell, and both groups of hens were inoculated with virus. When hens were infected with the H4N8 virus, respective mortalities of those on the calcium-deficient and standard diets were 19% (27/141) and 5% (7/143). The H5N2 viruses did not kill hens fed either diet. In standard pathogenicity tests, Alabama H4N8 viruses reisolated from the hens that died generally were more lethal for 4-week-old chickens than the stock virus. These results argue for characterization of the Alabama H4N8 virus as pathogenic rather than nonpathogenic as originally determined.


[Optimal application time of lidocaine adhesive tape examined using current perception threshold measurement].
We often use lidocaine adhesive tape (Penles, Wyeth Lederle Japan, Ltd., Tokyo, Japan) as a topical anesthetic prior to puncturing a vein with a needle. Since the tape is usually in place for a long time, we often experience problems with creasing and flaring when inserting the needle. We attempted to determine the optimal time for application of the tape as well as for vein puncture after its removal by measuring pain sensation in human subjects. Lidocaine tape was applied to the dorsum of volunteer hands for 2, 4, 6, and 12 hours, and we evaluated changes after removal by determining current perception threshold (CPT), pain score, touch sensation score, diameter of the vein, pruritus, and flare. CPT levels were found to increase within 1 hour after removal of the lidocaine tape with all 3 electrical stimulus rates used (2000 Hz, 250 Hz, 5 Hz). Further, pain and touch sensation scores were low within 2 hours of removal regardless of application time. Notably, with 4 and 6 hours of application, scores were stable 4 and 6 hours after removal. However, vein diameter and pruritus results did not change regardless of application time, while crease and flare were only observed within 30 minutes after removal. We concluded that lidocaine tape provided maximum pain relief when applied 4 to 6 hours prior to vein puncture and up to 1 hour after removal.


Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit.
Spontaneous mast cell tumors (MCT) are the most common malignant neoplasm in the dog, representing between 7% and 21% of all canine tumors, an incidence much higher than that found in humans. These tumors often behave in an aggressive manner, metastasizing to local lymph nodes, liver, spleen, and bone marrow. The proto-oncogene c-kit is known to play a critical role in the development and function of mast cells. Point mutations in the kinase domain of c-kit leading to tyrosine phosphorylation in the absence of ligand binding have been identified in three mastocytoma lines, (P815, RBL, and HMC-1), and some human patients with various forms of mastocytosis. We now demonstrate that although c-kit derived from canine MCT did not contain the previously described activating point mutations, 5 of the 11 tumors analyzed possessed novel mutations consisting of tandem duplications involving exons 11 and 12. We also show that one such duplication, detected in a canine mastocytoma cell line, was associated with constitutive phosphorylation of c-kit protein (KIT), suggesting that these mutations may contribute to the development or progression of canine MCT.


Functional impairment of monocyte-derived dendritic cells in patients with severe chronic kidney disease.
Dendritic cells (DCs) are antigen-presenting cells that are pivotal for the initiation of the primary immune response. Patients with chronic kidney disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an impaired immune response. Dysfunction of DCs may underlie this phenomenon. In this study, several different functions of monocyte-derived DCs (moDC) of patients with CKD class IV-V (glomerular filtration rate <30 ml/min) and patients on CIHD were studied in vitro and compared with age- and sex-matched healthy volunteers. We demonstrate that, independent of the maturation stimulus used, mature moDC from both groups of patients did not acquire the same level of terminal differentiation as moDC from controls, as shown by analysis of cell surface markers and the relative high macropinocytosis activity of moDC. The stimulation of allogeneic T-cells by immature moDC and mature moDC did not differ between patients and controls. However, in the presence of immature moDC or antigen-loaded maturated moDC from patients, less proliferation of autologous T-cells was observed in response to recall antigens. There was no difference between moDC from controls and patients in their ability to activate naive T-cells and to differentiate them into Th1 and Th2 cells. These results show that the terminal differentiation of moDC in patients with severe CKD is impaired. This impairment is not restricted to one maturation stimulus and is independent of treatment with haemodialysis.


Synthesis of a radiolabeled zwitterionic detergent and its use in protein purification.
Radiolabeling permits the detection of trace amounts of zwitterionic detergent remaining in extracted hydrophobic or membrane proteins. To develop a sensitive and specific assay for its presence, the commonly used zwitterionic membrane protein detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps) was synthesized in a tritiated form. Synthesis via 7-ketodeoxycholic acid gave [7-3H]Chaps in 53% yield with a specific activity of 0.85 mCi/mmol. A novel solvent extraction system for cholic acid obviated the need for chromatographic isolation of this intermediate. The protocol can be readily modified to yield [7-3H]Chaps of higher specific activity. [7-3H]Chaps was used to monitor the efficiency of various strategies for detergent removal from concentrated bacterial culture supernatants containing 0.2% (w/v) Chaps. Dialysis removed 95% of Chaps and the addition of detergent-affinity beads to the dialysis buffer resulted in 97% removal of Chaps. Gel-filtration chromatography removed 99.9% of Chaps, while a detergent-affinity bead chromatography column removed 99.99%. Overall, gel-filtration chromatography was the most convenient and economical method for the one-step removal of the zwittergent from complex biological mixtures.


Evasion mechanisms of pathogenic Neisseriae.
The outcome of the early stages of a neisserial infection is determined by receptor-mediated events that culminate in the attachment and invasion of human mucosal tissues. The factors participating in this process, including pili, opacity proteins (Opa), and perhaps lipopolysaccharide (LPS), undergo phase and antigenic variation allowing the pathogens to evade the human immune response. In addition antigenic variation is essential in the modulating pathogen host cell interactions. Likewise the production of distinct Opa proteins allows the bacteria to enter epithelial cells and thereby to escape the humoral host responses. Other mechanisms including antigenic mimicry by capsular polysaccharides and antigenic masquerade by immunoglobulin fragments confer additional resistance to the extracellular life style of these organisms. Finally alpha-protein, a putative hormone-like factor produced by pathogenic Neisseriae, may contribute to the complex evasion-program of these species.


Key Gene and Functional Pathways Identified in Unexplained Recurrent Spontaneous Abortion Using Targeted RNA Sequencing and Clinical Analysis.
Identifying the mechanisms underlying unexplained recurrent spontaneous abortion (URSA) can help develop effective treatments. This study provides novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in URSA. Nineteen patients with URSA and three healthy fertile women with regular menstruation (control group) were recruited. RNA was extracted from the two groups to determine the differential expression of immunoregulatory gene sequences. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological functions and pathways of the identified DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, qRT-PCR and ELISA were performed to validate the differential expression of the hub genes. We also explored the regulatory mechanism of Th1/Th2 imbalance. A total of 99 DEGs were identified, comprising 94 upregulated and five downregulated genes. Through GO analysis, nine immune cell function-related clusters were selected, and genes with significant differential expression were primarily enriched in eight immune regulatory functions related to the KEGG signalling pathway. Subsequently, five hub genes (TLR2, CXCL8, IFNG, IL2RA, and ITGAX) were identified using Cytoscape software; qRT-PCR confirmed the differential expression among the hub genes, whereas ELISA revealed a significant difference in extracellular IFN-γ and IL-8 levels. The levels of Th1 (IFN-γ) and the Th1/Th2 ratio were higher in the peripheral blood of URSA patients than in control group patients. These findings suggest that the occurrence of URSA may be associated with the abnormal expression of some specific immunoregulatory genes involved in T-cell activation and differentiation. Among the identified DEGs, IFNG may play a key role in regulating maternal immune response. Although further validation is required, our data provide an important theoretical basis for elucidating the pathogenesis of recurrent spontaneous abortion.


The Production of Inequality: The Gender Division of Labor Across the Transition to Parenthood.
Using longitudinal time diary and survey data from a community sample of dual-earner couples across the transition to parenthood, the authors examined change in divisions of paid and unpaid work and assessed the accuracy of survey data for time use measurement. Mothers, according to the time diaries, shouldered the majority of child care and did not decrease their paid work hours. Furthermore, the gender gap was not present prebirth but emerged postbirth with women doing more than 2 hours of additional work per day compared to an additional 40 minutes for men. Moreover, the birth of a child magnified parents' overestimations of work in the survey data, and had the authors relied only on survey data, gender work inequalities would not have been apparent. The findings have important implications for (a) the state of the gender revolution among couples well positioned to obtained balanced workloads and (b) the utility of survey data to measure parents' division of labor.