Risk Factors Associated With Unplanned Acute Care in Outpatient Chemotherapy With Oral Anticancer Drugs as Monotherapy or Combination Therapy With Injectable Anticancer Drugs.
Recently, the number of patients with cancer receiving outpatient chemotherapy using oral anticancer drugs has increased, but the currently available outpatient cancer chemotherapy is not safer than that available before. The present study aimed to identify risk factors associated with unplanned acute care (UAC) requiring outpatient chemotherapy-related consultation and hospitalisation. We conducted a case- control study among 1,674 patients who received oral anticancer drug treatment either alone or in combination with injectable anticancer drugs at National Cancer Center Hospital East, Japan, between December 1, 2014, and November 30, 2015. Body mass index (BMI) was identified as a risk factor for UAC during chemotherapy. Patients with a BMI of <18.5 kg/m2, classified as underweight according to the World Health Organization classification of nutritional status, had a significantly higher risk of UAC. A low BMI immediately before the occurrence of chemotherapy-related UAC is a risk factor for adverse effects; therefore, underweight patients need more careful monitoring and supportive care.


Clinical characteristics and antimicrobial susceptibility of Bacillus cereus blood stream infections.
Bacillus cereus is one of the pathogens causing nosocomial bloodstream infections (BSIs). However, few reports have documented the antimicrobial susceptibility and clinical characteristics of Bacillus cereus BSI and the importance of empirical therapy. The aim of this study was to investigate the clinical characteristics and antimicrobial susceptibility of B. cereus isolates from patients with BSI and to analyze the impact of appropriate empirical therapy on the outcome of patients with B. cereus BSI. All adult cases of bacteremia between April 2003 and March 2012 in a teaching hospital in Tokyo, Japan were reviewed retrospectively. Clinical data were collected from the patients' medical records and charts. Antimicrobial susceptibility testing was performed by broth microdilution method. The patients with B. cereus BSI were divided into an appropriate empirical therapy group and an inappropriate empirical therapy group. The primary outcome was all-cause mortality at 4 weeks after the start of BSI. The secondary outcome was early defervescence within 2 days after starting empirical therapy. There were 29 B. cereus bloodstream infection cases. No vancomycin, gentamicin, and imipenem-resistant isolates were found. However, 65.5 % were resistant to clindamycin and 10.3 % were resistant to levofloxacin. The main etiology was venous catheter-related (69 %). All-cause mortality at 4 weeks was not significantly different between the appropriate empirical therapy group (9 cases) and the inappropriate group (20 cases) in this study. However, early defervescence within 2 days after starting empirical therapy was significantly different (p = 0.032). The BSI of B. cereus is mostly caused by venous catheter-related infections. Appropriate empirical therapy is important to achieve early clinical resolution in B. cereus BSI. Vancomycin is one of the appropriate selections of empirical therapy for B. cereus BSI.


Display of small-area variation in health-related data: a methodology using resistant statistics.
Health care planning requires characterization of the population to be served. Examination of available demographic and epidemiologic data is one early step in this process. However, aggregate data for the entire geographic area of concern often fail to reveal important differences among geographically defined sub-populations--differences that influence the form an effective delivery system should take. We present a methodology based on exploratory data analysis (EDA) techniques that we have found useful in examining health-related data for our ambulatory care catchment area. Our examples use three population characteristics that have major implications for health care planning for the elderly: 1970-1980 change in population aged 65+; the percent of the population aged 65+ below poverty level; and the percent of single-person households among households with one or more persons aged 65+. With these data for the 25 municipalities of Middlesex County, New Jersey, we illustrate a two-step process: (1) the construction of stem-and-leaf displays that permit examination of a data distribution for asymmetry, concentrations around specific values, gaps in values, and outliers; and (2) the use of the median, the fourth-spread, and other information from the stem-and-leaf display in the systematic selection of data value classes to be given distinct shadings on a map of the selected geographic area. Discussion emphasizes the usefulness of graphic display of data in detecting similarities and unusual data values. Comparison of maps based on the EDA techniques and maps based on several traditional methods of value classing for the same data illustrates the influence of classing choices on the interpretation of cartographic displays of health-related data.


Predicting building types using OpenStreetMap.
Having accurate building information is paramount for a plethora of applications, including humanitarian efforts, city planning, scientific studies, and navigation systems. While volunteered geographic information from sources such as OpenStreetMap (OSM) has good building geometry coverage, descriptive attributes such as the type of a building are sparse. To fill this gap, this study proposes a supervised learning-based approach to provide meaningful, semantic information for OSM data without manual intervention. We present a basic demonstration of our approach that classifies buildings into either residential or non-residential types for three study areas: Fairfax County in Virginia (VA), Mecklenburg County in North Carolina (NC), and the City of Boulder in Colorado (CO). The model leverages (i) available OSM tags capturing non-spatial attributes, (ii) geometric and topological properties of the building footprints including adjacent types of roads, proximity to parking lots, and building size. The model is trained and tested using ground truth data available for the three study areas. The results show that our approach achieves high accuracy in predicting building types for the selected areas. Additionally, a trained model is transferable with high accuracy to other regions where ground truth data is unavailable. The OSM and data science community are invited to build upon our approach to further enrich the volunteered geographic information in an automated manner.


Ergothioneine, Ovothiol A, and Selenoneine-Histidine-Derived, Biologically Significant, Trace Global Alkaloids.
The history, chemistry, biology, and biosynthesis of the globally occurring histidine-derived alkaloids ergothioneine (10), ovothiol A (11), and selenoneine (12) are reviewed comparatively and their significance to human well-being is discussed.


Cost and Complications of Single-Level Lumbar Decompression in Those Over and Under 75: A Matched Comparison.
Retrospective database analysis. This study aimed to compare costs and complication rates following single-level lumbar decompression in patients under age 75 versus patients aged 75 and older. Lumbar decompression is a common surgical treatment for lumbar pathology; however, its effectiveness can be debated in elderly patients because complication rates and costs by age group are not well-defined. The Medicare database was queried through the PearlDiver server for patients who underwent single-level lumbar decompression without fusion as an index procedure. The 90-day complication and reoperation rates were compared between age groups after matching for sex and comorbidity burden. Same day and 90-day costs are compared. The matched cohort included 89,388 total patients (n = 44,694 for each study arm). Compared to the under 75 age group, the 75 and older age group had greater rates of deep venous thrombosis (odds ratio [OR] 1.443, P = 0.042) and dural tear (OR 1.560, P = 0.043), and a lower rate of seroma complicating the procedure (OR 0.419, P = 0.009). There was no difference in overall 90-day reoperation rate in patients under age 75 versus patients aged 75 and older (9.66% vs. 9.28%, P = 0.051), although the 75 and older age group had a greater rate of laminectomy without discectomy (CPT-63047; OR 1.175, P < 0.001), while having a lower rate of laminotomy with discectomy (CPT-63042 and CPT-63030; OR 0.727 and 0.867, respectively, P = 0.013 and <0.001, respectively). The 75 and older age group had greater same day ($3329.24 vs. $3138.05, P < 0.001) and 90-day ($5014.82 vs. $4749.44, P < 0.001) mean reimbursement. Elderly patients experience greater rates of select perioperative complications, with mildly increased costs. There is no significant difference in overall 90-day reoperation rates. 3.


Early use of OKT3 monoclonal antibody in renal transplantation to prevent rejection.
OKT3 monoclonal anti-T cell antibody was used during the first 2 weeks following cadaveric renal transplantation to prevent rejection. When compared with a control group receiving triple immunosuppression with cyclosporine, azathioprine, and prednisone, the OKT3, azathioprine, and prednisone group had significantly fewer acute rejections during the first month (6% v 50%; P less than 0.01), and the mean time of onset of the first rejection was significantly delayed (day 47 v day 8; P less than 0.01) in the OKT3 prophylaxis group. OKT3 was administered intraoperatively safely and without complications on the day of transplantation. The well-reported first dose reaction to OKT3 was similar in these patients when compared with patients receiving OKT3 for treatment of rejection. Anti-OKT3 antibody development occurred in half of the patients receiving OKT3, and did not prevent the subsequent use of OKT3 in these patients, whose rejections following OKT3 prophylaxis were steroid reversible. There were no deaths among the patients receiving prophylactic OKT3, and during a 15-month follow-up, only three of 34 kidneys were lost for any reason. In addition to its use for primary and steroid-resistant rejection, OKT3 may be useful early after transplantation to prevent rejection.


Size and domain structure of collagen VI produced by cultured fibroblasts.
Disulfide-bonded forms of collagen VI were analyzed by immunoblotting of fibroblast culture medium and cell extracts. The protein consists of pepsin and collagenase-resistant domains of about equal size indicating a molecular mass of 340 kDa for collagen VI monomers.


Grouper (Epinephelus coioides) IRAK-4 regulates activation of NF-κB and expression of inflammatory cytokines in grouper spleen cells.
IRAK-4 is a serine/threonine kinase that can bind to interleukin-1 receptor induced by interleukin-1. It plays a key role in the Toll-like receptor signaling pathway and is involved in innate and adaptive immune responses. In this study, piscine IRAK-4 significantly activated nuclear factor (NF)-κB signaling in grouper spleen cells. Grouper (Epinephelus coioides) IRAK-4 (EcIRAK-4) co-localized with EcMyD88 and did not impair EcMyD88-dependent NF-κB activation. Different doses of EcIRAK-4 caused different degrees of nuclear translocation of the transcription factor NF-κB p65 subunit, and it induced transcription of multiple pro-inflammatory cytokines. Using expression vectors of deletion domains or mutations at important sites of EcIRAK-4, we found that the EcIRAK-4 kinase domain is necessary for its signal transduction function. The conserved amino acid sites performed functions similar to those in mammals, and grouper-specific amino acids such as E339 also played important roles. These findings provide information about the functional characteristics of IRAK-4 in lower vertebrates.


Eicosanoid synthesis in children with cholestatic disease.
The possibility of malabsorption of triglycerides contained in the diets of children with cholestasis suggests a deficiency of essential fatty acids and, therefore, probable effects on eicosanoid metabolism. Children with either biliary atresia (BA) or syndromatic paucity of interlobular bile ducts (PILBD) were evaluated as to plasma and platelet total lipid fatty acid composition and synthesis of prostaglandins (PG) E1, PGE2, PGI2, PGF2, and thromboxane (TXB2) by whole blood incubated at 37 degrees C for 10 min. In both diseases linoleate deficiency was present as shown by low 18:2 fatty acids in plasma lipids. The children with BA had lower plasma arachidonate than controls but normal eicosanoid synthesis except for excess PGI2. Those with PILBD had low platelet arachidonate and were severely deficient in TXB2 synthesis (less than 10% of controls). Three children with PILBD were fed a supplement of structured triglyceride (Captex 810) intended to provide as much as 10% of energy as linoleate for 2-3 months. Results for these three cases suggested that insufficient linoleate was absorbed to increase plasma linoleate and differences in eicosanoids could not be attributed to linoleate supplementation.


The immune response of the chicken to vaccination against Newcastle disease with live virus and killed emulsified virus in relation to the length of time between two vaccinations.
Chicks with no specific antibodies were initially y vaccinated against Newcastle disease at 21 days old with the live 'La Sota' strain or beta-propiolactone-killed virus emulsified in mineral oils. After a second vaccination 15 or 21 days later with the live "La Sota' strain, the interference produced by the first vaccination on the antibody production induced by the second vaccination was investigated. It was found that the live virus vaccine used for the second immunization was affected by the antibodies induced by the first vaccination, as shown in previous work utilizing 1-day-old chicks.


The light-sensitive photoprotein berovin from the bioluminescent ctenophore Beroe abyssicola: a novel type of Ca(2+) -regulated photoprotein.
Light-sensitive Ca(2+) -regulated photoproteins are responsible for the bright bioluminescence of ctenophores. Using functional screening, four full-size cDNA genes encoding the same 208-amino-acid polypeptide were isolated from two independent cDNA libraries prepared from two Beroe abyssicola specimens. Sequence analysis revealed three canonical EF-hand calcium-binding sites characteristic of Ca(2+) -regulated photoproteins, but a very low degree of sequence identity (27-29%) with aequorin-type photoproteins, despite functional similarities. Recombinant berovin was expressed in Escherichia coli cells, purified, converted to active photoprotein and characterized. Active berovin has absorption maxima at 280 and 437 nm. The Ca(2+) -discharged protein loses visible absorption, but exhibits a new absorption maximum at 335 nm. The berovin bioluminescence is blue (λ(max) = 491 nm) and a change in pH over the range 6.0-9.5 has no significant effect on the light emission spectrum. By contrast, the fluorescence of Ca(2+) -discharged protein (λ(ex) = 350 nm) is pH sensitive: at neutral pH the maximum is at 420 nm and at alkaline pH there are two maxima at 410 and 485 nm. Like native ctenophore photoproteins, recombinant berovin is also inactivated by light. The Ca(2+) concentration-effect curve is a sigmoid with a slope on a log-log plot of ∼ 2.5. Although this curve for berovin is very similar to those obtained for obelin and aequorin, there are evident distinctions: berovin responds to calcium changes at lower concentrations than jellyfish photoproteins and its Ca(2+) -independent luminescence is low. Recombinant berovin was successfully expressed in mammalian cells, thereby demonstrating potential for monitoring intracellular calcium. Database The nucleotide sequences have been deposited in the GenBankTM/EBI Data Bank with accession numbers: apoberovin cDNA genes, JN673813 (BA1), JN673814 (BA2), JN673815 (BA3), JN673816 (BA4); fragment 18S rRNA, JN673817 (BA-rRNA5).


L-arginine transport in the human coronary and peripheral circulation.
Nitric oxide synthase (NOS) uses arginine for the production of nitric oxide (NO). High intracellular concentrations of arginine suggest that NOS activity should be independent of plasma arginine supply. However, under certain conditions, increased plasma arginine concentrations appear to be associated with increased NOS activity. The purpose of this study was to explore arginine transport within the human coronary and peripheral circulation Mass-labeled 15N2-arginine was infused to steady state before cardiac catheterization in 31 patients. After diagnostic angiography, a catheter was placed in the coronary sinus. The transcardiac concentration gradient (aorta-coronary sinus) of 15N2-arginine was used as a measure of arginine transport at baseline and during infusions of acetylcholine and N(G)-monomethyl-L-arginine (L-NMMA). No gradient was detected at rest. During the infusion of acetylcholine, a significant gradient was detected (2.5+/-1.2 micromol/L, P=0.01) corresponding to a fractional extraction of 11.7+/-7.5%. This is consistent with in vitro studies that suggest that stimulation of NOS induces arginine transport. During the infusion of L-NMMA, the concentration of 15N2-arginine increased in the coronary sinus, producing a gradient of -3.9+/-1.3 micromol/L (P=0.0002), corresponding to a fractional production of 20.5+/-5.0%. This is consistent with in vitro studies that suggest that L-NMMA induces the efflux of arginine from the cell to the extracellular space via transporter-mediated transstimulation. The use of steady-state 15N2-arginine to examine transorgan L-arginine gradients represents a novel tool for the study of L-arginine transport and the mechanisms of endothelial and NOS dysfunction.


Statistical breathing curve sampling to quantify interplay effects of moving lung tumors in a 4D Monte Carlo dose calculation framework.
The interplay between respiratory tumor motion and dose application by intensity modulated radiotherapy (IMRT) techniques can potentially lead to undesirable and non-intuitive deviations from the planned dose distribution. We developed a 4D Monte Carlo (MC) dose recalculation framework featuring statistical breathing curve sampling, to precisely simulate the dose distribution for moving target volumes aiming at a comprehensive assessment of interplay effects. We implemented a dose accumulation tool that enables dose recalculations of arbitrary breathing curves including the actual breathing curve of the patient. This MC dose recalculation framework is based on linac log-files, facilitating a high temporal resolution up to 0.1 s. By statistical analysis of 128 different breathing curves, interplay susceptibility of different treatment parameters was evaluated for an exemplary patient case. To facilitate prospective clinical application in the treatment planning stage, in which patient breathing curves or linac log-files are not available, we derived a log-file free version with breathing curves generated by a random walk approach. Interplay was quantified by standard deviations σ in D5%, D50% and D95%. Interplay induced dose deviations for single fractions were observed and evaluated for IMRT and volumetric arc therapy (σD95% up to 1.3 %) showing a decrease with higher fraction doses and an increase with higher MU rates. Interplay effects for conformal treatment techniques were negligible (σ<0.1%). The log-file free version and the random walk generated breathing curves yielded similar results (deviations in σ< 0.1 %) and can be used as substitutes for interplay assessment. It is feasible to combine statistically sampled breathing curves with MC dose calculations. The universality of the presented framework allows comprehensive assessment of interplay effects in retrospective and prospective clinically relevant scenarios.


Levels of organochlorine pesticide residues in some organs of the Ganges perch, Lates calcarifer, from the Ganges-Brahmaputra-Meghna Estuary, Bangladesh.
Levels of organochlorine pesticide residues (p,p' DDT, DDD, DDE, Aldrin, Dieldrin, Lindane, Heptachlor and BHC) were analysed in the dry and wet seasons in four organs (muscle, liver, gut and egg samples) of Ganges Perch, Lates calcarifer, collected during October-November-December, 1996 and May-June-July, 1997 from the Ganges-Brahmaputtra-Meghna estuary. The residues were analysed by using gas-chromatography (GC) in electron capture detector (ECD) mode and were verified by thin layer chromatography (TLC). Among the four organs analysed, the residues were found in the order egg > gut > muscle > liver. The pesticide residues were found in the order sigmaDDT > Heptachlor > Dieldrin > Aldrin. Higher levels of residues were found during the dry season due to high lipid content in fishes. A positive correlation was observed between the pesticide residues (sigmaDDT and sigmaOCs) and lipid contents of fish, and the correlation was found to be linear. The concentrations of pesticide residues in muscle, liver and gut were below the FAO/WHO (1993) recommended permissible limit except in eggs.


Protective effects of four new saponins from Gynostemma pentaphyllum against hydrogen peroxide-induced neurotoxicity in SH-SY5Y cells.
Gynostemma pentaphyllum has been used as a medicine-food homologious health product in China for a long time. This research aimed to isolate and identify its active compounds with protective effects against hydrogen peroxide induced SH-SY5Y cell death. Four new dammarane-type saponins were isolated from G. pentaphyllum using various chromatographic methods. They were identified as gypenoside S1 (1), gypenoside S3 (2), gypenoside S2 (3) and gypenoside S4 (4), respectively by HRESIMS and NMR spectra. Their cytotoxic activity was evaluated against three human cancer cell lines, A549 (lung), HepG2 (liver), SH-SY5Y (nerve), by MTT method. They showed low cytotoxicities with the IC50 values of more than 100 μM on three cancer cell lines. However, they appeared protective effects against hydrogen peroxide induced SH-SY5Y cell death in a dose-dependent manner. They recovered cell viability more than 69% at the concentration of 20 μM from 66%, while as vitamin C to 67%. Compound 3 and 4 recovered more than 79% at 100 μM. The present study suggests that G. pentaphyllum has antioxidative potential and the saponins from G. pentaphyllum are considered as the active compounds with safe and neuroprotecitve effect.


CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II.
The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2) and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11) in TNF-alpha-, IFN-gamma-, and IL-1beta-stimulated human alveolar epithelial cells type II (AEC-II). AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-gamma had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-gamma, alone or in combination with IL-1beta and TNF-alpha resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-gamma > > IL-1beta > or = TNF-alpha. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.


Apoptosis inducer NGFI-B is degraded by the proteasome and stabilized by treatment with EGF.
NGFI-B is a nuclear receptor and immediate early gene that is upregulated in many different tumour cell lines. As it is involved in cell death and survival, it has been suggested as a target for anti-cancer drugs. The protein level of NGFI-B is important for its functions and may be regulated through induction or stabilization. NGFI-B protein stability was studied using the protein synthesis inhibitor cycloheximide in CV1 cells transiently transfected with NGFI-B. Inhibiting the proteasome with MG132 stabilized NGFI-B, indicating that the proteasome is responsible for break-down of NGFI-B, as it is for many nuclear receptors. In order to determine regions responsible for the break-down of NGFI-B two N-terminal regions with high PEST-scores were deleted. Deletion of amino acids 122-195 containing a PEST-sequence which includes an ERK2 phosphorylation target, gave a more stable protein. In addition, treatment of the cells with the ERK2 activator EGF increased the stability of wild type NGFI-B. We then tested whether a mutation at threonine 142 influenced the stability of NGFI-B. We found that the phosphorylation-mimicking mutant NGFI-B T142E had an increased stability, while the non-phosphorylable mutant (T142A) showed similar stability to the wild type. Thus, EGF-stimulation of cells may be a mechanism for priming the cells for effects of NGFI-B by increasing its stability.


Consensus sequences for early iodination and hormonogenesis in human thyroglobulin.
Thyroglobulin from a human goiter, containing four atoms of iodine/molecule (660,000 daltons), was iodinated with Na 125I and KI in vitro to achieve a net addition of either 2 or 7.8 atoms of iodine/molecule. After fractionation by high performance liquid chromatography, iodinated tryptic peptides from S-cyanoethylated 125I-thyroglobulin were purified, sequenced, characterized by [125I]iodoamino acid distribution, and localized within thyroglobulins primary structure based upon the published cDNA sequence, (Malthiery, Y., and Lissitsky, S. (1987) Eur. J. Biochem. 165, 491-498). The addition of 2 atoms of iodine/molecule of thyroglobulin produced iodotyrosyls at five principal sites, with no 125I-hormone formation. The addition of 7.8 atoms iodinated the same sites more heavily, produced iodotyrosyls at 10 additional sites, and formed iodothyronines at 5 sites. After addition of 2 atoms of iodine, tyrosyl 24 and 11% of thyroglobulins 125I, while tyrosyl 2572 had 24%, but with 7.8 added atoms of iodine, tyrosyl 24 had more of the thyroglobulins [125I]iodothyronine (36 versus 26%). Since tyrosyls 149, 866, and 1466 were iodinated early but did not form the inner rings of iodothyronines, they are attractive candidates for donors of outer iodothyronyl rings. The sequences around the iodotyrosyls fall into three consensus groups, as follows: 1) Glu/Asp-Tyr, associated with synthesis of thyroxine (residues 24, 2572, and 1309), or iodotyrosine (residues 2586 and 991); 2) Ser/Thr-Tyr-Ser, associated with synthesis of iodothyronine (residue 2765) and iodotyrosine (1466 and 883); and 3) Glu-X-Tyr, 7 of the remaining 8 iodotyrosyls occur in this sequence, and we found iodine incorporation at each place this sequence appears in the thyroglobulin molecule. Iodine has been found at homologues of most of these sites in thyroglobulins of other species. We conclude that the primary structure of thyroglobulin, and particularly these consensus sequences, have a major role in the formation of thyroid hormones and their iodinated precursors.


Increased severe primary graft dysfunction in left ventricular assist device patients following united network for organ sharing allocation changes.
In 2018, the United Network for Organ Sharing (UNOS) implemented a new heart allocation system which prioritized patients on temporary support devices and left-ventricular assist device (LVAD) patients with complications. These changes have the potential to impact outcomes for patients bridged to transplant with an LVAD. We performed a retrospective study of 168 adult heart transplant recipients at our center between 2016 and 2020 evaluating post-transplant outcomes before and after UNOS allocation changes. Donor and recipient data were retrieved from chart review and national databases. The primary outcome of this study was severe primary graft dysfunction (PGD) with secondary outcomes of 30-day readmission, 30-day mortality, and 1-year mortality. Incidence of severe PGD was similar in the overall cohort before and after the changes (10% vs. 15%, respectively, p = .3) and increased in the LVAD-bridged cohort (12% vs. 40%, respectively, p < .01). Secondary outcomes of readmission and survival were similar between all groups. Blood transfusion was predictive of severe PGD in multivariable modeling (OR 1.3 [1.11-1.59], p < .01).


Lay health educators translate a weight-loss intervention in senior centers: a randomized controlled trial.
Older adults have high obesity rates and respond well to evidence-based weight-loss programs, such as the Diabetes Prevention Program (DPP) Lifestyle intervention. The goal of this study was to determine whether a translation of the DPP Lifestyle program delivered by lay health educators and conducted in senior centers is effective in promoting weight loss among older adults. An RCT with older adults nested within senior centers. Senior centers identified lay health educators to receive training and deliver the intervention program at the senior center. Senior centers were randomized to DPP Lifestyle program or an attention control intervention (cognitive training). Senior centers (N=15) located throughout Arkansas. Participants (N=228) were obese (BMI=34.5±4.9) older (aged 71.2±6.6 years) adults able to engage in moderate exercise. Follow-up data were collected at 4 months on 93% of the original cohort between February 2009 and July 2010. A 12-session translation of the Diabetes Prevention Program Lifestyle behavioral weight-control program delivered in group sessions by trained lay health educators. Body weight was assessed by digital scale. Percentage weight loss from baseline and proportion achieving ≥5% and ≥7% weight loss were examined. Analyses were completed in March 2011. Participants attending senior centers randomized to Lifestyle lost a significantly greater percentage of baseline weight (3.8%, 95% CI=2.9%, 4.6%) than those in the control senior centers (0.2%, 95% CI= -0.6%, -0.9%) after adjusting for baseline BMI and gender (p<0.001). Among participants attending senior centers offering the Lifestyle program, 38% lost ≥5% of baseline weight compared with 5% in the control arm (p<0.001). Similarly, significantly more participants (24%) in Lifestyle senior centers lost ≥7% than did control participants (3%, p=0.001). A behavioral lifestyle weight-loss intervention delivered by a lay health educator offers a promising vehicle for translation of evidence-based obesity treatment programs in underserved areas. This study is registered at Clinicaltrials.govNCT01377506.


Emerging roles of O-glycosylation in regulating protein aggregation, phase separation, and functions.
Protein O-glycosylation is widely identified in various proteins involved in diverse biological processes. Recent studies have demonstrated that O-glycosylation plays crucial and multifaceted roles in modulating protein amyloid aggregation and liquid-liquid phase separation (LLPS) under physiological conditions. Dysregulation of these processes is closely associated with human diseases such as neurodegenerative diseases (NDs) and cancers. In this review, we first summarize the distinct roles of O-glycosylation in regulating pathological aggregation of different amyloid proteins related to NDs and elaborate the underlying mechanisms of how O-glycosylation modulates protein aggregation kinetics, induces new aggregated structures, and mediates the pathogenesis of amyloid aggregates under diseased conditions. Furthermore, we introduce recent discoveries on O-GlcNAc-mediated regulation of synaptic LLPS and phase separation potency of low-complexity domain-enriched proteins. Finally, we identify challenges in future research and highlight the potential for developing new therapeutic strategies of NDs by targeting protein O-glycosylation.


Iododeoxyuridine (IdUrd) incorporation into DNA of human hematopoietic cells, normal liver and hepatic metastases in man: as a radiosensitizer and as a marker for cell kinetic studies.
Iododeoxyuridine (IdUrd) was administered as a continuous infusion for 14 days to patients with glioblastoma and sarcoma, and for 3 days to patients with metastatic colorectal carcinoma. In the first group, the maximum incorporation of IdUrd into DNA was determined, taking granulocytes as parameter. In the second group, selective incorporation into DNA of normal liver and hepatic metastases of colorectal cancer was investigated. The highest dose of 675 mg/sq.m./day for 14 days produced IdUrd plasma concentrations of 1.8 +/- 0.3 microM, and a substitution of dThd by IdUrd in the range of 7.1-11.7%. Coadministration of fluorodeoxyuridine did not show significant enhancement of IdUrd-incorporation in granulocytes. Three-day intravenous infusions of IdUrd 1000 mg/sq.m./day produced 1.7-4.5% IdUrd-incorporation in hepatic metastases. Three-day intraarterial infusions (hepatic artery) produced 3.8-10.5% dThd-replacement, whereas, in 9/10 patients this was less than 1% in normal liver. In tumor tissue there was a trend towards FdUrd-modulated enhancement of IdUrd-incorporation, although there was considerable scatter. Cell kinetic studies revealed that IdUrd-incorporation in monocytes and granulocytes was very similar. In lymphocytes, a much lower fraction incorporated IdUrd. Liver tumor contained a considerably higher fraction of IdUrd-labeled cells, compared with normal liver. Potential doubling times for the tumors were estimated to be 10 days.


Rest and stress transluminal attenuation gradient and contrast opacification difference for detection of hemodynamically significant stenoses in patients with suspected coronary artery disease.
This study evaluated the feasibility of stress 320 detector CT coronary angiography (CTA) derived transluminal attenuation gradient (TAG320) and contrast opacification (CO) difference to detect hemodynamically significant stenoses as determined by invasive fractional flow reserve (FFR ≤ 0.80). Twenty-seven patients, including 51 vessels on rest CTA were studied. 16 (31 %) vessels were not interpretable on stress CTA largely secondary to motion artefacts. Receiver operating characteristic curve analysis showed a comparable area under the curve (AUC) for rest and stress TAG320 (0.78 and 0.75) which was higher than CTA alone (0.68), and rest and stress CO difference (0.76 and 0.67). Compared with rest CTA, stress CTA demonstrated inferior image quality (Median Likert score 4 vs. 3, P < 0.0001) and required a higher mean radiation exposure (3.2 vs. 5.1 mSv, P < 0.0001). Stress TAG320 and CO difference is less feasible and was not superior in diagnostic performance when compared with rest TAG320 and CO difference.


Effects of chromic chloride on chick embryo fibroblast viability.
The objective of this study is to evaluate the effects of chromic chloride (CrCl3) on chick embryo fibroblast (CEF) viability. The cells were incubated with CrCl3 (0.02, 0.1, 0.5, 2.5, 12.5, and 62.5 μM), and the viability was determined using MTT assay, morphological detection and flow cytometry. The results show that lower concentrations of CrCl3 (0.02, 0.1, and 0.5 μM) did not damage CEF viability. At 0.1 μM, CrCl3 can increase CEF viability (P < 0.05). However, at higher concentrations of CrCl3 (2.5, 12.5, and 62.5 μM), the number of apoptotic and necrotic cells (P < 0.01) and intracellular reactive oxygen species (P < 0.01) increased. In addition, decreased mitochondrial membrane potential (P < 0.01) and enhanced intracellular calcium levels (P < 0.01) were observed after the exposure. Moreover, apoptotic morphological changes induced by these processes in CEF were confirmed using Hoechst 33258 staining. Cell death induced by higher concentrations of CrCl3 was caused by an apoptotic and a necrotic mechanism, whereas the main mechanism of oxidative stress and induced mitochondrial dysfunction was apoptotic death. The induced apoptotic death in CEF is concentration- and time-dependent.


Two-dimensional and color Doppler assessment of ventricular septal defect of congenital origin.
Two-dimensional echocardiography and color Doppler examinations were performed in 53 patients with 58 ventricular septal defects (VSD) proven surgically or anatomically. All patients also had angiocardiograms. Two-dimensional echocardiography/color Doppler examination detected all VSDs and correctly categorized the site and extension of VSDs in 50 of 58 (86%). All 40 perimembranous VSDs were diagnosed in the left ventricular outflow tract short-axis plane as an area of discontinuity adjacent to septal tricuspid valve leaflet attachment. Fourteen of 16 VSDs with inlet extension showed initial color flow signals along the septal tricuspid leaflet and along the ventricular septum. Of 23 perimembranous VSDs with outlet extension, 19 had flow signals moving directly toward the right ventricular outflow tract. One perimembranous VSD with trabecular extension showed flow signals directed anterolaterally toward the right ventricular free wall. Eleven of 13 muscular VSDs were similarly categorized correctly by color Doppler as inlet, outlet and trabecular. All 5 doubly committed VSDs were correctly diagnosed as an area of discontinuity adjacent to the pulmonary valve in the short-axis view with flow signals directly moving through VSD into right ventricular outflow and pulmonary artery. Angiography correctly detected all VSDs and correctly classified their site and extension in 45 of 58 (77.5%). It misclassified 8 of 40 perimembranous, 3 of 13 muscular and 2 of 5 doubly committed VSDs. Color Doppler compares favorably with angiocardiography in the detection and localization of VSDs.


A retrospective study on effects of storage time of liquid boar semen on reproductive performance in Norwegian swine.
The objective of this retrospective field study was to determine the effects of storing, for up to 62 h, heterospermic and homospermic semen in the short-term extender Beltsville thawing solution (BTS), on reproductive performance in Norwegian swine of four different breed combinations. The study was based on fertility records after single or double inseminations with semen collected at an AI station in Norway from January 1998 to June 2001. Increasing the duration of storage of homospermic semen, but not heterospermic semen, from an interval of 4-14 h to an interval of 52-62 h, was associated with a 0.5 piglet reduction in litter size. There were differences in reproductive performance among breed combinations that appeared to be associated with duration of semen storage. In conclusion, prolonged semen storage decreased reproductive performance; the extent varied among breeds and was prevented by the use of heterospermic versus homospermic semen.


Administration of 6-methoxybenzoxazolinone (MBOA) does not augment ovulatory responses in St. Croix White ewes superovulated with PMSG.
The objective of this investigation was to examine the effects of 6-methoxy-benzoxazolinone (MBOA), a plant compound that resembles melatonin and alters ovarian function in rodents, in combination with PMSG on superovulatory responses in the cycling ewe. In Experiment I, St. Croix White ewes (n = 44) were synchronized (intra-vaginal progestin sponge) for 14days followed by hCG (750 IU) at 1 day after sponge removal (day 0). Ewes were assigned to one of six treatments administered on day -1: Control (no PMSG or MBOA; n = 7); PMSG (1000 IU i.m.; n = 7); Low MBOA (0.43 mg/kg i.m.; n = 7); High MBOA (1.15 mg/kg i.m.; n = 7); Low MBOA + PMSG (n = 8); High MBOA + PMSG (n = 8). In Experiment II, St. Croix White ewes (n = 24) were synchronized (progestin CIDR) for 14 days followed by hCG on day 1 after CIDR removal (day 0). Ewes were assigned to one of three treatments administered on day -1: Control (n = 8); PMSG (n = 8); Low MBOA+PMSG (n = 8). Laparoscopy was performed on day 9 to assess numbers of corpora lutea (CL) and visible follicles on each ovary. Blood samples were collected on day -13, -1, 0, 1, and days 6 or 7-12 for analysis of serum progesterone (P4) by RIA. Treatment groups receiving PMSG (alone or with MBOA) exhibited greater (P < 0.05) serum concentrations of P4 post-synchrony than Control and MBOA-only groups. Ovulation rate was lower (P < 0.05) for Control and MBOA-only treated ewes than ewes receiving PMSG. Ovulation rate in ewes treated with MBOA alone was similar (P > 0.10) to Controls, and PMSG treatment alone did not differ (P > 0.10) from MBOA + PMSG treatment. Ewes treated with PMSG alone did not differ (P > 0.10) in follicle number from High MBOA + PMSG treated ewes, however, Low MBOA + PMSG treated ewes had greater numbers of follicles at day 9 (P < 0.05) than the PMSG or High MBOA + PMSG groups in Experiment I; although, this was not replicated in Experiment II with numbers of follicles in the Low MBOA + PMSG group being similar (P > 0.10) to PMSG alone. In summary, the addition of MBOA in combination with PMSG as part of a synchronization-superovuation protocol in the ewe did not increase ovulation rate.


New Coumarin Derivatives and Other Constituents from the Stem Bark of Zanthoxylum avicennae: Effects on Neutrophil Pro-Inflammatory Responses.
Three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2), and (Z)-avicennone (3), have been isolated from the stem bark of Zanthoxylum avicennae (Z. avicennae), together with 15 known compounds (4-18). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4, 9, 12, and 15 exhibited inhibition (half maximal inhibitory concentration (IC₅₀) values ≤7.65 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, 4, 8 and 9 inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤8.17 µg/mL. This investigation reveals bioactive isolates (especially 1, 2, 4, 8, 9, 12 and 15) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.


Baseline of Susceptibility to the Cry1F Protein in Mexican Populations of Fall Armyworm.
The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is currently the most important maize pest in Mexico. Its control is mainly based on the use of conventional insecticides. Additionally, Bt-maize expressing Cry1F protein represents an alternative to control this pest. We estimated the baseline susceptibility in Mexican populations of S. frugiperda to Cry1F protein. Twenty-eight geographical populations were field collected from Baja California Sur, Chihuahua, Coahuila, Durango, Sinaloa, Sonora, and Tamaulipas states. The F1 neonate larvae of each population were subjected to diet-overlay bioassay. After 7 d of Cry1F exposure, the percent mortality and the percent growth inhibition with respect to the untreated control were recorded (S-LAB). The LC50 ranged from 14.4 (6.3-24.0) (Cajeme 1, Sonora) to 161.8 ng/cm2 (92.0-320) (Ahumada 2, Chihuahua), while the LC95 was between 207.1 (145-363) (Obregón, Sonora) and 1,217 ng/cm2 (510.8-7,390.0) (Río Bravo 2, Tamaulipas). The sensitivity ratios at 50% mortality, (LC50 field/LC50 S-Lab) and 95% mortality were ≤6.45 and ≤5.05-fold, respectively. The 50% growth inhibition (GI50) ranged from 2.8 (0.008-9.3) (Obregón, Sonora) to 42.4 ng/cm2 (3.6-147.0) (Cajeme 1, Sonora). The GI95 was between 75.4 (San Luis Río Colorado, Sonora) to 1,198 ng/cm2 (Cajeme 1, Sonora). The relative inhibition at 50% of the growth, (RI50 = GI50 field /GI50 S-LAB) was ≤3.5 and at 95% (RI95) was ≤1.91-fold. These results indicated susceptibility to Cry1F protein in the evaluated populations of S. frugiperda.


[Influence of etiology and morphology of traumatic vascular injuries on outcome, risk of amputation and mortality].
In a retrospective trial 159 vascular injuries in 149 patients were registered between 1987-1996. Extremity vessels were injured in 76% of the cases. The same incidence was observed in blunt and penetrating mechanisms. Blunt vascular injuries were associated with an higher rate of live threatening organ damage, longer times of ischaemia (6.5 versus 3.0 h) and an higher mortality (9.7 versus 20.3%) than penetrating injuries. We have found an increased mortality rate in all cases with concomitant trauma of CNS, chest, abdomen or bones. The overall amputation rate in all peripheral vascular injuries has been 22.6%. The functional outcome has been reduced by nerve lesions, amputation and the sequelae of fractures.


[Comparative therapeutic investigations of pivmecillinam and amoxycillin (author's transl)].
The therapeutic value of pivmecillinam and amoxycillin in urinary tract infections was compared in a double blind study. No therapeutic superiority or inferiority of either substance could be demonstrated. The study shows that a therapeutic comparison of two antibiotics using everyday treatment is possible. Before the introduction of new antibiotics at least equal effectiveness of the substance should be documented with appropriate investigations.


Relationship between bifenthrin sediment toxic units and benthic community metrics in urban California streams.
The objective of this study was to use ecologically relevant field measurements for determining the relationship between bifenthrin sediment toxic units (TUs) (environmental concentrations/Hyalella acute LC50 value) and 15 benthic metrics in four urban California streams sampled from 2006 to 2011. Data from the following four California streams were used in the analysis: Kirker Creek (2006, 2007), Pleasant Grove Creek (2006, 2007, and 2008), Arcade Creek (2009, 2010, and 2011), and Salinas streams (2009, 2010, and 2011). The results from univariate analysis of benthic metrics versus bifenthrin TU calculations for the four California streams with multiple-year datasets combined by stream showed that there were either nonsignificant relationships or lack of metric data for 93 % of cases. For 7 % of the data (4 cases) where significant relationships were reported between benthic metrics and bifenthrin TUs, these relationships were ecologically meaningful. Three of these significant direct relationships were an expression of tolerant benthic taxa (either % tolerant taxa or tolerance values, which are similar metrics), which would be expected to increase in a stressed environment. These direct significant tolerance relationships were reported for Kirker Creek, Pleasant Grove Creek, and Arcade Creek. The fourth significant relationship was an inverse relationship between taxa richness and bifenthrin TUs for the 3-year Pleasant Grove Creek dataset. In summary, only a small percent of the benthic metric × bifenthrin TU relationships were significant for the four California streams. Therefore, the general summary conclusion from this analysis is that there is no strong case for showing consistent meaningful relationships between various benthic metrics used to characterize the status of benthic communities and bifenthrin TUs for these four California streams.


The EphA4 Signaling is Anti-catabolic in Synoviocytes but Pro-anabolic in Articular Chondrocytes.
The expression and activation of EphA4 in the various cell types in a knee joint was upregulated upon an intraarticular injury. To determine if EphA4 signaling plays a role in osteoarthritis, we determined whether deficient EphA4 expression (in EphA4 knockout mice) or upregulation of the EphA4 signaling (with the EfnA4-fc treatment) would alter cellular functions of synoviocytes and articular chondrocytes. In synoviocytes, deficient EphA4 expression enhanced, whereas activation of the EphA4 signaling reduced, expression and secretion of key inflammatory cytokines and matrix metalloproteases. Conversely, in articular chondrocytes, activation of the EphA4 signaling upregulated, while deficient EphA4 expression reduced, expression levels of chondrogenic genes (e.g., aggrecan, lubricin, type-2 collagen, and Sox9). EfnA4-fc treatment in wildtype, but not EphA4-deficient, articular chondrocytes promoted the formation and activity of acidic proteoglycan-producing colonies. Activation of the EphA4 signaling in articular chondrocytes upregulated Rac1/2 and downregulated RhoA via enhancing Vav1 and reducing Ephexin1 activation, respectively. However, activation of the EphA4 signaling in synoviocytes suppressed the Vav/Rac signaling while upregulated the Ephexin/Rho signaling. In summary, the EphA4 signaling in synoviocytes is largely of anti-catabolic nature through suppression of the expression of inflammatory cytokines and matrix proteases, but in articular chondrocytes the signaling is pro-anabolic in that it promotes the biosynthesis of articular cartilage. The contrasting action of the EphA4 signaling in synoviocytes as opposing to articular chondrocytes may in part be mediated through the opposite differential effects of the EphA4 signaling on the Vav/Rac signaling and Ephexin/Rho signaling in the two skeletal cell types.


I - Prostaglandin hyperalgesia, a cAMP/Ca2+ dependent process.
Prostaglandins stimulate cAMP increase in several biological systems including CNS. The possible participation of a cAMP/Ca2+ related mechanism in prostaglandin induced hyperalgesia in the rat paw, as measured by a modification of the Randall-Selitto method was investigated. A serie of agents was administered in the paw in an attempt to change either Ca2+ or cyclic AMP concentration at the nociceptive terminations. PGE2, dibutyryl cyclic AMP, isoprenaline, noradrenaline, adrenaline, Ca2+ionophore (A23187), BaCl2 caused a dose dependent hyperalgesia. The hyperalgesic effect of these substances was enhanced by methyl-xanthines. Cyclic GMP as well as agents which interfere with Ca2+ influx (verapamil and lanthanum) were local analgesics in normal and hyperalgesic paws.


The incidence of dorsal radiocarpal ligament tears in patients having diagnostic wrist arthroscopy for wrist pain.
The goal of this study was to examine the incidence of dorsal radiocarpal ligament (DRCL) tears in patients having diagnostic arthroscopy for chronic wrist pain. A chart review was performed of 64 patients who had diagnostic wrist arthroscopy for chronic wrist pain that was refractory to conservative measures. For each case, interosseous ligament instability/tears were graded according to the Geissler classification. Tears of the triangular fibrocartilage complex and the presence or absence of a DRCL tear were noted. There were 35 of 64 wrists (in 64 patients) with DRCL tears. The average duration of wrist pain prior to treatment was 20 months. Only 10 patients could recall a specific injury. Five patients had an isolated DRCL tear. A scapholunate interosseous ligament injury was identified in 13 patients, of whom 7 had a concomitant DRCL tear. A lunotriquetral interosseous ligament injury was present in 7 patients, of whom 2 had a concomitant DRCL tear. Two patients had a capitohamate ligament tear: 1 of these patients had a DRCL tear. There were 7 patients with a solitary triangular fibrocartilage complex tear: 6 of 7 were in association with a DRCL tear. One patient had a chronic ulnar styloid nonunion and a DRCL tear. Two or more lesions were present in 23 patients; DRCL tears were present in 12. DRCL tears are commonly seen with injuries to the primary wrist stabilizers. Recognition of this condition and further research into treatment methods are needed. Diagnostic IV.


Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000.
To describe the clinical and biologic evolution of HIV-1 infection in Africa. One hundred four HIV-1-infected individuals were identified prospectively from regular blood donors in Abidjan, Côte d'Ivoire. The date of seroconversion was estimated from results of sequential serologic tests. Biologic and clinical follow-up was performed every 6 months, starting as early as possible after seroconversion. Case management followed national guidelines. The median interval between estimated seroconversion and study inclusion was 9.7 months, and the median window of seroconversion was 2.8 months. At baseline, all but two patients were asymptomatic; the median CD4 + cell count was 527/mm 3 (interquartile range [IR], 395-684), and the median plasma HIV RNA level was 4.6 log 10 copies/ml (IR, 3.8-4.9). The median follow-up was 23.9 months, and 95% of the patients received primary prophylaxis with co-trimoxazole for opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3 developed tuberculosis, and 17 had a Centers for Disease Control and Prevention category B-defining event. The 3-year AIDS-free and symptom-free probabilities were 96.7% (95% confidence interval [CI], 87.0-99.2] and 79.3% (95% CI, 67.5-87.2), respectively. During the first 3 years of follow-up, we observed that the median plasma viral load stabilized at >4 log 10 copies/ml and that the median CD4 + cell count declined by 20 to 25/mm 3 per year. These African seroconverters were moderately immunosuppressed. The median HIV RNA level was high and varied very little during the first 3 years, and there were few clinical events.


Enrichment of microbial community generating electricity using a fuel-cell-type electrochemical cell.
A fuel cell was used to enrich a microbial consortium generating electricity, using organic wastewater as the fuel. Within 30 days of enrichment the maximum current of 0.2 mA was generated with a resistance of 1 kOhms. Current generation was coupled to a fall in chemical oxygen demand from over 1,700 mg l(-1) down to 50 mg l(-1). Denaturing gradient gel electrophoresis showed a different microbial population in the enriched electrode from that in the sludge used as the inoculum. Electron microscopic observation showed a biofilm on the electrode surface and microbial clumps. Nanobacteria-like particles were present on the biofilm surface. Metabolic inhibitors and electron acceptors inhibited the current generation. 16S ribosomal RNA gene analysis showed a diverse bacterial population in the enrichment culture. These findings demonstrate that an electricity-generating microbial consortium can be enriched using a fuel cell and that the electrochemical activity is a form of anaerobic electron transfer.


Female or Male Fertility Motivation? Which One Determines the Number of Children? (A Comparative Study).
In the last three decades, childbearing in Iran has decreased more than many countries in the world. The aim of this study was to explore the fertility motivation of Working women and their husbands and discover which one determines the number of children. This correlational study was conducted on 540 employed, married women and their husbands (270 couples) living in Mashhad, Iran, during 2017-2018. The participants were selected through multistage cluster sampling. Then, a random number table was used. Subsequently, questionnaires were distributed and completed at home, and collected after 24 h. Data were collected using a demographic characteristics form and the Childbearing Questionnaire (CBQ). The mean(SD) positive motivation scores of men and women differed significantly [92.77 (13.04) Vs. 92.22 (13.51) df = 4; p = 0.001;]. The mean (SD) negative motivation scores of men and women also differed significantly 55.42 (10.94) Vs. 56.78 (10.57) df = 4; p = 0.001;]. According to the scores obtained for the positive and negative fertility motivations of working women and their husbands, women were more in favor of having children and had an ambivalent motivation to bear children. Moreover, the working women's spouses were more indifferent to fertility. The results of this study can help reproductive health policymakers in childbearing.


The Elastin-Derived Peptide VGVAPG Does Not Activate the Inflammatory Process in Mouse Cortical Astrocytes In Vitro.
During vascular aging or in pathological conditions in humans, elastin is degraded and its by-products, the elastin-derived peptides (EDPs), enter the blood circulation. EDPs may be detected in the serum of healthy subjects or people who suffered a stroke. Moreover, recent evidence suggests a potential role of inflammatory mechanisms in neurological conditions, which are usually not categorized as inflammatory. Therefore, the present in vitro study was conducted to investigate the impact of the VGVAPG peptide on the activation of inflammatory process in mouse primary astrocytes, which were maintained in phenol red-free DMEM/F12 supplemented with 10% fetal bovine serum. The cells were exposed to VGVAPG or VVGPGA peptides for 24 and 48 h; this was followed by the determination of the activity of caspase-1 and levels of SOD, CAT, PPARγ, NF-κB, IL-1β, and IL-1βR1. Furthermore, rosiglitazone-a PPARγ agonist-was applied. Our study pioneered the finding that the VGVAPG peptide increases caspase-1 activity in astrocytes in vitro. The VGVAPG peptide simultaneously decreases the release of IL-1β into the cell-culture medium from astrocytes. The ELISA method revealed that the VGVAPG peptide increases the protein expression of SOD1 whereas it decreases the expression of IL-1βR1, CAT, and NF-κB. Therefore, the available data suggest that the VGVAPG peptide (concentration 10 nM) synergistically acts with agonists of PPARγ in mouse astrocytes. However, given the lack of sufficient data to explain the molecular mechanism of action of the VGVAPG peptide in the nervous system, more studies in this area are necessary.


Ecotoxicity and genotoxicity assessment of exhaust particulates from diesel-powered buses.
Diesel exhaust is one of the major sources of fine and ultra-fine particulate matter in urban air. Toxicity of diesel-powered engine emissions has been quite widely assessed; however, much less information is available on their ecotoxicity. In our study, the kinetic version of the Vibrio fischeri bioluminescence inhibition bioassay based on the ISO 21338:2010 standard was used to characterise the ecotoxicity of diesel-powered buses. It is a direct contact test in which solid samples are tested in suspension and test organisms are in direct contact with toxic particles. The age of the selected buses fell into a wide range; the oldest one was produced in 1987. Diesel engines of different emission standards (Euro0-Euro4) were included. Measured EC50 values of Euro0-Euro1 engine emissions fell into the same range, 1.24-0.96 μg ml(-1), respectively. On the contrary, emission of Euro4 vehicle proved to be non-toxic. Genotoxic potential of the samples was also estimated, using the colorimetric SOS-chromotest™. Genotoxicity was detected also for Euro0 and Euro1 buses, showing correlation with the ecotoxic potential. The fact that the particulates from Euro4 vehicles did not show ecotoxic/genotoxic effect implies that replacing old Euro1 and Euro2 buses can be a highly effective solution for reducing environmental hazard of automotive emissions. The whole-aerosol testing method is a cheap alternative that can be used in engine developments and emission control.


Non-linear changes in modelled terrestrial ecosystems subjected to perturbations.
Perturbed ecosystems may undergo rapid and non-linear changes, resulting in 'regime shifts' to an entirely different ecological state. The need to understand the extent, nature, magnitude and reversibility of these changes is urgent given the profound effects that humans are having on the natural world. General ecosystem models, which simulate the dynamics of ecosystems based on a mechanistic representation of ecological processes, provide one novel way to project ecosystem changes across all scales and trophic levels, and to forecast impact thresholds beyond which irreversible changes may occur. We model ecosystem changes in four terrestrial biomes subjected to human removal of plant biomass, such as occurs through agricultural land-use change. We find that irreversible, non-linear responses commonly occur where removal of vegetation exceeds 80% (a level that occurs across nearly 10% of the Earth's land surface), especially for organisms at higher trophic levels and in less productive ecosystems. Very large, irreversible changes to ecosystem structure are expected at levels of vegetation removal akin to those in the most intensively used real-world ecosystems. Our results suggest that the projected twenty-first century rapid increases in agricultural land conversion may lead to widespread trophic cascades and in some cases irreversible changes to ecosystem structure.


Gender of Authors in Laboratory Animal Medicine and Science in 2 Peer-Reviewed U. S. Journals.
Multiple recent surveys have examined the prevalence of female first or senior authors on publications for various scientific and medical disciplines. First and senior authorships are significant achievements for purposes of professional advancement, especially in academia. Such surveys can also provide information regarding diversity and inclusion. In this report, we present the findings of a survey performed to assess how frequently female contributors were first or senior authors in 2 of the most widely-circulated peer-reviewed journals of laboratory animal medicine and science in the United States; data were collected at 3 time points over a recent 20-y span. These data were then compared against estimated populations of potential female authors, as determined from membership rolls in the American Society of Laboratory Animal Practitioners and the American College of Laboratory Animal Medicine. Survey results suggest that female authors increased their representation as influential authors over time, in contrast to representation trends reported for other disciplines. However, whether this increase has mirrored the increase in women overall in the veterinary profession during this time span is unknown. In an era of greater attention and sensitivity to equity and inclusion, this survey is offered as a starting point for further conversation within the field of laboratory animal medicine and science.


Metabonomic Responses of Grazing Yak to Different Concentrate Supplementations in Cold Season.
Supplementation plays an important role in reversing the weight loss of grazing yaks during cold season. However, little is known about the effect of supplementation on the serum metabolites of grazing yaks. The objective of this study was to explore the effects of supplementary feeding on average daily gain (ADG) and serum metabolites with nuclear magnetic resonance (NMR)-based metabolomics method in growing yaks during cold season on the Qinghai-Tibetan plateau. Twenty 1.5-year-old female yaks (91.38 ± 10.43 kg LW) were evenly divided into three treatment groups and a control group (CON) (n = 5 per group). All the yaks were released to graze during daytime, whereas the yaks in the treatment groups were supplemented with highland barley (HLB), rapeseed meal (RSM), and highland barley plus rapeseed meal (HLB + RSM) at night. The whole experiment lasted for 120 days. Results indicated that the ADG of growing yak heifers was increased by concentrate supplementations, and ADG under HLB and HLB + RSM group was 37.5% higher (p < 0.05) than that with RSM supplementation. Supplementary feeding increased the plasma concentrations of total protein (TP), albumin (ALB), and blood urea nitrogen (BUN) of those in the CON group, and concentrations of BUN were higher in the RSM group than in the HLB and HLB + RSM group. Compared with the CON group, serum levels of glutamine, glycine, β-glucose were lower and that of choline was higher in the HLB group; serum levels of lactate were lower and that of choline, glutamate were higher in the HLB + RSM group. Compared with the HLB + RSM group, serum levels of glycerophosphoryl choline (GPC) and lactate were higher, and those of choline, glutamine, glutamate, leucine, N-acetyaspartate, α-glucose, and β-glucose were lower in the HLB group; serum levels of citrate, GPC and lactate were higher, and those of 3-Hydroxybutyrate, betaine, choline, glutamate, glutamine, N-acetylglycoprotein, N-acetyaspartate, α-glucose, and β-glucose were lower in the RSM group. It could be concluded that concentrate supplementations significantly improved the growth performance of growing yaks and supplementation with HBL or HLB plus RSM was better than RSM during the cold season. Supplementation with HBL or HLB plus RSM affected the serum metabolites of grazing yaks, and both treatments promoted lipid synthesis. Supplementation of yaks with HBL plus RSM could improve energy-supply efficiency, protein and lipid deposition compared with HLB and RSM.


Ultrasound-guided arthroscope insertion and decompression of a supraspinous fossa cyst.
A cyst arising in the scapular supraspinous fossa may cause shoulder pain; subsequently, enlargement of the cyst may result in severe compression of the adjacent suprascapular nerve, leading to muscle weakness and sensory disorder. Decompression of the nerve through cyst removal is effective in resolving these symptoms. However, treatment can also be performed less invasively through arthroscopy. Insertion of an arthroscope without visual guidance could cause tissue damage and, consequently, would become an invasive procedure itself. The use of ultrasonography to guide the scope to the cyst decreases the invasiveness of the procedure. Here, we present the case of a patient with a cyst arising in the scapular supraspinous fossa, in whom we could relatively readily and safely observe the cyst by advancing an arthroscope under ultrasonographic guidance. The suprascapular nerve was decompressed via cyst removal.


The inhibition of sodium, potassium-stimulated ATPase and corneal swelling: the role played by polyols.
Sodium, potassium-stimulated adenosine triphosphatase (Na,K-ATPase; E. C. 126.96.36.199) is considered to be the principal corneal enzyme responsible for deturgescence. Some metabolites are known to inhibit Na,K-ATPase, including glucose and galactose. In diabetes, some cells take up high levels of glucose and are converted to the polyhydroxy alcohol: sorbitol. In galactosemia, a similar uptake of galactose may cause the intracellular formation of the polyhydroxy alcohol: galactatol. This study tested the possibility that polyhydroxy alcohols (polyols), metabolized from carbohydrates, might decrease Na,K-ATPase activity. Cultured corneal endothelial cells were separately exposed to 20 mM of the polyols: sorbitol, galactitol, and xylitol. Media containing 5 mM glucose served as the control. Plasma membrane vesicles, containing the Na,K-ATPase, were isolated and tested for the enzyme's activity. We found that the enzyme, after exposure to polyols, had only 15%-20% of its normal activity when assayed with the control. Since corneal endothelial cells can generate polyols in diabetes mellitus, this result may explain why corneas are able to swell in individuals with poorly controlled diabetes.


Clinical findings using echocardiography and plasma cardiac troponin I and pathological findings in dogs with hypertrophic cardiomyopathy: A retrospective study.
Hypertrophic cardiomyopathy (HCM) is considered rare in dogs, and there is a lack of clinical data. Cardiac troponin I (cTnI) is a biomarker of cardiomyocyte damage and necrosis and can be used to diagnose cat and human HCM. We investigated whether the presence of cTnI in clinical data can be used in conjunction with echocardiography to diagnose canine HCM. This study comprised client-owned dogs with clinical evidence of concentric hypertrophy on echocardiographic images, serum total thyroxine levels of ≤5 µg/dl, systolic blood pressure of ≤180 mmHg, and absence of aortic stenosis. All cases were necropsied. Cardiomyocyte hypertrophy (mean diameter, 18.3 ± 1.8 µm), myocardial fiber disarray (70%), interstitial fibrosis (80%), and small vessel disease (100%) were assessed. In dogs with HCM, the left ventricles were concentric, almost symmetrical, and hypertrophied above the aortic diameter. The end-diastolic interventricular septum normalized to body weight [intraventricular septal thickness in diastole (IVSDN)] was 0.788 [interquartile range (IQR), 0.7-0.92], which exceeded the normal range (5%-95%, IQR: 0.33-0.52). In total, 70% of the dogs with HCM had syncope and dyspnea, and all dogs had high cTnI levels (median, 3.94 ng/ml), exceeding the upper limit of normal (0.11 ng/ml) and indicating cardiomyocyte damage. IVSDN and serum cTnI levels were correlated (ρ = 0.839, p = 0.01). Ventricular wall thickening and high serum cTnI levels can provide a presumptive diagnosis of HCM and prompt the initiation of treatment or additional diagnostic investigations.


Development and Validation of a Nomogram Model to Predict Acute Kidney Disease After Nephrectomy in Patients with Renal Cell Carcinoma.
To develop and validate a nomogram model to predict the occurrence of acute kidney disease (AKD) after nephrectomy. A retrospective cohort including 378 patients with renal cell carcinoma (RCC) who had undergone radical or partial nephrectomy between March 2013 and December 2017 at the First Affiliated Hospital of Zhengzhou University was analyzed. Of these, patients who had undergone surgery in an earlier period of time formed the training cohort (n=265) for nomogram development, and those who had undergone surgery thereafter formed the validation cohort (n=113) to confirm the model's performance. The incidence rate of AKD was measured. Univariate and multivariate logistics regression analysis was used to estimate the independent risk factors associated with AKD. The independent risk factors were incorporated into the nomogram. The accuracy and utility of the nomogram were evaluated by calibration curve and decision curve analysis, respectively. Overall, AKD occurred in 27.5% and 28.3% of patients in the training and validation cohorts, separately. The final nomogram included surgery approach, Charlson comorbidity index (CCI), and the decrement of eGFR. This model achieved good concordance indexes of 0.78 (95% CI=0.71-0.84) and 0.76 (95% CI=0.67-0.86) in the training and validation cohorts, respectively. The calibration curves and decision curve analysis (DCA) demonstrated the accuracy and the clinical usefulness of the proposed nomogram, separately. The nomogram accurately predicts AKD after nephrectomy in patients with RCC. The risk for patients' progress into AKD can be determined, which is useful in guiding clinical decisions.


Regulation of intermediary metabolism in rat cardiac myocyte by extracellular glycerol.
In the human heart, although all substrates compete for energy production, fatty acids (FA) represent the main substrate for ATP production. In the healthy heart, a balance between FA and carbohydrate utilization ensures that energy supply matches demand. This study was carried out to evaluate, in a model of spontaneously beating neonatal rat cardiomyocytes in culture, the hypothesis that glycerol could play a central role in the metabolic control of the routes involving long chain FAs and may then affect the balance between beta-oxidation and glucose oxidation. The intracellular-free glycerol significantly increased with extracellular glycerol concentration (0 to 660 microM). The synthesis of phospholipids was significantly increased in parallel with both extracellular glycerol (1.5 and 14.8 nmol glycerol/mg protein, at 82 and 660 microM of extracellular glycerol, respectively). The oxidation of glycerol increased proportionally to extracellular glycerol concentration (from 1 to 3 nmol glycerol/mg protein, at 82 microM and 660 microM extracellular glycerol, respectively, P<0.001). At its maximum, this oxidation represented 15% of the glucose oxidation, which was not affected by glycerol extracellular supply or intracellular availability. Conversely, extracellular glycerol significantly reduced the palmitate oxidation above (-47% at 660 microM glycerol), but not octanoate oxidation. Investigations on the mechanism of the decreased palmitate oxidation reveals a glycerol-dependent increase in malonyl-CoA associated with a significant decrease in CPT-1 activity which accounts for the difference between palmitate and octanoate. These results clearly demonstrate the importance of glycerol in regulating the cardiac metabolic pathways and energy balance.


The personal and professional impact of the future of nursing report.
Perioperative nurses can apply the four key messages outlined in the Institute of Medicine report The Future of Nursing: Leading Change, Advancing Health from personal and professional perspectives. Advocating to remove barriers to practice and educating the public about the perioperative nurse's role can help nurses practice to the full extent of their education and training. Nurses can achieve higher levels of education and training by taking advantage of new educational opportunities that offer a more seamless progression to an advanced degree. To act as full partners with other health professionals, nurses can participate in interdisciplinary teams and implement evidence-based practice, and they can contribute to effective workforce planning and policy making by helping to collect and analyze data that will improve practice environments. The key messages of the report address all nurses, whether they are direct care providers, advanced practice RNs, educators, or administrators.


Drug-induced QT Prolongation Atlas (DIQTA) for enhancing cardiotoxicity management.
Drug-induced prolongation of the QT interval is common in a variety of pharmaceutical treatments and can lead to serious clinical outcomes. Although substantial efforts have been made to prevent drug-induced QT interval prolongation, the lack of a centralized data source remains the main obstacle to further study of the underlying mechanism and the development of effective prediction strategies. To fill this gap, we propose a schema for stratifying the risk of marketed QT prolonging drugs based on US Food and Drug Administration (FDA)-approved drug labeling and developed a Drug-Induced QT Prolongation Atlas (DIQTA). Potential application of DIQTA was shown by precision dosing in off-label use and therapeutic strategy optimization, as well as the facilitation of artificial intelligence (AI)-based modeling in predictive toxicity.


Transfer of learning between hands to handle a novel object in old age.
Transferring information about object weight between hands for use in scaling prehension forces likely depends on the integrity of the structures linking the two sides of the brain. It is unknown whether healthy older adults, who demonstrate a modest decline in this connectivity, transfer fingertip force scaling for object weight between hands. In the present study, healthy older and young adults performed two tasks: gripping and lifting an object, and a ballistic finger abduction movement. For the grip and lift task, participants practiced lifting a novel object using a precision pinch grip with the right hand (RH) and then did so again with the left hand (LH). For the ballistic task, participants were trained to maximally accelerate the right index finger by abducting it. On the grip and lift task, all participants appeared to overestimate the object weight during the 1st RH lift, followed by a progressive reduction on successive lifts. This adaptation was transferred to the LH in both groups on their first lift and remained stable over subsequent lifts. In contrast, the training-induced peak abduction acceleration on the ballistic task transferred poorly to the LH in older with considerably better transfer in young adults. We conclude that the memory representations scaling the lift force for the grip and lift task generalized to the untrained hand, while the greater acceleration that was acquired during practice of the ballistic task showed an incomplete transfer to the opposite hand. These differences may indicate task-dependent interhemispheric transfer of learning in old age.


Lactobacillus protoplast transformation.
A method for the transformation of Lactobacillus protoplasts by plasmid DNA is reported. The procedure involves polyethylene glycol treatment of protoplasts to induce DNA uptake. A transformation efficiency ranging from 5 to 1000 transformants per microgram of DNA is achieved; the efficiency of protoplast regeneration ranged from 10 to 20%.


Assessing communication in children with psychiatric and communication disorders.
This article presents issues related to the communication assessment of children with psychiatric and communication disorders. Challenges inherent in assessing this population are discussed. Frequently used assessment instruments and procedures are described. Consideration is given to the assessment of very young or low-functioning children and older or high-functioning children.


What Online User Innovation Communities Can Teach Us about Capturing the Experiences of Patients Living with Chronic Health Conditions. A Scoping Review.
In order to adapt to societal changes, healthcare systems need to switch from a disease orientation to a patient-centered approach. Virtual patient networks are a promising tool to favor this switch and much can be learned from the open and user innovation literature where the involvement of online user communities in the innovation process is well-documented. The objectives of this study were 1) to describe the use of online communities as a tool to capture and harness innovative ideas of end users or consumers; and 2) to point to the potential value and challenges of these virtual platforms to function as a tool to inform and promote patient-centered care in the context of chronic health conditions. A scoping review was conducted. A total of seven databases were searched for scientific articles published in English between 1995 and 2014. The search strategy was refined through an iterative process. A total of 144 studies were included in the review. Studies were coded inductively according to their research focus to identify groupings of papers. The first set of studies focused on the interplay of factors related to user roles, motivations, and behaviors that shape the innovation process within online communities. Studies of the second set examined the role of firms in online user innovation initiatives, identifying different organizational strategies and challenges. The third set of studies focused on the idea selection process and measures of success with respect to online user innovation initiatives. Finally, the findings from the review are presented in the light of the particularities and challenges discussed in current healthcare research. The present paper highlights the potential of virtual patient communities to inform and promote patient-centered care, describes the key challenges involved in this process, and makes recommendations on how to address them.


Protein disulfide oxidoreductases and the evolution of thermophily: was the last common ancestor a heat-loving microbe?
Protein disulfide oxidoreductases (PDOs) are redox enzymes that catalyze dithiol-disulfide exchange reactions. Their sequences and structure reveal the presence of two thioredoxin fold units, each of which is endowed with a catalytic site CXXC motif. PDOs are the outcome of an ancient gene duplication event. They have been described in a number of thermophilic and hyperthermophilic species, where they play a critical role in the structural stabilization of intracellular proteins. PDOs are homologous to both the N-terminal domain of the bacterial alkyl hydroperoxide reductase (AhpF) and to the eukaryotic protein disulfide isomerase (PDI). Phylogenetic analysis of PDOs suggests that they first evolved in the crenarchaeota, spreading from them into the Bacteria via the euryarchaeota. These results imply that the last common ancestor (LCA) of all extant living beings lacked a PDO and argue, albeit weakly, against a thermophilic LCA.


Dibutyryl cyclic AMP inhibits the progression of experimental autoimmune encephalomyelitis and potentiates recruitment of endogenous neural stem cells.
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Cyclic AMP and its analogs enhance regeneration of adult mammalian central nervous system (CNS). Endogenous neural stem cells (NSCs) play a pivotal role in CNS regeneration, producing new neuron and glial cells. Here, we examined the effect of dibutyryl cyclic AMP (dbcAMP) on experimental autoimmune encephalomyelitis (EAE) symptoms, endogenous remyelination, and recruitment of NSCs. EAE was induced by immunizing mice using myelin oligodendrocyte glycoprotein peptide and pertussis toxin. Proliferative cells within CNS were labeled using repetitive systemic injections of 5-bromo-2-deoxyuridine (BrdU) before EAE induction. Myelin staining was performed using Luxol fast blue. The number of nestin(+) and BrdU(+) cells in subventricular zone (SVZ) and olfactory bulb (OB) was evaluated using immunohistochemistry. dbcAMP suppressed EAE progression and decreased the extent of demyelinated plaques in the lumbar spinal cord. EAE induction reduced the number of proliferative cells in SVZ and increased their population in OB. EAE also increased the number of nestin(+) cells in OB. We also found that dbcAMP increased the recruitment of NSCs into the OB and brain parenchyma of EAE mice. Our results suggest dbcAMP as a potential therapy for inducing myelin repair in the context of demyelinating diseases like multiple sclerosis. Its positive effect seems to be mediated, at least partially, by endogenous neural stem cells and their increased recruitment.


Isolation of peroxisomes from the dog kidney cortex.
The present study was undertaken to separate peroxisomes of the dog kidney cortex by the methods of discontinuous sucrose density gradient and zonal centrifugation. The separation of subcellular particles was evaluated by measuring the activities of reference enzymes, beta-glycerophosphatase for lysosomes, succinate dehydrogenase for mitochondria, glucose-6-phosphatase for microsomes, and catalase and D-amino acid oxidase for peroxisomes. The activities of D-amino acid oxidase and catalase were mainly observed in fractions 1 and 2 (1.6 and 1.7 M sucrose) obtained by discontinuous sucrose density-gradient centrifugation. Small amounts of acid phosphatase and succinate dehydrogenase contaminated these fractions. Considerably higher activity of catalase was determined in the supernatant, while D-amino acid oxidase showed a lower activity. By the method of zonal centrifugation, the highest specific activities of catalase and D-amino acid oxidase were found in fraction 50 (1.73 M sucrose) with no succinate dehydrogenase, acid phosphatase or glucose-6-phosphatase activity. These results suggested that peroxisomes of dog kidney cortex were clearly separated in 1.73 M sucrose from mitochondria, lysosomes and microsomes by zonal centrifugation.


Interaction of smoking and radon in rats: a biologically based mechanistic model.
Data on rats exposed to cigarette smoke before or after exposure to radon are used to estimate smoke-dependent parameters of the biologically based two-stage clonal expansion model. The baseline parameters and the action of radon acting on initiation and promotion were fixed based on earlier work. Cigarette smoke acting on transformation and inducing a reduction of the radon dose to the target cells after a smoking period gives an acceptable description of the data.


Psychrotrophic, proteolytic and lipolytic properties of Enterobacteriaceae isolated from milk and dairy products.
Most of the Enterobacteriaceae strains (73 out of 75) isolated in a previous study (Wessels et al., 1988) were psychrotrophic on agar plates, with the exception of Enterobacter cloacae strains. The Enterobacteriaceae strains were largely non-proteolytic on milk agar medium although limited numbers of E. cloacae, Serratia rubidaea and Klebsiella oxytoca strains were capable of proteolytic activity at 25 degrees C. The E. cloacae and K. oxytoca strains positive at 25 degrees C were also proteolytic at 7 degrees C. Most of the species tested were non-lipolytic on Victoria blue butterfat agar. The majority of Serratia marcescens and Klebsiella pneumoniae strains and a minority of E. cloacae and K. oxytoca strains, however, were lipolytic on this medium.


IL-1β is involved in docetaxel chemoresistance by regulating the formation of polyploid giant cancer cells in non-small cell lung cancer.
Docetaxel (Doc) is a cornerstone of chemotherapy; however, treatment with Doc often and inevitably leads to drug resistance and the formation of polyploid giant cancer cells (PGCCs). In this study, we investigated the effect of Doc on non-small cell lung cancer to explore the role of PGCCs in drug resistance and the molecular mechanisms that regulate this resistance. We found that Doc induced G2/M cell cycle arrest and cell death in A549 and NCI-H1299 cells. However, many cells remained alive and became PGCCs by decreasing the expression of key regulatory proteins related to the cell cycle and proliferation. Notably, the PGCCs showed typical features of senescence, especially upregulation of p21 and p-histone H2A.X expression. Moreover, the mRNA level of IL-1β in the senescence-associated secretory phenotype was increased significantly with the development of PGCCs. Inhibition of IL-1β reduced the expression of p-histone H2A.X and promoted polyploidy to enhance the proapoptotic effect of Doc. Taken together, our results suggested that IL-1β was involved in the formation of PGCCs and regulated the senescence of PGCCs, which contributed to drug resistance to Doc. Therefore, targeting IL-1β in PGCCs may be a novel approach to overcome drug resistance.


Nutrient density and bioaccessibility, and the antioxidant, satiety, glycemic, and alkalinizing potentials of fruit-based foods according to the degree of processing: a narrative review.
Epidemiological studies suggest that the protective effects of fruits against chronic diseases may vary according to their extent of processing. We therefore reviewed what the scientific literature states about the potential mechanisms underlying this "processing" effect by focusing on the most significant nutritional properties, namely, the nutritional density of bioactive compounds, the digestive bio-accessibility of nutrients, and the antioxidant, satietogenic, alkalizing and glycemic potentials. When possible, we have ranked fruits according to the international NOVA classification as un-/minimally processed, processed (mainly with added sugars), and ultra-processed fruits. Our literature review confirms that the more fruits are processed, the lower are their alkalizing, antioxidant and satietogenic potentials. For the glycemic index, the results are more difficult to interpret because fruits are a significant source of fructose with a very low glycemic index that "distorts" the "processing" effect. However, fruits in sirup tend to have a higher glycemic index, probably because of the highly bioavailable added sugars. Overall, the destructuration of the fruit fibrous matrix by thermal and mechanical treatments, combined with the addition of simple sugars, constitute the treatments that most degrade the fruit nutritive quality by diluting the nutritional density and attenuating the "matrix" effect. The new technological processes described as "nonthermal" (e.g., pulsed electric fields, high pressures, supercritical CO2, radiation, etc.) seem promising as they limit vitamin C and antioxidant phytonutrient losses in fruit while allowing satisfactory storage time. To preserve fruit longer, drying appears to be an interesting alternative to maintain the health potential of fruit, although it causes antioxidant losses. Finally, although "5 fruits and vegetables a day" is a well-known nutritional recommendation, in view of the results reviewed here, it would be relevant to be precise and include "preferably minimally processed".


Bisphosphonate related osteonecrosis of the jaws: spontaneous or dental origin?
Bisphosphonates are frequently used worldwide mostly in osteoporosis and skeletal bone metastases. However, a serious side-effect is bisphosphonate related osteonecrosis of the jaws (BRONJ). The mechanism behind BRONJ remains unclear. In literature several origins are suggested. Presence of the teeth in the jaws may play an important role. Therefore in this study 45 patients were analyzed retrospectively. Files of 45 patients with a diagnosis of BRONJ were analyzed, meaning clinical features, bisphosphonate use, dental history including luxating moment and (previous) treatment. In 97.5% (n = 44) a certain or presumable dental focus, such as extractions, a previous dental treatment or prosthesis complaints were found as initiating factor of BRONJ. In contrast to findings in literature, in our group of patients a dental focus was found in 44 of 45 cases. This implies a dentoalveolar start of BRONJ with subsequent spreading into the jaws in nearly all cases.


Concord, N.H., hospital cited for significant progress using Internet. Web site builds connections with a variety of constituents.
Concord Hospital, Concord, N.H., is one of the nation's "10 Most Improved Hospitals," based on its significant progress in using Internet technologies. The Hospital's Web site, www.concordhospital.org., has received other awards.


Increase of ibuprofen penetration through the skin by forming ion pairs with amino acid alkyl esters and exposure to the electromagnetic field.
A method of increasing the permeability of ibuprofen through the skin using a rotating magnetic field (RMF) is presented. This study evaluated whether 50 Hz RMF modifies ibuprofen's permeability through the skin. Ibuprofen and its structural modifications in the form of ibuprofenates of isopropyl esters of L-amino acids such as L-valine, L-phenylalanine, L-proline, and L-aspartic acid were used in the research. To this end, Franz cells with skin as membrane were exposed to 50 Hz RMF with 5% ibuprofen and its derivatives in an ethanol solution for 48 h. Following the exposures, the amount of penetrated compound was analysed. Regardless of the compound tested, a significant increase in drug transport through the skin was observed. The differences in the first 30 min of permeation are particularly noticeable. Furthermore, it was shown that using RMF increases the permeability of ibuprofen from 4 to 244 times compared to the test without the RMF. The greatest differences were observed for unmodified ibuprofen. However, it is noteworthy that the largest amounts of the active substance were obtained with selected modifications and exposure to RMF. The RMF may be an innovative and interesting technology that increases the penetration of anti-inflammatory and anti-ache drugs through the skin.


Pseudomonas aeruginosa septicaemia in a patient with severe Plasmodium falciparum.
This report describes a Danish patient with severe Plasmodium falciparum infection and Pseudomonas aeruginosa septicaemia. The patient had been sailing along the coast of West Africa for ten years without taking any antimalaria prophylaxis and without any apparent previous history of malaria. He presented with severe form of malaria, progressing rapidly into coma and died within a short time. P. aeruginosa was isolated from his blood taken on the day of admission. His neutrophils were all occupied by P. falciparum. The unusual combination of severe falciparum malaria infection and P. aeruginosa septicaemia with extensive involvement of neutrophils lends further support for the role of phagocytic defence in malaria.


Cuprolinic Blue: a specific dye for single-stranded RNA in the presence of magnesium chloride. I. Fundamental aspects.
Qualitative and quantitative aspects of the cationic dye Cuprolinic Blue were investigated with model films of polyacrylamide gel in which RNA, DNA and other biological polyanionic compounds had been incorporated. In the presence of 1 M MgCl2, Curpolinic Blue was found to bind specifically to single-stranded RNA, leaving native DNA, proteins, (acid) polysaccharides and phospholipids completely unstained. Under these conditions, Cuprolinic Blue is complexed by non-electrostatic bonds with non-stacke purine bases, mainly adenine. Optimal conditions for dye binding and differentiation have been defined. Both the Cuprolinic Blue-MgCl2 staining of single-stranded RNA and the Cuprolinic Blue staining of RNA and DNA in the absence of MgCl2 were found to obey the Lambert-Beer law. The advantages and possible applications of Cuprolinic Blue are compared with well-known (indirect) histochemical RNA staining procedures.


An investigation into dentists' perceptions of barriers to providing care of dental trauma to permanent maxillary incisors in children in Victoria, Australia.
Perceived barriers in the treatment of dental trauma may influence the optimum management of dental trauma. Any hesitation that dentists might have in managing dental trauma is important to investigate. The aim of this study was to investigate dentists' perceptions of barriers to providing care of dental trauma to permanent maxillary incisors in children. A self-completion questionnaire survey containing six questions on demographic data and 15 questions relating to barriers to treating dental trauma was mailed to 693 dentists in Victoria, Australia. The response rate achieved was 61 per cent. Of the respondents, 90 per cent had no hesitation in treating dental injuries and 80 per cent of these frequently agreed that dentists should treat all dental trauma. Approximately half the dentists (51.5 per cent) frequently found uncooperative children to be the main barrier to providing care. The overall consensus from the present study was that treating dental trauma is not unappealing for dentists in general practice.


Evaluation of schistocyte analysis by a novel automated digital cell morphology application.
The CellaVision Advanced Red Blood Cell (RBC) Software Application is a new software for advanced morphological analysis of RBC, which automatically performs a preliminary characterization and grouping of RBC into 21 morphological categories, including schistocytes. Upon automated classification, the software offers the possibility of reclassification of RBC by the operator. The aim of this study was to evaluate the schistocyte analysis by the CellaVision Advanced RBC Application. Schistocyte counts were evaluated comparing the automated count on a CellaVision DM96, both before and after reclassification, with the reference manual microscopic method according to the ICSH criteria. Thirty-six samples of hospitalized patients and 40 samples of controls were analyzed. Within-run, between-run and between-observer coefficients of variation were lower when counted with the CellaVision compared to the manual microscopic count. The very high sensitivity but rather poor specificity implicates the need for reclassification by the operator, following automated analysis. After reclassification, method comparison studies revealed good agreement with the manual microscopic method, with however slightly higher values of schistocytes for the automated analysis. The CellaVision Advanced RBC Software Application provides a sensitive and reproducible measurement of schistocytes in peripheral blood, but still requires manual revision. Furthermore, it is an easy-to-use software and an excellent teaching tool that might contribute to standardization in the investigation of schistocyte-related conditions.


Error estimation and global fitting in transverse-relaxation dispersion experiments to determine chemical-exchange parameters.
Off-resonance effects can introduce significant systematic errors in R2 measurements in constant-time Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation dispersion experiments. For an off-resonance chemical shift of 500 Hz, 15N relaxation dispersion profiles obtained from experiment and computer simulation indicated a systematic error of ca. 3%. This error is three- to five-fold larger than the random error in R2 caused by noise. Good estimates of total R2 uncertainty are critical in order to obtain accurate estimates in optimized chemical exchange parameters and their uncertainties derived from chi2 minimization of a target function. Here, we present a simple empirical approach that provides a good estimate of the total error (systematic + random) in 15N R2 values measured for the HIV protease. The advantage of this empirical error estimate is that it is applicable even when some of the factors that contribute to the off-resonance error are not known. These errors are incorporated into a chi2 minimization protocol, in which the Carver-Richards equation is used fit the observed R2 dispersion profiles, that yields optimized chemical exchange parameters and their confidence limits. Optimized parameters are also derived, using the same protein sample and data-fitting protocol, from 1H R2 measurements in which systematic errors are negligible. Although 1H and 15N relaxation profiles of individual residues were well fit, the optimized exchange parameters had large uncertainties (confidence limits). In contrast, when a single pair of exchange parameters (the exchange lifetime, tau(ex), and the fractional population, p(a)), were constrained to globally fit all R2 profiles for residues in the dimer interface of the protein, confidence limits were less than 8% for all optimized exchange parameters. In addition, F-tests showed that quality of the fits obtained using tau(ex), p(a) as global parameters were not improved when these parameters were free to fit the R2 profiles of individual residues. Finally, nearly the same optimized global tau(ex), p(a) values were obtained, when the 1H and 15N data sets for residues in the dimer interface, were fit independently; the difference in optimized global parameters, ca. 10%, was of marginal significance according to the F-test.