A major QTL corresponding to the Rk locus for resistance to root-knot nematodes in cowpea (Vigna unguiculata L. Walp.).
Genome resolution of a major QTL associated with the Rk locus in cowpea for resistance to root-knot nematodes has significance for plant breeding programs and R gene characterization. Cowpea (Vigna unguiculata L. Walp.) is a susceptible host of root-knot nematodes (Meloidogyne spp.) (RKN), major plant-parasitic pests in global agriculture. To date, breeding for host resistance in cowpea has relied on phenotypic selection which requires time-consuming and expensive controlled infection assays. To facilitate marker-based selection, we aimed to identify and map quantitative trait loci (QTL) conferring the resistance trait. One recombinant inbred line (RIL) and two F2:3 populations, each derived from a cross between a susceptible and a resistant parent, were genotyped with genome-wide single nucleotide polymorphism (SNP) markers. The populations were screened in the field for root-galling symptoms and/or under growth-chamber conditions for nematode reproduction levels using M. incognita and M. javanica biotypes. One major QTL was mapped consistently on linkage group VuLG11 of each population. By genotyping additional cowpea lines and near-isogenic lines derived from conventional backcrossing, we confirmed that the detected QTL co-localized with the genome region associated with the Rk locus for RKN resistance that has been used in conventional breeding for many decades. This chromosomal location defined with flanking markers will be a valuable target in marker-assisted breeding and for positional cloning of genes controlling RKN resistance.


Partial recall: Implications for the discrete slot limit of working memory capacity.
The nature of working memory capacity (WMC) has been a highly contested topic among cognitive scientists. Some advocate for the discrete nature of this construct, fixed to a set number of independent slots, each capable of storing a single chunk of bound information. Others advocate for a continuous limit, guided by a pool of immediately available resources spent across the to-be-remembered items. To understand the nature of WMC, it was first essential to separate capacity from other factors, such as performance consistency, which may impact overall WM performance. Recent work by Schor et al., (2020, Psychonomic Bulletin & Review, 27[5], 1006-1013) has provided a method for separating these constructs within a single visual array task. The present study used this statistical model to extract partial information, defined as accurate recall of a correct color, but not location, at a rate greater than expected through guessing. The successful memory of this information would demonstrate that capacity does not rely on the existence of empty slots, which discrete slot model advocates argue, are necessary for successful storage and recall of items. The present study found that participants were able to successfully recall partial information at a rate significantly greater than chance, but not beyond the individual working memory capacity limit. These findings help provide additional support for the discrete resource slot model, while simultaneously casting doubt on its strong object slot model alternative.


Clinical Practice: Nausea and vomiting in acute gastroenteritis: physiopathology and management.
Currently recommended management of acute gastroenteritis is supportive. Although the affected children habitually have vomiting, recommendations do not focus on the correction of this symptom. In this condition, elevated ketone bodies and stimuli initiated by gut mucosa damage produced by the enteral pathogen likely underlay nausea and vomiting. As compared to 0.9% saline, intravenous administration of a dextrose-containing bolus of 0.9% saline is associated with a greater reduction of circulating ketones and a shorter duration of nausea and vomiting. Nonetheless, this treatment strategy is not followed by a lower rate of hospitalization. Well-designed investigations suggest that antagonists of the type 3 serotonin receptor, most frequently oral ondansetron, reduce the rate of vomiting, improve the tolerance of oral rehydration, and reduce the need for intravenous rehydration. What is Known: • Although children with gastroenteritis habitually have vomiting, current recommendations do not focus on the correction of this symptom. What is New: • Recently acquired evidence supports the prescription of ondansetron, an antagonist of the type 3 serotonin receptor, to increase the success rate of oral rehydration therapy.


Alteration of synaptic plasticity by neonatal seizures in rat somatosensory cortex.
Seizures in newborns are associated with a high risk for subsequent epilepsy and adverse neurodevelopmental consequences. Understanding the mechanisms by which neonatal seizures adversely disturb the immature brain is important in developing therapeutic strategies. Using the convulsant agent flurothyl to mimic repetitive neonatal seizures we show that early-life seizures result in long-term alteration in the maintenance phase of long-term potentiation (LTP) in layer IV to layer II/III synapses of the somatosensory cortex without alteration of basal synaptic transmission, the induction phase of LTP and short-term depression. Such alterations may have a role in functional deficits seen following neonatal seizures.


Blood glucose limits in the diagnosis of impaired glucose tolerance during pregnancy. Relation to morbidity.
To evaluate the accuracy of diagnosing gestational diabetes mellitus (GDM) by a 2-h blood glucose value > or = 9.0 mmol/l in the 75 g oral glucose tolerance test (OGTT). The maternal and neonatal outcome in women with a 2-h blood glucose value just below this limit, 8.0-8.9 mmol/l, is analyzed. The outcome is compared to a randomly selected control group. A comparative study. There were 223 women in the group with a 2-h value of 8.0 to 8.9 mmol/l in the OGTT. This group was compared to a randomly selected control group of 391 women. Fetal outcome: perinatal mortality, birth weight, respiratory disturbances, symptomatic hypoglycemia, polycythemia, hyperbilirubinemia and traumatic deliveries. Maternal age, body mass index (BMI), pregnancy-induced hypertension (PIH) or preeclampsia and route of delivery. The women in the group with a 2-h glucose value of 8.0-8.9 mmol/l were, compared to the control group, significantly older, heavier, had a higher BMI, gave birth to heavier children and a significantly increased number of large-for-date infants, while there were no differences in neonatal mortality, morbidity or birth trauma. This study shows that using the 75 g 2-h OGTT with a B-glucose limit of > or = 9.0 mmol/l instead of > or = 8.0 mmol/l to diagnose GDM during pregnancy has no major adverse effects concerning maternal and neonatal outcome in the borderline interval of 8.0 to 8.9 mmol/l.


COVID-19 spatialization by empirical Bayesian model in São Paulo, Brazil.
The new Acute Respiratory Syndrome, COVID-19, has affected the health and the economy worldwide. Therefore, scientists have been looking for ways to understand this disease. In this context, the main objective of this study was the spatialization of COVID-19, thinking in distinguishing areas with high transmissibility yet, verifying if these areas were associated with the elderly population occurrence. The work was delineated, supposing that spatialization could support the decision-making to combat the outbreak and that the same method could be used for spatialization and prevent other diseases. The study area was a municipality near Sao Paulo Metropolis, one of Brazil's main disease epicenters. Using official data and an empirical Bayesian model, we spatialized people infected by region, including older people, obtaining reasonable adjustment. The results showed a weak correlation between regions infected and older adults. Thus, we define a robust model that can support the definition of actions aiming to control the COVID-19 spread.


Primary diffuse large B-cell lymphoma of the prostate: a case report and review of the literature.
Primary lymphoma of the prostate is an exceedingly rare disease, with diffuse large B-cell lymphoma being the most common known subtype in a small number of reported cases. Due to its low prevalence, there has been a chronic lack of targeted diagnostic guidelines and treatment procedures. In this article, we report a case of primary diffuse large B-cell lymphoma of the prostate in a 70-year-old Asian man who presented with symptoms of urinary tract obstruction. Histological and immunocytochemical studies of transurethral biopsy of the prostate showed diffuse large B-cell lymphoma. The patient was managed by a combination of eight courses of chemotherapy with a regimen including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and radiotherapy. Post-chemotherapy computed tomography scans showed complete remission. He remained disease free, until now, 15 months after the end of therapy. We also reviewed and analyzed relevant literature to illustrate the diagnosis, treatment, and prognosis of this disease. Diffuse large B-cell non-Hodgkin's lymphoma originating in the prostate is a rare and highly aggressive disease that lacks specificity in its clinical presentation and is easily misdiagnosed. This disease should be considered clinically in patients with significant prostate enlargement and insignificant prostate-specific antigen elevation. The diagnosis can be clarified with a prostate puncture biopsy. Chemotherapy is the main treatment for patients and may be supplemented with surgical treatment and radiotherapy.


Original sequence divergence among Pseudomonas putida CadRs drive specificity.
Bacteria, especially those living in soils, are in constant contact with metals. Transition metals like Fe or Zn, are required for proper growth. Some other metals like Cd or Hg are only toxic. Several systems exist to detoxify cells when these metals are present in concentrations harmful to biological systems. The expression of these systems is under control of specialized regulatory proteins able to detect metals and to regulate cognate detoxifying systems. In this work we report on the characterisation of the metallo-regulator CadR from Pseudomonas putida KT2440. By using gene reporter assays, we investigated the repertoire of metals detected by CadR. We show that CadR is much more responsive to Hg than to Cd, as compared to CadR from P. putida 06909. CadR from P. putida KT2440 differs in only 3 amino-acids in its metal-binding domain with respect to CadR from P. putida 06909. We show that these residues are important determinants of metal selectivity by engineering a modified CadR.


ATAF1 transcription factor directly regulates abscisic acid biosynthetic gene NCED3 in Arabidopsis thaliana.
ATAF1, an Arabidopsis thaliana NAC transcription factor, plays important roles in plant adaptation to environmental stress and development. To search for ATAF1 target genes, we used protein binding microarrays and chromatin-immunoprecipitation (ChIP). This identified T[A,C,G]CGT[A,G] and TT[A,C,G]CGT as ATAF1 consensus binding sequences. Co-expression analysis across publicly available microarray experiments identified 25 genes co-expressed with ATAF1. The promoter regions of ATAF1 co-expressors were significantly enriched for ATAF1 binding sites, and TTGCGTA was identified in the promoter of the key abscisic acid (ABA) phytohormone biosynthetic gene NCED3. ChIP-qPCR and expression analysis showed that ATAF1 binding to the NCED3 promoter correlated with increased NCED3 expression and ABA hormone levels. These results indicate that ATAF1 regulates ABA biosynthesis.


The cloacal plate: the missing link in anorectal and urogenital development.
To determine whether differences in the embryology of the anorectal and urogenital area, previously examined in sheep, pigs, rats, rabbits and guinea pigs, producing varying conclusions, may be secondary to differences in species development. Rat and human embryos were studied at the time of genital tubercle development and cloacal partition by standard serial-section histology, and by immunohistochemistry, dissection and scanning electron microscopy. The images obtained were compared with those previously reported for pig and sheep embryos. The cloacal plate, a vertically orientated midline plate of epithelial cells in the caudal half of the genital tubercle, was the key structure that varied between the different species. In rats the plate maintained a vertical height along its length, while in humans and pigs it reverted to a two-layer membrane dorsally, shortly before it degenerated to expose both the anorectal and urogenital tracts. In sheep the plate was taller ventrally than in the other species but also reverted to a short membrane dorsally that exposed the hindgut when it degenerated. The anterior part of the cloacal plate persisted in all embryos as the urethral plate, which then participated in the formation of the urethra in the male and the vestibule in the female. The animal that most closely resembled humans in anogenital development was the pig. The cloacal plate is the key to understanding early anorectal and urogenital development and yet it is barely recognized in published reports. An appreciation of its relevance helps to explain the variations in the described embryology of the region, and is mandatory when interpreting embryological findings in animal models of human anomalies. Given the similarities between porcine and human development, the pig may be the most legitimate animal model for the study of anorectal and urogenital anomalies in humans.


Ontogenesis of peptide-histidine-isoleucine (PHI)-containing neurons in the suprachiasmatic nucleus (SCN) of the rat.
The morphologic and ontogenetic changes in PHI (peptide-histidine-isoleucine)-containing neurons in the suprachiasmatic nucleus (SCN) of the rat were studied using immunohistochemistry. PHI immunoreactivity first appeared in neural perikarya and processes as early as day 18 of gestation, long before they became evident (day 10 postnatally) in other brain structures. PHI neurons in the SCN were initially small and exhibited faint staining. They gradually increased in number during fetal life, and were found throughout this nucleus by day 21. After birth, they rapidly increased in number and staining intensity. In the 20-day-old rat. PHI-containing perikarya were concentrated in the ventral and medial aspects of the SCN while fibers were located primarily within the dorsal and caudal portions, as in the adult rat. These findings suggest that PHI exerts a physiological role in the developing SCN.


Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987.
The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival. We conducted a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG) with GC in patients with locally advanced or metastatic urothelial carcinoma. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate, and toxicity. From 2001 to 2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and 314 patients were assigned to GC. After a median follow-up of 4.6 years, the median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR], 0.85; P = .075). OS in the subgroup of all eligible patients was significantly longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P = .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both treatments were well tolerated, with more thrombocytopenia and bleeding on GC than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on PCG than GC (13.2% v 4.3%, respectively; P < .001). The addition of paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit that did not reach statistical significance. Novel approaches will be required to obtain major improvements in survival of incurable urothelial cancer.


Traumatic colon injury in damage control laparotomy-A multicenter trial: Is it safe to do a delayed anastomosis?
Delayed colonic anastomosis after damage control laparotomy (DCL) is an alternative to colostomies during a single laparotomy (SL) in high-risk patients. However, literature suggests increased colonic leak rates up to 27% with DCL, and various reported risk factors. We evaluated our regional experience to determine if delayed colonic anastomosis was associated with worse outcomes. A multicenter retrospective cohort study was performed across three Level I trauma centers encompassing traumatic colon injuries from January 2006 through June 2014. Patients with rectal injuries or mortality within 24 hours were excluded. Patient and injury characteristics, complications, and interventions were compared between SL and DCL groups. Regional readmission data were utilized to capture complications within 6 months of index trauma. Of 267 patients, 69% had penetrating injuries, 21% underwent DCL, and the mortality rate was 4.9%. Overall, 176 received primary repair (26 in DCL), 90 had resection and anastomosis (28 in DCL), and 26 had a stoma created (10 end colostomies and 2 loop ileostomies in DCL). Thirty-five of 56 DCL patients had definitive colonic repair subsequent to their index operation. DCL patients were more likely to be hypotensive; require more resuscitation; and suffer acute kidney injury, pneumonia, adult respiratory distress syndrome, and death. Five enteric leaks (1.9%) and three enterocutaneous fistulas (ECF, 1.1%) were identified, proportionately distributed between DCL and SL (p = 1.00, p = 0.51). No difference was seen in intraperitoneal abscesses (p = 0.13) or surgical site infections (SSI, p = 0.70) between cohorts. Among SL patients, pancreas injuries portended an increased risk of intraperitoneal abscesses (p = 0.0002), as did liver injuries in DCL patients (p = 0.06). DCL was not associated with increased enteric leaks, ECF, SSI, or intraperitoneal abscesses despite nearly two-thirds having delayed repair. Despite this being a multicenter study, it is underpowered, and a prospective trial would better demonstrate risks of DCL in colon trauma. Therapeutic study, level IV.


Dppa2 and Dppa4 counteract de novo methylation to establish a permissive epigenome for development.
Early mammalian development entails genome-wide epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate DNA methylation dynamics, we coupled a single-cell ratiometric DNA methylation reporter with unbiased CRISPR screening in murine embryonic stem cells (ESCs). We identify key genes and regulatory pathways that drive global DNA hypomethylation, and characterize roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states. In their absence, developmental genes and evolutionarily young LINE1 elements, which are specifically bound by DPPA2, lose H3K4me3 and gain ectopic de novo DNA methylation in pluripotent cells. Consequently, lineage-associated genes and LINE1 acquire a repressive epigenetic memory, which renders them incompetent for activation during future lineage specification. Dppa2/4 thereby sculpt the pluripotent epigenome by facilitating H3K4me3 and bivalency to counteract de novo methylation, a function co-opted by evolutionarily young LINE1 to evade epigenetic decommissioning.


Electroencephalographic findings in antiepileptic drug trials: a review and report of 6 studies.
A recent survey has shown that the EEG is of doubtful value as an outcome variable in clinical antiepileptic drug (AED) trials. Analysis of findings in 6 trials shows that in only two no consistent effect was seen; that in two power spectral analysis provided additional information to confirm changes in background activity; that in one a close relationship could be established between reduction in frequency of epileptiform discharges and administration of the trial drug (lamotrigine), and that in one, even though no correlation was apparent during use of the AED, there was an increase in frequency of both discharges and seizures on withdrawal (CGP 11952). In general the EEG would appear to be unsuitable as an outcome variable for assessing drug efficacy in AED trials. On the other hand it may give insight into the mode of drug action. Conceivably more efficient use could be made of the EEG if the methodology--including patient selection, consideration of circadian rhythms and of combination AED therapy, and standardized long-term recording--were to be improved and automation and quantification techniques used.


From bites to barcodes: uncovering the hidden diversity of black flies (Diptera: Simuliidae) in Vietnam.
Prompt and precise identification of black flies (Simuliidae) is crucial, given their biting behaviour and significant impact on human and animal health. To address the challenges presented by morphology and chromosomes in black fly taxonomy, along with the limited availability of molecular data pertaining to the black fly fauna in Vietnam, this study employed DNA-based approaches. Specifically, we used mitochondrial and nuclear-encoded genes to distinguish nominal species of black flies in Vietnam. In this study, 135 mitochondrial cytochrome c oxidase subunit I (COI) sequences were established for 45 species in the genus Simulium in Vietnam, encompassing three subgenera (Gomphostilbia, Nevermannia, and Simulium), with 64 paratypes of 27 species and 16 topotypes of six species. Of these COI sequences, 71, representing 27 species, are reported for the first time. Combined with GenBank sequences of specimens from Malaysia, Myanmar, Thailand, and Vietnam, a total of 234 DNA barcodes of 53 nominal species resulted in a 71% success rate for species identification. Species from the non-monophyletic Simulium asakoae, S. feuerborni, S. multistriatum, S. striatum, S. tuberosum, and S. variegatum species groups were associated with ambiguous or incorrect identifications. Pairwise distances, phylogenetics, and species delimitation analyses revealed a high level of cryptic diversity, with discovery of 15 cryptic taxa. The current study also revealed the limited utility of a fast-evolving nuclear gene, big zinc finger (BZF), in discriminating closely related, morphologically similar nominal species of the S. asakoae species group. This study represents the first comprehensive molecular genetic analysis of the black fly fauna in Vietnam to our knowledge, providing a foundation for future research. DNA barcoding exhibits varying levels of differentiating efficiency across species groups but is valuable in the discovery of cryptic diversity.


A method is devised for isolation of pure nucleoli, devoid of perinucleolar chromatin, from rat hepatoma in a medium of high ionic strength (I = 1, MgCl(2) = 0.33 M).


The roles of pathways in the spinal cord lateral and dorsal funiculi in signaling nociceptive somatic and visceral stimuli in rats.
The spinothalamic tract (STT) is a major ascending nociceptive pathway, interruption of which by cordotomy is used for pain relief, whereas the dorsal column (DC) pathway is usually not considered to be involved in pain transmission. However, recent clinical studies showed good relief of visceral pain in cancer patients after a DC lesion. Electrophysiological recordings in animals suggest that the analgesic effect is due to interruption of axons ascending from postsynaptic dorsal column (PSDC) neurons located in the vicinity of the central canal. In this behavioral study, we used a decrease in exploratory activity in rats after a noxious stimulus as an indicator of perceived pain, independent of withdrawal reflexes. Intradermal capsaicin injection almost abolished exploratory activity in naïve animals or in rats after a DC lesion, but did not change it in rats after ipsilateral dorsal rhizotomy or a lesion of the lateral funiculus on the side opposite to the injection. In contrast, a bilateral DC lesion counteracted the decrease in exploratory activity induced by noxious visceral stimuli for at least 180 days after the surgery. Although neurons projecting in both the STT and the PSDC path can be activated by noxious stimuli of cutaneous or visceral origin, our results suggest that the STT plays a crucial role in the perception of acute cutaneous pain and that the DC pathway is important for transmission of visceral pain.


Understanding the influence of resilience on psychological outcomes - Comparing results from acute care nurses in Canada and Singapore.
Building resilience among nurses is one of the ways to support and retain nurses in the profession. Prior literature which evaluated influence of resilience on psychological outcomes, were conducted in relatively homogeneous populations. It is of interest to evaluate whether relationships between resilience and psychological outcomes remain consistent across nations and among different nursing populations. To evaluate a theoretical model of the impact of resilience on burnout (BO), secondary traumatic stress (STS) and compassion satisfaction (CS) by comparing results between nurses in Canada and Singapore. A self-reported questionnaire consisting of questions on demographics, resilience (Connor-Davidson Resilience Scale), and psychological adjustment (Professional Quality of Life) was administered via an online survey. One thousand three hundred and thirty-eight nurses working in two Academic Medical Centres in Singapore responded to the online survey. Similar data was also collected from 329 nurses in Canada. Hypotheses were tested using structural equation modeling. Resilience exerts a significant negative direct impact on STS, and a significant negative direct impact on BO. Additionally, resilience has a positive direct impact on compassion satisfaction. STS exerts a positive direct impact on BO while CS has a negative direct impact on BO. Current study affirmed significant associations between resilience and professional quality of life. Knowledge on resilience is key in informing design and implementation of resilience-building strategies that include professional development, and strengthening of interpersonal skills. A resilience-based approach will help reduce nurses' BO and STS while caring for their patients, and in turn reduce turnover.


Linking Parent-Child and Peer Relationship Quality to Empathy in Adolescence: A Multilevel Meta-Analysis.
Empathy, which is the ability to feel concern for and to understand others' feelings, is thought to develop in high quality relationships with parent and peers, but also to facilitate the quality of these relationships. While a wide literature has addressed this aspect, the heterogeneity of primary studies, in which different indicators of relationship quality (e.g., support, conflict) and empathy (i.e., affective and cognitive) have been examined, makes it difficult to draw conclusive answers. Therefore, it remained ambiguous how parent-child and peer relationship quality are associated with adolescents' empathy. In order to increase the understanding of these associations, a multilevel meta-analysis was performed, which allowed for including multiple effect sizes from each study. By a systematic literate search, 70 eligible studies were found that provided 390 effect sizes from 75 independent samples. The results showed a small positive correlation between parent-child relationship quality and empathy, and a small-to-moderate positive correlation between peer relationship quality and empathy, which was significantly stronger than the correlation with parent-child relationship quality. Hence, the meta-analytic results indicate that adolescents with higher quality relationships, especially with peers, indeed tend to show more concern for and understanding of others' emotions than adolescents with lower quality relationships. Moreover, the moderation analyses showed stronger correlations for the positive dimension of relationship quality than for the negative dimension, and stronger correlations for composite scores of affective and cognitive empathy than for separate scores of the empathy dimensions. However, no differences in correlations were found between the affective and cognitive empathy dimension, and no moderation effects were found for gender and age. Thus, this meta-analysis demonstrates robust positive associations between parent-child and peer relationship quality and empathy in adolescence, implying that good empathic abilities may be a protective factor for experiencing poor relationships.


Systemic lupus erythematosus presenting as chorea.
A child presenting with chorea developed the full clinical and laboratory findings of systemic lupus erythematosus after hospitalisation. He responded dramatically to haloperidol. 6 months after diagnosis he began to manifest renal involvement.


Electrophoretic behavior of adamantane derivatives possessing antiviral activity and their determination by capillary zone electrophoresis with indirect detection.
Separation and determination of adamantane derivatives with antiviral activity, namely amantadine (1-adamantan amine), memantine (1-amino-3,5-dimethyl adamantane) and rimantadine (alpha-methyl-1-adamantane methylamine), were examined by capillary zone electrophoresis. After optimization, an indirect detection method using 5 mM 4-methylbenzylamine in ethanol/water solution (1:4) as simultaneously absorbing and buffering background electrolyte with detection at 210 nm was found suitable for determination of the individual compounds (limit of detection was 0.35 mg L(-1) for memantine hydrochloride, S/N = 3). Baseline separation of all the three compounds was reached by addition of alpha- or beta-cyclodextrins to the electrolyte in concentrations of 20 and 2 mM, respectively.


Human osteogenesis involves differentiation-dependent increases in the morphogenically active 3' alternative splicing variant of acetylcholinesterase.
The extended human acetylcholinesterase (AChE) promoter contains many binding sites for osteogenic factors, including 1,25-(OH)2 vitamin D3 and 17beta-estradiol. In differentiating osteosarcoma Saos-2 cells, both of these factors enhanced transcription of the AChE mRNA variant 3' terminated with exon 6 (E6-AChE mRNA), which encodes the catalytically and morphogenically active E6-AChE isoform. In contrast, antisense oligodeoxynucleotide suppression of E6-AChE mRNA expression increased Saos-2 proliferation in a dose- and sequence-dependent manner. The antisense mechanism of action was most likely mediated by mRNA destruction or translational arrest, as cytochemical staining revealed reduction in AChE gene expression. In vivo, we found that E6-AChE mRNA levels rose following midgestation in normally differentiating, postproliferative fetal chondrocytes but not in the osteogenically impaired chondrocytes of dwarf fetuses with thanatophoric dysplasia. Taken together, these findings suggest morphogenic involvement of E6-AChE in the proliferation-differentiation balance characteristic of human osteogenesis.


Enhanced permeation and stratum corneum structural alterations in the presence of dithiothreitol.
Stratum corneum protein biochemical and biophysical structural contributions to the barrier properties of human epidermis were determined in the presence of the reducing agent dithiothreitol (DTT). Mannitol and sucrose permeation through human epidermis in the presence of 0 to 50 mM DTT in PBS (pH 7.4) was measured in symmetric, side-by-side diffusion cells (32 degrees C). DTT enhancement ratios, KP(DTT)/KP(PBS), ranging from 1.6 to 32, were dependent on skin donor and DTT concentrations. DTT did not alter stratum corneum uptake of mannitol or sucrose nor mannitol solubility in DTT/PBS solutions. Stratum corneum biophysical structure was ascertained by FTIR in solvent replacement experiments. DTT-induced protein conformational alterations were apparent in the emergence of an Amide I band near 1615 cm-1, which is generally associated with beta-sheet-like conformers. Therefore, DTT alters stratum corneum biophysical structure through interactions with proteins. After exposure of stratum corneum protein sheets to DTT/PBS solutions, the free thiol concentration increased from < 1 nmol SH/mg protein sheet to approx. 130 nmol/mg. The enhanced permeation which increased with increasing concentrations of DTT, was associated with diffusion mechanisms involving the cornified cells of the stratum corneum. These results indicate that corneocyte protein integrity does contribute to barrier function of the skin and influences the transport of polar solutes.


Frailty and uptake of angiotensin receptor neprilysin inhibitor for heart failure with reduced ejection fraction.
Frail older adults may be less likely to receive guideline-directed medical therapy (GDMT)-renin-angiotensin blockers, beta-blockers, and mineralocorticoid receptor antagonists-for heart failure with reduced ejection fraction (HFrEF). We aimed to examine the uptake of angiotensin receptor neprilysin inhibitor (ARNI) and GDMT in frail older adults with HFrEF. Using 2015-2019 Medicare data, we estimated the proportion of beneficiaries with HFrEF receiving ARNI and GDMT each year by frailty status, defined by a claims-based frailty index. Logistic regression was used to identify clinical characteristics associated with ARNI initiation. Cox proportional hazards regression was used to examine the association of GDMT use in 2015 and death or heart failure hospitalization in 2016-2019. Among 147,506-180,386 beneficiaries with HFrEF (mean age: 77 years; 27% women; 42.6-49.1% frail) in 2015-2019, the proportion of patients receiving ARNI increased in both non-frail (0.4%-16.4%) and frail (0.3%-13.7%) patients (p for yearly-trend-by-frailty = 0.970). Among those not receiving a renin-angiotensin system blocker, patients with age ≥ 85 years (odds ratio [95% CI], 0.89 [0.80-0.99]), dementia (0.88 [0.81-0.96]), and frailty (0.87 [0.81-0.94]) were less likely to initiate ARNI. The proportion of patients receiving all 3 GDMT classes increased in non-frail patients (22.0%-27.0%) but changed minimally in frail patients (19.6%-21.8%). Regardless of frailty status, treatment with at least 1 class of GDMT was associated with lower death or heart failure hospitalization than no GDMT medications (hazard ratio [95% CI], 0.94 [0.91-0.97], 0.92 [0.89-0.94], 0.94 [0.91-0.97] for 1, 2, and 3 classes, respectively). Our results suggest an evidence-practice gap in the use of ARNI and GDMT in Medicare beneficiaries with HFrEF, particularly those with frailty. Efforts to narrow this gap are needed to reduce the burden of HFrEF in older adults.


[Dosage monitoring as a quality control instrument in digital radiography].
Automatic image processing procedures ensure a constant image quality. Overexposed images constitute a danger zone on account of a subjectively better image appearance (improved signal-to-noise ratio). We have examined the software "Dose-Monitoring" both for the identification of false exposures and as a quality control tool. Firstly the correlation between dose and present IgM (mean grey tone from the crude histogram of a 12-bit image) was examined by exposing phantoms. A further-reaching comparison of the present IgM values of some MTRAs with the department average (nominal IgM) should detect tendencies for over- and underexposure. Finally a dose reduction in 12 forms of X-ray examination was evaluated with regard to IgM course controls (median IgM). A high correlation (0.987) between dose and mean grey tone (IgM). In some MRTAs tendency for over-/underexposure was detected. The dose reduction of defined types of X-ray examination lead to a trend to lower mean IgM values. Numerous factors have an influence on the IgM value thus making its evaluation difficult, even so it is a suitable parameter for uncovering tendencies to incorrect exposure and for identifying processes requiring optimization. The value of this tool lies in the quality assurance of dose fluctuations and a possible dose reduction.


Operant conditioning of skin resistance tonic levels.
The purpose of the current investigation was to determine whether increases and decreases in skin resistance tonic level could be controlled by individuals given discrete visual feedback of such activity. Thirty-six male undergraduate students served as subjects. They were assigned randomly in equal numbers to four groups; two of the groups received accurate feedback of skin resistance level changes and two received inaccurate feedback. The two accurate-feedback groups differed with respect to the order in which increases and decreases in skin resistance level were reinforced. Each noncontingent group was matched with one of the contingent groups in terms of reinforcement density. The results indicated that accurate feedback produced skin resistance level changes consistent with the type of reinforcement employed. However, operant control was not clearly sustained subsequent to a reversal in the type of tonic level change reinforced. Some problems related to the clinical application of skin resistance level training are discussed.


Principles for designing an optimal mRNA lipid nanoparticle vaccine.
mRNA Lipid nanoparticles (LNPs) have recently been propelled onto the center stage of therapeutic platforms due to the success of the SARS-CoV-2 mRNA LNP vaccines (mRNA-1273 and BNT162b2), with billions of mRNA vaccine doses already shipped worldwide. While mRNA vaccines seem like an overnight success to some, they are in fact a result of decades of scientific research. The advantage of mRNA-LNP vaccines lies in the modularity of the platform and the rapid manufacturing capabilities. However, there is a multitude of choices to be made when designing an optimal mRNA-LNP vaccine regarding efficacy, stability and toxicity. Herein, we provide a brief on what we consider to be the most important aspects to cover when designing mRNA-LNPs from what is currently known and how to optimize them. Lastly, we give our perspective on which of these aspects is most crucial and what we believe are the next steps required to advance the field.


Up regulated Tmbim1 activation promotes high fat diet (HFD)-induced cardiomyopathy by enhancement of inflammation and oxidative stress.
The prevalence of cardiomyopathy due to metabolic stress has up-regulated dramatically; nevertheless, its molecular mechanisms remain unclear. Here we suggested that transmembrane BAX inhibitor motif-containing 1 (Tmbim1) is down-regulated in the hearts of mice fed with high fat diet (HFD). We provided evidence that Tmbim1 knockout (KO) accelerated HFD-induced metabolic disorders in mice, as supported by the remarkable increase of fasting serum glucose and insulin levels. HFD-induced cardiac dysfunctions were greatly intensified by the loss of Tmbim1, along with higher levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum. In addition, Tmbim1 deletion significantly enhanced lipid accumulation in heart of mice administrated with HFD. Furthermore, Tmbim1 knockout reinforced myocardial inflammation, evidenced by increasing the expression of pro-inflammatory cytokines (interleukin 1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α)), and the activation of nuclear factor-κB (NF-κB) signaling pathway. Tmbim1 deficiency strengthened oxidative damage in hearts of HFD-fed mice, accompanied with a significant reduction of nuclear factor-erythroid 2 related factor 2 (Nrf-2) pathway. In palmitate (PA)-treated primary cardiomyocytes, Tmbim1 ablation markedly enhanced cell inflammation and oxidative stress, which were abolished by the suppression of ROS generation and NF-κB activation. Taken together, these findings suggested that Tmbim1 might be a key suppressor of metabolic stress-induced cardiomyopathy, which could be a promising target for the treatment of metabolic syndrome-triggered myocardial damage and heart failure.


Massive digoxin intoxication in childhood.
In a 10 year old boy 8 hours after taking about 16 mg beta-acetyl-digoxin a maximum serum digoxin level of 31.8 ng/ml was measured radioimmunologically. This is the highest digitalis level in childhood described to date. The serum potassium level rose to 7.4 mmol/l. Complete atrio-ventricular block, and salves of ventricular premature beats were the most serious rhythm disturbances. The absence of life threatening rhythm disturbances is attributed to the early use of diphenylhydantoin in small frequent doses.


[Not Available].
The effect of the administration of the mycotoxins OTA, ZEA and DON alone resp. in combination on animal health and the residue behavior of pigs from 50 - 60 kg living weight over 90 days was investigated in 4 separate studies. Due to its fast metabolisation the administration of 1000 µg DON resp. 250 µg ZEA per kg feed alone or in combination with other mycotoxins does not lead to detectable residues of these mycotoxins in organs and tissues. Therefore these mycotoxins should not be relevant to the consumer.There is an effect of the simultaneous administration of ZEA resp. DON on the metabolisation resp. secretion of OTA. OTA is of relevance from the point of view of residue toxicology.


Association of C-Reactive Protein and Motoric Cognitive Risk Syndrome in Community-Dwelling Older Adults: The China Health and Retirement Longitudinal Study.
Motoric cognitive risk syndrome (MCR) is a newly described pre-dementia syndrome characterized by cognitive complaints and slow gait and is associated with numerous adverse outcomes. Previous studies have indicated an association between C-reactive protein (CRP) and cognitive decline, but no clear relationship between CRP and MCR has been reported. The purpose of the study is to examine the associations between CRP with MCR and MCR subtypes. Participants were 5,642 adults aged ≥60 years from the China Health and Retirement Longitudinal Study (CHARLS). MCR was defined as cognitive complaints and slow gait speed without dementia or impaired mobility. Two subtypes of MCR were defined by whether memory impairment (MI) was also present, such as MCR-MI and MCR-non-MI. MI was evaluated through the immediate recall and delayed recall in a word recall test during the CHARLS and was defined as 1.0 standard deviation or more below the mean values of the test scores in this cohort. Of the participants, 421 (7.46%) met the criteria for MCR. After multivariate adjustment, participants with higher CRP levels had an increased likelihood of MCR (fourth quartile: adjusted odds ratio [OR]=1.44; 95% confidence interval [CI]: 1.06-1.95) compared with those in the first quartile group. The OR for MCR-MI was 2.04 (95% CI: 1.35-3.09) for the highest quartile of CRP compared to the lowest quartile. No significant associations between CRP levels and odds of MCR-non-MI were observed. Higher CRP levels were associated with increased odds of prevalent MCR-MI but not MCR-non-MI among community-dwelling older adults.


Factors related to quality of life after video-assisted thoracoscopic surgery in patients with stage I adenocarcinoma lung cancer: A longitudinal study.
This study aimed to assess the 5-year survival, quality of life for cancer- and lung-specific symptoms, and to identify predictive factors of quality of life during a 12-month period after video-assisted thoracic surgery (VATS) for early-stage lung adenocarcinoma. A convenience sample of 53 patients who had undergone VATS for lung cancer was used for this longitudinal, prospective study. All participants provided responses to the cancer-specific quality-of-life European Organization for Research and Treatment of Cancer questionnaire as well as a questionnaire for lung cancer-specific symptoms using structured interviews at baseline (T0) and 3-, 6-, 9-, and 12-months post-surgery (T1, T2, T3, and T4, respectively). Generalized estimating equation models were used to investigate whether quality of life scores improved from baseline measures and to determine characteristics associated with changes in scores for quality-of-life post-surgery. The mean age of participants was 58.5 years (SD = 8.76), and most were female (64.2%). Participants received either a wedge or sublobular lobectomy (47.2%) or a lobectomy (52.8%). The size of the primary tumour for most participants was <2 cm (78.7%). The five-year survival rate was 90%. Lung-specific symptoms of insomnia were worse at T1 compared with baseline. Significant improvements in scores for function and cancer symptoms were seen at T4 compared with scores at T0. Age, marital status, smoking, alcohol consumption, and a history of previous cancer were significantly associated with quality of life. Surgical resection with VATS resulted in good 5-year survival rates and long-term improvements in quality of life. Our findings suggest VATS for patients with early-stage lung adenocarcinoma should be considered as a means of improving long-term survival and quality of life.


Zero-heat-flux core temperature monitoring system: an observational secondary analysis to evaluate agreement with naso-/oropharyngeal probe during anesthesia.
General anesthesia impairs thermoregulation and contributes to perioperative hypothermia; core body temperature monitoring is recommended during surgical procedures lasting > 30 min. Zero-heat-flux core body temperature measurement systems enable continuous non-invasive perioperative monitoring. During a previous trial evaluating the benefits of preoperative forced-air warming, intraoperative temperatures were measured with both a zero-heat-flux sensor and a standard naso-/oropharyngeal temperature probe. The aim of this secondary analysis is to evaluate their agreement. ASA I-III patients, scheduled for elective, non-cardiac surgery under general anesthesia, were enrolled. A zero-heat-flux sensor was placed on the participant's forehead preoperatively. Following induction of anesthesia, a "clinical" temperature probe was placed in the nasopharynx or oropharynx at the anesthesiologist's discretion. Temperature measurements from both sensors were recorded every 10 s. Agreement was analyzed using the Bland-Altman method, corrected for repeated measurements, and Lin's concordance correlation coefficient, and compared with existing studies. Data were collected in 194 patients with a median (interquartile range) age of 60 (49-69) years, during surgical procedures lasting 120 (89-185) min. The zero-heat-flux measurements had a mean bias of - 0.05 °C (zero-heat-flux lower) with 95% limits of agreement within - 0.68 to + 0.58 °C. Lin's concordance correlation coefficient was 0.823. The zero-heat-flux sensor demonstrated moderate agreement with the naso-/oropharyngeal temperature probe, which was not fully within the generally accepted ± 0.5 °C limit. This is consistent with previous studies. The zero-heat-flux system offers clinical utility for non-invasive and continuous core body temperature monitoring throughout the perioperative period using a single sensor.


Graphene Inks Printed by Aerosol Jet for Sensing Applications: The Role of Dispersant on the Inks' Formulation and Performance.
This study presents graphene inks produced through the liquid-phase exfoliation of graphene flakes in water using optimized concentrations of dispersants (gelatin, triton X-100, and tween-20). The study explores and compares the effectiveness of the three different dispersants in creating stable and conductive inks. These inks can be printed onto polyethylene terephthalate (PET) substrates using an aerosol jet printer. The investigation aims to identify the most suitable dispersant to formulate a high-quality graphene ink for potential applications in printed electronics, particularly in developing chemiresistive sensors for IoT applications. Our findings indicate that triton X-100 is the most effective dispersant for formulating graphene ink (GTr), which demonstrated electrical conductivity (4.5 S·cm-1), a high nanofiller concentration of graphene flakes (12.2%) with a size smaller than 200 nm (<200 nm), a low dispersant-to-graphene ratio (5%), good quality as measured by Raman spectroscopy (ID/IG ≈ 0.27), and good wettability (θ ≈ 42°) over PET. The GTr's ecological benefits, combined with its excellent printability and good conductivity, make it an ideal candidate for manufacturing chemiresistive sensors that can be used for Internet of Things (IoT) healthcare and environmental applications.


Enzyme-assisted amplification of target cycle triggers the unlocking of locked hairpin probes for let-7a detection.
The detection of miRNA in cells is difficult owing to its substantially low cellular content. Therefore, developing a highly sensitive sensor to detect cellular miRNA remains a significant challenge. Herein, we report an enzyme-assisted biosensor with target cycle amplification that can trigger the unlocking of locked hairpin probes for sensitive and robust let-7a gene detection. In the research, three kinds of hairpin probes were skillfully designed. The hairpin probe comprises a complementary sequence of a target, primer, and recognition site of Nt. BbvCI restriction endonucleases. In addition, the alternating synergistic impact of polymerase and the nicking enzyme generates considerable triggers to unlock the locked hairpin probe LH1, consequently triggering a subsequent circulating strand displacement reaction to form a stable H1-H2 double strand to ensure sufficient distance between a fluorophore on H1 and a quenching group on bolt DNA (bDNA), and resulting in the recovery of fluorescence. Furthermore, this process does not require complicated operation procedures and instruments, and the target gene let-7a can be sensitively detected. Specifically, the detection limit of the biosensor is as low as 160 fM, and its linear range is 0.5 pM-250 nM. Moreover, this biosensor can be employed to detect let-7a in human serum with good selectivity.


Blockage of CD72 reduces B cell proliferation in immune thrombocytopenic purpura, involving interleukin 1 and macrophage migration inhibitory factor secretion.
This study aims to explore the expression and role of CD72 in B lymphocytes in immune thrombocytopenic purpura (ITP). The expression level of CD72 in B lymphocytes was detected by flow cytometry in 18 ITP patients and 19 controls of healthy donor or iron-deficiency anemia patients. B cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation (BrdU) in the culture of 17 ITP patients' and 11 controls' peripheral mononuclear cells (PMNCs). The secretion levels of antibodies against human platelet antigens (HPA), as well as B cell proliferation-related cytokine interleukin 1(IL-1) and macrophage migration inhibitory factor (MIF) in culture supernatants were measured by ELISA. CD72 was significantly increased in B cells of newly diagnosed or persistent ITP compared with ITP in remission. B cell proliferation in culture with CD72 antibody addition was significantly decreased both in ITP patients and in controls compared with isotype antibody addition. CD72 antibody did not significantly alter HPA antibody level in ITP patients. CD72 antibody increased IL-1 and MIF levels in ITP patients' cell culture supernatant but not in controls. CD72 expression elevation accompanies the active status of ITP. In vitro addition of CD72 antibody has a negative impact on B cell proliferation. The function of CD72 in B cell proliferation in ITP may be related to IL-1 and MIF secretion.


Allergen exposure boosts peripheral Th9 responses in patients with local allergic rhinitis.
Intranasal allergen exposure increases peripheral total Th2 and Th9 cells in patients with local allergic rhinitis (LAR). Peripheral T-cell response seems dominated by Th9 cells in patients with LAR, whereas Th2 responses prevail in patients with allergic rhinitis. Our results identify Th9 cells as potential therapeutic targets for patients with LAR.


Afaf, a novel vesicle membrane protein, is related to acrosome formation in murine testis.
As a cell-specific organelle, acrosome (Acr) and its formation are an important event for spermiogenesis. However, the Acr formation is far more complicated than has been proposed. In this study, we have cloned a novel membrane protein Afaf (Acr formation associated factor) that was expressed abundantly in the round spermatids, localized in the inner and outer membrane of forming Acrs, and declined in the maturing Acrs. In the transfected Hela cells, Afaf protein was localized in the plasma membrane, EEA1-positive early endosomes (EEs) and occasionally in the nuclei. Therefore, we propose that EEs and plasma membrane may be also directly involved in the Acr biogenesis.


Insights into upper limb kinematics and trunk control one year after task-related training in chronic post-stroke individuals.
Randomized clinical trial. Long-term follow-up of training investigations involving post-stroke individuals can lead to advancing clinical decisions. Extended task-related training (TRT) effects on reaching with the impaired upper limb were evaluated, using a pre-test/posttest/follow-up design. One-year follow-up examinations analyzed whether improved shoulder and elbow motion were maintained following prolonged practice of the upper limb. Long-term kinematic analysis on 21 moderately impaired post-stroke participants (upper extremity Fugl-Meyer between 19 and 40/66), as well as results from standardized outcome measures performed on these patients and another 16 post-stroke participants. Significant initial changes were maintained for kinematic shoulder and elbow motion, as well as functional measures. Compensatory reaching involving the trunk has been shown to be maintainable, but ultimately less efficient. Training that involves a conscious decision to control the trunk led to the most improved functional performance, and may lead to ideal restorative strategies. 2B.


Acute myocardial infarction is associated with increased susceptibility of serum lipids to copper-induced peroxidation in vitro.
Low-density lipoprotein (LDL) oxidation in the arterial intima plays a pivotal role in atherogenesis. Under physiologic conditions, several mechanisms protect LDL against oxidation, including hydrolysis of oxidation products by high-density lipoprotein (HDL)-associated enzymes. Some of these protective mechanisms are less effective under acute phase conditions. Conditions of acute phase response, including acute myocardial infarction (MI), may be expected to result in increased susceptibility of serum lipids to oxidation. The present study was undertaken to test this possibility. Using our previously developed spectroscopic method, we have monitored prospectively the kinetics of copper-induced oxidation of serum lipids obtained from 15 men during and after acute MI. This was tested within 6 h from the onset of chest pain, on Days 1, 3, and 7 of infarction and 1 year after recovery. The lag phase preceding oxidation of serum lipids was much shorter during the first week after MI when compared with values obtained after recovery (52-59 vs. 107 min, respectively, p <0.001). During the first week after MI, we observed no significant correlations between kinetic parameters and serum lipid composition, in contrast both to the correlations previously reported for hyperlipidemic patients and to the similar correlations observed in the present study after recovery. Acute MI is associated with an increased susceptibility of serum lipids to oxidation in vitro. This propensity for oxidation may reflect enhanced in vivo formation of free radicals and/or reduced efficiency of defense mechanisms. Both these possibilities may carry detrimental effects on the course, complications, and prognosis of the patients after acute MI.


Liver Resuscitation With Hypothermic Oxygenated Perfusion After Donation in Asystolic Type Iii With Regional Perfusion in Normothermia: A Case Report About First Experience in Spain.
Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia. A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation. After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.


Development of poly(vinyl alcohol) porous scaffold with high strength and well ciprofloxacin release efficiency.
Hydrophilic porous polymer scaffolds have shown great application in drug controlled release, while their mechanical properties and release efficiency still need further improvement. In the current study, the porous scaffolds of polyvinyl alcohol (PVA) prepared by quenching in liquid nitrogen and freeze drying method from different original concentration aqueous solutions were fabricated. Among different PVA scaffolds, the scaffold stemming from 18wt.% PVA aqueous solution exhibited the best mechanical properties, 10.5 and 1.54MPa tensile strengths for the dry and hydrogel states respectively. The inner morphology of such PVA scaffold was unidirectional honeycomb-like structure with average microchannel section of 0.5μm, and the scaffold showed porosity of 71% and rather low ciprofloxacin (Cip) release efficiency of 54.5%. Then poly(ethylene glycol) (PEG) was incorporated to enhance the Cip release efficiency. The release efficiency reached 89.3% after introducing 10wt.% PEG, and the mechanical properties of scaffold decreased slightly. Various characterization methods demonstrated that, adding PEG could help to enlarge the microchannel, create extra holes on the channel walls, weaken the interaction between PVA chains and Cip, and miniaturize the crystal size of Cip. All these effects benefit the dissolution and diffusion of Cip from scaffold, increasing its release capability. Moreover, based on biocompatible material composition, PVA/PEG scaffold is a non-cytotoxicity and have been verified that it can promote cell growth. And PVA/PEG scaffolds loaded with Cip can completely inhibit the growth of microorganism because of Cip sustaining release. The PVA scaffold would have a good potential application in tissue engineering, demanding high strength and well drug release capability.


Synthetic studies on nonthrombogenic biomaterials 14: synthesis and characterization of poly(ether-urethane) bearing a Zwitterionic structure of phosphorylcholine on the surface.
A new Zwitterionic compound of the phosphorylcholine analogue, 4-hydroxylbutyl phosphorylcholine (HBPC), was synthesized and characterized. HBPC was chemically tethered onto the surface of poly(ether-urethane) (PEU) films with hexamethylene diisocyanate (HDI) as a coupling agent. The existence of a phosphorylcholine structure on the PEU surface was demomstrated by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FT-IR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. The nonthrombogenicity of the modified films was evaluated by platelet-rich plasma (PRP) assay. The results showed that films grafted with HBPC have excellent platelet adhesion resistance.


Golf injuries--common and potentially avoidable.
Injuries sustained during golf rarely receive the recognition given to injuries from sports perceived as more violent or strenuous. However, golfing injuries are believed to occur frequently. The aim of this study was to explore the injury profile of female golfers, including treatment sought and the impact of the injury on performance and participation. Forty-one team captains were given questionnaires to distribute to their players. A total of 522 golfers participating in the Victorian Women's Pennant Competition in Victoria, Australia, from both the Metropolitan and Country competitions, completed the study. Over one-third (35.2%) of the golfers reported having sustained a golfing injury within the previous 12 months, with the lower back being the most commonly injured body region. Strains were the most frequent type of injury (67.9%). Of the 184 injuries reported, 154 sought treatment from a health professional. Physiotherapists were the most common health professional consulted. Performance was affected in 78.9% of cases, with 69.7% of the injured golfers missing games or practice sessions due to injury. Golfing injuries appear common and have a substantial impact upon the injured golfer. As lower back strains are the most common injury, strategies such as performing an appropriate warm-up could be investigated to determine the possible injury prevention benefits for golfers. This study has also highlighted that the majority of treatments are from allied health professionals, suggesting that a complete epidemiological description of golf injuries requires information from broader settings than general practice clinics and hospitals.


Control of peripheral vascular resistance in perfused hindquarters of dogs: lack of effect of nicotinic and muscarinic ganglion block.
The effects of nicotinic and muscarinic ganglion blockade were studied on the peripheral resistance of the perfused hindlimbs of the dog. Nicotinic ganglion blockade by chlorisondamine (1 mg/kg) significantly reduced reflex vasomotor responses but did not significantly alter hindlimb peripheral resistance. Combined nicotinic ganglion blockade by chlorisondamine (1 mg/kg) and muscarinic ganglion blockade by atropine (50mug/kg) abolished the reflex vasomotor response but did not alter hindlimb peripheral resistance. It was concluded that autoregulatory mechanisms are capable of maintaining a peripheral resistance after block of both muscarinic and nicotinic ganglion transmission.


Prenatal ontogenesis of pro-opiomelanocortin in the mouse central nervous system and pituitary gland: an in situ hybridization and immunocytochemical study.
Pro-opiomelanocortin (POMC) mRNA detected by in situ hybridization and POMC/ACTH (adrenocorticotropin)-containing neurons detected by immunocytochemistry were first observed in the presumptive arcuate nucleus of embryonic mouse brain on gestational day 10.5 (E10.5). Immunostained fibers were also evident on E10.5 in the lateral and dorsal diencephalon. In these areas, a dense network of processes developed by E11.5 and extended into the mesencephalon. Fibers were detected in the myelencephalon at this stage and a day later (E12.5) in the spinal cord. Adult-like patterns of POMC/ACTH fibers were established in the diencephalon, mesencephalon, metencephalon and the myelencephalon between E13.5 and E15.5. POMC-expressing cells in the anterior and intermediate lobes of the pituitary gland appeared on E12.5 and E14.5, respectively. The early expression of POMC and the rapid establishment of dense fiber tracts in the brain is consistent with a role for POMC-derived peptides in the development of the central nervous system.


Salting-out assisted liquid-liquid extraction with the aid of experimental design for determination of benzimidazole fungicides in high salinity samples by high-performance liquid chromatography.
A novel method for the simultaneous separation and determination of four benzimidazole fungicides (i.e., carbendazim, fuberidazole, thiophanate-methyl and thiophanate) in high salinity samples was developed by using salting-out assisted liquid-liquid extraction (SALLE) via water-miscible acetonitrile as the extractant coupled with high-performance liquid chromatography. Box-Behnken design and response surface were employed to assist the optimization of SALLE conditions, including volume of salting-out solvent, the pH of sample solution and salting-out solvent as variable factors. The optimal salting-out parameters were obtained as follows: 2 mL of acetonitrile was added to 2 mL of sample solution with pH=4 and then 2 mL salting-out solvent containing 5 mol L(-1) sodium chloride at a pH of 7 was added to the solution for extraction. This procedure afforded a convenient and cost-saving operation with good cleanup ability for the benzimidazole fungicides, such as good linear relationships (R>0.996) between peak area and concentration from 2.5 ng mL(-1) to 500 ng mL(-1), low limits of detection between 0.14 ng mL(-1) and 0.38 ng mL(-1) and the intra-day precisions of retention time below 1.0%. The method recoveries obtained at fortified three concentrations for three seawater samples ranged from 60.4% to 99.1%. The simple, rapid and eco-benign SALLE based method proved potentially applicable for trace benzimidazole fungicides analysis in high salinity samples.


Integrating Saharan dust forecasts into a regional chemical transport model: a case study over Northern Italy.
The Po Valley in Northern Italy is frequently affected by high PM10 concentrations, where both natural and anthropogenic sources play a significant role. To improve air pollution modeling, 3D dust fields, produced by means of the DREAM dust forecasts, were integrated as boundary conditions into the mesoscale 3D deterministic Transport Chemical Aerosol Model (TCAM). A case study of the TCAM and DREAM integration was implemented over Northern Italy for the period May 15-June 30, 2007. First, the Saharan dust impact on PM10 concentration was analyzed for eleven remote PM10 sites with the lowest level of air pollution. These remote sites are the most sensitive to Saharan dust intrusions into Northern Italy, because of the absence of intensive industrial pollution. At these remote sites, the observed maxima in PM10 concentration during dust events is evidence of dust aerosol near the surface in Northern Italy. Comparisons between modeled PM10 concentrations and measurements at 230 PM10 sites in Northern Italy, showed that the integrated TCAM-DREAM model more accurately reproduced PM10 concentration than the base TCAM model, both in terms of correlation and mean error. Specifically, the correlation median increased from 0.40 to 0.65, while the normalized mean absolute error median dropped from 0.5 to 0.4.


Triterpenoids impede the fibrillation and cytotoxicity of human islet amyloid polypeptide.
The inhibition of human islet amyloid polypeptide (hIAPP) deposition to block its toxicity is an important strategy for the prevention and treatment of type II diabetes mellitus (T2DM).Natural compounds with pharmacological properties and low toxicity can serve as a good point to discover potential inhibitors of protein misfolding, which may be useful for the treatment of various amyloidosis-related diseases. Previous studies have reported that triterpenoids, such as maslinic acid (MA) and momordicin I (MI), can modulate glucose metabolism partially by reducing insulin resistance. However, the internal antidiabetic mechanism of these triterpenoids remains unclear. In this study, we examined the inhibition and disaggregation of MAandits isomer MI on the fibrillation of hIAPP using various experimental and computational approaches. The assembly behaviors and peptide-induced cytotoxicity of hIAPP could be effectively resisted by MA and MI. Moreover, the interaction of the two triterpenoids with hIAPP displayed a spontaneous and exothermic process. Moreover, molecular dynamics simulation results of different peptides revealed that MA and MI could bind to Asn and other non-polar residues near the core C-terminal region and reduce the oligomerization of hIAPP. The binding affinity was predominantly contributed by hydrophobic, electrostatic and hydrogen bonding interactions. The present work provides valuable data for MA and MI to treat T2DM and amyloidosis-related diseases.


Use of constant wavelength synchronous spectrofluorimetry for identification of polycyclic aromatic hydrocarbons in air particulate samples.
We have developed a simple, rapid, inexpensive method for the identification of fluoranthene (Flan), benz(a)anthracene (BaA), benzo(a)pyrene (BaP), benzo(k)fluoranthene (BkF), pyrene (Pyr), benz(ghi)perylene (BghiP) in suspended particulate matter in an urban environment of Delhi. Suspended particulate matter samples of 24h duration were collected on glass fiber filter papers. Polycyclic aromatic hydrocarbons (PAHs) were extracted from the filter papers using dichloromethane (DCM) and hexane with ultrasonication method. Comparison of the characteristic emission of spectra of PAHs with standard spectra indicated the degree of condensation of aromatic compounds present in investigated mixtures. It was also possible to identify some individual compounds. However, this identification could be more effective with the use of the respective values of Δλ parameter for each particular component of the mixture.


CD24 promotes HCC progression via triggering Notch-related EMT and modulation of tumor microenvironment.
CD24 is known as a cell surface molecule in hematopoiesis and also described as a diagnostic marker for tumors. Previous studies suggested the important role of CD24 in hepatocellular carcinoma (HCC) pathogenesis. However, precise functions of CD24 in HCC are still unknown. Here, we found that CD24 is highly expressed in HCC both in mRNA and protein levels. Further, the epithelial-mesenchymal transition (EMT) and Notch1 signaling activations mediated by CD24 were elucidated as potential mechanisms of HCC promotion in Hepa1-6/Hepa1-6-CD24 cell models. Additionally, possible systemic immune reaction was explored through immune cells and Hepa1-6/Hepa1-6-CD24 cell co-culture. We demonstrated that the EMT process of HCC cell was effectively induced by CD24; also, the tumor immune microenvironment was changed by facilitating Notch-related EMT in vivo. These results reveal the underlying link between the HCC processes mediated by CD24. Moreover, as a clear tumor promoter, CD24 is considered a potential new target for HCC treatment.


The effect of ambient air pollution during early pregnancy on fetal ultrasonic measurements during mid-pregnancy.
Over the past decade there has been mounting evidence that ambient air pollution during pregnancy influences fetal growth. This study was designed to examine possible associations between fetal ultrasonic measurements collected from 15,623 scans (13-26 weeks gestation) and ambient air pollution during early pregnancy. We calculated mothers' average monthly exposures over the first 4 months of pregnancy for the following pollutants: particulate matter < 10 microm aerodynamic diameter (PM10), ozone, nitrogen dioxide, and sulfur dioxide. We examined associations with fetal femur length (FL), biparietal diameter (BPD), head circumference (HC), and abdominal circumference (AC). Final analyses included scans from only those women within 2 km of an air pollution monitoring site. We controlled for long-term trend, season, temperature, gestation, mother's age, socioeconomic status, and fetal sex. A reduction in fetal AC was associated with O3 during days 31-60 [-1.42 mm; 95% confidence interval (CI), -2.74 to -0.09], SO2 during days 61-90 (-1.67 mm; 95% CI, -2.94 to -0.40), and PM10 during days 91-120 (-0.78 mm; 95% CI, -1.49 to -0.08). Other results showed a reduction in BPD (-0.68 mm; 95% CI, -1.09 to -0.27) associated with SO2 during days 0-30, a reduction in HC (-1.02 mm; 95% CI, -1.78 to -0.26) associated with PM10 during days 91-120, and a reduction in FL associated with PM10 during days 0-30 (-0.28 mm; 95% CI, -0.48 to -0.08) and 91-120 (-0.23; 95% CI, -0.42 to -0.04). We found strong effects of ambient air pollution on ultrasound measures. Future research, including more individually detailed data, is needed to confirm our results.


[Treatments with synthetic antithyroid drugs during pregnancy. Evaluation of the neonatal thyroid function. 25 cases].
Twenty-four hyperthyroid women were treated with antithyroid drugs during 25 pregnancies. The thyroid function of the 21 children who lived was evaluated by standard clinical and laboratory methods. In 8 of these, T3, T4 and TSH were assayed between birth and the 5th day, with timed samplings during the first hours of life. There was no hypothyroxinaemia at birth, but the T4 peak was delayed; T3 was normal. The TSH peak was abnormal in 3 children, one of whom presented with clinical hypothyroidism. All abnormal findings disappeared spontaneously during the first few days of life, except for one child with congenital Grave's disease who had to be treated. On a 6 months to 6 years follow-up all children had normal growth and psychomotor development.


Efficacy and safety of oxaliplatin and gemcitabine with bevacizumab in advanced non-small cell lung cancer.
We conducted a multicenter phase II study to evaluate the efficacy and safety of oxaliplatin and gemcitabine with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Patients with chemotherapy-naive, nonsquamous, stage IIIB or IV NSCLC received gemcitabine 1000 mg/m on days 1 and 8, oxaliplatin 130 mg/m on day 1, and bevacizumab 15 mg/kg on day 1 every 21 days for 4 cycles. Patients with stable disease or response received maintenance bevacizumab every 3 weeks until progression. Primary end point was median time to progression (TTP). Nineteen of 44 eligible patients had partial response in the intent-to-treat analysis for an objective response rate of 43% (95% confidence interval [CI], 26.3-60.1%); 16 patients had stable disease for a disease control rate of 80% (95% CI, 72.0-87.0%). Median TTP was 5.5 months (95% CI, 3.8-6.9 months), which approached that seen in phase III studies. Median survival was 13.7 months (95% CI, 7.3-21.8 months). The most common grade 3 or 4 adverse events were hypertension (11%), neutropenia (9%), diarrhea (7%), dyspnea (7%), and thromboembolic events (7%). Pulmonary hemorrhage was not observed. The results of this phase II study suggest that oxaliplatin and gemcitabine with bevacizumab was active and reasonably well tolerated. Median TTP approached that in phase III studies. This combination represents another treatment option for advanced NSCLC.


Ciliate biology: dynamin goes nuclear.
Dynamin and dynamin-related proteins (DRPs) mediate an array of membrane fission processes. A Tetrahymena DRP has adopted a new role, assisting in nuclear differentiation, a finding that further highlights these proteins - and this ciliate - as biological innovators.


Transformation of LMTK- cells with purified HLA class I genes--IV. A determinant on beta 2-microglobulin is controlled by HLA heavy chain in a mouse-human hybrid complex: a biochemical analysis.
Transformation of LMTK- murine fibroblast cells with purified HLA class I heavy chain genes resulted in the expression of serologically detectable HLA-A3 molecules. Surprisingly, such cells also react with a murine monoclonal antibody specific for a serological determinant notably not expressed by murine but by human beta 2-microglobulin. The human HLA molecules expressed by the transformed cells were characterized on two-dimensional gels. The heavy chain was shown to be associated with a murine beta 2-microglobulin molecule, which could be distinguished from human beta 2-microglobulin by its higher isoelectric point. This heterodimer molecule was immunoprecipitated with the mouse anti-human beta 2-microglobulin monoclonal antibody showing that indeed the complex of mouse beta 2-microglobulin and human heavy chain expresses a human beta 2-microglobulin determinant.


The prevalence of primary dysmenorrhea among students and its association with musculoskeletal and myofascial pain.
To examine the association between dysmenorrhea and musculoskeletal pain amongst university students aged 20-35 and the association between dysmenorrhea and the occurrence of MTrPs. The study comprised two stages: a cross-sectional study evaluated the association between dysmenorrhea and musculoskeletal pain and a case-control study evaluated the association between dysmenorrhea and the occurrence of MTrPs in the abdominal and pelvic area. Initially, questionnaires such as demographics, menstruation characteristics, Numeric Pain Rating Scale (NPRS), measuring the average pain during menstruation and Nordic, were distributed to female students. Twenty subjects who suffered from menstrual pain of >3 on the NPRS (ones with the highest scores) were included in the second stage as cases. An additional 20 who had not suffered from menstrual pain (NPRS ≤3) were considered controls. All 40 subjects underwent an assessment of MTrPs by two examiners blinded to each other's results and to the group allocation of the subjects. We found that dysmenorrhea is a very prevalent condition among young female students. Most frequent complaints were: lower abdomen and back pain, tiredness, breast tenderness, mood changes, and an increased appetite. Pain during menstruation indicated a significant positive association with neck, low back, and hip/thigh pain during the last 12 months. The results of the palpitation conclusively showed more active MTrPs in the rectus abdominis, quadratus lumborum and paraspinal muscles in women suffering from pain during menstruation than in those who were not in pain. Our data provide an initial basis for the inclusion of a myofascial examination when evaluating women with dysmenorrhea.


The relationship between reincarceration and treatment of opioid use disorder with extended-release naltrexone among persons with HIV.
In the United States, a disproportionate number of persons with HIV (PWH) and opioid use disorder (OUD) are involved in the justice system. Medications for OUD (MOUD) can reduce convictions and incarceration time in persons with OUD. Extended-release naltrexone (XR-NTX) has been shown to reduce craving of opioids, recurrence of use, and overdose and help achieve or maintain HIV viral suppression in PWH with OUD involved with the justice system. This retrospective study aimed to describe factors associated with reincarceration and to evaluate if XR-NTX was associated with reduced reincarceration among PWH and OUD who were released to the community from incarceration. Data from participants released to the community from incarceration from a completed randomized controlled trial was analyzed using a generalized linear model to estimate odds ratios associated with reincarceration and a Kaplan-Meier survival analysis to determine time to reincarceration and non-reincarcerated individuals were compared. Of the 77 participants, 41 (53.2%) were reincarcerated during the 12-month study period. The mean time to reincarceration was 190 days (SD=108.3). Compared with participants who remained in the community, reincarcerated participants were more likely to have major depressive disorder at study baseline, increased opioid cravings, longer mean lifetime incarceration, and a higher physical quality of life score. XR-NTX was not significantly associated statistically with reincarceration in this analysis. Reducing reincarceration is a public health priority, given the high proportion of PWH and OUD in the U.S. justice system as well as high degrees of persons returning to the community and having care interrupted due to reincarceration. This analysis determined that potentially identifying depression in recently released individuals could improve HIV outcomes, decrease recurrence of opioid use, and reduce reincarceration.


Serotonin transporter activity of imidazolidine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives in aspect of their acid-base properties.
Affinities of arylpiperazinylalkyl derivatives of imidazo[2,1-f]purine-2,4-dione and imidazolidine-2,4-dione for serotonin transporter and their acid-base properties were evaluated. The dissociation constant (pK(a)) of compounds 1-22 were determinated by potentiometric titration and calculated using pKalc 3.1 module of the Pallas system. The data from experimental methods and computational calculations were compared and suitable conclusions were reached.


The kinetics of cohesive powder de-agglomeration from three inhaler devices.
The purpose of the current investigation is to understand the kinetics of de-agglomeration (k(d)) of micronised salbutamol sulphate (SS) and lactohale 300 (LH300) under varying air flow rates (30-180l min(-1)) from three dry powder inhaler devices (DPIs), Rotahaler (RH), Monodose Inhaler (MI) and Handihaler (HH). Cumulative fine particle mass vs. time profiles were obtained from the powder concentration, emitted mass and volume percent <5.4 μm, embedded in the particle size distributions of the aerosol at specific times. The rate of de-agglomeration (k(d)), estimated from non-linear least squares modelling, increased with increasing air flow rates. The k(d)vs. air flow rate profiles of SS and LH300 were significantly different at high air flow rates. The k(d) was highest from RH and lowest from MI. Differences in k(d) between the devices were related to device mode of operation while the differences between the materials were due to the powder bed structure. This approach provided a methodology to measure the rate constant for cohesive powder de-agglomeration following aerosolisation from commercial devices and an initial understanding of the influence of device, air flow rate and material on these rate constants.


Are beliefs about the importance of genetics for cancer prevention and early detection associated with high risk cancer genetic testing in the U.S. Population?
Public attitudes towards germline genetic testing for inherited cancers have been found to be generally positive. Past research demonstrated that diverse causal beliefs and contextual factors are associated with uptake of genetic testing. However, it is unclear how beliefs about genetically informed cancer prevention and early detection ultimately shape testing behaviors. We used data from the National Health Information National Trends Survey (HINTS 5 Cycle 4) to evaluate these beliefs and the relationship between beliefs related to cancer genetics and participation in cancer genetic testing. Overall, 5.24% of the total weighted sample underwent cancer genetic testing, of whom 70.5% (n = 141) had no personal history of cancer, whereas others had a personal diagnosis of breast, ovarian, or colorectal cancer (23.0%), or other cancers (6.5%). In adjusted multivariable analysis, testing was positively associated with personal history of breast, ovarian, or colorectal cancer (OR = 28.37, 95% CI: 10.19-79.04), female sex (OR = 2.97, 95% CI: 1.41-6.26), having high cancer worry (OR = 4.78, 95%: 2.19-10.45), and negatively associated with being Hispanic (OR = 0.37, 95%: 0.16-0.86) or non-Hispanic Asian (OR = 0.12, 95% CI: 0.04-0.33). Belief in the importance of genetics for early detection of cancer was associated with testing (OR = 18.03, 95% CI: 4.07-79.79), whereas belief in the importance of genetics for cancer prevention was not. The association between testing and belief about the importance of genetics for early detection of cancer, but not cancer prevention, is a surprising finding that warrants further research. Better understanding of these beliefs and their potential impact on test uptake may inform population genetic testing efforts.


Stroke and Helicopter Emergency Medical Service Transports: An Analysis of 25,332 Patients.
Helicopter emergency medical services (HEMS) are effective in time-sensitive illnesses, including stroke. Intravenous tissue plasminogen activator is beneficial for ischemic stroke within 4.5 hours of onset. This study analyzed the largest repository of US HEMS electronic medical record data characterizing demographic and logistical trends during stroke center accreditation. This study developed a methodology to aggregate, analyze, and report data from multiple providers. This is a descriptive study of aggregate, deidentified data from 67 US providers from 2004 to 2011. Retrospective data including age, ethnicity, total transport time, mission type, and locality were analyzed. The effect of primary stroke center (PSC) designation was assessed for 2011. A total of 25,332 patients were transported for "stroke." Stroke increased from 1.4% to 3.9% during the study. Ninety-six percent of transports arrived at definitive care within 2 hours. Seventy-two percent of transports were "interfacility," and 58% were from "rural" or "super-rural" localities. Seventy-nine percent of 2011 transports were to PSCs. Ethnicity and age were significant barriers to transport to PSCs (P < .001). HEMS has increased access to stroke care for super-rural, rural, and urban communities offering timely transport within the treatment window if symptoms are recognized within 2.5 hours of onset. This study created a methodology for future multicenter aggregate data studies.


Metastasis Within Three Years from Radical Nephroureterectomy as a Potential Surrogate for Overall Survival.
The only phase III trial that evaluated the role of adjuvant chemotherapy following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) was terminated early. Thus, eventual overall survival (OS) surrogacy, as per Prentice, cannot be assessed in this setting. We aimed to identify an intermediate clinical endpoint (ICE) that could serve as an OS surrogate after RNU for UTUC. We retrospectively analyzed 823 high-grade UTUC patients treated with RNU at 8 tertiary referral centers. We explored the role of any recurrence (aR), defined as recurrence in the urinary tract or in the resection bed as well the presence of distant metastasis (DM), defined as metastatic disease outside the urinary tract and regional lymph nodes, on OS through a time-varying Cox regression analyses fitted at the landmark points of 1, 2, 3, and 4 years from RNU. Models' discrimination was assessed using Harrell's c index, after internal validation. Median follow-up for survivors was 5.6 years (interquartile range: 2.0-8.8). Overall, 391 and 212 patients experienced aR and DM, respectively. In a time-varying model, aR and DM were predictors of OS: hazard ratio [HR]:1.20, 95% confidence interval [CI]: 1.13-1.28 (P < .001) and HR:1.26, 95% CI: 1.18-1.34 (P < .001), respectively. Progression to DM within 3 years from RNU was the most informative ICE for predicting OS (c index: 0.81; HR: 4.40; 95%CI: 2.45-7.92; P < .001), compared to DM within 1, 2, and 4 years (c indexes: 0.74, 0.76, and 0.78, respectively). Progression to DM within 3 years from RNU was further found superior for predicting OS compared to aR at any landmark points. Progression to DM within 3 years represents a potential OS surrogate for surgically-treated UTUC. This information could help in patient counseling, future study design and expedite results release of ongoing randomized controlled trials.


Mobilising the alumni of a Master of Public Health degree to build research and development capacity in low- and middle-income settings: The Peoples-uni.
Peoples-uni (People's Open Access Education Initiative) was established to help build Public Health capacity in low- and middle-income countries (LMICs) through postgraduate level online courses. Graduates are invited to join a virtual alumni group. We report the results of efforts to meet the need for health research capacity building by exploring how the course alumni could be mobilised to perform collaborative research into the health problems of their populations. Two online surveys of Peoples-uni graduates were conducted with graduates from the first two and first four cohorts in 2013 and 2014, respectively, to explore the formation of an alumni group that would collaborate to further the research and development agenda in LMICs. This was followed by feedback on research-related activity and outcomes via the online alumni and tutors' forum to estimate early indicators of alumni success in relation to capacity building in both the conduct and utilisation of research. Responses were received from 26 (87% response rate) graduates of the first survey and 42 (60% response rate) of the second survey. Overall, 92% of the respondents to the first survey supported the creation of an alumni group, especially if it helped to develop their own research skills and improve the health of their populations. Findings from the second survey showed that study with Peoples-uni was felt to have had a major or potential impact on the careers of the respondents, with 19% of graduates having progressed to a PhD programme to further their research skills, and a further 48% being in the process of applying or intending to apply for doctoral studies. Further feedback shows that at least one collaborative study has been completed and published by alumni members with other collaborative studies planned. Ongoing support has been provided to graduates to help them publish their work and apply for individual or collaborative research grants. Harnessing the alumni of a Masters level course to perform collaborative research has considerable potential to build research capacity in LMICs.


Phosphatidylcholine mobility in liver microsomal membranes.
Purified phosphatidylcholine exchange protein from bovine liver was used to exchange rat liver microsomal phosphatidylcholine for egg phosphatidylcholine. It was found that at 25 and 37 degrees C rat liver microsomal phosphatidylcholine was completely and rapidly available for replacement by egg phosphatidylcholine. In contrast, phosphatidylcholine in vesicles prepared from total microsomal lipids could only be exchanged for about 60%. At 8 and 0 degrees C complex exchange kinetics were observed for phosphatidylcholine in rat liver microsomes. The exchange process had neither effect on the permeability of the microsomal membrane to mannose 6-phosphate, nor on the permeability of the phosphatidylcholine vesicles to neodymium (III) cations. Purified phospholipase A2 from Naja naja could hydrolyze some 55-60% of microsomal phosphatidylcholine at 0 degrees C, but 70-80% at 37 degrees C. Microsomal phosphatidylcholine, remaining after phospholipase treatment at 37 degrees C, could be exchanged for egg phosphatidylcholine at 37 degrees C, but at a slower rate than with intact microsomes. Microsomal phosphatidylcholine remaining after phospholipase treatment at 0 and 37 degrees C had a lower content of arachidonic acid than the original phosphatidylcholine. These results are discussed with respect to the localization and transmembrane movement of phosphatidylcholine in liver microsomes.


Procalcitonin and neopterin correlation with aetiology and severity of pneumonia.
Clinical outcome of pneumonia depends on a multifaceted treatment approach. Not only diagnostic methods but also early indicators of the degree of inflammatory response can aid in therapeutic decisions. The objective was to evaluate the usefulness of procalcitonin and neopterin in distinguishing among aetiologies as well as severity in patients with pneumonia. A total of one hundred sixteen patients with clinical, radiographic and microbiological diagnosis of pneumonia were grouped by aetiology, pneumonia severity index, and by the presence of unilobar or multilobar radiographic pulmonary infiltrates. Procalcitonin and neopterin were measured by immunoassays. Patients with pneumococcal pneumonia presented elevated procalcitonin and neopterin levels, being higher in bacteraemic than in non-bacteraemic pneumonia. Patients with Legionella pneumonia presented elevated neopterin levels and slightly elevated procalcitonin levels. Patients with tuberculosis and Pneumocystis jirovecii pneumonia presented elevated neopterin and low or not detectable procalcitonin. Procalcitonin and neopterin levels were increased in high-risk classes of pneumonia severity index. Both parameters yielded significant correlation to the radiographic extent and also to young age. Procalcitonin and neopterin levels vary depending on age, aetiology and severity of pneumonia. Together with clinical and microbiological data, combined measurement can help to identify patients who might benefit from additional therapies.


Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats.
Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly by tail cuff plethysmography. Because there are potentially significant drawbacks associated with plethysmography, we determined whether blood pressure changes could be detected by long-term monitoring with telemetry in age-matched male Sprague-Dawley rats fed either a normal or high-fructose diet for 8 weeks. Fasting plasma glucose (171+/-10 versus 120+/-10 mg/dL), plasma insulin (1.8+/-0.5 versus 0.7+/-0.1 microg/L), and plasma triglycerides (39+/-2 versus 30+/-2 mg/dL) were modestly but significantly elevated in fructose-fed animals. Using the hyperinsulinemic euglycemic clamp technique, the rate of glucose infusion necessary to maintain equivalent plasma glucose was significantly reduced in fructose-fed compared with control animals (22.9+/-3.6 versus 41.5+/-2.9 mg/kg per minute; P<0.05). However, mean arterial pressure (24-hour) did not change in the fructose-fed animals over the 8-week period (111+/-1 versus 114+/-2 mm Hg; week 0 versus 8), nor was it different from that in control animals (109+/-2 mm Hg). Conversely, systolic blood pressure measured by tail cuff plethysmography at the end of the 8-week period was significantly greater in fructose-fed versus control animals (162+/-5 versus 139+/-1 mm Hg; P<0.001). Together, these data demonstrate that long-term fructose feeding induces mild insulin resistance but does not elevate blood pressure. We propose that previous reports of fructose-induced hypertension reflect a heightened stress response by fructose-fed rats associated with restraint and tail cuff inflation.


The contextual development of healthy living centres services: an examination of food-related initiatives.
The Healthy Living Centre (HLC) programme was designed to address the wider determinants of health, in particular social exclusion and socio-economic disadvantage, through targeting services at the most deprived local communities. This paper draws on data collected during an in-depth process evaluation of six Scottish HLC case study sites. Food-related services, which were found to cross-cut all the sites, were used to address social exclusion and to promote health. Three types of service, each linked to a social model of health, were found to be in operation: those which enhance skills; those which promote social inclusion; and those which influence food accessibility. The paper illustrates how food-related services have developed in the case study HLCs to take account of the differing needs of the communities and neighbourhoods that have been targeted. Consideration is then given to how HLCs adapt to meet the practicalities of improving health while addressing social exclusion through targeting health inequalities.


Comparison of outcome in a 9-day and 30-day alcoholism treatment program.
At 3 and 6 months after discharge no differences in abstinence rates were found between patients who completed a 9-day inpatient alcoholism treatment program and those who participated in a 21-day treatment program.


River plumes as a source of large-amplitude internal waves in the coastal ocean.
Satellite images have long revealed the surface expression of large amplitude internal waves that propagate along density interfaces beneath the sea surface. Internal waves are typically the most energetic high-frequency events in the coastal ocean, displacing water parcels by up to 100 m and generating strong currents and turbulence that mix nutrients into near-surface waters for biological utilization. While internal waves are known to be generated by tidal currents over ocean-bottom topography, they have also been observed frequently in the absence of any apparent tide-topography interactions. Here we present repeated measurements of velocity, density and acoustic backscatter across the Columbia River plume front. These show how internal waves can be generated from a river plume that flows as a gravity current into the coastal ocean. We find that the convergence of horizontal velocities at the plume front causes frontal growth and subsequent displacement downward of near-surface waters. Individual freely propagating waves are released from the river plume front when the front's propagation speed decreases below the wave speed in the water ahead of it. This mechanism generates internal waves of similar amplitude and steepness as internal waves from tide-topography interactions observed elsewhere, and is therefore important to the understanding of coastal ocean mixing.


Evidence that each nerve varicosity on the surface of the mouse vas deferens secretes ATP.
The secretion of ATP from visualised varicosities on the surface of the mouse vas deferens was determined. Small diameter microelectrodes (about 6 microns and 20 microns) were placed over a set of 2 to 5 varicosities visualised with DiOC2(5) in order to record excitatory junctional currents (e.j.c.s') arising from the evoked secretion of quanta. In high external calcium concentrations, [Ca2+]o, the amplitude-frequency distribution of e.j.c.s' was well described by binomial statistics in which binomial parameter n and the number of varicosities were approximately the same. Idazoxan (1 microM) had no effect on the e.j.c.s' or the binomial parameters p and n. Suramin (100 microM) blocked the e.j.c.s' as well as the spontaneous e.j.c.s' (s.e.j.c.s') in all cases, reducing n and p to zero. These results indicate that all varicosities secrete the transmitter blocked by suramin, presumably ATP.