Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates: A Secondary Analysis of the PENUT Randomized Clinical Trial.
Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI. To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes. This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022. Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]). The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64). In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance. ClinicalTrials.gov Identifier: NCT01378273.


Exploring pathways from driving errors and violations to crashes: The role of instability in driving.
This study explores how different driving errors, violations, and roadway environments contribute to safety-critical events through instability in driving speed. We harness a subsample (N = 9239) of the naturalistic driving study (NDS) data collected through the Second Strategic Highway Research Program (SHRP2). From a methodological standpoint, we use the safe systems approach relying on path analysis to jointly model outcomes. This accounts for the potential correlation between unobserved factors associated with both instability in driving speed and epoch (video stream) outcomes, i.e., baseline or event-free driving, near-crashes, and crashes. Tobit and ordered Probit regressions are estimated to model the coefficient of variation (COV) of speed and epoch outcomes, respectively. Results from the Tobit model indicate that driving errors and violations are associated with instability in the driving speed of the subject driver (COV of speed). The Probit model reveals that driving errors, violations, and instability in driving speed are associated with higher chances of crashes and near-crashes. Our key finding is that driving errors and violations not only induce event risk directly but also indirectly through instability in driving speed. For instance, recognition errors associate with higher crash risk by 6.78 % but this error is accompanied by instability in driving speed, which further increases event risk by 4.73 %, bringing the total increase in risk to 11.51 %. Moreover, significant correlations were found between unobserved factors reflected in the error terms of the two models. Ignoring such correlations can lead to inefficient parameter estimates. Based on the findings, practical implications are discussed, which can lead to effective countermeasures that effectively reduce crash risk.


Combinatorial and Computational Approaches to Identify Interactions of Macrophage Colony-stimulating Factor (M-CSF) and Its Receptor c-FMS.
The molecular interactions between macrophage colony-stimulating factor (M-CSF) and the tyrosine kinase receptor c-FMS play a key role in the immune response, bone metabolism, and the development of some cancers. Because no x-ray structure is available for the human M-CSF · c-FMS complex, the binding epitope for this complex is largely unknown. Our goal was to identify the residues that are essential for binding of the human M-CSF to c-FMS. For this purpose, we used a yeast surface display (YSD) approach. We expressed a combinatorial library of monomeric M-CSF (M-CSFM) single mutants and screened this library to isolate variants with reduced affinity for c-FMS using FACS. Sequencing yielded a number of single M-CSFM variants with mutations both in the direct binding interface and distant from the binding site. In addition, we used computational modeling to map the identified mutations onto the M-CSFM structure and to classify the mutations into three groups as follows: those that significantly decrease protein stability; those that destroy favorable intermolecular interactions; and those that decrease affinity through allosteric effects. To validate the YSD and computational data, M-CSFM and three variants were produced as soluble proteins; their affinity and structure were analyzed; and very good correlations with both YSD data and computational predictions were obtained. By identifying the M-CSFM residues critical for M-CSF · c-FMS interactions, we have laid down the basis for a deeper understanding of the M-CSF · c-FMS signaling mechanism and for the development of target-specific therapeutic agents with the ability to sterically occlude the M-CSF·c-FMS binding interface.


Comparison of the carcinogenic effects of two 2-nitro-naphthofurans injected sub-cutaneously in rats.
7-Methoxy-2-nitro-naphtho[2,1-b]furan (R 7000) and its methylated homolog in position 1 (R 7372) are among the most mutagenic agents presently known, as shown by the results obtained both in the Ames test and in the SOS Chromotest. Their carcinogenic effects were tested in rats. We were able to confirm the carcinogenic effects of these nitro-naphthofurans, the presence of a methyl group--while increasing the mutagenic effect of R 7000 10 times--induces a significant decrease of the carcinogenic effects in R 7372. The discrepancy between the mutagenic effects in bacterial assays and the carcinogenic effects of these two 2-nitro-naphthofurans remains to be explained.


Communication and related problems as perceived by aphasic individuals and their spouses.
Aphasics' and spouses' perceptions of the presence and degree of bothersomeness of communication-related problems and whether enrollment in a language treatment program affected these perceptions were examined. Aphasic-spouse perceptions were more concordant in the treated group; aphasic patients in the untreated group reported their problems did not bother them. Type and severity of aphasia were not related either to the reported frequency or to the degree of bothersomeness of problems. Interview data from spouses revealed that the speech-language pathologists' role extended beyond solely providing information about language behavior.


Correction: Oral Intake of Royal Jelly Has Protective Effects against Tyrosine Kinase Inhibitor-Induced Toxicity in Patients with Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled Trial. Medicines, 2019, 6, 2.
We, the authors, wish to make the following correction to our published paper [...].


Flock House virus: a nodavirus isolated from Costelytra zealandica (White) (Coleoptera: Scarabaeidae).
The physico-chemical properties of Flock House virus (FHV) were examined. FHV was shown to have a single-stranded RNA genome divided between two species of MW 1.1 and 0.46 million; the genome was infectious. FHV has a single, coat protein of 43,000 MW. The virus sediments at 142S and has a density of 1.351 g/ml in CsCl at pH 7. These properties indicate that FHV is a nodavirus but it is distinguishable from Nodamura virus and black beetle virus by differences in electrophoretic mobility, the size of the coat protein, particle density and stability in CsCl.


Vision, perception, navigation and 'cognition' in honeybees and applications to aerial robotics.
This review summarizes research carried out in the author's laboratory investigating the ways in which honeybees use vision to guide their flight and navigate in their environment, and describes how these principles have been used to design, build and test biologically-inspired systems for the guidance and navigation of unmanned aerial vehicles. It also outlines studies investigating the capacities of honeybees in the areas of visual perception, pattern recognition, and 'cognition'.


Vector microbiome: will global climate change affect vector competence and pathogen transmission?
Vector-borne diseases are among the greatest causes of human suffering globally. Several studies have linked climate change and increasing temperature with rises in vector abundance, and in the incidence and geographical distribution of diseases. The microbiome of vectors can have profound effects on how efficiently a vector sustains pathogen development and transmission. Growing evidence indicates that the composition of vectors' gut microbiome might change with shifts in temperature. Nonetheless, due to a lack of studies on vector microbiome turnover under a changing climate, the consequences for vector-borne disease incidence are still unknown. Here, we argue that climate change effects on vector competence are still poorly understood and the expected increase in vector-borne disease transmission might not follow a relationship as simple and straightforward as past research has suggested. Furthermore, we pose questions that are yet to be answered to enhance our current understanding of the effect of climate change on vector microbiomes, competence, and, ultimately, vector-borne diseases transmission.


The functions of endogenous C1q, a subcomponent of the first component of complement, as a receptor on the membrane of macrophages.
C1q, the Fc-recognizing subcomponent of the first component of complement is synthesized by peritoneal macrophages. During the secretion phase C1q serves as an Fc-binding protein in the membrane of macrophages. The Fc-mediated rosette formation was inhibited in a dose-dependent manner when macrophages were pretreated with anti-C1q F(ab')2, whereas C3b rosette formation was not affected. Furthermore, preincubation of peritoneal macrophages with anti-C1q F(ab')2 abolished, dose- and time-dependently, the polyanion-mediated stimulation of secretion of lysosomal enzymes. Polyanion-induced enzyme release was prevented after incubation of polyanions with highly purified C1q. The inhibition of Fc receptor activity by polyanions (i.e. dextran sulfate, liquoid, polyvinyl sulfate) is completely reversed upon treatment of these macrophages with protamine. These findings are compatible with the hypothesis that C1q produced by macrophages serves in the macrophage membrane as an endogenous receptor for Fc and polyanionic molecules. Thus, C1q mediates cell-bound biological receptor functions before it is released from these cells and is incorporated into the macromolecular C1 complex.


2-Hydroxy fatty acids from marine sponges. 2. The phospholipid fatty acids of the Caribbean sponges Verongula gigantea and Aplysina archeri.
The alpha-hydroxy fatty acids 2-hydroxy-eicosanoic (1) acid, 2-hydroxyheneicosanoic (2) acid, 2-hydroxydocosanoic (3) acid, 2-hydroxytetracosanoic (4) acid, 2-hydroxy-23-methyl-tetracosanoic acid and 2-hydroxypentacosanoic (5) acid were isolated from the Caribbean sponges Verongula gigantea and Aplysina archeri. The very long chain fatty acids 5,9-nonacosadienoic acid (29:2) and 5,9,23-tricontatrienoic acid (30:3) were also identified together with the iso-prenoid fatty acid 3,7,11,15-tetramethylhexadecanoic (phytanic) acid that seems to be common in the Aplysinidae. A. archeri contained an extremely long chain fatty acid tentatively characterized as dotricontaenoic (32:1) acid. These acids were found to occur in phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylcholine and traces of phosphatidylglycerol.


Family-Centered Care During Constraint-Induced Therapy After Chronic Stroke: A Feasibility Study.
This feasibility study evaluated a theory-based intervention (CARE-CITE) designed to engage carepartners (CPs) in supporting stroke survivor upper extremity rehabilitation. The study was a one-group design with pre- and posttest and 1 month follow-up (N = 7 dyads). Feasibility was determined by participant retention, CP and stroke survivor intervention adherence, and CP acceptability of the intervention (exit interview). Measures of CP depressive symptoms, fatigue, and family conflict around stroke recovery and stroke survivor upper extremity function are reported. Data were analyzed using descriptive statistics. All participants completed the study and adhered to the intervention, and CPs found CARE-CITE helpful. Descriptively, better scores were observed for CP's mental health, family conflict, stroke survivor confidence, and upper extremity tasks performed. These results provide initial evidence that CARE-CITE is feasible after chronic stroke and that CPs and stroke survivors may benefit from family-centered care. Improving CP skills in supporting rehabilitation activities may improve stroke survivor upper extremity function.


An SP1-like 5'-GACCACGCC-3' sequence is critical for activity of the inflammatory phospholipase A2 promoter and binds several non-zinc finger proteins.
We have previously shown that the promoter of the type IIa secreted phospholipase A2 gene contains a strong positive regulatory proximal element [-125 to -85] element B. Mutation of this element abolishes the activation of the phospholipase A2 promoter by C/EBPbeta in HepG2 cells. Liver nuclear proteins form three major and two minor complexes with this element. The [-107 to -99] 5'-GACCACGCC-3' sequence is critical for the formation of these complexes and the activity of the promoter. Although the sequence of element B is highly similar to those of Sp1 binding sites, it does not bind Sp1 or other zinc-finger proteins. Each major complex contains a single protein, the molecular masses of these proteins being 100, 90 and 75 kDa. These proteins have the same nucleotide requirements for binding, with the cytosines at positions -102, -100, -99 and the adenosine at -103 being the most important nucleotides. The activity of the phospholipase A2 promoter in HeLa cells was lower than in HepG2 cells, and was correlated with the absence of complex 3 in HeLa cell nuclear extracts. Our results suggest different roles for the proteins bound to the 5'-GACCACGCC-3' sequence. In particular, the 75-kDa protein which forms the third complex is critical for the activity of the promoter of the secretory phospholipase A2 gene.


Accuracy of intraoperative tissue staining in delineating deep surgical margins in oral carcinoma surgery.
The purpose of this study was to assess the accuracy of this tissue staining assessment of surgical specimens in delineating deep surgical margins in oral cancer surgery. Fifteen patients who underwent surgery for oral carcinoma were included in the study. Once the tumor was resected, a vertical section of the surgical specimen was taken from the central part of the tumor. The section was consecutively stained with 0.4% indigo carmine and 0.5% Congo red, and deep surgical margins were assessed using a digital microscope with a magnification power of 25-175x. The results of tissue staining analysis were compared with the corresponding results of conventional histopathological analysis with HE staining, which is considered the gold standard. The extent of carcinoma invasion could be visualized after the application of tissue staining solutions. Tissue staining analysis was accurate in 12 of the 15 patients (80%) in evaluating the closest deep surgical margin. There was no significant difference in the tumor-margin distance between tissue staining and histopathological assessment in these 12 patients (Wilcoxon signed-ranks test, P>0.63). The results of this study showed that intraoperative tissue staining of surgical specimens permitted visual inspection and assessment of tumor spread to surgical margin, although the method has some limitations. The method had a possible ability in controlling the deep surgical margin.


Inhibition of bile canalicular network formation in rat sandwich cultured hepatocytes by drugs associated with risk of severe liver injury.
Idiosyncratic drug-induced liver injury is a clinical concern with serious consequences. Although many preclinical screening methods have been proposed, it remains difficult to identify compounds associated with this rare but potentially fatal liver condition. Here, we propose a novel assay system to assess the risk of liver injury. Rat primary hepatocytes were cultured in a sandwich configuration, which enables the formation of a typical bile canalicular network. From day 2 to 3, test drugs, mostly selected from a list of cholestatic drugs, were administered, and the length of the network was semi-quantitatively measured by immunofluorescence. Liver injury risk information was collected from drug labels and was compared with in vitro measurements. Of 23 test drugs examined, 15 exhibited potent inhibition of bile canalicular network formation (<60% of control). Effects on cell viability were negligible or minimal as confirmed by lactate dehydrogenase leakage and cellular ATP content assays. For the potent 15 drugs, IC50 values were determined. Finally, maximum daily dose divided by the inhibition constant gave good separation of the highest risk of severe liver toxicity drugs such as troglitazone, benzbromarone, flutamide, and amiodarone from lower risk drugs. In conclusion, inhibitory effect on the bile canalicular network formation observed in in vitro sandwich cultured hepatocytes evaluates a new aspect of drug toxicity, particularly associated with aggravation of liver injury.


Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice.
During development, alterations in sensory experience modify the structure of cortical neurons, particularly at the level of the dendritic spine. Are similar adaptations involved in plasticity of the adult cortex? Here we show that a 24 hr period of single whisker stimulation in freely moving adult mice increases, by 36%, the total synaptic density in the corresponding cortical barrel. This is due to an increase in both excitatory and inhibitory synapses found on spines. Four days after stimulation, the inhibitory inputs to the spines remain despite total synaptic density returning to pre-stimulation levels. Functional analysis of layer IV cells demonstrated altered response properties, immediately after stimulation, as well as four days later. These results indicate activity-dependent alterations in synaptic circuitry in adulthood, modifying the flow of sensory information into the cerebral cortex.


Bilateral subacute lacrimal gland enlargement mimicking dacryoadenitis in a 7-year-old boy: a rare adverse effect of valproic acid (sodium valproate).
A healthy 7-year-old boy presented with bilateral symmetrical lacrimal gland enlargement; a week later salivary gland enlargement was also noted. Clinical investigations suggested no diagnosis, and surgical biopsy was considered. Valproic acid (sodium valproate), which he was taking for absence seizures, has been reported to cause salivary gland swelling in adults. Suspecting that a similar mechanism could be causal, the drug was discontinued. Complete resolution of the lacrimal and salivary gland enlargement rapidly ensued. This is the first report of lacrimal gland enlargement caused by valproic acid.


Pregnancy exposure to quetiapine - Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood and obstetrical outcomes.
This prospective study is the first to measure and correlate quetiapine concentrations in maternal blood, amniotic fluid and umbilical cord blood to account for the distribution of quetiapine. Concentrations of quetiapine are quantified in seven mother infant pairs at the time of delivery. Data are provided as median values, first (Q1) and third (Q3) quartiles and ranges. To account for the penetration ratio, the concentration of quetiapine in amniotic fluid and cord blood was divided by maternal concentrations. Correlations between daily dosage, maternal serum and umbilical cord blood concentrations were computed for seven patients while calculations for amniotic fluid were only available for six mother-infant pairs. The median daily dosage of quetiapine was 300mg (Q1: 300mg, Q3: 600mg, range 200-800mg). There was a strong and significant correlation between maternal serum and cord blood concentrations (r=0.893, p=0.007). The median penetration ratio into fetal circulation was 0.18 (Q1: 0.16, Q3: 0.32; range 0.13-0.42), suggesting a low penetration. The median penetration ratio into amniotic fluid was 0.44 (Q1: 0.15, Q3: 0.96; range 0.09-1.70). Quetiapine concentrations in amniotic fluid and cord blood give evidence that quetiapine is constantly accessible to the fetus with a relatively low penetration ratio. A high correlation between maternal serum and umbilical cord blood concentrations highlights a predictive role of quantifying drug concentrations in maternal serum for assessing drug concentrations in fetal circulation. Findings support the important role of therapeutic drug monitoring in supporting the efficacy and safety of psychopharmacological treatment strategies in highly vulnerable populations.


A review of treatment options in HER2-low breast cancer and proposed treatment sequencing algorithm.
The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)-status to HER2-low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2-low expression has emerged as a targetable biomarker, and anti-HER2 antibody-drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2-low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor-positive and triple-negative BC needs to be reconsidered, as approximately half of these BCs are HER2-low. Although there are different therapeutic agents for hormone receptor-positive and hormone receptor-negative HER2-low BCs, there is no consensus regarding the sequencing of these agents. In this article, the treatment options for HER2-low BC are enumerated and a treatment sequencing algorithm based on the current clinical evidence proposed.


Immunogenicity and immunological memory induced by a 7-valent pneumococcal CRM197 conjugate vaccine in symptomatic HIV-1 infected children.
A 7-valent CRM197 conjugate pneumococcal vaccine (PCV)-induced immune response were evaluated in all Greek symptomatic HIV-1 infected children and 21 age-matched controls. PCV immunogenicity was inferior in HIV patients compared with the controls although differences in geometric mean concentrations (GMC) were not significant (P>.05). Immune responses were strikingly different after anamnestic immunization, given in all study subjects, 12 months later. HIV-positive children achieved lower GMC for all serotypes compared with the controls (P=.002) and avidity for all except serotype 6B was inferior compared to baseline. Long-term PCV effectiveness is expected to be reduced among symptomatic HIV-1 infected children.


Enhancement of enzymatic hydrolysis and Klason lignin removal of corn stover using photocatalyst-assisted ammonia pretreatment.
Photocatalyst-assisted ammonia pretreatment was explored to improve lignin removal of the lignocellulosic biomass for effective sugar conversion. Corn stover was treated with 5.0-12.5 wt.% ammonium hydroxide, two different photocatalysts (TiO(2) and ZnO) in the presence of molecular oxygen in a batch reactor at 60 °C. Various solid-to-liquid ratios (1:20-1:50) were also tested. Ammonia pretreatment assisted by TiO(2)-catalyzed photo-degradation removed 70 % of Klason lignin under the optimum condition (12.5 % ammonium hydroxide, 60 °C, 24 h, solid/liquid=1:20, photocatalyst/biomass=1:10 with oxygen atmosphere). The enzymatic digestibilities of pretreated corn stover were 85 % for glucan and 75 % for xylan with NH(3)-TiO(2)-treated solid and 82 % for glucan and 77 % for xylan with NH(3)-ZnO-treated solid with 15 filter paper units/g-glucan of cellulase and 30 cellobiase units/g-glucan of β-glucosidase, a 2-13 % improvement over ammonia pretreatment alone.


Seroprevalence of neutralizing antibodies to human mastadenovirus serotypes 3 and 7 in healthy children from guangdong province.
Severe adenovirus pneumonia is becoming more common in children infected with human mastadenovirus (HAdV)-3 and HAdV-7 than in those infected with other types of adenoviruses. Recently, there has been a trend toward an increasing prevalence of pneumonia caused by HAdV-7, an important viral pathogen in Pediatric Intensive Care Unit infections. Children infected with HAdV-7 have more serious symptoms of acute respiratory infections and other complications than those infected with HAdV-3. No specific anti-adenovirus drugs or vaccines are available for treatment or prevention. Therefore, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAbs) against HAdV-3 and HAdV-7 in healthy children in Guangdong Province. We found that the seropositivity rates and antibody titers for HAdV-3 NAb were higher than those for HAdV-7 NAb. In children between 6 and 12 months of age, the seropositivity rates and titers were significantly low against HAdV-3 and HAdV-7. The HAdV-7-positive rate was significantly higher in the HAdV-3-positive samples than in the HAdV-3-negative samples. The HAdV-7 NAbs carried by the 0-6-month age group were dominated by low titers. These results reveal a low level of herd immunity against HAdV-3 and HAdV-7 in children, clarifying the importance of monitoring these two highly virulent adenoviruses, developing prophylactic vaccines, and predicting potential outbreaks.


Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial.
One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean+/-SD of total stool output (g kg(-1)) was 532+/-476 vs 479+/-354 and the duration (h) of diarrhoea was 108+/-68 vs 103+/-53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.


Parental anxiety before elective surgery in children. A British perspective.
This study measures the anxiety levels in 100 parents of children scheduled for elective surgery at the Royal Aberdeen Children's Hospital. Anxiety levels were quantified using the Leeds scale for self-assessment of anxiety. Forty-two per cent of parents were significantly anxious. Mothers were identified as being more pathologically anxious than fathers. The 'anxious' parents were specifically more anxious about the surgery, anaesthesia, postoperative pain and treatment, and hospitalisation in general. All parents, whether identified as anxious or not, agreed on factors likely to reduce anxiety: pre-operative information from staff, being able to accompany their child to the operating theatre and being present at induction of anaesthesia.


Effect of cyclooxygenase-2 inhibitor pretreatment on gas exchange after hydrochloric acid aspiration in rats.
The present study was carried out to determine the effect of cyclooxygenase-2 (COX-2) inhibitor on acid aspiration-induced lung injury in rats. Rats were allocated into one of four groups. Group H received intratracheal instillation of HCl. Group S received saline intratracheally. Group HC received COX-2 inhibitor (celecoxib) 10 mg/kg intravenously 30 min before intratracheal instillation of HCl. Group C underwent bronchoalveolar lavage (BAL) only. All rats were mechanically ventilated for 30 min before BAL. Arterial blood gas analysis was done immediately before BAL. Groups H, S, and HC were subdivided to each two groups. Groups H-1, S-1, and HC-1 underwent BAL 1 h after instillation, whereas groups H-8, S-8, and HC-8 underwent BAL 8 h after instillation. The BAL fluid was used to measure the prostaglandin E2 (PGE2) concentration. Intratracheal HCl resulted in impaired oxygenation. COX-2 inhibitor attenuated the impairment of oxygenation 8 h after instillation but not after 1 h. Intratracheal HCl caused an increase in PGE2 concentration. COX-2 inhibitor attenuated an increase in PGE2 concentration 8 h after instillation but not after 1 h. The results show that COX-2 inhibitor attenuates the oxygenation impairment and the increase in alveolar PGE2 concentration during the inflammatory phase of acid aspiration-induced lung injury in rats.


Oxidative electro-organic synthesis of dimeric hexahydropyrrolo-[2,3-b]indole alkaloids involving PCET: total synthesis of (±)-folicanthine.
An efficient electrochemical oxidation strategy for the total synthesis of a dimeric hexahydropyrrolo[2,3-b]indole alkaloid, (±)-folicanthine (1b), has been envisioned. Control experiments suggest that a PCET pathway involving stepwise electron transfer followed by proton transfer (ET-PT) was involved in the key oxidative dimerization process.


Characterization of microplastics in the septic tank via laser direct infrared spectroscopy.
Microplastics (MPs) are emerging pollutants that have been widely detected in the atmosphere, hydrosphere, lithosphere, and biosphere. Such wide spread of MPs indicates that the effective control in different environmental sectors is in an urgent need, and the first step in meeting this need is to identify the occurrence of MPs in the relevant environment. However, research on MPs in septic tanks has not been reported so far. This study investigated the distribution characteristics of MPs in septic tanks with a size detection limit of as low as 20 μm detected by laser direct infrared spectroscopy. Results showed that the number of MPs in the septic tank was reached 2803 (1489-4816) particles/g dry sludge, and the amount detected in the sediments was one order of magnitude higher than that in the scums. A total of 36 types of MPs were found in the septic tank, and 26 types were found in both sediments and scums, but the type in the scums was 21% higher than that in the sediments. The size was mostly 20-100 μm, accounting for 86.3% and 91.2% in the sediments and scums, respectively. Four shapes of MPs were detected in the septic tank, namely, fiber, bead, granule, and fragment. Our study revealed that septic tanks are both sinks and sources of MPs, which are reflected in the fact that MPs are not only large in number but also abundant in types. Thus, significant attention should be paid to septic tank-based microplastic pollution, which may lead to environmental and health risks without proper control and management.


Comparative study on the therapeutic ultrasound effects on erythrocyte membrane-bound and free acetylcholinesterase.
Kinetics of erythrocyte acetylcholinesterase activity alterations exposed to ultrasound of therapeutic intensities of 0.88 MHz and 0.05-1.5 W/cm2 was studied. The differences were studied between the mechanisms of the inactivation of membrane-bound and free enzyme: the diminution of active enzyme sites for membrane-bound acetylcholinesterase and the decrease of enzyme-substrate affinity for the free form during sonication. The combined mechanical stresses in the ultrasonic field did not produce inactivation of free enzyme, as compared to the membrane-bound enzyme. Exponential ultrasonic/acoustochemical inactivation curves were obtained for the soluted crystalline form of acetylcholinesterase.


Retracted: Identification of Candidate Therapeutic Target Genes and Profiling of Tumor-Infiltrating Immune Cells in Pancreatic Cancer via Integrated Transcriptomic Analysis.
[This retracts the article DOI: 10.1155/2022/3839480.].


The effect of delta9-tetrahydrocannabinol on body temperature and brain amine concentrations in the rat at differnt ambient temperatures.
1. Rats were injected intravenously with 2 mg/kg (-)-trans-delta9-tetrahydrocannabinol (delta9-THC) at ambient temperatures of 4 degrees, 21 degrees, 31 degrees and 37 degrees C. 2. The general behavior exhibited by rats treated with delta9-THC was similar at all four ambient temperatures. 3. Body temperatures were recorded continuously before and after drug administration. At 4 degrees and 21 degrees C, delta9-THC caused hypothermia whereas no change in body temperature occurred at 31 degrees and 37 degrees C. 4. The concentrations in the whole brain of noradrenaline (NA), dopamine, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined spectrophotofluorimetrically 1 h after drug administration. At 4 degrees C delta9-THC caused an increase of 5-HT, at 21 degrees C an increase of 5-HIAA, at 21 degrees C an increase of 5-HIAA AND A decrease of NA, and at 37 degrees C an increase of 5-HT and 5-HIAA. 5. At all ambient temperatures, delta9-THC increased the brain levels of 5-HT and/or 5-HIAA. A correlation between the delta9-THC-induced hypothermic response and the possible alteration of brain 5-HT metabolism cannot be excluded.


Pulsar NP 0532: properties and systematic polarization of individual strong pulses at 430 MHz.
This paper reports further detailed measurements of strong radio pulses from the pulsar NP 0532 in the Crab nebula, recorded at Arecibo.


Factors associated with pregnancy and pregnancy resolution in HIV seropositive women.
This study examines factors associated with pregnancy and pregnancy resolution among 238 HIV-infected women, 55 of whom experienced a recent pregnancy since learning of their HIV positive serostatus. Results suggest the importance of psychosocial and cultural factors, particularly those involving the primary sex partner, to reproductive decision-making in HIV-infected women. They also indicate a consistency of reproductive behavior before and after HIV infection, suggesting that the infection itself does not significantly alter existing childbearing trends. Biomedical considerations relating to the mother's health status and the risk of transmission to the child have a greater impact on decisions surrounding pregnancy resolution than they do on the probability of becoming pregnant.


Preparation and characterization of antibacterial poly(lactic acid) nanocomposites with N-halamine modified silica.
In this work, silica nanoparticles modified with a new N-halamine precursor (EBDMH-SiO2 NPs) were synthesized through immobilization of 3-(4'-epoxyethyl-benzyl)-5,5-dimethylhydantoin (EBDMH) on the surface of amino-functionalized silica NPs. Then, EBDMH-SiO2 NPs and poly(lactic acid) (PLA) were blended at 185 °C to prepare a novel environmentally friendly PLA based nanocomposite (PLA/EBDMH-SiO2). The addition of EBDMH-SiO2 NPs has great influences on the thermal properties of nanocomposite. DSC results show that the grass transition temperature (Tg), cold crystallization temperature (Tcc) and melting temperature (Tm) of PLA in nanocomposites gradually decrease with the increase of EBDMH-SiO2 NPs contents up to 5%. After that, further rise in EBDMH-SiO2 NPs content actually increases Tg, Tcc, and Tm. The overall crystallization and spherulite growth rate of PLA show the similar trend. Furthermore, the introduction of EBDMH-SiO2 NPs increases the storage modulus and viscosity of the melt of nanocomposite, providing an additional benefit for PLA blowing and injection molding. After chlorination, the N-halamine precursors on the nanocomposite surfaces are transformed into N-halamines, which provide strong antibacterial activities against E. coli (CMCC 44103) and S. aureus (ATCC 6538), pointing to good potentials of the PLA/EBDMH-SiO2 nanocomposites for antibacterial applications including food packaging, filters, and a wide range of hygienic products.


Acute rib fracture caused by preoperative positioning for direct lateral interbody fusion: A case report.
Degenerative spondylolisthesis is defined as forward slippage of a vertebra with respect to the underlying vertebra and is associated with the induction of lumbar canal stenosis. The use of anterior column support for degenerative lumbar conditions has been well documented. Direct lateral interbody fusion (DLIF) gains access via a lateral approach through the retroperitoneal fat and psoas muscle. It avoids many of the access-related complications yet comes with its own risks and limitations. The location of the iliac wing precludes exposure of the L5-S1 disc space and may make L4-5 surgery difficult. Therefore, accurate preoperative patient positioning is essential. A 71-year-old female with a body mass index (BMI) of 39.2 kg/m (height 155.9 cm, weight 79.5 kg) presented with lumbar pain radiating to the left lower limb. She complained of neurologic claudication with more than 100 m ambulation. Plain standing view on spine radiography revealed L4-5 spondylolisthesis and disc-space narrowing. Magnetic resonance imaging (MRI) revealed severe L4-5 bilateral foraminal stenosis. After the first surgery, simple rib cage radiography was performed to examine the source of her right-sided flank pain and it revealed acute fracture of the right ninth and tenth ribs. The patient was laterally positioned on the table in an extreme bending position. The intervertebral cage was inserted in the L4-5 disc space and disc height was restored. With respect to the rib fracture, treatment was conservative. The patient's radiating pain was immediately relieved and her lower back pain disappeared at 3 months after surgery. The patient reported right-sided flank pain after the first surgery. Simple rib cage radiography was performed and revealed fracture of the right ninth and tenth ribs. Follow-up assessments conducted 2 months later revealed complete bony union. DLIF avoids many access-related complications. However, it is associated with other intraoperative complications, including injury to the lumbar nerve root and plexus. In addition, there are preoperative complications associated with improper patient placement on the table. In this case, the patient's obesity and strict positional requirements resulted in rib fracture. We suggest that surgeons consider this complication and exercise care in preoperative positioning.


Sustained outgrowth of autotumor-reactive T lymphocytes from human ovarian carcinomas in the presence of tumor necrosis factor alpha and interleukin 2.
Tumor-infiltrating lymphocytes (TIL) freshly isolated from human ovarian carcinomas were phenotyped (up to 75% CD3+ HLA-DR+ cells) and cultured in the presence of recombinant interleukin 2 and tumor necrosis factor alpha. In short-term cultures, an initial outgrowth of CD3+ CD8+ T lymphocytes resulted in the enrichment of autotumor cytotoxicity under these culture conditions. The early peak of autotumor cytotoxicity was accompanied by interleukin 1 beta and interferon gamma production. The RNA message for interferon gamma was detected by in situ hybridization in TIL induced with interleukin 2 and tumor necrosis factor alpha but not in freshly isolated TIL. A combination of interleukin 2 and tumor necrosis factor alpha was also advantageous for selective outgrowth of CD3+ CD8+ T lymphocytes with autotumor reactivity in long-term cultures of ovarian TIL. At days 30-40 of growth, total lytic units of autotumor cytotoxicity per culture increased from a mean of 59 to 2155, and the percentage of CD3+ CD8+ T lymphocytes rose to 98% in some of the cultures. Thus, the combination of interleukin 2 and tumor necrosis factor alpha provided conditions favorable for sustained growth of autotumor-reactive CD3+ CD8+ TIL in vitro.


Nonneoplastic pineal cysts: a clinicopathologic study of twenty-one cases.
Twenty-one cases of nonneoplastic pineal cyst are presented. The patients were 13 women and 8 men, with a median age of 33 years. Sixteen patients were symptomatic. Symptomatic cysts had an average size of 16.5 mm. In most cases, symptoms and signs were related to increased intracranial pressure, cerebrospinal fluid obstruction, neuroophthalmologic dysfunction, brainstem and cerebellar compression, and mental status changes. Uncommon clinical presentations in three cases were related to increased cyst size caused by hemorrhage, sudden death, and postural syncope and loss of consciousness. Imaging studies showed a uniform hypodense or hypointense, nonenhancing pineal mass with occasional peripheral calcification and associated with hydrocephalus, aqueductal compression, tectal deformity, and hemorrhage within the cavity, in decreasing order of frequency. Fourteen patients underwent open cyst resection. Histologically, the intact lesions show a unilocular or multilocular cavity, surrounded by a wall comprised of variable amounts of glial tissue, remnants of pineal gland, and an external fibrous capsule. Follow-up information showed 12 patients alive and well without recurrence between 26 and 144 postoperative months. One patient who underwent stereotactic drainage had a recurrence. One symptomatic patient who did not have surgery died suddenly of causes related to the cyst. The present study supports the role of surgical excision for the treatment of symptomatic pineal cysts to obtain adequate tissue for diagnosis and relief of symptoms. The use of histochemical and immunohistochemical studies may prove useful in the distinction of these lesions with astrocytomas and cystic pineal parenchymal tumors.


Acute cholecystitis is an indication for laparoscopic cholecystectomy: a prospective study.
Acute cholecystitis has been considered as a relative or absolute contraindication to laparoscopic cholecystectomy. The purpose of this study is to present our experience of laparoscopic cholecystectomy as a safe and effective treatment of acute cholecystitis. Laparoscopic cholecystectomy was offered to 34 consecutive patients with acute calculous cholecystitis, diagnosed according to strict clinical and ultrasonographic criteria. We used only three trocars. The gallbladder was routinely aspirated and sharp graspers were used. We adopted the fundus-first method of dissection when safe identification of the Calot's triangle was difficult. The cystic duct was ligated whenever necessary. The procedure was completed in 31 patients. The mean length of the laparoscopic procedure was 43 minutes, their mean hospital stay was 2.8 days. For the open group the mean length of the operative procedure was 66 minutes, while the mean hospital stay was 5.3 days. The overall morbidity rate was low. The benefits of laparoscopic cholecystectomy can be safely extended to patients with acute cholecystitis. The operation must be done early in the course of the disease. The surgeon should have adequate laparoscopic experience and maintain a low threshold for conversion to open exploration. Modifications in technique should be adopted to achieve a successful outcome.


Bradycardia-induced polymorphic ventricular tachycardia after radiofrequency catheter modification of atrioventricular junction.
We report the case of a 59-year-old man with a dilated nonischemic cardiomyopathy who had chronic rapid atrial fibrillation despite several therapies. Radiofrequency modification of the atrioventricular (AV) junction slowed the mean ventricular rate from 120 beats per minute (bpm) to 60 bpm. Five hours after the procedure and during the following 1 week, despite ventricular pacing at 90 bpm, the patient developed nonsustained or sustained polymorphic ventricular tachycardias. Finally, pacing at 90 bpm was successfully used in this patient. In conclusion, patients who have undergone modification of AV conduction may be at high risk of life-threatening ventricular arrhythmias in the first week following the procedure.


Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa.
Using data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH). We included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10-19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10-13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models. Overall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10-13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10-13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10-13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10-13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42). Retention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10-13 vs. less than 10 years.


Activation of NLRP3 signaling contributes to cadmium-induced bone defects, associated with autophagic flux obstruction.
Cadmium (Cd) is a widespread environmental and industrial pollutant to cause various bone metabolic diseases. Our former study reported that Cd promoted adipogenesis and inhibited osteogenic differentiation of primary bone marrow-derived mesenchymal stem cells (BMSCs) by NF-κB inflammation signaling and oxidative stress, and Cd-induced osteoporosis of long bone and compromised repair of cranial bone defect in vivo. However, the underlying mechanisms of Cd-induced bone damage remain elusive. In this study, we used Sprague Dawley (SD) rat and NLRP3-knockout mouse models to elucidate the exact effects and molecular mechanisms of Cd-induced bone damage and aging. Herein we found that the exposure of Cd preferentially targeted a few specific tissues such as bone and kidney. Cd triggered NLRP3 inflammasome pathways and the accumulation of autophagosomes of primary BMSCs, and also Cd stimulated the differentiation and bone resorption function of primary osteoclasts. Moreover, Cd not only activated ROS/NLRP3/caspase-1/p20/IL-1β pathways, but also influenced Keap1/Nrf2/ARE signaling. The data revealed that autophagy dysfunction and NLRP3 pathways synergistically mediated the impairments of Cd in bone tissues. Loss of NLRP3 function partially alleviated Cd-induced osteoporosis and craniofacial bone defect in the NLRP3-knockout mouse model. Furthermore, we characterized the protective effects and potential therapeutic targets of the combined treatment of anti-aging agents (rapamycin+melatonin+NLRP3 selective inhibitor MCC950) on Cd-induced bone damage and inflammatory aging. These results illuminate that ROS/NLRP3 pathways and autophagic flux obstruction are involved in the Cd-induced toxic actions of bone tissues. Collectively, our study unveils some therapeutic targets and the regulatory mechanism to prevent Cd-caused bone rarefaction. The findings improve the mechanistic understanding of environmental Cd exposure-caused bone metabolism disorders and tissue damage.


Anatomic Double Bundle Posterior Cruciate Ligament Reconstruction Using an Internal Splint.
Techniques for reconstruction of posterior cruciate ligament (PCL) tears are rapidly evolving. One problem with current techniques is that laxity may develop early in the postoperative period, leading to relapsed posterior translation of the tibia. Therefore, maintaining tibial reduction during graft incorporation is a target for improvement. We describe using an internal splint to optimize the 4-tunnel, double-bundle allograft PCL reconstruction.


Analysis of the interaction between segmental relaxation patterns and global diastolic function by strain echocardiography.
Strain echocardiography can depict segmental mechanical activity with high temporal and spatial accuracy, and may allow assessment of segmental relaxation not possible with conventional echocardiography. Conventional and strain echocardiography were performed in healthy volunteers (young [group 1] and old [group 2]) and patients with normal 2-dimensional and stress echocardiography, with either normal global diastolic function (group 3a) or grade I or II global diastolic dysfunction (DD) (group 3b). Standard echocardiography criteria were used to define global DD. Early to late diastolic strain rate ratio less than 1.1 was defined as altered segmental relaxation. All participants had normal wall motion and ejection fraction. Participants of group 1 had normal segmental and global diastolic function. Participants of groups 2 and 3a demonstrated a wide range of altered segmental relaxation in the absence of global DD. All patients of group 3b had 12 or more segments with altered relaxation and global DD. Age and hypertension were associated with a larger number of altered segments, a lower mean early to late diastolic strain rate ratio, and global DD. A wide range of altered segmental relaxation can exist in the absence of global DD. Age and hypertension are associated with altered segmental relaxation and global DD. Assessment of segmental relaxation may be beneficial in the elderly and patients with hypertension.


Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein induce protective cell-mediated immunity in murine pre-B cell leukemia.
Two vaccines against an intracellularly expressed B cell idiotype were assessed for their ability to induce protective immunity in mice against challenge with a pre-B cell leukemia. One vaccine was based on a plasmid expression vector and the other was a recombinant vaccinia virus; both vaccines expressed a polypeptide derived from the complementarity-determining regions (CDR(2)-CDR(3)) of the leukemic clone-specific immunoglobulin heavy chain (IgH), as a fusion product with mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF). Mice inoculated with either vaccine showed significantly higher survival rates than controls after challenge with leukemia cells. However, protection from tumor challenge was optimal when the DNA vaccine was used for priming, followed by a booster immunization with the vaccinia virus recombinant. This vaccination protocol induced resistance not only to the first tumor challenge given shortly afterwards, but also to a second challenge given months later. Both CD4(+) and CD8(+) T cells contributed to protection in vaccinated mice. These data suggest that such a vaccine regimen might reduce the incidence of recurrence in patients with minimal residual disease after conventional therapy.


Discovery of 3,3'-pyrrolidinyl-spirooxindoles as cardioprotectant prohibitin ligands.
The scaffold proteins prohibitins-1 and 2 (PHB1/2) play many important roles in coordinating many cell signaling pathways and represent emerging targets in cardiology and oncology. We previously reported that a family of natural products derivatives, flavaglines, binds to PHB1/2 to exert cardioprotectant and anti-cancer effects. However, flavaglines also target the initiation factor of translation eIF4A, which doesn't contribute to cardioprotection and may even induce some adverse effects. Herein, we report the development of a convenient and robust synthesis of the new PHB2 ligand 2'-phenylpyrrolidinyl-spirooxindole, and its analogues. We discovered that these compounds displays cardioprotective effect against doxorubicin mediated cardiotoxicity and uncovered the structural requirement for this activity. We identified in particular some analogues that are more cardioprotectant than flavaglines. Pull-down experiments demonstrated that these compounds bind not only to PHB2 but also PHB1. These novel PHB ligands may provide the basis for the development of new drugs candidates to protect the heart against the adverse effects of anticancer treatments.


Differential scanning calorimetry of dipalmitoyl phosphatidylcholine analogues and of their interaction products with basic polypeptides.
The thermotropic behaviour of dipalmitoyl phosphatidylcholine analogues with a varying number (n) of CH2 groups between the phosphate and the quaternary ammonium has been investigated. The temperature (Tm) and the enthalpy (deltaH) of the phase transition are non-monotonous functions of the number of CH2 groups. Tm oscillates between 40 and 45 degrees C and deltaH between 7 and 13 kcal/mol for a variation of n between 2 and 11. It is concluded that the hydrocarbon chains in the head groups do not penetrate the hydrocarbon region and do not contribute directly to the melting of the acyl chains. It is suggested that their length may affect the critical balance between the attractive and the repulsive forces within the bidimensional lattice of the head groups. Copolypeptides of lysine with phenylalanine do not appreciably affect the Tm but have a pronounced effect on deltaH of the lipid phase transition, which depends strongly on the ratio of the two amino acids in the polypeptide. The effect of copolypeptide of any defined composition on deltaH is also a non-monotonous function of the number of CH2 groups in the phosphatidylcholine head group, but it does not parallel completely the oscilations in the Tm and deltaH of the pure lipids.


Deficiency of T-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses.
T-regulatory lymphocyte (Treg) adoptive transfer prevented angiotensin (Ang) II-induced hypertension and microvascular injury. Scurfy mice are deficient in Treg because of a mutation in the transcription factor forkhead box P3 (Foxp3) gene. Enhanced Ang II effects in the absence of Treg would unambiguously demonstrate their vascular protective role. We hypothesized that adoptive transfer of Scurfy vs. wild-type T cells will exacerbate Ang II-induced microvascular damage in T and B-cell-deficient recombination-activating gene 1 (Rag1) knockout mice. Rag1 knockout mice were injected with vehicle, 10(7) T cells from wild-type or Scurfy mice or 10 (6)wild-type Treg alone or in combination with Scurfy T cells, and then infused or not with Ang II (490 ng/kg per min, subcutaneous) for 14 days. Ang II increased SBP in all the groups, but DBP only in wild-type and Scurfy T-cell groups. Ang II-induced endothelial dysfunction and oxidative stress in perivascular adipose tissue (PVAT) of mesenteric arteries of the wild-type T-cell group, whereas these were exaggerated in the Scurfy T-cell group. Ang II enhanced microvascular remodeling and stiffness in vehicle and Scurfy T-cell groups. Ang II increased monocyte chemotactic protein-1 expression in the vascular wall and PVAT, monocyte/macrophage infiltration and proinflammatory polarization in PVAT and the renal cortex, and T-cell infiltration in the renal cortex only in the Scurfy T-cell group. Treg coinjection in the vehicle and Scurfy T-cell groups prevented or reduced the effects of Ang II. FOXP3+ Treg deficiency exaggerates Ang II-induced microvascular injury by modulating innate and adaptive immune responses.


Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).
Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.


Assessment of risk factors associated with development of oronasal fistula as a late complication after carbon-ion radiotherapy for head and neck cancer.
Oronasal fistulae (ONF) are one of the rare but serious complications of conventional photon radiotherapy. This study aimed to identify the risk factors for the development of ONF after carbon-ion radiotherapy (C-ion RT). The data of 62 cases of sinonasal and oral cavity cancers treated with C-ion RT and followed-up in excess of 5 years were retrospectively reviewed. The correlation between the clinical and dosimetric parameters and the development of ONF was analysed. A total of 80.6% cases had sinonasal malignancies, and most tumours had advanced T stages (96.8%). Maxillary invasion was observed in 16 cases (25.8%), and malignant melanoma was the most common histology (46.8 %). All the cases received a dose of between 57.6 Gy (RBE) and 64 Gy (RBE) in 16 fractions over 4 weeks. At a median follow up of 88.8 months, 23 cases (37.1%) developed small localised ONF; however, none were of grade III severity. On separate multivariate analyses of clinical parameters in the entire cohort and in cases without maxillary invasion, the number of teeth irradiated with more than 50 Gy (RBE) was found to be the common significant independent risk factor for development of ONF. The number of teeth irradiated with more than 50 Gy (RBE) is a significant independent risk factor for the development of ONF, which is a late complication of C-ion RT delivered in 16 fractions.


Electrolyte composition of the amniotic fluid in Bartter syndrome.
In three patients with neonatal Bartter syndrome associated with polyhydramnios, analysis of the amniotic fluid showed normal sodium, normal-to-low potassium, but high chloride concentrations. This finding clearly suggests a renal chloride reabsorption defect as the primary cause of the neonatal form of Bartter syndrome. It is suggested that whenever polyhydramnios occurs, the electrolyte composition of the amniotic fluid should first be analysed in order to establish the diagnosis of Bartter syndrome.


All G protein βγ complexes are capable of translocation on receptor activation.
Heterotrimeric G proteins transduce signals sensed by transmembrane G protein coupled receptors (GPCRs). A subfamily of G protein βγ subunit types has been shown to selectively translocate from the plasma membrane to internal membranes on receptor activation. Using 4D imaging we show here that Gβγ translocation is not restricted to some subunit types but rather all 12 members of the family of mammalian γ subunits are capable of supporting βγ translocation. Translocation kinetics varies widely depending on the specific γ subunit type, with t(1/2) ranging from 10s to many minutes. Using fluorescence complementation, we show that the β and γ subunits translocate as βγ dimers with kinetics determined by the γ subunit type. The expression patterns of endogenous γ subunit types in HeLa cells, hippocampal neurons and cardiomyocytes are distinctly different. Consistent with these differences, the βγ translocation rates vary widely. βγ translocation rates exhibit the same γ subunit dependent trends regardless of the specific receptor type or cell type showing that the translocation rates are intrinsic to the γ subunit types. βγ complexes with widely different rates of translocation had differential effects on muscarinic stimulation of GIRK channel activity. These results show that G protein βγ translocation is a general response to activation of GPCRs and may play a role in regulating signaling activity.


Hormones and the neuromuscular control of courtship in the golden-collared manakin (Manacus vitellinus).
Many animals engage in spectacular courtship displays, likely recruiting specialized neural, hormonal and muscular systems to facilitate these performances. Male golden-collared manakins (Manacus vitellinus) of Panamanian rainforests perform physically elaborate courtship displays that include novel forms of visual and acoustic signaling. We study the behavioral neuroendocrinology of this male's courtship, combining field behavioral observations with anatomical, biochemical and molecular laboratory-based studies. Seasonally, male courtship is activated by testosterone with little correspondence between testosterone levels and display intensity. Females prefer males whose displays are exceptionally frequent, fast and accurate. The activation of androgen receptors (AR) is crucial for optimal display performance, with AR expressed at elevated levels in several neuromuscular tissues. Apparently, courtship enlists an elaborate androgen-dependent network that includes spinal motoneurons, skeletal muscles and somatosensory systems. This work highlights the value of studying non-traditional species to illuminate physiological adaptations and, hopefully, stimulates future research on other species with complex behaviors.


The effect of wettability on drop attachment to glass rods.
The coalescence of droplets in fibrous filters depends on many parameters such as wettability, filter depth, flow velocity, and filter materials. The objective of this work is to determine the effect of the wettability on the coalescence mechanism. Experimental results from tests on coated glass rods are presented. Three different silanes are deposited on the glass rod surfaces to change the surface wettability. Flow of water-in-oil emulsion past the glass rods is observed. When the rod surface is wetting the dispersed phase coats the rod. When the surface is nonwetting the drops do not stick easily to the surface and do not coat it but slide around to the downstream side, where they are dragged off the rod. Such behavior is important in understanding the performance of coalescing filter media.


Borrelia burgdorferi is strong inducer of IFN-γ production by human primary NK cells.
Natural Killer (NK) cells belong to the innate lymphoid lineage and are highly present in the human skin. NK cells can produce a range of pro-inflammatory mediators, including cytokines and chemokines. The role of NK(-T) cells in the immune response towards Borrelia burgdorferi infection was studied. The production of interleukin (IL)-6, IL-1β and interferon-gamma (IFN-γ) by human primary peripheral blood mononuclear cells (PBMCs) exposed to B. burgdorferi was assessed. Interestingly, CD56+ (NK + NK-T) cells were the only cells within the PBMC-fraction that produced IFN-γ during the first 24 h of stimulation. Within the NK(-T) cell fraction, NK cells seemed to be responsible for the IFN-γ production. Since it was previously demonstrated that both TLR2 and NOD2 receptors are involved in the recognition of B. burgdorferi, the expression of both TLR2 and NOD2 mRNA on NK cells was determined. In contrast to TLR2, NOD2 mRNA was upregulated on CD56+ (NK + NK-T) cells after Borrelia exposure. Finally, to unravel the mechanisms underlying erythema migrans (EM) development, crosstalk between CD56+ (NK + NK-T) cells and keratinocytes was investigated. CD56+ (NK + NK-T) cells activated by B. burgdorferi produced soluble mediators strongly inducing the expression of antimicrobial peptides, such as β-defensin-2 and psoriasin in human keratinocytes. In conclusion, CD56+ (NK + NK-T) cells produced IFN-γ shortly after exposure to B. burgdorferi and released soluble mediators that were able to activate keratinocytes. These observations underscore the important role of CD56+ (NK + NK-T) cells during early host defence when Borrelia burgdorferi enters the human skin during a tick bite.


Catalysis with two-dimensional materials and their heterostructures.
Graphene and other 2D atomic crystals are of considerable interest in catalysis because of their unique structural and electronic properties. Over the past decade, the materials have been used in a variety of reactions, including the oxygen reduction reaction, water splitting and CO2 activation, and have been shown to exhibit a range of catalytic mechanisms. Here, we review recent advances in the use of graphene and other 2D materials in catalytic applications, focusing in particular on the catalytic activity of heterogeneous systems such as van der Waals heterostructures (stacks of several 2D crystals). We discuss the advantages of these materials for catalysis and the different routes available to tune their electronic states and active sites. We also explore the future opportunities of these catalytic materials and the challenges they face in terms of both fundamental understanding and the development of industrial applications.


A validated pediatric disease risk index for allogeneic hematopoietic cell transplantation.
A disease risk index (DRI) that was developed for adults with hematologic malignancy who were undergoing hematopoietic cell transplantation is also being used to stratify children and adolescents by disease risk. Therefore, to develop and validate a DRI that can be used to stratify those with AML and ALL by their disease risk, we analyzed 2569 patients aged <18 years with acute myeloid (AML; n = 1224) or lymphoblastic (ALL; n = 1345) leukemia who underwent hematopoietic cell transplantation. Training and validation subsets for each disease were generated randomly with 1:1 assignment to the subsets, and separate prognostic models were derived for each disease. For AML, 4 risk groups were identified based on age, cytogenetic risk, and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2, 3, 5), high (7, 8), and very high (>8) risk groups was 78%, 53%, 40%, and 25%, respectively (P < .0001). For ALL, 3 risk groups were identified based on age and disease status, including minimal residual disease status at transplantation. The 5-year leukemia-free survival for low (0 points), intermediate (2-4), and high (≥5) risk groups was 68%, 51%, and 33%, respectively (P < .0001). We confirmed that the risk groups could be applied to overall survival, with 5-year survival ranging from 80% to 33% and 73% to 42% for AML and ALL, respectively (P < .0001). This validated pediatric DRI, which includes age and residual disease status, can be used to facilitate prognostication and stratification of children with AML and ALL for allogeneic transplantation.


Evaluation of a Product-Centered Learning Behaviors for Adolescent and Adult Learners Using a Validated Learning Behavior Questionnaire: A Mixed-Method Analytical Cross-Sectional Study.
A learner transitions from being a primary learner to an adolescent learner and further to an adult learner in his/her academic life. The learners exhibit specific learning behaviors at all stages of learning, the mapping of which is required for optimization of learning. To assess the product-centered learning behaviors in adolescent and adult learners using a validated learning behavior questionnaire. To develop a self-monitoring checklist and a Set, Train Your Mind, Apply, and Reinforce (STAR) matrix from the learning behavior questionnaire. It was a mixed-method analytical cross-sectional study. A total of 944 learners participated in the study, out of which 456 were adolescent learners (11-16 years) from an English-medium school (Central Board of Secondary Education (CBSE)) and 488 were adult learners (18-23 years) from a health professional institute. The quantitative component of the study was the validated learning behavior questionnaire, in which the study participants had to rate listed items on a scale of 0, 1, and 2. The qualitative component of the study was the focus group discussions (FGDs), which were conducted each for group of adolescent and adult learners. All the responses were tabulated and statistically analyzed using STATA-14 software. The mean scores of product-centered learning behaviors was significantly higher in adult learners as compared to adolescent learners. The findings of the qualitative component evaluated were in tune with the findings of the analysis of the learning behavior questionnaire. The self-monitoring checklist and STAR matrix were generated from the validated learning behavior questionnaire. The evolved self-monitoring checklist and STAR matrix may aid in the assessment of learning behaviors and facilitate the inculcation of learning behaviors amongst adolescent and adult learners.


A short-term NaCl exposure increases the Na(+) conductance of outward-rectified cation currents in the pith cells of sweet pepper.
The regulatory role of pith cells in the stem in Na(+) recirculation in sweet pepper was investigated by evaluating the transport characteristics of the plasma membrane of this cell type and comparison with those of root cells. Ion conductivity and Na(+) permeability of the plasma membranes of protoplasts of both cell types were studied with the patch-clamp technique in the whole-cell configuration, before and after addition of NaCl to the bath medium. Protoplasts of both pith and root cells showed outward rectifying currents with a reversal potential (V(r)) near to the equilibrium potential of K(+) (EK). Addition of NaCl to the bath medium caused a stronger shift of the reversal potential, V(r), in pith protoplasts than in root protoplasts, indicating that the outward rectified currents are permeable to Na(+), especially in the pith cells. After plant exposure to exogenous NaCl via the nutrient solution for 1 week, V(r) in the root cells was closer to EK than in the control plants and hardly shifted upon addition of Na(+). This indicated that the net permeability of the OR channel complement in the plasma membrane to Na(+) was lower following exposure to Na(+). V(r) in the pith protoplasts, on the other hand, shifted significantly more than in the control plants, suggesting an increase of the permeability to Na(+). Moreover, the Na(+) channel blocker amiloride blocked the currents in this cell type. It is concluded that pith cells have appropriate features of outward rectified currents to enable Na(+) accumulation or release when NaCl is present in or removed from the nutrient medium. Probably, exogenous NaCl even induced expression and formation of Na(+)-permeable channels in pith cells.


Insight in schizophrenia-course and predictors during the acute treatment phase of patients suffering from a schizophrenia spectrum disorder.
To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight. Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale ("lack of insight and judgement"). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients. Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p<0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p=0.0004), less suicidality (p=0.0218), suffering from multiple illness-episodes (p<0.0001) and worse adherence (p=0.0012) at admission were identified to be significant predictors of poor insight at discharge. The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.


Phenolic Compounds and Their Fates In Tropical Lepidopteran Larvae: Modifications In Alkaline Conditions.
Lepidopteran larvae encounter a variety of phenolic compounds while consuming their host plants. Some phenolics may oxidize under alkaline conditions prevailing in the larval guts, and the oxidation products may cause oxidative stress to the larvae. In this study, we aimed to find new ways to predict how phenolic compounds may be modified in the guts of herbivorous larvae. To do so, we studied the ease of oxidation of phenolic compounds from 12 tropical tree species. The leaf extracts were incubated in vitro in alkaline conditions, and the loss of total phenolics during incubation was used to estimate the oxidizability of extracts. The phenolic profiles of the leaf extracts before and after incubation were compared, revealing that some phenolic compounds were depleted during incubation. The leaves of the 12 tree species were each fed to 12 species of lepidopteran larvae that naturally feed on these trees. The phenolic profiles of larval frass were compared to those of in vitro incubated leaf extracts. These comparisons showed that the phenolic profiles of alkali-treated samples and frass samples were similar in many cases. This suggested that certain phenolics, such as ellagitannins, proanthocyanidins, and galloylquinic acid derivatives were modified by the alkaline pH of the larval gut. In other cases, the chromatographic profiles of frass and in vitro incubated leaf extracts were not similar, and new modifications of phenolics were detected in the frass. We conclude that the actual fates of phenolics in vivo are often more complicated than can be predicted by a simple in vitro method.


Diabetes, Aging, and Insulin's Reponic Features: Review.
The aging process and the concomitant physiological changes that come with increasing age have been a focus of researchers and the general population for centuries. The pursuit of knowledge and understanding of the aging process was famously articulated by Aristotle, stating, "education is the best provision for old age." This remains true today in our quest to understand the physiological underpinnings of aging and the incessant attempt to slow or reverse many of the processes. The need to understand normal aging physiology is important to guide future targeted interventions to promote autonomy and prevent impairment of functioning. The risk of frailty, "vulnerability to stressors" and impaired or decreased functioning of a multitude of body systems is a major public health consideration for adults 65 years or older. While there has been a plethora of research on the aging effects of different systems throughout the body, the following literature review will focus on our recent understanding of the components of nutrient handling, specifically the endocrine system in older adults. By understanding the normal physiological changes that occur in response to nutrients, future interventions can be targeted to promote an extension of optimal functioning throughout the lifespan.


Cigarette smoking at time of in vitro fertilization cycle initiation has negative effect on in vitro fertilization-embryo transfer success rate.
To assess cigarette smoking of female patients prior to starting in vitro fertilization cycle and possible affect on subsequent in vitro fertilization-embryo transfer outcome. Retrospective study involving 340 consecutive patient questionnaires filled out at time of in vitro fertilization program entry. Only cycles resulting in embryo transfer after transvaginal ultrasound directed ovum retrieval (n = 253) were considered. The three patient pregnancy outcomes of not pregnant, spontaneous abortion, and live birth, were cross-referenced with smoking and nonsmoking patients. No significant difference found in overall pregnancy rate per embryo transfer for smokers (35%) vs nonsmokers (31%). However, the abortion rate was significantly higher for the smokers (73%) vs nonsmokers (24%) with a P value < 0.001. Results suggest preentry in vitro fertilization cycle cigarette smoking has adverse affect on potential pregnancy outcome by increasing spontaneous abortion. Preconception health consultation concerning adverse cigarette smoking effects should be implemented prior to program entry.


Unique and outstanding quantum dots (QD)/tunicate cellulose nanofibrils (TCNF) nanohybrid platform material for use as 1D ink and 2D film.
Quantum dots (QD)/polymer materials have wide applications in biological imaging, clinical diagnostics, anti-counterfeiting materials, light-emitting devices and solar cells. The development of QD/cellulose nanofibrils (CNF) hybrids with a more perfect structure and excellent properties is important for improving known applications. A unique tunicate CNF (TCNF) was homogeneously blended with outstanding CdSe/CdS core/shell QD to prepare a novel QD/TCNF hybrid. The QD were monodispersed on a single TCNF fibril surface as an evenly distributed monolayer with an extremely high packing density and no visible aggregation. The prepared hybrid is an excellent platform nanomaterial which was demonstrated by its good writing fidelity when applied as a 1D ink and by its good processability in the preparation of 2D films with acceptable transparency and flexibility. This one-step direct blending approach provides a facile shortcut to effectively fabricate cellulose-based high-performance functional QD nanomaterials at the single-fibril level.


Resveratrol suppresses IL-6-induced ICAM-1 gene expression in endothelial cells: effects on the inhibition of STAT3 phosphorylation.
Resveratrol, a polyphenolic phytoaxelin present in red wine, has been suggested to protect against atherosclerosis and cardiovascular disease because of its antioxidant effects. Intercellular adhesion molecule (ICAM-1), induced by cytokines, has been hypothesized to play a role in the early events during atherosclerosis. In this study we tested the effects of resveratrol upon both IL-6-induced ICAM-1 gene expression and its underlying signaling pathways in endothelial cells (ECs). Resveratrol was found to inhibit both TNFalpha- and IL-6-induced ICAM-1 gene expression at the promoter, transcriptional and protein levels. Resveratrol also abrogates the tyr705 phosphorylation of STAT3 in IL-6-treated ECs, in a dose- and time-dependent manner. Although quercetin had similar effects, resveratrol showed higher inhibitory properties following 2-4 h pretreatments. Resveratrol has been shown to induce the activity of endothelial nitric oxide synthase (eNOS) and increase NO production. Consistent with this, the treatment of ECs with a NO donor (SNAP) reduces IL-6-induced STAT3 phosphorylation. Conversely, exposure of ECs to a NOS inhibitor reversed the effects of resveratrol upon IL-6-induced STAT3 phosphorylation. Furthermore, ECs transfected with constitutively active Rac1 (RacV12) showed increases in ICAM-1 promoter activity, intracellular reactive oxygen species (ROS) levels and STAT3 phosphorylation, and these increases were attenuated by resveratrol treatment. In summary, we demonstrate for the first time that resveratrol inhibits IL-6-induced ICAM-1 gene expression, in part, by interfering with Rac-mediated pathways via the attenuation of STAT3 phosphorylation. This study therefore provides important new insights that may contribute to the proposed beneficial effects of resveratrol in endothelial responses to cytokines during inflammation.


Needs and Considerations for Standardization of Kidney Disease Education in Patients with Advanced CKD.
Kidney health advocacy organizations and leaders in the nephrology community have repeatedly emphasized the need to increase home dialysis utilization in the United States. Limited awareness and understanding of options for the management of kidney failure among patients living with advanced CKD is a significant barrier to increasing the selection and use of home dialysis. Studies have shown that providing targeted comprehensive patient education before the onset of kidney failure can improve patients' awareness of kidney disease and substantially increase the informed utilization of home dialysis. Unfortunately, in the absence of validated evidence-based education protocols, outcomes associated with home dialysis use vary widely among published studies, potentially affecting the routine implementation and reporting of these services among patients with advanced CKD. This review provides pragmatic guidance on establishing effective patient-centered education programs to empower patients to make informed decisions about their KRT and, in turn, increase home dialysis use.


Lysine-rich extracellular rings formed by hbeta2 subunits confer the outward rectification of BK channels.
The auxiliary beta subunits of large-conductance Ca(2+)-activated K(+) (BK) channels greatly contribute to the diversity of BK (mSlo1 alpha) channels, which is fundamental to the adequate function in many tissues. Here we describe a functional element of the extracellular segment of hbeta2 auxiliary subunits that acts as the positively charged rings to modify the BK channel conductance. Four consecutive lysines of the hbeta2 extracellular loop, which reside sufficiently close to the extracellular entryway of the pore, constitute three positively charged rings. These rings can decrease the extracellular K(+) concentration and prevent the Charybdotoxin (ChTX) from approaching the extracellular entrance of channels through electrostatic mechanism, leading to the reduction of K(+) inflow or the outward rectification of BK channels. Our results demonstrate that the lysine rings formed by the hbeta2 auxiliary subunits influences the inward current of BK channels, providing a mechanism by which current can be rapidly diminished during cellular repolarization. Furthermore, this study will be helpful to understand the functional diversity of BK channels contributed by different auxiliary beta subunits.


Plant versus local soil inorganic ionic composition: The relationship to biomass smoke.
We examine the relationship between soil and plant inorganic chemical composition as a precursor to biomass smoke aerosol particle (PM2.5) properties in desert landscapes of the Southwestern United States. Past work underscored the importance of plant species and in particular the dependence of smoke PM2.5 water uptake on the water-soluble inorganics important in select plant species (e.g., halophytes) versus absent in other species (e.g., conifers). This study extends this work by looking at a range of soil types and salinity in examining native and invasive species in the Desert Southwest US region. Eighteen plant samples and surrounding soils were taken from four ecosystems in New Mexico, USA. Results here support the conclusion that plant species are the primary controller over the inorganic plant composition that is relevant to biomass smoke and controls its hygroscopicity. The role of soil type is secondary to plant inorganic composition but is found to be important on the ecosystem level in determining what plant species are viable in a given ecosystem. This ultimately affects the smoke properties, including PM2.5 hygroscopicity (water uptake), produced in landscape fires. Knowledge of ecosystem features including plant species distribution and soil salinity may be combined as a first-order predictor of PM2.5 hygroscopicity of the primary smoke emissions. This can be particularly useful when combined with knowledge of burn characteristics such as flame temperature, which also plays a key role in determining PM2.5 water uptake response.


Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer.
Controversy persists as to whether positive operative margins are an independent prognostic factor for resected pancreatic cancer. This study evaluated the impact of the resection margin status on the patterns of recurrence and prognosis after resection for pancreatic cancer. A total of 208 patients with pancreatic cancer who underwent resection with curative intent were studied retrospectively. All patients underwent pancreatectomy (164 pancreatoduodenectomies, 42 distal pancreatectomies, and 2 total pancreatectomies) intended to achieve R0 resection. They were divided into three groups on the basis of the following margin status: R(>1 mm), R(0-1 mm), and R(0 mm). The postoperative survival and recurrence patterns were evaluated in relation to the margin status. Multivariate analyses were performed to evaluate the factors influencing the overall survival. The resection margin was R(>1 mm) in 134 patients (65%), R(0-1 mm) in 40 (19%), and R(0 mm) in 34 patients (16%). The margin status correlated with the rate of local recurrence; 8% in R(>1 mm), 20% in R(0-1 mm), and 50% in R(0 mm) patients. In contrast, the incidence of recurrence at other sites, such as the lymph nodes, peritoneum, liver and other distant organs, were almost identical among the three groups. The median survival time was 26 months in R(>1 mm), 30 months in R(0-1 mm), and 23 months in R(0 mm) patients (P = not significant). The multivariate analyses revealed that lymph node metastases and poor differentiation were correlated with poor survival. In the setting of pancreatectomy, when we evaluated the definitions of R0 resection, the margin status influenced the local recurrence rate but had no impact on the patients' survival.


What lies behind the quality assurance of your materials?
In dentistry, all reputable manufacturers comply with international standards. This is important for quality assurance of dental materials. How such standards came into being and have evolved, however, is perhaps less well-known. This paper covers the necessity and formulation of standards and illustrates their application with reference to materials that may be considered as potential alternatives to dental amalgam. In addition, the uncertainties around such a framework following Brexit are summarised. Robust standards are essential for consumer protection and international trade.


The product of the nuclear gene PET309 is required for translation of mature mRNA and stability or production of intron-containing RNAs derived from the mitochondrial COX1 locus of Saccharomyces cerevisiae.
Expression of the Saccharomyces cerevisiae mitochondrial COX1 locus, which contains several introns and is co-transcribed with the downstream genes AAP1, OLI2 and ENS2, is controlled by at least 18 nuclear-encoded proteins. The PET309 gene, encoding one of these proteins, was cloned, sequenced and shown to contain an open reading frame of 965 codons. Isonuclear PET309+ and delta pet309::URA3 strains carrying mitochondrial genomes that differ in the number of COX1 introns, were generated. Analysis of RNA species from these strains demonstrated an inverse relationship between the number of introns present in the precursor RNA and the amount of COX1 and AAP1/OLI2/ENS2 RNAs accumulated in a pet309 mutant. Hence, PET309 plays a role either in transcription of intron-containing primary transcripts from the COX1-AAP1-OLI2-ENS2 transcription unit or in stabilization of primary transcripts. PET309 is also required in translation of COX1 mRNA. A mitochondrial bypass suppressor of the pet309 deletion mutation was isolated, and shown to consist of a DNA rearrangement at the COX1 locus, such that the 5' untranslated leader region (UTR) of the COB gene was fused to COX1 at nucleotide -174 of its 5' UTR. This result suggests that Pet309p acts through the COX1 5' UTR to activate initiation of translation of the COX1 coding region.


Foiled Aspirations: The Influence of Unauthorized Status on the Educational Expectations of Latino Immigrant Youth.
Latino immigrant adolescents have the highest high school dropout rates of any race-ethnic or nativity group in the United States. One potential reason for high dropout rates among Latino immigrant youth is that many are unauthorized entrants. These unauthorized Latino immigrant youth have few opportunities to attend college, and, as they become aware of barriers to their educational progress and employment, they may lower their educational expectations. Using data from the Latino Adolescent Migration, Health, and Adaptation Project (N=275), we examine the association of unauthorized entry into the U.S. with the educational expectations of Latino immigrant youth. We find that adolescents entering the U.S. without authorization have lower educational expectations than those who enter with authorization. These differences in their expectations persist after controlling for differences in their pre-migration, migration, and post-migration experiences. Policies and programs that reduce barriers to higher education and labor market opportunities can potentially help to foster higher educational expectations among unauthorized immigrant youth and may promote their high school completion.


Effects of acrolein on human platelet aggregation.
Acrolein, a component of tobacco smoke, potentiated platelet aggregation and increased thromboxane A2 (TXA2) formation caused by thrombin and arachidonic acid (AA). Acrolein produced these effects at concentrations in the range 50-5000 microM. Acrolein had no effect on platelet responses to ADP, epinephrine, collagen or the ionophore A23187. Acrolein increased the mobilization of [3H]arachidonic acid from prelabelled platelets in response to thrombin and arachidonic acid. The increased availability of substrate could partly explain the enhanced production of TXA2 and increased aggregation observed in the presence of acrolein. These findings could provide an explanation for the increased incidence of vascular disease in cigarette smokers.


Mobile mechanical signal generator for macrophage polarization.
The importance of mechanical signals in regulating the fate of macrophages is gaining increased attention recently. However, the recently used mechanical signals normally rely on the physical characteristics of matrix with non-specificity and instability or mechanical loading devices with uncontrollability and complexity. Herein, we demonstrate the successful fabrication of self-assembled microrobots (SMRs) based on magnetic nanoparticles as local mechanical signal generators for precise macrophage polarization. Under a rotating magnetic field (RMF), the propulsion of SMRs occurs due to the elastic deformation via magnetic force and hydrodynamics. SMRs perform wireless navigation toward the targeted macrophage in a controllable manner and subsequently rotate around the cell for mechanical signal generation. Macrophages are eventually polarized from M0 to anti-inflammatory related M2 phenotypes by blocking the Piezo1-activating protein-1 (AP-1)-CCL2 signaling pathway. The as-developed microrobot system provides a new platform of mechanical signal loading for macrophage polarization, which holds great potential for precise regulation of cell fate.


Treatment for Helicobacter pylori infection and risk of Parkinson's disease in Denmark.
It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson's disease (PD). We used nationwide Danish registers to investigate this hypothesis. We identified 4484 patients with a first time PD diagnosis between 2001 and 2008 from the Danish National Patient Register (DNPR) and 22, 416 population controls from the Danish Civil Registration System (CRS). Information on drug use was obtained from the National Prescription Registry (NPR). We used logistic regression to compute odds ratios (OR) for the association between treatment for HP and risk of PD. Prescriptions for HP-eradication drugs and proton pump inhibitors (PPI) 5 or more years prior to the diagnosis of PD were associated with a 45% and 23% increase in PD risk, respectively. Hospitalizations and outpatient visits for gastritis and peptic/duodenal ulcers, however, were not associated with PD. Our population-based study suggests that chronic HP infections and/or gastritis contribute to PD or that these are PD-related pathologies that precede motor symptoms.


Asymmetry of Escherichia coli F1-ATPase as a function of the interaction of alpha-beta subunit pairs with the gamma and epsilon subunits.
The asymmetry of Escherichia coli F1-ATPase (ECF1) has been explored in chemical modification experiments involving two mutant enzyme preparations. One mutant contains a cysteine (Cys) at position 149 of the beta subunit, along with conversion of a Val to Ala at residue 198 to suppress the deleterious effect of the Cys for Gly at 149 mutation (mutant beta G149C:V198A). The second mutant has these mutations and also Cys residues at positions 381 of beta and 108 of the epsilon subunit (mutant beta G149C:V198A:E381C/epsilon S108C). On CuCl2 treatment of this second mutant, there is cross-linking of one copy of the beta subunit to gamma via the Cys at 381, a second to the epsilon subunit (between beta Cys381 and epsilon Cys108), while the third beta subunit in the ECF1 complex is mostly free (some cross-linking to delta); thereby distinguishing the three beta subunits as beta gamma, beta epsilon, and beta free, respectively. Both mutants have ATPase activities similar to wild-type enzyme. Under all nucleotide conditions, including with essentially nucleotide-free enzyme, the three different beta subunits were found to react differently with N-ethylmaleimide (NEM) which reacts with Cys149, dicyclohexyl carbodiimide (DCCD) which reacts with Glu192, and 7-chloro-4-nitrobenzofurazan (NbfCl) which reacts with Tyr297. Thus, beta gamma reacted with DCCD but not NEM or NbfCl; beta free was reactive with all three reagents; beta epsilon reacted with NEM, but was poorly reactive to DCCD or NbfCl. There was a strong nucleotide dependence of the reaction of Cys149 in beta epsilon (but not in beta free) with NEM, indicative of the important role that the epsilon subunit plays in functioning of the enzyme.


Diagnosis of Bladder Carcinoma: A Clinician's Perspective.
In 2014, more than 74,000 new cases and 15,000 deaths from bladder cancer were estimated to occur. The most reliable prognostic factors for survival are pathologic stage and histologic grade. Accordingly, a good understanding of the pathologic features of these cancers is essential to guide optimal clinical treatment, which requires a multidisciplinary team of pathologists, urologists, radiation oncologists, and medical oncologists. This review highlights several clinical scenarios in which detailed pathologic evaluation and accurate reporting impact clinical management.


Recombination in phage lambda: one geneticist's historical perspective.
Several features of bacteriophage lambda suit it for the study of genetic recombination. Central among them are those that make it possible to correlate inheritance of DNA with the inheritance of information encoded by DNA through density-label equilibrium centrifugation. Such studies have revealed relationships between DNA replication and recombination, have identified roles for double-strand breaks in the initiation of recombination, and have elucidated the role of the recombination-stimulating sequence, chi.


Levodopa effective parkinsonism associated with aqueductal stenosis: a case report and review of the literature.
A case of aqueductal stenosis (AS) associated with marked parkinsonism is described. A ventriculoperitoneal (V-P) shunt was performed in an 18-year-old female because of hydrocephalus associated with non-neoplastic aqueductal stenosis. The patient developed acute parkinsonism with Parinaud's sign after the shunt revision. She had a marked response to levodopa and the parkinsonism improved. Subsequently, levodopa therapy was gradually discontinued without any manifestation of parkinsonism. The pathophysiology of this type of parkinsonism probably involved presynaptic dopaminergic dysfunction. However, the etiology of this complication has not been confirmed.