Medical Cannabis Use and Pain: An Experience Sampling Study.
Background: Little research has tested associations of pain and MC use after long-term treatment and through methods that have external validity outside experimental settings. The study examined associations of pain, associated painful experiences, and long-term medical cannabis (MC) use in chronic pain (CP) patients using a naturalistic daily diary study that provided novel and externally valid data. Methods: Data were obtained from 78 MC users with CP three times daily over a 10-day period (nobservations = 1,688). Mixed-effects models were used to test the associations between MC use and momentary experiences of pain, affect, and fatigue. Results: Within persons, elevated experiences of pain intensity were associated with greater intention to use MC within the next hour. No evidence was found that the time lapse since last MC use was associated with pain levels, negative affect, or fatigue. Conclusions: The results imply that after long-term use, CP patients intend to use MC in response to pain experiences. Yet, they may not actually achieve the pain relief. More research is needed to examine whether continued MC use despite lack of pain relief is related to relief of other symptoms (e.g., dependence, withdrawal) or positive benefits (e.g., general sense of well-being) or tolerance.


Anthropometric Parameters of HIV-Infected and HIV-Uninfected Mothers and their Premature Infants.
This study aimed to assess the maternal anthropometric parameters of human immunodeficiency virus (HIV)-infected and HIV-uninfected mothers as well as to assess the neonatal anthropometric parameters of premature infants in relation to maternal anthropometric parameters (weight, height and mid-upper-arm circumference), HIV status and anti-retroviral therapy (ART) regimen. Study participants included HIV-infected and HIV-uninfected mothers who gave birth to premature infants. All HIV-infected mothers received ART. The incidence of intra-uterine growth restriction (IUGR) among premature infants was high. Maternal anthropometric parameters, HIV status and ART exposure showed no association with IUGR in this study. Sufficient maternal ART exposure may positively influence head circumference at birth, which might determine the neurodevelopmental outcome of these infants.


A laparoscopic approach to the abdominal aorta for thoracic stent-graft deployment: evaluation in a porcine model.
To develop laparoscopic techniques for aortic stent-graft placement as an alternative to the femoral approach. Endovascular stent-grafts were placed in 8 pigs via a totally laparoscopic retroperitoneal approach. After needle puncture, a guidewire was inserted into the abdominal aorta, followed by an 18-F sheath through which a Talent stent-graft was deployed in the descending thoracic aorta without aortic clamping. All the endovascular tools were inserted into the retroperitoneal area via the ports. After the sheath was withdrawn, hemostasis was achieved by suturing the aortic puncture under aortic cross-clamping. After sacrificing the animals, the thoracic aorta was removed to verify the position and deployment of the stent-grafts. Seven (87.5%) of 8 procedures were successfully completed; the first animal died from hemorrhage due to inadvertent injury to the posterior infrarenal aortic wall. The accurate deployment and position of the stent-grafts were verified visually after sacrifice. Mean (+/- SD) procedural, implantation, and aortic cross-clamping times were 205 +/- 56, 22 +/- 9, and 30 +/- 19 minutes, respectively. Mean blood loss was 120 +/- 56 mL. Thoracic aortic stent-grafting using a laparoscopic approach to the infrarenal aorta is feasible. More studies will be required to define the place of combined endovascular and laparoscopic procedures as an alternative to the femoral surgical approach for stent-graft placement.


[Post-infarct ventricular tachycardia. Electrophysiological aspects, endocardial and epicardial electromapping and surgical therapy].
Seven patients (6 men and 1 woman), aged 45-67 years, with previous myocardial infarction and recurrent sustained ventricular tachycardia (VT), refractory to medical treatment, underwent encircling endocardial ventriculotomy, according to a modified Guiraudon's technique, associated with surgical resection of ventricular aneurysm. Before surgery all patients underwent electrophysiologic study, to evaluate the modalities of onset and interruption of VT; endocardial mapping at multiple sites was carried out in order to define the site of origin of VT and the sequence of endocardial activation: during VT in 5/5 patients the earliest activation occurred in the left ventricle at mid septum (2 cases), in the low (1 case) and high (1 case) septal regions and in the latero-basal region (1 case); the arrhythmias always originated at the border between fibrous and viable tissue. Intraoperative mapping was carried out from 18-29 points of the epicardial surface, both in sinus rhythm (7 cases) and during VT in the 6 patients in whom the arrhythmia was inducible with electrical stimulation. During sinus rhythm fragmented electrical activity of low voltage and prolonged duration was recorded from the epicardial surface of the aneurysm in all cases; during VT the site of earliest activation was localized in the low posterior (3 cases), high lateral (2 cases) and high posterior (1 case) regions of the left ventricle. Intraoperative endocardial mapping during VT confirmed the site of origin of the arrhythmia, as determined by preoperative mapping, in the 3 cases in whom it was performed. In all cases encircling endocardial ventriculotomy around the area of earliest activation or, when the origin of VT was not precisely determined, along the border zone of the aneurysm, was associated with conventional surgical procedures (aneurysmectomy: 6 cases; incision-suture: 1 case; aorto-coronary bypass: 1 case; mitral valve replacement: 1 case). One patient died in the early post-operative course with a low-output syndrome. During a follow-up of 6-35 months, one patient died two months after surgery because of intractable heart failure; the remaining patients are alive and well, with no recurrence of VT; none of them required antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)


Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study.
Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis. A single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α2-plasmin inhibitor (PI), plasmin-α2-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days. A total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively). Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.


High-performance cation electrokinetic concentrator based on a γ-CD/QCS/PVA composite and microchip for evaluating the activity of P-glycoprotein without any interference from serum albumin.
The development of cation electrokinetic concentrators (CECs) has been hindered by the lack of commercial anion-exchange membranes (AEMs). This paper introduces a γ-cyclodextrin-modified quaternized chitosan/polyvinyl alcohol (γ-CD/QCS/PVA) composite as an AEM, which is combined with a microchip to fabricate a CEC. Remarkably, the CEC only concentrates cationic species, thereby overcoming the interference of the highly abundant, negatively charged serum albumin in the blood sample. P-Glycoprotein (P-gp) is recognized as an efflux transporter protein that influences the pharmacokinetics (PK) of various compounds. The CEC was used to evaluate the activity of P-gp by detecting the positively charged rhodamine 123 (Rho123 is a classical substrate of P-gp) with no interference from serum albumin in the serum sample. Using the CEC, the enrichment factor (EF) of Rho123 exceeded 105-fold under DC voltage application. The minimal sample consumption of the CEC (<10 μL) enables reduction of animal sacrifice in animal experiments. Here, the CEC has been applied to evaluate the transport activity of P-gp in in vitro and in vivo experiments by detecting Rho123 in the presence of P-gp inhibitors or agonists. The results are in good agreement with those reported in previous reports. Therefore, the CEC presents a promising application potential, owing to its simple fabrication process, high sensitivity, minimal sample consumption, lack of interference from serum albumin and low cost.


Structural insights into tail-anchored protein binding and membrane insertion by Get3.
Tail-anchored (TA) membrane proteins are involved in a variety of important cellular functions, including membrane fusion, protein translocation, and apoptosis. The ATPase Get3 (Asna1, TRC40) was identified recently as the endoplasmic reticulum targeting factor of TA proteins. Get3 consists of an ATPase and alpha-helical subdomain enriched in methionine and glycine residues. We present structural and biochemical analyses of Get3 alone as well as in complex with a TA protein, ribosome-associated membrane protein 4 (Ramp4). The ATPase domains form an extensive dimer interface that encloses 2 nucleotides in a head-to-head orientation and a zinc ion. Amide proton exchange mass spectrometry shows that the alpha-helical subdomain of Get3 displays considerable flexibility in solution and maps the TA protein-binding site to the alpha-helical subdomain. The non-hydrolyzable ATP analogue AMPPNP-Mg(2+)- and ADP-Mg(2+)-bound crystal structures representing the pre- and posthydrolysis states are both in a closed form. In the absence of a TA protein cargo, ATP hydrolysis does not seem to be possible. Comparison with the ADP.AlF(4)(-)-bound structure representing the transition state (Mateja A, et al. (2009) Nature 461:361-366) indicates how the presence of a TA protein is communicated to the ATP-binding site. In vitro membrane insertion studies show that recombinant Get3 inserts Ramp4 in a nucleotide- and receptor-dependent manner. Although ATP hydrolysis is not required for Ramp4 insertion per se, it seems to be required for efficient insertion. We postulate that ATP hydrolysis is needed to release Get3 from its receptor. Taken together, our results provide mechanistic insights into posttranslational targeting of TA membrane proteins by Get3.


Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment.
More people die annually from cardiovascular diseases than from any other cause. In particular, patients who suffer from myocardial infarction may be affected by ongoing adverse remodeling processes of the heart that may ultimately lead to heart failure. The introduction of stem and progenitor cell-based applications has raised substantial hope for reversing these processes and inducing cardiac regeneration. However, current stem cell therapies using single-cell suspensions have failed to demonstrate long-lasting efficacy due to the overall low retention rate after cell delivery to the myocardium. To overcome this obstacle, the concept of 3D cell culture techniques has been proposed to enhance therapeutic efficacy and cell engraftment based on the simulation of an in vivo-like microenvironment. Of great interest is the use of so-called microtissues or spheroids, which have evolved from their traditional role as in vitro models to their novel role as therapeutic agents. This review will provide an overview of the therapeutic potential of microtissues by addressing primarily cardiovascular regeneration. It will accentuate their advantages compared to other regenerative approaches and summarize the methods for generating clinically applicable microtissues. In addition, this review will illustrate the unique properties of the microenvironment within microtissues that makes them a promising next-generation therapeutic approach.


Quantitative imaging in oncology patients: Part 2, oncologists' opinions and expectations at major U.S. cancer centers.
The purpose of this article is to examine oncologists' opinions and expectations concerning imaging and tumor measurements in patients with cancer. An electronic mail survey was sent to 2,400 medical, gynecologic, and radiation oncologists at 55 U.S. National Cancer Institute-funded cancer centers. The survey contained questions about departmental demographics, opinions regarding imaging for patients with cancer, PET/CT utilization, and utilization of the Response Evaluation Criteria in Solid Tumors (RECIST) system in therapy protocols that use imaging as a therapeutic end point. A total of 492 responses (21%) were received. Sixty percent (294) of respondents were medical oncologists, 9% (45) were gynecologic oncologists, 26% (127) were radiation oncologists, and 5% (25) answered "Other." Ninety-eight percent (431/438) of respondents provide clinical care, and 99% (420/425) have participated in clinical trials. Most respondents (94% [410/438]) expect some or all tumors to be measured at the time of standard initial clinical imaging. Over half (65% [275/426]) think that tumor measurements should be bidimensional. Only 25% (101/400) of respondents' institutions have department rules on the implementation of RECIST measurements. Sixty-eight percent of participants (269/397) think that RECIST is flawed but serviceable. Over half of respondents (56% [221/398]) were not familiar with RECIST 1.1 modifications. Most oncologists at National Cancer Institute-sponsored cancer centers expect tumor measurements to be made in the routine imaging of patients with cancer. Almost two thirds of respondents think that bidimensional measurements of index lesions are satisfactory in routine oncologic imaging. Little consensus exists in the implementation of RECIST measurements for clinical trials at these centers.


Premature ventricular contraction-induced cardiomyopathy in children.
Adults with high premature ventricular contraction burden can develop left ventricular dilation, dysfunction, and strain, consistent with a cardiomyopathy, which is reversible with radiofrequency ablation of the premature ventricular contractions. Evidence in children with similar ectopy burden is limited. We performed a single-centre retrospective review to examine the prevalence of premature ventricular contraction-induced cardiomyopathy, natural history of ventricular ectopy, and progression to ventricular tachycardia in children with frequent premature ventricular contractions. Children aged between 6 months and 18 years, with premature ventricular contractions comprising at least 20% of rhythm on 24-hour Holter monitor, were included in our study. Those with significant structural heart disease, ventricular tachycardia greater than 1% of rhythm at the time of premature ventricular contraction diagnosis, or family history of cardiomyopathy - except tachycardia-induced - were excluded. Cardiomyopathy was defined by echocardiographic assessment. A total of 36 children met the study criteria; seven patients (19.4%, 95% CI 6.2-32.6%) met the criteria for cardiomyopathy, mostly at initial presentation. Ectopy decreased to <10% of beats without intervention in 16.7% (95% CI 4.3-29.1%) of the patients. No patient progressed to having ventricular tachycardia as more than 1% of beats on follow-up Holter. Radiofrequency ablation was performed in three patients without cardiomyopathy. Our study demonstrates a higher prevalence of cardiomyopathy among children with high premature ventricular contraction burden than that previously shown. Ectopy tended to persist throughout follow-up. These trends suggest the need for a multi-centre study on frequent premature ventricular contractions in children. In the interim, regular follow-up with imaging to evaluate for cardiomyopathy is warranted.


Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate kinase: insights into the allosteric regulation.
Nucleoside Monophosphate Kinases (NMPKs) family are key enzymes in nucleotide metabolism. Bacterial UMPKs depart from the main superfamily of NMPKs. Having no eukaryotic counterparts they represent attractive therapeutic targets. They are regulated by GTP and UTP, while showing different mechanisms in Gram(+), Gram(-) and archaeal bacteria. In this work, we have characterized the mycobacterial UMPK (UMPKmt) combining enzymatic and structural investigations with site-directed mutagenesis. UMPKmt exhibits cooperativity toward ATP and an allosteric regulation by GTP and UTP. The crystal structure of the complex of UMPKmt with GTP solved at 2.5 Å, was merely identical to the modelled apo-form, in agreement with SAXS experiments. Only a small stretch of residues was affected upon nucleotide binding, pointing out the role of macromolecular dynamics rather than major structural changes in the allosteric regulation of bacterial UMPKs. We further probe allosteric regulation by site-directed mutagenesis. In particular, a key residue involved in the allosteric regulation of this enzyme was identified.


Cell proliferation enhances entry of Listeria monocytogenes into intestinal epithelial cells by two proliferation-dependent entry pathways.
Bacterial entry into intestinal host cells is the result of a fairly sophisticated manipulation of host cell machinery by the pathogens. To study further the potential cell target of Listeria spp., the in-vitro entry of L. monocytogenes strains into intestinal cells was examined in relation to the metabolism, proliferation and differentiation of the cells by the alamarBlue assay, [3H] thymidine incorporation, and brush border-associated enzyme activities, respectively. The study showed that cell metabolism was not involved in the entry of L. monocytogenes in three cell models (two human and one porcine). On the other hand, entry was closely related to the proliferation process and poorly related to the differentiation state of the cells. The use of L. monocytogenes mutants lacking invasion proteins showed that InlA and InlB acted in synergy to mediate the entry of L. monocytogenes into proliferative cells, whereas InlA alone seemed to be involved in the entry into non-proliferative cells. These two entry pathways could correspond to the two cellular processes used by L. monocytogenes to enter proliferative and non-proliferative cells, as suggested by the use of cytochalasin D, nocodazole, chloroquine and monodansylcadaverine. Taken together, we propose a hypothesis in which the entry of L. monocytogenes is mediated by interaction between randomly distributed E-cadherin on the surface of proliferative cells. In contrast, the entry into non-proliferative cells may involve pp60c-src, a proto-oncogenic tyrosine kinase signal that modifies E-cadherin localisation. In conclusion, these results suggest that L. monocytogenes may preferentially enter crypt cells in vivo by a microfilament-dependent process, whereas the few bacteria that infect villus cells enter by an E-cadherin-internalin interaction that mediates microtubule-dependent endocytosis.


Severe imported malaria in children in France. A national retrospective study from 1996 to 2005.
Malaria is a leading cause of imported febrile illnesses in pediatric travelers, but few studies have addressed severe imported pediatric malaria. We aimed to determine the risk factors and the features of imported pediatric severe malaria. We conducted a retrospective, descriptive study using the French National Reference Center for Imported Malaria database, in children aged 0-15 years who were hospitalized with a falciparum malaria from January 1st 1996 to December 31th 2005. Uncomplicated and severe cases of falciparum malaria were compared to identify risk factors for severe cases. In the hospitals that reported more than five severe cases during the study period, we evaluated severe cases for prognostic factors and assessed the accuracy WHO criteria for predicting severity. Given the rarity of deaths, adverse outcomes were defined as requiring major therapeutic procedures (MTPs)-e.g., sedation, mechanical ventilation, nasal oxygen therapy, blood transfusions, hemodialysis, fluid resuscitation-or pediatric intensive care unit (PICU) admission. Of 4150 pediatric malaria cases included in the study, 3299 were uncomplicated and 851 (20.5%) were severe. Only one death was recorded during this period. Predictors for severe falciparum malaria were: age <2 years (OR = 3.2, 95% CI = 2.5-4.0, p <0.0001) and a travel in the Sahelian region (OR = 1.7, 95% CI = 1.3-2.0, p = 0.0001). Of 422 severe malaria cases, a stay in a Sahelian region, lack of chemoprophylaxis, age <2 years or thrombocytopenia <100 x 10^3/mm^3 predicted adverse outcomes. Except for the hyperparasitemia threshold of 4%, the main WHO 2000 criteria for severe malaria reliably predicted adverse outcomes. In our study, the threshold of parasitemia most predictive of a poor outcome was 8%. In imported pediatric malaria, children younger than 2 years deserve particular attention. The main WHO 2000 criteria for severity are accurate, except for the threshold of hyperparasitemia, which should be revised.


[The development of a method for viral inactivation using thiophosphamide].
Using three-functional alkylating compound thiophosphamide complete inactivation of the influenza and herpesviruses of type 1 and 2 was achieved. The method provides full inactivation of DNA- and RNA-containing viruses and preservation of their immunogenic properties.


Music affects learning of a braille-like task by sighted subjects.
24 consistently right-handed male college students felt sets of four Braille symbols with either the right or the left index finger and identified by touch alone which two of the four symbols in each set were identical. During the task music was played to either the right ear, the left ear, both ears, or neither ear. Significantly fewer errors were made when the music was in the ear contralateral to whichever hand performed the task. The ipsilateral, binaural, and no-music groups did not differ significantly from each other. It is suggested that monaural music to the ear contralateral to the engaged hand led to reduced interhemispheric competition acting on the hemisphere controlling the hand. Such a facilitating effect may be of practical importance in tasks during which one hemisphere received the bulk of the task-related sensory input and/or processes the final order from the brain to the task-related muscles.


Endometrial Biopsy: American College of Nurse-Midwives.
Endometrial biopsy can be used to diagnose endometrial hyperplasia, endometrial cancer, and uterine infections. This cost-effective procedure has minimal side effects, and complications are rare. The purpose of this clinical bulletin is to provide clinicians with guidance about endometrial biopsy including the procedure's advantages and disadvantages, indications and contraindications, and side effects. In addition, step-by-step instructions for performing endometrial biopsy, the equipment required, selection of sampling devices, and care before and after the procedure are discussed.


Application of double low-dose mode in left atrial-pulmonary venous computed tomography angiography.
This study adopted a 256-slice iCT scanner with the double low-dose mode in left atrial-pulmonary venous computed tomography angiography (CTA) and explored its effect on image quality. 120 patients were included and randomly classified into the Observation group and Control group. Patients in the Control group underwent routine left atrial CTA, while patients in the Observation group performed a double low-dose mode. Other scanning parameters were consistent in the two groups. The Full model-based iterative reconstruction (MBIR) technique was applied to fulfill image reconstruction in observation group. Continuous variables, ordered categorical variables were analyzed by statistical test. The CT values of left atrial in the Observation group were significantly higher than those in the Control group. The exposure doses (ED) and iodine intake were lower in the Observation group, as compared to the Control group. The left atrial-pulmonary venous CTA with the 256-slice iCT scanner in a double low-dose mode can reduce the ED of radiation and iodine contrast while providing high quality images. Comparatively, the ED in the Observation group was reduced by 13% compared with the control, and the iodine intake was reduced by approximately 33%.


Purification of the residual entanglement.
Entanglement purification is an indispensable ingredient in extended quantum communication networks and usually determines the efficiency and communication rate of quantum communication protocols. Different from all existing entanglement purification protocols (EPPs) where two or more copies of low quality mixed entangled states are selected from the same ensemble, here we describe a general and optimal EPP for arbitrary initial mixed states from different ensembles. We show that the successful operation of EPP may not obtain a higher fidelity mixed state, while the discarded source pair, which is usually regarded as a failure in existing EPPs, may have residual entanglement and can be reused to increase the yield of entanglement purification. We give the criterions of both the successful purification to obtain a higher fidelity mixed state and the existence of residual entanglement. Moreover, we reveal that entanglement purification procedure causes some entanglement loss. Finally, we provide an optimal approach to reduce the entanglement loss. This approach can also be used to increase the yield of entanglement purification. Our EPP may have potential application in long-distance quantum communications.


Sequence divergence within transposable element families in the Drosophila melanogaster genome.
The availability of the sequenced Drosophila melanogaster genome provides an opportunity to study sequence variation between copies within transposable element families. In this study,we analyzed the 624 copies of 22 transposable element (TE) families (14 LTR retrotransposons, five non-LTR retrotransposons, and three transposons). LTR and non-LTR retrotransposons possessed far fewer divergent elements than the transposons,suggesting that the difference depends on the transposition mechanism. However,there was not a continuous range of divergence of the copies in each class,which were either very similar to the canonical elements,or very divergent from them. This sequence homogeneity among TE family copies matches the theoretical models of the dynamics of these repeated sequences. The sequenced Drosophila genome thus appears to be composed of a mixture of TEs that are still active and of ancient relics that have degenerated and the distribution of which along the chromosomes results from natural selection. This clearly demonstrates that the TEs are highly active within the genome,suggesting that the genetic variability of the Drosophila genome is still being renewed by the action of TEs.


Effect of chronic dietary nitrate and different iodine supply on porcine thyroid function, somatomedin-C-level and growth.
Due to the lately increased oral nitrate intake of humans and animals the influence of 3% KNO3 in the diet on growth and the thyroid hormone and somatomedin-C-concentration in the serum was to be tested in an experiment with growing pigs in case of different iodine supply. The investigations were undertaken in 3 groups with 9 piglets each. The animals were 6 weeks old: 1. nitrate-exposed, 2. pair-fed to group 1 (without nitrate), 3. ad libitum without nitrate. The mean daily weight gains amounted to 242, 274 and 393 g respectively, after a five-week test period. Compared to the ad libitum control group, the T4-, T3-, rT3- and Sm-C-level of nitrate-exposed animals was significantly lower after 5 weeks. There were no statistically relevant differences between nitrate-exposed and pair-fed animals with regard to the T3- and Sm-C-level. After the 5-week test period with an iodine supply covering the requirement the rations of all 3 groups were supplemented with further 0.8 mg iodine/kg. The T4-, T3- and rT3-levels of the animals of group 1 normalized within one week. The Sm-C-levels of the nitrate-exposed and pair-fed group were still decreased. The investigations show that an increased nitrate intake via food and drinking water influences the thyroid hormone metabolism. It should be taken into consideration in the etiology of endemic struma. Furthermore, excessive nitrate intakes influence the Sm-C-concentration and thus growth due to food intake depression.


Preparing hemagglutinating antigen from isolates of infectious bronchitis virus.
The hemagglutinating (HA) activity of 14 strains of infectious bronchitis virus (IBV) was investigated. The optimal conditions for IBV antigen preparation include inoculation of 10- or 11-day-old specific pathogen-free embryonated eggs and incubation for 30 hours at 37 C. Embryos were inoculated via the allantoic cavity with 0.1 ml of a low embryonic passage of the virus (10(7) to 10(8) EID50/ml). Allantoic fluid was harvested and pooled, and a 100-fold concentration of virus particles was achieved by centrifugation for 3 hours at 30,000 x g. Virus pellets were resuspended in Tris-hydrochloride buffer containing 3 units of phospholipase-C (type-1) enzyme/ml and incubated for 2 hours at 37 C. All IBV strains tested demonstrated positive HA activity with chicken red blood cells. The antigen was stored in liquid state or lyophilized at 4 C.


Regulation of Na+-K+-ATPase Leads to Disturbances of Isoproterenol-induced Cardiac Dysfunction via Interference of Ca2+ -dependent Cardiac Metabolism.
Reductions in Na+-K+-ATPase (NKA) activity and expression are often observed in the progress of various reason-induced heart failure (HF). However, NKA α1 mutation or knockdown cannot cause spontaneous heart disease. Whether the abnormal NKAα1 directly contributes to HF pathogenesis remains unknown. Here, we challenge NKA α1 +/- mice with isoproterenol to evaluate the role of NKA α1 haploinsufficiency in isoproterenol (ISO)-induced cardiac dysfunction. Genetic knockdown of NKAα1 accelerated ISO-induced cardiac cell hypertrophy, heart fibrosis, and dysfunction. Further studies revealed decreased Krebs cycle, fatty acid oxidation, and mitochondrial OXPHOS in the hearts of NKA α1 +/- mice challenged with ISO. In ISO-treated conditions, inhibition of NKA elevated cytosolic Na+, further reduced mitochondrial Ca2+ via mNCE, and then finally downregulated cardiac cell energy metabolism. In addition, a supplement of DRm217 alleviated ISO-induced heart dysfunction, mitigated cardiac remodeling, and improved cytosolic Na+ and Ca2+ elevation and mitochondrial Ca2+ depression in the NKAα1+/- mouse model. The findings suggest that targeting NKA and mitochondria Ca2+ could be a promising strategy in the treatment of heart disease.


[Adrenal incidentaloma: case report and synthesis of indication and thresholds of surgery therapy].
With the term of incidental mass, any mass is identified, occasionally discovered with imaging techniques, in the absence of specific symptoms. In 1982, the term "incidentaloma" was introduced to indicate lesions detected on adrenal regions, found unexpectedly. The incidence percentages vary from 0.6%-3% in CT followed by other indications , to 10% and 25% in all patients who underwent an ultrasound, CT or MRI. An appropriate diagnostic protocol is mandatory to identify and to choose the proper treatment for the functioning lesions, as well as the malignant or potentially malignant lesions (1, 2). Incidentalomas with diameters under 1 cm seem to not have a pathologic significance, and are considered like manifestation of the gland involution in advanced-age subjects, and can remain unseen for a long time. The use of diagnostic imaging techniques has made it possible to identify these masses, even those of small size, in the course of diagnostic surveys done under various guidelines. The mass dimensions are a fundamental parameter used to distinguish benign lesions from malign ones (2, 3). Most Authors suspect malignity in masses above 5-6 cm, while considering those with a diameter under 3 cm to be benign. Whereas the rest remain undefined, thereby valued and treated according to criteria not perfectly established.


Tensile bond strength of silicone-based soft denture liner to two chemically different denture base resins after various surface treatments.
This study evaluated the effect of various surface treatments on the tensile bond strength of a silicone-based soft denture liner to two chemically different denture base resins, heat-cured polymethyl methacrylate (PMMA), and light-activated urethane dimethacrylate or Eclipse denture base resin. PMMA test specimens were fabricated and relined with a silicone-based soft denture liner (group AC). Eclipse test specimens were prepared according to the manufacturer's recommendation. Before they were relined with a silicone-based soft denture liner, each received one of three surface treatments: untreated (control, group EC), Eclipse bonding agent applied (group EB), and laser-irradiated (group EL). Tensile bond strength tests (crosshead speed = 5 mm/min) were performed for all specimens, and the results were analyzed using the analysis of variance followed by Tukey's test (p = 0.05). Eclipse denture base and PMMA resins presented similar bond strengths to the silicone-based soft denture liner. The highest mean force was observed in group EL specimens, and the tensile bond strengths in group EL were significantly different (p < 0.05) from those in the other groups.


Accelerated aging during chronic oxidative stress: a role for PARP-1.
Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose) polymerase-1 (PARP-1) and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.


Delivering health promotion during school closures in public health emergencies: building consensus among Canadian experts.
School-based health promotion is drastically disrupted by school closures during public health emergencies or natural disasters. Climate change will likely accelerate the frequency of these events and hence school closures. We identified innovative health promotion practices delivered during COVID-19 school closures and sought consensus among education experts on their future utility. Fifteen health promotion practices delivered in 87 schools across Alberta, Canada during COVID-19 school closures in Spring 2020, were grouped into: 'awareness of healthy lifestyle behaviours and mental wellness', 'virtual events', 'tangible supports' and 'school-student-family connectedness'. Two expert panels (23 school-level practitioners and 20 decision-makers at the school board and provincial levels) rated practices on feasibility, acceptability, reach, effectiveness, cost-effectiveness and other criteria in three rounds of online Delphi surveys. Consensus was reached if 70% or more participants (strongly) agreed with a statement, (strongly) disagreed or neither. Participants agreed all practices require planning, preparation and training before implementation and additional staff time and most require external support or partnerships. Participants rated 'awareness of healthy lifestyle behaviours and mental wellness' and 'virtual events' as easy and quick to implement, effective and cost-effective, sustainable, easy to integrate into curriculum, well received by students and teachers, benefit school culture and require no additional funding/resources. 'Tangible supports' (equipment, food) and 'school-student-family connectedness' were rated as most likely to reach vulnerable students and families. Health promotion practices presented herein can inform emergency preparedness plans and are critical to ensuring health remains a priority during public health emergencies and natural disasters.


Population pharmacokinetics of fluconazole in young infants.
Fluconazole is being increasingly used to prevent and treat invasive candidiasis in neonates, yet dosing is largely empirical due to the lack of adequate pharmacokinetic (PK) data. We performed a multicenter population PK study of fluconazole in 23- to 40-week-gestation infants less than 120 days of age. We developed a population PK model using nonlinear mixed effect modeling (NONMEM) with the NONMEM algorithm. Covariate effects were predefined and evaluated based on estimation precision and clinical significance. We studied fluconazole PK in 55 infants who at enrollment had a median (range) weight of 1.02 (0.440 to 7.125) kg, a gestational age at birth (BGA) of 26 (23 to 40) weeks, and a postnatal age (PNA) of 2.3 (0.14 to 12.6) weeks. The final data set contained 357 samples; 217/357 (61%) were collected prospectively at prespecified time intervals, and 140/357 (39%) were scavenged from discarded clinical specimens. Fluconazole population PK was best described by a one-compartment model with covariates normalized to median values. The population mean clearance (CL) can be derived for this population by the equation CL (liter/h) equals 0.015 . (weight/1)(0.75) . (BGA/26)(1.739) . (PNA/2)(0.237) . serum creatinine (SCRT)(-4.896) (when SCRT is >1.0 mg/dl), and using a volume of distribution (V) (liter) of 1.024 . (weight/1). The relative standard error around the fixed effects point estimates ranged from 3 to 24%. CL doubles between birth and 28 days of age from 0.008 to 0.016 and from 0.010 to 0.022 liter/kg/h for typical 24- and 32-week-gestation infants, respectively. This population PK model of fluconazole discriminated the impact of BGA, PNA, and creatinine on drug CL. Our data suggest that dosing in young infants will require adjustment for BGA and PNA to achieve targeted systemic drug exposures.


Canine viral enteritis: prevalence of parvo-, corona- and rotavirus infections in dogs in the Netherlands.
After a brief review of the present knowledge about canine viral enteritis, the role played by parvoviral, coronaviral and rotaviral infections in contagious diarrhoea in dogs in the Netherlands is discussed. For this purpose a serologic survey, pathologic findings in dogs, and the demonstration of parvoviral antigen with an immunofluorescence test and with a newly developed haemadsorption-elution-haemagglutination assay (HEHA) are presented. It is concluded that infections with canine parvovirus, coronavirus and rotavirus appear widespread among dog populations in the Netherlands.


The core seed mycobiome of Pseudotsuga menziesii var. menziesii across provenances of the Pacific Northwest, USA.
Fungal symbionts occur in all plant tissues, and many aid their host plants with critical functions, including nutrient acquisition, defense against pathogens, and tolerance of abiotic stress. "Core" taxa in the plant mycobiome, defined as fungi present across individuals, populations, or time, may be particularly crucial to plant survival during the challenging seedling stage. However, studies on core seed fungi are limited to individual sampling sites, raising the question of whether core taxa exist across large geographic scales. We addressed this question using both culture-based and culture-free techniques to identify the fungi found in individual seeds collected from nine provenances across the range of coastal Douglas-fir (Pseudotsuga menziesii var. menziesii), a foundation tree species in the Pacific Northwest and a globally important timber crop that is propagated commercially by seed. Two key findings emerged: (i) Seed mycobiome composition differed among seed provenances. (ii) Despite variation in the seed mycobiome, we detected four core members, none of which is a known pathogen of Douglas-fir: Trichoderma spp., Hormonema macrosporum, Mucor plumbeus, and Talaromyces rugulosus. Our results support the concept of a core seed microbiome, yet additional work is needed to determine the functional consequences of core taxa for seedling germination, growth, survival, and competition.


Does a calmodulin-dependent Ca2+-regulated Mg2+-dependent ATPase contribute to hepatic microsomal calcium uptake?
Solubilization of microsomal proteins followed by calmodulin affinity chromatography resulted in the separation of two distinct Ca2+-Mg2+-ATPases (Ca2+-regulated Mg2+-dependent ATPases), one being insensitive to calmodulin (ATPase-1), the other being stimulated about 5-fold by calmodulin (ATPase-2). ATPase-2 accounts for only 8% of total microsomal Ca2+-Mg2+-ATPase-activity. ATPase-1 and -2 can also be distinguished by different pH optima, different sensitivity towards inhibition by vanadate and LaCl3, and different apparent Mr values of the phosphoenzyme intermediates (115,000 and 150,000 for ATPase-1 and ATPase-2 respectively). ATPase-1 from liver co-migrated with Ca2+-Mg2+-ATPase from rat skeletal-muscle sarcoplasmic reticulum, whereas ATPase-2 from liver co-migrated with calmodulin-dependent Ca2+-Mg2+-ATPase derived from rat skeletal-muscle sarcolemma. After separation of parenchymal and nonparenchymal liver cells, a calmodulin-dependent Ca2+-Mg2+-ATPase of Mr 150,000 was found only in the non-parenchymal cells. The kinetic parameters of ATPase-2 and the similarity of the apparent Mr of its phosphoenzyme intermediate to that of skeletal-muscle sarcolemma Ca2+-Mg2+-ATPase makes it likely that the calmodulin-sensitive Ca2+-Mg2+-ATPase found in rat liver microsomal fractions reflects a contamination with plasma membranes (possibly from non-parenchymal cells) rather than a true location in the endoplasmic reticulum of parenchymal liver cells.


Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts.
The hammerhead ribozyme is a small catalytic RNA molecule. Potential hammerhead ribozymes that possess a catalytic domain and flanking sequence complementary to a target mRNA can cleave in trans at a putative cleavage site within the target molecule. We have investigated the potential of hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene (FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of the elastin-associated microfibrils. Mutations in the FBN1 gene are responsible for Marfan syndrome (MFS), a common systemic disorder of the connective tissue. Many FBN1 mutations responsible for MFS appear to act in a dominant-negative fashion, raising the possibility that reduction of the amount of product from the mutant FBN1 allele might be a valid therapeutic approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to the 5' end of the human FBN1 mRNA has been designed and synthesized, and shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor-mediated endocytosis of a ribozyme-transferrin-polylysine complex, specifically reduces both cellular FBN1 mRNA and the deposition of fibrillin in the extracellular matrix. These results suggest that the use of hammerhead ribozymes is a valid approach to the study of fibrillin gene expression and possibly to the development of a therapeutic approach to MFS.


Rapidly progressive dementia: prion diseases and other rapid dementias.
Dementias that occur over weeks to months require a different differential than the slowly progressive dementias that occur over years. Because of the rapidity of decline in cognition, the evaluation of the patient is usually urgent and requires an extensive workup with multiple tests running in parallel. Creutzfeldt-Jakob disease, perhaps the prototypic rapidly progressive dementia (RPD), is often the first diagnosis many neurologists consider when faced with a patient with rapid cognitive decline. Many conditions other than prion disease, however, can present with RPD. Other etiologies include autoimmune conditions, cancers, uncommon presentations of other more common neurodegenerative dementias, and others. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis. Some topics, such as other neurodegenerative dementias and autoimmune dementias, are covered in other chapters in this issue, and will be mentioned here only briefly.


5-HT1A receptors mediate (+)8-OH-DPAT-stimulation of extracellular signal-regulated kinase (MAP kinase) in vivo in rat hypothalamus: time dependence and regional differences.
Brain serotonin 1A (5-HT1A) receptors play an important role in mood disorders and can modulate various intracellular signaling mechanisms. We previously reported that systemic administration of either full or partial 5-HT1A agonists increases neuroendocrine responses and that tandospirone, an azapirone partial agonist, can activate (phosphorylate) extracellular signal-regulated kinase (ERK) in the hypothalamic paraventricular nucleus (PVN). In contrast, decreased levels of phosphoERK (pERK) have been reported in hippocampus following in vivo administration of either azapirone or aminotetralin 5-HT1A agonists, such as 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The present study investigated the time-dependent activation of MAP kinase in hypothalamus by (+)8-OH-DPAT to determine the regional differences and receptor specificity of the changes in pERK. Adult male rats received a systemic injection of (+)8-OH-DPAT (200 microg/kg, s.c.). The time-dependent changes in ERK activation were examined in hypothalamic nuclei as well as other brain regions associated with modulation of mood. (+)8-OH-DPAT produced a rapid increase (at 5 min) and transient return (at 15 min) of pERK levels in PVN and medial basal hypothalamus. In contrast, pERK levels in hippocampus were reduced at both 5 and 15 min after (+)8-OH-DPAT. Pretreatment with the 5-HT1A receptor-specific antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100635) completely blocked the (+)8-OH-DPAT-mediated changes in pERK levels in PVN, medial basal hypothalamus, and hippocampus. No significant (+)8-OH-DPAT-induced changes in pERK were observed in dorsal raphe or amygdala. In conclusion, these results demonstrate that 8-OH-DPAT activation of MAP kinase signaling in vivo is a transient and region-specific phenomenon and in rat hypothalamus and hippocampus is mediated by 5-HT1A receptors.


Peripheral mechanisms contribute to comorbid visceral hypersensitivity induced by preexisting orofacial pain and stress in female rats.
Stress exacerbates many chronic pain syndromes including irritable bowel syndrome (IBS). Among these patient populations, many suffer from comorbid or chronic overlapping pain conditions and are predominantly female. Nevertheless, basic studies investigating chronic psychological stress-induced changes in pain sensitivity have been mostly carried out in male rodents. Our laboratory developed a model of comorbid pain hypersensitivity (CPH) (stress in the presence of preexisting orofacial pain inducing chronic visceral pain hypersensitivity that significantly outlasts transient stress-induced pain hypersensitivity (SIH)) facilitating the study of pain associated with IBS. Since CPH and SIH are phenotypically similar until SIH resolves and CPH persists, it is unclear if underlying mechanisms are similar. In the present study, the visceromotor response (VMR) to colorectal distention was recorded in the SIH and CPH models in intact females and ovariectomized rats plus estradiol replacement (OVx + E2). Over several months, rats were determined to be susceptible or resilient to stress and the role of peripheral corticotrophin-releasing factor (CRF) underlying in the pain hypersensitivity was examined. Stress alone induced transient (3-4 weeks) visceral hypersensitivity, though some rats were resilient. Comorbid conditions increased susceptibility to stress prolonging hypersensitivity beyond 13 weeks. Both models had robust peripheral components; hypersensitivity was attenuated by the CRF receptor antagonist astressin and the mast cell stabilizer disodium cromoglycate (DSCG). However, DSCG was less effective in the CPH model compared to the SIH model. The data indicate many similarities but some differences in mechanisms contributing to comorbid pain conditions compared to transient stress-induced pain.


Vitiligo: pathogenetic hypotheses and targets for current therapies.
Vitiligo is a multifactorial disorder characterized by the appearance of white maculae that may spread over the entire body skin. Depigmentation arises from the loss of functioning melanocytes. Non segmental vitiligo (NSV) is the most common form of the disease: it is usually progressive and may be associated with familiarity and autoimmunity. Segmental vitiligo (SV) frequently stabilizes few years after its onset. Vitiligo etiology involves multiple pathogenetic factors, most of them working in concert. Impaired antioxidative defences lead to accumulation of reactive oxygen species (ROS), which affect melanocytes. Mitochondrial membrane lipid peroxidation may participate to ROS overproduction. A temporal sequence may connect oxidative stress and autoimmunity. Overall, a genetic predisposition renders vitiligo melanocytes more susceptible to precipitating factors than normal healthy melanocytes. The definition of isolated or superimposed manifestations of polygenic skin disorders has been proposed for SV and SV-NSV association. Keratinocytes and melanocytes are both affected and apoptosis, ageing or melanocythorragy are the ultimate effects of the complex deregulation in vitiligo skin. Pathogenetic therapies mainly act by inducing immunosuppression and stimulation of melanocyte proliferation and migration. Here the most popular hypotheses for the pathogenesis of vitiligo are summarized. Fundamental cellular, biochemical and molecular alterations accounting for melanocyte destruction in vitiligo are also described. Last, pathogenetic approaches in the treatment of such a complex disease are discussed, with particular consideration on the cellular and molecular targets of the current therapies.


Experimental Observation of Current Reversal in a Rocking Brownian Motor.
A reversal of the particle current in overdamped rocking Brownian motors was predicted more than 20 years ago; however, an experimental verification and a deeper insight into this noise-driven mechanism remained elusive. Here, we investigate the high-frequency behavior of a rocking Brownian motor for 60 nm gold spheres based on electrostatic interaction in a 3D-shaped nanofluidic slit and electro-osmotic forcing of the particles. We measure the particle probability density in situ with 10 nm spatial and 250 μs temporal resolution and compare it with theory. At a driving frequency of 250 Hz, we observe a current reversal that can be traced to the asymmetric and increasingly static probability density at high frequencies.


Fruit and vegetable consumption among older adults by tooth loss and socio-economic status.
The aim of this study was to examine consumption of fruit and vegetables in relation to tooth loss and income. Data were collected in 2004-06, using a three-stage, stratified clustered sample, involving a computer-assisted telephone interview (CATI), oral examination and mailed questionnaire followed by a food frequency questionnaire. A total of 14 123 adults responded to the CATI (49% response) of whom 5505 (44% of those interviewed) agreed to undergo an oral epidemiological examination. In the nutrition sub-study, a total of n = 1218 persons were approached in New South Wales and Queensland, with n = 1129 responding (92.7% response rate). Among respondents aged 55 years or more 34.5% had <21 teeth. Adjusting for income the prevalence of infrequent consumption ('never or less than once a month') was associated with [PR = prevalence ratio (95% CI)] fewer teeth for the fruits, 'peach, nectarine, plum, apricot' PR = 1.91 (1.12, 3.25) and 'grapes or berries' PR = 1.69 (1.03, 2.76), and for the vegetables 'stir-fried or mixed' PR = 2.34 (1.14, 4.78), 'sweetcorn' PR = 1.45 (1.001, 2.10), 'mushrooms' PR = 1.62 (1.05, 2.50), 'lettuce' PR = 3.99 (1.31, 12.17) and 'soy beans' PR = 1.11 (1.01, 1.21). An inadequate dentition was associated with lower consumption of a range of fruits and vegetables indicating that dentition-related impairment of chewing ability could have adverse consequences on nutritional intake among Australian adults.


Stem cell isolation.
High-dose chemotherapy with autologous hematopoietic progenitor cell support is increasingly used to treat a variety of malignant diseases. A drawback of this technique is the potential for infusing clonogenic tumor cells with the autograft, producing relapse of the disease in the patient. The use of positive selection techniques to isolate stem cells and thus reduce or eliminate tumor cell contamination has been extensively studied over the past few years. Preliminary clinical results have demonstrated that these procedures deplete 2 to 7 logs of tumor cells and do not impair engraftment. It is too early to assess the ultimate clinical benefit of this strategy. Additional applications of CD34-selection include ex vivo expansion of and gene transfer into hematopoietic progenitor cells and T-cell depletion of allogeneic grafts to reduce the incidence of graft-versus-host disease.


The Neutrophil Percentage to Albumin Ratio as a New Predictor of In-Hospital Mortality in Patients with ST-Segment Elevation Myocardial Infarction.
BACKGROUND Neutrophil and albumin are respective indicators of inflammation and malnutrition. Whether combining those 2 markers can predict acute prognosis in patients with ST-segment elevation myocardial infarction (STEMI) remains unknown. This study aimed to investigate the prognostic value of neutrophil percentage to albumin ratio (NPAR) for in-hospital mortality in STEMI patients. MATERIAL AND METHODS There were 1024 patients hospitalized with acute STEMI retrospectively enrolled in this study. Demographic, clinical, and admission laboratory data were extracted from medical record. NPAR was calculated as neutrophil percentage numerator divided by albumin in the admission blood samples. In-hospital mortality was designed as the primary outcome in the study, major adverse cardiac events (MACE) and cardiac death were recorded as the secondary clinical outcomes. RESULTS The rates of in-hospital mortality, MACE, and cardiac death in high NPAR group were significantly higher than those in the low NPAR group (P<0.001, P=0.004, P<0.001). The Kaplan-Meier analysis showed worse outcomes in higher NPAR group (P<0.001). NPAR levels and age independently predicted in-hospital mortality. A NPAR value >1.9 was identified as an effective cut point in STEMI for in-hospital mortality (P<0.001, sensitivity 82%, specificity 52%). CONCLUSIONS Admission NPAR was independently correlated with in-hospital mortality in patients with STEMI.


Correlation between Autism Treatment Evaluation Checklist (ATEC) and Childhood Autism Rating Scale (CARS) in the evaluation of autism spectrum disorder.
Identification of health issues in children with autism spectrum disorder (ASD) is paramount to provide appropriate care and interventions. The Autism Treatment Evaluation Checklist (ATEC) is the one of the few current measures that assesses ASD-associated health problems thus informing intervention decisions. However, little research has been conducted to compare ATEC with other more recognized measures such as the Childhood Autism Rating Scale (CARS). It is unclear whether these two scales can be used interchangeably or whether high scores on one scale are comparable to the other. The aim of the current study was to compare the correlation between ATEC and CARS in the evaluation of children with ASD. This prospective cross-sectional study was conducted at the Developmental and Behavioural Paediatrics Outpatient Clinic at King Saud University, King Khalid University hospital (KKUH) in Riyadh, Saudi Arabia. Forty children with a prior diagnosis of ASD seen during the period from October 2014 to August 2015 were included. Each child was assessed using ATEC and CARS independently during the same visit. The Spearman's rank correlation coefficient test was used. The overall mean CARS score was 34.125 ± 5.535 (range from 22 to 42) and the mean ATEC score was 40.95± 9.1934.1 (range from 24 to 72). The Spearman's rank correlation coefficient (rs) was 0.015, and p-value was 0.926 (> 0.05) meaning that there was no correlation between CARS and ATEC scales. No correlation between CARS and ATEC scale was found. ATEC should not be used instead of CARS to delineate co-morbid health issues. Future studies are needed to assess the validity of ATEC and its correlation with other well established scales.


The Effects of Thymoquinone on Viability, and Anti-apoptotic Factors (BCL-XL, BCL-2, MCL-1) in Prostate Cancer (PC3) Cells: An In Vitro and Computer-Simulated Environment Study.
Purpose: Since active plant ingredients can induce apoptosis in many tumors, in this study we evaluate the apoptotic effects of thymoquinone (TQ) on PC3 cells. Also, we predicted the interaction of TQ with BCL-XL, BCL-2, and MCL-1anti-apoptotic factors by computer-simulated environment. Methods: PC3 cells were treated with different concentrations of TQ (0- 80 µM) and IC50 was determined using 3-(4, 5-dimethylthiaztol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptotic and cytotoxicity effects of TQ were analyzed using flowcytometry and comet assay, respectively. Changes in energy and the molecular interactions of TQ with BCL-XL, BCL-2 and MCL-1 anti-apoptotic factors were investigated using simulation. Results: IC50 value was 40 µM. TQ led to the destruction of the genome of PC3 cells and inducing apoptosis. Molecular dynamics (MD) revealed that the root mean-square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and the number of hydrogen and hydrophobic bonds between TQ and residues of BCL-2, BCL-XL and MCL-1were significantly (P<0.001) changed. TQ makes a more stable and stronger connection with BCL-XL compared to BCL-2 and MCL-1 and inhibits BCL-XL non-competitively. Conclusion: Our results demonstrated that TQ not only led to apoptosis, at least partly, due to reduction in the Coil, Turn, and Bend structure of BCL-XL but also caused a decrease in the Rg and RMSD value of BCL-XL, MCL-1, and BCL-2.


Transplantomics: Toward Precision Medicine in Transplantation Research.
Precision medicine is an emerging integrative approach for disease prevention, early detection, and treatment which takes into account individual variability in genetic and other molecular measurements, medical history, environmental exposures, and lifestyle. The development and availability of genomic and other molecular profiling technologies provide an unprecedented opportunity to apply precision medicine strategies in transplantation research. Developing integrative computational methods to analyze these diverse types of data provides new opportunities to impact diagnostics and therapeutics. In this article, we discuss ways we can leverage molecular data sets to develop new hypotheses for disease mechanisms, identify new disease biomarkers, and reposition drugs for diseases with unmet needs. We specifically discuss computational methods that can be applied to achieve these goals in the context of organ transplant.


High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis.
Multiple sclerosis is an inflammatory, degenerative disease of the central nervous system. The most obvious pathological change in multiple sclerosis is multifocal demyelination of the white matter, but grey matter demyelination may be of equal or even greater importance for its clinical manifestations. In order to assess the pathogenetic role of lesions in the grey and white matter, and to explore the association between demyelinated and non-lesional brain tissue, tools are needed to depict each of these tissue components accurately in vivo. Due to its sensitivity in detecting white matter lesions, T(2)-weighted magnetic resonance imaging at 1.5 T is important in the diagnosis of multiple sclerosis. However, magnetic resonance imaging at 1.5 T largely fails to detect grey matter lesions. In this study, we used T(2)-weighted magnetic resonance imaging at 9.4 T to detect grey matter lesions in fixed post-mortem multiple sclerosis motor cortex. Furthermore, we produced T(1), T(2) and magnetization transfer ratio maps, and correlated these indices with quantitative histology [neuronal density, intensity of immunostaining for myelin basic protein (reflecting myelin content) and phosphorylated neurofilament (reflecting axonal area)] using t-tests and multivariate regression. In 21 tissue samples, 28 cortical grey matter lesions were visible on both T(2)-weighted magnetic resonance imaging and sections immunostained for myelin basic protein, 15/28 being mixed white and grey matter and 11/28 subpial cortical grey matter lesions; 2/28 cortical grey matter lesions involved all layers of the cortex. Compared with non-lesional cortex, cortical grey matter lesions showed reduction of neuronal density (98/mm(2), SD = 34/mm(2;) versus 129/mm(2), SD = 44; P < 0.01), phosphorylated neurofilament (1/transmittance = 1.16; SD = 0.09 versus 1.24; SD = 0.1; P < 0.01) and magnetization transfer ratio (31.1 pu; SD = 11.9 versus 37.5 pu; SD = 8.7; P = 0.01), and an increase of T(2) (25.9; SD = 5 versus 22.6 ms; SD = 4.7; P < 0.01). Associations were detected between phosphorylated neurofilament and myelin basic protein (r = 0.58, P < 0.01), myelin basic protein and T(2) (r = -0.59, P < 0.01), and neuronal density and T(1) (r = -0.57, P < 0.01). All indices correlated with duration of tissue fixation, however, including the latter in the analysis did not fundamentally affect the associations described. Our data show that T(2)-weighted magnetic resonance imaging at 9.4 T enables detection of cortical grey matter lesion in post-mortem multiple sclerosis brain. The quantitative associations suggest that in cortical grey matter T(1) may be a predictor of neuronal density, and T(2) of myelin content (and-secondarily-axons). Successful translation of these results into in vivo studies using high field magnetic resonance imaging (e.g. 3 T and 7 T) will improve the assessment of cortical pathology and thereby have an impact on the diagnosis and natural history studies of patients with multiple sclerosis, as well as clinical trial designs for putative treatments to prevent cortical demyelination and neuronal loss.


Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Relapsed or Refractory Large B-Cell Lymphoma: Practical Implications for the Community Oncologist.
Axicabtagene ciloleucel is the first U.S. Food and Drug Administration-approved autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for the treatment of patients with relapsed or refractory large B-cell lymphoma after ≥2 prior systemic therapies. Although axicabtagene ciloleucel is administered only at authorized treatment centers, community oncologists play a critical role in the CAR T-cell treatment journey, recognizing potentially eligible patients for referral and then, after treatment, closely collaborating with treatment centers to monitor and manage patients long term. ZUMA-1, the pivotal, multicenter, phase I/II study of 108 patients treated with axicabtagene ciloleucel, resulted in an objective response rate of 83%, including 58% complete responses. With a 27.1-month median follow-up, 39% of patients had ongoing responses. CAR T-cell therapy is associated with the potentially life-threatening adverse events (AEs) of cytokine release syndrome and neurologic events, which generally occur early after treatment. In ZUMA-1, cytokine release syndrome and neurologic events were generally reversible and grade ≥3 cytokine release syndrome and neurologic events occurred in 11% and 32% of patients, respectively. Frequent prolonged AEs included hypogammaglobulinemia, B-cell aplasia, and cytopenias requiring supportive care until recovery of hematopoietic function. Rate of treatment-related mortality was low, at <2%. With appropriate management of common AEs, axicabtagene ciloleucel offers the potential for long-term durable responses in patients who otherwise lack curative treatment options. IMPLICATIONS FOR PRACTICE: Community oncologists should be familiar with key aspects of chimeric antigen receptor (CAR) T-cell indications and eligibility to help recognize and refer potential patients for this paradigm-changing treatment option at the appropriate time during the disease course. To ensure optimal long-term outcomes for patients who have been treated with CAR T-cell therapy, oncologists must also be familiar with common prolonged AEs and their monitoring and management.


In vivo and in vitro processing of seed reserve protein in the endoplasmic reticulum: evidence for two glycosylation steps.
Cotyledons of the common bean (Phaseolus vulgaris L.) synthesize large amounts of the reserve protein phaseolin. The polypeptides are synthesized on membrane-bound polysomes, pass through the endoplasmic reticulum (ER) and accumulate in protein bodies. For a study of the biosynthesis and processing of phaseolin, developing cotyledons were labeled with radioactive amino acids, glucosamine and mannose, and isolated fractions (polysomal RNA, polysomes, and rough ER) were used for in vitro protein synthesis. Newly synthesized phaseolin present in the ER of developing cotyledons can be fractioned into four glycopolypeptides by SDS PAGE. In vitro synthesis with polysomal RNA results in the formation of two polypeptides by polysome run-off shows that glycosylation is a co-translational event. The two unglycosylated polypeptides formed by polysome run-off are slightly smaller than the two polypeptides formed by in vitro translation of isolated RNA, indicating that a signal peptide may be present on these polypeptides. Run-off synthesis with rough ER produces a pattern of four polypeptides similar to the one obtained by in vivo labeling. The two abundant glycopolypeptides formed by polysome run-off. This result indicates the existence of a second glycosylation event for the abundant polypeptides. Inhibition of glycosylation by Triton X-100 during chain-completion with rough ER was used to show that these two glycosylation steps normally occur sequentially. Both glycosylation steps are inhibited by tunicamycin. Analysis of carhohydrate to protein ratios of the different polypeptides and of trypsin digests of polypeptides labeled with [(3)H]glucosamine confirmed the conclusion that some glycosylated polypeptides contain two oligosaccharide chains, while others contain only one. An analysis of tryptic peptide maps shows that each of the unglycosylated polypeptides is the precursor for one glycosylated polypeptide with one oligosaccharide chain and one with two oligosaccharide chains.


Deaths after intravenous misuse of transdermal fentanyl.
Fentanyl is a potent synthetic opioid used as a general anesthetic and analgetic. Fatal outcome from intravenous misuse of transdermal fentanyl is rare, and there are few such reports in literature. Here we report two cases of fatal intravenous injection of the content from fentanyl patches. Both were male drug addicts, found dead within a one week interval in the same apartment. Post-mortem femoral blood was screened for amphetamines, cannabinoids, cocaine, and opioids with immunological methods (EMIT II) and further with headspace gas chromatography for alcohol and with liquid chromatography mass spectrometry (LC-MS) for different drugs, including fentanyl. Confirmatory analysis of fentanyl and morphine was performed by gas chromatography-mass spectrometry (GC-MS). In the first case, the toxicological analysis revealed fentanyl (2.7 ng/mL), morphine (31.4 ng/mL), and ethanol (1.1 g/L) in postmortem blood and amphetamine, cannabinoids, morphine, and ethanol (1.4 g/L) in postmortem urine. In the second case, the analysis revealed fentanyl (13.8 ng/mL), 7-aminoclonazepam (57.1 ng/mL), and sertralin (91.9 ng/mL) in postmortem blood and a small amount of ethanol (0.1 g/L) in postmortem urine. Police investigation revealed that both the deceased had bought the patches from the same source. The present cases demonstrate the possibility of intravenous misuse of transdermal patches and the risk of fatal outcome.


Kinetics of superoxide scavenging by dismutase enzymes and manganese mimics determined by electron spin resonance.
This study presents an e.s.r. assay for superoxide dismutase (SOD). Enzymic reactions were studied in which Cu,Zn-SOD, Mn-SOD and Fe-SOD each competed with the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) for superoxide anion (O2-) at pH 7.8 O2- from dissolved KO2 (potassium superoxide) in dimethyl sulphoxide was added directly to the enzyme solutions containing DMPO. The results show that, in this competition reaction system, the kinetics of the reactions between the enzymes and O2- follow a function y = f[( SOD]0.5). The rate constant, kSOD = 6.4 x 10(9) M-1. S-1, determined for Cu,Zn-SOD is approximately an order of magnitude larger than those for Mn-SOD and Fe-SOD. A comparative study of reported SOD mimics, including Mn2+, MnO2-desferrioxamine mesylate (Desferal) and MnO2-Desferal-ascorbate, was done. The results show that solutions of these complexes are approximately three orders of magnitude less active than Cu,Zn-SOD and approximately two orders of magnitude less active than Mn-SOD or Fe-SOD. The results also suggest that the reactivity toward O2- in solutions of these complexes originates from the Mn2+ present and not from the MnO2-Desferal complexes.


Wi-COVID: A COVID-19 symptom detection and patient monitoring framework using WiFi.
The current SARS-CoV-2, better know as COVID-19, has emerged as a serious pandemic with life-threatening clinical manifestations and a high mortality rate. One of the major complications of this disease is the rapid and dangerous pulmonary deterioration that can lead to critical pneumonia conditions, resulting in death. The current healthcare system around the world faces the potential problem of lacking resources to assist a large number of patients at the same time; then, the non-critical patients are mostly referred to perform self-isolation/quarantine at home. This pandemic has placed new demands on the health systems world, asking for novel, rapid and secure ways to monitor patients in order to detect and quickly report patient's symptoms to the healthcare provider, even if they are not in the hospital. While tremendous efforts have been done to develop technologies to detect the virus, create the vaccine, and stop the spread of the disease, it is also important to develop IoT technologies that can help track and monitor diagnosed COVID-19 patients from their homes. In this paper, we explore the possibility of monitoring respiration rates (RR) of COVID-19 patients using a widely-available technology at home - WiFi. Using the at-home WiFi signals, we propose Wi-COVID, a non-invasive and non-wearable technology to monitor the patient and track RR for the healthcare provider. We first introduce the currently available applications that can be done using WiFi signals. Then, we propose the framework scheme for an end-to-end non-invasive monitoring platform of the COVID-19 patients using WiFi. Finally, we present some preliminary results of the proposed framework. We envision the proposed platform as a life-changing technology that leverages WiFi technology as a non-wearable and non-invasive way to monitor COVID-19 patients at home.


Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid.
Capillary dropout is an initial event in diabetic retinopathy, but the etiology is unknown. Recent evidence suggests that similar events may occur in the diabetic choroid. We have developed a method to evaluate the relationship between the polymorphonuclear leukocytes (PMNs) and capillary dropout in the human diabetic choroid using alkaline phosphatase (APase) histochemistry to label blood vessels and nonspecific esterase activity to identify PMNs. The number and distribution of PMNs in diabetic and nondiabetic choroidal capillaries (choriocapillaris) were analyzed in the flat perspective and the tissue then flat embedded in glycol methacrylate for histological sectioning. The total number of PMNs was increased within the choriocapillaris in five diabetic eyes (170.9 +/- 12.9 PMNs/mm2 of choroid) compared with five nondiabetic eyes (84.2 +/- 16.9 PMNs/mm2; P < 0.001). PMNs were almost always within blood vessel lumens and not in interstitial tissue. In the diabetic choroid, increased numbers of PMNs were present in areas of choriocapillaris with pathological changes (loss in APase activity and choroidal neovascularization) compared with nonpathological choriocapillaris (205.1 +/- 46.9 PMNs/mm2 in pathological versus 152.3 +/- 23.4 PMNs/mm2 in nonpathological areas; P < 0.001). PMNs were often queued up within the lumens of capillaries, demonstrating loss in APase activity. We have observed an increased number of PMNs in diabetic choroid compared with control nondiabetic choroids, and PMNs in diabetic choroid were associated with loss in APase activity, which was related to loss in viable endothelial cells. The results suggest that PMNs contribute to vaso-occlusive processes and endothelial cell injury in the diabetic choroid.


Kinetics of α-glucosidase inhibition by different fractions of three species of Labiatae extracts: a new diabetes treatment model.
Glucosidases are a group of enzymes playing crucial roles in digestion of carbohydrates. Glucosidase inhibitors can reduce carbohydrate digestion rate and have the potential to prevent development of type 2 diabetes. The Labiatae is one of the largest plant families grown globally and many studies that have isolated new pharmaceutical compounds. In folk medicine, some of Labiatae plants such as Zataria multiflora Boiss, Salvia mirzayanii Rech. F. & Esfand, and Otostegia persica Boiss are consumed for the treatment of diabetes. This study investigates the inhibitory effects of different fractions of three mentioned species extracts on α-glucosidase. Ethanol extracts of these plants leaves were fractionated using petroleum ether, chloroform, ethyl acetate, and n-butanol solutions. The duration of this study was 12 months. To measure enzyme inhibition, 5 μL of the enzyme, 20 μL of substrate and samples were used and for evaluation mode of inhibition, constant amounts of α-glucosidase were incubated with rising concentrations of substrate (PNPG). The results revealed that the ethyl acetate fraction of Zataria multiflora (IC50 = 0.35 ± 0.01 mg/mL) and petroleum ether fraction of Salvia mirzayanii (IC50 = 0.4 ± 0.11 mg/mL) were the most potent inhibitors of α-glucosidase in comparison with the other samples and acarbose as the standard (IC50 = 7 ± 0.19 mg/mL). All of the samples exhibited noncompetitive-uncompetitive inhibition. It can be inferred from this study that α-glucosidase inhibitory potential of the studied extracts may be a marker of antidiabetic potential of these extracts.


SUMO modification of heterogeneous nuclear ribonucleoproteins.
Small ubiquitin-related modifiers (SUMOs) are proteins that are posttranslationally conjugated to other cellular proteins, particularly those that localize and function in the nucleus. Enzymes regulating SUMO modification localize in part to nuclear pore complexes (NPCs), indicating that modification of some proteins may occur as they are translocated between the nucleus and the cytoplasm. Substrates that are regulated by SUMO modification at NPCs, however, have not been previously identified. Among the most abundant cargos transported through NPCs are the heterogeneous nuclear ribonucleoproteins (hnRNPs). HnRNPs are involved in various aspects of mRNA biogenesis, including regulation of pre-mRNA splicing and nuclear export. Here, we demonstrate that two subsets of hnRNPs, the hnRNP C and M proteins, are substrates for SUMO modification. We demonstrate that the hnRNP C proteins are modified by SUMO at a single lysine residue, K237, and that SUMO modification at this site decreases their binding to nucleic acids. We also show that Nup358, a SUMO E3 ligase associated with the cytoplasmic fibrils of NPCs, enhances the SUMO modification of the hnRNP C and M proteins. Based on our findings, we propose that SUMO modification of the hnRNP C and M proteins may occur at NPCs and facilitate the nucleocytoplasmic transport of mRNAs.


Hemodynamic Optimization in Cardiac Resynchronization Therapy: Should We Aim for dP/dtmax or Stroke Work?
This study evaluated the acute effect of dP/dtmax- versus stroke work (SW)-guided cardiac resynchronization therapy (CRT) optimization and the related acute hemodynamic changes to long-term CRT response. Hemodynamic optimization may increase benefit from CRT. Typically, maximal left ventricular (LV) pressure rise dP/dtmax is used as an index of ventricular performance. Alternatively, SW can be derived from pressure-volume (PV) loops. Forty-one patients underwent CRT implantation followed by invasive PV loop measurements. The stimulation protocol included 16 LV pacing configurations using each individual electrode of the quadripolar lead with 4 atrioventricular (AV) delays. Conventional CRT was defined as pacing from the distal electrode with an AV delay of approximately 120 ms. Compared with conventional CRT, dP/dtmax-guided optimization resulted in a one-third additional dP/dtmax increase (17 ± 11% vs. 12 ± 9%; p < 0.001). Similarly, SW-guided optimization resulted in a one-third additional SW increase (80 ± 55% vs. 53 ± 48%; p < 0.001). Comparing both optimization strategies, dP/dtmax favored contractility (8 ± 12% vs. 5 ± 10%; p = 0.015), whereas SW optimization improved ventricular-arterial (VA) coupling (45% vs. 32%; p < 0.001). After 6 months, mean LV ejection fraction (LVEF) change was 10 ± 9% with 23 (56%) patients becoming super-responders to CRT (≥10% LVEF improvement). Although acute changes in SW were predictive for long-term CRT response (area under the curve: 0.78; p = 0.002), changes in dP/dtmax were not (area under the curve: 0.65; p = 0.112). PV-guided hemodynamic optimization in CRT results in approximately one-third SW improvement on top of conventional CRT, caused by a mechanism of enhanced VA coupling. In contrast, dP/dtmax optimization favored LV contractility. Ultimately, acute changes in SW showed larger predictive value for long-term CRT response compared with dP/dtmax.


Survival of clostridial spores in animal tissues.
Spores injected intravenously into mice in numbers in excess of 10(2)/g of body weight were initially dispersed to most organs, but after a few days the remaining spores were concentrated in the liver, from which they were eliminated with a half-life of about 6 days. Intraperitoneal injection did not result in contamination of organs unless initial spore numbers exceeded 10(5)/g of body weight, in which case the spores behaved in the same manner as those injected intravenously. Oral administration of spores did not result in any contamination of tissues.


Nmr study of the solution structures of TcO(2)F(3) and ReO(2)F(3).
Both TcO(2)F(3) and ReO(2)F(3) are infinite chain, fluorine-bridged polymers in the solid state. Their solution structures have been studied by (19)F and (99)Tc NMR spectroscopy in SO(2)ClF solution and shown to exhibit cyclic (MO(2)F(3))(3) (M = Tc, Re) and (ReO(2)F(3))(4) structures that have been confirmed by simulation of the (19)F NMR spectra. The trimers dominate in both the technetium and rhenium systems, with both the tetramer and trimer existing in equilibrium in the rhenium system. A low concentration of a higher, possibly pentameric, cyclic rhenium polymorph is also present in equilibrium with the trimer and tetramer.


Comprehensive DNA barcode coverage of North American birds.
DNA barcoding seeks to assemble a standardized reference library for DNA-based identification of eukaryotic species. The utility and limitations of this approach need to be tested on well-characterized taxonomic assemblages. Here we provide a comprehensive DNA barcode analysis for North American birds including 643 species representing 93% of the breeding and pelagic avifauna of the USA and Canada. Most (94%) species possess distinct barcode clusters, with average neighbour-joining bootstrap support of 98%. In the remaining 6%, barcode clusters correspond to small sets of closely related species, most of which hybridize regularly. Fifteen (2%) currently recognized species are comprised of two distinct barcode clusters, many of which may represent cryptic species. Intraspecific variation is weakly related to census population size and species age. This study confirms that DNA barcoding can be effectively applied across the geographical and taxonomic expanse of North American birds. The consistent finding of constrained intraspecific mitochondrial variation in this large assemblage of species supports the emerging view that selective sweeps limit mitochondrial diversity.


Towards more sustainable food systems. Addressing food waste at school canteens.
Food Waste is a global significant issue for ethical, environmental and economic reasons, while its management is difficult due to its frequent low visibility. Individual choices and preferences are closely related to the generation of food waste although likely to be modified through education and awareness campaigns. In particular, school canteens are big generators of food waste and, at the same time, provide a great opportunity to improve habits regarding nutrition and education on sustainability, thus impacting the future of the food system. The end purpose of this research is identifying the causes of food waste and unveiling best practices towards its reduction. To achieve this goal, we have designed and developed a mixed methods research approach including semi-structured interviews with managers and staff in schools and catering firms and waste audits at four school canteens - measuring waste from over 10,000 pupil's trays. In order to avoid potential bias due to meal preference, the audit lasted three to five consecutive weekdays per school, thus comprising different menus. We estimated overall food waste between 60 and 100 g per pupil per day. Plate waste represented the highest source of waste, although a big disparity was found among the schools based on their different educational perspectives. Key food waste determinants found were: first, top management standpoint towards food waste and sustainability in general. Secondly, we observed relevant differences among the three catering business models studied, regarding the stages where food waste is usually produced. Finally, food waste was also impacted by the diverse resource availability among the schools. Despite this, the human factor arose as the most relevant one when aiming to minimise food waste.


Platelet Refractoriness: Examining Associated Morbidity and Mortality.
Platelet refractoriness is defined as the failure of platelets to show adequate increment after platelet transfusion. Platelets are important to the normal clotting and hemostasis process in the prevention of bleeding. Platelet refractoriness is a significant clinical concern because of resulting hemorrhagic emergencies, increased length of hospital stays, higher inpatient costs, and decreased survival. As part of the healthcare team, oncology nurses play a crucial role in early detection and using evidence-based management strategies for platelet refractoriness to limit the potential for associated morbidity and mortality.


Carnitine palmitoyltransferase 1C contributes to progressive cellular senescence.
Stable transfection manipulation with antibiotic selection and passaging induces progressive cellular senescence phenotypes. However, the underlying mechanisms remain poorly understood. This study demonstrated that stable transfection of the empty vector induced PANC-1 cells into cellular senescence. Metabolomics revealed several acylcarnitines and their upstream regulatory gene, carnitine palmitoyltransferase 1C (CPT1C) involved in fatty acid β-oxidation in mitochondria, were strikingly decreased in senescent PANC-1 cells. Low CPT1C expression triggered mitochondrial dysfunction, inhibited telomere elongation, impaired cell survival under metabolic stress, and hindered the malignance and tumorigenesis of senescent cells. On the contrary, mitochondrial activity was restored by CPT1C gain-of-function in senescent vector PANC-1 cells. PPARα and TP53/CDKN1A, crucial signaling components in cellular senescence, were downregulated in senescent PANC-1 cells. This study identifies CPT1C as a key regulator of stable transfection-induced progressive PANC-1 cell senescence that inhibits mitochondrial function-associated metabolic reprogramming. These findings confirm the need to identify cell culture alterations after stable transfection, particularly when cells are used for metabolomics and mitochondria-associated studies, and suggest inhibition of CPT1C could be a promising target to intervene pancreatic tumorigenesis.


The double-edged role of copper in the fate of amyloid beta in the presence of anti-oxidants.
The biological fate of amyloid beta (Aβ) species is a fundamental question in Alzheimer's disease (AD) pathogenesis. The competition between clearance and aggregation of Aβs is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Aβs, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Aβ degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants. The degraded fragments were identified using SDS-Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. In addition, we performed electrophysiological analysis to investigate the synaptic functions in brain slices, and found that in the presence of a significant excess of vitamin C, Cu(ii) could prevent an Aβ-induced deficit in synaptic transmission in the hippocampus. Collectively, our evidence strongly indicated that a proper combination of copper and anti-oxidants might have a positive effect on the prevention of AD. This double-edged function of copper in AD has been largely overlooked in the past. We believe that our report is very important for fully understanding the function of copper in AD pathology.


Prevalence of Nonfatal Serious Injury Due to Motor Vehicle Accidents Among Malaysian School-Going Adolescents: Findings From the Adolescent Health Survey 2017.
Serious injury due to motor vehicle accidents (MVAs) significantly contributes to the adolescents' health status. The objective of this study was to estimate the prevalence of nonfatal injury due to MVAs and its associated factors among Malaysian school-going adolescents. Nationally representative samples were selected via 2-stage stratified cluster sampling. Data was collected using a validated self-administered questionnaire. Logistic regression analysis was conducted to examine the associations between the variables. A total of 1088 out of 27 497 adolescents reported that they had sustained serious injury due to MVAs with a prevalence of 4.1% (95% confidence interval [CI] = 3.7-4.5). Serious injury due to MVAs among adolescents was positively associated with being current cigarette smokers (adjusted odds ratio [aOR] = 2.5; 95% CI = 2.2-2.9), followed by Malay ethnicity (aOR = 2.4; 95% CI = 1.9-3.0), current drug users (aOR = 2.3; 95% CI = 1.9-3.0), boys (aOR = 2.1; 95% CI = 1.8-2.4), Indian ethnicity (aOR = 1.8; 95% CI = 1.2-2.5), and those who were in upper secondary school (aOR = 1.3; 95% CI = 1.2-1.5). Targeted intervention and curbing substance use among boys may reduce the morbidities from MVAs and its resulting complications.


Hit or Run: Exploring Aggressive and Avoidant Reactions to Interpersonal Provocation Using a Novel Fight-or-Escape Paradigm (FOE).
Interpersonal provocation presents an approach-avoidance conflict to the provoked person: responding aggressively might yield the joy of retribution, whereas withdrawal can provide safety. Experimental aggression studies typically measure only retaliation intensity, neglecting whether individuals want to confront the provocateur at all. To overcome this shortcoming of previous measures, we developed and validated the Fight-or-Escape paradigm (FOE). The FOE is a competitive reaction time (RT) task in which the winner can choose the volume of a sound blast to be directed at his/her opponent. Participants face two ostensible opponents who consistently select either high or low punishments. At the beginning of each trial, subjects are given the chance to avoid the encounter for a limited number of times. In a first experiment (n = 27, all women), we found that fear potentiation (FP) of the startle response was related to lower scores in a composite measure of aggression and avoidance against the provoking opponent. In a second experiment (n = 34, 13 men), we altered the paradigm such that participants faced the opponents in alternating rather than in random order. Participants completed the FOE as well as the Dot-Probe Task (DPT) and the Approach-Avoidance Task (AAT). Subjects with higher approach bias scores in the AAT avoided the provoking opponent less frequently. Hence, individuals with high threat reactivity and low approach motivation displayed more avoidant responses to provocation, whereas participants high in approach motivation were more likely to engage in aggressive interactions when provoked. The FOE is thus a promising laboratory measure of avoidance and aggression.


Laminin in the anterior pituitary gland of the rat. Laminin in the gonadotrophic cells correlates with their functional state.
The distribution pattern of laminin in the rat anterior pituitary gland under physiological and hormonally altered conditions was studied immunohistochemically. Intense immunoreactivity of the capillaries and of the basement membranes surrounding parenchymal cells was found. Five to 10% of the parenchymal cells of normal adult rat pituitary gland exhibited also intense positive cytoplasmic staining. These were identified as gonadotrophic cells on the basis of their topographic distribution and typical 700-nm light bodies. By immunoelectron microscopy it was shown that the light bodies contain laminin and tubulin. After treatment with estrogen, which is known to suppress the function of the gonadotrophic cells, virtually no cytoplasmic laminin was found. Ultrastructurally, the number of light bodies in the gonadotrophic cells diminished significantly, from approximately 3 to 8 per cell to 0 to 1 per cell in a given section. In contrast, after castration, the number of laminin positive cells increased to a number above that found in the normal adult male rat, and the number of light bodies increased two to four times. Based on these results, it appears that the presence of cytoplasmic laminin and the number of light bodies reflects the hormonal activity of the gonadotrophic cells of the rat pituitary gland.


Exocrine pancreatic insufficiency in dogs and cats.
Exocrine pancreatic insufficiency (EPI) is a malabsorptive syndrome caused by insufficient secretion of digestive enzymes from pancreatic acini. The most common causes of EPI in dogs and cats are pancreatic acinar atrophy and chronic pancreatitis. EPI is diagnosed by measurement of species-specific immunoassays for serum trypsin-like immunoreactivity, the concentration of which directly reflects the mass of functioning pancreatic acinar tissue. EPI is treated by pancreatic enzyme replacement therapy, nutritional management (low-residue diets with moderate fat content), and supplementation of cobalamin. Some dogs and cats have persistent clinical signs despite these treatments. Growing evidence suggests that these clinical signs may be due to enteric microbiota dysbiosis or the presence of concurrent diseases such as chronic enteropathies. Management of these abnormalities may improve outcome in dogs and cats with EPI. The long-term prognosis for dogs and cats with EPI is generally good if high-quality medical therapy is provided. Future studies are needed to further understand the causes of persistent dysbiosis in animals with EPI following initiation of pancreatic enzyme replacement therapy and assess the efficacy of treatments to ameliorate these abnormalities.


Neurometamorphosis of the ear in the gypsy moth, Lymantria dispar, and its homologue in the earless forest tent caterpillar moth, Malacosoma disstria.
The adult gypsy moth, Lymantria dispar (Lymantriidae: Noctuoidea) has a pair of metathoracic tympanic ears that each contain a two-celled auditory chordotonal organ (CO). The earless forest tent caterpillar moth, Malacosoma disstria (Lasiocampidae: Bombycoidea), has a homologous pair of three-celled, nonauditory hindwing COs in their place. The purpose of our study was to determine whether the adult CO in both species arises from a preexisting larval organ or if it develops as a novel structure during metamorphosis. We describe the larval metathoracic nervous system of L. dispar and M. disstria, and identify a three-celled chordotonal organ in the anatomically homologous site as the adult CO. If the larval CO is severed from the homologue of the adult auditory nerve (IIIN1b1) in L. dispar prior to metamorphosis, the adult develops an ear lacking an auditory organ. Axonal backfills of the larval IIIN1b1 nerve in both species reveal three chordotonal sensory neurons and one nonchordotonal multipolar cell. The axons of these cells project into tracts of the central nervous system putatively homologous with those of the auditory pathway in adult L. dispar. Following metamorphosis, M. disstria moths retain all four cells (three CO and one multipolar) while L. dispar adults possess two cells that service the auditory CO and one nonauditory, multipolar cell. We conclude that the larval IIIN1b1 CO is the precursor of both the auditory organ in L. dispar and the putative proprioceptor CO in M. disstria and represents the premetamorphic condition of these insects. The implications of our results in understanding the evolution of the ear in the Lepidoptera and insects in general are discussed.


Cigarette smoking and lesbian and bisexual women in the Bronx.
This study investigated the prevalence of cigarette smoking, smoking patterns, and smoking cessation efforts of Black and Hispanic lesbian and bisexual women from a poor, urban community. One-on-one interviews were conducted with a convenience sample of 130 self-identified Black and Hispanic lesbian and bisexual women from the Bronx, NY. Bivariate statistics were used to determine differences between Black and Hispanic respondents in smoking prevalence, frequency, desire to quit, and impact on family unit. Fifty-five percent of Black respondents and sixty-two percent of Hispanic respondents were current smokers. Hispanics were more likely than Blacks to have a partner (p < 0.04), 2 or more children (p < 0.05), and an asthmatic in their household (p < 0.02). Hispanics were less likely than Blacks to have ever attempted to quit (p < 0.04) and to have made a serious attempt to quit in the past year (p < 0.02). Culturally sensitive interventions are needed to help Hispanic lesbian and bisexual women move from the pre-contemplative to action stage of quitting. The large proportion of current smokers requires greater access to effective smoking cessation tools.