An innovative non-invasive technique for subcutaneous tumour measurements.
In oncological drug development, animal studies continue to play a central role in which the volume of subcutaneous tumours is monitored to assess the efficacy of new drugs. The tumour volume is estimated by taking the volume to be that of a regular spheroid with the same dimensions. However, this method is subjective, insufficiently traceable, and is subject to error in the accuracy of volume estimates as tumours are frequently irregular. This paper reviews the standard technique for tumour volume assessment, calliper measurements, by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. Additionally, we explore the impact of six different tumour morphologies on volume estimation and the detection of treatment effects using a computational tumour growth model. Finally, we propose an alternative method to callipers for estimating volume-BioVolumeTM, a 3D scanning technique. BioVolume simultaneously captures both stereo RGB (Red, Green and Blue) images from different light sources and infrared thermal images of the tumour in under a second. It then detects the tumour region automatically and estimates the tumour volume in under a minute. Furthermore, images can be processed in parallel within the cloud and so the time required to process multiple images is similar to that required for a single image. We present data of a pre-production unit test consisting of 297 scans from over 120 mice collected by four different operators. This work demonstrates that it is possible to record tumour measurements in a rapid minimally invasive, morphology-independent way, and with less human-bias compared to callipers, whilst also improving data traceability. Furthermore, the images collected by BioVolume may be useful, for example, as a source of biomarkers for animal welfare and secondary drug toxicity / efficacy.


Combined trabeculectomy and extracapsular cataract extraction with mitomycin C.
To evaluate the long-term intraocular pressure (IOP) reduction effect and safety of adjunctive mitomycin C (MMC) (0.02%) in combined trabeculectomy and extracapsular cataract extraction (ECCE) procedure. Thirty of forty-one consecutive patients who underwent MMC trabeculectomy and ECCE with a minimum follow-up of 12 months were evaluated. The mean IOP was reduced significantly (p < 0.001) from preoperative 19.2 +/- 3.2 mmHg to postoperative 12.1 +/- 2.7 mmHg, while the mean number of medications decreased from 2.1 to 0.2 at 1-year follow-up. Twenty-seven (90%) patients had IOPs controlled at 15 mmHg or less, and 26 (86.7%) patients required no medication. Net astigmatism and polar value converted from keratometric readings were 1.43 +/- 0.94 diopters and 0.07 +/- 1.38 diopters, respectively, in 1-year follow-up, which were not significantly different from the preoperative values. Intraocular pressure could be maintained in the low teens without the need for medication in a majority of patients even one year after the combined procedure. No adverse effect on corneal endothelium or limbal wound healing was detected with intraoperative application of 0.02% MMC.


Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation.
T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. Reducing the splicing efficiency at 4 to 6 h poststimulation significantly impaired murine T cell activation, which was dependent on the expression dynamics of the Egr1-Nab2-interleukin-2 (IL-2) pathway. This time window overlaps the time of peak IL-2 de novo transcription, which, we suggest, represents a permissive time window in which decreased splicing (or transcription) efficiency reduces mature IL-2 production, thereby hampering murine T cell activation. Notably, the distinct expression kinetics of the Egr1-Nab2-IL-2 pathway between mouse and human render human T cells refractory to this vulnerability. We propose that the rational temporal modulation of splicing or transcription during peak de novo expression of key effectors can be used to fine-tune stimulation-dependent biological outcomes. Our data also show that critical consideration is required when extrapolating mouse data to the human system in basic and translational research.


Rapamycin and CHIR99021 Coordinate Robust Cardiomyocyte Differentiation From Human Pluripotent Stem Cells Via Reducing p53-Dependent Apoptosis.
Cardiomyocytes differentiated from human pluripotent stem cells can serve as an unexhausted source for a cellular cardiac disease model. Although small molecule-mediated cardiomyocyte differentiation methods have been established, the differentiation efficiency is relatively unsatisfactory in multiple lines due to line-to-line variation. Additionally, hurdles including line-specific low expression of endogenous growth factors and the high apoptotic tendency of human pluripotent stem cells also need to be overcome to establish robust and efficient cardiomyocyte differentiation. We used the H9-human cardiac troponin T-eGFP reporter cell line to screen for small molecules that promote cardiac differentiation in a monolayer-based and growth factor-free differentiation model. We found that collaterally treating human pluripotent stem cells with rapamycin and CHIR99021 during the initial stage was essential for efficient and reliable cardiomyocyte differentiation. Moreover, this method maintained consistency in efficiency across different human embryonic stem cell and human induced pluripotent stem cell lines without specifically optimizing multiple parameters (the efficiency in H7, H9, and UQ1 human induced pluripotent stem cells is 98.3%, 93.3%, and 90.6%, respectively). This combination also increased the yield of cardiomyocytes (1:24) and at the same time reduced medium consumption by about 50% when compared with the previous protocols. Further analysis indicated that inhibition of the mammalian target of rapamycin allows efficient cardiomyocyte differentiation through overcoming p53-dependent apoptosis of human pluripotent stem cells during high-density monolayer culture via blunting p53 translation and mitochondrial reactive oxygen species production. We have demonstrated that mammalian target of rapamycin exerts a stage-specific and multifaceted regulation over cardiac differentiation and provides an optimized approach for generating large numbers of functional cardiomyocytes for disease modeling and in vitro drug screening.


The 2 × 2 Achievement Goals in Sport and Physical Activity Contexts: A Meta-Analytic Test of Context, Gender, Culture, and Socioeconomic Status Differences and Analysis of Motivations, Regulations, Affect, Effort, and Physical Activity Correlates.
Approach-avoidance achievement goals are studied extensively in the context of competitive sports and physical activity, including leisure and physical education. Building upon past meta-analyses, the purpose of this quantitative review was to provide basic descriptive data, estimated means for testing of several research questions (i.e., context, gender, culture, and socioeconomic status), and meta-analyzing outcome correlates (i.e., self-determination constructs, affect, effort, and physical activity). A total of 116 studies up to 1 December 2018, met inclusion criteria. These 116 studies, totaling a sample size of 43,133 participants (M sample size = 347.85 + 359.36), from 22 countries with 92.7% of samples, are drawn from participants less than 30 years of mean age. From the 116 unique studies, nearly half (49.6%) were from a sport context and the rest from leisure-time physical activity (PA) (19.4%) and physical education (PE) (31.0%) contexts. A number of different analyses were conducted to examine our research questions. Support was found for several of our research questions: The mastery-approach goal was endorsed more than all the other goals, while sport participants endorsed the performance-approach goal more than PA and PE groups; females endorsed the mastery-avoidance goal more than males; more culturally individualistic countries endorsed the mastery-approach goal; and countries from lower socioeconomic and interdependent countries endorsed the mastery-avoidance goal than higher socioeconomic and independent countries. Concerning, the meta-analyzed correlates, most relationships were hypothesized through the performance-approach goal, and both avoidance goals appeared to be too similar in relationships with the correlates raising theoretical concerns. Overall, the mastery-approach goals had the most meaningful biased corrected effect size values (rc) with the outcome correlates, such as relative autonomy (0.47), intrinsic motivation (0.52), effort (0.40), positive affect (0.42), physical activity intent (0.38). Based on the present and past meta-analytic results, the 2 × 2 achievement goals as currently measured was questioned. Future research suggestions included fundamental questionnaire issues, the need for latent profile analysis or other more advanced statistics, and whether the 2 × 2 achievement goal framework is the most appropriate framework in physical activity contexts.


Treatment of juvenile idiopathic arthritis: a revolution in care.
A generation ago, children with arthritis faced a lifetime of pain and disability. Today, there are a multitude of treatment options, including a variety of biologics targeting key cytokines and other inflammatory mediators. While non-steroidal anti-inflammatory drugs and corticosteroids were once the mainstay of therapy, they are now largely used as bridge or adjunctive therapies. Among the conventional disease-modifying anti-rheumatic drugs, methotrexate remains first-line therapy for most children with juvenile idiopathic arthritis (JIA) due to its long track record of safety and effectiveness in the management of peripheral arthritis. Sulfasalazine and leflunomide may also have a secondary role. The tumor necrosis factor inhibitors (TNFi) have shown tremendous benefit in children with polyarticular JIA and likely in enthesitis-related arthritis and psoriatic JIA as well. There may be additional benefit in combining TNFi with methotrexate. Abatacept and tocilizumab also appear to benefit polyarticular JIA; the role of rituximab remains unclear. For the treatment of systemic JIA, while the TNFi are of less benefit, blockade of interleukin-1 or interleukin-6 is highly effective. Additionally, interleukin-1 blockade appears to be effective treatment of macrophage activation syndrome, one of the most dangerous complications of JIA; specifically, anakinra in combination with cyclosporine and corticosteroids may obviate the need for cytotoxic approaches. In contrast, methotrexate along with the TNFi and abatacept are effective agents for the management of uveitis, another complication of JIA. Overall, the biologics have demonstrated an impressive safety record in children with JIA, although children do need to be monitored for rare but potentially dangerous adverse events, such as tuberculosis and other infections; paradoxical development of additional autoimmune diseases; and possibly an increased risk of malignancy. Finally, there may be a window of opportunity during which children with JIA will demonstrate most optimal responses to aggressive therapy, underscoring the need for rapid diagnosis and initiation of treatment.


Optimization of Sugar Replacement with Date Syrup in Prebiotic Chocolate Milk Using Response Surface Methodology.
Chocolate milk is one of the most commonly used non-fermentative dairy products, which, due to high level of sucrose, could lead to diabetes and tooth decay among children. Therefore, it is important to replace sucrose with other types of sweeteners, especially, natural ones. In this research, response surface methodology (RSM) was used to optimize the ingredients formulation of prebiotic chocolate milk, date syrup as sweetener (4-10%w/w), inulin as prebiotic texturizer (0-0.5%w/w) and carrageenan as thickening agent (0-0.04%w/w) in the formulation of chocolate milk. The fitted models to predict the variables of selected responses such as pH, viscosity, total solid, sedimentation and overall acceptability of chocolate milk showed a high coefficient of determination. The independent effect of carrageenan was the most effective parameter which led to pH and sedimentation decrease but increased viscosity. Moreover, in most treatments, date syrup and inulin variables had significant effects which had a mutual impact. Optimization of the variables, based on the responses surface 3D plots showed that the sample containing 0.48% (w/w) of inulin, 0.04% (w/w) of carrageenan, and 10% of date syrup was selected as the optimum condition.


Differential effects of luminal arginine and glutamine on metalloproteinase production in the postischemic gut.
Matrix metalloproteinases (MMPs) are a group of endopeptidases induced under inflammatory conditions in the intestine which possess the capacity to degrade components of the extracellular matrix. We have previously demonstrated that MMP-2 expression correlates with increased inducible nitric oxide synthase (iNOS) production in the stomach and that iNOS is upregulated in the postischemic gut by the luminal nutrient arginine and repressed by luminal glutamine. We therefore hypothesized that arginine would enhance expression of MMP-2 in the postischemic gut. Jejunal sacs were created in rats at laparotomy and filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 minutes of superior mesenteric artery occlusion (SMAO) and 6 hours of reperfusion and compared with shams. Jejunum was harvested, and membrane type-1 matrix metalloproteinase (MT1-MMP), MMP-2, and iNOS protein expression was determined by Western analysis and MMP-9 production by gelatin zymography. MMP-2, MT1-MMP, MMP-9, and iNOS were all increased after SMAO compared with shams. Arginine maintained while glutamine inhibited the increase in iNOS, MT1-MMP, and MMP-2 expression in the postischemic gut. Pretreatment of the arginine group with a selective iNOS inhibitor blunted the induction of MMP-2 in the postischemic gut. There was no differential modulation of MMP-9 by the luminal nutrients. The arginine-induced upregulation of iNOS may contribute to increased activity of MT1-MMP and MMP-2. The mechanism for this differential regulation by arginine warrants further investigation.


Methylene Blue to Treat Refractory Latex-Induced Anaphylactic Shock: A Case Report.
Anaphylaxis occurs in 1/5000-1/20,000 of anesthesia cases and may evolve with shock and cardiovascular collapse in up to 54% of cases. Mortality varies from 3% to 10%. Latex is the second leading cause of anaphylaxis during the perioperative period. We report a case of latex-induced anaphylactic shock refractory to the usual catecholamine treatment that was reversed with the aid of methylene blue. Exaggerated activation of the nitric oxide-cyclic guanosine monophosphate pathway is observed in refractory shock. Methylene blue selectively inhibits this pathway.


[Trypsin immobilization in silica gel].
Trypsin immobilization in an inorganic polymer, i.e. silica gel, was investigated. Properties of the immobilized enzyme were examined. It was found that the enzyme retained its activity, depending on the gel genesis and dehydration of the carrier. The effect of stabilizing supplements on the enzyme activity was studied. The enzyme immobilization was accompanied by an increase in its thermostability.


Injury risk factors in junior tennis players: a prospective 2-year study.
The aim was to investigate injury risk factors in junior tennis players. Fifty-five players, 35 boys and 20 girls, answered a questionnaire about training habits, time of exposure, previous injuries and equipment factors. A battery of clinical tests and functional performance tests were also carried out. All tennis-related injuries that occurred during a 2-year period were identified and recorded. An injury was defined as an injury if it was impossible to participate in regular tennis training or playing matches during at least one occasion, a time loss injury. Potential injury risk factors were tested in a forward stepwise logistic regression model for injury. Thirty-nine players sustained totally 100 new and recurrent injuries. Injuries to the lower extremity were the most common ones (51%) followed by the upper extremity (24%) and the trunk (24%). Injured players performed more singles per week (P<0.0001) and played more tennis hours per year (P=0.016) than the uninjured players. Playing tennis more than 6 h/week was found to be a risk factor for back pain. A previous injury regardless of location was identified as an injury risk factor, and a previous injury to the back was a risk factor for back pain.


Severe preeclampsia presenting as third nerve palsy.
Preeclampsia is a common complication of pregnancy and often manifests in severe cases with neurological symptoms. We present the first documented case of preeclampsia associated with third nerve palsy. A 19-year-old primigravida presented at 31 2/7 weeks' gestation with preeclampsia. In addition to classic preeclampsia symptoms, the patient had atypical visual disturbances. Exhaustive neurological and ophthalmological examinations revealed a third nerve palsy with no etiology other than preeclampsia. Deteriorating renal function necessitated preterm delivery. She ultimately underwent a cesarean section. Two months postpartum, the patient has shown complete spontaneous resolution of third nerve palsy. In this case of severe preeclampsia manifested by third nerve palsy, we hypothesize that the mechanism is attributed to vasospasm of the vessels supplying the oculomotor nerve.


Unusual pattern of beta-phenylethylamine deamination in the rat heart.
The present study was aimed to determine type A and B MAO activities in rat heart and renal cortex homogenates and evaluate the sensitivity of deamination of 3H-5-HT and 14C-beta-PEA to selective MAO-A and MAO-B inhibitors, respectively Ro 41-1049 and lazabemide. Deamination of beta-PEA in the rat heart was not affected (Vmax = 53+/-10 vs 42+/-6 nmol mg protein(-1) h(-1)) by lazabemide (250 nM), but was significantly reduced (Vmax = 10+/-1 nmol mg protein(-1) h(-1)) by Ro 41-1049 (250 nM). Deamination of beta-PEA in the rat heart is a low affinity process (when compared with that in the kidney) with high Km values (244+/-98 vs 18.6+/-5.8 microM). On the other hand, deamination of 5-HT in the rat heart and renal cortex revealed high Km values, which were similar to those for beta-PEA in the heart. Deamination of beta-PEA (1000 microM) in the rat heart was inhibited in a concentration-dependent manner by Ro 41-1049 with a Ki value of 32 nM (22, 48; 95% confidence limits), but not by the selective MAO-B inhibitor lazabemide (up to 500 nM). Inhibition of 5-HT (1000 microM) deamination in the rat heart by Ro 41-1049 was also a concentration-dependent process with a Ki value of 21 (16, 26) nM. Deamination of 5-HT (1000 microM) in the rat renal cortex, was inhibited in a concentration-dependent manner by Ro 41-1049 with a Ki value of 12 (8, 17) nM. Deamination of beta-PEA in the renal cortex was inhibited by lazabemide with a Ki of 5 (3, 7) nM. In the rat heart, in contrast to that in the renal cortex, the specific MAO-B substrate beta-PEA is deaminated by a form of MAO which most probably corresponds to MAO-A.


A single infection with Chlamydia pneumoniae is sufficient to exacerbate atherosclerosis in ApoE deficient mice.
Several studies have demonstrated a strong link between Chlamydia pneumoniae (Cp) infection and atherosclerosis progression/exacerbation. Here, we try to understand whether a single administration of Cp could exacerbate atherosclerosis. Apoe(-/-) mice were intranasally infected with Cp followed by a high fat diet. Mice were sacrificed at different time points after Cp infection to monitor the development of the atheroma. Cp infection increased lipid content in the aortic sinus of Apoe(-/-) mice starting from 8 weeks. This was associated with increased numbers of active myeloid dendritic cells and plasmacytoid DCs which were co-localized with T-cells in the atherosclerotic plaque. The serum levels of IFN-γ showed a Th1-like environment typical of atherosclerosis. In conclusion, we demonstrate that one dose of Cp could exacerbate atherosclerotic lesion development, triggering innate immune cell accumulation early on that allowed the involvement of Th1-like cells in the exacerbation of the atherosclerotic plaque at later time points.


Potentially preventable hospitalizations in dementia: family caregiver experiences.
Health crises in persons living with dementia challenge their caregivers to make pivotal decisions, often under pressure, and to act in new ways on behalf of their care recipient. Disruption of everyday routines and heightened stress are familiar consequences of these events. Hospitalization for acute illness or injury is a familiar health crisis in dementia. The focus of this study is to describe the lived experience of dementia family caregivers whose care recipients had a recent unplanned admission, and to identify potential opportunities for developing preventive interventions. Family caregivers (n = 20) of people with dementia who experienced a recent hospitalization due to an ambulatory care sensitive condition or fall-related injury completed phone interviews. Interviews used semi-structured protocols to elicit caregivers' reactions to the hospitalization and recollections of the events leading up to it. Analysis of interview data identified four major themes: (1) caregiver is uncertain how to interpret and act on the change; (2) caregiver is unable to provide necessary care; (3) caregiver experiences a personal crisis in response to the patient's health event; (4) mitigating factors may prevent caregiver crises. This study identifies a need for clinicians and family caregivers to work together to avoid health crises of both caregivers and people with dementia and to enable caregivers to manage the health of their care recipients without sacrificing their own health and wellness.


An essential step of kinetochore formation controlled by the SNARE protein Snap29.
The kinetochore is an essential structure that mediates accurate chromosome segregation in mitosis and meiosis. While many of the kinetochore components have been identified, the mechanisms of kinetochore assembly remain elusive. Here, we identify a novel role for Snap29, an unconventional SNARE, in promoting kinetochore assembly during mitosis in Drosophila and human cells. Snap29 localizes to the outer kinetochore and prevents chromosome mis-segregation and the formation of cells with fragmented nuclei. Snap29 promotes accurate chromosome segregation by mediating the recruitment of Knl1 at the kinetochore and ensuring stable microtubule attachments. Correct Knl1 localization to kinetochore requires human or Drosophila Snap29, and is prevented by a Snap29 point mutant that blocks Snap29 release from SNARE fusion complexes. Such mutant causes ectopic Knl1 recruitment to trafficking compartments. We propose that part of the outer kinetochore is functionally similar to membrane fusion interfaces.


Draxin alters laminin organization during basement membrane remodeling to control cranial neural crest EMT.
Premigratory neural crest cells arise within the dorsal neural tube and subsequently undergo an epithelial-to-mesenchymal transition (EMT) to leave the neuroepithelium and initiate migration. Draxin is a Wnt modulator that has been shown to control the timing of cranial neural crest EMT. Here we show that this process is accompanied by three stages of remodeling of the basement membrane protein laminin, from regression to expansion and channel formation. Loss of Draxin results in blocking laminin remodeling at the regression stage, whereas ectopic maintenance of Draxin blocks remodeling at the expansion stage. The latter effect is rescued by addition of Snail2, previously shown to be downstream of Draxin. Our results demonstrate an essential function for the Wnt modulator Draxin in regulating basement membrane remodeling during cranial neural crest EMT.


Pro-migratory actions of the prostacyclin receptor in human breast cancer cells that over-express cyclooxygenase-2.
Metastasis is the major cause of death in cancer patients. Elevated expression of cyclooxygenase-2 (COX-2) is observed in many human cancers and over-production of downstream prostaglandins (PGs) has been shown to stimulate metastasis. A role for increased PGE2 production has been proposed, but whether other PGs contribute is currently unclear. In this study the pro-migratory actions of individual PGs were evaluated in MDA-MB-468 breast cancer cells that stably over-expressed COX-2 (MDA-COX-2 cells); cell migration was quantified using 3D-matrigel droplet assays. Inhibition of the prostacyclin and PGE synthases, but not alternate prostanoid synthases, prevented the increase in MDA-COX-2 cell migration produced by arachidonic acid (AA); direct treatment of cells with the stable prostacyclin analogue cicaprost also promoted migration. Pharmacological antagonism and knockdown of the IP receptor decreased cell migration, while antagonists of the alternate DP, EP2, FP, and TP prostanoid receptors were inactive. In support of these findings, activation of the IP receptor also enhanced migration in the MDA-MB-468, MDA-MB-231 and A549 cell lines, and IP receptor knock-down in MDA-COX-2 cells decreased the expression of a number of pro-migratory genes. In further studies, the prostacyclin/IP receptor and PGE2/EP4 receptor pathways were found to be functionally independent and the inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) selectively impaired the IP-receptor-dependent migration in MDA-COX-2 cells. Taken together, the prostacyclin/IP/PI3K-p38 MAPK axis has emerged as a novel pro-migratory pathway in breast cancer cells that over-express COX-2. This information could be utilized in novel treatment strategies to minimize tumor metastasis.


Kinetics and efficiency of polyadenylation of late polyomavirus nuclear RNA: generation of oligomeric polyadenylated RNAs and their processing into mRNA.
The rate and efficiency of polyadenylation of late polyomavirus RNA in the nucleus of productively infected mouse kidney cells were determined by measuring incorporation of [3H]uridine into total and polyadenylated viral RNAs fractionated by oligodeoxythymidylic acid-cellulose chromatography. Polyadenylation is rapid: the average delay between synthesis and polyadenylation of viral RNA in the nucleus is 1 to 2 min. However, only 10 to 25% of viral RNA molecules become polyadenylated. Polyadenylated RNAs in the nucleus are a family of molecules which differ in size by an integral number of viral genome lengths (5.3 kilobases). These RNAs are generated by repeated passage of RNA polymerase around the circular viral DNA, accompanied by addition of polyadenylic acid to a unique 3' end situated 2.2 + n(5.3) kilobases from the 5' end of the RNAs (n can be an integer from 0 to at least 3). Between 30 and 50% of the sequences in nuclear polyadenylated RNA are conserved during processing and transport to the cytoplasm as mRNA. This is consistent with the molar ratios of nuclear polyadenylated RNAs in the different size classes, and it suggests that most polyadenylated nuclear RNA is efficiently processed to mRNA. Thus, the low overall conservation of viral RNA sequences between nucleus and cytoplasm is explained by (i) low efficiency of polyadenylation of nuclear RNA and (ii) removal of substantial parts of polyadenylated RNAs during splicing. The correlation between inefficient termination of transcription and inefficient polyadenylation of transcripts suggests that these two events may be causally linked.


Impact of Cultural Exposure and Message Framing on Oral Health Behavior: Exploring the Role of Message Memory.
Health messages are more effective when framed to be congruent with recipient characteristics, and health practitioners can strategically choose message features to promote adherence to recommended behaviors. We present exposure to US culture as a moderator of the impact of gain-frame versus loss-frame messages. Since US culture emphasizes individualism and approach orientation, greater cultural exposure was expected to predict improved patient choices and memory for gain-framed messages, whereas individuals with less exposure to US culture would show these advantages for loss-framed messages. 223 participants viewed a written oral health message in 1 of 3 randomized conditions-gain-frame, loss-frame, or no-message control-and were given 10 flosses. Cultural exposure was measured with the proportions of life spent and parents born in the US. At baseline and 1 week later, participants completed recall tests and reported recent flossing behavior. Message frame and cultural exposure interacted to predict improved patient decisions (increased flossing) and memory maintenance for the health message over 1 week; for example, those with low cultural exposure who saw a loss-frame message flossed more. Incongruent messages led to the same flossing rates as no message. Memory retention did not explain the effect of message congruency on flossing. Flossing behavior was self-reported. Cultural exposure may only have practical application in either highly individualistic or collectivistic countries. In health care settings where patients are urged to follow a behavior, asking basic demographic questions could allow medical practitioners to intentionally communicate in terms of gains or losses to improve patient decision making and treatment adherence.


[Gastroesophageal reflux disease model].
The model of gastroesophageal reflux disease by administration of 0.2-0.25 ml of a 1% solution of methylene blue to fundal division of rat stomach was created. After 1-5 minutes electromotor activity of the lower third of the esophagus was observed. Mucosa staining was noted.


[A patellar giant-cell tumor with soft tissue involvement: an alternative treatment method and review of the literature].
In this article, we report a case of a giant-cell tumor of the patella which occurred in an atypical location with soft tissue involvement, which makes our case clinically and radiologically unique. A 24-year-old patient was admitted to our clinic with a complaint of anterior knee pain. Radiological examination and percutaneous fine needle biopsy showed a diagnosis of giant-cell tumor of the patella. The patient underwent patellectomy with en-bloc resection of the lesion with totally involved soft tissue components and the extensor mechanism was reconstructed with two Achilles allografts. After surgery, the diagnosis was confirmed by histopathological examination. At 12 months, the patient had no recurrence with 110° flexion and 30° extension of the range of motion of the knee. Lysholm knee score was 72. At 90°/sec isokinetic muscle strength test, the muscle strength loss was found to be 51.1% in the extensor and 21.1% in the flexor, compared to non-involved knee. In conclusion, giant cell tumors are difficult to treat, as they are destructive lesions with high recurrence rates. Despite reduced range of motion and muscle strength, based on our study results, we believe that our surgical treatment modality may be an alternative for the treatment of patellar giant cell tumors.


Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study.
We have investigated immunohistochemically the effects of melatonin on Leydig cells in rat. Three groups of Wistar rats were used. Rats in group I and II were sham-pinealectomized (control) and pinealectomized, respectively, whereas rats in group III were pinealectomized and injected daily with melatonin for 2 months. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum testosterone levels were determined with the use of a chemiluminescent enzyme immunoassay. Testicular tissue was collected and processed for semiquantitative evaluation of immunohistochemical testosterone staining. Intensity of immunostaining was determined on a scale between 0 (no staining) and 5 (heavy staining). In pinealectomized rats, serum testosterone levels were significantly increased as compared to sham-pinealectomized rats. Daily administration of melatonin after pinealectomy resulted in significant decreased serum testosterone levels as compared to levels in control and pinealectomized rats. Immunostaining of testosterone was moderate (3+) in sham-pinealectomized rats, heavy (5+) in pinealectomized rats and low (1+) in pinealectomized rats that were treated with melatonin, respectively. The results of our study indicate that pinealectomy induces increased testosterone secretion in Leydig cells and this increased secretion can be prevented by administration of melatonin.


John von Neumann: the founding father of artificial life.
Aside from being known for his contributions to mathematics and physics, John von Neumann is considered one of the founding fathers of computer science and engineering. Not only did he do pioneering work on sequential computing systems, but he also carried out a major investigation of parallel architectures, leading to his work on cellular automata. His exceptional vision and daring, borrowing from biology the concept of genomic information even before the discovery of DNA's double helix, led him to propose the concept of self-reproducing automata.


Anti-TNF-α therapy may cause neonatal neutropenia.
Although anti-tumor necrosis factor (anti-TNF) antibodies are associated with a clear risk of agranulocytosis in adults and are known to cross the placenta, monitoring of the absolute neutrophil count (ANC) in neonates born to mothers receiving these biological agents is not currently recommended. Here, we report on the first case series of 4 newborn patients with severe neutropenia born to mothers treated for ulcerative colitis with infliximab during pregnancy (including the third trimester). The newborns presented with severe neutropenia at birth, which was subsequently complicated by skin infections. The newborns' ANCs returned to the normal range within 8 to 14 weeks, at which time infliximab could not be detected in the blood. Anti-TNF agents probably exert a direct, toxic effect on the bone marrow. Furthermore, the detection of a CD16 autoantibody in 1 mother-newborn pair suggests that infliximab can induce autoimmune neutropenia. Abnormally high levels of the CD16 autoantibody in newborn serum or immaturity of the fetal bone marrow might explain why neutropenia was observed in the child but not in the mother. We recommend the systematic measurement of ANC on cord blood at birth and (in the event of an infection) in the weeks thereafter.


Attitudes Toward Influenza Vaccination Administration in the Emergency Department Among Patients: A Cross-Sectional Survey.
Influenza is a serious, vaccine-preventable illness. The current vaccination rates in Canada are below target rates, highlighting the potential need for more convenient ways to receive vaccinations. Wait times to be seen in Canadian emergency departments are escalating, and using the time spent waiting to offer and administer an influenza vaccine could potentially improve ease of access to immunization for some Canadians. The aim of this cross-sectional study was to gauge public interest and identify perceived barriers and facilitators to influenza vaccine availability in a Canadian emergency and trauma center. Anonymous questionnaires were completed by a convenience sample of adult patients classified as low acuity (n = 151) as 1 arm of a 2-arm study. Of the unvaccinated patients, 34.6% expressed willingness to be vaccinated in the emergency department. The patients who had received a vaccine in the previous year were significantly more willing to accept the vaccine in the emergency department (χ2 [1] = 23.78, P < 0.001). The 3 top factors associated with having received vaccination in the previous year include trust in vaccine information (χ2 [2] = 27.34, P < 0.001), immunity preferences (χ2 [2] = 32.25, P < 0.001), and beliefs about efficacy (χ2 [2] = 44.90, P < 0.001). Patients classified as low acuity were supportive of ED influenza vaccination. In addition, some of the unvaccinated participants had unmet education needs (ie, regarding trustworthy sources of vaccine information, immunity, and vaccine efficacy) that would require addressing before they would likely consider receiving influenza vaccination in future during their ED visit.


New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms.
Hyperekplexia is a syndrome of readily provoked startle responses, alongside episodic and generalized hypertonia, that presents within the first month of life. Inhibitory glycine receptors are pentameric ligand-gated ion channels with a definitive and clinically well stratified linkage to hyperekplexia. Most hyperekplexia cases are caused by mutations in the α1 subunit of the human glycine receptor (hGlyR) gene (GLRA1). Here we analyzed 68 new unrelated hyperekplexia probands for GLRA1 mutations and identified 19 mutations, of which 9 were novel. Electrophysiological analysis demonstrated that the dominant mutations p.Q226E, p.V280M, and p.R414H induced spontaneous channel activity, indicating that this is a recurring mechanism in hGlyR pathophysiology. p.Q226E, at the top of TM1, most likely induced tonic activation via an enhanced electrostatic attraction to p.R271 at the top of TM2, suggesting a structural mechanism for channel activation. Receptors incorporating p.P230S (which is heterozygous with p.R65W) desensitized much faster than wild type receptors and represent a new TM1 site capable of modulating desensitization. The recessive mutations p.R72C, p.R218W, p.L291P, p.D388A, and p.E375X precluded cell surface expression unless co-expressed with α1 wild type subunits. The recessive p.E375X mutation resulted in subunit truncation upstream of the TM4 domain. Surprisingly, on the basis of three independent assays, we were able to infer that p.E375X truncated subunits are incorporated into functional hGlyRs together with unmutated α1 or α1 plus β subunits. These aberrant receptors exhibit significantly reduced glycine sensitivity. To our knowledge, this is the first suggestion that subunits lacking TM4 domains might be incorporated into functional pentameric ligand-gated ion channel receptors.


Muscle activation and knee biomechanics during squatting and lunging after lower extremity fatigue in healthy young women.
Muscle activations and knee joint loads were compared during squatting and lunging before and after lower extremity neuromuscular fatigue. Electromyographic activations of the rectus femoris, vastus lateralis and biceps femoris, and the external knee adduction and flexion moments were collected on 25 healthy women (mean age 23.5 years, BMI of 23.7 kg/m(2)) during squatting and lunging. Participants were fatigued through sets of 50 isotonic knee extensions and flexions, with resistance set at 50% of the peak torque achieved during a maximum voluntary isometric contraction. Fatigue was defined as a decrease in peak isometric knee extension or flexion torque ≥25% from baseline. Co-activation indices were calculated between rectus femoris and biceps femoris; and between vastus lateralis and biceps femoris. Fatigue decreased peak isometric extension and flexion torques (p<0.05), mean vastus lateralis activation during squatting and lunging (p<0.05), and knee adduction and flexion moments during lunging (p<0.05). Quadriceps activations were greater during lunging than squatting (p<0.05). Thus, fatigue altered the recruitment strategy of the quadriceps during squatting and lunging. Lunging challenges quadriceps activation more than squatting in healthy, young women.


Calciomics: integrative studies of Ca2+-binding proteins and their interactomes in biological systems.
Calcium ion (Ca(2+)), the fifth most common chemical element in the earth's crust, represents the most abundant mineral in the human body. By binding to a myriad of proteins distributed in different cellular organelles, Ca(2+) impacts nearly every aspect of cellular life. In prokaryotes, Ca(2+) plays an important role in bacterial movement, chemotaxis, survival reactions and sporulation. In eukaryotes, Ca(2+) has been chosen through evolution to function as a universal and versatile intracellular signal. Viruses, as obligate intracellular parasites, also develop smart strategies to manipulate the host Ca(2+) signaling machinery to benefit their own life cycles. This review focuses on recent advances in applying both bioinformatic and experimental approaches to predict and validate Ca(2+)-binding proteins and their interactomes in biological systems on a genome-wide scale (termed "calciomics"). Calmodulin is used as an example of Ca(2+)-binding protein (CaBP) to demonstrate the role of CaBPs on the regulation of biological functions. This review is anticipated to rekindle interest in investigating Ca(2+)-binding proteins and Ca(2+)-modulated functions at the systems level in the post-genomic era.


Polymerization and oxidation of phenols in supercritical water.
The treatment of toxic and difficult-to-degrade phenolic compounds has become a key issue in the coking, pharmaceutical, and chemical industries. Considering the polymerization and oxidation of phenolic compounds in supercritical water partial oxidation/supercritical water oxidation (SCWPO/SCWO), the present study reviewed the removal efficiency and reaction pathway of phenolic compounds and phenolic waste/wastewater under different reaction conditions. Temperature is the dominant factor affecting the SCWO reaction. When the oxidizing ability is insufficient, the organics polymerize to form phenolic compounds. The gradual increase of oxidant equivalent causes the intermediate product to gradually oxidize to CO2 and H2O completely. Finally, the free radical reaction mechanism is considered to be a typical SCWO reaction mechanism.


Characteristic aroma components of rennet casein.
Rennet casein, produced by enzymatic (rennet) precipitation of casein from pasteurized skim milk, is used in both industrial (technical) and food applications. The flavor of rennet casein powder is an important quality parameter; however, the product often contains an odor described as like that of animal/wet dog. Two commercial rennet casein powders were evaluated to determine the compounds responsible for the typical odor. Aroma extracts were prepared by high-vacuum distillation of direct solvent (ether) extracts and analyzed by gas chromatography-olfactometry (GCO), aroma extract dilution analysis (AEDA), and GC-mass spectrometry (MS). Odorants detected by GCO were typical of those previously reported in skim milk powders and consisted mainly of short-chain volatile acids, phenolic compounds, lactones, and furanones. Results of AEDA indicated o-aminoacetophenone to be a potent odorant; however, sensory descriptive sensory analysis of model aroma systems revealed that the typical odor of rennet casein was principally caused by hexanoic acid, indole, guaiacol, and p-cresol.


Vascular and renal prostaglandins as counter-regulatory systems in heart failure.
Vasoconstrictors and vasodilators are both activated in patients with severe heart failure. Vasodilatory prostaglandins are increased in parallel with the degree of activation of neurohumoral vasoconstrictor systems, and may serve to offset the circulatory effects of systemic and regional vasoconstriction. Enhanced vasoconstrictive and vasodilatory activities appear to be especially important in patients with hyponatraemia. These patients may be particularly susceptible to clinical deterioration when given drugs that inhibit prostaglandin synthesis (e.g. indomethacin) and may be more likely to improve when treated with agents that enhance the production of endogenous prostaglandin (e.g. angiotensin converting enzyme inhibitor). Exogenous PGE2 reduces afterload and may be a useful therapeutic agent. Research on vascular and renal prostaglandins should further our knowledge of the pathophysiology and therapy of congestive heart failure.


Supplementing clinic-based skills training with manual-based community support sessions: effects on social adjustment of patients with schizophrenia.
Although skills training is a validated psychosocial treatment for schizophrenia, generalization of the skills to everyday life has not been optimal. This study evaluated a behaviorally oriented method of augmenting clinic-based skills training in the community with the aim of improving opportunities, encouragement, and reinforcement for outpatients to use their skills in their natural environment. Sixty-three individuals with schizophrenia were randomly assigned to 60 weeks of clinic-based skills training alone or of clinic-based skills training supplemented with manual-based generalization sessions in the community. Patients were also randomly assigned to receive either haloperidol or risperidone. Therapists' fidelity to the manuals was measured. Patients' acquisition of the skills from pre- to posttraining was evaluated. The primary outcome measures were the Social Adjustment Scale-II and the Quality of Life Scale. Seventy-one percent of the patients completed the trial. Only six participants experienced psychotic exacerbations during the trial. There was no evidence of a differential medication effect on social functioning. Social functioning improved modestly in both psychosocial conditions over time; participants who received augmented skills training in the community showed significantly greater and/or quicker improvements. Given judicious and effective antipsychotic medication that limited exacerbations to less than 10% during the trial, a wide range of outpatients with schizophrenia demonstrated substantial learning of illness management and social skills in the clinic. When clinic-based skills training was augmented by in vivo training and consultation, transfer of the skills to everyday life was enhanced. These benefits were established regardless of the medications prescribed.


Identification of genetic determinants of the sexual dimorphism in CNS autoimmunity.
Multiple sclerosis (MS) is a debilitating chronic inflammatory disease of the nervous system that affects approximately 2.3 million individuals worldwide, with higher prevalence in females, and a strong genetic component. While over 200 MS susceptibility loci have been identified in GWAS, the underlying mechanisms whereby they contribute to disease susceptibility remains ill-defined. Forward genetics approaches using conventional laboratory mouse strains are useful in identifying and functionally dissecting genes controlling disease-relevant phenotypes, but are hindered by the limited genetic diversity represented in such strains. To address this, we have combined the powerful chromosome substitution (consomic) strain approach with the genetic diversity of a wild-derived inbred mouse strain. Using experimental allergic encephalomyelitis (EAE), a mouse model of MS, we evaluated genetic control of disease course among a panel of 26 consomic strains of mice inheriting chromosomes from the wild-derived PWD strain on the C57BL/6J background, which models the genetic diversity seen in human populations. Nineteen linkages on 18 chromosomes were found to harbor loci controlling EAE. Of these 19 linkages, six were male-specific, four were female-specific, and nine were non-sex-specific, consistent with a differential genetic control of disease course between males and females. An MS-GWAS candidate-driven bioinformatic analysis using orthologous genes linked to EAE course identified sex-specific and non-sex-specific gene networks underlying disease pathogenesis. An analysis of sex hormone regulation of genes within these networks identified several key molecules, prominently including the MAP kinase family, known hormone-dependent regulators of sex differences in EAE course. Importantly, our results provide the framework by which consomic mouse strains with overall genome-wide genetic diversity, approximating that seen in humans, can be used as a rapid and powerful tool for modeling the genetic architecture of MS. Moreover, our data represent the first step towards mechanistic dissection of genetic control of sexual dimorphism in CNS autoimmunity.


Management of acute shoulder pain in an adolescent lacrosse athlete: a case report.
Acute onset of shoulder pain in adolescent athletes typically is related to trauma. The subject of this case report, a 13 year-old male, was injured when he collided with another athlete while his right arm was extended. He experienced immediate onset of significant right shoulder pain. Manual assessment in the emergency department revealed anterior tenderness and loss of function due to pain - most notably limitations in both active internal rotation and abduction. A plain film showed a radiographic density anterior to the humeral head but a donation site (where a bony avulsion may have occurred) was not delineated. Magnetic resonance imaging clearly identified a lesser tuberosity avulsion (thus the site of origin of the bony material) encompassing the insertion of the subscapularis muscle with retraction of approximately one centimeter. Open surgical repair (reduction and fixation) was performed with excellent results. 5 (Single Case report).


WhatsApp video call communication between oncological patients and their families during COVID-19 outbreak.
On March 8th, 2020 the Italian Government implemented extraordinary measures to limit COVID-19 viral transmission. The aim of the study was to verify if the use of WhatsApp facilitates communication, improves health information, perception of safe and security, reduce emotional stress during the COVID-19 emergency. In this study we identified two period, in the pre-COVID 1-month period (February 9th - March 8th, 2020) 34 patients underwent elective surgery for malignancies (21) and benign (13) diseases, respectively. We provided patients' families on a daily basis with clinical information face-to-face in the ward regarding their postoperative course. In the post-COVID 1-month period (March 9th - April 5th, 2020), 15 patients with malignancies were treated. In this period, patients and their families given a consent form to let the surgical team to communicate clinical data using WhatsApp. At the end of the study period we collected a satisfaction anonymous questionnaire of both patients and families. Statistically significant differences were observed in the pre- vs. post- COVID period regarding the number of surgical procedures (P=0.004). In the post-COVID period, the satisfaction questionnaire showed a good reliability (Cronbach's α 0.912) and a high percentage of satisfaction of patients and their families for the adopted communication tool, reassurance, privacy protection and reduction of emotional stress. WhatsApp is a safe and fast technology, it offers the opportunity to facilitate clinical communications, reduce stress, improve patient security, obtain clinical and psychological positive implications in patient's care preserving their privacy in the COVID-19 emergency period.


INES: Interactive tool for construction and extrapolation of partitioned survival models.
INES (INteractive model for Extrapolation of Survival and cost) provides an open-access tool powered by R that implements three-state partitioned survival models (PSM). This article describes the properties of the tool, and the situations where INES may or may not be suitable. INES is designed to be used by investigators or healthcare professionals who have a good grasp of the principles of economic evaluation and understand the strengths and weaknesses of partitioned survival models, but are not sufficiently familiar with a statistical package such as Excel or R to be able to construct and test a de-novo PSM themselves. INES is delivered to the user via a batch file. Once downloaded to the user's hard drive, it interacts with the user via a portable version of R with web interactivity built in Shiny. INES requires absolutely no knowledge of R and the user does not need to have R or any of its dependences installed. Hence the user will deal with a standalone Shiny app. Inputs (digitalized survival curves, unit costs, posology, hazard ratios, discount rate) can be uploaded from a template spreadsheet. The INES application provides a seamlessly integrated package for estimating a set of parametric hazard functions for progression free and overall survival, selecting an appropriate function from this menu, and applying this as an input to a PSM to calculate mean costs and quality-adjusted life years. Examples are given that may serve as a tutorial. INES offers a rapid, flexible, robust and transparent tool for parametric survival analysis and calculating a PSM that can be used in many different contexts.


Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro.
Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest-activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophospholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlated with transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.


[Suppurative bacterial acute parotitis in adults. Clinic and microbiological findings in 10 admitted patients].
We report the clinic and microbiological findings that were obtained in 10 adult patients admitted by our ENT Service with diagnosis of suppurative bacterial acute parotitis. S. aureus and Streptococcus sp were the most isolated organisms. All the patients were treated by hidratation, endovenous antibiotic therapy sometimes modified according to the antibiogram results, analgesics and antiinflammatories with success. In 3 times it was necessary to drain the purulent collection and in one of them there was a retroauricular abscess secondary to sialoadenitis.


Caregiver burden among Chinese family caregivers of patients with lung cancer: A cross-sectional survey.
To investigate the status of caregiver burden and to identify the factors related to caregiver burden among Chinese family caregivers of patients with lung cancer. A cross-sectional design with convenience sampling was used in this study. Participants (N = 116) from the oncology inpatient ward at one teaching hospital in Chengdu were recruited from June 2015 to June 2016. The following measurement tools were used: a demographic questionnaire, the Social Support Rating Scale, the General Self-efficacy Scale, and the Zarit Burden Interview. Multiple linear regression analysis was used to identify factors associated with caregiver burden. The average ZBI score was 38.8 (SD = 13.4). Patient age (p < 0.01), medical and other types of insurance (p < 0.01), disclosure of the diagnosis to patients (p < 0.01), and social support of the caregiver (p < 0.05) were related to caregiver burden. Fifty-three percent of the variance in caregivers' burden was explained by these identified factors. Caregiver burden was higher among Chinese caregivers of lung cancer patients compared with the results of previous studies. Patient age, medical and other types of insurance, disclosure of cancer diagnosis to the patient, and caregivers' social support are factors associated with caregiver burden. The results suggest that social support, comprehensive healthcare insurance initiatives, and culture-based communication skill training are potential areas for future intervention.


Modeling and analysis of reservation frame slotted-ALOHA in wireless machine-to-machine area networks for data collection.
Reservation frame slotted-ALOHA (RFSA) was proposed in the past to manage the access to the wireless channel when devices generate long messages fragmented into small packets. In this paper, we consider an M2M area network composed of end-devices that periodically respond to the requests from a gateway with the transmission of fragmented messages. The idle network is suddenly set into saturation, having all end-devices attempting to get access to the channel simultaneously. This has been referred to as delta traffic. While previous works analyze the throughput of RFSA in steady-state conditions, assuming that traffic is generated following random distributions, the performance of RFSA under delta traffic has never received attention. In this paper, we propose a theoretical model to calculate the average delay and energy consumption required to resolve the contention under delta traffic using RFSA.We have carried out computer-based simulations to validate the accuracy of the theoretical model and to compare the performance for RFSA and FSA. Results show that there is an optimal frame length that minimizes delay and energy consumption and which depends on the number of end-devices. In addition, it is shown that RFSA reduces the energy consumed per end-device by more than 50% with respect to FSA under delta traffic.


[Malignant fibrous histiocytoma with granular cells].
This report describes a malignant tumor of soft tissue which combined granular cells with an histologic pattern of malignant fibrous histiocytoma. Immunohistological and ultrastructural studies were performed. Neo-plastic cells were devoid of S-100 Protein but contained lysozyme. Ultrastructural findings showed granular cells containing numerous lysosomes and non-granular cells exhibiting fibroblastic and histiocytic differentiations. This lesion prompts us to consider either a malignant granular cell tumor or a malignant fibrous histiocytoma.


Economic feasibility of solar water and space heating.
The economic feasibility in 1977 and 1978 of solar water and combined water and space heating is analyzed for single-family detached residences and multi-family apartment buildings in four representative U.S. cities: Boston, Massachusetts; Washington, D.C.; Grand Junction, Colorado; and Los Angeles, California. Three economic decision criteria are utilized: payback period, years to recovery of down payment, and years to net positive cash flow. The cost competitiveness of the solar systems compared to heating systems based on electricity, fuel oil, and natural gas is then discussed for each city, and the impact of the federal tax credit for solar energy systems is assessed. It is found that even without federal incentives some solar water and space heating systems are competitive. Enactment of the solar tax credit, however, greatly enhances their competitiveness. The implications of these findings for government tax and energy pricing policies are discussed.


Nutri-action analysis as a research strategy to improve nutrition information, education and communication interventions in Asia.
What is lacking in nutrition information, education and communication (IEC) work today is accurate knowledge about the processes which bring about beneficial nutritional behavior changes. In this paper, Nutri-action Analysis is proposed as a mechanism for nutrition planners to gain this knowledge and seek ways to improve the effectiveness of nutrition IEC interventions. It suggests that a more holistic and dynamic approach is necessary to conceptualize nutrition IEC and increase its effectiveness in bringing about changes in behaviors which lead to nutritional status improvement. Nutri-Action Analysis, as a research strategy, is illustrated by a three-stage procedure: (i) pre-action, (ii) action, and (iii) post-action. This process leads investigators to begin conducting a macro-analysis of nutrition IEC in general and within their specific contexts in order to understand the system and identify the best approach to be adopted for a nutrition IEC intervention in their particular context. What is discovered should then be tested in a community-based operational research study using both quantitative and qualitative data so that it is possible to subsequently conduct a synthesis focusing on process determinants.


Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation.
In kidney transplantation, complement activation was found to be induced by donor brain death, renal ischemia-reperfusion injury and allograft rejection. There are three known pathways of complement activation: the classical, lectin and the alternative pathway. The lectin complement pathway can be activated upon pattern recognition by mannan binding lectin (MBL) or ficolins (FCN). Single nucleotide polymorphisms (SNPs) in the genes encoding the lectin pathway proteins determine their functional activity and serum levels. The aim of this study was to investigate the role of the lectin gene profile of the donor and recipient on post-transplant outcome. A total of 12 functional SNPs in the MBL2, FCN2 and MBL-associated serine proteases 2 (MASP2) genes of 1271 donor-recipient pairs were determined. Lectin genotypic variants were analyzed for association with primary non-function (PNF), delayed graft function (DGF), biopsy proven acute rejection, death-censored graft survival and patient survival. Multivariate analyses found no association of donor and recipient MBL2 and MASP2 genotype with allograft outcome. Analysis of separate functional SNPs and haplotypes in the FCN2 gene of the donor and recipient did not reveal an association with transplant outcome. Also, the joint effect of the MBL2 and FCN2 genotype was not associated with allograft outcome.This study shows that the genetic profile of the lectin pathway of complement activation of the donor and recipient is not associated with allograft outcome after kidney transplantation.


The effect of the measures taken during the coronavirus pandemic on specialty trainees in obstetrics and gynaecology in the United Kingdom: an online questionnaire survey in one region.
The coronavirus pandemic (COVID-19) has had unprecedented effects on healthcare delivery. A 34-question online survey was sent to obstetrics and gynaecology trainees within the West Midlands to assess the impact of the pandemic on training, working practices and well-being. 101 responses were received from obstetrics and gynaecology trainees. Trainees reported a significant reduction in both elective and emergency surgeries as well as outpatient clinics. Over one third of respondents felt additional training time may be required following reduction of clinical opportunities. 44% of trainees felt their workload increased significantly. 55% of trainees felt the pandemic had a significant negative impact on their physical and mental well-being. Obstetrics and gynaecology trainees in the West Midlands have adapted to the challenges of the COVID-19 pandemic despite significant impact on their training, working practices and wellbeing. It is important to tailor training to improve trainees' education and combat lost training time during the pandemic. This should be considered for long-term shaping of the obstetrics and gynaecology training pathway.IMPACT STATEMENTWhat is already known on this subject? Little research is available about the impact of the COVID-19 pandemic on obstetrics and gynaecology trainees. This is the first study of its kind to assess the effect of the pandemic on obstetrics ang gynaecology trainees in the United Kingdom.What do the results of this study add? The results of this study have shown that obstetrics and gynaecology training has been heavily affected during the COVID-19 pandemic. There have been significant impacts on their training, working patterns and physical and mental wellbeing.What are the implications of these findings for clinical practice and/or further research? These findings can be used to mould the obstetrics and gynaecology training pathway based on the feedback given by the trainees during the pandemic. The survey questions can also be utilised as a framework for similar research projects across the United Kingdom Deaneries, among other specialties and around the world.


British and Pakistani children's understanding of death: cultural and developmental influences.
This study explored British and Pakistani 4- to 7-year-olds' (N = 188) understanding of death. The aim was to examine possible influences on the acquisition of the subcomponents of the death concept by investigating how they are understood by children of different ages and cultural and religious backgrounds. Three groups of children were compared: White British and British Muslim living in London, and Pakistani Muslim living in rural Pakistan. In line with previous research (Slaughter, 2005, Aust. Psychol., 40(3), 179), irreversibility of death was one of the first subcomponents to be acquired, while causality was the last. The two groups of British children shared many similarities in their understanding of inevitability, applicability, irreversibility, and cessation. Pakistani Muslim children understood irreversibility earlier than did children in both British groups. In all three cultural groups, children's responses demonstrated very limited understanding of causality. Our findings support the view that aspects of a mature understanding of death develop between the ages of 4 and 7 years and that the process of understanding death as a biological event is, to a great extent, universal. They also suggest that aspects of children's reasoning are influenced by culturally specific experiences, particularly those arising from living in rural versus urban settings.


Can routine offering of influenza vaccination in office-based settings reduce racial and ethnic disparities in adult influenza vaccination?
Influenza vaccination remains below the federally targeted levels outlined in Healthy People 2020. Compared to non-Hispanic whites, racial and ethnic minorities are less likely to be vaccinated for influenza, despite being at increased risk for influenza-related complications and death. Also, vaccinated minorities are more likely to receive influenza vaccinations in office-based settings and less likely to use non-medical vaccination locations compared to non-Hispanic white vaccine users. To assess the number of "missed opportunities" for influenza vaccination in office-based settings by race and ethnicity and the magnitude of potential vaccine uptake and reductions in racial and ethnic disparities in influenza vaccination if these "missed opportunities" were eliminated. National cross-sectional Internet survey administered between March 4 and March 14, 2010 in the United States. Non-Hispanic black, Hispanic and non-Hispanic white adults living in the United States (N = 3,418). We collected data on influenza vaccination, frequency and timing of healthcare visits, and self-reported compliance with a potential provider recommendation for vaccination during the 2009-2010 influenza season. "Missed opportunities" for seasonal influenza vaccination in office-based settings were defined as the number of unvaccinated respondents who reported at least one healthcare visit in the Fall and Winter of 2009-2010 and indicated their willingness to get vaccinated if a healthcare provider strongly recommended it. "Potential vaccine uptake" was defined as the sum of actual vaccine uptake and "missed opportunities." The frequency of "missed opportunities" for influenza vaccination in office-based settings was significantly higher among racial and ethnic minorities than non-Hispanic whites. Eliminating these "missed opportunities" could have cut racial and ethnic disparities in influenza vaccination by roughly one half. Improved office-based practices regarding influenza vaccination could significantly impact Healthy People 2020 goals by increasing influenza vaccine uptake and reducing corresponding racial and ethnic disparities.


Development, technical performance, and clinical evaluation of a NucliSens basic kit application for detection of enterovirus RNA in cerebrospinal fluid.
The combination of nucleic acid sequence-based amplification and electrochemiluminescence detection was used to develop an internally controlled, highly sensitive and specific assay for the detection of enterovirus (EV) RNA in cerebrospinal fluid (CSF). The analytical performance of the assay was determined using both in vitro-transcribed EV RNAs and viral culture isolates. The sensitivity of the assay was 10 EV RNA copies per amplification reaction. The assay detected all enteroviral isolates tested with no cross-reactivity to 21 nonenteroviral species, including rhinovirus and parechovirus. The clinical performance of the assay was evaluated by testing 992 CSF specimens collected from adult and pediatric patients. NucliSens EV results from a subset of 327 CSF samples were compared to viral culture of nasopharyngeal specimens and rectal swabs (n = 195) and/or CSF (n = 212). Of the 212 CSF samples, 96 samples were positive by either the NucliSens EV assay (94/96; 97.9%) or culture (63/96; 65.6%), and 61/96 (63.5%) were positive by both methods. The inclusion of an EV-specific internal control monitored the entire process, including the efficiency of nucleic acid extraction, amplification, and detection. In total, only five blood-clotted CSF samples (0.5%) were inhibited. The NucliSens EV assay demonstrated superior sensitivity over viral culture (P < 0.001), excellent specificity, clear delineation of positive samples, and minimal amplification inhibition.


A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications.
Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. No findings reached genome-wide significance (p = 8.4 × 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 × 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. We conclude that 1) meta-analyses of consumption data may contribute usefully to gene discovery; 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; and 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).


Sensorimotor integration in chronic stroke: Baseline differences and response to sensory training.
The integration of somatosensory information from the environment into the motor cortex to inform movement is essential for motor function. As motor deficits commonly persist into the chronic phase of stroke recovery, it is important to understand potential contributing factors to these deficits, as well as their relationship with motor function. To date the impact of chronic stroke on sensorimotor integration has not been thoroughly investigated. The current study aimed to comprehensively examine the influence of chronic stroke on sensorimotor integration, and determine whether sensorimotor integration can be modified with an intervention. Further, it determined the relationship between neurophysiological measures of sensorimotor integration and motor deficits post-stroke. Fourteen individuals with chronic stroke and twelve older healthy controls participated. Motor impairment and function were quantified in individuals with chronic stroke. Baseline neurophysiology was assessed using nerve-based measures (short- and long-latency afferent inhibition, afferent facilitation) and vibration-based measures of sensorimotor integration, which paired vibration with single and paired-pulse TMS techniques. Neurophysiological assessment was performed before and after a vibration-based sensory training paradigm to assess changes within these circuits. Vibration-based, but not nerve-based measures of sensorimotor integration were different in individuals with chronic stroke, as compared to older healthy controls, suggesting that stroke differentially impacts integration of specific types of somatosensory information. Sensorimotor integration was behaviourally relevant in that it related to both motor function and impairment post-stroke. Finally, sensory training modulated sensorimotor integration in individuals with chronic stroke and controls. Sensorimotor integration is differentially impacted by chronic stroke based on the type of afferent feedback. However, both nerve-based and vibration-based measures relate to motor impairment and function in individuals with chronic stroke.


Neurogenerative Disease Diagnosis in Cepstral Domain Using MFCC with Deep Learning.
Because underlying cognitive and neuromuscular activities regulate speech signals, biomarkers in the human voice can provide insight into neurological illnesses. Multiple motor and nonmotor aspects of neurologic voice disorders arise from an underlying neurologic condition such as Parkinson's disease, multiple sclerosis, myasthenia gravis, or ALS. Voice problems can be caused by disorders that affect the corticospinal system, cerebellum, basal ganglia, and upper or lower motoneurons. According to a new study, voice pathology detection technologies can successfully aid in the assessment of voice irregularities and enable the early diagnosis of voice pathology. In this paper, we offer two deep-learning-based computational models, 1-dimensional convolutional neural network (1D CNN) and 2-dimensional convolutional neural network (2D CNN), that simultaneously detect voice pathologies caused by neurological illnesses or other causes. From the German corpus Saarbruecken Voice Database (SVD), we used voice recordings of sustained vowel /a/ generated at normal pitch. The collected voice signals are padded and segmented to maintain homogeneity and increase the number of samples. Convolutional layers are applied to raw data, and MFCC features are extracted in this project. Although the 1D CNN had the maximum accuracy of 93.11% on test data, model training produced overfitting and 2D CNN, which generalized the data better and had lower train and validation loss despite having an accuracy of 84.17% on test data. Also, 2D CNN outperforms state-of-the-art studies in the field, implying that a model trained on handcrafted features is better for speech processing than a model that extracts features directly.


Gap detection by early-deafened cochlear-implant subjects.
Two studies investigating gap-detection thresholds were conducted with cochlear-implant subjects whose onset of profound hearing loss was very early in life. The Cochlear Limited multiple-electrode prosthesis was used. The first study investigated the effects of pulse rate (200, 500, and 1000 pulses/s) and stimulus duration (500 and 1000 ms) on gap thresholds in 15 subjects. Average gap thresholds were 1.8 to 32.1 ms. There was essentially no effect of pulse rate and for almost all subjects, no effect of stimulus duration. For two subjects, performance was poorer for the 1000-ms stimulus duration. The second study investigated the relationships between gap thresholds, subject variables, and speech-perception scores. Data from the first study were combined with those from previous studies [Busby et al., Audiology 31, 95-111 (1992); Tong et al., J. Acoust. Soc. Am. 84, 951-962 (1988)], providing data from 27 subjects. A significant negative correlation was found between age at onset of deafness and gap thresholds and most variability in gap thresholds was for the congenitally deaf subjects. Significant negative correlations were found between gap thresholds and word scores for open-set Bamford-Kowal-Bench (BKB) sentences in the auditory-visual condition and lipreading enhancement scores for the same test.


Consistent Thermo-Capillarity and Thermal Boundary Conditions for Single-Phase Smoothed Particle Hydrodynamics.
A model for capillary phenomena including temperature-dependency and thermal boundary conditions is presented in the numerical framework of smoothed particle hydrodynamics (SPH). The model requires only a single fluid phase and is therefore computationally more efficient than surface tension schemes which need an explicit fluid-fluid or fluid-gas interface. The model makes use of a surface identification mechanism based on the SPH renormalization tensor. All relevant properties of the continuum surface force (CSF) based approach, i.e., the delta function, normal vector and curvature, are calculated in a consistent manner. The model is parametrized by physical material properties and is successfully validated by means of a large set of analytical test cases. The applicability of the proposed model to more complex scenarios is demonstrated.


Corporate coalitions and policy making in the European Union: how and why British American Tobacco promoted "Better Regulation".
Over the past fifteen years, an interconnected set of regulatory reforms, known as Better Regulation, has been adopted across Europe, marking a significant shift in the way that European Union policies are developed. There has been little exploration of the origins of these reforms, which include mandatory ex ante impact assessment. Drawing on documentary and interview data, this article discusses how and why large corporations, notably British American Tobacco (BAT), worked to influence and promote these reforms. Our analysis highlights (1) how policy entrepreneurs with sufficient resources (such as large corporations) can shape the membership and direction of advocacy coalitions; (2) the extent to which "think tanks" may be prepared to lobby on behalf of commercial clients; and (3) why regulated industries (including tobacco) may favor the use of "evidence tools," such as impact assessments, in policy making. We argue that a key aspect of BAT's ability to shape regulatory reform involved the deliberate construction of a vaguely defined idea that could be strategically adapted to appeal to diverse constituencies. We discuss the theoretical implications of this finding for the Advocacy Coalition Framework, as well as the practical implications of the findings for efforts to promote transparency and public health in the European Union.


A Double-Blinded Randomized Trial to Compare the Effectiveness of Minimally Invasive Procedures Using Patient-Reported Outcomes.
The Institute of Medicine has included the comparison of minimally invasive surgical techniques in its research agenda. This study seeks to evaluate a model for the comparison of minimally invasive procedures using patient-reported outcomes. A double-blinded randomized controlled trial (NCT01489436) was conducted. Baseline data were obtained, standardized anesthesia was induced, and patients were randomized to single-port (SP) or 4-port (FP) laparoscopic cholecystectomy. Perioperative care was standardized. The outcomes were pain (Visual Analog Scale) on postoperative day 1 (primary) and quality of life (Patient-Reported Outcomes Measures Information System and Linear Analog Self-Assessment), serum cytokines, and heart rate variability (secondary). Analysis was intention to treat. Using identical occlusive dressings, patients and the outcomes assessor remained blinded until postoperative day 2. Fifty-five patients were randomized to each arm. There was no difference in demographics. Visual Analog Scale pain score on postoperative day 1 was significantly different from baseline in each group (SP: 1.6 ± 1.9 to 4.2 ± 2.4 vs FP: 1.8 ± 2.3 to 4.2 ± 2.2), but not different from each other (p = 0.83). Patients in the FP arm reported significantly less fatigue on postoperative day 7 than patients in the SP group (3.1 ± 2.1 vs 4.2 ± 2.2; p = 0.009). Fewer patients in the FP group required postoperative oral narcotics before discharge (40% vs 60%; p = 0.056). Cytokines levels and heart rate variability were similar between arms. In patients followed for >1 year, no difference in umbilical hernia rates was noted. Early postoperative quality of life data captured differences in fatigue, indicating improved recovery after FP within a controlled trial. Physiologic measures were similar, suggesting that the differences between SP and FP are minimal.


Mutant p53 as a guardian of the cancer cell.
Forty years of research have established that the p53 tumor suppressor provides a major barrier to neoplastic transformation and tumor progression by its unique ability to act as an extremely sensitive collector of stress inputs, and to coordinate a complex framework of diverse effector pathways and processes that protect cellular homeostasis and genome stability. Missense mutations in the TP53 gene are extremely widespread in human cancers and give rise to mutant p53 proteins that lose tumor suppressive activities, and some of which exert trans-dominant repression over the wild-type counterpart. Cancer cells acquire selective advantages by retaining mutant forms of the protein, which radically subvert the nature of the p53 pathway by promoting invasion, metastasis and chemoresistance. In this review, we consider available evidence suggesting that mutant p53 proteins can favor cancer cell survival and tumor progression by acting as homeostatic factors that sense and protect cancer cells from transformation-related stress stimuli, including DNA lesions, oxidative and proteotoxic stress, metabolic inbalance, interaction with the tumor microenvironment, and the immune system. These activities of mutant p53 may explain cancer cell addiction to this particular oncogene, and their study may disclose tumor vulnerabilities and synthetic lethalities that could be exploited for hitting tumors bearing missense TP53 mutations.


Efficacy and safety of an orodispersible vardenafil formulation for the treatment of erectile dysfunction in elderly men and those with underlying conditions: an integrated analysis of two pivotal trials.
Men with erectile dysfunction (ED) are typically older and have one or more underlying cardiovascular conditions. To determine the efficacy and safety of a new orodispersible tablet (ODT) formulation of vardenafil for the treatment of ED, and whether age, or the presence of underlying conditions affects treatment outcomes. This is an integrated analysis of data from two phase III, double-blind, multicenter, randomized, parallel-group, placebo-controlled studies that compared 10 mg on-demand vardenafil ODT with placebo in a general population of men with ED, stratified so that approximately 50% of patients were aged ≥ 65 years. Results were reported by age (<6 5 vs. ≥ 65 years) and presence/absence of diabetes, dyslipidemia, or hypertension. Primary measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3). Of the 701 men randomized (51% aged ≥ 65 years), 686 were included in the intent-to-treat population (placebo, n = 334; vardenafil ODT, n = 352). Vardenafil ODT was significantly superior to placebo for all primary efficacy measures, regardless of age, baseline ED severity, or underlying condition (P < 0.0001 for vardenafil vs. placebo for each endpoint). IIEF-EF scores and SEP2/3 success rates in older patients and men with underlying conditions were not significantly different to those of younger patients or men without underlying conditions. Adverse events (AEs) were mostly mild to moderate in severity, occurring with higher incidence in the vardenafil vs. placebo group. The most frequently reported drug-related AEs in the vardenafil group were headache, flushing, nasal congestion, dizziness, and dyspepsia, consistent with the known safety profile of phosphodiesterase type 5 inhibitors. Vardenafil ODT significantly improves erectile function in men with ED regardless of age, baseline ED severity, or underlying condition.


Restriction analysis of the ribosomal DNA internal transcribed spacer region of Culex restuans and mosquitoes in the Culex pipiens complex.
Members of the Culex pipiens Linn. complex in the eastern, southern, and central United States are the primary vectors of St. Louis encephalitis virus. Although species and subspecies in the complex can be identified as 4th-instar larvae and by characters on the male genitalia, adult females cannot be identified accurately. In this study a ribosomal DNA (rDNA) segment that includes the internal transcribed spacer region (ITS) was amplified from Culex pipiens pipiens Linn., Culex quinquefasciatus Say, and Culex restuans Theobald. The DNA was amplified from single abdomens or single legs. The amplified rDNA segment from Cx. restuans is 90 base pairs smaller than those from members of the Cx. pipiens complex. Ribosomal DNA was amplified separately from 3 individuals for each population of Cx. pipiens and analyzed by restriction digestion. Intrapopulation variation is seen, because for each population, bands are present that are common to all 3 individuals within the population, but are also unique to that population. These results indicate that this method may provide a means for distinguishing among the mosquitoes in the Cx. pipiens complex.


Attention and temporal discrimination: factors controlling responding under a cyclic-interval schedule.
Pigeons were exposed to a cyclic schedule in which each cycle was composed of twelve 1-min fixed intervals followed by four 3-min fixed intervals; four such cycles comprised an experimental session. The pigeons responded at a much higher average rate during the 3-min intervals than during the 1-min intervals. Other effects were a depression of responding during the first short interval of each cycle and a shortening of postreinforcement pause during the second short interval. The main effect is attributable to a relatively fixed pattern of responding after reinforcement; this pattern consisted in a pause of approximately constant duration followed by responding at an approximately constant rate until the next reinforcement, resulting in much higher average response rates during the longer interreinforcement intervals. The other effects seem attributable to relatively slight differences between the pattern of responding characteristic of later long intervals and the pattern during later short intervals of each cycle. A major implication is that the pigeon is largely insensitive to the sequential properties of many interval-reinforcement schedules. A description of interval-schedule "frustration" phenomena in terms of the inhibitory effects of reinforcement is discussed in relation to these results.


In vitro regulation of kidney 25-hydroxyvitamin D3-hydroxylase enzyme activities by vitamin D3 metabolites. Molecular specificity and mechanism of action.
An acute chick kidney tubule model was used to evaluate the molecular specificity of steroids which act to inhibit kidney 25-hydroxyvitamin D3-1-hydroxylase and induce 25-hydroxyvitamin D3-24-hydroxylase enzyme activities. Such hydroxylase-regulatory activity was confined to the vitamin D family of secosteroids. Vitamin D3 per se was not active. Rather, expression of hydroxylase-regulatory activity required acquisition of a C-25 hydroxyl grouping. Of the metabolites tested, 25-hydroxyvitamin D3 demonstrated the greatest hydroxylase-regulatory activity. Metabolites of 25-hydroxyvitamin D3 which contained hydroxyl groups at carbon atoms 1, or 24, or both, were also active in regulating the kidney hydroxylase enzymes. The hydroxylase-regulatory action of 1,25-dihydroxyvitamin D3 was blocked by inhibitors of RNA or protein synthesis, implicating a requirement for de novo protein synthesis. It was suggested that the regulatory process involves both hydroxylase-enzyme synthesis and turnover as well as enzyme-level modulation of endogenous enzyme activities.


Comparison of mechanical and optical properties of a newly marketed universal composite resin with contemporary universal composite resins: An in vitro study.
The purpose of this study was to evaluate the surface roughness, microhardness, color change, and translucency of a newly marketed universal nanohybrid composite resin (CR) (G-aenial A'CHORD) comparing with four contemporary universal CRs including two nanofilled (Filtek and Estelite Asteria) and two nanohybrid CRs (Charisma Dimond and Neo Spectra ST HV in vitro). Sixty-five specimens (8.0 mm × 2.0 mm) were fabricated (n = 13, per group). After finishing and polishing, specimens were subjected to surface roughness and microhardness tests. Color and translucency of the specimens were evaluated at baseline and after darkening with coffee solution at day 1 and day 7. A representative specimen from each group was investigated under scanning electron microscopy (SEM). Data was analyzed statistically (p < .05). There were significant differences among the groups in terms of surface roughness, microhardness, color, and translucency. The surface roughness was recorded as: Charisma Diamond > Neo Spectra ST HV, Filtek > Estelite Asteria, G-aenial A'CHORD, whereas Vickers Hardness number was as: Filtek, Charisma Diamond > Neo Spectra ST HV > G-aenial A'CHORD, Estelite Asteria. Color change was as: Charisma Diamond > Neo Spectra ST HV, Filtek, G-aenial A'CHORD > Estelite Asteria and the translucency was as: Neo Spectra ST HV > G-aenial A'CHORD, Filtek > Estelite Asteria, Charisma Diamond. SEM examinations revealed smooth surfaces for G-aenial A'CHORD, Neo Spectra ST HV and Estelite Asteria. Mechanical and optical properties of universal composite resins with different compositions show variations.


Bilateral microperc in a severe kyphoscoliosis.
Percutaneous nephrolithotomy is the standard modality for large renal calculi in normal and abnormal renal anatomic situations. This case report describes a 57-year-old male patient who presented with bilateral kidney stones and severe kyphoscoliosis. He had successfully been treated with a bilateral microperc technique.


[Diagnosing psychiatric disorders in people with (very) mild intellectual disabilities].
There is a good chance that you, as a psychiatrist, will come in to contact with patients who have a borderline or mild intellectual disability (50 > iq < 85). Referral to specialised care is not always an option and may not always be necessary. However, diagnosing psychiatric disorders in these patients can present challenges. To increase our knowledge about the diagnosing of psychiatric disorders in people with borderline or mild intellectual disabilities. In this article we describe some key considerations in making a diagnosis or a differential diagnosis of psychiatric disorders in people with an intellectual disability. RESULTS/ In the differential diagnosis of psychiatric symptoms and behavioral problems in persons with a borderline or mild intellectual disability, one needs to take into account the patient's cognitive and social emotional level and any possible underlying somatic conditions; in addition, one must search for the cause of the intellectual disability paying attention to the context and the facilities offered by the care system.


The more things change, the more things stay the same: maternal attitudes 3 to 18 months postpartum.
Becoming a parent precipitates changes in new mothers' psychological and social domains. Previous literature has focused exclusively on pregnancy and the early postpartum, but parenting is an evolving process, necessitating adaption to changing circumstances. We extended previous literature and investigate the changes in the postpartum from 3 to 18 months that occur in maternal attitudes. Using the Childbearing Attitudes Questionnaire, we collected data on mothers' ratings of maternal worries, self-efficacy, mother-infant bonding, relationship with the partner and interest in sex (n = 171 women). Data were analysed with a latent growth curve. Results demonstrated stability in all maternal attitudes after 3 months postpartum. Further, different maternal attitudes are affected by different variables. Maternal worries and self-efficacy are associated with parity, postpartum depression and child temperament. Interestingly, a negative evaluation of the relationship with the partner was only associated with breastfeeding status, while interest in sex was associated with parity, socio-economic status (SES) and depressive symptoms. Despite general stability, different maternal attitudes related to different sets of variables. These patterns of attitudes in relation to relevant variables are discussed in terms of the literature on self-efficacy and gender roles, with important implications for clinical interventions.


Lipid-related markers and cardiovascular disease prediction.
The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated. To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction. Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years). Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk. The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines. In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.


Lowered social motivation is associated with adolescent attention deficit hyperactivity disorder and social anxiety symptoms.
Difficulties in social skills are highly prevalent in children and adolescents with attention deficit hyperactivity disorder (ADHD), however, the reasons for these social difficulties are poorly understood. This study aimed to understand social motivation in children (aged 5-8) and adolescents (aged 13-17) with and without ADHD, and the relationship between social anxiety and social motivation in youth with ADHD. 204 parents of children and adolescents with and without ADHD completed online questionnaires on social motivation, social anxiety, and ADHD symptoms. Adolescents with ADHD had significantly lower social motivation than typically developing adolescents, and children with ADHD. Higher social anxiety significantly predicted lowered social motivation in participants with ADHD. These findings indicate a unique pattern of social motivation in ADHD, specifically a reduction during adolescence, reflecting social intervention inefficacy. Additionally, these findings establish a link between social motivation and social anxiety, suggesting that they may act as barriers to social intervention.