Pediatric interventions to support reading aloud: how good is the evidence?
Pediatricians and family practitioners increasingly provide free picture books and anticipatory guidance about reading aloud as part of routine health supervision for infants and young children, and arrange for volunteers to read aloud to children in the waiting rooms. These interventions comprise the Reach Out and Read (ROR) model, which has been adopted by more than 2000 clinical sites nationally. To date, 12 published studies have evaluated ROR and its variations, including three prospective, controlled trials. All but one have shown associations between ROR and increased reading aloud; additionally, four studies have linked program exposure to clinically meaningful increases in child language. Nonetheless, conclusive evidence of efficacy is lacking. This article provides a systematic, critical review of the literature, focusing on theoretical assumptions, issues of study design and measurement, and directions for future research.


Potential nonclassical effects of vitamin D in transplant recipients.
Vitamin D cannot be considered any more as only necessary to prevent rickets or osteomalacia. Calcitriol produced in the kidney is known to have classical endocrine phosphocalcic properties. More recently, vitamin D has been shown to play an important role in reducing the risk of many chronic diseases including type 2 diabetes mellitus, cardiovascular diseases, cancers, and autoimmune and infectious diseases. These effects may be secondary to local production of calcitriol and to its autocrine and paracrine actions on cellular proliferation and differentiation, apoptosis, insulin and renin secretion, interleukin and bactericidal proteins production. These pleiotropic effects are mostly documented by observational and experimental studies or small intervention trials that most often evaluated intermediate parameters. In renal transplant recipients, vitamin D insufficiency, defined as less than 30 ng/ml, is a frequent finding with more than 80% of patients displaying this profile. One may speculate that it could be a part of the explanation for the increased incidence of some complications observed after transplantation. Large intervention trials may therefore be of interest in this specific population.


Assessment of synthetic peptides of severe acute respiratory syndrome coronavirus recognized by long-lasting immunity.
In order to determine highly immunogenic severe acute respiratory syndrome coronavirus (SARS-CoV) epitope peptides capable of inducing long-lasting immunity, we first screened immunoglobulin-G (IgG) antibodies reactive to 197 different overlapping 15-mers from the SARS-CoV proteins in the sera of three infected patients. Forty-two peptides among them were reactive to the sera from all three patients. Consequently, we tested for the reactivity of these 42 peptides to patients' sera (n = 45) at 6-month post-infection. The significantly higher levels of IgG antibodies specific to three (S791, M207 and N161) of 42 peptides were detectable in the post-infection sera from 23 (51%), 27 (60%) and 19 (42%) of 45 patients, respectively. These three peptides, recognized by their long-lasting immunity, may provide a better understanding of the immunogenicity of SARS-CoV.


Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension.
HIV-infected patients receiving antiretroviral therapy often demonstrate excess visceral fat. A growth hormone-releasing factor, tesamorelin, may selectively reduce visceral fat in this population. We investigated the effects of tesamorelin (GHRH(1-44)) in HIV-infected patients with central fat accumulation. A 12-month study of 404 HIV-infected patients with excess abdominal fat in the context of antiretroviral therapy was conducted between January 2007 and October 2008. The study consisted of 2 sequential phases. In the primary efficacy phase (months 0-6), patients were randomly assigned to receive tesamorelin [2 mg subcutaneous (SC) every day] or placebo in a 2:1 ratio. In the extension phase (months 6-12), patients receiving tesamorelin were rerandomized to continue on tesamorelin (2 mg SC every day) or switch to placebo. Patients initially randomized to placebo switched to tesamorelin. Patients and investigators were blinded to treatment assignment throughout the study. The primary endpoint was visceral adipose tissue (VAT). Secondary endpoints included body image, IGF-I, safety measures, including glucose, and other body composition measures. VAT decreased by -10.9% (-21 cm(2)) in the tesamorelin group vs. -0.6% (-1 cm(2)) in the placebo group in the 6-month efficacy phase, P < 0.0001. Trunk fat (P < 0.001), waist circumference (P = 0.02), and waist-hip-ratio (P = 0.001) improved, with no change in limb or abdominal SC fat. Insulin-like growth factor-1 increased (P < 0.001), but no change in glucose parameters was observed. Patient rating of belly appearance distress (P = 0.02) and physician rating of belly profile (P = 0.02) were significantly improved in the tesamorelin vs. placebo-treated groups. The drug was well tolerated. VAT was reduced by approximately 18% (P < 0.001) in patients continuing tesamorelin for 12 months. The initial improvements over 6 months in VAT were rapidly lost in those switching from tesamorelin to placebo. Tesamorelin reduces visceral fat by approximately 18% and improves body image distress in HIV-infected patients with central fat accumulation. These changes are achieved without significant side effects or perturbation of glucose.


Deep Learning and Improved HMM Training Algorithm and Its Analysis in Facial Expression Recognition of Sports Athletes.
Facial expressions are an auxiliary embodiment of information conveyed in the communication between people. Facial expressions can not only convey the semantic information that people want to express but also convey the emotional state of the speaker at the same time. But for sports athletes in training and competitions, it is usually not convenient to communicate directly. This paper is based on deep learning and an improved HMM training algorithm to study the facial expression recognition of sports athletes. It proposes the construction of deep learning of multilayer neural network, and the rank algorithm is introduced to carry out face recognition experiments with traditional HMM and class-specific HMM methods. The experimental results show that, with the increase of rank value, the class-specific recognition rate is up to 90%, the detection rate is 98% and the time-consuming is 2.5 min, which is better than HMM overall.


Immune response to Giardia duodenalis.
The intestinal protozoan Giardia duodenalis is a widespread opportunistic parasite of humans and animals. This parasite inhabits the upper part of the small intestine and has a direct life cycle. After ingestion of cysts, which are the infective stage, the trophozoites emerge from the cysts in the duodenum and attach to the small intestinal mucosa of the host. Since the migration of trophozoites from the lumen of the intestine into surrounding tissues is an unusual occurrence, the immune response to Giardia remains localized. The identification of antigens that play a role in acquired immunity has been difficult because of the occurrence of antigenic variation and because, Giardia being an ubiquitous organism, it is possible that the antigenic profiles of isolates from different geographic areas will vary. Innate-immunity mechanisms play a role in the control and/or severity of the infection. Both humoral and cell-mediated immune responses play a role in acquired immunity, but the mechanisms involved are unknown. A variety of serological assays have been used to detect circulating antibodies in serum. Because of the biological characteristics of the parasite and the lack of suitable antigens, the sensitivity of serological assays remains poor. On the other hand, detection of antigens in feces of infected patients has met with success. Commercial kits are available, and they are reported to be more sensitive than microscopic examination for the detection of giardiasis on a single specimen.


Damage Characteristics of PELE Projectile with Gradient Density Inner Core Material.
The PELE (penetration with enhanced lateral efficiency) projectile is a new type of safe ammunition which can form a large number of fragments after perforating the target, and does not depend on any pyrotechnics. The damage characteristics of PELE projectile mainly include the penetration ability and fragmentation effect. There are many factors affecting the damage characteristics of PELE projectile, and this paper attempts to study the damage characteristics of PELE projectile, from the point of view of changing the single core material. Therefore, four different inner core combination types were designed in this paper, namely, zero gradient-I type (PE), zero gradient-II type (Al), positive gradient type (PE + Al), and negative gradient type (Al + PE). With the help of a more mature numerical simulation method, the studies were carried out from several aspects, such as the axial residual velocity of projectile, the radial scattering velocity of fragments, the radial scattering radius of fragments, and the residual length of projectile. The axial residual velocity of projectile can characterize the penetration ability of projectile, the radial scattering velocity and radial scattering radius of fragments can predict the damage area of fragments, and the residual length of projectile can reflect the fragment conversion rate of casing. The results indicate that the negative gradient inner core combination is superior to the other three combinations in terms of the penetration ability and fragmentation effect. Under the same impact velocity, the maximum radial velocity and radial scattering radius of fragments mainly depend on the front inner core material, and these two parameters will increase appropriately with the increase of the strength of front inner core material. Similarly, the residual length of projectile can be reduced, or the fragment conversion rate can be enhanced, by properly reducing the strength of rear inner core material. The conclusions obtained in this paper can provide a reference for engineering applications.


Time course of leukocyte accumulation in human muscle after eccentric exercise.
To investigate the time course of leukocyte accumulation in eccentric exercised human muscles and its relation to recovery of muscle function and soreness. Eleven young males performed 300 unilateral, maximal voluntary, eccentric actions with the musculus quadriceps femoris (30 degrees x s(-1)). Before and at regular intervals for 7 d after exercise, force-generating capacity was measured with maximal concentric knee extensions (60 degrees x s(-1)). Accumulation of radiolabeled (autologous) leukocytes was measured with scintigraphy. Biopsies from musculus vastus lateralis were obtained 0.5, 4, 8, 24, 96, and 168 h after exercise from both the exercised leg and the control leg. Muscle cross-sections were stained with antibodies against leukocytes (CD16 and CD68). Muscle soreness was rated on a visual analog scale. Immediately after exercise, the subjects' ability to generate force was reduced by 47 +/- 5%. Muscle function recovered slowly and was not fully restored after 1 wk. Radiolabeled leukocytes accumulated in the muscles during the first hour (3-24 h) after exercise, and leukocytes were at the same time observed histologically, primarily in the endomysium and perimysium. A part of the accumulated radiolabeled leukocytes appeared to be located within local blood vessels. The highest numbers of CD16(+) and CD68(+) cells were found 4 and 7 d after exercise. There was a positive correlation between accumulation of radiolabeled leukocytes and muscle weakness measured 1-3 d after exercise (r = 0.8, P < 0.05) and, surprisingly, a negative correlation between radiolabeled leukocyte accumulation and muscle soreness (r = -0.96, P < 0.01). Exercise-induced muscle damage initiated a rapid local inflammatory response that gradually increased over the next days. Halted recovery of muscle function was associated with local accumulation of leukocytes, whereas muscle soreness could not be explained by the presence of leukocytes.


Short-Term Creatine Supplementation May Alleviate the Malnutrition-Inflammation Score and Lean Body Mass Loss in Hemodialysis Patients: A Pilot Randomized Placebo-Controlled Trial.
Creatine supplementation has been proposed to alleviate muscle loss in various populations, but has not been investigated in hemodialysis (HD) patients. Thus, our objective was to evaluate whether creatine supplementation could attenuate the loss of lean body mass (LBM) and malnutrition-inflammation score (MIS) in HD patients. A randomized, placebo-controlled, double blind, parallel-design study included HD patients, of both sexes, aged 18-59 years. The patients were allocated to a Placebo Group (PG; n = 15; received maltodextrin, 1st week: 40 g/day and 2nd-4th weeks: 10 g/day) and a Creatine Group (CG; n = 15; received creatine plus maltodextrin, 1st week: 20 g/day of creatine plus 20 g/day of maltodextrin and 2nd-4th weeks: 5 g/day of creatine plus 5 g/day of maltodextrin). Pre and post the intervention, patients were evaluated for food intake, MIS, body composition and biochemical parameters. CG group attenuated the MIS (Pre: 5.57 ± 0.72 vs. Post: 3.85 ± 0.47 score, P = 0.003) compared with PG (Pre: 5.71 ± 0.97 vs. Post: 5.36 ± 0.95 score, P = 0.317) (supplement × time P = 0.017, effect size: 0.964). The change of LBM was greater in CG than in PG (CG: Δ0.95 vs PG: Δ0.13 kg). At post-intervention, 28.6% of PG patients presented LBM loss and 71.4% remain stable. In contrast, 14.4% of CG patients had LBM loss, 42.8% remain stable and 42.8% gained. Food intake and quality of life did not change. CG increased the BMI and gait speed in post-compared to pre-moment, but no difference among the groups. In HD patients, four weeks of creatine supplementation may alleviate the MIS as well as attenuate the LBM loss compared to placebo.


A nurse-based pilot program to reduce cardiovascular risk factors in a primary care setting.
To evaluate the effectiveness of a nurse-based cardiovascular disease (CVD) risk factor reduction program among patients at a primary care outpatient clinic. Preintervention and postintervention longitudinal, prospective pilot study to evaluate patients' achievement of CVD risk factor reduction. A total of 436 patients at a primary care clinic in suburban Minneapolis, Minnesota, were enrolled in 2 years; 286 patients were followed up with additional visits. The nurse intervention included comprehensive CVD risk assessment, patient education, and counseling. Algorithms guided the development of individualized care plans based on laboratory test values, blood pressure readings, tobacco use, and history of cardiovascular events. Physicians were consulted for serious changes in patients' medical conditions or for medication changes. Three measures were compared from baseline to the end of the program: blood pressure, low-density lipoprotein cholesterol levels, and tobacco use. Statistically significant reductions were achieved from baseline to the final nurse visit in systolic blood pressure (from 155.8 to 143.4 mm Hg), diastolic blood pressure (from 94.4 to 84.0 mm Hg), and dyslipidemia (low-density lipoprotein cholesterol, from 4.15 to 3.80 mmol/L [from 160 to 147 mg/dL]) (P < .001 for all). Of the 40 tobacco users who participated in the program, 12 discontinued use (30%). This pilot study provides preliminary evidence of the effectiveness of a nurse-based CVD risk reduction program. Further study is needed to target high-risk patients and to compare results in the nurse intervention group with those in patients receiving usual care.


Meralgia Paresthetica Successfully Treated with Palmithoylethanolamide.
Meralgia paresthetica (MP) is an uncommon entrapment mononeuropathy that is characterized by a sudden onset of paresthesia and numbness in the anterolateral surface of the thigh. Palmithoylethanolamide (PEA) is commonly used in the treatment of chronic pelvic pain and compressive neuropathies. Herein, we describe an otherwise healthy 28-year-old patient affected by posttraumatic MP for three months who was successfully treated with PEA (1200mg/day). Further studies are needed to better investigate the potential use of PEA as therapeutic drug in peripheral neuropathies, including MP, to avoid or delay more invasive surgical treatments.


The Association between Potential Exposure to Magazine Ads with Voluntary Health Warnings and the Perceived Harmfulness of Electronic Nicotine Delivery Systems (ENDS).
(1) Background: Several brands of electronic nicotine delivery systems (ENDS) carry voluntary health warning messages. This study examined how potential exposure to ENDS magazine ads with these voluntary health warnings were associated with the perceived harmfulness of ENDS. (2) Methods: Risk perception measures and self-reported exposure to ENDS ads were obtained from the 2014 Georgia State University (GSU) Tobacco Products and Risk Perceptions Survey of a nationally representative sample of U.S. adults. We examined the association between potential exposure to magazine ads with warnings and the perceived harms of ENDS relative to cigarettes, using binary logistic regressions and controlling for general ENDS ad exposure and socio-demographic characteristics. (3) Results: Potential exposure to ENDS magazine ads with warnings was associated with a lower probability of considering ENDS to be more or equally harmful compared to cigarettes, particularly among non-smokers (OR = 0.16; 95% CI: 0.04-0.77). In addition, ad exposure, ENDS use history, race/ethnicity, gender, education, and income were also associated with harm perceptions. (4) Conclusions: This study did not find evidence that magazine ads with warnings increased misperceptions that ENDS are equally or more harmful than cigarettes. With more ENDS advertisements carrying warnings, more research is needed to determine how the warnings in advertisements convey relative harm information to consumers and the public.


Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice.
Visceral leishmaniasis (VL) causes significant mortality and there is no effective vaccine. Previously, we have shown that genetically modified Leishmania donovani parasites, here described as live attenuated parasites, induce a host protective adaptive immune response in various animal models. In this study, we demonstrate an innate immune response upon infection with live attenuated parasites in macrophages from BALB/c mice both in vitro and in vivo. In vitro infection of macrophages with live attenuated parasites (compared to that with wild-type [WT] L. donovani parasites) induced significantly higher production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-12 [IL-12], gamma interferon [IFN-γ], and IL-6), chemokines (monocyte chemoattractant protein 1/CCL-2, macrophage inflammatory protein 1α/CCL-3, and IP-10), reactive oxygen species (ROS), and nitric oxide, while concomitantly reducing anti-inflammatory cytokine IL-10 and arginase-1 activities, suggesting a dominant classically activated/M1 macrophage response. The classically activated response in turn helps in presenting antigen to T cells, as observed with robust CD4(+) T cell activation in vitro. Similarly, parasitized splenic macrophages from live attenuated parasite-infected mice also demonstrated induction of an M1 macrophage phenotype, indicated by upregulation of IL-1β, TNF-α, IL-12, and inducible nitric oxide synthase 2 and downregulation of genes associated with the M2 phenotype, i.e., the IL-10, YM1, Arg-1, and MRC-1 genes, compared to WT L. donovani-infected mice. Furthermore, an ex vivo antigen presentation assay showed macrophages from live attenuated parasite-infected mice induced higher IFN-γ and IL-2 but significantly less IL-10 production by ovalbumin-specific CD4(+) T cells, resulting in proliferation of Th1 cells. These data suggest that infection with live attenuated parasites promotes a state of classical activation (M1 dominant) in macrophages that leads to the generation of protective Th1 responses in BALB/c mice.


Effect of Copper Foil Crystal Orientation on Graphene Quality Synthesized by Chemical Vapor Deposition.
Line defects such as wrinkles are believed to change the electrical properties of graphene. However, they are often observed in graphene grown via chemical vapor deposition; hence, it is important to study the impact of the substrate condition on graphene quality. In this work, graphene was synthesized on various copper domains with different crystal orientations and surface morphologies. During the synthesis process, three typical crystal orientations were obtained Cu(001), Cu(101), and Cu(111) showing different surface morphologies with various densities of wrinkles. Graphene wrinkles along with copper wrinkles were studied using atomic force microscopy and Kelvin probe force microscopy. The quality of graphene on different crystal orientations and morphologies was evaluated as well. It was found that different crystallographic orientations lead to different degrees of wrinkle and roughness. In addition, these wrinkle defects exhibited characteristic surface potential variations and the density of substrate wrinkles was closely associated with the uniformity of graphene and led to a disordered structure and low crystallinity.


Naming times for the Snodgrass and Vanderwart pictures in Spanish.
We present new Spanish norms for object familiarity and rated age of acquisition for 140 pictures taken from Snodgrass and Vanderwart (1980), together with data on visual complexity, image agreement, name agreement, word length (in syllables and phonemes), and five measures of word frequency. The pictures were presented to a group of 64 Spanish subjects, and oral naming latencies were recorded. In a multiple regression analysis, age of acquisition, object familiarity, name agreement, word frequency, and word length made significant independent contributions to predicting naming latency.


[Fibrinolysis in a regional hospital].
From January 1, 1989 to September 30, 1990, 116 patients with acute myocardial infarction were hospitalized at the regional hospital of Langenthal. Of those 116 patients, 27 (23%) were treated with intravenous streptokinase; in 12 of them (44%) CPK reached its peak within 6 hours after starting lysis; all were admitted within 4 hours after the beginning of chest pain. Of the fibrinolyzed patients, 18 (67%) had arrhythmias which needed to be treated. In 10 of these 18 patients CPK reached its peak within 6 hours. Of the 89 patients not treated with streptokinase, 27 (30%) did not fulfill the entry criteria of the protocol, 16 (18%) had exclusion criteria, and 46 (52%) had exclusion criteria as well as absent inclusion criteria. In only 4 patients (4.5%) was lysis not possible because they entered hospital later than 6 hours after the beginning of pain, and 8 patients (9%) exceeded the upper age limit of 70 years. Of the 116 patients, 13 (11.2%) died; 12 were not treated with streptokinase. Our study shows that fibrinolytic treatment with streptokinase is a safe and effective therapy for patients with acute myocardial infarction and can easily be performed in a regional hospital.


[Ectopic parotid gland in the mandible and masseter muscle].
An unusual case of double salivary ectopy of parotid gland is described into the masseter muscle and the mandibular ramus in a 45 year-old patient. He first was seen for a slow course tumefaction of the cheek. Imaging demonstrated the intramasseteric localization of the tumefaction and revealed a bone defect in the upper medial part of the mandibular ramus. The intramasseteric salivary ectopy has been confirmed by histologic examination.


Our early experiences with single-incision laparoscopic surgery: the first 32 patients.
Most of the laparoscopic surgeons have been attempting to reduce incisional morbidity and improve cosmetic outcomes by using fewer and smaller ports. Single-incision laparoscopic surgery (SILS) is a new laparoscopic procedure. Herein we would like to present our experiences. Between January 2009 and October 2009, data of the 32 patients who were operated through SILS are evaluated prospectively. There were 22 females and 10 males with a mean age of 45.1±14.8 years. Ten splenectomies for idiopathic thrombocytopenic purpura, 16 cholecystectomies for acute cholecystitis or asymptomatic gallstones, 3 appendectomies for acute appendicitis, one distal pancreatosplenectomy for Renal Cell Cancer metastases, 1 adrenalectomy for Conn Syndrome and 1 case of liver resection for hepatic adenoma were carried out. The most common splenectomy indication was idiopathic thrombocytopenic purpura, cholecystectomy indication was acute cholecystitis (n=8), and asymptomatic cholelithiasis (n=8), appendectomy indication was acute appendicitis, distal pancreatosplenectomy indication was renal cell cancer metastases, adrenalectomy indication was Conn syndrome and liver resection indication was left hepatic mass in between segments 1 and 2. SILS was carried out successfully in 31 patients. Only in 1 patient conversion was required owing to bleeding. All procedures were carried out through a 2-cm umbilical incision. There was no mortality and morbidity recorded. In experienced hands of minimally invasive surgeons, SILS incision laparoscopic surgery could be carried out successfully in a wide range of surgical operations. However, to be able to show the differences between Standard laparoscopic surgery and single SILS, prospective randomized comparative studies are required.


CT pelvimetry: the foveae are not an accurate landmark for the level of the ischial spines.
The most important distance measured during CT pelvimetry is the interspinous diameter of the pelvis as seen on axial scans, because most cases of obstructed labor occur at the level of the ischial spines. As the spines are difficult to identify on the anteroposterior digital scout radiograph, the fovea of the femoral head has been used as a landmark to determine the level of the appropriate axial slice. We assessed the accuracy of this landmark on CT scans in 23 women undergoing CT pelvimetry and in 20 nonpregnant women having pelvic CT scans. In each case the relationship between the level of the foveae and the level of the ischial spines was determined. True interspinous distances were measured and compared with the apparent interspinous distances at the level of the foveae. In none of the women were the ischial spines above the foveae. In 15 (65%) of 23 pregnant women and in seven (35%) of 20 nonpregnant women, the ischial spines were below the foveae. An incorrect scanning level led to an overestimation of interspinous distance by an average of 1.0 cm. We conclude that for CT pelvimetry, the fovea as seen on the anteroposterior digital radiograph is an inaccurate landmark for the level of the ischial spines.


Utility of Core-Shell Nanomaterials in the Catalytic Transformations of Renewable Substrates.
In recent years, core-shell nano-catalysts have received increasing attention due to their tunable properties and broad applications in catalysis. Control of the two components of these materials allows their catalytic properties to be tuned to various sustainable processes in synthetic and energy-related applications. This Concept article describes recent state-of-the-art core-shell materials and their application as heterogeneous catalysts for a range of sustainable catalytic transformations, focusing on two important classes of renewable substrates, CO2 and biomass. In the discussion, emphasis is directed to the role of the constituent parts of the core-shell structure and how they can be manipulated to enhance activity.


[Superficial bladder cancer: prophylaxis of recurrence and progression].
Superficial bladder cancer has a good prognosis compared with invasive bladder cancer. However, recurrence of the tumor is frequent and tumor stage and/or grade progress at the time of recurrence in many cases. Intravesical chemotherapy has been employed as a prophylactic method after trans-urethral resection (TUR). Although intravesical chemotherapy has been proved to be effective in delaying the first recurrence of tumor after TUR, it cannot improve the ultimate prognosis of superficial bladder cancer. Many primary, solitary, non-invasive (Ta) and grade 1 tumors do not recur or progress in stage and grade. In these cases, prophylactic intravesical chemotherapy is not essential. Bacille Calmette-Guérin (BCG) should be considered superior overall, to any chemotherapeutic agents. Comparative studies will give information about the best clinical schedule for the treatment of superficial bladder cancer.


Contribution of blood lactate to the energy expenditure of weight training.
Bioenergetic interpretations of energy transfer specify that rapid anaerobic, substrate-level adenosine triphosphate (ATP) turnover with lactate production is not appropriately represented by an oxygen uptake measurement. Two types of weight training, 60% of 1 repetition maximum (1RM) with repetitions to exhaustion and 80% of 1RM with limited repetitions, were compared to determine if blood lactate measurements, as an estimate of rapid substrate-level ATP turnover, provide a significant contribution to the interpretation of total energy expenditure as compared with oxygen uptake methods alone. The measurement of total energy expenditure consisted of blood lactate, exercise oxygen uptake, and a modified excess postexercise oxygen consumption (EPOC); oxygen uptake-only measurements consisted of exercise oxygen uptake and EPOC. When data from male and female subjects were pooled, total energy expenditure was significantly higher for reps to exhaustion (arm curl, +27 kJ; bench press, +27 kJ; leg press, +38 kJ; p < 0.03) and limited reps (arm curl, +12 kJ; bench press, +23 kJ; leg press, + 24 kJ; p < 0.05) when a separate measure of blood lactate was part of the interpretation. When the data from men and women were analyzed separately, blood lactate often made a significant contribution to total energy expenditure for reps to exhaustion (endurance-type training), but this trend was not always statistically evident for the limited reps (strength-type training) protocol. It is suggested that the estimation of total energy expenditure for weight training is improved with the inclusion, rather than the omission, of an estimate of rapid anaerobic substrate-level ATP turnover.


Blood coagulation and fibrinolysis during normal pregnancy.
Fifty-six pregnant women (gestational age 6-40 weeks) were evaluated for their coagulation activation (fibrin monomers and thrombin-antithrombin III complex) and for their fibrinolysis profile by determining tissue plasminogen activator, plasminogen activator inhibitor, plasminogen, alpha 2-antiplasmin and D-dimer. Fibrin monomers and thrombin-antithrombin III complexes were found to be significantly increasing with gestational age. All the fibrinolytic parameters showed a steady growth with the progress of the pregnancy, with the exception of tissue plasminogen activator which showed a significant decrease with gestational age, but mainly within the reference range. These results suggest a stimulation of the coagulation system and an activation of fibrinolysis with ongoing pregnancy, although the increasing alpha 2-antiplasmin and plasminogen levels and the decreasing tissue plasminogen activator concentrations do not conform to this trend.


Adaptation of yeasts Saccharomyces cerevisiae and Brettanomyces bruxellensis to winemaking conditions: a comparative study of stress genes expression.
Brettanomyces is the major microbial cause for wine spoilage worldwide and causes significant economic losses. Like Saccharomyces cerevisiae, it is well adapted to winemaking, but molecular pathways involved in this acclimatization are still unknown. In this work, we report a time-scale comparison between the two yeasts coping with alcoholic fermentation. Orthologs of some well-characterized stress genes of S. cerevisiae were searched by sequence alignment in the Dekkera/Brettanomyces partial genome; nine genes were finally selected on the basis on their similarity and involvement in adaptation to wine. Transcript analysis during a model grape juice fermentation indicates that a subset of genes (i.e., ATP1, ERG6, VPS34) shows peculiar expression patterns in Brettanomyces bruxellensis but also that some common regulations of stress response exist between the two yeasts, although with different timing (i.e., for MSN4, SNF1, HSP82, NTH1). This suggests that B. bruxellensis efficient survival in such challenging conditions is due to mechanisms unique to it, together with a conserved yeast stress response. This study, although limited by the poor genetic data available on B. bruxellensis, provides first insights into its gene expression remodeling in winemaking and opens new frames for further investigations.


Exotoxin-encoding gene content in community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus.
Reports of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) causing hospital infections are increasing, and it is questionable whether the existing molecular definition of CA-MRSA is suitable for the characterization of all strains involved. The 821 methicillin-resistant S. aureus (MRSA) isolates recovered from patients in Health Region East, Norway during the period 1991-2006 were characterized by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene typing, and their content of exotoxin-encoding genes. Cluster analysis based on exotoxin-encoding gene content was performed to separate the MRSA isolates into valid clusters with respect to microbiological characteristics. The analysis gave a four-cluster structure, and the four toxin clusters differed in the genetic lineages they included and in the diversity of the genetic lineages. A few genetic lineages were present in several toxin clusters. These results support the theory that mobile genetic elements encoding virulence genes do not move randomly among genetic lineages, but are restricted by the clonal lineages' genetic background. Using the molecular criteria, MLST type, SCCmec type and the presence of the lucS/F-Panton-Valentine leukocidin (PVL) gene to define a CA-MRSA isolate, it was found that the CA-MRSA isolates mainly grouped together in two toxin clusters with a low prevalence of exotoxin-encoding genes. Statistical analyses supported the conclusion that toxin clusters with CA-MRSA genetic lineages were characterized by a low prevalence of exotoxin-encoding genes, whereas toxin clusters with hospital-acquired MRSA genetic lineages were characterized by a higher prevalence of exotoxin-encoding genes.


Capillary supply and cardiac performance in the rabbit after chronic dobutamine treatment.
Growth of capillaries in the adult heart can occur after long term vasodilator treatment. This study investigated the effects of increased stroke volume and/or force of contraction in addition to coronary blood flow on myocardial capillary growth. Coronary blood flow, cardiac function, and capillary supply were evaluated after chronic treatment with the inotrope dobutamine, at a dose shown to increase contraction force (dP/dt) acutely by 20% (p less than 0.05) and coronary blood flow by 60% (NS). New Zealand Red rabbits received dobutamine (20 micrograms.kg-1.min-1 by intravenous infusion) for 2 weeks prior to measurements, under pentobarbitone anaesthesia, of coronary blood flow by radiolabelled microspheres, left ventricular dP/dtmax and maximum noradrenaline induced cardiac work, computed from cardiac output (thermodilution) and blood pressure. Capillary density.mm-2 was estimated in frozen 12 microns sections of left ventricular myocardium stained for alkaline phosphatase. Capillary density was 29% greater after 2 weeks dobutamine infusion than in saline infused controls, which exceeds increases observed after longer infusions of vasodilators alone. Cardiac function was improved; maximum stroke work was significantly higher, stroke volume capacity larger, and dP/dt increased more during noradrenaline challenge. Coronary blood flow was unchanged in dobutamine treated hearts, hence efficiency of utilisation of coronary flow in terms of work was enhanced. Heart to body weight ratio was also greater after dobutamine, at 0.238(SEM 0.008) v 0.206(0.120), p less than 0.05. Greater capillary growth can be elicited in the heart by increased stretch and/or force of contraction of myocytes in addition to moderate changes in blood flow than by increased blood flow alone. Chronic dobutamine treatment induced adaptive enhancement of maximal cardiac work capacity.


Usability and training differences between two personal insulin pumps.
The purpose of this study was to determine if there were usability and training differences between the Medtronic MiniMed Paradigm Revel Insulin Pump and the Tandem Diabetes Care t:slim Insulin Pump during use by representative users, performing representative tasks, in a simulated use environment. This study utilized a between-subjects experimental design with a total of 72 participants from 5 sites across the United States. Study participants were randomized to either the Revel pump group or the t:slim Pump group. Participants were 18 years of age or older and managed their diabetes using multiple daily insulin injections. Dependent variables included training time, training satisfaction, time on task, task failures, System Usability Scale (SUS) ratings, perceived task difficulty, and a pump survey that measured different aspects of the pumps and training sessions. There was a statistically significant difference in training times and error rates between the t:slim and Revel groups. The training time difference represented a 27% reduction in time to train on the t:slim versus the Revel pump. There was a 65% reduction in participants' use error rates between the t:slim and the Revel group. The t:slim Pump had statistically significant training and usability advantages over the Revel pump. The reduction in training time may have been a result of an optimized information architecture, an intuitive navigational layout, and an easy-to-read screen. The reduction in use errors with the t:slim may have been a result of dynamic error handling and active confirmation screens, which may have prevented programming errors.


Informed Consent for Bedside Procedures in Pediatric and Neonatal ICUs: A Nationwide Survey.
Primary objectives were to discover current practices of informed consent for bedside procedures in the PICU and neonatal ICU and how trainees learn to obtain consent. We also attempted to gauge if program directors felt that one method of consent was subjectively superior to another in the way it fulfilled established ethical criteria for informed consent. An online anonymous survey. Participants were asked about how and by whom informed consent is currently obtained, training practices for fellows, and attitudes about how different consent methods fulfill ethical criteria. All U.S. fellowship programs for neonatology (n = 98) and pediatric critical care (n = 66) in the fall of 2017. Neonatal and pediatric critical care fellowship program directors. None. The overall response rate was 50% (82 of 164). The most common method for obtaining consent in both ICU types was via a written, separate (procedure-specific) consent (63% neonatal ICUs, 83% PICUs); least common was verbal consent (8% neonatal ICUs and 6% PICUs). Fellows were reported as obtaining consent most often (91%), followed by mid-level practitioners (71%) and residents (66%). Residents were one-fifth as likely to obtain consent in the PICU as compared with the neonatal ICU. Sixty-three percent of fellowship directors rated their programs as "strong" or "very strong" in preparing trainees to obtain informed consent. Twenty-eight percent of fellowship directors reported no formal training on how to obtain informed consent. Most respondents' ICUs use separate procedure-specific written consents for common bedside procedures, although considerable variability exists. Trainees reportedly most often obtain informed consent for procedures. Although most fellowship directors report their program as strong in preparing trainees to obtain consent, this study reveals areas warranting improvement.


Controlling Charge-Transport in Metal-Organic Frameworks: Contribution of Topological and Spin-State Variation on the Iron-Porphyrin Centered Redox Hopping Rate.
Metal-organic frameworks (MOFs) are an emerging class of compositions for electro- and photoelectrocatalytic energy conversion processes. Understanding and improving the charge-transport processes within these high surface area molecular redox catalyst assemblies are critical since the charge carrier conductivity is inherently limited in MOFs. Here, we examine a series of four chemically identical but structurally different hydrolytically robust ZrIV-MOFs constructed from tetrakis(4-carboxyphenyl)porphyrinato iron(III), TCPP(FeIII) to understand how their topological construction affects redox hopping conductivity. While a structural variation fixes center-to-center distances to define the hopping rate, we probe that altering the central metal spin-state can further tune the TCPP(FeIII/II) reorganization energy of the self-exchange process. Significant increase in the hopping rate was observed upon axial coordination of 1-methyl imidazole (MIM), which converts a weakly halide bound high-spin (HS) TCPP(FeIII/II) to the six-coordinated low-spin (LS) complex. Our electrochemical and resonance Raman data reveal that pore geometry that defines the Fe-Fe distance in these frameworks dictate the steric demand to accommodate two MIM-molecules, and thus, the population of LS vs HS species is a function of topology in the presence of an excess ligand.


The Potential Effect of Insulin on AChE and Its Interactions with Rivastigmine In Vitro.
There is no definite cure for Alzheimer's disease (AD) due to its multifactorial origin. Drugs that inhibit acetylcholinesterase (AChE), such as rivastigmine, are promising symptomatic treatments for AD. Emerging evidence suggests that insulin therapy can hinder several aspects of AD pathology. Insulin has been shown to modify the activity of AChE, but it is still unknown how insulin and AChE interact. Combination therapy, which targets several features of the disease based on existing medications, can provide a worthy therapy option for AD management. However, to date, no studies have examined the potential interaction of insulin with AChE and/or rivastigmine in vitro. In the present study, we employed the Response Surface Methodology (RSM) as an in vitro assessment to investigate the effect of insulin on both AChE activity and rivastigmine inhibitory action using a common spectrophotometric assay for cholinesterase activity, Ellman's method. Our results showed that insulin, even at high concentrations, has an insignificant effect on both the activity of AChE and rivastigmine's inhibitory action. The variance of our data is near zero, which means that the dispersion is negligible. However, to improve our understanding of the possible interaction of insulin and rivastigmine, or its target AChE, more in silico modelling and in vivo studies are needed.


Muscle regeneration during hindlimb unloading results in a reduction in muscle size after reloading.
The hindlimb-unloading model was used to study the ability of muscle injured in a weightless environment to recover after reloading. Satellite cell mitotic activity and DNA unit size were determined in injured and intact soleus muscles from hindlimb-unloaded and age-matched weight-bearing rats at the conclusion of 28 days of hindlimb unloading, 2 wk after reloading, and 9 wk after reloading. The body weights of hindlimb-unloaded rats were significantly (P < 0.05) less than those of weight-bearing rats at the conclusion of hindlimb unloading, but they were the same (P > 0.05) as those of weight-bearing rats 2 and 9 wk after reloading. The soleus muscle weight, soleus muscle weight-to-body weight ratio, myofiber diameter, number of nuclei per millimeter, and DNA unit size were significantly (P < 0.05) smaller for the injured soleus muscles from hindlimb-unloaded rats than for the soleus muscles from weight-bearing rats at each recovery time. Satellite cell mitotic activity was significantly (P < 0.05) higher in the injured soleus muscles from hindlimb-unloaded rats than from weight-bearing rats 2 wk after reloading, but it was the same (P > 0.05) as in the injured soleus muscles from weight-bearing rats 9 wk after reloading. The injured soleus muscles from hindlimb-unloaded rats failed to achieve weight-bearing muscle size 9 wk after reloading, because incomplete compensation for the decrease in myonuclear accretion and DNA unit size expansion occurred during the unloading period.


Melanocortin-5 receptor: a marker of human sebocyte differentiation.
Melanocortin receptors (MC1R-MC5R) and their ligands (melanocyte-stimulating hormone (MSH) and adrenocorticotrophin hormone (ACTH)) have been shown to influence physiological functions of cells and organs, including exocrine glands. Since relatively little is known about MC5R expression and function in the human sebaceous gland, we examined expression of MC5R by immunohistochemistry and RT-PCR in human sebaceous cells in vivo and in vitro. In human skin, MC5R was detected only in differentiating, lipid-laden sebaceous cells but not in basal, undifferentiated sebaceous cells. Similarly, in cultured human sebocytes MC5R was only detectable at the onset of differentiation and in fully differentiated cells displaying prominent lipid granules. The lipid profile of the cultured and differentiated human sebocytes was shown to be human sebum-specific using (14)C-acetate labeling and high performance thin layer chromatography. Our studies suggest that MC5R is a marker of human sebocyte differentiation.


Ankle intrinsic stiffness is modulated by postural sway.
Dynamic ankle stiffness, which defines the relationship between joint position and the torque acting about it, determines the joint resistance to external perturbations. The contribution of joint stiffness to stance control is usually assumed to be constant; however, the stiffness may be modulated due to the ongoing sway during stance. This paper describes the results of the direct estimation of ankle intrinsic stiffness and its modulation with background torque during stance. Three subjects stood on a standing apparatus, while subjected to pulse perturbations of ankle position. The angle of center of mass, and ankle torque and angle were measured and individual torque responses to each position perturbation were analyzed. Each response lasted 90 milliseconds, where the mean of the torque record in the first 25 milliseconds was considered as its background torque. Ensemble of the responses with similar background torques were used to estimate the joint intrinsic stiffness. The estimated parameters showed that elastic element of the ankle intrinsic stiffness varied significantly (by a factor of 3) with background torque, i.e. the higher the background torque, the higher the stiffness. Thus ankle stiffness is not constant but varies greatly with postural sway.


Clinical observation of neoadjuvant chemotherapy with pyrotinib plus trastuzumab in HER2-positive breast cancer: a cohort study.
Pyrotinib is a new small-molecule tyrosine kinase inhibitor (TKI). However, the efficacy of pyrotinib in neoadjuvant therapy for HER2-positive breast cancer is unknown. This paper is a population-based cohort study, and the purpose is to evaluate the efficacy and safety of pyrotinib plus trastuzumab in a neoadjuvant setting for HER2-positive early or locally advanced breast cancers, and to compare it with that of pertuzumab plus trastuzumab. This cohort study included 166 patients with HER2-positive breast cancer who received neoadjuvant therapy and underwent surgery. Case groups: Group I: 63 patients received pyrotinib + trastuzumab; Group II: 50 patients received pertuzumab + trastuzumab. The control group consisted of 53 patients treated with trastuzumab alone in combination with neoadjuvant chemotherapy. Univariate logistic regression analysis was applied. Enumeration data were processed by Fisher's exact test. The total pathological complete response (tpCR) rate of Group I was 63.49% (40/63); the breast pathological complete response (bpCR) rate was 76.19% (48/63); and the objective response rate (ORR) was 100% (63/63). Compared with the tpCR rate of 54.00% (27/50), bpCR rate of 58.00% (29/50), and ORR 100% (50/50) of Group II, there was no statistical difference. Regarding adverse events (AEs), diarrhea (n=56, 88.89%) was the most frequent in the group I, including 7 participants who developed grade 3 diarrhea (11.11%), followed by leukopenia (n=48, 76.19%). In the meantime, there was only 1 patient experienced grade IV thrombocytopenia. Hormone receptor (HR)-negative patients were more likely to reach tpCR as compared to HR-positive patients (61.54% vs. 37.50%, P=0.002, 95% CI: 1.423 to 4.997), and the tpCR rate of tumor, node, metastasis (TNM) stage III 37.04% (20/54) was significantly lower than that of stage II 54.46% (61/112), which was statistically significant (P=0.048, 95% CI: 1.064 to 4.041). No recurrence or metastasis was found during short-term follow-up. Pyrotinib plus trastuzumab combined with neoadjuvant chemotherapy showed good short-term efficacy in HER2-positive breast cancer, and the AEs developed were all manageable. More sample data is required to further support the comparison with pertuzumab plus trastuzumab.


2-Acylamino-6-pyridones: breaking of an intramolecular hydrogen bond by self-association and complexation with double and triple hydrogen bonding counterparts. Uncommon steric effect on intermolecular interactions.
2-Acylamino-6-pyridones (acyl = RCO, where R = Me, Et, i-Pr, t-Bu, and 1-adamantyl) were previously characterized by X-ray diffractometry and solid-state NMR techniques by us. One of these compounds was used recently in organocatalysis. The series is now studied in solution and by computational methods recommended for noncovalent interactions (DFT/M05). These compounds showed interesting behavior during dilution and titration experiments monitored by (1)H NMR. 2-Acylamino-6-pyridones change their conformation at higher concentrations, forming double hydrogen-bonded dimers and trimers in which an uncommon steric effect is observed. To the best of our knowledge, this is the first example of such behavior of hydrogen-bonded molecules. Heterocomplexation of the studied compounds happens via double or triple hydrogen bonding, depending on the properties of the counterpart. The computation data support and explain the effects observed experimentally, including the tautomeric, closed/open form equilibrium and intermolecular interaction preferences.


Achieving optimal SERS through enhanced experimental design.
One of the current limitations surrounding surface-enhanced Raman scattering (SERS) is the perceived lack of reproducibility. SERS is indeed challenging, and for analyte detection, it is vital that the analyte interacts with the metal surface. However, as this is analyte dependent, there is not a single set of SERS conditions that are universal. This means that experimental optimisation for optimum SERS response is vital. Most researchers optimise one factor at a time, where a single parameter is altered first before going onto optimise the next. This is a very inefficient way of searching the experimental landscape. In this review, we explore the use of more powerful multivariate approaches to SERS experimental optimisation based on design of experiments and evolutionary computational methods. We particularly focus on colloidal-based SERS rather than thin film preparations as a result of their popularity. © 2015 The Authors. Journal of Raman Spectroscopy published by John Wiley & Sons, Ltd.


"Turn-of-the-Nut" Method Is Not Appropriate for Use in Cancellous Bone.
The level to which bone screws are tightened is determined subjectively by the operating surgeon. It is likely that the tactile feedback that surgeons rely on is based on localized tissue yielding, which may predispose the screw-bone interface to failure. A limited number of studies have investigated the ratio between clinical tightening torque and stripping torque. The purpose of this study was to measure, for the first time, the ratio between yield torque (T yield) and stripping torque (T max) during screw insertion into the cancellous bone and to compare these torques with clinical levels of tightening reported in the literature. Additionally, a rotational limit was investigated as a potential end point for screw insertion in cancellous bone. A 6.5-mm outer diameter commercial cancellous bone screw was inserted into human femoral head specimens (n = 89). Screws were inserted to failure, while recording insertion torque, compression under the screw head, and rotation angle. The median, interquartile ranges, and coefficient of variation were calculated for each of the following parameters: T yield, T max, T yield/T max, slope, T plateau, and rotation angle. The median ratio of T yield/T max and rotation angle was 85.45% and 96.5 degrees, respectively. The coefficient of variation was greatest for the rotation angle compared with the ratio of T yield/T max (0.37 vs. 0.12). The detection of yield may be a more precise method than the rotation angle in cancellous bone; however, bone-screw constructs that exhibit a T yield close to T max may be more susceptible to stripping during insertion. Future work can identify factors that influence the ratio of T yield/T max may help to reduce the incidence of screw stripping.


Human papillomavirus related diseases in Malaysians.
The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.


Development of transgenic rice plants overexpressing the Arabidopsis H+/Ca2+ antiporter CAX1 gene.
The gene of the Arabidopsis thaliana H+/Ca2+ transporter, CAX1 (cation exchanger 1) was introduced into Japonica cultivars of rice (Ilpumbyeo) by Agrobacterium-mediated transformation, and a large number of transgenic plants were produced. The neomycin phosphotransferase II (NPTII) gene was used as a selectable marker. The activity of neomycin phosphotransferase could be successfully detected in transgenic rice callus. The introduction of the CAX1 gene was also proven by PCR using CAX1-specific oligonucleotide primers in regenerated plants. Stable integration and expression of the CAX1 gene in T0 plants and T1 progeny were confirmed by DNA hybridization, Northern blot analysis, and luminescent analysis.


Investigation of the Efficacy and Safety of Topical Vibration Anesthesia to Reduce Pain From Cosmetic Botulinum Toxin A Injections in Chinese Patients: A Multicenter, Randomized, Self-Controlled Study.
Vibration has been proved to be effective to reduce pain during facial cosmetic injections, but it has not been studied in Chinese patients. To investigate the efficacy and safety of vibration for pain reduction associated with cosmetic botulinum toxin A (BTX-A) injections in Chinese patients. In this prospective, randomized, split-face and right-left, self-controlled study, 53 patients received BTX-A injections for rhytid reduction, lower face, shoulder, and leg reshaping. Injections were given in a split-face and right-left design randomly assigned. A vibration stimulus was coadministered with BTX-A injections on one side, whereas the other side received BTX-A injections only. Patients completed a questionnaire immediately after treatment and were followed up 2 weeks later. A visual analog scale of pain sensation was statistically analyzed. The patients experienced both clinically and statistically significant pain reduction when a vibration was coadministered with injections. Patients reported less pain on the treated side compared with the control side. Overall, 75% of patients preferred to receive vibration with their next treatment. No adverse events were reported. Vibration is an effective and safe way to reduce pain during cosmetic BTX-A injections and may have applications in other cosmetic procedures.


[Expression and significance of PD-1 and PD-L1 in the specimens of epithelial ovarian cancer].
Objective: To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. Methods: The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ,included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. Results: (1) PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC (type Ⅱ) than those of low-grade (type Ⅰ) and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (P<0.05). Conclusions: The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.


Novel Robotic Platforms for the Accurate Sampling and Monitoring of Water Columns.
The hydrosphere contains large amounts of suspended particulate material, including living and non-living material that can be found in different compositions and concentrations, and that can be composed of particles of different sizes. The study of this particulate material along water columns plays a key role in understanding a great variety of biological, chemical, and physical processes. This paper presents the conceptual design of two patented robotic platforms that have been conceived for carrying out studies of water properties at desired depths with very high accuracy in the vertical positioning. One platform has been specially designed for operating near to a reservoir bottom, while the other is intended to be used near the surface. Several experimental tests have been conducted in order to validate the proposed approaches.


Evaluation of diagnostic utility of imprint cytology in paediatric renal tumours with special references to Ki 67 proliferative marker.
Pediatric renal neoplasms comprise about 7%-8% of all neoplasms in children. Wilms tumour (WT) is the most common among pediatric renal tumours. The study was undertaken to study the epidemiological occurrence of pediatric renal tumours in a tertiary care hospital and to ascertain the validity and reliability of touch smear imprint cytology in intraoperative diagnosis of renal tumours and correlate with subsequent histopathological diagnosis and to assess the expression of proliferation marker Ki-67 in different components and stages of WT. It was a single-institution-based prospective and observational study, conducted for 2 years (from October 2013 to September 2015) in the department of pathology at our hospital. A total of fifty cases were enrolled in this study, all were below 15 years of age. Imprint cytology showed sensitivity, specificity, and diagnostic accuracy of 83%, 98%, and 95.74%, respectively, in diagnosing benign and malignant renal tumours. There was statistically significant correlation of imprint cytology with confirmatory histopathological examination of excision specimen (P < 0.001). Immunohistochemical analysis of Ki-67 was done in all WT cases. Epithelial component had higher proliferative index than blastemal component with P = 0.0082, which was highly statistically significant. Imprint cytology is found to be a less expensive, simple, and rapid method, which can be used as an adjunct to histopathology. Correlation between proliferation index as measured with Ki-67 antibody and tumour stage was found. Ki-67 is thus a relevant marker for assessing the proliferative activity.


Synthesis of the alpha and beta subunits of coupling factor 1 by polysomes from pea chloroplasts.
Washed thylakoids of pea chloroplasts, containing tightly bound polysomes, incorporate radioactive amino acids into protein when supplied with soluble factors from Escherichia coli. Polyacrylamide gel electrophoresis with lithium dodecyl sulfate, followed by autoradiography of the labeled products, showed the synthesis of a number of different polypeptides. Two of the most heavily labeled products were in the region expected for the alpha and beta subunits of coupling factor 1, at 57 and 54 kDa. Positive identification of the subunits was made using monospecific antibodies. Furthermore, the same two polypeptides made by soluble polysomes located in the chloroplast stroma were found. While the major proportion of the newly formed alpha and beta subunits made by thylakoid-bound polysomes remained with the thylakoids after protein synthesis occurred, no evidence was found of incorporation into complete, EDTA-extractable coupling factor 1.


H-bonding and positive charge at the N5/O4 locus are critical for covalent flavin attachment in trametes pyranose 2-oxidase.
Flavoenzymes perform a wide range of redox reactions in nature, and a subclass of flavoenzymes carry covalently bound cofactor. The enzyme-flavin bond helps to increase the flavin's redox potential to facilitate substrate oxidation in several oxidases. The formation of the enzyme-flavin covalent bond--the flavinylation reaction--has been studied for the past 40 years. For the most advocated mechanism of autocatalytic flavinylation, the quinone methide mechanism, appropriate stabilization of developing negative charges at the flavin N(1) and N(5) loci is crucial. Whereas the structural basis for stabilization at N(1) is relatively well studied, the structural requisites for charge stabilization at N(5) remain less clear. Here, we show that flavinylation of histidine 167 of pyranose 2-oxidase from Trametes multicolor requires hydrogen bonding at the flavin N(5)/O(4) locus, which is offered by the side chain of Thr169 when the enzyme is in its closed, but not open, state. Moreover, our data show that additional stabilization at N(5) by histidine 548 is required to ensure high occupancy of the histidyl-flavin bond. The combination of structural and spectral data on pyranose 2-oxidase mutants supports the quinone methide mechanism. Our results demonstrate an elaborate structural fine-tuning of the active site to complete its own formation that couples efficient holoenzyme synthesis to conformational substates of the substrate-recognition loop and concerted movements of side chains near the flavinylation ligand.


C-terminal di-leucine motif of dopamine D₁ receptor plays an important role in its plasma membrane trafficking.
The dopamine D₁ receptor (D₁R), a G protein-coupled receptor, plays a critical role in regulating blood pressure through its actions on renal hemodynamics and epithelial ion transport, which are highly linked to its intracellular trafficking. In this study, we generated a series of C-terminal mutants of D₁R that were tagged with or without enhanced yellow fluorescent protein, and analyzed the consequences of these mutants on the plasma membrane trafficking of D₁R and cyclic AMP response to D₁R stimulation. D₁R with mutations within the endocytic recycling signal (amino acid residues 360-382) continued to be functional, albeit decreased relative to wild-type D₁R. Mutation of the palmitoylation site (347C>S) of D₁R did not impair its trafficking to the plasma membrane, but abolished its ability to increase cyclic AMP accumulation. In contrast, replacement of di-leucines (344-345L>A) by alanines resulted in the retention of D₁R in the early endosome, decreased its glycosylation, and prevented its targeting to the plasma membrane. Our studies suggest that di-L motif at the C-terminus of D₁R is critical for the glycosylation and cell surface targeting of D₁R.


The 1.6 Å resolution structure of a FRET-optimized Cerulean fluorescent protein.
Genetically encoded cyan fluorescent proteins (CFPs) bearing a tryptophan-derived chromophore are commonly used as energy-donor probes in Förster resonance energy transfer (FRET) experiments useful in live cell-imaging applications. In recent years, significant effort has been expended on eliminating the structural and excited-state heterogeneity of these proteins, which has been linked to undesirable photophysical properties. Recently, mCerulean3, a descendant of enhanced CFP, was introduced as an optimized FRET donor protein with a superior quantum yield of 0.87. Here, the 1.6 Å resolution X-ray structure of mCerulean3 is reported. The chromophore is shown to adopt a planar trans configuration at low pH values, indicating that the acid-induced isomerization of Cerulean has been eliminated. β-Strand 7 appears to be well ordered in a single conformation, indicating a loss of conformational heterogeneity in the vicinity of the chromophore. Although the side chains of Ile146 and Leu167 appear to exist in two rotamer states, they are found to be well packed against the indole group of the chromophore. The Ser65 reversion mutation allows improved side-chain packing of Leu220. A structural comparison with mTurquoise2 is presented and additional engineering strategies are discussed.


Ionisation of cysteine residues at the termini of model alpha-helical peptides. Relevance to unusual thiol pKa values in proteins of the thioredoxin family.
The physical basis of the unusually low pKa values of an active site cysteine thiol group in proteins with the thioredoxin fold is unknown. The electrostatic field associated with an alpha-helix pointing with its N terminus towards the cysteine residue has been implicated to lower the thiol pKa value by up to 5 pH units in glutaredoxin and DsbA. Here, the influence of the presence of an alpha-helical conformation on the ionisation of a cysteine thiol group located at or near the helix terminus is investigated in highly helical synthetic peptides with the generic sequence Ac-AAAAAAAAARAAAARAAAARAA-(NH2). The thiol pKa values have been determined by monitoring the pH dependence of the absorbance at 240 nm, of the alpha-helix content measured by the mean residue ellipticity at 222 nm, and of the chemical shifts of protons close to the sulphur atom of the cysteine residue. The favourable interaction between the thiolate anion at the N terminus and the alpha-helix decreases the thiol pKa value by up to 1.6 pH units when compared to a normal thiol pKa value measured in an unfolded control peptide, corresponding to a stabilisation energy of 2.1 kcal/mol. At the C terminus, the thiol pKa value is increased, but by only 0.2 pH units. The observations are consistent with an interaction of the alpha-helix dipole with the cysteine thiolate anion, involving both its charge and hydrogen-bonding. Subtle conformational effects in different model peptides appear to influence the ionisation of the thiol group significantly, with an N terminal Cys-Pro sequence having the most favourable interaction with the alpha-helix.


Postpartum Laboratory Follow-up in Women With Hepatitis B in Massachusetts From 2007 to 2012.
To determine postpartum hepatitis B virus (HBV) laboratory testing rates and identify factors associated with a lack of follow-up testing in Massachusetts. Screening for HBV infection in pregnant women is standard of care. Guidelines recommend that patients with chronic HBV have ongoing care and laboratory testing, but little is known about postpartum maternal HBV care outcomes. We conducted a retrospective cohort study using Massachusetts Virtual Epidemiologic Network, an electronic public health surveillance system maintained by the Massachusetts Department of Public Health. We identified women who tested hepatitis B surface antigen positive during their first reported (index) pregnancy in Massachusetts from 2007 to 2012 and measured HBV-related laboratory tests reported to Massachusetts Department of Public Health during and after pregnancy. We identified 983 hepatitis B surface antigen positive pregnant women. Half (492/983) did not have evidence of additional postpartum HBV laboratory testing following their index pregnancy. Women who had postpartum laboratory tests reported were younger [mean age (SD): 29 (5.3) vs. 31 (5.5) y, P=0.0001] and more likely to have >1 pregnancy during the study period (41% vs. 1%, P<0.0001). There were no differences in race, ethnicity, and US born status. On multivariable logistic regression, older age predicted a lower likelihood of having postpartum laboratory testing (odds ratio, 0.77; 95% confidence interval, 0.70-0.90). Postpartum maternal HBV follow-up laboratory testing occurred in only half of Massachusetts women and did not vary by race, ethnicity, or US born status. Our results were limited to a single state surveillance database, which likely underestimates the number of tests ordered.


Oxygen-ion beam polishing of a 5-cm-diameter diamond film.
A 5-cm diameter, 1-microm (peak to valley) rough diamond film has been polished to optical quality by an oxygen-ion beam. The rms and peak-to-valley roughness values of the polished surface have been lowered to 5.5 and 55.4 nm, respectively. Reactive ion beam polishing provides a low-temperature (140 degrees C), noncontact, and precisely controllable approach to improving the surface quality of diamond films. This progress is essential to the use of diamond coatings in optical applications.


Does the Andersen Behavioral Model for health services use predict how health impacts college students' academic performance?
Objective: The purpose of this research study is to examine the use of the Andersen Behavioral Model of Health Services Use in predicting how health impacts the academic performance of college students through predisposing, enabling, and need factors. Participants: Data were collected from 428 college students attending a large university in the Southeast. Methods: Students answered questions about their demographic characteristics, health, healthcare use, and academics using a survey adapted from the 2018 National College Health Assessment (NCHA) II conducted by the American College Health Association (ACHA). Bivariate and multivariate statistical analyses were run on the data and summarized. Results: Enabling factors were more likely to predict health impact on academic performance, while predisposing factors were least likely to predict these impacts. Conclusion: Results indicate that the Andersen Model is a useful model for framing the relationship between health and academic performance among college students.


TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.
Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855).


The mechanistic immunosuppressive role of the tumour vasculature and potential nanoparticle-mediated therapeutic strategies.
The tumour vasculature is well-established to display irregular structure and hierarchy that is conducive to promoting tumour growth and metastasis while maintaining immunosuppression. As tumours grow, their metabolic rate increases while their distance from blood vessels furthers, generating a hypoxic and acidic tumour microenvironment. Consequently, cancer cells upregulate the expression of pro-angiogenic factors which propagate aberrant blood vessel formation. This generates atypical vascular features that reduce chemotherapy, radiotherapy, and immunotherapy efficacy. Therefore, the development of therapies aiming to restore the vasculature to a functional state remains a necessary research target. Many anti-angiogenic therapies aim to target this such as bevacizumab or sunitinib but have shown variable efficacy in solid tumours due to intrinsic or acquired resistance. Therefore, novel therapeutic strategies such as combination therapies and nanotechnology-mediated therapies may provide alternatives to overcoming the barriers generated by the tumour vasculature. This review summarises the mechanisms that induce abnormal tumour angiogenesis and how the vasculature's features elicit immunosuppression. Furthermore, the review explores examples of treatment regiments that target the tumour vasculature.


Pathogenic, but Not Nonpathogenic, Rickettsia spp. Evade Inflammasome-Dependent IL-1 Responses To Establish an Intracytosolic Replication Niche.
Rickettsia species (spp.) are strict obligate intracellular bacteria, some of which are pathogenic in their mammalian host, including humans. One critical feature of these stealthy group of pathogens is their ability to manipulate hostile cytosolic environments to their benefits. Although our understanding of Rickettsia cell biology and pathogenesis is evolving, the mechanisms by which pathogenic Rickettsia spp. evade host innate immune detection remain elusive. Here, we show that disease severity in wild-type (WT) C57BL/6J mice infected with Rickettsia typhi (the etiologic agent of murine typhus) and Rickettsia rickettsii (the etiologic agent of Rocky Mountain spotted fever), but not with the nonpathogenic species Rickettsia montanensis, correlated with levels of bacterial burden as detected in the spleens of mice, as well as the serum concentrations of proinflammatory cytokine interleukin-1α (IL-1α) and, to a lesser extent, IL-1β. Antibody-mediated neutralization of IL-1α confirmed a key role in controlling mortality rates and bacterial burdens of rickettsia-infected WT mice. As macrophages are a primary source of both IL-1α and IL-1β cytokines, we determined the mechanism of the antirickettsial activities using bone marrow-derived macrophages. We found that pathogenic R. typhi and R. rickettsii, but not nonpathogenic R. montanensis, eluded pro-IL-1α induction and benefited predominantly from the reduced IL-1α secretion, via a caspase-11-gasdermin D (Gsdmd)-dependent pathway, to facilitate intracytosolic replication. Adoptive transfer experiments identified that IL-1α secretion by macrophages was critical for controlling rickettsiosis in WT mice. In sum, we identified a previously unappreciated pathway by which pathogenic, unlike nonpathogenic, rickettsiae preferentially target the caspase-11-Gsdmd-IL-1α signaling axis in macrophages, thus supporting their replication within the host. IMPORTANCE Currently, no vaccines are available to prevent rickettsioses, while vector-borne rickettsial infections in humans are on the rise globally. In fact, the insufficient understanding of how pathogenic Rickettsia species circumvent host immune defense mechanisms has significantly hindered the development of more effective therapeutics. Here, we identified a previously unappreciated role for the caspase-11-Gsdmd-IL-1α signaling axis in limiting the replication of pathogenic R. rickettsia and R. typhi species in murine macrophages and wild-type (WT) C57BL/6J mice. Adoptive transfer studies further identified IL-1α-secreting macrophages as critical mediators in controlling rickettsial infection in WT mice. Collectively, these findings provide insight into the potential mechanism of how pathogenic, but not nonpathogenic, Rickettsia spp. benefit from a reduction in the caspase-11-Gsdmd-mediated release of IL-1α to support host colonization.


Effect of estrogens on renal responsiveness to parathyroid hormone in elderly female subjects.
The effect of estrogens on the renal responsiveness to parathyroid hormone (PTH) was examined by PTH loading tests with synthetic human-PTH (1-34) in 8 normal elderly females (mean +/- SD age, 81.0 +/- 7.1 yr) before and after administration of estrogen (Premarin 1.25 mg/day for 4 weeks). Basal urinary adenosine cyclic 3', 5'-monophosphate (cAMP) excretion showed a tendency to increase after estrogen administration (5.47 +/- 1.68 vs 6.60 +/- 2.67 nmol/100 ml GFR) and the theoretical renal phosphorous threshold showed a tendency to decrease from 3.22 +/- 0.98 to 2.73 +/- 0.56 mg/dl. The blood ionized calcium concentration did not change after estrogen administration (4.44 +/- 0.16 vs 4.32 +/- 0.20 mg/dl) and serum phosphorous (P) decreased significantly (3.65 +/- 0.47 vs 3.01 +/- 0.42 mg/dl, p less than 0.05). There was no increase in mean serum immunoreactive PTH (0.34 +/- 0.10 vs 0.34 +/- 0.05 ngeq/ml). The urinary excretions of cAMP in response to PTH loading [100 U of human-PTH (1-34), intravenously] significantly (p less than 0.05) increased (94.8 +/- 57.0 vs 196.7 +/- 118.3 nmol/100 ml GFR/h) after estrogen administration. Moreover the changes in urinary excretion of cAMP (r = 0.698, p less than 0.01) and P (r = 0.555, p less than 0.05) induced by the PTH loading were positively correlated with serum estradiol in elderly females, assessed as groups before and after estrogen administration. These results suggest that estrogens may enhance the renal responsiveness to exogenous PTH administration.


A variety of regulatory mechanisms are involved in the nitrogen-dependent modulation of the nodule organogenesis program in legume roots.
Combined nitrogen (N) sources are known to strongly affect initiation, development and functioning of Nitrogen-Fixing-Nodules whose formation is triggered by lipochitin-oligosaccharide signals secreted in the rhizospere by the Rhizobium partner. The rapid effects of N supply on nodule initiation have been mainly described when N sources are present at the moment of Rhizobium inoculation or purified Nod Factors addition. We recently reported that high ammonium nitrate growth conditions might also strongly affect the nodulation competence of Lotus japonicus plants, prior to the Rhizobium inoculation. This is a long-term effect, which suggests a change of the general nutritional status as the signal controlling the reduced nodulation capacities. The mechanisms underlying these inhibitory pathways are apparently different and the identification of the molecular actors involved may provide new insights into the linkage between N environmental changes and root organogenesis programs.


A biosocial developmental model of borderline personality: Elaborating and extending Linehan's theory.
Over the past several decades, research has focused increasingly on developmental precursors to psychological disorders that were previously assumed to emerge only in adulthood. This change in focus follows from the recognition that complex transactions between biological vulnerabilities and psychosocial risk factors shape emotional and behavioral development beginning at conception. To date, however, empirical research on the development of borderline personality is extremely limited. Indeed, in the decade since M. M. Linehan initially proposed a biosocial model of the development of borderline personality disorder, there have been few attempts to test the model among at-risk youth. In this review, diverse literatures are reviewed that can inform understanding of the ontogenesis of borderline pathology, and testable hypotheses are proposed to guide future research with at-risk children and adolescents. One probable pathway is identified that leads to borderline personality disorder; it begins with early vulnerability, expressed initially as impulsivity and followed by heightened emotional sensitivity. These vulnerabilities are potentiated across development by environmental risk factors that give rise to more extreme emotional, behavioral, and cognitive dysregulation. (PsycINFO Database Record (c) 2009 APA, all rights reserved).


Identification of human papillomaviruses in tumors of the oral cavity in an Indian community.
Oral cancers and other squamous cell cancers of the head and neck are common cancers in India, primarily due to tobacco chewing/smoking and alcohol consumption. Recent reports indicate involvement of human papillomavirus (HPV), HPV 16, in a subset of squamous cell carcinoma of head and neck (SCCHN) cases. To investigate the types of HPVs present in 83 oral cancers and 19 other head and neck tumors, degenerate primers directed to consensus regions in the HPV L1 open reading frame (ORF) were employed to amplify genomic DNA from tumor and when available, the adjacent normal mucosa. PCR-amplified products were cloned and sequenced. Similar studies were done on exfoliated buccal cells of 102 individuals visiting a dental hospital for dental complaints. HPV was detected in 32 out of 102 patients (31%), in either the tumor or the adjacent normal mucosa, while 5% (5/102) of the comparative group were found to be HPV-positive. Sequence analysis revealed a number of cutaneous HPVs, predominantly HPV types of the genus Beta-Papillomavirus, in the oral cavity. Multiple HPV infections were also commonly observed in patients (14/102; 14%). HPV 16 and 18 were each detected in 6 patients (6/102; 6%). Neither high-risk HPVs nor multiple infections were observed in the mouthwash samples of the comparative group. We report that the oral cavity harbors a variety of different HPVs. These viruses, in conjunction with the carcinogens present in tobacco could contribute to carcinogenesis.


Protective behavior survey, West Nile virus, British Columbia.
We investigated personal protective behaviors against West Nile virus infection. Barriers to adopting these behaviors were identified, including the perception that DEET (N,N-diethyl-m-toluamide and related compounds) is a health and environmental hazard. Televised public health messages and knowing that family or friends practiced protective behaviors were important cues to action.


The contribution of the lateral posterior and anteroventral thalamic nuclei on spontaneous recurrent seizures in the pilocarpine model of epilepsy.
The pilocarpine model of epilepsy in rats is characterised by the occurrence of spontaneous seizures (SRSs) during the chronic period that recur 2-3 times per week during the whole animal life. In a previous study on brain metabolism during the chronic period of the pilocarpine model it was possible to observe that, among several brain structures, the lateral posterior thalamic nuclei (LP) showed a strikingly increased metabolism. Some evidences suggest that the LP can participate in an inhibitory control system involved in the propagation of the seizures. The aim of the present study was to verify the role of LP in the expression and frequency of spontaneous seizures observed in the pilocarpine model. Ten adult male rats presenting SRSs were monitored for behavioural events by video system one month before and one month after LP ibotenic acid lesion. Another group of chronic epileptic rats (n=10) had the anteroventral thalamic nuclei (AV) lesioned by ibotenic acid. After the surgical procedure, the animals were sacrified and the brains were processed for histological analysis by the Nissl method. The LP group seizure frequency was 3.1+/-1.9 before ibotenic acid injection and showed an increase (16.3+/-7.2 per week) after LP lesion. No changes in SRSs frequency were observed in the AV group after ibotenic lesion in these nuclei. These results seem to suggest that LP play a role in the seizure circuitry inhibiting the expression of spontaneous seizures in the pilocarpine model.


Genomic prediction and genomic heritability of grain yield and its related traits in a safflower genebank collection.
Safflower, a minor oilseed crop, is gaining increased attention for food and industrial uses. Safflower genebank collections are an important genetic resource for crop enhancement and future breeding programs. In this study, we investigated the population structure of a safflower collection sourced from the Australian Grain Genebank and assessed the potential of genomic prediction (GP) to evaluate grain yield and related traits using single and multi-site models. Prediction accuracies (PA) of genomic best linear unbiased prediction (GBLUP) from single site models ranged from 0.21 to 0.86 for all traits examined and were consistent with estimated genomic heritability (h2 ), which varied from low to moderate across traits. We generally observed a low level of genome × environment interactions (g × E). Multi-site g × E GBLUP models only improved PA for accessions with at least some phenotypes in the training set. We observed that relaxing quality filtering parameters for genotype-by-sequencing (GBS), such as missing genotype call rate, did not affect PA but upwardly biased h2 estimation. Our results indicate that GP is feasible in safflower evaluation and is potentially a cost-effective tool to facilitate fast introgression of desired safflower trait variation from genebank germplasm into breeding lines.


Central nervous system tumors in children under 5 years of age: a report on treatment burden, survival and long-term outcomes.
The challenges of treating central nervous system (CNS) tumors in young children are many. These include age-specific tumor characteristics, limited treatment options, and susceptibility of the developing CNS to cytotoxic therapy. The aim of this study was to analyze the long-term survival, health-related, and educational/occupational outcomes of this vulnerable patient population. Retrospective study of 128 children diagnosed with a CNS tumor under 5 years of age at a single center in Switzerland between 1990 and 2019. Median age at diagnosis was 1.81 years [IQR, 0.98-3.17]. Median follow-up time of surviving patients was 8.39 years [range, 0.74-23.65]. The main tumor subtypes were pediatric low-grade glioma (36%), pediatric high-grade glioma (11%), ependymoma (16%), medulloblastoma (11%), other embryonal tumors (7%), germ cell tumors (3%), choroid plexus tumors (6%), and others (9%). The 5-year overall survival (OS) was 78.8% (95% CI, 71.8-86.4%) for the whole cohort. Eighty-seven percent of survivors > 5 years had any tumor- or treatment-related sequelae with 61% neurological complications, 30% endocrine sequelae, 17% hearing impairment, and 56% visual impairment at last follow-up. Most patients (72%) attended regular school or worked in a skilled job at last follow-up. Young children diagnosed with a CNS tumor experience a range of complications after treatment, many of which are long-lasting and potentially debilitating. Our findings highlight the vulnerabilities of this population, the need for long-term support and strategies for rehabilitation, specifically tailored for young children.


Retinoblastoma presenting with a cheek mass.
This is a report of a case of retinoblastoma that mimicked Burkitt's lymphoma by presenting with a left proptosis and a right cheek mass. With the aid of fine-needle aspiration cytology, the diagnosis was established as retinoblasstoma and a left modified exenteration was performed. The patient had adjuvant chemotherapy and radiotherapy to the left orbit and the right maxilla with regression. At 12 months postoperatively, there was no evidence of recurrence, and the patient was still hale and hearty. In conclusion, this patient had left retinoblastoma with metastasis to the contralateral jaw. It is important to note that orbital Burkitt's lymphoma can be a differential diagnosis of retinoblastoma.


Global Diversity and Updated Phylogeny of Auricularia (Auriculariales, Basidiomycota).
Auricularia has a worldwide distribution and is very important due to its edibility and medicinal properties. Morphological examinations and multi-gene phylogenetic analyses of 277 samples from 35 countries in Asia, Europe, North and South America, Africa, and Oceania were carried out. Phylogenetic analyses were based on ITS, nLSU, rpb1, and rpb2 sequences using methods of Maximum Likelihood and Bayesian Inference analyses. According to the morphological and/or molecular characters, 37 Auricularia species were identified. Ten new species, A. camposii and A. novozealandica in the A. cornea complex, A. australiana, A. conferta, A. lateralis, A. pilosa and A. sinodelicata in the A. delicata complex, A. africana, A. srilankensis, and A. submesenterica in the A. mesenterica complex, are described. The two known species A. pusio and A. tremellosa, respectively belonging to the A. mesenterica complex and the A. delicata complex, are redefined, while A. angiospermarum, belonging to the A. auricula-judae complex, is validated. The morphological characters, photos, ecological traits, hosts and geographical distributions of those 37 species are outlined and discussed. Morphological differences and phylogenetic relations of species in five Auricularia morphological complexes (the A. auricula-judae, the A. cornea, the A. delicata, the A. fuscosuccinea and the A. mesenterica complexes) are elaborated. Synopsis data on comparisons of species in the five complexes are provided. An identification key for the accepted 37 species is proposed.


Determination of fluoride in fluoride tablets and solutions by ion-selective electrode: collaborative study.
A proposed method using the fluoride (F) ion-selective electrode has been developed for determining the fluoride ion concentration in tablets and solutions containing sodium fluoride. The method has been subjected to collaborative study. Eight samples consisting of 2 authentic fluoride solutions, 2 commercial fluoride solutions, and 4 commercial fluoride tablets were sent to each of 11 collaborators together with a copy of the method. Single assays on the authentic fluoride solutions known to contain 1 mg F/5 mL were performed with average recoveries of 99.5 and 99.6% and relative coefficients of variation (CV) of 2.11 and 1.91%, respectively. Single assays of 2 commercial fluoride solutions declared at 1 mg F/5 mL gave mean values of 0.994 and 0.990 mg and relative CV values of 1.88 and 2.36%, respectively. Single assays of 2 commercial fluoride tablet preparations declared at 0.5 mg F gave mean values of 0.485 and 0.478 mg and relative CV values of 3.12 and 3.71%, respectively. Single assays of 2 commercial fluoride tablet preparations declared at 1 mg F gave mean values of 0.991 and 0.981 mg and relative CV values of 2.99 and 2.85%, respectively. The method has been adopted official first action.


Joint position statement on persistent foramen ovale (PFO) and diving. South Pacific Underwater Medicine Society (SPUMS) and the United Kingdom Sports Diving Medical Committee (UKSDMC).
This consensus statement is the result of a workshop at the SPUMS Annual Scientific Meeting 2014 with representatives of the UK Sports Diving Medical Committee (UKSDMC) present, and subsequent discussions including the entire UKSDMC. Right-to-left shunt across a persistent or patent foramen ovale (PFO) is a risk factor for some types of decompression illness. It was agreed that routine screening for PFO is not currently justifiable, but certain high risk sub-groups can be identified. Divers with a history of cerebral, spinal, inner-ear or cutaneous decompression illness, migraine with aura, a family history of PFO or atrial septal defect and those with other forms of congenital heart disease are considered to be at higher risk. For these individuals, screening should be considered. If screening is undertaken it should be by bubble contrast transthoracic echocardiography with provocative manoeuvres, including Valsalva release and sniffing. Appropriate quality control is important. If a shunt is present, advice should be provided by an experienced diving physician taking into account the clinical context and the size of shunt. Reduction in gas load by limiting depth, repetitive dives and avoiding lifting and straining may all be appropriate. Divers may consider transcatheter device closure of the PFO in order to return to normal diving. If transcatheter PFO closure is undertaken, repeat bubble contrast echocardiography must be performed to confirm adequate reduction or abolition of the right-to-left shunt, and the diver should have stopped taking potent anti-platelet therapy (aspirin is acceptable).