Biochemical study of heterosis for brain myelin content in mice.
Heterosis (hybrid vigor) for brain myelin content has been examined in detail in (C57BL/6J x DBA/2J)F1 hybrid mice at 17 days of age. The amount of myelin isolated from the F1 hybrid brain is greater than that isolated from either parental strain. In addition, the total protein content in the myelin of the three genotypes showed the following trend: F1 greater than DBA greater than C57. However, no discernible differences in myelin protein compositions could be detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the whole brain for several myelin-associated constituents such as GM1 ganglioside, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), 5'-nucleotidase, and carbonic anhydrase indicated that heterosis exists for these components. No heterosis was found for such nonmyelin constituents as gangliosides GD1a, GT, GQ, RNA, DNA, and choline acetyltransferase. A developmental study of the whole brain CNPase indicated that the heterotic effect was greatest during the most active period of myelination (17-30 days). We conclude that the heterotic effect is specific for myelin content and is probably the result of an accelerated myelin synthesis. The heterotic effect should have great potential as a new model for studying aspects of myelinogenesis.


Prevention of Sudden Death and Management of Ventricular Arrhythmias in Arrhythmogenic Cardiomyopathy.
Arrhythmogenic cardiomyopathy is an umbrella term for a group of inherited diseases of the cardiac muscle characterized by progressive fibro-fatty replacement of the myocardium. As suggested by the name, the disease confers electrical instability to the heart and increases the risk of the development of life-threatening arrhythmias, representing one of the leading causes of sudden cardiac death (SCD), especially in young athletes. In this review, the authors review the current knowledge of the disease, highlighting the state-of-the-art approaches to the prevention of the occurrence of SCD.


Cardiovascular morbidity and mortality of the metabolic syndrome.
Cardiovascular disease remains the single leading cause of morbidity and mortality in the United States. The metabolic syndrome has received increased attention in recent years, partly because of the growing prevalence of obesity and its association with cardiovascular disease. This article reviews current evidence from longitudinal observational studies that evaluated the impact of metabolic syndrome on cardiovascular morbidity and mortality in various population subsets. The approach to cardiovascular risk assessment in individuals who have multiple risk factors and the clinical implications of diagnosing the metabolic syndrome are also discussed.


[Ergospirometric studies on patients with diabetes mellitus and the effect of biguanides on physical performance].
24 diabetic patients had submaximal exercise testing before, and 4 days after, biguanide treatment. Biguanide treatment resulted in a significantly decreased exercise capacity. This is explained by increased anaerobic energy production, which results in a decrease of the performance of an individual.


Randomized, double-blind, placebo-controlled trial of vaginal misoprostol for management of early pregnancy failures.
To determine whether misoprostol medical management of early pregnancy failures is more effective than expectant management. Patients diagnosed with early pregnancy failures, closed cervix, and minimal vaginal bleeding were randomized to 800 microg of misoprostol or placebo placed vaginally. Patients were evaluated by ultrasound imaging 24 hours and 48 hours after study drug administration, with repeat administration if 24-hour imaging showed a persistent gestational sac. Treatment success was defined as expulsion of uterine contents within 48 hours. Patient follow-up occurred 2 weeks after expulsion of uterine contents. Treatment success occurred in 15 of 18 (83%) misoprostol patients and 2 of 16 (13%) placebo patients (P < .0001). Side effects were similar between groups except for vaginal bleeding, which was more common in the misoprostol group (P = .001). Patient satisfaction and pain perception were similar between groups. Misoprostol appears to be highly effective for treating early pregnancy failures, with few side effects and high patient satisfaction.


The efficiency and versatility of catalytic RNA: implications for an RNA world.
Because RNA is chemically and structurally dissimilar from protein, the finding of catalytic activity in RNA was initially surprising. Quantitative measurements of reaction rates show that RNA can be as efficient a catalyst as protein. On the other hand, the potential versatility of RNA to catalyze diverse types of reactions has only begun to be explored. Understanding the efficiency and versatility of RNA as a catalyst helps us evaluate origin-of-life scenarios involving self-replicating RNA, and may explain why RNA catalysis remains important in contemporary cells.


Primary amenorrhea in four adolescents revealed 5α-reductase deficiency confirmed by molecular analysis.
To determine the genetic cause of primary amenorrhea. Case series. Pediatric endocrinology, endocrinology, and gynecology departments of academic hospitals. Three adolescents and one young woman 46, XY patients with srd5A2 gene mutations. Genetic analysis of srd5A2. We report four srd5A2 gene mutations in three adolescents and one young woman with 46,XY primary amenorrhea. All presented clitoromegaly and two presented hypospadias; all had been reared as females. Virilization of the external genitalia was noted in the pubertal period in all four patients. Three were maintained in the female sex of rearing by personal choice, and the fourth switched gender. We identified the homozygous substitutions p.L55Q (exon 1), p.Q56R (exon 1), and p.N193S (exon 4), in patients 1, 2, and 3, respectively. Patient 4 had compound heterozygous mutations, a new c.34delG (exon 1) associated with p.R246W (exon 5). All patients had high plasma T levels (ranges, 16.2-23.2 nmol/L; normal female teenage range, 0.35-2 nmol/L). Our data clearly demonstrate that 5α-reductase deficiency should be considered in XY adolescents with primary amenorrhea and no breast development associated with virilization at puberty and high plasma T. Positive parental consanguinity should reinforce the diagnostic orientation.


Stimulating effect of graphene oxide on myogenesis of C2C12 myoblasts on RGD peptide-decorated PLGA nanofiber matrices.
In the field of biomedical engineering, many studies have focused on the possible applications of graphene and related nanomaterials due to their potential for use as scaffolds, coating materials and delivery carriers. On the other hand, electrospun nanofiber matrices composed of diverse biocompatible polymers have attracted tremendous attention for tissue engineering and regenerative medicine. However, their combination is intriguing and still challenging. In the present study, we fabricated nanofiber matrices composed of M13 bacteriophage with RGD peptide displayed on its surface (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) and characterized their physicochemical properties. In addition, the effect of graphene oxide (GO) on the cellular behaviors of C2C12 myoblasts, which were cultured on PLGA decorated with RGD-M13 phage (RGD/PLGA) nanofiber matrices, was investigated. Our results revealed that the RGD/PLGA nanofiber matrices have suitable physicochemical properties as a tissue engineering scaffold and the growth of C2C12 myoblasts were significantly enhanced on the matrices. Moreover, the myogenic differentiation of C2C12 myoblasts was substantially stimulated when they were cultured on the RGD/PLGA matrices in the presence of GO. In conclusion, these findings propose that the combination of RGD/PLGA nanofiber matrices and GO can be used as a promising strategy for skeletal tissue engineering and regeneration.


Effect of "heat shock" treatments on QPX disease and stress response in the hard clam, Mercenaria mercenaria.
The hard clam, Mercenaria mercenaria, is one of the most valuable commercial mollusk species along the eastern coast of the United States. Throughout the past 2 decades, the hard clam industry in the Northeast was significantly impacted by disease outbreaks caused by a lethal protistan parasite known as Quahog Parasite Unknown (QPX). QPX is an opportunistic pathogen and the infection has been shown to be a cold water disease, where warmer conditions (above 21°C) lead to disease reduction and clam healing. In vitro studies also showed a sharp reduction in parasite growth and survivorship at temperatures exceeding 27°C. In this study, we evaluated the effect of short-term exposures to high temperatures on QPX disease dynamic and clam recovery. Infected clams were collected from an enzootic site and subsequently submitted to one of ten "heat shock" treatments involving a gradient of temperatures and exposure times. QPX prevalence was compared before and 10weeks after heat shock to assess the effect of each treatment on disease progress. Expression of several stress-related genes was measured 1 and 7days after heat shock using qPCR to evaluate the effect of each treatment on clam physiology. Anti-QPX activity in clam plasma was also measured in an attempt to link changes in defense factors to thermal stress and disease progress. Our results suggest that brief exposures to moderate high temperatures promote the greatest remission while imposing the mildest stress to clams. These results are discussed with the aim of providing the industry with possible strategies to mitigate QPX disease.


The future of whales in our Anthropocene ocean.
Slowing down ships presents one of several promising avenues for reducing harm to whales in an increasingly noisy and busy ocean.


Should I accept or reject my assignment?
This article examines the implications of one's decision to accept or reject a nursing assignment and presents alternatives to achieving equitable nursing assignments.


Technology-driven dyadic interaction in caregiving.
Due to the ongoing pandemic and the resulting community lockdowns, people with dementia and their family might be at risk of social deprivation and increased relationship strains. Technological means have the potential to engage participants in meaningful positive interactions. The tablet-based activation system I-CARE offers social activities specifically designed for people with dementia and their caregivers, by offering user-specific contents adapted to their needs and sensitivities. Little is known about the impact of Covid-19 on social health for this population. The ongoing study, presented as a part of the Marie-Curie Innovative-Training-Network action, H2020-MSCA-ITN, grant agreement 813196, assesses how COVID-19 has impacted community-dwelling dementia caregiving dyads. Contextual factors of technology use and motivations for inviting technology into social interactions is explored. As a part an ongoing pre-post mixed-methods feasibility study, baseline assessments through semi-structured interviews were conducted and subjected to inductive thematic statement analysis by two independent researchers. Participants differed in how COVID-19 restrictions impacted their lives and how they coped with dementia, revealing different motivations for inviting technology into their lives. Dyads who were socially active pre-COVID-19, and who managed use technology to maintain social participation during COVID-19, reported to have been less negatively impacted by COVID-19 restrictions. Four subthemes within "Social technology during COVID-19" were identified. During and beyond this pandemic, social technology is a valuable tool to promote social participation in this population. Successful uptake of technology is dependent on customizing to individuals' needs and conditions.


Puberty and olfactory preferences of males.
The preferences of 302 males, aged 8-9, 14 and 16 years, for ten food related odors were determined using a hedonic scale. The aim was to establish if major changes in preferences occur during the period which encompasses puberty. Small but significant differences between the 8-9 year group and the others were obtained for meat and chicken odors; between the 14 year group and the others for peanut butter odor; and there was a change from dislike to like with age for coffee odor. The results were almost all confirmed in a retest. The general lack of differences between the responses of the three age groups indicated that no major change occurs in preferences for food odors between the ages of 8 and 16 years. Although these results indicate that olfactory preferences for food odors are not affected by puberty, they do not eliminate the possibility that preferences may be altered for odors related to sex and emotion [13].


Cavotricuspid isthmus ablation by means of very high power, short-duration, temperature-controlled lesions.
A very high-power short-duration (vHPSD) strategy of radiofrequency (RF) ablation aims to minimize conductive heating and increase resistive heating. We evaluated the feasibility, efficacy and safety of the vHPSD ablation of the cavotricuspid isthmus (CTI) in patients presenting with typical atrial flutter (AFL). This prospective non-randomized study enrolled 28 consecutive patients (FAST Group) with typical AFL undergoing CTI ablation. The vHPSD ablation was performed applying 90 W, for 4 s, with an irrigation of 8 ml/min. Thirty consecutive patients who, previously, underwent CTI ablation by means of a contact force surrounding flow catheter guided by ablation index (500) served as control group (AI Group). In the FAST Group, the mean CTI length was 29 ± 6 mm, and the mean number of RF tags was 20 ± 9. The CTI bidirectional "first pass" block was reached in 25 (89%) patients. There were no major procedural complications. After a mean follow-up of 6 ± 2 months, one (3.5%) patient had arrhythmia recurrence. The vHPSD ablation was as effective as AI-guided ablation in achieving acute CTI block (rate of first pass 89% vs 93%, p = 0.59), with a shorter RF time (88 ± 40 s vs 492 ± 269 s, p < 0.001) and similar procedure (30 ± 4 min vs 34 ± 10 min, p = 0.5) and fluoroscopy time (103 ± 29 vs 108 ± 52 s, p = 0.7). At 8 months, the freedom from AFL recurrence was 96% in the FAST group and 97% in the AI group. Our preliminary data show that the vHPSD ablation represents an effective and safe ablation strategy to achieve bidirectional block for the treatment of typical AFL.


Single-photon emission computed tomography (SPECT) in pediatric epilepsy.
Single Photon Emission Computerized Tomography (SPECT) is a valuable tool in the assessment of epileptic patients. Radiotracers that distribute according to regional cerebral blood flow permit the identification of altered perfusion to an epileptogenic zone both ictally and interictally. This technique has proven especially useful in temporal lobe epilepsy.


The health professions and the performance of future health systems in low-income countries: support or obstacle?
This paper discusses the present and future role of the health professions in health services delivery systems in low-income countries. Unlike richer countries, most low-income countries do not have a tradition of labour market regulation and the capacity of the professions themselves to regulate the provision of health services by their members tends to be weak. The paper looks at the impact of professional monopolies on the performance of health services delivery systems, e.g. equity of access, effectiveness of services, efficiency in the use of scarce resources, responsiveness to users' needs, including protection against the financial impact of utilising health services. It identifies issues which policy-makers face in relation to opening the health labour market while guaranteeing the safety and security of services provided by professionals. The suggestion is made that a "social contract", granting privileges of practice in exchange of a commitment to actively maintain and enhance the quality of their services, may be a viable course of action. This would require that the actors in the policy process collaborate in strengthening the capacity of regulatory agencies to perform their role.


Examining sleep, fatigue, and daytime sleepiness in pediatric multiple sclerosis patients.
About 2-5% of patients with multiple sclerosis (MS) experience their first symptoms before age 18. Sleep disorders occur frequently in MS. The prevalence of sleep problems and their impact on fatigue and daytime sleepiness in pediatric MS is unknown. To determine whether pediatric MS patients have more sleep disturbances, fatigue, and daytime sleepiness compared with an age-, sex-, and race-matched control group. Patients and age-, sex-, and race-matched controls were surveyed to quantify daytime sleepiness via the modified Epworth Sleepiness Scale, sleep quality and hygiene through the Adolescent Sleep Wake and Hygiene Scale, respectively, and fatigue using the PediatricQL Multidimensional Fatigue Scale. Pediatric MS patients (n = 30) and age-, sex-, and race-matched controls (n = 52) had similar levels of fatigue; however, when compared with previously published historical controls, both groups reported worse fatigue across all dimensions (p < 0.05). Pediatric MS patients also had similar sleep quality compared with the matched controls, but reported better sleep hygiene on the 'sleep stability' dimension (p < 0.05). In addition, pediatric MS patients had less daytime sleepiness than the matched controls (p < 0.05). Although patients with MS reported similar levels of fatigue, they have better sleep hygiene, which could possibly account for the decreased amount of excessive daytime sleepiness. Also, when compared with historical controls, the MS and control samples reported more fatigue. Thus, caution must be taken when using published control data, especially when not properly matched.


Short-term and long-term prognosis after myocardial infarction: prognostic value of coronary anatomy and left ventriculography.
To assess prospectively short-term (1 year) and long-term (4 years) prognostic variables from heart catheterization, 325 consecutive patients of 65 years or less who survived a myocardial infarction were studied. In all coronary angiography and left ventriculography was performed 4-6 weeks after infarction. First year mortality rate was significantly higher in patients with an ejection fraction less than 0.30 (20%) than in patients with an ejection fraction greater than or equal to 0.30 (2%, P less than 0.001). During 4-year follow-up cumulative mortality was 44% in patients with an ejection fraction less than 0.30 vs 11% in patients with an ejection fraction greater than or equal to 0.30 (P less than 0.001). In patients who survived the first year after infarction, however, a low ejection fraction less than 0.30 was not associated with higher mortality rate during the subsequent 3 years. Mortality in patients with one-, two- or three-vessel disease was equally distributed in the first year. After 4 years patients with three-vessel disease had a significant higher mortality (32%) than patients with two- or one-vessel disease (12 and 11%, respectively; P less than 0.05). Reinfarction rate was higher in patients with an ejection fraction less than 0.30 (14%) than in patients with an ejection fraction greater than or equal to 0.30 (3%, P less than 0.05) in the first year. During 4-year follow-up reinfarction rate was 38% in patients with an ejection fraction less than 0.30 vs. 13% in patients with an ejection fraction greater than or equal to 0.30 (P less than 0.05). Again, in patients who survived the first year without reinfarction, an ejection fraction less than 0.30 had no prognostic value for recurrent myocardial infarction during the subsequent three years. Three-vessel disease had no higher reinfarction rate in the first year of follow-up: during 4 years, patients with three-vessel disease had a reinfarction rate (32%) compared to patients with two- and one-vessel disease (14 and 11%, respectively; P less than 0.05). It is concluded that an ejection fraction less than 0.30 is a major risk factor for cardiac death and reinfarction only in the first year after myocardial infarction. Beyond the first year, a subgroup of patients with three-vessel disease is at risk for both cardiac death and reinfarction during the three subsequent years.


Irradiation increases proteolysis in erythrocyte ghosts: a spin label study.
X- and gamma-irradiation of human erythrocyte membranes (250-1000 Gy) was found to decrease the ratio of weakly to strongly immobilized signal height of membrane-bound maleimide spin label (Mal-6). Subsequent incubation of spin-labeled membranes at ambient temperature (21 degrees C) induced a progressive increase in this ratio, faster for membranes irradiated with low doses which was hampered by protease inhibitors. These results demonstrate that ionizing radiation stimulates proteolysis of erythrocyte membrane proteins by membrane-associated proteases.


Intracranial pressure (ICP) monitoring as a guide to prognosis in a lightning-injured, comatose child.
Every year there are many deaths due to lightning injuries in the United States. A case is presented of a young child who suffered cardiopulmonary arrest following being struck by lightning strike and in whom ICP monitoring was utilized. We postulate that ICP and CPP measurements may be useful as prognostic indicators for comatose lightning victims and, therefore, may help in the management of the patient.


Montelukast and Nightmares: Further Characterisation Using Data from VigiBase.
Montelukast is a medicine indicated for use in asthma. Psychiatric disorders including nightmares have not been described in clinical trials but during recent years have been included in the product information as having been reported post-marketing, without further description of the events. Previous descriptions in the scientific literature were based on limited numbers of reports or lacked detailed case information. The study aim was to further characterise post-marketing adverse drug reactions for nightmares, suspected to be induced by montelukast, to facilitate safer use of the medicine by providing additional information to patients and healthcare professionals. We clinically reviewed reports of nightmares with montelukast present in VigiBase, World Health Organization's global database of suspected adverse reactions to medicinal products, developed and maintained by the Uppsala Monitoring Centre, until 3 May, 2020. There were 1118 reports of nightmares with montelukast in VigiBase, which provided valuable descriptions of the nightmares as well as information about the impact on the daily lives, with many cases describing a severe impact of the nightmares. About half of the reports were classified as serious. Two thirds concerned children, with the largest age group represented being children aged 5-10 years. In most cases, the nightmares disappeared upon discontinuation of the drug but for some patients it took a long time until the nightmares ceased. The nature and potential severity of this adverse drug reaction, as described in these reports, present important knowledge for patients and healthcare providers that could help reduce drug-induced harm. This study highlights the value of post-marketing reports for further characterisation of known adverse drug reactions. The benefit-risk balance should be continuously monitored while patients are taking montelukast.


Oxidative stress response induced in an atrazine phytoremediating plant: physiological responses of Pennisetum glaucum to high atrazine concentrations.
This research presented here, for the first time, elucidates the responses of several antioxidants in Pennisetum leaves exposed to varying concentrations of atrazine (0 - 200 mg•kg-1). Pennisetum has been reported to be resistant to atrazine; however, its physiological response to high concentrations (≥ 50 mg•kg-1) of atrazine is not well documented. The contents of reduced (AsA) and oxidized (DHA) ascorbate increased significantly with increase in atrazine concentration and exposure time; but the increase was more evident under higher (50 and 100 mg•kg-1) atrazine concentrations. Increase in atrazine concentration to 200 mg•kg-1 significantly decreased AsA, but increased DHA content, throughout the experiment. Seedlings treated with 200 mg•kg-1 atrazine showed significantly lowest reduced glutathione (GSH) content; while oxidized glutathione (GSSG) was not significantly affected, after 68d. Seedlings treated with 100 mg•kg-1 atrazine showed increased Glutathione-S-Transferase (GST) activity after 48 d and 68 d; while treatment with 200 mg•kg-1 atrazine significantly increased Glutathione reductase (GR) after 58d. This result suggests that Pennisetum may tolerate lower atrazine concentrations; However, higher concentrations (≥50 mg•kg-1) which could have longer residency period in the soil, could induce more physiological damage to the plant.


Latent class analysis of emotions experienced during compulsive hair-pulling episodes.
Reasons for compulsive hair pulling are heterogeneous and not fully understood. Given that many people who experience compulsive hair pulling do not respond to treatment, identifying subgroups can inform potential mechanisms and treatment design. We sought to identify empirical subgroups among participants in an online treatment program for trichotillomania (N = 1728). A latent class analysis was used to identify patterns of emotions associated with compulsive hair-pulling episodes. Six classes of participants were found which reflected three predominant themes. One theme reflected expected patterns, where emotional changes were seen following pulling. Two other themes were more surprising, where one reflected high overall emotional activation that did not show consistent change in response to pulling, and another showed low emotional activation overall. These results suggest that there are multiple types of hair-pulling and a sizeable group of people may benefit from treatment adjustments. Participants did not receive semi-structured diagnostic assessment. A majority of participants were Caucasian, and future research would benefit from increased participant diversity. Emotions associated with compulsive hair-pulling were measured across an entire treatment program, but the relationship between specific intervention components and change in specific emotions was not systematically collected. While previous research has addressed overall phenomenology and comorbidity, the present study is the first to identify empirical subgroups of people who experience compulsive hair-pulling at the level of individual pulling episodes. Identified participant classes had distinguishing features that can aid in personalizing treatment to individual symptom presentations.


The crystal structure and biochemical properties of DHBPS from Streptococcus pneumoniae, a potential anti-infective target for Gram-positive bacteria.
The enzymes involved in riboflavin biosynthesis are considered to be potential anti-bacterial drug targets because these proteins are essential in bacterial pathogens but are absent in humans. 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) is one of the key enzymes in the biosynthesis of riboflavin. DHBPS catalyzes the conversion of ribulose-5-phosphate (Ru5P) to 3,4-Dihydroxy-2-butanone-4-phosphate (DHBP) and formate. The purified SpDHBPS enzyme, in the presence of Mg(2+) ion, catalyzed the conversion of Ru5P to DHBP at a rate of 109nmolmin(-1)mg(-1) with an apparent Km value of 181μM at 37°C. Surprisingly, our experiments first revealed that DHBPS showed activity in the presence of the trivalent metal ion, Fe(3+). Furthermore, we determined the crystal structure of DHBPS from Gram-positive bacteria, Streptococcus pneumoniae, with 2.0Å resolution. The overall architecture of SpDHBPS was similar to its homologs, which comprise one β-sheet (five-stranded) and eight α-helices, adopting a three-layered α-β-α sandwich fold. Similar to the homologs, gel-filtration experiments verified that the enzyme was arranged as a dimer. Although the overall fold of DHBPS was similar, the significant structural differences between the species at the active site region may be utilized to develop antibacterial agents that are species-specific.


Prevalence and reversibility of lung hyperinflation in adult asthmatics with poorly controlled disease or significant dyspnea.
In asthma, inflammation affects both the proximal and distal airways and may induce significant hyperinflation (HI). This study sought to evaluate the prevalence of HI in asthmatic patients with poorly controlled disease and/or dyspnea. Poor asthma control was defined by an Asthma Control Test (ACT) score <20 (n = 287), and dyspnea was defined as a modified Medical Research Council score ≥1 (n = 18). HI was defined as either a residual volume/total lung capacity (RV/TLC) above the upper limit of normal (RV-HI) or a functional residual capacity (FRC) >120% predicted (FRC-HI). HI reversibility after administration of salbutamol (400 μg) was defined as a decrease in RV >20% or a reduction in FRC >10%. Changes in dyspnea and chest tightness were evaluated on a visual analogue scale. Both RV-HI and FRC-HI were observed in 48% of the 305 patients (mean ± SD age: 49 ± 17; FEV1 : 75 ± 18% predicted) included in the study. The prevalence of HI was higher in patients with a FEV1 <60% predicted (93% for RV-HI and 71% for FRC-HI, vs 21% and 41% in patients with a FEV1 > 80%). In patients with HI, the ACT score was lower and chest tightness higher. HI reversibility was obtained in 38% of the asthmatics with FRC-HI and 29% of the asthmatics with RV-HI, whereas FEV1 reversibility was obtained in half of these patients. HI is highly prevalent in poorly controlled asthmatics suggesting small airway dysfunction and may represent an additional criteria for evaluating responsiveness to bronchodilators.


How to diagnose hantavirus infections and detect them in rodents and insectivores.
Hantaviruses are carried by rodents and insectivores in which they cause persistent and generally asymptomatic infections. Several hantaviruses can infect humans and many of them cause either haemorrhagic fever with renal syndrome (HFRS) in Eurasia or hantavirus cardiopulmonary syndrome (HCPS) in the Americas. In humans hantavirus infections are diagnosed using IgM-capture tests but also by RT-PCR detection of viral RNA. For detection of hantavirus infections in rodents and insectivores, serology followed by immunoblotting of, for example, lung tissue, and RT-PCR detection of viral RNA may be used, and if of interest followed by sequencing and virus isolation. For sero/genotyping of hantavirus infections in humans and carrier animals neutralisation tests/RNA sequencing are required. Hantaviruses are prime examples of emerging and re-emerging infections and it seems likely that many new hantaviruses will be detected in the near future.


Bias in the superimposition of lateral cephalograms in adult patients with anterior open bite.
Anterior open bite malocclusion can be treated nonsurgically using fixed appliances, clear aligners, or temporary anchorage devices (TADs). Proponents of clear aligners and TADs often attribute bite closure to molar intrusion and counterclockwise rotation of the mandibular plane. These changes may be supported by superimpositions. However, the process of creating a superimposition is subjective and may be influenced by practitioner bias. The initial and final lateral cephalograms from 30 adult anterior patients with open bite were used in this study. Ten patients were treated with fixed appliances, 10 with clear aligners, and 10 with TADs. We asked 6 orthodontic graduate students and 6 orthodontic practitioners to complete superimpositions using these radiographs in 3 separate sessions. In the first session, the raters were told that all patients only received treatment with fixed appliances. In the second session, the raters were told that all patients were treated with clear aligners only, and in the third session, they were told all patients were treated with fixed appliances and TADs. Superimpositions were performed using Dolphin software, and each superimposition was saved as a Portable Document Format image. Change in the mandibular plane was the primary outcome and was assessed categorically (closed, no change, opened). Cephalometric values were measured and used to investigate the dental and skeletal changes associated with treatment. Although the raters demonstrated a slight tendency toward the mandibular plane closing or staying the same when told the treatment was clear aligners or TADs, these differences were not statistically significant. A high degree of intrarater and interrater variability in the mandibular plane change was present in all 3 superimposition sessions. The measurements from the lateral cephs showed significant changes for overbite and incisor vertical and angular movements. Almost no change was observed in anterior facial height, mandibular plane angle, or vertical movement of the first molars. This study did not observe a significant amount of superimposition bias. However, there was considerable intrarater and interrater reliability. This suggests that the same initial and final cephs may be interpreted very differently on the basis of the subjective superimposition of the raters.


Source level interpretation of mixed biological stains using coding region SNPs.
The association of body fluids/cell types and donors in mixed biological traces is an important, but challenging task required to evaluate the value of evidence given forensic propositions concerning the source of the DNA. The linking of a DNA profile with evidence from presumptive tests or RNA analysis is not straightforward. Coding region SNPs (cSNPs) are a novel type of evidential markers that are both cell type specific and individual specific. They thereby provide a direct link between a donor and a body fluid in mixed biological stains. In this proof-of-concept paper we consider the evaluation of cSNP profiles given source level propositions and explore the use of the open-source software EuroForMix to compute likelihood ratios. The discrimination power of the cSNPs for various body fluids is investigated with simulations. We provide case examples where the type of biological material is questioned and where cSNP profiles can be used to assign a donor to a body fluid, and discuss how the results can be reported in court.


Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease.
Chronic kidney disease (CKD) is associated with substantial morbidity and mortality. We developed a mouse model that mimics human CKD with inflammation, extracellular matrix deposition, tubulointerstitial fibrosis, increased proteinuria, and associated reduction in glomerular filtration rate over time. Using this model, we show that genetic deficiency of SMOC2 or therapeutic silencing of SMOC2 with small interfering RNAs (siRNAs) after disease onset significantly ameliorates inflammation, fibrosis, and kidney function loss. Mechanistically, we found that SMOC2 promotes fibroblast to myofibroblast differentiation by activation of diverse cellular signaling pathways including MAPKs, Smad, and Akt. Thus, targeting SMOC2 therapeutically offers an approach to prevent fibrosis progression and CKD after injury.


Total and specific IgE in serum and cerebrospinal fluid of rats and guinea pigs infected with Angiostrongylus cantonensis.
The total and specific IgE response to Angiostrongylus cantonensis infection was evaluated according to host permissiveness. Total IgE levels measured by a double antibody radioimmunoassay (RIA) increased slowly in the permissive host (the rat), reaching a maximum between 4 and 8 weeks after infection. This maximum was earlier but significantly lower in the non-permissive host (the guinea pig). IgE antibodies specific for adult worms or L1 or L3 larvae of A. cantonensis were measured by a radioallergosorbent test (RAST). In the case of adult worms and L1 antigens, specific IgE antibody levels showed large variations in relation to the duration of infection in rats. In contrast to total IgE levels, the specific IgE response to L3 larvae was lower in rats than in guinea pigs in both the serum and cerebrospinal fluid (CSF). These results suggest variations in the total vs specific IgE response according to host permissiveness or non-permissiveness to A. cantonensis infection. These results are discussed in the context of the possible participation of IgE antibodies in immune defence.


An mGlu4-Positive Allosteric Modulator Alleviates Parkinsonism in Primates.
Levodopa remains the gold-standard treatment for PD. However, it becomes less effective as the disease progresses and produces debilitating side effects, such as motor fluctuations and l-dopa-induced dyskinesia. Modulation of metabotropic glutamate receptor 4 represents a promising antiparkinsonian approach in combination with l-dopa, but it has not been demonstrated in primates. We studied whether a novel positive allosteric modulator of the metabotropic glutamate receptor 4, PXT002331 (foliglurax), could reduce parkinsonism in primate models. We assessed the therapeutic potential of PXT002331 in three models of MPTP-induced parkinsonism in macaques. These models represent three different stages of disease evolution: early stage and advanced stage with and without l-dopa-induced dyskinesia. As an adjunct to l-dopa, PXT002331 induced a robust and dose-dependent reversal of parkinsonian motor symptoms in macaques, including bradykinesia, tremor, posture, and mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having therapeutic efficacy on both parkinsonian motor impairment and l-dopa-induced dyskinesia. PXT002331 brain penetration was also assessed using PET imaging in macaques, and pharmacodynamic analyses support target engagement in the therapeutic effects of PXT002331. This work provides a demonstration that a positive allosteric modulator of metabotropic glutamate receptor 4 can alleviate the motor symptoms of PD and the motor complications induced by l-dopa in primates. PXT002331 is the first compound of its class to enter phase IIa clinical trials. © 2018 International Parkinson and Movement Disorder Society.


Covalent organic framework wrapped by graphene oxide as an efficient sulfur host for high performance lithium-sulfur batteries.
The practical application of lithium-sulfur battery is seriously limited by the loss of active substances and the deterioration of cycle stability caused by the 'shuttle effect' of lithium polysulfides (LiPSs). In this work, graphene oxide (GO) coated covalent organic framework (COF) compound materials were synthesized as sulfur host material in spray-drying process. The polar groups on COF can efficiently adsorb LiPSs through lithiophilic interaction, which can reduce the 'shuttle effect' caused by soluble LiPSs. Besides, GO in the outer layer can wrap discrete sulfur to reduce the loss of active substances, which further improves the cycle stability of the cathode. The COF@GO/S cathode exhibits a high initial specific capacity of 848.4 mAh g-1and retains a capacity of 601.1 mAh g-1after 500 cycles at 1 C counting with a low capacity fading of 0.058% per cycle.


Cholesterol-conjugated siRNAs silence gene expression in mucosal dendritic cells in cervicovaginal tissue in mice.
RNA interference (RNAi) provides a powerful way to investigate the role of genes in disease pathogenesis and modulate gene expression to treat disease. In 2018, the FDA approved patisiran, the first RNAi-based drug, hence paving the way for a novel class of RNAi therapeutics. Harnessing RNAi to inhibit vaginal HIV transmission requires effective gene silencing in immune cells, which remains difficult. Knockdown in accessible mucosal tissues may be easier than systemic gene silencing. Vaginally applied cholesterol-conjugated small interfering RNAs (chol-siRNAs) blocked herpes simplex virus transmission in mice without tissue damage or immunostimulation. To investigate using flow cytometry, confocal microscopy, and quantitative imaging if chol-siRNAs silence gene expression in vaginal immune cells in mice. Although chol-siRNAs and lipoplexed-siRNAs silence gene expression in dendritic cells (DCs) in vitro, most internalized siRNAs concentrate within multivesicular bodies, where they are inaccessible to the cellular RNAi machinery. When applied intravaginally in vivo, chol-siRNAs penetrate the vaginal mucosa, including the lamina propria, and are efficiently internalized by intraepithelial (IE) and lamina propria (LP) DCs, and CD11b+ CD45+ cells, but not by T cells. Chol-siRNAs induce partial gene silencing in IE and LP DCs throughout the genital mucosa in vivo but are inactive in F4/80+ CD11b+ macrophages and T cells. As mucosal DCs play an essential role for mucosal viral entry and dissemination, chol-siRNAs could be harnessed to target various host factors that are critical for viral uptake, DC migration and trans-infection of virions to T cells, hence allowing the development of a preventive vaginal HIV microbicide. Furthermore, chol-siRNAs could help elucidate the pathways of HIV transmission and understand the immunologic function of DCs in the genital tract.


Reaction of Ca2+ and phosphate ester.
The reaction of calcium ions and organic phosphate ester monomer at varying pHs was examined. Above pH 10, poorly crystallized hydroxyapatite was formed, which had lower crystallinity than that synthesized with inorganic phosphate as a source of P under the same conditions. On the other hand, the results of X-ray diffraction, chemical analysis, infrared absorption analysis and differential thermal analysis suggested that, crystalline organic calcium phosphate ester was formed below pH 10, whilst for the synthesis with inorganic phosphate hydroxyapatite was formed at pH 7.4.


Designing and testing of an effective oil-in-water microemulsion drug delivery system for in vivo application.
The phase behavior of a new psedoternary system of clove oil/Tween 20 has been studied. Several compositions from the single-phase region were selected and their stability toward time, temperature, and electrolytes has been examined. A particular composition(clove oil/Tween 20/water as 5/30/65) was chosen as the drug delivery system from the clear oil-in-water zone of the pseudoternary system. The droplet dimension and the polydispersity state of the particular composition was determined by dynamic light scattering. A bioactive compound quarcetin was encapsulated in the vehicle. The efficacy of the drug in the vehicle was examined against leishmaniasis in hamster models. The hepatotoxicity of the vehicle (o/w microemulsion) with and without the drug quarcetin was examined by estimating serum alkaline phosphatase, glutamate pyruvate transaminase, urea, and creatinine.


Impact of high-risk classification by FISH: an eastern cooperative oncology group (ECOG) study E4A03.
Lenalidomide with dexamethasone is a standard induction treatment regimen for newly diagnosed myeloma (although a Federal Drug Administration indication is still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide plus dexamethasone in low or high doses), we queried whether a fluorescence in situ hybridization (FISH)-based genetic classification into high risk (HR) and standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of 445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14), t(14;16), or 17p13 deletions. Median survival follow-up approached 3 years. Patients with FISH data tended to be younger and healthier compared to the rest of the study population and, consequently, had superior overall survival (OS) results. Within the FISH cohort, shorter OS in the HR versus SR group (P = 0·004) corresponded to a hazard ratio of 3·48 [95% confidence interval: (1·42-8·53)], an effect also observed in multivariate analysis. Two-year OS rates were 91% for SR MM and 76% for HR MM. There was also evidence of interaction between risk status and treatment (P = 0·026). HR patients were less likely to attain good partial response (SR 46% and HR 30%, Odds Ratio = 2·0 [0·7-5·6]), but overall response rates were not different. FISH-based risk classification retained prognostic significance in patients receiving lenalidomide-based induction.


C-reactive protein, frailty and overnight hospital admission in elderly individuals: A population-based study.
C-reactive protein (CRP), an important inflammatory biomarker, has been linked to various diseases (e.g., cardiovascular disease). Here, we aimed to investigate the associations of high sensitivity C-reactive protein (hsCRP) with frailty and overnight hospital admission in an elderly Chinese population. We used cross-sectional data from 1478 participants (aged 70-84 years) who were randomly recruited from 31 villages in Jiang'an township, Rugao city, China. Frailty status was defined using a modified frailty phenotype. The number of overnight hospital admissions was ascertained. The sample mean age was 75.3 years, and 53.0% of participants were female (n=784). The mean level of hsCRP was 3.6 mg/L. From the low (hsCRP≤1.00 mg/L) to high hsCRP (hsCRP≥3.0mg/L) group, the proportion of overnight hospital admission increased linearly (8.7%, 10.6%, vs. 15.5%; P for trend=0.007). For frailty, the age- and sex-adjusted odds ratios (ORs) were 1.21 (95% CI: 0.89, 1.64) for participants in the intermediate hsCRP group and 1.49 (95% CI: 1.05, 2.09) for participants in the high hsCRP group compared with those in the low hsCRP group. For overnight hospital admission, the corresponding ORs were 1.26 (95% CI: 0.72, 2.19) and 1.94 (95% CI: 1.08, 3.48), respectively. After adjustment for other covariates, the significance of these associations remained. Elevated levels of hsCRP were associated with increased risks of frailty and overnight hospital admission among elderly individuals in Rugao. More public health concerns about inflammation and subsequent outcomes are needed to improve the quality of life in elderly populations.


Rsf-1 is overexpressed in non-small cell lung cancers and regulates cyclinD1 expression and ERK activity.
Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 in primary lung cancer and its biological roles in non-small cell lung cancer (NSCLC) have not been reported. The molecular mechanism of Rsf-1 in cancer aggressiveness remains ambiguous. In the present study, we analyzed the expression pattern of Rsf-1 in NSCLC tissues and found that Rsf-1 was overexpressed at both the mRNA and protein levels. There was a significant association between Rsf-1 overexpression and TNM stage (p=0.0220) and poor differentiation (p=0.0013). Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression resulted in a decrease of colony formation ability and inhibition of cell cycle progression. Rsf-1 knockdown also induced apoptosis in these cell lines. Further analysis showed that Rsf-1 knockdown decreased cyclin D1 expression and phospho-ERK levels. In conclusion, Rsf-1 is overexpressed in NSCLC and contributes to malignant cell growth by cyclin D1 and ERK modulation, which makes Rsf-1 a candidate therapeutic target in lung cancer.


Prolonged carriage of ESBL-producing enterobacterales and potential cross-transmission among residents in geriatric long-term care facilities.
Previous studies indicated residents in geriatric long-term care facilities (LTCFs) had much higher prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage than the general population. Most ESBL-E carriers are asymptomatic. The study tested the hypothesis that residents with ESBL-E carriage may accumulate inside geriatric LTCFs through potential cross-transmission after exposure to residents with prolonged ESBL-E carriage. 260 residents from four Japanese LTCFs underwent ESBL-E testing of fecal specimens and were divided into two cohorts: Cohort 1,75 patients with ≥ 2 months residence at study onset; Cohort 2, 185 patients with < 2 months residence at study onset or new admission during the study period. Three analyses were performed: (1) ESBL-E carriage statuses in Cohort 1 and Cohort 2; (2) changes in ESBL-E carriage statuses 3-12 months after the first testing and ≥ 12 months after the second testing; and (3) lengths of positive ESBL-E carriage statuses. Compared with the residents in Cohort 1, a significantly larger proportion of residents in Cohort 2 were positive for ESBL-E carriage (28.0% in Cohort 1 vs 40.0% in Cohort 2). In the subsequent testing results, 18.3% of residents who were negative in the first testing showed positive conversion to ESBL-E carriage in the second testing, while no patients who were negative in the second testing showed positive conversion in the third testing. The maximum length of ESBL-E carriage was 17 months. The findings indicated that some residents acquired ESBL-E through potential cross-transmission inside the LTCFs after short-term residence. However, no residents showed positive conversion after long-term residence, which indicates that residents with ESBL-E carriage may not accumulate inside LTCFs. Practical infection control and prevention measures could improve the ESBL-E prevalence in geriatric LTCFs.


Performance of Tao-Mo Semilocal Functional with rVV10 Dispersion-Correction: Influence of Different Correlation.
We construct van der Waals corrected semilocal density functionals based on the Tao-Mo (TM) (Phys. Rev. Lett. 2016, 117, 073001) metageneralized gradient approximation combined with the revised Vydrov-Voorhis (rVV10) long-range correlation. We found that the combination of TM (TM exchange with TM correlation) and TMTPSS (TM exchange with TPSS correlation) semilocal functionals with rVV10 nonlocal correlation is suitable for both molecular and solid-state applications. The performance of both the functionals (TM + rVV10L and TMTPSS + rVV10L, where L stands for layers) is also demonstrated for the noble-gas solids, noncovalent interaction of molecules, and physisorption of rare gas on metal surfaces. We observe that although the rVV10L parameter is fixed from the layered materials, these perform equivalently better for different dispersion-dominated molecular systems. Physical insights of different correlation effects and choice of the rVV10 parameter on the functional performance are also justified.


Effect of the length of the second stage of labor on pelvic floor dysfunction.
Pelvic floor dysfunction refers to any combination of incontinence, overactive bladder, pelvic organ prolapse, and sexual dysfunction. Pelvic floor dysfunction affects approximately 25% to 30% of women and is linked to parity and age. Some obstetrical risk factors have been highlighted, though the second stage of labor has not been as thoroughly investigated. Allowing a longer second stage has been suggested as a method of reducing the rates of cesarean delivery in nulliparous women, though it has also been linked to pelvic floor injuries. This study aimed to determine the effect of the length of the second stage of labor on self-reported pelvic floor dysfunction. This was a single-center prospective cohort study in a tertiary referral obstetrical unit. Nulliparous women attending routine antenatal clinics were recruited to complete the Australian Pelvic Floor Questionnaire during pregnancy and again 3 months after delivery. The primary outcome in this study was the effect of the length of the second stage of labor on total pelvic floor scores when analyzed using multiple regression. The models were adjusted for the mother's age, mother's body mass index, length of the second stage of labor, fetal birthweight, mode of delivery, and perineal trauma. The secondary outcomes included the comparison of maternal, obstetrical, and functional pelvic floor outcomes based on the mode of delivery and the length of the second stage of labor. Among the 295 women who were recruited, the length of the second stage of labor and body mass index were associated with self-reported bladder dysfunction on multiple regression, whereas maternal age was protective. Compared with those with 60 to 120 minutes or <60 minutes of second stage of labor, women with that longer than 120 minutes had higher rates of stress incontinence (85.7% [>120 minutes] vs 41.7% [60-120 minutes] or 52.5% [<60 minutes], P=.001), urinary urgency (89.3% [>120 minutes] vs 39.6% [60-120 minutes] or 53.8% [<60 minutes], P<.001), and fecal incontinence (10.7% [>120 minutes] vs 0% [60-120 minutes] or 1.2% [<60 minutes], P=.027). There were no differences in the rates of sexual activity or dyspareunia. Women delivering vaginally had higher rates of stress incontinence (57.6% vs 38.0%, P=.006) than those undergoing cesarean delivery, though there were no differences in other pelvic floor symptoms or pelvic floor scores. A prolonged second stage of labor is associated with more self-reported bladder dysfunction at 3 months postnatal in primiparous women. Women with a longer second stage of labor should be informed about the risk of short-term bladder dysfunction, though the prevalence of long-term sequelae is unknown.


Improving cross-cultural awareness. A review of Australian indigenous health for UK dentists.
The aim of this paper is to give an insight into the unique health issues faced by the indigenous population of Australia and their direct relationship to oral health, to help overseas dentists wishing to work in Australia to treat these groups of patients successfully and effectively. This applies equally to indigenous Australians living in remote Australia as well as to those living in general suburbia. A Medline search was carried out for any articles in dental and medical journals pertaining to Australian indigenous health and Australian oral health. Wherever possible, articles cited were obtained in full and where this was not possible, abstracts were obtained. Where no abstract was available, the article was not considered for evaluation. Articles were reviewed by a single observer and were subject to meeting inclusion criteria indicated in the review. Articles were divided into historical, diet, oral health and general health categories. Subjective descriptions were then made. The adoption of a 'westernised' diet by the Australian indigenous community has placed them as a high risk population for dental caries and periodontal disease. They also show some of the highest rates in the world for Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Rheumatic Fever. The UK dentist should be aware of these health issues and their relationship to indigenous oral health before embarking on work within Australia.


Semilunar changes in estradiol and cortisol coincident with gonadal maturation and spawning in the killifish Fundulus heteroclitus.
Radioimmunoassay techniques were used to measure estradiol-17 beta (E2) and cortisol in the serum and ovarian fluid of Fundulus heteroclitus throughout complete semilunar spawning cycles. The cyclic nature of spawning activity was confirmed by monitoring the gonadosomatic index and noting the times at which ovulated eggs were found within the ovarian lumen. Levels of serum E2, ovarian fluid E2, and serum cortisol all exhibited cycles which paralleled the semilunar cycle of gonadal maturity and spawning in this euryhaline killifish. Elevations of serum cortisol were temporally associated with ovulation, whereas ovarian fluid E2 levels peaked several days prior to ovulation. Serum E2 remained elevated after ovarian fluid E2 levels had returned to baseline. Cortisol concentrations in ovarian fluid did not cycle and no correlation was apparent between serum cortisol and glucose concentrations.


Vascular endothelial growth factor encoded by Parapoxviruses can regulate metabolism and survival of triple negative breast cancer cells.
Dysbiotic microbiomes are linked to many pathological outcomes including different metabolic disorders like diabetes, atherosclerosis and even cancer. Breast cancer is the second leading cause of cancer associated death in women, and triple negative breast cancer (TNBC) is the most aggressive type with major challenges for intervention. Previous reports suggested that Parapoxvirus signatures are one of the predominant dysbiotic viral signatures in TNBC. These viruses encode several genes that are homologs of human genes. In this study, we show that the VEGF homolog encoded by Parapoxviruses, can induce cell proliferation, and alter metabolism of breast cancer and normal breast cells, through alteration of MAPK-ERK and PI3K-AKT signaling. In addition, the activity of the transcription factor FoxO1 was altered by viral-encoded VEGF through activation of the PI3K-AKT pathway, leading to reprogramming of cellular metabolic gene expression. Therefore, this study provides new insights into the function of viral-encoded VEGFs, which promoted the growth of the breast cancer cells and imparted proliferative phenotype with altered metabolism in normal breast cells.


Feeding Behavior, Growth Performance and Meat Quality Profile in Broiler Chickens Fed Multiple Levels of Xylooligosaccharides.
A total of 240 1-day-old Arbor Acres broiler chickens were randomly distributed to 4 treatment groups with 6 replicates and 10 birds per replicate. Chickens were fed with corn-soybean meal diet supplementation with additions of 0, 150, 300, and 450 mg/kg XOS for 42 days. At 4 weeks of age, the average feeding time was reduced in the 450 mg/kg XOS group (p < 0.05), and the percentage of feeding time was increased in the 300 mg/kg XOS group (p < 0.05). At 5 weeks of age, broilers fed with 300 mg/kg XOS had increased the percentage of feeding time (p < 0.05), and 450 mg/kg XOS had increased the feeding frequency and percentage of feeding time (p < 0.05). At 6 weeks of age, the feeding frequency was highest in the 450 mg/kg XOS group (p < 0.05). During 4 to 6 weeks of age, the average feeding time was increased in 300 mg/kg XOS group (p < 0.05), the frequency was improved in the 450 mg/kg XOS group (p < 0.05), and the percentage of feeding time was longer in the XOS group than that in the control group (p < 0.05). The average daily gain was improved during days 22-42 and days 1-42 in the 150 mg/kg XOS group (p < 0.05). Broilers fed with 300 mg/kg XOS had an increased eviscerated rate (p < 0.05). The pH45min of breast muscle was highest in the 450 mg/kg XOS group (p < 0.05), as well as the pH45min and pH24h of thigh muscle, which improved in the 300 mg/kg and 450 mg/kg XOS groups (p < 0.05). In addition, the cooking loss of thigh muscle was reduced in the 300 mg/kg XOS group (p < 0.05). In conclusion, dietary supplementation with XOS had positive effects on the feeding behavior, growth performance, and meat quality of broiler chickens.


Cellular assays combined with metabolomics highlight the dual face of phenolics: From high permeability to morphological cell damage.
The Caco-2 cellular permeability of phenolic aqueous extracts from blackcurrant press cake (BC), Norway spruce bark (NS), scots pine bark (SP), and sea buckthorn leaves (SB) was evaluated by combining high-resolution mass spectrometry and atomic force microscopy. Besides, Caco-2 and HepG2 cells allowed the study of intracellular oxidative stress assessed in both apical and basolateral domains. Overall, BC and NS showed the highest total phenolic contents, 4.38 and 3.76 µg/mL, respectively. Multivariate statistics discriminated NS and BC from SP and SB extracts because of their phenolic profile. Polyphenols were classified as highly permeable, thus suggesting their potentially high bioavailability through the gastrointestinal tract. All the phenolic subclasses showed efflux ratio values < 1, except for BC flavonols, flavan-3-ols, and stilbenes. Regarding cellular damage, NS and BC extracts, when acting on the basolateral cellular side, caused epithelial leakage and morphological shape cell damage on Caco-2 cells associated with ROS production.


Radiobiological prediction of normal tissue toxicities and tumour response in the radiotherapy of advanced non-small-cell lung cancer.
A number of randomized studies have been carried out in the UK and USA to determine the optimal radiotherapy dose schedule for advanced non-small-cell lung cancer (NSCLC). We have examined eight radiotherapy regimens from data taken from four randomized phase III studies carried out in the UK (1264 patients): 10 Gy single fraction; 17 Gy in two fractions over 8 days; 30 Gy in ten fractions over 14 days; 22.5 Gy in five fractions in 5 days; 27 Gy in six fractions over 11 days; 30 Gy in six fractions over 11 days; 36 Gy in 12 fractions over 16 days; and 39 Gy in 13 fractions over 17 days. We compared the clinical results in palliation, toxicity and survival with four regimens taken from one randomized study from the USA (365 patients): 40 Gy in 20 fractions over 4 weeks; 40 Gy 'split course' in ten fractions in 4 weeks; 50 Gy in 25 fractions over 5 weeks; and 60 Gy in 30 fractions over 6 weeks. Using the linear-quadratic (LQ) radiobiological model, we have calculated the radiobiological equivalent dose (BED) for acute-reacting tissues (BED10), late-reacting tissues (BED1.7) and tumour (BED25), and related the predicted response to the observed response in each tissue. There was a good correlation between the predicted response and the reported response in the case of late-reacting tissue toxicity and tumour response. The model confirmed that, in good performance status patients, a higher value for BED25 correlated with a higher degree of local control and survival and that radiotherapy regimens with a higher value for BED1.7 were associated with five cases of cord myelopathy, if the spinal cord was not shielded. In poor performance status patients the model suggested that the optimal regimen was a single fraction of 10 Gy because this resulted in an equivalent degree of symptom control as other regimens, needed only one hospital visit and was less likely to result in cord damage, thus, allowing for the possibility of retreatment at a later date.


Maternal deaths in Iceland over 25 years.
Maternal death, during pregnancy or within 42 and 365 days from the end of pregnancy, was evaluated for a small high-income nation with comprehensive healthcare. Cases were identified using record linkage by running national census information on all deaths of women aged 15-49 years during 1985-2009 against the national birth register and computerized hospital admission files for pregnancy-related diagnoses as well as actual case records where needed. Death certificates and hospital records were reviewed. Thirty deaths were identified; 26 at ≥ 22 weeks (= birth) and four earlier in pregnancy. For 107,871 deliveries, the overall mortality was 27.8/100,000. There were five direct deaths (4.6/100,000 deliveries), five indirect deaths (4.6/100,000 deliveries) and 19 coincidental deaths (17.6/100,000 deliveries). Using WHO criteria (direct and indirect in pregnancy or at ≤ 42 days postpartum) the ratio was 5.6/100,000 deliveries (95% confidence interval 1.1-10.1) and 5.5/100,000 live births (maternal mortality ratio, based on six deaths). Direct deaths were caused by sepsis, severe preeclampsia and choriocarcinoma, indirect by suicide, pre-existing cardiac and diabetic illness. No woman died of postpartum hemorrhage, anesthesia or ectopic pregnancy. Suboptimal care occurred. Maternal mortality in Iceland over a 25-year period up to the end of year 2010 was low, between 5 and 6/100,000 births. A comprehensive national healthcare system with accessible antenatal care in a society with good general living conditions and universal education probably contributed to this.


Wide coverage of the tetraploid cotton genome using newly developed microsatellite markers.
Microsatellite [simple-sequence repeat (SSR)] markers were developed and positioned on the genetic map of tetraploid cotton. Three hundred and ninety-two unique microsatellite sequences, all but two containing a (CA/GT) repeat, were isolated, and the deduced primers were used to screen for polymorphism between the Gossypium hirsutum and G. barbadense parents of the mapping population analyzed in our laboratory. The observed rate of polymorphism was 56%. The 204 polymorphic SSRs revealed 261 segregating bands, which ultimately gave rise to 233 mapped loci. The updated status of our genetic map is now of 1,160 loci and 5,519 cM, with an average distance between two loci of 4.8 cM. The presence of a total of 466 microsatellite loci, with an average distance of 12 cM between two SSR loci, now provides wide coverage of the genome of tetraploid cotton and thus represents a powerful means for the production of a consensus map and for the effective tracking of QTLs.


Acute PR3-ANCA vasculitis in an asymptomatic COVID-19 teenager.
We present the case of an acute onset ANCA positive vasculitis in an asymptomatic COVID-19 infected teenager, resulting in significant colonic damage. The patient was initially diagnosed with Henoch-Schönlein purpura and presented with worsening symptoms with significant necrosis of her perineum and rectum requiring surgical debridement and diverting colostomy. As a part of her work-up, she tested positive for COVID-19 total IgG/IgM antibodies and ANCA antibodies. This case complements previously reported cases of COVID-19 induced autoimmune disease in children but is novel in describing extensive intestinal disease as a result of an autoimmune vasculitis in a child.


Development of prostate bed delineation consensus guidelines for MRI-guided radiotherapy and assessment of its impact on interobserver variability.
The use of MRI in radiotherapy planning is becoming more widespread, particularly with the emergence of MRI-guided radiotherapy (MRIgRT) systems. Existing guidelines for defining the prostate bed clinical target volume (CTV) show considerable heterogeneity. This study aims to establish baseline interobserver variability (IOV) for prostate bed CTV contouring on MRI, develop international consensus guidelines and evaluate its effect on IOV. Participants delineated the CTV on three MRI scans, obtained from the xxx xxx MR-Linac, as per their normal practice. Radiation oncologist contours were visually examined for discrepancies and interobserver comparisons were evaluated against Simultaneous Truth and Performance Level Estimate (STAPLE) contours using overlap metrics (Dice similarity coefficient and Cohen's Kappa), distance metrics (mean distance to agreement and Hausdorff distance) and volume measurements.. A literature review of post-radical prostatectomy local recurrence patterns was performed and presented alongside IOV results to the participants. Consensus guidelines were collectively constructed and IOV assessment was repeated using these guidelines. Sixteen radiation oncologists' contours were included in the final analysis. Visual evaluation demonstrated significant differences in the superior, inferior and anterior borders. Baseline IOV assessment indicated moderate agreement for the overlap metrics whilst volume and distance metrics demonstrated greater variability. Consensus for optimal prostate bed CTV boundaries was established during a virtual meeting. Post-guideline development, a decrease in IOV was observed. The maximum volume ratio decreased from 4.7 to 3.1 and volume coefficient of variation reduced from 40% to 34%. The mean Dice similarity coefficient rose from 0.72 to 0.75 and the mean distance to agreement decreased from 3.63mm to 2.95mm. Interobserver variability in prostate bed contouring exists amongst international genitourinary experts, although this is lower than previously reported. Consensus guidelines for MRI-based prostate bed contouring have been developed and this has resulted in an improvement in contouring concordance. However, IOV persists and strategies such as an education program, development of a contouring atlas and further refinement of the guidelines may lead to additional improvements.


Skeletal complications and survival in renal cancer patients with bone metastases.
Skeletal metastases occur in around one third of patients with advanced or metastatic renal cell carcinoma (RCC). Skeletal involvement is commonly an aggressive, lytic process which causes substantial morbidity through skeletal complications and occurrence of skeletal related events (SREs). However, compared with bone metastases in breast and prostate cancer, there is a paucity of data relating to the demographics of bone metastases in RCC and their sequelae in terms of SREs and survival. The study population included all patients (N=803) with advanced or metastatic RCC treated in a tertiary centre serving a regional population of 2.6 million between 1998 and 2007. Demographic and survival data and information relating to metastatic disease were extracted from electronic records. Thirty-two percent (N=254) of the study population presented with (N=131) or later developed (N=123) bone metastases and 83% of these (N=210) also developed metastases elsewhere. The mean number of SREs experienced by the bone metastatic patients over the course of their disease was 2.4 and only 37 patients experienced no SRE. A high proportion of patients (80%) received radiotherapy for bone pain and there was a surprising and strikingly high incidence of spinal cord/nerve root compression, which was experienced by 28% patients. Although bisphosphonate use increased following the availability of zoledronic acid in 2004, approximately 50% patients with bone metastases did not receive bisphosphonate treatment. The skeletal morbidity rate (number of SREs per patient years at risk) was 1.0 and 1.4 for patients who received or did not receive bisphosphonates, respectively. The median survival following diagnosis of RCC was similar in patients who developed bone metastases (20.4 months) and those who did not (20.9 months). Median survival from diagnosis of metastases was 13.3 months for those who never developed bone metastases, 10.6 months for those who presented with them, 19.6 months for those who developed them later and 22.6 months for patients who had bone only metastases. This is the largest study to date focusing specifically on skeletal complications in RCC. A striking finding was the high incidence of spinal cord/nerve root compression and more research into this area is needed. Clearer, internationally accepted guidelines are recommended for the management of this patient group.


A side-specific nomogram for extraprostatic extension may reduce the positive surgical margin rate in radical prostatectomy.
Nomograms predicting side-specific extraprostatic extension (EPE) may be applied to reduce positive surgical margin (PSM) rates in patients planned for radical prostatectomy (RP). This study evaluates the impact of implementing an externally validated nomogram for side-specific EPE on PSM rate and degree of nerve-sparing. In patients planned for RP, the side-specific nomogram predictions (based on MRI, ISUP grade group, and PSA density), with an advised threshold of 20% for safe nerve-sparing, were presented preoperatively to the urological surgeon. The surgeon completed a survey before RP about the planning with respect to side-specific nerve-sparing and change of management due to the result of the nomogram. PSM rates and degree of nerve-sparing were compared to a retrospective control group treated in the months prior to the introduction of the nomogram. A total of 100 patients were included, 50 patients in both groups representing 200 prostate lobes. Of the patients, 37% had histologically confirmed EPE, and 40% a PSM. In 12% of the 100 lobes planned after nomogram presentation, a change in management due to the nomogram was reported. A per-prostate lobe analysis of all the lobes showed comparable rates of full nerve-sparing (45% vs. 30%; p = 0.083) and lower rates of PSM on the lobes with histological EPE (45% vs. 85%; p < 0.05) in the intervention (nomogram) group versus the control group. Implementing a predictive nomogram for side-specific EPE in the surgical planning for nerve-sparing leads to lower rates PSM on the side of the histological EPE without compromising nerve-sparing.


Administration of Exogenous Progesterone Protects Against Brucella abortus Infection-Induced Inflammation in Pregnant Mice.
Progesterone has been recognized as essential for the establishment and maintenance of pregnancy, and is typically known as an immunosuppressive agent. However, its effects on mediating Brucella infection-induced inflammation have not been evaluated. Here we demonstrated that Brucella abortus infection inhibits progesterone levels in the pregnant mouse by suppressing the production of progesterone by placenta. Progesterone treatment significantly reduced the secretion of inflammatory cytokines in serum, macrophages, and trophoblasts of B. abortus-infected mice, leading to decreased placentitis and enhancing the pup viability. Mechanistically, this decreased inflammatory response results from inhibition of NF-kB activation by progesterone. Moreover, progesterone treatment suppresses B. abortus growth within trophoblasts associated with an inability of bacteria to escape the late endosome compartment in vitro. Collectively, our data illustrate that progesterone treatment might be useful therapeutically in protection against placentitis or abortion caused by B. abortus infection.


Prostate mechanical imaging: a new method for prostate assessment.
To evaluate the ability of prostate mechanical imaging (PMI) technology to provide an objective and reproducible image and to assess the prostate nodularity. We evaluated the PMI device developed by Artann Laboratories in a pilot clinical study. For the 168 patients (ages 44 to 94) who presented to an urologist for prostate evaluation, PMI-produced images and assessment of prostate size, shape, consistency/hardness, mobility, and nodularity were compared with digital rectal examination (DRE) findings. The PMI and DRE results were further tested for correlation against a transrectal ultrasound of the prostate (TRUS) guided biopsy for a subgroup of 21 patients with an elevated prostate-specific antigen level. In 84% of the cases, the PMI device was able to reconstruct three-dimensional (3D) and 2D cross-sectional images of the prostate. The PMI System and DRE pretests were able to determine malignant nodules in 10 and 6 patients, respectively, of the 13 patients with biopsy-confirmed malignant inclusions. The PMI System findings were consistent with all 8 biopsy negative cases, whereas the DRE had 1 abnormal reading for this group. The correlation between PMI and DRE detection of palpable nodularity was 81%, as indicated by the area under the receiver operating characteristic curve. Estimates of the prostate size provided by PMI and DRE were statistically significantly correlated. The PMI has the potential to enable a physician to obtain, examine, and store a 3D image of the prostate based on mechanical and geometrical characteristics of the gland and its internal structures.


Diclofenac sodium and Imipenem action on rat intestinal mucosa: a biomechanical and histological study.
To study diclofenac sodium induced histological and mechanical alterations and their prevention with Imipenem in rat intestine. Male Wistar rats (n=240) were randomly assigned to four experimental groups: GI: n=60 treated with 0.9% saline IM; GII: n=60 treated with 6 mg/kg body weight diclofenac sodium IM for four days; GIII: n=60 treated with 30 mg/kg body weight Imipenem IM for four days, and GIV n=60 treated with diclofenac sodium plus Imipenem at the above doses IM for 4 days. Each group was further divided into 4 subgroups of 15 rats each and sacrificed at 4, 7, 14, and 21 days of follow-up, respectively. Abdominal cavity macroscopy and histology, and small bowel breaking strength were analyzed at each sacrifice moment. There were no histological or mechanical alterations in normal control rats throughout the study. Ulcerated lesions in intestinal mucosa were observed and breaking strength decreased in all diclofenac sodium treated rats. Ulcerated lesions in intestinal mucosa were prevented by Imipenem in all rats. Diclofenac sodium induced ulcerated lesions in rat intestinal mucosa can be prevented by Imipenem treatment.


HLA-F transcriptional and protein differential expression according to its genetic polymorphisms.
Many specificities single out HLA-F: its structure, expression regulation at cell membrane and function. HLA-F mRNA is detected in the most cell types and the protein is localized in the ER and Golgi apparatus. When expressed at cell surface, HLA-F may be associated to β2-microglobulin and peptide or expressed as an open-conformer molecule. HLA-F reaches the membrane upon activation of different primary cell types and cell-lines. HLA-F has its highest affinity for the KIR3DS1-activating NK receptor, but also binds inhibitory immune receptors. Some studies reported that HLA-F expression is associated with its genotype. Higher HLA-F mRNA expression associated with F*01:01:02, and 3 noncoding SNPs, rs1362126, rs2523405, and rs2523393, located in HLA-F-AS1 or upstream the HLA-F sequence were associated with HLA-F mRNA expression. Given the implication of HLA-F in many clinical setting, and the undisclosed process of its expression regulation, we aim to confirm the effect of the aforementioned SNPs with HLA-F transcriptional and protein expression. We analyzed the distribution, frequency and linkage disequilibrium of these SNPs at worldwide scale in the 1000 Genomes Project samples. Influence on the genotype of each SNP on HLA-F expression was explored using RNAseq data from the 1000 Genomes Project, and using Q-PCR and intracellular cytometry in PBMC from healthy individuals. Our results show that the SNPs under studied displayed remarkably different allelic proportion according to geography and confirm that rs1362126, rs2523405, and rs2523393 displayed the most concordant results, with the highest effect size and a double-dose effect.


Protective effect and mechanism of action of xanthan gum on the color stability of black rice anthocyanins in model beverage systems.
We investigated the effect and mechanism of action of xanthan gum (XG) on the color stability of black rice anthocyanins (BRA) in model beverage systems (pH 3.0) containing l-ascorbic acid under different conditions. The color stability of BRA was significantly enhanced in the presence of XG under accelerated storage conditions (40 °C), particularly at 0.25% (w/v). The degradation of BRA followed a first-order reaction rate (R2 > 0.89) during storage and thermal processing conditions. The addition of XG effectively improved the storage stability of BRA in the presence of l-ascorbic acid, particularly at 4 °C in the dark. Moreover, the thermal stability of BRA was enhanced by XG under thermal treatment (80 °C, 90 °C and 100 °C). The FTIR spectrum, X-ray diffraction and molecular simulation results showed that the interaction between XG and BRA was driven mainly by hydrogen bonds and hydrophobic interactions, leading to the increased stability of BRA. Our study demonstrated the benefits of using XG to improve the color stability of BRA in model beverage systems, further expanding the practical application of XG in anthocyanin-rich beverages.


Synergistic effect on biofilm formation between Fusobacterium nucleatum and Capnocytophaga ochracea.
The formation of dental plaque biofilm by specific Gram-negative rods and spirochetes plays an important role in the development of periodontal disease. The aim of this study was to characterize biofilm formation by Fusobacterium nucleatum and Capnocytophaga ochracea. Coaggregation between F. nucleatum and Capnocytophaga species was determined by visual assay. Biofilm formation was assessed by crystal violet staining. Enhancement of biofilm formation by F. nucleatum via soluble factor of C. ochracea was evaluated by addition of culture supernatant and a two-compartment separated co-culture system. Production of autoinducer-2 by the tested organisms was evaluated using Vibrio harveyi BB170. F. nucleatum strains coaggregated with C. ochracea ATCC 33596 or ONO-26 strains. Ethylenediamine tetraacetic acid, N-acetyl-d-galactosamine or lysine inhibited coaggregation. Heating or proteinase K treatment of F. nucleatum cells affected coaggregation, whereas the same treatment of C. ochracea cells did not. Co-culture of F. nucleatum with C. ochracea in the same well resulted in a statistically significant increase in biofilm formation. Enhancement of F. nucleatum biofilm formation by a soluble component of C. ochracea was observed using the two-compartment co-culture system (P < 0.05) and confirmed by addition of culture supernatant of C. ochracea (P < 0.01). The present findings indicate that induction of coaggregation and intracellular interaction by release of a diffusible molecule by C. ochracea play a significant role in the formation of biofilm by F. nucleatum and C. ochracea.


Humanitarian migrant women's experiences of maternity care in Nordic countries: A systematic integrative review of qualitative research.
Maternal morbidity and sub-optimal maternity care are more common in humanitarian migrants in comparison to country-born population in the Nordic countries. Statistical reviews on the issue are plenty, whereas little synthesis on humanitarian migrants' lived experiences exists. This systematic integrative literature review investigated humanitarian migrant women's experiences on maternity care in Nordic countries, aiming to address possible hindrances for optimal care. Electronic search in PubMed, CINAHL, SocIndex, Scopus, PsycINFO and Web of Science yielded 474 papers. PICoS inclusion and exclusion criteria were used. Critical appraisal was conducted utilising 32-item COREQ tool. The findings of the review articles were synthesised through thematic analysis. Ten qualitative studies were included in the review. Altogether 198 women in Sweden, Norway and Finland had participated interviews or focus group discussions. Analysis of the women's reported experiences of care emerged three themes: Diminished negotiation power on care, Sense of insecurity, and Experienced care-related discrimination. Humanitarian migrant women's maternal morbidity and sub-optimal care has multiple potential explanations, and their experiences of care reflect those earlier reported. Recommendations for tackling the addressed hindrances are: (1) enabling humanitarian migrant women's negotiation power by acknowledging their vulnerability but also competency, (2) increasing the sense of security, and (3) improving care providers' cultural competence.


Patient-specific plates for facial fracture surgery: A retrospective case series.
Surgeons often encounter challenges when treating maxillofacial fractures using conventional methods that involve trimming or bending ready-made titanium plates for open reduction and internal fixation (ORIF) since it can be time-consuming, imprecise, and inconvenient. This retrospective case series aimed to introduce a novel bone reduction method that utilizes virtual planning, patient-specific surgical guides, and titanium plates. Seven patients with mandibular symphysis or subcondylar fractures resulting from facial trauma underwent cone-beam computed tomography (CBCT) or facial CT scans, and their medical histories were documented. Virtual surgery was conducted based on three-dimensional (3D) stereolithography images derived from CT scans using the FaceGide software (MegaGen, Daegu, Korea). ORIF was performed using patient-specific surgical guides and plates that were designed, printed, and milled. Radiographic, clinical, and occlusal evaluations were conducted at two weeks and six weeks postoperatively. Subsequently, 3D images from virtual surgery and postoperative CT scans were compared. The comparison of 3D virtual surgery and postoperative images revealed minimal surface differences of less than 1 mm. T-scan evaluations indicated that there were no statistically significant differences between the two- and six-week postoperative assessments. Favorable clinical outcomes were observed. This novel method demonstrated stable outcomes in terms of occlusion and healing, with no notable complications. Consequently, this approach may serve as a viable alternative to conventional methods. Facial fracture surgery that utilizes patient-specific surgical guides and plates within a digital workflow can facilitate meticulous surgical planning, reducing the risk of complications and minimizing operation time.


Conditions of lateral surface confinement that promote tissue-cell integration and inhibit biofilm growth.
Surfaces with cell adhesiveness modulated at micro length scales can exploit differences between tissue/bacterial cell size, membrane/wall plasticity, and adhesion mechanisms to differentially control tissue-cell/material and bacteria/material interactions. This study explores the short-term interactions of Staphylococcus aureus and osteoblast-like cells with surfaces consisting of cell-adhesive circular patches (1-5 μm diameter) separated by non-adhesive electron-beam patterned poly(ethylene glycol) hydrogel thin films at inter-patch distances of 0.5-10 μm. Osteoblast-like U2OS cells both bind to and spread on the modulated surfaces, in some cases when the cell-adhesive area comprises only 9% of the total surface and in several cases at least as well as on the continuously adhesive control surfaces. In contrast, S. aureus adhesion rates are 7-20 times less on the modulated surfaces than on the control surfaces. Furthermore, the proliferation of those bacteria that do adhere is inhibited by the lateral confinement imposed by the non-adhesive boundaries surrounding each patch. These findings suggest a new approach to create biomaterial surfaces that may promote healing while simultaneously reducing the probability of infection.


Transcription of the LAT gene is regulated by multiple binding sites for Sp1 and Sp3.
The LAT gene encodes an adaptor molecule that links receptor engagement to critical downstream signaling events. Previously, we identified the proximal promoter for the human LAT gene and found that it contains binding sites for members of the Ets and Runx transcription factor families. In the present study, we show that the promoter also contains 5 GC-rich elements that contribute to promoter activity and that are capable of binding the transcription factors Sp1 and Sp3. Overexpression of either Sp1 or full-length Sp3 was shown to augment LAT promoter activity, while siRNA-mediated knockdown of each transcription factor was demonstrated to have an inhibitory effect. We also discovered a cell-type specific DNase hypersensitive site that maps to the Sp1/Sp3 and adjacent Ets and Runx binding sites. Collectively, these results provide compelling data that implicates Sp1 and Sp3 in the transcriptional regulation of the human LAT gene.


Aortic arch aneurysm repair with a new branched device.
Aortic arch pathologies remain a technical challenge. The major difficulties in endovascular repair involve anatomic factors and technical aspects. The location of the disease may restrict an adequate proximal sealing zone, and alignment of the endograft is fundamental to acute success and long-term stability. We describe the successful endovascular repair of a 61-mm aortic arch aneurysm using a new branched device.


Gut microbiota: Guardians of the female gut health.
The role of gut microbiota and their sex-specific differences in colorectal cancer remain to be explored. In the current issue of Cancer Cell, Li et al. discovered that estrogen facilitates the colonization of Carnobacterium maltaromaticum in the mouse gut and exerts its anti-colorectal cancer effects by increasing the production of vitamin D3.


Functional and surgical treatments in patients with spinal muscular atrophy (SMA).
Spinal muscular atrophies (SMA type 1, 2, 3) present with various severities according to the motor semeiology related to lesions of the peripheral nervous system (lesions of the anterior horn cells motoneuron or even brain stem). Early motor deficiency causes skeletal deformities responsible for the alteration or even absence of motor skills acquisition. The management of these patients involves several practitioners: pediatric neurologist, pediatric pneumologist, physical medicine and rehabilitation therapist, pediatric orthopedic surgeon, psychologist, physiotherapist, etc. Therefore, this multidisciplinary management must take place in a reference center. This has allowed for improvement of the natural history of SMA. Despite the severity of clinical presentation, especially in SMA type 1 or 2, the functional aspect is always to be taken into account in the first instance. Furthermore, the natural history of the disease is currently being modified by the emergence of innovative therapies that will change the evolution of the disease and its management. Indeed, current treatment objectives are the comfort of installation and the fight against neuro-orthopedic degradation. Although the rise in the number of innovative therapies has led to increased expectancies, such as motor function improvement, practitioners should be aware that these innovative treatments should be balanced against child development and the disease's natural history. Scoliosis surgery is almost systematic in SMA type 2 because of trunk muscular deficiency, especially intercostal muscle insufficiency, and spino-pelvic complex disorder. However, surgical techniques have evolved to become less invasive and more growth friendly in order to follow child development. The final goal of surgery in SMA patients is to obtain a 3-dimensional deformity correction along with a spino-pelvic realignment in order to allow for a comfortable seated position, which is the position of function in these patients, and to allow for better ventilation. Faced with this global approach and innovative therapies, global assessment is warranted not solely in an isolated manner, as is usually the case during hospital stays with traditional scales, but rather during daily activities. This is the case of daily monitoring, which allows for motor skill and activity assessments throughout the day. The principle is to characterize, according to SMA type and treatment, the activity type (standing, seated, walking), duration, intensity and frequency. The ultimate goal would be to identify the variety and occurrence of motor activities, and finally to clarify if the different treatments, including innovative therapies, lead to functional improvement in these patients. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.


Prevalence of thyroid nodules and characteristics of thyroid ultrasound in children with goiter: a single center experience.
Goiter is a common presenting sign of various thyroid diseases in children. Thyroid nodules are clinically and/or radiologically significant findings due to their high malignancy rate. The ultrasound (US) characteristics of pediatric patients with goiter are rarely reported in literature; thus, the purpose of this study is to assess the characteristics of thyroid US and the prevalence of thyroid nodules in pediatric patients with goiter. A retrospective review of children and adolescents under the age of 18 (2015-2020) referred for neck ultrasound due to goiter in clinical examination. A total of 262 patients were included with a mean age of 13.77 ± 3.7 years. Thyroid antibodies were positive in 119/262 (45.4%) patients. Thyroid US reported to be abnormal in 210/262 (80%) patients. Thyroid nodule were found in 33.6% (n = 88/262) of patients with goiter and in 41.9% (n = 88/210) of patients with abnormal thyroid US result. Patients with positive antibodies had more of heterogeneity and hypervascularity of the gland on thyroid US (P < 0.001). On the other hand, thyroid nodules were more likely to be presented in patients with negative thyroid antibodies (P = 0.025). The heterogeneity within the thyroid positive group was significantly correlated with increasing TPOAb (P < 0.001) and TSH levels (P < 0.028). Heterogeneity on US had a positive predictive value (P = 0.041), while hypervascularity had low prediction for thyroid nodules (P = 0.022). Age, gender, family history of thyroid diseases, antibodies status and echogenicity in US did not show any significant associations with thyroid nodules. Papillary thyroid carcinoma was diagnosed in six patients and one of these patients was positive for thyroid antibodies. Thyroid nodules are quite common in our population. Thyroid nodules were significantly associated with heterogeneity in US. Although, no clinical or biochemical factors could predict the presence of thyroid nodules on thyroid US in our cohort, the absence of thyroid antibodies should lower the threshold for performing thyroid US.


Delayed biventricular repair of interrupted aortic arch with left ventricular outflow tract obstruction in 22q11.2 deletion syndrome: a case report.
In patients with critical left ventricular outflow tract obstruction but adequately sized ventricles, the treatment of choice is biventricular repair. Several options have been proposed, including neonatal Yasui or Ross-Konno operation. However, each of these procedures carries a high mortality risk, especially in syndromic neonates. Here, we report the case of a patient with 22q11.2 deletion syndrome and a diagnosis of interrupted aortic arch type B2, ventricular septal defect and left ventricular outflow tract obstruction. As a means to avoid high-risk neonatal surgery in this patient, we pursued a strategy of delayed biventricular repair involving initial hybrid Norwood palliation followed by a Yasui-type operation at 3 months. Although this strategy turned out to be successful, proactive monitoring for the development of ductal stent stenosis during follow-up after the hybrid procedure remains crucial to prevent hemodynamic complications such as cardiac failure and systemic hypoperfusion.


Technique for decompressive craniectomy using Seprafilm as a dural substitute and anti-adhesion barrier.
Surgeons in abdominal and gynecological fields have pioneered the use of Seprafilm (a chemically modified sodium hyaluronate/carboxymethylcellulose absorbable adhesion barrier, Genzyme Biosurgery, Cambridge, MA, USA) to prevent adhesion but its use outside these specialties is not well documented. The authors have used Seprafilm for craniectomy closure in several patients as a dural substitute and anti-adhesion barrier. During emergent craniectomy, the dura mater is reapproximated and a layer of Seprafilm is placed over the dura as an onlay and anti-adhesion barrier. During subsequent surgery for bone flap replacement, dissection between the dural plane and overlying tissues has been completed easily. There has been minimal adhesion to the underlying Seprafilm/dural layer. The Seprafilm has been incorporated into the surrounding dural plane. No postoperative complications have been noted. Seprafilm's anti-adhesive properties and biodegradable characteristics make it useful as a dural onlay for craniectomy in which a second surgery is planned.


Biased localization of actin binding proteins by actin filament conformation.
The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology, but how proteins localize differentially to these structures within a shared cytoplasm remains unclear. Here, we show that the actin-binding domains of accessory proteins can be sensitive to filament conformational changes. Using a combination of live cell imaging and in vitro single molecule binding measurements, we show that tandem calponin homology domains (CH1-CH2) can be mutated to preferentially bind actin networks at the front or rear of motile cells. We demonstrate that the binding kinetics of CH1-CH2 domain mutants varies as actin filament conformation is altered by perturbations that include stabilizing drugs and other binding proteins. These findings suggest that conformational changes of actin filaments in cells could help to direct accessory binding proteins to different actin cytoskeletal structures through a biophysical feedback loop.


Clarifying the effect of biodiversity on productivity in natural ecosystems with longitudinal data and methods for causal inference.
Causal effects of biodiversity on ecosystem functions can be estimated using experimental or observational designs - designs that pose a tradeoff between drawing credible causal inferences from correlations and drawing generalizable inferences. Here, we develop a design that reduces this tradeoff and revisits the question of how plant species diversity affects productivity. Our design leverages longitudinal data from 43 grasslands in 11 countries and approaches borrowed from fields outside of ecology to draw causal inferences from observational data. Contrary to many prior studies, we estimate that increases in plot-level species richness caused productivity to decline: a 10% increase in richness decreased productivity by 2.4%, 95% CI [-4.1, -0.74]. This contradiction stems from two sources. First, prior observational studies incompletely control for confounding factors. Second, most experiments plant fewer rare and non-native species than exist in nature. Although increases in native, dominant species increased productivity, increases in rare and non-native species decreased productivity, making the average effect negative in our study. By reducing the tradeoff between experimental and observational designs, our study demonstrates how observational studies can complement prior ecological experiments and inform future ones.