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Background: Lymphatic malformations (LMs) represent a potentially life-threatening, rare disease of the lymphatic system characterized by development of abnormal vessels, outpouchings, or cysts filled with lymphatic fluid. There are three morphologic types of LMs based on the size of the individual cysts: macrocystic (typically > 2 cm), microcystic (generally < 2 cm), and mixed (includes aspects of both). Macrocystic LMs typically exist beneath the skin and often can involve vascular components and/or organs. Microcystic LMs often have a cutaneous component and clinically present with lymphorrhea, bleeding, pain, itching, malodor, and functional deficits. There are no treatments approved by the US Food and Drug Administration (FDA) for either macrocystic or microcystic lymphatic malformations. The totality of the epidemiologic literature for LM is limited to the incidence of the disease among various birth cohorts. This is the first nationally representative study to estimate the national managed prevalence for patients with microcystic LM or combined LM with a cutaneous component annually across physician specialties likely to manage this condition. We conducted a retrospective observational survey of a nationally representative sample of patient-care physicians in the United States most likely to manage lymphatic malformations with a cutaneous component (LMC). Once recruited, target physicians participated via an electronic questionnaire. We weighted study physician self-estimates of the number of LMC patients treated in the past 12 months to reflect the specialists' corresponding proportion in the national universe. All patient information was anonymous; no personally identifiable information was collected.Results: Of the 420 physicians who visited the study website, 316 agreed to be screened and to participate (75.2% participation rate). Our survey results indicated the estimated number of unique annually managed LMC patients by target specialists is 79,920 (CI 66,600-93,250). This number corresponds to managed prevalence of 24.1 LMC patients per 100,000 population (CI 19.6/100,000-28.4/100,000).Conclusions: The study indicates that while rare, LMC affects a substantial number of people in the US (79,920) who are being managed by one or more specialists. By better understanding the prevalence of people living with LMC who require treatment, efforts to both increase disease awareness and to identify underserved populations in need of potential new treatments can be better focused. [ABSTRACT FROM AUTHOR]

Uber is a regulatory entrepreneur: a company that seeks to change the law in its favor. In the United States, Uber's regulatory entrepreneurship changed the American taxi industry and the laws that regulate it. But the company's venture into France presented unique challenges. This Comment examines Uber's regulatory entrepreneurship in France and analyzes the factors that hindered Uber's quest to revolutionize the French taxi industry. It discusses the tension between Uber and the French government and the policies behind both sides' goals. It also seeks a compromise between Uber and the French regulators: one that acknowledges the issues with both Uber's aggressive business model and France's heavy government regulations. [ABSTRACT FROM AUTHOR]

Background Peripheral neuronal impairment compromises foot health in patients with diabetes. Clinically, xerosis is the most common mild complication, but it should not be underestimated. An effective treatment must be able to restore the cutaneous barrier and prevent water loss, to maintain adequate hydration and protection. Objective This study aimed to assess the efficacy of an emollient cream on foot xerosis in patients with diabetes. Methods This is a prospective, multicenter, randomized, double-blind contralateral vehicle-controlled study in 57 patients with diabetes. Patients were treated twice daily for 27 ± 2 days with the study emollient containing glycerol 15%, liquid and soft paraffin 10%, glycerol monostearate, stearic acid, polydimethylcyclosiloxane, silicone oil, macrogol 600, trolamine, propyl parahydroxybenzoate and purified water (Dexeryl®; Pierre Fabre Medicament, Boulogne, France) or its vehicle (glycerol monostearate, stearic acid, polydimethylcyclosiloxane, silicone oil, macrogol 600, trolamine, propyl parahydroxybenzoate and purified water). Efficacy was assessed after a 28-day treatment period using a validated score [Xerosis Assessment Scale ( XAS) score], instrumental measurements and subjective assessment. Results The XAS score decreased to 3.2 ± 2.6 points with the emollient and 4.1 ± 2.3 with the vehicle ( P = 0.001). Improvement was observed from day 14 ( P = 0.012). Compared with the vehicle, the emollient also significantly improved the overall skin score, hydration index, D-Squame® (CuDerm Corporation, Dallas, TX, USA) test, skin roughness and patients' opinions. Conclusion Treatment with an emollient is effective for improving foot xerosis in patients with diabetes. [ABSTRACT FROM AUTHOR]

Decreasing blood viscosity has been proposed since the advent of hemodilution as a means for increasing perfusion in many pathological conditions, and increased plasma viscosity is associated with the presence of pathological conditions. However, experimental studies show that microvascular functions as represented by functional capillary density in conditions of significantly decreased viscosity is impaired, a problem corrected by increasing plasma and blood viscosity. Blood viscosity, primarily dependent on hematocrit (Hct) is a determinant of peripheral vascular resistance, and therefore blood pressure. In the healthy population Hct presents a variability, which is not reflected by the variability of blood pressure. This is due to a regulatory process at the level of the endothelium, whereby the increase of Hct (and therefore blood viscosity) leads to increased shear stress and the production of the vasodilator nitric oxide (NO), a finding supported by experimental studies showing that the acute increase of Hct lowers blood pressure. Studies that in the healthy population show that blood pressure and Hct have a weak positive correlation. However, when the effect of blood viscosity is factored out, blood pressure and Hct are negatively and significantly correlated, indicating that as blood viscosity increases, the circulation dilates. Conversely, lower Hct and blood viscosity conditions lead to a constricted circulation, associated with a condition of decreased NO bioavailability, and therefore a pro-inflammatory condition. [ABSTRACT FROM AUTHOR]

The World Health Organization-Composite International Diagnostic Interview (WHO-CIDI) is a highly structured interview for the assessment of mental disorders, based on the definitions and criteria of the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Over the past decade it has become evident that the CIDI does not sufficiently address the assessment needs of women. Women are affected by most mental disorders, particularly mood and anxiety disorders, approximately twice as frequently as men. Women-specific disorders, such as Premenstrual Syndrome (PMS), Premenstrual Dysphoric Disorder (PMDD), psychiatric disorders during pregnancy and postpartum as well as during the perimenopause, menopause and beyond are not addressed by the standard CIDI diagnostic modules. In addition, the CIDI in its current form does not address the potential effect that female reproductive milestones may have on diagnosis, treatment and prevention of mental disorders in women. Our aim was to develop a new women specific platform (CIDI-VENUS; CIDI-V) to be embedded in the existing CIDI that will address the above mentioned current deficiencies. Guided by a team of experts in the field of Women's Mental Health from Canada and Germany the following modules were developed: 1) A complete menstrual history and comprehensive contraceptive history with a link to the Premenstrual Symptoms Screening Tool (PSST). 2) A complete perinatal history of pregnancies, miscarriages, terminations, still births, death of a child, with details of current pregnancy including gestation and expected date of confinement, labour history and breastfeeding, history of tobacco, alcohol, and other substance use including prescription drugs during pregnancy and postpartum, a section on specific phobias and on recurrent obsessive/compulsive thoughts/behaviours (OCD) related to the baby with a link to the Perinatal Obsessive-Compulsive Scale (POCS), as well as a link to the Edinburgh Postnatal Depression Scale (EPDS). 3). A detailed history of use of hormone therapy (e.g. pills, patches, implants, etc.) with a focus on (peri-) menopausal women, differentiating between physical and psychological symptoms with a link to the Menopause Visual Analogue Scales (M-VAS) and to the Greene Climacteric Scale. 4) An iterative module concluding each CIDI section to specify the course of mental disorders during the reproductive stages and menopausal transition. While retaining core diagnostic sections and diagnostic algorithms, the CIDI-V is enriched by women-specific diagnostic modules, providing a wealth of clinically relevant information about women's mental health, not available anywhere else in our current psychiatric diagnostic instruments. [ABSTRACT FROM AUTHOR]

Increased plasma and blood viscosity are usually associated with pathological conditions; however there are several situations in which the elevation of both parameters results in increased perfusion and the lowering of peripheral vascular resistance. In extreme hemodilution blood viscosity is too low and insufficient to maintain functional capillary density, a problem that in experimental studies is shown to be corrected by increasing plasma viscosity up to 2.2 cP. This effect is mediated by Nitric oxide (NO) production via restoration of shear stress at the endothelium as shown by microelectrode perivascular measurements of NO concentration. Moderate elevations of blood viscosity by increasing hematocrit (∼10% of baseline) result in reductions of blood pressure by 10 mmHg of baseline. This effect is also NO mediated since it is absent after N-nitro-L-arginine methyl ester (L-NAME) treatment and in endothelial NO synthase deficient mice. These results show that the rheological properties of plasma affect vessel diameter in the microcirculation leading to counterintuitive responses to the increase in viscosity. [ABSTRACT FROM AUTHOR]

The increase of plasma and blood viscosity is usually associated with pathological conditions; however, elevation of both parameters often results in increased perfusion and the lowering of peripheral vascular resistance. In extreme haemodilution, blood viscosity is too low and insufficient to maintain functional capillary density, a problem that in experimental studies is shown to be corrected by increasing plasma viscosity up to 2.2 cP. This effect is mediated by mechanotransduction-induced nitric oxide (NO) production via shear stress in the endothelium as shown by microelectrode perivascular measurements of NO concentration. Moderate elevations of blood viscosity by increasing haematocrit (∼10%) result in comparable reductions of blood pressure and peripheral vascular resistance, an effect also NO-mediated as it is absent after Nω-nitro-L-arginine methyl ester treatment and in endothelial nitric oxide synthase-deficient mice. These findings show that the rheological properties of plasma affect vessel diameter in the microcirculation leading to counterintuitive responses to the changes in blood and plasma viscosity. Application of these findings to haemorrhagic shock resuscitation leads to the concept of hyperosmotic-hyperviscous resuscitation as a modality for maintaining the recovery of microvascular function. [ABSTRACT FROM AUTHOR]

Studies the lithologic transition and bed thickness periodicities in turbidite successions of the Antola Formation in Italy. Range of lateral facies subdivisions; Analysis of key issues of interest; Implications on sedimentology.

BackgroundAgainst the background of very limited evidence, the present study aimed to prospectively examine the impact of maternal postpartum post-traumatic stress disorder (PTSD) symptoms on four important areas of child development, i.e. gross motor, fine motor, communication and social–emotional development.MethodThis study is part of the large, population-based Akershus Birth Cohort. Data from the hospital's birth record as well as questionnaire data from 8 weeks and 2 years postpartum were used (n = 1472). The domains of child development that were significantly correlated with PTSD symptoms were entered into regression analyses. Interaction analyses were run to test whether the influence of postpartum PTSD symptoms on child development was moderated by child sex or infant temperament.ResultsPostpartum PTSD symptoms had a prospective relationship with poor child social–emotional development 2 years later. This relationship remained significant even when adjusting for confounders such as maternal depression and anxiety or infant temperament. Both child sex and infant temperament moderated the association between maternal PTSD symptoms and child social–emotional development, i.e. with increasing maternal PTSD symptom load, boys and children with a difficult temperament were shown to have comparatively higher levels of social–emotional problems.ConclusionsExamining four different domains of child development, we found a prospective impact of postpartum PTSD symptoms on children's social–emotional development at 2 years of age. Our findings suggest that both boys and children with an early difficult temperament may be particularly susceptible to the adverse impact of postpartum PTSD symptoms. Additional studies are needed to further investigate the mechanisms at work. [ABSTRACT FROM PUBLISHER]

Abstract: Foot care prevention programs can reduce the occurrence of foot ulcerations and amputations. The most important factor related to the development of foot ulcer is peripheral neuropathy, associated with loss of pain. Neuropathy can be associated with peripheral vascular disease and foot deformities. Five cornerstones for prevention should be respected, including regular examination of the feet and footwear, identification of high-risk patients, education of the patient and family, appropriate footwear, and treatment of nonulcerative pathology. After examination of the foot using the Semmes-Weinstein monofilament test, each patient can be assigned to one of the four risk categories to guide management. Foot care programs should be provided to high-risk categories of patients. Education plays an important role in prevention. The aim is to increase motivation and skills and enhance compliance with footwear advice. Items may include daily feet inspection and regular washing. Appropriate foot wear should protect against trauma. High-risk patients should participate in a foot care program set up by a multidisciplinary foot care team. [Copyright &y& Elsevier]

Cheese yield mainly depends on the amount and proportion of milk constituents; however, genetic variants of the proteins present in milk may also have an important effect. The objective of this research was to study the effect of the variants A and B of β-lactoglobulin (LG) on cheese yield using a model system consisting of skim milk powder fortified with different levels of a mixture containing α-lactalbumin and β-LG genetic variants (A, B, or A-B) in a 1:2 ratio. Fortified milk samples were subjected to pasteurization at 65°C for 30 min. Miniature cheeses were made by acidifying (pH = 5.9) fortified milk and incubating with rennet for 1 h at 32°C. The clot formed was cut, centrifuged at 2,600 x g for 30 min at 20°C and drained for determining cheese yield. Cheese-yielding capacity was expressed as actual yield (grams of cheese curd per 100 g of milk) and dry weight yield (grams of dried cheese curd per 100 g of milk). Free-zone capillary electrophoresis was used for determining β-LG A or B recovery in the curd during rennet-induced coagulation. The presence of β-LG variant B resulted in a significantly higher actual and dried weight cheese yield than when A or A-B were present at levels ≤0.675% of whey protein (WP) addition. Results of free-zone capillary electrophoresis allowed us to infer that β-LG B associates with the casein micelles during renneting, as shown by an increase in the recovery of this variant in the curd when β-LG B was added up to a maximum at 0.45% (equivalent to 0.675% WP). In general, actual or dried weight cheese yield increased as WP addition was increased from 0.225 to 0.675%. However, when WP addition ranged from 0.675 to 0.90%, a drastic drop in cheese yield was observed. This behavior may be because an increase in the aggregation of casein micelles with a concomitant inclusion of whey protein in the gel occurs at low levels of WP addition, whereas once the association of WP with the casein micelles reach a saturation point at addition levels higher than 0.675%, rearrangements of the gel network result in larger whey expulsion and syneresis. This knowledge is expected to be useful to maximize cheese yield and optimize processing conditions during cheese and cheese analogs manufacturing. [ABSTRACT FROM AUTHOR]

Abstract: With the main objective of test an inoculum of chitin-degrading rumen bacteria, 15 lambs with an average BW of 22.8kg were allotted at random (5 per treatment) to diets containing: T1=soybean meal, corn meal and corn stover (control treatment), T2=inclusion on the diet of 250g of shrimp shell waste (SSW) per 1000g (DM bases), in replacement of ingredients contained in T1, and T3=T2+inoculum made of Streptococcus milleri (chitin-degrading bacterium; 0.12ganimal−1 d−1). In general, the feed intake, weight gain and feed conversion were similar (P<0.05) between T1 and T3, but the lambs feed SSW without inoculum (T2) presented the lowest values. Concentration of total and cellulolytic bacteria was similar among treatments after 30d, but decreased in T2 and T3 after 60d. The population of chitinolytic bacteria increased (P<0.05) in the rumen of lambs fed 25% SSW. This increment was observed in lambs feed with or without inoculum. It is concluded that SSW can be efficiently used as a feedstuff for ruminants without any requirement of an adaptation period to the diet and decreasing the diet cost, if an inoculum of chitinolytic bacteria is added. [Copyright &y& Elsevier]

Due to its high prevalence and cost of care, estimated at 19 billion euros in France in 2018, diabetes is a major public health issue. Once adjusted, and according to the confidence ellipse, the remote monitoring procedure was estimated to be "cost saving". Conclusions The EDUC@DOM telemonitoring and tele-education program is cost-saving and allow the optimization of type 2 diabetic patient's care and in particular their glycemic balance. [Extracted from the article]

Background: The role of anxiety and depressive disorders prior to pregnancy for changes in peripartum psychopathological symptoms has not been resolved yet.Methods: A regional-epidemiological sample of 306 women was prospectively followed in seven waves from early pregnancy until 16 months postpartum. Lifetime DSM-IV anxiety and depressive disorders were assessed at baseline with the CIDI-V. Psychopathological symptoms (somatization, obsession-compulsion, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism) were measured with the BSI three times during pregnancy and three times after delivery.Results: Multilevel analyses revealed that women with versus without lifetime anxiety (β=0.22 to β=0.32) and depressive (β=0.24 to β=0.34) disorders prior to pregnancy experienced higher peripartum psychopathological symptoms. All symptoms linearly decreased during pregnancy (β=-0.02 to β=-0.07 per month). Somatization (β=-0.46) was lower, whereas paranoid ideation (β=0.26) and obsession-compulsion (β=0.21) were higher after delivery than during pregnancy. Though, obsession-compulsion linearly decreased after delivery (β=-0.02). Lifetime anxiety disorders prior to pregnancy interacted with linear changes in anxiety (β=-0.04) and phobic anxiety (β=-0.05) during pregnancy. That is, only women with, but not without anxiety disorders prior to pregnancy experienced a linear decline in anxiety and phobic anxiety during pregnancy.Limitations: Lifetime anxiety and depressive disorders were assessed in early pregnancy and might be biased.Conclusions: Peripartum psychopathological symptoms are higher in women with versus without lifetime anxiety and depressive disorders prior to pregnancy, but symptom changes only slightly vary by lifetime diagnostic status. [ABSTRACT FROM AUTHOR]

Due to the high ATP demand of myocardium, cardiac function is highly dependent on an efficient mitochondrial respiration. Ischemia and reperfusion injury (I/R) has severe impact on the function of the mitochondrial respiratory system. In donation after circulatory death (DCD), extent of I/R damage is decisive for posttransplant graft function. We aimed to investigate the mitochondrial respiration using high-resolution respirometry (HRR) in a porcine ex-situ heart perfusion (ESHP) model. 12 German domestic pigs (65-75kg) were used to simulate two different organ donation protocols: "donation after brain death" (DBD) (n=6) and DCD (n=6). ESHP was performed for 6 hours. Mitochondrial function in tissue homogenates of porcine myocardium was assessed by HRR. Samples were obtained at baseline (b), and after 1, 3, and 6 hours of ESHP. Comparison of repeated measurements were performed with two-way ANOVA followed by Sidak's post hoc test. The oxidative phosphorylation capacity after addition of NADH-generating substrates, fatty acids and succinate decreased slightly in the DCD group. A significant difference after 6 hours of perfusion was found (DBD 200.5±27.9 vs DCD 143.4±22.7 pmol−1·s−1·mL−1, p=0.038). The flux control ratio of the NADH-linked (Complex I) respiration declined in the DCD group (6h: DBD 0.16 vs DCD 0.05, p=0.007) (Figure 1). The mitochondrial outer membrane damage, assessed by cytochrome c addition was significantly lower after 6 hours of ESHP (p<0.001) without a difference between the groups. We performed the first in-depth analysis of mitochondrial respiratory function during ESHP in a DCD model. Interestingly, mitochondrial respiration is preserved over 3 hours in DCD hearts with a decline in function after 6 hours. Importantly, the initial mitochondrial outer membrane damage recovered over time in both groups. Next, the predictive value of HRR might be evaluated in clinical practice to promote organ acceptance in the future. [ABSTRACT FROM AUTHOR]

Background: Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.Methods: In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety.Results: The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects.Conclusions: Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .). [ABSTRACT FROM AUTHOR]

This study aims to prospectively examine peripartum changes in social support in women with and without anxiety and depressive disorders prior to pregnancy. Data come from the Maternal Anxiety in Relation to Infant Development (MARI) Study, a prospective-longitudinal investigation among n = 306 expectant mothers. DSM-IV anxiety and depressive disorders were assessed in early pregnancy using the Composite International Diagnostic Interview for Women (CIDI-V). Social support was assessed with the Social Support Questionnaire during pregnancy as well as 4 and 16 months postpartum. Perceived social support in the total sample declined from prepartum to postpartum. Levels of prepartum and postpartum social support were lower in women with comorbid anxiety and depressive disorders compared to those with pure depressive disorder(s), pure anxiety disorder(s), or comorbid anxiety and depressive disorders prior to pregnancy. Moreover, social support more strongly declined from prepartum to postpartum in women with comorbid anxiety and depressive disorders compared to those without anxiety and depressive disorder prior to pregnancy. Findings suggest that women with a previous history of comorbid anxiety and depressive disorders are at particular risk for deficient social support during pregnancy and after delivery and might thus profit from targeted early interventions. [ABSTRACT FROM AUTHOR]

The purpose of this study is to prospectively examine peripartum changes in partnership characteristics among women with and without anxiety and depressive disorders prior to pregnancy. In the prospective-longitudinal Maternal Anxiety in Relation to Infant Development (MARI) study, n = 306 expectant mothers completed up to seven waves of assessment from early pregnancy until 16 months postpartum. Lifetime anxiety and depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) were evaluated at baseline using the Composite International Diagnostic Interview for Women (CIDI-V, Martini et al. ). Partnership characteristics were assessed during pregnancy as well as 4 and 16 months postpartum using the Partnership Questionnaire (Hahlweg ). Linear regressions were applied to test associations between diagnostic status prior to pregnancy and peripartum partnership characteristics. Compared to women without anxiety and depressive disorders prior to pregnancy, women with comorbid anxiety and depressive disorders reported less tenderness during pregnancy, less postpartum tenderness, satisfaction, and overall partnership quality as well as a lower decrease in communication from pre- to postpartum. Women with pure depressive disorders and comorbid anxiety and depressive disorders prior to pregnancy indicated a higher increase in quarreling from pre- to postpartum. Findings suggest that women with depressive (and comorbid anxiety) disorders prior to pregnancy are at elevated risk for an unfavorable peripartum partnership development and might thus profit from targeted family interventions during this period. [ABSTRACT FROM AUTHOR]

Background Maternal depression has been associated with excessive infant crying, feeding and sleeping problems, but the specificity of maternal depression, as compared with maternal anxiety remains unclear and manifest disorders prior to pregnancy have been widely neglected. In this prospective longitudinal study, the specific associations of maternal anxiety and depressive disorders prior to, during and after pregnancy and infants' crying, feeding and sleeping problems were investigated in the context of maternal parity. Methods In the Maternal Anxiety in Relation to Infant Development (MARI) Study, n = 306 primiparous and multiparous women were repeatedly interviewed from early pregnancy until 16 months post partum with the Composite International Diagnostic Interview for Women (CIDI-V) to assess DSM-IV anxiety and depressive disorders. Information on excessive infant crying, feeding and sleeping problems was obtained from n = 286 mothers during postpartum period via questionnaire and interview (Baby-DIPS). Results Findings from this study revealed syndrome-specific risk constellations for maternal anxiety and depressive disorders as early as prior to pregnancy: Excessive infant crying (10.1%) was specifically associated with maternal anxiety disorders, especially in infants of younger and lower educated first-time mothers. Feeding problems (36.4%) were predicted by maternal anxiety (and comorbid depressive) disorders in primiparous mothers and infants with lower birth weight. Infant sleeping problems (12.2%) were related to maternal depressive (and comorbid anxiety) disorders irrespective of maternal parity. Conclusions Primiparous mothers with anxiety disorders may be more prone to anxious misinterpretations of crying and feeding situations leading to an escalation of mother-infant interactions. The relation between maternal depressive and infant sleeping problems may be better explained by a transmission of unsettled maternal sleep to the fetus during pregnancy or a lack of daily structure and bedtime routine with the infant. Maternal disorders prior to pregnancy require more attention in research and clinical practice. [ABSTRACT FROM AUTHOR]

Background Treatment with direct-acting antiviral drugs in interferon-free regimens is currently recommended for viral hepatitis C recurrence after liver transplantation. There are limited data regarding its results in this population, and no optimal treatment scheme has yet been singled out. Methods We report our real-world results in liver transplant (LT) recipients. All patients were hepatitis C virus (HCV) monoinfected and completed a 12-week treatment course, followed 12 weeks later by HCV polymerase chain reaction testing with 12 IU/mL sensibility. Liver fibrosis was graded with the use of biopsies taken <12 months before treatment and stratified as early (0–1) or moderate to advanced (2–4) according to the Metavir score. Results Median postoperative time was 5.2 years. Genotype 3 was found in 66.7% of the sample. The following regimens were prescribed: daclatasvir-sofosbuvir with ( n = 11) or without ( n = 28) ribavirin. Genotypes 1 and 3 were evenly distributed between the regimens. Sustained virologic response (SVR) was obtained in 24 out of 28 patients (85.7%) who received daclatasvir-sofosbuvir and in all patients (100%) who received daclatasvir-sofosbuvir-ribavirin (global SVR 89.7%). All patients that failed treatment had genotype 3 HCV. Fibrosis was evaluated in 79.5% of the sample: 48.4% had early and 51.6% had moderate to advanced fibrosis, for which ribavirin was more commonly prescribed ( P = .001). Conclusions The SVR rate in our LT recipients was similar to that previously reported in the literature. The addition of ribavirin to DAA treatment appears to be justified in this population. [ABSTRACT FROM AUTHOR]

The effectiveness of liver preservation solutions remains in evidence. Cold ischemia time, steatosis, expanded criterion donors, operational cost, and survival represent important roles in its success. In a prospective cohort study between August 2009 and April 2014, 178 patients were allocated into an Institut Georges Lopez – 1 (IGL-1) solution group (63.5%) or histidine-tryptophan-ketoglutarate (HTK) group (36.5%). There were no differences among recipient’s characteristics including age, skin color, gender, Model for End-stage Liver Disease score, acute rejection, cholestasis, and reperfusion syndrome incidences. Also, donors, age average, skin color, donor risk index, time in intensive care unit, hemodynamic variables, infections, and steatosis incidences were similar. The average cold ischemia time was 494 minutes in the IGL-1 group and 489 minutes in the HTK group ( P = .77). Alanine aminotransferase and aspartate aminotransferase serum levels on the first postoperative day were 707 and 1185 mg/dL, respectively, with IGL-1 and 1298 and 2291 mg/dL, respectively, with HTK ( P = .016) and similar at day 15 ( P > .88). The incidence of delayed graft function was 4.5% with IGL-1 and 4.6% with HTK ( P = .90). The incidence primary nonfunction was 2.7% with IGL-1 and 3.1% with HTK ( P = .71). The incidence of perioperative death was 11.5% with IGL-1 and 13.8% with HTK ( P = .94). The survival in 30 months was 86% in IGL-1 group and 82% in HTK group ( P = .66). Both preservation solutions are efficient to liver transplantations with deceased donors. Major prospective trials are necessary to evaluate each preservation solution’s particularities. The preservation solution availability in each transplantation center must guide its use at the present moment. [ABSTRACT FROM AUTHOR]

Continuous infusion of intravenous prostaglandin E1 (PgE1, 2.5 mug/kg/min) was used to determine how vasodilation affects oxygen consumption of the microvascular wall and tissue pO(2) in the hamster window chamber model. While systemic measurements (mean arterial pressure and heart rate) and central blood gas measurements were not affected, PgE1 treatment caused arteriolar (64.6 +/- 25.1 microm) and venular diameter (71.9 +/- 29.5 microm) to rise to 1.15 +/- 0.21 and 1.06 +/- 0.19, respectively, relative to baseline. Arteriolar (3.2 x 10(-2) +/- 4.3 x 10(-2) nl/s) and venular flow (7.8 x 10(-3) +/- 1.1 x 10(-2)/s) increased to 1.65 +/- 0.93 and 1.32 +/- 0.72 relative to baseline. Interstitial tissue pO(2) was increased significantly from baseline (21 +/- 8 to 28 +/- 7 mmHg; P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the microvascular wall decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the vascular wall, decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). This reduction reflects a 20% decrease in oxygen consumption by the vessel wall and up to 50% when cylindrical geometry is considered. The venular vessel wall gradient decreased from 12 +/- 4 to 9 +/- 4 mmHg (P < 0.001). Thus PgE1-mediated vasodilation has a positive microvascular effect: enhancement of tissue perfusion by increasing flow and then augmentation of tissue oxygenation by reducing oxygen consumption by the microvascular wall. [ABSTRACT FROM AUTHOR]

Aims Diabetic foot ulcers (DFUs) are at risk of infection and impaired healing, placing patients at risk of lower extremity amputation. DFU care requires debridement and dressings. A prospective, multicentre study compared clinical efficacy and safety of AQUACEL® Hydrofiber® dressings containing ionic silver (AQAg) with those of Algosteril® calcium alginate (CA) dressings in managing out-patients with Type 1 or 2 diabetes mellitus and non-ischaemic Wagner Grade 1 or 2 DFUs. Methods Patients stratified by antibiotic use on enrolment were randomly assigned to similar protocols including off-loading, AQAg ( n = 67) or CA ( n = 67) primary dressings and secondary foam dressings for 8 weeks or until healing. Clinical efficacy measures were healing outcomes and primarily healing speed. Adverse events were recorded. Results AQAg and CA groups were comparable at baseline. All ulcer healing outcomes improved in both groups. The mean time to healing was 53 days for AQAg ulcers and 58 days for CA ulcers ( P = 0.34). AQAg-treated ulcers reduced in depth nearly twice as much as CA-treated ulcers (0.25 cm vs. 0.13 cm; P = 0.04). There was more overall ulcer improvement and less deterioration in AQAg subjects ( P = 0.058), particularly in the subset initially using antibiotics ( P = 0.02). Safety profiles of both groups were similar. Conclusion When added to standard care with appropriate off-loading, AQAg silver dressings were associated with favourable clinical outcomes compared with CA dressings, specifically in ulcer depth reduction and in infected ulcers requiring antibiotic treatment. This study reports the first significant clinical effects of a primary wound dressing containing silver on DFU healing. [ABSTRACT FROM AUTHOR]

Analytics of single biological cells allows quantitative investigation from a structural, functional and dynamical point of view and opens novel possibilities to an unamplified subcellular analysis. In this article, we report on three different experimental methods and their applications to single cellular systems with a subcellular sensitivity down to the single molecule level. First, the subcellular surface structure of living bacteria ( Corynebacterium glutamicum) was investigated with atomic force microscopy (AFM) at the resolution of individual surface layer (S-layer) proteins; discrimination of bacterial strains that lack the expression of hexagonally packed surface layer proteins was possible. Second, quantitative measurement of individual recognition events of membrane-bound receptors on living B-cells was achieved in single cell manipulation and probing experiments with optical tweezers (OT) force spectroscopy. And third, intracellular dynamics of translocating photoactivatable GFP in plant protoplasts ( Nicotiana tabacum BY-2) was quantitatively monitored by two-photon laser scanning microscopy (2PLSM). [ABSTRACT FROM AUTHOR]

To characterize the mechanism by which heterotrimeric G-proteins interpret the signals coining from various neurotransmitters of diverse efficacies (agonists and partial agonists) acting on α2A-adrenergic receptors, we used a fluorescent resonance energy transfer-based approach to study the effects of these partial agonists on the activation process of both the α2A-adrenergic receptor and its cognate Gi-protein. We show that ligands of different efficacies switch the receptor into distinct conformational states, which in turn set the speed and extent of the Gi-protein signaling. Thus, in cells the efficacy by which a receptor responds to diverse ligands is caused by the ability of the G-protein to differentiate between distinct receptor conformations. The data provide a new key characteristic underlying the mechanism of partial agonism at G-protein-coupled receptors. [ABSTRACT FROM AUTHOR]

During porphyrin biosynthesis the oxygen-independent coproporphyrinogen III oxidase (HemN) catalyzes the oxidative decarboxylation of the propionate side chains of rings A and B of coproporphyrinogen III to form protoporphyrinogen IX. The enzyme utilizes a 5′-deoxyadenosyl radical to initiate the decarboxylation reaction, and it has been proposed that this occurs by stereo-specific abstraction of the pro-S-hydrogen atom at the β-position of the propionate side chains leading to a substrate radical. Here we provide EPR-spectroscopic evidence for intermediacy of the latter radical by observation of an organic radical EPR signal in reduced HemN upon addition of S-adenosyl-L-me- thionine and the substrate coproporphyrinogen III. This signal (gav = 2.0029) shows a complex pattern of well resolved hyperfine splittings from at least five different hydrogen atoms. The radical was characterized using regiospecifically labeled (deuterium or 15N) coproporphyrinogen III molecules. They had been generated from a multienzyme mixture and served as efficient substrates. Reaction of HemN with coproporphyrinogen III, perdeuterated except for the methyl groups, led to the complete loss of resolved proton hyperfine splittings. Substrates in which the hydrogens at both α- and β-positions, or only at the β-positions of the propionate side chains, or those of the methylene bridges, were deuterated showed that there is coupling with hydrogens at the α-, β-, and methylene bridge positions. Deuterium or 15N labeling of the pyrrole nitrogens without labeling the side chains only led to a slight sharpening of the radical signal. Together, these observations clearly identified the radical signal as substrate-derived and indicated that, upon abstraction of the pro-S-hydrogen atom at the β-position of the propionate side chain by the 5′-deoxyadenosyl radical, a comparatively stable delocalized substrate radical intermediate is formed in the absence of electron acceptors. The observed hyperfine constants and g values show that this coproporphyrinogenyl radical is allylic and encompasses carbon atoms 3′, 3, and 4. [ABSTRACT FROM AUTHOR]

The microvascular distribution of oxygen was studied in the arterioles and venules of the awake hamster window chamber preparation to determine the contribution of vascular smooth muscle contraction to oxygen consumption of the microvascular wall during arginine vasopressin (AVP)-induced vasoconstriction. AVP was infused intravenously at the clinical dosage (0.0001 IU·kg-1·min-1) and caused a significant arteriolar constriction, decreased microvascular flow and functional capillary density, and a substantial rise in arteriolar vessel wall transmural PO2 difference. AVP caused tissue PO2 to be significantly lowered from 25.4 ± 7.4 to 7.2 ± 5.8 mmHg; however, total oxygen extraction by the microcirculation increased by 25%. The increased extraction, lowered tissue PO2, and increased wall oxygen concentration gradient are compatible with the hypothesis that vasoconstriction significantly increases vessel wall oxygen consumption, which in this model appears to constitute an important oxygen-consuming compartment. This conclusion was supported by the finding that the small percentage of the vessels that dilated in these experiments had a vessel wall oxygen gradient that was smaller than control and which was not determined by changes in tissue PO2. These findings show that AVP administration, which reduces oxygen supply by vasoconstriction, may further impair tissue oxygenation by the additional oxygen consumption of the microcirculation. [ABSTRACT FROM AUTHOR]