Standardized one-day evaluation before urinary reconstructive surgery for neurogenic lower urinary tract dysfunction: Feasibility and impact on surgical strategy and care pathway.

OBJECTIVES: To describe a concept of standardized preoperative one-day evaluation before urinary reconstructive or diversion surgery for the treatment of neurogenic lower urinary tract (LUT) dysfunction, and to evaluate its feasibility and its impact on the care pathway. MATERIALS AND METHODS: All patients who underwent a one-day standardized evaluation before a urinary reconstructive or derivation surgery for the treatment of neurogenic LUT dysfunction between January 2017 and December 2021 in our institution were included. Data were collected retrospectively from standardized reports. The main outcome was the rate of completion of the tests and consultations planned during this evaluation. Secondary outcomes included the findings from the one-day evaluation and changes in the urological surgical strategy at different time points within one year. RESULTS: One hundred and thirty-one patients benefited from this one-day standardized evaluation. The overall completeness rate of the data collected was 77.5%, increasing from 62.3% in 2017 to 89.3% in 2021. The urological surgical plan was modified for 19.1% of patients following this preoperative evaluation. The indication was then confirmed for 114 patients (87.0%) by the multidisciplinary meeting and was carried out unchanged during the following year for 89 patients (67.9%). An associated colostomy procedure was proposed for 18.3% of patients and was finally performed in 11.5%. CONCLUSION: A standardized multidisciplinary preoperative one-day evaluation before performing reconstructive or diversion surgery for the treatment of neurogenic LUT dysfunction seems feasible and makes it possible to optimize the surgical plan and adapt the course of care.

The effect of selenium source on the oxidative status and performance of broilers reared at standard and high ambient temperatures.

1. This study investigated the oxidative status of broilers fed diets containing selenium (Se) from 14 to 35 d of age and reared at two different constant temperatures. Measurements of oxidative status included blood glutathione peroxidase (GSH-Px) and plasma total antioxidant status (TAS). Other variables included feed intake (FI), weight gain (WG), feed conversion ratio (FCR), Se levels in breast and liver tissue, jejunal villus morphometry, percentage weight of organs in relation to body weight; apparent metabolisable energy adjusted for nitrogen (AMEn); dry matter retention (DMR); fat retention (FR) and nitrogen retention (NR).2. The experiment started at 14 d of age, when 240 birds were randomly allocated to 48 pens (12 pens in four rooms). Treatments included a control diet 1 (SFC; 209.4 g/kg CP and 12.98 MJ/kg ME and no added Se containing saturated fat); diet 2 (SFSe) the control plus 12.605 mg/kg Se additive; diet 3 (USFC) was a second control diet (208.2 g/kg CP and 13.10 MJ/kg ME with no added Se containing unsaturated fat as rapeseed oil); diet 4 (USFSe) was the latter control plus 12.605 mg/kg Se additive. Two rooms were kept at a standard temperature of 20°C (ST) and two rooms were kept at high temperature of 35°C (HT).3. A temperature x Se interaction existed for GSH-Px in birds reared at ST (P < 0.05), and these birds had the highest levels of Se in liver tissue (P < 0.05). Fat x Se interactions were evident in breast tissue with highest levels in USFSe (P < 0.05). Adding Se improved jejunal VH: CD in USFSe fed birds (P < 0.001).4. Birds reared at ST had higher FI and WG than those reared at HT (P < 0.001), and had lower FCR than those reared at HT (P < 0.05). AMEn (MJ/kg DM) and FR were higher in birds fed USF diets, and lowest in birds fed SF (P < 0.50 and P < 0.001 respectively). NR was highest in birds raised at ST (P < 0.50).5. Broiler growth performance was reduced by HT. Oxidative status and Se in liver tissue was improved by adding Se in both diets.

Genomic heterogeneity of Dichelobacter nodosus within and between UK sheep flocks and between age groups within a flock.

BACKGROUND: Footrot and interdigital dermatitis are endemic infectious diseases in all sheep farming regions, impairing welfare and production. The development of efficacious vaccines against the primary causative pathogen has been hampered by the extensive antigenic diversity of Dichelobacter nodosus. Understanding the heterogeneity of the pathogen within and between flocks is essential if the feasibility of bespoke vaccine production is to be assessed for use in the U.K. RESULTS: In this study 56 ewe and lamb isolates from 9 flocks were compared by D. nodosus serogroup and Multi Locus Sequence Type which provides significantly enhanced discriminatory power for molecular epidemiology. Serogroup heterogeneity between flocks ranged from two to five unique serogroups per flock. Three flocks contained isolates of two serogroups, two flocks contained isolates of three serogroups and one flock included isolates of five serogroups. Analysis of 25 isolates from one flock with high prevalence of lameness, identified that serogroup and sequence type was significantly correlated with age. Significantly higher proportion of lambs were infected with serogroup B (principally ST85) as opposed to serogroup H (principally ST86), which predominated amongst adult sheep. CONCLUSIONS: Genomic heterogeneity of the pathogen was significantly lower within flock compared to heterogenicity observed between flocks. Furthermore, this study indicates that within a flock, the host-pathogen dynamics and susceptibility to particular D. nodosus strains may be age dependent.

The effect of feeding different sources and levels of selenium on growth performance and antioxidant status of broilers raised at two different temperatures.

1. This study examined the effects of different dietary sources and levels of selenium (Se) on growth performance, hepatic and breast meat Se content, glutathione peroxidase (GSH-Px) activity and total antioxidant status (TAS) in blood, when fed to broilers from 14 to 35 d of age and reared at two different temperatures (20°C and 35°C). 2. Five hundred and sixty male Ross 308 broilers were reared in a single floor pen and fed the same proprietary starter diet from 0 to 14 d age (229.9 g/kg CP and 12.67 MJ/kg ME, without Se supplementation). 3. The experiment started at 14 d age, and the birds randomly assigned to 112 raised-floor pens (0.36 m2 area, 5 birds/pen). Each of the seven experimental diets were offered to birds in 16 pens within four rooms. Two rooms were at 20°C and two rooms were maintained at 35°C. The experimental diets were fed from 14 to 35 d age and contained 214.9 g/kg CP and 13.11 MJ/kg ME. The experimental diets were as follows; control diet containing background Se only (0.189 mg/kg; C); low level sodium selenite (0.376 mg/kg; LSS): high level sodium selenite (0.558 mg/kg; HSS); low level commercial B Traxim® Se (0.244 mg/kg) (LBT); high level B Traxim® Se (0.448 mg/kg; HBT); low level selenised yeast (0.290 mg/kg; LSY); high level selenised yeast (0.487 mg/kg; HSY). 4. Birds consumed more when raised at 20°C compared to birds reared at 35°C (P ≤ 0.05). Birds fed lower Se level reared at 35°C had higher weight gain versus those fed higher Se level (P < 0.05). Birds fed SY had the lowest feed intake, weight gain and FCE (P < 0.05). The greatest GSH-Px activity was observed in birds fed SS diets (P < 0.001). There were interactions between diet x level for TAS, which were highest in birds fed LBT compared to birds fed HBT (P < 0.05). Breast Se content was higher in birds fed HSY compared to LSY (P < 0.001). The highest hepatic Se was seen in birds fed SY and lowest in C (P < 0.001). 5. Birds fed BT diets showed similar levels of Se to those birds fed inorganic Se, and similar levels of GSH-Px to birds fed SY. Further comparative work with broilers fed BT and other Se supplemented diets may elucidate the findings from this report.

Effect of feeding different sources of selenium on growth performance and antioxidant status of broilers.

1. This study was conducted to determine the effect of different sources of selenium (Se) on breast and liver tissue deposition, apparent metabolisable energy (AME), growth performance and antioxidant status of broilers, measured as Se content in liver and breast tissues and glutathione peroxidase (GSH-Px) in blood, when used in 0-35 d broiler chicken diets. 2. A total of 200 male Ross 308 broilers were used in the feeding trial, which comprised two dietary phases, a starter from 0 to 21 d and finisher from 21 to 35 d of age. Four treatments with 10 replications each were used. A control diet (C) was formulated that was sufficient in protein and energy (230 and 215 g/kg of crude protein and 12.67 and 13.11 MJ/kg of metabolisable energy, respectively), for both phases, but contained background Se only from the feed ingredients. Diet 2 (IS) was supplemented with 10.35 g/t inorganic, elemental source of Se. Diet 3 (SY) was supplemented with 136.36 g/t selenised yeast, an organic source derived from Saccharomyces cerevisiae. Diet 4 (SS) was supplemented with 0.666 g/t sodium selenite, an inorganic source. 3. Birds fed the SY diet consumed less and weighed less than those fed IS or C (P < 0.05; 0-35 d of age), but there was no difference compared to birds fed SS diets. There were no differences in FCR or dietary AME between broilers fed different Se sources. All diets containing supplementary Se increased concentrations in the liver and breast muscle, and for GSH-Px levels in blood compared to birds fed the C diet (P < 0.001). Birds fed SY diets had greater Se levels in liver and breast tissues compared to birds fed any of the other diets (P < 0.001). 4. Diets supplemented with Se had variable effects on broiler growth performances and antioxidant status. Feeding Se from a yeast source has higher transfer into breast tissues. Feeding different sources and levels of Se to birds in a more challenging situation to induce oxidative stress may bring more conclusive results.

[Non continent urinary diversion and other bladder managements in patients with multiple sclerosis]. / Dérivation urinaire non continente et modes mictionnels alternatifs chez les patients atteints de sclérose en plaques.

INTRODUCTION: To compare non-continent urinary diversion (NCUD) and other bladder managements in patients with multiple sclerosis (MS), in terms of satisfaction and burden of care. MATERIAL AND METHODS: All patients with MS that were proposed a NCUD in our center for refractory lower urinary tract disorders between January 2005 and March 2018 were eligible. Patients were attributed to two distinct groups: "NCUD" and "Other bladder management". The primary endpoint was the satisfaction related to the bladder management quoted by a numerical rating scale (NRS) from 0 to 10. The secondary endpoints included, among other things, the evaluation of the burden of care associated with the bladder management. RESULTS: Twenty-three patients were included in the "NCUD" group and 11 in the "Other bladder management" group, with 4 patients pursuing with spontaneous voiding, 3 with intermittent catheterization, 2 that have undergone a sphincterotomy, 1 still performing self-intermittent catheterization and 1 with a supra-pubic catheter. The "NCUD" group had a significant higher NRS than the "Other bladder management" group (8.22±1.78 vs. 6.27±2.45; P=0.0056). The daily average duration of care was 16.42minutes in the "NCUD" group and 35.6minutes in the "Other bladder management" group (P=0.1111) CONCLUSION: This exploratory study, even if not conclusive, brings to light the preliminary results needed to elaborate a high level of evidence protocol regarding the satisfaction and the burden of care associated with NCUD in MS patients. LEVEL OF EVIDENCE: 4.

Navigating the highlights of phase III trials: a watchful eye on evidence-based radiotherapy.

BACKGROUND: Phase III randomized controlled trials (RCTs) are the cornerstone of evidence-based oncology. However, there is no exhaustive review describing the radiotherapy RTCs characteristics. The objective of the present study was to describe features of all phase III RCTs including at least a radiation therapy. METHODS AND MATERIALS: Requests were performed in the Medline database (via PubMed). The latest update was performed in April 2016, using the following MESH terms: 'clinical trials: phase III as topic', 'radiotherapy', 'brachytherapy', as keywords. RESULTS: A total of 454 phase III RCTs were identified. Studies were mainly based on open (92.1%) multicenter (77.5%) designs, analyzed in intend to treat (67.6%), aiming at proving superiority (91.6%) through overall survival assessment (46.5%). Most frequently studied malignancies were head and neck (21.8%), lung (14.3%) and prostate cancers (9.9%). Patients were mainly recruited with a locally advanced disease (73.7%). Median age was 59 years old. Out of 977 treatment arms, 889 arms experienced radiotherapy, mainly using 3D-conformal radiotherapy (288 arms, 32.4%). Intensity-modulated techniques were tested in 12 arms (1.3%). The intervention was a non-cytotoxic agent addition in 89 studies (19.6%), a radiation dose/fractionation modification in 74 studies (16.3%), a modification of chemotherapy regimen in 63 studies (13.9%), a chemotherapy addition in 63 studies (13.9%) and a radiotherapy addition in 53 trials (11.7%). With a median follow-up of 50 months, acute all-grade and grade 3-5 toxicities were reported in 49.6% and 69.4% of studies, respectively. Radiotherapy technique, follow-up and late toxicities were reported in 60.1%, 74%, and 31.1% of studies, respectively. CONCLUSION: Phase III randomized controlled trials featured severe limitations, since a third did not report radiotherapy technique, follow-up or late toxicities. The fast-paced technological evolution creates a discrepancy between literature and radiotherapy techniques performed in daily-routine, suggesting that phase III methodology needs to be reinvented.

Comparative effectiveness of linezolid versus vancomycin as definitive antibiotic therapy for heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococcal central-line-associated bloodstream infections in a neonatal intensive care unit.

Objectives: Heterogeneously resistant vancomycin-intermediate coagulase-negative staphylococci (hVICoNS) are emerging pathogens causing central-line-associated bloodstream infections (CLABSIs) in neonatal intensive care unit (NICU) patients. Given the burden of disease associated with CLABSI and the current lack of therapeutic guidelines, we aimed to compare the effectiveness of linezolid versus vancomycin used as the definitive antibiotic therapy for hVICoNS CLABSI. Methods: We performed a retrospective cohort study of infants with hVICoNS CLABSI from a single NICU between 2009 and 2014, treated with either linezolid or vancomycin as definitive antibiotic therapy. CLABSI duration, early and late recurrence and in-hospital mortality were compared using propensity score-adjusted proportional hazards and logistic regression models. Results: Of 89 infants with hVICoNS CLABSI, 33 (37.1%) treated with linezolid were compared with 56 (62.9%) treated with vancomycin. The median duration of CLABSI was 5 (range 1-12) versus 4 days (range 0-14) ( P = 0.11), early recurrences were 3.0% versus 7.1% ( P = 0.42), late recurrences 0% versus 14.3% ( P = 0.02) and mortality 27.3% versus 28.6% ( P = 0.90), when treated with linezolid versus vancomycin, respectively. When adjusting using a continuous propensity score, linezolid had an HR of 0.78 (95% CI 0.48-1.27) for CLABSI duration, an OR of 0.23 (95% CI 0.02-2.56) for early recurrence and an OR of 0.9 (95% CI 0.3-2.67) for mortality, relative to vancomycin. Conclusions: There was no statistically significant difference between linezolid and vancomycin when used as definitive treatment for hVICoNS CLABSI in NICU patients, in terms of CLABSI duration, recurrence or all-cause mortality.

Descriptive study of the parkinsonian population in the north of France: Epidemiological analysis and healthcare consumption.

BACKGROUND: The "neurodegenerative diseases plan" under elaboration for the Hauts-de-France region requires better knowledge of the patient population and care pathways. In France, the prevalence of Parkinson's disease (PD) has been estimated from cohorts to be about 1-3 per 1000 inhabitants, but exhaustive data are scarce for the general population. The purpose of this study was to evaluate the prevalence of PD in the Hauts-de-France region and to assess PD-related healthcare consumption. METHOD: A descriptive study was conducted to identify the parkinsonian population in the Hauts-de-France region (including the administrative districts of Pas-de-Calais and Picardie) for the year 2014. Parkinsonian patients were identified from health insurance fund reimbursement data using the following criteria: (i) reimbursement for a PD-specific medication; (ii) attribution of long-duration disease status coded as PD; (iii) hospital stay with PD diagnosis in the standard discharge report contained in the French medico-economic database on hospital activity (PMSI). RESULTS: The raw prevalence of PD in the region was 5.03 per 1000 inhabitants aged 20 years and older. The standardized prevalence by health territory ranged from 4.0 to 9.0 per 1000 inhabitants aged 20 years and older. During the 1-year study period, 33.5% of patients had a neurology consultation, 57.1% attended a physiotherapy session, and 7.7% received speech therapy. Most of patients (79.6%) were treated with levodopa, sometimes in combination with a catechol-O-methyl transferase inhibitor (14.4%). Dopaminergic agonists were prescribed in 33.5% of cases. A neuroleptic was prescribed for 6.9% of the population (clozapine for 25.9%). CONCLUSION: The prevalence of PD is high in the Hauts-de-France region with a heterogeneous distribution by health territory. Neurology consultations were attended by a minority of patients in 2014. This work provides perspectives for necessary improvement in specialized care for this disease, both in terms of follow-up consultations and home care.

Effect of "Touch Rugby" Training on the Cardiovascular Autonomic Control In Sedentary Subjects.

This study aimed to explore the effects of "touch-rugby" training on the cardiovascular autonomic control in sedentary subjects. 22 adults (30-64 years old) were included in this study. Before (pre-test) and after (post-test) the period of training, cardio-respiratory recordings were achieved at rest and during a graded maximal exercise on a treadmill. The Smoothed-Pseudo-Wigner-Ville Distribution provided instantaneous time frequency components of RR intervals and systolic blood pressure variability in low- and high-frequency bands. The baroreflex sensitivity was assessed in low-frequency and high-frequency bands. Between pre-test and post-test, resting heart rate (74±10 vs. 69±12 beats.min(-1), p<0.05) and systolic blood pressure (118±19 vs. 103±22 mm Hg, p<0.01) decreased. Root mean square of successive differences (34.6±30.1 vs. 47.6±34.8 ms, p<0.001), high-frequency RR variability (590±288 vs. 1262±767 ms², p<0.001) increased whereas low-frequency/high-frequency ratio decreased (3.5±3.4 vs. 1.5±0.9, p<0.05). The high-frequency baroreflex sensitivity increased (13.4±10.1 vs. 26.0±20.9 ms.mmHg(-1), p<0.05). Playing touch rugby with one session weekly over 3 months modified the cardiovascular autonomic control of sedentary subjects. A decrease in the sympathetic tone combined with both an increase in the vagal tone and a decrease in systolic blood pressure at rest were observed. Therefore, such training appears to be beneficial to cardiac health.

Expression of both estrogen receptor-beta 1 (ER-ß1) and its co-regulator steroid receptor RNA activator protein (SRAP) are predictive for benefit from tamoxifen therapy in patients with estrogen receptor-alpha (ER-α)-negative early breast cancer (EBC).

BACKGROUND: Roles of Estrogen Receptor-beta 1 (ER-ß1) and its co-regulator Steroid Receptor RNA Activator Protein (SRAP) in breast cancer remain unclear. Previously, ER-ß1 and SRAP expression were found positively correlated in breast cancer and, therefore, expression of these two molecules could characterize cancers with a distinct clinical outcome. PATIENTS AND METHODS: ER-ß1 and SRAP expression was determined by immunohistochemistry (IHC) in tissue microarrays from a randomized, placebo-controlled trial (NCIC-CTG-MA12), designed to determine the benefit of tamoxifen following chemotherapy in premenopausal early breast cancer (EBC). Expression was dichotomized into low and high using median IHC scores. Relationships with survival used Cox modeling. RESULTS: In the whole cohort, ER-ß1 and SRAP were not prognostic. However, high ER-ß1 and SRAP significantly predicted tamoxifen responsiveness [overall survival, interaction test, P = 0.03; relapse-free survival (RFS), interaction test, P = 0.01]. Stratification by ER-α-status found predictive benefit only in ER-α-negative cases. The difference in RFS between tamoxifen and placebo was greater in patients whose tumors expressed both high SRAP and ER-ß1[hazard ratio = 0.07; 95% confidence interval (CI) 0.01-0.41; P = 0.003] versus those with low SRAP or ER-ß1 (interaction test, P = 0.02). The interaction test was not significant in ER-α-positive cohorts. CONCLUSIONS: This study provides evidence that both ER-ß1 and SRAP could be predictive biomarkers of tamoxifen benefit in ER-α-negative premenopausal EBC.

High genetic diversity and zoonotic potential of Staphylococcus aureus strains recovered from bovine intramammary infections in Colombians dairy herds.

Genotyping of Staphylococcus aureus isolated from mastitis has become a fundamental tool to understand its complex epidemiology and to evaluate spillover events. The aim of this study was to describe the frequency of genotypes of the S. aureus strains isolated from intramammary infections by spa typing technique, and to evaluate the association between genotypes and the ability to form biofilm under in vitro conditions. Sixty-six strains of S. aureus recovered from bovines intramammary infections on 56 dairy herds located in 14 municipalities of the department of Antioquia were characterized. The majority of strains (65/66) were isolated from milk samples collected from dairy cows with subclinical intramammary infections. Nineteen different spa types were found in this study, t521 (19.70%), t267 (15.15%), and t605 (12.12%) being the most frequent. The strains from the t605 spa type showed the highest biofilm production. The high frequency of spa types with zoonotic potential found in this study, identified cattle as an important reservoir of theses clones for people in close proximity, such as milkers and consumers of unpasteurized dairy products.

Delayed response to environmental conditions and infra-seasonal dynamics of the short-beaked common dolphin distribution.

Cetaceans adjust their distribution and abundance to encountered conditions across years and seasons, but we poorly understand such small-scale changes for many species, especially in winter. Crucial challenges confront some populations during this season, such as the high levels of fisheries-induced mortality faced by the common dolphin (Delphinus delphis) in the Northeast Atlantic shelves. For such species, understanding the winter fine-scale dynamics is crucial. We aimed to identify the dolphin distribution drivers during the winters of 2020 and 2021, with a focus on determining the lag between changes in oceanographic conditions and dolphin distribution. The changes were related to temporal delays specific to the nature and cascading effects that oceanographic processes had on the trophic chain. By determining the most important conditions and lags to dolphin distributions, we shed light on the poorly understood intrusions of dolphins within coastal waters during winter: they displayed a strong preference for the coastal-shelf waters front and extensively followed its spatial variations, with their overall densities increasing over the period and peaking in March-April. The results presented here provide invaluable information on the winter distribution dynamics and should inform management decisions to help reduce the unsustainable mortalities of this species in the by-catch of fisheries.

[Advantages and limitations of renin inhibition with aliskiren]. / Intérêts et limites de l'inhibition de la rénine par l'aliskiren.

In the current context of renin-angiotensin-aldosterone system (RAAS) blockade, angiotensin (Ang) converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), or their combination, have proved to be effective in providing cardiovascular and renal protection. However, renin inhibition has long been recognized as the preferred site for blockade of the RAAS because renin represents the first, highly-regulated and rate-limiting step of the system. Up to now, the first orally active renin inhibitors initially tested in humans did not meet the necessary all the criteria (specificity, potency, and pharmacokinetic profile) to become clinically useful drugs. The synthesis of aliskiren, a potent alkane carboxamide renin inhibitor, now provides an orally active compound which, according to its pharmacological profile in normotensive subjects and in patients with hypertension, diabetic nephropathy or heart failure suggests that this drug may be of value for the treatment of patients with cardiovascular and renal disorders. However, long-term studies are needed to demonstrate the efficacy of aliskiren in these clinical settings. The results of the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Disease Endpoints (ALTITUDE) trial which has already included 8600 patients with type 2 diabetes, proteinuria and a high cardiovascular risk and compared the effects of aliskiren vs. a placebo on a composite endpoint including renal and cardiovascular morbidity and mortality should be provided in 2012.

Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective: To assess the safety of inulin and sinistrin use in France. Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.

[Monogenetic dystonia: revisiting the dopaminergic hypothesis]. / Dystonies monogéniques: l'hypothèse dopaminergique revisitée.

Dystonias are clinically and genetically heterogeneous neurological disorders that affect movement, and are the focus of much investigative work. The recent identification of mutations in the gene THAP1 in DYT6 dystonia reopens the very interesting question of the in fine involvement of dopamine in the different types of dystonia. In this review, we will go through the recent literature in order to evaluate the many contributions to this theory as well as to highlight the difficulties in identifying a global regulatory pathway for the different forms of this disease that we are just starting to decipher.

[Predictors of asthenia in breast and prostate cancer patients undergoing curative radiotherapy]. / Facteurs de risque d'asthénie en cours de la radiothérapie des cancers du sein et de la prostate.

PURPOSE: Patients frequently report asthenia during radiation. The present study aimed at identifying the correlation between numerous clinical and tumoral factors and asthenia in breast and prostate cancer patients treated by curative radiotherapy. MATERIALS AND METHODS: A retrospective study was conducted at the Lucien Neuwirth Cancer Institute (France). All breast and prostate cancer patients undergoing curative radiotherapy during 2015 were screened (n=806). Patient's self-evaluation of asthenia and radiotherapy tolerance was assessed through verbal analogic scale (0/10 to 10/10). Data about toxicities, travel distance and travel time, tumor's characteristics, radiotherapy treatment planning, previous cancer therapies, were collected from medical records. RESULTS: 500 patients were included (350 in the breast cancer group and 150 in the prostate cancer group). In all, 86% of patients in the breast cancer group reported asthenia, with a 5/10 median score. In all, 54% of patients in the prostate cancer group reported asthenia, with a 2/10 median score. Univariate analysis showed correlation between asthenia and radiotherapy tolerance as well as tumor staging, in the prostate cancer group. No other correlation was evidenced. CONCLUSION: Radiotherapy-related fatigue is a common side effect. This study showed that most of the factors related to patients or disease that are commonly used to explain fatigue during curative treatments, seem finally to be not correlated with asthenia.

The Case for a Hubble Constant of 30 km s-1 Mpc-1.

Although recent determinations of the distance to the Virgo cluster based on Cepheid variable stars represent an important step in pinning down the Hubble constant, after 65 years a definitive determination of the Hubble constant still eludes cosmologists. At present, most of the observational determinations place the Hubble constant between 40 and 90 kilometers per second per megaparsec (km s(-1) Mpc(-1)). The case is made here for a Hubble constant that is even smaller than the lower bound of the accepted range on the basis of the great advantages, all theoretical in nature, of a Hubble constant of around 30 kilometers per second per megaparsec. Such a value for the Hubble cures all of the ills of the current theoretical orthodoxy, that is, a spatially flat universe composed predominantly of cold dark matter.

Influence of mouse prolactin-inducible protein in saliva on the aggregation of oral bacteria.

INTRODUCTION: Mouse prolactin-inducible protein (mPIP) is secreted in mouse saliva and has been found to bind oral bacteria, showing the highest affinity for streptococci. Comparisons between the oral flora of mPIP knockout mice and their wild-type controls showed differences in the genera colonizing the two groups of mice. These findings suggested a role for mPIP in the colonization of the mouse oral cavity, possibly modulating the oral flora. In this in vitro study, we focused on the contribution of this protein to aggregation of oral bacteria, a process thought to promote the clearance of bacteria from the oral cavity, and one that could influence the composition of the oral bacterial community. METHODS: The aggregation of selected human and mouse oral streptococci was measured spectrophotometrically. The aggregation of oral bacteria by saliva from mPIP knockout mice, which lack mPIP, was compared with that of saliva from wild-type mice. RESULTS: Both wild-type saliva and mPIP knockout mouse saliva induced aggregation of human strain Streptococcus gordonii SK120 and mouse streptococci strains M105/6 and M106/2. Bacterial aggregation induced by the saliva of wild-type mice was significantly higher than the aggregation induced by saliva from mPIP knockout mice for all the bacterial strains. CONCLUSION: In this study it was confirmed that mPIP plays a role in the aggregation of oral bacteria. The salivary components promoting aggregation of oral bacteria are considered to be part of the oral defense mechanisms so these findings provide insight into a possible function of mPIP in host defense by promoting aggregation of oral bacteria.

Generation and initial characterization of the prolactin-inducible protein (PIP) null mouse: accompanying global changes in gene expression in the submandibular gland.

The human prolactin-inducible protein/gross cystic disease fluid protein-15 (hPIP/GCDFP-15) is a secretory glycoprotein found primarily in apocrine tissues including the breast and salivary glands. With largely unknown functions, PIP has been implicated in breast cancer and metastasis, host defense processes and T lymphocyte apoptosis. To begin to address PIP function in vivo, we generated the PIP null mouse (Pip-/-). Additionally, to determine the effect of the loss of PIP on gene expression and to gain insight into some of the molecular mechanisms underlying PIP function, microarray analysis of the submandibular gland was also undertaken. Pip-/- mice developed normally with no overt differences in behaviour or gross morphology and were fertile. However, histological examination of 3-month-old Pip-/- mice sometimes showed enlarged submandibular lymph nodes, lymphocytic aggregations within the prostate lobes, and enlarged medulla in the thymus. Functional analysis of gene expression revealed sets of multiple differentially expressed genes associated with cell death and survival, lipid metabolism, inflammation, immune disease, and cancer, as a consequence of mPIP abrogation. Taken together, these studies lend support to an immunomodulatory role for PIP in vivo and provide further insights into potentially novel signaling pathways and regulatory networks for PIP.