Frequency-Dependent Squeezed Vacuum Source for the Advanced Virgo Gravitational-Wave Detector.

In this Letter, we present the design and performance of the frequency-dependent squeezed vacuum source that will be used for the broadband quantum noise reduction of the Advanced Virgo Plus gravitational-wave detector in the upcoming observation run. The frequency-dependent squeezed field is generated by a phase rotation of a frequency-independent squeezed state through a 285 m long, high-finesse, near-detuned optical resonator. With about 8.5 dB of generated squeezing, up to 5.6 dB of quantum noise suppression has been measured at high frequency while close to the filter cavity resonance frequency, the intracavity losses limit this value to about 2 dB. Frequency-dependent squeezing is produced with a rotation frequency stability of about 6 Hz rms, which is maintained over the long term. The achieved results fulfill the frequency dependent squeezed vacuum source requirements for Advanced Virgo Plus. With the current squeezing source, considering also the estimated squeezing degradation induced by the interferometer, we expect a reduction of the quantum shot noise and radiation pressure noise of up to 4.5 dB and 2 dB, respectively.

Evaluation of the Antimicrobial Effect on Enterococcus Faecalis of Bioceramic Cements with and without Silver Nanoparticles.

OBJECTIVE: To compare the antimicrobial effect of bioceramic endodontic cements with and without silver nanoparticles on Enterococcus faecalis. MATERIALS AND METHODS: Six groups were evaluated (n=8), and divided according to the materials: MTA Flow + AgNP ; MTA Flow Group; Bio C Repair + AgNP; Bio C Repair; PBS Cimmo + AgNP; PBS Cimmo. The groups were maintained for 72 h in the suspension of Enterococcus faecalis in Simulated Body Fluid (SBF). Samples of 100 µL were removed from the suspension at 0, 24, 48 and 72 h and seeded in triplicate in a Petri dish. Colony forming units (CFU) were counted using a colony counter. All procedures described were performed in a laminar flow chamber. Two-way ANOVA followed by Tukey's post hoc test and paired t-test were used for statistical analyses (α = 0.05). RESULTS: The addition of silver nanoparticles resulted in a statistically significant difference for MTA and CIMMO PBS cements (p⟨0.05), with the lowest bacterial growth being shown by the MTA group. For all groups, only the times of 48 and 72 h presented results without differences. CONCLUSION: The addition of silver nanoparticles to bioceramic cements was efficient to promote an acceleration of bacterial death.

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO's and Advanced Virgo's Third Observing Run.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M_{⊙} and 1.0 M_{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M_{⊙}

Managing taste and odour metabolite production in drinking water reservoirs: The importance of ammonium as a key nutrient trigger.

Taste and odour (T&O) compounds (most commonly 2-MIB and Geosmin) in drinking water are becoming an increasingly global problem for water management. Here, the trigger(s) for 2-MIB and Geosmin production were investigated in Plas Uchaf reservoir (North Wales, UK) with detailed water sample analysis between 2015 and 2016. Historical abstraction data from this reservoir and 4 reservoirs in Somerset (England, UK) were compared statistically using Self-Organising Map (SOM) analysis. In-reservoir measurements (2015-2016) revealed an 85% reduction in ammonium from the primary external loading source led to lower 2-MIB and Geosmin concentrations, with peak concentrations of 2-MIB declining from 60 to 21  ng l-1 and Geosmin declining from 140 to 18  ng l-1. No other measured water chemistry parameter showed a significant difference between years. The SOM results support the in-reservoir findings, revealing 2-MIB and Geosmin to be associated with high ammonium relative to nitrate for all 5 reservoirs. We conclude that ammonium is key for stimulating cyanobacterial productivity and production of T&O compounds. Whilst it is well understood that adequate availability of phosphorus is required for rapid growth in cyanobacteria, and hence should still be considered in management decisions, we suggest that monitoring sources and concentrations of ammonium is key for managing T&O outbreaks in drinking water reservoirs.

Diarrhoeagenic Escherichia coli and Escherichia albertii in Brazil: pathotypes and serotypes over a 6-year period of surveillance.

Diarrhoeagenic Escherichia coli (DEC) is a leading cause of infectious diarrhoea worldwide. In recent years, Escherichia albertii has also been implicated as a cause of human enteric diseases. This study describes the occurrence of E. coli pathotypes and serotypes associated with enteric illness and haemolytic uremic syndrome (HUS) isolated in Brazil from 2011 to 2016. Pathotypes isolated included enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and Shiga toxin-producing E. coli (STEC). PCR of stool enrichments for DEC pathotypes was employed, and E. albertii was also sought. O:H serotyping was performed on all DEC isolates. A total of 683 DEC and 10 E. albertii strains were isolated from 5047 clinical samples. The frequencies of DEC pathotypes were 52.6% (359/683) for EPEC, 32.5% for EAEC, 6.3% for ETEC, 4.4% for EIEC and 4.2% for STEC. DEC strains occurred in patients from 3 months to 96 years old, but EPEC, EAEC and STEC were most prevalent among children. Both typical and atypical isolates of EPEC and EAEC were recovered and presented great serotype heterogeneity. HUS cases were only associated with STEC serotype O157:H7. Two E. albertii isolates belonged to serogroup O113 and one had the stx2f gene. The higher prevalence of atypical EPEC in relation to EAEC in community-acquired diarrhoea in Brazil suggests a shift in the trend of DEC pathotypes circulation as previously EAEC predominated. This is the first report of E. albertii isolation from active surveillance. These results highlight the need of continuing DEC and E. albertii surveillance, as a mean to detect changes in the pattern of pathotypes and serotypes circulation and provide useful information for intervention and control strategies.

Renal safety after one year of sofosbuvir-based therapy for chronic hepatitis C: A Brazilian "real-life" study.

WHAT IS KNOWN AND OBJECTIVE: Sofosbuvir(SOF)-based regimens have been administrated with excellent efficacy in chronic hepatitis C. Few uncontrolled ("real-life") studies consider the assessment of renal function when evaluating their post-treatment outcomes. This study aims to evaluate renal biomarkers in a "real-life" experience with chronic hepatitis C patients treated with SOF therapy in a long-term follow-up. METHODS: Serum and urinary biomarkers were analysed before, at the end of therapy (EoT), after 12 weeks (sustained virological response-SVR) and one year (1y) post-treatment. Patients were categorized according to baseline glomerular filtration rate (GFR-cut-off 45 mL/min/1.73 m2 ). RESULTS: Ninety-four patients with a mean age of 59.9 ± 8.5 years were included; 98.9% of patients reached SVR. Significant improvement in renal biomarkers was observed in patients with GFR ≥45 mL/min/1.73 m2 , as indicated by a progressive increase in mean GFR values until 1y. No evidence of tubular dysfunction was identified. Patients with baseline GFR <45 mL/min/1.73 m2 did not experience alterations in renal biomarkers; however, a mean change of +10.7 in GFR values was observed. We noticed significant upper stage transition in the CKD classification, and 58.7% of patients achieved G1 stage at 1y (P < .0001). WHAT IS NEW AND CONCLUSION: In a "real-life experience" of a Brazilian centre, SOF therapy appears to guarantee renal safety for patients with chronic hepatitis C followed until one year after treatment.

Relationship among physiological quality, heterosis, and amylase gene expression in maize seeds.

In this study, we analyzed heterosis, amylase enzyme gene expression, and the physiological quality of maize seeds with different genotypes and sizes, which were subjected to aging and not subjected to aging. We used seeds from 2 maize lines that differed with regard to physiological quality, the hybrid, and the reciprocal hybrid; they were classified into 2 sizes and were subjected to aging and not subjected to aging. Physiological quality was assessed by performing tests for germination, emergence, emergence speed index, and artificial aging. Expressions of the genes alpha amylase B73, alpha amylase (LOC542522), isoamylase mRNA clone 353244, and the endogenous controls ubiquitin and alcohol dehydrogenase in the seeds were studied using quantitative real-time-polymerase chain reaction. We observed heterosis for seed quality and for expression of amylase genes in the genotypes studied. We found no difference in seed quality between large and small seeds.

Physiological quality and gene expression during the development of habanero pepper (Capsicum chinense Jacquin) seeds.

Phytohormones have different characteristics and functions, and they may be subject to changes in their gene expression and synthesis during seed development. In this study, we evaluated the physiological qualities of habanero peppers (Capsicum chinense Jacquin) during seed development and the expression of genes involved in germination. Seeds were obtained from fruits harvested at different stages of development [i.e., 14, 21, 28, 35, 42, 49, 56, 63, and 70 days after anthesis (DAA)]. Immediately after harvesting, the seeds were subjected to various tests to determine moisture content, germination, first count germination, and seedling emergence. Real-time polymerase chain reaction was used to evaluate the expression of various genes, including MAN2, NCED, B73, ICL6, and GA3ox. Electrophoresis was used to assess the expression of various enzymes, including α-amylase, isocitrate-lyase, and endo-ß-mannanase. Habanero peppers harvested at 70 DAA and subjected to 7 days of rest exhibited higher germination rates and vigor compared to those harvested at all other developmental stages. Peppers harvested at 63 DAA without drying exhibited higher α amylase and AmyB73 gene expression levels. Peppers harvested at 70 DAA with 7 days of rest exhibited higher endo-ß-mannanase expression levels. MAN2 gene expression increased during the development of non-dried seeds until 70 DAA. Peppers harvested at 42 DAA exhibited the highest isocitrate-lyase and ICL6 gene activity levels in comparison to those at all other developmental stages.

Ultrasound Effect in the Removal of Intraradicular Posts Cemented with Different Materials.

AIM: This study evaluated the effect of ultrasonic vibration on the tensile strength required to remove intraradicular post cemented with different materials. MATERIALS AND METHODS: Bovine teeth were selected, and 7 mm of the cervical root canals were prepared to size 5 Largo drill, the posts were cemented with zinc phosphate, Enforce (resin) or Rely X (glass ionomer). The specimens were divided into six groups (n = 10), according to the following procedures: GI-cementation with zinc phosphate associated with traction force; GII-cementation with zinc phosphate associated with ultrasonic activation and traction force; G111-cementation with Enforce associated with traction force; GIV-cementation with Enforce associated with ultrasonic activation and traction force; GV-cementation with Rely X associated with traction force; and GVI-cementation with Rely X associated with ultrasonic activation and traction force. The tensile test was conducted using the electromechanical testing machine, the force was determined by a specialized computer program and ultrasonic activation using the Jet Sonic Four Plus (Gnatus) device in 10P. RESULTS: Concerning to average ranking, GI showed statistically significant difference in comparison with GII and GVI (p < 0.05); there was no statistical difference in GIII and GIV when compared to other groups (p > 0.05). CONCLUSION: The ultrasound favored the intraradicular post traction regardless of the employed cement in greater or lesser extent. CLINICAL SIGNIFICANCE: The post removal is a routine practice in the dental office, therefore, new solutions and better alternatives are need to the practitioner. We did not find in the literature many articles referring to this practice. Thus, the results from this study are relevant in the case planning and to promote more treatment options.

Physiological quality and gene expression related to heat-resistant proteins at different stages of development of maize seeds.

We quantified and characterized the expression of heat-resistant proteins during seed development of maize lines with distinct levels of tolerance to high drying temperature. A corn field was planted for multiplication of seeds of different lines, two tolerant and two non-tolerant to high drying temperatures. Harvest of the seeds was carried out at various stages of development and they were then subjected to tests of moisture content, germination, first count of germination, accelerated aging, and cold test. The seeds were stored in a freezer for later analysis of expression of heat-resistant proteins by means of real-time PCR, electrophoresis, and spectrophotometry. We observed that heat-resistant proteins are expressed in a differential manner in seeds from different lines and at different stages of development. The expression of heat-resistant proteins was earlier in lines tolerant to high drying temperatures. Greater germination and vigor values was found for seeds collected at the last stage of development.

Frequency of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis and Ureaplasma species in cervical samples.

We investigated the relative frequencies of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis and Ureaplasma sp. in cervical samples. PCR analyses were performed in ectocervical and endocervical samples from 224 patients attending public health services in Belo Horizonte and Contagem, Minas Gerais Brazil. A high prevalence of colonisation of the cervix (6.3% for C. trachomatis, 4.0% for N. gonorrhoeae, 0.9% for M. genitalium, 21.9% for M. hominis, 38.4% for Ureaplasma sp.) was demonstrated not only for pathogens classically associated to cervicitis (C. trachomatis and N. gonorrhoeae), but also for M. hominis and Ureaplasma sp. These findings may be useful to guide more adequate diagnosis to interrupt transmission and to avoid negative impacts on the female reproductive tract.

Chemoprevention assessment, genotoxicity and cytotoxicity of flavonoids from Inga laurina leaves (FABACEAE).

This study aimed to identify and evaluate the cytotoxicity, genotoxicity, antigenotoxicity and chemoprevention assessment of flavonoids myricetin-3-O-(2″-O-galloyl)-α-rhamnopyranoside and myricetin-3-rhamnoside from Inga laurina leaves extract. The Quinone reductase induction as a biomarker for cancer chemoprevention was evaluated in murine hepatocellular carcinoma, the cytotoxicity was evaluated by sulforhonamide B assay and genotoxicity was evaluated by comet assay using HepG2 cell line. The results demonstrated that the flavonoids didn´t show cytotoxicity in HepG2 cells. In the chemoprevention evaluations were not able to promote the induction of Quinone Reductase and also no genotoxic effect was observed by evaluation of the comet assay in none of the concentrations tested. In the antigenotoxicity test, all compounds had a protective effect against damage induced by hydrogen peroxide and were repaired against damage. Although none of the flavonoids were capable of inducing the enzyme Quinone Reductase at the concentrations tested, the antigenotoxicity results showed a powerful chemoprotective action.

[Diffusion tensor imaging of the corticospinal pathway and its association with the prognosis of acute cerebral infarction: experience with a cohort in Mexico]. / Imagen del tensor de difusión de la vía corticoespinal y su asociación con el pronóstico del infarto cerebral agudo: experiencia de una cohorte en México.

INTRODUCTION: Magnetic resonance diffusion tensor imaging through the fraction of anisotropy allows evaluation of the integrity of the motor pathways after cerebral infarction. AIMS: To correlate the fraction of anisotropy with the clinical scales and the prognosis of cerebral infarction. SUBJECTS AND METHODS: Prospective study of patients with cerebral infarction to compare the fraction of anisotropy in different regions of interest with functional evaluations and with controls free of infarction. A subgroup of subjects with rehabilitation underwent an initial MRI scan and another at three months, with clinical follow-up for six months. RESULTS: Thirty-eight consecutive patients with middle cerebral artery infarction were included. The fraction of anisotropy values were lower in the ipsilateral corticospinal pathway than the fraction of anisotropy of the corticospinal pathway of the controls. The values of the fraction of anisotropy in the ipsilateral corticospinal pathway were associated with the value of the functional scale on admission. Changes in the fraction of anisotropy values between the initial MRI and the scan performed at three months correlated with the score on the functional scale and the modified Rankin scale at three and six months. CONCLUSIONS: The value of the fraction of anisotropy in the ipsilateral internal capsule is associated with the presence of a lesion and with its presenting symptoms. Changes in the fraction of anisotropy at three months suggest long-term clinical recovery.

TITLE: Imagen del tensor de difusión de la vía corticoespinal y su asociación con el pronóstico del infarto cerebral agudo: experiencia de una cohorte en México.Introducción. La imagen del tensor de difusión por resonancia magnética a través de la fracción de anisotropía permite evaluar la integridad de las vías motoras después de un infarto cerebral. Objetivo. Correlacionar la fracción de anisotropía con las escalas clínicas y el pronóstico del infarto cerebral. Sujetos y métodos. Estudio prospectivo de pacientes con infarto cerebral para comparar la fracción de anisotropía en diferentes regiones de interés con evaluaciones funcionales y con controles sin infarto. En un subgrupo con rehabilitación, se realizó una resonancia magnética inicial y a los tres meses, con un seguimiento clínico durante seis meses. Resultados. Se incluyó a 38 pacientes consecutivos con infarto cerebral de la arteria cerebral media. Los valores de la fracción de anisotropía fueron menores en la vía corticoespinal ipsilateral que en la vía corticoespinal de los controles. Los valores de la fracción de anisotropía en la vía corticoespinal ipsilateral se asociaron con el valor de la escala funcional en el momento de su admisión. Los cambios en los valores de la fracción de anisotropía entre la resonancia magnética inicial y a los tres meses se correlacionaron con la puntuación en la escala funcional y en la escala de Rankin modificada a los tres y a los seis meses. Conclusiones. El valor de la fracción de anisotropía en la cápsula interna ipsilateral se asocia a la presencia de lesión y a su presentación clínica. Los cambios en la fracción de anisotropía a los tres meses sugieren la recuperación clínica a largo plazo.

Inga edulis fruits: a new source of bioactive anthocyanins.

The extraction conditions and chromatographic analysis from seeds of Inga edulis were optimized and provided one anthocyanin from aqueous fraction and a mixture of three anthocyanins from methanolic fraction. The pure anthocyanin obtained was subjected to structural modifications and the products obtained were subjected to chemical and pharmacological assays, as well as quantum chemical calculations based on DFT and TD-DFT methods. Hence, the anthocyanin fractions were evaluated for their chemical-pharmacological potential through chemical and biological assays: antioxidant activity by the DPPH, determination of the Solar Protection Factor (SPF) and cytotoxic activity (hepatocellular carcinoma infected with hepatitis C virus). The results indicated that even the anthocyanin and derivatized compounds having high antioxidant potential showed an SPF lower than six, which is lower than the minimum accepted by current Brazilian legislation. In addition, none of compounds presented significant cytotoxic activity against the tumour cell line studied.

Development of a method for the detection of infectious myonecrosis virus by reverse-transcription loop-mediated isothermal amplification and nucleic acid lateral flow hybrid assay.

We report the development of a reverse-transcription loop-mediated isothermal amplification and nucleic acid lateral flow method (RT-LAMP-NALF) for detection of infectious myonecrosis virus (IMNV). The RT-LAMP-NALF method combines simplified nucleic acid extraction, a reverse-transcription loop-mediated isothermal amplification platform, and one-step visual colorimetric confirmation of the IMNV amplified sequences using a generic NALF qualitative detection test strip. The sensitivity of RT-LAMP (using two and three primer pairs) and nested RT-LAMP (using three primer pairs) was compared by real-time reverse-transcription-polymerase chain reaction (RT-PCR) using TaqMan probe. The detection of RT-LAMP (three primer pairs) products was accomplished by using a NALF-test strip. The RT-LAMP-NALF showed equivalent sensitivity to RT-LAMP (using three primer pairs), and it was found to be 100 and 10 times more sensitive than one-step RT-PCR and RT-LAMP (two primer pairs), respectively. On the other hand, the RT-LAMP-NALF was 10 and 100 times less sensitive than nested RT-PCR and real-time RT-PCR, respectively. The simplified RNA extraction method ranged from 4.4 x 10(6) to 2.2 x 10(8) IMNV copy numbers microL(-1) RNA, and it was similar with the standard RNA extraction (from 1.2 x 10(6) to 6.3 x 10(7) IMNV copy numbers microL(-1) RNA). These results clearly demonstrate that the RT-LAMP-NALF method is specific, sensitive, can shorten the time for analysis, and has potential application for IMNV diagnosis in resource-poor diagnostic settings.

Immune response mediated by Th1 / IL-17 / caspase-9 promotes evolution of periodontal disease.

INTRODUCTION: Periodontitis is characterized by inflammatory mediators beyond T lymphocyte function and phenotype (Th1/Th2/Th17). The clinical diversity in periodontitis makes it difficult to characterize the immune response in patients. This study evaluated the profile of the adaptive immune response in the periodontal disease model. METHODS: 72 rats (Wistar) were divided into a control group (CTL/day 0) and periodontitis (PD15/15 days and PD60/60 days). In the PD15 and PD60 groups, periodontal disease was induced by ligature with a silk thread placed in the cervical region of the upper first molar. After euthanasia, the periodontal tissue was analyzed by flow cytometry (CD4, CD8, CD25, CD44), semi-quantitative RT-PCR (T-bet, GATA-3, RORγt), semi-quantitative RT-PCR and ELISA IFN-γ, TNF-α, IFN-γ, IL-4, IL-6, IL-10, IL-17) and by Western blotting (Caspase-9, PCNA). RESULTS: The number of CD4+CD25+, CD4+CD44+, CD8+CD25+ and CD8+CD44+ cells and expression levels of T-bet and GATA-3 are increased in the PD60 group compared to PD15 and CTL. The RORγ-t gene transcript increased in the PD15 group in relation to PD60 and CTL. The cytokines IFN-γ, TNF-α and IL-17 increased in the PD60 group in relation to PD15. The expression of Caspase-9 was higher in the PD60 group than in PD15. CONCLUSIONS: The results suggest that the evolution of gingivitis to periodontitis is related to the accumulation of activated Th1 cells (IFN-γ and TNF-α) associated with the presence of increased IL-17. Studies with inhibitors of these cytokines in periodontal disease may lead to therapy directed at blocking the inflammatory process in this pathology, interrupting bone loss.

Identification of differentially expressed genes induced by hydroxyurea in reticulocytes from sickle cell anaemia patients.

1. The major effect associated with hydroxyurea (HU) treatment of sickle cell anaemia (SCA) patients is an increase in fetal haemoglobin (HbF) synthesis, which inhibits the polymerization of haemoglobin S. 2. Hydroxyurea improves clinical symptoms by reducing the frequency of pain and vaso-occlusive crises, acute chest syndrome, transfusion requirements and hospitalization. 3. The molecular mechanisms responsible for HU-mediated induction of fetal globin transcription are not completely understood. Therefore, the aim of the present study was to identify differentially expressed genes participating in these mechanisms. 4. We established two suppression subtractive hybridization (SSH) libraries from reticulocytes obtained from SCA patients either not on or on HU treatment. The gene expression of some of the genes identified was subsequently evaluated by real-time polymerase chain reaction (PCR). 5. Genes identified with altered expression included SUDS3, FZD5 and PHC3, which may be associated with the regulation of globin expression. 6. This is the first demonstration of an association between HU treatment and the expression of genes identified in erythroid cells.

The Beneficial Effects of Physical Activity: Is It Down to Your Genes? A Systematic Review and Meta-Analysis of Twin and Family Studies.

BACKGROUND: There is evidence for considerable heterogeneity in the responsiveness to regular physical activity (PA) which might reflect the influence of genetic factors. The aim of this systematic review was to assess whether the response to a PA intervention for measures of body composition and cardiorespiratory fitness is (i) correlated within twin pairs and/or families and (ii) more correlated in monozygotic twins (MZ) compared to dizygotic twins (DZ), which would be consistent with genetic effects. METHODS: We performed electronic database searches, combining key words relating to "physical activity" and "genetics", in MEDLINE, CINAHL, EMBASE, SPORTS Discuss, AMED, PsycINFO, WEB OF SCIENCE, and SCOPUS from the earliest records to March 2016. Twin and family studies were included if they assessed body composition and/or cardiorespiratory fitness following a PA intervention, and provided a heritability estimate, maximal heritability estimate, or within MZ twin pair correlation (rMZ). Data on heritability (twin studies), maximal heritability (family studies), and the rMZ were extracted from included studies, although heritability estimates were not reported as small sample sizes made them uninformative. RESULTS: After screening 224 full texts, nine twin and five family studies were included in this review. The pooled rMZ in response to PA was significant for body mass index (rMZ = 0.69, n = 58), fat mass (rMZ = 0.58, n = 48), body fat percentage (rMZ = 0.55, n = 72), waist circumference (rMZ = 0.50, n = 27), and VO2max (rMZ = 0.39, n = 48), where "n" represents the total number of twin pairs from all studies. Maximal heritability estimates ranged from 0-21% for measures of body composition, and 22-57% for cardiorespiratory fitness. Twin studies differed in sample age, baseline values, and PA intervention, although the exclusion of any one study did not affect the results. CONCLUSIONS: Shared familial factors, including genetics, are likely to be a significant contributor to the response of body composition and cardiorespiratory fitness following PA. Genetic factors may explain individual variation in the response to PA. TRIAL REGISTRATIONS: PROSPERO Registration No CRD42015020056 .

Transplantation of Human Adipose Mesenchymal Stem Cells in Non-Immunosuppressed GRMD Dogs is a Safe Procedure.

The possibility to treat Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, through cell therapy with mesenchymal stromal cells (MSCs) has been widely investigated in different animal models. However, some crucial questions need to be addressed before starting human therapeutic trials, particularly regarding its use for genetic disorders. How safe is the procedure? Are there any side effects following mesenchymal stem cell transplantation? To address these questions for DMD the best model is the golden retriever muscular dystrophy dog (GRMD), which is the closest model to the human condition displaying a much longer lifespan than other models. Here we report the follow-up of 5 GRMD dogs, which were repeatedly transplanted with human adipose-derived mesenchymal stromal cells (hASC), derived from different donors. Xenogeneic cell transplantation, which was done without immunosuppression, was well tolerated in all animals with no apparent long-term adverse effect. In the present study, we show that repeated heterologous stem-cell injection is a safe procedure, which is fundamental before starting human clinical trials.

Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A receptors.

Estrogen deficiency has been associated with stress, anxiety and depression. Estrogen receptors have been identified in the median raphe nucleus (MRN). This structure is the main source of serotonergic projections to the hippocampus, a forebrain area implicated in the regulation of defensive responses and in the resistance to chronic stress. There is evidence showing that estrogen modulates 5-HT1A receptor functions. In the MRN, somatodendritic 5-HT1A receptors control the activity of serotonergic neurones by negative feedback. The present study evaluated the effect of intra-MRN injection of estradiol benzoate (EB) (600 or 1200ng/0.2microl) on the performance of ovariectomised rats submitted to the elevated plus-maze test of anxiety and to the open-field test. Additionally, the same effect was evaluated with a previous intra-MRN injection of WAY 100635(100ng/0.2microl), an antagonist of 5-HT1A receptors. The results showed that both doses of EB increased the percentage of entries and the percentage of time spent into the open arms, suggestive of an anxiolytic effect. The highest dose of the drug also increased the number of entries into the enclosed arm and locomotion in the open field, indicating a stimulatory motor effect. WAY 100635 antagonised the effect of estradiol in the elevated plus-maze and in the open-field. The results show that estrogen receptors of the MRN are implicated in the regulation of anxiety-related behaviour. The results also support claims that the effect of estrogen involves a change in 5-HT1A receptor function.