Dynamical estimates of chaotic systems from Poincar\'e recurrences

We show that the probability distribution function that best fits the distribution of return times between two consecutive visits of a chaotic trajectory to finite size regions in phase space deviates from the exponential statistics by a small power-law term, a term that represents the deterministic manifestation of the dynamics, which can be easily experimentally detected and theoretically estimated. We also provide simpler and faster ways to calculate the positive Lyapunov exponents and the short-term correlation function by either realizing observations of higher probable returns or by calculating the eigenvalues of only one very especial unstable periodic orbit of low-period. Finally, we discuss how our approaches can be used to treat data coming from complex systems.Comment: subm. for publication. Accepted fpr publication in Chao

Learnings from Regional Market Dynamics of Originator and Biosimilar Infliximab and Etanercept in Germany.

Drug budget and prescription control measures are implemented regionally in Germany, meaning that the uptake of pharmaceuticals, including biosimilars, can vary by region. We examine regional market dynamics of tumor necrosis factor alpha (TNFα) inhibitor originators and biosimilars in Germany and studied the influence of biosimilar policies on these dynamics. This study is based on: (1) a literature review in which German biosimilar policies are identified, (2) the analysis of dispensing data (2010-2018) for the class of TNFα inhibitors, and (3) ten semi-structured interviews investigating prescribers' and insurers' views on factors potentially influencing biosimilar uptake. The analysis of biosimilar market shares of infliximab and etanercept revealed wide variations across the 17 German Regional Associations of Statutory Health Insurance Accredited Physicians (PA regions). Quantitative analyses indicated that biosimilar market shares for infliximab and etanercept were significantly lower in former East Germany when compared to former West Germany regions. Through qualitative interview analyses, this study showed that the use of infliximab and etanercept biosimilars across Germany is primarily influenced by (1) the regional-level implementation of biosimilar quotas and the presence of monitoring/sanctioning mechanisms to ensure adherence to these quotas, (2) the different insurer-manufacturer discount contracts, and (3) gainsharing arrangements established at the insurer-prescriber level

Methylene blue? Therapeutic alternative in the management of septic shock refractory to norepinephrine

Introduction: Methylene blue is receiving special interest in perioperative and intensive care of patients with distributive shock due to its ability to block the action of nitric oxide and to antagonize deep vasodilation. Objective: The objective is to illustrate the use of the methylene blue, summarizing the perioperative management of a case with secondary vasoplegic syndrome due to a norepinephrine refractory septic shock and the response to methylene blue, reviewing the latest evidence of this therapeutic alternative. In practice:We describe the case of a 60-year-old man, paraplegic, with septic shock due to a long evolution decubitus pressure ulcer. After two hours of surgery, the patient remained with hemodynamic deterioration despite high doses of vasopressin (3 IU/hour) and norepinephrine (2 µg/kg /min), therefore methylene blue was administered with two intravenous bolus doses of 50 mg without adverse effects. After half an hour hemodynamic improvement was evidenced, allowing to decrease norepinephrine infusion and normalizing blood pressure. Finally, debridement of necrotic tissue, amputation and disarticulation of left coxofemoral joint was performed with subsequent transfer to the ICU and discharge to the spinal cord injury ward twenty eight days later. Conclusions: As it has been demonstrated in our patient, methylene blue is a therapeutic alternative to manage patients with persistent hypotension despite the use of various vasopressors during the management of vasoplegic syndrome secondary to septic shock

Y chromosome haplotype characterization of Tunisian sheep breeds

This study aimed to investigate Y chromosomal haplotypes in the main Tunisian sheep breeds. For this purpose, we sequenced 2 regions of SRY (549-bp and 598-bp fragments) and 1 region in each of the AMELY and DBY genes in Barbarin, Western Thin Tail, Sicilo Sarde, and Black Thibar breeds. In addition, we analyzed the diversity at the SRYM18 microsatellite locus and detected 4 alleles of 139, 141, 143, and 145 bp. The sequencing analysis did not reveal any polymorphism in the AMELY or DBY regions; however, 2 samples carried the G allele in the 549-bp fragment of SRY. A total of 5 haplotypes, H4, H5, H6, H8, and H12, were found in the 4 breeds. The most common haplotype was H8 (55.5%), followed by H6 (34.5%), while other haplotypes were observed at low frequencies. H4 and H5 haplotypes were observed only in Western Thin Tail and Black Thibar breeds, respectively. In spite of the small area of Tunisia, a high Y chromosome diversity was observed. The results underlined the genetic relation of Tunisian sheep breeds with Middle Eastern, African, and European sheep breedsPublishe

Learnings from Regional Market Dynamics of Originator and Biosimilar Infliximab and Etanercept in Germany

Drug budget and prescription control measures are implemented regionally in Germany, meaning that the uptake of pharmaceuticals, including biosimilars, can vary by region. We examine regional market dynamics of tumor necrosis factor alpha (TNFα) inhibitor originators and biosimilars in Germany and studied the influence of biosimilar policies on these dynamics. This study is based on: (1) a literature review in which German biosimilar policies are identified, (2) the analysis of dispensing data (2010–2018) for the class of TNFα inhibitors, and (3) ten semi-structured interviews investigating prescribers’ and insurers’ views on factors potentially influencing biosimilar uptake. The analysis of biosimilar market shares of infliximab and etanercept revealed wide variation

Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK

The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segureña) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150–154 Mb), Oar6 (4–49 Mb) and Oar13 (68–74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection.Publishe

Experimental Study of the Mechanical Transmission of Rabbit Hemorrhagic Disease Virus (RHDV2/b) by Aedes albopictus (Diptera: Culicidae) and Phlebotomus papatasi (Diptera: Psychodidae)

Rabbit hemorrhagic disease (RHD) is caused by a lagovirus mainly affecting European rabbits (Oryctolagus cuniculus), although other European and North American lagomorph species are also susceptible to fatal infection by the new viral variant RHDV2/b. In the present work, direct mechanical transmission of the rabbit hemorrhagic disease virus (RHDV2/b variant) by the hematophagous Diptera Aedes albopictus (Skuse) (Diptera: Culicidae) and the sand fly Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) was tested. For each species, six and three laboratory rabbits were exposed to bites of dipterous females partially fed on RHDV2/b viral suspension 2 h and 24 h prior to exposure, respectively. The rabbits were then monitored for clinical changes and mortality for 35 d, and seroconversion was assessed by indirect ELISA. No rabbit died or showed clinical signs of disease, and seroconversion was recorded in two rabbits challenged with P. papatasi females fed the viral suspension 2 h prior to exposure. The number of RHDV2/b RNA copies/female was higher in Ae. albopictus than in P. papatasi but the decrease over time of RNA load in Ae. albopictus was greater than that in P. papatasi. The results of this study suggest the inability of Ae. albopictus to serve as a direct mechanical vector of RHDV2/b, but sand flies could play a role in the local transmission of RHD.Publishe

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level

<p>Abstract</p> <p>Background</p> <p>Anxiety levels in rats are correlated with interleukin-2 (IL-2) levels in the brain. The aim of the present study was to investigate the effects of dioscorea (wild yam), a Chinese medicine, on emotional behavior and IL-2 levels in the brain of ovariectomized (OVX) rats.</p> <p>Methods</p> <p>One month after ovariectomy, female Wistar rats were screened in the elevated plus-maze (EPM) test to measure anxiety levels and divided into low anxiety (LA) and high anxiety (HA) groups, which were then given dioscorea (250, 750, or 1500 mg/kg/day) by oral gavage for 27 days and were tested in the EPM on day 23 of administration and in the forced swim test (FST) on days 24 and 25, then 3 days later, the brain was removed and IL-2 levels measured.</p> <p>Results</p> <p>Compared to sham-operated rats, anxiety behavior in the EPM was increased in half of the OVX rats. After chronic dioscorea treatment, a decrease in anxiety and IL-2 levels was observed in the HA OVX rats. Despair behavior in the FST was inhibited by the highest dosage of dioscorea.</p> <p>Conclusion</p> <p>These results show that OVX-induced anxiety and changes in neuroimmunological function in the cortex are reversed by dioscorea treatment. Furthermore, individual differences need to be taken into account when psychoneuroimmunological issues are measured and the EPM is a useful tool for determining anxiety levels when examining anxiety-related issues.</p

Atg7-Mediated Autophagy Is Involved in the Neural Crest Cell Generation in Chick Embryo

Autophagy plays a very important role in numerous physiological and pathological events. However, it still remains unclear whether Atg7-induced autophagy is involved in the regulation of neural crest cell production. In this study, we found the co-location of Atg7 and Pax7+ neural crest cells in early chick embryo development. Upregulation of Atg7 with unilateral transfection of full-length Atg7 increased Pax7+ and HNK-1+ cephalic and trunk neural crest cell numbers compared to either Control-GFP transfection or opposite neural tubes, suggesting that Atg7 over-expression in neural tubes could enhance the production of neural crest cells. BMP4 in situ hybridization and p-Smad1/5/8 immunofluorescent staining demonstrated that upregulation of Atg7 in neural tubes suppressed the BMP4/Smad signaling, which is considered to promote the delamination of neural crest cells. Interestingly, upregulation of Atg7 in neural tubes could significantly accelerate cell progression into the S phase, implying that Atg7 modulates cell cycle progression. However, β-catenin expression was not significantly altered. Finally, we demonstrated that upregulation of the Atg7 gene could activate autophagy as did Atg8. We have also observed that similar phenotypes, such as more HNK-1+ neural crest cells in the unilateral Atg8 transfection side of neural tubes, and the transfection with full-length Atg8-GFP certainly promote the numbers of BrdU+ neural crest cells in comparison to the GFP control. Taken together, we reveal that Atg7-induced autophagy is involved in regulating the production of neural crest cells in early chick embryos through the modification of the cell cycle