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70 Ma). The diversification of Lotus in Macaronesia involved between four and six independent colonization events from four sections currently distributed in Africa and Europe. A major aspect shaping the current distribution of taxa involved intra-island colonization of mainly new habitats and inter-island colonization of mostly similar habitats, with Gran Canaria and Tenerife as the major sources of diversification and of further colonization events. Section Pedrosia is the most diverse in terms of colonization events, number of species, and habitat heterogeneity, including a back-colonization event to the continent. Subsections within Pedrosia radiated into diverse habitat types recently (late Pleistocene, ca 0.23-0.29 Ma) and additional molecular markers and sampling would be necessary to understand the most recent dispersal events of this group within the Canary Islands and Cape Verde.Hybridization can leave genealogical signatures in an organism's genome, originating from the parental lineages and persisting over time. This potentially confounds phylogenetic inference methods that aim to represent evolution as a strictly bifurcating tree. We apply a phylotranscriptomic approach to study the evolutionary history of, and test for inter-lineage introgression in the Salamandridae, a Holarctic salamanders group of interest in studies of toxicity and aposematism, courtship behavior, and molecular evolution. Although the relationships between the 21 currently recognized salamandrid genera have been the subject of numerous molecular phylogenetic studies, some branches have remained controversial and sometimes affected by discordances between mitochondrial vs. nuclear trees. To resolve the phylogeny of this family, and understand the source of mito-nuclear discordance, we generated new transcriptomic (RNAseq) data for 20 salamandrids and used these along with published data, including 28 mitochondsize a scenario with hybridization and mitochondrial capture among ancestral lineages of (1) Lissotriton into Ichthyosaura and (2) Triturus into Calotriton, plus introgression of nuclear genes from Triturus into Lissotriton. Furthermore, both mitochondrial capture and nuclear introgression may have occurred among lineages assigned to Cynops. More comprehensive genomic data will, in the future, allow testing this against alternative scenarios involving hybridization with other, extinct lineages of newts.

Minimally invasive surgery (MIS) decreases postoperative morbidity after radical hysterectomy (RH) for early-stage cervical cancer. However, a randomized trial and large retrospective data question its safety after observing lower rates of survival than open surgery [1,2]. The causes of this higher recurrence rate are not definitely established but may result from cancer exposure to peritoneum during vaginal section and cancerous-cells spillage enhanced by pneumoperitoneum or uterine manipulator. The aim of this surgical film (video1) was to present a standardized step-by-step approach for robotic RH according to the recent recommendations from the ARCAGY-GINECO surgeon's group [3].

A step-by-step video demonstration of the technique.

A tertiary center specialized in gynecologic oncology and minimally invasive surgery.

A 48 year-old woman was diagnosed with a 1B2 stage endocervical adenocarcinoma (FIGO-2018) with a tumor-size of 27 mm. Surgery was planned after preoperative pulsed-dose-rate utero-vagisize ranging 2-4 cm or presenting lympho-vascular invasion [5].The introduction of immune checkpoint inhibitors (ICI) has ushered in a new, golden age for cancer immunotherapy. However, their clinical success remains limited in several solid cancer types because of the low intrinsic immunogenicity of tumors and the development of immune escape mechanisms. Cancer stem cells (CSC), a small population of cancer cells that are responsible for tumor onset, metastatic spread and relapse after treatment, play a pivotal role in resistance to ICIs. The development of novel therapies that can target CSCs would thus improve the outcomes of current immunotherapy regimens. In this light, vaccines that target CSCs are a promising strategy. This paper briefly describes the immunologic properties of CSCs and their antigenic profile, and reviews current preclinical and clinical approaches that combine CSC-targeting vaccines with different synergistic therapies for the development of more effective antineoplastic treatments.Metabolism plays a significant role in the regulation of aging at different levels, and metabolic reprogramming represents a major driving force in aging. Metabolic reprogramming leads to impaired organismal fitness, an age-dependent increase in susceptibility to diseases, decreased ability to mount a stress response, and increased frailty. The complexity of age-dependent metabolic reprogramming comes from the multitude of levels on which metabolic changes can be connected to aging and regulation of lifespan. This is further complicated by the different metabolic requirements of various tissues, cross-organ communication via metabolite secretion, and direct effects of metabolites on epigenetic state and redox regulation; however, not all of these changes are causative to aging. Studies in yeast, flies, worms, and mice have played a crucial role in identifying mechanistic links between observed changes in various metabolic traits and their effects on lifespan. Here, we review how changes in the organismal and organ-specific metabolome are associated with aging and how targeting of any one of over a hundred different targets in specific metabolic pathways can extend lifespan. An important corollary is that restriction or supplementation of different metabolites can change activity of these metabolic pathways in ways that improve healthspan and extend lifespan in different organisms. Due to the high levels of conservation of metabolism in general, translating findings from model systems to human beings will allow for the development of effective strategies for human health- and lifespan extension.A series of substituted imidazoline derivatives were synthesized and characterized. Compounds were tested in-vivo for their antihypertensive, analgesic, antiaggressive, depressant, antidepressant, and ALD50 activities. The compounds 3a, 3c, 4c, 5a, and 6c showed cardiovascular as well as central nervous system activities and are potential candidate as drug among all fifteen compounds tested. All these compounds have shown better activity for antihypertensive, analgesic, antiaggressive, and depressant-antidepressant, properties than reference compounds clonidine, morphine, diazepam, and imipramine respectively. Most of the compounds have shown ALD50 > 500 mg/kg with maximum in 4a and 5a (>1000 mg/kg).Various (North)-methanocarba adenosine derivatives, containing rigid bicyclo[3.1.0]hexane ribose substitution, were screened for activity against representative viruses, and inhibition was observed after treatment of Enterovirus A71 with a 2-chloro-N6-1-cyclopropyl-2-methylpropan-1-yl derivative (17). µM activity was also seen when testing 17 against other enteroviruses in the Picornaviridae family. Based on this hit, structural congeners of 17, containing other N6-alkyl groups and 5' modifications, were synthesized and tested. Oxalacetic acid chemical structure The structure activity relationship is relatively narrow, with most modifications of the adenine or the methanocarba ring reducing or abolishing the inhibitory potency. 4'-Truncated 31 (MRS5474), 4'-fluoromethyl 48 (MRS7704) and 4'-chloromethyl 49 nucleosides displayed EC50 ~3-4 µM, and 31 and 48 achieved SI ≥10. However, methanocarba analogues of ribavirin and N6-benzyladenosine, shown previously to have anti-EV-A71 activity, were inactive. Thus, we identified methanocarba nucleosides as a new scaffold for enterovirus inhibition with a narrow structure activity relationship and no similarity to previously published anti-enteroviral nucleosides.

Oblique lateral interbody fusion (OLIF)-has become a widely used, efficient surgical tool for various degenerative lumbar conditions. Postoperative ileus (POI) is a relatively common complication after anterior lumbar interbody fusion due to the manipulation of the intestine during the surgical approach. However, to our knowledge, little is known about POI following OLIF even though it also involves bowel manipulation during a surgical procedure.

To assess the incidence of POI and identify independent risk factors for POI development after OLIF.

Retrospective cohort study.

All consecutive patients who underwent OLIF and percutaneous pedicle screw instrumentation from August 2012 until October 2019 at a single institution OUTCOME MEASURES Patient demographics (sex, age, body weight, height, and body mass index), comorbidities (diabetes mellitus, gastroesophageal reflux disease, antithrombotic medication, previous abdominal surgery, and previous lumbar surgery), and perioperative details (preoperative derienced POI after OLIF and percutaneous pedicle screw instrumentation. Patients with POI had a significantly longer postoperative length of hospital stay than those without POI (8.61 ± 2.66 vs 6.48 ± 2.64, p=.001). Multivariate logistic regression analysis identified inadvertent endplate fracture (adjusted odds ratio=6.017, p=.001) and the amount of intraoperative remifentanil (adjusted odds ratio=1.057, p=.024) as independent risk factors for the occurrence of POI following OLIF.

This study identified inadvertent endplate fracture and the amount of intraoperative remifentanil as independent risk factors for the development of POI after OLIF.

This study identified inadvertent endplate fracture and the amount of intraoperative remifentanil as independent risk factors for the development of POI after OLIF.Acute organophosphate (OP) poisoning, particularly by suicide attempts, generates high mortality and morbidity. Few studies have systematically addressed the consequences of acute OP intoxication on cognition and memory of survivors. Preclinical evidence suggests that acute OP-induced effects are associated with inhibiting the brain acetylcholinesterase (AChE) enzyme. The OP triazophos has been used worldwide, although its effects on mnemonic processing are yet to be investigated. Based on the above, the present study investigated whether acute triazophos intoxication interferes with the expression and extinction of contextual fear memory in rats. Hippocampal and amygdalar AChE activity and plasma butyrylcholinesterase (BChE) were measured at the end of the experiment to confirm the cholinergic overstimulation. Independent cohorts of animals intoxicated with triazophos were evaluated in the novel object recognition (NOR) test, a less aversive associative memory task. At the dose of 15 mg/kg, triazophos administered immediately after contextual fear conditioning impaired the extinction but not the expression of freezing behavior. Triazophos poisoning induced no changes in the discrimination index in the NOR test. Triazophos inhibited the AChE activity in a time- and brain region-dependent manner. Our findings suggest that fear memory extinction deficits induced by acute triazophos intoxication are accompanied by hippocampal AChE inhibition. The deficient fear extinction associated with acute OP poisoning may represent a behavioral and biochemical phenotype helpful to study mechanisms of neurotoxicity and treatment approach of OP suicide survivors.