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The life cycle of many dinoflagellates includes at least one nonflagellated benthic stage (cyst). In the literature, the different types of dinoflagellate cysts are mainly defined based on morphological (number and type of layers in the cell wall) and functional (long- or short-term endurance) differences. These characteristics were initially thought to clearly distinguish pellicle (thin-walled) cysts from resting (double-walled) dinoflagellate cysts. The former were considered short-term (temporal) and the latter long-term (resting) cysts. However, during the last two decades further knowledge has highlighted the great intricacy of dinoflagellate life histories, the ecological significance of cyst stages, and the need to clarify the functional and morphological complexities of the different cyst types. Here we review and, when necessary, redefine the concepts of resting and pellicle cysts, examining both their structural and their functional characteristics in the context of the life cycle strategies of several dinoflagellate species.

Photoactivatable molecules enable ablation of malignant cells under the control of light, yet current agents can be ineffective at early stages of disease when target cells are similar to healthy surrounding tissues. In this work, we describe a chemical platform based on amino-substituted benzoselenadiazoles to build photoactivatable probes that mimic native metabolites as indicators of disease onset and progression. Through a series of synthetic derivatives, we have identified the key chemical groups in the benzoselenadiazole scaffold responsible for its photodynamic activity, and subsequently designed photosensitive metabolic warheads to target cells associated with various diseases, including bacterial infections and cancer. We demonstrate that versatile benzoselenadiazole metabolites can selectively kill pathogenic cells - but not healthy cells - with high precision after exposure to non-toxic visible light, reducing any potential side effects in vivo. This chemical platform provides powerful tools to exploit cellular metabolic signatures for safer therapeutic and surgical approaches. Metabolites can distinguish pathogenic from healthy cells, but they are hard to couple to current photosensitizers without altering their biological activity. Here the authors design a new family of photosensitizers that retain metabolite function to target pathogenic cells and ablate them by photodynamic therapy.

Dinoflagellates are haploid eukaryotic microalgae in which rapid proliferation causes dense blooms, with harmful health and economic effects to humans. The proliferation mode is mainly asexual, as the sexual cycle is believed to be rare and restricted to stressful environmental conditions. However, sexuality is key to explaining the recurrence of many dinoflagellate blooms because in many species the fate of the planktonic zygotes (planozygotes) is the formation of resistant cysts in the seabed (encystment). Nevertheless, recent research has shown that individually isolated planozygotes in the lab can enter other routes besides encystment, a behavior of which the relevance has not been explored at the population level. In this study, using imaging flow cytometry, cell sorting, and Fluorescence In Situ Hybridization (FISH), we followed DNA content and nuclear changes in a population of the toxic dinoflagellate Alexandrium minutum that was induced to encystment. Our results first show that planozygotes behave like a population with an \"encystment-independent\" division cycle, which is light-controlled and follows the same Light:Dark (L:D) pattern as the cycle governing the haploid mitosis. Resting cyst formation was the fate of just a small fraction of the planozygotes formed and was restricted to a period of strongly limited nutrient conditions. The diploid-haploid turnover between L:D cycles was consistent with two-step meiosis. However, the diel and morphological division pattern of the planozygote division also suggests mitosis, which would imply that this species is not haplontic, as previously considered, but biphasic, because individuals could undergo mitotic divisions in both the sexual (diploid) and the asexual (haploid) phases. We also report incomplete genome duplication processes. Our work calls for a reconsideration of the dogma of rare sex in dinoflagellates.

Objective. To develop a valid and reliable scale to measure entrepreneurship competences of nursing students, by assessing the level of development of diverse entrepreneurship dimensions. Methods. An Entrepreneurship Measurement Instrument, Catalonia (IME.Cat) was constructed, by adapting two existing instruments, and a psychometric study was performed to address the validity of the content and the construct, and the reliability. The internal consistency and the discrimination capacity of the instrument’s items were examined. Results. The IME.Cat scale showed a high reliability (α=0.89) for the complete set of items. The Cronbach’s α value of the individual dimensions were: Problem management=0.78; Creativity=0.76; Personal confidence =0.64; and Risk acceptance =0.46. The corrected homogeneity indices for each of the item in the instrument were high (>0.40). The Confirmatory Factorial Analysis validated the proposed structure of the items according to dimension. Conclusion. The IME.Cat scale showed solid psychometric values for assessing the entrepreneurship competences of nursing students within its dimensions, which are fundamental for the professional development of nursing.

Background. It is unknown if tenofovir disoproxil fumarate (TDF), which is often coformulated with the lipid-neutral emtricitabine (FTC), has a lipid-lowering effect. Methods. We performed a randomized, crossover, double-blind, placebo-controlled clinical trial on human immunodeficiency virus type 1 (HIV-1)–infected subjects with HIV-1 RNA < 50 copies/mL during ≥6 months on stable darunavir/ritonavir (800/100 mg once daily) or lopinavir/ritonavir (400/100 mg twice daily) monotherapy, fasting total cholesterol (TC) ≥200 mg/dL or low-density lipoprotein cholesterol (LDL-c) ≥130 mg/dL, and no lipid-lowering drugs. In arm 1, TDF/FTC was added for 12 weeks, followed by 12 weeks of placebo (washout) and 12 additional weeks of placebo (placebo period). Subjects in arm 2 added placebo for 12 weeks (placebo period) followed by TDF/FTC for 12 weeks and placebo for 12 additional weeks (washout). The primary endpoint was change in median fasting TC levels. Results. Of 46 subjects enrolled, 56% received darunavir/ritonavir and 44% lopinavir/ritonavir. Exposure to TDF/FTC reduced TC from 234 to 205 mg/dL (P < .001), LDL-c from 155 to 128 mg/dL (P < .001), and high-density lipoprotein cholesterol (HDL-c) from 50.3 to 44.5 mg/dL (P < .001). It also decreased the proportion of subjects with fasting TC ≥200 mg/dL from 86.7% to 56.8% (P = .001), and LDL-c ≥130 mg/dL from 87.8% to 43.9% (P < .001). After 12 weeks, TDF/FTC exposure was associated with lower TC and LDL-c levels than placebo (P = .001 and P = .002, respectively). The TC/HDL-c ratio and triglyceride levels did not change with TDF/FTC exposure. Conclusions. Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF. Clinical Trials Registration. NCT01458977.

BackgroundFirst-pass effect (FPE) has been established as a key metric for technical success and strongly correlates with better clinical outcomes. Most data supporting improved outcomes with the use of a balloon guide catheter (BGC) predate the advent of last-generation large-bore intracranial aspiration catheters. We aim to evaluate the impact of BGC in FPE and clinical outcomes in a large cohort of patients treated with contemporary technology.MethodsPatients were recruited from the prospectively ongoing ROSSETTI registry. This registry includes all consecutive patients with anterior circulation large-vessel occlusion (LVO) from 10 comprehensive stroke centers in Spain. Demographic, clinical, angiographic, and clinical outcome data were compared between BGC and non-BGC groups. FPE was defined as the achievement of mTICI2c–3 after a single device pass.Results426 patients were included out of which 271 (63.62%) used BCG. BGC-treated patients had higher FPE rate (45.8% vs 27.7%; P<0.001), higher final mTICI ≥2 c recanalization rate (76.8% vs 50.3%, respectively; P<0.001), shorter procedural time [median (IQR), 30 (19–58) vs 43 (33–71) min; P<0.001], higher NIHSS difference from admission to 24 hours [median (IQR), 8 (2–12) vs 3 (0–10); P=0.001], and lower mortality rate (17.6% vs 29.8%, P=0.026) compared with non-BGC patients. BGC use was an independent predictor of FPE (OR 2.197, 95% CI 1.436 to 3.361; P<0.001), and excellent clinical outcome at 3 months (OR 0.34, 95% CI 0.17 to 0.68; P=0.002).ConclusionsOur results support the benefit of BGC use on angiographic and clinical outcomes in anterior circulation LVO ischemic stroke remain significant even when considering recent improvements in intracranial aspiration technology.

Purpose The purpose of this paper is to explain how a buying organization’s desorptive capacity relative to its supply network enhances the organization’s supply chain competence. The research also analyzes the contingent role of the balanced and combined dimensions of ambidexterity in this relationship. Design/methodology/approach Empirical results are obtained through analysis of survey data from a sample of 270 European firms. Hierarchical regression analysis is used to test the hypotheses. Findings The results confirm, first, the positive and significant relationship between the buying organization’s desorptive capacity and supply chain competence; and, second, the key moderating role of organizational ambidexterity, especially in its combined dimension, in this relationship. Practical implications The study suggests that desorptive capacity is key to the organization’s contribution to supply chain competitiveness. The authors also provide practitioners with better understanding of the extent to which they should attempt to balance exploration and exploitation or/and to maximize both simultaneously when seeking greater benefit from desorptive capacity. Originality/value This study extends desorptive capacity research to supply chain management. It responds to calls in the desorptive capacity literature for deeper understanding of the benefits of desorptive capacity and of the role organizational ambidexterity plays in the success of desorptive capacity. By analyzing the independent effects of the combined and balanced dimensions of ambidexterity, the authors advance conceptual and operational understanding of the role of ambidexterity needed in the literature.

: Dinoflagellates belonging to the genus Gambierdiscus produce ciguatoxins (CTXs), which are metabolized in fish to more toxic forms and subsequently cause ciguatera fish poisoning (CFP) in humans. Five species of Gambierdiscus have been described from the Canary Islands, where CTXs in fish have been reported since 2004. Here we present new data on the distribution of Gambierdiscus species in the Canary archipelago and specifically from two islands, La Palma and La Gomera, where the genus had not been previously reported. Gambierdiscus spp. concentrations were low, with maxima of 88 and 29 cells·g −1 wet weight in samples from La Gomera and La Palma, respectively. Molecular analysis (LSUrRNA gene sequences) revealed differences in the species distribution between the two islands: only G. excentricus was detected at La Palma whereas four species, G. australes, G. caribaeus, G. carolinianus, and G. excentricus, were identified from La Gomera. Morphometric analyses of cultured cells of the five Canary Islands species and of field specimens from La Gomera included cell size and a characterization of three thecal arrangement traits: (1) the shape of the 20 plate, (2) the position of Po in the anterior suture of the 20 plate, and (3) the length–width relationship of the 2”” plate. Despite the wide morphological variability within the culture and field samples, the use of two or more variables allowed the discrimination of two species in the La Gomera samples: G. cf. excentricus and G. cf. silvae. A comparison of the molecular data with the morphologically based classification demonstrated important coincidences, such as the dominance of G. excentricus, but also differences in the species composition of Gambierdiscus, as G. caribaeus was detected in the study area only by using molecular methods

Esophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome. Post-translational methylation in histone can be partially modulated by histone lysine demethylases (KDMs), which specifically removes methyl groups in certain lysine residues. KDMs deregulation was associated with tumor aggressiveness and therapy failure. Thus, we sought to unveil the role of Jumonji C domain histone lysine demethylases (JmjC-KDMs) in ESCC radioresistance acquisition. The effectiveness of RT upon ESCC cells under hypoxic conditions was assessed by colony formation assay. KDM3A/KDM6B expression, and respective H3K9me2 and H3K27me3 target marks, were evaluated by RT-qPCR, Western blot, and immunofluorescence. Effect of JmjC-KDM inhibitor IOX1, as well as KDM3A knockdown, in in vitro functional cell behavior and RT response was assessed in ESCC under hypoxic conditions. In vivo effect of combined IOX1 and ionizing radiation treatment was evaluated in ESCC cells using CAM assay. KDM3A, KDM6B, HIF-1α, and CAIX immunoexpression was assessed in primary ESCC and normal esophagus. Herein, we found that hypoxia promoted ESCC radioresistance through increased KDM3A/KDM6B expression, enhancing cell survival and migration and decreasing DNA damage and apoptosis, in vitro. Exposure to IOX1 reverted these features, increasing ESCC radiosensitivity and decreasing ESCC microtumors size, in vivo. KDM3A was upregulated in ESCC tissues compared to the normal esophagus, associating and colocalizing with hypoxic markers (HIF-1α and CAIX). Therefore, KDM3A upregulation in ESCC cell lines and primary tumors associated with hypoxia, playing a critical role in EC aggressiveness and radioresistance. KDM3A targeting, concomitant with conventional RT, constitutes a promising strategy to improve ESCC patients’ survival.

BackgroundThe optimal endovascular treatment (EVT) technique for middle cerebral artery (MCA) M2 segment occlusions remains unknown. We aim to analyze whether reperfusion rate, procedure times, procedure-related complications, and clinical outcome differed between patients with isolated M2 occlusions who underwent stent-retriever (SR) alone versus combined SR and contact aspiration (CA) as a front-line EVT.MethodsPatients who underwent EVT for isolated MCA-M2 occlusion were recruited from the prospectively ongoing ROSSETTI registry. Patients were divided regarding the EVT approach into SR alone versus SR+CA and propensity score matching was used to achieve baseline balance. Demographic, procedural, safety, and clinical outcomes were compared between groups. Multivariable logistic regression analysis was performed to identify independent predictors of first-pass effect (FPE) and 90-day modified Rankin scale (mRS) 0–2.Results214 patients underwent EVT for M2 occlusion, 125 treated with SR alone and 89 with SR+CA. Propensity score matchnig analysis selected 134 matched patients. The rates of FPE (42% vs 40%, p=1.000) and 90-day mRS 0–2 (60% vs 51%, p=0.281) were comparable between groups. Patients treated with SR alone had lower need of rescue therapy (p=0.006), faster times to reperfusion (p<0.001), and lower procedure-related complications (p=0.031). Higher initial Alberta Stroke Program Early CT Score was an independent predictor of FPE. Age, baseline National Institutes of Health Stroke Scale score, and procedure duration were significant predictors of good clinical outcome at 3 months.ConclusionsAs front-line modality in M2 occlusions, the SR alone approach results in similar rates of reperfusion and good clinical outcomes to combined SR+CA and might be advantageous due to faster reperfusion times and fewer adverse events.