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Malaria is a mosquito-borne disease that, despite intensive control and mitigation initiatives, continues to pose an enormous public health burden. Plasmodium vivax is one of the principal causes of malaria in humans. Antibodies, which play a fundamental role in the host response to P. vivax, are acquired through exposure to the parasite. Here, we introduce a stochastic, within-host model of antibody responses to P. vivax for an individual in a general transmission setting. We begin by developing an epidemiological framework accounting for P. vivax infections resulting from new mosquito bites (primary infections), as well as the activation of dormant-liver stages known as hypnozoites (relapses). By constructing an infinite server queue, we obtain analytic results for the distribution of relapses in a general transmission setting. We then consider a simple model of antibody kinetics, whereby antibodies are boosted with each infection, but are subject to decay over time. By embedding this model for antibody kinetics in the epidemiological framework using a generalised shot noise process, we derive analytic expressions governing the distribution of antibody levels for a single individual in a general transmission setting. Our work provides a means to explore exposure-dependent antibody dynamics for P. vivax, with the potential to address key questions in the context of serological surveillance and acquired immunity.In experimental tasks that involve stimuli that vary along a quantitative continuum, some choice biases are commonly found. Take, for instance, a matching-to-sample task where animals must, following the presentation of sample stimuli (that differ in duration), choose between two or more comparison stimuli. In tests where no sample is presented there is usually a bias towards the comparison that is correct following the shortest sample. To examine some aspects of these choice biases, pigeons were trained in a symbolic matching-to-sample task with two durations of keylight as samples, where key pecking had to be maintained during sample presentation. Firstly, even though animals were required to attend to the sample, a preference for the "short" comparison in no-sample testing was found. This result disproves an account where this effect was hypothesized to happen due to non-programmed learning resulting from the animals failing to attend to some trials. Secondly, even though a bias for "short" was found in both no-sample and delay testing, the extent of the biases differed between tasks, thus suggesting that forgetting the sample presented during a delay does not necessarily land the animal in a state similar to presenting no sample at all to begin with.
Anaplastic lymphoma kinase (ALK) rearrangements represent a seldom event in non-small cell lung cancer (NSCLC). Given the oncogene alteration, ALK targeting represents the main therapeutic strategy. Here, we review evidence regarding ALK inhibitors (ALKi) clinical activity, safety profiles, financial costs, and biomarkers of efficacy.
During the past 10years, multiple ALKi have been developed, and four different compounds are currently available as upfront options for ALK+ NSCLC patients crizotinib, ceritinib, alectinib, and brigatinib. Second-generation (2G) ALKi demonstrated superior clinical activity in terms of median progression-free survival (mPFS), objective response rate (ORR), intracranial disease control, and duration of response (DOR) when compared with crizotinib. 2G ALKi represent the current gold-standard first-line treatment for ALK-rearranged metastatic NSCLC. Among all available options, in our opinion, alectinib has likely the best profile of clinical activity and safety, thus emerging as the best upfront therapy. More insights will come from ongoing trials and analysis of biomarkers.
During the past 10 years, multiple ALKi have been developed, and four different compounds are currently available as upfront options for ALK+ NSCLC patients crizotinib, ceritinib, alectinib, and brigatinib. Second-generation (2G) ALKi demonstrated superior clinical activity in terms of median progression-free survival (mPFS), objective response rate (ORR), intracranial disease control, and duration of response (DOR) when compared with crizotinib. 2G ALKi represent the current gold-standard first-line treatment for ALK-rearranged metastatic NSCLC. Among all available options, in our opinion, alectinib has likely the best profile of clinical activity and safety, thus emerging as the best upfront therapy. More insights will come from ongoing trials and analysis of biomarkers.Radiations emitted by low power radiation sources have been applied for therapeutic proposals due to their capacity of inactivating bacteria and cancer cells in photodynamic therapy and stimulating tissue cells in photobiomodulation. Exposure to these radiations could increase cell proliferation in bacterial cultures under stressful conditions. Cells in infected or not infected tissue injuries are also under stressful conditions and photobiomodulation-induced regenerative effect on tissue injuries could be related to effects on stressed cells. The understanding of the effects on cells under stressful conditions could render therapies based on photobiomodulation more efficient as well as expand them. Thus, the objective of this review was to update the studies reporting photobiomodulation on prokaryotic and eukaryotic cells under stress conditions. Exposure to radiations emitted by low power radiation sources could induce adaptive responses enabling cells to survive in stressful conditions, such as those experienced by bacteria in their host and by eukaryotic cells in injured tissues. Adaptive responses could be the basis for clinical photobiomodulation applications, either considering their contraindication for treatment of infected injuries or indication for treatment of injuries, inflammatory process resolution, or tissue regeneration.This study aimed to systematically review and analyze the present randomized clinical trials (RCTs) regarding the clinical efficacy of a diode laser (DL) adjuvant to scaling and root planning (SRP) in patients with chronic periodontitis (CP) who have diabetes mellitus (DM). Five databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trails, Web of Science, and Chinese BioMedical Literature Databases) were searched. A meta-analysis was implemented to evaluate periodontal parameters including probing depth (PD) and clinical attachment level (CAL) as primary outcomes. Hemoglobin A1c (HbA1c), plaque index (PI), and the gingival index (GI) were also observed as secondary outcomes. Independent scanning of 239 papers resulted in 9 RCTs. Puromycin purchase Moderate evidence demonstrated that the test groups showed significant benefits for PD reduction, CAL gain, and HbA1c reduction after 3 and 6 months. Significant differences in PI and GI reduction were not found except for GI reduction within 1 month. The collective evidence suggested that the DL with SRP had significant improvements in clinical results compared to SRP alone.
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