Perspectives of primary care physicians in Spain on malaria: a cross-sectional survey and retrospective review of cases.

BACKGROUND: In Spain, the risk of imported malaria has increased in recent years due to the rise in international travel and migration. Little is known about the knowledge, information sources, clinical practice, and specific needs of primary care physicians (PCPs) concerning malaria despite the pivotal role played by these professionals in managing the health of tourists. The objective of this study was to assess the knowledge, attitudes, and practices of PCPs in Spain regarding malaria. METHODS: This research analyses data from (1) a cross-sectional nationwide survey assessing the knowledge and attitudes of PCPs regarding malaria, and (2) a retrospective review of 373 malaria cases appearing in primary care medical records (PCMRs) in the Madrid area over the past 15 years to determine how cases were documented, managed, or characterized in the primary care setting. RESULTS: The survey findings reveal a modest level of self-perceived familiarity with malaria (221/360, 57.6%), even though 32.8% of the practitioners reported having delivered care for confirmed or suspected cases of the disease, these practitioners had greater knowledge of malaria (80.4%) compared to physicians who reported not having delivered care for malaria (19.6%, p < 0.001). Ten percent of the survey participants did not know the name of the mosquito that transmits malaria, and only 40.7% would promptly request malaria testing for a traveller with symptoms after a trip to an endemic area. Responses provided by younger PCPs varied to a greater extent than those of their more experienced colleagues regarding prevention practices and patient management. A review of PCMRs showed that only 65% of all patients were recorded as such. Among those registered, only 40.3% had a documented malaria episode, and of those, only 16.6% received proper follow-up. Only 23.7% of the patients with a PCMR had a record that specifically indicated travel to an endemic country or travel classified as visiting friends and relatives (VFR). CONCLUSIONS: The findings of this study underscore the critical role of PCPs in the field of travel medicine, particularly given the increase in imported malaria cases. These results highlight the need for targeted training in travel medicine and the need to ensure optimal patient education in care settings.

On the relevance of query definition in the performance of 3D ligand-based virtual screening.

Ligand-based virtual screening (LBVS) methods are widely used to explore the vast chemical space in the search of novel compounds resorting to a variety of properties encoded in 1D, 2D or 3D descriptors. The success of 3D-LBVS is affected by the overlay of molecular pairs, thus making selection of the template compound, search of accessible conformational space and choice of the query conformation to be potential factors that modulate the successful retrieval of actives. This study examines the impact of adopting different choices for the query conformation of the template, paying also attention to the influence exerted by the structural similarity between templates and actives. The analysis is performed using PharmScreen, a 3D LBVS tool that relies on similarity measurements of the hydrophobic/philic pattern of molecules, and Phase Shape, which is based on the alignment of atom triplets followed by refinement of the volume overlap. The study is performed for the original DUD-E+ database and a Morgan Fingerprint filtered version (denoted DUD-E+-Diverse; available in https://github.com/Pharmacelera/Query-models-to-3DLBVS ), which was prepared to minimize the 2D resemblance between template and actives. Although in most cases the query conformation exhibits a mild influence on the overall performance, a critical analysis is made to disclose factors, such as the content of structural features between template and actives and the induction of conformational strain in the template, that underlie the drastic impact of the query definition in the recovery of actives for certain targets. The findings of this research also provide valuable guidance for assisting the selection of the query definition in 3D LBVS campaigns.

Real-Time Object Detection for Autonomous Solar Farm Inspection via UAVs.

Robotic missions for solar farm inspection demand agile and precise object detection strategies. This paper introduces an innovative keypoint-based object detection framework specifically designed for real-time solar farm inspections with UAVs. Moving away from conventional bounding box or segmentation methods, our technique focuses on detecting the vertices of solar panels, which provides a richer granularity than traditional approaches. Drawing inspiration from CenterNet, our architecture is optimized for embedded platforms like the NVIDIA AGX Jetson Orin, achieving close to 60 FPS at a resolution of 1024 ×1376 pixels, thus outperforming the camera's operational frequency. Such a real-time capability is essential for efficient robotic operations in time-critical industrial asset inspection environments. The design of our model emphasizes reduced computational demand, positioning it as a practical solution for real-world deployment. Additionally, the integration of active learning strategies promises a considerable reduction in annotation efforts and strengthens the model's operational feasibility. In summary, our research emphasizes the advantages of keypoint-based object detection, offering a practical and effective approach for real-time solar farm inspections with UAVs.

Screening and Biological Evaluation of Soluble Epoxide Hydrolase Inhibitors: Assessing the Role of Hydrophobicity in the Pharmacophore-Guided Search of Novel Hits.

The human soluble epoxide hydrolase (sEH) is a bifunctional enzyme that modulates the levels of regulatory epoxy lipids. The hydrolase activity is carried out by a catalytic triad located at the center of a wide L-shaped binding site, which contains two hydrophobic subpockets at both sides. On the basis of these structural features, it can be assumed that desolvation is a major factor in determining the maximal achievable affinity that can be attained for this pocket. Accordingly, hydrophobic descriptors may be better suited to the search of novel hits targeting this enzyme. This study examines the suitability of quantum mechanically derived hydrophobic descriptors in the discovery of novel sEH inhibitors. To this end, three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophores were generated by combining electrostatic and steric or alternatively hydrophobic and hydrogen-bond parameters in conjunction with a tailored list of 76 known sEH inhibitors. The pharmacophore models were then validated by using two external sets chosen (i) to rank the potency of four distinct series of compounds and (ii) to discriminate actives from decoys, using in both cases datasets taken from the literature. Finally, a prospective study was performed including a virtual screening of two chemical libraries to identify new potential hits, which were subsequently experimentally tested for their inhibitory activity on human, rat, and mouse sEH. The use of hydrophobic-based descriptors led to the identification of six compounds as inhibitors of the human enzyme with IC50 < 20 nM, including two with IC50 values of 0.4 and 0.7 nM. The results support the use of hydrophobic descriptors as a valuable tool in the search of novel scaffolds that encode a proper hydrophilic/hydrophobic distribution complementary to the target's binding site.

Development and application of an in-house library and workflow for gas chromatography-electron ionization-accurate-mass/high-resolution mass spectrometry screening of environmental samples.

This work presents an optimized gas chromatography-electron ionization-high-resolution mass spectrometry (GC-EI-HRMS) screening method. Different method parameters affecting data processing with the Agilent Unknowns Analysis SureMass deconvolution software were optimized in order to achieve the best compromise between false positives and false negatives. To this end, an accurate-mass library of 26 model compounds was created. Then, five replicates of mussel extracts were spiked with a mixture of these 26 compounds at two concentration levels (10 and 100 ng/g dry weight in mussel, 50 and 500 ng/mL in extract) and injected in the GC-EI-HRMS system. The results of these experiments showed that accurate mass tolerance and pure weight factor (combination of reverse-forward library search) are the most critical factors. The validation of the developed method afforded screening detection limits in the 2.5-5 ng range for passive sampler extracts and 1-2 ng/g for mussel sample extracts, and limits of quantification in the 0.6-3.2 ng and 0.1-1.8 ng/g range, for the same type of samples, respectively, for 17 model analytes. Once the method was optimized, an accurate-mass HRMS library, containing retention indexes, with ca. 355 spectra of derivatized and non-derivatized compounds was generated. This library (freely available at https://doi.org/10.5281/zenodo.5647960 ), together with a modified Agilent Pesticides Library of over 800 compounds, was applied to the screening of passive samplers, both of polydimethylsiloxane and polar chemical integrative samplers (POCIS), and mussel samples collected in Galicia (NW Spain), where a total of 75 chemicals could be identified.

On the Use of Ridge Gap Waveguide Technology for the Design of Transverse Stub Resonant Antenna Arrays.

This paper presents some considerations on the design of a novel antenna consisting of the combination of a transverse stubs (TS) array excited by Ridge Gap Waveguides (RGWs), as well as a discussion of the experimental results obtained from a prototype that was manufactured and measured. A combination of Continuous Transverse Stubs (CTSs) is used as the starting point. Subsequently, the CTSs are modified to include some metallic blockers that split each CTS into a combination (array) of shorter TSs. This is performed in order to excite each individual TS column using a different RGW; thus, ensuring a close to uniform field distribution in the transverse plane of the TS arrays. Hence, the directivity of the antenna is increased. As a series-feed configuration is considered, the antenna keeps a resonant behaviour, having a narrow-band response. A Corporate Feeding Network (CFN) using the aforementioned RGW technology placed in the same layer as the rest of the antenna is included in the design. The radiating area of the antenna is, finally, 5.88λ0×7.12λ0 with a simulated peak gain of 26.2 dBi and a Side Lobe Level (SLL) below -13 dB. A prototype is manufactured and tested. The simulated and measured radiation patterns maintain similar shapes to those of the simulations, with very similar angular widths in both main planes, although the frequency corresponding to the highest directivity changes to 31.8 GHz. A matching bandwidth of 517 MHz and a gain of 24.5 is, finally, achieved at that frequency.

Assessing the Performance of Mixed Strategies To Combine Lipophilic Molecular Similarity and Docking in Virtual Screening.

The accuracy of structure-based (SB) virtual screening (VS) is heavily affected by the scoring function used to rank a library of screened compounds. Even in cases where the docked pose agrees with the experimental binding mode of the ligand, the limitations of current scoring functions may lead to sensible inaccuracies in the ability to discriminate between actives and inactives. In this context, the combination of SB and ligand-based (LB) molecular similarity may be a promising strategy to increase the hit rates in VS. This study explores different strategies that aim to exploit the synergy between LB and SB methods in order to mitigate the limitations of these techniques, and to enhance the performance of VS studies by means of a balanced combination between docking scores and three-dimensional (3D) similarity. Particularly, attention is focused to the use of measurements of molecular similarity with PharmScreen, which exploits the 3D distribution of atomic lipophilicity determined from quantum mechanical-based continuum solvation calculations performed with the MST model, in conjunction with three docking programs: Glide, rDock, and GOLD. Different strategies have been explored to combine the information provided by docking and similarity measurements for re-ranking the screened ligands. For a benchmarking of 44 datasets, including 41 targets, the hybrid methods increase the identification of active compounds, according to the early (ROCe%) and total (AUC) enrichment metrics of VS, compared to pure LB and SB methods. Finally, the hybrid approaches are also more effective in enhancing the chemical diversity of active compounds. The datasets employed in this work are available in https://github.com/Pharmacelera/Molecular-Similarity-and-Docking.

Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches.

Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued efforts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature.

Development and Validation of Molecular Overlays Derived from Three-Dimensional Hydrophobic Similarity with PharmScreen.

Molecular alignment is a standard procedure for three-dimensional (3D) similarity measurements and pharmacophore elucidation. This process is influenced by several factors, such as the physicochemical descriptors utilized to account for the molecular determinants of biological activity and the reference templates. Relying on the hypothesis that the maximal achievable binding affinity for a drug-like molecule is largely due to desolvation, we explore a novel strategy for 3D molecular overlays that exploits the partitioning of molecular hydrophobicity into atomic contributions in conjunction with information about the distribution of hydrogen-bond (HB) donor/acceptor groups. A brief description of the method, as implemented in the software package PharmScreen, including the derivation of the fractional hydrophobic contributions within the quantum mechanical version of the Miertus-Scrocco-Tomasi (MST) continuum model, and the procedure utilized for the optimal superposition between molecules, is presented. The computational procedure is calibrated by using a data set of 402 molecules pertaining to 14 distinct targets taken from the literature and validated against the AstraZeneca test, which comprises 121 experimentally derived sets of molecular overlays. The results point out the suitability of the MST-based hydrophobic parameters for generating molecular overlays, as correct predictions were obtained for 94%, 79%, and 54% of the molecules classified into easy, moderate, and hard sets, respectively. Moreover, the results point out that this accuracy is attained at a much lower degree of identity between the templates used by hydrophobic/HB fields and electrostatic/steric ones. These findings support the usefulness of the hydrophobic/HB descriptors to generate complementary overlays that may be valuable to rationalize structure-activity relationships and for virtual screening campaigns.

Violence in paradise: Cranial trauma in the prehispanic population of Gran Canaria (Canary Islands).

OBJECTIVES: This paper addresses the prevalence and pattern of physical violence in the prehispanic society of Gran Canaria and discusses its link with the social structure and insular context in which that people lived. MATERIALS AND METHODS: 347 prehispanic crania from Guayadeque Ravine (575-1415 AD) have been examined in order to determine the frequency, types, location, and timing of trauma. RESULTS: Craniofacial injuries are present in 27.4% of the crania examined. Only 2% display perimortem trauma. Most of the injuries (84.3%) correspond to depressed blunt force trauma, with an ellipsoidal or circular shape. Most of these are in the anterior aspect of the cranium. Males are significantly more affected than females. DISCUSSION: The aboriginal population of Gran Canaria show a high frequency of traumatic injuries to the skull compared to other archaeological groups. Their frequent location in the anterior aspect suggests regular face-to-face confrontations. However, the lethal injuries typically occurring in large-scale combat are scarce. Practices such as ritualized combat, mentioned in ethnohistorical sources, would help to channel and mitigate inter-group conflict. The predominance of depressed blunt force trauma is in accordance with the weapons used by those populations: hand-thrown stones, clubs and sticks. The higher frequency in males indicates that they took part in direct violence more than females did. The hierarchical organization of their society may have led to frequent situations of conflict. The insular nature of a territory barely 1,500 m2 in size was a determining factor in competition for access to food resources, especially at times of climate crises or population growth.

Kinship analysis and allelic dropout: a forensic approach on an archaeological case.

BACKGROUND: This study relies on the discovery of two pit burials (LTA and LTB) of the Bronze Age Cogotas I archaeological culture (circa 3600-2950 BP) in Spain. LTA was a single burial and LTB contained three skeletal remains of two adults and a newborn or foetus at term. AIM: The central question posed by this find was whether the LTB tomb constituted a traditional nuclear family (father, mother and son or daughter). METHODS: Ancient and forensic DNA protocols were employed to obtain reliable results. Autosomal, X-STR markers and mitochondrial DNA were amplified. Subsequently, different kinship probabilities were estimated by means of LR values calculated using the Familias 3 software. Furthermore, an allelic dropout sensitivity test was developed in order to evaluate the influence of allelic dropout phenomena on the results. RESULTS: It was possible to determine the molecular sex of all individuals and to establish a maternal relationship between the perinatal individual and one of the adults. CONCLUSION: The remains in the LTB tomb were not a traditional nuclear family (father, mother and son/daughter) and it was probably a tomb where two women, one of them pregnant, were buried.

Design, synthesis and biological evaluation of N-methyl-N-[(1,2,3-triazol-4-yl)alkyl]propargylamines as novel monoamine oxidase B inhibitors.

Different azides and alkynes have been coupled via Cu-catalyzed 1,3-dipolar Huisgen cycloaddition to afford a novel family of N1- and C5-substituted 1,2,3-triazole derivatives that feature the propargylamine group typical of irreversible MAO-B inhibitors at the C4-side chain of the triazole ring. All the synthesized compounds were evaluated against human MAO-A and MAO-B. Structure-activity relationships and molecular modeling were utilized to gain insight into the structural and chemical features that enhance the binding affinity and selectivity between the two enzyme isoforms. Several lead compounds, in terms of potency (submicromolar to low micromolar range), MAO-B selective recognition, and brain permeability, were identified. One of these leads (MAO-B IC50 of 3.54µM, selectivity MAO-A/MAO-B index of 27.7) was further subjected to reversibility and time-dependence inhibition studies, which disclosed a slow and irreversible inhibition of human MAO-B. Overall, the results support the suitability of the 4-triazolylalkyl propargylamine scaffold for exploring the design of multipotent anti-Alzheimer compounds endowed with irreversible MAO-B inhibitory activity.

New challenges in kidney cancer management: integration of surgery and novel therapies.

Despite early renal carcinoma diagnosis is more frequent nowadays, ~25-30 % of patients have metastatic disease at presentation and another ~30 % develop recurrent or metastatic disease after radical treatment for localized disease. In recent years, treatment of renal carcinoma is increasing in complexity due to the inclusion of a number of effective systemic treatments prolonging survival and increasing the therapeutic strategies for tumor debulking, or even achieving surgical complete responses and prolonged disease-free intervals. Initial multimodal approaches with immunotherapeutic agents are now being validated in patients treated with the new-targeted agents. Patients are now able to receive an optimal therapeutic strategy seeking a longer survival with an acceptable life quality and avoiding unnecessary comorbidities. In this context and as an initial therapeutic approach, it is imperative to promote patients' selection with established prognostic models within a multidisciplinary team to assess the recommendation of a cytoreductive nephrectomy (CN), metastasectomy, and/or systemic treatment. In the context of mRCC, when feasible and in patients with favorable prognostic factors, the strategy should be to consider a CN or metastasectomy for tumor debulking in order to achieve free intervals of prolonged disease. By contrast, it is recommended to evaluate whether to perform a biopsy for histological diagnosis without nephrectomy in the following situations: high surgical risk, bulky metastatic disease or in specific sites (brain or liver) or ECOG PS 3/4. The following review covers from initial to recent studies on the integration of systemic treatment and surgery in the context of metastatic disease for an optimal multimodal management in renal carcinoma.

Quantum mechanical-based strategies in drug discovery: Finding the pace to new challenges in drug design.

The expansion of the chemical space to tangible libraries containing billions of synthesizable molecules opens exciting opportunities for drug discovery, but also challenges the power of computer-aided drug design to prioritize the best candidates. This directly hits quantum mechanics (QM) methods, which provide chemically accurate properties, but subject to small-sized systems. Preserving accuracy while optimizing the computational cost is at the heart of many efforts to develop high-quality, efficient QM-based strategies, reflected in refined algorithms and computational approaches. The design of QM-tailored physics-based force fields and the coupling of QM with machine learning, in conjunction with the computing performance of supercomputing resources, will enhance the ability to use these methods in drug discovery. The challenge is formidable, but we will undoubtedly see impressive advances that will define a new era.

Screening of organic chemicals associated to virgin low-density polyethylene microplastic pellets exposed to the Mediterranean Sea environment by combining gas chromatography and liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry.

In this work, organic chemicals associated with microplastics (MPs) exposed to a coastal anthropogenized environment for up to eight weeks have been screened for, in order to discern the (de)sorption dynamics of chemicals in the marine ecosystem. Low-density polyethylene (LDPE) pellets were studied since they represent primary MPs used by the plastic industry and a relevant input of MPs into the oceans. To maximize the coverage of chemicals that could be detected, both liquid and gas chromatography coupled to quadrupole-time-of-flight (GC-QTOF and LC-QTOF, respectively) were used. In the case of LC-QTOF, an electrospray ionization source was employed, and the compounds were investigated by combining suspect and non-target screening workflows. The GC-QTOF was equipped with an electron ionization source and compounds were screened in raw and derivatized (silylated) extracts by deconvolution and contrast to high- and low-resolution libraries. A total of 50 compounds of multifarious classes were tentatively identified. Among them, melamine and 2-ethylhexyl salicylate (EHS) were detected in the original MPs but were rapidly desorbed. Melamine was completely released into the marine environment, while EHS was partly released but a portion remained bound to the MPs. On the other hand, many other chemicals of both anthropogenic (e.g. phenanthrene or benzophenone) and natural origin (e.g. betaine and several fatty acids) accumulated onto MPs over time. Quantification of 12 unequivocally identified chemicals resulted into a total concentration of 810 µg/kg after MPs exposure for 8 weeks.

EUS-guided coil versus cyanoacrylate therapy for the treatment of gastric varices: a multicenter study (with videos).

BACKGROUND: Therapy of gastric varices (GV) is still challenging. Cyanoacrylate (CYA) injection is the recommended treatment for bleeding GV, but has a known adverse event rate, which could be reduced if EUS is used for guidance. Otherwise, EUS-guided coil application (ECA) may be an alternative. OBJECTIVES: To compare CYA and ECA embolization of feeding GV for feasibility, safety, and applicability. DESIGN: Retrospective analysis of a prospectively maintained database. SETTING: Multicenter study, tertiary referral centers. PATIENTS AND INTERVENTIONS: Thirty consecutive patients with localized GV who received either CYA injection or ECA were included with follow-up for 6 months after treatment. RESULTS: There were 11 patients in the coil group and 19 patients in the CYA group. The GV obliteration rate was 94.7% CYA versus 90.9% ECA; mean number of endoscopy sessions was 1.4 ± 0.1 (range 1-3). Adverse events occurred in 12 of 30 patients (40%) (CYA, 11/19 [57.9%]; ECA, 1/11 [9.1%]; P < .01); only 3 were symptomatic, and an additional 9 (CYA group) had glue embolism on a CT scan but was asymptomatic. No further adverse events occurred during follow-up. Six patients (20%) died unrelated to the procedures or bleeding. LIMITATIONS: Nonrandomized; EUS expertise necessary. CONCLUSIONS: EUS-guided therapy for GV by using CYA or ECA is effective in localized GV. ECA required fewer endoscopies and tended to have fewer adverse events compared with CYA injection. Larger comparative studies are needed to prove these data.

Intravenous Ascorbic Acid for the Prevention of Postreperfusion Syndrome in Orthotopic Liver Transplantation: Protocol for a Randomized Controlled Trial.

BACKGROUND: Liver transplantation is the last therapeutic option for patients with end-stage liver disease. Postreperfusion syndrome (PRS), defined as a fall in mean arterial pressure of more than 30% within the first 5 minutes after reperfusion of at least 1 minute, can occur in liver transplantation as a deep hemodynamic instability with associated hyperfibrinolysis immediately after reperfusion of the new graft. Its incidence has remained unchanged since it was first described in 1987. PRS is related to ischemia-reperfusion (I/R) injury, whose pathophysiology involves the release of several mediators from both the donor and the recipient. The antioxidant effect of ascorbic acid has been studied in resuscitating patients with septic shock and burns. Even today, there are publications with conflicting results, and there is a need for further studies to confirm or rule out the usefulness of this drug in this group of patients. The addition of ascorbic acid to preservation solutions used in solid organ transplantation is under investigation to harness its antioxidant effect and mitigate I/R injury. Since PRS could be considered a manifestation of I/R injury, we believe that the possible beneficial effect of ascorbic acid on the occurrence of PRS should be investigated. OBJECTIVE: The aim of this randomized controlled trial is to assess the benefits of ascorbic acid over saline in the development of PRS in adult liver transplantation. METHODS: We plan to conduct a single-center randomized controlled trial at the Hospital Universitario Ramón y Cajal in Spain. A total of 70 participants aged 18 years or older undergoing liver transplantation will be randomized to receive either ascorbic acid or saline. The primary outcome will be the difference between groups in the incidence of PRS. The randomized controlled trial will be conducted under conditions of respect for fundamental human rights and ethical principles governing biomedical research involving human participants and in accordance with the international recommendations contained in the Declaration of Helsinki and its subsequent revisions. RESULTS: The enrollment process began in 2020. A total of 35 patients have been recruited so far. Data cleaning and analysis are expected to occur in the first months of 2024. Results are expected around the middle of 2024. CONCLUSIONS: We believe that this study could be particularly relevant because it will be the first to analyze the clinical effect of ascorbic acid in liver transplantation. Moreover, we believe that this study fills an important gap in the knowledge of the potential benefits of ascorbic acid in the field of liver transplantation, particularly in relation to PRS. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database 2020-000123-39; https://tinyurl.com/2cfzddw8; ClinicalTrials.gov NCT05754242; https://tinyurl.com/346vw7sm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50091.

The genomic history of the indigenous people of the Canary Islands.

The indigenous population of the Canary Islands, which colonized the archipelago around the 3rd century CE, provides both a window into the past of North Africa and a unique model to explore the effects of insularity. We generate genome-wide data from 40 individuals from the seven islands, dated between the 3rd-16rd centuries CE. Along with components already present in Moroccan Neolithic populations, the Canarian natives show signatures related to Bronze Age expansions in Eurasia and trans-Saharan migrations. The lack of gene flow between islands and constant or decreasing effective population sizes suggest that populations were isolated. While some island populations maintained relatively high genetic diversity, with the only detected bottleneck coinciding with the colonization time, other islands with fewer natural resources show the effects of insularity and isolation. Finally, consistent genetic differentiation between eastern and western islands points to a more complex colonization process than previously thought.

Effects of Caffeine Consumption on Attention Deficit Hyperactivity Disorder (ADHD) Treatment: A Systematic Review of Animal Studies.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. ADHD impairments arise from irregularities primarily in dopamine (DA) and norepinephrine (NE) circuits within the prefrontal cortex. Due to ADHD medication's controversial side effects and high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caffeine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evidence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal studies is lacking. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to 1 September 2021. Caffeine treatment increases attention and improves learning, memory, and olfactory discrimination without altering blood pressure and body weight. These results are supported at the neuronal/molecular level. Nonetheless, the role of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that the cognitive effects of caffeine found in animal models could be translated to human ADHD, particularly during adolescence.

Assisted versus referred pharmacy smoking interventions for patients with thoracic malignancies or pulmonary nodules.

BACKGROUND: Tobacco use is the foremost preventable cause of death, disease, and disability in the United States. Continued tobacco use in malignant disease contributes to treatment failure and disease progression. Pharmacists are pivotal to tobacco cessation counseling, management, and follow up. METHODS: This retrospective, observational, single-center, cohort study of ambulatory cancer patients was designed to assess the impact of assisted versus "Ask, Advise, Refer" (AAR) pharmacy-driven smoking cessation interventions on patient-reported quit rates at 30- and 90-days. Those included were currently smoking or recently quit adults with a thoracic malignancy or nodule. Those in the assisted intervention were offered nicotine replacement therapy (NRT) for free according to a personalized quit plan. After July 1, 2020, patients were enrolled in the AAR intervention, whereby participants were referred to obtain NRT through insurance or external resources. Both clinical interventions were provided as standard of care. RESULTS: 129 participants were included (assisted n = 83; AAR n = 46) with baseline characteristics evenly matched. After excluding those unable to be reached at 30-days, 30 (44.8%) in the assisted intervention quit smoking versus 11 (27.5%) in the AAR intervention, p = 0.08. Lung cancer patients were more likely to report quitting at 30-days in the assisted intervention, 16 (64.0%) versus 5 (29.4%) in the AAR intervention, p = 0.03. After excluding those unable to be reached at 90-days, 30 (45.5%) in the assisted intervention quit versus 11 (35.5%) in the AAR intervention, p = 0.35. CONCLUSIONS: Pharmacy-led smoking cessation initiatives that include providing NRT are especially impactful on smoking cessation in lung cancer patients.