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The Spanish optical telegraph was planned by the Ministry of the Interior in 1844 for civilian governmental use. It was a ‘tower and telescope’ telegraph developed by Colonel José María Mathé, with a design clearly inspired by military sensibilities and considerations. This paper first analyses the contemporary military reference point of the embrasure tower as a military stronghold campaign. It goes on to examine the historical antecedents of watchtowers or signal towers from the 16th century and the freestanding or outpost towers from the 17th century. This is followed by a description of the architectural type of telegraph tower and an analysis of its variants, which gradually differed from the model typology in both form and materiality. Finally, it examines the military telegraph towers of the second and third Carlist wars. Thus, the historical and typological study emphasizes the military inspiration of the optical telegraph towers that has often gone unremarked in order to optimize the heritage characterization of the remaining structures.

Recent studies have demonstrated the metabolic benefits of phenolic compounds on human health. However, traditional analytical methods used for quantification of total phenolic compounds are time-consuming, laborious, require a high volume of reagents, mostly toxic substances, and involve several steps that can result in systematic and instrumental errors. Spectroscopic techniques have been used as alternatives to these methods for the determination of bioactive compounds directly in the food matrix by minimal sample preparation, without using toxic reagents. Therefore, this overview presents the advantages of nondestructive methods focusing on infrared spectroscopy (IR), for the quantification of total phenolic compounds in fruits. In addition, the main difficulties in applying these spectroscopic techniques are presented, as well as a comparison between the quantification of total phenolic compounds by traditional and IR methods. This review concludes by focusing on model building, highlighting that IR data are mainly processed using the partial least-squares (PLS) regression method to predict total phenolic content. The development of portable and inexpensive IR instruments, combined with multivariate data processing, could give to the consumers a straightforward technology to evaluate the total phenolic content of fruits prior to purchase. [ABSTRACT FROM AUTHOR]

We present new absolute archaeointensity data from six archaeological sites situated in the Okayama Prefecture, Japan. The materials studied are well-dated fragments from pottery, ceramic coffins and haniwa artefacts. Their ages range from 160 AD to 675 AD, covering the Late Yayoi and Kofun periods. Rock magnetic experiments suggest the presence of magnetite and/or Ti-magnetite as the main carrier of the remanence, with a possible minor contribution of higher coercivity minerals. After thermal demagnetization experiments, the most magnetically stable samples were selected for archaeointensity analysis performed following the double-heating method proposed by Thellier and modified by Coe. Partial thermoremanent magnetization (pTRM) checks and pTRM tail-checks were performed for monitoring possible chemical alterations during heating. All measurements were corrected for both anisotropy and cooling-rate effects. Successful archaeointensity determinations, following rigorous selection criteria, were obtained for samples from all the investigated archaeological sites. Compared with literature data from Japan, the new high-quality data show significantly lower intensity values. They also reveal possible fast secular variation changes during the Late Yayoi period and very weak geomagnetic intensity field around 630 AD. Such values offer evidence of a possible recurrence of weak intensity field in East Asia, suggesting an ancient recurrence of the West Pacific Anomaly. The new data might change the archaeomagnetic field models interpretations in the area, even though more data are still necessary to better understand the secular variation in Japan and the temporal evolution of the geomagnetic field's behaviour in East Asia. [ABSTRACT FROM AUTHOR]

Copyright of TST - Transportes, Servicios y Telecomunicaciones is the property of Asociacion Iberica de Historia Ferroviaria and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses the work "Metodología de la investigación en la enseñanza-aprendizaje del español como segunda lengua (L2)/lengua extranjera (LE)" directed by Isabel Santos Gargallo and Susana Pastor Cesteros. The work addresses research methodology in the field of teaching and learning Spanish as L2/LE, filling a gap in the Spanish bibliography. The book consists of 18 chapters that cover everything from research design to results and knowledge transfer. The chapters are written by experts with extensive experience in teaching Spanish as a second language or foreign language. The work is considered a reference for undergraduate and graduate programs in applied linguistics. [Extracted from the article]

Copyright of HOLOS is the property of Instituto Federal do Rio Grande do norte - IFRN and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The West Nile virus (WNV), primarily transmitted by mosquitoes, is one of the most widespread flaviviruses globally, with past outbreaks occurring in the USA and Europe. Recent studies in parts of Africa, including Kenya, have identified the West Nile virus Koutango lineage (WN-KOUTV) among phlebotomine sandfly populations, however, our understanding of this virus remains limited. This study aimed to characterize WN-KOUTV from phlebotomine sandflies. Sandflies were sampled between 12th -16th March 2021 and 16th -20th March 2023 from six villages each in Baringo and Isiolo Counties, using CDC light traps. Female sandflies were taxonomically identified and pooled based on genus and site of collection. Virus isolation was performed in Vero cells. Viral genomes were determined using next-generation sequencing. Phylogenetic and molecular clock analyses were done to decipher the virus's evolutionary relationships. Comparative analyses of amino acid sequences were performed to determine variations. Protein modeling in Pymol was conducted to elucidate variations in key protein regions. Evolutionary pressure analysis investigated the selection pressures on the virus. In vitro experiments were done to investigate the virus growth kinetics in mammalian Vero E6 and mosquito C6/36 cells. We report the isolation of WN-KOUTV from Salabani in Baringo and Aremet in Isiolo, Kenya. The isolated WN-KOUTVs clustered with previously identified WN-KOUTV strains. Comparative analysis revealed a unique amino acid at NS5 653. The WN-KOUTV lineage as a whole is under purifying selective pressure, with diversifying pressure acting at site NS3 267. The current WN-KOUTV replicated in Vero E6 and C6/36 cells comparable to West Nile virus Lineage 1a, isolated from mosquitoes. Subsequent isolations of WN-KOUTV in phlebotomine sandflies suggest potential vectors, however, vector competence studies would confirm this. Replication in mammalian and insect cell lines suggests there may exist a vector/host relationship. We speculate the close genetic relationship of WN-KOUTV strains from East and West Africa may potentially be enabled by bird migratory routes between the two regions. If proven, this could point to a potential future pandemic pathway for this virus.

Ticks are arachnid ectoparasites that rank second only to mosquitoes in the transmission of human diseases including bacteria responsible for anaplasmosis, ehrlichiosis, spotted fevers, and Lyme disease among other febrile illnesses. Due to the paucity of data on bacteria transmitted by ticks in Kenya, this study undertook a bacterial metagenomic-based characterization of ticks collected from Isiolo, a semi-arid pastoralist County in Eastern Kenya, and Kwale, a coastal County with a monsoon climate in the southern Kenyan border with Tanzania. A total of 2,918 ticks belonging to 3 genera and 10 species were pooled and screened in this study. Tick identification was confirmed through the sequencing of the Cytochrome C Oxidase Subunit 1 (COI) gene. Bacterial 16S rRNA gene PCR amplicons obtained from the above samples were sequenced using the MinION (Oxford Nanopore Technologies) platform. The resulting reads were demultiplexed in Porechop, followed by trimming and filtering in Trimmomatic before clustering using Qiime2-VSearch. A SILVA database pretrained naïve Bayes classifier was used to classify the Operational Taxonomic Units (OTUs) taxonomically. The bacteria of clinical interest detected in pooled tick assays were as follows: Rickettsia spp. 59.43% of pools, Coxiella burnetii 37.88%, Proteus mirabilis 5.08%, Cutibacterium acnes 6.08%, and Corynebacterium ulcerans 2.43%. These bacteria are responsible for spotted fevers, query fever (Q-fever), urinary tract infections, skin and soft tissue infections, eye infections, and diphtheria-like infections in humans, respectively. P. mirabilis, C. acnes, and C. ulcerans were detected only in Isiolo. Additionally, COI sequences allowed for the identification of Rickettsia and Coxiella species to strain levels in some of the pools. Diversity analysis revealed that the tick genera had high levels of Alpha diversity but the differences between the microbiomes of the three tick genera studied were not significant. The detection of C. acnes, commonly associated with human skin flora suggests that the ticks may have contact with humans potentially exposing them to bacterial infections. The findings in this study highlight the need for further investigation into the viability of these bacteria and the competency of ticks to transmit them. Clinicians in these high-risk areas also need to be appraised for them to include Rickettsial diseases and Q-fever as part of their differential diagnosis.

Human mobility represents a privileged field for analysing epidemic propagation, as well as identification and control practises at a world scale. Migrants are at the same time agents of disease dissemination and vulnerable persons highly exposed to epidemics in transit spaces such as city ports, ships, and settlement sites in the countries of origin. This paper aims to analyse how a country with a long and strong tradition in transatlantic and European migration, such as Portugal, incorporated concerns of Public Health in the policies and management of massive migration exits from the nineteenth century until the 1950s, particularly through the directives for the control and prevention of epidemics. In this way, we will analyse the intersection of two general state policies, epidemic control and migration surveillance.

Many low-threshold experiments observe sharply rising event rates of yet unknown origins below a few hundred eV, and larger than expected from known backgrounds. Due to the significant impact of this excess on the dark matter or neutrino sensitivity of these experiments, a collective effort has been started to share the knowledge about the individual observations. For this, the EXCESS Workshop was initiated. In its first iteration in June 2021, ten rare event search collaborations contributed to this initiative via talks and discussions. The contributing collaborations were CONNIE, CRESST, DAMIC, EDELWEISS, MINER, NEWS-G, NUCLEUS, RICOCHET, SENSEI and SuperCDMS. They presented data about their observed energy spectra and known backgrounds together with details about the respective measurements. In this paper, we summarize the presented information and give a comprehensive overview of the similarities and differences between the distinct measurements. The provided data is furthermore publicly available on the workshop’s data repository together with a plotting tool for visualization.

Evolutionary body size decrease has profound consequences for the morphology of an organism. In the evolution of the Characidae, the most species-rich family of Neotropical fishes, a prominent trend is the reduction of body size. The most typical effect is the simplification and reduction of morphological features through terminal deletion processes, resulting in the loss of skeletal elements and structures. To provide further information on the matter, we present a detailed description of the skeleton of Hyphessobrycon piabinhas, a poorly known, small representative of the largest genus of Characidae. We further discuss the identity and phylogenetic relationships of H. piabinhas. It belongs to the subfamily Stethaprioninae and exhibits considerable morphological similarity to other congeners from neighboring drainage systems. We identify several morphological simplifications in H. piabinhas and discuss them based on ontogenetic data available for Characiformes. These developmentally truncated elements are also present in many other small representatives of the family and seem to be among the first morphological modifications to occur in the context of body size reduction of Characidae. We argue that structural losses are not strictly correlated with sizes below 26 mm SL, although the most notable simplifications are typically observed in the miniatures., (© 2024 Wiley Periodicals LLC.)

Lay Abstract: Families may find information about autism online, and health care and education providers may use online tools to screen for autism. However, we do not know if online autism screening tools are easily used by families and providers. We interviewed primary care and educational providers, asking them to review results from online tools that screen for autism. Providers had concerns about how usable and accessible these tools are for diverse families and suggested changes to make tools easier to use., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.B.-F. is on the Scientific Advisory Board of EarliTec Diagnostics Inc. No other authors have conflicts of interest to disclose.

Background: Hospital acquired infections (HAI) and liberal use of broad-spectrum antibiotics are common in intensive care unit(ICU)s of low-middle income countries. We investigated the long-term association of a stepwise multifaceted educational program with the incidence of HAIs and antibiotics use in a Brazilian ICU. We also evaluated the program's cost impact., Methods: We retrieved data from a prospective daily collected database of a twelve bedrooms ICU, all admitted patients within a period of eleven years were enrolled., Findings: From 03/15/2007 to 09/11/2019, we admitted 3059 patients where 2406 (79%) survived the ICU stay. Median age was 51 years-old, and median SAPS3 was 53. The initial density of catheter related blood infection (4.3 events / 1000 patients-day), urinary tract infection (9.2 event / 1000 patients-day) and ventilator associated pneumonia (54.9 events / 1000 patients-day) felt during the observed period to (0.35 events / 1000 patients-day), (0 events / 1000 patients-day), and (1.5 events / 1000 patients-day) respectively. The days of antibiotic therapy also decreased from 797.9 days of therapy / 1000 patients day to 292.3 days of therapy / 1000 patients day. The total cost per patient also decreased. The adjusted mortality rate was steady during the studied period from 23.2% to 22.9%., Interpretation: A stepwise multifaceted educational program is an effective way to reduce hospital-associated infections, improve the rational use of antibiotics, and reduce costs. This impact occurred in a long term, and is probably consistent., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Appendiceal mucinous neoplasms may present without symptoms or with chronic pain in the right lower quadrant. This report describes a case of a 35-year-old woman who presented with chronic right lower quadrant pain and was found to have a low-grade appendiceal mucinous neoplasm (LAMN). Physical examination revealed localized tenderness in the right lower quadrant with no additional symptoms. Preoperative laboratory results were normal, and a CT scan revealed a cystic appendiceal lesion with an internal calcification, initially mistaken for a fecalith, which led to the decision for exploratory laparotomy. Intraoperative findings confirmed the presence of a cystic-like appendiceal lesion, and an open appendectomy was performed. Histopathological examination revealed a low-grade appendiceal mucinous neoplasm (LAMN) confined to the mucosa, without evidence of metastatic disease. The patient had an uneventful recovery and required no additional treatment. This case highlights that surgical intervention with proper technique for confined appendiceal neoplasms, combined with effective preoperative imaging and thorough histopathological examination, is crucial for diagnosis and effective management, ensuring favorable outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Meza-Martinez et al.)

COVID-19 causes more severe and frequently fatal disease in patients with pre-existing comorbidities such as hypertension and heart disease. SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2), which is fundamental in maintaining arterial pressure through the renin-angiotensin system (RAS). Hypertensive patients commonly use medications such as angiotensin-converting enzyme inhibitors (ACEi), which can modulate the expression of ACE2 and, therefore, potentially impact the susceptibility and severity of SARS-CoV-2 infection. Here we assessed whether treatment of ACE2-humanized (K18-hACE2) mice with the ACEi Lisinopril affects lung ACE2 levels and the outcome of experimental COVID-19. K18-hACE2 mice were treated for 21 days with Lisinopril 10 mg/kg and were then infected with 10 5  PFU of SARS-CoV-2 (Wuhan strain). Body weight, clinical score, respiratory function, survival, lung ACE2 levels, viral load, lung histology, and cytokine (IL-6, IL-33, and TNF-α) levels were assessed. Mice treated with Lisinopril for 21 days showed increased levels of ACE2 in the lungs. Infection with SARS-CoV-2 led to massive decrease in lung ACE2 levels at 3 days post-infection (dpi) in treated and untreated animals, but Lisinopril-treated mice showed a fast recovery (5dpi) of ACE2 levels. Higher ACE2 levels in Lisinopril-treated mice led to remarkably higher lung viral loads at 3 and 6/7dpi. Lisinopril-treated mice showed decreased levels of the pro-inflammatory cytokines IL-6 and TNF-α in the serum and lungs at 6/7dpi. Marginal improvements in body weight, clinical score and survival were observed in Lisinopril-treated mice. No differences between treated and untreated infected mice were observed in respiratory function and lung histology. Lisinopril treatment showed both deleterious (higher viral loads) and beneficial (anti-inflammatory and probably anti-constrictory and anti-coagulant) effects in experimental COVID-19. These effects seem to compensate each other, resulting in marginal beneficial effects in terms of outcome for Lisinopril-treated animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Silva-Santos, Pagni, Gamon, de Azevedo, Bielavsky, Darido, de Oliveira, de Souza, Wrenger, Durigon, Luvizotto, Ackerman, Marinho, Epiphanio and Carvalho.)

A cell's ability to survive and to evade cancer is contingent on its ability to retain genomic integrity, which can be seriously compromised when nucleic acid phosphodiester bonds are disrupted. DNA Ligase 1 (LIG1) plays a key role in genome maintenance by sealing single-stranded nicks that are produced during DNA replication and repair. Autosomal recessive mutations in a limited number of individuals have been previously described for this gene. Here we report a homozygous LIG1 mutation (p.A624T), affecting a universally conserved residue, in a patient presenting with leukopenia, neutropenia, lymphopenia, pan-hypogammaglobulinemia, and diminished in vitro response to mitogen stimulation. Patient fibroblasts expressed normal levels of LIG1 protein but exhibited impaired growth, poor viability, high baseline levels of gamma-H2AX foci, and an enhanced susceptibility to DNA-damaging agents. The mutation reduced LIG1 activity by lowering its affinity for magnesium 2.5-fold. Remarkably, it also increased LIG1 fidelity > 50-fold against 3' end 8-Oxoguanine mismatches, exhibiting a marked reduction in its ability to process such nicks. This is expected to yield increased ss- and dsDNA breaks. Molecular dynamic simulations, and Residue Interaction Network studies, predicted an allosteric effect for this mutation on the protein loops associated with the LIG1 high-fidelity magnesium, as well as on DNA binding within the adenylation domain. These dual alterations of suppressed activity and enhanced fidelity, arising from a single mutation, underscore the mechanistic picture of how a LIG1 defect can lead to severe immunological disease., (© 2024. The Author(s).)

Even slight structural differences between phytocannabinoid isomers are usually enough to cause a change in their biological properties. In this study, we used in vitro CB1 agonism/antagonism assays to compare the receptor binding functionality of THCV (tetrahydrocannabivarin) and HHC (hexahydrocannabinol) isomers and applied molecular docking to provide an explanation for the difference in the activities. No CB1 agonism was observed for ∆9- and ∆8-THCV. Instead, both isomers antagonized CP 55940, with ∆9-THCV being approximately two times more potent than the ∆8 counterpart (IC 50 = 52.4 nM and 119.6 nM for ∆9- and ∆8-THCV, respectively). Docking simulations found two binding poses for THCV isomers, one very similar to ∆9-THC and one newly discovered pose involving the occupation of side pocket 1 of the CB1 receptor by the alkyl chain of the ligand. We suggested the latter as a potential antagonist pose. In addition, our results established 9 R -HHC and 9 S -HHC among partial agonists of the CB1 receptor. The 9 R -HHC (EC 50 = 53.4 nM) isomer was a significantly more potent agonist than 9 S (EC 50 = 624.3 nM). ∆9-THC and 9 R -HHC showed comparable binding poses inside the receptor pocket, whereas 9 S -HHC adopted a new and different binding posture that can explain its weak agonist activity.

Cyclic nucleotide binding domains (CNB) confer allosteric regulation by cAMP or cGMP to many signaling proteins, including PKA and PKG. PKA of phylogenetically distant Trypanosoma is the first exception as it is cyclic nucleotide-independent and responsive to nucleoside analogues (Bachmaier et al., 2019). Here, we show that natural nucleosides inosine, guanosine and adenosine are nanomolar affinity CNB ligands and activators of PKA orthologs of the important tropical pathogens Trypanosoma brucei , Trypanosoma cruzi, and Leishmania . The sequence and structural determinants of binding affinity, -specificity and kinase activation of PKAR were established by structure-activity relationship (SAR) analysis, co-crystal structures and mutagenesis. Substitution of two to three amino acids in the binding sites is sufficient for conversion of CNB domains from nucleoside to cyclic nucleotide specificity. In addition, a trypanosomatid-specific C-terminal helix (αD) is required for high affinity binding to CNB-B. The αD helix functions as a lid of the binding site that shields ligands from solvent. Selectivity of guanosine for CNB-B and of adenosine for CNB-A results in synergistic kinase activation at low nanomolar concentration. PKA pulldown from rapid lysis establishes guanosine as the predominant ligand in vivo in T. brucei bloodstream forms, whereas guanosine and adenosine seem to synergize in the procyclic developmental stage in the insect vector. We discuss the versatile use of CNB domains in evolution and recruitment of PKA for novel nucleoside-mediated signaling., Competing Interests: VO, GG, YV, SB, GM, JB, EL, MB No competing interests declared, FS CEO/CSO of BIOLOG Life Science Institute GmbH & Co. KG, (© 2023, Ober, Githure, Volpato Santos et al.)

Prolonged and excessive use of biocides during the coronavirus disease era calls for incorporating new antiviral polymers that enhance the surface design and functionality for existing and potential future pandemics. Herein, we investigated previously unexplored polyamines with nucleophilic biguanide, guanidine, and hydantoin groups that all can be halogenated leading to high contents of oxidizing halogen that enables enhancement of the biocidal activity. Primary amino groups can be used to attach poly(N-vinylguanidine) (PVG) and poly(allylamine-co-4-aminopyridine-co-5-(4-hydroxybenzylidene)hydantoin) (PAH) as well as a broad-spectrum commercial biocide poly(hexamethylene biguanide) (PHMB) onto a solid support. Halogenation of polymer suspensions was conducted through in situ generation of excess hypobromous acid (HBrO) from bromine and sodium hydroxide or by sodium hypochlorite in aqueous solutions, resulting in N-halamines with high contents of active > N-Br or > N-Cl groups. The virucidal activity of the polymers against human respiratory coronavirus HCoV-229E increased dramatically with their halogenation. Brominated PHMB-Br showed activation activity value > 5 even at 1 mg/L, and complete virus inhibition was observed with either PHMB-Br or PAH-Br at 10 mg/mL. Brominated PVG-Br and PAH-Br possessed fungicidal activity against C. albicans, while PHMB was fungistatic. PHMB, PHMB-Br and PAH polymers demonstrated excellent bactericidal activity against the methicillin-resistant S. aureus and vancomycin-resistant E. faecium. Brominated polymers (PHMB-Br, PVG-Br, PAH-Br) were not toxic to the HeLa monolayers, indicating acceptable biocompatibility to cultured human cells. With these features, the N-halamine polymers of the present study are a worthwhile addition to the arsenal of biocides and are promising candidates for development of non-leaching coatings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The question of an increased cardiovascular risk has been recently raised in adults with phenylketonuria (PKU). As low-grade systemic inflammation increases cardiovascular risk, the INGRAPH study aimed to evaluate low-grade inflammation in adult PKU patients compared to healthy controls and to determine the potential influence of Phe-controlled diet on inflammation. Twenty early-treated adult PKU patients, including a subgroup of 15 classical PKU patients, and 20 healthy volunteers were included. PKU patients and healthy subjects were matched on age, sex and body mass index class. Plasma concentrations of CRP, IFNg, IL1a, IL1b, IL2, IL6, IL10, and TNFα were measured in PKU patients and compared to controls. Plasma CRP was not different in the PKU group as compared to controls. No significant differences were observed between the two groups concerning plasma cytokines concentrations. Plasma CRP and cytokine profile were not different between "on diet" and "off diet" PKU patients. All these results were similar considering only the classical PKU subgroup. No differences were shown in plasma CRP and pro-inflammatory cytokines between adult PKU patients and healthy controls. Further studies are needed, including more patients and extensive characterization of systemic low-grade inflammation, as cardiovascular risk appears to be a new concern in adult PKU population., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Cigarette smoking remains an important health concern and is still a leading cause of preventable mortality. Nicotine is the substance responsible for sustained tobacco use and dependence. Identification of biomarkers underlying nicotine dependence behavior is important to identify people at risk for this dependence. In the present study, we identified biochemical and genetic biomarkers of nicotine dependence detected by the Fagerström Test for Nicotine Dependence (FTDN) in Mexican smokers. The nicotine metabolites nicotine-N'-oxide, trans-3'-hydroxycotinine-glucuronide (3HC-O-Gluc), and nicotine-N-Gluc (Gluc) were useful to differentiate nicotine-dependent from non-dependent subjects (p < .0001) with an area under the curve (AUC) of 0.7818. Genetic variants in CYP2A6, FMO3, and UGT2B7 (rs2431413, rs28363545, and rs7439326, respectively) were associated with nicotine dependence (p = .03, p = .01, p = .01, respectively). Variations in the enzymatic activity of CYP2A6 were associated with altered nicotine-N'-oxide and 3HC-O-Gluc levels. Decreased urinary levels of 3HC-O-Gluc and increased nicotine-N'-oxide were associated with a decrease in the functional activity of CYP2A6. A strong positive correlation was observed between the ratio of urinary 3HC/cotinine, a measure of CYP2A6 activity, and the levels of 3HC-O-Gluc (p < .0001, r = .6835), while a strong negative correlation was observed with nicotine-N'-oxide (p < .0001, r = .6522) in nicotine-dependent subjects. No correlations were observed in non-nicotine-dependent subjects. These data suggest that particular urinary nicotine metabolites and genetic variants involved in nicotine metabolism are useful to identify subjects with nicotine dependence in the Mexican population., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)