Analysis of a case of Multiple pterygium syndrome due to a novel variant of CHRNG gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS).@*METHODS@#A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis.@*RESULTS@#The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS.@*CONCLUSION@#The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.

Genetic variability in the neurobiology of nicotine dependence: effects on smoking behavior / A variabilidade genética na neurobiologia da adição à nicotina: reflexos no comportamento tabágico

Abstract Background Smoking dependence is a chronic disease and a public health problem. The neurobiology of nicotine addiction can explain smoking behavior. This system has genetic variability that has been associated with vulnerability to dependence. Genetic variability in the neurobiology of smoking can help to understand why individuals exposed to drugs may or may not become addicted. Objective This study aims to address genetic variability in the neurobiology of smoking addiction with a focus on polymorphic genes related to the nicotinic response and the dopaminergic reward pathway. Method This work involved a search of the main scientific research on genetic variability in the neurobiology of smoking and its effects on smoking behavior. One hundred and five studies were selected, most of which highlighted polymorphisms in the genes of nicotinic receptors, dopamine receptors, and nicotine metabolism. Results The majority of studies have focused on genes related to the activation of the dopaminergic reward system by nicotine. Combinations between different polymorphisms were also highlighted, showing that interactions can determine a genetic profile of predisposition to smoking addiction. Additionally, gender and ethnicity were identified as relevant factors. Conclusion Knowledge of the genetic bases involved in the individual response to smoking can enable a better understanding of inter-individual differences in smoking behavior, and contribute to improving the treatment of addiction.

Resumo Introdução A dependência nicotínica é uma doença crônica e um problema de saúde pública. O comportamento tabágico pode ser explicado pela neurobiologia da adição, cujas variações genéticas têm sido associadas à dependência. A variabilidade genética na neurobiologia do tabagismo pode ajudar a entender por que indivíduos expostos a drogas podem ou não se tornar viciados. Objetivo Este estudo tem como objetivo abordar a variabilidade genética na neurobiologia do tabagismo com foco em genes polimórficos relacionados à resposta nicotínica e à via de recompensa dopaminérgica. Método Uma pesquisa foi realizada nas principais bases de dados científicos sobre a variabilidade genética na neurobiologia do tabagismo e seus efeitos no comportamento do tabagismo. 105 estudos foram selecionados, em sua maioria destacando polimorfismos nos genes de receptores nicotínicos, receptores de dopamina e de metabolismo da nicotina. Resultados A maioria dos estudos concentrou-se em genes relacionados à ativação do sistema de recompensa dopaminérgico pela nicotina. Determinadas combinações entre genótipos de diferentes polimorfismos também se destacaram, mostrando que interações gênicas podem determinar um perfil genético de predisposição ao tabagismo. Além disso, gênero e etnia foram identificados como fatores relevantes. Conclusão O conhecimento das bases genéticas envolvidas na resposta individual ao tabagismo pode permitir uma melhor compreensão das diferenças interindividuais no comportamento tabágico e contribuir para melhoria dos tratamentos disponíveis para a dependência.

Association of CHRNA4 gene polymorphisms with response to antidepressant among ethnic Han Chinese / 中华医学遗传学杂志

OBJECTIVE@#To assess the association of single nucleotide polymorphisms (SNPs) CHRNA4 gene with response to selective serotonin re-uptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD).@*METHODS@#For 304 patients receiving drug treatment for major depression, 2 SNPs, namely rs4522666 and rs4603829, of the CHRNA4 gene were determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th and 6th weeks treatment.@*RESULTS@#The frequency of GG genotype/G allele for rs4522666 differed significantly from that of TT and GT genotypes/T allele between responders and non-responders (P=0.015 and P=0.006, respectively). No significant difference was found in genotypic and allelic frequencies of rs4603829 between the two groups (P> 0.05).@*CONCLUSION@#SNPs of the CHRNA4 gene may play an important role in the response to antidepressant drugs among ethnic Han Chinese with MDD.

A Novel Immunomodulatory Mechanism Dependent on Acetylcholine Secreted by Human Bone Marrow-derived Mesenchymal Stem Cells

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are used to treat autoimmune or inflammatory diseases. Our aim was to determine the immunomodulatory mechanisms elicited by MSCs during inflammation. METHODS AND RESULTS: We cocultured MSCs with peripheral blood mononuclear cells for a mixed lymphocyte reaction or stimulated them by phytohemagglutinin. Morphological changes of MSCs and secretion of acetylcholine (ACh) from MSCs were measured. The effects of an ACh antagonist and ACh agonist on lymphocyte proliferation and proinflammatory-cytokine production were determined. The inflammatory milieu created by immune-cell activation caused MSCs to adopt a neuronlike phenotype and induced them to release ACh. Additionally, nicotinic acetylcholine receptors (nAChRs) were upregulated in activated peripheral blood mononuclear cells. We observed that ACh bound to nAChR on activated immune cells and led to the inhibition of lymphocyte proliferation and of proinflammatory-cytokine production. MSC-mediated immunosuppression through ACh activity was reversed by an ACh antagonist called α-bungarotoxin, and lymphocyte proliferation was inhibited by an ACh agonist, ACh chloride. CONCLUSIONS: Our findings point to a novel immunomodulatory mechanism in which ACh secreted by MSCs under inflammatory conditions might modulate immune cells. This study may provide a novel method for the treatment of autoimmune diseases by means of MSCs.

Melatonin inhibits nicotinic acetylcholine receptor functions in bovine chromaffin cells

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free Ca²⁺ concentration ([Ca²⁺](i)) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced [Ca²⁺](i) increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.

Basal Forebrain Cholinergic-induced Activation of Cholecystokinin Inhibitory Neurons in the Basolateral Amygdala

The basolateral amygdala (BLA) receives dense projections from cholinergic neurons of the basal forebrain. Acetylcholine can contributes to amygdala-dependent behaviors: formation and extinction of fear memory and appetitive instrumental learning. However, the cholinergic mechanism at the circuit level has not been defined yet. We demonstrated that cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons exhibits a retrograde form of short-term synaptic inhibition, depolarization-induced suppression of inhibition (DSI). Activation of nicotinic receptors was sufficient to evoke action potentials in cholecystokinin (CCK)-positive inhibitory neurons, which strongly inhibit pyramidal neurons through their perisomatic synapses. Our cell type-specific monosynaptic retrograde tracing also revealed that CCK neurons are innervated by basal forebrain cholinergic neurons. Therefore, our data indicated that CCK inhibitory neurons mediate the cholinergic-induced di-synaptic inhibition of BLA pyramidal neurons.

Neuroimmune interactions and kidney disease

The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.

The role of central cholinergic system in epilepsy / 浙江大学学报·医学版

Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy. In the network level, cholinergic projection neurons as well as their interaction with other neurons may regulate the development of epilepsy, especially the cholinergic circuit from basal forebrain to hippocampus, while cholinergic local interneurons have not been reported to be associated with epilepsy. With the development of optogenetics and other techniques, dissect and regulate cholinergic related epilepsy circuit has become a hotspot of epilepsy research.

The crystal structure of Ac-AChBP in complex with α-conotoxin LvIA reveals the mechanism of its selectivity towards different nAChR subtypes

The α3* nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The α-conotoxin (α-CTx) LvIA has been identified as the most selective inhibitor of α3β2 nAChRs known to date, and it can distinguish the α3β2 nAChR subtype from the α6/α3β2β3 and α3β4 nAChR subtypes. However, the mechanism of its selectivity towards α3β2, α6/α3β2β3, and α3β4 nAChRs remains elusive. Here we report the co-crystal structure of LvIA in complex with Aplysia californica acetylcholine binding protein (Ac-AChBP) at a resolution of 3.4 Å. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvIA plays an important role in the selectivity of LvIA towards α3β2 and α3/α6β2β3 nAChRs by making a salt bridge with Lys-155 of the rat α3 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat β2 subunit in the α3β2 nAChR model, revealing the reason for its more potent selectivity towards the α3β2 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target α3β2 nAChRs, with significant implications for the design of new therapeutic α-CTxs.

Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents / 대한마취과학회지

Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs.

Toxicidad por neonicotinoides: revisión de tema y reporte de dos casos / Toxicity by neonicotinoids: Two case reports and topic review / Toxicidade por neonicotinóides: revisão do assunto e reporte de dois casos

Las intoxicaciones por plaguicidas son la segunda causa de intoxicación en Colombia. Los neonicotinoides son un nuevo grupo de insecticidas que actúa a través de los receptores nicotínicos. Las principales manifestaciones clínicas que se han asociado con dicha intoxicación son alteraciones neurológicas y autonómicas. En este reporte se presentan dos casos de pacientes que ingirieron tiametoxan e imidacloprid y presentaron compromiso del sensorio y de sus signos vitales, por lo que se acudió a manejo en unidad de cuidados intensivos. El objetivo de este reporte es sensibilizar sobre el creciente uso de estos plaguicidas y la necesidad de identificarlos para hacer un diagnóstico diferencial con otras sustancias, realizar un uso adecuado de ayudas diagnósticas y un manejo inicial pertinente para asegurar la vía área y corregir alteraciones hemodinámicas para prevenir complicaciones.

Pesticide poisoning is the second cause of poisoning in Colombia. Neonicotinoids are a new group of insecticides that act through nicotinic receptors. The main clinical manifestations that have been associated with such poisoning are neurological and autonomic disturbances. In this paper, we present two cases in which two patients ingested thiamethoxan and imidacloprid, showing neurologic compromise and affecting their vital signs, requiring management in the intensive care unit. The aim of this article is to raise awareness about the growing use of such pesticides and identify the need to make a differential diagnosis with other insecticides, making appropriate use of diagnostic aids and appropriate initial management of the airway and correcting the abnormalities in their hemodynamic profile to prevent complications.

As intoxicações por praguicidas são a segunda causa de intoxicação na Colômbia. Os neonicotinóides são um novo grupo de inseticidas que atua através dos receptores nicotínicos. As principais manifestações clínicas que se há associado com dita intoxicação são alterações neurológicas e autonómicas. Neste reporte se apresentam dois casos de pacientes que ingeriram tiametoxan e imidacloprid e apresentaram compromisso do sensório e de seus signos vitais, pelo que se acudiu ao manejo em unidade de tratamentos intensivos. O objetivo deste reporte é sensibilizar sobre o crescente uso destes praguicidas e a necessidade de identificá-los para fazer um diagnóstico diferencial com outras substâncias, realizar um uso adequado de ajudas diagnósticas e um manejo inicial pertinente para assegurar a via área e corrigir alterações hemodinâmicas para prevenir complicações.

Alpha-4 subunit of nicotinic acetylcholine receptor polymorphisms exhibit no association with smoking behavior among malay males in Kelantan, Malaysia

Background: Smoking behavior is influenced by both genetic and environmental factors. Nicotine is the major addictive substance in cigarettes. Nicotinic acetylcholine receptors [nAChRs] are thought to play an important role in nicotine addiction of smokers. One of the genes, alpha-4 subunit of nicotinic acetylcholine receptor [CHRNA4] gene was reported to be associated with smoking behavior in many populations

Aim: The aim of this study is to determine association between alpha-4 subunit of nicotinic acetylcholine receptor single nucleotide polymorphism [rs2236196 and rs2273502 loci] and smoking behavior among Malay Males

Methods: The study was conducted in Malay smokers [n = 248] and non-smoking controls [n = 248]. DNA was extracted from leucocytes and the two SNPs were determined by a polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. The PCR product was digested with restriction enzymes AfeI and Sau96I, respectively

Results and conclusion: We found that the AA genotype frequency for CHRNA4 rs2236196 polymorphism in the smoker group was 80.6% while in nonsmoker 77.0%. No mutation [GG genotype] was detected in both groups. The AG genotype for the smoker group was 19.4% while in the nonsmoker group 23.0%. There was no significant difference observed in the genotype [X[2] = 5.106, p = 0.078] and allele frequencies between both study groups. On the other hand, no mutation of CHRNA4 rs2273502 [TT genotype] was detected in the non-smoker group while the frequencies of genotype CC and heterozygous CT in non-smokers were 75.8% and 24.2%, respectively. In the smoker group, the frequencies were 73.4%, 2.0% and 24.6%, for TT, CC and CT, respectively. There was no significant difference observed in rs2273502 [X[2] = 5.16, p = 0.078] and smoking behavior of the subjects. In conclusion, the results revealed that CHRNA4 rs2273502 and rs2236196 gene polymorphisms are not statistically significantly associated with smoking behavior in our population

Imidacloprid inhibits IgE-mediated RBL-2H3 cell degranulation and passive cutaneous anaphylaxis

BACKGROUND: Imidacloprid has been commonly used as a pesticide for crop protection and acts as nicotinic acetylcholine receptor agonists. Little information about the relationship between imidacloprid and allergy is available. OBJECTIVE: This study aims to examine the effects of imidacoprid on IgE-mediated mast cell activation. METHODS: The rat basophilic leukemia cell line RBL-2H3 (RBL-2H3 cells) were treated with 10⁻³ – 10⁻¹² mol/L imidacloprid, followed by measuring the mediator production, influx of Ca²⁺ in IgE-activated RBL-2H3 cells, and the possible effects of imidacoprid on anti-dinitrophenyl IgE-induced passive cutaneous anaphylaxis (PCA). RESULTS: It was shown that imidacoprid suppressed the production of histamine, β-hexosaminidase, leukotriene C4, interleukin-6, tumor necrosis factor-α, and Ca²⁺ mobilization in IgE-activated RBL-2H3 cells and decreased vascular extravasation in IgE-induced PCA. CONCLUSION: It is the first time to show that imidacloprid suppressed the activation of RBL-2H3 cells.

A Missense Mutation in Epsilon-subunit of Acetylcholine Receptor Causing Autosomal Dominant Slow-channel Congenital Myasthenic Syndrome in a Chinese Family / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS).</p><p><b>METHODS</b>Clinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out.</p><p><b>RESULTS</b>The patients revealed variability in clinical and electrophysiological features. However, weakness, scoliosis, and repetitive-compound muscle action potential were found in all affected members in the family. A heterozygous C>T missense mutation at nucleotide 865 in acetylcholine receptor epsilon-subunit (CHRNE) gene that causes a leucine-to-phenylalanine substitution at position 289 (L289F) was found.</p><p><b>CONCLUSIONS</b>We reported a SCCMS family of Chinese origin. In the family, classical clinical phenotype with phenotypic variability among different members was found. Genetic testing could help diagnose this rare disease.</p>

Cytisine, a Partial Agonist of α4β2 Nicotinic Acetylcholine Receptors, Reduced Unpredictable Chronic Mild Stress-Induced Depression-Like Behaviors

Cytisine (CYT), a partial agonist of α4β2-nicotinic receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress.

Differential Effects of Quercetin and Quercetin Glycosides on Human α7 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

Quercetin is a flavonoid usually found in fruits and vegetables. Aside from its antioxidative effects, quercetin, like other flavonoids, has a various neuropharmacological actions. Quercetin-3-O-rhamnoside (Rham1), quercetin-3-O-rutinoside (Rutin), and quercetin-3-(2(G)-rhamnosylrutinoside (Rham2) are mono-, di-, and tri-glycosylated forms of quercetin, respectively. In a previous study, we showed that quercetin can enhance α7 nicotinic acetylcholine receptor (α7 nAChR)-mediated ion currents. However, the role of the carbohydrates attached to quercetin in the regulation of α7 nAChR channel activity has not been determined. In the present study, we investigated the effects of quercetin glycosides on the acetylcholine induced peak inward current (I(ACh)) in Xenopus oocytes expressing the α7 nAChR. I(ACh) was measured with a two-electrode voltage clamp technique. In oocytes injected with α7 nAChR copy RNA, quercetin enhanced I(ACh), whereas quercetin glycosides inhibited I(ACh). Quercetin glycosides mediated an inhibition of I(ACh), which increased when they were pre-applied and the inhibitory effects were concentration dependent. The order of I(ACh) inhibition by quercetin glycosides was Rutin≥Rham1>Rham2. Quercetin glycosides-mediated I(ACh) enhancement was not affected by ACh concentration and appeared voltage-independent. Furthermore, quercetin-mediated I(ACh) inhibition can be attenuated when quercetin is co-applied with Rham1 and Rutin, indicating that quercetin glycosides could interfere with quercetin-mediated α7 nAChR regulation and that the number of carbohydrates in the quercetin glycoside plays a key role in the interruption of quercetin action. These results show that quercetin and quercetin glycosides regulate the α7 nAChR in a differential manner.

Análisis de frecuencias alélicas y genotípicas de las variantes CYP2A6*12 y rs16969968 de CHRNA5 y su asociación con el hábito de fumar y el índice de masa corporal (IMC) en sujetos jóvenes del noreste de México / Association between genotype and allele frequencies of CYP2A6*12 and rs16969968 in CHRNA5 variants with smoking and body mass index in young subjects from Northeast Mexico

Background: Several studies have reported that variants rs16969968 G>A of the CHRNA5 gene and CYP2A6*12 of the CYP2A6 gene are associated with smoking and smoking refusal, respectively. In addition, some studies report that a higher cigarette consumption is associated with low body mass index (BMI). Aim: To analyze the allele and genotypic frequencies of these variants and their impact on smoking and BMI. Material and Methods: A blood sample was obtained and a survey about smoking habits was answered by 319 university students aged 18 to 35 years (127 women, 171 smokers), living in Northeastern Mexico. Genetic variants were studied by polymerase chain reaction/restriction fragment length polymorphism and their frequencies were associated with smoking and BMI. Results: No associations were found between the analyzed variants and smoking in the study groups. However, there was an association among non-smoking subjects between the A allele of rs16969968 and high a BMI (p < 0.01). Conclusions: This last variant may be involved in food-addiction disorders.

Anthropometric indicators of obesity in the prediction of high body fat in adolescents / Indicadores antropométricos de obesidade na predição de gordura corporal elevada em adolescentes

OBJECTIVE: To determine the anthropometric indicators of obesity in the prediction of high body fat in adolescents from a Brazilian State. METHODS: The study included 1,197 adolescents (15-17 years old). The following anthropometric measurements were collected: body mass (weight and height), waist circumference and skinfolds (triceps and medial calf). The anthropometric indicators analyzed were: body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and conicity index (C-Index). Body fat percentage, estimated by the Slaughter et al equation, was used as the reference method. Descriptive statistics, U Mann-Whitney test, and ROC curve were used for data analysis. RESULTS: Of the four anthropometric indicators studied, BMI, WHtR and WC had the largest areas under the ROC curve in relation to relative high body fat in both genders. The cutoffs for boys and girls, respectively, associated with high body fat were BMI 22.7 and 20.1kg/m², WHtR 0.43 and 0.41, WC 75.7 and 67.7cm and C-Index 1.12 and 1.06. CONCLUSIONS: Anthropometric indicators can be used in screening for identification of body fat in adolescents, because they are simple, have low cost and are non-invasive. .

OBJETIVO: Determinar os indicadores antropométricos de obesidade na predição da gordura corporal elevada em adolescentes de um estado brasileiro. MÉTODOS: O estudo incluiu 1.197 adolescentes (15-17 anos). As seguintes medidas antropométricas foram coletadas: massa corporal e estatura, perímetro da cintura e dobras cutâneas (tríceps e perna medial). Os indicadores antropométricos analisados foram: índice de massa corporal (IMC), perímetro da cintura (PC), razão cintura-estatura (RCE) e índice de conicidade (IC). A gordura corporal elevada, estimada pela equação de Slaughter et al., foi usada como método de referência. Estatística descritiva, teste U de Mann-Whitney e curva ROC foram usadas para a análise dos dados. RESULTADOS: Dos quatro indicadores antropométricos estudados, o IMC, a RCE e o PC tiveram as maiores áreas sob a curva ROC em relação à gordura corporal elevada relativa em ambos os sexos. Os pontos de corte para os rapazes e as moças, respectivamente, associados com gordura corporal elevada foram IMC 22,7 e 20,1 kg/m2, RCE 0,43 e 0,41, PC 75,7 e 67,7 cm e IC 1,12 e 1,06. CONCLUSÕES: Os indicadores antropométricos podem ser usados como ferramenta para identificação da gordura corporal em adolescentes, por serem um método simples, de baixo custo e não invasivo. .

Washington y Ginebra llegan a Buenos Aires: notas sobre la historia del hábito de fumar y su medicalización / Washington and Geneva arrive in Buenos Aires: notes on the history of the habit of smoking and its medicalization

Durante gran parte del siglo XX tanto los gobiernos civiles como los militares no encontraron en el tabaquismo un tema prioritario. Recién en la última década del siglo el movimiento internacional contra el cigarrillo, liderado por la Organización Mundial de la Salud, organizaciones norteamericanas y académicos, empezó a tener algún impacto en la escena política argentina. Fue en ese contexto que un nuevo grupo profesional logró impulsar la constitución de un amplio bloque político antitabaco. En ese proceso, el voluntarismo centrado en programas individuales para dejar de fumar que había marcado gran parte de las iniciativas del siglo XX, terminó desplazado por políticas públicas destinadas a producir ambientes libres de humo y a combatir la exposición pasiva al humo de tabaco ajeno.

For much of the twentieth century both the civilian and military governments did not consider smoking a priority concern. It was only in the last decade of the twentieth century that the international movement against cigarettes, led by the World Health Organization, US organizations and academics, began to have some impact on Argentina's political scene. It was in this context that a new professional group managed to foment the creation of a broad anti-smoking political bloc. In this process, voluntarism focused on individual programs to quit smoking that had marked much of the initiatives of the twentieth century, ended up being replaced by public policies designed to ensure smoke free environments and combat passive smoking.

Interaction between smoking and nicotine acetylcholine receptor subunits alpha 5 gene rs17486278 polymorphisms on lung cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the association and interaction between smoking and the nicotine acetylcholine receptor subunits alpha 5(CHRNA5) gene polymorphisms on lung cancer in Chinese men.</p><p><b>METHODS</b>A case-control study was employed with a total of 204 male lung cancer patients and 821 healthy control subjects enrolled in the study. All the subjects were interviewed under a structured questionnaire with the contents on socio-demographic status and smoking behavior. Venous blood samples were collected to measure single nucleotide polymorphism of rs17486278 in CHRNA5. A series of multivariate logistic regression models were performed to assess the association and interaction between smoking and the CHRNA5 gene polymorphisms on lung cancer.</p><p><b>RESULTS</b>After controlling for potential confounding factors, data from the multivariate logistic regression analysis showed that individuals with smoking >15 cigarettes per day would significantly increase the risk of lung cancer when compared to the non-smokers (OR = 3.49, 95%CI:2.29-5.32). However, no associations between CHRNA5 rs17486278 polymorphisms and lung cancer were found. Furthermore, those who smoked 1-15 cigarettes per day had a positive interactive effect between rs17486278 CC genotype and lung cancer (OR = 16.13, 95% CI:1.27-205.33). Results from further stratified analysis on smoking behaviors and rs17486278 genotypes indicated that when compared with non-smokers on rs17486278 AA genotype, those individuals who smoked 1-15 cigarettes per day with rs17486278 CC genotype, individuals smoking >15 cigarettes per day with AA genotype and individuals smoking >15 cigarettes per day with AC genotype, all had a higher risk of developing lung cancer, with their OR value as 8.14(95% CI:1.17-56.56), 3.84 (95% CI:1.30-11.40) and 5.32 (95% CI:1.78-15.93), respectively.</p><p><b>CONCLUSION</b>There was an interaction between smoking and CHRNA5 gene polymorphism on lung cancer.</p>