The Digastric Muscle: Its Anatomy and Functions Revisited / El Músculo Digástrico: Revisión de su Anatomía y Funciones

SUMMARY: As one of the suprahyoid muscles, the digastric muscle is characterized by two separate bellies of different embryologic origins. The origin of the anterior belly is the digastric fossa, while the origin of the posterior belly is the mastoid notch. They share a common insertion: the intermediate tendon. When the digastric muscle contracts, the hyoid bone is raised. Opening of the jaw and swallowing of food boli are associated with digastric muscle activity. This review discusses the general anatomic features of the digastric muscle and its variation, primary functions, and clinical implications focused on surgical reconstruction and rejuvenation.

Como uno de los músculos suprahioideos, el músculo digástrico se caracteriza por dos vientres separados, de diferentes orígenes embriológicos. El origen del vientre anterior es la fosa digástrica, mientras que el origen del vientre posterior es la incisura mastoidea. Comparten una inserción común, El tendón intermedio. Cuando el músculo digástrico se contrae, el hueso hioides se eleva. La apertura de la mandíbula y la deglución del bolo alimenticio se asocian con la actividad del músculo digástrico. Esta revisión analiza las características anatómicas generales del músculo digástrico y su variación, funciones primarias e implicaciones clínicas centradas en la reconstrucción y el rejuvenecimiento quirúrgico.

Cis- and trans-eQTM analysis reveals novel epigenetic and transcriptomic immune markers of atopic asthma in airway epithelium.

BACKGROUND: Expression quantitative trait methylation (eQTM) analyses uncover associations between DNA methylation markers and gene expression. Most eQTM analyses of complex diseases have focused on cis-eQTM pairs (within 1 megabase). OBJECTIVES: This study sought to identify cis- and trans-methylation markers associated with gene expression in airway epithelium from youth with and without atopic asthma. METHODS: In this study, the investigators conducted both cis- and trans-eQTM analyses in nasal (airway) epithelial samples from 158 Puerto Rican youth with atopic asthma and 100 control subjects without atopy or asthma. The investigators then attempted to replicate their findings in nasal epithelial samples from 2 studies of children, while also examining whether their results in nasal epithelium overlap with those from an eQTM analysis in white blood cells from the Puerto Rican subjects. RESULTS: This study identified 9,108 cis-eQTM pairs and 2,131,500 trans-eQTM pairs. Trans-associations were significantly enriched for transcription factor and microRNA target genes. Furthermore, significant cytosine-phosphate-guanine sites (CpGs) were differentially methylated in atopic asthma and significant genes were enriched for genes differentially expressed in atopic asthma. In this study, 50.7% to 62.6% of cis- and trans-eQTM pairs identified in Puerto Rican youth were replicated in 2 smaller cohorts at false discovery rate-adjusted P < .1. Replicated genes in the trans-eQTM analysis included biologically plausible asthma-susceptibility genes (eg, HDC, NLRP3, ITGAE, CDH26, and CST1) and are enriched in immune pathways. CONCLUSIONS: Studying both cis- and trans-epigenetic regulation of airway epithelial gene expression can identify potential causal and regulatory pathways or networks for childhood asthma. Trans-eQTM CpGs may regulate gene expression in airway epithelium through effects on transcription factor and microRNA target genes.

Geniohyoid Muscle: Anatomy and Clinical Implications in Dentistry / Músculo Geniohioideo: Anatomía e Implicaciones Clínicas en Odontología

SUMMARY: The geniohyoid muscle is one of the suprahyoid muslces, and arises from the inferior mental spine and inserts into the hyoid bone. The muscle is a narrow paired one and its main action is pulling the hyoid upward and forward. Its function is very important in deglutition as well as respiration. Therefore, this muscle has been extensively researched, especially in the context of dysphagia and sleep apnea. This review deals with the general anatomic features, main functions, and abnormal states of the geniohyoid muscle, and the clinical implications of these.

El músculo geniohioideo es uno de los músculos suprahioideos que surge de la espina mental inferior y se inserta en el hueso hioides. Son un par de músculo delgados y su acción principal es elevar y estirar el hueso hioides hacia arriba y hacia adelante. Su función es importante tanto en la deglución como en la respiración. Por lo tanto, este músculo ha sido ampliamente investigado, especialmente en el contexto de la disfagia y la apnea del sueño. Esta revisión trata de las características anatómicas generales, funciones principales y estados anormales del músculo geniohioideo, y las implicaciones clínicas de estos.

Mylohyoid muscle revisited: anatomic features with clinical implications in dentistry / Revisión del músculo milohioideo: características anatómica con implicaciones clínicas en odontología

SUMMARY: The mylohyoid muscle, one of the suprahyoid group, forms the floor of the mouth. Its main function is swallowing. It is a margin between the sublingual and the submandibular spaces and is important in the pathway of oral and maxillofacial infection. In prosthodontics, it is one of anatomic landmarks that limits the lingual margin of the mandibular denture. Currently, the muscle receives much interest in the fields of maxillofacial reconstruction and rejuvenation. The hemorrhagic issue around the mandibular lingual region is usually involved with the mylohyoid especially in the dental implant installation. This review covers anatomic features of the mylohyoid muscle with diverse clinical implications.

RESUMEN: El músculo milohioideo es un músculo del grupo suprahioideo que forma el piso de la cavidad oral. Su función principal es la deglución. Es conocido como un límite entre los espacios sublingual y submandibular y es importante en la vía de infección oral y maxilofacial. En la prostodoncia, es uno de los hitos anatómicos que limita el margen lingual de la dentadura mandibular. Actualmente, el músculo recibe mucho interés en los campos de la reconstrucción y el rejuvenecimiento maxilofacial. El problema hemorrágico alrededor de la región lingual mandibular generalmente está relacionado con el músculo milohioideo, especialmente en la instalación de implantes dentales. Esta revisión cubre las características anatómicas del músculo milohioideo con diversas implicaciones clínicas.

A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups.To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (SNP) in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents.In the meta-analysis of GWAS, an SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbation (95% CI 1.34-1.79, p=6.3×10-9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (ß=0.10, p=2.18×10-7).SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1).

Mycobacterium tuberculosis progresses through two phases of latent infection in humans.

Little is known about the physiology of latent Mycobacterium tuberculosis infection. We studied the mutational rates of 24 index tuberculosis (TB) cases and their latently infected household contacts who developed active TB up to 5.25 years later, as an indication of bacterial physiological state and possible generation times during latent TB infection in humans. Here we report that the rate of new mutations in the M. tuberculosis genome decline dramatically after two years of latent infection (two-sided p < 0.001, assuming an 18 h generation time equal to log phase M. tuberculosis, with latency period modeled as a continuous variable). Alternatively, assuming a fixed mutation rate, the generation time increases over the latency duration. Mutations indicative of oxidative stress do not increase with increasing latency duration suggesting a lack of host or bacterial derived mutational stress. These results suggest that M. tuberculosis enters a quiescent state during latency, decreasing the risk for mutational drug resistance and increasing generation time, but potentially increasing bacterial tolerance to drugs that target actively growing bacteria.

Expression Quantitative Trait Methylation Analysis Reveals Methylomic Associations With Gene Expression in Childhood Asthma.

BACKGROUND: Nasal (airway) epithelial methylation profiles have been associated with asthma, but the effects of such profiles on expression of distant cis-genes are largely unknown. RESEARCH QUESTION: To identify genes whose expression is associated with proximal and distal CpG probes (within 1 Mb), and to assess whether and how such genes are differentially expressed in atopic asthma. STUDY DESIGN AND METHODS: Genome-wide expression quantitative trait methylation (eQTM) analysis in nasal epithelium from Puerto Rican subjects (aged 9-20 years) with (n = 219) and without (n = 236) asthma. After the eQTM analysis, a Gene Ontology Enrichment analysis was conducted for the top 500 eQTM genes, and mediation analyses were performed to identify paths from DNA methylation to atopic asthma through gene expression. Asthma was defined as physician-diagnosed asthma and wheeze in the previous year, and atopy was defined as at least one positive IgE to allergens. Atopic asthma was defined as the presence of both atopy and asthma. RESULTS: We identified 16,867 significant methylation-gene expression pairs (false-discovery rate-adjusted P < .01) in nasal epithelium from study participants. Most eQTM methylation probes were distant (average distance, ∼378 kb) from their target genes, and also more likely to be located in enhancer regions of their target genes in lung tissue than control probes. The top 500 eQTM genes were enriched in pathways for immune processes and epithelial integrity and were more likely to have been previously identified as differentially expressed in atopic asthma. In a mediation analysis, we identified 5,934 paths through which methylation markers could affect atopic asthma through gene expression in nasal epithelium. INTERPRETATION: Previous epigenome-wide association studies of asthma have estimated the effects of DNA methylation markers on expression of nearby genes in airway epithelium. Our findings suggest that distant epigenetic regulation of gene expression in airway epithelium plays a role in atopic asthma.

Development of novel avenues to overcome challenges facing CAR T cells.

There has been dramatic success in treating patients with adoptive transfer of autologous T cells genetically modified to express a chimeric antigen receptor redirecting them to the antigen CD19. Despite this success, the application of chimeric antigen receptor T-cell therapy in solid malignancies has encountered many challenges that need to be overcome if similar success across other cancers is to become a reality. These challenges can be classified into 6 categories: the heterogeneity of tumor cell clones and tumor-associated antigen expression; poor T-cell trafficking into the tumor site; poor T-cell survival and persistence; the presence of suppressive immune cells; the secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation of T-cell intrinsic inhibitory pathways. We outline specific representative hurdles in each of these categories and summarize the progress made in understanding them and developing strategies to overcome them.

Importance of cough and M. tuberculosis strain type as risks for increased transmission within households.

RATIONALE: The degree to which tuberculosis (TB) is transmitted between persons is variable. Identifying the factors that contribute to transmission could provide new opportunities for TB control. Transmission is influenced by host, bacterial and environmental factors. However, distinguishing their individual effects is problematic because measures of disease severity are tightly correlated, and assessing the virulence of Mycobacterium tuberculosis isolates is complicated by epidemiological and clinical confounders. OBJECTIVES: To overcome these problems, we investigated factors potentially associated with TB transmission within households. METHODS: We evaluated patients with smear-positive (≥2+), pulmonary TB and classified M. tuberculosis strains into single nucleotide polymorphism genetic cluster groups (SCG). We recorded index case, household contact, and environmental characteristics and tested contacts with tuberculin skin test (TST) and interferon-gamma release assay. Households were classified as high (≥70% of contacts with TST≥10 mm) and low (≤40%) transmission. We used logistic regression to determine independent predictors. RESULT: From March 2008 to June 2012, we screened 293 TB patients to enroll 124 index cases and their 731 contacts. There were 23 low and 73 high transmission households. Index case factors associated with high transmission were severity of cough as measured by a visual analog cough scale (VACS) and the Leicester Cough Questionnaire (LCQ), and cavitation on chest radiograph. SCG 3b strains tended to be more prevalent in low (27.3%) than in high (12.5%) transmission households (p = 0.11). In adjusted models, only VACS (p<0.001) remained significant. SCG was associated with bilateral disease on chest radiograph (p = 0.002) and marginally associated with LCQ sores (p = 0.058), with group 3b patients having weaker cough. CONCLUSIONS: We found differential transmission among otherwise clinically similar patients with advanced TB disease. We propose that distinct strains may cause differing patterns of cough strength and cavitation in the host leading to diverging infectiousness. Larger studies are needed to verify this hypothesis.

Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil.

Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.