Potential involvement of beta-lactamase homologous proteins in resistance to beta-lactam antibiotics in gram-negative bacteria of the ESKAPEE group.

BACKGROUND: Enzymatic degradation mediated by beta-lactamases constitutes one of the primary mechanisms of resistance to beta-lactam antibiotics in gram-negative bacteria. This enzyme family comprises four molecular classes, categorized into serine beta-lactamases (Classes A, C, and D) and zinc-dependent metallo-beta-lactamases (Class B). Gram-negative bacteria producing beta-lactamase are of significant concern, particularly due to their prevalence in nosocomial infections. A comprehensive understanding of the evolution and dissemination of this enzyme family is essential for effective control of these pathogens. In this study, we conducted the prospecting, phylogenetic analysis, and in silico analysis of beta-lactamases and homologous proteins identified in 1827 bacterial genomes with phenotypic data on beta-lactam resistance. These genomes were distributed among Klebsiella pneumoniae (45%), Acinetobacter baumannii (31%), Pseudomonas aeruginosa (14%), Escherichia coli (6%), and Enterobacter spp. (4%). Using an HMM profile and searching for conserved domains, we mined 2514, 8733, 5424, and 2957 proteins for molecular classes A, B, C, and D, respectively. This set of proteins encompasses canonical subfamilies of beta-lactamases as well as hypothetical proteins and other functional groups. Canonical beta-lactamases were found to be phylogenetically distant from hypothetical proteins, which, in turn, are closer to other representatives of the penicillin-binding-protein (PBP-like) and metallo-beta-lactamase (MBL) families. The catalytic amino acid residues characteristic of beta-lactamases were identified from the sequence alignment and revealed that motifs are less conserved in homologous groups than in beta-lactamases. After comparing the frequency of protein groups in genomes of resistant strains with those of sensitive ones applying Fisher's exact test and relative risk, it was observed that some groups of homologous proteins to classes B and C are more common in the genomes of resistant strains, particularly to carbapenems. We identified the beta-lactamase-like domain widely distributed in gram-negative species of the ESKAPEE group, which highlights its importance in the context of beta-lactam resistance. Some hypothetical homologous proteins have been shown to potentially possess promiscuous activity against beta-lactam antibiotics, however, they do not appear to expressly determine the resistance phenotype. The selective pressure due to the widespread use of antibiotics may favor the optimization of these functions for specialized resistance enzymes.

Erosive Tooth Wear, Wine Intake, and Genetic Variation in COMT and MMP2.

INTRODUCTION: Erosive tooth wear (ETW) is a multifactorial condition of increasing prevalence in the younger population. This study aimed to explore the association between different ETW phenotypes with MMP2 and COMT single-nucleotide variants, and selected environmental factors. METHODS: Saliva samples, erosive wear and dental caries experience data, and dietary/behavioral information from 16-18-year-old patients (n= 747) were used. Genotypes were obtained and phenotypes were further analyzed considering diet and behavioral data, using logistic regression as implemented in PLINK, with an alpha of 0.05. RESULTS: When comparing individuals' ETW-free with those with mild ETW, an association was found with COMT rs6269 (p = 0.02). The comparison between ETW-free individuals with individuals with severe ETW also showed an association with COMT rs6269 under the recessive model (p = 0.03). Logistic regression showed that in the presence of less common alleles of MMP2 rs9923304 and COMT rs6269, ETW were more likely to occur when individuals drank wine. The GG genotype of COMT rs6269 was associated with the presence of lower (p = 0.02) and higher (p = 0.02) caries experience when individuals with ETW only in enamel were compared with individuals with ETW involving dentin. CONCLUSION: The results support a role of genes in ETW, with wine consumption being identified as a significant modulator, suggesting that gene-environment interactions may contribute to the development of erosive tooth wear.

Association between molar hypomineralization, genes involved in enamel development, and medication in early childhood: A preliminary study.

BACKGROUND: Molar hypomineralization (MH) is defined as a multifactorial condition, and thus, its presence may be defined by interactions between environmental and genetic factors. AIM: To evaluate the association between MH, genes involved in enamel development, and the use of medication during pregnancy in early childhood. DESIGN: One hundred and eighteen children, 54 with and 64 without MH, were studied. The data collected included demographics, socioeconomic data, and the medical history of mothers and children. Genomic DNA was collected from saliva. Genetic polymorphisms in ameloblastin (AMBN; rs4694075), enamelin (ENAM; rs3796704, rs7664896), and kallikrein (KLK4; rs2235091) were evaluated. These genes were analyzed by real-time polymerase chain reaction using TaqMan chemistry. The software PLINK was used to compare allele and genotype distributions of the groups and to assess the interaction between environmental variables and genotypes (p < .05). RESULTS: The variant allele KLK4 rs2235091 was associated with MH in some children (odds ratio [OR]: 3.75; 95% confidence interval [CI] = 1.65-7.81; p = .001). Taking medications in the first 4 years of life was also associated with MH (OR: 2.94; 95% CI = 1.02-6.04; p = .041) and specifically in association with polymorphisms in ENAM, AMBN, and KLK4 (p < .05). The use of medications during pregnancy was not associated with MH (OR: 1.37; 95% CI = 0.593-3.18; p = .458). CONCLUSION: The results of this study suggest that taking medication in the postnatal period appears to contribute to the etiology of MH in some evaluated children. There may be a possible genetic influence of polymorphisms in the KLK4 gene with this condition.

Family-based GWAS for dental class I malocclusion and clefts.

BACKGROUND: Individuals born with cleft lip and/or palate who receive corrective surgery regularly have abnormal growth in the midface region such that they exhibit premaxillary hypoplasia. However, there are also genetic contributions to craniofacial morphology in the midface region, so although these individuals appear to have Class III skeletal discrepancy, their molar relationship may be Class I. Past genome-wide association studies (GWASs) on skeletal Class II and III malocclusion suggested that multiple genetic markers contribute to these phenotypes via a multifactorial inheritance model, but research has yet to examine the genetic markers associated with dental Class I malocclusion. Thus, our goal was to conduct a family based GWAS to identify genes across the genome that are associated with Class I malocclusion, as defined by molar relations, in humans with and without clefts. METHODS: Our cohort consisted of 739 individuals from 47 Filipino families originally recruited in 2006 to investigate the genetic basis of orofacial clefts. All individuals supplied blood samples for DNA extraction and genotyping, and a 5,766 single nucleotide polymorphism (SNP) custom panel was used for the analyses. We performed a transmission disequilibrium test for participants with and without clefts to identify genetic contributors potentially involved with Class I malocclusion. RESULTS: In the total cohort, 13 SNPs had associations that reached the genomic control threshold (p < 0.005), while five SNPs were associated with Class I in the cohort of participants without clefts, including four associations that were identified in the total cohort. The associations for the SNPs ABCA4 rs952499, SOX1-OT rs726455, and RORA rs877228 are of particular interest, as past research found associations between these genes and various craniofacial phenotypes, including cleft lip and/or palate. CONCLUSIONS: These findings support the multifactorial inheritance model for dental Class I malocclusion and suggest a common genetic basis for different aspects of craniofacial development.

Genome-wide association study of multiethnic nonsyndromic orofacial cleft families identifies novel loci specific to family and phenotypic subtypes.

Nonsyndromic orofacial clefts (OFCs) are among the most common craniofacial birth defects worldwide, and known to exhibit phenotypic and genetic heterogeneity. Cleft lip plus cleft palate (CLP) and cleft lip only (CL) are commonly combined together as one phenotype (CL/P), separately from cleft palate alone. In comparison, our study analyzes CL and CLP separately. A sample of 2218 CL and CLP cases, 4537 unaffected relatives of cases, and 2673 pure controls with no family history of OFC were selected from the Pittsburgh Orofacial Cleft (Pitt-OFC) multiethnic study.genome-wide association studies were run for seven specific phenotypes created based on the cleft type(s) observed within these families, as well as the combined CL/P phenotype. Five novel genome-wide significant associations, 3q29 (rs62284390), 5p13.2 (rs609659), 7q22.1 (rs6465810), 19p13.3 (rs628271), and 20q13.33 (rs2427238), and nine associations (p ≤ 1.0E-05) within previously confirmed OFC loci-PAX7, IRF6, FAM49A, DCAF4L2, 8q24.21, ARID3B, NTN1, TANC2 and the WNT9B:WNT3 gene cluster-were observed. We also found that single nucleotide polymorphisms within a subset of the associated loci, both previously known and novel, differ substantially in terms of their effects across cleft- or family-specific phenotypes, indicating not only etiologic differences between CL and CLP, but also genetic heterogeneity within each of the two OFC subtypes.

ACTN3 genotype influences masseter muscle characteristics and self-reported bruxism.

OBJECTIVES: Main aim of the study was to explore the association between genetic polymorphisms in ACTN3 and bruxism. Secondary objectives included masseter muscle phenotypes assessment between bruxers and non-bruxers and according to genetic polymorphisms in ACTN3. MATERIALS AND METHODS: Fifty-four patients undergoing orthognathic surgery for correction of their malocclusion were enrolled. Self-reported bruxism and temporomandibular disorders status were preoperatively recorded. Saliva samples were used for ACTN3 genotyping. Masseter muscle samples were collected bilaterally at the time of orthognathic surgery to explore the muscle fiber characteristics. RESULTS: There were significant differences in genotypes for rs1815739 (R577X nonsense) (p = 0.001), rs1671064 (Q523R missense) (p = 0.005), and rs678397 (intronic variant) (p = 0.001) between bruxers and non-bruxers. Patients with self-reported bruxism presented a larger mean fiber area for types IIA (p = 0.035). The mean fiber areas in individuals with the wild-type CC genotype for rs1815739 (R577X) were significantly larger for type IIA fibers (1394.33 µm2 [572.77 µm2 ]) than in those with the TC and TT genotypes (832.61 µm2 [602.43 µm2 ] and 526.58 µm2 [432.21 µm2 ] [p = 0.014]). Similar results for Q523R missense and intronic variants. CONCLUSIONS: ACTN3 genotypes influence self-reported bruxism in patients with dentofacial deformity through specific masseter muscle fiber characteristics.

Polymorphisms associated with oral clefts as potential markers for oral pre and malignant disorders.

OBJECTIVE: To investigate whether genes in the Wnt pathway, which have been previously associated with both oral clefts and oral squamous cell carcinoma, are also associated with oral potentially malignant disorders (leukoplakia, erythroplakia and lichen planus). MATERIALS AND METHODS: Case-control study: Dataset consisted of clinical information linked to DNA samples from affected subjects diagnosed with oral potential malignant disorders and oral cancer and their matched controls. Individual samples, clinical history, and potential risk factors were obtained through the Dental Registry and DNA Repository project of the School of Dental Medicine, University of Pittsburgh. The rs1533767 (WNT11), rs9879992 (GSK3B), and rs3923087 (AXIN2) were tested. After genomic DNA had been extracted, genotyping was performed blindly to clinical diagnosis status. Representation of genotypes and alleles in affected subjects in comparison to the unaffected individuals was determined using PLINK. Additional analysis was performed to investigate associations between environmental (socioeconomic/lifestyle) risk factors and the oral pathologies studied using STATA. RESULTS: Two of the SNPs tested (rs9879992 in GSK3B and rs3923087 in AXIN2) were statistically, significantly associated with the pathologies studied (p = 0.039 and 0.038, respectively). CONCLUSION: Single-nucleotide polymorphisms in genes in the Wnt pathway were associated with oral potentially malignant disorders.

Association of Locus Xq26.1-27.3 with Erosive Tooth Wear Phenotypes in a Group of Adolescents.

Erosive tooth wear is a multifactorial condition of an increasing prevalence. There is a need for discovering individual genetic predisposition for the development of this condition. Considering that the chromosome X locus was previously shown to be associated with dental caries, the aim of the present study was to look for the association between this locus and erosive tooth wear when dietary habits are considered as a co-factor. Saliva samples, erosive wear experience data, and dietary information from 16- to 18-year-old dental patients (n = 705) were used. Genotyping analyses were performed, and thereafter, analyses considering diet and oral hygiene data, using logistic regression, with the assumption that erosive tooth wear is a complex gene-environment model. Genotypic analyses revealed an association between chromosome X marker rs1324156 and erosive tooth wear phenotype. Logistic regression analysis showed that, in the presence of less common allele of rs12687601 and rs1324156, erosive tooth wear more likely develops when associated with numerous dietary variables from the questionnaire. These results indicate that erosive tooth wear may be the result of gene-environment interactions.

Molar-incisor hypomineralization in a cohort of individuals born with cleft lip and palate.

OBJECTIVE: This study aimed to investigate the frequency of molar-incisor hypomineralization (MIH) in individuals born with cleft lip and or cleft palate. SETTINGS AND SAMPLE: Three hundred eighty-six individuals born with cleft lip and/or palate before orthodontic treatment. METHODS: All the individuals were submitted to a clinical examination and intraoral standardized photos. The registration of MIH was taken by two orthodontists and analysed in association with the cleft type and laterality. The Kruskal-Wallis test and the regression test were used to compare the frequency of molars and incisors affected according to cleft type and laterality, sex and age. RESULTS: We found a frequency of 67.87% of MIH in the studied sample. The frequency varied from 25% (in individuals born with cleft palate) to 77% in individuals born with bilateral cleft lip and palate). The number of affected molars was statistically different depending on cleft type and laterality (P < .001- Kruskal-Wallis test). Differences were found between individuals born with unilateral cleft lip and palate and unilateral cleft lip and alveolus (P = .03), and with isolated cleft palate (P = .03), and between individuals born with bilateral cleft lip and palate and born with unilateral cleft lip and alveolus (P = .01), and cleft palate (P = .01). Sex (P = .21) and age (P = .36) had no influence on the frequency of MIH. A positive correlation was found between the number of molars affected and incisors affected (P < .001). CONCLUSION: Individuals born with cleft lip and palate have a higher frequency of MIH, and the complexity of cleft type was associated with the number of affected molars.

COMT rs4818 less common allele is associated with psychological and psychiatric worse indicators in a cohort of individuals born with cleft lip and palate.

OBJECTIVE: Individuals born with cleft lip and palate may face difficulties in speech function, nutrition, facial aesthetics, and long-term care. These difficulties may increase the risk of psychological and psychiatric diseases. This work aimed to test if the variant allele of COMT was carried more frequently among individuals that have psychological and psychiatric outcomes within a cohort of patients born with cleft lip and palate. METHOD: DNA extraction from saliva of two hundred and fifteen individuals born with cleft lip with and/or palate and genotyping was performed, and the frequency of COMT rs4818 alleles was determined. The domain 'Psychological Function' of Cleft-Q™ was used to generate scores for analysis. The scores were computed, and differences in genotype or allele frequencies between individuals with psychological function scores 60 or above and 59 or below were compared. The history of psychiatric illness (family history of psychiatric disease or self-reported psychiatric illness) was registered. RESULTS: Genotype and allele frequencies were compared between individuals with and without a family history of psychiatric illness. Individuals with lower Psychological Function (Cleft-Q™) scores were more likely to be GG (P = .04) or carriers of allele G (P < .001). The reported psychiatric illness and positive family history of psychiatric illness were compared to COMT rs4818 allele and genotype frequencies of individuals without these indicators, and individuals with psychiatric illness and positive family history of psychiatric illness were more likely to carry allele G (P = .03 and P = .008, respectively). CONCLUSION: The study confirms previously suggested role of COMT rs4818 in psychiatric and psychological outcomes in a distinct cohort of patients born with cleft lip and palate.

Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts.

Enamel hypoplasia causes reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. A genome-wide association of enamel hypoplasia was performed in multiple cohorts, overall comprising 7,159 individuals ranging in age from 7-82 years. Mixed-models were used to test for genetic association while simultaneously accounting for relatedness and genetic population structure. Meta-analysis was then performed. More than 5 million single-nucleotide polymorphisms were tested in individual cohorts. Analyses of the individual cohorts and meta-analysis identified association signals close to genome-wide significance (P < 510-8), and many suggestive association signals (510-8 < P < 510-6) near genes with plausible roles in tooth/enamel development. The strongest association signal (P = 1.5710-9) was observed near BMP2K in one of the individual cohorts. Additional suggestive signals were observed near genes with plausible roles in tooth development in the meta-analysis, such as SLC4A4 which can influence enamel hypoplasia. Additional human genetic studies are needed to replicate these results and functional studies in model systems are needed to validate our findings.

Coast-or Inland Residence and Differences in the Occurrence of Cleft Lip and Cleft Palate.

OBJETIVE: To analyze if differences in lifestyle and environment between coastal and inland areas are associated with differences in frequency of orofacial cleft types. DESIGN: Populational cross-sectional study. SETTING: All live borns with orofacial cleft registered at Brazilian Live Birth Information System between 1999 and 2020. PARTICIPANTS: 33,699 live borns with orofacial cleft. INTERVENTION: Data from borns with orofacial cleft were collected at Brazilian Live Birth Information System. MAIN OUTCOME MEASURE: Differences in frequencies between the cleft types and covariates were determined using chi-square. Bivariate analysis was done to obtain the prevalence ratio of types of clefts by geographic origin. Multiple logistic regression analysis was used to determine adjusted odds ratios, controlling for covariates, establishing a significance level of p value <0.05. RESULTS: The frequency of cleft types was statistically significant different according to geographic origin (inland x coast). For syndromic clefts, the prevalence ratio for cleft lip with/without palate was 3.6 times higher inland (p value = 0.000). Regarding non-syndromics, the prevalence ratio for cleft lip with/without palate was two times higher inland (p value = 0.000). Logistic regression suggested cleft lip with/without palate was 6.33 more likely to occur in inland regions (p value = 0.000). CONCLUSION: Geographic origin was associated with the type of cleft in Brazil, with a higher prevalence of cleft lip with/without palate in inland areas, compared to cleft palate, which was higher in the coast.

CLEFT RR- New app to Calculate Recurrence Risk in Cleft lip and Palate.

OBJECTIVE: To describe the Cleft Recurrence Risk (Cleft RR) App, designed to be used on genetic counseling for cleft lip and/ or palate. DESIGN: A validation study, single cohort. SETTING: Tertiary care children's Hospital. PATIENTS, PARTICIPANTS: The manual obtained the results of 100 cases undergoing genetic counseling at the cleft lip and palate treatment center. INTERVENTIONS: The application for genetic counseling for cleft lip and/ or palate is designed to calculate quickly the recurrence risk considering the ancestry, cleft type, sex, and family history and thus encourage the implementation of genetic counseling in cleft lip and palate centers around the world. MAIN OUTCOME MEASURE(S): The data were submitted to the Bland-Altman statistics. RESULTS: After defining parameters the application development follows the steps: development, prototyping, and documentation. The validation of the calculated data was performed by comparing the results of 100 cases undergoing genetic counseling at the cleft lip and palate treatment center obtained by the manual method with the results obtained by the mobile app method; the data were submitted to the Bland-Altman statistics and a high concordance was found. CONCLUSIONS: The mobile app for use by healthcare professionals proved to be simple to use, easy to apply, and provided accurate results. Cleft Recurrence Risk is an application for smartphones developed for genetic counseling in cleft lip and palate, supplementary use by health professionals, and should not replace professional performance.

Patients Air Medical Transport During the COVID-19 Pandemic: A Retrospective Cohort Study.

INTRODUCTION: Air medical transport during the coronavirus disease 2019 pandemic was essential for transferring critically ill patients. This study aimed to comparatively analyze air-transported patients with and without coronavirus disease 2019 according to their clinical condition and complications that occurred during the flight. METHODS: This was a retrospective cohort study that analyzed the digital records of adult patients transported by fixed-wing aircraft from the interior of the state of Amazonas to the state capital Manaus, Brazil, from June 2019 to May 2021. Pearson's chi-squared, Fisher exact, and Wilcoxon-Mann-Whitney tests were applied (significance level of P < .05). RESULTS: The sample consisted of 741 patients (60.59% men, median age 54 years). The incidence of complications during the flight was 7.28%, with emphasis on dyspnea, psychomotor agitation, and pain. There was a significant difference between patients with (n = 466) and without coronavirus disease 2019 (n = 275) regarding the variables age (P < .001), comorbidities (P < .001), body mass index (P < .001), impact (P < .001) and priority (P = .002) of the transfer, physiological severity (P < .001), use of vasoactive drugs when boarding the aircraft (P = .033), and occurrence of respiratory complications during air medical transport (P = .003). DISCUSSION: Patients with coronavirus disease 2019 were older, had more comorbidities and were severely ill, and had higher body mass index, frequency of vasoactive drug use, and respiratory complications. Although there are minimal differences among these patients, the role that interhospital transfer plays in reducing burden on local, less well-equipped hospitals is a primary role of medical transport, particularly during pandemics.

A randomized clinical trial of hyaluronic acid gel pulpotomy in primary molars with 1 year follow-up.

OBJECTIVE: This randomized clinical study aimed to evaluate the success of hyaluronic acid (HA) as a pulpotomy medicament of human primary molars and to compare it with formocresol (FC) and ferric sulphate (FS) pulpotomy treatments up to 12 months. MATERIALS AND METHODS: The study was conducted with 130 primary molars of 44 children. The ethical approval and registration to clinical trials (No: NCT04115358) were completed. After the removal of all the coronal pulp tissue, a 0.5% HA gel, or a FC, or a 20% FS solution were applied randomly to the radicular pulp tissues of the primary molars. Then, the pulp chambers were filled with a zinc oxide eugenol cement and restored either with a composite filling material or with a stainless-steel crown. The treatment success rates of the 3 groups were followed and compared clinically and radiographically at 1st-, 3rd-, 6th- and 12th-months. RESULTS: Primary molars treated with FC, FS and HA dressings were clinically successful 77.5%, 86.8% and 87.5% respectively after 12th-month follow-up (p > .05). Radiographic successes of FC, FS and HA groups were lower than clinical successes (57.6%, 68.8%, 57.9% respectively at the 12th-month) but the difference between the groups was not statistically significant (p > .05). Equivalence analysis assuming not more than 10% difference between the materials suggested that HA was not inferior to FC or FS. CONCLUSIONS: Within the limitations of this study, our randomized clinical trial shows that HA is a promising pulpotomy medicament in primary molars. However, further studies are justified to further improve the HA material success.

Occlusal problems, mental health issues and non-carious cervical lesions.

Non-carious cervical lesions (NCCLs) are characterized by a loss of hard dental tissue near the cement-enamel junction with multifactorial etiology. The aim of this study was to demonstrate that occlusal factors as attrition, malocclusion, and bruxism, and mental disorders as depression, stress, and anxiety are involved in the etiology of NCCLs. Salivary samples and clinical data of 340 individuals selected from 6,112 participants were obtained from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project. The affected group was formed by individuals with NCCL (34 females, 34 males, mean age 55.34 years). In addition, the comparison group was formed by individuals without NCCL (136 females, 136 males, mean age 55.14 years). Eleven single-nucleotide polymorphisms (SNPs) previously associated with mental disorders were genotyped and tested for association with NCCLs. When all occlusal factors were combined there was found a significant association with NCCL (p = 0.000001/adjusted OR 4.38, 95% CI 2.50-7.69). Attrition (OR 3.56, 95% CI 2.00-6.32) and malocclusion (OR 5.09, 95% CI 1.65-15.68) as separate variables showed statistically significant associations with NCCL. There was a significant difference in stress history between the two groups (OR 2.17, 95% CI 1.08-4.39). No associations between NCCLs and the SNPs selected were found. However, when the occlusal factors were analyzed as covariates, associations were found between bruxism and seven of the selected SNPs. Our results suggest that occlusal factors might be associated with NCCLs.

Rapid triage performed by nurses: Signs and symptoms associated with identifying critically ill patients in the emergency department.

AIM: Aim of this study is to identify signs and symptoms associated with identifying critically ill patients by rapid triage assessment performed by nurses in an emergency department. BACKGROUND: In some emergency services, the immediate assessment of critically ill patients occurs before opening the hospital formal registration and it is based on the nurse's experience. Studies on the topic are essential to improve this process. DESIGN: This is a cross-sectional, quantitative study. METHODS: This study was conducted in a Brazilian emergency department in 2017. Adult patients who presented potentially life-threatening symptoms underwent rapid triage to determine the medical urgency. Those identified as being critically ill were classified as high priority and streamed to the emergency room. RESULTS: A total of 154 (84.6%) patients were classified as high priority from the total of 182 evaluations. Altered state of consciousness (35.2%) and altered skin perfusion (25.3%) were frequently identified. Signs and symptoms associated with identifying critically ill patients by rapid triage were alterations in ventilation (OR 6.09; p = 0.028), neurological dysfunction (OR 44.96; p < 0.001) and pain (OR 5.80; p = 0.004). CONCLUSION: Nurses should value neurological and ventilation alterations and pain in patients during rapid triage, since these signs and symptoms are associated with high care priority.

PAX7 gene polymorphism in muscular temporomandibular disorders as potentially related to muscle stem cells.

BACKGROUND: Temporomandibular disorders (TMD) are a group of painful and debilitating disorders, involving the masticatory muscles and/or the temporomandibular joint (TMJ). Chronic TMD pain can be associated with genetic changes in the key muscle development genes. OBJECTIVE: To evaluate the association between polymorphisms in the PAX7 (paired box 7) gene and masticatory myalgia in patients with temporomandibular disorders (TMD). MATERIALS AND METHODS: This is a case-control study. Patients with TMD were divided into two groups: (a) presence of muscular TMD (n = 122) and (b) absence of muscular TMD (n = 49). Genomic DNA was obtained from saliva samples from all participants to allow for genotyping single nucleotide polymorphisms in PAX7 (rs766325 and rs6659735). Over-representation of alleles was tested using chi-square or Fisher's exact tests. Values of p < 0.05 were considered to be statistically significant. RESULTS: Individuals without muscular TMD were less likely to have the PAX7 rs6659735 GG genotype (p = 0.03). No associations were found for PAX7 rs766325. CONCLUSIONS: Alterations in PAX7 may influence muscular pathophysiology and individuals with TMD and the rs6659735 homozygous genotype (GG) are seemingly associated with muscular involvement of the disorder. No associations were found in the region rs766325.

Genetic variants in tooth agenesis-related genes might be also involved in tooth size variations.

OBJECTIVE: The present study aimed to evaluate if genetic variants in PAX9, MSX1, TGFα, FGF3, FGF10, FGF13, GLI2 and GLI3 are involved in TS of permanent teeth. MATERIALS AND METHODS: Pretreatment dental records from orthodontic patients were assessed prior to recruitment. Patients with tooth agenesis and congenital anomalies (including oral cleft) and/or syndromes were excluded. Dental casts were used to measure the maximum crown dimensions of all fully erupted permanent teeth except second and third molars in mesiodistal direction. Teeth with caries, occlusal wear, mesiodistal restorations, and obvious deformities were not evaluated. Genomic DNA samples were used for genotyping. The allelic discrimination of 13 genetic variants was performed. The associations between TS and genotype were analyzed by linear regression, adjusted by gender at a significance level of p ≤ 0.05. RESULTS: Genetic polymorphisms in the tooth agenesis-related genes studied here were associated with increased and decreased TS, in both maxilla and mandible (p < 0.05). CONCLUSION: This study reported associations of novel tooth agenesis-related gene variants with permanent tooth size variations. CLINICAL RELEVANCE: The presence of some genetic variants could allow the prediction of permanent tooth size.

Multiple Structural Microform Defects Suggest Role of Modifier Genes.

ABSTRACT: One of the biggest challenges in clinical genetics is establishing associations between specific germline mutations and the resulting spectrum of phenotypes. The careful characterization of clinical presentations continues to be a tool for establishing these genotype phenotype correlations. The authors intend, by presenting a case study, proposing that the concomitant occurrence of a combinations of mild structural anomalies in the same individual may be due to changes in genes that can be linked by related pathways. A new born with cleft lip and palate was referred at the Cleft Lip and Palate Center. The anamnese was performed and collected data of familiar history, parental consanguinity, and information about pregnancy period. The careful characterization of clinical presentations and the genetic pathways was studied. It is possible that there is no single mutation that can be clearly identified as the etiology of the combination of the defects displayed in the present case.