Predictors of Quality of Work Life in Health Care Workers at Adult Critical Care Units: A Cross-sectional Study.

Aim and background: Satisfaction with the quality of work life reflects the inadequate distribution of the workforce in critical care units and is not enough; on many occasions, they work in precarious conditions and with high levels of physical, emotional, spiritual, and social demands, impacting the quality of care. Aim: To identify predictors of the quality of work life of healthcare workers in adult critical care units (ACCU). Materials and methods: Quantitative study, cross-sectional analytical design with stratified two-stage sampling; three instruments were applied to 209 healthcare professionals in adult critical care units in different sites in a region of Colombia, concerning Quality of Life at Work-GOHISALO, Copenhagen Psychosocial Questionnaire-COPSOQ and Professional Quality of Life-ProQoL V. Multiple ordinal logistic regression was performed with exposure variables from the COPSOQ and ProQoL domains; the outcome variables were the dimensions of the Quality of Work Life instrument. Ethical standards for research involving human subjects were ensured. Results: According to the results of the multiple logistic models, quality of work life is predicted by job integration and predictability (OR = 6.93; 95% CI = 3.6-13.9), leisure time management and double presence (OR = 4.5; 95% CI = 1.22-8.79). Both job satisfaction and job security are related to leadership quality (OR=3.82; 95% CI = 2.27-6.55 and OR = 3.18; 95% CI = 1.22-8.79), respectively. Conclusions: The quality of work life of healthcare workers in adult intensive care units is predicted by quantitative demands, double presence, emotional demands, work pace, predictability, vertical trust, and quality of leadership. How to cite this article: Quinones-Rozo LP, Canaval-Erazo GE, Sandoval-Moreno LM. Predictors of Quality of Work Life in Health Care Workers at Adult Critical Care Units: A Cross-sectional Study. Indian J Crit Care Med 2024;28(4):355-363.

Prospective cohort study of incidence and risk factors for catheter-associated urinary tract infections in 145 intensive care units of 9 Latin American countries: INICC findings.

PURPOSE: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in Latin American Countries. METHODS: From 01/01/2014 to 02/10/2022, we conducted a prospective cohort study in 145 ICUs of 67 hospitals in 35 cities in nine Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru. To estimate CAUTI incidence, we used the number of UC-days as the denominator, and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: gender, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, UC-type, hospitalizationtype, ICU type, facility ownership, and time period. RESULTS: 31,631 patients, hospitalized for 214,669 patient-days, acquired 305 CAUTIs. The pooled CAUTI rate per 1000 UC-days was 2.58, for those using suprapubic catheters, it was 2.99, and for those with indwelling catheters, it was 2.21. The following variables were independently associated with CAUTI: age, rising risk 1% yearly (aOR = 1.01; 95% CI 1.01-1.02; p < 0.0001 female gender (aOR = 1.28; 95% CI 1.01-1.61; p = 0.04), LOS before CAUTI acquisition, rising risk 7% daily (aOR = 1.07; 95% CI 1.06-1.08; p < 0.0001, UC/DU ratio (aOR = 1.14; 95% CI 1.08-1.21; p < 0.0001, public facilities (aOR = 2.89; 95% CI 1.75-4.49; p < 0.0001. The periods 2014-2016 and 2017-2019 had significantly higher risks than the period 2020-2022. Suprapubic catheters showed similar risks as indwelling catheters. CONCLUSION: The following CAUTI RFs are unlikely to change: age, gender, hospitalization type, and facility ownership. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations.

Transcriptome analyses of murine right and left maxilla-mandibular complex.

OBJECTIVE: The objective of the study was to investigate differential gene expression between murine right and left maxilla-mandibular (MxMn) complexes. SETTING AND SAMPLE POPULATION: Wild-type (WT) C57BL/6 embryonic (E) day 14.5 (n = 3) and 18.5 (n = 3) murine embryos. METHODS: The E14.5 and 18.5 embryos were harvested and hemi-sectioned the MxMn complexes into right and left halves in the mid-sagittal plane. We isolated total RNA using Trizol reagent and further purified using the RNA-easy kit (QIAGEN). We confirmed equal expression of house-keeping genes in right and left halves using RT-PCR and then performed paired-end whole mRNA sequencing in LC Sciences (Houston, TX) followed by differential transcript analyses (>1 or <-1 log fold change; p < .05; q < .05; and FPKM >0.5 in 2/3 samples). The Mouse Genome Informatics and Online Mendelian Inheritance in Man databases as well as gnomAD constraint scores were used to prioritize differentially expressed transcripts. RESULTS: There were 19 upregulated and 19 downregulated transcripts at E14.5 and 8 upregulated and 17 downregulated transcripts at E18.5 time-points. These differentially expressed transcripts were statistically significant and shown to be associated with craniofacial phenotypes in mouse models. These transcripts also have significant gnomAD constraint scores and are enriched in biological processes critical for embryogenesis. CONCLUSIONS: We identified significant differential expression of transcripts between E14.5 and 18.5 murine right and left MxMn complexes. These findings when extrapolated to humans, they may provide a biological basis for facial asymmetry. Further experiments are required to validate these findings in murine models with craniofacial asymmetry.

[Deaths from traffic injuries and social inequality in Colombia, 2019Mortalidade por acidentes de trânsito e desigualdades sociais na Colômbia, 2019]. / Mortalidad por lesiones de tránsito y desigualdades sociales en Colombia, 2019.

Objective: To evaluate the association between social inequalities and deaths from traffic injuries in Colombia in 2019. Methods: This ecological study evaluated the association between social inequalities and deaths from traffic injuries among users of the road transport system in Colombia in 2019, based on secondary information sources, using the department level as the administrative and geographic unit of study. A descriptive statistical analysis of health indicators and equity stratifiers was performed. Absolute and relative measures were used to determine social inequality gaps. Results: In 2019, 6 580 people died from road traffic injuries in Colombia. The majority of them (82%) were men. The most critical user condition was being a motorcyclist. The age group with the most victims was approximately 30 years old. Departments with populations between 500 000 and 2 000 000 were the most represented. The most critical equity stratifier was the number of registered motorcycles per 100 000 population. Significant inequality gaps between departments were observed. Conclusions: Inequalities in deaths from road traffic injuries in Colombia were observed. Policies and actions should focus on helping to reduce identified inequities, resulting in better quality of life, well-being, and health for the population.

Objetivo: Avaliar a relação entre desigualdades sociais e mortalidade por acidentes de trânsito na Colômbia no ano de 2019. Métodos: Este estudo ecológico avaliou a relação entre desigualdades sociais e mortalidade por acidentes de trânsito entre usuários do sistema de transporte rodoviário na Colômbia em 2019, com base em fontes secundárias de informação e departamentos como unidades administrativas e geográficas do estudo. Foi feita uma análise estatística descritiva do indicador de saúde e dos estratificadores de equidade, e foram utilizadas medidas absolutas e relativas para determinar as lacunas de desigualdade social. Resultados: Em 2019, 6 580 pessoas morreram na Colômbia em decorrência de acidentes de trânsito, em sua maioria homens (82%). A categoria de usuário mais afetada foi a de motociclistas, e a faixa etária com o maior número de vítimas girava em torno dos 30 anos. Departamentos com população entre 500 mil e 2 milhões de habitantes tiveram a maior participação. O estratificador de equidade com a condição mais crítica de desigualdade foi o número de motocicletas registradas por 100 mil habitantes. Foram evidenciadas lacunas significativas de desigualdade entre os departamentos. Conclusões: Foram reconhecidas desigualdades na mortalidade por acidentes de trânsito na Colômbia. É preciso implementar políticas e ações que contribuam para a redução das desigualdades identificadas, o que resultará em qualidade de vida, bem-estar e saúde para os cidadãos.

Molecular characterization of mucopolysaccharidosis type IVA patients in the Andean region of Colombia.

Colombia has a high prevalence of mucopolysaccharidosis (MPS) type IVA. Nevertheless, data regarding the mutation spectrum for MPS IVA in this population have not been completely characterized. Forty-seven families and 53 patients from seven different Colombian regions were tested for MPS IVA mutations. We compared the sequences with the N-acetylgalactosamine-6-sulfatase (GALNS) reference sequence NM_000512.4, and gene variants were reported. Bioinformatics analysis was performed using SWISS-MODEL. The mutant proteins were generated by homology from the wild-type GALNS 4FDJ template obtained from the PDB database, and visualization was performed using Swiss-PDBViewer and UCSF Chimera. The predictive analysis was run using different bioinformatic tools, and the deleterious annotation of genetic variants was performed using a neural network. We found that 79% and 21% of the cohort was homozygous and compound heterozygous, respectively. The most frequent mutation observed was p.Gly301Cys (78.3% of alleles), followed by p.Arg386Cys (10.4% of alleles). A novel mutation (p.Phe72Ile) was described and classified in silico as a pathogenic variant. This study reveals the mutation spectrum of MPS IVA in Colombia. The high prevalence of the p.Gly301Cys mutation suggests a founder effect of this variant in the Colombian population that causes diseases in the Andean region (via migration). These data can facilitate genetic counseling, prenatal diagnosis, and the design of therapeutic interventions.

Citrinin against breast cancer: A cytogenotoxicological study.

Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.

The Influence of Sex and Ancestry on Three-Dimensional Palate Shape.

ABSTRACT: Modern human palate shape has been reported to vary by sex and ancestry, but limitations in the methods used to quantify shape and in population coverage have led to inconsistent findings. In the present study, the authors aim to characterize the effects of sex and ancestry on normal-range three-dimensional palate shape through landmark-based morphometrics.Three-dimensional digital dental casts were obtained and landmarked from 794 adults of European (n = 429), African (n = 295), and East Asian (n = 70) ancestry. Principal component analysis was conducted to identify patterns of shape variation present in our cohort, and canonical variates analysis was performed to test for shape differences between sexes and ancestries.Principal component analysis showed that 3 principal components, explaining 76.52% of variance, linked higher palatal vault with either a relative reduction in anteroposterior or mediolateral dimensions. Canonical variates analysis showed that males had wider and shorter palates with more posteriorly located maximum vault depth than females. Individuals of African ancestry, having higher vaults with more posteriorly located maximal depths, also had wider and shorter palates, whereas individuals of European ancestry had narrower and longer palates with more anteriorly located maximum vault depths. Individuals of East Asian ancestry showed the shallowest vaults.It was found that both sex and ancestry influence palate shape, suggesting a possible genetic component underlying this variation. Additionally, our findings indicate that vault height tends to co-vary with anteroposterior or mediolateral dimensions. Further investigation of these morphological patterns may shed light on possible links to common congenital anomalies such as orofacial clefting.

Parents of Children With Nonsyndromic Orofacial Clefting Show Altered Palate Shape.

OBJECTIVE: The unaffected relatives of individuals with nonsyndromic orofacial clefts have been shown to exhibit subtle craniofacial differences compared with the general population. Here, we investigate whether these morphological differences extend to the shape of the palate. DESIGN: We conducted a geometric morphometric analysis to compare palate shape in the clinically unaffected parents of children with nonsyndromic cleft lip with or without cleft palate and adult controls of European, Asian, and African ancestry. We conducted pairwise group comparisons using canonical variates analysis, and then confirmed and characterized findings of shape differences using Euclidean distance matrix analysis. RESULTS: Significant differences in palate shape were detected in unaffected mothers (but not fathers) compared to demographically matched controls. The differences in shape were ancestry-specific; mothers of Asian-derived and African-derived ancestry showed wider and shorter palates with higher posterior palatal vaults, while mothers of European-derived ancestry showed narrower palates with higher anterior palatal vaults. CONCLUSIONS: Our findings suggest that altered palate shape is a subclinical phenotypic feature, which may be indicative of elevated orofacial cleft risk. The risk phenotype varied by sex and ancestry, suggesting possible etiologic heterogeneity among demographic groups. Understanding the genetic basis of these informative palate shape traits may reveal new genes and pathways relevant to nonsyndromic orofacial clefting.

A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals.

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes-cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a "cleft map" of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 [CP], WNT5A [CLP]), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21.

Orofacial clefts (OFCs) are among the most prevalent craniofacial birth defects worldwide and create a significant public health burden. The majority of OFCs are non-syndromic, and the genetic etiology of non-syndromic OFCs is only partially determined. Here, we analyze whole genome sequence (WGS) data for association with risk of OFCs in European and Colombian families selected from a multicenter family-based OFC study. This is the first large-scale WGS study of OFC in parent-offspring trios, and a part of the Gabriella Miller Kids First Pediatric Research Program created for the study of childhood cancers and structural birth defects. WGS provides deeper and more specific genetic data than using imputation on present-day single nucleotide polymorphic (SNP) marker panels. Genotypes of case-parent trios at single nucleotide variants (SNV) and short insertions and deletions (indels) spanning the entire genome were called from their sequences using human GRCh38 genome assembly, and analyzed for association using the transmission disequilibrium test. Among genome-wide significant associations, we identified a new locus on chromosome 21 in Colombian families, not previously observed in other larger OFC samples of Latin American ancestry. This locus is situated within a region known to be expressed during craniofacial development. Based on deeper investigation of this locus, we concluded that it contributed risk for OFCs exclusively in the Colombians. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, and underscores the need for larger samples when studying for OFCs and other birth defects in populations with diverse ancestry.

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.

The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10-8) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development.

Association of low-frequency genetic variants in regulatory regions with nonsyndromic orofacial clefts.

Genome-wide scans have shown that common risk alleles for orofacial clefts (OFC) tend to be located in noncoding regulatory elements and cumulatively explain only part of the heritability of OFCs. Low-frequency variants may account for some of the "missing" heritability. Therefore, we scanned low-frequency variants located within putative craniofacial enhancers to identify novel OFC risk variants and implicate new regulatory elements in OFC pathogenesis. Analyses were performed in a multiethnic sample of 1,995 cases of cleft lip with or without cleft palate (CL/P), 221 cases with cleft palate (CP) only, and 1,576 unaffected controls. One hundred and nineteen putative craniofacial enhancers identified from ChIP-Seq studies in craniofacial tissues or cell lines contained multiple low-frequency (0.01-1%) variants, which we genotyped in participants using a custom Illumina panel. Two complementary statistical approaches, sequence kernel association test and combined multivariate and collapsing, were used to test association of the aggregated low-frequency variants across each enhancer region with CL/P and CP. We discovered a significant association between CP and a branchial arch enhancer near FOXP1 (mm60; p-value = .0002). Additionally, we observed a suggestive association between CL/P and a forebrain enhancer near FOXE1 (hs1717; p-value = .001). These findings suggest that low-frequency variants in craniofacial enhancer regions contribute to the complex etiology of nonsyndromic OFCs.

Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10-8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.

Nonsyndromic orofacial clefts (OFCs) are a heterogeneous group of common craniofacial birth defects with complex etiologies that include genetic and environmental risk factors. OFCs are commonly categorized as cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which have historically been analyzed as distinct entities. Genes for both CL/P and CP have been identified via multiple genome-wide linkage and association studies (GWAS); however, altogether, known variants account for a minority of the estimated heritability in risk to these craniofacial birth defects. We performed genome-wide meta-analyses of CL/P, CP, and all OFCs across two large, multiethnic studies. We then performed population-specific meta-analyses in sub-samples of Asian and European ancestry. In addition to observing associations with known variants, we identified a novel genome-wide significant association between SNPs located in an intronic TP63 enhancer and CL/P (p = 1.16 × 10-8). Several novel loci with compelling candidate genes approached genome-wide significance on 4q21.1 (SHROOM3), 12q13.13 (KRT18), and 8p21 (NRG1). In the analysis of all OFCs combined, SNPs near FOXE1 reached genome-wide significance (p = 1.33 × 10-9). Our results support the highly heterogeneous nature of OFCs and illustrate the utility of meta-analysis for discovering new genetic risk factors.

Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common human birth defects with complex etiology. Although genome-wide association studies have successfully identified a number of risk loci, these loci only account for about 20% of the heritability of orofacial clefts. The "missing" heritability may be found in rare variants, copy number variants, or interactions. In this study, we investigated the role of low-frequency variants genotyped in 1995 cases and 1626 controls on the Illumina HumanCore + Exome chip. We performed two statistical tests, Sequence Kernel Association Test (SKAT) and Combined Multivariate and Collapsing (CMC) method using two minor allele frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of NSCL/P. Low-frequency variants in other genes were associated with decreased risk of NSCL/P. These results demonstrate that low-frequency variants contribute to the genetic etiology of NSCL/P.

Hypertelorism and Orofacial Clefting Revisited: An Anthropometric Investigation.

OBJECTIVE: Since the 1960s, multiple studies have reported a tendency toward hypertelorism in individuals with nonsyndromic orofacial clefts (OFCs). However, the association between specific cleft types and increased interorbital distance has been inconsistent. Using three-dimensional (3D) surface imaging, we tested whether different forms of clefting showed evidence of increased interorbital distance. METHODS: Intercanthal and outercanthal distances and intercanthal indices were calculated from 3D facial surface images of 287 individuals with repaired OFCs. Raw measurements were converted to sex and age-normalized Z-scores. Mean Z-scores for individuals with cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) were compared with reference normative values (controls) and one another directly using t tests and analysis of variance. RESULTS: The CLP group showed a significant increase in intercanthal width (P = .001) and intercanthal index (P < .001) compared with reference norms. The CP group showed a significant decrease (P < .001) in outercanthal width. The CL group showed no difference from reference norms. The proportion of clinically hyperteloric individuals was generally low but highest in the CLP group (7.4%). Cleft severity had little effect on interorbital spacing. CONCLUSIONS: Individuals with CLP exhibited on average a tendency toward mild hypertelorism, driven primarily by an increase in intercanthal distance. This tendency was not seen in CL or CP.

Passive Smoke Exposure as a Risk Factor for Oral Clefts-A Large International Population-Based Study.

Maternal cigarette smoking is a well-established risk factor for oral clefts. Evidence is less clear for passive (secondhand) smoke exposure. We combined individual-level data from 4 population-based studies (the Norway Facial Clefts Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases and 9,626 controls. We categorized first-trimester passive and active smoke exposure. Multivariable logistic models adjusted for possible confounders (maternal alcohol consumption, use of folic acid supplements, age, body size, education, and employment, plus study fixed effects). Children whose mothers actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.11, 1.46). Children of passively exposed nonsmoking mothers also had an increased risk (OR = 1.14, 95% CI: 1.02, 1.27). Cleft risk was further elevated among babies of smoking mothers who were exposed to passive smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a modest association between first-trimester passive smoking and oral clefts that was consistent across populations, diverse study designs, and cleft subtypes. While this association may reflect subtle confounding or bias, we cannot rule out the possibility that passive smoke exposure during pregnancy is teratogenic.

The 3D Facial Norms Database: Part 1. A Web-Based Craniofacial Anthropometric and Image Repository for the Clinical and Research Community.

With the current widespread use of three-dimensional (3D) facial surface imaging in clinical and research environments, there is a growing demand for high-quality craniofacial norms based on 3D imaging technology. The principal goal of the 3D Facial Norms (3DFN) project was to create an interactive, Web-based repository of 3D facial images and measurements. Unlike other repositories, users can gain access to both summary-level statistics and individual-level data, including 3D facial landmark coordinates, 3D-derived anthropometric measurements, 3D facial surface images, and genotypes from every individual in the dataset. The 3DFN database currently consists of 2454 male and female participants ranging in age from 3 to 40 years. The subjects were recruited at four US sites and screened for a history of craniofacial conditions. The goal of this article is to introduce readers to the 3DFN repository by providing a general overview of the project, explaining the rationale behind the creation of the database, and describing the methods used to collect the data. Sex- and age-specific summary statistics (means and standard deviations) and growth curves for every anthropometric measurement in the 3DFN dataset are provided as a supplement available online. These summary statistics and growth curves can aid clinicians in the assessment of craniofacial dysmorphology.

Genome-wide study of gene-by-sex interactions identifies risks for cleft palate.

Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP. CL/P is more common in males and CP is more frequently observed in females, so we hypothesized there would also be sex-specific differences for CP. Using a trio-based cohort, we performed sex-stratified genome-wide association studies (GWAS) based on proband sex followed by a genome-wide gene-by-sex (GxS) interaction testing. There were 13 loci significant for GxS interactions, with the top finding in LTBP1 (RR=3.37 [2.04 - 5.56], p=1.93x10 -6 ). LTBP1 plays a role in regulating TGF-B bioavailability, and knockdown in both mice and zebrafish lead to craniofacial anomalies. Further, there is evidence for differential expression of LTBP1 between males and females in both mice and humans. Therefore, we tested the association between the imputed genetically regulated gene expression of genes with significant GxS interactions and the CP phenotype. We found significant association for LTBP1 in cell cultured fibroblasts in female probands (p=0.0013) but not in males. Taken altogether, we show there are sex-specific risks for CP that are otherwise undetectable in a combined sex cohort, and LTBP1 is a candidate risk gene, particularly in females.

Assessing the impact of a multidimensional approach and an 8-component bundle in reducing incidences of ventilator-associated pneumonia across 35 countries in Latin America, Asia, the Middle East, and Eastern Europe.

BACKGROUND: Ventilator associated pneumonia (VAP) occurring in the intensive care unit (ICU) are common, costly, and potentially lethal. METHODS: We implemented a multidimensional approach and an 8-component bundle in 374 ICUs across 35 low and middle-income countries (LMICs) from Latin-America, Asia, Eastern-Europe, and the Middle-East, to reduce VAP rates in ICUs. The VAP rate per 1000 mechanical ventilator (MV)-days was measured at baseline and during intervention at the 2nd month, 3rd month, 4-15 month, 16-27 month, and 28-39 month periods. RESULTS: 174,987 patients, during 1,201,592 patient-days, used 463,592 MV-days. VAP per 1000 MV-days rates decreased from 28.46 at baseline to 17.58 at the 2nd month (RR = 0.61; 95% CI = 0.58-0.65; P < 0.001); 13.97 at the 3rd month (RR = 0.49; 95% CI = 0.46-0.52; P < 0.001); 14.44 at the 4-15 month (RR = 0.51; 95% CI = 0.48-0.53; P < 0.001); 11.40 at the 16-27 month (RR = 0.41; 95% CI = 0.38-0.42; P < 0.001), and to 9.68 at the 28-39 month (RR = 0.34; 95% CI = 0.32-0.36; P < 0.001). The multilevel Poisson regression model showed a continuous significant decrease in incidence rate ratios, reaching 0.39 (p < 0.0001) during the 28th to 39th months after implementation of the intervention. CONCLUSIONS: This intervention resulted in a significant VAP rate reduction by 66% that was maintained throughout the 39-month period.