Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.

Advances in conduits and anastomotic techniques employed in esophageal cancer resections: A review.

Esophageal surgery has evolved significantly since the first esophagectomy, with advancements in diagnosis allowing medicine to keep pace with the disease's increasing incidence. Multimodal treatment improves outcomes, but surgical resection remains imperative for local control, with various techniques in existence but none demonstrating clear superiority. More recently, minimally invasive and robotic surgery have further reduced perioperative morbidity. This review discusses techniques for esophageal resection, with attention to the options available for anastomosis and reconstructive conduits.

Associations of offspring birthweight and placental weight with subsequent parental coronary heart disease: survival regression using the walker cohort.

Low birth weight (BW) is consistently correlated with increased parental risk of subsequent cardiovascular disease, but the links with offspring placental weight (PW) are mostly unexplored. We have investigated the associations between parental coronary heart disease (CHD) and offspring BW and PW using the Walker cohort, a collection of 48,000 birth records from Dundee, Scotland, from the 1950s and 1960s. We linked the medical history of 13,866 mothers and 8,092 fathers to their offspring's records and performed Cox survival analyses modelling maternal and paternal CHD risk by their offspring's BW, PW, and the ratio between both measurements. We identified negative associations between offspring BW and both maternal (hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.88-0.95) and paternal (HR: 0.96, 95% CI: 0.93-1.00) CHD risk, the stronger maternal correlation being consistent with previous reports. Offspring PW to BW ratio was positively associated with maternal CHD risk (HR: 1.14, 95% CI: 1.08-1.21), but the associations with paternal CHD were not significant. These analyses provide additional evidence for intergenerational associations between early growth and parental disease, identifying directionally opposed correlations of maternal CHD with offspring BW and PW, and highlight the importance of the placenta as a determinant of early development and adult disease.

Associations between parental type 2 diabetes risk and offspring birthweight and placental weight: a survival analysis using the Walker cohort.

AIMS/HYPOTHESIS: Low birthweight (BW) is associated with the development of type 2 diabetes. Genome-wide analyses have identified a strong genetic component to this association, with many BW-associated loci also involved in glucose metabolism. We hypothesised that offspring BW and placental weight (PW) are correlated with parental type 2 diabetes risk, reflecting the inheritance of diabetes risk alleles that also influence fetal growth. METHODS: The Walker cohort, a collection of birth records from Dundee, Scotland, from the 1950s and the 1960s was used to test this hypothesis by linking BW and PW measurements to parental health outcomes. Using data from SCI-Diabetes and the national death registry, we obtained health records for over 20,000 Walker parents. We performed Fine-Gray survival analyses of parental type 2 diabetes risk with competing risk of death, and Cox regression analyses of risk of death, independently in the maternal and paternal datasets, modelled by offspring BW and PW. RESULTS: We found significant associations between increased paternal type 2 diabetes risk and reduced offspring BW (subdistribution hazard ratio [SHR] 0.92 [95% CI 0.87, 0.98]) and PW (SHR 0.87 [95% CI 0.81, 0.94]). The association of maternal type 2 diabetes risk with offspring BW or PW was not significant. Lower offspring BW was also associated with increased risk of death in both mothers (HR 0.91 [95% CI 0.89, 0.94]) and fathers (HR 0.95 [95% CI 0.92, 0.98]), and higher offspring PW was associated with increased maternal mortality risk (HR 1.08 [95% CI 1.04, 1.13]) when adjusted for BW. CONCLUSIONS/INTERPRETATION: We identified associations between offspring BW and reduced paternal type 2 diabetes risk, most likely resulting from the independent effects of common type 2 diabetes susceptibility alleles on fetal growth, as described by the fetal insulin hypothesis. Moreover, we identified novel associations between offspring PW and reduced paternal type 2 diabetes risk, a relationship that might also be caused by the inheritance of diabetes predisposition variants. We found differing associations between offspring BW and PW and parental risk of death. These results provide novel epidemiological support for the use of offspring BW and PW as predictors for future risk of type 2 diabetes and death in mothers and fathers.

Frequency and type of digital procedures used for the intraoral prosthetic rehabilitation of patients with head and neck cancer: A systematic review.

STATEMENT OF PROBLEM: In spite of a digital workflow playing an important role in the intraoral prosthetic rehabilitation of patients with head and neck cancer, information about how it has been implemented and its clinical implications is sparse. PURPOSE: The purpose of this systematic review was to evaluate the use of a digital workflow in the intraoral prosthetic rehabilitation of patients with head and neck cancer by analyzing the frequency and type of the digital procedures used. MATERIAL AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The following terms were applied for the search conducted in the MEDLINE-PubMed, Cochrane, and SciELO databases: (prosthesis OR dental OR rehabilitation) AND (digital OR CAD-CAM OR intraoral scanner) AND (Cancer OR head neck). Articles that specified data on intraoral prosthetic treatment and analyzed the use of a digital workflow in the different prosthetic phases such as digital scanning and computer-aided design and computer-aided manufacturing (CAD-CAM) in patients with head and neck cancer were included. Data from the frequency and type of digital procedures were analyzed. RESULTS: Thirteen articles were included, and all had incorporated CAD-CAM techniques in at least 1 of the prosthetic treatment stages (scanning, design, and/or fabrication). Only 1 patient was rehabilitated by using a completely digital workflow. The most frequent prosthetic treatment was an obturator (82.6%). Regarding the image capture method, the most used method was cone beam computed tomography (CBCT) (60.9%). CONCLUSIONS: Most reports described the partial use of a digital workflow in the intraoral prosthetic rehabilitation of patients treated for head and neck cancer. A digital workflow is used for specific stages but not for the entire process. More studies are needed to evaluate digital systems, ideally comparing parameters with the conventional method, and to determine whether this technique has more relevant clinical implications.

The role of genetics in fetal programming of adult cardiometabolic disease.

Disturbances affecting early development have broad repercussions on the individual's health during infancy and adulthood. Multiple observational studies throughout the years have shown that alterations of fetal growth are associated with increased cardiometabolic disease risks. However, the genetic component of this association only started to be investigated in the last 40 years, when single genes with distinct effects were investigated. Birth weight (BW), commonly reported as the outcome of developmental growth, has been estimated to be 20% to 60% heritable. Through Genome-Wide Association (GWA) meta-analyses, 190 different loci have been identified being associated with BW, and while many of these loci designate genes involved in glucose and lipid metabolism, with clear ties to fetal development, the role of others is not yet understood. In addition, due to its influence over the intrauterine environment, the maternal genotype also plays an important part in the determination of offspring BW, with the same loci having independent effects of different magnitude or even direction. There is still much to uncover regarding the genetic determinants of BW and the interactions between maternal, offspring, and even paternal genotype. To fully understand these, diverse and novel cohorts from multiple ancestries collecting extensive neonatal phenotype will be needed. This review compiles, chronologically, the main findings in the investigation of the genetics of BW.

Implementation of a mass canine rabies vaccination campaign in both rural and urban regions in southern Malawi.

Rabies is a devastating zoonotic disease causing nearly 60,000 deaths globally each year. The disease causes Malawi an economic loss of 13 million USD and kills almost 500 people annually. Domestic dogs are the main reservoir for rabies and vaccinating over 70% of the dog population is the most efficient method to reduce its incidence in both humans and canines. However, achieving such coverages is often difficult and depend on many geospatial factors. Rural and pastoral regions are considered difficult to vaccinate efficiently due to low dog densities, and reports of campaigns spanning large areas containing vastly different communities are lacking. This study describes a mass canine vaccination campaign covering rural and urban regions in southern Malawi. The campaign achieved an average vaccination coverage of 83.4% across 3 districts, and vaccinated over 89,000 dogs through a combined static point and door-to-door effort. A dog population of 107,574 dogs was estimated (dog:human ratio of 1:23). The canine population was found to be almost completely owned (99.2%) and mostly kept for security purposes (82.7%). The dogs were mainly adults, males, and not neutered. Regression analysis identified education level and proportion of young dogs as the only factors influencing (positively and negatively, respectively) whether vaccination coverage over 70% was achieved in a region, independently of variables such as population density or poverty. A second regression analysis was performed predicting absolute vaccination coverage. While education level and the proportion of confined dogs were associated with positive vaccination coverage, higher proportions of young animals and female dogs were associated with a decrease in coverage. This study confirms the feasibility of homogeneously vaccinating over 70% of the dogs in a large area including rural and urban communities. These findings can inform the logistics of future campaigns and might be used as a template to facilitate high-number, high-coverage vaccination campaigns to other regions in sub-Saharan Africa.

Development of a high number, high coverage dog rabies vaccination programme in Sri Lanka.

BACKGROUND: Rabies is estimated to cause 59,000 deaths and economic losses of US$8.6 billion every year. Despite several years of rabies surveillance and awareness programmes, increased availability of post-exposure prophylaxis vaccinations and dog population control, the disease still remains prevalent in Sri Lanka. This study reports the roll-out of a high number, high coverage canine rabies vaccination campaign in Sri Lanka, providing estimates for the vaccination coverage achieved, analysing the local dog demographics, and identifying barriers of attendance to static vaccination clinics. METHODS: A mass dog vaccination campaign was undertaken in Negombo, Sri Lanka. The campaign was composed of static point and door-to-door vaccination stages, with a final survey of vaccination coverage. A large volume of data on the distribution, health, and signalment of vaccinated dogs was collected through a mobile phone application. A logistic regression model was developed to investigate which socio-spatial and dog-related factors influenced attendance of owners to static vaccination points. RESULTS: The campaign vaccinated over 7800 dogs achieving a vaccination coverage of 75.8%. A dog:human ratio of 1:17 was estimated. Most dogs were owned, and the dog population was mostly male, adult, and non-sterilized. Unawareness, unavailability and handling problems were the most common reasons given by owners to explain failure to attend a static vaccination point. The regression analysis showed that increasing distance to a static point, in addition to young age and poor health of the dog, were associated with a decrease in the likelihood of attendance to a static vaccination points. CONCLUSION: This study demonstrates the feasibility of high number, high coverage vaccination campaigns in Sri Lanka. The information on dog ecology and barriers of attendance to static point vaccination clinics will facilitate development of future vaccination campaigns.

Stripping of PFA Fluoropolymer Coatings Using a Nd:YAG Laser (Q-Switch) and an Yb Fiber Laser (CW).

Fluoropolymers such as PFA are used as coatings for the protection of metal substrates due to their high chemical inertia and non-stick properties. These are "wear and tear" coatings and they degrade, at which point they should be removed for a new application. The removal of these types of coating by laser is of interest due to the process's flexibility, precision, ease of automation, and environmental sustainability. The efficiency of the procedure was shown with the use of a source in a pulsed Nd:YAG and a source in continuous mode of fiber (Yb). The rates of stripping (cm2/min) and fluence (J/cm2) were analyzed and related to the power of the laser sources. Variations of the substrate after stripping were studied: roughness and hardness. The properties of the coating, thickness, roughness, water sliding angle, and microhardness were also evaluated. It was concluded that the laser in continuous mode was more efficient than the pulsed laser; laser removal of fluoropolymers has a strong relationship with reflectivity, and the mechanical and surface properties of the substrate after stripping remained virtually unchanged.

Study on the Main Influencing Factors in the Removal Process of Non-Stick Fluoropolymer Coatings Using Nd:YAG Laser.

The coatings with fluoropolymer resins rich in fluorinated ethylene propylene (FEP) and polytetrafluoroethylene (PTFE) are applied as anti-adherent coatings on aluminum⁻magnesium substrates for use in food containers. In many cases, due to wear, they must be stripped for the application of a new coating on the same substrate. There are several processes for this: blasting, plasma, pyrolysis, chemical processes, laser, high pressure water, and combinations of these. This work focuses on the characterization of the main factors that condition the FEP coating removal process by a continuous wave (CW) Nd:YAG laser, and on the determination of the efficiency of this type of technology used for this purpose. Stripping surface per unit of time and energy consumption per unit area has been determined among other efficiency indicators. Regarding the characterization of the coating object of study, its thickness, surface roughness, contact angle, microhardness and absorbance-reflectance responses have been determined, and the results have been compared with those obtained in the case of PTFE. In addition, to evaluate the mechanical damage caused in the substrate after coating removal by (CW) Nd:YAG laser, the tensile strength, Vickers hardness, Ra and Rz roughness, and the substrate thickness have been measured and analyzed.

Microstructural Tuning of a Laser-Cladding Layer by Means of a Mix of Commercial Inconel 625 and AISI H13 Powders.

The aim of this work is to evaluate the microstructural evolutions developed by mixing a corrosion-resistant and high-performance material with a high-hardness material in a coating obtained by laser-cladding technology. In this paper, five different mixtures of Inconel 625 alloy and AISI H13 steel powders have been deposited on a plate of 42CrMo4 steel using a 2.2 kW diode pumped Nd:YAG laser. The effect of adding tool steel to a Ni-based superalloy has been analyzed by the characterization of each cladded sample using optical microscopy and scanning electron microscopy (SEM). The precipitates observed in the samples have been analyzed by energy dispersive X-ray spectroscopy (EDS X-ray). SEM micrographs and EDS analysis indicate the existence of Laves phase. It has been observed that the presence of these precipitates is stabilized in a certain range of AISI H13 addition.

Asociación de la eficacia de la terapia Cyriax en pacientes con epicondilitis: metaanálisis / Association of the efficacy of Cyriax therapy in patients with epicondylitis: meta-analysis

Resumen Introducción La epicondilitis o codo de tenista es una enfermedad frecuente en el codo, tiene un perfil ocupacional claro, al igual que otras tendinopatías crónicas de las extremidades superiores, y puede aparecer asociada a ellas simultáneamente. La fricción transversal profunda (o Cyriax) ha sido una de las intervenciones fisioterapéuticas sugeridas para el tratamiento de la tendinopatía. Sin embargo, las conclusiones de las investigaciones han sido inconsistentes. Por lo tanto, este estudio intentó aclarar la asociación entre el tratamiento con Cyriax y el codo de tenista a través de un metaanálisis. Material y métodos Se recuperaron las bases de datos de PubMed y EBSCO para recopilar todas las publicaciones sobre la asociación entre el tratamiento con Cyriax y la epicondilitis. Resultados La búsqueda bibliográfica consistió en 10 artículos (que incluyeron 240 casos y 227 controles) para un análisis cualitativo y seis más (que incluyeron 121 casos y 122 controles) para el cuantitativo. Conclusión Este metaanálisis no pudo apoyar una asociación significativa entre la terapia con Cyriax y la epicondilitis. Por lo tanto, se sugiere implementar esta fisioterapia sólo como un tratamiento complementario.

Abstract Introduction Epicondylitis or tennis elbow is a common disease of the elbow that has a clear occupational profile, like other upper extremity chronic tendinopathies, and can appear associated with them simultaneously. Deep transverse friction (or Cyriax) has been one of the physiotherapy interventions suggested for the management of tendinopathy. However, the conclusions of the investigations have been inconsistent. Therefore, this study aimed to clarify the association between Cyriax treatment and tennis elbow through a meta-analysis. Material and methods The PubMed and EBSCO databases were retrieved to collect all publications on the association between Cyriax treatment and epicondylitis. Results The literature search consisted of 10 articles (that included 240 cases and 227 controls) for a qualitative analysis and six more (that included 121 cases and 122 controls) for the quantitative one. Conclusion This meta-analysis could not support a significant association between Cyriax therapy and epicondylitis. Therefore, it is suggested to implement this physical therapy only as a complementary treatment.

Putative association between the -1415 T/C polymorphism of spermidine/spermine N1-acetyltransferase (SSAT1) gene and alcohol use disorders in women and men.

BACKGROUND: The activity of N-methyl-D-aspartate (NMDA) glutamate receptor, which responds to the levels of polyamines, modifies the neurotoxicity caused by ethanol. We aimed to investigate if the functionality of the spermidine/spermine N1-acetyltransferase (SSAT1) gene could be associated with a differential risk for alcoholism. METHODS: We studied a sample of 586 subjects: 104 alcohol-dependent patients, 273 patients with psychiatric disorders but without substance dependence, and 209 healthy controls. After gender stratification, the allele frequency distribution of the SSAT1 gene was compared between these three groups. RESULTS: In females, the TC genotype was significantly more frequent in alcohol-dependent patients than in non-alcohol-dependent psychiatric controls (χ(2 )= 7.509 df = 2, p = 0.023). A trend was found when alcohol-dependent females were compared with the healthy control group (χ(2 )= 4.897 df = 2, p = 0.086). No statistical differences were found among the males. DISCUSSION AND CONCLUSION: Gender differences in the regulation of SSAT1 gene expression may possibly be due to gender-specific effects of stress, ethanol toxicity, and/or polyamines levels. Further studies are needed to confirm our findings.

New perspectives in glutamate and anxiety.

Anxiety and stress-related disorders, namely posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (ODC), social and specific phobias, and panic disorder, are a major public health issue. A growing body of evidence suggests that glutamatergic neurotransmission may be involved in the biological mechanisms underlying stress response and anxiety-related disorders. The glutamatergic system mediates the acquisition and extinction of fear-conditioning. Thus, new drugs targeting glutamatergic neurotransmission may be promising candidates for new pharmacological treatments. In particular, N-methyl-d-aspartate receptors (NMDAR) antagonists (AP5, AP7, CGP37849, CGP39551, LY235959, NPC17742, and MK-801), NMDAR partial agonists (DCS, ACPC), α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) antagonists (topiramate), and several allosteric modulators targeting metabotropic glutamate receptors (mGluRs) mGluR1, mGluR2/3, and mGluR5, have shown anxiolytic-like effects in several animal and human studies. Several studies have suggested that polyamines (agmatine, putrescine, spermidine, and spermine) may be involved in the neurobiological mechanisms underlying stress-response and anxiety-related disorders. This could mainly be attributed to their ability to modulate ionotropic glutamate receptors, especially NR2B subunits. The aim of this review is to establish that glutamate neurotransmission and polyaminergic system play a fundamental role in the onset of anxiety-related disorders. This may open the way for new drugs that may help to treat these conditions.

Understanding the impact of divalent cation substitution on hydroxyapatite: an in vitro multiparametric study on biocompatibility.

Hydroxyapatite (HA), a stable and biocompatible material for bone tissue therapy, may present a variable stoichiometry and accept a large number of cationic substitutions. Such substitutions may modify the chemical activity of HA surface, with possible impact on biocompatibility. In this work, we assessed the effects of calcium substitution with diverse divalent cations (Pb(2+), Sr(2+), Co(2+), Zn(2+), Fe(2+), Cu(2+), or Mg(2+)) on the biological behavior of HA. Physicochemical analyses revealed that apatite characteristics related to crystallinity and calcium dissolution/uptake rates are very sensitive to the nature of cationic substitution. Cytocompatibility was evaluated by mitochondrial activity, membrane integrity, cell density, proapoptotic potential, and adhesion tests. With the exception of Zn-HA, all the substituted HAs induced some level of apoptosis. The highest apoptosis levels were observed for Mg-HA and Co-HA. Cu-HA was the only material to impair simultaneously mitochondrial activity, membrane integrity, and cell density. The highest relative cell densities after exposure to the modified HAs were observed for Mg-HA and Zn-HA, while Co-HA significantly improved cell adhesion onto HA surface. These results show that changes on surface dissolution caused by cationic substitution, as well as the increase of metal species released to biological media, were the main responsible factors related to alterations on HA biocompatibility.

Reflexiones sobre el paciente en terapia intensiva y el personal de salud / Thoughts about the ICU patient and healthcare providers

Teniendo en cuenta el epígrafe de A. Cortina, y con la sola y sana intención de tratar de vivir en una sociedad más justa es que intentaremos reflexionar sobre nuestra diaria tarea de profesionales de la salud en las Unidades de Terapia Intensiva. Sobre todo sabiendo que una sociedad no siempre puede sentarse a esperar las reformas legales correspondientes, ya que éstas marchan a otro ritmo y hay muchas situaciones que no pueden esperar demasiado. Es por esto que habitualmente la ética se anticipa al derecho.

Performance of a pilot-scale biotrickling filter in controlling the volatile organic compound emissions in a furniture manufacturing facility.

A 0.75-m3 pilot-scale biotrickling filter was run for over 1 yr in a Spanish furniture company to evaluate its performance in the removal of volatile organic compounds (VOCs) contained in the emission of two different paint spray booths. The first one was an open front booth used to manually paint furniture, and the second focus was an automatically operated closed booth operated to paint pieces of furniture. In both cases, the VOC emissions were very irregular, with rapid and extreme fluctuations. The pilot plant was operated at an empty bed residence time (EBRT) ranging from 10 to 40 sec, and good removal efficiencies of VOCs were usually obtained. When a buffering activated carbon prefilter was installed, the system performance was improved considerably, so a much better compliance with legal constraints was reached. After different shutdowns in the factory, the period to recover the previous performance of the biotrickling reactor was minimal. A weekend dehydration strategy was developed and implemented to control the pressure drop associated with excessive biomass accumulation.

SAT-1 -1415T/C polymorphism and susceptibility to schizophrenia.

Patients suffering from psychosis show increased blood and fibroblast total polyamine levels. Spermidine/spermine N1-acetyltransferase (SSAT-1) and its coding gene (SAT-1) are the main factors regulating polyamine catabolism. The aim of the present study was to examine the association between the SAT-1 -1415T/C single nucleotide polymorphism (SNP) and schizophrenia. A case-control design was used in order to compare the genotypes for the SNP between schizophrenia patients (n=180, 83 females and 97 males), other non-psychotic psychiatric patients (n=413, 256 females and 157 males), and healthy controls (n=251, 101 females and 150 males). No significant differences in the distribution of the genotypes of the SAT-1 -1415T/C SNP were found groups among groups. We failed to demonstrate a significant association between the SAT-1 -1415T/C SNP and schizophrenia, but a mild association between allele C and psychopathology was found in the female group.

Positive association between SAT-1 -1415T/C polymorphism and anxiety.

Limbic glutamatergic neurotransmission plays a pivotal role in the pathogenesis of anxiety disorders. Polyamines modulate the activity of several ionotropic glutamate receptors and have been involved in the regulation of fear-conditioning response. Spermidine/spermine N1-acetyltransferase (SSAT-1) is the main enzyme regulating polyamine catabolism. The aim of the present study was to examine the association between anxiety disorders and the -1415T/C (rs1960264) single nucleotide polymorphism (SNP) of the gene (SAT1) coding for SSAT-1. A case-control design was used in order to compare the genotypes for the -1415T/C (rs1960264) SNP between anxiety patients (n = 218), other non-anxiety psychiatric patients (n = 362), and healthy controls (n = 251). DSM-IV diagnoses were provided using MINI 4.4. Genomic DNA was extracted from peripheral blood samples collected from participants. In males, there was a significant difference in the distribution of the two genotypes (T and C) for the SAT-1 -1415T/C SNP between anxiety patients, non-anxiety psychiatric controls, and healthy controls. The T genotype was significantly more frequent in males suffering from anxiety disorders than in male psychiatric controls and healthy controls. This is the first study linking polymorphic variants of genes involved in polyamine metabolism with anxiety disorders.

Opto-digital tomographic reconstruction of the Wigner distribution function of complex fields.

An optical-digital method has been developed to obtain the Wigner distribution function of one-dimensional complex fields. In this technique an optical setup is employed to experimentally achieve the Radon-Wigner spectrum of the original signal through intensity measurements. Digital tomographic reconstruction is applied to the experimental spectrum to reconstruct the two-dimensional Wigner distribution function of the input. The validity of our proposal is demonstrated with experimental data, and the results are compared with computer simulations.