TypeTaxonScript: sugarifying and enhancing data structures in biological systematics and biodiversity research.

Object-oriented programming (OOP) embodies a software development paradigm grounded in representing real-world entities as objects, facilitating a more efficient and structured modelling approach. In this article, we explore the synergy between OOP principles and the TypeScript (TS) programming language to create a JSON-formatted database designed for storing arrays of biological features. This fusion of technologies fosters a controlled and modular code script, streamlining the integration, manipulation, expansion, and analysis of biological data, all while enhancing syntax for improved human readability, such as through the use of dot notation. We advocate for biologists to embrace Git technology, akin to the practices of programmers and coders, for initiating versioned and collaborative projects. Leveraging the widely accessible and acclaimed IDE, Visual Studio Code, provides an additional advantage. Not only does it support running a Node.js environment, which is essential for running TS, but it also efficiently manages GitHub versioning. We provide a use case involving taxonomic data structure, focusing on angiosperm legume plants. This method is characterized by its simplicity, as the tools employed are both fully accessible and free of charge, and it is widely adopted by communities of professional programmers. Moreover, we are dedicated to facilitating practical implementation and comprehension through a comprehensive tutorial, a readily available pre-built database at GitHub, and a new package at npm.

Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura / Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review / Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

Efficacy and safety of visnadine in the treatment of symptoms of sexual dysfunction in heterosexual women: a systematic review of randomized clinical trials.

OBJECTIVE: To synthesize the primary evidence on the efficacy and safety of visnadine on symptoms of sexual dysfunction (SD) in heterosexual women. METHODS: We conducted a systematic review of randomized clinical trials (RCTs) with a primary search without language restriction in PubMed/Medline, Scopus, Embase, Web of Science, Cochrane Library, and international clinical trial registries. Trials reporting the use of visnadine by any route in women with SD were eligible. We performed screening, data extraction, and risk of bias assessment in a double-blind approach. The primary outcomes were the Female Sexual Function Index (FSFI) and its domains. Secondary outcomes were safety, arousal, lubrication, pleasure, orgasm, negative sensations, duration, and overall satisfaction. RESULTS: Initially, 242 records were retrieved. We selected nine papers for full-text reading and finally included two RCTs: one with a parallel design and one with a crossover design with a total of 96 patients. One study compared visnadine aerosol with a placebo, while the other compared different frequencies of visnadine aerosol use. Visnadine use showed a statistically significant improvement (p < 0.05) in overall FSFI scores, regardless of the frequency of use. A meta-analysis was not possible due to the high clinical and methodological heterogeneity between available studies. CONCLUSION: RCTs regarding the use of visnadine for the Female SD are scarce and methodologically limited. This preliminary evidence shows visnadine as a potentially effective and safe option to alleviate some of the clinical symptoms of SD in heterosexual women. However, future better-designed randomized studies with larger sample numbers are required.

Snakebite-Associated Infections: A Systematic Review and Meta-Analysis.

Snakebites still constitute a significant public health problem in developing countries and are considered a neglected tropical condition by the WHO. Snake accidents are associated with substantial morbidity and mortality and may produce secondary complications, such as severe infections. The objective of this systematic review was to determine the prevalence of snakebite infections and characterize the bacteria isolated from these infections. A systematic literature review in five databases was carried out to assess the prevalence of snakebite infection. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence and 95% CIs. Cochran's Q test and the I2 statistic were used to assess between-study heterogeneity. The pooled prevalence of infection due to snakebite was 27.0% (95% CI: 22.0-32.0%), with high heterogeneity among studies (I2 = 99.7%). The prevalence was higher in Asia (32%) than in the Americas (21%). Snakebite infections required surgical interventions in 68% (95% CI: 37.0-98.0%). The leading group of pathogens identified corresponded to Gram-negative bacteria (63%), particularly Morganella morganii (32%), but also, Gram-positive cocci (40%), especially Enterococcus spp. (23%) and Staphylococcus aureus (15%). However, multiple other pathogens, including anaerobes, were found. A high prevalence of snakebite-associated infection has been described, primarily due to M. morganii, with the corresponding implications for empirical therapy. Rational use of antimicrobials is recommended, and this should guide initial empirical treatment. Moreover, isolation and identification of the possible bacteria present in snakebite wounds is recommended in all cases to confirm or rule out associated infection.

Cellular energy regulates mRNA degradation in a codon-specific manner.

Codon optimality is a major determinant of mRNA translation and degradation rates. However, whether and through which mechanisms its effects are regulated remains poorly understood. Here we show that codon optimality associates with up to 2-fold change in mRNA stability variations between human tissues, and that its effect is attenuated in tissues with high energy metabolism and amplifies with age. Mathematical modeling and perturbation data through oxygen deprivation and ATP synthesis inhibition reveal that cellular energy variations non-uniformly alter the effect of codon usage. This new mode of codon effect regulation, independent of tRNA regulation, provides a fundamental mechanistic link between cellular energy metabolism and eukaryotic gene expression.

Prevalence of computer vision syndrome: A systematic review and meta-analysis

Purpose This review aimed to estimate the prevalence of computer vision syndrome (CVS) in the general population and subgroups. Methods A search was conducted in the following the databases: PubMed, SCOPUS, EMBASE, and Web of Science until February 13, 2023. We included studies that assessed the prevalence of CVS in any population. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the methodological quality. A meta-analysis of the prevalence of CVS was done using a random-effects model, assessing the sources of heterogeneity using subgroup and meta-regression analyses. Results A total of 103 cross-sectional studies with 66 577 participants were included. The prevalence of CVS was 69.0% (95% CI: 62.3 to 75.3; I2: 99.7%), ranging from 12.1 to 97.3% across studies. Point prevalence was higher in women than in men (71.4 vs. 61.8%), university students (76.1%), Africa (71.2%), Asia (69.9%), contact lens wearers (73.1% vs. 63.8%) in studies conducted before the COVID-19 pandemic (72.8%), and in those that did not use the CVS-Q questionnaire (75.4%). In meta-regression, using the CVS-Q scale was associated with a lower prevalence of CVS. Conclusion Seven out of ten people suffer from CVS. Preventive strategies and interventions are needed to decrease the prevalence of this condition which can affect productivity and quality of life. Future studies should standardize a definition of CVS. (AU)

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review.

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role. Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients. This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.

Mancha3D Code: Multipurpose Advanced Nonideal MHD Code for High-Resolution Simulations in Astrophysics.

The Mancha3D code is a versatile tool for numerical simulations of magnetohydrodynamic (MHD) processes in solar/stellar atmospheres. The code includes nonideal physics derived from plasma partial ionization, a realistic equation of state and radiative transfer, which allows performing high-quality realistic simulations of magnetoconvection, as well as idealized simulations of particular processes, such as wave propagation, instabilities or energetic events. The paper summarizes the equations and methods used in the Mancha3D (Multifluid (-purpose -physics -dimensional) Advanced Non-ideal MHD Code for High resolution simulations in Astrophysics 3D) code. It also describes its numerical stability and parallel performance and efficiency. The code is based on a finite difference discretization and a memory-saving Runge-Kutta (RK) scheme. It handles nonideal effects through super-time-stepping and Hall diffusion schemes, and takes into account thermal conduction by solving an additional hyperbolic equation for the heat flux. The code is easily configurable to perform different kinds of simulations. Several examples of the code usage are given. It is demonstrated that splitting variables into equilibrium and perturbation parts is essential for simulations of wave propagation in a static background. A perfectly matched layer (PML) boundary condition built into the code greatly facilitates a nonreflective open boundary implementation. Spatial filtering is an important numerical remedy to eliminate grid-size perturbations enhancing the code stability. Parallel performance analysis reveals that the code is strongly memory bound, which is a natural consequence of the numerical techniques used, such as split variables and PML boundary conditions. Both strong and weak scalings show adequate performance up to several thousands of processors (CPUs).

Variations in the Prevalence of Childhood Anemia by Ethnicity Before and During the COVID-19 Pandemic in Peru.

We aimed to determine the variations in the prevalence of childhood anemia according to the ethnic group before and during the COVID-19 pandemic in Peru. Secondary analysis of the Demographic and Family Health Survey during 2016-2021. The outcome variable was anemia, and the exposure variable was maternal ethnicity. Also, we included sociodemographic and clinical confounding variables. We constructed generalized linear models of the Poisson family with a logarithmic link function. We evaluated 85,905 records; 30.34% had anemia, 50.83% were mestizo, 25.98% were Quechua, and 2% were Aymara. Compared with mestizos, Quechua children (PR: 1.11; 95% CI: 1.07-1.15; p < 0.001), Aymara (PR: 1.35; 95% CI: 1.27-1 .44; p < 0.001), natives of the Amazon (PR: 1.20; 95% CI: 1.12-1.28; p < 0.001) and those who belonged to other indigenous peoples (PR: 1.29; 95% CI: 1.05-1.57; p = 0.013) had a higher prevalence of childhood anemia. On the contrary, compared to mestizos, white children had a lower prevalence of anemia (PR: 0.93; 95% CI: 0.89-0.99; p = 0.019). During the COVID-19 pandemic, compared to mestizos, only Quechua (PR: 1.15; 95% CI: 1.08-1.23; p < 0.001) and Aymara (PR: 1.38; 95% CI: 1.23-1.55; p < 0.001) had a higher prevalence of childhood anemia. Except for Afro-descendants, children from 6 to 59 months of age who belong to an ethnic minority had a higher probability of having childhood anemia than mestizos. However, only Quechua and Aymara children had higher odds of anemia during the COVID-19 pandemic than mestizos.

Ethnic Minority Participation in Clinical Trials from Latin America and the Caribbean: A Scoping Review.

We summarize the clinical trials (CTs) main characteristics, including members of ethnic minorities from Latin America. We carried out a systematic search in six databases. We made a descriptive synthesis of CTs, summarizing the characteristics, interventions, main findings, results, and conclusions reported. 4411 studies were acquired in search strategy, leaving 24 CTs in the final selection. Of these, ten were randomized, four were non-randomized, and the remainder had other designs. Most of the studies were carried out in the population of infants and children (08), ten of the studies included only women, and two studies included men. Nine studies were conducted in Mexico, with the Mayan ethnic minority being mostly evaluated (05). In only 15 it was mentioned that their research was approved by a research ethics committee. Finally, half of the CTs reported funding from international agencies and third reported funding from government agencies. Our results show that that CTs in ethnic minorities are limited and reduced to a few native peoples of the continent.

Access to HIV/STI testing among male and female Venezuelan migrants in Peru: evidence from a nationwide survey.

BACKGROUND: Human immunodeficiency virus (HIV) infection and sexually transmitted infections (STIs) are major global public health issues. Migrants represent a vulnerable group that faces multiple barriers to access to healthcare services, including HIV/STI testing. This study aimed to assess the factors associated with access to HIV/STI testing in male and female Venezuelan migrants in Peru. METHODS: This was a cross-sectional study involving secondary data analysis of the 2022 Venezuelan Population Residing in Peru Survey. The study was conducted in the eight most populated cities inhabited by Venezuelan migrants and refugees. For each city, the sampling design was probabilistic, stratified, and independent. The outcome variable was whether participants had access to HIV or other STI testing during their stay in Peru. Statistical analysis was stratified by sex owing to potential effect modification. Crude and adjusted prevalence ratios were calculated using generalized linear models Poisson family with log link function. Confidence intervals were calculated to 95%. RESULTS: A total of 3,723 male and 3,984 female migrants were included. Access to HIV/STI testing among male and female migrants was 19.85% and 25.16%, respectively. Among male migrants, being LGBTI, health insured, and married or cohabiting were associated with increased access to HIV/STI testing. Among females, those aged 18-44 years, those who were married or cohabiting and were health insured, and those residing for more than 1 year in Peru were significantly more likely to have access to HIV/STI testing. Moreover, physical/mental disability and unemployed status were associated with a lower probability of HIV/STI testing in females. CONCLUSIONS: Only two in ten Venezuelan migrants and refugees in Peru were screened for HIV/STI, with fewer males than females. Sex-specific sociodemographic, health-related, and migration-related variables were independently associated with access to HIV/STI testing.

Association between self-perceived consultation time and understanding of the prescribed treatment: An analysis of a national survey in Peru.

OBJECTIVE: To assess the relationship between the self-perceived consultation time and the knowledge of the proposed treatment. METHODS: Secondary data from a 2015 national survey of health services in Peru were analyzed. The self-perceived consultation time was calculated by asking how long it took from when you entered the consultation until you departed. It was then categorized as low, medium, and high. Five self-reported questions were used to construct a knowledge of the prescribed treatment. Adjusted regression models from the Poisson family models were used to evaluate the relationship. We report adjusted prevalence ratios (aPR) with their 95% confidence intervals (95%CI). RESULTS: A total of 9939 outpatients were analyzed, with 58% women; the average age was 44 years; and 45.4% had higher education. Using low self-perceived consultation time as references, medium and high consultation times were associated with understanding the prescribed treatment (aPR=1.17; 95%CI, 1.04-1.33 and aPR=1.30; 95%CI, 1.20-1.40, respectively). CONCLUSION: Patients who reported a medium and high self-perceived consultation time better understood the prescribed treatment. IMPLICATIONS FOR PRACTICE: Healthcare professionals should strive to maximize consultation time to ensure effective communication and improve patient knowledge of treatments, improving overall patient satisfaction and health outcomes.

Modeling fragment counts improves single-cell ATAC-seq analysis.

Single-cell ATAC sequencing coverage in regulatory regions is typically binarized as an indicator of open chromatin. Here we show that binarization is an unnecessary step that neither improves goodness of fit, clustering, cell type identification nor batch integration. Fragment counts, but not read counts, should instead be modeled, which preserves quantitative regulatory information. These results have immediate implications for single-cell ATAC sequencing analysis.

Partial replacement of soybean meal with microalgae biomass on in vitro ruminal fermentation may reduce ruminal protein degradation.

The objective of this study was to evaluate the effects of partially replacing soybean meal (SBM) with algal sources on in vitro ruminal fermentation. Using 6 fermenters in a 3 × 3 replicated Latin square with 3 periods of 10 d each, we tested 3 treatments: a control diet (CRT) with SBM at 17.8% of the diet dry matter (DM); and 50% SBM biomass replacement with either Chlorella pyrenoidosa (CHL); or Spirulina platensis (SPI). The basal diet was formulated to meet the requirements of a 680-kg Holstein dairy cow producing 45 kg/d of milk with 3.5% fat and 3% protein. All diets had a similar nutritional composition (16.0% CP; 34.9% NDF; 31.0% starch, DM basis) and fermenters were provided with 106 g DM/d split into 2 portions. After 7 d of adaptation, samples were collected for 3 d of each period for analyses of ruminal fermentation at 0, 1, 2, 4, 6, and 8 h after morning feeding for evaluation of the ruminal fermentation kinetics. For the evaluation of the daily production of total metabolites and for the evaluation of nutrient degradability, samples from the effluent containers were collected daily. Statistical analysis was performed with the MIXED procedure of SAS with treatment, time, and their interactions considered as fixed effects; day, square, and fermenter were considered as random effects. Orthogonal contrasts (CRT vs. algae; and CHL vs. SPI) were used to depict the treatment effect, and significance was declared when P ≤ 0.05. Fermenters that received algae-based diets had a greater propionate molar concentration and molar proportion when compared with the fermenters fed CRT diets. In addition, those algae-fed fermenters had lower branched short-chain fatty acids (BSCFA) and isoacids (IA), which are biomarkers of ruminal protein degradation, along with lower ammonia (NH3-N) concentration and greater nonammonia nitrogen (NAN). When contrasting with fermenters fed SPI-diets, fermenters fed based CHL-diets had a lower molar concentration of BSCFA and IA, along with lower NH3-N concentration and flow, and greater NAN, bacterial nitrogen flow, and efficiency of nitrogen utilization. Those results indicate that CHL protein may be more resistant to ruminal degradation, which would increase efficiency of nitrogen utilization. In summary, partially replacing SBM with algae biomass, especially with CHL, is a promising strategy to improve the efficiency of nitrogen utilization, due to the fact that fermenters fed CHL-based diets resulted in a reduction in BSCFA and IA, which are markers of protein degradation, and it would improve the efficiency of nitrogen utilization. However, further validation using in vivo models are required.

Telomerase activity and telomere length in women with breast cancer or without malignancy: A systematic review and meta-analysis.

AIM: We performed a systematic review and meta-analysis to assess whether telomerase activity and telomere length are associated with breast cancer. METHODS: PubMed, Web of Science, Embase, LILACS, Scielo, Embase, and CNKI databases were searched to obtain relevant articles published through May 10, 2023, following PRISMA guidelines and a registered PROSPERO protocol (CRD42022335402). We included observational studies reporting telomerase activity or telomere length in patients with breast cancer compared with women with benign lesions or normal tissue (control women). The Newcastle-Ottawa Scale was used to evaluate the quality of studies. Data were expressed as odds ratios (OR) and 95 % confidence intervals (CI). Random effects and inverse variance methods were used to meta-analyze associations. The I2 test was used to assess heterogeneity. RESULTS: The meta-analysis of telomerase shows significantly greater activity in patients with breast cancer than in those without malignancies (OR = 23.46, 95 % CI 14.07-39.11, p < 0.00001, I2 = 72 %). There were non-significant differences in relative telomere length (OR = 1.16, 95 % CI = 0.90-1.49, p = 0.26, I2 = 86 %) and leukocyte telomere length (OR = 2.32, 95 % CI = 0.89-6.08, p = 0.09, I2 = 98 %) between women with and without breast cancer. In subgroup analyses by world regions of studies, both telomerase activity and telomere length displayed the same trends as in their respective meta-analyses. In sensitivity analyses, variables showed their respective same trends. CONCLUSION: Telomerase activity is higher in patients with breast cancer than in women without malignancies. There were no significant differences in either relative telomere length or leukocyte telomere length in women with and without breast cancer. PROSPERO protocol CRD42022335402.

Prevalence of computer vision syndrome: A systematic review and meta-analysis.

PURPOSE: This review aimed to estimate the prevalence of computer vision syndrome (CVS) in the general population and subgroups. METHODS: A search was conducted in the following the databases: PubMed, SCOPUS, EMBASE, and Web of Science until February 13, 2023. We included studies that assessed the prevalence of CVS in any population. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the methodological quality. A meta-analysis of the prevalence of CVS was done using a random-effects model, assessing the sources of heterogeneity using subgroup and meta-regression analyses. RESULTS: A total of 103 cross-sectional studies with 66 577 participants were included. The prevalence of CVS was 69.0% (95% CI: 62.3 to 75.3; I2: 99.7%), ranging from 12.1 to 97.3% across studies. Point prevalence was higher in women than in men (71.4 vs. 61.8%), university students (76.1%), Africa (71.2%), Asia (69.9%), contact lens wearers (73.1% vs. 63.8%) in studies conducted before the COVID-19 pandemic (72.8%), and in those that did not use the CVS-Q questionnaire (75.4%). In meta-regression, using the CVS-Q scale was associated with a lower prevalence of CVS. CONCLUSION: Seven out of ten people suffer from CVS. Preventive strategies and interventions are needed to decrease the prevalence of this condition which can affect productivity and quality of life. Future studies should standardize a definition of CVS.

Primary and secondary leptomeningeal gliomatosis in dogs.

Leptomeningeal gliomatosis (LG) is characterized by extensive dissemination of neoplastic glial cells in the subarachnoid space either without an intraparenchymal glioma (primary LG or PLG) or secondary to an intraparenchymal glioma (secondary LG or SLG). Given the low frequency of LG in human and veterinary medicine, specific diagnostic criteria are lacking. Here, we describe 14 cases of canine LG that were retrospectively identified from 6 academic institutions. The mean age of affected dogs was 7.3 years and over 90% of patients were brachycephalic. Clinical signs were variable and progressive. Relevant magnetic resonance image findings in 7/14 dogs included meningeal enhancement of affected areas and/or intraparenchymal masses. All affected dogs were euthanized because of the poor prognosis. Gross changes were reported in 12/14 cases and consisted mainly of gelatinous leptomeningeal thickening in the brain (6/12 cases) or spinal cord (2/12 cases) and 1 or multiple, gelatinous, gray to red intraparenchymal masses in the brain (6/12 cases). Histologically, all leptomeningeal neoplasms and intraparenchymal gliomas were morphologically consistent with oligodendrogliomas. Widespread nuclear immunolabeling for OLIG2 was observed in all neoplasms. The absence of an intraparenchymal glioma was consistent with PLG in 3 cases. The remaining 11 cases were diagnosed as SLG.

Telomere Length in Patients with Gestational Diabetes Mellitus and Normoglycemic Pregnant Women: a Systematic Review and Meta-analysis.

We performed a systematic review and meta-analysis of studies assessing telomere length in blood leukocytes or mononuclear cells in women with gestational diabetes mellitus (GDM) and normoglycemic pregnant women (NPW) and their infants. The review protocol was registered in PROSPERO (CRD42022300950). Searches were conducted in PubMed, Embase, LILACS, CNKI, and Wang Fang, from inception through November 2022. The primary outcomes were maternal and offspring telomere length. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Random-effect meta-analyses were applied to estimate standardized mean differences (SMDs) and their 95% confidence interval (CI). The meta-analysis of four studies showed no significant maternal telomere length difference (SMD = -0.80, 95% CI: -1.66, 0.05) in women with GDM compared to NPW. In the sensibility analysis omitting one study with a small sample of women, the telomere length becomes significantly reduced in women with GDM (SMD = -1.10, 95% CI: -2.18, -0.02). GDM patients had increased glucose (SMD = 0.28, 95% CI: 0.09, 0.46) and glycosylated hemoglobin than NPW (SMD = 0.62, 95% CI: 0.23, 1.01) while total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides did not display differences between women with and without GDM. There was no significant difference in cord blood telomere length in offspring from women with GDM and NPW (SMD = 0.11, 95% CI: -0.52, 0.30). Cord blood insulin levels (SMD = 0.59, 95% CI: 0.33, 0.85) and birthweight (SMD = 0.59, 95% CI: 0.39, 0.79) were higher in offspring from pregnant women with GDM than in those from NPW. There were no significant differences in maternal and offspring telomere length between pregnancies with and without GDM.

Inhibition of PORCN Blocks Wnt Signaling to Attenuate Progression of Oral Carcinogenesis.

PURPOSE: Oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, referred to as oral dysplasia. We recently reported that oral dysplasia is associated with aberrant activation of the Wnt/ß-catenin pathway, due to overexpression of Wnt ligands in a Porcupine (PORCN)-dependent manner. Pharmacologic inhibition of PORCN precludes Wnt secretion and has been proposed as a potential therapeutic approach to treat established cancers. Nevertheless, there are no studies that explore the effects of PORCN inhibition at the different stages of oral carcinogenesis. EXPERIMENTAL DESIGN: We performed a model of tobacco-induced oral cancer in vitro, where dysplastic oral keratinocytes (DOK) were transformed into oral carcinoma cells (DOK-TC), and assessed the effects of inhibiting PORCN with the C59 inhibitor. Similarly, an in vivo model of oral carcinogenesis and ex vivo samples derived from patients diagnosed with oral dysplasia and OSCC were treated with C59. RESULTS: Both in vitro and ex vivo oral carcinogenesis approaches revealed decreased levels of nuclear ß-catenin and Wnt3a, as observed by immunofluorescence and IHC analyses. Consistently, reduced protein and mRNA levels of survivin were observed after treatment with C59. Functionally, treatment with C59 in vitro resulted in diminished cell migration, viability, and invasion. Finally, by using an in vivo model of oral carcinogenesis, we found that treatment with C59 prevented the development of OSCC by reducing the size and number of oral tumor lesions. CONCLUSIONS: The inhibition of Wnt ligand secretion with C59 represents a feasible treatment to prevent the progression of early oral lesions toward OSCC.