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The prevalence of Beckwith-Wiedemann spectrum (BWSp) is tenfold increased in children conceived through assisted reproductive techniques (ART). More than 90% of ART-BWSp patients reported so far display imprinting center 2 loss-of-methylations (IC2-LoM), versus 50% of naturally conceived BWSp patients. We describe a cohort of 74 ART-BWSp patients comparing their features with a cohort of naturally conceived BWSp patients, with the ART-BWSp patients previously described in literature, and with the general population of children born from ART. We found that the distribution of UPD(11)pat was not significantly different in ART and naturally conceived patients. We observed 68.9% of IC2-LoM and 16.2% of mosaic UPD(11)pat in our ART cohort, that strongly differ from the figure reported in other cohorts so far. Since UPD(11)pat likely results from post-fertilization recombination events, our findings allows to hypothesize that more complex molecular mechanisms, besides methylation disturbances, may underlie BWSp increased risk in ART pregnancies. Moreover, comparing the clinical features of ART and non-ART BWSp patients, we found that ART-BWSp patients might have a milder phenotype. Finally, our data show a progressive increase in the prevalence of BWSp over time, paralleling that of ART usage in the last decades., (© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Health systems provides care only to those people who spontaneous demand for attention; excluding those who dont perceive illness or are not aware enough to consult. Alternative healthcare models based on the nominal-personalized care like "University Center for Integrated Care of Referred Health Care" (CUIDARAS) may have better results. In order to demonstrate benefits of this model, it was performed an experience based in colorectal cancer (CRC) detection and care that focused the entire population of the town., Methods: It is an intervention study for early detection of CRC. A survey and a physical examination were performed in each adult from "CH" town. Two visits were made. Blood in stool test (BIST) was self-collected, analyzed and results delivered with appointment for a programmed video-colonoscopy (VCC) when test was positive., Results: people enrolled (n546) had 59.9+/-6.4 yrs. Adherence was 93.8% of the target population; 99.2% performed BIST; while 95.3% a positive BIST had access to VCC and treatment. Overall cost of the experience (stool test, VCC, biopsy, local treatment) was 7685 USD, while costs associated to an advanced CRC classic treatment was USD 9577/patient (USD 26098 if treatment included bevacizumab)., Conclusion: The present study based on preventive actions like blood in stool test, applied as a screening to all inhabitants in town, had 93.8% of adherence and high level of CRC early detection. A health model based on personalized care (CUIDARAS), achieved more effective results in terms health care and disease prevention, with a favorable benefit/cost ratio compared with classical health care provide by current system. Key words: Model of care; colorectal cancer; CUIDARAS; personalized care.

SARS-CoV-2 variants with concerning characteristics have emerged since the end of 2020. Surveillance of SARS-CoV-2 variants was performed on a total of 4,851 samples from the capital city and 10 provinces of Argentina, during 51 epidemiological weeks (EWs) that covered the end of the first wave and the ongoing second wave of the COVID-19 pandemic in the country (EW 44/2020 to EW 41/2021). The surveillance strategy was mainly based on Sanger sequencing of a Spike coding region that allows the identification of signature mutations associated with variants. In addition, whole-genome sequences were obtained from 637 samples. The main variants found were Gamma and Lambda, and to a lesser extent, Alpha, Zeta, and Epsilon, and more recently, Delta. Whereas, Gamma dominated in different regions of the country, both Gamma and Lambda prevailed in the most populated area, the metropolitan region of Buenos Aires. The lineages that circulated on the first wave were replaced by emergent variants in a term of a few weeks. At the end of the ongoing second wave, Delta began to be detected, replacing Gamma and Lambda. This scenario is consistent with the Latin American variant landscape, so far characterized by a concurrent increase in Delta circulation and a stabilization in the number of cases. The cost-effective surveillance protocol presented here allowed for a rapid response in a resource-limited setting, added information on the expansion of Lambda in South America, and contributed to the implementation of public health measures to control the disease spread in Argentina., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Torres, Mojsiejczuk, Acuña, Alexay, Amadio, Aulicino, Debat, Fay, Fernández, Giri, Goya, König, Lucero, Nabaes Jodar, Pianciola, Sfalcin, Acevedo, Bengoa Luoni, Bolatti, Brusés, Cacciabue, Casal, Cerri, Chouhy, Dus Santos, Eberhardt, Fernandez, Fernández, Fernández Do Porto, Formichelli, Gismondi, Irazoqui, Campos, Lusso, Marquez, Muñoz, Mussin, Natale, Oria, Pisano, Posner, Puebla, Re, Sosa, Villanova, Zaiat, Zunino, Acevedo, Acosta, Alvarez Lopez, Álvarez, Angeleri, Angelletti, Arca, Ayala, Barbas, Bertone, Bonnet, Bourlot, Cabassi, Castello, Castro, Cavatorta, Ceriani, Cimmino, Cipelli, Colmeiro, Cordero, Cristina, Di Bella, Dolcini, Ercole, Espasandin, Espul, Falaschi, Fernandez Moll, Foussal, Gatelli, Goñi, Jofré, Jaramillo, Labarta, Lacaze, Larreche, Leiva, Levin, Luczak, Mandile, Marino, Massone, Mazzeo, Medina, Monaco, Montoto, Mugna, Musto, Nadalich, Nieto, Ojeda, Piedrabuena, Pintos, Pozzati, Rahhal, Rechimont, Remes Lenicov, Rompato, Seery, Siri, Spina, Streitenberger, Suárez, Suárez, Sujansky, Talia, Theaux, Thomas, Ticeira, Tittarelli, Toro, Uez, Zaffanella, Ziehm, Zubieta, Mistchenko, Valinotto and Viegas.)

Background: IgG4-related disease can manifest diversely, including autoimmune pancreatitis and IgG4-related cholangiopathy. We are reporting a very unusual cause of pancreatic cancer triggered in a previously unknown IgG4-related disease., Case Summary: A 75-year-old man was diagnosed with a 43 mm × 33 mm pancreatic head tumor after consulting for abdominal pain and jaundice. A pancreaticoduodenectomy was carried out uneventfully, and the histopathology report showed an early stage of acinar-cell pancreatic cancer. The patient reconsulted on the 30 th postoperative day with fever, jaundice and asthenia. Magnetic resonance cholangiopancreatography evidenced an extense bile duct stricture. A percutaneous biliary drainage proved to be ineffective, even after exchanging it with larger bore drainage. Reviewing the surgical specimen, features compatible with IgG4-related disease were observed. Consequently, empiric treatment with steroids was initiated achieving excellent results., Conclusion: IgG4-related disease may cause chronic inflammation of the pancreas and can condition pancreatic malignancies., Competing Interests: Conflict-of-interest statement: The authors declare that no conflict of interest exists., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications., Case Summary: A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up., Conclusion: HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated., Competing Interests: Conflict-of-interest statement: The authors declare that no conflict of interest exists.

The objective of this experimental study was to evaluate the effects of cricoarytenoid (CA) joint preservation versus disarticulation on rima glottidis (RG) area with the epiglottis open and closed under both low and high suture tension. Canine cadaver larynges were used. A unilateral arytenoid lateralization (UAL) was performed with low or high suture tension and with the CA joint preserved or disarticulated. Rima glottidis area was measured with the epiglottis in an open and closed position. Results indicated that RG area was increased over baseline when UAL was performed with both low and high suture tension when the epiglottis was in an open position. High suture tension resulted in a greater increase in RG area compared to low suture tension, both when the CA was preserved and disarticulated. There was no difference in RG area when the CA was disarticulated versus preserved at either suture tension. Rima glottidis area was not significantly increased over baseline when the epiglottis was in a closed position except in the group with CA joint preservation and high suture tension. Although this study suggests that UAL can be performed with or without CA disarticulation, further studies are warranted before UAL without CA disarticulation can be recommended clinically.

Objective: Evaluate the effect of a perioperative intravenous continuous rate infusion (CRI) of metoclopramide on the incidence of aspiration pneumonia in the short term postoperative period in dogs undergoing unilateral arytenoid lateralization., Study Design: Prospective, randomized, multi-center clinical trial., Animals: 61 client-owned dogs with idiopathic laryngeal paralysis and normal preoperative thoracic radiographs., Methods: All dogs underwent unilateral arytenoid lateralization with a uniform anesthetic, analgesic, and management protocol. Dogs in the treatment group received an intravenous CRI of metoclopramide for 24 hours perioperative. All dogs were assessed for clinical signs of aspiration pneumonia based on the results of physical examination and owner interview up to the point of suture removal (10-14 days postoperative). Any dog with suspected aspiration pneumonia had thoracic radiographs performed., Results: Six dogs developed aspiration pneumonia in the short term postoperative period (2/28 control dogs and 4/33 treated dogs), accounting for an overall frequency of 10% with no significant difference between control and treated dogs. No variables measured in the study were significantly different between control and treated dogs., Conclusions: Perioperative metoclopramide, at the doses used in this study, did not affect the incidence of aspiration pneumonia in the short term postoperative period in dogs with idiopathic laryngeal paralysis undergoing unilateral arytenoid lateralization., (© Copyright 2016 by The American College of Veterinary Surgeons.)

Background: MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated., Objective: We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients., Methods: We isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations., Results: Of the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex-stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development., Conclusions: Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.

Age-friendly initiatives are increasingly promoted as a policy solution to healthy aging, The primary objective of this article was to examine older adults' and key stakeholders' perceptions of the factors that either help or hinder a community from becoming age-friendly in the context of rural Manitoba, a Canadian prairie province. Twenty-four older adults and 17 key informants completed a qualitative interview. The findings show that contextual factors including size, location, demographic composition, ability to secure investments, and leadership influence rural communities' ability to become age-friendly. Government must consider the challenges these communities face in becoming more age-friendly and develop strategies to support communities., (© The Author(s) 2013.)

Objective: To determine the in vitro effects of differing growth factor treatments on the fibrochondrogenic potential of fibroblast-like synoviocytes from cruciate ligament deficient femorotibial joints of dogs., Study Design: In vitro study., Sample Population: Synoviocytes from dogs (n = 8) with naturally occurring cruciate ligament insufficiency., Methods: Synoviocytes were cultured in monolayer and synthesized into tensioned synoviocyte bioscaffolds (TSB) suspended in media containing TGF-β3, or FGF-2, TGF-β1, and IGF-I. The 1,9-dimethylmethylene blue (DMMB) assay and toluidine blue stain assessed glycosaminoglycan content; hydroxyproline assay, and collagen I and II immunohistochemistry assessed collagen content. Biomechanical properties were determined by materials testing/force-deformation curves., Results: All tissue cultures formed tensioned fibrous tissue-like constructs. Mean tissue cellularity and cellular viability was significantly greater in the triple growth factor-treated TSB by 0.09% and 44%, respectively. Percentage collagen content, and relative gene expression for collagen I, II, and aggrecan was not significantly different between groups. Median percentage of GAG content was significantly greater in triple growth factor-treated TSB by 1.6%. Biomechanical properties were not different in compression. Triple growth factor-treated TSB were significantly stronger in toughness, peak load to failure, and stiffness in tension., Conclusions: TGF-β3 cultured bioscaffolds failed to outperform triple growth factor-treated TSB. Architectural extracellular matrix (ECM) organization and cellularity likely explained the differences between groups. TGF-β3 alone cannot be recommended at this time for in vitro formation of autologous fibrocartilage bioscaffolds for meniscal deficiency., (© Copyright 2014 by The American College of Veterinary Surgeons.)

Meniscal injury is a common cause of canine lameness. Tissue engineered bioscaffolds may be a treatment option for dogs suffering from meniscal damage. The aim of this study was to compare in vitro meniscal-like matrix formation and biomechanical properties of porcine intestinal submucosa sheets (SIS), used in canine meniscal regenerative medicine, to synoviocyte-seeded SIS bioscaffold (SSB), cultured with fetal bovine serum (SSBfbs) or chondrogenic growth factors (SSBgf). Synoviocytes from nine dogs were seeded on SIS and cultured for 30days with 17.7% fetal bovine serum or recombinant chondrogenic growth factors (IGF-1, TGFβ1 and bFGF). The effect on fibrochondrogenesis was determined by comparing mRNA expression of collagen types Iα and IIα, aggrecan, and Sry-type homeobox protein-9 (SOX9) as well as protein expression of collagens I and II, glycosaminoglycan (GAG), and hydroxyproline. The effect of synoviocyte seeding and culture conditions on biochemical properties was determined by measuring peak load, tensile stiffness, resilience, and toughness of bioscaffolds. Pre-culture SIS contained 13.6% collagen and 2.9% double-stranded DNA. Chondrogenic growth factor treatment significantly increased SOX9, collagens I and IIα, aggrecan gene expression (P<0.05), and histological deposition of fibrocartilage extracellular matrix (GAG and collagen II). Culture with synoviocytes increased SIS tensile peak load at failure, resilience, and toughness of bioscaffolds (P<0.05). In conclusion, culturing SIS with synoviocytes prior to implantation might provide biomechanical benefits, and chondrogenic growth factor treatment of cultured synoviocytes improves in vitro axial meniscal matrix formation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. It is the most common endocrine disorder in women of reproductive age with an enigmatic pathophysiologic and molecular basis. The high prevalence of affected individuals and the wide range of phenotypic expression can be explained by the interaction of a number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various population groups (ethnic groups, twins, and PCOS families). Although evidence of familial segregation and clustering of the disease in first-degree relatives of women diagnosed with PCOS has been presented, no particular pattern of inheritance has emerged. Some of the problems in genetic studies have been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features, and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify the propositus and to determine affected status in the kindred, the genetic studies available suggest a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.

Fibronectin in the extracellular matrix of tissues acts as a substrate for cell adhesion and migration during development. Heterogeneity in the structure of fibronectin is largely due to the alternative splicing of at least three exons (IIIB, IIIA, and V) during processing of a single primary transcript. Fibronectin mRNA alternative splicing patterns change from B+A+V+ to B+A-V+ during chondrogenesis. In this report, immunohistochemical analysis demonstrates that while fibronectin protein containing the region encoded by exon IIIB is present throughout the limb at all stages of development, fibronectin protein containing the region encoded by exon IIIA disappears from cartilaginous regions just after condensation in vivo and in high-density mesenchymal micromass cultures in vitro. Treatment of mesenchymal micromass cultures prior to condensation with an antibody specific for the region encoded by exon IIIA disrupts the formation of cellular condensations and inhibits subsequent chondrogenesis in a dose- and time-dependent manner. Furthermore, microinjection of the exon IIIA antibody into embryonic chick limb primordia in vivo results in malformations characterized by smaller limbs and loss of limb skeletal elements. These results strongly suggest that the presence of the region encoded by exon IIIA in mesenchymal fibronectin is necessary for the condensation event that occurs during chondrogenesis., (Copyright 1997 Academic Press.)

Polycystic ovary (PCO) syndrome is strongly associated with insulin resistance and the accompanying adverse metabolic profile. To distinguish the mechanisms of this association, we determined the interactions of PCO with obesity and the influence of ameliorating direct androgenic actions via short-term treatment with the antiandrogen flutamide. Insulin sensitivity was determined by the hyperinsulinemic euglycemic clamp in groups of lean and obese PCO women and weight-matched controls. Compared with control values, insulin-mediated glucose utilization in PCO women was significantly lower in lean (1.96 +/- 0.17 v 1.24 +/- 0.10, P < .01) and obese (1.23 +/- 0.18 v 1.03 +/- 0.09 mmol/m2/min, P < .01) subjects. ANOVA indicated that the effects of obesity and androgenicity are independent and additive. In both lean and obese PCO women, treatment with flutamide for 1 or 3 months markedly improved the clinical and biochemical androgenic features, but did not significantly influence the overall insulin sensitivity. A large disparity between individuals in the response to treatment correlated significantly with a simultaneous reduction in plasma levels of dehydroepiandrosterone sulfate (DHEA-S). Thus in women, PCO and obesity exert synergistic effects on insulin resistance. The decreased insulin sensitivity is mediated via indirect androgenic actions or nonandrogenic mechanisms. In some individuals, a direct effect of androgens might have been masked by a decrease in DHEA-S levels.

A prospective study of choledocholithiasis was performed using 110 patients with presumptive diagnoses of acute gallstone pancreatitis. The incidence of migrating and persistent bile duct stones was determined using stool screening and intraoperative cholangiography, and the clinical significance of continued stone obstruction of the papilla was investigated using ultrasound assessment of migration time and a second evaluation of prognostic signs. Pancreatic inflammation was confirmed at surgery in 51 patients, of whom only 27 had stones in the stools (n = 22) or the bile duct (n = 5), suggesting that choledocholithiasis may not be the sole triggering factor of acute gallstone pancreatitis. Neither delayed migration nor persistent stone obstruction of the papilla promoted pancreatic inflammation.