Associations of COVID-19 Lockdowns on Eating Behaviors and Body Mass Index in Patients with a History of Bariatric Surgery: a Cross-Sectional Analysis.

INTRODUCTION: Few studies have explored the impact of the COVID-19 pandemic on the eating behaviors, dietary quality, and changes in weight of postoperative bariatric surgery patients. METHODS: A cross-sectional survey on eating behaviors and attitudes toward food was emailed or given to patients who had bariatric surgery before March 2020. Patient charts were reviewed for weight measures. RESULTS: Seventy-five (71.43%) patients experienced weight recurrence with an average increase in body mass index (BMI) of 2.83 kg/m2 (SD: 2.19). The majority of patients reported no symptoms of binge eating (n = 81, 77.14%) with 16 (15.24%) qualifying for loss of control eating (LOCE). LOCE was significantly associated with grazing behavior (p = 0.04), emotional over-eating (p = 0.001), and food responsiveness (p = 0.002). LOCE was negatively associated with dietary quality (p = 0.0009) and satiety responsiveness (p = 0.01). Grazing behavior was significantly associated with emotional over-eating (p < 0.0001) and food responsiveness (p < 0.0001) as well as negatively associated with dietary quality (p < 0.0001). Slow eating was negatively associated with grazing (p = 0.01), emotional over-eating (p = 0.003), and food responsiveness (p < 0.0001). When included in a regression model controlling for age and sex, emotional over-eating was a significant predictor of weight recurrence (ß = 0.25; p = 0.04). CONCLUSION: Our results suggest that maladaptive eating behaviors contributed to LOCE and poor dietary quality during the COVID-19 pandemic; however, slow eating may be protective against grazing, emotional over-eating, and food responsiveness.

Feline maxillary sarcoma: clinicopathologic features of spindle cell sarcomas from the maxilla of 25 cats.

CASE SERIES SUMMARY: Feline maxillary sarcomas are aggressive spindle cell neoplasms that occur within the maxilla, palate and upper lip of cats. This diagnosis includes fibrosarcoma and sarcomas with indeterminate histomorphology, excluding melanocytic tumors and sarcomas that can be differentiated by histomorphology. In this study of feline maxillary sarcomas in 25 cats, the cats' ages ranged from 4 to 16 years (median 12.5). These sarcomas presented as smooth thickenings or mass lesions of the gingiva and palate, often involving both the right and left quadrants of the maxilla. Radiographic bone loss was typically absent to mild at the time of diagnosis. Histologically, feline maxillary sarcomas were composed of spindle cells with varying amounts of fibrous stroma and mild inflammation. Metastasis was not documented for any cat in the study, although clinical staging was limited. Cats were often euthanized because of local recurrence following incomplete tumor excision and local tumor progression. Median survival time from the date of histologic diagnosis was 70 days (n = 12). RELEVANCE AND NOVEL INFORMATION: Feline maxillary sarcomas are aggressive neoplasms that may be difficult to differentiate from a benign, reactive process or other types of spindle cell neoplasms. Our findings indicate that feline maxillary sarcoma has distinctive clinical and histopathologic features, and the information provided in this paper will facilitate early and specific diagnosis of this tumor.

Antioxidant supplementation of mouse embryo culture or vitrification media support more in-vivo-like gene expression post-transfer.

RESEARCH QUESTION: What is the effect on mouse fetal gene expression of combined antioxidants (acetyl-L-carnitine, N-acetyl-L-cysteine and alpha-lipoic acid; A3) when used in culture media and vitrification/warming solutions? DESIGN: A laboratory-based analysis of an animal model. Embryo transfers were conducted on in-vivo-flushed blastocysts, or blastocysts cultured or vitrified with and without A3. Transcriptional profiles of E14.5 fetal liver and placental tissue in all groups were quantified using RNA-Seq and functional analyses (gene ontology [GO] biological processes and Kyoto Encyclopedia of Genes and Genomes [KEGG] pathway analysis). RESULTS: Both in-vitro culture in the presence of 20% oxygen and vitrification of blastocysts significantly perturbed fetal liver and placental gene expression. Notably, supplementation of in-vitro culture media or vitrification/warming solutions with A3 reduced the number of differentially expressed genes (DEG) and biological processes altered, establishing a more in-vivo-like gene expression profile, particularly within the E14.5 placenta. Specifically, A3 supplementation significantly reduced the expression of genes associated with pre-eclampsia and intrauterine growth restriction, along with genes involved in metabolism, cell senescence and cancer associated pathways. However, despite these improvements, several biological processes remained over-represented following both in-vitro culture and vitrification, even in the presence of A3. CONCLUSION: Both in-vitro culture in the presence of 20% oxygen and vitrification of blastocysts significantly perturbed fetal liver and placental gene expression, with the number of DEG greater following vitrification. Supplementation with A3 reduced the number of DEG and biological processes altered, establishing a more in-vivo-like gene expression profile, particularly in the placenta. Notably, A3 supplementation of in-vitro culture media significantly reduced the expression of genes associated with pre-eclampsia and intrauterine growth restriction.

A microenvironment of high lactate and low pH created by the blastocyst promotes endometrial receptivity and implantation.

RESEARCH QUESTION: Is the blastocyst's idiosyncratic metabolic production of lactate, and creation of a specialized microenvironment at the implatation site, an important mediator of maternal-fetal signalling to promote endometrial receptivity and implantation? DESIGN: Hormonally primed ECC-1 and Ishikawa cells were used to assess functional changes to the endometrial epithelium after exposure to lactic acid (LA), LA with neutralized pH (nLA) or acidic pH (pHL). Tight junction integrity (transepithelial resistance [TER]), cellular proliferation or changes to gene expression by RT-PCR were analysed. The effect of LA on Endometrial stromal cells decidualization and migratory capacity, and HUVEC endothelial tube formation and angiogenesis, were also assessed. RESULTS: Treatment of ECC-1 cells with 2.5 mM (P = 0.0037), 5 mM (P = 0.0044), 7.5 mM and 10 mM (P = 0.003) (P = 0.0021) LA significantly decreased the rate of cellular proliferation while TER was decreased with exposure to 2.5 mM LA (P = 0.024), 5 mM LA (P = 0.021) and 7.5 mM LA (P = 0.033). Exposure to nLA or pHL had no effect on proliferation or TER. Upregulation of GLUT4 (P = 0.002), GPR81 (P = 0.048), VEGF, SNAI1 (both P < 0.001) and RELA (P = 0.023) mRNA expression was observed after exposure of Ishikawa cells to combined LA plus pHL. Lactic acid increased the migratory capacity of decidualized stromal cells (P = 0.047) without changing the extent of decidualization. HUVEC tube formation was significantly increased by 5 mM LA exposure (P = 0.009). CONCLUSIONS: The identification of LA as an important mediator in the maternal-fetal dialogue underpinning implantation is supported. Further examination of the role of LA within the infertile or compromised endometrium could improve natural and assisted pregnancy success and needs further investigation.

Neoplasia and Proliferative Lesions of New World Camelids: A Systematic Literature Review and Retrospective Study of Cases Submitted to Colorado State University From 1995 to 2020.

Camelid pathology submissions to veterinary diagnostic laboratories are on the rise given the increasing popularity and population of llamas and alpacas especially in the western United States. When compared to other animals, the field of camelid neoplasia has a relative paucity of cases reported in the literature. The Colorado State University Veterinary Diagnostic Laboratories (CSU-VDL) has had a steady increase in the numbers of camelid pathology submissions allowing for a robust review of diagnoses of neoplasia in new world camelids. Here we present a retrospective analysis of camelid neoplastic and proliferative lesions diagnosed at the CSU-VDL from 1995 to 2020, followed by an extensive literature review. Results show increasing incidence of camelid neoplasia reported in the literature, therefore becoming a common diagnosis in llamas and alpacas. Proliferative and neoplastic lesions were diagnosed in 8.8% of new world camelid submissions to CSU-VDL with the most common tumors being lymphomas, squamous cell carcinomas, fibromas, and adenocarcinomas. Risk factors are female sex and increased age except in the case of lymphoma, which tends to occur in younger camelids. Lymphomas, melanomas, and adenocarcinomas (especially of gastrointestinal tract) carry an increased risk of multiple-organ system involvement often with widespread metastases. Conditions described in camelids for the first time include osteosarcoma, cutaneous hemangiosarcoma, myxosarcoma, pilomatricoma, ovarian theca cell tumor, congenital nevus with malignant transformation, and various other neoplasia. This article will provide an operational guide for camelid neoplasia to further assist veterinary laboratory diagnosticians, researchers, and practicing veterinarians in the field of camelid medicine and pathology.

A pilot study investigating a novel particle-based growth factor delivery system for preimplantation embryo culture.

STUDY QUESTION: Can vascular endothelial growth factor (VEGF)-loaded silica supraparticles (V-SPs) be used as a novel mode of delivering VEGF to the developing preimplantation embryo in vitro? SUMMARY ANSWER: Supplementation of embryo culture media with V-SPs promoted embryonic development in a manner equivalent to media supplemented with free VEGF. WHAT IS KNOWN ALREADY: VEGF is a maternally derived growth factor that promotes preimplantation embryonic development in vitro. However, its use in clinical media has limitations due to its low stability in solution. STUDY DESIGN, SIZE, DURATION: This study was a laboratory-based analysis utilising a mouse model. V-SPs were prepared in vitro and supplemented to embryonic culture media. The bioactivity of V-SPs was determined by analysis of blastocyst developmental outcomes (blastocyst development rate and total cell number). PARTICIPANTS/MATERIALS, SETTING, METHODS: SPs were loaded with fluorescently labelled VEGF and release kinetics were characterised. Bioactivity of unlabelled VEGF released from V-SPs was determined by analysis of embryo developmental outcomes (blastocyst developmental rate and total cell number) following individual mouse embryo culture in 20 µl of G1/G2 media at 5% oxygen, supplemented with 10 ng/ml recombinant mouse VEGF in solution or with V-SPs. The bioactivity of freeze-dried V-SPs was also assessed to determine the efficacy of cryostorage. MAIN RESULTS AND THE ROLE OF CHANCE: VEGF release kinetics were characterised by an initial burst of VEGF from loaded spheres followed by a consistent lower level of VEGF release over 48 h. VEGF released from V-SPs resulted in significant increases in total blastocyst cell number relative to the control (P < 0.001), replicating the effects of medium freely supplemented with fresh VEGF (P < 0.001). Similarly, freeze dried V-SPs exerted comparable effects on embryonic development (P < 0.05). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this proof of principle study, the effects of V-SPs on embryonic development were only analysed in a mouse model. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that SPs represent a novel method by which a targeted dose of therapeutic agents (e.g. bioactive VEGF) can be delivered to the developing in vitro embryo to promote embryonic development, an approach that negates the breakdown of VEGF associated with storage in solution. As such, V-SPs may be an alternative and effective method of delivering bioactive VEGF to the developing in vitro embryo; however, the potential use of V-SPs in clinical IVF requires further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the University of Melbourne. The authors have no conflict of interest to declare.

Clinical evidence based review and systematic scientific review in the identification of malignant transformation of inverted papilloma.

BACKGROUND: Inverted papilloma (IP) is an unusual type of benign tumor that has high recurrence rates and the potential to transform into squamous cell carcinomas (SCC). The mechanism of the transformation process from IP to IP-SCC is uncertain and there is no consensus regarding the best practice for IP-SCC detection. The goal of this study is to identify the best clinical methods to detect for IP-SCC. METHODS: An evidence-based review was performed using Medline and Ovid to obtain all articles up to October 10th, 2019 pertaining to identification of IP malignant transformation. All manuscripts discussing clinical methods or biomarkers were included. RESULTS: Based on clinical research studies, convoluted cerebriform pattern and apparent diffusion coefficient values on Magnetic Resonance Imaging (MRI) can help differentiate benign IP from SCC and increased SUVmax on PET/CT is associated with higher probability of malignancy although not as specific. No consensus about the best biomarker for IP-SCC has been reached among researchers and continues to be exploratory. CONCLUSION: Endoscopy with biopsy is the gold standard practice to identify IP-SCC; however, MRI is the preferred imaging modality to recognize malignant transformation in cases where biopsy is difficult. Multiple biomarkers have shown positive results, but no single indicator with clinical significance for monitoring malignant transformation process has been found.

A clinicopathological study of 17 cases of ocular surface xanthogranuloma in dogs.

OBJECTIVE: To evaluate the clinical, histopathological, and immunohistochemical features of 17 cases of ocular surface xanthogranuloma (OSX) in dogs. METHODS: Archived records from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were searched for cases of canine OSX. Cases were evaluated for lipid-laden macrophages and Touton giant cells. Seventeen cases matching those criteria were identified (1993-2018). Clinical and epidemiological data were collected from the submission forms and additional follow-up survey. RESULTS: Ocular surface xanthogranuloma in dogs presented as small bland nodules. OSX commonly occurred at the limbus (8/17) or cornea (4/17). Three of 17 affected animals were less than 1-year-old and the average age was 6.9 years (range 0.7-14 years). Fourteen of 17 cases did not report any lipid or metabolic abnormalities. Histologically, lesions were composed mainly of dense sheets of vacuolated lipid-laden macrophages and Touton giant cells with scant additional inflammatory cells and an intact overlying epithelium. No recurrence was noted in cases where complete surgical resection was achieved, and medical treatment either pre or post-resection led to only partial resolution. CONCLUSIONS: Xanthogranulomas are histiocytic lesions characterized by abundant lipid-laden macrophages. The authors use the term, ocular surface xanthogranuloma, to describe nodules with rigidly defined cellular characteristics. Although these lesions share characteristics with human limbal xanthogranulomas, further investigation is needed to suggest the different subsets that have been reported in the medical literature. Complete surgical excision is the most effective treatment for OSX in dogs, and intralesional triamcinolone and topical steroids can be useful adjunctive therapies to surgery.

Mitochondrial Fusion by M1 Promotes Embryoid Body Cardiac Differentiation of Human Pluripotent Stem Cells.

Human induced pluripotent stem cells (iPSCs) can be differentiated in vitro into bona fide cardiomyocytes for disease modelling and personalized medicine. Mitochondrial morphology and metabolism change dramatically as iPSCs differentiate into mesodermal cardiac lineages. Inhibiting mitochondrial fission has been shown to promote cardiac differentiation of iPSCs. However, the effect of hydrazone M1, a small molecule that promotes mitochondrial fusion, on cardiac mesodermal commitment of human iPSCs is unknown. Here, we demonstrate that treatment with M1 promoted mitochondrial fusion in human iPSCs. Treatment of iPSCs with M1 during embryoid body formation significantly increased the percentage of beating embryoid bodies and expression of cardiac-specific genes. The pro-fusion and pro-cardiogenic effects of M1 were not associated with changes in expression of the α and ß subunits of adenosine triphosphate (ATP) synthase. Our findings demonstrate for the first time that hydrazone M1 is capable of promoting cardiac differentiation of human iPSCs, highlighting the important role of mitochondrial dynamics in cardiac mesoderm lineage specification and cardiac development. M1 and other mitochondrial fusion promoters emerge as promising molecular targets to generate lineages of the heart from human iPSCs for patient-specific regenerative medicine.

Interplay between Metabolites and the Epigenome in Regulating Embryonic and Adult Stem Cell Potency and Maintenance.

The environment surrounding stem cells has the ability to elicit profound, heritable epigenetic changes orchestrated by multiple epigenetic mechanisms, which can be modulated by the level of specific metabolites. In this review, we highlight the significance of metabolism in regulating stem cell homeostasis, cell state, and differentiation capacity, using metabolic regulation of embryonic and adult muscle stem cells as examples, and cast light on the interaction between cellular metabolism and epigenetics. These new regulatory networks, based on the dynamic interplay between metabolism and epigenetics in stem cell biology, are important, not only for understanding tissue homeostasis, but to determine in vitro culture conditions which accurately support normal cell physiology.

Bisphenol A affects early bovine embryo development and metabolism that is negated by an oestrogen receptor inhibitor.

Increasing evidence supports an association between exposure to endocrine disruptors, such as the xenoestrogen bisphenol A (BPA), a commonly used plasticiser, and the developmental programming of offspring health. To date however animal studies to investigate a direct causal have mainly focussed on supra-environmental BPA concentrations, without investigating the effect on the early embryo. In this study we investigated the effect of acute BPA exposure (days 3.5 to 7.5 post-fertilisation) at environmentally relevant concentrations (1 and 10 ng/mL) on in vitro bovine embryo development, quality and metabolism. We then examined whether culturing embryos in the presence of the oestrogen receptor inhibitor fulvestrant could negate effects of BPA and 17ß-oestradiol (E2). Exposure to BPA or E2 (10 ng/mL) decreased blastocyst rate and the percentage of transferrable quality embryos, without affecting cell number, lineage allocation or metabolic gene expression compared to untreated embryos. Notably, blastocysts exposed to BPA and E2 (10 ng/mL) displayed an increase in glucose consumption. The presence of fulvestrant however negated the adverse developmental and metabolic effects, suggesting BPA elicits its effects via oestrogen-mediated pathways. This study demonstrates that even acute exposure to an environmentally relevant BPA concentration can affect early embryo development and metabolism. These may have long-term health consequences on an individual.

Distinct profiles of human embryonic stem cell metabolism and mitochondria identified by oxygen.

Oxygen is a powerful regulator of cell function and embryonic development. It has previously been determined that oxygen regulates human embryonic stem (hES) cell glycolytic and amino acid metabolism, but the effects on mitochondria are as yet unknown. Two hES cell lines (MEL1, MEL2) were analyzed to determine the role of 5% (physiological) and 20% (atmospheric) oxygen in regulating mitochondrial activity. In response to extended physiological oxygen culture, MEL2 hES cells displayed reduced mtDNA content, mitochondrial mass and expression of metabolic genes TFAM, NRF1, PPARa and MT-ND4. Furthermore, MEL2 hES cell glucose consumption, lactate production and amino acid turnover were elevated under physiological oxygen. In stark contrast, MEL1 hES cell amino acid and carbohydrate use and mitochondrial function were relatively unaltered in response to oxygen. Furthermore, differentiation kinetics were delayed in the MEL1 hES cell line following BMP4 treatment. Here we report the first incidence of metabolic dysfunction in a hES cell population, defined as a failure to respond to oxygen concentration through the modulation of metabolism, demonstrating that hES cells can be perturbed during culture despite exhibiting the defining characteristics of pluripotent cells. Collectively, these data reveal a central role for oxygen in the regulation of hES cell metabolism and mitochondrial function, whereby physiological oxygen promotes glucose flux and suppresses mitochondrial biogenesis and gene expression.

Low female birth weight and advanced maternal age programme alterations in next-generation blastocyst development.

Low birth weight is associated with an increased risk for adult disease development with recent studies highlighting transmission to subsequent generations. However, the mechanisms and timing of programming of disease transmission to the next generation remain unknown. The aim of this study was to examine the effects of low birth weight and advanced maternal age on second-generation preimplantation blastocysts. Uteroplacental insufficiency or sham surgery was performed in late-gestation WKY pregnant rats, giving rise to first-generation (F1) restricted (born small) and control offspring respectively. F1 control and restricted females, at 4 or 12 months of age, were naturally mated with normal males. Second-generation (F2) blastocysts from restricted females displayed reduced expression of genes related to growth compared with F2 control (P<0.05). Following 24 h culture, F2 restricted blastocysts had accelerated development, with increased total cell number, a result of increased trophectoderm cells compared with control (P<0.05). There were alterations in carbohydrate and serine utilisation in F2 restricted blastocysts and F2 restricted outgrowths from 4-month-old females respectively (P<0.05). F2 blastocysts from aged restricted females were developmentally delayed at retrieval, with reduced total cell number attributable to reduced trophectoderm number with changes in carbohydrate utilisation (P<0.05). Advanced maternal age resulted in alterations in a number of amino acids in media obtained from F2 blastocyst outgrowths (P<0.05). These findings demonstrate that growth restriction and advanced maternal age can alter F2 preimplantation embryo physiology and the subsequent offspring growth.

Oxygen-regulated expression of GLUT-1, GLUT-3, and VEGF in the mouse blastocyst.

The oxygen concentration used in the incubation atmosphere during embryo culture influences embryo development rates and embryo quality. In somatic cells, oxygen levels can influence the expression of a range of genes, including glucose transporters, glycolytic enzymes, and angiogenic growth factors. Many of these oxygen-regulated genes have important roles in embryonic development and metabolism. The aim of this study was to determine whether oxygen regulates gene expression in the preimplantation mouse blastocyst. Mouse embryos were cultured from the 1-cell to morula stage under 7% oxygen, followed by culture under 20, 7, or 2% oxygen to the blastocyst stage. Expression of glucose transporter (GLUT)-1, GLUT-3, and vascular endothelial growth factor (VEGF) in blastocysts was measured by real-time reverse transcription PCR. Development from morula to blastocyst was not altered by culture under different oxygen conditions. Expression of GLUT-1, GLUT-3, and vascular endothelial growth (VEGF) was increased by 2- to 4-fold in embryos cultured under 2% oxygen, when compared to embryos cultured under 20 or 7% oxygen, and when compared to embryos developed in vivo (all P < 0.001). These results suggest that the preimplantation mouse embryo has the capacity to detect and respond to low oxygen availability with changes in expression of oxygen-regulated genes.