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Progesterone depletion ends in Lamin B1 loss as well as induction involving cellular dying inside mouse button trophoblast massive tissues.
BRAF and MEKis have revolutionized the management of BRAFV600 -mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF-D) related to these treatments has not been thoroughly evaluated to date. The main objective of this study was to describe characteristics of LVEF-D in melanoma patients treated with BRAF and/or MEKis. Metastatic melanoma patients treated with BRAF and/or MEKis between March 1, 2012 and May 18, 2018 were included retrospectively (Lyon Sud University Hospital, Hospices Civils de Lyon). LVEF-D was defined as a reduction in LVEF ≥10% from baseline to a value less then 55%; normalization was defined as a value ≥55%. Among the 88 patients included, 12 (13.6%) experienced a LVEF-D, including 10 grade 2 and 2 grade 3. The median onset of which was 11 months (IQR [3-21]). No patient previously treated with beta-blockers (n = 12) experienced a LVEF-D. Analysis of laboratory parameters, electrocardiogram, and transthoracic echocardiography during the follow-up did not find any predictive marker of LVEF-D. All patients who benefited from a specific treatment of LVEF-D had a normalization of LVEF at the end of follow-up. LVEF recovery was significantly better for patients treated with angiotensin converting enzyme inhibitors and beta-blockers than those who did not (P = .019). Ophthalmological adverse events were significantly more frequent in patients who experienced a LVEF-D (P = .006) and the latter did not influence overall-survival (P = .117) or progression-free-survival (P = .297). LVEF-D is a common and easily manageable adverse event due to BRAF and MEKis. Its association with ocular toxicity suggests a close ophthalmological monitoring when LVEF-D occurs. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.BACKGROUND Chorea-acanthocytosis (ChAc; OMIM #200150) is a rare autosomal recessive condition with onset in early adulthood that is caused by mutations in the vacuolar protein sorting 13A (VPS13A) gene encoding chorein. Several diagnostic genomic DNA (gDNA) sequencing approaches are widely used. However, their limitations appear not to be acknowledged thoroughly enough. METHODS Clinically, we deployed magnetic resonance imaging, blood smear analysis, and clinical chemistry for the index patient's characterization. The molecular analysis of the index patient next to his parents covered genomic DNA (gDNA) sequencing approaches, RNA/cDNA sequencing, and chorein specific Western blot. RESULTS We report a 33-year-old male patient without functional protein due to compound heterozygosity for two VPS13A large deletions of 1168 and 1823 base pairs (bp) affecting, respectively, exons 8 and 9, and exon 13. To our knowledge, this represents the first ChAc case with two compound heterozygous large deletions identified so far. Of note, standard genomic DNA (gDNA) Sanger sequencing approaches alone yielded false negative findings. CONCLUSION Our case demonstrates the need to carry out detection of chorein in patients suspected of having ChAc as a helpful and potentially decisive tool to establish diagnosis. Furthermore, the course of the molecular analysis in this case discloses diagnostic pitfalls in detecting some variations, such as deletions, using only standard genomic DNA (gDNA) Sanger sequencing approaches and exemplifies alternative methods, such as RNA/cDNA sequencing or qRT-PCR analysis, necessary to avoid false negative results. © 2020 The Authors. Linsitinib IGF-1R inhibitor Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.Eating habits begin forming early in life when parental beliefs and behaviours often play a major role in shaping dietary intake. We aimed to assess maternal beliefs about the cost, social status, and nutritional value of foods in Samoa-a setting with an alarming burden of childhood obesity-and to determine how those beliefs may be related to child dietary intake. Samoan mothers (n = 44) sorted photographs of 26 foods commonly consumed in children in Samoa by cost, social status, and nutritional value (healthfulness). Responses were then assessed for their association with child dietary intake (reported using a food frequency questionnaire) using Pearson correlations. Mothers indicated that traditional Samoan foods were healthier, of higher social status, and lower cost compared with non-traditional/imported food items. Compared with nutritional experts and a market survey of food prices, mothers demonstrated strong nutritional (r = .87, 95% CI [0.68, 0.95], p less then .001) and consumer (r = .84, 95% CI [0.68, 0.93], p less then .001) knowledge. The perceived cost of food was more strongly associated (r = -.37, 95% CI [-0.66, 0.02], p = .06) with child dietary intake than either healthfulness or social status, with decreasing consumption reported with increasing food cost. Our findings contradicted the notion that the high social status of imported foods may be contributing to increased intake and rising prevalence of childhood obesity in this developing country setting. Despite their nutritional knowledge, Samoan mothers may need additional support in applying their knowledge/beliefs to provide a healthy child diet, including support for access to reasonably priced healthy foods. © 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.A 12-year-old female Shih-tzu dog was presented with a 2-month history of cutaneous non-pruritic multiple ulcerated or crusted nodules of less than 1.5 cm in diameter on eyelids, lips, abdomen, groin, thighs and perianal region. Several diagnostic tests were performed, including fine needle aspiration and skin biopsy of the cutaneous nodules. Cytologic interpretation was round cell neoplasm with multilobated (clover-leaf shaped) nuclei. Histopathology revealed round neoplastic cells with prominent anisocytosis and anisokaryosis, and numerous mitotic figures; however, the origin of the cells was not identified. Immunohistochemical evaluation indicated that these cells were positive for CD79a and MUM-1, but negative for CD3, CD20 and Pax 5. The patient was treated with chemotherapy, and the skin condition improved. Despite good response to chemotherapy, the patient was euthanized due to poor general health. © 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.INTRODUCTION Three-dimensional (3D) printed models can be constructed utilising computed tomography (CT) data. This project aimed to determine the effect of changing the slice reconstruction interval (SRI) on the spatial replication accuracy of 3D-printed anatomical models constructed by fused deposition modelling (FDM). METHODS Three bovine vertebrae and an imaging phantom were imaged using a CT scanner. The Queensland State Government's Animal Care and Protection Act 2001 did not apply as no animals were harmed to carry out scientific activity. The data were reconstructed into SRIs of 0.1, 0.3, 0.5 and 1 mm and processed by software before 3D printing. Specimens and printed models were measured with calipers to calculate mean absolute error prior to statistical analysis. RESULTS Mean absolute error from the original models for the 0.1, 0.3, 0.5 and 1 mm 3D-printed models was 0.592 ± 0.396 mm, 0.598 ± 0.479 mm, 0.712 ± 0.498 mm and 0.933 ± 0.457 mm, respectively. Paired t-tests (P less then 0.05) indicated a statistically significant difference between all original specimens and corresponding 3D-printed models except the 0.1 mm vertebrae 2 (P = 0.061), 0.3 mm phantom 1 (P = 0.209) and 0.3 mm vertebrae 2 (P = 0.097). CONCLUSION This study demonstrated that changing the SRI influences the spatial replication accuracy of 3D-printed models constructed by FDM. Matching the SRI to the primary spatial resolution limiting factor of acquisition slice width or printer capabilities optimises replication accuracy. © 2020 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.Renin is the rate-limiting enzyme of the renin-angiotensin system (RAS) cascade, which drives the pathophysiological progression of heart failure. Species differences in the amino acid sequence of the catalytic domain of renin limit evaluations of the potency and efficacy of human renin inhibitors in animal models, and a high dose of inhibitors is usually needed to show its organ protective effects in rodents. In the present study, we developed a novel murine heart failure model (triple-tg) to enable us to evaluate the cardioprotective effect of renin inhibitors at more relevant doses for humans, by cross-breeding calsequestrin transgenic (CSQ-tg) mice with human renin and human angiotensinogen double transgenic mice. The triple-tg mice exhibited increased plasma renin activity (PRA), worsened cardiac hypertrophy, and higher mortality compared to CSQ-tg mice. Triple-tg mice treated with 10 mg/kg of TAK-272 (imarikiren / SCO-272), an orally active direct renin inhibitor, exhibited improvements in heart failure phenotypes, such as cardiac hypertrophy and survival rate; however, a dose of 300 mg/kg was required to improve symptoms in CSQ-tg mice. Our results suggest that this newly generated triple-tg heart failure model is useful to evaluate the cardioprotective effects of human renin inhibitors at clinically relevant doses, thereby minimizing the concerns of off-target effects related to much higher drug exposure than that achieved in clinical study. This article is protected by copyright. All rights reserved.BACKGROUND Congenital aniridia involves total or partial hypoplasia of the iris and is due to a deficiency in PAX6 gene expression. WAGR syndrome is comprised of Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. Numerous genitourinary pathologies may be associated with WAGR syndrome, necessitating an evaluation of the genitourinary anatomy. The WT1 is vital for the development of kidneys, ovaries in females, and testes in males. WT1 gene mutations result in a WT1 protein with a decreased ability to bind to DNA, leading to uncontrolled growth, and cell division in the kidney which permits the development of Wilms tumor. A congenital ureteral valve is an exceedingly rare cause of obstructive uropathy. RESULTS A renal and bladder ultrasound demonstrated a renal cyst. A voiding cystourethrogram revealed grade 3 vesicoureteral reflux, and a MAG3 renal scan showed ureteropelvic junction obstruction and hydronephrosis. A ureteral stent was inserted at 3 months of age after which the renal cyst resolved. The patient was urinary tract infection-free at 27 months of age. Genetic testing confirmed a heterozygous alteration in PAX6 (c.495delG, p.Thr166Leufs*41) and no abnormalities of WT1, excluding WAGR syndrome. CONCLUSION The genitourinary risks potentially associated with aniridia necessitate prompt genetic analysis to evaluate for WAGR syndrome. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.INTRODUCTION Elevated levels of pro-inflammatory cytokines have been reported in meta-analyses of multi-episode schizophrenia patients when compared to controls. However, little is known about whether these same relationships are present in the early course of schizophrenia. OBJECTIVE To assess first episode schizophrenia patients for depression and to assay blood samples collected at baseline and at 6 months for interleukin-6 (IL-6). MATERIALS AND METHODS Trained raters used the Brief Psychiatric Rating Scale to assess depressive symptoms and a standard lab assay kit to assess for IL-6 levels in plasma. CONCLUSIONS Decreases in pro-inflammatory IL-6 levels were significantly related to decreases in depressive symptoms. Within a subset of patients in a 6-month aerobic exercise protocol, the number of exercise sessions completed was significantly correlated with the amount of decrease in IL-6. The reductions observed in IL-6 with aerobic exercise suggest exercise is a promising intervention to reduce brain inflammation effects in schizophrenia patients.
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