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Birth Defects Research. Part A,... Aug 2012One of the more pervasive tenets of teratology is the "all-or-none" phenomenon, which refers to the concept that embryonic exposure that occurs before organogenesis... (Review)
Review
One of the more pervasive tenets of teratology is the "all-or-none" phenomenon, which refers to the concept that embryonic exposure that occurs before organogenesis results in either no adverse embryonic outcome or in embryonic death. This concept has been used extensively in genetic counseling of pregnant women who have inadvertently undergone an exposure in the very early stages of pregnancy, frequently before the pregnancy has been recognized. Herein, we review the data that supports the all-or-none concept and the exceptions to this general rule. In the absence of further human evidence to the contrary, and given the many women exposed to medications or environmental agents before learning of their pregnancies, it would be prudent to continue to counsel pregnant women using the all-or-none hypothesis to avoid needless interruption of pregnancy out of unfounded fear of an adverse pregnancy outcome.
Topics: Animals; Blastocyst; Counseling; Female; Humans; Maternal Exposure; Mutagens; Organogenesis; Radiation, Ionizing; Risk Assessment; Teratogens; Teratology; Time Factors; Zygote
PubMed: 22807395
DOI: 10.1002/bdra.23029 -
Journal of Hospital Medicine Apr 2019
Topics: Education, Medical, Graduate; Hospitals; Humans; Internship and Residency
PubMed: 30933680
DOI: 10.12788/jhm.3185 -
The Journal of Heart and Lung... May 2023
Topics: Humans; Heart-Lung Transplantation; Heart Transplantation; Graft Rejection; Lung Transplantation
PubMed: 37080658
DOI: 10.1016/j.healun.2022.10.015 -
International Journal of Molecular... Mar 2019Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed... (Review)
Review
Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of amplified breast cancers has improved meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.
Topics: Ado-Trastuzumab Emtansine; Antineoplastic Agents, Immunological; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Maytansine; Protein Kinase Inhibitors; Receptor, ErbB-2; Trastuzumab
PubMed: 30841523
DOI: 10.3390/ijms20051115 -
Investigative Ophthalmology & Visual... Jan 2022Patients diagnosed with diabetes are inclined to have abnormalities on stability of tear film and disorder of meibomian gland (MG). This study aims to explore the...
PURPOSE
Patients diagnosed with diabetes are inclined to have abnormalities on stability of tear film and disorder of meibomian gland (MG). This study aims to explore the pathological change of MG induced by diabetes in a rat model.
METHODS
Sprague-Dawley (SD) rats were intraperitoneally injected with streptozotocin (STZ) to establish a diabetic animal model. Lipid accumulation in MG was detected by Oil Red O staining and LipidTox staining. Cell proliferation status was determined by Ki67 and P63 immunostaining, whereas cell apoptosis was confirmed by TUNEL assay. Gene expression of inflammatory cytokines and adhesion molecules IL-1α, IL-1β, ELAM1, ICAM1, and VCAM1 were detected by RT-PCR. Activation of ERK, NF-κB, and AMPK signaling pathways was determined by Western Blot analysis. Oxidative stress-related factors NOX4, 4HNE, Nrf2, HO-1, and SOD2 were detected by immunostaining or Western Blot analysis. Tom20 and Tim23 immunostaining and transmission electron microscopy were performed to evaluate the mitochondria functional and structure change.
RESULTS
Four months after STZ injection, there was acini dropout in MG of diabetic rats. Evident infiltration of inflammatory cells, increased expression of inflammatory factors, and adhesion molecules, as well as activated ERK and NF-κB signaling pathways were identified. Oxidative stress of MG was evident in 4-month diabetic rats. Phospho-AMPK was downregulated in MG of 2-month diabetic rats and more prominent in 4-month rats. After metformin treatment, phospho-AMPK was upregulated and the morphology of MG was well maintained. Moreover, inflammation and oxidative stress of MG were alleviated after metformin intervention.
CONCLUSIONS
Long-term diabetes may lead to Meibomian gland dysfunction (MGD). AMPK may be a therapeutic target of MGD induced by diabetes.
Topics: Animals; Blood Glucose; Cytokines; Disease Models, Animal; Hyperglycemia; Male; Meibomian Gland Dysfunction; Meibomian Glands; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 35072689
DOI: 10.1167/iovs.63.1.30 -
The American Journal of Bioethics : AJOB Aug 2022
Topics: Education, Medical; Female; Humans; Physicians; Pregnancy
PubMed: 35917422
DOI: 10.1080/15265161.2022.2089282 -
Journal of Cachexia, Sarcopenia and... Feb 2019This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings.
RATIONALE
This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings.
METHODS
In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications.
RESULTS
A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories.
CONCLUSION
A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.
Topics: Adult; Body Mass Index; Consensus; Eating; Global Health; Humans; Malnutrition; Phenotype; Sarcopenia; Weight Loss
PubMed: 30920778
DOI: 10.1002/jcsm.12383 -
Acta Crystallographica. Section E,... Sep 2008The title compound, C(25)H(28)O(7), was prepared by the base-catalysed reaction of 3,4,5-trimethoxy-benzaldehyde with cyclo-penta-none. The mol-ecule has...
The title compound, C(25)H(28)O(7), was prepared by the base-catalysed reaction of 3,4,5-trimethoxy-benzaldehyde with cyclo-penta-none. The mol-ecule has crystallographic twofold rotation symmetry and adopts an E-configuration about the central olefinic bonds. The two benzene rings and the central cyclo-penta-none ring are almost coplanar [dihedral angle = 4.7 (2)°].
PubMed: 21201165
DOI: 10.1107/S1600536808029474 -
Investigative Ophthalmology & Visual... Feb 2021To describe the molecular epidemiology of nonsyndromic retinitis pigmentosa (RP) and Usher syndrome (US) in Italian patients.
PURPOSE
To describe the molecular epidemiology of nonsyndromic retinitis pigmentosa (RP) and Usher syndrome (US) in Italian patients.
METHODS
A total of 591 probands (315 with family history and 276 sporadics) were analyzed. For 155 of them, we performed a family segregation study, considering a total of 382 relatives. Probands were analyzed by a customized multigene panel approach. Sanger sequencing was used to validate all genetic variants and to perform family segregation studies. Copy number variants of selected genes were analyzed by multiplex ligation-dependent probe amplification. Four patients who tested negative to targeted next-generation sequencing analysis underwent clinical exome sequencing.
RESULTS
The mean diagnostic yield of molecular testing among patients with a family history of retinal disorders was 55.2% while the diagnostic yield including sporadic cases was 37.4%. We found 468 potentially pathogenic variants, 147 of which were unpublished, in 308 probands and 66 relatives. Mean ages of onset of the different classes of RP were autosomal dominant RP, 19.3 ± 12.6 years; autosomal recessive RP, 23.2 ± 16.6 years; X-linked RP, 13.9 ± 9.9 years; and Usher syndrome, 18.9 ± 9.5 years. We reported potential new genotype-phenotype correlations in three probands, two revealed by TruSight One testing. All three probands showed isolated RP caused by biallelic variants in genes usually associated with syndromes such as PERCHING and Senior-Loken or with retinal dystrophy, iris coloboma, and comedogenic acne syndrome.
CONCLUSIONS
This is the largest molecular study of Italian patients with RP in the literature, thus reflecting the epidemiology of the disease in Italy with reasonable accuracy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; DNA Mutational Analysis; Extracellular Matrix Proteins; Female; Follow-Up Studies; Genetic Association Studies; Genetic Testing; Humans; Incidence; Italy; Male; Middle Aged; Molecular Epidemiology; Mutation; Pedigree; Phenotype; Retinitis Pigmentosa; Retrospective Studies; Usher Syndromes; Exome Sequencing; Young Adult
PubMed: 33576794
DOI: 10.1167/iovs.62.2.13 -
Journal of Clinical Anesthesia Dec 2023
PubMed: 37769408
DOI: 10.1016/j.jclinane.2023.111266