Primordial dwarfism (PD) is a clinically and genetically heterogeneous condition. Various molecular mechanisms are known to underlie the disease including impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA damage response, defective spliceosomal machinery, and abnormal replication licensing. Here, we describe a syndromic form of PD associated with severe intellectual disability and distinct facial features in a large multiplex Saudi family. Analysis reveals a novel underlying mechanism for PD involving depletion of 7SK, an abundant cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show that 7SK levels are tightly linked to LARP7 expression across cell lines, and that this chaperone is ubiquitously expressed in the mouse embryo. The 7SK is known to influence the expression of a wide array of genes through its inhibitory effect on the positive transcription elongation factor b (P-TEFb) as well as its competing role in HMGA1-mediated transcriptional regulation. This study documents a critical role played by ncRNA in human development and adds to the growing list of molecular mechanisms that, when perturbed, converge on the PD phenotype.
Cortical blindness as a complication of hemodialysis is not widely known, though visual disturbances related to uremia have been known for a long time. We recently observed cortical blindness caused by bilateral occipital infarcts in a patient after hemodialysis.
PurposeTo estimate the prevalence of amblyopia among medical students in Saudi Arabia, and investigate the impact of amblyopia on their Academic performance.MethodsThis is a cross-sectional study which targeted 478 of male medical students from the College of Medicine at King Khalid University. A questionnaire was used to investigate the demographics of participants. Distance visual acuity was assessed monocularly using tumbling “E” chart in all participants. Then detailed ophthalmic evaluation was performed for any student with two or more lines difference between the two eyes or visual acuity of ≤20/40 in either eye.ResultsA sample of 478 male medical students, of whom 12(2.5%) were found to have amblyopia. Anisometropic amblyopia was the most common type (10/12, 83.3%) followed by strabismic amblyopia (2/12, 16.7%). There is a significant relation between past ocular history and amblyopia (p-value = 0.008). Up to 25% of amblyopic students not diagnosed before and 25% of them agree that amblyopia affects their social & psychiatric status. There was no effect of amblyopia on the academic performance (P-value = 0.5).ConclusionAmblyopia was found in 2.5% of male medical students. Amblyopia had a moderate effect on the students' lives, but it did not affect their academic performance.
Injury to lacrimal glands represents a major health problem after radiation therapy of the head and neck malignancies. Accordingly, this study aimed to investigate significant ultrastructural changes of lacrimal glands and some of their underlying mechanisms following the exposure to different fractionated doses of irradiation. In this study, 28 Sprague Dawley (SD) rats were assigned to four groups (seven rats each): Group I acted as control and received no irradiation. Groups II-IV received fractionated irradiation of 5 Gy (100 cGy/fraction daily for 5 days), 9 Gy (300 cGy/fraction daily for 3 days), and 20 Gy (one fraction), respectively. One month after the experiment, examination of lacrimal glands with transmission electron microscopy (TEM) demonstrated dose-dependent ultrastructural changes in the lacrimal acinar and intralobular ductal epithelial cells. In the acinar cells, there were swollen rough endoplasmic reticulum, irregularly shaped nuclei with chromatin condensation, mitochondrial damage, and retention of secretory granules. Intaralobular ductal epithelial cells showed loss of surface microvilli and damage to mitochondria. In addition to the potential direct effects of irradiation on lacrimal acinar and intralobular ductal epithelial cells, damage to blood vessels and nerve endings seemed to mediate some of the underlying mechanisms of these irradiation-induced ultrastructural changes. In conclusion, using TEM reveals that lacrimal gland is highly sensitive to even small doses of irradiation therapy; in addition, swelling of rough endoplasmic reticulum and aberrant nuclei are the most encountered structural changes. Damage to blood vessels and nerve endings might mediate some of the underlying mechanisms of irradiation-induced secondary injury in lacrimal glands.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.