A homozygous SP7/OSX mutation causes osteogenesis and dentinogenesis imperfecta with craniofacial anomalies.

Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects of type 1 collagen, a triple helix composed of two α1 and one α2 chains encoded by COL1A1 and COL1A2, respectively. The main extra-skeletal manifestations of OI include blue sclerae, opalescent teeth, and hearing impairment. Moreover, multiple genes involved in osteoblast maturation and type 1 collagen biosynthesis are now known to cause recessive forms of OI. In this study a multiplex consanguineous family of two affected males with OI was recruited for genetic screening. To determine the causative, pathogenic variant(s), genomic DNA from two affected family members were analyzed using whole exome sequencing, autozygosity mapping, and then validated with Sanger sequencing. The analysis led to the mapping of a homozygous variant previously reported in SP7/OSX, a gene encoding for Osterix, a transcription factor that activates a repertoire of genes involved in osteoblast and osteocyte differentiation and function. The identified variant (c.946C > T; p.Arg316Cys) in exon 2 of SP7/OSX results in a pathogenic amino acid change in two affected male siblings and develops OI, dentinogenesis imperfecta, and craniofacial anomaly. On the basis of the findings of the present study, SP7/OSX:c. 946C > T is a rare homozygous variant causing OI with extra-skeletal features in inbred Arab populations.

Ventilator associated lung injury in severe COVID-19 pneumonia patients - Case Reports: Ventilator associated lung injury in COVID-19.

Management of severe coronavirus disease 2019 requires advanced respiratory support modalities including invasive mechanical ventilation (IMV), continuous positive airway pressure (C-PAP), and non-invasive ventilation ((NIV). IMV leads to either subtle forms of lung injury (pulmonary edema, lung cysts) or more severe form of lung injury manifested as subcutaneous emphysema, pneumomediastinum, and pneumothorax (herein collectively termed barotrauma). We have described two cases showing the two end of spectrum of ventilator associated lung injury (VALI).

When medicine transforms art.

A 40-year-old female with a history of type 1 diabetes mellitus and solitary pancreas transplant, presented with pancreatic graft rejection 1-year post-transplant. Incidentally, a 1.1 cm right lower lobe cavity was identified during her workup. Given the augmentation of immunosuppression, voriconazole was empirically started for possible invasive pulmonary aspergillosis. As the patient was a painter, this resulted in a significant change in the colors of her paintings. Ultimately, she was diagnosed with pulmonary coccidioidomycosis and her visual disturbances resolved after the voriconazole was changed to fluconazole. Voriconazole causes visual disturbances in 20%-30% of the patients most commonly phototopsias; dyschromatopsias typically involving the tritan axis have also been reported. This case illustrates well the potential impact of voriconazole on spectral sensitivity and color perception.

A Nonliquid Crystal Display Screen Computer for Treatment of Photosensitivity and Computer Screen Intolerance in Post-Concussion Syndrome.

Liquid crystal display (LCD) screens refresh at a rate of 60 times per second, which can be perceived by concussed individuals who have photosensitivity, leading to computer intolerance. A non-LCD computer screen that refreshes at a much lower rate could relieve this photosensitivity and computer screen intolerance in patients with post-concussion syndrome (PCS). Twenty-nine patients with PCS, computer intolerance, and photosensitivity performed a reading task for a maximum of 30 min, with an LCD computer or a non-LCD device, and were given a comprehension test after completion of the reading task. The Sport Concussion Assessment Tool 3 was administered before and after each reading task. Symptom scores, amount of time spent reading, and performance on the comprehension tests were compared between the two devices. Patients also completed a self-report questionnaire of their subjective experience. The LCD screen computer produced significantly greater symptom exacerbation (median difference = 5, W = 315, p < 0.01) and a greater number of symptoms (median difference = 1, W = 148, p < 0.01) than the non-LCD screens. The non-LCD screen resulted in a longer symptom-free reading time (median = 48 sec, W = 147, p < 0.01), but not a greater number of words read (median = 281, W = 148, p = 0.098). Females were more likely to have greater symptom exacerbation with the LCD screen (U = 14.0, p < 0.01). No significant difference was found in performance on the comprehension test. Subjective reports showed that the non-LCD experience was more favorable, and most patients stated they would recommend this device for other patients with PCS. This study is the first to show the clinical utility of non-LCD screen computers in the management of photosensitivity and computer screen intolerance in patients with PCS. The non-LCD screen computer has the potential to facilitate return-to-work or return-to-school in concussed individuals.

Nonmotor Symptoms of Parkinson's Disease as Predictors of Dementia.

Some nonmotor symptoms (NMS) of Parkinson's disease (PD) have been shown to increase the risk of developing dementia. A total of 52 PD patients without dementia at baseline were examined for NMS over 36 months. Mini-Mental State Examination, Dementia Rating Scale-2, and caregiver-derived (Clinical Dementia Rating) scores were employed to rate patients as having either clear progression or not. Some 20 of 48 participants (41.7%) had clear cognitive decline. Univariate binary regression analysis was statistically significant for age (odds ratio [OR] (CI 95%)=1.24, 1.07-1.45, p=0.006) and orthostatic hypotension (OH) (OR (CI 95%)=4.91, 1.24-19.5, p=0.024). Multivariate analysis showed that only age (OR (CI 95%)=1.19, 1.0-1.41, p=0.05) and OH (OR (CI 95%)=5.57, 1.0-30.97, p=0.05) were correlated with an increased risk of cognitive decline. The presence of OH at baseline may be a significant predictor of progression to dementia in PD.

Prophylactic uterine artery embolization assisted cesarean section for the prevention of intrapartum hemorrhage in high-risk patients.

PURPOSE: To evaluate the safety and efficacy of prophylactic uterine artery embolization (UAE)-assisted cesarean section for the prevention of intrapartum hemorrhage. MATERIALS AND METHODS: Twelve consecutive pregnant women (mean age 31 years; range 25-38) with uterine scarring and placenta previa and/or placenta accreta underwent UAE in conjunction with cesarean section to prevent intrapartum hemorrhage. For UAE, the left uterine artery was catheterized prophylactically under fluoroscopic guidance before the cesarean section incision was made. After the infant had been delivered, bilateral UAE was performed with the placenta still in situ. After successful bilateral UAE, the placenta was detached from the uterine wall. RESULTS: Technical success was achieved in all 12 cases. Ten patients retained their uterus, and the other 2 underwent hysterectomy. The mean operative blood loss was 1,391 mL (range 600-3,600 mL). The total mean fluoroscopy time and mean absorbed dose (air kerma) were 9 min 40 s (range 4 min 35 s-15 min 24 s) and 91.79 mGy (range 30.2-171), respectively. The average fetal fluoroscopy time was 1 min 42 s (range 41 s to 3 min 16 s) with an average X-ray dose of 17.66 mGy (range 6.04-23.90). CONCLUSION: UAE-assisted cesarean section is safe and effective in the prevention of intrapartum hemorrhage in patients with uterine scarring and/or placental abnormalities.

Hypertension increases the risk of cerebral microbleed in the territory of posterior cerebral artery: a study of the association of microbleeds categorized on a basis of vascular territories and cardiovascular risk factors.

BACKGROUND: It has been suggested that the etiology of cerebral microbleeds (CMBs) differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We hypothesized that there were associations between cerebral arterial branches, cardiovascular risk factors, and the occurrence of CMBs. We examined these relationships in the current study. METHODS: Three hundred ninety-three patients with CMBs were analyzed in this study. The CMBs were listed according to the various arterial territories, and these were assessed for their relationship with cardiovascular risk factors, markers of small vessel disease, and their presence and location using multiple logistic regression. RESULTS: Systolic blood pressure had a significant association with CMBs in the territory of the posterior cerebral artery and the deep and infratentorial locations. The presence of lacunar infarcts, hemorrhage, and white matter changes were associated with CMBs in nearly all arterial territories. CONCLUSIONS: Hypertension increases the risk of microbleeds in the territory of the posterior cerebral artery and the deep and infratentorial locations. Cerebral amyloid angiopathy may be responsible for the microbleeds in the lobar area of brain.

Clinical applications of susceptibility-weighted imaging in detecting and grading intracranial gliomas: a review.

Susceptibility-weighted imaging (SWI) is a technique that exploits the susceptibility difference between tissues to provide contrast for different regions of the brain. In essence, it uses the deoxygenated hemoglobin of veins, hemosiderin of hemorrhage, etc. as intrinsic contrast agents, allowing for much better visualization of blood and microvessels even without administration of an external contrast agent. It is a fast-evolving field that is being constantly improved and increasingly implemented with updates in relevant technology. Multiple studies have been done on the role of SWI in the management of various neurologic disorders and it is also being seen as a further step in the neuroradiologist's goal of being able to noninvasively grade tumors in order to influence therapy. This article briefly reviews the evolution of SWI since its conception and provides the reader with a comprehensive summary of various studies that have been done on its application for detecting and grading intraaxial brain tumors, specifically gliomas. Other useful magnetic resonance techniques that have shown promise in grading gliomas are also discussed.

Correlation between cognitive function and the association fibers in patients with Alzheimer's disease using diffusion tensor imaging.

White matter (WM) changes, along with well-characterized cortical abnormalities, occur in patients with Alzheimer's disease (AD). We investigated the integrity of WM tracts within association fibers by the use of fractional anisotropy (FA), and the relationship between FA values and cognitive function in patients with AD. Neuropsychological examination and conventional MRI, as well as diffusion tensor imaging, (DTI) were conducted on 12 patients with mild to moderate AD and 18 cognitively healthy volunteers. DTI was performed to measure FA in the bilateral inferior fronto-occipital fasciculus (IFOF) and the superior longitudinal fasciculus (SLF). Mini-Mental State Examination (MMSE) scores and Montreal Cognitive Assessment (MoCA) values were used to evaluate cognitive function and the Clinical Dementia Rating (CDR) scale was used as a staging tool for dementia severity. FA measures were analyzed and correlated with neuropsychological data. No patient showed any WM tract abnormality on either T1-weighted or T2-weighted MRI. However, the FA values in the bilateral IFOF and SLF and the MoCA scores in patients with AD were significantly decreased (p<0.05) compared to the controls. Furthermore, the decreased FA values in the SLF were positively correlated with cognitive function (MMSE scores - right: r=0.672, p=0.033, left: r=0.919, p<0.01; MoCA values - right: r=0.747, p=0.013, left: r=0.679, p=0.031). Our findings confirmed that the loss of integrity of microstructural WM connectivity has a role in the cognitive decline of patients with AD. The data also suggest that the FA values of the SLF may be used as a clinical marker of cognitive function.