Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.

Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with a severe form of intractable epilepsy, severe developmental delay, progressive microcephaly, visual disturbance and similar minor dysmorphisms. Whole exome sequencing identified a recurrent, homozygous variant (chr2:64083454A > G) in the essential UDP-glucose pyrophosphorylase (UGP2) gene in all probands. This rare variant results in a tolerable Met12Val missense change of the longer UGP2 protein isoform but causes a disruption of the start codon of the shorter isoform, which is predominant in brain. We show that the absence of the shorter isoform leads to a reduction of functional UGP2 enzyme in neural stem cells, leading to altered glycogen metabolism, upregulated unfolded protein response and premature neuronal differentiation, as modeled during pluripotent stem cell differentiation in vitro. In contrast, the complete lack of all UGP2 isoforms leads to differentiation defects in multiple lineages in human cells. Reduced expression of Ugp2a/Ugp2b in vivo in zebrafish mimics visual disturbance and mutant animals show a behavioral phenotype. Our study identifies a recurrent start codon mutation in UGP2 as a cause of a novel autosomal recessive DEE syndrome. Importantly, it also shows that isoform-specific start-loss mutations causing expression loss of a tissue-relevant isoform of an essential protein can cause a genetic disease, even when an organism-wide protein absence is incompatible with life. We provide additional examples where a similar disease mechanism applies

The Association of Physical Inactivity with Cancer Risk and Survival in Unique Ovarian Cancer Subgroups

Background: While extant research has shown that physical activity increases survival, improves quality of life, and reduces chemotherapy-related adverse effects, previous literature on physical activity and ovarian cancer has been inconsistent. In this dissertation, the association between physical inactivity and the risk of developing invasive EOC was evaluated in distinct subgroups: highly fatal invasive EOC and women aged 75 or above, and younger women aged younger than 45, diagnosed with invasive Epithelial Ovarian Cancer (EOC). This dissertation also included an evaluation of physical inactivity’s influence on the CD8+ TILs expression level among women who participated in both the Ovarian Cancer Consortium Association (OCAC) and Ovarian Tissue Tumor Analysis Consortium (OTTA). Methods: Data from several case-control studies that participated in OCAC were pooled, in order to provide information on the relationship between physical inactivity and invasive EOC risk in distinct subgroups. To assess the risk of developing highly fatal invasive EOC, the first study compared 300 women who died within 12 months after receiving their diagnosis, matched on the basis of age and study site, to 1,216 controls. And 453 cases matched to age and study site were compared to 681 controls; 822 older women with invasive EOC were matched on age and study site to 1,189 controls for the second study. These populations’ risk of developing invasive EOC was assessed using a pooled analytic technique, in which multivariable logistic regression was used to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). To evaluate the influence of prediagnostic physical inactivity on the CD8+ TILs expression level, Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% CIs for the last study in this dissertation. Results: The results indicate a statistically significant elevation in the risk of developing both highly fatal invasive EOC and EOC in older women aged 75 or above, compared to physically active women. Also, the results show an increased mortality risk among physically inactive women with negative CD8+ TILs upon primary debulking surgery. The elevation in the mortality rates increased as the level of CD8+ TILs expression decreased, showing a dose-response relationship, observed from low to moderate CD8+ TILs expression. Conclusion: This dissertation’s findings suggest that not engaging in a regular recreational physical activity is associated with increased risk of distinctive EOC subgroup. The results indicate a strong relationship between physical inactivity and developing a highly fatal type of invasive EOC. Further, physical inactivity increases the risk of invasive EOC among women aged 75 or above. The observations for this age group are more distinct than those observed among the general population of EOC patients. Further, a similar pattern occurred for the distributions of the CD8+ TILs among active versus inactive groups, but there was a profound elevation in the mortality risk among inactive women. Consequently, our observations suggest that physical activity status may play a role in CD8+ TILs activation. Further research is needed at the mechanistic level to evaluate the effect of physical inactivity on the immune systems of EOC patients

Unusual Clinical Presentation of a Primary Cutaneous Follicle Center Lymphoma on the Scalp of a Middle-Aged Female: Case Report and Review of the Literature

Primary cutaneous follicle center lymphoma (PCFCL) is a rare type of indolent, low-grade cutaneous B-cell lymphoma with an excellent prognosis. It usually presents with erythematous nodules and plaques on the head, neck, or back. The diagnosis is primarily based on histopathology, immunohistochemistry, and molecular studies. We describe a case of PCFCL causing a well-defined alopecic atrophic patch. The patch developed in the area of a large subcutaneous nodule that regressed after treatment with rituximab infusion. We hypothesize that the alopecia could have been caused by pressure

The Role of Vitamins and Minerals in Hair Loss: A Review

People commonly inquire about vitamin and mineral supplementation and diet as a means to prevent or manage dermatological diseases and, in particular, hair loss. Answering these queries is frequently challenging, given the enormous and conflicting evidence that exists on this subject. There are several reasons to suspect a role for micronutrients in non-scarring alopecia. Micronutrients are major elements in the normal hair follicle cycle, playing a role in cellular turnover, a frequent occurrence in the matrix cells in the follicle bulb that are rapidly dividing. Management of alopecia is an essential aspect of clinical dermatology given the prevalence of hair loss and its significant impact on patients’ quality of life. The role of nutrition and diet in treating hair loss represents a dynamic and growing area of inquiry. In this review we summarize the role of vitamins and minerals, such as vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, iron, selenium, and zinc, in non-scarring alopecia. A broad literature search of PubMed and Google Scholar was performed in July 2018 to compile published articles that study the relationship between vitamins and minerals, and hair loss. Micronutrients such as vitamins and minerals play an important, but not entirely clear role in normal hair follicle development and immune cell function. Deficiency of such micronutrients may represent a modifiable risk factor associated with the development, prevention, and treatment of alopecia. Given the role of vitamins and minerals in the hair cycle and immune defense mechanism, large double-blind placebo-controlled trials are required to determine the effect of specific micronutrient supplementation on hair growth in those with both micronutrient deficiency and non-scarring alopecia to establish any association between hair loss and such micronutrient deficiency. Plain Language Summary: Plain language summary available for this article

Behavior, knowledge, and attitude of surgeons and patients toward preoperative smoking cessation

Introduction: Tobacco smoking is a well-known risk factor for postoperative complications. Quitting smoking prior to surgery helps overcome those complications. Problem: Surgeons' attention for educating their patients about the importance of smoking cessation prior to surgery is one of the most effective ways to reduce smoking-related surgical complications. The extent of advised patients by their surgeons has not been identified. Methods: A descriptive, comparative cross-sectional study using a survey was conducted in 2013 including eligible patients in King Khalid University Hospital. Simultaneously, 69 surgeons were included. All participant data were randomly collected and analyzed using Chi-square analysis. Results: The frequency of smokers is more in surgical patients (37.5%) when compared to ex-smokers (12.5%) and passive smokers (8.3%), which were ex- and passive smokers, and it demonstrated an increased risk (P = 0.001) for surgery group compared to the nonsurgery group (P = 0.001). When comparing with nonsurgery group, most surgical patients agreed to quit smoking before surgery (95.3%)Š. More than half (58.8%) of the patients said that they have been advised by their treating surgeons to quit smoking before surgery. Concerning the surgeons, 66 nonvascular and nonpediatric surgeons responded to the questionnaire (response rate: 22.83%). The majority of the surgeons (60.9%) were interacting with smoker patients. With regard to smoking cessation, 69.6% surgeons have advised smoker patients to stop smoking for more than 2 weeks before surgery. More than half of the surgeons (53.6%) believed that patients quit smoking after preoperative smoking cessation advice. Conclusion: The surgeons and patients who participated in this study were aware that smoking cessation improves outcomes, but most of the surgeons did not provide brief advice about time duration to stop smoking

Estimating transfection efficiency in differentiated and undifferentiated neural cells

Abstract Objective Delivery of constructs for silencing or over-expressing genes or their modified versions is a crucial step for studying neuronal cell biology. Therefore, efficient transfection is important for the success of these experimental techniques especially in post-mitotic cells like neurons. In this study, we have assessed the transfection rate, using a previously established protocol, in both primary cortical cultures and neuroblastoma cell lines. Transfection efficiencies in these preparations have not been systematically determined before. Results Transfection efficiencies obtained herein were (10–12%) for neuroblastoma, (5–12%) for primary astrocytes and (1.3–6%) for primary neurons. We also report on cell-type specific transfection efficiency of neurons and astrocytes within primary cortical cultures when applying cell-type selective transfection protocols. Previous estimations described in primary cortical or hippocampal cultures were either based on general observations or on data derived from unspecified number of biological and/or technical replicates. Also to the best of our knowledge, transfection efficiency of pure primary neuronal cultures or astrocytes cultured in the context of pure or mixed (neurons/astrocytes) population cultures have not been previously determined. The transfection strategy used herein represents a convenient, and a straightforward tool for targeted cell transfection that can be utilized in a variety of in vitro applications

Increasing Traffic Flows with DSRC Technology: Field Trials and Performance Evaluation

As traffic congestion becomes a huge problem for most developing and developed countries across the world, intelligent transportation systems (ITS) are becoming a hot topic that is attracting attention of researchers and the general public alike. In this paper, we demonstrate a specific implementation of an ITS system whereby traffic lights are actuated by DSRC radios installed in vehicles. More specifically, we report the design of prototype of a DSRC-Actuated Traffic Lights (DSRC-ATL) system. It is shown that this system can reduce the travel time and commute time significantly, especially during rush hours. Furthermore, the results reported in this paper do NOT assume or require all vehicles to be equipped with DSCR radios. Even with low penetration ratios, e.g., when only 20% of all vehicles in a city are equipped with DSRC radios, the overall performance of the designed system is superior to the current traffic control systems