A de novo marker chromosome derived from 9p in a patient with 9p partial duplication syndrome and autism features: genotype-phenotype correlation

<p>Abstract</p> <p>Background</p> <p>Previous studies focusing on candidate genes and chromosomal regions identified several copy number variations (CNVs) associated with increased risk of autism or autism spectrum disorders (ASD).</p> <p>Case Presentation</p> <p>We describe a 17-year-old girl with autism, severe mental retardation, epilepsy, and partial 9p duplication syndrome features in whom GTG-banded chromosome analysis revealed a female karyotype with a marker chromosome in 69% of analyzed metaphases. Array CGH analysis showed that the marker chromosome originated from 9p24.3 to 9p13.1 with a gain of 38.9 Mb. This mosaic 9p duplication was detected only in the proband and not in the parents, her four unaffected siblings, or 258 ethnic controls. Apart from the marker chromosome, no other copy number variations (CNVs) were detected in the patient or her family. Detailed analysis of the duplicated region revealed: i) an area extending from 9p22.3 to 9p22.2 that was previously identified as a critical region for the 9p duplication syndrome; ii) a region extending from 9p22.1 to 9p13.1 that was previously reported to be duplicated in a normal individual; and iii) a potential ASD locus extending from 9p24.3 to 9p23. The ASD candidate locus contained 34 genes that may contribute to the autistic features in this patient.</p> <p>Conclusion</p> <p>We identified a potential ASD locus (9p24.3 to 9p23) that may encompass gene(s) contributing to autism or ASD.</p

Nurses experience of caring for patients with COVID-19 : a phenomenological study

Introduction: COVID-19 has impacted all dimensions of life and imposed serious threat on humankind. Background: In Jordan, understanding how nurses experienced providing care for patients with COVID-19 offers a framework of knowledge about similar situations within the context of Arabic culture. Aim: To explore nurses' experience with providing hands-on care to patients with active COVID-19 infection in an Arabic society. Methods: A descriptive phenomenological study interviewed 10 nurses through a purposive sampling approach until data saturation was reached. The research site was hospital designated to receive patients with active COVID-19 infection. Semi-structured interviews were used to collect the data. Findings: Three themes were generated from the data: the impact of the COVID-19 outbreak on nurses' health; unfamiliar work and social environments; and conforming to professional standards. Discussion: There are specific risks to the physical and mental wellbeing of nurses who provide hands-on care to patients with COVID-19 in an Arabic society. Implication for nursing and health policy: Health care institutions should consider establishing programs that promote nurses' wellbeing and support their productivity in a crisis. A danger pay allowance should be considered for nurses during extraordinary circumstances, such as pandemics

Bioactive Lipids and Cationic Antimicrobial Peptides as New Potential Regulators for Trafficking of Bone Marrow-Derived Stem Cells in Patients with Acute Myocardial Infarction

Acute myocardial infarction (AMI) triggers mobilization of stem cells from bone marrow (BM) into peripheral blood (PB). Based on our observation that the bioactive sphingophospholipids, sphingosine-1 phosphate (S1P), and ceramide-1 phosphate (C1P) regulate trafficking of hematopoietic stem cells (HSCs), we explored whether they also direct trafficking of non-hematopoietic stem cells (non-HSCs). We detected a 3–6-fold increase in circulating CD34+, CD133+, and CXCR4+ lineage-negative (Lin−)/CD45− cells that are enriched in non-HSCs [including endothelial progenitors (EPCs) and very small embryonic-like stem cells (VSELs)] in PB from AMI patients (P\u3c0.05 vs. controls). Concurrently, we measured a 3-fold increase in S1P and C1P levels in plasma from AMI patients. At the same time, plasma obtained at hospital admission and 6 h after AMI strongly chemoattracted human BM-derived CD34+/Lin− and CXCR4+/Lin− cells in Transwell chemotaxis assays. This effect of plasma was blunted after depletion of S1P level by charcoal stripping and was further inhibited by the specific S1P1 receptor antagonist such as W146 and VPC23019. We also noted that the expression of S1P receptor 1 (S1P1), which is dominant in naïve BM, is reduced after the exposure to S1P at concentrations similar to the plasma S1P levels in patients with AMI, thus influencing the role of S1P in homing to the injured myocardium. Therefore, we examined mechanisms, other than bioactive lipids, that may contribute to the homing of BM non-HSCs to the infarcted myocardium. Hypoxic cardiac tissue increases the expression of cathelicidin and β-2 defensin, which could explain why PB cells isolated from patients with AMI migrated more efficiently to a low, yet physiological, gradient of stromal-derived factor-1 in Transwell migration assays. Together, these observations suggest that while elevated S1P and C1P levels early in the course of AMI may trigger mobilization of non-HSCs into PB, cathelicidin and β-2 defensin could play an important role in their homing to damaged myocardium

Clinical Utility and Concordance of Upper Urinary Tract Cytology and Biopsy in Predicting Clinicopathologic Features of Upper Urinary Tract Urothelial Carcinoma

5% of urothelial carcinoma occurs in the upper urinary tract (UUT), a challenging location to biopsy. We aim to evaluate concordance between biopsy, cytology, and resection specimens in a large upper tract urothelial carcinoma (UTUC) cohort.117 UTUC resections with UUT biopsy and/or cytology specimens from 2000–2016 were retrieved; pathologic material was re-reviewed, evaluated for concordance, and correlated with clinical information. 14% pre-operative biopsies, including 8 from renal pelvis and 6 from ureter, lacked neoplastic diagnoses. 77% diagnostic biopsies included subepithelial tissue; 11% demonstrated reclassification of grade and 30% demonstrated reclassification of invasion status. 26% of renal pelvis UTUC and 36% ureter UTUC were invasive only on resection. Of 18 UTUC reclassified from noninvasive high-grade papillary urothelial carcinoma (HGPUC) to invasive HGPUC, 39% had prior radical cystectomy (versus 8% invasive UTUC and 11% noninvasive UTUC with concordant biopsies). Most high-grade UTUC (88%) and some low-grade UTUC (58%) resections had abnormal cytology results. Biopsy-resection pairs with concordant invasion status and pairs with discordant invasion status showed similar rates of recurrence (38% versus 38%) and metastasis (25% versus 27%). 14% of UUT biopsies lacked diagnostic neoplastic material. Grade concordance between biopsy and resection was high (89%), but 30% of cases showed invasion only on resection. Subepithelial tissue was less commonly present in ureter biopsies, particularly from mid or proximal ureter. UTUC in patients with prior cystectomy were more likely to show invasion on resection but not biopsy

Knowledge, Attitude and Training Physiotherapist Palliative Care - Gaza Strip

Background: Palliative care encompasses holistic management of patients and families facing life-threatening and life-limiting conditions. There is currently little known about Gaza strip physiotherapists’ palliative care knowledge, attitudes, beliefs, experience and training needs. Objectives: Palliative care rehabilitation has been positively associated with a high and prolonged level of independent function, which also reduces the burden on care providers(1,2). This study aimed to investigate the existing knowledge, attitudes, beliefs, training and experience of palliative care by physiotherapists working in Gaza strip. Methodology: A quantitative cross-sectional descriptive study using a face to face questionnaire included sociodemographic data, physiotherapist’s knowledge, attitude experience and training (modified PTiPC-KABE Scale)(3), the study includes eight major hospitals in the Gaza-Strip. The sample size was 120 participants, 110 were included. SPSS (version 22 for Windows) for descriptive statistics, Chi-Square, Student's t and compare mean -tests were used for the statistical analysis. Results: The total number of respondents was 110(93.3%); male 45%,and females 55%.Years of experience Palliative care intends to hasten death was significant in (p = 0.017), Palliative care does not enhance quality of life (p = 0.117), I feel a sense of personal failure when a patient dies(p=0.035), Palliative care considers dying as a complicated process (p =0.026), Caring for dying patients is traumatic for me(p = 0.004), The provision of palliative care requires emotional detachment(p = 0.009), The physical environment of my workplace is ideal for providing palliative care and rehabilitation(p = 0.026), I am often exposed to death in my workplace(p = 0.034), Conclusions: Many of Gaza's physiotherapists perform in palliative care despite inadequate training and limited knowledge in this area. Further learning and training opportunities for graduates and postgraduate students are required for physiotherapists in palliative care

The effectiveness of different explicit vocabulary-teaching strategies on learners’ retention of technical and academic words

The effectiveness of explicit instruction, within the context of strategy development in learners, has been widely accepted for several years. However, the methods used within explicit vocabulary instruction are varied and comparatively few studies have directly compared methods. This study investigates the type of instruction (in a visual or written context) as well as the timing of the activity (before or after the main activity). Seventy Arabic learners of English were tested in a 2*2 design. Results showed a positive effect for pre-teaching vocabulary in a visual condition. We conclude that this pre-emptive multimodal approach heightens the learners’ ability to notice vocabulary items thus providing an effective strategy to increase vocabulary intake

Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study

<p>Abstract</p> <p>Background</p> <p>Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL.</p> <p>Methods</p> <p>The study prospectively included 71 patients, (47 males, 24 females) with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0) who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1), while 33 patients did not receive adjuvant radiotherapy (group 2). Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded.</p> <p>Results</p> <p>The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03). The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4 - 102.3, p < 0.0001) and radiotherapy (odd ratio 0.19, 95% CI 0.05 - 0.78, p < 0.02). With Cox regression, the only independent multivariate predictor of radio-sensitivity was the Bcl-XL expression with odd ratio 4.6 and a p value < 0.0001. All patients tolerated the treatment with no life threatening or late complications during the period of follow up.</p> <p>Conclusions</p> <p>Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.</p

Additive manufacturing of Ti-alloy: Thermal analysis and assessment of properties

In this study, 3D printing of Ti6Al4V alloy is realized and the characteristics of the printed layer are examined. The morphological structures and metallurgical changes in the printed layer are assessed. Temperature and stress fields are simulated in line with the experimental conditions. Since the air gaps are present in between the loose alloy powders prior to the printing, the effective properties incorporating the air fraction are determined and the effective properties are used in the simulations. Thermal conductivity of the loose alloy powders with the presence of air gaps is determined by incorporating the virtual experimental technique. It is found that the printed layer is free from micro-cracks and large scale asperities; however, some small pores sites are observed because of the release of air around the loose powders during the printing. Microhardness of the printed surface is higher in the top surface of the printed layer than that of as-received solid alloy. In addition, the friction coefficient of the printed surface remains lower than that of the conventionally produced solid surface. The columnar structures are formed in the mid-section of the printed layer and slanted grains are developed in the region of the top and the bottom surface of the printed layer.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors acknowledge the financial support of King Fahd University of Petroleum and Minerals (KFUPM) in Saudi Arabia, Gazi University and TAI (SAYP Project DDKIG1) in Turkey and King Abdullah City for Atomic and Renewable Energy (K.A.CARE) to accomplish this work

JunD/AP-1-Mediated Gene Expression Promotes Lymphocyte Growth Dependent on Interleukin-7 Signal Transduction

Interleukin-7 (IL-7) is an essential cytokine for lymphocyte growth that has the potential for promoting immune reconstitution. This feature makes IL-7 an ideal candidate for therapeutic development. As with other cytokines, signaling through the IL-7 receptor induces the JAK/STAT pathway. However, the broad scope of IL-7 regulatory targets likely necessitates the use of other signaling components whose identities remain poorly defined. To this end, we used an IL-7 dependent T-cell line to examine how expression of the glycolytic enzyme, Hexokinase II (HXKII) was regulated by IL-7 in a STAT5-independent manner. Our studies revealed that IL-7 promoted the activity of JNK (Jun N-terminal Kinase), and that JNK, in turn, drove the expression of JunD, a component of the Activating Protein 1 (AP-1) transcription factors. Gel shifts showed that the AP-1 complex induced by IL-7 contained JunD but not c-Fos or c-Jun. Inhibition of JNK/JunD blocked glucose uptake and HXKII gene expression, indicating that this pathway was responsible for promoting HXKII expression. Because others had shown that JunD was a negative regulator of cell growth, we performed a bioinformatics analysis to uncover possible JunD-regulated gene targets. Our search revealed that JunD could control the expression of proteins involved in signal transduction, cell survival and metabolism. One of these growth promoters was the oncogene, Pim-1. Pim-1 is an IL-7-induced protein that was inhibited when the activities of JNK or JunD were blocked, showing that in IL-7 dependent T-cells JunD can promote positive signals transduced through Pim-1. This was confirmed when the IL-7-induced proliferation of CD8 T-cells was impaired upon JunD inhibition. These results show that engagement of the IL-7 receptor drives a signal that is more complex than the JAK/STAT pathway, activating JNK and JunD to induce rapid growth stimulation through the expression of metabolic and signaling factors like HXKII and Pim-1