Characterization of aggresome formation in choroid plexus carcinoma.

Protein misfolding is inevitable, 30% of newly synthesized polypeptides can end up misfolded, and such proteins are either refolded or eliminated by cellular quality control pathways. These pathways include the ubiquitin proteosome system and autophagy. In recent years, protein misfolding has been implicated in the pathophysiology of many diseases such as diabetes, neurological disorders and cancer. Studies from our laboratory have shown that choroid plexus carcinoma tumors are characterized by the formation of aggresomes at the microtubules organizing centers (MTOC) in formalin fixed and paraffin embedded (FFPE) tumor tissues. This was further confirmed by the development of choroid plexus carcinoma cell line (CCHE-45) which was characterized by the constitutive formation of aggresomes at MTOC. Aggresome formation implies presence of toxic protein over load and/or defective autophagy. The role of autophagic flux in the removal of aggresomes was further investigated. CCHE-45 cells displayed an increase in both basal and induced autophagic flux. Furthermore, microtubule-associated protein light chain 3 A- variant 1 (LC3A-V1) expression was silenced by promoter methylation in these cells. Restoring LC3A-V1 resulted in the elimination of the aggresomes and the recruitment of Lysosomal-Associated Membrane Protein (LAMP2) independent from autophagosome formation. Based on these findings we suggest that quality control autophagy in CCHE-45 is mediated by LC3A in aggresomes clearance. We propose that perturbation in the autophagic pathway by the absence of LC3A expression leads to a failure in aggresome degradation thus overcoming misfolded protein overload

The Nexus of Regional Poverty and Education in Egypt: A Micro Analysis

The poverty pattern has changed from an urban/ rural pattern to a geographical/regional pattern. These changes may be explained by several aspects. The employment aspect is one of the main determinants for socioeconomic status. The inability of household members to participate in income-generating activities is considered an important explanation of poverty trends and the relationship between poverty and employment can be explained by the loss of earnings or the decline in real incomes. This can be related to several aspects, pattern of jobs and its regularity, human resource development indicators and investment indicators. The objective of this paper is to understand the changes in poverty levels in Egypt in total and by region by studying their relationship to regional composition and trends of employment and educational characteristics. The study starts a theoretical review about poverty and employment, which will constitute the basis for the micro level analysis in order to propose a framework for a pro-poor employment strategy. Keywords: Regional Poverty; Education; Egypt; Investment in Schooling JEL Classifications: H75, I20, I3

Cloning, expression and functional activity of deoxyhypusine synthase from Plasmodium vivax

BACKGROUND: Plasmodium vivax is the most widespread human malaria parasite. However, genetic information about its pathogenesis is limited at present, due to the lack of a reproducible in vitro cultivation method. Sequencing of the Plasmodium vivax genome suggested the presence of a homolog of deoxyhypusine synthase (DHS) from P. falciparum, the key regulatory enzyme in the first committed step of hypusine biosynthesis. DHS is involved in cell proliferation, and thus a valuable drug target for the human malaria parasite P. falciparum. A comparison of the enzymatic properties of the DHS enzymes between the benign and severe Plasmodium species should contribute to our understanding of the differences in pathogenicity and phylogeny of both malaria parasites. RESULTS: We describe the cloning of a 1368 bp putative deoxyhypusine synthase gene (dhs) sequence from genomic DNA of P. vivax PEST strain Salvador I (Accession number AJ549098) after touchdown PCR. The corresponding protein was expressed and functionally characterized as deoxyhypusine synthase by determination of its specific activity and cross-reactivity to human DHS on a Western blot. The putative DHS protein from P. vivax displays a FASTA score of 75 relative to DHS from rodent malaria parasite, P. yoelii, and 74 relative to that from the human parasite, P. falciparum strain 3D7. The ORF encoding 456 amino acids was expressed under control of IPTG-inducible T7 promoter, and expressed as a protein of approximately 50 kDa (theoretically 52.7 kDa) in E. coli BL21 DE3 cells. The N-terminal histidine-tagged protein was purified by Nickel-chelate affinity chromatography under denaturing conditions. DHS with a theoretical pI of 6.0 was present in both eluate fractions. The specific enzymatic activity of DHS was determined as 1268 U/mg protein. The inhibitor, N-guanyl-1, 7-diaminoheptane (GC7), suppressed specific activity by 36-fold. Western blot analysis performed with a polyclonal anti-human DHS antibody revealed cross-reactivity to DHS from P. vivax, despite an amino acid identity of 44% between the proteins. CONCLUSION: We identify a novel DHS protein in the more benign malaria parasite,P. vivax, on the basis of specific enzymatic activity, cross-reactivity with a polyclonal antibody against human DHS, and amino acid identity with DHS homologs from the rodent malaria parasite, P. yoelii, and human P. falciparum strains

An adaptive framework for real-time data reduction in AMI

In existing Advanced Metering Infrastructure (AMI), data collection intervals for each smart meter (SM) typically vary from 15 to 60 min. If we have 1 million SMs that transmit data every 15 min, these SMs will export 4 million records per hour. This leads to dramatically increasing bandwidth usage, energy consumption, traffic cost and I/O congestion. In this work, we present an adaptive framework for minimizing the amount of data transfer from SMs. The reduction in the framework is forecasting-based; when an SM reading is close to the forecasted value, the SM does not transmit the reading. In order for the framework to be adaptive to the ever-changing pattern of SM data, it is provided with a pool of forecasting methods. A supervised-learning scheme is employed to switch in real-time to the forecasting method most suitable to the current data pattern. The experimental results demonstrate that the proposed framework achieves data reduction rates up to 98% with accuracy 96%, depending on the operational parameters of the framework and consumer behavior (statistical features of SM data)

Role of expression of atrial natriuretic peptide gene in essential hypertension among Egyptian patients

Introduction: Essential Hypertension has been a great burden on public health services for a long time, with many life-threatening complications. Therefore, we decided to study Atrial Natriuretic peptide (ANP) gene expression as one of the most important blood pressure controlling genes, in order to use ANP gene as a potential diagnostic or therapeutic marker in the near future.Methods: One hundred essential hypertensive patients and 100 normotensive controls were included. Study Subjects were subjected to ANP gene expression analysis, together with blood pressure measurement, Lab investigations, and BMI analysis.Results: There was a statistical difference between ANP gene expression and blood pressure, with lower ANP gene expression level (median of 0.3) being present among hypertensive patients and higher ANP gene expression level (median of 1.6) among normotensive controls (p < 0.001).Discussion: We proved that ANP gene expression to be low in essential hypertension patients compared with normotensive individuals

Развитие человеческого капитала, социальная интеграция и новая экономическая зона Суэцкого канала

Creating society for all individuals by social inclusion is the best way to fight poverty and social exclusion. The construction of socially inclusive communities should be supported and encouraged by all partners in society not only the government. Thus, societies should create partnerships among all actors. These partnerships should promote complementary strategies for change, addressing the broad range of economic, social and environmental policies. It is time for economic zones to play their part in achieving social inclusion and sustainable development. Special Economic Zones are known for supporting the strategy of economic reform, decreasing the unemployment ratio and attracting new investments. The paper aims to propose design elements for creating socially inclusive Suez Canal Economic Zone. For this purpose, we introduced essential strategies of building an inclusive society. Moreover, we analysed inclusive growth indicators and the main characteristics of firms and workers in the Suez Canal Zone. The results include attracting foreign direct investment and increasing exports, achieving sustainable and inclusive green strategies that encompassing exports and investment creation, enabling capacity building, generating employment opportunities, assuring trickling down effect and creating linkages with the local economy to improve socio-economic conditions and eliminating regional disparities.Создание общества для всех с помощью социальной интеграции лучший способ борьбы с бедностью и социальной изоляцией, который должно поддерживать не только правительство, но и сами члены общества. Непременным элементом социальной интеграции являются партнерские отношения между всеми участниками. Партнерам необходимо продвигать дополнительные стратегии изменений, охватывающих широкий спектр проблем экономической, социальной и экологической политики. В настоящее время важную роль в достижении социальной интеграции и устойчивого развития играют экономические зоны, создание которых способствует проведению экономических реформ, снижению уровня безработицы и привлечению новых инвестиций. В настоящей статье описаны элементы, необходимые для создания социально-интегрированной экономической зоны Суэцкого канала, а также представлены основные стратегии построения социально-интегрированного общества. Проанализированы показатели инклюзивного роста и основные характеристики организаций и работников, занятых в зоне Суэцкого канала. Полученные результаты включают в себя: привлечение прямых иностранных инвестиций и рост экспорта; создание устойчивых и инклюзивных «зеленых» стратегий; создание возможностей для наращивания потенциала; обеспечение занятости и связей с региональной экономикой для улучшения социально-экономических условий и устранения региональных диспропорций

Genotypes and serotype distribution of macrolide resistant invasive and non- invasive Streptococcus pneumoniae isolates from Lebanon

<p>Abstract</p> <p>Background</p> <p>This study determined macrolide resistance genotypes in clinical isolates of <it>Streptococcus pneumoniae </it>from multiple medical centers in Lebanon and assessed the serotype distribution in relation to these mechanism(s) of resistance and the source of isolate recovery.</p> <p>Methods</p> <p>Forty four macrolide resistant and 21 macrolide susceptible <it>S. pneumoniae </it>clinical isolates were tested for antimicrobial susceptibility according to CLSI guidelines (2008) and underwent molecular characterization. Serotyping of these isolates was performed by Multiplex PCR-based serotype deduction using CDC protocols. PCR amplification of macrolide resistant <it>erm </it>(encoding methylase) and <it>mef </it>(encoding macrolide efflux pump protein) genes was carried out.</p> <p>Results</p> <p>Among 44 isolates resistant to erythromycin, 35 were resistant to penicillin and 18 to ceftriaxone. Examination of 44 macrolide resistant isolates by PCR showed that 16 isolates harbored the <it>erm</it>(B) gene, 8 isolates harbored the <it>mef </it>gene, and 14 isolates harbored both the <it>erm</it>(B) and <it>mef </it>genes. There was no amplification by PCR of the <it>erm</it>(B) or <it>mef </it>genes in 6 isolates. Seven different capsular serotypes 2, 9V/9A,12F, 14,19A, 19F, and 23, were detected by multiplex PCR serotype deduction in 35 of 44 macrolide resistant isolates, with 19F being the most prevalent serotype. With the exception of serotype 2, all serotypes were invasive. Isolates belonging to the invasive serotypes 14 and 19F harbored both <it>erm</it>(B) and <it>mef </it>genes. Nine of the 44 macrolide resistant isolates were non-serotypable by our protocols.</p> <p>Conclusion</p> <p>Macrolide resistance in <it>S. pneumoniae </it>in Lebanon is mainly through target site modification but is also mediated through efflux pumps, with serotype 19F having dual resistance and being the most prevalent and invasive.</p

Tumor Mutation Burden Prediction Model in Egyptian Breast Cancer patients based on Next Generation Sequencing

Objectives: This study aimed to identify the tumor mutation burden (TMB) value in Egyptian breast cancer (BC) patients. Moreover, to find the best TMB prediction model based on the expression of estrogen (ER), progesterone (PR), human epidermal growth factor receptor 2 (HER-2), and proliferation index Ki-67. Methods: The Ion AmpliSeq Comprehensive Cancer Panel was used to determine TMB value of 58 Egyptian BC tumor tissues. Different machine learning models were used to select the optimal classification model for prediction of TMB level according to patient’s receptor status. Results: The measured TMB value was between 0 and 8.12/Mb. Positive expression of ER and PR was significantly associated with TMB ≤ 1.25 [(OR =0.35, 95% CI: 0.04–2.98), (OR = 0.17, 95% CI= 0.02-0.44)] respectively. Ki-67 expression positive was significantly associated with TMB >1.25 than those who were Ki-67 expression negative (OR = 9.33, 95% CI= 2.07-42.18). However, no significant differences were observed between HER2 positive and HER2 negative groups. The optimized logistic regression model was TMB = −27.5 −1.82 ER – 0.73 PR + 0.826 HER2 + 2.08 Ki-67. Conclusion: Our findings revealed that TMB value can be predicted based on the expression level of ER, PR, HER-2, and Ki-67

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely