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Abstract The impact of LRRK2 variants on the risk of Parkinson’s disease in Egyptians remains unknown. We examined 1210 Egyptians (611 PD patients and 599 controls) from 16 governorates across Egypt for 12 LRRK2 pathogenic variants. The p.Gly2019Ser was the only variant detected, with a prevalence of 4.1% in sporadic cases, 6.5% in familial cases, and 0.68% in controls. Among p.Gly2019Ser carriers, all were heterozygous bar one homozygous patient, and all shared the common haplotype 1. Demographics and UPDRS scores did not differ between carriers and non-carriers, with most patients being males and developed PD in their fifties. Young and Early-onset PD prevalence was 37.5% in carriers and 33% in non-carriers. Familial cases were 16.6% in carriers and 11.5% in non-carriers. This study affirms that like other Mediterranean populations, Egyptians with PD have a higher prevalence of the p.Gly2019Ser variant compared to the global average. LRRK2 inhibitors could be promising therapeutic options for further exploration in this population.

Abstract Background Recently, the countries in the Mediterranean basin (which share cultural ties) have been showing a common trend of declining social support for the elderly, with deficiencies in social care models for this demographic. Thus, this Delphi panel study analyzed the gaps in social and integrated care among the participating countries in a European research project. Methods This three-round Delphi panel study focused on the European countries of Greece and Spain and the non-European countries of Egypt, Lebanon, and Tunisia. In this project, experts were identified according to their level of expertise in the subject matter, their gender, and their membership in different social groups. Subsequently, they were asked to identify the current situation of social care, set future goals, and locate the gaps regarding the social and healthcare models for older people in the participating countries. The median score (Mdn) and interquartile range (IQR) were calculated to assess the degree of consensus on the different priorities. Results Among the participating countries, there was a lack of state agreements to maintain social care models, a lack of coordination between public and private institutions to provide social care services, territorial inequalities in terms of access and coverage of rights, and job insecurity for professionals. The desired situation was to integrate social and healthcare services with a person-centered social care model, thus promoting autonomy and empowering users and families in participation and decision-making. Conclusions This Delphi study reveals significant disparities in social and healthcare policies for older adults across Mediterranean countries, highlighting shared challenges and specific national needs. European nations like Greece and Spain face fragmented systems, while non-European countries such as Lebanon, Egypt, and Tunisia lack specialized geriatric services and social security. All countries urgently need better professional training, social and economic empowerment of older adults, and integrated national strategies. These findings offer key insights for policymakers to develop equitable, sustainable solutions for aging populations.

The consumption of fat raises the risk of coronary heart disease and a number of chronic diseases such as obesity. However, removing fat or reducing its level in the final product may give it undesirable properties since fat plays an important role in the quality of food, mainly its texture and flavor. Therefore, natural or artificial fat replacers are utilized in food formulations instead of natural fat. Fat mimics are based on carbohydrates, proteins, and/or lipids, with energy values of 0–38 kJ/g (0–9 kcal/g). They mimic physical properties and sensory attributes of fat but have less energy and calories. Fat substitutes have physical and functional characteristics of conventional fat molecules which are directly replaced with synthetic molecules that provide no calories or structured lipid molecules. Dairy products represent a principal part of consumer diet all over the world. Therefore, this review aimed to expound how fat replacers can be used to overcome the defects of fat absence or reduction in dairy products. It was reviewed different types and sources of fat replacers, both micro- and nanoparticulated, and highlighted their application in cheese, ice cream, frozen yogurt, fermented milk, and fatty dairy products. Some of the currently applied micro-particulated proteins include Simplesse® (whey protein), APV LeanCreme™, and Dairy-Lo® (micro-particulate protein + micro-particulate cellulose). While whey protein has a great role in the dairy sector today, there is a need for further research in this field.

Introduction: Parkinson’s disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which some have reported lower phenylalanine and tyrosine levels in PD patients compared to controls.Methods: In this study, we have collected plasma from 27 PD patients, 18 reference controls, and 8 high-risk controls to perform a metabolomic study using liquid chromatography-electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS).Results: Our findings revealed higher intensities of trans-cinnamate, a phenylalanine metabolite, in patients compared to reference controls. Thus, we hypothesize that phenylalanine metabolism has been shifted to produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead of producing tyrosine, a dopamine precursor, via phenylalanine hydroxylase (PAH).Discussion: Given that these metabolites are precursors to several other metabolic pathways, the intensities of many metabolites such as dopamine, norepinephrine, and 3-hydroxyanthranilic acid, which connects phenylalanine metabolism to that of tryptophan, have been altered. Consequently, and in respect to Metabolic Control Analysis (MCA) theory, the levels of tryptophan metabolites have also been altered. Some of these metabolites are tryptamine, melatonin, and nicotinamide. Thus, we assume that these alterations could contribute to the dopaminergic, adrenergic, and serotonergic neurodegeneration that happen in the disease.

Abstract Background Validated self-reporting tools are required to evaluate the functional outcome and health-related quality of life (HRQOL) for those who had extremity bone sarcomas in their childhood or adolescence. Our study pursued cross-cultural adaptation and validation of the pediatric Toronto Extremity Salvage Score (pTESS) and Toronto Extremity Salvage Score (TESS) to assess the functional outcome for Egyptian children and adult survivors following surgeries of extremity bone sarcomas. In the modified versions of pTESS and TESS, mental domains were added to allow the evaluation of HRQOL using a specific instrument for childhood bone cancer. Methods The internal consistency and test–retest reliability of the studied forms were assessed with Cronbach’s alpha and Intra-class coefficients (ICC), respectively. For convergent validity, correlations between scores of the generic Pediatric Quality of Life Inventory (PedsQL 4.0) and pTESS /TESS scores were reported. Factor Analysis was feasible for pTESS-leg; due to the insufficient samples, only the average inter-item correlation coefficients were reported for the remaining versions. Results Out of 233 participants, 134 responded to pTESS-leg, 53 to TESS-leg, 36 to pTESS-arm, and only 10 to TESS-arm. All versions showed excellent internal consistency (Cronbach’s alpha >0.9), good test–retest reliability (ICC >0.8), moderate to strong correlations with PedsQL, and acceptable average inter-item correlation coefficients (≥0.3). Three factors were extracted for the pTESS-leg, in which all mental items were loaded on one separate factor with factor loadings exceeding 0.4. Active chemotherapy, less than one year from primary surgery, or tibial tumors were associated with significantly inferior pTESS/TESS scores in the lower extremity group. Conclusion The Egyptian pTESS and TESS are valid and reliable self-reporting tools for assessing the functional outcome following surgeries for extremity bone sarcomas. The modified pTESS and TESS versions, which include additional mental domains, enabled the assessment of the overall health status of our population. Future studies should include a larger sample size and evaluate the ability of pTESS/TESS to track progress over time.

Abstract The biological basis of the neurodegenerative movement disorder, Parkinson’s disease (PD), is still unclear despite it being ‘discovered’ over 200 years ago in Western Medicine. Based on current PD knowledge, there are widely varying theories as to its pathobiology. The aim of this article was to explore some of these different theories by summarizing the viewpoints of laboratory and clinician scientists in the PD field, on the biological basis of the disease. To achieve this aim, we posed this question to thirteen “PD experts” from six continents (for global representation) and collated their personal opinions into this article. The views were varied, ranging from toxin exposure as a PD trigger, to LRRK2 as a potential root cause, to toxic alpha-synuclein being the most important etiological contributor. Notably, there was also growing recognition that the definition of PD as a single disease should be reconsidered, perhaps each with its own unique pathobiology and treatment regimen.

Abstract Background Fenugreek (Trigonella foenum-graecum L.) is one of the oldest cultivated medicinal plants, as well as it is rich with medicinal antioxidant components. The effect of foliar spraying with molybdenum, cysteine on growth, quality and productivity of fenugreek was evaluated in a conducted greenhouse experiment during 2019/2020 and 2020/2021 growing seasons. Results Results showed that there were different effects of molybdenum, cysteine and their interaction on morphological characters, photosynthetic pigments, seed yield and yield components and some chemical components of fenugreek plants. However, there was a variety of polypeptide bands with different molecular weights ranging from 18.94 to 250 kDa and was detected with polymorphic ratio 61.91%. Moreover, multiple bands varied in their molecular weight were detected in all tested plants using ISSR primers. The polymorphic percentage reached 70.00, 73.33, 76.19, 72.22, 77.77 and 70.59% in all tested plants with primer IS-01, Is-02, IS-03, IS-04, Is-05 and IS-06, respectively. Conclusions It was cleared that foliar spraying with molybdenum, cysteine and their interaction enhanced and improved growth, quality and productive characters of fenugreek. Moreover, there were molecular changes in fenugreek under study and generated bands using the six ISSR primers.

Audio classification tasks like speech recognition and acoustic scene analysis require substantial labeled data, which is expensive. This work explores active learning to reduce annotation costs for a sound classification problem with rare target classes where existing datasets are insufficient. A deep convolutional recurrent neural network extracts spectro-temporal features and makes predictions. An uncertainty sampling strategy queries the most uncertain samples for manual labeling by experts and non-experts. A new alternating confidence sampling strategy and two other certainty-based strategies are proposed and evaluated. Experiments show significantly higher accuracy than passive learning baselines with the same labeling budget. Active learning generalizes well in a qualitative analysis of 20,000 unlabeled recordings. Overall, active learning with a novel sampling strategy minimizes the need for expensive labeled data in audio classification, successfully leveraging unlabeled data to improve accuracy with minimal supervision.

Parkinson’s disease is a debilitating multisystemic disorder affecting both the central and peripheral nervous systems. Accumulating evidence suggests a potential interaction between gut microbiota and the pathophysiology of the disease. As a result of the degradation of dopaminergic neurons, PD patients develop motor impairments such as tremors, rigidity, and slowness of movement. These motor features are preceded by gastrointestinal issues, including constipation. Given these gastrointestinal issues, the gut has emerged as a potential modulator of the neurodegenerative cascade of PD. Several studies have been carried out to broaden our understanding of the gut–microbiota–brain axis in PD. As a result, a decrease in short-chain fatty acid synthesizing bacteria has been observed in multiple studies. Some studies, on the other hand, have shown an enrichment of mucin- and levodopa-degrading microbes. In this review, we compiled the available evidence from the literature on the bidirectional communication between the gut microbiome system and the brain in PD. We also addressed the association between dysbiosis and the clinical symptoms of PD and host–drug metabolism. Finally, we touched on some of the therapeutic interventions that may restore eubiosis and modulate the gut structure to restrain disease progression.

Abstract Given the many challenges facing healthcare access in many developing countries and the added limitations observed in emergencies like COVID-19 pandemic, the authors here discuss an alternative and feasible approach to overcome all these limitations.

Background and objective: The symptoms of most neurodegenerative diseases, including Parkinson’s disease (PD), usually do not occur until substantial neuronal loss occurs. This makes the process of early diagnosis very challenging. Hence, this research used variant call format (VCF) analysis to detect variants and novel genes that could be used as prognostic indicators in the early diagnosis of prodromal PD. Materials and Methods: Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI), and we analyzed prodromal patients with gVCF data collected in the 2021 cohort. A total of 304 participants were included, including 100 healthy controls, 146 prodromal genetic individuals, 21 prodromal hyposmia individuals, and 37 prodromal individuals with RBD. A pipeline was developed to process the samples from gVCF to reach variant annotation and pathway and disease association analysis. Results: Novel variant percentages were detected in the analyzed prodromal subgroups. The prodromal subgroup analysis revealed novel variations of 1.0%, 1.2%, 0.6%, 0.3%, 0.5%, and 0.4% for the genetic male, genetic female, hyposmia male, hyposmia female, RBD male, and RBD female groups, respectively. Interestingly, 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300, and PPP6R2) that were recently detected in PD patients were detected in the prodromal stage of PD. Conclusions: Genetic biomarkers are crucial for the early detection of Parkinson’s disease and its prodromal stage. The novel PD genes detected in prodromal patients could aid in the use of gene biomarkers for early diagnosis of the prodromal stage without relying only on phenotypic traits.

Background: Many patients with gastrointestinal (GIT) cancer have locally advanced or metastatic disease. Staging laparoscopy can support more accurate staging of gastrointestinal cancer by guiding the most appropriate treatment and avoiding morbidity associated with non-therapeutic laparotomy. Aim of the Work: The aim of the current study was to investigate the value of staging laparoscopy by assessing the avoidable surgery rate in gastrointestinal cancer patients who underwent surgery with curative intent.Patients and Methods: A randomized prospective study included patients, whom had gastro-intestinal tumor already diagnosed either by tissue histopathology or radiological study. Staging laparoscopy was done, and operable tumors compared to non-operable ones.Results: This study was conducted on 28 patents with GIT tumors who were underwent staging laparoscopy, most of them were males (89.3%) with the mean age 52±8 years and mean of their weight is 56±6 kg. About 42.9% of tumors involved in our study had local invasion, 25% had multiple LN, 7.14% had malignant ascites, 10.7% had peritoneal deposit, 25% had stage N1-3 and 17.8% had M1 stage by staging laparoscopy. There is no statistically significant difference between operable and non-operable cases as regards location of the tumor and the imaging done.Conclusion: Laparoscopic staging may help with more precise staging of digestive malignancies, providing recommendations for the best course of treatment and preventing the morbidity linked to unnecessary laparotomies. The process makes it possible to examine intra-abdominal organs up close and provides a way to collect biopsy samples and aspiration cytology data.

The scarcity of fresh water is a primary problem in remote regions. Thus, an economical and related water distillation solar still coupled with a solar collector was designed and studied experimentally. This study aims to investigate and evaluate the performance of an active single-slope solar still (ASSSS) coupled with a solar evacuated tube collector (ETC) as the water heater. The results showed that the average distillate productivity of ASSSS combined with U pipe solar (ETC) was 1.085 l/m2 in December 2020, but 3.12 l/m2 in August 2021. These quantities of the water distiller were higher than those of a passive solar distiller with a single slope (PSSSS). The average value of the water temperature increased using the ASSSS coupled with ETC in August 2021 at 79.1°C, whereas it was 71°C in August 2021 for PSSSS. These results indicate that the ASSSS is more effective than the PSSSS.

Paraquat (PQ), rotenone (RO), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are neurotoxicants that can damage human health. Exposure to these neurotoxicants has been linked to neurodegeneration, particularly Parkinson’s disease. However, their mechanisms of action have not been fully elucidated, nor has the relative vulnerability of neuronal subtypes to their exposures. To address this, the current study investigated the cytotoxic effects of PQ, RO, and MPTP and their relative effects on cellular bioenergetics and oxidative stress on undifferentiated human neuroblastoma (SH-SY5Y) cells and those differentiated to dopaminergic (DA) or cholinergic (CH) phenotypes. The tested neurotoxicants were all cytotoxic to the three cell phenotypes that correlated with both concentration and exposure duration. At half-maximal effective concentrations (EC50s), there were significant reductions in cellular ATP levels and reduced activity of the mitochondrial complexes I and III, with a parallel increase in lactate production. PQ at 10 µM significantly decreased ATP production and mitochondrial complex III activity only in DA cells. RO was the most potent inhibitor of mitochondrial complex 1 and did not inhibit mitochondrial complex III even at concentrations that induced a 50% loss of cell viability. MPTP was the most potent toxicant in undifferentiated cells. All neurotoxicants significantly increased reactive oxygen species, lipid peroxidation, and nuclear expression of Nrf2, with a corresponding inhibition of the antioxidant enzymes catalase and superoxide dismutase. At a 10 µM exposure to PQ or RO, oxidative stress biomarkers were significant in DA cells. Collectively, this study underscores the importance of mitochondrial dysfunction and oxidative stress in PQ, RO, and MPTP-induced cytotoxicity and that neuronal phenotypes display differential vulnerability to these neurotoxicants.

Amidst the outbreak of the Corona Virus Disease 2019 (COVID-19), there has been a pivotal shift in nutritional focus towards adopting healthier lifestyles to enhance immune function. The successive resurgence of COVID-19 serves as a stark reminder that prioritizing the enhancement of our own immune systems is of paramount importance. Eggs are nutritious, productive, cost-effective, and affordable for consumption. Likewise, eggs are exclusive among the numerous ways consumers can obtain high-quality animal protein. Egg proteins and their peptide derivatives are abundant and biologically active and have significant therapeutic effects on chronic diseases induced by a variety of factors, including metabolic syndrome, making eggs an important raw material for the study of proteins and peptide-active substances. This paper reviewed methods for the isolation and purification of avian egg proteins and their derived peptides; the effects of the proteins and peptides in enhancing the body’s immunity, lowering blood pressure and expression levels of inflammatory factors; as well as the potential of the proteins and peptides in reducing the risk of chronic diseases such as osteoporosis and cardiovascular disease. This review was written with the expectation that it would provide a comprehensive understanding of the potential value of poultry egg proteins for maintaining health.

Abstract Further studies are required to investigate the impact of the COVID-19 pandemic on Parkinson’s disease (PD) progression. This study investigated the motor and non-motor progression of people with PD (PWP) at 6 months during the COVID-19 pandemic compared with that during the pre-pandemic period. Patients were recruited from Ain Shams University Hospitals, Cairo, in the period between April 2019 and December 2020. Fifty patients were included, of whom 17 and 33 patients were followed for 6 months before and during the pandemic, respectively. All patients were assessed at baseline and at 6 months using the MDS-UPDRS, Schwab and England scale (S&E), Hoehn and Yahr scale (H&Y), Berg Balance Scale, Timed Up and Go test (TUG), International Physical Activity Questionnaire, New Freezing of Gait Questionnaire, Non-Motor Symptoms Scale, and Beck Depression Inventory (BDI). Both groups were matched in age, gender, and disease characteristics. Patients followed during the pandemic showed more significant worsening of the total, part I and motor part of MDS-UPDRS, and balance scores (p

Abstract Background Clinical progression of Parkinson’s disease (PD) is highly heterogeneous, and its predictors are generally lacking. Identifying predictors of early disease progression is important for patients’ management and follow-up. The current study aims to identify clinical, neuroimaging and biochemical baseline predictors of motor progression in patients with PD. Forty-five PD patients were assessed at baseline, 6 months and 1 year using MDS-UPDRS total and subscores, Hoehn and Yahr (H&Y), Schwab and England (S&E), International Physical Activity Questionnaire (IPAQ). Baseline New Freezing of Gait Questionnaire (NFOG-Q), Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), and Time Up and Go Test (TUG), Non-Motor Symptoms Scale (NMSS), Beck Depression Inventory (BDI), PD questionnaire 39 (PDQ-39), MRI brain, uric acid, lipid profile and glycated hemoglobin were performed. Results Significant worsening of MDS-UPDRS total, part III scores, H&Y, S&E and IPAQ (p

IntroductionFalling is a major health problem among old age persons and are the sixth cause of mortality and morbidity among them. Assessing the prevalence of falls among elderly in an Egyptian community and investigating its associated risk factors using the Arabic translation of the SHARE-Questionnaire.Subjects and methodsThis cross-sectional analytic study was a part of the pilot for AL-SEHA project. It included 289 old age people (50+ years age) residing in the study areas. The main project data were collected using the Arabic translation of the SHARE (Survey of Health, Aging, and Retirement in Europe) questionnaire. The original project data were collected by investigators from five universities, then uploaded to the internet server domain of the American University in Cairo (AUC) Social Research Center.ResultsThe prevalence of falls was 11.07% (95% CI: 7.95–15.21). Falls were significantly more among 70 years or older (p < 0.001), unemployed or housewives (p = 0.026), have a family caregiver (p = 0.022), and home facilities for disability (p = 0.015). They had significantly higher rates of ischemic heart disease, hypertension, dyslipidemia, stroke, and diabetes mellitus. The most frequently reported problems were the fear of fall and dizziness (62.5%). The multivariate analysis identified the history of stroke and diabetes mellitus, the fear of fall and dizziness, and the total number of health problems and the score of difficulty in performing physical activities as significant independent predictors of fall occurrence. The history of stroke was the strongest risk factor (OR 33.49, CI: 3.45–325.40).Discussion and recommendationsThe prevalence of falls among old age persons in the studied community is not alarmingly high. It is highest among stroke patients. Community interventions and rehabilitation programs are recommended to train and educate old age people, especially those at risk such as stroke and diabetic patients, and those with dizziness to improve their physical fitness and reduce the fear of fall among them.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians–an admixed North African/Middle Eastern population–using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10−8) and eight novel suggestive loci (Pcorrected < 1.0 × 10−5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10−95 < p < 1.0 × 10−2) across diverse tissues. These loci are involved in cellular proliferation and invasion—pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

Abstract Alzheimer disease (AD) is a chronic neurodegenerative condition that affects an individual's cognitive function over an extended period. Treatment and prevention for AD have long been sought after; however, no strategy has yet been successful, as individuals with cognitive impairment usually present to the clinic when they have reached an advanced stage of the disease. The disease is progressive and multifactorial in its pathogenesis. Precision medicine (PM) is the new era of medicine comprising a holistic approach in dealing with diseases. With scientific innovations, PM has improved our disease knowledge, altered diagnoses and therapy approaches resulting in a more precise, predictive, preventative and personalized patient care. PM in AD focuses, among other things, on stratifying individuals according to their risk factors of developing the disease and applying preventative strategies and personalized treatment approaches for a better outcome. In this mini‐review, we have focused on a few modifiable and non‐modifiable risk factors and presented recommendations for future consideration to implement.

Abstract Background and Aim Colorectal cancer (CRC) accounts for over 8% of all deaths each year, with 1.2 million new cases diagnosed annually worldwide. It represents the seventh most common cancer in Egypt. Early detection of peritoneal metastasis is a major challenge in such cases. It helps with the decision of the immediate application of intraperitoneal chemotherapy after resection. Meta‐analysis studies reported contrast evidence for a possible prognostic role of intraperitoneal free cancer cells (IPCCs) in peritoneal recurrence and survival after curative resection. In this work, we aim to evaluate the prevalence and impact of detecting free malignant cells in peritoneal fluid on survival and local recurrence and to estimate the incidence of peritoneal carcinomatosis (PC) during follow up. Methods Design: This was a prospective cohort study. Settings: From June 2016 to December 2018, samples were collected from 104 patients who underwent abdominal surgery for colorectal cancer in the Egyptian National Cancer Institute. A total of 96 Egyptian CRC patients who underwent curative resection were enrolled. Intraoperative peritoneal lavage was performed to detect IPCC by conventional cytology. Patients with no residual tumor after surgery and no evidence of PC were followed up for a median 14 months. The cumulative 12‐month overall survival rate for patients with IPCC was 100% versus 86% for patients with negative cytology. Results Our results demonstrated that the prevalence of IPCC in the peritoneal lavage was 11.5%. Peritoneal and local recurrence occurred at a higher rate in patients with cytology positive lavage (9.1% vs 6.3% and 9.1% vs 3.8%, respectively), although this was statistically insignificant. Distant metastasis occurred significantly in patients with positive cytology (45.5% vs 8.9%) with P‐value

Introduction Males have a higher prevalence of waterpipe tobacco smoking (WTS) than females in most Eastern Mediterranean Region (EMR) countries, with a smaller gender gap than that of cigarette smoking. The objective of this study was to determine gender differences among university students with respect to WTS initiation, smoking behavior, tobacco flavors, and expenditure on WTS, in four EMR countries. Methods A cross-sectional online survey was conducted based on convenient samples of ever waterpipe smokers among university students in four EMR countries (Egypt, Jordan, Occupied Palestinian Territories, and the United Arab Emirates) in 2016. The total samples included 2470 participants. Study participants were invited through flyers, university portals, emails and Facebook, followed by emails with links to the internet survey. Results Females (80.4%) were more likely than males (66.4%, p

At present, millions of internet users are contributing a huge amount of data. This data is extremely heterogeneous, and so, it is hard to analyze and derive information from this data that is considered an indispensable source for decision-makers. Due to this massive growth, the classification of data and analysis has become an important research subject. Extracting information from this data has become a necessity. As a result, it was necessary to process these enormous volumes of data to uncover hidden information and therefore improve data analysis and, in turn, classification accuracy. In this paper, firstly, we focus on developing an ensemble machine-learning model based on active learning which identifies the most effective feature extraction strategy for heterogeneous data analysis, and compare it with traditional machine-learning algorithms. Secondly, we evaluate the proposed model during the experiments; five heterogeneous datasets from various domains were used, such as a Health Care Reform dataset, Sander Frandsen dataset, Financial Phrase Bank dataset, SMS Spam Collection dataset, and Textbook sales dataset. According to the results, the novel approach for data analysis performed better than conventional methods. Finally, the study’s findings confirmed the validity of the suggested technique, meeting the study’s goal of using ensemble methods with active learning to raise the model’s overall accuracy for effectively classifying and analyzing heterogeneous data, reducing the time and money spent training the model, and delivering superior analysis performance as well as insights into other elements of extracting information from heterogeneous data.

North Africans are underrepresented in current genome-wide data sets. Here, the authors provide an Egyptian genome reference, consisting of de novo assembly of the genome of an Egyptian individual and genome-wide genetic variation from a representative cohort of 110 Egyptian individuals.

To help address the increasing challenges related to the provision of dementia care, dementia registries have emerged around the world as important tools to gain insights and a better understanding of the disease process. Dementia registries provide a valuable source of standardized data collected from a large number of patients. This review explores the published research relating to different dementia registries around the world and discusses how these registries have improved our knowledge and understanding of the incidence, prevalence, risk factors, mortality, diagnosis, and management of dementia. A number of the best-known dementia registries with high research output including SveDem, NACC, ReDeGi, CREDOS and PRODEM were selected to study the publication output based on their data, investigate the key findings of these registry-based studies. Registries data contributed to understanding many aspects of the disease including disease prevalence in specific areas, patient characteristics and how they differ in populations, mortality risks, as well as the disease risk factors. Registries data impacted the quality of patients’ lives through determining the best treatment strategy for a patient based on previous patient outcomes. In conclusion, registries have significantly advanced scientific knowledge and understanding of dementia and impacted policy, clinical practice care delivery.

Finding a link between a hormone and microRNAs (miRNAs) is of great importance since it enables the adjustment of genetic composition or cellular functions without needing gene-level interventions. The dicer-mediated cleavage of precursor miRNAs is an interface link between miRNA and its regulators; any disruption in this process can affect neurogenesis. Besides, the hormonal regulation of miRNAs can occur at the molecular and cellular levels, both directly, through binding to the promoter elements of miRNAs, and indirectly, via regulation of the signaling effects of the post-transcriptional processing proteins. Estrogenic hormones have many roles in regulating miRNAs in the brain. This review discusses miRNAs, their detailed biogenesis, activities, and both the general and estrogen-dependent regulations. Additionally, we highlight the relationship between miR-29, miR-9, and estrogens in the nervous system. Such a relationship could be a possible etiological route for developing various neurodegenerative disorders.

During pandemics, the ethicists, public health professionals, and human rights advocates raise a red flag about different public health actions that should, at best, be addressed through integrated, global policies. How to rationalize the healthcare resources and prioritize the cases is not a recent challenge but the serious concern about that is how to achieve this while not increasing the vulnerability of the disadvantaged population. Healthcare professionals use different scoring systems as a part of their decision-making so the medical teams and triage committees can allocate resources for predictable health outcomes and prognosis as well as to appropriately triage the patients accordingly. However, the value of the existing scoring systems to manage COVID-19 cases is not well-established yet. Part of this problem includes managing non-COVID patients with chronic medical conditions like non-communicable diseases and addressing their medical needs during the pandemic complex context in a way to avoid worsening their conditions and, on the other hand, avoid hindering the establishment of comprehensive standards for dealing with COVID-19. In this article, we discuss this dilemma as well as how preexisting ethical standards were challenged by COVID-19. We also discuss how monitoring the consistent application of ethical standards during the medical trials of new medications, vaccines, or unproven medical interventions is also a critical issue.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare hereditary neurodegenerative disease characterized by an accumulation of iron within the brain. In the present report, we describe a family with 4 affected siblings presenting with variable clinical manifestations, e.g., parkinsonian features, dystonia and slow disease progression over 5 years. Exome sequencing revealed a causative variant in the pantothenate kinase 2 gene (PANK2). Variant NM_024960.6:c.710C > T was homozygous in all affected subjects. Our report describes the first genetically confirmed cases of PKAN in the Egyptian population. Studying genetics of neurodegenerative diseases in different ethnicities is very important for determining clinical phenotypes and understanding pathomechanisms of these diseases.

Acute or chronic exposures to pesticides have been linked to neurotoxicity and the potential development of neurodegenerative diseases (NDDs). This study aimed to consider the neurotoxicity of three widely utilized pesticides: malathion, chlorpyrifos, and paraquat within the hippocampus (HC), corpus striatum (CS), cerebellum (CER), and cerebral cortex (CC). Neurotoxicity was evaluated at relatively low, medium, and high pesticide dosages. All pesticides inhibited acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in each of the brain regions, but esterase inhibition was greatest in the HC and CS. Each of the pesticides also induced greater disruption to cellular bioenergetics within the HC and CS, and this was monitored via inhibition of mitochondrial complex enzymes I and II, reduced ATP levels, and increased lactate production. Similarly, the HC and CS were more vulnerable to redox stress, with greater inhibition of the antioxidant enzymes catalase and superoxide dismutase and increased lipid peroxidation. All pesticides induced the production of nuclear Nrf2 in a dose-dependent manner. Collectively, these results show that pesticides disrupt cellular bioenergetics and that the HC and CS are more susceptible to pesticide effects than the CER and CC.

Modern research has proven that the “typical patient” requiring standardized treatments does not exist, reflecting the need for more personalized approaches for managing individual clinical profiles rather than broad diagnoses. In this regard, precision psychiatry has emerged focusing on enhancing prevention, diagnosis, and treatment of psychiatric disorders through identifying clinical subgroups, suggesting personalized evidence-based interventions, assessing the effectiveness of different interventions, and identifying risk and protective factors for remission, relapse, and vulnerability. Literature shows that recent advances in the field of precision psychiatry are rapidly becoming more data-driven reflecting both the significance and the continuous need for translational research in mental health. Different etiologies underlying depression have been theorized and some factors have been identified including neural circuitry, biotypes, biopsychosocial markers, genetics, and metabolomics which have shown to explain individual differences in pathology and response to treatment. Although the precision approach may prove to enhance diagnosis and treatment decisions, major challenges are hindering its clinical translation. These include the clinical diversity of psychiatric disorders, the technical complexity and costs of multiomics data, and the need for specialized training in precision health for healthcare staff, besides ethical concerns such as protecting the privacy and security of patients' data and maintaining health equity. The aim of this review is to provide an overview of recent findings in the conceptualization and treatment of depression from a precision mental health perspective and to discuss potential challenges and future directions in the application of precision psychiatry for the treatment of depression.

The public health crisis of the novel coronavirus disease (COVID-19) is alarming since January 2020. COVID-19 genome (SARS-CoV-2) is related to other highly pathogenic coronaviruses SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus). Amino acid substitutions in some of SARS-CoV-2 proteins resulted in mutations proposing more virulent and contagious properties for this novel virus. Coronavirus penetrates the host cell via endocytosis and once infected, immune responses are triggered to fight against the pathogen. Innate immune response activates major transcription factors to secrete proinflammatory cytokines and type 1 interferon response (T1INF) to induce antiviral immunity. While adaptive immunity initiates cascade of B-cells antibody mediated and T-cells cellular mediate immunities, several mechanisms are raised by SARS-CoV-2 to evade host immune response. Consequently, a surge of proinflammatory cytokines, known as cytokine storm (CS) are released. Failure to manage CS results in several pathological complications as acute respiratory distress syndrome (ARDS). Although researches have not discovered an effective treatment against SARS-CoV-2, recent therapeutic approaches recommending the use of anti-inflammatories in combination with antivirals and some repurposed drugs for COVID-19 patients. Future medications should be designed to target essential hallmarks in the CS to improve clinical outcomes.

The use of social media networks is becoming a current phenomenon in the world today where people are sharing posts and tweets, connect with different groups, and share their opinions about things. This data is extremely heterogeneous and so it is hard to analyze and derive information from this data that is considered an indispensable source for decision-makers. New techniques are therefore needed to handle these huge amounts of data to find the hidden information thus improve the results of the analysis. We are developing a framework for the analysis of heterogeneous data using machine learning (ML) techniques. In contrast to most of the literature frameworks that focus on a specific type of heterogeneous data for evaluating the proposed framework, we have analyzed 15k tweets data from six American airlines. These tweets are collected from the open stream of Twitter, also predict, classify each tweet as a negative or positive review, and test the ability of deep learning (DL) algorithms by comparing it with traditional ML algorithms. The findings confirmed the validity of the proposed framework and helped to achieve the study objective by providing excellent analysis performance and provide insights into additional aspects of information extraction from heterogeneous data.

Alzheimer's disease (AD) is the commonest neurodegenerative disorder with a wide array of manifestations, courses, and contributing causes. Despite being clinically characterized a long time ago; no treatment has been developed that could improve the pathology or slow down the disease manifestation- so far. Indian Catechu methanolic extract (ICME) has proved to have multiple beneficial effects that support its use in several disorders- especially those with complex etiology. In the present study, we evaluated the neuroprotective effect of ICME in a rat model of AD using Aluminum Chloride (AlCl3). The results showed that ICME could have a positive impact on the course of AD through its anticholinesterase effect and significant antioxidant effect which was reflected on the animals both on behavioral tests as well as hallmark pathological findings.

This article addresses the preparation and characterization of polymer composites of polypropylene (PP) containing recycled wool or cotton micro-powder. The PP composites were produced in a lab-scale twin-screw extruder. The recycled wool or cotton powder was obtained from wool and cotton waste fibers (from textile industry) by freeze milling technique. The amount of powder (wool or cotton) was varied from 1% to 10 %. Cotton and wool powders were homogenously distributed in the polymer matrix, as observed from scanning electron microscopic (SEM) images. Thermal, physical, and mechanical properties of the obtained composites were investigated by differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), tensile strength, dyeability as well as the moisture uptake behavior is also explored. The overall results clarify that wool or cotton powders could be used as effective reinforcing materials for the production of PP composites with enhanced properties.

We report the case of a 50-year-old lady who presented to the emergency department complaining of a two-day history of colicky right upper quadrant (RUQ) pain, which radiated through to her back, associated with nausea, anorexia, and two episodes of vomiting that day. She was found to be tender in the RUQ. Her blood tests were notable for an elevated white cell count. Initial impression was of acute cholecystitis. Ultrasound of her abdomen did not identify any features of acute cholecystitis; however, a large volume of free fluid was identified within the abdomen. CT of the abdomen/pelvis was obtained which identified dilated loops of small bowel, interloop ascites, and a whirl sign highly suggestive of midgut volvulus. During laparoscopy, the midgut volvulus was found to have resolved. No cause for the volvulus could be identified, and the patient was discharged home well on postoperative day two.

Introduction Waterpipe tobacco smoking (WTS) continues to be very common in the Eastern Mediterranean Region (EMR), partially because of cultural acceptance but also because of misconceptions of its harm. This paper aimed to describe the beliefs towards waterpipe harm of university students who smoked waterpipe in five EMR countries. Methods This study was conducted in 2016 across five EMR countries: Egypt, Jordan, Occupied Palestinian Territories, Oman and United Arab Emirates (UAE). Participants were recruited from among university students in each country. Students’ characteristics, smoking behavior, flavor preference and knowledge of WTS harm were collected using an internet-based survey. Participants were included if they were ever waterpipe tobacco smokers and between 18 and 29 years of age. Bivariate analyses assessed variations in student-perceived WTS harm across the countries. Linear regression analysis was used to assess WTS perceived harm differences between students in the different countries. Results A total of 2 544 university students participated from the five countries. Among ever smoking students, 66% reported WTS in the past 30 days, with the highest proportions (40%) from Occupied Palestinian Territories (OPT) and (41%) Jordan. Dual smoking of waterpipe and cigarettes was highest among students from Egypt. Most participants from the five countries had high level of perceived harm related to WTS during pregnancy. Less than 50% of the students believed that WTS could lead to the death of the smoker, can be harmful for non-smokers and have an addictive effect. Female students, those older than 22 years, and those who didn’t smoke waterpipe in the last 30 days significantly had a higher level of WTS perceived harm. Participating students believed that cigarettes are more addictive and contain more nicotine compared to waterpipe. Conclusions Misperceptions of waterpipe harm are common among university students in the five EMR countries. Immediate public health action is needed, including enforcement of waterpipe tobacco control regulations along with awareness campaigns.

The high-risk pedigree (HRP) design is an established strategy to discover rare, highly-penetrant, Mendelian-like causal variants. Its success, however, in complex traits has been modest, largely due to challenges of genetic heterogeneity and complex inheritance models. We describe a HRP strategy that addresses intra-familial heterogeneity, and identifies inherited segments important for mapping regulatory risk. We apply this new Shared Genomic Segment (SGS) method in 11 extended, Utah, multiple myeloma (MM) HRPs, and subsequent exome sequencing in SGS regions of interest in 1063 MM / MGUS (monoclonal gammopathy of undetermined significance-a precursor to MM) cases and 964 controls from a jointly-called collaborative resource, including cases from the initial 11 HRPs. One genome-wide significant 1.8 Mb shared segment was found at 6q16. Exome sequencing in this region revealed predicted deleterious variants in USP45 (p.Gln691* and p.Gln621Glu), a gene known to influence DNA repair through endonuclease regulation. Additionally, a 1.2 Mb segment at 1p36.11 is inherited in two Utah HRPs, with coding variants identified in ARID1A (p.Ser90Gly and p.Met890Val), a key gene in the SWI/SNF chromatin remodeling complex. Our results provide compelling statistical and genetic evidence for segregating risk variants for MM. In addition, we demonstrate a novel strategy to use large HRPs for risk-variant discovery more generally in complex traits.

Neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by progressive neuronal loss and pathological accumulation of some proteins. Developing new biomarkers for both diseases is highly important for the early diagnosis and possible development of neuro-protective strategies. Serum antibodies (AIAs) against neuronal proteins are potential biomarkers for AD and PD that may be formed in response to their release into systemic circulation after brain damage. In the present study, two AIAs (tubulin and tau) were measured in sera of patients of PD and AD, compared to healthy controls. Results showed that both antibodies were elevated in patients with PD and AD compared to match controls. Curiously, the profile of elevation of antibodies was different in both diseases. In PD cases, tubulin and tau AIAs levels were similar. On the other hand, AD patients showed more elevation of tau AIAs compared to tubulin. Our current results suggested that AIAs panel could be able to identify cases with neuro-degeneration when compared with healthy subjects. More interestingly, it is possible to differentiate between PD and AD cases through identifying specific AIAs profile for each neurodegenerative states.

Early diagnosis of neurodegenerative diseases is of paramount importance for successful treatment. Lack of sensitive and early biomarkers for diagnosis of diseases like Parkinson’s disease (PD) is a handicapping problem for all movement disorders specialists. Using serum autoimmune antibodies (AIAs) against neural proteins is a new promising strategy to diagnose brain disorders through non-invasive and cost-effective method. In the present study, we measured the level of AIAs against α-synuclein (α-syn), which is an important protein involved in the pathogenesis of PD. In our study patients with PD (46 patients), Alzheimer’s disease (AD) (27 patients) and healthy controls (20 patients) were evaluated according to their sera α-syn AIAs levels. Interestingly, α-syn AIAs were significantly elevated in PD group compared to AD and healthy controls, which advocates their use for diagnosis of PD.

BACKGROUND:Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients. METHODS:Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months. RESULTS:Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS. CONCLUSION:In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.

Using objectively analysed hydrographic data,currents have been calculated off the Egyptian Mediterraneancoast at the surface and at 30, 50, 75, 100, 200 and 300 mdepths for the four seasons. The surface circulation is dominated by an anticyclonic circulationoff Salum Bay in winter, spring and summer. In nearshore areas,the current flows eastwards at the shallower levels but westwardsat the deeper levels. Off the Nile Delta, the current is almost eastward with a highervelocity in summer and autumn, while in spring it is very weak.Off the area between Port Said and Rafah, there is a clear cycloniccirculation appearing in all seasons except winter. At 50 and75 m depth, the velocity of the circulation is weak. At 100 m depth,the circulation that appeared between Matruh and Alamen in summer decreasesin area and magnitude at the former depths. At 200 and 300 m in winter, the current velocity is quite low. Inspring the current flows southwards off the area between Rafahand Port Said. In summer, the current off the area between PortSaid and Rafah is quite strong and flows to the south. The situationin autumn is quite similar to that in summer, except in the easternarea, where the current is a westward one.

The P301S mutation in exon 10 of the tau gene causes a hereditary tauopathy. While mitochondrial complex I inhibition has been linked to sporadic tauopathies. Piericidin A is a prototypical member of the group of the piericidins, a class of biologically active natural complex I inhibitors, isolated from streptomyces spp. with global distribution in marine and agricultural habitats. The aim of this study was to determine whether there is a pathogenic interaction of the environmental toxin piericidin A and the P301S mutation.Transgenic mice expressing human tau with the P301S-mutation (P301S+/+) and wild-type mice at 12 weeks of age were treated subcutaneously with vehicle (N = 10 P301S+/+, N = 7 wild-type) or piericidin A (N = 9 P301S+/+, N = 9 wild-type mice) at a dose of 0.5 mg/kg/d for a period of 28 days via osmotic minipumps. Tau pathology was measured by stereological counts of cells immunoreative with antibodies against phosphorylated tau (AD2, AT8, AT180, and AT100) and corresponding Western blot analysis.Piericidin A significantly increased the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S+/+ mice, but only to a variable and mild extent in wild-type mice. Furthermore, piericidin A led to increased levels of pathologically phosphorylated tau only in P301S+/+ mice. While we observed no apparent cell loss in the frontal cortex, the synaptic density was reduced by piericidin A treatment in P301S+/+ mice.This study shows that exposure to piericidin A aggravates the course of genetically determined tau pathology, providing experimental support for the concept of gene-environment interaction in the etiology of tauopathies.

Experimental models of Parkinson’s disease (PD) are of great importance for improving the design of future clinical trials. Various neurotoxic models are available, including 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat and rotenone. However, no model is considered perfect; each has its own limitations. Based on epidemiological data, a new trend of using environmental toxins in PD modeling seems attractive and has dominated public discussions of the disease etiology. A search for new environmental toxin-based models would improve our knowledge of the pathology of the condition. Here, we discuss some toxins of natural origin (e.g. cycad-derived toxins, epoxomicin, Nocardia asteroides bacteria, Streptomyces venezuelae bacteria, annonacin and DOPAL) that possibly represent a contributory environmental component to PD.

Background: Pramipexole is one of a new generation of dopamine agonists. Recently there have been questions regarding its neuroprotective effects. These effects have been tested against various insults, which have yielded conflicting results. Methods: In this study, we introduced a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/paraquat to induce a severe Parkinson’s disease model. The mice, after receiving the combination of toxins, were evaluated using mortality rates and immunohistochemistry for degenerating tyrosine hydroxylase-positive neurons. Results and conclusions: Pramipexole was tested for its capacity to offer protection against neurotoxic the effects of MPTP/paraquat in this model; however, the results showed no improvement with pramipexole therapy.

Background: Optimization of workflow for breast cancer samples with equivocal human epidermal growth factor receptors 2 (HER2)/neu score 2 + results in routine practice, remains to be a central focus of the on-going efforts to assess HER2 status. According to the College of American Pathologists/American Society of Clinical Oncology guidelines equivocal HER2/neu score 2 + cases are subject for further testing, usually by fluorescence in situ hybridization (FISH) investigations. It still remains on open question, whether quantitative digital image analysis of HER2 immunohistochemistry (IHC) stained slides can assist in further refining the HER2 score 2 + . Aim of this Work: To assess utility of quantitative digital analysis of IHC stained slides and compare its performance to FISH in cases of breast cancer with equivocal HER2 score 2 + . Materials and Methods: Fifteen specimens (previously diagnosed as breast cancer and was evaluated as HER 2– score 2 +) represented the study population. Contemporary new cuts were prepared for re-evaluation of HER2 immunohistochemical studies and FISH examination. All the cases were digitally scanned by iScan (Produced by BioImagene [Now Roche-Ventana]). The IHC signals of HER2 were measured using an automated image analyzing system (MECES, www.Diagnomx.eu/meces). Finally, a comparative study was done between the results of the FISH and the quantitative analysis of the virtual slides. Results: Three out of the 15 cases with equivocal HER2 score 2 + , turned out to be positive (3 +) by quantitative digital analysis, and 12 were found to be negative in FISH too. Two of these three positive cases proved to be positive with FISH, and only one was negative. Conclusions: Quantitative digital analysis is highly sensitive and relatively specific when compared to FISH in detecting HER2/neu overexpression. Therefore, it represents a potential reliable substitute for FISH in breast cancer cases, which desire further refinement of equivocal IHC results.