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Virulence Characteristics of Biofilm-Forming Acinetobacter baumannii in Clinical Isolates Using a Galleria mellonella Model

Research Authors
Mahmoud A F Khalil , Fatma A Ahmed , Ahmed F Elkhateeb , Eman E Mahmoud , Mona I Ahmed , Randa I Ahmed , Amal Hosni , Saad Alghamdi, Ahmed Kabrah , Anas S Dablool, Helal F Hetta , Sawsan S Moawad , Enas Mamdouh Hefzy
Research Date
Research File
paper 2.pdf (987.28 KB)
Research Member

Molecular and HPLC-based approaches for detection of aflatoxin B1 and ochratoxin A released from toxigenic Aspergillus species in processed meat

Research Authors
Abdelazeem M Algammal, Mahmoud E Elsayed, Hany R Hashem, Hazem Ramadan, Norhan S Sheraba, Eman M El-Diasty, Sarah M Abbas, Helal F Hetta
Research Date
Research File
paper 1.pdf (909.06 KB)
Research Member

Development and evaluation of dexamethasone-loaded bioadhesive polymeric nanocapsules for mitigating cardiac and gastric adverse effects of free dexamethasone

Impact of L-Arginine on diabetes-induced neuropathy and myopathy: Roles of PAI-1, Irisin, oxidative stress, NF-κβ, autophagy and microRNA-29a

Research Abstract

Background

T2DM is a chronic disorder with progressive neuromuscular alterations. L-arginine (ARG) is the most common semi-essential amino acid having several metabolic functions.

Aim

to investigate the impact of L-arginine in combating diabetic-induced neuromyopathy and its possible mechanisms.

Materials & Methods

24 rats were divided into CON, CON+ARG, DC, DC+ARG. Behavioral tests, Body weight (BW), fasting blood glucose (FBG), insulin, total antioxidant capacity (TAC), malondialdehyde (MDA), plasminogen activator inhibitor-1 (PAI-1), and irisin were done. Creatine kinase-MM (CK-MM), interleukin 4 (IL-4), interleukin 6 (IL-6), TAC, MDA, expression of microRNA-29a mRNA & light chain 3 protein were determined in muscle. Histological and NF-κβ immunohistochemical expression in muscle and nerve were assessed.

Results

ARG supplementation to diabetic rats improved altered behavior, significantly increased BW, insulin, TAC, irisin and Il-4, decreased levels of glucose, microRNA-29a, NF-κβ and LC3 expression, PAI-1, CK-MM and restored the normal histological appearance.

Conclusions

ARG supplementation potently alleviated diabetic-induced neuromuscular alterations.
Research Authors
Heba M Galal, Alaa T Abdelhafez, Manal M Sayed, Walaa MS Gomaa, Tohamy Anwar Tohamy, Asmaa MS Gomaa, Tarek H El-Metwally
Research Date
Research Journal
Tissue and Cell
Research Year
2024

Biallelic variation in the choline and ethanolamine transporter FLVCR1 underlies a severe developmental disorder spectrum

Research Abstract

Purpose

FLVCR1 encodes a solute carrier protein implicated in heme, choline, and ethanolamine transport. Although Flvcr1−/− mice exhibit skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia (DBA), biallelic FLVCR1 variants in humans have previously only been linked to childhood or adult-onset ataxia, sensory neuropathy, and retinitis pigmentosa.

Methods

We identified individuals with undiagnosed neurodevelopmental disorders and biallelic FLVCR1 variants through international data sharing and characterized the functional consequences of their FLVCR1 variants.

Results

We ascertained 30 patients from 23 unrelated families with biallelic FLVCR1 variants and characterized a novel FLVCR1-related phenotype: severe developmental disorders with profound developmental delay, microcephaly (z-score −2.5 to −10.5), brain malformations, epilepsy, spasticity, and premature death. Brain malformations ranged from mild brain volume reduction to hydranencephaly. Severely affected patients share traits, including macrocytic anemia and skeletal malformations, with Flvcr1−/− mice and DBA. FLVCR1 variants significantly reduce choline and ethanolamine transport and/or disrupt mRNA splicing.

Conclusion

These data demonstrate a broad FLVCR1-related phenotypic spectrum ranging from severe multiorgan developmental disorders resembling DBA to adult-onset neurodegeneration. Our study expands our understanding of Mendelian choline and ethanolamine disorders and illustrates the importance of anticipating a wide phenotypic spectrum for known disease genes and incorporating model organism data into genome analysis to maximize genetic testing yield.
Research Authors
Daniel G Calame, Jovi Huixin Wong, Puravi Panda, Dat Tuan Nguyen, Nancy CP Leong, Riccardo Sangermano, .........., Nourelhoda A. Haridy, ........, Henry Houlden, Fowzan S Alkuraya, Kinga Bujakowska, Reza Maroofian, James R Lupski, Long N Nguyen
Research Date
Research Journal
Genetics in Medicine
Research Publisher
Elsevier
Research Vol
Volume 27
Research Website
https://www.sciencedirect.com/science/article/abs/pii/S1098360024002077
Research Year
2025

Platinum and Taxane-Induced Neuropathy and Its Impact on Quality of Life: A Single Institution Study.

Research Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and challenging complication of platinum and taxane agents and can have a significant impact on patients' quality of life (QoL).
Objective: This study aims to detect the frequency and severity of CIPN in patients receiving Platinum and Taxane compounds and their effect on QoL.
Methods: This prospective study enrolled 47 patients receiving neurotoxic chemotherapy (taxanes and platinum-based agents) at Assiut University Hospital's Clinical Oncology Department between March 2023 and July 2024, with a median 6-month follow-up. CIPN was detected, graded, and assessed clinically by using the NCI-CTCAE v5.0 criteria and electrophysiologically through nerve conduction studies conducted in collaboration with the Neurology Department. Health-related quality of life (HRQoL) was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
Results: In this study, altered sensory symptoms occurred in 80-86.7% of patients across all regimens. Neuropathy grading revealed grade II in 44% of patients, grade I in 29%, and grade III in 25%. Platinum-based regimens were
significantly associated with grade II neuropathy (p<0.001), while platinum+taxane combinations showed the highest rate of grade III neuropathy (p=0.05). Nerve conduction studies demonstrated significant post-chemotherapy reductions in sensory nerve action potential (SNAP) and motor conduction velocities (MCV) (p<0.001). Higher CIPN grades correlated significantly with worse global health status (commonly with patients received platinum + taxane combinations), reduced physical function, and increased symptom burden on both QLQ-C30 and NCI-CTCAE V5 scales (p<0.014).
Conclusion: CIPN is a frequent and devastating complication in patients receiving taxane and platinum-based chemotherapy, with significant clinical, neurophysiological, and QoL implications. Future research should focus on strategies to prevent and mitigate this debilitating side effect.

Research Authors
Hassan MA El-Morshidy SM, Haridy NA, Mohamed TZ, Fathey WK
Research Date
Research Journal
SECI Oncology
Research Pages
253-261
Research Vol
Volume 13
Research Website
https://secioj.journals.ekb.eg/article_457677.html
Research Year
2025

Mutations in the key autophagy tethering factor EPG5 link neurodevelopmental and neurodegenerative disorders including early‐onset parkinsonism

Research Abstract

Objective

Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate the extended, age-dependent EPG5-related disease spectrum.

Methods

We investigated clinical, radiological, and molecular features from the largest cohort of EPG5-related patients identified to date, complemented by experimental investigation of cellular and animal models of EPG5 defects.

Results

Through worldwide collaboration, we identified 211 patients, 97 of them previously unpublished, with recessive EPG5 variants. The phenotypic spectrum ranged from antenatally lethal presentations to milder isolated neurodevelopmental disorders. A novel Epg5 knock-in mouse model of a recurrent EPG5 missense variant featured motor impairments and defective autophagy in brain areas particularly relevant for the neurological disorders in milder presentations. Novel age-dependent neurodegenerative manifestations in our cohort included adolescent-onset parkinsonism and dystonia with cognitive decline, and myoclonus. Radiological features suggested an emerging continuum with brain iron accumulation disorders. Patient fibroblasts showed defects in PINK1-Parkin-dependent mitophagic clearance and α-synuclein overexpression, indicating a cellular basis for the observed neurodegenerative phenotypes. In Caenorhabditis elegans, EPG5 knockdown caused motor impairments, defective mitophagic clearance, and changes in mitochondrial respiration comparable to observations in C. elegans knockdown of parkinsonism-related genes.

Interpretation

Our findings illustrate a lifetime neurological disease continuum associated with pathogenic EPG5 variants, linking neurodevelopmental and neurodegenerative disorders through the common denominator of defective autophagy.

Research Authors
Hormos Salimi Dafsari, Celine Deneubourg, Kritarth Singh, Reza Maroofian, Zita Suprenant, Ay Lin Kho, Neil J Ingham, Karen P Steel, Preethi Sheshadri,............, Nourelhoda A. Haridy,.............., Henry Houlden, Manolis Fanto, Heinz Jungbluth
Research Date
Research Journal
Annals of Neurology
Research Pages
932-950
Research Publisher
John Wiley & Sons, Inc.
Research Vol
Volume 98
Research Website
https://onlinelibrary.wiley.com/doi/full/10.1002/ana.78013
Research Year
2025

Nerve ultrasound as an adjunct to nerve conduction studies in Guillain–Barré syndrome diagnosis: a prospective Egyptian case–control study

Research Abstract

Background

Ongoing research aims to correlate ultrasound (US) findings with nerve conduction studies (NCS) results for the diagnosis of Guillain–Barré syndrome (GBS). NCS is currently the gold standard for confirming GBS diagnosis. This study aimed to compare nerve cross-sectional area (CSA) between GBS patients and controls and among different GBS subtypes, determine the correlation between CSA and NCS parameters, and identify a potential CSA cut-off value for early GBS screening. This study included 41 patients with GBS and 35 matched controls. Participants underwent comprehensive history taking, physical examination, NCS, and US measurement of CSA of peripheral nerves in upper and lower limbs. Receiver operating characteristic (ROC) analysis was performed to assess the ability of US CSA measurements to discriminate between GBS cases and controls.

Results

GBS patients had larger US nerve CSA than controls. No significant variations in CSA existed among different GBS electrophysiological subtypes. ROC curve analysis showed that median nerve CSAs at mid-forearm, pronator quadratus, and pronator teres were highly accurate for diagnosing GBS, with an area under the curve (AUC) of 1. Ulnar and posterior tibial nerve CSA were less precise. No substantial correlation existed between CSA and NCS parameters in the same nerve, although some association with clinical rating scales was present.

Conclusions

This study suggests nerve US may complement NCS in early GBS diagnosis, proposing CSA cut-off values for median, ulnar, and posterior tibial nerves. Further larger studies with standardized US protocols are needed to validate the reproducibility and diagnostic utility of these cut-offs.

Research Authors
Khalid O Mohamed, Hassan M Farweez, Shahera Sayed Ahmed Abd El Maged, Nourelhoda A Haridy
Research Date
Research Journal
The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
Research Publisher
Springer Berlin Heidelberg
Research Vol
Volume 61
Research Website
Khalid O Mohamed, Hassan M Farweez, Shahera Sayed Ahmed Abd El Maged, Nourelhoda A Haridy
Research Year
2025

Sleep disorders in a sample of Egyptian patients with Parkinson's disease: a case–control polysomnography study

Research Abstract

Background

Up to 96% of patients with Parkinson's disease (PD) experience sleep disturbances, which can emerge before motor symptoms. This study aims to determine the type of sleep disturbances in PD compared to controls using Parkinson's Disease Sleep Scale-2 (PDSS-2) and polysomnography (PSG). Twenty-four PD patients with sleep difficulties and 24 matched controls were included in this prospective case–control study. Sleep disturbances were diagnosed using screening questionnaires and PDSS-2. Patients were clinically assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). All participants were evaluated using Beck Depression Inventory (BDI), Montreal Cognitive Assessment (MoCA), and full-night video PSG.

Results

The PD group had significantly higher BDI and lower MoCA scores than the controls. PD patients had significantly lower sleep efficiency (87.32% versus 95.48%) and longer sleep latency (29 versus 2.45 min), shorter REM latency (37.97 versus 78.94 min), higher N2 sleep percentage (65.32% versus 51.43%), and lower REM sleep percentage (15.89% versus 19.22%). PD patients also had a higher arousal index (11.35 ± 9.46/h versus 3.44 ± 2.93/h), more periodic leg movements (7 ± 6.64 versus 2.21 ± 2.39), and a higher apnea–hypopnea index (7.96 ± 4.91 versus 4.12 ± 3.71). Sleep latency showed a negative correlation with MoCA and a positive correlation with disease duration. REM sleep percentage was negatively correlated with BDI. Arousal index /hour was negatively correlated with age onset.

Conclusions

This study confirms significant sleep architecture differences between PD patients and controls, emphasising the importance of comprehensive sleep assessment and management in PD care.

Research Authors
Eman M Khedr, Jaidaa Mekky, Mohammad A Korayem, Gellan K Ahmed, Nourelhoda A Haridy
Research Date
Research Journal
The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
Research Publisher
Springer Berlin Heidelberg
Research Vol
Volume 61
Research Website
Volume 61
Research Year
2025

APOE genetic variability in an Egyptian cohort of PD

Research Abstract

Background: The apolipoprotein E (APOE) gene, encompassing three alleles (ε2, ε3, ε4), is a critical player in lipid metabolism and has been extensively studied for its role in neurodegenerative diseases. This study examines APOE genetic variability and its association with PD in an Egyptian cohort.

Methods: A total of 891 participants, including 422 PD patients and 469 healthy controls, were included in this study. APOE genotyping was performed using Kompetitive Allele Specific PCR (KASP) to detect the rs429358 and rs7412 SNPs, which define the APOE alleles. APOE alleles were categorized based on the genotypes into ε2, ε3, and ε4 groups. Clinical assessments of PD patients included age at onset, disease severity (MDS-UPDRS), and demographic factors. Statistical analyses compared APOE distributions between PD and control groups and examined associations with clinical variables.

Results: The ε3 allele was the most prevalent in the cohort (77.3%), aligning with global and African trends. The ε2 allele was observed in 11.4%, and the ε4 allele in 11.3%, with both frequencies being lower than reported African estimates. The ε3/ε3 genotype was predominant in both PD patients (72.51%) and controls (72.07%). The ε4/ε4 genotype was absent in PD cases and rare among controls (0.64%). No significant association was found between APOE genotypes and PD risk, age at onset, or disease severity.

Conclusion: Our findings do not support a significant role for APOE in PD susceptibility or severity in Egyptians.

Research Authors
Eman M Khedr, Martina B William, Aliaa El-Hosseiny, Ali Soliman Shalash, Gharib Fawi, Mohamed H Yousef, Shaimaa Ibrahim El-Jaafary, Hamin Lee, Alina Jama, Mohamed Koraym, Asmaa Helmy, Yara Salah, David Adel, Nourelhoda A Haridy, ......., Mohamed Salama
Research Date
Research Journal
Frontiers in Neuroscience
Research Publisher
Frontiers
Research Vol
Volume 19
Research Website
Frontiers
Research Year
2025
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