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Fulltext The prevalence of urinary tract infections in type 2 diabetic patients: a systematic review and meta-analysis

Salari N, Karami MM, Bokaee S, Chaleshgar M, Shohaimi S, Akbari H, et al.

Eur J Med Res, 2022 Feb 05;27(1):20.
PMID: 35123565 DOI: 10.1186/s40001-022-00644-9

BACKGROUND: Urinary tract infection is the most common infection in type 2 diabetic patients. Various studies have reported different outbreaks of urinary tract infections in type 2 diabetic patients. Therefore, the present study aimed to determine the prevalence of urinary tract infections in type 2 diabetic patients during a systematic review and meta-analysis in order to develop interventions to reduce the incidence of urinary tract infections in type 2 diabetic patients.
METHODS: In this study, systematic review and meta-analysis of study data related to the prevalence of urinary tract infection in type 2 diabetic patients were conducted using keywords including type 2 diabetes, urinary tract infection, diabetes, prevalence, meta-analysis and their English equivalents in SID, MagIran, IranMedex, IranDoc, Google Scholar, Cochrane, Embase, Science Direct, Scopus, PubMed and Web of Science (WoS) databases from 1993 to 2020. In order to perform the analysis of qualified studies, the model of random-effects was used, and the inconsistency of studies with the I2 index was investigated. Data analysis was performed with Comprehensive Meta-Analysis (Version 2).
RESULTS: Based on a total of 15 studies with a sample size of 827,948 in meta-analysis, the overall prevalence of urinary tract infection in patients with type 2 diabetes was 11.5% (95% confidence interval: 7.8-16.7%). The prevalence of urinary tract infections in diabetic Iranian patients increased with increasing number of years of research, (p
Squamous odontogenic tumor of the mandible: a case report demonstrating immunoexpression of Notch1, 3, 4, Jagged1 and Delta1

Siar CH, Nakano K, Ng KH, Tomida M, Nagatsuka H, Kawakami T

Eur J Med Res, 2010 Apr 08;15(4):180-4.
PMID: 20554499

BACKGROUND: Squamous odontogenic tumor (SOT) is a rare benign odontogenic epithelial neoplasm. A slow-growing painless expansive swelling is the common presenting symptom. Histopathologically, SOT can be easily misdiagnosed as an acanthomatous ameloblastoma. Although Notch receptors and ligands have been shown to play a role in cell fate decisions in ameloblastomas, the role of these cell signaling molecules in SOT is unknown.
CASE REPORT: This paper describes a case of SOT affecting the anterior mandible of a 10-year-old Indian female. The patient was treated by local surgical excision and there has been no follow-up clinical record of recurrence 5 years after primary treatment. Histo?pathological examination revealed a solid, locally-infiltrative neoplasm composed of bland-looking squamatoid islands scattered in a mature fibrous connective tissue stroma and the diagnosis was SOT. Immunohistochemical evaluation showed positive reactivity of varying intensity in the neoplastic epithelial cells for Notch1, Notch3, Notch4, and their ligands Jagged1 and Delta1. Expression patterns showed considerable overlap. No immunoreactivity was detected for Notch2 and Jagged2.
CONCLUSIONS: Present findings suggest that Notch receptors and their ligands play differential roles in the cytodifferentiation of SOT.
An unsuspected ameloblastoma in the subpontic region of the mandible with consideration of pathogenesis from the radiographic course

Siar CH, Nakano K, Chelvanayagam PI, Ng KH, Nagatsuka H, Kawakami T

Eur J Med Res, 2010 Mar 30;15(3):135-8.
PMID: 20452900

The purpose of this report is to document a case of unsuspected ameloblastoma involving the right man dibular subpontic region in a 38-year-old Cambodian female patient. This lesion was purportedly preceded by multiple radiolucencies which were diagnosed as radicular cysts and treated a few times in the past years by enucleation followed by endodontic therapy of the affected teeth. Bridgework restoration of the partially edentulous area was performed. This case report demonstrates radiographic changes that occurred in the periods before and after the diagnosis of ameloblastoma. The case may represent an example of radicular cysts and ameloblastoma occurring as a collision phenomenon, or the ameloblastoma may have arisen as a result of neoplastic transformation of the lining epithelium in an inflammatory odontogenic epithelial cyst.
Angiogenic squamous dysplasia-like phenomenon in oral epithelial precursor lesions

Siar CH, Oo VP, Nagatsuka H, Nakano K, Ng KH, Kawakami T

Eur J Med Res, 2009 Jul 22;14(7):315-9.
PMID: 19661015

STATEMENT OF THE PROBLEM: Dysplasia, the morphological yardstick of epithelial precursor lesions, is the collective term for a variety of architectural and cytological changes within the altered oral epithelium. Angiogenic squamous dysplasia (ASD), a distinct morphological characteristic in pre-invasive bronchial lesions, describes the presence of capillary tufts that are closely juxtaposed to and projecting into the dysplastic bronchial epithelium.
OBJECTIVE: To determine whether ASD-like phenomenon occurs in oral epithelial precursor lesions, and to speculate on its relevance.
METHODS: Twenty cases each of mild, moderate and severe oral dysplasia (inclusive of carcinoma-in-situ), and 10 normal oral mucosa (normal controls) were serial sectioned for H and E staining, and for microvessel density (MVD) scoring with CD31, CD34 and CD105. Microcapillary pattern images were digitally captured for 3-D reconstruction.
RESULTS: Oral ASD foci consisting of CD31- and CD34-positive capillary loops abutting onto the overlying dysplastic oral epithelium (and causing it to assume an irregular or papillary surface configuration) were identified in moderate (3/20; 15%) and severe dysplasia (13/20; 65%), but not in normal oral mucosa and mild dysplasia. MVD score demonstrated increasing vascularity as epithelium progressed from normal to severe dysplasia (p<0.05). CD105 demonstrated increase neovascularization in all dysplasia grades (p<0.05).
CONCLUSIONS: These preliminary findings taken together suggest that: 1. ASD-like phenomenon may be an important intermediary biomarker in oral precursor lesions; and 2. architectural alterations of the entire disturbed mucosa may be a more useful pre-malignancy index.
Notch signaling and ghost cell fate in the calcifying cystic odontogenic tumor

Siar CH, Kawakami T, Buery RR, Nakano K, Tomida M, Tsujigiwa H, et al.

Eur J Med Res, 2011 Nov 10;16(11):501-6.
PMID: 22027644

Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs) are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites). Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (CCOT), their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4) and three ligands (Jagged1, Jagged2 and Delta1) was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0), mild (+), moderate (2+) and strong (3+). Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1-Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.
Strawberry gingivitis as the first presenting sign of Wegener's granulomatosis: report of a case

Siar CH, Yeo KB, Nakano K, Nagatsuka H, Tsujigiwa H, Tomida M, et al.

Eur J Med Res, 2011 Jul 25;16(7):331-4.
PMID: 21813375

Wegener's granulomatosis is a rare multi-system disease characterized by the classic triad of necrotizing granulomas affecting the upper and lower respiratory tracts, disseminated vasculitis and glomerulonephritis. Oral lesions as a presenting feature are only encountered in 2% of these cases. Hyperplastic gingival lesions or strawberry gingivitis, is a characteristic sign of Wegener's granulomatosis. The latter consists of reddish-purple exophytic gingival swellings with petechial haemorrhages thus resembling strawberries. Recognition of this feature is of utmost importance for timely diagnosis and definitive management of this potentially fatal disease. A case of strawberry gingivitis as the first presenting sign of Wegener's granulomatosis affecting a 50-year-old Malay male is reported here. The differential diagnosis of red lesions that may present in the gingiva is discussed.
Immunolocalization of notch signaling protein molecules in a maxillary chondrosarcoma and its recurrent tumor

Siar CH, Ha KO, Aung LO, Nakano K, Tsujigiwa H, Nagatsuka H, et al.

Eur J Med Res, 2010 Oct 25;15(10):456-60.
PMID: 21156405

BACKGROUND: notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified.
METHOD: tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1) expression.
RESULTS: both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I). Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members.
CONCLUSIONS: Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.
Fulltext Correction: First isolation and identification of Cystobasidium calyptogenae from the oral samples of an elderly patient presenting with angular cheilitis

Karajacob AS, Goh JPE, Kallarakkal TG, Tay ST

Eur J Med Res, 2022 Dec 06;27(1):277.
PMID: 36471451 DOI: 10.1186/s40001-022-00884-9
Fulltext Study on the transferability of the knowledge-based VMAT model to predict IMRT plans in prostate cancer radiotherapy

Bi S, Sun X, Sohaimi WFBW, Yusoff ALB

Eur J Med Res, 2023 Aug 31;28(1):309.
PMID: 37653551 DOI: 10.1186/s40001-023-01278-1

OBJECTIVE: The aim of this study was to investigate the feasibility of VMAT library-derived model transfer in the prediction of IMRT plans by dosimetry comparison among with three groups of IMRT plans: two groups of automatic IMRT plans generated by the knowledge-based the volumetric modulated arc therapy (VMAT) model and intensity-modulated radiation therapy (IMRT) model and one group of manual IMRT plans.
METHODS: 52 prostate cancer patients who had completed radiotherapy were selected and randomly divided into 2 groups with 40 and 12 separately. Then both VMAT and IMRT plans were manually designed for all patients. The total plans in the group with 40 cases as training datasets were added to the knowledge-based planning (KBP) models for learning and finally obtained VMAT and IMRT training models. Another 12 cases were selected as the validation group to be used to generated auto IMRT plans by KBP VMAT and IMRT models. At last, the radiotherapy plans from three groups were obtained: the automated IMRT plan (V-IMRT) predicted by the VMAT model, the automated IMRT plan (I-IMRT) predicted by the IMRT model and the manual IMRT plan (M-IMRT) designed before. The dosimetric parameters of planning target volume (PTV) and organ at risks (OARs) as well as the time parameters (monitor unit, MU) were statistically analyzed.
RESULTS: The dose limit of all plans in the training datasets met the clinical requirements. Compared with the training plans added to VMAT model, the dosimetry parameters have no statistical differences in PTV (P > 0.05); the dose of X% volume (Dx%) with D25% and D35% in rectal and the maximum dose (Dmax) in the right femoral head were lower (P = 0.04, P = 0.01, P = 0.00) while D50% in rectal was higher ( 0.05), but the Dmax in left femoral heard and D15% in the right femoral head were lower and have significant differences (P 0.05).
CONCLUSION: Compared with the manual plan, the IMRT plans generated by the KBP models had a significant advantage in dose control of both OARs and PTV. Compared to the I-IMRT plans, the V-IMRT plans was not only without significant disadvantages, but it also achieved slightly better control of the low-dose region, which meet the clinical requirements and can used in the clinical treatment. This study demonstrates that it is feasible to transfer the KBP VMAT model in the prediction of IMRT plans.
Association between CYP3A4/CYP3A5 genetic polymorphisms and treatment outcomes of atorvastatin worldwide: is there enough research on the Egyptian population?

Maslub MG, Radwan MA, Daud NAA, Sha'aban A

Eur J Med Res, 2023 Sep 27;28(1):381.
PMID: 37759317 DOI: 10.1186/s40001-023-01038-1

INTRODUCTION: Atorvastatin is regarded as the most frequently prescribed statin worldwide for dyslipidemia. However, clinical response and risk of adverse effects to statin therapy are associated with genetic variations. Numerous research linked statins pharmacokinetics (PK) variations to genetic polymorphisms in cytochromes P450 (CYPs) metabolic enzymes.
OBJECTIVE: This article reviews the association between CYP3A4/5 genetic variations and response to atorvastatin therapy globally, which includes atorvastatin PK, and the risk for adverse reactions, with a hint to the Egyptians.
METHODS: Up to March 30, 2022, electronic medical databases like PubMed, Web of Science, MEDLINE, and Egyptian Knowledge Bank (EKB) were searched. All articles that highlighted the relationship between CYP3A4/5 genetic polymorphisms and atorvastatin efficacy/safety profile were included in this review.
RESULTS: Initially, 492 articles were retrieved after an exhaustive search. There were 24 articles included according to the inclusion criteria. Findings of association studies of CYP3A4/5 genetic polymorphisms with response to atorvastatin varied among different ethnicities. CYP3A4*1B was associated with better therapeutic outcomes after atorvastatin therapy in Chileans and vice versa in Americans. Caucasians with myalgia while using atorvastatin were at significant risk of suffering severe muscle damage if they were carriers of CYP3A5*3/*3. As far as we can report for the Egyptian population, the impact of CYP3A4/5 genetic variations on the response to atorvastatin therapy was understudied.
CONCLUSION: More pharmacogenetic studies amongst diverse populations worldwide, like the Egyptian population, are necessary to detect further atorvastatin-gene interactions.
CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin

Maslub MG, Daud NAA, Radwan MA, Sha'aban A, Ibrahim AG

Eur J Med Res, 2024 Nov 10;29(1):539.
PMID: 39523378 DOI: 10.1186/s40001-024-02109-7

BACKGROUND: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians.
OBJECTIVE: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians.
METHODS: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes.
RESULTS: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P
The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery

Awuah WA, Ahluwalia A, Ghosh S, Roy S, Tan JK, Adebusoye FT, et al.

Eur J Med Res, 2023 Nov 16;28(1):529.
PMID: 37974227 DOI: 10.1186/s40001-023-01504-w

Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.
Family planning behaviours among women with diabetes mellitus: a scoping review

Awang Dahlan S, Idris IB, Mohammed Nawi A, Abd Rahman R

Eur J Med Res, 2024 Jan 11;29(1):41.
PMID: 38212858 DOI: 10.1186/s40001-023-01626-1

INTRODUCTION: Diabetes mellitus in pregnancies is associated with adverse outcomes both for the mothers and babies. Postponing pregnancy in unoptimized conditions and stabilisation of glucose should be prioritized. This scoping review is aimed to determine the scope and at the same time map the types of evidence available that is related to family planning behaviours among women with diabetes mellitus, with a particular focus on their factors which influence family planning usage and subsequently enable the identification of knowledge gaps in preventing unintended pregnancies among this high-risk population.
METHODS: This scoping review is guided by the methodological framework by Arksey and O'Malley's and Prisma-ScR checklist. PubMed, EBSCO and OVID were searched for empirical studies between 2000 and February 2022 using the search terms "family planning", "contraceptive" and "diabetes mellitus". Data were summarized according to the study characteristics and levels of factors influencing family planning behaviours.
RESULTS: Thirty-five articles that met the eligibility criteria included 33 quantitative studies, one qualitative study and one mixed-methods study. The prevalence of family planning methods used by women with diabetes mellitus varied ranging from 4.8 to 89.8% among the studied population. Women with diabetes mellitus were reported to be less likely to utilise any family planning methods compared to women without diabetes mellitus.
CONCLUSIONS: Most of the evidence to date on family planning behaviours among women with diabetes mellitus focuses on the role of individual level sociodemographic factors. Few studies focused on exploring determinants at multiple levels. In this review we found that there is limited evidence on disease control and pregnancy intention in relation to their family planning practices. Future studies with more clinical and contextual factors are needed to guide the strengthening of family planning services for high-risk group women specifically for women with diabetes mellitus.

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