Bladder trauma: a guideline of the guidelines.

OBJECTIVES: To identify and review the most up-to-date guidelines pertaining to bladder trauma in a unifying document as an updated primer in the management of all aspects relating to bladder injury. METHODS: In accordance with the PRISMA statement, the most recent guidelines pertaining to bladder injury were identified and subsequently critically appraised. An electronic search of PubMed and Scopus databases was carried out in September 2023. RESULTS: A total of six guidelines were included: European Association of Urology (EAU) guidelines on urological trauma (2023), EAU guidelines on paediatric urology (2022), Urotrauma: American Urological Association (AUA) (2020), Kidney and Uro-trauma: World Society of Emergency Surgery and the American Association for the Surgery of Trauma (WSES-AAST) guidelines (2019), Management of blunt force bladder injuries: A practice management guideline from the Eastern Association for the Surgery of Trauma (EAST) (2019), and EAU guidelines on iatrogenic trauma (2012). Recommendations were summarised with the associated supporting level of evidence and strength of recommendation where available. CONCLUSION: Several widely recognised professional organisations have published guidelines relating to the diagnosis, investigation, classification, management, and follow-up related to bladder injury. There is consensus amongst all major guidelines in terms of diagnosis and management but there is some discrepancy and lack of recommendation with regards to the follow-up of bladder injuries, iatrogenic bladder injury, paediatric bladder trauma, and spontaneous bladder rupture. The role of increasing minimally invasive techniques seem to be gaining traction in the select haemodynamically stable patient. Further research is required to better delineate this treatment option.

Spontaneous (idiopathic) rupture of the urinary bladder: a systematic review of case series and reports.

OBJECTIVES: To perform a systematic review of all cases of spontaneous rupture of the urinary bladder (SRUB) and to describe the demographic data, associated comorbidities, clinical presentation, diagnosis, relevant laboratory findings, associated factors, management, morbidity and mortality associated with the presentation of SRUB. METHODS: The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). A search was carried out across the following electronic databases: PubMed, Web of Science, Scopus, Google Scholar and the Cochrane Database of Systematic Reviews. Full texts of selected studies were analysed, and data extracted. The review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: A total of 278 articles comprising 240 case reports and 38 case series, with a total of 351 patients were included. The median (interquartile range [IQR]) age of all included patients was 47.5 (33-65) years. The median (IQR) time to presentation was 48 (24-96) h, with the major presenting symptom being abdominal pain (76%). In patients in whom the diagnosis was made prior to any intervention, the condition was misdiagnosed in 64% of cases. The diagnosis was confirmed during explorative open surgery in 42% of cases. Pelvic radiation (13%) and alcohol intoxication (11%) were the most common associated factors. Intraperitoneal rupture (89%) was much more common, with the dome of the bladder being most frequently involved (55%). The overall mortality was 15%. CONCLUSION: This review identified a number of key factors that appear to be associated with an increased incidence of SRUB. It also emphasized the high rate of misdiagnosis and challenge in confirming the diagnosis. Overall, it highlighted the importance of the need for increased awareness and maintaining a high index of suspicion for this condition.

Major heritable renal cell carcinoma syndromes: novel treatment options and future perspectives.

PURPOSE OF REVIEW: To provide an overview of diagnosis, genetic abnormalities, clinical signs and treatment options for the major heritable renal cell carcinoma (RCC) syndromes. RECENT FINDINGS: RCC in major hereditary syndromes are disorders which are typically autosomal dominant. They predispose patients to early onset of RCC and may exhibit other extrarenal manifestations. Early recognition of these diseases allows correct screening at appropriate ages as well as early detection of RCC. Moreover, expedient identification may optimize the management of extra renal manifestations as well as allow for genetic testing and screening of at-risk relatives. SUMMARY: The risk of RCC in these major heritable syndromes is higher than sporadic disease. They occur at earlier age groups and can be multifocal or bilateral. Tumours are observed until at least 3 cm before any intervention, while nephron sparing surgery is widely considered as the treatment of choice except for hereditary leiomyomatosis with renal cell cancer, of which radical nephrectomy is treatment of choice. Intervention should be timeous as there is a highly reported incidence of early metastasis. Molecular therapies have been used in the setting of patients with metastasis, some of which show favourable outcomes.

The Effect of Aflatoxin B1 on Tumor-Related Genes and Phenotypic Characters of MCF7 and MCF10A Cells.

The fungal toxin aflatoxin B1 (AB1) and its reactive intermediate, aflatoxin B1-8, 9 epoxide, could cause liver cancer by inducing DNA adducts. AB1 exposure can induce changes in the expression of several cancer-related genes. In this study, the effect of AB1 exposure on breast cancer MCF7 and normal breast MCF10A cell lines at the phenotypic and epigenetic levels was investigated to evaluate its potential in increasing the risk of breast cancer development. We hypothesized that, even at low concentrations, AB1 can cause changes in the expression of important genes involved in four pathways, i.e., p53, cancer, cell cycle, and apoptosis. The transcriptomic levels of BRCA1, BRCA2, p53, HER1, HER2, cMyc, BCL2, MCL1, CCND1, WNT3A, MAPK1, MAPK3, DAPK1, Casp8, and Casp9 were determined in MCF7 and MCF10A cells. Our results illustrate that treating both cells with AB1 induced cytotoxicity and apoptosis with reduction in cell viability in a concentration-dependent manner. Additionally, AB1 reduced reactive oxygen species levels. Phenotypically, AB1 caused cell-cycle arrest at G1, hypertrophy, and increased cell migration rates. There were changes in the expression levels of several tumor-related genes, which are known to contribute to activating cancer pathways. The effects of AB1 on the phenotype and epigenetics of both MCF7 and MCF10A cells associated with cancer development observed in this study suggest that AB1 is a potential risk factor for developing breast cancer.

Identification of Alkaloid Compounds Arborinine and Graveoline from Ruta angustifolia (L.) Pers for their Antifungal Potential against Isocitrate lyase (ICL1) gene of Candida albicans.

Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised individuals. Their metabolic adaptation depends on glyoxylate cycle to survive in nutrient-limited host. The long term usage of fungistatic drugs and the lack of cidal drugs frequently result in strains that could resist commonly used antifungals and display multidrug resistance (MDR). In search of potential therapeutic intervention and novel fungicidals, we have explored a plant alkaloids, namely arborinine and graveoline for its antifungal potential. Alkaloids belongs to Rutaceae family have been reported with numerous antimicrobial activities. In this study, we aimed to isolate and identify the antifungal active alkaloids of R. angustifolia and assess antifungal effect targeting C. albicans isocitrate lyase (ICL) gene which regulates isocitrate lyase, key enzyme in glyoxylate cycle contributing to the virulence potential of C. albicans. Alkaloids were extracted by bioassay guided isolation technique which further identified by TLC profile and compared with the standard through HPLC and NMR analysis. The antifungal activities of the extracted alkaloids were quantified by means of MIC (Minimum Inhibitory Concentration). The gene expression of the targeted gene upon treatment was analysed using RT-qPCR and western blot. Additionally, this study looked at the drug-likeness and potential toxicity effect of the active alkaloid compounds in silico analysis. Spectroscopic analysis showed that the isolated active alkaloids were characterized as acridone, furoquinoline, 4-quinolone known as arborinine and graveoline. Results showed that each compound significantly inhibited the growth of C. albicans at the dose of 250 to 500 µg/mL which confirm its antifungal activity. Each alkaloid was found to successfully downregulate the expression of both ICL1 gene CaIcl1 protein. Finally, ADMET analysis suggests a good prediction of chemical properties, namely absorption, distribution, metabolism, excretion and toxicity (ADMET) that will contribute in drug discovery and development later on.

Systematic review: bacterial colonisation of conduits and neobladders-when to test, watch, and treat.

BACKGROUND: Urinary diversion procedures frequently result in bacterial colonisation. There is an increased incidence of developing urinary tract infections (UTIs) in this patient population. Current guidelines, however, recommend against treating this colonisation. This systematic review aimed to determine when and how to test, monitor, and treat bacteriuria in patients with urinary diversion. METHODS: A systematic search strategy was conducted based on keywords "urinary diversion" and "bacteriuria", on MEDLINE, Embase, and Google Scholar. Articles were screened and included only if they reported on (i) testing methods for bacteriuria, (ii) surveillance of bacteriuria over time, or (iii) when and how to treat bacteriuria. Results were summarised and reported using a narrative synthesis. RESULTS: Altogether, 26 studies were included in this review. Inconsistencies were noted in the definitions of bacteriuria, with most studies reporting bacteriuria as > 104 cfu/mL (8/17 studies). Bacteriuria prevalence varied greatly (range 9.1-100%). Monitoring bacteriuria over time may help detect a reduction in bacteriuria, as demonstrated in three studies (follow-up range 5-18 months; sample size 18-56). The link between preceding bacteriuria and subsequent UTIs has not been fully explored yet. Short-term antimicrobial therapy may be useful in the immediate post-operative setting; however, long-term prophylactic treatment is ineffective in preventing bacteriuria. CONCLUSIONS: We recommend consistent reporting of bacteriuria definitions, the benefits of monitoring bacteriuria over time, and use of short-term antimicrobial therapy; bacteriuria should not be treated with long-term therapy.

A Deep Learning-Based End-to-End Composite System for Hand Detection and Gesture Recognition.

Recent research on hand detection and gesture recognition has attracted increasing interest due to its broad range of potential applications, such as human-computer interaction, sign language recognition, hand action analysis, driver hand behavior monitoring, and virtual reality. In recent years, several approaches have been proposed with the aim of developing a robust algorithm which functions in complex and cluttered environments. Although several researchers have addressed this challenging problem, a robust system is still elusive. Therefore, we propose a deep learning-based architecture to jointly detect and classify hand gestures. In the proposed architecture, the whole image is passed through a one-stage dense object detector to extract hand regions, which, in turn, pass through a lightweight convolutional neural network (CNN) for hand gesture recognition. To evaluate our approach, we conducted extensive experiments on four publicly available datasets for hand detection, including the Oxford, 5-signers, EgoHands, and Indian classical dance (ICD) datasets, along with two hand gesture datasets with different gesture vocabularies for hand gesture recognition, namely, the LaRED and TinyHands datasets. Here, experimental results demonstrate that the proposed architecture is efficient and robust. In addition, it outperforms other approaches in both the hand detection and gesture classification tasks.

'Prostate Cancer Risk Calculator' mobile applications (Apps): a systematic review and scoring using the validated user version of the Mobile Application Rating Scale (uMARS).

PURPOSE: The use of mobile phone applications (Apps) has modernised the conventional practice of medicine. The diagnostic ability of the current Apps in prostate specific antigen monitoring, and its diagnostic ability within prostate cancer (PCa) risk calculators have not yet been appraised. We aimed to review, rate and assess the everyday functionality, and utility of all the currently available PCa risk calculator Apps. METHODS: A systematic search on iTunes, Google Play Store, Blackberry World and Windows Apps Store, was performed on 23/11/2017, using the search term 'prostate cancer risk calculator'. After applying the exclusion criteria, each App was individually assessed and rated using pre-set criteria and grading was performed using the validated uMARS scale. RESULTS: In total, 83 Apps were retrieved. After applying our exclusion criteria, only 9 Apps were relevant, with 2 duplicated, and the remaining 7 were suitable for critical review. Data sizes ranged from 414 kb to 10.1 Mb. The cost of the Apps ranged from South African rand (ZAR) 0.00 to ZAR 29.99. The overall mean category uMARS scores ranged from 2.8/5 to 4.5/5. Apps such as Rotterdam Prostate Cancer Risk Calculator, Coral-Prostate Cancer Nomogram Calculator and CPC Risk Calculator, performed the best. CONCLUSIONS: The current PCa risk calculator mobile Apps available may be beneficial in counselling the concerned at risk patient. These Apps have potential to assist both the patient and the urologist alike. The PCa risk calculator App 'predictability' may be further enhanced by the incorporation of newly validated risk factors and predictors for PCa.

The ultrasonographic "whirlpool sign" in testicular torsion: valuable tool or waste of valuable time? A systematic review and meta-analysis.

PURPOSE: A positive whirlpool sign (WS) is defined as the presence of a spiral-like pattern when the spermatic cord is assessed during ultrasonography (US), using standard, high-resolution ultrasonography (HRUS) and/or color Doppler sonography (CDS), in the presence of testicular torsion. The objective of this review was to assess the validity and accuracy of this sign by performing a comprehensive systematic literature review and meta-analysis. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a comprehensive literature search was performed (August, 2017), using the following databases: BMJ Best Practice, Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Selected studies were further assessed for relevance and quality using the Oxford 2010 Critical Appraisal Skills Program (CASP). RESULTS: Of the studies assessed, a total of 723 participants were included, with a mean of 72.3 (SD 71.9) participants. Of the participants, 226 (31.3%) were diagnosed with testicular torsion (TT). Meta-analysis of the studies that provided sufficient data resulted in a pooled sensitivity and specificity of the WS of 0.73 (95% CI, 0.65-0.79) and 0.99 (95% CI, 0.92-0.99), respectively. Removal of all neonates increased the pooled sensitivity to 0.92 (95% CI, 0.70-0.98) while the pooled specificity remained almost unchanged at 0.99 (95% CI, 0.95-1.00). The estimated summary effect of all studies with sufficient data was 4.34 (95% CI, 1.01-7.67; n = 394; p = 0.001). A large degree of heterogeneity was suggested by an I2 statistic of 88.27% (95% CI, 68.60-98.68%). Removal of neonatal subjects increased the estimated summary effect to 5.32 (95% CI, 1.59-9.05; n = 375; p = 0.001). CONCLUSION: The WS, when correctly diagnosed, may be viewed as a very definitive sign for TT in the pediatric and adult populations. However, its role in neonates is limited.

Lack of consensus in atypical congenital obstructive urethral lesions in children: Snapshot of the web-based ObsCUre (obstruction to the child urethra) study.

Background: Atypical Congenital Obstructive Urethral Lesions (ACOUL) are uncommon causes of urethral obstruction in children. They include Cobb's collar or Moorman's ring, Type III posterior urethral valve (PUV), congenital urethral narrowing and anterior urethral valves. This study is aimed to evaluate the knowledge and current practice amongst clinicians attending to ACOUL. An international online case based questionnaire was performed. Materials and methods: A survey was administered to members of international urological societies. It included 22 clinical questions on cases with ACOUL (14 questions suitable for statistical analysis) using cases of Type I PUV as controls. Two sets of paired questions evaluated change in opinion(s) after additional information was provided. Results: One hundred twenty-one participants responded with 71% reporting exposure of less than 5 cases per annum. In questions regarding diagnosis between 11.6% (14/121) and 21.5% (26/121) of participants identified the ACOUL as PUV. Among them, 66% of respondents agreed on ACOUL's causative role in urethral obstruction. Gini coefficient was consistently lower for ACOUL compared to PUV: diagnosis (mean 0.33 vs. 0.44) and prognosis (0.23 vs. 0.43). High intra-rater concordance (kappa 0.420.57) was observed for paired questions-a mean of 5.79% (7.44% and 4.13% for questions 10 and 12, 16 and 17, respectively) of participants changed their answers from an alternate diagnosis to the correct diagnosis of ACOUL after viewing endoscopic images. High variation in management of ACOUL was noted (Gini 0.51). Conclusions: This global snapshot survey identified substantial inconsistency among clinicians dealing with ACOUL. Although rarely encountered in clinical practice, better overall education of ACOUL is warranted.

Design and Validation of a Novel 3D-Printed Retrograde Intrarenal Surgery Trainer.

OBJECTIVE: To report on the design of a novel 3D-printed retrograde intrarenal surgery (RIRS) benchtop trainer and detail its validation against real-life experiences. METHODS: Digital Imaging and Communications in Medicine (DICOM) files of 2 patients with normal computed tomography of the kidney and bladder were converted into stereolithography files to create 3D triangular mesh models. These images were further refined using Autodesk Meshmixer. These 3D models were fabricated through additive manufacturing, a process commonly known as 3D printing, and assembled in a polypropylene case. After development, the model was validated by 40 experienced urologists and urology residents in their final year of training. They were asked to rate the components of the simulation using a 9-point questionnaire. RESULTS: The model's value in understanding the principles of RIRS and simulating contextual anatomy had mean scores of 9.43 (standard deviation [SD] = 0.74) and 9.21 (SD = 1.03), respectively. Mean scores for specific steps in RIRS were 8.07 (SD 1.47) for cannulating the ureteric orifice, 8.61 (SD 1.24) for inserting the ureteric access sheath, 9.29 (SD 0.97) for performing a renoscopy and evaluating all the calyces, 9.46 (SD 0.87) for laser lithotripsy, and 9.17 (SD 0.94) for manual stone retrieval. Participants scored the model with a mean score of 9.04 (SD 0.87) regarding realism and a mean score of 9.18 (SD 0.89) when evaluating its ability to enhance a trainee's confidence in RIRS. CONCLUSION: The model performed well for all components of RIRS. This model allows high fidelity of the simulation and is cost-effective, portable, durable, reusable, and compatible with standard ureteroscopes.

Utilization of barley and parsley for the management of urolithiasis among the Saudi Arabian population.

Objective: To determine the utilization of barley and parsley for managing urolithiasis among the Saudi Arabian population. Methods: This is a prospective cross-sectional survey-based study. The survey comprised questions about the use of barley, parsley, and other therapies for managing urolithiasis. A WhatsApp® message with the link to the study survey was sent out to family, friends, patients, and other acquaintances residing in the Kingdom of Saudi Arabia (KSA). Results: A total of 1014 respondents completed the survey, of which 44.8% indicated that they utilized barley, 38.3% stated that they used parsley, and 4.2% indicated that they utilized other non-medical remedies to treat or prevent kidney stones. In contrast, only 29.5% stated that they utilized potassium citrate and/or magnesium citrate, and only 14.4% indicated that they consumed greater amounts of water to treat or prevent kidney stones. Conclusion: Our study findings indicate that among the Saudi Arabian population, non-conventional therapies such as barley and parsley are more commonly utilized for managing urolithiasis rather than established therapies such as increasing water intake and the use of potassium-citrate/ magnesium-citrate. There is a need to conduct large-scale clinical studies to evaluate the efficacy and safety of barley, parsley, and other non-conventional therapies for treating urolithiasis.

Pathological response in resectable non-small cell lung cancer: a systematic literature review and meta-analysis.

BACKGROUND: Surrogate endpoints for overall survival in patients with resectable non-small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment outcome indicators and accelerate drug approval. This study's main objectives were to investigate the association among pathological complete response, major pathological response, event-free survival and overall survival and to determine whether treatment effects on pathological complete response and event-free survival correlate with treatment effects on overall survival. METHODS: A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable non-small cell lung cancer. Analysis at the patient level using frequentist and Bayesian random effects (hazard ratio [HR] for overall survival or event-free survival by pathological complete response or major pathological response status, yes vs no) and at the trial level using weighted least squares regressions (hazard ratio for overall survival or event-free survival vs pathological complete response, by treatment arm) were performed. RESULTS: In both meta-analyses, pathological complete response yielded favorable overall survival compared with no pathological complete response (frequentist, 20 studies and 6530 patients: HR = 0.49, 95% confidence interval = 0.42 to 0.57; Bayesian, 19 studies and 5988 patients: HR = 0.48, 95% probability interval = 0.43 to 0.55) and similarly for major pathological response (frequentist, 12 studies and 1193 patients: HR = 0.36, 95% confidence interval = 0.29 to 0.44; Bayesian, 11 studies and 1018 patients: HR = 0.33, 95% probability interval = 0.26 to 0.42). Across subgroups, estimates consistently showed better overall survival or event-free survival in pathological complete response or major pathological response compared with no pathological complete response or no major pathological response. Trial-level analyses showed a moderate to strong correlation between event-free survival and overall survival hazard ratios (R2 = 0.7159) but did not show a correlation between treatment effects on pathological complete response and overall survival or event-free survival. CONCLUSION: There was a strong and consistent association between pathological response and survival and a moderate to strong correlation between event-free survival and overall survival following neoadjuvant therapy for patients with resectable non-small cell lung cancer.

Statistical Analysis of Factors Associated with Diarrhea in Yemeni Children under Five: Insights from the 2022-2023 Multiple Indicator Cluster Survey.

Diarrheal disease remains a significant cause of preventable morbidity and mortality in the pediatric population, particularly among children below five years of age. Although the occurrence of diarrheal episodes is on the decline, its impact continues to escalate at a concerning rate among children under the age of five, especially in developing countries. The objective of this paper is to investigate the factors associated with diarrhea in Yemeni children younger than five years, drawing on data from the latest edition of the Multiple Indicator Cluster Survey (MICS) Yemen conducted in 2022-2023. To identify factors associated with the prevalence of childhood diarrhea, bivariate analysis and multivariable logistic regression were utilized. The findings of this study suggest that age group 6-23, unimproved sanitation, and low-income households are associated with high risk of diarrhea in children under five years of age in Yemen. The study contributes additional evidence regarding factors that should be prioritized in public health strategies geared towards reducing diarrheal prevalence among Yemeni children.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model.

BACKGROUND: Breast cancer is a multifaceted and formidable disease with profound public health implications. Cell demise mechanisms play a pivotal role in breast cancer pathogenesis, with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence. AIM: To investigate the impact of ATP-induced cell death (AICD) on breast cancer, enhancing our understanding of its mechanism. METHODS: The foundational genes orchestrating AICD mechanisms were extracted from the literature, underpinning the establishment of a prognostic model. Simultaneously, a microRNA (miRNA) prognostic model was constructed that mirrored the gene-based prognostic model. Distinctions between high- and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized, with the aim of delineating common influence mechanisms, substantiated through enrichment analysis and immune infiltration assessment. RESULTS: The mRNA prognostic model in this study encompassed four specific mRNAs: P2X purinoceptor 4, pannexin 1, caspase 7, and cyclin 2. The miRNA prognostic model integrated four pivotal miRNAs: hsa-miR-615-3p, hsa-miR-519b-3p, hsa-miR-342-3p, and hsa-miR-324-3p. B cells, CD4+ T cells, CD8+ T cells, endothelial cells, and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways, while miRNA risk scores significantly enriched 29 signaling pathways, with 16 pathways being jointly enriched. CONCLUSION: Of paramount significance, distinct mRNA and miRNA signature models were devised tailored to AICD, both potentially autonomous prognostic factors. This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools, offering an unparalleled window for innovative interventions. Essentially, this paper reveals the hitherto enigmatic link between AICD and breast cancer, potentially leading to revolutionary progress in personalized oncology.

Catalytically distinct IDH1 mutants tune phenotype severity in tumor models.

Mutations in isocitrate dehydrogenase 1 (IDH1) impart a neomorphic reaction that produces the oncometabolite D-2-hydroxyglutarate (D2HG), which can inhibit DNA and histone demethylases to drive tumorigenesis via epigenetic changes. Though heterozygous point mutations in patients primarily affect residue R132, there are myriad D2HG-producing mutants that display unique catalytic efficiency of D2HG production. Here, we show that catalytic efficiency of D2HG production is greater in IDH1 R132Q than R132H mutants, and expression of IDH1 R132Q in cellular and mouse xenograft models leads to higher D2HG concentrations in cells, tumors, and sera compared to R132H-expressing models. Reduced representation bisulfite sequencing (RRBS) analysis of xenograft tumors shows expression of IDH1 R132Q relative to R132H leads to hypermethylation patterns in pathways associated with DNA damage. Transcriptome analysis indicates that the IDH1 R132Q mutation has a more aggressive pro-tumor phenotype, with members of EGFR, Wnt, and PI3K signaling pathways differentially expressed, perhaps through non-epigenetic routes. Together, these data suggest that the catalytic efficiency of IDH1 mutants modulate D2HG levels in cellular and in vivo models, resulting in unique epigenetic and transcriptomic consequences where higher D2HG levels appear to be associated with more aggressive tumors.

Distribution of erythrocyte binding antigen 175 (EBA-175) gene dimorphic alleles in Plasmodium falciparum field isolates from Sudan.

BACKGROUND: The Erythrocyte Binding Antigen (EBA) 175 has been considered as one of the most important Plasmodium falciparum (P. falciparum) merozoite ligands that mediate invasion of the erythrocytes through their sialated receptor: Glycophorin A (GPA). The effect of the EBA 175 dimorphic alleles (F and C) on the severity of the disease is not yet fully understood. Therefore this study was designed to assess the distribution of the divergent dimorphic alleles of P. falciparum EBA-175 (F and C) in three different geographical areas in Sudan and the possible association of this dimorphism with the severity of the disease. METHODS: A sum of 339 field isolates of P. falciparum obtained from patients in three different geographical areas in Sudan were screened for the dimorphic alleles (F, C) of the EBA-175 using nested PCR. RESULTS: The percentage of F, C, and mixed F/C alleles were; 41%, 51%, and 8% respectively. F and C alleles showed significantly different distributions in the various geographic areas (p = 0.00). There was no significant association between malaria clinical manifestation and P. falciparum EBA-175 F and C alleles frequencies. CONCLUSIONS: This study showed a significant differential distribution of F and C alleles in different geographical malaria endemic areas. No significant association was observed between F and C alleles and different malaria phenotypes.

Comparison of microscopy, rapid immunoassay, and molecular techniques for the detection of Giardia lamblia and Cryptosporidium parvum.

Giardia lamblia and Cryptosporidium parvum are recognized as the most common protozoan infections in Saudi Arabia. Microscopic examination of stool samples, either direct or concentrated, for the recovery of G. lamblia cysts and trophozoites and C. parvum oocysts is still the most commonly used for the diagnosis of both parasites. We compared the conventional parasitological techniques of iodine-stained wet mount for G. lamblia and Kinyoun's acid-fast for C. parvum against ImmunoCard STAT® Cryptosporidium/Giardia and real-time polymerase chain reaction (PCR) detecting the 18S rRNA gene of G. lamblia and conventional PCR detecting the same gene of C. parvum at a tertiary hospital in Dhahran, Saudi Arabia. Out of 148 stool samples, 19 and 12 true positives were identified for G. lamblia and C. parvum, respectively, using a composite reference standard. In this case, true positives and negatives were considered as those with at least two positive or negative results out of the three tests. Both ImmunoCard STAT! and PCR methods were more sensitive than the microscopic tests of a single stool specimen of 85.7% (CI=62.6-96.2%) and 85.7% (CI=56.2-97.5%) for G. lamblia and C. parvum, respectively. However, specificity of microscopic tests was higher than other techniques for both parasites. Although PCR seems to be most sensitive for both G. lamblia and C. parvum, its low specificity may render its superiority over other techniques. When a single stool sample is used for detection of G. lamblia and C. parvum, better results can be obtained when coupled with serological testing. Although PCR is the most sensitive method for the detection of both G. lamblia and C. parvum, its use requires attention in relation to the increased possible false positives.