Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease

AIM: Treatment of frequently relapsing or steroid-dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long-term efficacy and safety are still limited. METHODS: We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid-dependent, biopsy-proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re-treatment. Biochemical and clinical parameters were monitored over an extended follow-up period of up to 43 months. RESULTS: Median steroid-free survival after RTX was 25 months (range 4-34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 µ. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow-up period. CONCLUSIONS: Rituximab therapy is effective at maintaining prolonged steroid-free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid-dependent MCD

Acupuncture Efficacy in the Treatment of Persistent Primary Nocturnal Enuresis

Introduction: This study aimed to assess the therapeutic efficacy of traditional Chinese acupuncture in the treatment of persistent primary nocturnal enuresis (PNE).Methods: Fifty children and adolescents suffering from persistent PNE were recruited from the Pediatrics and Urology Outpatient Clinic of Zagazig University Hospital during the year 2010. They included 31 boys and 19 girls, with a mean age of 116± years (range 9–17 years). The children and their parents underwent thorough counseling followed by two courses of treatment, each course administered over 10 consecutive days. Patients were instructed to continue regular follow-up, every three months, after starting the therapy. The response rate (cure, improvement, or failure) was monitored by recording dry nights and the number of spontaneous arousals to void per week on a calendar. Children who showed partial or no response after six months of observation received another two courses of acupuncture therapy, and were followed up for a further six months period.Results: After the initial two courses of treatment, the cure rate at six months was 76% with an additional 18% achieving partial improvement. Twelve children needed another two courses of treatment. After one year of follow-up, 92% of patients showed complete cure and 8% showed failure of acupuncture therapy.Conclusion: Acupuncture treatment in patients with PNE appears effective in increasing the percentage of dry nights, with stable results even after the end of treatment courses. Further controlled studies are needed to confirm these results and to elucidate the therapeutic mechanism of acupuncture.Keywords: Acupuncture Therapy; Nocturnal Enuresis; Traditional Medicin

Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

Detection and molecular characterization of vancomycin resistant Staphylococcus aureus from clinical isolates

Until now, few strains of vancomycin resistant Staphylococcus aureus (VRSA) have been reported worldwide. The disk diffusion method for determination of vancomycin sensitivity frequently misclassifies intermediately susceptible isolates to fully susceptible. However, non-automated minimum inhibitory concentration (MIC) detection methods are the gold standards. In the present study, 439 Gram positive clinical isolates were collected. Among them, 220 Staphylococcus aureus were identified. Multiplex polymerase chain reaction (PCR) detection method for vancomycin resistant S. aureus (VRSA) was developed for detection of both vanA gene (for vancomycin resistance) and nuc gene (specific for S. aureus) in a single step PCR compared to conventional non-automated disc diffusion and MIC detection methods. Molecular typing of VRSA isolates was performed using randomly amplified polymorphic (RAPD) DNA assay technique. The results show 10 VRSA isolates detected by disc diffusion method and MIC determination. Five out of them harbored vanA gene that were detected by multiplex PCR and most of them showed low clonal diversity.Key words: Molecular characterization, multiplex polymerase chain reaction (PCR), vancomycin resistant Staphylococcus aureus (VRSA), vanA gene, nuc gene, randomly amplified polymorphic DNA (RAPD) assay technique

Stress among Mansoura (Egypt) baccalaureate nursing students

Background: Over the last years, details regarding levels of stress and sources of stress have emerged in studies of nursing students in Western population To date, there only few similar reports on clinical stress, anxiety, depression among the Arab population .This study was conducted to examine the level of perceived stress among baccalaureate Mansoura nursing students and to highlight the possible predicting factors. Methods: In this cross- sectional study, Data were obtained from 373 students using a self-administered questionnaire, including questions on sociodemographics, list of possible stressors, perceived stress, physical wellbeing factors, anxiety and depressive symptoms. Results: Prevalence of high stress level, anxiety and depression were 40.2%, 46.6% and 27.9%, respectively. On average each student reported a mean of 4.6 stressors and academic pressures were the most frequent stressors .In regression analysis the number of stressors and global sickness index score were predictors of high stress level. Conclusion: These findings call for introduction of stress management programs and psychiatric care into nursing health services of the University.Key words: Nursing students, stress, Depression, Anxiety, Arab culture, Egyp

Cultivating sustainable architecture and built environments through cross-cultural education

\ua9 2025, Madhavi P. Patil, Yasser Osman Moharam Mahgoub, Ashraf M. Salama, Zeinab Tahoun, Lorraine Johnston, Neveen Hamza and Affaf Al-Oufy.Purpose: This paper examines the thrust, process and implementation of TNE programmes, using the TRANSABE-EDU collaborative project as a case study in architecture and built environment (ABE) postgraduate education. The project seeks to develop transdisciplinary, transnational education (TNE) programmes in ABE by integrating the educational strengths and cultural insights of British and Egyptian institutions. Design/methodology/approach: This study employs a comprehensive methodology, integrating systematic literature reviews, stakeholder engagement, benchmarking analyses and content analysis to develop a framework for transdisciplinary TNE programmes. Data were gathered using bibliometric tools, qualitative content analysis and stakeholder workshops in Egypt and the UK. Findings: The study identifies critical gaps, including the lack of interdisciplinary approaches and limited integration of emerging technologies. It highlights key opportunities for enhancing collaboration through TNE programmes, such as developing joint degree offerings, embedding sustainability throughout curricula and harnessing digital platforms for collaborative learning. Research limitations/implications: As an insightful case study for the British Council, the TRANSABE-EDU project demonstrates practical methods for conceptualising and administering TNE programmes. The outcomes would set benchmarks for establishing transdisciplinary courses in ABE, elevating future TNE initiatives’ quality and long-term viability. The empirical validation of the curriculum is outside the scope of this paper and will be independently conducted, with results to be presented in a subsequent paper. Practical implications: The practical implications of this study address diverse beneficiaries. Academic administrators and policymakers should prioritise investment in state-of-the-art learning management systems that support hybrid, flexible teaching methods tailored to diverse international student bodies. Institutions should implement continuous professional development programmes placing emphasis on enhancing digital literacy, cross-cultural communication and transdisciplinary teaching practices. Coordinated policy efforts, such as establishing global accreditation standards for TNE provisions and streamlining administrative processes, are crucial to sustain and expand high-quality TNE programmes. Originality/value: This research connects cross-cultural collaboration with transdisciplinary approaches in ABE education. It offers a pioneering framework for TNE programmes that prioritise sustainability, cultural relevance and innovative pedagogical techniques

Local IL-17 Production Exerts a Protective Role in Murine Experimental Glomerulonephritis

IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of glomerulonephritis and IL-17 deficient mice are protected from nephrotoxic nephritis. However, a regulatory role for IL-17 has recently emerged. We describe a novel protective function for IL-17 in the kidney. Bone marrow chimeras were created using wild-type and IL-17 deficient mice and nephrotoxic nephritis was induced. IL-17 deficient hosts transplanted with wild-type bone marrow had worse disease by all indices compared to wild-type to wild-type bone marrow transplants (serum urea p<0.05; glomerular thrombosis p<0.05; tubular damage p<0.01), suggesting that in wild-type mice, IL-17 production by renal cells resistant to radiation is protective. IL-17 deficient mice transplanted with wild-type bone marrow also had a comparatively altered renal phenotype, with significant differences in renal cytokines (IL-10 p<0.01; IL-1β p<0.001; IL-23 p<0.01), and macrophage phenotype (expression of mannose receptor p<0.05; inducible nitric oxide synthase p<0.001). Finally we show that renal mast cells are resistant to radiation and produce IL-17, suggesting they are potential local mediators of disease protection. This is a novel role for intrinsic cells in the kidney that are radio-resistant and produce IL-17 to mediate protection in nephrotoxic nephritis. This has clinical significance as IL-17 blockade is being trialled as a therapeutic strategy in some autoimmune diseases

Probiotic Microbes Sustain Youthful Serum Testosterone Levels and Testicular Size in Aging Mice

The decline of circulating testosterone levels in aging men is associated with adverse health effects. During studies of probiotic bacteria and obesity, we discovered that male mice routinely consuming purified lactic acid bacteria originally isolated from human milk had larger testicles and increased serum testosterone levels compared to their age-matched controls. Further investigation using microscopy-assisted histomorphometry of testicular tissue showed that mice consuming Lactobacillus reuteri in their drinking water had significantly increased seminiferous tubule cross-sectional profiles and increased spermatogenesis and Leydig cell numbers per testis when compared with matched diet counterparts This showed that criteria of gonadal aging were reduced after routinely consuming a purified microbe such as L. reuteri. We tested whether these features typical of sustained reproductive fitness may be due to anti-inflammatory properties of L. reuteri, and found that testicular mass and other indicators typical of old age were similarly restored to youthful levels using systemic administration of antibodies blocking pro-inflammatory cytokine interleukin-17A. This indicated that uncontrolled host inflammatory responses contributed to the testicular atrophy phenotype in aged mice. Reduced circulating testosterone levels have been implicated in many adverse effects; dietary L. reuteri or other probiotic supplementation may provide a viable natural approach to prevention of male hypogonadism, absent the controversy and side-effects of traditional therapies, and yield practical options for management of disorders typically associated with normal aging. These novel findings suggest a potential high impact for microbe therapy in public health by imparting hormonal and gonad features of reproductive fitness typical of much younger healthy individuals.National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant U01 CA164337)National Institutes of Health (U.S.) (Grant RO1CA108854

Inside and out: the activities of senescence in cancer.

The core aspect of the senescent phenotype is a stable state of cell cycle arrest. However, this is a disguise that conceals a highly active metabolic cell state with diverse functionality. Both the cell-autonomous and the non-cell-autonomous activities of senescent cells create spatiotemporally dynamic and context-dependent tissue reactions. For example, the senescence-associated secretory phenotype (SASP) provokes not only tumour-suppressive but also tumour-promoting responses. Senescence is now increasingly considered to be an integrated and widespread component that is potentially important for tumour development, tumour suppression and the response to therapy.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nrc377