The interplay of p38 MAPK signaling and mitochondrial metabolism, a dynamic target in cancer and pathological contexts.

Mitochondria play a crucial role in cellular metabolism and bioenergetics, orchestrating various cellular processes, including energy production, metabolism, adaptation to stress, and redox balance. Besides, mitochondria regulate cellular metabolic homeostasis through coordination with multiple signaling pathways. Importantly, the p38 mitogen-activated protein kinase (MAPK) signaling pathway is a key player in the intricate communication with mitochondria, influencing various functions. This review explores the multifaced interaction between the mitochondria and p38 MAPK signaling and the consequent impact on metabolic alterations. Overall, the p38 MAPK pathway governs the activities of key mitochondrial proteins, which are involved in mitochondrial biogenesis, oxidative phosphorylation, thermogenesis, and iron homeostasis. Additionally, p38 MAPK contributes to the regulation of mitochondrial responses to oxidative stress and apoptosis induced by cancer therapies or natural substances by coordinating with other pathways responsible for energy homeostasis. Therefore, dysregulation of these interconnected pathways can lead to various pathologies characterized by aberrant metabolism. Consequently, gaining a deeper understanding of the interaction between mitochondria and the p38 MAPK pathway and their implications presents exciting forecasts for novel therapeutic interventions in cancer and other disorders characterized by metabolic dysregulation.

Autophagy inhibition potentiates energy restriction-induced cell death in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) significantly contributes to cancer-related mortality due to the limited response of HCC to current anticancer therapies, thereby necessitating more effective treatment approaches. Energy restriction mimetic agents (ERMAs) have emerged as potential therapies in targeting the Warburg effect, a unique metabolic process in cancer cells. However, ERMAs exhibit limited efficacy when used as monotherapy. Additionally, ERMAs have been found to induce autophagy in cancer cells. The role of autophagy in cancer survival remains a subject of debate. Thus, it is crucial to ascertain whether ERMA-induced autophagy is a mechanism for cell survival or cell death in HCC. Our study aims to investigate the effect of autophagy inhibition on the survival of HCC cells treated with ERMAs while also examining the potential of combining an autophagy inhibitor such as spautin-1 with ERMAs to enhance HCC cell death. Our results suggest a cytoprotective role for ERMA-induced autophagy in HCC cells, as combining the autophagy inhibitor spautin-1 with ERMAs effectively suppressed ERMA-induced autophagy and synergistically enhanced their antitumor activity. The treatment combination promoted HCC death through apoptosis, cell cycle arrest, and inhibition of AKT and ERK activation, which are known to play a key role in cellular proliferation. Collectively, our findings highlight a potential strategy to combat HCC by combining energy restriction with autophagy inhibition.

New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAFV600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study.

A new series of bis-triazole 19a-l was synthesised for the purpose of being hybrid molecules with both anti-inflammatory and anti-cancer activities and assessed for cell cycle arrest, NO release. Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC50 = 9-16 µM compared to tamoxifen (IC50 = 27.9 µM). and showed good inhibitory activity against HEP-3B with IC50 = 4.5-14 µM compared to sorafenib (IC50 = 3.5 µM) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC50 = 5.3-13.7 µM compared to 5-FU with IC50 = 4.8 µM (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC50 = 3-4.5 µM compared to 5-FU with IC50 = 6 µM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC50 of 22.40, 23.20, 22.70, 30.30 µM), EGFR (IC50 of 0.112, 0.205, 0.169 and 0.066 µM) and B-RAFV600E (IC50 of 0.09, 0.06, 0.07 and 0.05 µM).

Knowledge, awareness, and attitude among pharmacists regarding the risk estimation of cardiovascular disease in Jordan: Immersion of lipid-lowering agents.

The Risk Estimation of Cardiovascular Disease (CVD) is an important factor for predicting the incidence of cardiovascular events in a given population. This study aimed to assess the knowledge, awareness, and attitude of pharmacists in Jordan regarding the risk estimation of CVD and the use of lipid-lowering agents. The study is particularly interested in investigating the extent to which pharmacists are immersed in this area of practice, which can significantly impact patient health outcomes. The study employed a cross-sectional design, with a sample of pharmacists drawn from various regions in Jordan. Data were collected through a self-administered questionnaire, which was designed to explore pharmacists' knowledge of CVD risk estimation tools and their awareness of lipid-lowering agents' efficacy and side effects. The questionnaire also assessed pharmacists' attitudes towards the use of these agents in practice and their perceptions of the barriers to implementing CVD risk estimation tools. The study's findings shed light on the suboptimal levels of overall knowledge score of pharmacists in Jordan regarding CVD risk estimation and lipid-lowering agents' use. The results provided insights into the gaps that exist in pharmacists' knowledge and practice and help to identify areas for improvement. Ultimately, the present findings inform strategies to enhance pharmacists' engagement in CVD risk estimation and improve patient outcomes in Jordan and highlight the urgent need for ongoing education and training for pharmacists to improve their knowledge and skills in managing patients with dyslipidemia.

Targeting aldehyde dehydrogenase enzymes in combination with chemotherapy and immunotherapy: An approach to tackle resistance in cancer cells.

Modern cancer chemotherapy originated in the 1940s, and since then, many chemotherapeutic agents have been developed. However, most of these agents show limited response in patients due to innate and acquired resistance to therapy, which leads to the development of multi-drug resistance to different treatment modalities, leading to cancer recurrence and, eventually, patient death. One of the crucial players in inducing chemotherapy resistance is the aldehyde dehydrogenase (ALDH) enzyme. ALDH is overexpressed in chemotherapy-resistant cancer cells, which detoxifies the generated toxic aldehydes from chemotherapy, preventing the formation of reactive oxygen species and, thus, inhibiting the induction of oxidative stress and the stimulation of DNA damage and cell death. This review discusses the mechanisms of chemotherapy resistance in cancer cells promoted by ALDH. In addition, we provide detailed insight into the role of ALDH in cancer stemness, metastasis, metabolism, and cell death. Several studies investigated targeting ALDH in combination with other treatments as a potential therapeutic regimen to overcome resistance. We also highlight novel approaches in ALDH inhibition, including the potential synergistic employment of ALDH inhibitors in combination with chemotherapy or immunotherapy against different cancers, including head and neck, colorectal, breast, lung, and liver.

The protective effect of rivaroxaban with or without aspirin on inflammation, oxidative stress, and platelet reactivity in isoproterenol-induced cardiac injury in rats.

Coronary artery diseases are principal sources of mortality and disability in global human population. Progressively, rivaroxaban is being evaluated for the prevention of atherosclerotic thrombi, particularly with anti-platelet agents. Hence, the current report aimed to investigate the cardioprotective effect of rivaroxaban on isoproterenol (ISO)-induced cardiac injury model in rats and the possible synergistic effect when combined with aspirin. Male Wistar rats were randomly assigned into five different groups. Cardiac injury was induced by subcutaneous injection of ISO (85 mg/kg) for 2 consecutive days. Rat tail bleeding time was performed prior to sacrifice. Cardiac enzymes, platelet activity, inflammatory, and oxidative stress biomarkers levels were measured using enzyme-linked immunoassay (ELISA). Pre-administration of rivaroxaban alone and on combination with aspirin prevented ISO-induced increase in cardiac thiobarbituric acid reactive substances (TBARS), interleukin 6 (IL-6), and thromboxane B2 (TXB2) levels. Moreover, a significant prolongation of bleeding time was demonstrated among aspirin, rivaroxaban, and aspirin plus rivaroxaban treated groups. On the other hand, the combination treatment of aspirin plus rivaroxaban showed no marked difference in these biomarkers and bleeding time relative to either drug administered separately. However, a prominent decrease of cardiac 6-keto prostaglandin F1α (6-Keto-PGF1α) level was displayed in the combination treatment when compared with ISO and rivaroxaban-treated groups, whereas no significant improvement was seen in cardiac glycoprotein V (GPV) levels except in aspirin-treated group. The study results demonstrated that rivaroxaban decreases cardiac oxidative stress, inflammation, and platelets reactivity. However, the addition of rivaroxaban to aspirin did not seem to show synergistic antioxidant, anti-inflammatory, or antiplatelet effect.

Design and synthesis of new quinoline derivatives as selective C-RAF kinase inhibitors with potent anticancer activity.

This article describes the design, synthesis, and biological screening of a new series of diarylurea and diarylamide derivatives including quinoline core armed with dimethylamino or morpholino side chain. Fifteen target compounds were selected by the National Cancer Institute (NCI, USA) for in vitro antiproliferative screening against a panel of 60 cancer cell lines of nine cancer types. Compounds 1j-l showed the highest mean inhibition percentage values over the 60-cell line panel at 10 µM with broad-spectrum antiproliferative activity. Subsequently, compounds 1j-l were subjected to a dose-response study to measure their GI50 and total growth inhibition (TGI) values against the cell lines. Three of the tested molecules exerted higher potency against most of the cell lines than the reference drug, sorafenib. Compound 1l indicated a higher potency than sorafenib against 53 of tested cancer cell lines. Compounds 1j-l demonstrated promising selectivity against cancer cells than normal cells. Moreover, compound 1l induced apoptosis and necrosis in RPMI-8226 cell line in a dose-dependent manner. In addition, compounds 1j-l were tested against C-RAF kinase as a potential molecular target. The three compounds showed high potency, and the most potent C-RAF kinase inhibitor was compound 1j with an IC50 value of 0.067 µM. In addition, Compounds 1j-l were further tested at 1 µM concentration against a panel of another twelve kinases and they showed a high selectivity for C-RAF kinase. Molecular modeling studies were performed to illuminate on the putative binding interactions of these motifs in the active site of C-RAF kinase. Additional studies were conducted to measure aqueous solubility, partition coefficient, and Caco-2 permeability of the most promising derivatives.

Aging entails distinct requirements for Rb at maintaining adult neurogenesis.

Cell cycle proteins play essential roles in regulating embryonic and adult neurogenesis in the mammalian brain. A key example is the Retinoblastoma protein (Rb) whose loss disrupts the whole neurogenic program during brain development, but only results in increased progenitor proliferation in the adult subventricular zone (SVZ) and compromised long-term neuronal survival in the adult olfactory bulb (OB). Whether this holds true of neurogenesis in the aged brain remains unknown. In this study, we find no evidence of irregular proliferation or early commitment defects in the mid-aged (12-month-old) and old-aged (20-month-old) SVZ following tamoxifen-inducible Rb knockout (Rb iKO) in mice. However, we highlight a striking defect in early maturation of Rb-deficient migrating neuroblasts along the rostral migratory stream (RMS), followed by massive decline in neuronal generation inside the aged OB. In the absence of Rb, we also show evidence of incomplete cell cycle re-entry (CCE) along with DNA damage in the young OB, while we find a similar trend towards CCE but no clear signs of DNA damage or neurodegenerative signatures (pTau or Synuclein accumulation) in the aged OB. However, such phenotype could be masked by the severe maturation defect reported above in addition to the natural decline in adult neurogenesis with age. Overall, we show that Rb is required to prevent CCE and DNA damage in adult-born OB neurons, hence maintain neuronal survival. Moreover, while loss of Rb alone is insufficient to trigger seeding of neurotoxic species, this study reveals age-dependent non-monotonic dynamics in regulating neurogenesis by Rb.

Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors.

This article reports on novel imidazothiazole derivatives as first-in-class potent and selective ErbB4 (HER4) inhibitors. There are no other reported selective inhibitors of this kinase in the literature, that's why they are considered as first-in-class. In addition, none of the reported non-selective ErbB4 inhibitors possesses imidazothiazole nucleus in its structure. Therefore, there is novelty in this work in both kinase selectivity and chemical structure. Compounds Ik and IIa are the most potent ErbB4 kinase inhibitor (IC50 = 15.24 and 17.70 nM, respectively). Compound Ik showed promising antiproliferative activity. It is selective towards cancer cell lines than normal cells. Its ability to penetrate T-47D cell membrane and inhibit ErbB4 kinase inside the cells has been confirmed. Moreover, both compound Ik and IIa have additional merits such as weak potency against hERG ion channels and against CYP 3A4 and 2D6. Molecular docking and dynamic simulation studies were carried out to explain binding interactions.

Flow Cytometric Analyses of p53-Mediated Cell Cycle Arrest and Apoptosis in Cancer Cells.

Phenotypic analysis of the effects of a gene of interest may be limited because stable expression of some genes leads to adverse consequences in cell survival, such as disturbance of cell cycle progression, senescence, autophagy, and programmed cell death. One of the best examples is tumor suppressor p53. p53 functions as a tumor suppressor by inducing cell cycle arrest and apoptosis in response to genotoxic and environmental insults. The choice and timing of either pathways induced by p53 depend on cellular context, cell types, and the degree of cellular/genomic damage (For review, see (Chen J, Cold Spring Harb Perspect Med 6:a026104, 2016)). The uncertainty makes the studies on the long-term effects of p53 in cells challenging. This chapter describes a method of flow cytometric analysis of ectopic expression of p53 to better quantify cell cycle distribution and apoptosis in cells treated with DNA damaging agents. The method can be easily adapted to other genes of interest to study their contributions to the fate of variety of cell types in response to endogenous or exogenous stresses.

In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer.

Poly ADP-ribose polymerase (PARP) inhibitors are promising targeted therapy for epithelial ovarian cancer (EOC) with BRCA mutations or defective homologous recombination (HR) repair. However, reversion of BRCA mutation and restoration of HR repair in EOC lead to PARP inhibitor resistance and reduced clinical efficacy of PARP inhibitors. We have previously shown that triapine, a small molecule inhibitor of ribonucleotide reductase (RNR), impaired HR repair and sensitized HR repair-proficient EOC to PARP inhibitors. In this study, we performed in silico screening of small molecule libraries to identify novel compounds that bind to the triapine-binding pocket on the R2 subunit of RNR and inhibit RNR in EOC cells. Following experimental validation of selected top-ranking in silico hits for inhibition of dNTP and DNA synthesis, we identified, DB4, a putative RNR pocket-binding inhibitor markedly abrogated HR repair and sensitized BRCA-wild-type EOC cells to the PARP inhibitor olaparib. Furthermore, we demonstrated that the combination of DB4 and olaparib deterred the progression of BRCA-wild type EOC xenografts and significantly prolonged the survival time of tumor-bearing mice. Herein we report the discovery of a putative small molecule inhibitor of RNR and HR repair for combination with PARP inhibitors to treat PARP inhibitor-resistant and HR repair-proficient EOC.

Design, synthesis, biological evaluation, and modeling studies of novel conformationally-restricted analogues of sorafenib as selective kinase-inhibitory antiproliferative agents against hepatocellular carcinoma cells.

Sorafenib is one of the clinically used anticancer agents that inhibits several kinases. In this study, novel indole-based rigid analogues of sorafenib were designed and synthesized in order to enhance kinase selectivity and hence minimize the side effects associated with its use. The target compounds possess different linkers; urea, amide, sulfonamide, or thiourea, in addition to different terminal aryl moieties attached to the linker in order to investigate their impact on biological activity. They were tested against Hep3B, Huh7, and Hep-G2 hepatocellular carcinoma (HCC) cell lines to study their potency. Among all the tested target derivatives, compound 1h exerted superior antiproliferative potency against all the three tested HCC cell lines compared to sorafenib. Based on these preliminary results, compound 1h was selected for further biological and in silico investigations. Up to 30 µM, compound 1h did not inhibit 50% of the proliferation of WI-38 normal cells, which indicated promising selectivity against HCC cells than normal cells. In addition, compound 1h exerted superior kinase selectivity than sorafenib. It is selective for VEGFR2 and VEGFR3 angiogenesis-related kinases, while sorafenib is a multikinase inhibitor. Superior kinase selectivity of compound 1h to sorafenib can be attributed to its conformationally-restricted indole nucleus and the bulky N-methylpiperazinyl moiety. Western blotting was carried out and confirmed the ability of compound 1h to inhibit VEGFR2 kinase inside Hep-G2 HCC cells in a dose-dependent pattern. Compound 1h induces apoptosis and necrosis in Hep-G2 cell line, as shown by caspase-3/7 and lactate dehydrogenase (LDH) release assays, respectively. Moreover, compound 1h is rather safe against hERG. Thus, we could achieve a more selective kinase inhibitor than sorafenib with retained or even better antiproliferative potency against HCC cell lines. Furthermore, molecular docking and dynamic simulation studies were carried out to investigate its binding mode with VEGFR2 kinase. The molecule has a unique orientation upon binding with the kinase.

Histological Assessment of Cre-loxP Genetic Recombination in the Aging Subventricular Zone of Nestin-CreERT2/Rosa26YFP Mice.

The use of inducible transgenic Nestin-CreERT2 mice has proved to be an essential research tool for gene targeting and studying the molecular pathways implicated in adult neurogenesis, namely, inside the adult subgranular zone (SGZ) of the dentate gyrus and the adult subventricular zone (SVZ) lining the lateral ventricles. Several lines of Nestin-CreER-expressing mice were generated and used in adult neurogenesis research in the past two decades; however, their suitability for studying neurogenesis in aged mice remains elusive. Here, we assessed the efficiency of Cre-loxP genetic recombination in the aging SVZ using the Nestin-CreERT2/Rosa26YFP line designed by Lagace et al. (J Neurosci 27(46):12623-12629, 2007). This analysis was performed in 12-month-old (middle-aged) mice and 20-month-old (old) mice compared to 2-month-old (young adult) mice. To evaluate successful recombination, our approach relies on the histological assessment of Cre mRNA level of expression and the YFP reporter gene's expression inside the aging SVZ by combining in situ hybridization and immunohistochemistry. Using co-immunolabeling, this approach also provides the advantage of estimating the percentage of recombined progeny [(GFP+Nestin+)/Nestin+] and the rate of cell proliferation [(GFP+Ki67+)/GFP+] inside the aging SVZ niche.

Perspectives on female genital cutting among immigrant women and men in Boston.

This study documents the perceptions and experiences of immigrant women and men in the US related to female genital cutting (FGC). This paper examines the effects of migration on these perceptions, with the goal of optimizing health services and informing public policy to support women who have undergone FGC. This qualitative study consisted of individual interviews conducted from 2014 to 2015 with 42 women and men living in Boston, Massachusetts, who immigrated from a variety of communities where FGC has been practiced. Most participants felt strongly against the continuation of the practice, describing a change in their personal and community viewpoints over time, which they attributed to education, religion and immigration. The men in our study collectively took a stand against FGC and believed that they had a particular duty to raise awareness in their families and their communities about its physical and emotional harms. Our study provides strong support for the inclusion of men, religious leaders, and immigrants in FGC-related efforts. Our unique preliminary exploration of the role of members of the diaspora provides some support for initiatives that would involve emigrants in the effort to curb FGC in their home countries. Changing views in the diaspora could play a significant role in affecting opinions and practices in contexts where FGC is prevalent. Finally, our findings do not support the fear that "vacation cutting" might be common among US immigrants. We should therefore exercise caution in our promotion of legislation and clinical practices that target this fear.

Dysuria: An Unusual Complication Of Pubic Exostosis In A Child 10 Years

Exostosis or osteochondromas are benign bone tumors frequently.These benign tumors may be symptomatic or be manifested on the occasion of a complication. We report the case of a child boy 1O years, admitted to our training multiple exostosis, with a loca-tion iliopubic left that proved by painful induration left of the base of the penis. Induration the increasing volume, it bothered the child during urination. Conventional radiography and CT were in favor of a pedunculated osteochondroma of the left iliac ramus compressing the urethra. The child underwent surgical tumor resection and pathological examination confirmed the diagnosis of osteochondroma. The evolution was good with disappearance of urinary symptoms down two years without recurrence

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Comprehensive characterization and optimization of anti-LRRK2 (leucine-rich repeat kinase 2) monoclonal antibodies.

Missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a major cause of PD (Parkinson's disease). Several antibodies against LRRK2 have been developed, but results using these polyclonal antibodies have varied widely leading to conflicting conclusions. To address this challenge, the Michael J. Fox Foundation for Parkinson's Research generated a number of monoclonal antibodies targeting epitopes across the LRRK2 protein. In the present paper, we report optimized protocols and results for ten monoclonal antibodies for immunoblotting, immunohistochemistry, immunoprecipitation and kinase activity assays, in rat, mouse and human brain tissue. Several efficacious antibodies were identified, but results demonstrate that the mouse monoclonal N241A/34 is suitable for most applications, with the best overall rabbit monoclonal antibody being c41-2. These antibodies produced a dominant band of the expected size via immunoblotting and a lack of labelling in tissue derived from LRRK2-knockout animals under optimized conditions. A significant proportion of LRRK2 protein localizes to insoluble fractions and no evidence of truncated LRRK2 protein was detected in any fraction from rodent or human tissues. An assay was developed for the robust detection of LRRK2 kinase activity directly from frozen mouse and human brain tissue, but precipitous declines in activity were observed that corresponded to increasing post-mortem intervals and processing times. Finally, we demonstrate the highest levels of brain-localized LRRK2 in the striatum, but note differential expression patterns between rat and mouse in both striatum and cortex. Anti-LRRK2 monoclonal antibodies that are unlimited in availability together with the proposed standardized protocols should aid in the definition of LRRK2 function in both health and disease.

Subclinical atherosclerosis in patients with chronic psoriasis: a potential association.

BACKGROUND: The immunological abnormalities that lead to the development of psoriasis suggest that these patients may be at increased risk for other inflammatory state which may enhance atherosclerosis. OBJECTIVE: To assess the presence of subclinical atherosclerosis in psoriatic patients who haven't associated traditional cardiovascular risk factors, and to correlate these findings with colour Doppler echocardiographic parameters. METHODS: The study included 80 patients with chronic psoriasis together with 50 age and sex matched healthy volunteers served as control group. Patients who had classic cardiovascular risk factors or had cardiovascular or cerebrovascular events were excluded. Carotid artery intima-media thickness (IMT) and carotid plaques were measured in the carotid arteries by using high-resolution B-mode ultrasound. Also, echocardiographic study was performed using ultrasound imaging system in all cases and controls. RESULTS: Patients with psoriasis had increased carotid artery IMT compared with controls (means 0.9 +/- 0.2 mm vs. 0.7 +/- 0.1 mm; P < 0.001). Carotid IMT positively correlated with patients age, duration of the disease and severity of psoriasis. There was no significant difference in echocardiographic parameters in psoriatic patients compared with controls, also no significant correlation between carotid IMT and echocardiographic parameters were observed in psoriatic patients. CONCLUSION: The increased carotid artery IMT in patients with chronic psoriasis suggesting that chronic psoriasis is associated with subclinical atherosclerosis with increased risk of cardiovascular disease. So, dermatologists should advice their patients to avoid traditional cardiovascular risk factors and to routinely checkup to reduce cardiovascular morbidity and mortality.

Effect of student's teaching about weaning on rural mother's knowledge, attitude and practice (KAP).

PIP: Teaching women the merits of breast feeding, how to use locally available and suitable solid foods to feed infants, and proper methods of weaning can have a considerable and direct positive impact upon infants' nutritional status. 50 mothers aged 15-40 of mean age 24 years from Shoubramant village participated in a study to assess the effect of teaching about weaning. 76% of mothers and 54% of fathers were illiterate. The mothers were interviewed at baseline on their weaning knowledge and practice, then re-interviewed after having been taught relevant information by community nursing students. Mothers' weaning-related knowledge, attitude, and practice were significantly improved by the nutrition education intervention. Mothers' level of education was found to be an important factor affecting knowledge, attitude, and practice.^ieng

HLA antigen frequencies in children with cardiac disease in Cairo.

The study of Histocompatibility Locus Antigen (HLA) frequencies in 48 cases with congenital heart disease (CHD) in children in Cairo showed high incidence of A10. Cases with atrial septal defect have shown a significant association with A3 besides A10. There is also a significant association between B12-45 and right loop anomalies (Fallot's and pulmonary stenosis) together with A10. On the other hand, children with rheumatic heart disease have shown strong positive association with HLA group B8 and negative association with A28.

Campylobacter diarrhoea and an association of recent disease with asymptomatic shedding in Egyptian children.

A hospital-based case-control diarrhoea survey was conducted in Cairo, Egypt to determine the age-specific frequency of campylobacter infection among diarrhoeic and non-diarrhoeic children aged new born to 5 years. Campylobacter was the most common bacterial enteropathogen isolated from diarrhoeic stools. The overall prevalence of campylobacter isolations was 25.9% from stools of 143 diarrhoeic children compared to 15.2% of 132 non-diarrhoeic control children (P = 0.028) during the 4-month period of study. Children less than 1 year of age were at greatest risk of campylobacter infection with 32.6% of diarrhoeic patients culture positive, compared to 14.3% of controls. Asymptomatic shedding in controls was positively associated with a recent diarrhoeal episode (P = 0.019) and may be an important source of new infections.