Altering maternal calcium and phosphorus dietary intake induces persistent sex-specific changes in the dentition of the offspring.

BACKGROUND: The maternal diet is essential to offspring development, but the specific effects on tooth morphology are still unknown. The aim of this study was to evaluate the effects of altering maternal calcium (Ca) and phosphorus (P) supplementation during gestation and lactation on offspring dentition. METHODS: Pregnant mice were fed an experimental diet containing a threefold increase in Ca and a threefold decrease in P compared to the standard mouse chow diet at embryonic Day 0.5 (E0.5). Offspring mice were maintained on standard or experimental diets from post-natal Day 0 to weaning, then fed control diets until 6 weeks of age. Six-week-old offspring heads were collected and scanned using micro-computed tomography. Dental morphometrics of offspring maxillary and mandibular first and third molars (n = 5-6 per diet/per sex) were determined. A two-way ANOVA test was employed to verify the existence of any significant differences between groups. The significance level was set at P < .05. RESULTS: A two-way ANOVA revealed a statistically significant interaction between the effects of diet and sex on the upper and lower dentition. Moreover, experimental diet-fed female offspring exhibited smaller molars with shorter mesiodistal width and larger pulp chambers relative to controls, while experimental diet-fed male offspring possessed larger molars with wider mesiodistal width and smaller pulp chambers. CONCLUSION: Our findings reveal that altering the maternal and offspring dietary Ca:P ratio during gestation, lactation and weaning led to significant, sex-specific changes in the offspring dentition. The differences in dentition appeared to be correlated with the sex-specific changes in the craniofacial skeleton.

A molecular prevalence survey on Anaplasma infection among domestic ruminants in Khartoum State, Sudan.

This study was conducted in Khartoum State, Sudan to determine the prevalence and the risk factors associated with Anaplasma and Ehrlichia species infections in domestic ruminants. Blood samples were collected from a total of 594 animals from 32 different farms distributed in the three provinces of Khartoum State. Among the 196 cattle, 200 sheep, and 198 goats examined using PCR, 13.27%, 32.50%, and 35.86% were infected with Anaplasma spp., respectively, with an overall prevalence of 27.27%. Cattle were infected with A. marginale (10.71%), A. centrale (2.04%), and A. ovis (0.51%), while sheep and goats were infected with A. ovis being significantly higher compared with cattle. No Ehrlichia spp. was detected in domestic ruminant in Khartoum State. Prevalence rates of Anaplasma infections were highly associated with breed, location, season, and sex. The prevalence rates of Anaplasma infection were significantly higher in exotic goat breeds compared with indigenous, and the infection in sheep and cattle was significantly higher in summer and in autumn in goats. The Anaplasma spp. infection rate in goats was significantly higher in females. The infection rate was also significantly higher in Khartoum North in both sheep and goats. It could be concluded that Anaplasma infection is prevalent in small and large ruminants in Khartoum State. Therefore, further studies on the epidemiology of anaplasmosis, possible tick, lice, and flea vectors and reservoirs in Sudan are important.

Analysis of hepatitis B virus-mixed genotype infection by ultra deep pyrosequencing in Sudanese patients, 2015-2016.

PURPOSE: The frequency of detection of HBV co-infection with multiple HBV genotypes is influenced by the detection method; usually co-infections are detected by multiplex PCR or hybridization assays, and are rarely confirmed by sequencing and conventional cloning. The objective of this study was to confirm by ultra-deep pyrosequencing (UDPS) mixed HBV infections, previously detected by multiplex-nested PCR. METHODS: Sixteen samples from HBV co-infected Sudanese patients detected by multiplex-nested PCR, were amplified targeting the P/S region and sequenced by UDPS. RESULTS: The only genotypes identified using UDPS were D and E, while A, B, C and F genotypes, previously detected by multiplex-nested PCR, were not detected. Specifically, 10 samples were shown to be mono-infected (D or E); in 3 out of 10 mono-infected D patients, a subtype combination was observed: D1 + D7 in 2 cases and D2 + D6 in 1 case. The remaining 6 subjects were D + E co-infected (harboring different mixtures of D subtypes). CONCLUSIONS: Overall, UDPS is more effective than multiplex-nested PCR for identifying multiple HBV genotypes and subtypes infections.

A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7.

Ceramides are central intermediates of sphingolipid metabolism with dual roles as mediators of cellular stress signaling and mitochondrial apoptosis. How ceramides exert their cytotoxic effects is unclear and their poor solubility in water hampers a search for specific protein interaction partners. Here, we report the application of a photoactivatable and clickable ceramide analog, pacCer, to identify ceramide binding proteins and unravel the structural basis by which these proteins recognize ceramide. Besides capturing ceramide transfer protein (CERT) from a complex proteome, our approach yielded CERT-related steroidogenic acute regulatory protein D7 (StarD7) as novel ceramide binding protein. Previous work revealed that StarD7 is required for efficient mitochondrial import of phosphatidylcholine (PC) and serves a critical role in mitochondrial function and morphology. Combining site-directed mutagenesis and photoaffinity labeling experiments, we demonstrate that the steroidogenic acute regulatory transfer domain of StarD7 harbors a common binding site for PC and ceramide. While StarD7 lacks robust ceramide transfer activity in vitro, we find that its ability to shuttle PC between model membranes is specifically affected by ceramides. Besides demonstrating the suitability of pacCer as a tool to hunt for ceramide binding proteins, our data point at StarD7 as a candidate effector protein by which ceramides may exert part of their mitochondria-mediated cytotoxic effects.

Anti-ulcerative colitis activity of Calotropis procera Linn.

The aim of the present study was to evaluate the anti-ulcerative colitis activity of Calotropis procera. Different extracts of the investigated plant were evaluated; total alcohol extract, polar extract and non-polar extract. All the investigated extracts at doses 200 &400 mg/kg possessed a dose-dependent anti-ulcerative colitis potential when administrated for 5 consecutive days after colitis induction by acetic acid in rats. They reduced different parameters of UC. Only polar extract at both doses (200, 400 mg/kg) was more effective than the standard drug Prednisolone (50 mg/kg), it produced percent protection of control colitis by 63.8% and78.4% respectively, while the standard drug Prednisolone produced 54.9% protection. The anti-ulcerative colitis activity may be attributed to the active principles i.e. flavonoids. Preliminary phytochemical screening showed that the plant contains flavonoids, unsaturated sterols and/or triterpenoides, cardiac glycosides, carbohydrates or glycosides, proteins and/or amino acids, tannins and coumarins. The total alcohol extract was safe up to 4000 mg/kg and there were no side effects reported on liver and kidney functions.

Comparative nutritional value and antimicrobial activities between three Euphorbia species growing in Saudi Arabia.

Plants are excellent sources of nutrition and highly bioactive substances that might use in the development of new drugs and pharmaceutical agents. Three species of the Genus Euphorbia (Family Euphorpiaceae), namely; Euphorbia granulata Forssk, Euphorbia helioscobia L., and Euphorbia hirta Linn growing in Ryiadh, KSA were air-dried, powdered, and their active materials were extracted with alcohol. The nutritional value phytochemical constituents and antimicrobial activity of the plants were determined. The chemical contents were similar in the three species; however, lipid profile of the plants showed that the stearic acid and lignoceric acid were detected only in E. helioscopia and E. hirta, while palmitoleic acid was detected only in E. hirta. The percentage of unsaturated fatty acid methyl esters were 52.48%, 69.39% and 66.52% in Euphorbia granulate, Euphorbia helioscobia, E. hirta, respectively. Three compounds, 1-ethoxypentacosane, heptacosan-1-ol and ß-sitosterol were isolated from the three plant extracts and identified using different spectroscopic analysis. The percentage of crude protein was 43.65%, 25.00% and 18.75% in E. granulata, E. helioscobia, and E. hirta, respectively. The free amino acids and amino acid composition were quantitatively determined using amino acid analyzer. All the plant extracts were active against bacterial and fungal test organisms, however, the antimicrobial activity were varied according to both the Euphorbia species and the test organism.

The Association of High Prevalence of Trophozoites in Peripheral Blood with Lower Antibody Response to P. falciparum Infected Erythrocytes among Asymptomatic Children in Sudan.

Background. The most prominent variant surface antigens (VSAs) of Plasmodium falciparum are the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, which serves as a parasite-sequestering ligand to endothelial cells. In this study we have examined the antibody reactivity of autologous plasma from symptomatic and asymptomatic malaria infected children against the infected erythrocytes' surface antigens using flow cytometry. Methods. Ethidium-bromide-labelled erythrocytic mature forms of P. falciparum parasites obtained from symptomatic and asymptomatic children were sequentially incubated with autologous plasma and fluorescein isothiocyanate-conjugated (FITC) antihuman IgG. Plasma antibody reactivity was detected by flow cytometry. Results. Asymptomatic children had more prevalence of trophozoites in peripheral blood (66%) compared to symptomatic children (16%), p = 0.002. The mean percentage of infected RBCs reacting with autologous sera was 89.78 among symptomatic children compared to 79.62 among asymptomatic children (p = 0.09). Moreover, the mean fluorescence intensity (MFI) in the asymptomatic was significantly higher compared to symptomatic children (p value = 0.040). Conclusion. Variant surface antigens on Plasmodium falciparum infected RBCs from symptomatic malaria children tend to be better recognized by IgG antibodies. This may suggest a role of some IgG antibodies in severity of malaria.

Cytology-histology correlation of atypical glandular cells on cervical Papanicolaou tests: A study of 628 cases.

INTRODUCTION: The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test. MATERIALS AND METHODS: A total of 714 patients with AGC identified on cervical Papanicolaou tests were studied for their clinicopathologic features, such as follow-up histology and patient age. We investigated the histologic follow-up results for each individual subcategories of AGC and their correlation with patients' age. RESULTS: Most of the glandular cell abnormalities (80.0%) in the study group were classified as "atypical glandular cells, not otherwise specified (NOS)". About 28.9% of patients' follow-up histology showed malignant or precancerous lesions. The mean age of patients with malignant or precancerous lesions was significantly higher than that of patients with benign or non-precancerous lesions. The malignant histologies included 52 cases of endometrial cancers and 31 cases of cervical carcinomas. The second most common subcategory was "atypical glandular cells, favor neoplastic" (5.0%), while "atypical endocervical cells, favor neoplastic" constituted about 2.7% of cases in our study. The average age of patients with "atypical glandular cells, favor neoplastic" was significantly higher than that of patients with "atypical endocervical cells, favor neoplastic". The follow-up histology of about 82.1% of "atypical glandular cells, favor neoplastic" showed endometrial (73.9%) or cervical malignancies (26.1%). The follow-up histology of about 70.6% of "atypical endocervical cells, favor neoplastic" showed endometrial (50.0%) or cervical cancers (50.0%). Other glandular abnormalities included 25 of 714 cases of "atypical endometrial cells" (3.5%) and 6 of 714 cases of "atypical endocervical cells" (0.8%). CONCLUSION: Based on our data, we have observed significantly more endometrial malignancies in both "atypical glandular cells, NOS" and "atypical glandular cells, favor neoplastic" subcategories and even some in "atypical endocervical cells, favor neoplastic" category. This predominance of endometrial malignancies is also associated with patients' age and tumor types.

Modulation of the Sirtuin-1 signaling pathway in doxorubicin-induced nephrotoxicity (synergistic amelioration by resveratrol and pirfenidone).

The current study was conducted to determine the precise mechanisms of Sirtuin-1 (Sirt-1), TGF- ß (Transforming Growth Factor-ß), and long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (LncRNA MALAT-1) in signaling pathways in doxorubicin (DOX)-induced nephrotoxicity. The potential therapeutic effect of Resveratrol and Pirfenidone in DOX toxicity was also assessed. Thirty-six male adult rats were evenly distributed into four groups: Group 1: control rats. Group 2: DOX exposed rats' group, each animal received 7.5 mg/kg DOX as a single intravenous dose, Group 3: DOX exposed group subjected to oral resveratrol (20 mg/kg/daily for two weeks), Group 4: DOX exposed group subjected to oral Pirfenidone (200 mg/kg once daily for 10 days). At the planned time, animals were sacrificed. Renal tissue was collected to assess matrix metalloproteinase-9 (MMP9), inflammatory and apoptotic markers: tumor necrosis factor-alpha (TNF- ß, caspase-3, cyclo-oxygenase-2 (COX-2), and oxidative stress markers: nitric oxide (NO), Glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). Sirtuin-1 (Sirt-1), TGF-ß, and LncRNA MALAT-1 were quantitatively assessed by real-time RT-PCR in the whole blood. Results showed that the DOX group exhibited a significant increase in oxidative stress markers, and inflammatory, and apoptotic markers in the renal tissue. Histologically, the renal tubule lining cells exhibited vacuolar alterations in the cytoplasm, glomerular atrophy, and vascular congestion. Furthermore, renal degeneration was evident, as confirmed by the heightened immuno-expression of MMP9. Exposure to DOX resulted in a significant decrease in Sirtuin-1 (Sirt-1) with a significant increase in the TGFß, and LncRNA MALAT-1 gene expression. However, pre-treatment with either resveratrol/or Pirefenidone ameliorated the histological renal alterations, regulated the pathways of Sirt-1, TGFß, and LncRNA MALAT-1, and decreased all oxidative stress, inflammatory and apoptotic markers. In conclusion, DOX exposure leads to renal toxicity by inducing renal degeneration, oxidative stress, and apoptosis. Administration of either resveratrol or Pirfenidone counteracted these changes and protected the kidney against DOX-induced renal damage.

Implication of endoplasmic reticulum stress and mitochondrial perturbations in remote liver injury after renal ischemia/reperfusion in rats: potential protective role of azilsartan.

Objectives: Distant liver injury is a complication of renal ischemia-reperfusion (I/R) injury, which imposes mortality and economic burden. This study aimed to elucidate the cross-talk of endoplasmic reticulum (ER) stress and mitochondrial perturbations in renal I/R-induced liver injury, and the potential hepatoprotective effect of azilsartan (AZL).Methods: Male albino Wister rats were pre-treated with AZL (3 mg/kg/day, PO) for 7 days then a bilateral renal I/R or sham procedure was performed. Activities of liver enzymes were assessed in plasma. The structure and ultra-structure of hepatocytes were assessed by light and electron microscopy. Markers of ER stress, mitochondrial biogenesis and apoptosis were analyzed in livers of rats.Results: Renal ischemic rats showed higher plasma levels of liver enzymes than sham-operated rats, coupled with histological and ultra-structural alterations in hepatocytes. Mechanistically, there was up-regulation of ER stress markers and suppression of mitochondrial biogenesis-related proteins and enhanced apoptosis in livers of renal ischemic rats. These abnormalities were almost abrogated by AZL pretreatment.Discussion: Our findings uncovered the involvement of mitochondrial perturbations, ER stress and apoptosis in liver injury following renal I/R, and suggested AZL as a preconditioning strategy to ameliorate remote liver injury in patients susceptible to renal I/R after adequate clinical testing.

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.

The relation between social media mentions and academic citations in orthodontic journals: A preliminary study.

BACKGROUND: To study the relation between social media mentions and academic citations for articles published in peer-reviewed orthodontic journals. METHODS: Articles published in early 2018 in seven peer-reviewed orthodontic journals were retrospectively analyzed in September 2022. Citation counts of the articles were evaluated using two databases: Google Scholar (GS) and Web of Science (WoS). The Altmetric Attention Score, Twitter, Facebook mentions, and Mendeley reads were tracked using the Altmetric Bookmarklet. The citation counts and social media mentions were correlated using Spearman rho. RESULTS: A total of 84 articles were identified during the initial search; 64 (76%) were original studies and systematic review articles and included in the analysis. A total of 38% of the articles had at least one mention on social media. Over the study period, the average number of citations of the articles mentioned on social media was higher than the non-mentioned articles for GS and WoS, respectively. Moreover, significant positive correlations existed between the Altmetric Attention Score and the number of citations in GS and WoS (rs = 0.31, P = 0.001 and rs = 0.26, P = 0.04). CONCLUSIONS: Social media mentions and citations of articles published in peer-reviewed orthodontic journals are correlated, with a clear difference in the number of citations in articles mentioned on social media versus those not mentioned, indicating possible increased reach of articles disseminated on social media.

IgA Vasculitis in an Adult Linked to Cryptosporidium and Giardia Co-Infection: A Comprehensive Case Study.

BACKGROUND Immunoglobulin A (IgA) vasculitis is a small-vessel vasculitis characterized by the deposition of IgA immune complexes primarily in the skin, kidneys, and gastrointestinal tract. While it predominantly affects children, cases in adults are associated with more severe manifestations. Evidence suggests that infectious triggers play a pivotal role in its etiology. Often, it follows a self-limiting course and doesn't necessitate intervention. CASE REPORT We present the case of a 51-year-old man who presented with a maculopapular rash, arthralgia, and abdominal pain. An examination revealed a purpuric rash on lower extremities and abdomen. A lower extremity duplex ultrasound identified deep vein thrombosis (DVT) in the right leg. Skin biopsy of the rash confirmed the diagnosis of IgA vasculitis, demonstrating perivascular neutrophilic infiltrate and IgA complex deposition. Stool studies revealed co-infection with Cryptosporidium and Giardia. The patient was treated with a prednisone taper with significant improvement in symptoms. CONCLUSIONS This case highlights the potential role of Cryptosporidium as a trigger for IgA vasculitis. The presence of concurrent infections underscores the complex interplay between infections and the development of IgA vasculitis. The co-infection with Giardia suggests that a secondary infection may be involved, further complicating the disease's etiology. The observation of DVT suggests a possible link between IgA vasculitis and a prothrombotic state. This report serves to expand the knowledge of IgA vasculitis triggers and associated complications, guiding clinicians in diagnosing and managing similar cases while emphasizing the importance of vigilance in adults with these symptoms.

Impact of Quiet Time on Psychological Outcomes of Neonatal Intensive Care Unit Nurses in Jeddah, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Although quiet time is implemented in neonatal intensive care units (NICUs) for the benefit of infants, it may also positively impact the psychological outcomes of healthcare professionals. Several studies have examined the impact of quiet-time implementation on patients; however, there is a paucity of research assessing its impact on the psychological outcomes of NICU nurses, particularly in Saudi Arabia. OBJECTIVE AND METHODS: This study aimed to assess the impact of quiet time on the psychological outcomes (stress, anxiety, and depression) of NICU nurses in Jeddah, Saudi Arabia. A cross-sectional design was used for this study. A total of 87 NICU nurses from two hospitals participated in this study. One group did not practice quiet time, while the second group did. A questionnaire survey assessed participants' demographic characteristics, and their depression, anxiety, and stress were assessed using the depression, anxiety, and stress scale-21 (DASS-21). The data were analyzed for frequency, percentage, mean, and standard deviation (SD). Bivariate analysis, independent t-tests, and one-way analysis of variance were used to test the differences between variables and groups. Pearson's correlation coefficient (r) was used to analyze the relationships between continuous variables and perceived stress, anxiety, and depression. RESULTS: A substantial number of NICU nurses perceived stress, anxiety, and depression; however, there were no significant differences in perceived stress, anxiety, and depression between the nurses who worked in NICUs that applied quiet time and NICUs that did not (P ≤ 0.05). CONCLUSION: This study found no statistically significant relationship between quiet-time implementation and perceived stress, anxiety, or depression among NICU nurses. Further research with a larger sample size or increased quiet-time implementation may be required.

Insights antifibrotic mechanism of methyl palmitate: impact on nuclear factor kappa B and proinflammatory cytokines.

Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment is evident. The present study was designed to assess the potential antifibrotic effect of MP and whether MP can attenuate the severity of oxidative stress and inflammatory response in chronic liver injury. Male albino rats were treated with either CCl(4) (1 ml/kg, twice a week) and/or MP (300 mg/kg, three times a week) for six weeks. CCl(4)-intoxication significantly increased liver weight, serum aminotransferases, total cholesterol and triglycerides while decreased albumin level and these effects were prevented by co-treatment with MP. As indicators of oxidative stress, CCl(4)-intoxication caused significant glutathione depletion and lipid peroxidation while MP co-treatment preserved them within normal values. As markers of fibrosis, hydroxyproline content and α-SMA expression increased markedly in the CCl(4) group and MP prevented these alterations. Histopathological examination by both light and electron microscope further confirmed the protective efficacy of MP. To elucidate the antifibrotic mechanisms of MP, the expression of NF-κB, iNOS and COX-2 and the tissue levels of TNF-α and nitric oxide were assessed; CCl(4) increased the expression of NF-κB and all downstream inflammatory cascade while MP co-treatment inhibited them. Collectively these findings indicate that MP possesses a potent antifibrotic effect which may be partly a consequence of its antioxidant and anti-inflammatory properties.

Unraveling the molecular principles by which ceramides commit cells to death.

Ceramides are central intermediates of sphingolipid metabolism that can activate a variety of tumor suppressive cellular programs, including cell cycle arrest, senescence and apoptosis. Indeed, perturbations in ceramide generation and turnover are frequently linked to cancer cell survival and resistance to chemotherapy. Consequently, the potential of ceramide-based therapeutics in the treatment of cancer has become a major focus of interest. A growing body of evidence indicates that ceramides can act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are scarce. In our recent study (Dadsena S et al., 2019, Nat Commun 10:1832), we used a photoactivatable ceramide probe combined with computer simulations and functional studies to identify the voltage-dependent anion channel VDAC2 as a critical effector of ceramide-induced mitochondrial apoptosis. Collectively, our findings provide a novel molecular framework for how ceramides execute their widely acclaimed anti-neoplastic activities.

New Delhi metallo-ß-lactamase-producing Acinetobacter isolates among late-onset VAP patients: multidrug-resistant pathogen and poor outcome.

BACKGROUND: Acinetobacter spp. are increasingly important microbes involved in late-onset ventilator-associated pneumonia (VAP). PURPOSE: The aims of this study were to determine the prevalence of New Delhi metallo-ß-lactamase (MßL) (blaNDM-1)-producing Acinetobacter spp. among late-onset VAP patients in different intensive care units (ICUs) of Menoufia and Kasr Al Ainy University Hospitals, to investigate the possible risk factors contributing to the acquisition of blaNDM-1-producing Acinetobacter infection, and to correlate between antimicrobial resistance pattern and therapeutic efficacy as well as clinical outcomes of these patients. MATERIALS AND METHODS: Sixty-four Acinetobacter isolates were collected from mechanically ventilated patients with suspected late-onset VAP and subjected to antimicrobial susceptibility testing. The modified Hodge test (MHT) and combined disk tests (CDT) were applied for blaNDM-1 MßL detection. Acinetobacter isolates with phenotypically confirmed MßLs production were subjected to a PCR assay to verify the presence of blaNDM-1 gene. The most obvious risk factors for acquisition of carbapenem resistance in VAP patients and treatment outcomes were also analyzed. RESULTS: Out of 64 Acinetobacter isolates, 42 (65.6%) proved to be blaNDM-1 positive. The sensitivity and specificity of MHT were 52.38% and 41.67%, while for CDT they were 92.86% and 83.33%, respectively. Acinetobacter isolates showed high susceptibility to colistin (85.7%). The clinical response was better among VAP patients who received combined carbapenem plus colistin therapy than those who received colistin alone. Relapse of infection was detected in 12.5% (8/64) of VAP cases. The reported mortality reached 46.8% (30/64) of which 27 (64.3%) were infected with blaNDM-1-positive isolates. Prolonged duration of mechanical ventilation, longer hospital and ICU stays, and prior exposure to antibiotic therapy were by far the most important factors predisposing to carbapenem resistance among VAP patients. CONCLUSION: A worldwide spread of Acinetobacter spp. expressing carbapenemases represents a significant threat to the medical community. The current study addressed the high prevalence of blaNDM-1-producing Acinetobacter isolates among late-onset VAP patients.

Ceramides bind VDAC2 to trigger mitochondrial apoptosis.

Ceramides draw wide attention as tumor suppressor lipids that act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are largely unknown. Using a photoactivatable ceramide probe, we here identify the voltage-dependent anion channels VDAC1 and VDAC2 as mitochondrial ceramide binding proteins. Coarse-grain molecular dynamics simulations reveal that both channels harbor a ceramide binding site on one side of the barrel wall. This site includes a membrane-buried glutamate that mediates direct contact with the ceramide head group. Substitution or chemical modification of this residue abolishes photolabeling of both channels with the ceramide probe. Unlike VDAC1 removal, loss of VDAC2 or replacing its membrane-facing glutamate with glutamine renders human colon cancer cells largely resistant to ceramide-induced apoptosis. Collectively, our data support a role of VDAC2 as direct effector of ceramide-mediated cell death, providing a molecular framework for how ceramides exert their anti-neoplastic activity.

The Association of Fractalkine Receptor (T280M) Polymorphism in the Pathogenesis of Acute Coronary Syndrome in the Egyptian Population.

BACKGROUND: Fractalkine (FKN) in its free and membrane bound-forms and its receptor CX3CR1are reported to have an atherosclerotic effect. The relationship of Single Nucleotide Polymorphisms (SNPs) in FKN and CX3CR1genes with the Coronary Artery Disease (CAD) risk showed conflicting results in different populations. The aim of this study was to investigate the influence of CX3CR1 threonine 280 methionine (T280M) polymorphism in the predisposition of Acute Coronary Syndrome (ACS) in Egyptians. METHODS: 200 Egyptian subjects were recruited for the study. They were divided into 100 ACS patients and 100 healthy controls. Genotyping of CX3CR1 T280M was performed using a Polymerase Chain Reaction-restriction Fragment Length Polymorphism (PCR-RFLP). Serum FKN was assayed by Enzyme - Linked - Immuno- Sorbent-Assay (ELISA). RESULTS: T and M allele frequencies for CX3CR1gene were not significantly different between ACS and Controls (p=0.76). Moreover, none of the genotypes had an atheroprotective effect. Serum analysis showed higher levels of FKN in ACS patients (p=0.041). FKN levels were not significantly different among genotypes of control and ACS groups (p=0.34) and (p=0.38) respectively. CONCLUSION: This study shows that CX3CR1 T280M polymorphism does not affect the incidence of ACS the Egyptian population. Moreover, none of the genotypes were associated with higher FKN levels.