Dissecting the Function of Ack Family Kinases in Drosophila Through Understanding Their Interactions with Dock and CDC42

Deregulation of Ack (Activated Cdc42-associated Kinase) family of non-receptor tyrosine kinases in mammals correlates with poor prognosis in cancers and has been implicated in promoting metastasis. In Drosophila, Ack family is constituted of two kinases: Ack and PR2. To further understand the in vivo function of this family we have conducted two projects: First we, we characterized the developmental defects of a null mutation in Drosophila Ack, which bears a high degree of sequence similarity to mammalian ACK1 but lacks a CRIB domain. We show that Ack, while not essential for viability, is critical for sperm formation. This function depends on Ack tyrosine kinase activity and is required cell autonomously in differentiating male germ cells at or after the spermatocyte stage. Ack associates predominantly with endocytic clathrin sites in spermatocytes, but disruption of Ack function has no apparent effect on clathrin localization and receptor-mediated internalization of Boss (Bride of sevenless) protein in eye discs. Instead, Ack is required for the subcellular distribution of Dock (dreadlocks), the Drosophila homolog of the SH2- and SH3-containing adapter protein Nck. Moreover, Dock forms a complex with Ack, and the localization of Dock in male germ cells depends on its SH2 domain. Together, our results suggest that Ack-dependent tyrosine phosphorylation recruits Dock to promote sperm differentiation. Second, despite the fact that ACK1 has been originally identified by its ability to bind to activated Cdc42, the physiological relevance of this binding has not been described. To test the significance of this interaction, we have established an over-expression system of various Cdc42 constructs in Drosophila germ cells. Similar to Drosophila embryos, expression of constitutively active Cdc42 (Cdc42G12V) in Drosophila spermatocytes results in cytokinesis defects, suggesting the step(s) affected by excessive Cdc42 activity is both meiotic and mitotic. Cdc42G12V is recruited to the site of cytokinesis ring constriction in germ cells where an increase in the level of tyrosine phosphorylation is also observed. This implies that a tyrosine kinase/substrate responds to Cdc42 activation. Indeed, loss-of-function mutations in PR2 but not Ack suppresses Cdc42G12V-dependent cytokinesis defect, suggesting that PR2 acts downstream of Cdc42. Moreover, PR2 is co-IPed with activated Cdc42 but not wild type Cdc42. Finally we show that Cdc42 G12V alters the subcellular localization of PR2 recruiting it to the site of cellular division

First trimester spontaneous rupture of an unscarred uterus in a multiparous woman: a case report

The rupture of an unscarred uterine is a rare life-threatening event that usually occurs late in pregnancy or during labor. Spontaneous uterine rupture, as in our case, is extremely uncommon and rarely diagnosed before laparotomy. Herein, we present a case of spontaneous uterine rupture in a 32 year old multiparous woman with no previous uterine surgery. The patient presented with acute abdomen at 11 weeks of gestation. Preoperative diagnosis based on clinical and ultra-sonographic findings was ruptured ectopic pregnancy. However, emergency laparotomy showed uterine rupture with extrusion of a dead fetus within intact amniotic sac in the abdomen. The defect was repaired in layers and the patient was discharged in a good condition after five days of hospital stay. Multiparity is a risk factor for spontaneous uterine rupture even in the first trimester. It should be kept in mind in any pregnant multiparous woman presenting with acute abdomen and shock. The absence of vaginal spotting and lack of history of uterine surgery give a false sense of security

The spectrum of MEFV gene mutations and genotype-phenotype correlation in Egyptian patients with familial Mediterranean fever

Background: Familial Mediterranean fever (FMF) is an autosomal recessive disease mainly affecting subjects of the Mediterranean origin. It is an auto-inflammatory periodic disorder that is caused by mutations in the Mediterranean fever gene (MEFV) located on chromosome 16.Methods: The current study was designed to assess the prevalence and frequency of different MEFV gene mutations among 104 FMF clinically diagnosed Egyptian patients and to evaluate the change extent in the values of some biochemical markers (ESR, CRP, Fibrinogen-C, SAA and IL1) in different participants with different FMF severity scores.Results: According to allele status 28 patients (27%) were homozygous mutation carriers, 38 (36.5%) were with compound heterozygous mutations and 38 (36.5%) were identified as heterozygous for one of the studied mutations. Of the studied mutations, M694I, E148Q, V726A, M680I, and M694V accounted for 28.1%, 26.8%, 16.9%, and 11.3% of mutations respectively. The R761H and P369S mutations were rarely encountered mutations (1.4%). The clinical features with M694I were associated with more severe clinical course. There is a drastic elevation in the levels of estimated parameters as their levels were increased as long as the severity of the disease increased.Conclusions: The diagnosis of FMF cannot be performed on the basis of genetic testing or clinical criteria alone. So, we recommended the combination between clinical and molecular profiling for FMF diagnosis and scoring

Comparative evaluation of the material of the artificial levees : A case study along the Tisza and Maros Rivers, Hungary

Artificial levees have major importance in protecting human livesand infrastructure as they are essential elements of the flood protectionmeasures. Nevertheless, the lack of the necessary information about theirstructure and internal composition might cause high risks. To monitor theirstability, integrated surveys are needed, including geophysical andgeotechnical methods. Levees along the rivers in Hungary were constructedmore than 150 years ago, and they were heightened several times; therefore,investigations are required to assure their performance in flood riskmitigation. Our investigation aimed to utilise non-invasive geophysicaltechniques, primarily electrical resistivity imaging, with the validationof geotechnical investigations to map and compare the compositional andstructural variations of two very different levee sections along RiverTisza and River Maros. Integrating the analysed drilling data with ERTprofiles showed that the main composition of the investigated Tisza leveesection is fine and medium silt with an average resistivity 30 Ωm, however,the investigated section of Maros levee was built of not only of fine andmedium silt but also of medium and coarse sand exhibiting higherresistivity values reaching up to 2200 Ωm. Several physical parameters weremeasured to study the nature of constituting levee materials like moisturecontent, grain-size, porosity, bulk-density, saturated hydraulicconductivity, and resistivity. It was found that most of them show aconnection with resistivity, but the hydraulic conductivity did not show adirect connection, however the latter could exhibit the aquitard nature ofTisza levee materials and the non-aquitard nature of Maros levee materials

The effect of caffeine ingestion in prevention of post-operative ileus after caesarean section: a randomized controlled trial

Background: Caesarian section (CS) has become more prevalent than the vaginal delivery in Egypt. Many complications could occur after an abdominal surgery. One of the commonest but yet serious complications is the postoperative ileus that can possibly be prevented by caffeine ingestion. The aim of the study is to assess the value of caffeine ingestion in promoting intestinal motility and prevention of postoperative ileus after CS.Methods: This is a randomized controlled trial that was conducted on 560 cases who were recruited from emergency unit and inpatient wards in Ain Shams University maternity hospital. The patients were divided into two groups where the intervention group received caffeinated coffee while the other group received decaffeinated coffee.Results: There was statistically significant difference between the two groups regarding the bowel function after CS (p <0.05). The intervention group had improved intestinal functions after the CS. Patients from the intervention group had audible intestinal sound sooner than the control group. In addition, they passed flatus and were able to tolerate food in less time.Conclusions: Consuming caffeinated coffee after CS contributes significantly to faster restoration of intestinal function. Coffee is a popular drink and can be used to decrease the incidence of postoperative ileus-related complications

Predictive values of ultrasound-based scoring system in morbidly adherent placenta for high risk group

Background: The objective of the present study was to find out the predictive values of an ultrasound-based scoring system in diagnosis of morbidly adherent placenta (MAP) for high risk group. Obstetrics and Gynecology Department, Faculty of Medicine, South Valley University, Egypt.Methods: 63 full term pregnant women (≥37 weeks of gestation) with high risk of morbidly adherent placenta underwent elective cesarean section. Placental assessment by 2 D ultrasound based on ultrasound scoring system in morbidly adherent placenta, these data were recorded for further comparison with intraoperative data for degree of placental adherence.Results: Incidence of MAP was 7.93% (4.76% had a focal form and 3.17% had a complete form of accreta). As regarding to scoring system, 82.5 of cases had a low risk (< 5), 9.5% had a moderate risk (6-7) and 7.93% had a high risk (8-12) of development of morbidly adherent placenta with p value <0.0001. The sensitivity, specificity, positive and negative predictive values of the US scoring system for morbidly adherent placenta were (92.3%, 94.1%, 87.453% and 98.2%) respectively.Conclusions: Ultrasound based scoring system had a high predictive value (sensitivity, specificity, positive and negative predictive values) in diagnosis of morbidly adherent placenta for pregnant women have any risk factors for developing MAP

Effect of esomeprazole on maternal serum soluble fms-like tyrosine kinase-1 and endoglin in patients with early-onset preeclampsia

Objective: This study evaluates the effect of esomeprazole on the maternal serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) in patients with early-onset preeclampsia.Methods: A randomized, double-blind, placebo-controlled trial was carried out in a tertiary University hospital between March 2018, and September 2019 (Clinical Trials.Gov: NCT03213639). The study included women between 28 and 31+6 weeks gestational age who had been diagnosed as preeclampsia without severe features. They were randomly assigned in a 1:1 ratio into an esomeprazole group, which received esomeprazole 40 mg orally once a day, and a placebo group, which received one placebo tablet daily. Blood samples were obtained to assess levels of serum sFlt-1and sEng using ELISA testing. The primary outcome was the difference between the mean serum level of sFlt-1 and sEng at the start of treatment and at the termination of pregnancy in both groups.Results: Eighty-eight patients were randomly assigned into both groups (44 in each). No statistically significant difference was found in the levels of sFlt-1 between both groups at admission and termination of pregnancy. The number of days of treatment for the esomeprazole group was slightly longer than the placebo group (11.4±9.4 vs. 10.3±6.3 days, P=0.515). No statistically significant difference in the rate of maternal and fetal complications occurred between the two groups. No side effects from the study medications were reported.Conclusions: Esomeprazole, at the dosage used in this study did not effectively lower the serum levels of sFlt-1 and sEng in patients with early-onset preeclampsia. Furthermore, it did not prolong the duration of pregnancy, nor did it decrease maternal or fetal complications

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Cinnamon and ginger extracts attenuate diabetes-induced inflammatory testicular injury in rats and modulating SIRT1 expression

The current study aimed to evaluate the efficacy of simultaneous administration of Zingiber officinale (ginger) and Cinnamomum cassia (cinnamon) extracts in mitigating testicular changes associated with diabetes mellitus in rats and to investigate its molecular mode of action. After induction of diabetes using streptozotocin, 36 male rats were divided to six groups namely control, diabetic, metformin-treated, cinnamon-treated, ginger-treated and combined, each group having 6 rats. Fasting blood glucose, serum insulin, testosterone was measured. Expression of inflammatory mediators; tumor necrosis factor-alpha (TNF-α), Nuclear factor kappa B (NF-κB) and Sirtuin 1 (SIRT1) was assessed in the testicular tissue. Histopathological changes in the testis were observed and spermatogenesis and apoptosis were assessed immunohistochemically. The histological and biochemical studies of the untreated group confirmed structural changes in testes induced by diabetes. Oral administration of ginger and cinnamon increased insulin level significantly increased while the blood glucose level significantly decreased in diabetic rats, improving structural testicular changes considerably. Joint intake of ginger and cinnamon increased antihyperglycemic, antioxidant and anti-inflammatory effects markedly improving the testicular injury compared to the administration of either of them. SIRT1 expression in the testis significantly increased in ginger plus cinnamon-treated rats. These results indicate that when administrated together, ginger and cinnamon synergistically enhanced antioxidant, antiapoptotic and anti-inflammatory effects and induced antihyperglycemic effect comparable to metformin. The combination of ginger and cinnamon also upregulated SIRT1 in the testis