Increased Reactive Oxygen Species and Cell Cycle Defects Contribute to Anemia in the RASA3 Mutant Mouse Model s

RASA3 is a Ras GTPase activating protein that plays a critical role in blood formation. The autosomal recessive mouse model scat (severe combined anemia and thrombocytopenia) carries a missense mutation in Rasa3. Homozygotes present with a phenotype characteristic of bone marrow failure that is accompanied by alternating episodes of crisis and remission. The mechanism leading to impaired erythropoiesis and peripheral cell destruction as evidenced by membrane fragmentation in scat is unclear, although we previously reported that the mislocalization of RASA3 to the cytosol of reticulocytes and mature red cells plays a role in the disease. In this study, we further characterized the bone marrow failure in scat and found that RASA3 plays a central role in cell cycle progression and maintenance of reactive oxygen species (ROS) levels during terminal erythroid differentiation, without inducing apoptosis of the precursors. In scat mice undergoing crises, there is a consistent pattern of an increased proportion of cells in the G0/G1 phase at the basophilic and polychromatophilic stages of erythroid differentiation, suggesting that RASA3 is involved in the G1 checkpoint. However, this increase in G1 is transient, and either resolves or becomes indiscernible by the orthochromatic stage. In addition, while ROS levels are normal early in erythropoiesis, there is accumulation of superoxide levels at the reticulocyte stage (DHE increased 40% in scat; p = 0.02) even though mitochondria, a potential source for ROS, are eliminated normally. Surprisingly, apoptosis is significantly decreased in the scat bone marrow at the proerythroblastic (15.3%; p = 0.004), polychromatophilic (8.5%; p = 0.01), and orthochromatic (4.2%; p = 0.02) stages. Together, these data indicate that ROS accumulation at the reticulocyte stage, without apoptosis, contributes to the membrane fragmentation observed in scat. Finally, the cell cycle defect and increased levels of ROS suggest that scat is a model of bone marrow failure with characteristics of aplastic anemia

Robot-assisted laparoscopic surgery for treatment of urinary tract stones in children: report of a multicenter international experience

This study aimed to report a multi-institutional experience with robot-assisted laparoscopic surgery (RALS) for treatment of urinary tract stones in children. The medical records of 15 patients (12 boys), who underwent RALS for urolithiasis in 4 international centers of pediatric urology over a 5-year period, were retrospectively collected. The median patient age was 8.5 years (range 4–15). Eleven/fifteen patients (73.3%) had concurrent uretero–pelvic junction obstruction (UPJO) and 2/15 patients (13.3%) had neurogenic bladder. Stones were in the renal pelvis in 8/15 (53.3%), in the lower pole in 3/15 (20%), in the bladder in 2/15 (13.3%), and in multiple locations in 2/15 (13.3%). One patient (6.6%) had bilateral multiple kidney stones. The median stone size was 10.8 mm (range 2–30) in upper tract location and 27 mm (range 21–33) into the bladder. Eleven patients with concomitant UPJO underwent simultaneous robot-assisted pyelolithotomy and pyeloplasty in 12 kidney units. Two patients with isolated staghorn stones received robot-assisted pyelolithotomy. Robot-assisted cystolithotomy was performed in two patients with bladder stones. The median operative time was 131.8 min (range 60–240). The stone-free rate was 80% following initial surgery and 100% after secondary treatment. Clavien 2 complications (hematuria, infections) were recorded in 5/15 patients (33.3%). Three/fifteen patients (20%) with residual renal stones were successfully treated using ureterorenoscopy (Clavien 3b). RALS was a feasible, safe and effective treatment option for pediatric urolithiasis in selected cases such as large bladder stones, bilateral kidney stones, staghorn stones or concomitant anomalies such as UPJO requiring simultaneous pyeloplasty

Structure of worldwide populations of Lasioderma serricorne (Coleoptera: Anobiidae) as revealed by amplified fragment length polymorphism profiles

The cigarette beetle Lasioderma serricorne through transportation affects the infestation of stored tobacco. Using amplified fragment length polymorphism (AFLP), DNA polymorphisms were assessed in 16 populations of L. serricorne collected from 15 countries. The dendrograms constructed from profile distance matrices revealed well-supported colony clusters. There was no clear clustering as a function of the geographic origin of the samples. The results suggest extensive insect dispersal among geographical regions due to movement of infested commodities worldwide. This first AFLP population study of a stored-product insect demonstrates the potential of AFLP for distinguishing L. serricorne population

Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an open-label randomized control trial.

BACKGROUND & AIMS: Eating habits may influence the life span and the quality of ageing process by modulating inflammation. The RISTOMED project was developed to provide a personalized and balanced diet, enriched with or without nutraceutical compounds, to decrease and prevent inflammageing, oxidative stress and gut microbiota alteration in healthy elderly people. This paper focused on the effect on inflammation and metabolism markers after 56 days of RISTOMED diet alone or supplementation with three nutraceutical compounds. METHODS:A cohort of 125 healthy elderly subjects was recruited and randomized into 4 arms (Arm A, RISTOMED diet; Arm B, RISTOMED diet plus VSL#3 probiotic blend; Arm C, RISTOMED diet plus AISA d-Limonene; Arm D, RISTOMED diet plus Argan oil). Inflammatory and metabolism parameters as well as the ratio between Clostridium cluster IV and Bifidobacteria (CL/B) were collected before and after 56 days of dietary intervention, and their evolution compared among the arms. Moreover, participants were subdivided according to their baseline inflammatory parameters (erythrocytes sedimentation rate (ESR), C-Reactive Protein, fibrinogen, Tumor Necrosis Factor-alfa (TNF-α), and Interleukin 6) in two clusters with low or medium-high level of inflammation. The evolution of the measured parameters was then examined separately in each cluster. RESULTS:Overall, RISTOMED diet alone or with each nutraceutical supplementation significantly decreased ESR. RISTOMED diet supplemented with d-Limonene resulted in a decrease in fibrinogen, glucose, insulin levels and HOMA-IR. The most beneficial effects were observed in subjects with a medium-high inflammatory status who received RISTOMED diet with AISA d-Limonene supplementation. Moreover, RISTOMED diet associated with VSL#3 probiotic blend induced a decrease in the CL/B ratio. CONCLUSIONS:Overall, this study emphasizes the beneficial anti-inflammageing effect of RISTOMED diet supplemented with nutraceuticals to control the inflammatory status of elderly individuals

Robot-assisted laparoscopic pyeloplasty (RALP) in children with horseshoe kidneys: results of a multicentric study

This multicentric study aimed to report our experience with robot-assisted laparoscopic pyeloplasty (RALP) in children with horseshoe kidney (HSK). METHODS: The records of 14 patients (11 boys and 3 girls with an average age of 9 years), who underwent RALP for repair of pelvi-ureteric junction obstruction (PUJO) in HSK in five international pediatric urology units over a 5-year period, were retrospectively reviewed. A dismembered pyeloplasty with no division of isthmus was performed in all the cases. RESULTS: The average operative time including docking was 143.5 min (range 100-205). No conversions to laparoscopy or open surgery or intra-operative complications occurred. Patients were discharged on postoperative day 2 following catheter and drain removal. The JJ stent was removed at mean 33 days postoperatively. Overall success rate was 92.8%. As for postoperative complications, we recorded a urinary tract infection (UTI) and stent-related irritative symptoms, managed with medical therapy, in two patients (II Clavien) and an anastomotic stricture in one patient needing surgical revision with no further recurrence (IIIb Clavien). At follow-up, all the patients (one after redo-surgery) reported complete resolution of symptoms, improvement of hydronephrosis on ultrasound and no residual obstruction on diuretic renogram. CONCLUSIONS: Our experience suggested that RALP in HSK is safe, feasible and with good medium-term outcomes in expert hands. An accurate pre-operative planning associated with a standardized technique is key points to achieve good surgical and functional outcomes in these challenging cases. The da Vinci robot technology offers the advantages of MIS procedures and overcomes the technical challenges of laparoscopic approach

Prevalence of multidrug-resistant bacteria colonisation among asylum seekers in western Switzerland.

The recent increase of migration to Europe represents a risk of increased the prevalence of multidrug-resistant (MDR) bacteria. We conducted a cross-sectional study among asylum seekers admitted at two hospitals in Switzerland. Of the 59 patients included, 9 (14%) were colonised by a MDR bacteria, including 5 (8.5%) methicilin-resistant Staphylococcus aureus (MRSA) and 4 (6.8%) extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. No patient carried both ESBL-producing bacteria and MRSA. None of the patients carried a vancomycin-resistant Enterococcus (VRE) or a carbapenem-resistant Enterobacteriaceae (CRE). Colonisation with MDR bacteria was not associated with hospitalisation abroad or recent arrival in Switzerland. Whole genome sequencing analysis allowed us to exclude transmission between patients. The prevalence of MDR bacteria carriage is moderate among asylum seekers in western Switzerland. Further surveillance studies are necessary to determine if there is a risk of dissemination of pathogens into the local population

Low Energy States of 3181Ga50^{81}_{31} Ga_{50} : Elements on the Doubly-Magic Nature of 78^{78}Ni

Excited levels were attributed to $^{81}_{31}$Ga$_{50}$ for the first time which were fed in the $\beta$-decay of its mother nucleus $^{81}$Zn produced in the fission of $^{nat}$U using the ISOL technique. We show that the structure of this nucleus is consistent with that of the less exotic proton-deficient N=50 isotones within the assumption of strong proton Z=28 and neutron N=50 effective shell effects.Comment: 4 pages, REVTeX 4, 5 figures (eps format