The PS 10 MHz High Level RF System Upgrade

In view of the upgrade of the injectors for the High Luminosity LHC, significantly higher bunch intensity is required for LHC-type beams. In this context an upgrade of the main accelerating RF system of the Proton Synchrotron (PS) is necessary, aiming at reducing the cavity impedance which is the source of longitudinal coupled-bunch oscillations. These instabilities pose as a major limitation for the increase of the beam intensity as planned after LS2. The 10 MHz RF system consists in 11 ferrite loaded cavities, driven by tube-based power amplifiers for reasons of radiation hardness. The cavity-amplifier system is equipped with a wide-band feedback that reduces the beam induced voltage. A further reduction of the beam loading is foreseen by upgrading the feedback system, which can be reasonably achieved by increasing the loop gain of the existing amplification chain. This paper describes the progress of the design of the upgraded feedback system and shows the results of the tests on the new amplifier prototype, installed in the PS during the 2015-16 technical stop. It also reports the first results of its performance with beam, observed in the beginning of the 2016 run

Molecular evidence of incipient speciation within Anopheles gambiae s.s. in West Africa

We karyotyped and identified by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis Anopheles gambiae s.s. samples collected in several African countries. The data show the existence of two non-panmictic molecular forms, named S and M, whose distribution extended from forest to savannahs, Mosquitoes of the S and M forms are homosequential standard for chromosome-2 inversions in forest areas. In dry savannahs, S is characterized mainly by inversion polymorphisms typical of Savanna and Bamako chromosomal forms, while M shows chromosome-2 arrangements typical of Mopti and/or Savanna and/or Bissau, depending on its geographical origin. Chromosome-2 inversions therefore seem to be involved in ecotypic adaptation rather than in mate-recognition systems. Strong support for the reproductive isolation of S and M in Ivory Coast comes from the observation that the kdr allele is found at high frequencies in S specimens and not at all in chromosomal identical M specimens. However, the kdr allele does not segregate with molecular forms in Benin

RCC1L (WBSCR16) isoforms coordinate mitochondrial ribosome assembly through their interaction with GTPases

Mitochondrial translation defects can be due to mutations affecting mitochondrial-or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently been described to interact with the mitochondrial large ribosomal subunit. In humans, three different RCC1L isoforms have been identified that originate from alternative splicing but share the same N-Terminus, RCC1LV1, RCC1LV2 and RCC1LV3. All three isoforms were exclusively localized to mitochondria, interacted with its inner membrane and could associate with homopolymeric oligos to different extent. Mitochondrial immunoprecipitation experiments showed that RCC1LV1 and RCC1LV3 associated with the mitochondrial large and small ribosomal subunit, respectively, while no significant association was observed for RCC1LV2. Overexpression and silencing of RCC1LV1 or RCC1LV3 led to mitoribosome biogenesis defects that resulted in decreased translation. Indeed, significant changes in steady-state levels and distribution on isokinetic sucrose gradients were detected not only for mitoribosome proteins but also for GTPases, (GTPBP10, ERAL1 and C4orf14), and pseudouridylation proteins, (TRUB2, RPUSD3 and RPUSD4). All in all, our data suggest that RCC1L is essential for mitochondrial function and that the coordination of at least two isoforms is essential for proper ribosomal assembly

A Case of Osteonecrosis of the Jaw in a Patient with Crohn's Disease Treated with Infliximab

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse drug reaction, occurring in patients undergoing treatments with antiresorptive or antiangiogenic agents, such as bisphosphonates, denosumab, or bevacizumab, for different oncologic and non-oncologic diseases. The aim of this study was to report a case of MRONJ in a patient taking infliximab, an anti-TNF-alpha antibody used to treat Crohn's disease, rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Case Report: A 49-year-old female patient affected by Crohn's disease, who had been undergoing 250 mg intravenous infliximab every six weeks for 12 years, with no history of antiresorptive or antiangiogenic agent administration, came to our attention for post-surgical MRONJ, associated with a wide cutaneous necrotic area of her anterior mandible. Following antibiotic cycles, the patient underwent surgical treatment with wide bone resection and debridement of necrotic tissues; after prolonged follow-up (16 months), the patient completely healed without signs of recurrence. Conclusions: Prevention of MRONJ by dental check-up before and during treatments with antiresorptive treatments (bisphosphonates or denosumab) is a well-established procedure. Although further studies are required to confirm the role of infliximab in MRONJ, based on the results of this study, we propose that patients who are going to be treated with infliximab should also undergo dental check-up before starting therapy, to possibly avoid MRONJ onset

Intra-instar larval cannibalism in Anopheles gambiae (s.s.) and Anopheles stephensi (Diptera: Culicidae)

BACKGROUND: Cannibalism has been observed in a wide range of animal taxa and its importance in persistence and stability of populations has been documented. In anopheline malaria vectors the inter-instar cannibalism between fourth- and first-instar larvae (L4-L1) has been shown in several species, while intra-instar cannibalism remains poorly investigated. In this study we tested the occurrence of intra-instar cannibalism within larvae of second-, third- and fourth-instar (L2, L3 and L4) of Anopheles gambiae (s.s.) and An. stephensi. Experiments were set up under laboratory conditions and the effects of larval density, duration of the contact period among larvae and the presence of an older larva (i.e. a potential cannibal of bigger size) on cannibalism rate were analysed. Cannibalism was assessed by computing the number of missing larvae after 24 and 48 h from the beginning of the experiments and further documented by records with a GoPro videocamera. RESULTS: Intra-instar cannibalism was observed in all larval instars of both species with higher frequency in An. gambiae (s.s.) than in An. stephensi. In both species the total number of cannibalistic events increased from 0-24 to 0-48 h. The density affected the cannibalism rate, but its effect was related to the larval instar and to the presence of older larvae. Interestingly, the lower cannibalism rate between L4 larvae was observed at the highest density and the cannibalism rate between L3 larvae decreased when one L4 was added. CONCLUSIONS: The present study provides experimental evidence of intra-instar cannibalism in the malaria vectors An. gambiae (s.s.) and An. stephensi and highlights the possible occurrence of complex interactions between all larval instars potentially present in the breeding sites. We hypothesize that the high density and the presence of a potential cannibal of bigger size could affect the readiness to attack conspecifics, resulting into low risk larval behavior and lower cannibalism rate. The understanding of cannibalistic behavior and the factors affecting it is of utmost importance for malaria vectors, as nutrition during larval development can strongly affect the fitness of adult female mosquitoes and ultimately their vector ability

Osteonecrosis of the jaws in patients assuming oral bisphosphonates for osteoporosis: A retrospective multi-hospital-based study of 87 Italian cases

BACKGROUND: Bisphosphonates (BPs) are currently the chief drugs for the prevention/treatment of osteoporosis; one of their adverse effects is the osteonecrosis of the jaw (BRONJ). The primary endpoints of this multi-center cross-sectional study are: i) an observation of the clinical features of BRONJ in 87 osteoporotic, non-cancer patients; and ii) an evaluation of their demographic variables and comorbidities. METHODS: 87 BRONJ patients in therapy for osteoporosis with BPs from 8 participating clinical Italian centers were consecutively identified and studied. After BRONJ diagnosis and staging, comorbidities and data relating to local and drug-related risk factors for BRONJ were collected. RESULTS: 77/87 (88.5%) patients in our sample used alendronate as a BP type; the duration of bisphosphonate therapy ranged from 2 to 200 months, and 51.7% of patients were in treatment for ≤ 38 months (median value). No comorbidities or local risk factors were observed in 17 (19.5%) patients, indicating the absence of cases belonging to BRONJ forms triggered by surgery. BRONJ localization was significantly associated with age: an increased risk of mandible localization (p=0.002; OR=6.36, 95%CI=[1.89; 21.54]) was observed for those over 72 yrs. At multivariate analysis, the increased risk of BRONJ in the mandible for people over 72 yrs (OR'=6.87, 95%CI=[2.13; 2.21]) was confirmed for a BP administration >56 months (OR'=4.82, 95%CI=[2.13; 22.21]). CONCLUSION: Our study confirms the fundamental necessity of applying protocols of prevention in order to reduce the incidence of BRONJ in osteoporotic, non-cancer patients in the presence of comorbidities and/or local risk factor as well as, less frequently, in their absence

Human Subcutaneous Dirofilariasis, Russia

We report 14 cases of human subcutaneous dirofilariasis caused by Dirofilaria repens, diagnosed from February 2003 through July 2004, in patients from Rostov-on-Don, Russia. Serologic analysis showed evidence of high risk of exposure to D. repens. Surveillance studies on prevalence and prevention effectiveness of canine infection are needed to control this emerging zoonosis

Identification of the Midgut Microbiota of An. stephensi and An. maculipennis for Their Application as a Paratransgenic Tool against Malaria

The midgut microbiota associated with Anopheles stephensi and Anopheles maculipennis (Diptera: Culicidae) was investigated for development of a paratransgenesis-based approach to control malaria transmission in Eastern Mediterranean Region (EMR). Here, we present the results of a polymerase chain reaction (PCR) and biochemical-based approaches to identify the female adult and larvae mosquitoe microbiota of these two major malaria vectors, originated from South Eastern and North of Iran. Plating the mosquito midgut contents from lab-reared and field-collected Anopheles spp. was used for microbiota isolation. The Gram-negative and Gram-positive bacterial colonies were identified by Gram staining and specific mediums. Selected colonies were identified by differential biochemical tests and 16S rRNA gene sequence analysis. A number of 10 An. stephensi and 32 An. maculipennis adult mosquitoes and 15 An. stephensi and 7 An. maculipennis larvae were analyzed and 13 sequences of 16S rRNA gene bacterial species were retrieved, that were categorized in 3 classes and 8 families. The majority of the identified bacteria were belonged to the γ-proteobacteria class, including Pseudomonas sp. and Aeromonas sp. and the others were some closely related to those found in other vector mosquitoes, including Pantoea, Acinetobacter, Brevundimonas, Bacillus, Sphingomonas, Lysinibacillus and Rahnella. The 16S rRNA sequences in the current study aligned with the reference strains available in GenBank were used for construction of the phylogenetic tree that revealed the relatedness among the bacteria identified. The presented data strongly encourage further investigations, to verify the potential role of the detected bacteria for the malaria control in Iran and neighboring countries