Role of fosfomycin tromethamine in modulating non-specific defence mechanisms in chronic uremic patients towards ESBL-producing Escherichia coli.

Antimicrobial agents and polymorphonuclear cells (PMNs) have the potential to interact in such a way that improve the therapy for infectious diseases. In immunocompromised patients highly susceptible to microbial infections with high morbidity and mortality, several metabolic and functional alterations in PMNs, mostly related to microbicidal activity, are observed. Therefore, the antibiotic of choice should have a good antimicrobial effect without impairing host defences. The aim of this study is to evaluate in vitro effects of sub-inhibiting fosfomycin tromethamine (FT) concentrations on the primary functions of PMNs from healthy subjects and immunocompromised patients (haemodialysed and renal transplant recipients), against an ESBL-producing Escherichia coli, the most common aetiological agent in urinary tract infections (UTIs). FT is considered a first line drug in the eradication of UTIs due to its appropriate antimicrobial spectrum, oral bioavailability and minimal risk of microbial resistance. Our results provide evidence that FT is able to induce enhancement of the depressed phagocytic response of PMNs from patients on chronic haemodialysis and from renal transplant recipients, restoring their primary functions in vitro against ESBL-producing E. coll All these data permit the conclusion that uremic-infected patients might additionally benefit from the immunomodulating properties of FT

A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes “normal” or “good” kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1–2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage “non-ideal” situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial “third element”

Cross-section measurement of two-photon annihilation in-flight of positrons at s=20\sqrt{s}=20 MeV with the PADME detector

The inclusive cross-section of annihilation in flight $e^+e^-\rightarrow\gamma\gamma$ of 430 MeV positrons with atomic electrons of a thin diamond target has been measured with the PADME detector at the Laboratori Nazionali di Frascati. The two photons produced in the process were detected by an electromagnetic calorimeter made of BGO crystals. This measurement is the first one based on the direct detection of the photon pair and one of the most precise for positron energies below 1 GeV. This measurement represents a necessary step to search for dark sector particles and mediators weakly coupled to photons and/or electrons with masses ranging from 1 MeV to 20 MeV with PADME. The measurement agrees with the Next to Leading Order QED prediction within the overall 6% uncertainty.Comment: Submitted to PR

Commissioning of the PADME experiment with a positron beam

The PADME experiment is designed to search for a hypothetical dark photon A' produced in positron-electron annihilation using a bunched positron beam at the Beam Test Facility of the INFN Laboratori Nazionali di Frascati. The expected sensitivity to the A'-photon mixing parameter ϵ is 10-3, for A' mass ≤ 23.5 MeV/c 2 after collecting ∼1013 positrons-on-target. This paper presents the PADME detector status after commissioning in July 2019. In addition, the software algorithms employed to reconstruct physics objects, such as photons and charged particles, and the calibration procedures adopted are illustrated in detail. The results show that the experimental apparatus reaches the design performance, and is able to identify and measure standard electromagnetic processes, such as positron bremsstrahlung and electron-positron annihilation into two photons

Characterisation and performance of the PADME electromagnetic calorimeter

The PADME experiment at the LNF Beam Test Facility searches for dark photons produced in the annihilation of positrons with the electrons of a fixed target. The strategy is to look for the reaction e+ + e− → γ + A0, where A0 is the dark photon, which cannot be observed directly or via its decay products. The electromagnetic calorimeter plays a key role in the experiment by measuring the energy and position of the final-state γ. The missing four-momentum carried away by the A0 can be evaluated from this information and the particle mass inferred. This paper presents the design, construction, and calibration of the PADME’s electromagnetic calorimeter. The results achieved in terms of equalisation, detection efficiency and energy resolution during the first phase of the experiment demonstrate the effectiveness of the various tools used to improve the calorimeter performance with respect to earlier prototypes