SARS-CoV-2 caused a surge in antibiotic consumption causing a silent pandemic inside the pandemic. A retrospective analysis of Italian data in the first half of 2022.

BACKGROUND: The phenomenon of antibiotic resistance shows no sign of stopping, despite global policies to combat it that have been in place for several years. The risk of forms of pathogenic microorganisms that are increasingly resistant to common antibiotics has led health authorities around the world to pay greater attention to the phenomenon. The worrying situation, has led to further recommendations from the World Health Organization (WHO) and national recommendations in Italy through the new National Plan against Antibiotic Resistance 2022-2025 (PNCAR 2022-2025). AIM: This manuscript aims to raise the awareness of all health professionals to follow what is suggested by regulatory agencies and scientific societies. METHOD: We conducted a retrospective study of antibiotic pharmacoutilization in Italy, in the Campania region at the Azienda Sanitaria Locale (ASL) Napoli 3 Sud, on consumption in the first half of 2022 in a population of more than 1 million people. RESULT: The results indicate that consumption, based on defined daily doses (DDDs), is above the national average. Probably the COVID-19 pandemic has influenced this growth in prescriptions. CONCLUSIONS: Our study suggests an informed and appropriate use of antibiotics, so as to embark on a virtuous path in the fight against antibiotic resistance.

Combining 3D human in vitro methods for a 3Rs evaluation of novel titanium surfaces in orthopaedic applications.

In this study, we report on a group of complementary human osteoblast in vitro test methods for the preclinical evaluation of 3D porous titanium surfaces. The surfaces were prepared by additive manufacturing (electron beam melting [EBM]) and plasma spraying, allowing the creation of complex lattice surface geometries. Physical properties of the surfaces were characterized by SEM and profilometry and 3D in vitro cell culture using human osteoblasts. Primary human osteoblast cells were found to elicit greater differences between titanium sample surfaces than an MG63 osteoblast-like cell line, particularly in terms of cell survival. Surface morphology was associated with higher osteoblast metabolic activity and mineralization on rougher titanium plasma spray coated surfaces than smoother surfaces. Differences in osteoblast survival and metabolic activity on titanium lattice structures were also found, despite analogous surface morphology at the cellular level. 3D confocal microscopy identified osteoblast organization within complex titanium surface geometries, adhesion, spreading, and alignment to the biomaterial strut geometries. Mineralized nodule formation throughout the lattice structures was also observed, and indicative of early markers of bone in-growth on such materials. Testing methods such as those presented are not traditionally considered by medical device manufacturers, but we suggest have value as an increasingly vital tool in efficiently translating pre-clinical studies, especially in balance with current regulatory practice, commercial demands, the 3Rs, and the relative merits of in vitro and in vivo studies. Biotechnol. Bioeng. 2016;113: 1586-1599. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

Sherrington-Kirkpatrick model for spin glasses: Solution via the distributional zeta function method.

We discuss the Sherrington-Kirkpatrick mean-field version of a spin glass within the distributional zeta function method (DZFM). In the DZFM, since the dominant contribution to the average free energy is written as a series of moments of the partition function of the model, the spin-glass multivalley structure is obtained. Also, an exact expression for the saddle points corresponding to each valley and a global critical temperature showing the existence of many stables or at least metastable equilibrium states is presented. Near the critical point, we obtain analytical expressions of the order parameters that are in agreement with phenomenological results. We evaluate the linear and nonlinear susceptibility and we find the expected singular behavior at the spin-glass critical temperature. Furthermore, we obtain a positive definite expression for the entropy and we show that ground-state entropy tends to zero as the temperature goes to zero. We show that our solution is stable for each term in the expansion. Finally, we analyze the behavior of the overlap distribution, where we find a general expression for each moment of the partition function.

Validation of all-atom phosphatidylcholine lipid force fields in the tensionless NPT ensemble.

A recently defined charge set, to be used in conjunction with the all-atom CHARMM27r force field, has been validated for a series of phosphatidylcholine lipids. The work of Sonne et al. successfully replicated experimental bulk membrane behaviour for dipalmitoylphosphatidylcholine (DPPC) under the isothermal-isobaric (NPT) ensemble. Previous studies using the defined CHARMM27r charge set have resulted in lateral membrane contraction when used in the tensionless NPT ensemble, forcing the lipids to adopt a more ordered conformation than predicted experimentally. The current study has extended the newly defined charge set to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphatidylcholine (PDPC). Molecular dynamics simulations were run for each of the lipids (including DPPC) using both the CHARMM27r charge set and the newly defined modified charge set. In all three cases a significant improvement was seen in both bulk membrane properties and individual atomistic effects. Membrane width, area per lipid and the depth of water penetration were all seen to converge to experimental values. Deuterium order parameters generated with the new charge set showed increased disorder across the width of the bilayer and reflected both results from experiment and similar simulations run with united atom models. These newly validated models can now find use in mixed biological simulations under the tensionless ensemble without concern for lateral contraction.

Lemierre syndrome and nosocomial transmission of Fusobacterium necrophorum from patient to physician.

BACKGROUND: Human-to-human transmission of Fusobacterium necrophorum has not been described before. CASE PRESENTATION: We present the case of a 15-year-old girl with Lemierre Syndrome and possible nosocomial transmission of F. necrophorum to her treating physician in hospital. CONCLUSION: Early diagnosis and treatment of anaerobic pharyngitis is critical to prevent Lemierre Syndrome. Respiratory precautions should be recommended to medical staff caring for patients with suspected Lemierre Syndrome to prevent nosocomial transmission.

A systematic review on the efficacy and safety of IL-6 modulatory drugs in the treatment of COVID-19 patients.

The pandemic caused by the new SARS-CoV2 coronavirus has led to an effort to find treatments that are effective against this disease that the World Health Organization calls COVID-19. In severe cases of COVID-19, there is an increase in cytokines, among which IL-6 seems to play an important role. A search has been performed for studies using IL-6 blocking drugs (tocilizumab, siltuximab, and sarilumab) in PubMed, Web of Science, and Scopus. Also, a search of ongoing trials registered at clinicaltrials.gov was performed. We found very little published clinical experience with these drugs, consisting mainly of case reports or case series with few patients. The results of clinical trials are necessary to clarify the role of these drugs in patients with COVID-19.

[Evaluation of patients' satisfaction of home care services]. / Valutazione della soddisfazione dei pazienti seguiti in cure domiciliari.

The satisfaction level of a patient that receives home care, is an indicator that is rarely ever evaluated. This is also due to the fact that it is objectively difficult to gather data concerning this issue and there are a countless number of variables that could influence an evaluation. The objective of this study is to quantify the satisfaction level of those that use the Home Care Services of the Trento District. A validated questionnaire with 30 questions was used to explore the organizational, relational and professional aspects, communication, information and patient education in addition to the satisfaction level of certain aspects that concerned the availability/delivery of medical supplies and aids. Together with this information, data was also gathered concerning the patient's formal and informal social network. 122 patients, that received care by the nursing services of the territory and that received home care at least twice a week, were enrolled in the survey. The responses that emerged from this sample of patients, concerning the satisfaction level, were very positive. Each aspect had a high satisfaction percentage that was always beyond 75%. This survey must be used within the trust's continuous quality improvement plan, by addressing the needs that have been expressed and not, by empowering human and organizational resources and by integrating the numerous health care operators that work within the territory to improve citizens' health.

The effect of oxygen pickup during selective laser melting on the microstructure and mechanical properties of Ti-6Al-4V lattices.

Additive manufacturing techniques such as Selective Laser Melting (SLM) can produce complex shapes with relatively thin sections and fine detail. However, common materials for the process, such as Ti-6Al-4V, have microstructure and properties that are sensitive to the pickup of interstitial impurities, such as oxygen, which the material will be exposed to during the process. This problem would be especially severe for parts with thin sections, where surface effects can be more significant, and where poor properties may coincide with locally-elevated stress. Here we explore the effects of oxygen level in thin sections with the use of lattice materials (materials which can be considered to consist exclusively of near-surface material). Oxygen levels are artificially raised using repeated melting passes to result in more pickup, leading to significantly reduced ductility and hence reduced strength measured in compression. A ductile to brittle transition in strut failure mechanism is found with increasing number of melting passes, with significant modification in chemistry and crystallographic structure, despite the presence of a similar fine plate-like microstructure throughout.

Additive manufacturing titanium components with isotropic or graded properties by hybrid electron beam melting/hot isostatic pressing powder processing.

A methodology has been demonstrated to consolidate Ti-6Al-4V powder without taking it to the liquid state by novel combination of the electron beam melting additive manufacture and hot isostatic pressing processes. This results in improved static mechanical properties (both strength and yield) in comparison to standard EBM processed material. In addition, the ability to generate microstructurally graded components has been demonstrated by generating a component with a significant change in both microstructure and mechanical properties. This is revealed by the use of electron backscattered diffraction and micro hardness testing to produce maps showing a clear distinction between materials consolidated in different ways. The variation in microstructure and mechanical properties is attributed to the different thermal history experienced by the material at different locations. In particular, it is found that the rapid cooling experienced during EBM leads to a typical fine α lath structure, whereas a more equiaxed α grains generated by diffusion is found in HIP consolidated powder.

Role of imaging techniques in the diagnosis and follow-up of muscle-invasive bladder carcinoma. / Papel de las técnicas de imagen en el diagnóstico y seguimiento del carcinoma vesical músculo invasivo.

INTRODUCTION: Muscle-invasive bladder malignancies represent 20-30% of all bladder cancers. These patients require imaging tests to determine the regional and distant staging. OBJECTIVE: To describe the role of various imaging tests in the diagnosis, staging and follow-up of muscle-invasive bladder cancer. To assess recent developments in radiology aimed at improving the sensitivity and specificity of local staging and treatment response. ACQUISITION OF EVIDENCE: We conducted an updated literature review. SYNTHESIS OF THE EVIDENCE: Computed tomography and magnetic resonance imaging (MRI) are the tests of choice for performing proper staging prior to surgery. Computed tomography urography is currently the most widely used technique, although it has limitations in local staging. Ultrasonography still has a limited role. Recent developments in MRI have improved its capacity for local staging. MRI has been suggested as the test of choice for the follow-up, with promising results in assessing treatment response. Positron emission tomography could improve the detection of adenopathies and extrapelvic metastatic disease. CONCLUSIONS: Imaging tests are essential for the diagnosis, staging and follow-up of muscle-invasive bladder cancer. Recent technical developments represent important improvements in local staging and have opened the possibility of assessing treatment response.

Understanding and mitigating hydrogen embrittlement of steels: a review of experimental, modelling and design progress from atomistic to continuum.

Hydrogen embrittlement is a complex phenomenon, involving several length- and timescales, that affects a large class of metals. It can significantly reduce the ductility and load-bearing capacity and cause cracking and catastrophic brittle failures at stresses below the yield stress of susceptible materials. Despite a large research effort in attempting to understand the mechanisms of failure and in developing potential mitigating solutions, hydrogen embrittlement mechanisms are still not completely understood. There are controversial opinions in the literature regarding the underlying mechanisms and related experimental evidence supporting each of these theories. The aim of this paper is to provide a detailed review up to the current state of the art on the effect of hydrogen on the degradation of metals, with a particular focus on steels. Here, we describe the effect of hydrogen in steels from the atomistic to the continuum scale by reporting theoretical evidence supported by quantum calculation and modern experimental characterisation methods, macroscopic effects that influence the mechanical properties of steels and established damaging mechanisms for the embrittlement of steels. Furthermore, we give an insight into current approaches and new mitigation strategies used to design new steels resistant to hydrogen embrittlement.

Preliminary evaluations of the undesirable patient dose from a BNCT treatment at the ENEA-TAPIRO reactor.

Boron neutron capture therapy (BNCT) is an experimental technique for the treatment of certain kinds of tumors. Research in BNCT is performed utilizing both thermal and epithermal neutron beams. Epithermal neutrons (0.4 eV-10 keV) penetrate more deeply into tissue and are thus used in non-superficial clinical applications such as the brain glioma. In the last few years, the fast reactor TAPIRO (ENEA-Casaccia Rome) has been employed as a neutron source for research into BNCT applications. Recently, an 'epithermal therapeutic column' has been designed and its construction has been completed. The Monte Carlo code MCNPX was employed to optimize the design of the column and to evaluate the dose profiles and the therapeutic parameters in the cranium of the anthropomorphic phantom ADAM. In the same context, some preliminary evaluations of the undesirable doses to the patient were performed with MCNPX. A hermaphrodite phantom derived from ADAM and EVA was employed to evaluate the energy deposition in some organs during a standard BNCT treatment. The total dose consists of the contributions from the primary neutron beam, the neutron interactions with boron and the neutron induced photons generated in the epithermal column structures and in the patient's tissues. The paper summarizes the computational procedure and provides a general dosimetric framework of the patient radiological protection aspects related to a BNCT treatment scenario at the TAPIRO reactor.

Dose distributions in phantoms irradiated in thermal columns of two different nuclear reactors.

In-phantom dosimetry studies have been carried out at the thermal columns of a thermal- and a fast-nuclear reactor for investigating: (a) the spatial distribution of the gamma dose and the thermal neutron fluence and (b) the accuracy at which the boron concentration should be estimated in an explanted organ of a boron neutron capture therapy patient. The phantom was a cylinder (11 cm in diameter and 12 cm in height) of tissue-equivalent gel. Dose images were acquired with gel dosemeters across the axial section of the phantom. The thermal neutron fluence rate was measured with activation foils in a few positions of this phantom. Dose and fluence rate profiles were also calculated with Monte Carlo simulations. The trend of these profiles do not show significant differences for the thermal columns considered in this work.

Tailoring the thermal conductivity of the powder bed in Electron Beam Melting (EBM) Additive Manufacturing.

Metallic powder bed additive manufacturing is capable of producing complex, functional parts by repeatedly depositing thin layers of powder particles atop of each other whilst selectively melting the corresponding part cross-section into each layer. A weakness with this approach arises when melting overhanging features, which have no prior melted material directly beneath them. This is due to the lower thermal conductivity of the powder relative to solid material, which as a result leads to an accumulation of heat and thus distortion. The Electron Beam Melting (EBM) process alleviates this to some extent as the powder must first be sintered (by the beam itself) before it is melted, which results in the added benefit of increasing the thermal conductivity. This study thus sought to investigate to what extent the thermal conductivity of local regions in a titanium Ti-6Al-4V powder bed could be varied by imparting more energy from the beam. Thermal diffusivity and density measurements were taken of the resulting sintered samples, which ranged from being loosely to very well consolidated. It was found that the calculated thermal conductivity at two temperatures, 40 and 730 °C, was more than doubled over the range of input energies explored.

Expression of genes related to activity of oxaliplatin and 5-fluorouracil in endoscopic biopsies of primary esophageal cancer in patients receiving oxaliplatin, 5-flourouracil and radiation: characterization and exploratory analysis with survival.

With a goal of identifying relations between gene expression and response (mucosal or pathological) or survival in esophageal cancer patients (stages II to IV) receiving oxaliplatin, 5-fluorouracil (5FU) and radiation, we measured in endoscopic primary tumor biopsies from 38 patients, the expression of seven genes (gammaGCS, gammaGT, MRP-2, ERCC-1, XPA, TS and DPD) prior to treatment, 1 week following oxaliplatin alone and at the end of the combined radio-chemotherapy cycle using real time QRT-PCR. A higher pretreatment level of XPA was related to shorter survival with a hazard ratio of 2.43 (90% confidence interval 1.09 to 5.43) using Cox regression modeling. However, multivariate analysis with a Cox model indicated low expression of XPA or TS and combined stages II and III had a higher probability of survival (for XPA: hazard ratio 3.0 and 90% C.I. of 1.3 to 6.9, with adjustment for stage included; for TS: hazard ratio is 1.98 with 90% C.I. of 0.94 to 4.20. The expression of TS, gammaGCS, ERCC-1 and MRP-2 declined from D 1 to the end of the cycle (p<0.05, sign test). A validation and further understanding of the findings need to be carried out in a larger study with a more homogeneous population of patients.

A fatal case of systemic fat embolism resulting from gluteal injections of vitamin e for cosmetic enhancement.

Recently in Mexico the number of cosmetic surgeries has increased. These procedures are often carried out by unqualified people using obsolete and contraindicated products such as injectable oil, which cause uncorrectable disfigurement or more serious complications, even death, after reaching the systemic circulation. We report the case of a fat embolism syndrome (FES) caused by injections of vitamin E (tocopherol) in order to increase the volume of the buttocks. This case of a FES caused by injections of vitamin E was confirmed by gas chromatography coupled to mass spectrometry.

Canine myiasis by Lucilia eximia in North America.

Myiasis is the invasion of Diptera larvae in live vertebrates tissues. It has been registered in tropical areas, but not in urban animals of North America. Moreover, there is no information about lesions description, laboratory tests, and treatment applied to canines. We report a myiasis located in the dorsum of an overweight male canine. Insect larvae were identified as Lucilia eximia, an opportunistic species that scarcely infest live vertebrates, and with no records in North America animals before. Abnormalities of complete blood count like leukocytosis by neutrophilia and serum biochemical changes like elevations in alanine aminotransferase, aspartate aminotransferase, creatine kinase, globulins and amylase were detected. Because Lucilia is characterized by lower host-specificity and infestation outbreaks occur worldwide, it is imperative to continue increasing the understanding of Lucilia myiasis, its clinical presentation, risk factors, therapy and correct entomological classification. Otherwise, more cases could occur in animals and humans.

Monte Carlo optimisation of a BNCT facility for treating brain gliomas at the TAPIRO reactor.

An epithermal boron neutron capture therapy facility for treating brain gliomas is currently under construction at the 5 kW fast-flux reactor TAPIRO located at ENEA, Casaccia, near Rome. In this work, the sensitivity of the results to the boron concentrations in healthy tissue and tumour is investigated and the change in beam quality on modifying the moderator thickness (within design limits) is studied. The Monte Carlo codes MCNP and MCNPX were used together with the DSA in-house variance reduction patch. Both usual free beam parameters and the in-phantom treatment planning figures-of-merit have been calculated in a realistic anthropomorphic phantom ('ADAM').