Cluster of legionnaires’ disease in an Italian prison

Background: Legionella pneumophila (Lp) is the most common etiologic agent causing Legionnaires’ Disease (LD). Water systems offer the best growth conditions for Lp and support its spread by producing aerosols. From 2015 to 2017, the Regional Reference Laboratory of Clinical and Environmental Surveillance of Legionellosis of Palermo monitored the presence of Lp in nine prisons in Western Sicily. During this investigation, we compared Lp isolates from environmental samples in a prison located in Palermo with isolates from two prisoners in the same prison. Methods: We collected 93 water samples from nine Sicilian prisons and the bronchoalveolar lavages (BALs) of two prisoners considered cases of LD. These samples were processed following the procedures described in the Italian Guidelines for the Prevention and Control of Legionellosis of 2015. Then, genotyping was performed on 19 Lp colonies (17 from water samples and 2 from clinical samples) using the Sequence-Based Typing (SBT) method, according to European Study Group for Legionella Infections (ESGLI) protocols. Results: Lp serogroup (sg) 6 was the most prevalent serogroup isolated from the prisons analyzed (40%), followed by Lp sg 1 (16%). Most of all, in four penitentiary institutions, we detected a high concentration of Lp >104 Colony Forming Unit/Liter (CFU/L). The environmental molecular investigation found the following Sequence Types (STs) in Lp sg 6: ST 93, ST 292, ST 461, ST 728, ST 1317 and ST 1362, while most of the isolates in sg 1 belonged to ST 1. We also found a new ST that has since been assigned the number 2451 in the ESGLI-SBT database. From the several Lp sg 1 colonies isolated from the two BALs, we identified ST 2451. Conclusions: In this article, we described the results obtained from environmental and epidemiological investigations of Lp isolated from prisons in Western Sicily. Furthermore, we reported the first cluster of Legionnaires’ in an Italian prison and the molecular typing of Lp sg 1 from one prison’s water system and two BALs, identified the source of the contamination, and discovered a new ST

Transitions of protein traffic from cardiac ER to junctional SR

The junctional sarcoplasmic reticulum (jSR) is an important and unique ER subdomain in the adult myocyte that concentrates resident proteins to regulate Ca(2+) release. To investigate cellular mechanisms for sorting and trafficking proteins to jSR, we overexpressed canine forms of junctin (JCT) or triadin (TRD) in adult rat cardiomyocytes. Protein accumulation over time was visualized by confocal fluorescence microscopy using species-specific antibodies. Newly synthesized JCTdog and TRDdog appeared by 12-24h as bright fluorescent puncta close to the nuclear surface, decreasing in intensity with increasing radial distance. With increasing time (24-48h), fluorescent puncta appeared at further radial distances from the nuclear surface, eventually populating jSR similar to steady-state patterns. CSQ2-DsRed, a form of CSQ that polymerizes ectopically in rough ER, prevented anterograde traffic of newly made TRDdog and JCTdog, demonstrating common pathways of intracellular trafficking as well as in situ binding to CSQ2 in juxtanuclear rough ER. Reversal of CSQ-DsRed interactions occurred when a form of TRDdog was used in which CSQ2-binding sites are removed ((del)TRD). With increasing levels of expression, CSQ2-DsRed revealed a novel smooth ER network that surrounds nuclei and connects the nuclear axis. TRDdog was retained in smooth ER by binding to CSQ2-DsRed, but escaped to populate jSR puncta. TRDdog and (del)TRD were therefore able to elucidate areas of ER-SR transition. High levels of CSQ2-DsRed in the ER led to loss of jSR puncta labeling, suggesting a plasticity of ER-SR transition sites. We propose a model of ER and SR protein traffic along microtubules, with prominent transverse/radial ER trafficking of JCT and TRD along Z-lines to populate jSR, and an abundant longitudinal/axial smooth ER between and encircling myonuclei, from which jSR proteins traffic

A NEW CASE OF LOUSE-BORNE RELAPSING FEVER IN SICILY: CASE REPORT AND MINI REVIEW

Body lice transport B. recurrentis from man to man and humans are the only host. The presence of lice in Italy and an increasing number of cases in migrants can contribute to the onset of autochthonous cases. In this paper, we report a new case of Louse-borne Relapsing Fever (LBRF) diagnosed among migrants in Sicily exactly one year after the first case was recorded. We reviewed all cases reported in Europe from February 2016 until now. Our study identified two new cases of LBRF in migrants arrived in Europe: one who came from Somalia and one from Mali. Here we report data on a new case in Sicily. The number of migrants and refugees to transit in Sicily has increased, and this has led to the introduction of infectious diseases. Therefore, in our opinion it is essential to upgrade control of the sanitation conditions of migrants

A Multiscale In Silico Investigation of the Mechanics and Dynamics of Ex Vivo Coagulation

Theories describing the coagulation cascade have been around for decades and have greatly expanded in functional detail over the past several years. However, there still exists a void in the literature on the quantification of the microscale contribution of individual blood cell mechanics on the macroscale behavior of blood clots. This is due, in part, to the fact that the trans-scale relationships between blood components are not fully understood. In this work, we aim to bridge the gap between the known cell-scale phenomena of coagulation, specifically platelet and fibrin interactions, and the measurable mechanics and dynamics of whole blood clots. The developed multiscale model consists of two main components: (1) a phenomenological model of activated platelet adhesion and contraction and (2) a mechanistic model of fibrin viscoelasticity and strain-hardening extensibility. The components of the multiscale model include stand-alone discrete element method (DEM)-based cell-scale models for the primary components of blood. The unique mechanical and dynamical behaviors observed experimentally in single-platelet and single-fiber studies can be captured by this technique due to the inclusion of phenomenological force models, namely piecewise linear functions for the adhesion exhibited by activated platelets and Hill functions for the nonlinear elastic modulus of fibrin. The isolated platelet adhesion and fibrin extension models were developed and calibrated separately before they were combined to study the emergent behavior of platelet and fibrin assemblies. The platelet and fibrin compositions were varied between simulations to assess the morphological and mechanistic differences of in silico-formed aggregates. Applying the model within a dynamic framework was also used to obtain a macroscale metric of in silico aggregate behavior that is comparable to one from existing clinical whole-blood diagnostic devices like the thromboelastogram, or TEG. Specifically, we can quantify the platelet contribution to the strength of platelet and fibrin in silico aggregates. We observed a nonlinear relationship between platelet concentration and platelet contribution that corroborates experimental studies. The culmination of the modeling efforts from this dissertation is a tool that can be used and expanded to better understand the mechanistic detail of platelet and fibrin contributions during coagulation

Volume regulation by Amphiuma red blood cells. The membrane potential and its implications regarding the nature of the ion-flux pathways

After osmotic perturbation, the red blood cells of Amphiuma exhibited a volume-regulatory response that returned cell volume back to or toward control values. After osmotic swelling, cell-volume regulation (regulatory volume decrease; RVD) resulted from net cellular loss of K, Cl, and osmotically obliged H2O. In contrast, the volume-regulatory response to osmotic shrinkage (regulatory volume increase; RVI) was characterized by net cellular uptake of Na, Cl, and H2O. The net K and Na fluxes characteristic of RVD and RVI are increased by 1-2 orders of magnitude above those observed in studies of volume-static control cells. The cell membrane potential of volume-regulating and volume-static cells was measured by impalement with glass microelectrodes. The information gained from the electrical and ion-flux studies led to the conclusion that the ion fluxes responsible for cell-volume regulation proceed via electrically silent pathways. Furthermore, it was observed that Na fluxes during RVI were profoundly sensitive to medium [HCO3] and that during RVI the medium becomes more acid, whereas alkaline shifts in the suspension medium accompany RVD. The experimental observations are explained by a model featuring obligatorily coupled alkali metal-H and Cl-HCO3 exchangers. The anion- and cation-exchange pathways are separate and distinct yet functionally coupled via the net flux of H. As a result of the operation of such pathways, net alkali metal, Cl, and H2O fluxes proceed in the same direction, whereas H and HCO3 fluxes are cyclic. Data also are presented that suggest that the ion-flux pathways responsible for cell-volume regulation are not activated by changes in cell volume per se but by some event associated with osmotic perturbation, such as changes in intracellular pH

VIRULENCE FACTORS AND ANTIMICROBIAL RESISTANCE OF ESCHERICHIA COLI ST131 IN COMMUNITY-ONSET HEALTHCARE-ASSOCIATED INFECTIONS IN SICILY, ITALY

Escherichia coli ST131 is an emerging resistant agent recently called \u201csuperbug\u201d in England. This strain is responsible of community-acquired urinary tract infections and nowadays showing increasing resistance to antibiotics like fluoroquinolones and cephalosporins. Survey of virulent bacterial clone is relevant to control its spreading in community. We aim to assess the circulation of resistant clones Escherichia coli ST131 outside of the hospital to prompt control of outbreak in our geographical area. We selected 105 E. coli resistant isolates from community-acquired urinary infections and performed a multiplex PCR to evaluate if they belonged to the ST131 type. We investigated their set of virulence factors; in particular, kpsMII, papA, sfaS, focG, iutA, papC, hlyD and afa genes, and finally, we evaluated beta lactamases genes and quinolone resistance determinants. E. coli ST 131 clone was present in 66.6% of our isolates and showed positivity to a wide range of resistance genes, in particular blaCTX-M-15 among beta lactamases and plasmid-related quinolone resistance genes (qnrA, qnrS and aac (6\u2019)-Ib-cr). Moreover, 81% of the strains showed positivity to at least one of the virulence factor genes. Our results suggested a high presence of E. coli ST131 in community. We suggest antibiotic stewardship for outpatient clinicians and facilities to contain the spread of \u201csuperbug\u201d agents

HELICOBACTER PYLORI AND EPSTEIN\u2013BARR CO-INFECTION IN GASTRIC DISEASE

The incidence of gastrointestinal diseases and in particular gastric cancer (GC) is high worldwide. Over the last few years, numerous studies have speculated that Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) can be correlated with gastric cancerogenesis. Virulence factors of H. pylori can contribute to the variability of clinical outcomes: among the most important virulence factors is the pathogenicity island (CagPAI), vacA and oipA gene. EBV infection usually persists in B cells and induces an inflammatory reaction in cooperation with H. pylori. In Sicily, H. pylori and EBV infections are particularly prevalent, and to our knowledge no study has addressed this yet. The aim of our study was to examine the association of H. pylori and EBV infection in patients with gastric diseases in Sicily. Gastric biopsies were collected from 24 adult patients with chronic gastritis active (CGA) and from 24 adult patients without any gastric disease (NGD) who underwent upper gastrointestinal endoscopy. H. pylori infection was diagnosed by PCR for ureaseA gene while EBV-DNA was detected by Real time PCR for region Bam HI-W. Moreoever, we investigated the presence of CagPaI and the status of vacA and oipA genes. Percentage of resistance to Clarithromycin of H. pylori was evaluated also. We established that H. pylori and EBV infection was present in 42% of patients, while dual infection with H. pylori and EBV-DNA was present in 54% of the patients with CGA. In patients with NGD we found that H. pylori and EBV infection was present in 46% and in 21% of patients respectively, while co-infection was present in 33% of patients. CagPAI was present in only 20% of patients with GCA and in 9% of patients with NGD. As regards vacA alleles, s2i2m2 were predominant, present in 80% and 82% of patients with CGA and NGD respectively. The status \u201cON\u201d of oipA gene was present in the same percentage. Finally, we found that 38% of patients positive for H. pylori infection showed resistance to Clarithromycin. In our study, there was a strong association between the simultaneous presence of H. pylori and EBV infection in patients with CGA compared to patients with NGD. Furthermore, our data confirmed the high percentage of resistance among H. pylori strains circulating in Sicily, underlining the importance of establishing a therapy that is effective in eradicating them and reducing the frequency of coinfections and evolution towards gastric cancerogenesi

Experience: A Comparative Analysis of Multivariate Time-Series Generative Models: A Case Study on Human Activity Data

\ua9 2024 Copyright held by the owner/author(s). Human activity recognition (HAR) is an active research field that has seen great success in recent years due to advances in sensory data collection methods and activity recognition systems. Deep artificial intelligence (AI) models have contributed to the success of HAR systems lately, although still suffering from limitations such as data scarcity, the high costs of labelling data instances, and datasets\u27 imbalance and bias. The temporal nature of human activity data, represented as time series data, impose an additional challenge to using AI models in HAR, because most state-of-the-art models do not account for the time component of the data instances. These limitations have inspired the time-series research community to design generative models for sequential data, but very little work has been done to evaluate the quality of such models. In this work, we conduct a comparative quality analysis of three generative models for time-series data, using a case study in which we aim to generate sensory human activity data from a seed public dataset. Additionally, we adapt and clearly explain four evaluation methods of synthetic time-series data from the literature and apply them to assess the quality of the synthetic activity data we generate. We show experimentally that high-quality human activity data can be generated using deep generative models, and the synthetic data can thus be used in HAR systems to augment real activity data. We also demonstrate that the chosen evaluation methods effectively ensure that the generated data meets the essential quality benchmarks of realism, diversity, coherence, and utility. Our findings suggest that using deep generative models to produce synthetic human activity data can potentially address challenges related to data scarcity, biases, and expensive labeling. This holds promise for enhancing the efficiency and reliability of HAR systems

A Scalable Method for Partitioning Workflows with Security Requirements over Federated Clouds

The significant increase in the use of cloud computing, has led to an interest in partitioning applications over a set of public and private clouds in order to meet a range of non-functional requirements including performance (for example where private cloud resources alone are insufficient), dependability (e.g. To allow the application to continue to operate even if one cloud fails) and security (for example to ensure that sensitive data is restricted to sufficiently secure clouds and networks). This paper describes a novel deployment planning algorithm to partition complex workflow-based applications over federated clouds, while meeting security requirements. The security issues are based on our previous work which extends the Bell-La Padula model to encompass cloud computing. Selecting the cheapest option for partitioning a workflow over a set of resources has been shown to be an NP-hard problem, which can take impractically long for partitioning large workflows over multiple clouds. We therefore introduce a novel adaptive partitioning algorithm to handle these large workflow applications, which significantly reduces the time required to choose a sufficiently good partitioning option. This is based on generating an initial partitioning, and then adapting it to see if a better solution can be found by bringing together on the same node services with significant communication costs. The algorithm has been implemented and evaluated by using both randomly generated and real world scientific workflows. The experiment results show that our algorithm is thousand times quicker than the exhaustive algorithm presented in our previous work. Yet, on average it generates only 25% more costly solutions. We also compared this algorithm with two other methods commonly used to partition workflows over a set of clouds

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials oflowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute strokeremains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitricoxide donor, might improve outcome when administered very early after stroke onset.Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled,blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receivetransdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbasedambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment,whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure offunctional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis washierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in allparticipants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. Thistrial is registered with ISRCTN, number ISRCTN26986053.Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min(IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) hadtransient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTNgroup, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001),and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference inmRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1):3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for pooroutcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2:3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found nodifference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group[p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatmentgroups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patientswith presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra acute prehospital settin