Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

Minimally-invasive percutaneous treatments for low back pain and leg pain: a randomized controlled study of thermal disc decompression versus mechanical percutaneous disc decompression

BACKGROUND CONTEXT: Minimally invasive techniques have recently been developed as alternative treatments to surgical interventions, especially for small or contained herniated disc.PURPOSE: Aim of our study is to assess the efficacy of the mechanical percutaneous disc decompression (PDD) in comparison with the percutaneous radiofrequency targeted disc decompression (TDD).STUDY DESIGN: We conducted a single-center noninferiority trial in which patients who had low back pain with radicular leg pain (RLP) from a contained herniated disc were randomly assigned in a 1:1 ratio to undergo either PDD or TDD.PATIENT SAMPLE: From January 2016 to January 2017 a total of 327 patients were assessed for eligibility of whom 200 underwent randomization in the trial; 100 patients underwent the PDD and 100 underwent the TDD.OUTCOME MEASURES: The primary outcome measure was the proportion of patients who reported >50% reduction in Numeric Rating Scale (NRS) leg pain score. Secondary outcome measure included the proportion of patients who reported >30% improvement in Oswestry Disability Index (ODI) score.METHODS: Outcomes of this trial were measured with the use of patient-reported data obtained from validated questionnaires to assess the low back pain with RLP before intervention and at 6 and 12 months after interventions. MRI was performed before intervention and at 6 and 12 months after interventions. In addition to NRS and ODI scores, we collected the following data: age, gender, length of hospitalizations and return to work rate.RESULTS: When using an intention to treat analysis with those lost to follow-up and requiring a second procedure counting as failures, there were no statistically significant difference between the two treatment groups in the primary and secondary outcomes at 6 months: >50% reduction in NRS leg pain (PDD vs. TDD)=67% versus 65%; >30% ODI improvement (PDD vs. TDD)=57% versus 55%. Similarly, there were no statistically significant differences between groups in outcomes at 12 months: >50% reduction in NRS leg pain (PDD vs. TDD)=51% (95% CI 41%-60%) versus 40% (95% CI: 30%-49%); >30% ODI improvement (PDD vs. TDD)=42% (95% CI 32%-51%) versus 30% (95% CI: 21%-39%). A nonintention to treat analysis which discounted those lost to follow-up showed the only statistically significant finding was the percentage of those reporting >30% ODI at the 12 month follow-up time, favoring the PDD group: (PDD vs. TDD)=58% (95% CI 46%-69%) versus 42% (95% CI: 22%-43%).CONCLUSIONS: PDD and TDD are comparable treatments for patients presenting with low back pain with RLP unresponsive to medical therapy caused by contained disc herniations. (C) 2021 Elsevier Inc. All rights reserved

Activation of peroxydisulfate and peroxymonosulfate by zero-valent iron and FeCu bimetals for 4-chlorophenol oxidation in water

This work systematically evaluates the application of disc-milled iron‐copper (FeCu) bimetals for activating peroxydisulfate (PDS) and peroxymonosulfate (PMS), providing insights into both systems behavior. 4-chlorophenol (4-CP) was chosen as the model pollutant to evaluate the performance of bimetals compared to traditional iron-based activators (Fe2+ and Fe0). The influence of different factors was addressed, including i) bimetals composition (0, 5, and 50 % Cu content), ii) disc-milling, and iii) bimetals concentration. FeCu bimetal with 5 % Cu content showed a better synergy when combined with PMS, resulting in the highest 4-CP degradation, dechlorination, and mineralization (92 %, 62 %, and 60 %, respectively, within 120 min). Different quenchers and PMSO were used to identify the main reactive species in the bimetallic systems, showing the production of Fe4+ with both oxidants and a relevant contribution of 1O2 in the case of PMS. Finally, practical considerations for implementing the FeCu systems have been carefully evaluated, including the potential secondary effects on water quality due to iron and copper release, as well as the stability and reusability of these activators. Adjusting the final pH to 8.0 effectively precipitated dissolved metals, ensuring compliance with Italian environmental quality standards (Fe ≤ 2 mg/L and Cu ≤ 0.1 mg/L). Moreover, Fe5Cu bimetals have shown outstanding stability in repeated uses. Thus, this study introduces a novel, and eco-friendly approach for synthesizing active FeCu bimetals capable of efficiently activating oxidants, offering a promising solution for environmental pollution remediation. While optimal treatment conditions are thoroughly discussed, further studies are needed for full-scale application

Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: Complexity and vaccine implications

BackgroundFew studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM).MethodsWe described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II.ResultsMedian age was 44years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm(3) (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p=0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p=0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p=0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up.ConclusionsWe believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site

Ephemeris refinement of 21 Hot Jupiter exoplanets with high timing uncertainties

Transit events of extrasolar planets offer a wealth of information for planetary characterization. However, for many known targets, the uncertainty of their predicted transit windows prohibits an accurate scheduling of follow-up observations. In this work, we refine the ephemerides of 21 Hot Jupiter exoplanets with the largest timing uncertainty. We collected 120 professional and amateur transit light curves of the targets of interest, observed with 0.3m to 2.2m telescopes, and analyzed them including the timing information of the planets discovery papers. In the case of WASP-117b, we measured a timing deviation compared to the known ephemeris of about 3.5 hours, for HAT-P-29b and HAT-P-31b the deviation amounted to about 2 hours and more. For all targets, the new ephemeris predicts transit timings with uncertainties of less than 6 minutes in the year 2018 and less than 13 minutes until 2025. Thus, our results allow for an accurate scheduling of follow-up observations in the next decade

Delayed diagnosis of coeliac disease increases cancer risk

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Railway Systems and the 'Universal Good of the State': Technologies of Government in the 19th-Century Papal State

Informed by Foucault’s concept of governmentality, the paper focuses on nineteenth-century General Commissariat for the Railroad Industry in the Papal State. Unlike in liberal States, where government intervention in the affairs of railway companies was limited, the pressing need to reinforce the Pope’s pastoral power, strengthen the bond between the believers and the Holy See and ensure equity and the efficiency of the new infrastructure meant that the Commissariat acted as a governmental centre of calculation. Accounting technologies in the form of budgets, cost accounting systems and penetrating audits enabled the government to intervene in the operations of private railway companies. The study analyses the role of accounting and auditing practices in the pursuit of non-liberal goals in an industry which is traditionally perceived as critical to the development of a liberal economy, one in which accounting was traditionally used to maintain investors’ confidence in the capitalist system

Clinical and molecular characterization of COVID-19 hospitalized patients

Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression