Bromine, iodine and sodium along the EAIIST traverse: Bulk and surface snow latitudinal variability.

During the East Antarctic International Ice Sheet Traverse (Eaiist, december 2019), in an unexplored part of the East Antarctic Plateau, snow samples were collected to expand our knowledge of the latitudinal variability of iodine, bromine and sodium as well as their relation in connection with emission processes and photochemical activation in this unexplored area. A total of 32 surface (0-5 cm) and 32 bulk (average of 1 m depth) samples were taken and analysed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Our results show that there is no relevant latitudinal trend for bromine and sodium. For bromine they also show that it has no significant post-depositional mechanisms while its inland surface snow concentration is influenced by spring coastal bromine explosions. Iodine concentrations are several orders of magnitude lower than bromine and sodium and they show a decreasing trend in the surface samples concentration moving southward. This suggests that other processes affect its accumulation in surface snow, probably related to the radial reduction in the ozone layer moving towards central Antarctica. Even though all iodine, bromine and sodium present similar long-range transport from the dominant coastal Antarctic sources, the annual seasonal cycle of the ozone hole over Antarctica increases the amount of UV radiation (in the 280-320 nm range) reaching the surface, thereby affecting the surface snow photoactivation of iodine. A comparison between the bulk and surface samples supports the conclusion that iodine undergoes spring and summer snow recycling that increases its atmospheric lifetime, while it tends to accumulate during the winter months when photochemistry ceases.

[Impact of the COVID-19 pandemic above a universal electronic consultation program (e-consultation) between general practitioners and cardiologists]. / Impacto de la pandemia por COVID-19 sobre un programa de consulta electrónica universal (e-consulta) entre médicos de Atención Primaria y cardiólogos.

Blackground and objective: Virtual healthcare models, usually between healthcare professionals and patients, have developed strongly during the coronavirus disease 2019 (COVID-19) pandemic, but there are not data of models between clinicians. Our objective is to analyse the impact of the COVID-19 pandemic on the activity and health outcomes of the universal e-consultation program for patient referrals between primary care physicians and the Cardiology Department in our area. Methods: Patients with at least one e-consultation between 2018 and 2021 were selected. We analysed the impact of the COVID-19 pandemic on activity and waiting time for care, hospitalizations and mortality, taking as a reference the consultations carried out during 2018. Results: We analysed 25,121 patients. Through logistic regression analysis, it was observed that a shorter delay in care and resolution of the e-consultation without the need for face-to-face care were associated with a better prognosis. The COVID-19 pandemic periods (2019-2020 and 2020-2021) were not associated with worse health outcomes compared to 2018. Conclusions: The results of our study show a significant reduction in e-consult referrals during the first year of the COVID-19 pandemic with a subsequent recovery in the demand for care without the pandemic periods being associated with worse outcomes. The reduction in the time elapsed for solving the e-consult and no need for in-person visit were associated with better outcomes.

Search for Neutrino-Induced Neutral-Current Δ Radiative Decay in MicroBooNE and a First Test of the MiniBooNE Low Energy Excess under a Single-Photon Hypothesis.

We report results from a search for neutrino-induced neutral current (NC) resonant Δ(1232) baryon production followed by Δ radiative decay, with a ⟨0.8⟩ GeV neutrino beam. Data corresponding to MicroBooNE's first three years of operations (6.80×10^{20} protons on target) are used to select single-photon events with one or zero protons and without charged leptons in the final state (1γ1p and 1γ0p, respectively). The background is constrained via an in situ high-purity measurement of NC π^{0} events, made possible via dedicated 2γ1p and 2γ0p selections. A total of 16 and 153 events are observed for the 1γ1p and 1γ0p selections, respectively, compared to a constrained background prediction of 20.5±3.65(syst) and 145.1±13.8(syst) events. The data lead to a bound on an anomalous enhancement of the normalization of NC Δ radiative decay of less than 2.3 times the predicted nominal rate for this process at the 90% confidence level (C.L.). The measurement disfavors a candidate photon interpretation of the MiniBooNE low-energy excess as a factor of 3.18 times the nominal NC Δ radiative decay rate at the 94.8% C.L., in favor of the nominal prediction, and represents a greater than 50-fold improvement over the world's best limit on single-photon production in NC interactions in the sub-GeV neutrino energy range.

'Rainbow pattern': a dermoscopic sign of invasive melanoma.

BACKGROUND: The 'rainbow pattern' was initially described as a highly specific dermoscopic feature of Kaposi sarcoma. Since then, it has been reported in many benign and malignant cutaneous tumours, including a few malignant melanomas (MMs). AIM: To determine the frequency and presentation of this dermoscopic pattern in primary cutaneous MMs in comparison to other cutaneous tumours. METHODS: The presence of a rainbow pattern was evaluated in a sample of 1100 dermoscopic images of different melanocytic and nonmelanocytic cutaneous neoplasms. RESULTS: The rainbow pattern was observed in 23 of 245 (9.4%) MM and 44 of 855 (5.1%) non-MM neoplasms. MMs presenting this feature were generally thicker: 82.6% > 1 mm and 43.0% > 2 mm. Compared with non-MMs, rainbow pattern in MMs was more commonly focal (82.7% vs. 36.4% nonfocal, P = 0.001) and associated with > 2 dermoscopic structures associated with MM (100% vs. 9% with fewer, P = 0.001). CONCLUSION: The rainbow pattern is a dermoscopic sign that can occasionally be observed in invasive MMs. In MMs, this feature is usually associated with other dermoscopic criteria of MM and located in a focal and eccentric area, as opposed to a diffuse and isolated presentation in non-MM neoplasms.

Three-dimensional endoanal ultrasound to assess the validity of Goodsall's Rule and the Midline Rule in predicting the path of perianal fistula-in-ano and the location of the internal opening.

BACKGROUND: Correct identification of the internal opening is essential in the management of perianal fistulae. The aim of this study was to assess the validity of Goodsall's Law and the Midline Rule in predicting the path of perianal fistula-in-ano and the location of the internal opening using 3-dimensional endoanal ultrasound. METHODS: An observational study including patients diagnosed with fistula-in-ano, at our institution from January 2006 to December 2020 was performed. Location and distance from the anal verge of the external opening, internal opening, and the path of the fistulous tract were recorded during physical examination and endoanal ultrasound. Goodsall's and Midline rules were applied to all fistulae according to the location of the external opening. The location of the internal opening as predicted by either rule was then compared to the real location of the internal opening identified during endoanal ultrasound examination. RESULTS: Nine hundred and nine patients [657 (72.3%) males, mean age 50.78 (49.84-51.72) years] were included. 665 (73.2%) of fistulae were transsphinteric. Concordance between predicted internal opening site and the true internal opening location was 0.601 (good match) for Goodsall's rule, and 0.416 (moderate match) for the Midline rule. Goodsall's rule proved to be more predictive in the anterior plane (p < 0.001). Both rules were more likely to make a correct diagnosis in posterior fistulae located 4.5-7.5 mm from the anal verge. CONCLUSIONS: Both Midline and Goodsall's rules are highly predictive of the course of fistula tracts located in the posterior plane, and are lower for anterior located fistulae, female patients and when the external opening is located further from the anal verge.

Cold Spray: Over 30 Years of Development Toward a Hot Future.

Cold Spray (CS) is a deposition process, part of the thermal spray family. In this method, powder particles are accelerated at supersonic speed within a nozzle; impacts against a substrate material triggers a complex process, ultimately leading to consolidation and bonding. CS, in its modern form, has been around for approximately 30 years and has undergone through exciting and unprecedented developmental steps. In this article, we have summarized the key inventions and sub-inventions which pioneered the innovation aspect to the process that is known today, and the key breakthroughs related to the processing of materials CS is currently mastering. CS has not followed a liner path since its invention, but an evolution more similar to a hype cycle: high initial growth of expectations, followed by a decrease in interest and a renewed thrust pushed by a number of demonstrated industrial applications. The process interest is expected to continue (gently) to grow, alongside with further development of equipment and feedstock materials specific for CS processing. A number of current applications have been identified the areas that the process is likely to be the most disruptive in the medium-long term future have been laid down.

The acquisition of clinical experience during GP training - how can we mitigate for the impact of COVID-19?

The COVID-19 pandemic has profoundly impacted the way general practice is run and this is expected to have had a knock-on effect upon GP training. A questionnaire-based study was designed to investigate what was happening to GP trainees 16 months into the pandemic in terms of opportunities to develop clinical experience and clinical decision-making. We also asked trainers and trainees for ideas on how we might mitigate for the effects of COVID-19. In particular, there has been decreased exposure to clinical examination during the pandemic and there appear to be gaps in opportunities to learn from urgent and unscheduled care settings and to develop skills in rapid clinical decision-making. It is interesting to consider what general practice will look like when the pandemic is over and how this will this affect the GP training curriculum going forwards. Although response rates were low, we were able to determine some emerging themes for national, local and educational review going forwards to help shape and improve GP training for the future.

[Position statement of the Latin American Dysphagia Society for the management of oropharyngeal and esophageal dysphagia during the COVID-19 pandemic]. / Posicionamiento de la Sociedad Latinoamericana de Disfagia para el manejo de la disfagia orofaríngea y esofágica durante la pandemia COVID-19.

INTRODUCTION: The SARS-CoV-2 virus that causes the COVID-19 disease is transmitted through the inhalation of droplets or aerosols and inoculation via the oronasal or ocular routes, transforming the management of swallowing disorders into a challenge for healthcare teams, given their proximity to the aerodigestive tract and the high probability of aerosol generation during patient evaluation and treatment. AIM: To provide essential guidance for Latin American multidisciplinary teams, regarding the evaluation and treatment of oropharyngeal and esophageal dysphagia, at the different levels of healthcare. The position statement was formulated for the purpose of maintaining medical service continuity, in the context of a pandemic, and minimizing the propagation and infection risks of the virus. METHODS: Thirteen experts in swallowing disorders were summoned by the Latin American Dysphagia Society to formulate a series of clinical suggestions, based on available evidence and clinical experience, for the management of dysphagia, taking the characteristics of Latin American healthcare systems into account. RESULTS: The position statement of the Latin American Dysphagia Society provides a series of clinical suggestions directed at the multidisciplinary teams that manage patients with oropharyngeal and esophageal dysphagia. It presents guidelines for evaluation and treatment in different contexts, from hospitalization to home care. CONCLUSIONS: The present statement should be analyzed by each team or healthcare professional, to reduce the risk for COVID-19 infection and achieve the best therapeutic results, while at the same time, being mindful of the reality of each Latin American country.

Risk of a Second Skin Cancer in a Cohort of Patients With Nonmelanoma Skin Cancer -Basal Cell Carcinoma or Squamous Cell Carcinoma-Treated With Mohs Micrographic Surgery: A National Prospective Cohort Study. / Riesgo de aparición de segundas neoplasias cutáneas en una cohorte de pacientes diagnosticados de carcinoma queratinocítico (carcinoma basocelular y carcinoma epidermoide) tratados con cirugía de Mohs. Estudio de cohortes prospectivo nacional.

OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Direct PCR on Tissue Samples To Detect Mycobacterium tuberculosis Complex: an Alternative to the Bacteriological Culture.

Bovine tuberculosis (bTB) is an ongoing issue in several countries within the European Union. Microbiological culture is the official confirmation technique for the presence of Mycobacterium tuberculosis complex (MTBC) members in bovine tissues, but several methodological issues, such as moderate sensitivity and long incubation times, require the development of more sensitive and rapid techniques. This study evaluates the analytical and diagnostic performance, comparative to culture, of a real-time PCR targeting the MTBC-specific IS6110 transposon using a panel of bovine tissue samples sourced from the Spanish bTB eradication campaign. Robustness and repeatability were evaluated in an interlaboratory trial between European Union National Reference Laboratories. The limit of detection with 95% confidence was established at 65 fg/reaction of purified genomic equivalents. Diagnostic sensitivity (Se) and specificity (Sp) were, respectively, 96.45% and 93.66%, and the overall agreement (κ) was 0.88. Cross-reactivity was detected against two mycobacterial isolates identified as Mycobacterium marinum and "Mycobacterium avium subsp. hominissuis," and whole-genome sequencing (WGS) analysis of the latter isolate revealed an IS6110-like sequence with 83% identity. An identical IS-like element was found in other Mycobacterium avium complex species in the NCBI nucleotide and WGS databases. Despite this finding, this methodology is considered a valuable alternative to culture, and the strategy of use should be defined depending on the control or eradication programs.

Search for a Higgs Portal Scalar Decaying to Electron-Positron Pairs in the MicroBooNE Detector.

We present a search for the decays of a neutral scalar boson produced by kaons decaying at rest, in the context of the Higgs portal model, using the MicroBooNE detector. We analyze data triggered in time with the Fermilab NuMI neutrino beam spill, with an exposure of 1.93×10^{20} protons on target. We look for monoenergetic scalars that come from the direction of the NuMI hadron absorber, at a distance of 100 m from the detector, and decay to electron-positron pairs. We observe one candidate event, with a standard model background prediction of 1.9±0.8. We set an upper limit on the scalar-Higgs mixing angle of θ<(3.3-4.6)×10^{-4} at the 95% confidence level for scalar boson masses in the range (100-200) MeV/c^{2}. We exclude, at the 95% confidence level, the remaining model parameters required to explain the central value of a possible excess of K_{L}^{0}→π^{0}νν[over ¯] decays reported by the KOTO collaboration. We also provide a model-independent limit on a new boson X produced in K→πX decays and decaying to e^{+}e^{-}.

Skin and sepsis: contribution of dermatology to a rapid diagnosis.

In patients who develop sepsis, whether due to primary, secondary or metastatic lesions, the skin is frequently affected. However, there are unresolved aspects regarding the general clinical manifestations in the skin or the prognosis and/or therapeutic implications. The main challenge in the approach to sepsis is its early diagnosis and management. In this review, we address the sepsis-skin relationship and the potential impact of early dermatological intervention on the septic patient through ten basic questions. We found little evidence of the participation of the dermatologist in sepsis alert programs. There are early skin changes that may alert clinicians on a possible sepsis, such as skin mottling or variations in acral skin temperature. In addition, the skin is an accessible and highly cost-effective tissue for etiological studies of some forms of sepsis (e.g., meningococcal purpura) and its involvement defines the prognosis of certain patients (e.g., infective endocarditis).

Linezolid-resistant MRSA-CC398 carrying the cfr gene, and MRSA-CC9 isolates from pigs with signs of infection in Spain.

AIMS: To perform the molecular characterization of 23 Staphylococcus aureus isolates from pigs with signs of infections recovered in Spanish farms during 2018-2019. METHODS AND RESULTS: The antimicrobial resistance pattern and virulence profile were determined. The molecular typing was performed by different molecular techniques. The transferability of the cfr gene was assessed by conjugation and its genetic environment was determined by PCR mapping. In all, 21 isolates were methicillin-resistant S. aureus (MRSA) carrying the mecA gene (SCCmecV or non-typeable SCCmec), whereas the remaining two were methicillin-susceptible (MSSA). All but one MRSA isolates (n = 20) belonged to the CC398, being the spa t011 the most prevalent (n = 11). The remaining MRSA and the two MSSA isolates were ascribed to ST9/CC9. The S. aureus isolates exhibited resistance to (number of resistant isolates): ß-lactamics (21), erythromycin and/or clindamycin (20), aminoglycosides (7), tetracycline (22), fluoroquinolones (14), chloramphenicol (5) and linezolid (1). The S. aureus isolates did not carry any of the virulence genes studied. One MRSA belonging to the CC398 showed linezolid resistance mediated by the cfr gene. The cfr gene was co-located with fexA in the Tn558 variant previously reported in the S. aureus plasmid pSCFS7. CONCLUSIONS: Two major livestock-associated genetic lineages were detected among pigs with signs of infection in Spain. The presence of the cfr gene among LA-MRSA-CC398 is of great concern not only for veterinary medicine, but also for humans in close contact. SIGNIFICANCE AND IMPACT OF THE STUDY: This work describes the molecular characterization of S. aureus isolates recovered from pigs with signs of infection and we report, as far as we know, the first description of MRSA-CC9 from pigs in Spain. Moreover, the detection of a MRSA-CC398 isolate carrying the multiresistance cfr gene highlights the need for continuous surveillance and awareness of LA-MRSA.

[Caution with the use of dexamethasone in patients with COVID-19 in its initial phases]. / Precaución con el uso de dexametasona en pacientes con COVID-19 en sus fases iniciales.

INTRODUCTION: The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. METHOD: A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. RESULTS: All patients received a 6 mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. CONCLUSION: Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

The use of microindentation for the study of bone properties in type 1 diabetes mellitus patients.

Diabetes mellitus is associated with a higher risk of fracture. In this study, we analysed the bone quality of premenopausal women with type 1 diabetes mellitus by microindentation. No differences in bone quality were identified between patients and healthy controls, suggesting that intensive insulin therapy can preserve bone health. PURPOSE: To compare the bone quality of women with type 1 diabetes mellitus (T1DM) and healthy controls, and to determine the relationship with bone mineral density (BMD). METHODS: This was a cross-sectional study of 45 premenopausal women with T1DM and 21 healthy controls, matched according to age and BMI. Clinical parameters, BMD and bone tissue mechanical properties (assessed using the bone material strength index [BMSi]) were evaluated in each group using microindentation. In T1DM patients, glycosylated haemoglobin (HbA1c), the number of hypoglycaemic events and the status of chronic complications were also analysed. RESULTS: No differences in BMSi or BMD between T1DM patients and healthy controls were identified. In the T1DM patients, the mean HbA1c was 7.52% ± 1.00% and the mean time elapsed since diagnosis was 22.6 ± 12.2 years. Eight patients (17.7%) met the criteria for metabolic syndrome (MetS), and microvascular complications were present in 12 patients (26.7%). Neither the number of features of MetS present nor the presence of microangiopathy was found to be associated with BMSi. CONCLUSIONS: T1DM premenopausal patients showed bone tissue properties comparable to those shown by controls. Further larger-scale studies should be conducted to confirm these results.

First Measurement of Differential Charged Current Quasielasticlike ν_{µ}-Argon Scattering Cross Sections with the MicroBooNE Detector.

We report on the first measurement of flux-integrated single differential cross sections for charged-current (CC) muon neutrino (ν_{µ}) scattering on argon with a muon and a proton in the final state, ^{40}Ar (ν_{µ},µp)X. The measurement was carried out using the Booster Neutrino Beam at Fermi National Accelerator Laboratory and the MicroBooNE liquid argon time projection chamber detector with an exposure of 4.59×10^{19} protons on target. Events are selected to enhance the contribution of CC quasielastic (CCQE) interactions. The data are reported in terms of a total cross section as well as single differential cross sections in final state muon and proton kinematics. We measure the integrated per-nucleus CCQE-like cross section (i.e., for interactions leading to a muon, one proton, and no pions above detection threshold) of (4.93±0.76_{stat}±1.29_{sys})×10^{-38} cm^{2}, in good agreement with theoretical calculations. The single differential cross sections are also in overall good agreement with theoretical predictions, except at very forward muon scattering angles that correspond to low-momentum-transfer events.

Recycled or reclaimed? The effect of terminology on water reuse perceptions.

Successful water recycling initiatives depend on public acceptance. In this study, we compared risk percpetions of water labeled as recycled or reclaimed.We recruited 1264 subjects in an online panel (Qualtrics) and randomly assigned them either treatment (recycled or reclaimed) water and asked about the contents and perceived risk. Participants in the reclaimed condition were more likely to perceive the water to have harmful ingredients compared to the recycled condition. The odds of direct use acceptance for those in the recycled condition are 1.41 times (or 41%) more likely than those in the reclaimed condition. Similar results were found for indirect uses. A major finding of this study is that terminology influences the perceived contaminants and risk of reused water. Prior studies have found strong evidence that the way reused water is communicated can influence public perception. Policy impilcations favor the use of recycled water, likely due to the positive connotation recycling has in the U.S. today..

[Smell and taste disorders in Spanish patients with mild COVID-19]. / Afectación del sentido del olfato y el gusto en la enfermedad leve por coronavirus (COVID-19) en pacientes españoles.

Introduction: Coronavirus disease 2019 (COVID-19) has spread rapidly throughout the world. Smell and/or taste disorders have emerged as a very frequent symptom as the disease has spread in Europe. Spain is one of the European countries with the highest number of infections. Objective: This study aimed to investigate the clinical progression of smell and taste disorders in Spanish patients with mild COVID-19. Methods: An online survey was used to conduct a cross-sectional study of patients who presented sudden smell and/or taste disorders during the 2 months of total lockdown due to COVID-19 in Spain. Results: In our sample, 91.18% of respondents with impaired smell and/or taste and who were able to undergo PCR testing were positive for SARS-CoV-2 infection. Anosmia and ageusia presented in isolation in 6.5% of participants. The remaining 93.5% presented other mild symptoms: headache (51.6%), cough (51.6%), myalgia (45.2%), asthaenia (38.7%), nasal congestion or rhinorrhoea (35.5%), fever (41.9%), low-grade fever (29.0%), odynophagia (25.8%), or diarrhoea (6.5%). The mean duration of anosmia was 8.33 days, with patients subsequently manifesting hyposmia; complete resolution occurred after a mean of 17.79 days. In 22.6% of respondents, olfactory deficits persisted. All participants recovered their sense of taste. Conclusions: Olfactory and gustatory disorders are prevalent symptoms in mild COVID-19. Most patients do not present associated nasal congestion or rhinorrhoea and a small group of patients present these alterations in isolation.

Inflammation status in HIV-positive individuals correlates with changes in bone tissue quality after initiation of ART.

BACKGROUND: The mechanisms behind ART-induced bone changes in HIV-infected patients are poorly known. We aimed to analyse changes in inflammatory and bone markers in HIV after tenofovir disoproxil fumarate initiation, and the associations with changes in the bone strength parameters. METHODS: HIV-positive participants starting tenofovir disoproxil fumarate-based ART underwent dual-energy X-ray absorptiometry (QDR 4500 SL®, Hologic, Waltham, MA, USA) for bone mineral density (BMD), a microindentation test (OsteoProbe®, Active Life Scientific, Santa Barbara, CA, USA) for bone quality [bone material strength index (BMSi)] and phlebotomy at baseline and 48 weeks after ART. A panel of inflammatory biomarkers and bone turnover markers were measured by ELISA. HIV-negative controls underwent identical procedures once. Values are expressed as medians and IQRs, and non-parametric tests were used to perform the analysis. RESULTS: Twenty HIV-infected individuals and 20 HIV-negative control individuals were matched in terms of age and gender. HIV individuals showed higher levels of inflammatory markers. We found no differences in bone turnover markers. HIV-positive individuals presented lower BMSi values at baseline compared with controls [86 (83-90) versus 89 (88-93), respectively; P = 0.034]. We found no difference in BMD (at either of the sites evaluated). BMSi tended to increase with treatment. IL-1ß at baseline was positively correlated with changes in BMSi after ART (rho = 0.564, P = 0.014). Baseline levels of sclerostin tended to be negatively correlated with changes in BMSi (rho = -0.402, P = 0.097). We found a negative correlation between time since HIV diagnosis and changes in BMSi (rho = -0.466, P = 0.04). CONCLUSIONS: We observed a correlation between changes in bone quality and the inflammatory environment in HIV-positive individuals. Moreover, among the underlying mechanisms we highlight the Wnt pathway as having a potentially significant role in ART bone quality recovery.

Tissue talks: immunophenotype of cells infiltrating the graft explains histological findings and the benefits of belatacept at 10 years.

Previously, we found a substantial number of regulatory T cells (Tregs ) and fewer senescent and T helper type 17 (Th17) and a decrease in interstitial fibrosis (IF) in 12-month graft biopsies in belatacept versus cyclosporin (CNI)-treated patients [Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT) study]. Seven years after kidney transplantation (KT), mean estimated glomerular filtration rate (eGFR), patient and graft survival were significantly higher with belatacept versus CNI treatment. The aim of this study was to determine whether the immunophenotypes of inflammatory and regulatory cell subsets infiltrating the grafts contribute to the BENEFIT's clinical findings a decade after KT. Twenty-three adult patients with functionally stable KT treated with belatacept and 10 treated with CNI were enrolled. Biopsies were analyzed by histomorphometry and immunohistochemistry for proliferation, senescence, apoptosis, inflammatory and regulatory cell markers in a blinded manner. Significantly lower percentages of inflammatory/fibrogenic cells [interleukin (IL)-22+ /Th17/Th2/M1 macrophages] were observed in patients treated with belatacept than in patients treated with CNI. By contrast, remarkably higher percentages of regulatory cells [Tregs /Bregs / plasmacytoid dendritic regulatory cells (pDCregs )/M2] were found in belatacept-treated patients than in CNI-treated patients. Conspicuously lower percentages of apoptosis and senescence and higher proliferation markers were found in belatacept-treated patients than in CNI-treated patients. Consequently, there was significantly more inflammation in the microvascular compartments as well as increased tubular atrophy and IF in CNI-treated patients. These findings strongly suggest that regulatory mechanisms, along with the absence of deleterious effects of CNI, contribute to the long-term graft histology and function stability in patients treated with belatacept.