Development and delivery of a physical therapy intervention for adults with lupus arthritis via telemedicine and it's efficacy on quality of life, fatigue, mental health, desease activity and sedentary behaviours.

openBackground: il Lupus Eritematoso Sistemico (LES) è una patologia autoimmune sistemica caratterizzata da manifestazioni eterogenee; i tratti in comune dei pazienti lupici sono però artromialgie, aumento della sedentarietà e della fatigue, riduzione della qualità di vita e del benessere psicologico. Durante la pandemia, a causa del distanziamento sociale si sono avute difficoltà all’accesso di ambienti chiusi come palestre, con conseguente aumento della sedentarietà. Tuttavia, tramite l’utilizzo del web si sono create modalità per esercizi home-based. Scopo: creazione di un programma fisioterapico da svolgere a casa in pazienti adulti con LES, fruibile attraverso lezioni di gruppo online, e verifica dell’efficacia del programma su fatigue, attività di malattia, sedentarietà, qualità di vita e benessere mentale. Materiali e metodi: è stata svolta una ricerca bibliografica degli ultimi 10 anni per identificare gli interventi più efficaci da effettuare in un programma trimestrale. Sono poi stati reclutati i partecipanti e divisi su base volontaria in due gruppi: Gruppo A, lezioni sincrone due volte a settimana via Zoom; Gruppo B, lezioni asincrone, con video su Youtube. I pazienti avevano età tra i 40 e i 65 anni, storia di atropatia lupica ma non artrite attiva al reclutamento. Gli outcome registrati nell’intervento sono stati: scala VAS adattata per l’attività di malattia, FACIT-F, IPAQ, HAQ, HADS al t0 (inizio del trattamento), t6 (6 settimane), t12 (12 settimane, termine del trattamento), t24 (12 settimane dalla fine nel trattamento) e t36 (24 settimane dalla fine del trattamento). Inoltre sono stati esaminati aderenza al trattamento ed effetti avversi. Per l’analisi statistica ci si è avvalsi del software SPSS. Risultati: dalla ricerca bibliografica sono stati identificati 16 studi per stilare il programma di intervento. Sono così state pianificate lezioni di 50-55 min. Diciassette pazienti hanno concluso l’intervento per il Gruppo B, 7 per il Gruppo A. Le condizioni di partenza tra i due gruppi erano simili e durante lo studio non si sono evidenziate differenze tra Zoom e Youtube. La VAS_ptgh, l’HADS e la FACIT hanno mostrano un miglioramento, dimostrando il beneficio portato dall’intervento, con permanenza dei risultati anche al t24 per l’HADS. L’HAQ score peggiora nell’intervento (t12), ma la severità resta invariata. L’IPAQ e le altre VAS adattate tendono a migliorare tra t0 e t12 per regredire nei follow-up. Il Gruppo A ha registrato aderenza alle lezioni maggiore. Gli effetti avversi sono stati riportati in 4 pazienti su 24. Non si sono osservate riacutizzazioni di malattia. Conclusioni: le sedute di fisioterapia eseguite in modalità telematica hanno dimostrato una buona fattibilità e un’ottima sicurezza. L’intervento ha avuto complessivamente buoni risultati. Questo studio è stato il primo a dimostrare che interventi di questo tipo sono fattibili e sicuri in pazienti affetti da LES

Determination of perfluoroalkyl acids in different tissues of graminaceous plants

A method for the determination of 12 perfluoroalkylacids (PFAA) in vegetal samples was proposed. The analytical procedure was developed to optimize the detention of short-chain PFAA (C<8) due to their higher potential to be translocated and bioaccumulated in plants than long-chain congeners. The method, based on ultrasonic extraction, clean-up and HPLC-MS/MS analysis, determined PFAA in the different plant tissues allowing to study the PFAA distribution and partition in vegetal compartments. The performance of this analytical procedure was validated by analysing samples (root, stem and leaf) of reed grass. The validated method was then applied to graminaceous plants from an agricultural area impacted by a fluorochemical plant discharge (Northern Italy). The PFAA congeners were detected in the most of samples with PFAA concentrations in whole plant ranging from < LOD to 10.4 ng g-1 ww and with a greater rate of PFAA accumulation in corn cob than corn kernel. The proposed approach is particularly relevant in edible plant investigation because PFAA levels recorded in the comestible fractions provide information for human risk assessment due to vegetable consumption. Furthermore data on the remaining not edible parts, intended for breeding forage, are also useful for the assessment of the PFAA transfer in the breeding trophic chain

Complementary encoding of spatial information in hippocampal astrocytes

Calcium dynamics into astrocytes influence the activity of nearby neuronal structures. However, because previous reports show that astrocytic calcium signals largely mirror neighboring neuronal activity, current information coding models neglect astrocytes. Using simultaneous two-photon calcium imaging of astrocytes and neurons in the hippocampus of mice navigating a virtual environment, we demonstrate that astrocytic calcium signals encode (i.e., statistically reflect) spatial information that could not be explained by visual cue information. Calcium events carrying spatial information occurred in topographically organized astrocytic subregions. Importantly, astrocytes encoded spatial information that was complementary and synergistic to that carried by neurons, improving spatial position decoding when astrocytic signals were considered alongside neuronal ones. These results suggest that the complementary place dependence of localized astrocytic calcium signals may regulate clusters of nearby synapses, enabling dynamic, context-dependent variations in population coding within brain circuits

Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies

BackgroundCancer patients are more vulnerable to COVID-19 and are thus given high priority in vaccination campaigns. In solid cancer patients treated with checkpoint inhibitors, we evaluated the amount of anti-RBD and neutralizing antibodies and antibody avidity after two or three doses of the vaccine.MethodsThirty-eight solid cancer patients, 15 untreated hematological patients and 21 healthy subjects were enrolled in the study. Blood was collected before the first dose (T0), 21 days after the second (T2) and in 18 solid cancer patients also 15 days after the third dose of vaccine (T3). IgG, IgM and IgA anti-RBD antibodies were detected by ELISA. Neutralizing antibodies were measured testing the inhibition of RBD binding to ACE2. Antibody avidity was evaluated in 18 patients by a urea avidity ELISA.ResultsIgG anti-RBD antibodies were produced in 65.8% of the cancer patients at T2, and in 60% of hematological patients at levels lower than healthy controls. IgM and IgA anti-RBD antibodies were also produced in 5.3% and 21% cancer patients, respectively. At T3, a significant increase in anti-RBD IgG levels was observed. Neutralizing antibodies were produced in 68.4% of cancer patients as compared with 93% of untreated hematological patients and 100% of controls, at titers lower than in healthy subjects. At T3, neutralizing antibodies and avidity of IgG anti-RBD increased; 6/18 patients negative at T2 developed neutralizing antibodies at T3.ConclusionThe data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies

Cue-target contingencies modulate voluntary orienting of spatial attention: dissociable effects for speed and accuracy

Voluntary orienting of spatial attention is typically investigated by visually presented directional cues, which are called predictive when they indicate where the target is more likely to appear. In this study, we investigated the nature of the potential link between cue predictivity (the proportion of valid trials) and the strength of the resulting covert orienting of attention. Participants judged the orientation of a unilateral Gabor grating preceded by a centrally presented, non-directional, color cue, arbitrarily prompting a leftwards or rightwards shift of attention. Unknown to them, cue predictivity was manipulated across blocks, whereby the cue was only predictive for either the first or the second half of the experiment. Our results show that the cueing effects were strongly influenced by the change in predictivity. This influence differently emerged in response speed and accuracy. The speed difference between valid and invalid trials was significantly larger when cues were predictive, and the amplitude of this effect was modulated at the single trial level by the recent trial history. Complementary to these findings, accuracy revealed a robust effect of block history and also a different time-course compared with speed, as if it mainly mirrored voluntary processes. These findings, obtained with a new manipulation and using arbitrary non-directional cueing, demonstrate that cue-target contingencies strongly modulate the way attention is deployed in space

Early primary tumor response in metastatic RCC patients treated with immune checkpoint inhibitors-based combinations

Background: 25-30% of renal cell carcinoma presents with metastases (mRCC) at diagnosis. The activity of immune checkpoint inhibitor (ICI)-combinations on the primary tumor (PT) is debated. Patients andMethods: mRCC patients (pts) with PT who received first-line nivolumab plus ipilimumab (N/I) or pembrolizumab plus axitinib (P/A) were included. We investigated the early primary tumor response (EPTR) at the first radiological assessment. Results: 73 pts were included. The median early reduction of the PT longest diameter was 12.4% with P/A versus 6.2% with N/I (p = 0.42). We evaluated if the type of EPTR could affect the metastases response. Among pts with PT stable disease (SD), 8.3% had metastatic disease progression (PD) with P/A and 34.8% with N/I. Early PT partial response (PR) was associated with no metastatic PD with both N/I and P/A. The 2 pts with PT PD had also metastatic PD to P/A. Of the 3 PT with PD to N/I, 1 had metastatic SD and 2 PD. In the overall population, of the 94.1% without PT progression (PR+SD), 47.5% had metastatic PR, 35.6% SD, 16.9% PD. Conclusions: ICIs-combinations achieved an early PT PR in about 10-20%, without any complete responses. Only a small percentage of PT had an early PD, mainly associated with metastatic PD. However, among those PT without an early progression, metastatic PR can be achieved in approximately 50% of cases

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside ICU

Aim We aim at characterizing a large population of Coronavirus 19 (COVID-19) patients with moderate-to-severe hypoxemic acute respiratory failure (ARF) receiving CPAP outside intensive care unit (ICU), and ascertaining whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included COVID-19 adult patients, treated with CPAP outside ICU for hypoxemic ARF from March 1 st to April 15th, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay (LOS), and 60- day in-hospital mortality. Results The study includes 537 patients with a median age of 69 (IQR, 60-76) years. Males were 391 (73%). According to predefined CPAP therapeutic goal, 397 (74%) patients were included in full treatment subgroup, and 140 (26%) in the do-not intubate (DNI) subgroup. Median CPAP duration was 4 (IQR, 1-8) days, while hospital LOS 16 (IQR, 9-27) days. Sixty-day in-hospital mortality was overall 34% (95%CI, 0.304-0.384), and 21% (95%CI, 0.169-0.249) and 73% (95%CI, 0.648-0.787) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95%CI, 0.345-0.488) for 180 (45%) CPAP failures requiring intubation, while 2% (95%CI, 0.008- 0.035) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality [HR, 1.093 (95%CI, 1.010-1.184)]. Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures

RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy.

Chronic progressive external ophthalmoplegia (CPEO) is common in mitochondrial disorders and is frequently associated with multiple mtDNA deletions. The onset is typically in adulthood, and affected subjects can also present with general muscle weakness. The underlying genetic defects comprise autosomal-dominant or recessive mutations in several nuclear genes, most of which play a role in mtDNA replication. Next-generation sequencing led to the identification of compound-heterozygous RNASEH1 mutations in two singleton subjects and a homozygous mutation in four siblings. RNASEH1, encoding ribonuclease H1 (RNase H1), is an endonuclease that is present in both the nucleus and mitochondria and digests the RNA component of RNA-DNA hybrids. Unlike mitochondria, the nucleus harbors a second ribonuclease (RNase H2). All affected individuals first presented with CPEO and exercise intolerance in their twenties, and these were followed by muscle weakness, dysphagia, and spino-cerebellar signs with impaired gait coordination, dysmetria, and dysarthria. Ragged-red and cytochrome c oxidase (COX)-negative fibers, together with impaired activity of various mitochondrial respiratory chain complexes, were observed in muscle biopsies of affected subjects. Western blot analysis showed the virtual absence of RNase H1 in total lysate from mutant fibroblasts. By an in vitro assay, we demonstrated that altered RNase H1 has a reduced capability to remove the RNA from RNA-DNA hybrids, confirming their pathogenic role. Given that an increasing amount of evidence indicates the presence of RNA primers during mtDNA replication, this result might also explain the accumulation of mtDNA deletions and underscores the importance of RNase H1 for mtDNA maintenance.This work was supported by the Medical Research Council, the Pierfranco and Luisa Mariani Foundation, Telethon grant GGP11011, the Italian Ministry of Health (grant GR2010-2316392), and European Research Council advanced grant FP7-322424