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Background: The efficacy of public measures for reducing the transmission of the COVID-19 infection relies on citizens’ voluntary adherence with prescribed actions. Drawing on prior literature about compliant behavior, this study aimed to identify factors associated with people engagement in health-protective behaviors by including a conjoint complement of instrumental/self-oriented, normative/community-based, and affective variables. Method: A cross-sectional study involving a non-representative sample of 4045 Italian citizens was carried out during the first stage of the pandemic (April–May 2020). Variables associated with health-protective behaviors were perceived personal and societal concerns and perceived effectiveness of the institutional response to the outbreak (instrumental dimensions), and family and friends perceived norms and sense of community responsibility (normative dimensions). Two negative emotions (anxiety and fear) were included as mediators between personal and societal concerns and outcome behaviors. Results: Results showed the importance of both self-interest and community-based factors. Indeed, self-interest concerns, family perceived norms, and sense of community responsibility were significant predictors of people’s decisions to engage in health-protective behaviors. Conclusions: The research findings show that compliance with public health prescriptions is a multimodal phenomenon and integrating self-interest and community-based factors can offer a better understanding of people’s decision to engage in health-protective behaviors. Further, this study unveils that a shared sense of community is effective in encouraging adherence to recommended behaviors so as behavioral changes can be sustained by targeting the recommendations not only on risk minimization for oneself but also on the allocation of personal responsibility toward the belonging community.

Objectives To assess the changes in speed, stroke frequency, acceleration, and shoulder range of motion (ROM) associated with different wheelchair axle positions in people with chronic C7 tetraplegia. Methods This repeated-measures study was conducted at the Chronic Spinal Cord Injury Unit, FLENI Escobar, Argentina. The speed, stroke frequency, acceleration, and shoulder ROM during wheelchair propulsion were measured in nine participants with C7 spinal cord injury (SCI) in four different axle positions (forward and up, forward and down, backward and down, backward and up). Two strokes performed at maximum speed were analyzed on a smooth level vinyl floor in a motion analysis laboratory. Data were analyzed for significant statistical differences using the Friedman test and the Wilcoxon signed rank test. Results Our study showed significant differences in the speed with axle position 1 (1.57 m/s) versus 2 (1.55 m/s) and position 2 (1.55 m/s) versus 4 (1.52 m/s). The shoulder ROM showed a significant difference in the sagittal plane in position 2 (59.34 degrees) versus 3 (61.64 degrees), whereas the stroke frequency and the acceleration parameters showed no statistically significant differences with the different rear axle positions. Conclusions Our study showed that modifying the rear axle position can improve the propulsion speed and produce changes in the shoulder ROM in the wheelchair propulsion of individuals with C7 SCI.

Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

Background: A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still on debate, due to conflicting evidence emerged from different observational studies. Objective: We performed a systematic review with meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared to general population. Data source: PubMed-MEDLINE and Scopus were independently searched until 13 October 2021. Study eligibility criteria: Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19. Primary endpoint was 30-day mortality. Participants: Patients with confirmed COVID-19. Intervention: Solid organ transplant recipients. Assessment of risk of bias: Quality of included studies was independently assessed according to ROBINS-I tool for observational studies. Methods of data synthesis: Meta-analysis was performed by pooling odds ratio (OR) retrieved from studies providing adjustment for confounders using a random-effect model with inverse variance method. Multiple subgroup and sensitivity analyses were conducted to investigate source of heterogeneity. Results: 3,501 articles were screened, and thirty-one observational studies (N=590,375; 5,759 SOT recipients vs. 584,616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in primary analysis including studies providing adjustment for confounders (N=17; 3,752 SOT recipients vs. 159,745 general population; OR 1.13, 95%CI 0.94-1.35; I2=33.9%). No evidence of publication bias was reported. Higher risk of ICU admission (OR 1.56, 95%CI 1.03-2.63) and occurrence of acute kidney injury (OR 2.50 95%CI 1.81-3.45) was found in SOT recipients. Conclusions: No increased risk in mortality was found in SOT recipients affected by COVID-19 compared to general population when adjusted for demographic and clinical features and COVID-19 severity.

PURPOSE: Patients with neurogenic bladder (NB) often perform clean intermittent catheterization (CIC) and are predisposed to bladder colonization. Antibiotics are not routinely indicated in those with asymptomatic bacteriuria (ASB). The original purpose of this study was to compare patients that received antibiotics for ASB and those that did not. However, because the non-antibiotic group was very small, the final analysis evaluated treatment patterns of ASB in children with NB. METHODS: A retrospective chart review was completed, including patients who presented with urinary tract infection (UTI) and NB managed by CIC. Patients with symptoms of UTI were excluded. Basic demographics, urinalysis, culture results, and antibiotic prescriptions were collected. RESULTS: The sample included 272 patient encounters for 109 unique patients. Of these, 50.7% were female, and the median age was 10.25 years. More than half the urine cultures (56.2%) grew gram-negative organisms, and 31.3% contained 2 or more organisms. Nearly all encounters received treatment with antibiotics. Twenty-three encounters with no culture performed or the culture resulted in no growth received antibiotic therapy. CONCLUSIONS: Antibiotic resistance and antibiotic stewardship are primary concerns in healthcare today. This organization’s current practice pattern shows high antibiotic use for ASB in patients with NB. Future studies are required to identify outcomes associated with treatment versus non-treatment in these patients.

Background: Aim of the present report was to investigate the repercussions of COVID-19 pandemic on the procedural volumes and on the main indications of pediatric digestive endoscopy in Italy. Methods: An online survey was distributed at the beginning of December 2020 to Italian digestive endoscopy centers. Data were collected comparing two selected time intervals: the first from 1st of February 2019 to 30th June 2019 and the second from 1st February 2020 to 30th June 2020. Results: Responses to the survey came from 24 pediatric endoscopy Units. Globally, a reduction of 37.2% was observed between 2019 and 2020 periods with a significant decrease in median number of procedures (111 vs 57, p < 0.001). Both the median number of procedures performed for new diagnoses and those for follow-up purposes significantly decreased in 2020 (63 vs 36, p < 0.001 and 42 vs 21, p< 0.001, respectively). We reported a drastic reduction of procedures performed for suspected Celiac Disease and Functional Gastrointestinal Disorders (55.1% and 58.0%, respectively). Diagnostic endoscopies for suspected IBD decreased of 15.5%, whereas procedures for Mucosal Healing (MH) assessment reduced of 48.3%. Conclusions: Our study provides real-world data outlining the meaningful impact of COVID-19 on pediatric endoscopy practice in Italy.

Limited evidence concerning optimal azole dosing regimens currently exists for antifungal prophylaxis in hemato-oncological pediatric patients.Hemato-oncological children receiving intravenous or oral isavuconazole or voriconazole for primary antifungal prophylaxis at IRCCS Azienda Ospedaliero-Universitaria of Bologna during November 2020 to October 2021 and undergoing CPA programs based on real-time therapeutic drug monitoring (TDM) were retrospectively analyzed. CPAs for isavuconazole and voriconazole and the number of dosage adjustments were collected. Normalized trough concentrations [(C min )/dose/kg] were calculated for both drugs at each TDM assessment, and the coefficient of variation was determined. The efficacy and safety of the drugs were evaluated.Sixteen hemato-oncological pediatric patients received azole prophylaxis (mean age and weight: 9.1 ± 4.9 years and 32.6 ± 16.0 kg; 6 isavuconazole and 10 voriconazole). Sixty and 89 CPAs were delivered as isavuconazole and voriconazole, respectively. Dosage adjustments were needed in 3.3% of cases for isavuconazole and 53.9% of cases for voriconazole ( P0.001). At first TDM, achievement of the desired target during standard dosing regimens was higher for isavuconazole (83.3%) than for voriconazole (10.0%; P = 0.008). Dispersion of normalized concentrations was higher for voriconazole (CV = 139.1% vs. CV = 79.4%). Elevation of ALT and aspartate aminotransferase levels between baseline and the third month was higher in patients receiving voriconazole (median, 28 vs. 90 U/L; P = 0.038, and 19 vs. 65.5 U/L; P = 0.002).Our findings suggest that there is limited variability in isavuconazole exposure in hemato-oncological pediatric patients receiving azole prophylaxis , resulting in a low need for CPA-guided dosage adjustments.

Cardiovascular involvement is a common complication of COVID-19 infection and is associated to increased risk of unfavorable outcome. Advanced imaging modalities (coronary CT angiography and Cardiac Magnetic Resonance) play a crucial role in the diagnosis, follow-up and risk stratification of patients affected by COVID-19 pneumonia with suspected cardiovascular involvement. In the present manuscript we firstly review current knowledge on the mechanisms by which SARS-CoV-2 can trigger endothelial and myocardial damage. Secondly, the implications of the cardiovascular damage on patient's prognosis are presented. Finally, we provide an overview of the main findings at advanced cardiac imaging characterizing COVID-19 in the acute setting, in the post-acute syndrome, and after vaccination, emphasizing the potentiality of CT and CMR, the indication and their clinical implications.

Patients with moyamoya arteriopathy are at high risk for developing ischemic stroke in the perioperative period. We sought to evaluate whether preoperative clinical and neuroimaging biomarkers are associated with postoperative stroke and transient ischemic attack in children with moyamoya following revascularization surgery. We performed a retrospective chart review of pediatric patients who underwent revascularization surgery for moyamoya in the last 15 years. Fifty-three patients who underwent 69 surgeries met the inclusion criteria. We recorded clinical predictors of stroke or transient ischemic attack within 7 days following surgery. We used Suzuki stage and Composite Cerebrovascular Stenosis Score to analyze neuroimaging. Significant risk factors for developing postoperative stroke or transient ischemic attack were younger age at surgery ( P = .004) and transient ischemic attack less than 1 month prior to surgery ( P

Tumours are nowadays the second world-leading cause of death after cardiovascular diseases. During the last decades of cancer research, lifestyle and random/genetic factors have been blamed for cancer mortality, with obesity, seden-tary habits, alcoholism, and smoking contributing as supposed major causes. However, there is an emerging consensus that environmental pollution should be considered one of the main triggers. Unfortunately, all this preliminary scien-tific evidence has not always been followed by governments and institutions, which still fail to pursue research on can-cer's environmental connections. In this unprecedented national-scale detailed study, we analyzed the links between cancer mortality, socio-economic factors, and sources of environmental pollution in Italy, both at wider regional and finer provincial scales, with an artificial intelligence approach. Overall, we found that cancer mortality does not have a random or spatial distribution and exceeds the national average mainly when environmental pollution is also higher, despite healthier lifestyle habits. Our machine learning analysis of 35 environmental sources of pollution showed that air quality ranks first for importance concerning the average cancer mortality rate, followed by sites to be reclaimed, urban areas, and motor vehicle density. Moreover, other environmental sources of pollution proved to be relevant for the mortality of some specific cancer types. Given these alarming results, we call for a rearrangement of the priority of cancer research and care that sees the reduction and prevention of environmental contamination as a priority action to put in place in the tough struggle against cancer.

Our aim in this paper is to study a mathematical model for high grade gliomas, taking into account lactates kinetics, as well as chemotherapy and antiangiogenic treatment. In particular, we prove the existence and uniqueness of biologically relevant solutions. We also perform numerical simulations based on different therapeutical situations that can be found in the literature. These simulations are consistent with what is expected in these situations.

Trimethylguanosine synthase 1 (TGS1) is a highly conserved enzyme that converts the 5′-monomethylguanosine cap of small nuclear RNAs (snRNAs) to a trimethylguanosine cap. Here, we show that loss of TGS1 in Caenorhabditis elegans, Drosophila melanogaster and Danio rerio results in neurological phenotypes similar to those caused by survival motor neuron (SMN) deficiency. Importantly, expression of human TGS1 ameliorates the SMN-dependent neurological phenotypes in both flies and worms, revealing that TGS1 can partly counteract the effects of SMN deficiency. TGS1 loss in HeLa cells leads to the accumulation of immature U2 and U4atac snRNAs with long 3′ tails that are often uridylated. snRNAs with defective 3′ terminations also accumulate in Drosophila Tgs1 mutants. Consistent with defective snRNA maturation, TGS1 and SMN mutant cells also exhibit partially overlapping transcriptome alterations that include aberrantly spliced and readthrough transcripts. Together, these results identify a neuroprotective function for TGS1 and reinforce the view that defective snRNA maturation affects neuronal viability and function.

Objective To investigate the effects of Action Observation and Motor Imagery administered the day before surgery on functional recovery in patients after total hip arthroplasty. Design Randomised controlled trial. Setting Humanitas Clinical and Research Center, Milan, Italy Participants Eighty inpatients with end-stage hip osteoarthritis undergoing total hip arthroplasty. Interventions All patients followed a standardized postoperative rehabilitation program. Experimental group (AO + MI) performed two 12-minute Action Observation and Motor Imagery sessions on the preoperative day, whereas control group underwent usual care consisting of education without any additional preoperative activity. Outcome measures A blinded physiotherapist assessed participants for functional mobility (Timed Up and Go – TUG) (primary outcome), maximum walking speed (10-Meter Walk Test – 10MWT), pain (Numeric Pain Rating Scale – NPRS) and fear of movement (Tampa Scale of Kinesiophobia – TSK) the day before and at four days after surgery. Results No between-group differences were found at baseline. Although TUG and 10MWT worsened in both groups ( p Conclusions Patients undergoing Action Observation and Motor Imagery on the day before surgery showed less functional decline than control group in the first days after total hip arthroplasty. This intervention may contribute to a safer discharge with higher functional abilities in patients hospitalized for total hip arthroplasty.

The aim of this study was to evaluate the paternal programming of sex-dependent alterations in fetoplacental growth and placental lipid metabolism regulated by peroxisome proliferator-activated receptor (PPAR) target genes in F1 diabetic males born from F0 pregestational diabetic rats. F1 control and diabetic male rats were mated with control female rats. On day 21 of gestation, F2 male and female fetoplacental growth, placental lipid levels, and protein and mRNA levels of genes involved in lipid metabolism and transport were evaluated. Fetal but not placental weight was increased in the diabetic group. Triglyceride, cholesterol and free fatty acid levels were increased in placentas of male fetuses from the diabetic group. The mRNA levels of Pparα and Pparγ coactivator 1α (Pgc-1α) were increased only in placentas of male fetuses from the diabetic group. Protein levels of PPARα and PGC-1α were decreased only in placentas of male fetuses from the diabetic group. No differences were found in Pparγ mRNA and protein levels in placentas from the diabetic group. The mRNA levels of genes involved in lipid synthesis showed no differences between groups, whereas the mRNA levels of genes involved in lipid oxidation and transport were increased only in placentas of male fetuses from the diabetic group. In conclusion, paternal diabetes programs fetal overgrowth and sex-dependent effects on the regulation of lipid metabolism in the placenta, where only placentas of male fetuses show an increase in lipid accumulation and mRNA expression of enzymes involved in lipid oxidation and transport pathways.

Autobiographical memories are thought to be retrieved using two possible ways: a generative one, which is effortful and follows a general-to-specific pathway, and a direct one, which is automatic and relatively effortless. These two retrieve processes are known to differ on the quantitative side (especially considering retrieval times), from a qualitative point of view; however, evidence is missing. Here, we aimed to disentangle this question by taking advantage of a dual-task paradigm in which the different tasks tax different executive functions. Participants were asked to perform an autobiographical memory task under three different conditions: no cognitive load, non-visual cognitive load and visual cognitive load. On the quantitative side, results replicated previous findings with generative processes being slower compared with direct ones. Conversely, on the qualitative side, results indicated that the retrieval times of both direct and generative retrieval processes varied similarly according to the dual-task condition, thus supporting the idea that the same memory process could underlie both retrievals.

Terrorist attacks with large numbers of civilian victims are not uncommon in war-torn countries, and present a unique challenge for health care facilities with limited resources. However, these events are largely underreported and little is known about how the mass casualty events (MCEs) are handled outside of a military setting.This study is a retrospective analysis of the MCE which ensued the Kabul Airport suicide attack (August 26, 2021) at the Kabul EMERGENCY NGO Hospital (Afghanistan).Within 6 hours, 93 causalities presented at our hospital. Of them, 36 severe injured were admitted. Mean age was 30.8 years (SD, 10.1 years). The most common injury mechanism was shell fragments. The most common injury site was head (63%; 23/36), followed by limbs (55.5%; 20/36) and thoracoabdominal region (30.5%; 11/36). Combined injuries occurred in 38.9% of cases. Patients receiving surgery presented more combined injuries in comparison with patients receiving only medical treatment (47.1% vs. 31.6%). Thoracoabdomen (25.0% vs. 15.4%) and/or extremity injury (42.9% vs. 28.6%) were more prevalent in the surgical group. Thirty major surgical procedures were carried out on 17 patients in the 9 hours following the first arrival. The rate of intensive care unit/high dependency unit admission was 36.1% and the 30-day in-hospital mortality was 16.6% (6/36). All deaths were recorded in the first 24 hours, and none of them received surgery.A large number of wounded patients must be anticipated after suicide bombing attacks. The authors report the challenges faced and key aspects of their management of MCEs.Prognostic/Epidemiological; Level IV.

Background: Despite the low spatial resolution of 2D-multisegment late gadolinium enhancement (2D-MSLGE) sequences, it may be useful in uncooperative patients instead of standard 2D single segmented inversion recovery gradient echo late gadolinium enhancement sequences (2D-SSLGE). The aim of the study is to assess the feasibility and comparison of 2D-MSLGE reconstructed with artificial intelligence reconstruction deep learning noise reduction (NR) algorithm compared to standard 2D-SSLGE in consecutive patients with ischemic cardiomyopathy (ICM). Methods: Fifty-seven patients with known ICM referred for a clinically indicated CMR were enrolled in this study. 2D-MSLGE were reconstructed using a growing level of NR (0%,25%,50%,75%and 100%). Subjective image quality, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were evaluated in each dataset and compared to standard 2D-SSLGE. Moreover, diagnostic accuracy, LGE mass and scan time were compared between 2D-MSLGE with NR and 2D-SSLGE. Results: The application of NR reconstruction ≥50% to 2D-MSLGE provided better subjective image quality, CNR and SNR compared to 2D-SSLGE (p < 0.01). The best compromise in terms of subjective and objective image quality was observed for values of 2D-MSLGE 75%, while no differences were found in terms of LGE quantification between 2D-MSLGE versus 2D-SSLGE, regardless the NR applied. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 2D-MSLGE NR 75% were 87.77%,96.27%,96.13%,88.16% and 94.22%, respectively. Time of acquisition of 2D-MSLGE was significantly shorter compared to 2D-SSLGE (p < 0.01). Conclusion: When compared to standard 2D-SSLGE, the application of NR reconstruction to 2D-MSLGE provides superior image quality with similar diagnostic accuracy.

Purpose Non-invasive respiratory support could reduce the incidence of intubation in patients with Acute Hypoxemic Respiratory Failure (AHRF). The optimal interface or modality of non-invasive respiratory support is debated. We sought to evaluate the differences between patients who succeeded or failed non-invasive respiratory support, with a specific focus on the type of non-invasive respiratory support (i.e. helmet CPAP versus face mask NIV). Materials and methods In a single-center observational retrospective study, we investigated baseline, clinical characteristics and AHRF management by non-invasive respiratory support between January 2015 to December 2016. Data on gas exchange and respiratory mechanics, non-invasive respiratory support duration, ICU length of stay and mortality were collected. Results 110 patients with AHRF were included of which 41 patients (37%) were intubated. The use of helmet CPAP (p = 0.016) and a lower fluid balance (p = 0.038) were independently associated with a decreased rate of intubation after adjustment for confounders. Face mask NIV patients trended to a higher respiratory frequency at 1 h after treatment [28 (22–36) versus 24 (18–29) hours, p = 0.067], and showed a longer ICU stay (p = 0.009) compared to patients treated with helmet CPAP. Conclusions Helmet CPAP and a lower fluid balance were independent predictors of a lower intubation rate in AHRF patients in ICU. Prospective studies aimed at identifying the optimal interface and modality of non-invasive respiratory support in AHRF patients are needed.

Cognitive maps are assumed to be fundamentally spatial and grounded only in perceptual processes, as supported by the discovery of functionally dedicated cell types in the human brain, which tile the environment in a maplike fashion. Challenging this view, we demonstrate that spatial representations—such as large-scale geographical maps—can be as well retrieved with high confidence from natural language through cognitively plausible artificial-intelligence models on the basis of nonspatial associative-learning mechanisms. More critically, we show that linguistic information accounts for the specific distortions observed in tasks when college-age adults have to judge the geographical positions of cities, even when these positions are estimated on real maps. These findings indicate that language experience can encode and reproduce cognitive maps without the need for a dedicated spatial-representation system, thus suggesting that the formation of these maps is the result of a strict interplay between spatial- and nonspatial-learning principles.

The management of breast cancer brain metastases (BCBM) has historically involved local therapies. However, as novel systemic treatments have become more effective in controlling visceral disease, BCBM have also been better controlled. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in brain metastases in patients with lung cancer and melanoma and represent a promising option for patients with triple-negative BCBM, a group with limited systemic therapy options. In this review we summarize current data about the role of ICIs in the treatment BCBM. We identified 15 clinical trials that evaluated ICIs ± chemotherapy in patients with breast cancer. The studies were mostly focused on triple-negative breast cancer (TNBC). Of these trials, 4 excluded patients with BCBM, while 11 allowed patients with stable, treated or asymptomatic BCBM. In total, 2692 patients were enrolled in the identified clinical trials, but only 91 trial patients (3.3%) had BCBM. Furthermore, only 2 of these clinical trials reported BCBM-specific outcomes and none of the clinical trials reported BCBM-specific adverse events. Up to 45% of patients with TNBC will develop BCBM; however, only 3.3% of the patients included in the clinical trials that led to the U.S. Food and Drug Administration approvals for ICIs in advanced breast cancer had brain metastases. This review reinforces that efficacy data are greatly needed for patients with BCBM—this is an area of unmet need in oncology. More inclusive clinical trials and real-world data that evaluate the safety and efficacy of ICIs in patients with BCBM are greatly needed.

BACKGROUND: Optoelectronic systems and force platforms represent the gold standard for postural sway assessment, but pose disadvantages in terms of equipment, cost and preparation time. OBJECTIVE: Wearable inertial measurement units (IMUs) have been proposed to overcome these issues, but have never been compared to an optoelectronic system. The study aim was therefore to investigate agreement between inertial measurement unit and optoelectronic system in postural sway assessment. METHODS: Thirty healthy volunteers performed four balance tasks. IMU was placed on the sacrum (S2) with a retroreflective marker over the sensor and subjects’ performance was simultaneously recorded by both systems. Total (TOT), anterior-posterior (AP) and medial-lateral (ML) length of trace, range, speed, root mean squared (RMS), and confidence ellipse were computed. RESULTS: ICCs revealed excellent correlations for Length-TOT, Length-AP and Speed-AP, good correlation for Length-ML, Speed-ML, Confidence Ellipse, Range-AP and RMS-AP, and moderate correlation for range-ML and RMS-ML. Bland-Altman plot showed greater estimation for Length-TOT, Length-AP, Speed-AP, confidence ellipse and RMS-AP using optoelectronic system, and for Length-ML, Range-AP, Range-ML, Speed-ML, RMS-ML using IMU. Both systems revealed the same differences among tasks. CONCLUSION: The excellent to good agreement of IMU for length of trace and speed parameters and its user-friendly application suggest its potential implementations in clinical practice.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are essential players in the regulation of gene expression. The majority of the twenty different hnRNP proteins act through the modulation of pre-mRNA splicing. Most have been shown to regulate the expression of critical genes for the progression of tumorigenic processes and were also observed to be overexpressed in several types of cancer. Moreover, these proteins were described as essential components for the maturation of some microRNAs (miRNAs). In the human genome, over 70% of miRNAs are transcribed from introns; therefore, we hypothesized that regulatory proteins involved with splicing could be important for their maturation. Increased expression of the miR-17-92 cluster has already been shown to be related to the development of many cancers, such as thyroid, lung, and lymphoma. In this article, we show that overexpression of hnRNP A1 and hnRNP C in BCPAP thyroid cancer cells directly affects the expression of miR-17-92 miRNAs. Both proteins associate with the 5'-end of this cluster, strongly precipitate miRNAs miR-17 and miR-18a and upregulate the expression of miR-92a. Upon overexpression of these hnRNPs, BCPAP cells also show increased proliferation, migration, and invasion rates, suggesting upregulation of these proteins and miRNAs is related to an enhanced tumorigenic phenotype.

Objectives: La Peyronie's disease tends to be underdiagnosed and undertreated. In Italy it affects about 7% of the population aged between 50 and 70 years old. The aim of this study is to evaluate the quality of life of patients undergoing iontophoretic therapy with verapamil and treatment outcomes at a two-year interval. Materials and methods: This study evaluated 128 patients subjected to treatment cycles over a period of two years. Questionnaires were administered to the patients at the beginning and end of each cycle of iontophoretic therapy in order to monitor the degree of presumed anxiety, depression, pain and the associated quality of life. Result: This prospective descriptive observational study included 128 patients aged between 42 and 74 years presenting pain during erection and/or coital intercourse, which ceased in 108 cases, diminished in 12 and remained present in 4. Concerning the penile deviation, which was present in all patients (128 cases), it disappeared in 6 cases, regressed in 90 cases, while it remained unchanged in 32 cases. As for the plaque consistency on palpation, in 42 patients the plaque was no longer present, in 50 cases the consistency diminished, while in 36 patients it remained unchanged. None of the cases evidenced an aggravation of the clinical condition. 57% of the evaluated patients had high levels of anxiety in the first cycle of iontophoretic sessions and low levels of depression. Anxiety decreased in 32% of cases. Depression was not related to pain but to sexual dysfunction. About 80 % of the patients assessed had an increase in quality of life at the end of the two-year follow-up. Conclusions: In conclusion, it can be claimed that iontophoresis combined with verapamil therapy can improve patients' quality of life and offer them psychophysical well-being and an acceptable sexual relationship, thus decreasing anxiety and depression levels.

To assess clinical and cardiac magnetic resonance (CMR) imaging features of patients with peri-myocarditis following Coronavirus Disease 2019 (COVID-19) vaccination.We retrospectively collected a case series of 27 patients who underwent CMR in the clinical suspect of heart inflammation following COVID-19 vaccination, from 16 large tertiary centers. Our patient's cohort was relatively young (36.6 ± 16.8 years), predominately included males (n = 25/27) with few comorbidities and covered a catchment area of approximately 8 million vaccinated patients.CMR revealed typical mid-subepicardial non-ischemic late gadolinium enhancement (LGE) in 23 cases and matched positively with CMR T2 criteria of myocarditis. In 7 cases, typical hallmarks of acute pericarditis were present. Short-term follow-up (median = 20 days) from presentation was uneventful for 25/27 patients and unavailable in two cases.While establishing a causal relationship between peri-myocardial inflammation and vaccine administration can be challenging, our clinical experience suggests that CMR should be performed for diagnosis confirmation and to drive clinical decision-making and follow-up.• Acute onset of dyspnea, palpitations, or acute and persisting chest pain after COVID-19 vaccination should raise the suspicion of possible myocarditis or pericarditis, and patients should seek immediate medical attention and treatment to help recovery and avoid complications. • In case of elevated troponin levels and/or relevant ECG changes, cardiac magnetic resonance should be considered as the best non-invasive diagnostic option to confirm the diagnosis of myocarditis or pericarditis and to drive clinical decision-making and follow-up.

Nicolina Conti,1 Milo Gatti,2,3 Emanuel Raschi,2 Igor Diemberger,1,4 Luciano Potena4 1Cardiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum - University of Bologna, Bologna, Italy; 2Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy; 3SSD Clinical Pharmacology, IRCSS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 4Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyCorrespondence: Emanuel RaschiPharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, via Irnerio 48, Bologna, 40126, ItalyTel +39-051-2091802Email emanuel.raschi@unibo.itAbstract: Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. It was first approved in Sweden in 2000 for the short-term treatment of acutely decompensated severe chronic heart failure when conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate. After more than 20 years, clinical applications have considerably expanded across critical care and emergency medicine, and levosimendan is now under investigation in different cardiac settings (eg, septic shock, pulmonary hypertension) and for non-cardiac applications (eg, amyotrophic lateral sclerosis). This narrative review outlines key milestones in levosimendan history, by addressing regulatory issues, pharmacological peculiarities and clinical aspects (efficacy and safety) of a drug that did not receive great attention in the heart failure guidelines. A brief outlook to the ongoing clinical trials is also offered.Keywords: levosimendan, heart failure, cardiogenic shock, cardiac surgery, amyotrophic lateral sclerosis

Introduction: The present study aimed at evaluating Italian epidemiological trends of pediatric inflammatory bowel diseases (IBD) over the period 2009–2018. Materials and methods: Data from 1969 patients enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition Registry, by 49 pediatric IBD centers throughout the country, were analyzed, comparing three different time intervals (2009–2012, 2013–2015, 2016–2018). Results: The number of new IBD diagnoses ranged from 175 to 219 per year, evenly distributed over the examined period of time. From 2009 to 2018, the minimal incidence ranged from 1.59 to 2.04 /105 inhabitants aged < 18 years, with an overall slight predominance of ulcerative colitis (UC) over Crohn's disease (CD) (ratio: 1.1). Mean diagnostic delay was 6.8 months for CD and 4.1 months for UC, with a significant reduction for CD when comparing the three-time intervals (p =0.008). The most frequent disease locations according to the Paris classification were ileocolonic for CD (41.3%) and pancolitis for UC (54.6%). Conclusions: The minimal incidence rate in Italy seems to have stabilized over the last two decades, even if it has increased when compared to previous reports. UC is still slightly more prevalent than CD in our country. Diagnostic delay significantly decreased for CD, reflecting an improved diagnostic capacity.

The exact semantic processes subserving the formation of false memories are still poorly understood. Here, we directly probed the semantic origins of false memories in a typical Deese-Roediger-McDermott (DRM) task, by predicting participants' performance in this task through data-driven distributional semantic models. Participants were required to study lists of words and then to perform a recognition task. Our findings indicate that the participants' performance is better accounted for by a local rather than a global strategy on the task at hand: the single lists composing the task activate specific semantic clusters that are responsible for the occurrence of false memories. In particular, memory performance followed a continuous semantic gradient, with higher false recognitions occurring for higher sematic similarity between the lures (i.e., the false memory items) and the words in the relative lists. Crucially, our findings also show that semantic memory is differently involved in veridical and false memories, with this pattern being consistent across two reanalyses of data from previous studies and being replicated in an independent experiment. We thus outline an empirically-driven theoretical framework to account for the semantic processes supporting veridical and false memories formation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Bolus and continuous nutrition are commonly used enteral nutrition (EN) administration methodologies. Currently, there is insufficient evidence to establish which is the most effective method for reducing gastrointestinal complications in adult patients. The aim of this review is to evaluate the impact of bolus/intermittent EN compared with continuous EN for the following outcomes: diarrhea, constipation, emesis/vomiting, gastric residual volume, aspiration, and glycemic control in adult patients receiving intragastric prepyloric EN in the hospital setting. Bibliographical research was performed on the following databases: PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. The review included all randomized and nonrandomized controlled trials of patients aged ≥18 years with preserved gastrointestinal function. Meta-analysis was performed by Review Manager V.5.3. Seven studies including 551 patients were included in the meta-analysis. Five of these studies reported that the diarrhea rate was higher in the bolus feeding group (risk ratio [RR] = 2.50; 95% CI, 1.17-5.34; P = 0.02), and another five of these studies indicated that the aspiration rate was higher in the continuous feeding group (RR = 0.55; 95% CI, 0.35-0.87; P = 0.01). There were no significant differences for the other outcomes. In conclusion, intermittent EN appears to reduce the incidence of aspiration in the hospital setting; however, it may increase the risk of diarrhea. For future research, we hypothesize the joint use of continuous nutrition until the patient reaches tolerance and then passing to bolus nutrition, thus reducing the incidence of aspiration and enabling a physiological nutrition intake.

Background FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine. Methods Patients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO). Next, patients were randomized to SOC or SOC + IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters were analyzed. Results Six patients enrolled to safety lead-in, 10 randomized to SOC, and 10 to SOC + IO. There was no difference in median PFS comparing SOC versus SOC + IO (8.8 months (95% CI: 3.3-17.0 months) versus 10.1 months (95% CI: 3.6-16.1 months), respectively; hazard ratio 1.061 [P = .91; 95% CI: 0.380-2.966]). The objective response rate was 50% in both arms. Of patients analyzed, most (8/11) who received SOC + IO developed multifunctional CD4+/CD8+ T-cell responses to cascade antigens MUC1 and/or brachyury, compared to 1/8 who received SOC alone (P = .020). We detected post-treatment changes in immune parameters that were distinct to the SOC and SOC + IO treatment arms. Accrual closed after an unplanned analysis predicted a low likelihood of meeting the primary endpoint. Conclusions SOC + IO generated multifunctional MUC1- and brachyury-specific CD4+/CD8+ T cells despite concurrent chemotherapy. Although a tumor-directed immune response is necessary for T-cell–mediated antitumor activity, it was not sufficient to improve PFS. Adding agents that increase the number and function of effector cells may be required for clinical benefit.

Objective Several pharmacological treatments have been proposed for the treatment of complex regional pain syndrome type-I (CRPS-I) in adults, but data regarding the efficacy of various agents for this disease is scarce. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to analyse the efficacy of the various pharmacological approaches in adults with CRPS-I. Methods We systematically searched PubMed, Scopus, and Web of Science databases from the inception date to 30 June 2021 to identify placebo-controlled or active-controlled RCTs using bisphosphonates, ketamine, CSs, anti-epileptics, NSAIDs/COXIBs, opiates, antidepressants, scavengers/magnesium sulphate or IVIGs for the treatment of CRPS-I. The primary outcomes included changes in the visual analogue scale (VAS) or numeric rating scale (NRS) for pain before and after treatment. Results We included 20 placebo-controlled or active-controlled RCTs (including a total of 818 adults with CRPS-I) that used bisphosphonates (n = 7), ketamine (n = 2), CSs (n = 2), anti-epileptics (n = 1), NSAIDs/selective inhibitors of cyclooxygenase-2 (COXIBs) (n = 2), scavengers/magnesium sulphate (n = 5), or IVIGs (n = 1) to treat CRPS-I during a median follow-up of 26 weeks. Treatment with bisphosphonates showed a significant reduction in the values of the VAS/NRS pain scale compared with placebo or reference therapy (random effects weighted mean difference [WMD]: −23.8, 95% CI: −28.0 to −19.6; I2 = 36.4%). Treatment with ketamine also documented a reduction in the values of the VAS/NRS for pain (random effects WMD: −8.27, 95% CI: −12.9 to −3.70; I2 = 0%). Treatment with other agents did not reduce the values of the VAS/NRS assessments of pain. Conclusion This systematic review and meta-analysis supports the recommendation of parenteral bisphosphonates as the first-line agent in the treatment of CRPS-I. Trial registration Open Science Framework registries, https://osf.io/et9gu/, osf.io/et9gu.

Hodgkin lymphoma (HL) is today one of the most curable pediatric cancers. Despite survival rates now exceeding 90%, survivors of pediatric HL are still at higher risk to develop late effects of cancer therapy. Premature aging has been proposed as a paradigm to explain the onset of long-term complications in these subjects. High levels of advanced glycation end products (AGEs), together with chronic inflammation and oxidative unbalance, have been shown to be among the main factors contributing to aging. The present study aims to evaluate glycoxydation, inflammatory status, and oxidative stress in plasma and peripheral blood mononuclear cells (PBMC) obtained from 20 adult survivors of pediatric HL and 40 age- and sex-matched healthy controls. After the isolation of PBMC and the collection of plasma, we performed the analyses of gene expression by qRT-PCR and measured inflammatory and oxidative-stress markers. AGEs plasma levels, expressed as Nϵ-carboxymethyl-lysine and methylglyoxal hydroimidazolone, were markedly higher in HL survivors than in healthy subjects. HL survivors also showed a condition of higher oxidative stress, as demonstrated by an increased expression of NADPH oxidase on PBMC. Antioxidant defenses, evaluated in terms of alpha-tocopherol, GSSG/GSH ratio and catalase plasma levels, were strongly impaired in survivors. This pro-oxidative condition led to the over-expression of both NLRP3 and NFkB genes in PBMC and, consequently, to increased plasma levels of interleukin(IL)-1β and IL-6. Finally, the expression of the receptors for AGEs in PBMC confirmed the dysregulated AGE pathways. Data show AGEs accumulation in survivors of pediatric HL. The consequent activation of the receptor for AGEs leads to the persistent activation of intracellular signaling toward inflammation. These results suggest that the co-existence of AGEs accumulation, unbalanced oxidative status, and inflammation could play a role in the onset of late complications in HL survivors.

IntroductionGlucocorticoids are still a mainstream of rheumatoid arthritis (RA) treatment. Reducing glucocorticoids should be attempted in all patients. However, choosing the right tapering strategy is challenging. The primary aim of our study is to determine the dose–response association between glucocorticoid tapering and risk of flare in RA.MethodsWe conducted a case-crossover study to determine the factors associated to higher risk of flare in patients with RA. In case-crossover studies time-varying factors are assessed before events (hazard periods) and before control periods. We defined hazard periods as the 6 months immediately preceding flares of RA. Control periods were the 6 months prior to visits without flare. Exposure of interest was the tapering of glucocorticoids to various doses.Results508 patients with RA were included in the study and 267 (52.5%) had at least a flare and served as the case-crossover study population. 1545 visits were available for analysis and 345 (22.3%) flares were recorded. Discontinuation of glucocorticoids (ie, tapering to doses of 0 mg/day) and tapering to 0–2.5 mg/day was associated with higher risk of flare (adjusted OR (aOR) of 1.45, 95% CI: 1.13 to 2.24 and aOR of 1.37; 95% CI: 1.06 to 2.01, respectively). Tapering to doses >2.5 mg/day was not associated with significantly higher risk of flare.ConclusionsWe found that tapering to doses of >2.5 mg/day was generally effective in terms of risk of flare. Flare risk was higher when glucocorticoids were tapered to doses ≤2.5 mg/day. Our study might help design new tapering strategies in patients with RA on biological disease-modifying antirheumatic drugs.

With regard to Dr. Wimalawansa’s comment [...]