Second Data Release from the European Pulsar Timing Array: Challenging the Ultralight Dark Matter Paradigm.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0} eV≲m≲10^{-23.3} eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3 GeV/cm^{3}.

Dermal substitute: a safe and effective way in surgical management of adults post-burn dorsal foot contractures.

OBJECTIVE: Neglected dorsal foοt burns may result in typical fοrefοοt defοrmities characterised by cοntractures leading tο hyperextensiοn οf the tοes and gait disturbance. These defοrmities usually cause a significant impairment in daily activities and difficulty in wearing shοes. This article presents a recοnstructiοn series οf severe fοrefοοt defοrmities by means of dermal regeneratiοn templates (also known as dermal substitutes) and split thickness skin grafts. PATIENTS AND METHODS: We retrοspectively reviewed οur institutiοnal burn database from 2010 to 2020 focusing on all those dοrsal fοοt cοntractures treated with the use οf a dermal regeneratiοn template. The patients' demοgraphics, burn injury mechanisms, depth, lοcalizatiοn, surface, treatments and fοllοw-up were described. RESULTS: Twelve patients underwent this prοcedure and the mean affected area was 75 cm2. The mean time between the dermal regeneratiοn template applicatiοn and the split thickness skin graft was 19.6 days. Just fοr one patient, an additiοnal skin grafting prοcedure was required. The mean fοllοw-up was 4.6 years. We did not register specific cοmplicatiοns at bοth the recipient (forefoot) and dοnοr sites (scalp). All patients were able tο wear shοes and walk after the procedure. Nο recurrence οf cοntractures were οbserved. All patients were satisfied with cοsmetic results, and they did not request any additiοnal prοcedure οf cοsmetic imprοvement. CONCLUSIONS: The use οf the dermal regeneratiοn template can be cοnsidered as an extremely safe and efficient treatment οf severe post-burn fοrefοοt defοrmities.

Safety, pitfalls, and misunderstandings about the use of ozone therapy as a regenerative medicine tool. A narrative review.

Despite various opinions and healthy controversy on Ozone Therapy (OT), the practices of this therapy have increased worldwide. Main areas of study with consistent scientific outcomes are the topical treatment of both disk herniation and periodontal disease. On the other hand, there is a net dissociation of the scientific resonance concerning systemic oxygen/ozone treatments. It is our intention to discuss in logical terms the numerous papers that commendably reported adverse reactions attributable to OT, focusing our attention mainly to the techniques of administration and not to the simple contact of ozone with biological material. The case reports on OT treatments safety concerns discussed on international journals, make it possible to state that most safety issues are secondary to infections or traumatic reactions due to malpractice. Commonly, the molecule of ozone itself is not responsible of severe reactions at the therapeutic modalities. The millions of patients treated so far from the thousands of physicians correctly practicing OT world widely in the last 40 years demonstrate the safety of this simple and cost-effective regenerative medicine tool. The promising therapeutic implications also for the current COVID-19 emergency are a further stimulus to the standardization of this therapeutic resource with multiple application specificities.

Non-discogenic low back pain treated with oxygen-ozone: outcome in selected applications.

Low back pain and sciatica are highly debilitating conditions affecting all socioeconomic groups at an increasingly early age. They are caused by different often concomitant spinal disorders: disc or facet joint disease, spondylolysis (with or without listhesis), vertebral body and interapophyseal arthrosis, spinal stenosis, radicular and synovial cysts and, more rarely, infections and primary or metastatic cancer. Treatment of low back pain and/or sciatica requires an accurate diagnosis based on thorough history-taking and physical examination followed by appropriate imaging tests, namely computed tomography, and/or magnetic resonance scans in addition to standard and morphodynamics X-rays of the spine. In recent years, several reports have demonstrated the utility of oxygen-ozone therapy in reducing the size of herniated discs. The present study reports on the outcome of oxygen-ozone treatment in 576 patients with non-discogenic low back pain caused by degenerative disease of the posterior vertebral compartment (facet synovitis, Baastrup syndrome, spondylolysis and spondylolisthesis, facet degeneration).

Psycho-social characteristics in patients with discopathy: Quality of Life, coping strategy and mood state.

The pathologies of the musculoskeletal apparatus are the most common cause of chronic diseases, with a huge impact on people and society. Scientific literature has discovered how experiencing chronic pain directly affects peoples' well-being, lifestyle, social relationships and can also cause psychological distress. The present study aims to investigate pain experience in patients with hernias or protrusions of the cervical and lumbosacral tract on a sample of 120 patients, recruited from patients of Poliambulatorio Oberdan, medical centre in Brescia (Italy) specialized in physical rehabilitation and CT-guided oxygen ozone therapy. In a bio-psychosocial perspective, the research aimed to investigate how the perception of pain, the mood state associated with it, the coping strategies adopted and the quality of life differ according to each patient's gender and to the more or less prolonged use of pain medication. The data were collected by means of medical and psychological anamnestic interviews and self-report tests (WHOQOL-BREF, COPE-NVI, POMS). The quantitative analysis, carried out through SPSS 25 (2017) software, showed how functional impairment of one's autonomy (walking, driving) affects mood states. In particular, the female sample expressed a more deflected mood, despite the greater use of relational and/or transcendent support (coping strategies) compared to men. The study suggests that the greater impairment of the moods of women can be attributed both to the caregiving role they play, which often results in a greater fatigue and difficulties in redefining this role following the algic condition, and more general differences in the expression of suffering, which, on a cultural level, sees men emotionally coerced. The analysis also shows how taking pain medication for a long period of time has a negative impact on the quality of life. The results suggest that the patients treated with analgesic therapy tend to adopt avoidant coping styles, which usually escalate into postponement of the time when dealing with a stressful situation and, if used in the long run, may lead to worsening health condition.

Oxygen-ozone therapy as adjuvant in the current emergency in SARS-COV-2 infection: a clinical study.

The aim of the multicentre study promoted by Nuova FIO is to evaluate the beneficial effects of the systemic Oxygen-Ozone (O2O3) therapy in patients suffering from SARS COV-2 disease in the early phases of the disease, before worsening, up to the need of tracheal intubation. The study is based on the rationale on that the systemic oxygen-ozone treatment could be effective, positively influencing the disease evolution and/or being able to mitigate the onset of the cytokine storm syndrome at least partially.

A Systematic Review of Outcomes and Patient Satisfaction Following Surgical and Non-surgical Treatments for Hair Loss.

INTRODUCTION: This systematic review aims to examine surgical and non-surgical treatments and identify those procedures that are most effective in terms of patient satisfaction. MATERIALS AND METHODS: A systematic review protocol was developed a priori in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. The search was conducted in accordance with the PRISMA guidelines, the Cochrane handbook. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, and Cochrane databases was performed to identify studies on hair loss causes and hair loss treatment with different surgical and non-surgical techniques RESULTS: Our search generated a total of 781 articles; 646 studies were excluded based on the content of the abstracts, and an additional 105 studies were excluded based on the content of the complete article. We performed a review of the 30 remaining studies, which had sufficient data for inclusion, and met all the aforementioned inclusion criteria. Of the 30 studies, four were about minoxidil, four about finasteride, two about dutasteride, three about phototherapy, six about platelet-rich plasma injection, four about follicular unit transplantation technique, six about follicular unit extraction technique, and one about patient satisfaction following surgical treatment without a specified surgical technique. Only three studies used a patient-reported outcome measurement. CONCLUSIONS: Our study is the first comprehensive systematic review of hair loss, looking at the problem from different points of view, and focusing on finding the best solution for the patient. In the literature, there is currently no algorithm for the management of patients who go to a plastic surgeon for a solution to the problem of hair loss. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The Rise of the Stop the Bleed Campaign in Italy.

BACKGROUND: The B-Con Basic 1.0 protocol is a medical training designed to teach how to control massive external haemorrhages in emergency conditions. Spread throughout the United States since 2013, thanks to the Stop the Bleed campaign, it has seen a progressive international spread during 2016-2018. We report here data from the first 18 months of our training in Italy. METHODS: Since January 2017, military Operators enlisted to the Volunteer Military Corps of the Italian Red Cross and registered to the ACS B-Con instructor database have provided B-Con courses. These instructors have provided extensive training, involving learners among military and civilian populations, especially health professionals and students. Further, they have obtained a formal adhesion to the National Stop the Bleed Day 2018. RESULTS: Through August 2018, we trained 1186 learners in Italy on the B-Con protocol. The learners were mainly military personnel and law enforcement agents (620 [52%]) but also students and civilian health personnel (566 [48%]). CONCLUSION: The B-Con protocol has been very well received in Italy by military and police personnel. Good results have been assessed among civilian health professionals and medical students, especially by those operators involved in the field of emergency medicine.

Thermoelectricity and thermodiffusion in charged colloids.

The Seebeck and Soret coefficients of ionically stabilized suspension of maghemite nanoparticles in dimethyl sulfoxide are experimentally studied as a function of nanoparticle volume fraction. In the presence of a temperature gradient, the charged colloidal nanoparticles experience both thermal drift due to their interactions with the solvent and electric forces proportional to the internal thermoelectric field. The resulting thermodiffusion of nanoparticles is observed through forced Rayleigh scattering measurements, while the thermoelectric field is accessed through voltage measurements in a thermocell. Both techniques provide independent estimates of nanoparticle's entropy of transfer as high as 82 meV K(-1). Such a property may be used to improve the thermoelectric coefficients in liquid thermocells.

A simply designed cell for thermal conductivity measurements of low vapor-pressure liquids.

We have built a simply designed cell for the measurement of the thermal conductivity of liquids under steady state conditions from room temperature to about 60 °C. Thermal conductivities measured in the range between 0.2 and 0.7 Wm(-1) K(-1) show deviations of a few percent from reference thermal-conductivity data. The cell is made of two concentric parallel plates separated by a 0.44 mm thick sample. It is easily assembled and loaded with the sample for a quick and routine use.

Huge Seebeck coefficients in nonaqueous electrolytes.

The Seebeck coefficients of the nonaqueous electrolytes tetrabutylammonium nitrate, tetraoctylphosphonium bromide, and tetradodecylammonium nitrate in 1-octanol, 1-dodecanol, and ethylene-glycol are measured in a temperature range from T = 30 °C to T = 45 °C. The Seebeck coefficient is generally of the order of a few hundreds of microvolts per Kelvin for aqueous solution of inorganic ions. Here we report huge values of 7 mV/K at 0.1 M concentration for tetrabutylammonium nitrate in 1-dodecanol. These striking results open the question of unexpectedly large kosmotrope or "structure making" effects of tetraalkylammonium ions on the structure of alcohols.

The new Alzheimer's criteria in a naturalistic series of patients with mild cognitive impairment.

To test the validity of the new diagnostic criteria for Alzheimer's disease (AD) in a naturalistic series of patients with mild cognitive impairment (MCI). Ninety consecutive MCI patients were enrolled in a longitudinal study on the natural history of cognitive impairment. Medial temporal (MT) atrophy on MRI was defined as hippocampal volume below the fifth percentile of the distribution in healthy elders, abnormal CSF was based on Sjogren's cutoffs for Abeta42 and tau, and temporoparietal hypometabolism on 18F-FDG PET based on Herholz's t sum score. Patients were followed clinically to detect conversion to AD (MCI-AD), non-AD dementia (MCI-nAD), or no conversion (MCI-NC). The 24 MCI-AD and 15 MCI-nAD patients had sociodemographic, clinical, and neuropsychological baseline features similar to the 51 MCI-NC patients. All MCI patients with MT atrophy converted to AD, as did all those with abnormal CSF, but only 48 and 35% of those without MT atrophy or abnormal CSF converted (p on logrank test = 0.0007 and 0.001). Prediction of AD conversion was enhanced when positivity to either MT atrophy or abnormal CSF was considered, with only 15% of those MCI patients negative on both converting to AD (p < 0.0005). Markers were not predictive of non-AD dementia conversion. The accuracy of either MT atrophy or abnormal CSF in discriminating MCI-AD from MCI-NC was good (AUC 0.82, 95% CI 0.70-0.95). MT atrophy and abnormal CSF are the single most robust predictors of conversion to AD in MCI patients, and their combination enhances prediction. AD markers are not predictive of conversion to non-AD dementia.

Metabolic compensation and depression in Alzheimer's disease.

BACKGROUND/AIMS: The aim of this study was to map metabolic compensation and depression in Alzheimer's disease (AD) on a voxel-by-voxel basis. METHODS: Twenty-one healthy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. RESULTS: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity. Significant metabolic compensation was found in the amygdala, while exceeding hypometabolism was mainly located in the posterior cingulate cortex. CONCLUSION: Metabolic depression can be due to both distant effects of atrophy and to additional hypometabolism-inducing factors, such as amyloid deposition. Conversely, metabolic compensation could reflect spared synaptic plasticity of the surviving neurons. The investigation of the metabolic compensation mechanism could help in the comprehension of the AD underlying pathology.

Functional compensation in incipient Alzheimer's disease.

Aim of this study was to investigate the functional compensation mechanism in incipient Alzheimer's disease (AD). Seventeen elderly healthy subjects and nine amnestic MCI patients with incipient AD underwent brain MR scan and 99mTc ECD SPECT. We processed all images with SPM2, we created t maps, showing the wholebrain GM atrophy and functional changes, and we properly masked them with each other in order to assess relatively preserved perfusion or depression. Incipient AD showed GM atrophy in the medial temporal and temporoparietal lobes, in the insula and in the retrosplenial cortex, and GM hypoperfusion in the medial temporal and temporoparietal lobes. Relatively preserved perfusion, we could hypothesize to be compensatory in the setting of neuronal loss, was found in the posterior cingulate, in the head of the hippocampus, in the amigdala, and in the insula bilaterally, while functional depression occurred in bilateral parahippocampal gyri. In AD, a perfusional compensatory mechanism takes place in the neocortex, while perfusional depression occurs in the medial temporal lobe. These results help understand the reactive phenomena induced by the brain to try and counteract the pathological changes of AD.

Mapping the effect of APOE epsilon4 on gray matter loss in Alzheimer's disease in vivo.

Previous studies suggest that in Alzheimer's disease (AD) the Apolipoprotein E (APOE) epsilon4 allele is associated with greater vulnerability of medial temporal lobe structures. However, less is known about its effect on the whole cortical mantle. Here we aimed to identify APOE-related patterns of cortical atrophy in AD using an advanced computational anatomy technique. We studied 15 AD patients carriers (epsilon4+, age: 72+/-10 SD years, MMSE: 20+/-3 SD) and 14 non-carriers (epsilon4-, age: 69+/-9, MMSE: 20+/-5) of the epsilon4 allele and compared them to 29 age-and-sex matched controls (age: 70+/-9, MMSE: 28+/-1). Each subject underwent a clinical evaluation, a neuropsychological battery, and high-resolution MRI. UCLA's cortical pattern matching technique was used to identify regions of local cortical atrophy. epsilon4+ and epsilon4- patients showed similar performance on neuropsychological tests (p>.05, t-test). Diffuse cortical atrophy was detected for both epsilon4+ (p=.0001, permutation test) and epsilon4- patients (p=.0001, permutation test) relative to controls, and overall gray matter loss was about 15% in each patients group. Differences in gray matter loss between carriers and non-carriers mapped to the temporal cortex and right occipital pole (20% greater loss in carriers) and to the posterior cingulate, left orbitofrontal and dorsal fronto-parietal cortex (5-15% greater loss in non-carriers). APOE effect in AD was not significant (p>.74, ANOVA), but a significant APOE by region (temporal vs fronto-parietal cortex) interaction was detected (p=.002, ANOVA), in both early and late-onset patients (p<.05, ANOVA). We conclude that the epsilon4 allele modulates disease phenotype in AD, being associated with a pattern of differential temporal and fronto-parietal vulnerability.

New guidelines on the use of iodinated contrast media: a report on an implementation project.

PURPOSE: The aim of this paper is to report on the implementation of new guidelines on the use of injectable iodinated contrast media (ICM) at our workplace and specific protocols for the preparation of patients at risk. MATERIALS AND METHODS: Operators received training with continuing medical education (CME) credits. The new documentation (patient history/screening form and informed consent form) is available on the hospital Web site and requests serum creatinine determination with estimation of glomerular filtration rate (GFR) for every patient. Additional tests are required for high-risk patients only. RESULTS: Attendance rates were 57.2% among referring physicians and 74.5% among Radiology Department personnel. The Cockcroft-Gault formula was used to estimate GFR in adults. The main problem encountered in the implementation process was that referring physicians failed to evaluate the GFR in 80% of patients, with low GFR being discovered in the Radiology Department on the day of examination in 20% of patients, resulting in a need to reschedule the examination. CONCLUSIONS: Although not an easy task, implementation of the new guidelines for ICM use is both feasible and necessary. An additional refresher training course for personnel and GFR evaluation of the patient on referral are indispensable to ensure proper preparation of patients at increased risk of adverse reactions to ICM.

A permutation test for determining significance of clusters with applications to spatial and gene expression data.

Hierarchical clustering is a common procedure for identifying structure in a data set, and this is frequently used for organizing genomic data. Although more advanced clustering algorithms are available, the simplicity and visual appeal of hierarchical clustering has made it ubiquitous in gene expression data analysis. Hence, even minor improvements in this framework would have significant impact. There is currently no simple and systematic way of assessing and displaying the significance of various clusters in a resulting dendrogram without making certain distributional assumptions or ignoring gene-specific variances. In this work, we introduce a permutation test based on comparing the within-cluster structure of the observed data with those of sample datasets obtained by permuting the cluster membership. We carry out this test at each node of the dendrogram using a statistic derived from the singular value decomposition of variance matrices. The p-values thus obtained provide insight into the significance of each cluster division. Given these values, one can also modify the dendrogram by combining non-significant branches. By adjusting the cut-off level of significance for branches, one can produce dendrograms with a desired level of detail for ease of interpretation. We demonstrate the usefulness of this approach by applying it to illustrative data sets.

Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment.

OBJECTIVE: Aim of this study was to find cerebral perfusion correlates of conversion to dementia in patients with amnestic MCI. METHODS: 17 healthy subjects (age = 69 +/- 3, 9 females), and 23 amnestic MCI patients (age = 70 +/- 6, 10 females) underwent brain MR scan and (99m)Tc ECD SPECT. Conversion to AD was ascertained on average 19 +/- 10 months after baseline: 9 had converted (age = 69 +/- 3, 4 females), and 14 had not (age = 71 +/- 8, 6 females). We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing amnestic MCI patients converted to AD and non-converted to dementia vs controls. We assessed the effect of gray matter atrophy on the above results with SPM2 using an optimized Voxel-Based Morphometry (VBM) protocol. We compared significant hypoperfusion with significant atrophy on a voxel-byvoxel basis. RESULTS: In comparison with normal controls, amnestic MCI patients who converted to AD showed hypoperfusion in the right parahippocampal gyrus and left inferior temporal and fusiform gyri,whereas those who did not convert showed hypoperfusion in the retrosplenial cortex, precuneus and occipital gyri, mainly on the left side. We found no overlap between significant atrophy and significant hypoperfusion regions. CONCLUSIONS: Parahippocampal and inferior temporal hypoperfusion in amnestic MCI patients appears as a correlate of conversion to AD; hypoperfusion in the retrosplenial cortex is involved in memory impairment but does not seem the key prognostic indicator of conversion to dementia.

[Management and preparation of endoscopic suite, patients, relatives. Instrumentarium reprocessing]. / Organizzazione e preparazione della sala endoscopica, pazienti, familiari. Reprocessing dello strumentario.

Endoscopic ultrasonography (EUS) investigates the inner side of the digestive tract and the adjacent structures, associating the endoscopic image to the ultrasonographic vision made by a miniaturized ultrasonograph. The technological innovations and a greater attention to the users, have made more complex the organization, the process and the management of the patients. In such panorama, the technical operator of endoscopy, is the competent professional that coordinates the whole necessary organization for diagnostic-therapeutic interventions assuring their feasibility, guaranteeing efficiency and safety of environmental hygiene and strumentario and a specific and competent relief approach to the patients and their relatives.

[Early infantile and late infantile form of Krabbe disease: CT and MRI findings]. / Leucodistrofia di Krabbe tipo 1 e 2: valutazione TC ed RM.

The Authors present the CT and MR findings in three patients with Krabbe disease: early infantile, late infantile and juvenile. Three children, 5 and 9 months old respectively with Krabbe disease, were studied with CT and MR. the children presented with spasticity and signs of peripheral neuropathy, blindness and no interaction with the environment. In all patient CT revealed nonenhancing discrete dense lesions, simmetrically distribuited in the posterior limb of the internal capsule and posterior thalami and focal hypodensities of the midcerebellar peduncles and dentate nuclei, with mild cerebral atrophy. In one patients CT demonstrated bilateral calcifications of paraventricular white matter. Mr, in all, showed a generalized increase in T2 values of the periventricular white matter. The thalami and adjacents regions had markedly shortened T1 and slightly shortenede T2. The cerebellum and the brainstem appeared mottled with scattered areas of increased T2. MR confirmed the cerebral atrophy. In conclusion CT and MR findings in Krabbe disease (early infantile and late infantile) are usually not specific. However when they are both performed at the onset of neurological symptoms they can alert clinicians to the possibility of Krabbe disease.