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}.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

beta-lactoglobulin under high pressure studied by small-angle neutron scattering.

We used small-angle neutron scattering to study the effects of the high hydrostatic pressure on the structure of beta-lactoglobulin. Experiments were carried out at pH 7 on the dimeric form of the protein in a pressure range going from 50 MPa to 300 MPa. These measurements allow the protein size and the interactions between macromolecules to be studied during the application of pressure. Increasing pressure up to 150 MPa leads to a swollen state of the protein that gives rise to an increase of the radius of gyration by about 7%. Within this pressure range, we also show that the interaction between macromolecules weakens although it remains repulsive. The measurements show an aggregation process occurring above 150 MPa. From the spectra analysis, it appears that the aggregation occurs mainly by association of the dimeric units.

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.

Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial.

PURPOSE: Adjuvant chemotherapy for soft tissue sarcoma is controversial because previous trials reported conflicting results. The present study was designed with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents. PATIENTS AND METHODS: Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter > or = 5 cm or any size recurrent tumor) in extremities or girdles were eligible. Stratification was by primary versus recurrent tumors and by tumor diameter greater than or equal to 10 cm versus less than 10 cm. One hundred four patients were randomized, 51 to the control group and 53 to the treatment group (five cycles of 4'-epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through 5, with hydration, mesna, and granulocyte colony-stimulating factor). RESULTS: After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P =.04); and the median overall survival (OS) was 75 months for treated and 46 months for untreated patients (P =.03). For OS, the absolute benefit deriving from chemotherapy was 13% at 2 years and increased to 19% at 4 years (P =.04). CONCLUSION: Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths.

Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.

PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.

Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group.

PURPOSE: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40). CONCLUSION: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.