Beneficial effects of a program of Mindfulness by remote during COVID-19 lockdown.

OBJECTIVE: In the emergency context of COVID-19 pandemic and lockdown, mindfulness relaxation techniques can provide a safe and effective strategy to obtain in a reasonably short time some degree of relief from suffering and to guarantee a greater confidence with emotional reactions in the general population. SUBJECTS AND METHODS: The Mindfulness-Based Stress Reduction program for coping with COVID-19 emergency was designed as an 8-week program during the early phase of lockdown consisting in practice meditation exercises at least once a day guided and structured by certified instructors entered on a free online platform. At the end of the program all participants completed a survey. RESULTS: A total of 108 surveys were completed (67.6% male; 32.4% female). Despite the difficult moment of lockdown and the fear linked to the pandemic, 61.9% of interviewed subjects declared a state of general well-being from fair to good linked to the practice of mindfulness. Female subjects (p=0.001), married subjects (p=0.05) and people taking pharmacologic therapy demonstrated (p=0.009) significant improvement in daily management of emotions and practical requests during the early phase of the COVID-19 outbreak. CONCLUSIONS: Mindfulness meditation may be effective in helping people to regulate emotions and to support their mental health during this period of worry and uncertainty.

Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice.

BACKGROUND: Lipoxin A4 (LXA4) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA4 has effect on ultraviolet (UV) radiation-induced skin inflammation. OBJECTIVE: To investigate the effects of systemic administration with LXA4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. METHODS: Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm2). RESULTS: Pretreatment with LXA4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP+ cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-33). Depending on the time point, LXA4 increased the levels of anti-inflammatory cytokines (TGF-ß and IL-10). LXA4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA4 also reduced UV radiation-induced gp91phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression. CONCLUSION: LXA4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2.

Search for solar axions by the CERN axion solar telescope with 3He buffer gas: closing the hot dark matter gap.

The CERN Axion Solar Telescope has finished its search for solar axions with (3)He buffer gas, covering the search range 0.64 eV ≲ ma ≲ 1.17 eV. This closes the gap to the cosmological hot dark matter limit and actually overlaps with it. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of gaγ ≲ 3.3 × 10(-10) GeV(-1) at 95% C.L., with the exact value depending on the pressure setting. Future direct solar axion searches will focus on increasing the sensitivity to smaller values of gaγ, for example by the currently discussed next generation helioscope International AXion Observatory.

Search for sub-eV mass solar axions by the CERN Axion Solar Telescope with 3He buffer gas.

The CERN Axion Solar Telescope (CAST) has extended its search for solar axions by using (3)He as a buffer gas. At T=1.8 K this allows for larger pressure settings and hence sensitivity to higher axion masses than our previous measurements with (4)He. With about 1 h of data taking at each of 252 different pressure settings we have scanned the axion mass range 0.39 eV≲m(a)≲0.64 eV. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of g(aγ)≲2.3×10(-10) GeV(-1) at 95% C.L., the exact value depending on the pressure setting. Kim-Shifman-Vainshtein-Zakharov axions are excluded at the upper end of our mass range, the first time ever for any solar axion search. In the future we will extend our search to m(a)≲1.15 eV, comfortably overlapping with cosmological hot dark matter bounds.

Improved search for nu(mu) --> nu(e) oscillation in a long-baseline accelerator experiment.

We performed an improved search for nu(mu) --> nu(e) oscillation with the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment, using the full data sample of 9.2 x 10(19) protons on target. No evidence for a nu(e) appearance signal was found, and we set bounds on the nu(mu) --> nu(e) oscillation parameters. At Deltam(2)=2.8 x 10(-3) eV(2), the best-fit value of the K2Knu(mu) disappearance analysis, we set an upper limit of sin(2)2theta(mue) < 0.13 at a 90% confidence level.

Search for coherent charged pion production in neutrino-carbon interactions.

We report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed, and an upper limit of is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.

Evidence for muon neutrino oscillation in an accelerator-based experiment.

We present results for nu(mu) oscillation in the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment. K2K uses an accelerator-produced nu(mu) beam with a mean energy of 1.3 GeV directed at the Super-Kamiokande detector. We observed the energy-dependent disappearance of nu(mu), which we presume have oscillated to nu(tau). The probability that we would observe these results if there is no neutrino oscillation is 0.0050% (4.0 sigma).

Angiofibroblastoma of the skin: a report of seven cases in support of a distinctive entity.

BACKGROUND: Angiofibroblastoma of the skin is a recently described benign tumor with fibroblastic differentiation. The tumor is composed of stellate and spindle fibroblasts embedded in a fibromyxoid and fibrous matrix that contains numerous capillary-sized blood vessels. METHODS: All cases of fibromyxoid tumors of the skin from the files of two dermatopathologic centers and from consultation cases, together with clinical data and histopathologic specimens, were reviewed. Additionally, immunohistochemical studies were performed in all cases. RESULTS: Seven cases of angiofibroblastoma of the skin were found, including two cases previously reported. All cases showed similar histopathologic findings. The morphologic versatility of fibroblasts, however, explains some of the microscopic variations that were observed in three cases of this series. Immunohistochemical studies support the fibroblastic nature of the neoplasms. CONCLUSIONS: Our series provides data suggesting that angiofibroblastoma of the skin represents a distinctive entity, which should be considered in the differential diagnosis of other fibromyxoid tumors of the skin.

Fibrous spindle cell lipoma: report of a new variant.

Spindle cell lipoma is a benign tumor characterized by mature fatty tissue alternating with short fascicles of small spindle cells in a stroma that varies from fibrous to myxoid. The variable proportion of these elements among different examples of the neoplasm confers to spindle cell lipoma a variable microscopic appearance that can make the diagnosis difficult. Furthermore, in some instances, spindle cell lipoma may resemble liposarcoma, hemangiopericytoma, neurilemmoma, and other neoplasms representing a histopathologic pitfall. We report on two cases of spindle cell lipoma with abundant fibrous stroma reminiscence of fibroma and fibrolipoma. The name fibrous spindle lipoma is proposed for this tumor.

The nuclear localization domain of the MEF2 family of transcription factors shows member-specific features and mediates the nuclear import of histone deacetylase 4.

Targeting of myocyte enhancer binding factor 2 (MEF2) proteins to the nucleus depends on a C-terminal bipartite nuclear localization signal (NLS). By expression of green fluorescent protein (GFP)/MEF2 fusion proteins in transfected myoblasts, we show that MEF2C contains an additional 13 amino acids domain, located immediately upstream of the NLS, which contributes to its nuclear retention. We also show that the NLS present in MEF2 proteins is required for efficient nuclear localization of histone deacetylase 4 (HDAC4). In muscle cells, transfected HDAC4 is largely cytoplasmic or, to a lesser extent, pancellular. Co-transfection of either MEF2A or MEF2C causes HDAC4 to accumulate in the nucleus in association with MEF2. This effect strongly depends on MEF2 NLS; it also requires the specific interaction of HDAC4 with MEF2, since the isolated NLS is not sufficient for targeting HDAC4 to the nucleus and other nuclear proteins, such as NF-Y, cannot substitute MEF2. Therefore, we demonstrate that HDAC4, different from HDAC5, is mainly a cytoplasmic resident protein, requiring a trans-acting NLS for nuclear localization. The physiological implications of MEF2 carrying its own inhibitor to the nucleus are discussed.

Desmoplastic leiomyosarcoma of the skin.

This report focuses on two unusual cases of cutaneous leiomyosarcoma composed of sparse numbers of neoplastic cells embedded in abundant sclerotic stroma throughout the entire neoplasm. To the best of our knowledge, only one example of this rare lesion has been described previously as "sclerotic primary cutaneous leiomyosarcoma." However, the resemblance of this tumor to other desmoplastic tumors of the skin is striking and, therefore, we propose the term desmoplastic leiomyosarcoma of the skin for this neoplasm. Because of the sparse cellularity and the abundant stroma, desmoplastic leiomyosarcoma of the skin can be easily misinterpreted, especially in small biopsies. It should be included in the differential diagnosis of inflammatory skin diseases associated with sclerosis, such as radiation dermatitis, and of desmoplastic tumors of the skin, including desmoplastic melanocytic nevus, desmoplastic melanoma, and desmoplastic squamous cell carcinoma.

Angiomatoid Spitz nevus: a distinct variant of desmoplastic Spitz nevus with prominent vasculature.

Five cases of a distinctive variant of desmoplastic Spitz nevus are reported. To the best of our knowledge, this tumor has never been described previously. Clinically, it presents itself as a solitary papule on the extremities of young adults. Microscopically, it shows predominance of solitary melanocytes with epithelioid appearance over cell nests. They are embedded in a prominent fibrous stroma with many densely arranged, small blood vessels with plump endothelia not seen in other Spitz nevi. Because of its resemblance to a vascular tumor, the name angiomatoid Spitz nevus is proposed for this lesion. Absence of recurrences or metastases after complete excision in all cases supports the benign nature of the tumor.

Panniculitis: definition of terms and diagnostic strategy.

Inflammation of the subcutaneous tissue represents a dynamic process that shows different histopathologic findings at different stages of development; therefore, the stage of evolution of a lesion at the time of biopsy influences the microscopic appearance significantly. Furthermore, location and type of inflammation may vary among different examples of the same panniculitis independent of the stage of evolution. For these reasons, the histopathologic diagnosis of panniculitides is often difficult. Currently, the most common approach to diagnosis is differentiation between predominantly septal and predominantly lobular panniculitis, followed by the distinction between lesions with and without vasculitis. Although these criteria are important for diagnosis, they are often insufficiently specific. To determine an alternative method of diagnosis, 329 cases of panniculitis were histopathologically analyzed using the following parameters: location and type of inflammatory infiltrate within and around the subcutaneous tissue, presence or absence of fat necrosis, type of necrosis, presence or absence of vascular changes, and presence or absence of associated findings (e.g., hemorrhage, sclerosis). On the basis of the results of this study and of an extensive review of the literature, tables of histopathologic findings for the diagnosis of panniculitides are presented.

Benign lymphangiomatous papules of the skin following radiotherapy: a report of five new cases and review of the literature.

AIMS: The aim of this report is to summarize the clinicopathological findings of five cases of a pseudosarcomatous vascular proliferation of the skin at the site of radiotherapy following surgery for carcinoma of the breast and carcinoma of the endometrium. To our knowledge, only five cases of this presumably rare pseudomalignant proliferation have been reported previously. METHODS AND RESULTS: All patients were females ranging in age from 44 to 70 years. The lesions appeared as solitary or multiple papules or vesicles localized to the field of radiation. Microscopically, they were composed of vascular spaces that exhibited atypical features without qualifying for a diagnosis of angiosarcoma. CONCLUSIONS: Our cases provide additional evidence supporting the benign nature of this atypical vascular proliferation, not recurring, never developing metastases and being cured readily by local excision. Clinical, histopathological and ultrastructural findings suggest a lymphatic origin. Whether these lesions represent a neoplastic or a reactive condition secondary to radiotherapy is unclear. The name 'benign lymphangiomatous papules of the skin following radiotherapy' is proposed.

Early synthesis and correlation of serum anti-thyroid antibodies with clinical parameters in multiple sclerosis.

A high frequency of anti-thyroid antibodies has been demonstrated in multiple sclerosis (MS), but there is a lack of data on the possible association of thyroid autoimmunity with disease activity. To assess whether anti-thyroid antibodies are synthesized early in MS or are induced over the course of the disease and whether or not they are correlated with clinical findings, we assayed serum anti-peroxidase and anti-thyroglobulin antibodies in 129 relapsing-remitting MS patients at the time of diagnosis and prior to any immunosuppressive or immunomodulatory treatment. Anti-peroxidase antibodies were detected in 28/129 (21.7%) MS patients, compared to 12/130 (9.2%) neurological controls (P=0.006) and 8/152 (5.3%) normal healthy subjects (P<0.0001). High titres of anti-thyroglobulin antibodies were detected in 11/129 (8.5%) MS patients compared to 6/130 (4.6%) patients with other neurological diseases (P=0.22) and 5/152 (3.3%) normal healthy subjects (P=0.07). Anti-peroxidase antibodies were associated with initial relapse in 14 of 28 (50%) of the patients compared to 18/101 (18%) without antibodies (P=0.001). Similarly, anti-thyroglobulin antibodies were associated with first relapse in 8/11 (73%) of the patients compared to 11/118 (9.3%) of those without (P<0.0001). However, there was no correlation between anti-thyroid antibody titres and disease duration or CSF IgG index values. By contrast, a significant inverse correlation was found between anti-thyroglobulin antibody titres and EDSS score (r(s)=-0. 75; P=0.008). Our findings demonstrate that anti-peroxidase and anti-thyroglobulin antibodies are synthesized early in relapsing-remitting MS and are associated with early clinical disease activity. Furthermore, high titres of anti-thyroglobulin antibodies are associated with low disability scores, suggesting a possible protective role of these antibodies that deserves further investigation.

Construction and in vitro functional evaluation of a low-density lipoprotein receptor/transferrin fusion protein as a therapeutic tool for familial hypercholesterolemia.

A cDNA sequence encoding a soluble form of the human low-density lipoprotein receptor (LDL-R) was produced by RT-PCR amplification. This form of the receptor contains the N-terminal cysteine-rich domain, the EGF homology domain, and the serine/threonine-rich domain, but lacks the membrane anchor as well as the cytoplasmic domain. By the same technical approach a cDNA sequence encoding rabbit transferrin was generated. In-frame fusion of the two cDNAs produced a sequence encoding a chimeric protein potentially capable of binding LDL on the N-terminal side and the transferrin receptor on the C-terminal side. It was expected that LDL bound to the chimeric protein could be internalized, targeted to an acidic compartment, and processed through the pathway of the transferrin receptor. Cells transfected with the LDL-R/transferrin cDNA translate, glycosylate, and secrete the corresponding protein in the culture medium. The secreted protein binds LDL in a ligand-blotting experiment. Finally, the chimeric protein mediates the binding and internalization of LDL in mutant cells lacking the LDL receptor. In fact, Watanabe rabbit fibroblasts, incubated with the chimeric protein show a fourfold increase in LDL binding, a fivefold increase in LDL internalization, and a sixfold increase in LDL degradation, with respect to unincubated fibroblasts.

Pigmented atypical fibroxanthoma.

AIM: The purpose of this report is to call attention to a pigmented variant of atypical fibroxanthoma that resembles malignant melanoma, both clinically and histopathologically. METHODS AND RESULTS: Thirty-eight cases of atypical fibroxanthoma were examined for the presence of pigmented areas. Four such cases were found. Neoplastic cells showed erythrophagocytosis and accumulation of haemosiderin pigment in the cytoplasm. In three cases, immunohistochemical studies using a battery of antibodies were performed. Neoplastic cells were strongly positive for vimentin and weakly positive for CD68, whereas they were negative for melanocytic markers, including S100 protein, HMB45, and the monoclonal antibody NK1-C3 to melanoma-associated antigen. CONCLUSIONS: Pigmented atypical fibroxanthoma represents a poorly recognized variant of the neoplasm that may be easily misinterpreted as malignant melanoma. To the best of our knowledge, this is the first report of erythrophagocytosis in atypical fibroxanthoma.