Fatigue can influence the development of late-onset pain in post-COVID-19 syndrome: An observational study.

BACKGROUND: Late-onset pain is frequent following COVID-19, and many pathogenetic mechanisms have been proposed. Identifying the main features of patients may help in designing tailored rehabilitative interventions. METHODS: We enrolled post-COVID-19 patients with an increase in pain intensity of two points on the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) at 52 weeks compared to the pre-COVID-19 condition. All subjects were retrospectively monitored at 12, 26, and 52 weeks. A specific pain assessment was performed to determine the characteristics and mechanisms of pain. Catastrophizing, kinesiophobia, and other psychological symptoms were evaluated. The pressure pain threshold (PPT) and temporal summation (TS) were measured and compared in age- and sex-matched healthy controls to analyse pain characteristics. RESULTS: A total of 67 patients were recruited, with 20 of them presenting an increase in pain at 52 weeks. Subjects of the two subgroups were similar in demographic and clinical characteristics at baseline; significant differences in fatigue, anxiety, mobility, ability to perform daily activities, and general health perception were recorded at 26 weeks. Fatigue significantly predicted pain onset (ß = 0.54, p = 0.002). Sixteen different body regions were identified as painful, with a pain intensity of 6.0 ± 1.9. Most of the samples did not show neuropathic or nociplastic mechanisms. No differences in PPT and TS were recorded between patients and healthy controls. CONCLUSIONS: Almost one out of three patients hospitalized for COVID-19 developed pain 1 year later, and fatigue seems responsible for chronicity. An overlapping of conditions may explain late-onset post-COVID-19 pain, and a comprehensive approach must be considered for patient management. SIGNIFICANCE: Late-onset pain is frequent in post-COVID-19 syndrome and an overlapping of different mechanisms seems to be responsible for its development. Among many predisposing factors, fatigue in the months before seems to be one of the primary causes of pain one year following infection and its management may help to identify new strategies for prevention and treatment of late-onset pain.

Internet use 101 in college: Do undergraduates want to learn healthier internet use?

Background: Internet overuse is an emerging public health emergency, especially for college students in the United States. The purpose of this study was to assess college students' internet usage and interest in learning healthy internet usage skills as part of a college curriculum. Study design: Participants completed an online anonymous questionnaire which included the short version of the Internet Addiction Test, a modified Youth Health Movement survey, and questions regarding their interest in healthy internet use coursework. Methods: A total of 402 participants were recruited via an email LISTSERV of current undergraduates and recent graduates who had taken at least one class within a child and adolescent mental health studies minor while enrolled in a large university. Results: Overall, 70% of participants reported that they use the internet excessively, and a majority of participants reported that internet use has negatively affected their sleep and increased their anxiety. Seventy percent of participants reported that they would benefit from instruction on healthy internet usage via formal courses for credit or online modules. Conclusions: Students are aware of the difficulty in managing their internet use in college and are motivated to engage in novel courses on healthy internet usage. Academic institutions should consider developing courses or modules on healthy internet use.

Light-Nuclei Spectra from Chiral Dynamics.

In recent years local chiral interactions have been derived and implemented in quantum Monte Carlo methods in order to test to what extent the chiral effective field theory framework impacts our knowledge of few- and many-body systems. In this Letter, we present Green's function Monte Carlo calculations of light nuclei based on the family of local two-body interactions presented by our group in a previous paper in conjunction with chiral three-body interactions fitted to bound- and scattering-state observables in the three-nucleon sector. These interactions include Δ intermediate states in their two-pion-exchange components. We obtain predictions for the energy levels and level ordering of nuclei in the mass range A=4-12, accurate to ≤2% of the binding energy, in very satisfactory agreement with experimental data.

Liquid B2O3 up to 1700 K: x-ray diffraction and boroxol ring dissolution.

Using high energy x-ray diffraction, the structure factors of glassy and molten B2O3 were measured with high signal-to-noise, up to a temperature of T = 1710(20) K. The observed systematic changes with T are shown to be consistent with the dissolution of hexagonal [B3O6] boroxol rings, which are abundant in the glass, whilst the high-T (>~1500 K) liquid can be more closely described as a random network structure based on [BO3] triangular building blocks. We therefore argue that diffraction data are in fact qualitatively sensitive to the presence of small rings, and support the existence of a continuous structural transition in molten B2O3, for which the temperature evolution of the 808 cm−1 Raman scattering band (boroxol breathing mode) has long stood as the most emphatic evidence. Our conclusions are supported by both first-principles and polarizable ion model molecular dynamics simulations which are capable of giving good account of the experimental data, so long as steps are taken to ensure a ring fraction similar to that expected from Raman spectroscopy. The mean thermal expansion of the B-O bond has been measured directly to be αBO = 3.7(2) × 10−6 K−1, which accounts for a few percent of the bulk expansion just above the glass transition temperature, but accounts for greater than one third of the bulk expansion at temperatures in excess of 1673 K.

Opportunistic metastatic porocarcinoma after saphenous venectomy for coronary bypass surgery.

Immunocompromised areas of the skin, caused by chronic lymphoedema, paraplegia, infections or traumas, represent a site of regional neuroimmunocutaneous destabilization, termed the immunocompromised cutaneous district (ICD), in which malignancies and other opportunistic disorders are more likely to occur. We report the case of a metastatic porocarcinoma (PC) occurring on a lymphoedematous limb in a 72-year-old man. We reviewed the literature to better understand the potential pathogenetic mechanisms behind this condition. It has been reported that removal of the leg vein destroys the medial group of the superficial lymphatic vessels and alters the normal lymph drainage of the leg, predisposing to recurrent cellulitis. Our observations suggest that saphenous venectomy can induce development of an ICD. We suggest that PC, a rare cutaneous tumour, should be included in the growing list of tumours arising in the ICD.

Osteopontin, a protein with cytokine-like properties: a possible involvement in pemphigus vulgaris.

Pemphigus is an autoimmune blistering disease characterized by severe and chronic course, histopathologically characterized by infiltration of a large quantity of eosinophils, neutrophils, and activated Th1 and Th2 cells around the blister. Polarization of Th cells to Th1 or Th2 phenotypes, a critical aspect of cell-mediated immunity, is influenced by production of early cytokines, including osteopontin. To determine the involvement of osteopontin in pemphigus vulgaris patients in active stage of the disease, auto-antibodies to desmoglein-1 and desmoglein-3 and plasmatic osteopontin levels were examined by ELISA tests. In this work, significant plasmatic level of osteopontin in PV patients with active stage of disease were found particularly in those patients with both skin and oral pemphigus. OPN might drive the immune responses playing an important role in pemphigus onset.

Double blind clinical trial in a series of 115 patients with seborrheic dermatitis: prevention of relapses using a topical modulator of Toll like receptor 2.

AIM: Seborrheic dermatitis is a chronic inflammatory disease aggravated by Malassezia species. Toll-like receptors (TLR) are part of innate immune system that can be activated by yeasts. Previous studies showed that an association of Umbelliferae extract with a lipid (TLR2-Regul™) decreases the IL-8 expression in human skin in contact with M. furfur. The aim of this study was to assess the activity of a topical formulated with TLR2-Regul™ in the prevention of seborrheic dermatitis (SD) relapses. METHODS: Immune-competent SD adult patients were treated for SD (topical imidazoles or steroids). Cleared patients were randomized and received a topical containing TLR2-Regul™ (A) or its vehicle (B). Erythema, scales and pruritus were assessed during two months. RESULTS: The study included 115 patients, mean age 43.4, sex ratio m/f 1.5. At week 4 the relapse rate was 26% (N.=15) in group A and 43% (N.=25) in group B. At W8 the relapse rate was 21% (N.=12) in group A and 40% (N.=23) (P=0.0309). CONCLUSION: In this series of 115 adults with seborrheic dermatitis, patients treated with a topical containing TLR-Regul™ showed a significantly less relapse rate compared with the excipient group (P<0.05). TLR modulation could represent a new therapeutic approach in the prevention of seborrheic dermatitis relapses.

Inhibition of HSV-1 replication by laser diode-irradiation: possible mechanism of action.

Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitro model of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1ß and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune response unblocking the suppression of proinflammatory mediators induced by accumulation of progeny virus in infected epithelial cells.

Cutaneous leishmaniasis treated with itraconazole.

Leishmaniasis is a human disease produced by a parasite of the Leishmania genus transmitted by prick of an infected female sandfly. The disease occurs clinically with either cutaneous, mucocutaneous or visceral form, depending on the infective species and the immune status of the patient. Antimonial drugs are the current treatment of choice for all clinical forms. We report a case of cutaneous Leishmaniasis in a young girl successfully treated with itraconazole.

Tinea capitis mimicking tufted hair folliculitis.

We report a case of tinea capitis mimicking tufted hair folliculitis in a 56-year-old European man, who presented with a 4-year history of pain and erythema in an area of scarring alopecia of the occipital scalp, with scales and tufts of hair emerging from individual follicles. Histological examination showed hair plugging, and a dense perifollicular infiltrate of plasma cells, lymphocytes, and neutrophils. There was widespread scarring and fibrosis. Bacterial cultures were negative for Staphylococcus aureus, but fungal cultures and periodic-acid-Schiff stain were positive for Trichophyton tonsurans. Videodermatoscopy of the lesion showed a pattern consistent with folliculitis decalvans. Diagnosis was made on the basis of the clinical, histological, microbiological and videodermatoscopy data. After 30 days of systemic antifungal treatment, there were a substantial clinical improvement and disappearance of pain. After 5 months, a residual cicatricial area was seen with some hair tufts emerging from a single orifice.

3-O-methylfunicone, a metabolite of Penicillium pinophilum, inhibits proliferation of human melanoma cells by causing G(2) + M arrest and inducing apoptosis.

OBJECTIVES: Melanoma cells take advantage of impaired ability to undergo programmed cell death in response to different external stimuli and chemotherapeutic drugs; this makes prevention of tumour progression very difficult. The aim of this study was to demonstrate whether 3-O-methylfunicone (OMF), a metabolite of Penicillium pinophilum, has the ability to arrest cell population growth and to induce apoptosis in A375P (parental) and A375M (metastasis derivatived) melanoma cell lines. MATERIALS AND METHODS: Cell proliferation and apoptosis were analysed by flow cytometry, DNA fragmentation, caspase-3 and caspase-9 activation, and PARP-1 cleavage. RESULTS: We demonstrated that OMF affected cell proliferation in a time- and dose-dependent manner, reaching the best effect at concentration of 80 microg/ml for 24 h. Flow cytometry revealed that OMF caused significant G(2) phase arrest, which was associated with marked decrease in cyclin B1/p34(cdc2) complex and p21 induction. OMF also induced marked decrease of survivin expression. Reduced levels of apoptosis were evident after silencing p21 expression in both cell lines. Finally, the effect exercised by OMF on hTERT and TEP-1 gene expression confirmed the ability of this molecule to interfere with replicative ability of cells. CONCLUSIONS: The results reported here seem to suggest that OMF as a promising molecule to include in strategies for treatment of melanoma.

[Midarm arteriovenous fistula: single-center experience]. / Fistola artero venosa midarm: esperienza monocentrica.

In uremic patients on hemodialysis, a first vascular access using native vessels tailored into a radiocephalic arteriovenous fistula (AVF) on the wrist is the gold standard in vascular access quality. However, among the uremic population the percentage of older patients affected by diabetes or by severe generalized vascular disease is growing. In these patients distal radiocephalic AVFs often have a limited survival. This induced us to design a technique for tailoring vascular accesses at a proximal site. In the past two years (2006-2007) we created 19 AVFs at the midarm position (midarm AVF) using the proximal section of the radial artery. Midarm AVF was the second choice in 70% of patients after failure of a distal AVF and the first choice in 30% of patients. The survival of this type of access has been excellent. We have registered only one thrombosis after 6 months. In four cases access was interrupted because of the death of the patients. The remaining 14 accesses are working perfectly well. Our experience leads us to conclude that midarm AVF is not only an important intermediate step after the failure of a distal AVF and before the application of a proximal AVF, but in a population of patients with diabetes and generalized vascular disease it should probably be proposed as the AVF of choice.

Cefuroxime-induced pemphigus erythematosus in a young boy.

Pemphigus erythematosus (Senear-Usher syndrome) is a variant of superficial pemphigus with features of both lupus erythematosus and pemphigus. It affects mainly middle-aged adults, and is rarely observed before the age of 20 years. The case of a 14-year-old boy who showed cutaneous lesions suggestive for pemphigus erythematosus is described. Not all laboratory and histopathological investigations confirmed the hypothesis, so a diagnosis of clinical pemphigus erythematosus was made. Systemic steroid therapy was effective in controlling the disease. This case is interesting because of the rare occurrence of pemphigus erythematosus in adolescence and the possibility of another drug being added to the list of pemphigus inducers.

Bombesin: a possible role in wound repair.

During tissue regeneration and wound healing of the skin, migration, proliferation and differentiation of keratinocytes are important processes. Here we assessed the effect of a neuropeptide, bombesin, on keratinocytes during regeneration from scratch wounding. Bombesin purified from amphibian skin, is homologous of mammalian gastrin-releasing peptide and is active in mammals. Its pharmacological effects mediate various physiological activities: hypertensive action, stimulating action on gastric secretion, hyperglycemic effect or increased insulin secretion. In vitro it shows a hyperproliferative effect on different experimental models and is involved in skin repair. The aim of this study was to elucidate the effect of Bombesin in an in vitro experimental model on a mechanically injured human keratinocyte monolayer. We evaluated different mediators involved in wound repair such as IL-8, TGFbeta, IL-1, COX-2, VEGF and Toll-like receptors 2 and 4 (TLR2 and TLR4). We also studied the effects of bombesin on cell proliferation and motility and its direct effect on wound repair by observing the wound closure after mechanical injury. The involvement of the bombesin receptors neuromedin receptor (NMBR) and gastrin-releasing peptide receptor (GRP-R) was also evaluated. Our data suggest that bombesin may have an important role in skin repair by regulating the expression of healing markers. It enhanced the expression of IL-8, TGFbeta, COX-2 and VEGF. It also enhanced the expression of TLR2, while TLR4 was not expressed. Bombesin also increased cell growth and migration. In addition, we showed that NMBR was more involved in our experimental model compared to GRP-R.