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Introduction: Plaque psoriasis is a chronic relapsing inflammatory skin disease that is associated with extensive disease burden that often requires long-term therapy. Treatment of psoriasis with 4 weeks of the aerosol foam formulation of calcipotriol/betamethasone dipropionate (Cal/BD; Enstilar®, LEO Pharma) has been demonstrated to be effective, well tolerated, and associated with high patient satisfaction. Cal/BD foam is approved as a first-line treatment in multiple countries, where several non-interventional studies (NIS) have corroborated the beneficial efficacy and safety profiles determined in the randomized clinical trials. Heterogenicity in these NIS, however, prevents the use of a data pooling strategy for comparisons of effectiveness outcomes across different patient populations. Methods: Therefore, here, we report on a post hoc analysis of effectiveness data consolidated from six prospective NIS to discern any differences in improvement in signs and symptoms of psoriasis attributable to Cal/BD foam treatment across the countries. In addition, we provide real-world experience of clinicians with Cal/BD foam treatment, factoring in changes in usage since these NIS were performed in their local markets. Results: This post hoc analysis of Cal/BD foam NIS brings together data outside of randomized clinical trials from six countries to provide real-world evidence in 1388 patients showing that 4 weeks of Cal/BD foam is an effective and safe treatment option with quick onset of action for patients with psoriasis. Conclusion: These results show that regardless of NIS location, Cal/BD foam remains a well-tolerated, efficacious option for patient care that could be used as a first-line topical therapy for mild-to-severe psoriasis. [ABSTRACT FROM AUTHOR]

Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11. [ABSTRACT FROM AUTHOR]

Peritoneal metastases from gastric cancer (PM-GC) have a detrimental prognostic impact on survival and there is a lack of consensus regarding treatment. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a chance for prolonged survival as compared to standard chemotherapy. This study aims to present our experience in the management of GC with CRS and HIPEC. This is a single-centre retrospective study. Patients were divided into two groups: patients with GC at high risk for developing PM-GC (adjuvant HIPEC group) and patients with PM-GC or positive peritoneal cytology (therapeutic CRS and HIPEC group). Overall survival (OS) and disease-free survival (DFS) were considered as outcome measures. A total of 41 patients with a GC primary received surgery and HIPEC: 14 patients (34.1%) were in the adjuvant HIPEC group, while 27 patients (65.9%) were in the therapeutic CRS and HIPEC group. In the adjuvant HIPEC group, the 1- and 3-year OS were 85.7% and 71.4%, while 1- and 3-year DFS were 71.4% and 64.3%, respectively. In the therapeutic CRS and HIPEC group, OS was 60.3% and 35.1% at 1 and 3 years, whereas 1- and 3-year DFS were 38% and 32.6%, respectively. Univariate survival analysis of patients in the therapeutic CRS and HIPEC group showed that the presence of lymph node metastasis and signet ring cell histology predicted worse OS, while PCI > 12 and lymph node metastasis were associated with decreased DFS. Treatment of highly selected patients with GC at high risk of peritoneal recurrence or established PM with CRS and HIPEC showed satisfactory results in terms of OS and DFS. [ABSTRACT FROM AUTHOR]

Adult atopic dermatitis (adult AD) is a systemic inflammatory disorder, whose relationship with immune-allergic and metabolic comorbidities is not well established yet. Moreover, treatment of mild-to-moderate and severe atopic dermatitis needs standardization among clinicians. The aim of this study was to evaluate the distribution of comorbidities, including metabolic abnormalities, rhinitis, conjunctivitis, asthma, alopecia and sleep disturbance, according to severity of adult AD, and describe treatments most commonly used by Italian dermatologists. Retrospective, observational, nationwide study of adult patients over a 2-year period was performed. Clinical and laboratory data were obtained through review of medical records of patients aged ≥ 18 years, followed in 23 Italian National reference centres for atopic dermatitis between September 2016 and September 2018. The main measurements evaluated were disease severity, atopic and metabolic comorbidities, treatment type and duration. Six-hundred and eighty-four adult patients with AD were included into the study. Atopic, but not metabolic conditions, except for hypertension, were significantly associated with having moderate-to-severe AD in young adult patients. Disease duration was significantly associated with disease severity. Oral corticosteroids and cyclosporine were the most widely used immunosuppressant. Our study seems confirm the close relationship between adult AD and other atopic conditions, further long-term cohort studies on patients affected by adult AD need to be performed to evaluate the complex relationship between adult AD disease severity and metabolic comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: Dimethyl fumarate (DMF) is approved as oral systemic treatment for moderate-to-severe psoriasis. Scarce evidence is available for DMF treatment in psoriatic patients at the time of COVID-19 pandemic. The objective of this study was to assess the long-term effectiveness and safety of DMF monotherapy in moderate-to-severe psoriasis during the COVID-19 pandemic period. Methods: This multicenter, retrospective study included patients with moderate-to-severe psoriasis who had received a 48-week DMF treatment during the COVID-19 pandemic. Selected outcomes were: variation of mean PASI, proportion of patients achieving PASI50 and PASI75, variation of mean PGA and face PGA, genital PGA, scalp PGA, mean itch VAS and mean DLQI. Results: Forty-four patients were enrolled, and four patients became COVID-19 positive during the observation period but did not discontinue DMF therapy. DMF produced a significant improvement of signs and symptoms of psoriasis as expressed by mean PASI variation from 13.07 at baseline to 6.11 at week 48 (p < 0.0001), itch VAS from 3.22 at baseline to 1.18 at week 48 (p < 0.001), PGA from 2.84 at baseline to 1.30 at week 48 (p < 0.0001) and DLQI from 13.09 at baseline to 6.07 at week 48 (p < 0.0001). The percentage of patients who achieved PASI50 and PASI75 was 4.55% at week 4 and 59.09% at week 48 and 0% at week 4 and 22.73% at week 48, respectively. A clinical important decrease of mean PGA score was observed in all subgroups, face psoriasis, genital psoriasis and scalp psoriasis. Adverse events were predictable and manageable. Conclusions: DMF monotherapy is an effective and safe treatment option in moderate-to-severe psoriasis also in patients who develop SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma, Immunohistochemistry, Lymph node metastases, Nevi, Nicotinamide N-methyltransferase 1 Immunohistochemical expression of NNMT in dermal melanocytic nevi (a; the scale bar corresponds to 100 m), primary cutaneous melanomas (b; the scale bar corresponds to 50 m) and lymph node metastases from cutaneous melanoma (c; the scale bar corresponds to 30 m). Keywords: Cutaneous melanoma; Immunohistochemistry; Lymph node metastases; Nevi; Nicotinamide N-methyltransferase EN Cutaneous melanoma Immunohistochemistry Lymph node metastases Nevi Nicotinamide N-methyltransferase 480 482 3 01/06/23 20230101 NES 230101 Davide Sartini and Elisa Molinelli have contributed equally to this work. [Extracted from the article]

More than 12 months have passed since the World Health Organization (WHO) declared Coronavirus Disease 19 (COVID-19), caused by the SARS-CoV2 virus, to be a pandemic on 11 March 2020. The entire world scientific community agrees that at this time vaccine is the most promising weapon to combat the infection and the severity of the disease. According to the document "Draft landscape of COVID-19 candidate vaccines" by WHO, 272 vaccines against SARS-CoV-2 virus are in development, although only four of these, produced by Pfizer-BioNTech (Pfizer, Inc. and BioNTech), Moderna, AstraZeneca, and Janssen companies, respectively, have been approved by European Medicines Agency and Italian Medicines Agency and subsequently distributed nationwide for use. These vaccines are the result of highly innovative procedures and are quite different from each other in terms of composition. Even clinicians in various medical fields may be unfamiliar with the effects of these vaccines. There is the strong emerging need for dermatologists to understand the crucial role of vaccines, with a focus on the need to vaccinate patients suffering from immune-mediated skin diseases, such as psoriasis, while taking the ongoing treatment into consideration regarding the timing of vaccination. Similarly, psoriasis patients aware of having an immune-mediated and inflammatory disease are increasingly asking the dermatologist information about the efficacy and safety of vaccines against SARS-CoV-2 virus. In this narrative review of the literature and critical analysis of the recommendations of the Italian Ministry of Health, we analyze the implications of the vaccination campaign on dermatological patients with psoriasis undergoing immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Correction to: Archives of Dermatological Research https://doi.org/10.1007/s00403-021-02243-w In this article the author group details were incorrectly displayed with Collaborators included in the main author group. The original article can be found online at https://doi.org/10.1007/s00403-021-02243-w. [Extracted from the article]

Introduction: Psoriasis cellular hallmarks, such as the imbalance between Th1/Th17 and Th2 cytokines and the dysregulated expression of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase, (iNOS) and indoleamine 2,3-dioxygenase (IDO), are all detectable in mesenchymal stem cells (MSCs) suggesting that psoriasis originates at mesenchymal level. Aim of the study: In this scenario, MSCs may become the new therapeutic target and interest in the effects of traditionally used drugs, such as Apremilast, on MSCs has greatly increased. Materials and Methods: MSCs from control subjects (C-MSCs) and from psoriatic patients before (PsO MSCs T0) and after in vivo treatment with Apremilast (PsO-MSCs T12) were isolated and characterized; subsequently, the effects of Apremilast on VEGF, iNOS and IDO expression were evaluated by immunocytochemistry (ICC). The expression of VEGF, iNOS and IDO was also detected in skin sections by immunohistochemistry (IHC). Results: The results indicate that in vivo administration of Apremilast is able to drive the altered profile of PsO-MSCs towards a more physiological pattern. In skin sections, the role of Apremilast is evident in reducing VEGF, iNOS and IDO expression. Conclusion: Apremilast treatment influences the expression of VEGF, iNOS and IDO not only by keratinocytes but also by MSCs, restoring their intrinsic profile and their natural anti-inflammatory action, and decreasing the auto-inflammatory process that underpins the development of psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Alopecia areata (AA) is a chronic inflammatory non-scarring type of hair loss. Current therapies for alopecia areata are rather limited and mainly involve the use of topical, intra-lesional or systemic steroids and topical immunotherapy, with variable benefit. Recent studies have demonstrated that vitamin D analogues could potentially promote hair growth in patients with patchy AA. Methods: We investigated the efficacy and safety of treatment with calcipotriol, a synthetic derivative of vitamin D (calcipotriol 0.005% ointment), versus treatment with the corticosteroid clobetasol (topical clobetasol 0.05% formulation), in a series of 35 patients with scalp AA, using an intrasubject design. Results: Patches treated with calcipotriol ointment showed greater and faster response rates than did those treated with topical clobetasol, although the differences were not statistically significant. The main strength of the study is its prospective design; the main limitation is the small number of participants. Conclusions: Treatment with the calcipotriol would appear to be reasonably effective in patients with mild to moderate patchy AA and was associated with only limited and reversible side effects. [ABSTRACT FROM AUTHOR]

Keywords: Actinic keratosis; Immunohistochemistry; Paraoxonase-2; Squamous cell carcinoma; Tumour biomarker EN Actinic keratosis Immunohistochemistry Paraoxonase-2 Squamous cell carcinoma Tumour biomarker 1929 1931 3 10/06/21 20211101 NES 211101 Davide Sartini and Roberto Campagna have contributed equally to this work. Squamous cell carcinoma (SCC) represents the second most frequent skin cancer after basal cell carcinoma (BCC), although it has been recently demonstrated an increasing trend in its incidence [[1]]. Actinic keratosis, Immunohistochemistry, Paraoxonase-2, Squamous cell carcinoma, Tumour biomarker. [Extracted from the article]

In the last decade, there has been a growing interest about the possible association between anaplastic large cell lymphoma (ALCL) and breast implants (BIA-ALCL). Many variables, such as breast implants texturization, have been investigated. Breast implants often lead to the formation of a periprosthetic capsule, characterized by inflammation. The presence of the inflamed capsule has been found in the majority of patients with BIA-ALCL. Inflammation may be sustained or counteracted by mesenchymal stem cells (MSCs) by the secretion of pro- or anti-inflammatory cytokines. MSCs were isolated from three capsules surrounding micro-textured (micro-MSCs) and from three capsules surrounding macro-textured (macro-MSCs) implants; after characterization, MSCs were co-cultured with KI-JK cells (a cell line derived from the cutaneous form of ALCL). The secretion of cytokines related to inflammation, the proliferation rate, and the expression of genes referred to pro-tumoral mechanisms were evaluated. Co-cultures of KI-JK cells with micro- or macro-MSCs gave the same results about the secretion of cytokines (increase of IL10, G-CSF, and TGF-β1 and decrease of IL4, IL5, IL12, IL13, IL17A, IFN-γ (p < 0.05) with respect to mock sample), expression of selected genes (increase for ACVR1, VEGF, TGF-βR2, CXCL12, and MKi67 (p < 0.05) with respect to control sample), and the proliferation rate (no variation between mock and co-cultured samples). Our results suggest that MSCs derived from capsules surrounding micro- and macro-textured implants display the same effects on the ALCL cells. [ABSTRACT FROM AUTHOR]

Glioblastomas (GBM) are aggressive brain tumors with very poor prognosis. While silver nanoparticles represent a potential new strategy for anticancer therapy, the silver/silver chloride nanoparticles (Ag/AgCl-NPs) have microbicidal activity, but had not been tested against tumor cells. Here, we analyzed the effect of biogenically produced Ag/AgCl-NPs (from yeast cultures) on the proliferation of GBM02 glioblastoma cells (and of human astrocytes) by automated, image-based high-content analysis (HCA). We compared the effect of 0.1-5.0 µg mL−1 Ag/AgCl-NPs with that of 9.7-48.5 µg mL−1 temozolomide (TMZ, chemotherapy drug currently used to treat glioblastomas), alone or in combination. At higher concentrations, Ag/AgCl-NPs inhibited GBM02 proliferation more effectively than TMZ (up to 82 and 62% inhibition, respectively), while the opposite occurred at lower concentrations (up to 23 and 53% inhibition, for Ag/AgCl-NPs and TMZ, respectively). The combined treatment (Ag/AgCl-NPs + TMZ) inhibited GBM02 proliferation by 54-83%. Ag/AgCl-NPs had a reduced effect on astrocyte proliferation compared with TMZ, and Ag/AgCl-NPs + TMZ inhibited astrocyte proliferation by 5-42%. The growth rate and population doubling time analyses confirmed that treatment with Ag/AgCl-NPs was more effective against GBM02 cells than TMZ (~ 67-fold), and less aggressive to astrocytes, while Ag/AgCl-NP + TMZ treatment was no more effective against GBM02 cells than Ag/AgCl-NPs monotherapy. Taken together, our data indicate that 2.5 µg mL−1 Ag/AgCl-NPs represents the safest dose tested here, which affects GBM02 proliferation, with limited effect on astrocytes. Our findings show that HCA is a useful approach to evaluate the antiproliferative effect of nanoparticles against tumor cells. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune arthritis, occurring in patients with psoriasis (Pso), that may affect the whole musculoskeletal system but also nails, eye, and gastrointestinal tract. Dermatologists and rheumatologists usually manage Pso and PsA separately, but early diagnosis and integrated management could achieve better outcomes of both skin and musculoskeletal manifestations, thus improving the health-related quality of life (HRQoL) of patients. In this work, we have described a model of integrated dermo-rheumatologic approach for the early diagnosis of PsA and to present the outcomes of the multidisciplinary management of PsA patients after 48 weeks of follow-up. Pso patients complaining musculoskeletal symptoms were enrolled in a DErmo-Rheumatologic Clinic (DERC) in order to screen, classify, and treat patients with PsA, employing an operative working procedure and a specific flowchart. The integrated dermatologic and rheumatologic management of PsA patients allowed a prompt establishment of the diagnosis and the best therapeutic approach in these patients, with a significant improvement of skin and articular diseases and, eventually, a consistent amelioration of HRQoL. Dermatologists and rheumatologists usually manage the “psoriatic disease” in separated outpatient clinics. In our study, we have demonstrated that a combined DERC, by means of a tight cooperation between the dermatologist and the rheumatologist, which use a specific working procedure and treatment flowchart, may achieve the optimal clinical management of these patients, with a consistent clinical remission of the disease and a significant amelioration of the HRQoL. [ABSTRACT FROM AUTHOR]

Introduction: Actinic keratosis (AK) is a cutaneous intraepithelial neoplasm appearing within areas referred as 'fields of cancerization'. AK can progress to invasive squamous cell carcinoma. Treatments that target both clinically visible and subclinical AKs in cancerization fields are able to reduce the risk of malignant progression. Ingenol mebutate gel is a new effective topical therapy for AK, used once daily for 2 or 3 days depending on the location of lesions. Case description: Three elderly patients with multiple non-hypertrophic AKs within a contiguous 25-cm treatment area on the face or scalp were treated with ingenol mebutate 0.015 % gel once daily for three consecutive days and followed up over a period of 57 days. Discussion and Evaluation: Although individual local responses to treatment varied, all patients had total clearance of AK lesions without any sign of recurrence. In addition, all patients said that they were satisfied with the effectiveness of ingenol mebutate treatment and the aesthetic outcome, and would be prepared to use this agent again to treat AK in the future, if necessary. Conclusions: These three cases demonstrate that ingenol mebutate 0.015 % gel is effective and well tolerated in a clinical setting, with effective clearance of AK lesions present on the face and scalp, and good patient acceptability. [ABSTRACT FROM AUTHOR]

The ocular involvement in psoriasis is not a completely well-known problem. The ophthalmologic involvement occurs in about 10 % of patients, particularly in case of arthropathic or pustular psoriasis. Ocular lesions are more common in males, and they often occur during psoriasis exacerbations. Our study aimed to assess the prevalence and type of ocular involvement in psoriasis, by a comparison between psoriasis and healthy subjects, and if/how a 12-week long systemic immunosuppressive therapy is able to modify them. This study involved thirty-two psoriatic patients and thirty-two healthy subjects. Dermatological evaluation was done using Psoriasis Area and Severity Index, Physician Global Assessment, and Dermatology Life Quality Index (PASI, PGA, and DLQI score). Ophthalmological evaluation included ocular surface involvement (Schirmer, Jones, break-up time-BUT, DR-1 camera), retinal pathologies, and ocular surface disease index. Laboratory investigations including the C-reactive protein (CRP) of all the patients were performed. At baseline, the values of Schirmer, Jones, and BUT tests in the patient group were significantly lower compared to controls; moreover, conjunctival hyperemia was more frequent in psoriatic patients than in healthy subjects. Ocular involvement was more prominent in the subset of psoriatic patients with sebo-psoriasis than in general psoriatic population. A statistically significant correlation was found in sebo-psoriasis between PASI and Schirmer, between PASI and Jones, and between PASI and BUT. On the other hand, the results obtained from DR1 camera showed statistically significant difference between psoriatic and sebo-psoriatic patients at the end of the follow-up. After 12 weeks of treatment, the mean values of PASI, PGA, DLQI, CRP, and BUT showed significant changes in psoriatic patients. Our findings suggest a high rate of ocular involvement in psoriatic patients, emphasizing the need of performing periodic ophthalmological examinations in order to avoid underestimating eye diseases and to allow early diagnosis and treatment of patients. [ABSTRACT FROM AUTHOR]

The expression of genes encoding for Th1, Th2 and Th17 cytokines has been extensively evaluated in differentiated skin cells of psoriatic patients. The microenvironment exerts a control on the phenotype of resident mesenchymal stem cells (MSCs) into the skin of psoriasis patients. Aim of the study was to extensively evaluate the relative expression of 43 genes encoding for Th1, Th2 and Th17 cytokines in MSCs isolated from skin of psoriasis patients. MSCs resident into psoriatic skin were isolated, characterized and profiled by PCR array for the relative expression of genes encoding for cytokines involved in Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy subjects were used as control. The MSCs isolated from skin of psoriasis patients showed a greater relative expression of the most part of the analyzed genes encoding for Th1 and Th17 cytokines: INF-γ, CCR5, CXCL9, CXCL10, IL6, IL8, TNF-α, IL23A, CCL2, CCL20, CXCL2, CXCL5, IL17C, IL17F, IL17RA, IL21, TLR2 than healthy subjects. On the contrary, the relative expression of genes encoding for Th2 cytokines: CCL1, CCL22, CXCL12, IL2, IL3, IL4, IL13B, IL 22, IL 27, TGF-β1, was similar between the MSCs isolated from psoriasis and healthy subjects. In conclusion, the MSCs isolated from psoriasis show an imbalance between the Th1-Th17 and Th2 pathways, which reflects the well-known abnormal balance observed in differentiated skin cells. This evidence could strengthen the hypothesis of an early involvement of resident MSCs in the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

Focal hyperhidrosis often has a substantial psychological and social impact on quality of life, since it interferes with daily activities. To date, for the treatment of focal hyperhidrosis, the botulinum toxin type A is an effective second line tool. The purpose of this study was to compare Onabotulinumtoxin A (Botox) and Incobotulinumtoxin A (Xeomin) administration in the treatment of palmar hyperhidrosis. In a double-blind clinical trial, 25 patients with moderate or severe palmar hyperhidrosis received in the same session intradermal injections of Onabotulinumtoxin A on one hand and Incobotulinumtoxin A on the other. Several measures of efficacy and safety were evaluated: disease severity improvement, sweat reduction, hand-grip strength decrease, pain/discomfort during the treatment, and patient's global satisfaction. All patients were responsive to the treatments (HDSS at T4 vs HDDs at T0; p < 0.0001), and no significant difference between Onabotulinumtoxin A and Incobotulinumtoxin A in terms of anhidrotic effect (Minor's test at T4; p = 0.51), long-term efficacy (Minor's test at T12; p = 0.76), (Minor's test at T24; p = 0.58), subjective pain related to the injections ( p = 0.88), muscle strength reduction after treatment ( p = 0.56), and global satisfaction with the treatment ( p = 0.26). Onabotulinum toxin A and Incobotulinumtoxin A seem to be comparable in terms of anhidrotic effect (short-term results), duration of benefits (long-term efficacy), muscle strength reduction (safety), pain related to injections (tolerability), and treatment satisfaction expressed by patients. [ABSTRACT FROM AUTHOR]

Botulinum toxin type A (BoNT/A) improves symptoms of palmar hyperhidrosis, but some drawbacks related to its injection in the hands still persist (e.g., muscle weakness caused by drug diffusion, pain during injections, or delayed functional recovery of the hand when using wrist block). In this open, controlled, non-randomized, intra-individual clinical trial, 50 patients with severe palmar hyperhidrosis received in the same session intradermal injections of BoNT/A through a new injection technique (NA/BoNT/A) based on the use of a specific adapter for needles (PCT/IT2011/000299) in one hand, and BoNT/A injection following the anaesthetic block of the wrist (WB/BoNT/A) in the other. Several measures of efficacy and safety were evaluated both before (T0) and four weeks after the treatment (T4): disease severity improvement, sweat reduction, handgrip strength decrease, pain/discomfort during the treatment, and patient's global satisfaction. All patients were also re-evaluated through the gravimetric assessment of sweat production in both hands at T12 and T24 to compare the long-term efficacy of the two treatments. All patients were responsive to the treatments, and disease severity was significantly decreased at T4 compared to baseline ( p < 0.0001). Both procedures were equally effective in reducing sweat production in the short term ( p = 0.08 at T4), but WB/BoNT/A caused a higher decrease of handgrip strength compared with WB/BoNT/A at T4 ( p < 0.0001). Finally, patients reported that NA/BoNT/A and WB/BoNT/A procedures were comparable for pain/discomfort ( p = 0.204); however, they were globally more satisfied with the NA/BoNT/A rather than WB/BoNT/A method ( p < 0.0001). No significant difference in percentage of clinical relapse at T12 and T24 was detected between hands treated via WB/BoNT/A or NA/BoNT/A ( p = 0.70). The use of the described adapter to inject BoNT/A in the hands seems to lead the clinicians to obtain same therapeutic results of conventional method based on the use of anaesthetic block of the wrist. Moreover, this new injective approach seems to increase the safety of the treatment by reducing the extent of muscle weakness and is preferred by patients mostly because it makes the functional recovery of the hand faster. [ABSTRACT FROM AUTHOR]

Background: Patients with psoriasis show a greater prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than their counterparts with NAFLD and without psoriasis. The link between these three pathological conditions is a chronic low-grade inflammatory status. In this study, we aimed to evaluate the effect of etanercept versus psoralen and UVA (PUVA) therapy on the hepatic fibrosis risk in patients with psoriasis, metabolic syndrome, and NAFLD (with NAFLD diagnosed by ultrasonography). Methods: Eighty-nine patients with chronic moderate-to-severe plaque-type psoriasis, metabolic syndrome, and NAFLD received etanercept or PUVA treatment. The two groups of patients were compared for anthropometric variables (body mass index and waist/hip ratio), lipid profile, glucose homeostasis, inflammatory status, risk of hepatic fibrosis, and ultrasonographic aspect of the liver, both at baseline (time [T] 0) and after 24 weeks of treatment (T24). Results: After 24 weeks of treatment, only in the group receiving etanercept, we detected significant reductions ( p < 0.05) in the aspartate transaminase (AST)/alanine transaminase (ALT) ratio, C-reactive protein (CRP) serum levels, fasting insulin levels, and homeostasis model assessment (HOMA) index, and a significant increase in the Quantitative Insulin-Sensitivity Check Index (QUICKI) ( p < 0.05). Conclusions: In patients with psoriasis, metabolic syndrome, and NAFLD, the risk of the development of hepatic fibrosis seems to be directly correlated with insulin resistance. Etanercept could be more efficacious to reduce the risk of developing hepatic fibrosis than PUVA therapy, and this preventive effect could be related to its anti-inflammatory and glucose homeostatic properties. We note that a limitation of the study was that the diagnosis of NAFLD was conducted by ultrasonography. [ABSTRACT FROM AUTHOR]

Giardia lamblia is a protozoan that inhabits the small intestine of vertebrates, attaching to the epithelial cells by means of cytoskeletal elements. G. lamblia trophozoites possess several microtubular structures, namely the adhesive disc, the median body, the funis and the four pairs of flagella. Several drugs that target cytoskeletal proteins have been used in the study of cytoskeletal function and dynamics. In this work, we used oryzalin, which binds to α-tubulin, as a tool to study the Giardia cytoskeleton. The trophozoites were treated with oryzalin, and its effects were analysed by immunofluorescency, transmission and scanning electron microscopies. Oryzalin inhibited Giardia proliferation. Treated cells were not able to complete cell division and had flagella showing extensive shortening. Strikingly, the drug did not interfere with the adhesive disc, in contrast to what happens when other drugs are used. [ABSTRACT FROM AUTHOR]

We investigate properties of a reported new mechanism for cell–cell interactions, tunneling nanotubes (TNT’s). TNT’s mediate actin-based transfer of vesicles and organelles and they allow signal transmission between cells. The effects of lateral pulling with polystyrene beads trapped by optical tweezers on TNT’s linking separate U-87 MG human glioblastoma cells in culture are described. This cell line was chosen for handling ease and possible pathology implications of TNT persistence in communication between cancerous cells. Observed nanotubes are shown to have the characteristic features of TNT’s. We find that pulling induces two different types of TNT bifurcations. In one of them, termed V-Y bifurcation, the TNT is first distorted into a V-shaped form, following which a new branch emerges from the apex. In the other one, termed I-D bifurcation, the pulled TNT is bent into a curved arc of increasingly broader span. Curves showing the variation of pulling force with displacement are obtained. Results yield information on TNT structure and elastic properties. [ABSTRACT FROM AUTHOR]

The association of high resolution field emission scanning electron microscopy (FESEM), with a more efficient system of secondary electron (SE) collection and in-lens specimen position, provided a great improvement in the specimen’s topographical contrast and in the generation of high-resolution images. In addition, images obtained with the use of the high-resolution backscattered electrons (BSE) detector provided a powerful tool for immunocytochemical analysis of biological material. In this work, we show the contribution of the FESEM to the detailed description of cytoskeletal structures of the protozoan parasites Herpetomonas megaseliae, Trypanosoma brucei and Giardia lamblia. High-resolution images of detergent extracted H. megaseliae and T. brucei showed the profile of the cortical microtubules, also known as sub-pellicular microtubules (SPMT), and protein bridges cross-linking them. Also, it was possible to visualize fine details of the filaments that form the lattice-like structure of the paraflagellar rod (PFR) and its connection with the axoneme. In G. lamblia, it was possible to observe the intricate structure of the adhesive disk, funis (a microtubular array) and other cytoskeletal structures poorly described previously. Since most of the stable cytoskeletal structures of this protozoan rely on tubulin, we used the BSE images to accurately map immunolabeled tubulin in its cytoskeleton. Our results suggest that the observation of detergent extracted parasites using FESEM associated to backscattered analysis of immunolabeled specimens represents a new approach for the study of parasite cytoskeletal elements and their protein associations. [ABSTRACT FROM AUTHOR]

Giardia lamblia is a diplomonad that parasitizes the small intestine of vertebrates. The trophozoite is multiflagellar and its cytoskeleton presents a complex organization of microtubular structures. One of these, the adhesive disk, consists of a microtubular spiral. The median body, whose function is not yet determined, is also composed by microtubules. The cell has eight flagella and two microtubule sheets, known as the funis. In this study we used several antibodies and immunofluorescence microscopy to help in the characterization of these structures. We observed that Giardia tubulin reacts with antibodies raised against very distinct immunogens. The antibodies used were against: (1) α-tubulin from chicken embryo brain, Trypanosoma brucei, sea urchin sperm, Paramecium, acetylated α-tubulin from Paramecium, and tyrosinated α-tubulin, (2) β-tubulin from chicken embryo brain and Physarum polycephalum, and (3) an antibody with specificity to β-tubulin having as immunogen the FtsZ bacterial protein. Each cytoskeletal structure of Giardia presented a distinct pattern of labeling by the several antibodies used. These data indicate that even being considered one of the most ancient of organisms, Giardia shares similarities (at least in relation to tubulin) with other organisms. They also open some questions about the organization and composition of its microtubular structures. [ABSTRACT FROM AUTHOR]

The effects of metronidazole and furazolidone on Giardia lamblia trophozoites were analyzed by video-light and transmission electron microscopy. In addition, growth curves were drawn based on four concentrations of the drugs. The IC50 was 4.6 µM for metronidazole and 2.9 µM for furazolidone. By light microscopy we observed that metronidazole-treated cells maintained the characteristic body shape, but many showed bubbles in the dorsal and ventral surfaces. The effects of furazolidone include changes in the morphology (the cells were roundish) and also cytoplasmic extrusions. When observed by transmission microscopy, cells treated with metronidazole appeared rounder than usual and membranous structures were observed in the cytoplasm. Cells treated with furazolidone showed the cytoplasm depleted of its contents and great changes in volume. Our results show that furazolidone was more effective than metronidazole and its effects were observed in cells treated with 1 µg/ml (the lowest concentration) as early as 6 h after the start of exposure. [ABSTRACT FROM AUTHOR]

In the present study we analyzed the prognostic significance of several clinical, hematological, and histological parameters recorded at diagnosis in a consecutive series of 72 patients with primary myelofibrosis (PMF). Univariate analysis showed that the most significant indicators of poor survival were the following: age greater than 60, splenomegaly, anemia (hemoglobin > 10 g/dl), leukopenia (WBC < 4 x 10(9)/l or leukocytosis > 14 x 10(9)/l), and any of these histological features: adipose tissue and megakaryocyte reduction, prominent osteoblastic rims along the trabecular bone, presence of peritrabecular megakaryocytes (Mk), absence of normal or giant Mk. The multivariate analysis showed that only the level of hemoglobin and the presence of both normal Mk and fever independently influenced the prognosis. These parameters were used to set up a prognostic scoring system, allowing a feasible prognosis to be made for each patient at the time of diagnosis and identifying those patients in urgent need of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

2-methyl-8-ethylquinoline (MEQUI) was synthesized from ethylene glycol and an excess of 2-ethylaniline, operating in the vapour phase on K10 montmorillonite. Its structure was confirmed by 1H-NMR (200 MHz) spectra recorded in CDCl3 and DMSO. The synthesis of MEQUI is favoured by increasing the reaction temperature and amount of ethylene glycol, operating in a partially reducing atmosphere and feeding small amounts of water inside the organic feed. A possible reaction pathway proposed was confirmed by feeding a 2-ethylaniline/crotonaldehyde mixture. [ABSTRACT FROM AUTHOR]

In biotin-deficient guinea-pigs the number of circulating neutrophils is increased; lymphocytes carrying B and T markers are decreased. Incubation with biotin increases significantly the number of lymphocytes carrying B and T markers, from biotin-deficient guinea-pigs; no increase was observed when the lymphocytes from normal guinea-pigs were incubated. [ABSTRACT FROM AUTHOR]

The uptake of anthropogenic CO2 emissions by oceans has started decreasing pH and carbonate ion concentrations of seawater, a process called ocean acidification (OA). Occurring over centuries and many generations, evolutionary adaptation and epigenetic transfer will change species responses to OA over time. Trans-generational responses, via genetic selection or trans-generational phenotypic plasticity, differ depending on species and exposure time as well as differences between individuals such as gender. Males and females differ in reproductive investment and egg producing females may have less energy available for OA stress responses. By crossing eggs and sperm from the calcareous tubeworm Hydroides elegans (Haswell, 1883) raised in ambient (8.1) and low (7.8) pH environments, we observed that paternal and maternal low pH experience had opposite and additive effects on offspring. For example, when compared to offspring with both parents from ambient pH, growth rates of offspring of fathers or mothers raised in low pH were higher or lower respectively, but there was no difference when both parents were from low pH. Gender differences may result in different selection pressures for each gender. This may result in overestimates of species tolerance and missed opportunities of potentially insightful comparisons between individuals of the same species. [ABSTRACT FROM AUTHOR]

Introduction: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations.On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement).Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4 months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy.These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.Methods: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations.On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement).Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4 months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy.These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.Results: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations.On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement).Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4 months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy.These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life.Conclusion: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project ‘Treat to Target Italia’ was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations.On the basis of the published literature, their clinical experience, and the results of a survey among Italian dermatologists, the SB identified four relevant topics: (1) clinical remission; (2) quality of life; (3) abrogation of systemic inflammation; (4) safety. They drafted 20 statements addressing these four topics and submitted them to a panel of 28 dermatologists, in a Delphi process, to achieve consensus (greater than 80% agreement).Consensus was reached on all statements. Treatment goals defining clinical remission should include a 90% improvement from baseline in the Psoriasis Area and Severity Index (PASI90 response) or an absolute PASI score of less than or equal to 3. Patient’s quality of life and satisfaction are important targets. If PASI targets are achieved, there should be no or very low impact of psoriasis on quality of life [Dermatology Life Quality Index (DLQI) score less than or equal to 3]. If PASI or DLQI goals are not achieved within 3–4 months, treatment should be changed. Abrogation of systemic inflammation may be crucial for preventing or delaying inflammatory comorbidities. Safety is an equally important target as efficacy.These 20 consensus statements define the parameters of a treat-to-target strategy for psoriasis in Italy. It is hoped that use of these in the management of patients with psoriasis will improve treatment outcomes and patient health-related quality of life. [ABSTRACT FROM AUTHOR]