Real-life effectiveness and safety of baricitinib in patients with severe alopecia areata: A 24-week Italian study.

BACKGROUND: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows and eyelashes, for which treatments are limited. Baricitinib, an oral inhibitor of Janus kinases 1 and 2, has been recently approved to treat alopecia areata. MATERIALS AND METHODS: We conducted a retrospective study involving 23 medical centres across Italy, enrolling patients affected by severe alopecia areata (SALT >50), for more than 6 months. Clinical and trichoscopic assessment was performed at each visit and impact on quality of life, anxiety and depression were evaluated using the Skindex-16 and the Hospital Anxiety and Depression Scale (HADS), respectively. RESULTS: A total of 118 patients were enrolled, with a mean age of 39 years and a mean SALT >95. The mean value of the SALT score decreased from an average of 96.6 (±8.23 sd) to 48 (±35.2 sd) after 24 weeks of treatment and 42.3% of patients achieved a SALT 30, 31.3% a SALT 20 and 20.3% a SALT 10 by Week 24. Trichoscopic signs showed fewer yellow dots and black dots significantly earlier than hair regrowth. Adverse events during the treatment period (mild laboratory test abnormalities) were reported in 12.7% patients. No drop-out were registered. CONCLUSION: Data on the effectiveness and safety of baricitinib are promising and support the use of this drug in severe forms of AA, also in the early stages. We also suggest performing trichoscopy in order to reveal early response to therapy.

Fluorescence advanced videodermoscopy: a new method of hairs and scalp evaluation. Comparison with trichoscopy.

INTRODUCTION: Non-invasive diagnostic methods in clinical dermatology are widely used to reduce the need for invasive techniques, with great advantages in terms of cost and time. Dermoscopy is the reference test for the in vivo diagnosis of cutaneous lesions, and when it is performed on the scalp region it is named trichoscopy. Fluorescence advanced videodermoscopy (FAV) has been lately proposed as a new non-invasive method for the in vivo skin examination at high magnification, with cell-level resolution. So far, it has shown promising results for the assessment of melanocytic and vascular lesions and for the in vivo diagnosis of parasitosis. OBJECTIVES: This observational study aims to perform, for the first time, a morphologic study of healthy scalp and scalp elementary lesions using FAV and to compare it with trichoscopy. METHODS: We enrolled 90 healthy individuals for the evaluation of the scalp using FAV. Then, we recruited 53 patients with alopecia and collected images of the elementary lesions using FAV and trichoscopy. RESULTS: Three hundred healthy scalp FAV images of different epidermal layers, papillary dermis, follicular ostia and healthy hair shafts were collected. Three hundred and eighty FAV and trichoscopic images of alopecic scalp elementary lesions were collected, showing that FAV provided a more detailed observation than trichoscopy, with higher magnification and cellular resolution. CONCLUSION: Fluorescence advanced videodermoscopy may represent a new valid technique of support to trichoscopy, adding further information, increasing chances of diagnosis and decreasing the need of invasive procedures.

Wannier-Mott Excitons in Nanoscale Molecular Ices.

The absorption of light to create Wannier-Mott excitons is a fundamental feature dictating the optical and photovoltaic properties of low band gap, high permittivity semiconductors. Such excitons, with an electron-hole separation an order of magnitude greater than lattice dimensions, are largely limited to these semiconductors but here we find evidence of Wannier-Mott exciton formation in solid carbon monoxide (CO) with a band gap of >8 eV and a low electrical permittivity. This is established through the observation that a change of a few degrees K in deposition temperature can shift the electronic absorption spectra of solid CO by several hundred wave numbers, coupled with the recent discovery that deposition of CO leads to the spontaneous formation of electric fields within the film. These so-called spontelectric fields, here approaching 4×10^{7} V m^{-1}, are strongly temperature dependent. We find that a simple electrostatic model reproduces the observed temperature dependent spectral shifts based on the Stark effect on a hole and electron residing several nm apart, identifying the presence of Wannier-Mott excitons. The spontelectric effect in CO simultaneously explains the long-standing enigma of the sensitivity of vacuum ultraviolet spectra to the deposition temperature.

Angioleiomyoma in a conger (Conger conger).

A wild adult male conger Conger conger, captured by a SCUBA diver in the waters of coastal Italy, was sent for laboratory analysis due to the presence of multiple productive ulcerous skin lesions localized in the dorso-lateral body area, caudally to the gill operculum under the dorsal fin. The main mass was sessile, ulcerated and hemorrhaging in appearance and was surrounded by several smaller masses, which originated peripherally from the same mass or were isolated, always with a tendency to ulceration. Histology confirmed that the newly formed tissue originated from derma invading the closer tissues. The tumour consisted of spindle cells, each with an ovoidal nucleus and rarely with evident nucleoli, which were arranged in parallel or storiform patterns and were often surrounding blood-filled spaces discontinuously lined by endothelial cells. Tumour tissue was richly vascularized and no mitoses were seen. The overlying epidermis was ulcerated. Masson's trichrome technique indicated the presence of a small amount of perivascular connective tissue. No excessive glycogen storage, bacteria, virus or fungi were detected by periodic acid-Schiff (PAS)-reaction. Immunohistochemistry showed dot-like or diffuse cytoplasmic positivity against smooth muscle actin and the monoclonal antibody D2-40. CD34 exhibited relevant immunoreactivity at plasma membranes. Growth fraction evaluated using MIB-1 was <1%. Immunoreactions for wide spectrum CK, CK5/6, CK8, CK18, EMA, desmin, myoglobin, S-100, CD20, CD68, GFAP, and NSE were negative. Histopathological and immunohistochemical results supported a diagnosis of angioleiomyoma, a benign tumour of the muscular cellular component of the blood vessels. To our knowledge, this is the first report of such neoplasms in fishes in which monoclonal antibodies work on fish tissues, facilitating a useful immunohistochemical approach for differential diagnosis.

Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia.

BACKGROUND: It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status. METHODS: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAF(c.1799T>A) mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC. RESULTS: Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15-2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27-2.58; P=0.001), and BRAF(c.1799T>A) mutation (HR 2.16; 95% CI 1.25-3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09-5.75; P=0.77). CONCLUSION: Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation.

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI. METHODS: We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras(G12D) mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells. RESULTS: In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1(+) and -CL1(+). In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours. CONCLUSION: Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.

Clinical study on the efficacy and tolerability of a topical regenerative treatment in patients with telogen effluvium and mild androgenetic alopecia.

Hair loss may change the quality of life since modern society considers hair an essential element in beauty definition. The most common causes of hair loss are androgenetic alopecia (AGA) and telogen effluvium (TE). AGA requires a lifetime use of minoxidil or finasteride (and sometimes they lose efficacy over the years), whereas TE has no standardized therapy available. Our study focuses on a novel topical regenerative preparation that, by mimicking autologous PRP, can safely and efficiently improve hair loss in patients affected by TE and AGA.

Preparation and antioxidant activity of tyrosyl and homovanillyl ethers.

Preparation of tyrosyl and homovanillyl lipophilic derivatives was carried out as a response to the food industry's increasing demand for new synthetic lipophilic antioxidants. Tyrosyl and homovanillyl ethers were synthesized in high yields by a three-step procedure starting from tyrosol (Ty) and homovanillic alcohol (HMV). The antioxidant activity of these new series of alkyl tyrosyl and homovanillyl ethers was evaluated by the Rancimat test in a lipophilic food matrix and by the FRAP, ABTS and ORAC assays and compared to free Ty and HMV as well as two antioxidants widely used in the food industry, butylhydroxytoluene (BHT) and α-tocopherol. The results pointed out the higher activity of homovanillyl series in comparison with tyrosyl series with all the assayed methods. However, while both synthetic series were less antioxidant than BHT and α-tocopherol in a lipophilic matrix after their Rancimat test evaluation, homovanillyl alkyl ethers showed the best reducing power and radical scavenging activity of all evaluated compounds. This batch of synthetic lipophilic compounds, derived from biologically active compounds such as Ty and HMV, provide interesting and potentially bioactive compounds.

Gas phase Elemental abundances in Molecular cloudS (GEMS) II. On the quest for the sulphur reservoir in molecular clouds: the H2S case.

CONTEXT: Sulphur is one of the most abundant elements in the Universe. Surprisingly, sulphuretted molecules are not as abundant as expected in the interstellar medium and the identity of the main sulphur reservoir is still an open question. AIMS: Our goal is to investigate the H2S chemistry in dark clouds, as this stable molecule is a potential sulphur reservoir. METHODS: Using millimeter observations of CS, SO, H2S, and their isotopologues, we determine the physical conditions and H2S abundances along the cores TMC 1-C, TMC 1-CP, and Barnard 1b. The gas-grain model Nautilus is used to model the sulphur chemistry and explore the impact of photo-desorption and chemical desorption on the H2S abundance. RESULTS: Our modeling shows that chemical desorption is the main source of gas-phase H2S in dark cores. The measured H2S abundance can only be fitted if we assume that the chemical desorption rate decreases by more than a factor of 10 when n H > 2 × 104. This change in the desorption rate is consistent with the formation of thick H2O and CO ice mantles on grain surfaces. The observed SO and H2S abundances are in good agreement with our predictions adopting an undepleted value of the sulphur abundance. However, the CS abundance is overestimated by a factor of 5 - 10. Along the three cores, atomic S is predicted to be the main sulphur reservoir. CONCLUSIONS: The gaseous H2S abundance is well reproduced, assuming undepleted sulphur abundance and chemical desorption as the main source of H2S. The behavior of the observed H2S abundance suggests a changing desorption efficiency, which would probe the snowline in these cold cores. Our model, however, highly overestimates the observed gas-phase CS abundance. Given the uncertainty in the sulphur chemistry, we can only conclude that our data are consistent with a cosmic elemental S abundance with an uncertainty of a factor of 10.

Gas phase Elemental abundances in Molecular cloudS (GEMS): I. The prototypical dark cloud TMC 1.

GEMS is an IRAM 30m Large Program whose aim is determining the elemental depletions and the ionization fraction in a set of prototypical star-forming regions. This paper presents the first results from the prototypical dark cloud TMC 1. Extensive millimeter observations have been carried out with the IRAM 30m telescope (3 mm and 2 mm) and the 40m Yebes telescope (1.3 cm and 7 mm) to determine the fractional abundances of CO, HCO+, HCN, CS, SO, HCS+, and N2H+ in three cuts which intersect the dense filament at the well-known positions TMC 1-CP, TMC 1-NH3, and TMC 1-C, covering a visual extinction range from A V ~ 3 to ~20 mag. Two phases with differentiated chemistry can be distinguished: i) the translucent envelope with molecular hydrogen densities of 1-5×103 cm-3; and ii) the dense phase, located at A V > 10 mag, with molecular hydrogen densities >104 cm-3. Observations and modeling show that the gas phase abundances of C and O progressively decrease along the C+/C/CO transition zone (A V ~ 3 mag) where C/H ~ 8×10-5 and C/O~0.8-1, until the beginning of the dense phase at A V ~ 10 mag. This is consistent with the grain temperatures being below the CO evaporation temperature in this region. In the case of sulfur, a strong depletion should occur before the translucent phase where we estimate a S/H ~ (0.4 - 2.2) ×10-6, an abundance ~7-40 times lower than the solar value. A second strong depletion must be present during the formation of the thick icy mantles to achieve the values of S/H measured in the dense cold cores (S/H ~8×10-8). Based on our chemical modeling, we constrain the value of ζ H2 to ~ (0.5 - 1.8) ×10-16 s-1 in the translucent cloud.

Sono-activated persulfate oxidation of diclofenac: Degradation, kinetics, pathway and contribution of the different radicals involved.

Degradation of a diclofenac aqueous solution was performed using persulfate anions activated by ultrasound. The objective of this study was to analyze different parameters affecting the diclofenac (DCF) removal reaction by the ultrasonic persulfate (US/PS) process and to evaluate the role played by various intermediate oxidative species such as hydroxyl- and sulfate radicals, superoxide radical anion or singlet oxygen in the removal process as well as to determine a possible reaction pathway. The effects of pH, initial persulfate anion concentration, ultrasonic amplitude and temperature on DCF degradation were examined. Sulfate and hydroxyl radicals were involved in the main reaction pathway of diclofenac. Diclofenac amide and three hydroxy-diclofenac isomers (3´-hydroxy diclofenac, 4´-hydroxy diclofenac and 5-hydroxy diclofenac) were identified as reaction intermediates.

Localization of cholecystokinin in the zebrafish retina from larval to adult stage.

The peptide hormone cholecistokinin (CCK) plays a key role in the central and peripheral nervous system. It is known to be involved in the digestive physiology and in the regulation of food intake. Moreover, the CCK expression has also been detected in the retina of different vertebrates, including fish, although its biological activity in this tissue remains to be elucidated. In literature no data are yet available about the CCK-immunoreactivity in the zebrafish retina during development. Therefore, the aim of the study was to investigate the distribution of sulfated cholecystokinin octapeptide (CCK8-S) as a well preserved form during evolution in the zebrafish retina from 3days post hatching (dph) until adult stage, using immunohistochemistry in order to elucidate the potential role of this protein in the development and maintenance of normal retinal homeostasis. The cellular distribution of CCK in the retina was similar from 3 dph to 40days post fertilization (dpf) when immunoreactivity was found in the photoreceptors layer, in the outer plexiform layer, in the inner plexiform layer and, to a lesser extent, in the ganglion cell layer (GCL). Immunohistochemical localization at 50 dpf as well as in the adult stage was observed in a subpopulation of amacrine cells in the proximal inner nuclear layer, in the inner plexiform layer, in displaced amacrine cells and in retinal ganglion cells in the GCL. Our results demonstrate for the first time the occurrence of CCK in the zebrafish retina from larval to adult stage with a different pattern of distribution, suggesting different roles of CCK during retinal cells maturation.

Prognostic factors of survival in complicated viral and alcoholic cirrhosis without hepatocellular carcinoma. A retrospective study.

AIM: In several studies, attention is needed to one specific complication, in particularly to hepatocellular carcinoma, which modifies the natural history of liver cirrhosis. Thus, we performed a retrospective cohort analysis to clarify which complications, alone or in combination, are predictive factors of mortality in patients with viral or alcoholic cirrhosis without hepatocellular carcinoma. METHODS: Case records of 255 patients with decompensated viral or alcoholic cirrhosis between January 1990 and December 2000 were retrospectively analyzed. Relevant clinical and laboratory parameters, and their relationship to mortality, were studied. RESULTS: The mean duration of follow-up period was 29 months in which 178 patients (69.8%) died and 77 (31.8%) survived. None of the patients underwent liver transplantation. The cumulative mortality rate of patients with complicated cirrhosis was 38.8% after 1 year, 51.7% after 2 years, 61.1% after 3 years and 65.1% after 8 years. A multivariate Cox's model identified the following variables as significant: age (P=0.001), gastrointestinal bleeding (GB)-ascites combination (P=0.000), encephalopathy-GB-ascites (P=0.028), hepatorenal syndrome (HRS) (P=0.000), GB-spontaneous bacterial peritonitis (SBP) (P=0.001), alkaline phosphatase (ALP) (P=0.004) and the Child-Pugh score (P=0.000). CONCLUSION: The mortality in a group of patients with alcoholic cirrhosis is longer than in those with viral cirrhosis . Moreover, ascites in combination with other complications, HRS and hemorrage-SBP association are independent predictors of mortality in patients with complicated liver cirrhosis.

Eficacia de un programa de intervención en la promoción de hábitos saludables en personal militar de la Armada con sobrepeso y obesidad / Effectiveness of a Program to Promotion of Healthy Habits in Military Personnel of the Navy With Overweight and Obesity

Antecedentes y objetivos:el sobrepeso y obesidad en personal de la Armada puede provocar pérdida de aptitud para el servicio y complicaciones en la participación de misiones. El objetivo principal de este estudio pretende demostrar que una intervención basada en la promoción de hábitos saludables durante doce meses, pudo disminuir el índice de masa corporal (IMC) y mejorar parámetros bioquímicos en personal con obesidad o sobrepeso. Material y métodos:estudio cuasi-experimental, longitudinal, correlacional y comparativo (pre-test y post-test), durante doce meses, con dos grupos, intervención (GI) y control (GC). La muestra compuesta por 42 militares (n=21 por grupo), con IMC superior a 28 kg/m2. Se ejecutó en dos periodos: el primero a bordo de una fragata durante una misión; el segundo desde el final de la misión hasta completar doce meses. Se realizaron 18 sesiones personalizadas enfocadas a fomentar hábitos saludables en la dieta y favorecer la actividad física. Se monitorizaron variables antropométricas y bioquímicas en el GI. Del GC se obtuvieron los datos de IMC al inicio y final del estudio. Resultados:se produjo una disminución de la media del IMC de 33,71 kg/m2 a 30,91 kg/m2 en el GI; la adherencia fue consistente (90,5 %). A partir de los seis meses se observó un descenso en el número de participantes del GI (76,2 %) y un aumento del IMC con respecto a los valores obtenidos en la primera mitad (de 30,91 a 31,82 kg/m2). Se demostró una disminución del IMC al final de la intervención (p<0,005). Se evidencia una mejora de HDL-colesterol (p<0,04) y de triglicéridos (p<0,029) estadísticamente significativa. No se apreciaron cambios significativos en el GC. Conclusiones:el efecto de la intervención basada en la promoción de hábitos de vida saludables disminuye el IMC en personal afecto de sobrepeso y obesidad y mejora determinados parámetros bioquímicos relacionados con esta.(AU)

Antecedent and objectives: overweight and obesity in Navy personnel can cause loss of physical aptitude and complications in the development of missions. The main objective is to demonstrate that an intervention based on the promotion of healthy habits for 12 months, can reduce the Body Mass Index (BMI) and improve biochemical parameters in personnel affected by overweight or obesity. Material and Methods: quasi-experimental study, correctional, longitudinal, correctional and comparative (pre-test and post-test) for 12 months, with two groups, intervention (IG) and control (CG). The sample included 42 military personnel (n=21 per group), with a BMI higher than 28 kg/m2. It was carried out in two periods: the first period was carried out on board a frigate, taking advantage of its participation during a mission; the second since the end of the mission until completing the 12 months. 18 personalized sessions were held, focused on promoting healthy habits in both diet and promote physical activity. Anthropometric and biochemical dates were monitored in the IG. In the CG, BMI data were obtained at the beginning and end of the study. Results: During the first period, in the IG there was a decrease in BMI of 33,71 to 30,91 kg/m2 (p<0.05); Adherence is consistent (90,5 %). After 6 months a decrease in the number of participants (76,2 %) and an increase in BMI with respect to the values of the first half (from 30,91 kg/m2 to 31,82 kg/m2) were observed. A decrease in BMI was demonstrated at the end of the intervention. There is an improvement in HDL-cholesterol (p<0.04) and triglycerides (p<0.029). No significant changes were seen in GC. Conclusions: the effect of the nursing intervention based on the promulgation of healthy life habits decreases the BMI in personnel affected by overweight and obesity and improves certain biochemical parameters related to this.(AU)