Squamous Cell Carcinoma and Ledderhose Disease: A Case Report

Ledderhose disease is disorder of the plantar aponeurosis. This disease is not so common and can be tackled with a surgical or conservative approach. A case of a 73-year-old man came to our attention who had a 26-year history of painless bilateral plantar nodules coalescing into an indurated mass. An ulcerative nodule had been noted in the last 16 months on the right foot, in the absence of trauma, not responsive to conservative treatment, so we decided to perform a biopsy. The histopatologic examination showed squamous cell carcinoma, with warty, well-differentiated, low-grade malignancy. Surgical treatment was suggested, so, in pneumoischemia, we made a surgical incision including the skin lesion. Then we proceeded to sculpture the anterolateral thigh fasciacutaneous flap to obtain adequate soft tissue coverage. The tumor was completely removed. Current reconstructive possibilities comprise a good anatomofunctional recovery even in the case of large demolition requests for the therapy of advanced cases of the disease described in this article. Correlation between Ledderhose disease and the formation of malignant tumors has not been made as yet, but perhaps an element that could unite these pathologies can be researched in the lively cell proliferation that characterizes both. It would be interesting to analyze the biological substrate, as well as the systemic and local levels, in patients where both diseases are manifested

Nurse's experience of assessing pain on patients in the end of life in west Sweden

Bakgrund: Att bedöma smärta på patienter i livets slutskede har en central del i vårdandet och det krävs både kunskap och erfarenhet av sjuksköterskan men även empati, lyhördhet och kommunikation är viktiga delar för att smärtbedömningen ska fungera optimalt. Situationen är dock inte helt enkel för sjuksköterskan och smärtbedömning är en komplex del vid vårdandet av patienter i livets slutskede. Syfte: Syftet med vår studie är att beskriva sjuksköterskors upplevelser av att bedöma smärta hos patienter i livets slutskede på en onkologisk avdelning i västra Sverige. Metod: För att besvara vårt syfte användes två olika kvalitativa metoder. Den ena metoden var en kvalitativ gruppintervju och den andra metoden utgick från ett formulär med öppna frågor som skickades ut till sjuksköterskor verksamma på avdelningen. Frågorna som ställdes var öppna och berörde samma område som intervjun. Resultat: Analysen resulterade i tre teman: Komplexiteten av att bedöma smärta under den sista levnadsveckan att använda sig av resurser när patienten inte kan kommunicera verbalt samt otillräckliga rutiner vid smärtbedömning och dokumentation. Slutsats: Smärta är komplext och därför krävs det dels tydliga direktiv, och rutiner på avdelningen samt mer utbildning inom området för att skapa trygghet hos sjuksköterskor när de ska bedöma smärta hos en patient i livets slutskede

Етичні імперативи в соціальних науках (За матеріалами наукового повідомлення на засіданні Президії НАН України 7 листопада 2012 року)

У повідомленні наведено результати досліджень у галузі етики соціальних наук. За допомогою дискурс-етичного підходу показано проблематичність тези про етичну нейтральність соціальних наук, пояснено онтологічну специфіку їхнього предмета й етичні особливості соціально-наукових досліджень, а також запропоновано імператив соціального науковця.В сообщении приведены результаты исследований в области этики социальных наук. С помощью дискурс-этического подхода продемонстрирована проблематичность тезиса об этической нейтральности социальных наук, объяснены онтологическая специфика их предмета и этические особенности социально-научных исследований, а также предложен императив исследователя, работающего в области социально-научных дисциплин.The report contains some results of investigations in ethics of social science. By means of the discourse ethics approach, the author shows the problematical character of the thesis of ethical neutrality of social sciences, explains the ontological peculiarity of their subject and the specificity of ethical situation in which social scientists do research, and proposes an imperative of social scientist

Diverse Beliefs and Time Variability of Risk Premia

Why do risk premia vary over time? We examine this problem theoretically and empirically by studying the effect of market belief on risk premia. Individual belief is taken as a fundamental primitive state variable. Market belief is observable; it is central to the empirical evaluation and we show how to measure it. Our asset pricing model is familiar from the noisy REE literature but we adapt it to an economy with diverse beliefs. We derive equilibrium asset prices and implied risk premium. Our approach permits a closed form solution of prices; hence we trace the exact effect of market belief on the time variability of asset prices and risk premia. We test empirically the theoretical conclusions. Our main result is that, above the effect of business cycles on risk premia, fluctuations in market belief have significant independent effect on the time variability of risk premia. We study the premia on long positions in Federal Funds Futures, 3- and 6-month Treasury Bills (T-Bills). The annual mean risk premium on holding such assets for 1-12 months is about 40-60 basis points and we find that, on average, the component of market belief in the risk premium exceeds 50% of the mean. Since time variability of market belief is large, this component frequently exceeds 50% of the mean premium. This component is larger the shorter is the holding period of an asset and it dominates the premium for very short holding returns of less than 2 months. As to the structure of the premium we show that when the market holds abnormally favorable belief about the future payoff of an asset the market views the long position as less risky hence the risk premium on that asset declines. More generally, periods of market optimism (i.e. "bull" markets) are shown to be periods when the market risk premium is low while in periods of pessimism (i.e. "bear" markets) the market's risk premium is high. Fluctuations in risk premia are thus inversely related to the degree of market optimism about future prospects of asset payoffs. This effect is strong and economically very significant

Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature.

The exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only

Repeatability and reproducibility of applanation resonance tonometry : a cross-sectional study

Background: To assess repeatability (intra-observer variability) and reproducibility (inter-operator variability) of intraocular pressure (IOP) measurements with servo-controlled Bioresonator Applanation Resonance Tonometry (ART) and to evaluate possible influential factors. Methods: The study included 178 patients (115 glaucoma and 63 controls; one eye per subject). IOP was measured once with a Goldmann applanation tonometer (GAT) and twice by ART (ART1, ART2), in randomized sequence, by a single operator to assess intra-operator variability. Each ART measurement consisted on 3 readings. To assess inter-operator variability 2 evaluators performed 2 measurements each (in random order) on the same patient. Repeatability and reproducibility were assessed by the coefficient of variation (CoV) and intraclass correlation coefficient (ICC). Results: In the entire cohort, ART1 was 0.4 \ub1 2.2 mmHg (-7.0 to 5.7 mmHg) higher than ART2 (p = 0.03) regardless of test order. Intra-operator CoV was 7.0% \ub1 6.3%, and ICC was 0.80-0.92. Inter-operator CoV ranged between 5.7% \ub1 6.1% and 8.2% \ub1 7.2%, and ICC between 0.86 and 0.97. ART1 and 2 were respectively 1.7 \ub1 3.1 and 1.3 \ub1 3.1 mmHg higher than GAT (p < 0.01). Test-retest difference with ART fell within \ub11 mmHg in 41% of cases, within \ub12 mmHg in 70%, within \ub13 mmHg in 85%. 15% had a test-retest difference higher than \ub1 3 mmHg; Bland-Altman 95% intervals of confidence were -3.9 and +4.6 mmHg. Results were unaffected by age, diagnosis, central corneal thickness, keratometry, operator, randomization sequence. Conclusions: In most cases ART repeatability and reproducibility were high, with no differences due to patients' characteristics. ART measurements overestimated GAT by a mean of 1.3-1.7 mmHg

FAM123A Binds to Microtubules and Inhibits the Guanine Nucleotide Exchange Factor ARHGEF2 to Decrease Actomyosin Contractility

The FAM123 gene family comprises three members, FAM123A, the tumor suppressor WTX(FAM123B) and FAM123C. WTX is required for normal development and causally contributes to human disease, in part through its regulation of β-catenin-dependent WNT signaling. The roles of FAM123A and FAM123C in signaling, cell behavior and human disease remain less understood. We defined and compared the protein-protein interaction networks for each member of the FAM123 family by affinity purification and mass spectrometry. Protein localization and functional studies suggest that the FAM123 family members have conserved and divergent cellular roles. In contrast to WTX and FAM123C, we found that microtubule-associated proteins were enriched in the FAM123A protein interaction network. FAM123A interacted with and tracked dynamic microtubules in a plus-end direction. Domain interaction experiments revealed a ‘SKIP’ amino acid motif in FAM123A that mediated interaction with the microtubule tip tracking proteins EB1 and EB3, and therefore with microtubules. Cells depleted of FAM123A showed compartment-specific effects on microtubule dynamics, increased actomyosin contractility, larger focal adhesions and decreased cell migration. These effects required binding of FAM123A to and inhibition of the guanine nucleotide exchange factor ARHGEF2, a microtubule-associated activator of RhoA. Together, these data suggest that the ‘family-unique’ SKIP motif enables FAM123A to bind EB proteins, localize to microtubules and coordinate microtubule dynamics and actomyosin contractility

Blindness and glaucoma: A multicenter data review from 7 academic eye clinics

Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (''controls''). Blindness was defined as visual acuity-0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6%at the beginning, and 15.5%and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years)//conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14%in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved//it could be predicted by high initial MD, high initial IOP, and old age

A 48-week update of a multicentre real-life experience of dupilumab in adult patients with moderate-to-severe atopic dermatitis

The long-term efficacy and safety of dupilumab has been demonstrated in clinical trials and only in few real-world studies. We conducted an extension analysis from a previous 16-week study on 109 adult patients affected by moderate-to-severe atopic dermatitis treated with dupilumab. Eczema-Area-and-Severity-Index (EASI), itch numerical-rating-score (itch-NRS), Dermatology-Life-Quality-Index (DLQI) scores, drug survival rate and occurrence of adverse events after 24 and 48 weeks of dupilumab treatment were retrospectively collected. Dupilumab demonstrated sustained improvement of disease severity, pruritus, and quality of life in our series with an increasing percentage of patients gaining EASI75 and EASI90 response during the study period. Few patients interrupted treatment resulting in a very high drug survival rate. We also confirmed the favorable safety profile of the drug with absence of serious adverse events and serious infections throughout the 48-week period. The prevalence of conjunctivitis was low and mainly occurred in the mid-term with resolution of the majority of cases at 48 weeks