What's new in dermatopathology 2023: WHO 5th edition updates.

The 5th edition WHO Classification of Skin Tumors (2022) has introduced changes to nomenclature and diagnostics. Important differences are discussed below. Changes in each category of skin tumor have been detailed, with particular emphasis on meaningful advances in our understanding of the molecular pathogenesis of the skin's diverse tumor landscape.

Histopathologic Spectrum of Alopecias Seen in a Jamaican Setting.

ABSTRACT: Alopecia is common in Jamaican, primarily Afro-Caribbean patients. We performed a retrospective review examining the histopathologic alopecia diagnoses over ∼5 years. Requisition forms and pathology reports were assessed. Demographic/clinical/technical/diagnostic and pathologic findings of chronicity/severity data were recorded. Three hundred thirty-eight biopsies were included. The majority were 4 mm punches, grossed horizontally. The F:M ratio was 4.8:1, mean age = 42.7 years, and mean duration of alopecia = 5.1 years. Cicatricial alopecias (CAs) predominated over non-CAs (NCAs). The top 10 diagnoses were central centrifugal CA (21.9%), folliculitis decalvans (10.9%), multifactorial alopecias (10.1%), pattern hair loss (8%), lichen planopilaris (7.1%), alopecia areata (6.2%), discoid lupus erythematosus (6.2%), nonclassifiable lymphocytic scarring alopecias (5.6%), frontal fibrosing alopecia (5.3%), and nonspecific NCAs (5%). This contrasted with other richly pigmented populations where discoid lupus erythematosus predominates. Other interesting findings included relatively frequent folliculitis decalvans and lichen planus pigmentosus in 40.9% of frontal fibrosing alopecia cases. Scarring/nonscarring clinicopathologic congruence occurred in 83.4%.Regarding histopathologic features of severity/chronicity, CAs had markedly decreased hair counts. Perifollicular fibrosis affecting retained hairs occurred in 75% of CAs, moderate to severe in >50% of these. Approximately 50% of NCA samples demonstrated advanced miniaturization (T:V ratio <2:1). In our study, relatively young women with chronic hair loss and CA are most frequently biopsied. Central centrifugal CA is the most common diagnosis. Local features of chronic/severe disease are seen microscopically. Clinical impression of scarring/nonscarring correlates well with histopathology.

What’s new in dermatopathology 2023: WHO 5th edition updates

The 5th edition WHO Classification of Skin Tumors (2022) has introduced changes to nomenclature and diagnostics. Important differences are discussed below. Changes in each category of skin tumor have been detailed, with particular emphasis on meaningful advances in our understanding of the molecular pathogenesis of the skin’s diverse tumor landscape.

Local dynamics of topological magnetic defects in the itinerant helimagnet FeGe.

Chiral magnetic interactions induce complex spin textures including helical and conical spin spirals, as well as particle-like objects such as magnetic skyrmions and merons. These spin textures are the basis for innovative device paradigms and give rise to exotic topological phenomena, thus being of interest for both applied and fundamental sciences. Present key questions address the dynamics of the spin system and emergent topological defects. Here we analyse the micromagnetic dynamics in the helimagnetic phase of FeGe. By combining magnetic force microscopy, single-spin magnetometry and Landau-Lifschitz-Gilbert simulations we show that the nanoscale dynamics are governed by the depinning and subsequent motion of magnetic edge dislocations. The motion of these topologically stable objects triggers perturbations that can propagate over mesoscopic length scales. The observation of stochastic instabilities in the micromagnetic structure provides insight to the spatio-temporal dynamics of itinerant helimagnets and topological defects, and discloses open challenges regarding their technological usage.

Contrast-induced acute kidney injury after computed tomography prior to transcatheter aortic valve implantation.

AIM: To identify independent predictors of contrast medium-induced acute kidney injury (CI-AKI) after enhanced multidetector-row computed tomography (MDCT) prior to transcatheter aortic valve implantation (TAVI) in high-risk patients. MATERIALS AND METHODS: The present single-centre study analysed retrospectively 361 patients who were assessed using MDCT prior to TAVI. CI-AKI was defined as an increase in serum creatinine (SCr) of ≥ 25% or ≥ 0.5 mg/dl in at least one sample over baseline (24 h before MDCT) and at 24, 48, and 72 h after MDCT. RESULTS: A total of 38 patients (10.5%) experienced CI-AKI. As compared to patients without CI-AKI, they presented more frequently with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2), (81.6% versus 64.4%, p = 0.045) and tended to receive higher volumes of iodinated contrast media (ICM; 55.3% versus 39%, p = 0.057). There was a significant interaction between baseline eGFR and the amount of intravenous ICM administered (pfor interaction = <0.001) identifying the amount of ICM >90 ml as independent predictive factor of CI-AKI only in patients with baseline eGFR <60 ml/min/1.73m(2) (OR 2.615; 95% CI: 1.21-5.64). CONCLUSION: One in ten elderly patients with aortic stenosis undergoing MDCT to plan a TAVI procedure experienced CI-AKI after intravenous ICM injection. Intravenous administration of <90 ml of ICM reduces this risk in patients with or without pre-existing impaired renal function. However, in the majority of patients renal function recovers before the TAVI procedure.

Biodegradable-polymer-based drug-eluting stent for left main coronary artery disease.

Percutaneous coronary interventions (PCI) have gained widespread acceptation among cardiologists and among the general population for a variety of clinical indications, comprising from stable angina to ST-elevation acute myocardial infarction, due to the undisputed clinical benefit they provide and to their large availability and accessibility. Nonetheless PCI in the left main coronary artery (LMCA) is still controversial. Traditionally the revascularization of the LMCA has been one of those exceptions in which surgery was preferred to PCI, although PCI still found a slot in non-surgically-suitable cases or as bailout intervention. Some evidence has been recently generated, that challenges this traditional approach, and also about the clinical advantages of new-generation intracoronary devices, among them the drug-eluting stents with biodegradable polymers in abluminal coating. This scenario opens new horizons for the treatment of LMCA disease, in which a more prominent role of PCI can be anticipated.

Use of gel permeation chromatography for clean-up in the analysis of coccidiostats in eggs by liquid chromatography-tandem mass spectrometry.

An analytical method for determination and confirmation of nine coccidiostatics in eggs is reported. Ethyl acetate is used as extraction solvent, with satisfactory results, and simple automated clean-up is based on gel-permeation chromatography (GPC) . The target compounds are then analysed by liquid chromatography-electrospray ionization-tandem mass spectrometry. The method was validated in-house in accordance with Commission Decision 2002/657/EC. Trueness and precision were determined at four concentrations, and the mean errors obtained were <10 %, with relative standard deviations ranging from 3 to 18 %. For three non-authorized coccidiostatics (clopidol, ethopabate, and ronizadole), decision limit and detection capability were in the ranges 0.12-0.16 and 0.18-0.23 µg kg(-1), respectively. The results obtained prove the suitability of this new analytical method for routine monitoring of these substances in eggs.

Amlodipine reduces predicted risk of coronary heart disease in high-risk patients with hypertension in Spain (The CORONARIA Study).

We evaluated the efficacy and safety of amlodipine besylate alone or in combination with other antihypertensive agents in high-risk hypertensive patients in Spanish primary care. In this 1-year, open-label, prospective cohort study, 7468 patients were treated with amlodipine 5 - 10 mg as a monotherapy or as an add-on therapy to attain blood pressure control (target of < 140/90 mmHg or, in patients with conditions such as diabetes or chronic kidney disease, < 130/85 mmHg). At 12 months, the primary outcome (change from baseline in predicted 10-year coronary heart disease risk) was -8.6%, down from 24.7% at baseline (relative risk reduction, 31.6%). Change in blood pressure from baseline (162.5/95.3 mmHg) was -26.7/-14.6 mmHg, and 38.6% of patients achieved their blood pressure target. In summary, significant reductions in predicted coronary heart disease risk and blood pressure were observed with amlodipine both as a monotherapy and as an add-on therapy. Amlodipine was well tolerated and compliance with treatment was good.

High-throughput multiclass method for antibiotic residue analysis by liquid chromatography-tandem mass spectrometry.

A simple and rapid method has been developed for the residue analysis of 39 antibiotics (tetracyclines, quinolones, penicillins, sulfonamides and macrolides) in foodstuffs of animal origin. The method combines an effective extraction technique, which uses water-methanol as extracting solvent, with ultra-high-pressure liquid chromatography-tandem mass spectrometry, allowing both confirmation and quantification in a single chromatographic run. The multiresidue method has been validated in chicken muscle matrix according to European Union Decision 2002/657/EC. It has been implemented as a routine method in a Public Health Laboratory, instead of the five plates test and LC methods previously used.

Steroid binding sites in liver membranes: interplay between glucocorticoids, sex steroids, and pituitary hormones.

Steroid hormones activate target cells through specific receptors that discriminate among ligands based upon recognition of distinct structural features. For most known steroids, membrane and nuclear receptors co-exist in many target cells. However, while the structure of the nuclear receptors and their function as transcriptional activators of specific target genes is generally well understood, the identity of the membrane receptors remains elusive. Using pharmacological and biochemical approaches, we are beginning to characterize receptors for glucocorticoids and anabolic-androgenic steroids in male rat liver membranes. Male rat liver endoplasmic reticulum contains two steroid binding sites which are functionally related and associated with a 90-134 kDa oligomeric protein: (1) the low-affinity glucocorticoid binding site (LAGS), composed at least in part of two peptides (37 and 53 kDa) that bind glucocorticoids and (2) the stanozolol binding protein (STBP), composed at least in part of three peptides (22, 31, and 55 kDa) that bind the synthetic androgen stanozolol. These steroid binding proteins have many properties different from those of classical nuclear receptors, with the salient differences being a failure to recognize "classical" ligands for nuclear receptors together with marked differences in biochemical properties and physiological regulation. The mechanism of interaction of glucocorticoids with the LAGS can be clearly distinguished from that with STBP. Moreover, STBP shows an extremely narrow pharmacological profile, being selective for ST and its analog, danazol, among more than 100 steroids and non-steroidal compounds that were assayed, including those that are able to displace glucocorticoids from the LAGS. The level of LAGS activity undergoes dramatic variations following changes from the physiological serum levels of thyroid hormones, glucocorticoids, GH, vitamin A, and E2. However, neither thyroid hormones nor GH have a critical role on STBP activity. The STBP is functionally related to LAGS. We have suggested a novel mechanism for STBP whereby membrane-associated glucocorticoid binding activity is targeted by stanozolol (and 16beta-hydroxylated stanozolol): stanozolol modulates glucocorticoid activity in the liver through negative allosteric modulation of the LAGS resulting in an effective increase in classical GR-signaling by increasing glucocorticoid availability to the cytosolic GR.

Restricted access materials for sample clean-up in the analysis of trace levels of tetracyclines by liquid chromatography. Application to food and environmental analysis.

Restricted access materials (RAM) based on alkyl diol silica (ADS) porous particles were evaluated for the sample clean-up in tetracyclines analysis in milk and water samples by liquid chromatography. RAM with C(4), C(8) and C(18) bonded to the inner pore surfaces were tested, with C(8) providing the best performance. A switching column LC system which combines an ADS C(8) RAM column and an analytical C(18) column connected to a fluorimetric detector was used for tetracyclines analysis. The RAM clean-up removed large peaks that otherwise appeared in the initial time window of the chromatograms, attributed to proteins in milk samples and humic substances in water samples. Thus, quantification of analytes in real samples, especially of the most polar compounds such as oxytetracycline and tetracycline, was clearly improved.

The JAZ family of repressors is the missing link in jasmonate signalling.

Jasmonates are essential phytohormones for plant development and survival. However, the molecular details of their signalling pathway remain largely unknown. The identification more than a decade ago of COI1 as an F-box protein suggested the existence of a repressor of jasmonate responses that is targeted by the SCF(COI1) complex for proteasome degradation in response to jasmonate. Here we report the identification of JASMONATE-INSENSITIVE 3 (JAI3) and a family of related proteins named JAZ (jasmonate ZIM-domain), in Arabidopsis thaliana. Our results demonstrate that JAI3 and other JAZs are direct targets of the SCF(COI1) E3 ubiquitin ligase and jasmonate treatment induces their proteasome degradation. Moreover, JAI3 negatively regulates the key transcriptional activator of jasmonate responses, MYC2. The JAZ family therefore represents the molecular link between the two previously known steps in the jasmonate pathway. Furthermore, we demonstrate the existence of a regulatory feed-back loop involving MYC2 and JAZ proteins, which provides a mechanistic explanation for the pulsed response to jasmonate and the subsequent desensitization of the cell.

High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability.

The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.

Taponamiento cardiaco como manifestación inicial de un lupus eritematoso sistémico de comienzo tardío / Cardiac tamponade as initial manifestation of late onset systemic lupus erythematosus

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Análisis de la relación (correlación y asociación) entre la p185 y las variables moleculares RE, RP, pS2 y Cat D, en una serie de pacientes con cáncer de mama y ganglias positivos / Analisis of the relationship (correlation and association) between p 185 and the molecular variables RE, RP, pS2, and Cat D in a series of breast cancer patients with positive lymph nodes

Propósito: Analizar los resultados obtenidos de los estudios comparativos entre la sobreexpresión de la oncoproteína p185 determinada cuantitativamente y las variables moleculares RE, RP, pS2 y Cat D. Material y métodos: En una serie de 217 pacientes con cáncer de mama y ganglios positivos, con la oncoproteína p185 determinada cuantitativamente mediante un método ELISA, se llevaron a cabo estudios comparativos de Relación (Correlación y Asociación) del contenido de la p185 con las variables moleculares RE, RP, pS2 y Catepsina D.Resultados: Con una mediana de seguimiento de 50 meses (rango 9-90 meses) en nuestra serie, el estudio de correlación de Pearson entre los transformados logarítmicos de los niveles de p185 y de los receptores estrogénicos y de los receptores de progesterona no mostró correlación alguna, mientras que sí la hubo para la pS2 y la Catepsina D. Resultados similares se obtuvieron en el estudio de correlación de Spearman. Cuando la serie tumoral fue dicotomizada, en el grupo de tumores p185-negativos se observó una correlación positiva para RE, RP, pS2y CD. En el grupo de tumores p185-positivos se encontró una correlación negativa para RE y RP y correlación positiva para la pS2 y CD. La influencia del estado de la p185 sobre el contenido de RE, RP, hS2,CD fue determinada mediante el análisis de Mann-Whitney mostrando que los tumores con la p185 sobreexpresada tenían una mediana de los niveles de RE y RIP muy baja, igual para la pS2 y más alta para la CD que los tumores con concentraciones de p185 inferiores a 260 fmol/mg (35 fmol/mg). Similares resultados se observaron cuando se llevó a cabo el análisis de tabla de contingencia, y cuando los tumores fueron estratificados en cuatro categorías de p185: muy baja (p185 600 fmol/mg).Conclusiones: Nuestros resultados sugieren la identificación de una subpoblación tumoral con un fenotipo más agresivo y, presumiblemente, con un peor comportamiento evolutivo (AU)

Molecular characterization of StCDPK1, a calcium-dependent protein kinase from Solanum tuberosum that is induced at the onset of tuber development.

We isolated a full-length cDNA clone (StCDPK1) encoding a calcium-dependent protein kinase (CDPK) by screening a stolon tip cDNA library from potato plants (Solanum tuberosum L.). The predicted amino acid sequence of the cDNA reveals a high degree of similarity with other members of the CDPK family except in the N-terminal region. As described for other CDPKs, StCDPK1 has a putative N-terminal myristoylation sequence. A coupled transcription/translation system was used to demonstrate that this post-translational modification occurs in vitro. The behaviour of the myristoylated form of StCDPK1 during its purification on a phenyl-Sepharose column mimics that of the endogenous potato enzyme suggesting that this modification occurs in vivo. In addition, a possible palmitoylation site is present in StCDPK1. Southern blot analysis suggests that more than one CDPK isoform is present in potato plants. Northern blot analysis of steady-state mRNA levels for StCDPK1 in different tissues of potato plants shows that the transcript is differentially expressed in tuberizing stolons. The transcript appears in the early steps of tuber formation before the induction of other genes, such as Pin2 and patatin. This result parallels previous data on CDPK activity in potato plants which was highest at the beginning of tuberization. Our results suggest that StCDPK1 is developmentally regulated. The early and transient expression of this CDPK isoform in the tuberization process suggests that this kinase could trigger a cascade of phosphorylation events involved in tuber induction.