Características clínicas e histopatológicas de los pacientes con enfermedades ampollares autoinmunes: estudio retrospectivo en el Hospital Privado Universitario de Córdoba / Clinical and histopathological characteristics of autoimmune blister diseases: a retrospective study in Private University Hospital of Córdoba

RESUMEN Las enfermedades ampollares autoinmunes (EAA) comprenden un conjunto heterogéneo de patologías de baja frecuencia de presentación con evolución crónica, remisiones, exacerbaciones y una importante morbimortalidad aun con tratamiento temprano y adecuado. Existen pocos estudios epidemiológicos en nuestra población que incluyan todo el espectro de enfermedades ampollares. Objetivos : Determinar las características clínico-epidemiológicas de las EAA, describir tratamientos realizados, tiempo de control de actividad de la enfermedad y tiempo desde iniciado el tratamiento hasta la remisión completa. Determinar recaídas de las patologías estudiadas, evaluando si existe relación entre las mismas y algún factor reconocido. Materiales y métodos : Estudio retrospectivo y descriptivo. Se incluyeron todos los pacientes con diagnóstico clínico, histopatológico y de inmunofluorescencia de las EAA que hayan tenido seguimiento por al menos un año en el servicio de dermatología del HPUC, en el período de enero de 2008 hasta noviembre de 2018. Resultados : Se incluyeron 53 pacientes de los cuales el 50,9% tenía Penfigoide Ampollar (PA), 22,6% Dermatitis Herpetiforme (DH) y 17% de Pénfigo vulgar (PV). La edad de los pacientes se encontró entre 21 y 90 años. Las ampollas tensas y erosiones fueron las presentaciones más comunes. Los tratamientos sistémicos se realizaron en el 74% de los casos. Registramos recaídas en el 63% de los casos y dos casos de muerte durante el tratamiento. Se estableció más frecuencia de enfermedad cardiovascular en los pacientes con PA. Conclusiones : Es el primer trabajo retrospectivo sobre EAA en nuestro medio. Nuestros hallazgos permiten determinar una frecuencia importante de PA en la consulta dermatológica y de DH, hecho no reportado en otros estudios con poblaciones similares.

ABSTRACT The autoimmune bullous diseases (ASD) comprise a heterogeneous group of pathologies with a low frequency of presentation that presents a chronic evolution, with remissions, exacerbations and an important morbidity and mortality even with early and adequate treatment. There are few epidemiological studies in our population that include the entire spectrum of bullous diseases. Objectives : To determine the clinical-epidemiological characteristics of AAS, describe treatments performed, control time of disease activity and time from treatment initiation to complete remission. Determine relapses of the studied pathologies, evaluating if there is a relationship between them and some recognized factor. Materials and methods : Retrospective and descriptive study. All patients with clinical, histopathological and immunofluorescence diagnosis of the AAS who had followed up for at least one year in the dermatology service of the HPUC, from January 2008 to November 2018 were included. Results: 53 were included. patients of which 50.9% had Bullous Pemphigoid (BP), 22.6% Dermatitis herpetiformis (DH) and 17% Pemphigus Vulgaris (PV). The age of the patients was between 21 and 90 years. Tense blistering forms and erosions were the most common forms of presentation. Systemic treatments were performed in 74% of the cases. We recorded relapses in 63% of the cases and two cases of death during the treatment. More frequency of cardiovascular disease was established in patients with BP. Conclusions : It is the first retrospective work on EAA in our environment. Our findings allow determining an important frequency of PA in the dermatological consultation and DH, fact this last, not reported in other studies with similar populations.

Deciphering interaction fingerprints from protein molecular surfaces using geometric deep learning.

Predicting interactions between proteins and other biomolecules solely based on structure remains a challenge in biology. A high-level representation of protein structure, the molecular surface, displays patterns of chemical and geometric features that fingerprint a protein's modes of interactions with other biomolecules. We hypothesize that proteins participating in similar interactions may share common fingerprints, independent of their evolutionary history. Fingerprints may be difficult to grasp by visual analysis but could be learned from large-scale datasets. We present MaSIF (molecular surface interaction fingerprinting), a conceptual framework based on a geometric deep learning method to capture fingerprints that are important for specific biomolecular interactions. We showcase MaSIF with three prediction challenges: protein pocket-ligand prediction, protein-protein interaction site prediction and ultrafast scanning of protein surfaces for prediction of protein-protein complexes. We anticipate that our conceptual framework will lead to improvements in our understanding of protein function and design.

White luminescence achieved by a multiple thermochromic emission in a hybrid organic-inorganic compound based on 3-picolylamine and copper(i) iodide.

Three copper(i) complexes have been obtained by the reaction of CuI with 3-picolylamine in acetonitrile solution and characterized by X-ray powder diffraction, both from synchrotron and laboratory radiation. Photophysical investigations in the solid state revealed highly efficient thermally-activated delayed fluorescence (TADF) with photoluminescence quantum yields (PLQYs) up to 18%. Notably, the complex [Cu2I2(3pica)]∞ displays a strong luminescence thermochromism due to the presence of both 1,3(X + M)LCT excited states and a lower-lying cluster-centered (3CC) one, leading to multiple emission at room temperature; as a result, a white luminescence is achieved with a PLQY of 4.5%.

Colagenosis perforante reactiva: A propósito de dos casos / Reactive perforating colagenosis: Report of two cases

Los desórdenes perforantes actualmente incluyen a la enfermedad de Kyrle, la elastosis perforante adquirida serpiginosa, la colagenosis perforante reactiva adquirida y la foliculitis perforante. Antes se consideraban entidades diferentes, pero debido a los hallazgos similares en la clínica e histopatología, se engloban dentro de este término unificador. Se manifiestan como pápulas y/o nódulos que presentan un tapón queratósico central. Su causa es desconocida, sin embargo, se las ha relacionado con distintas patologías sistémicas como la diabetes mellitus y la enfermedad renal crónica, entre otras. Se presentan dos casos de dermatosis perforante adquirida tipo colagenosis perforante reactiva, en un hombre de 69 años con antecedentes de diabetes mellitus tipo II y cirrosis hepática secundaria a infección por virus de hepatitis C y una paciente de 62 años con antecedente de diabetes mellitus tipo II.

Perforating disorders currently include Kyrle's disease, serpiginous perforating elastosis acquired, the acquired reactive perforating colagenosis and perforating folliculitis. Previously they were considered different entities, but due to similar findings in clinical and histopathology are now included within this umbrella term. The clinical findings are papules and / or nodules with a central keratotic plug and pruritus is the predominant symptom. It causes are still unknown; however they have been associated with various systemic diseases such as diabetes mellitus and chronic renal disease, among others. We report two cases of reactive perforating collagenosis one in a 69-year-old man with a history of type II diabetes mellitus and liver cirrhosis secondary to infection with hepatitis C and the other one in a 62-year-old woman with type II diabetes mellitus.

[60]Fullerene-porphyrin [n]pseudorotaxanes: self-assembly, photophysics and third-order NLO response.

By means of different spectroscopic techniques, we investigate a novel series of porphyrin derivatives (H2TPP), connected to dibenzo-24-crown-8 (DB24C8) moieties, which undergo self-assembly with different methano[60]fullerene units bearing dibenzylammonium (DBA) cations. The formation of both [2] and [3]pseudorotaxanes was proved by means of NMR, UV-Vis-NIR absorption and emission spectroscopies. With the support of molecular modelling studies, spectroscopic investigations showed the presence of a secondary interaction between the porphyrin and the C60 chromophores leading to the formation of different types of "face-to-face" assemblies. Remarkably, investigations of the non-linear optical response of these supramolecular systems showed that individual porphyrin and fullerene derivatives exhibit significantly lower second hyperpolarizability values when compared to their pseudorotaxanes functionalised counterparts. This proves that this class of supramolecular materials possesses relevant NLO response, which strongly depends on the structural arrangement of the chromophores in solution.

Evaluation of light-touch sensation in the buccal mucosa of leprosy patients.

OBJECTIVE: The aim of this study is to evaluate the light-touch sensation of the oral mucosa in leprosy patients. MATERIALS AND METHODS: A cross-sectional study included 228 adults, 133 being leprosy patients and 95 normal controls. To assess light-touch sensation, the five-filament standard Semmes-Weinstein kit in eight regions of the oral mucosa was used. Chi-square test was used to verify the differences in responses between the studied groups. RESULTS: Normal sensation was predominant in both groups, and diminished sensation was found also in the nonleprosy group. Normal controls showed diminished light-touch sensation in at least one point, which may be attributed to the definition of sensation normality. The chi-square test revealed no significant difference between the two groups (p = 0.43171). Severe diminished sensation was detected only in the leprosy group. CONCLUSION: It is concluded that altered light-touch sensation in the oral cavity may not be a common feature in leprosy. CLINICAL RELEVANCE: Decreased or lost sensation in skin lesions is a paramount in leprosy diagnosis; however, clinicians must be aware that this seems not to be true in the oral mucosa in leprosy cases for diagnosis purpose.

Evaluation of light-touch sensation in the buccal mucosa of leprosy patients

OBJECTIVE: The aim of this study is to evaluate the light-touch sensation of the oral mucosa in leprosy patients. MATERIALS AND METHODS: A cross-sectional study included 228 adults, 133 being leprosy patients and 95 normal controls. To assess light-touch sensation, the five-filament standard Semmes-Weinstein kit in eight regions of the oral mucosa was used. Chi-square test was used to verify the differences in responses between the studied groups. RESULTS: Normal sensation was predominant in both groups, and diminished sensation was found also in the nonleprosy group. Normal controls showed diminished light-touch sensation in at least one point, which may be attributed to the definition of sensation normality. The chi-square test revealed no significant difference between the two groups (p = 0.43171). Severe diminished sensation was detected only in the leprosy group. CONCLUSION: It is concluded that altered light-touch sensation in the oral cavity may not be a common feature in leprosy.CLINICAL RELEVANCE: Decreased or lost sensation in skin lesions is a paramount in leprosy diagnosis; however, clinicians must be aware that this seems not to be true in the oral mucosa in leprosy cases for diagnosis purpose.

Proceso de toma de decisión frente a embarazos no aceptados en mujeres mayores de 18 años que concurren al Hospital General de Agudos Teodoro Álvarez / Decision making process on an unwanted pregnancy in women older than 18 assisted in the Hospital General de Agudos Teodoro Álvarez

INTRODUCCIÓN Las Consejerías Integrales en Salud Sexual y Reproductiva, a través de la orientación en opciones frente a embarazos no aceptados, se presentan como estrategia para prevenir la principal causa de morbimortalidad materna en Argentina: las complicaciones de abortos inseguros. El dispositivo se encuentra en sus inicios; atraviesa un proceso de legitimación en el que se entrecruzan el reconocimiento de los derechos sexuales y reproductivos con los conflictos de valores morales y éticos asociados a la temática del aborto, dentro de un contexto legal restrictivo. OBJETIVOS Explorar las percepciones, los conocimientos y las prácticas en materia de decisiones reproductivas, considerando a las mujeres mayores de 18 años que consultan frente a un embarazo no aceptado. MÉTODOS El estudio se realizó en el Consultorio de Orientación en Opciones (COO) del Hospital General de Agudos Dr. Teodoro Álvarez, en la ciudad de Buenos Aires. Se utilizó un diseño exploratorio-descriptivo. El abordaje cuantitativo retrospectivo de los datos, recogidos previamente en historias clínicas (HC), fue acompañado de un abordaje cualitativo sobre entrevistas semiestructuradas (a mujeres que habían consultado espontáneamente al COO) y de observación participante de las consultas. RESULTADOS El procesamiento informático de las HC arrojó un perfil socio-demográfico heterogéneo. El análisis de contenido de las entrevistas y observaciones mostró que la mayoría de las mujeres llegaban decididas a interrumpir el embarazo. La influencia de terceros no se constituyó en un obstáculo para la toma autónoma de decisiones. Los principales facilitadores fueron el acompañamiento de otras personas significativas y la consejería. DISCUSIÓN Las mujeres logran un funcionamiento autónomo en el proceso de toma de decisión. El mayor obstáculo se vincula a la calidad y cantidad de información que poseen antes de la consulta. La consejería en opciones constituye un espacio que responde a sus expectativas.

Higher protein intake strategies in human milk fortification for preterms infants feeding. Auxological and neurodevelopmental outcome.

Postnatal growth restriction and failure to thrive still remain a major problem in Extremely Low Birth Weight (ELBW) infants . The goal for the nutritional care of these infants is to achieve rate of growth similar to those of the fetus in utero at the equivalent gestational age. Human milk fortified remains the best food for all these preterms. Two groups of preterm of weight 580-1250 g and gestational age 23-32 wk, were fed with different protein intake in the human/maternal milk fortified ( 3,5 g Kg-1 per day and 4,8 g Kg-1 per day in the control and intervention group respectively).The feeding tolerance, intrahospital growth, neurological outcome and anthropometric data until 12 months of corrected age, were evaluated. The protein supplemented group (PSG) showed an intrahospital highter growth rate ( mostly in head circumference, p 0,02, and length growth, p 0,04) only in the preterms with 580-980 g and 23-30 wk. In the same preterms, Griffith Development Mental Score at 3 and 12 months corrected age showed higher score than in the control group in the Performance (p 0,04) and Hearing/Language (p 0,03) items. The auxological evaluation in the postdischarge period showed in the PSG group mean z-score values for length higher than those in the control group at 9 (p 0,04) months of corrected age.

Shared resource laboratories: impact of new design criteria to consolidate flow cytometry diagnostic service.

INTRODUCTION: The Shared Resource Laboratory (SRL) model recently described for research activities would also appear to be highly suitable for diagnostic services. Using modern SRL design criteria and benchmarks, the aim of our study was to verify whether the consolidation of a diagnostic cytofluorimetric activity could improve the overall service. METHODS: Outcome indicators such as impact on analytical quality, clinical satisfaction, team work involvement, and economic performance were evaluated in the planning and setting up of a new central laboratory. Comparison with preconsolidation status allowed us to investigate possible indicators of improvement. RESULTS: A total of 30 140 cytofluorimetric analyses performed before and after consolidation at the Central Laboratory in Pievesestina in north-central Italy were evaluated. The overall score of the clinical satisfaction questionnaire (range, between 1 and 5) increased from 4.3 to 4.9. Full-time equivalent (FTE) operators were reduced from 9 to 4.5 and cytofluorimeters from 6 to 2; economic indicator analyses showed a 17.75% reduction in unitary test costs. CONCLUSIONS: The adoption of new benchmarks and design criteria increased the quality of cytofluorimetric analysis, thus improving specialized diagnostic services and promoting the shared resource clinical laboratory.

A case of hypocalcemia-related epilepsia partialis continua.

Epilepsia partialis continua (EPC) is a syndrome clinically defined as continuous spontaneous jerking confined to one part of the body, sometimes aggravated by action or sensory stimuli, occurring over hours, days or even years. In adults the more frequent recognized cause of EPC is an acute cerebrovascular disease. Acute severe hypocalcemia is a highly epileptogenic ionic disturbance, abnormally increasing neuronal excitability. In this short communication we describe the first probable case of acute hypocalcemia-related EPC. Eight months after a left parietal lobe cardioembolic stroke, a 74-year-old woman experienced a generalized tonic-clonic seizure for the first time in her life, at the beginning of a Clostridium difficile enterocolitis. Four days later, while the abdominal symptoms were clinically improving, continuous semi-rhythmic jerks of right face, shoulder and arm began suddenly. Despite several appropriated antiepileptic treatments those involuntary movements did not cease. On routine biochemical examination we noted a total calcium serum level of 1.2 mmol/L (normal range 2.1-2.8 mmol/L), not previously known. After intravenous calcium gluconate supplementation, the jerks started to fade, disappearing completely as a total calcium serum level of 1.9 mmol/L was reached. Two separated CT brain scans did not reveal new cerebral lesions. Neurophysiological studies did not show any cortical activity related to jerks. Taken together, the treatment refractoriness and the clinical improvement after ionic imbalance correction point towards a highly possible role of hypocalcemia in sustaining the activity of a previously silent epileptogenic focus.

Pollen discrimination and classification by Fourier transform infrared (FT-IR) microspectroscopy and machine learning.

The discrimination and classification of allergy-relevant pollen was studied for the first time by mid-infrared Fourier transform infrared (FT-IR) microspectroscopy together with unsupervised and supervised multivariate statistical methods. Pollen samples of 11 different taxa were collected, whose outdoor air concentration during the flowering time is typically measured by aerobiological monitoring networks. Unsupervised hierarchical cluster analysis provided valuable information about the reproducibility of FT-IR spectra of the same taxon acquired either from one pollen grain in a 25 x 25 microm2 area or from a group of grains inside a 100 x 100 microm2 area. As regards the supervised learning method, best results were achieved using a K nearest neighbors classifier and the leave-one-out cross-validation procedure on the dataset composed of single pollen grain spectra (overall accuracy 84%). FT-IR microspectroscopy is therefore a reliable method for discrimination and classification of allergenic pollen. The limits of its practical application to the monitoring performed in the aerobiological stations were also discussed.

p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.

BACKGROUND: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.

Potential of telomerase expression and activity in cervical specimens as a diagnostic tool.

AIMS: To evaluate the potential use of the immunohistochemical expression of telomerase and the measurement of its activity as diagnostic tools in the uterine cervix. METHODS: The fluorescent telomeric repeat amplification protocol (TRAP) assay was used to evaluate telomerase activity in a series of 43 cervical scrapings. Twenty five cases were cytologically classified as inflammatory, and/or metaplastic, and/or acanthotic, and 18 cases presented cell alterations compatible with mild, moderate, or severe cervical intraepithelial neoplasia (CIN). Immunohistochemistry was performed on a retrospective series of 86 archival, paraffin wax embedded blocks using a recently developed anti-hTERT (human telomerase reverse transcriptase) monoclonal antibody. RESULTS: Telomerase activity was expressed as arbitrary enzymatic units (AEU). Median values were 38.0 AEU for inflammatory non-dysplastic cell specimens, 33.5 AEU for CIN I, 41.0 AEU for CIN II, and 28.0 AEU for CIN III. The median percentage of immunoreactive dysplastic cells, as detected by immunohistochemistry, was significantly (p = 0.024) lower in CIN I (45%) than in more severe dysplastic (CIN II 70%, CIN III 80%) lesions. In contrast, no differences were seen in the enzymatic activity detected by the TRAP assay among the different dysplastic lesions. CONCLUSIONS: These data indicate that, using a molecular extra situ method, the telomerase activity of inflammatory and non-dysplastic elements masks the expected differences between mild and severe dysplasia. Conversely, an in situ approach permits the accurate identification of telomerase positive dysplastic cells.

Synthesis of sub-micromolar inhibitors of MraY by exploring the region originally occupied by the diazepanone ring in the liposidomycin structure.

The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was improved from 5300 to 140 nM. This improvement was correlated with the length and lipophilicity of substituents, but was found to be independent of the nature of the chemical bond generated. In addition, some of these inhibitors presented encouraging antibacterial activities.

Transglutaminase activity during senescence and programmed cell death in the corolla of tobacco (Nicotiana tabacum) flowers.

Corolla life span of undetached flowers of Nicotiana tabacum was divided into stages from the closed corolla (stage 1) through anthesis (stage 5) to death (stage 9). Senescence began around stage 6 in the proximal part, concomitantly with DNA laddering. Nuclear blebbing, DNA laddering, cell wall modification, decline in protein, water, pigment content and membrane integrity were observed during senescence and PCD. Transglutaminase activity was measured as mono- and bis-derivatives of putrescine (mono-PU; bis-PU) and bis-derivatives of spermidine (bis-SD). Bis-derivatives decreased with the progression of senescence, while mono-PU increased during early senescence; derivatives were present in different amounts in the proximal and distal parts of the corolla. In excised flowers, exogenous spermine delayed senescence and PCD, and caused an increase in free and acid-soluble conjugated PA levels. Bis-PU was the most abundant PA-derivative before DNA laddering stage; thereafter, bis-PU generally decreased and mono-PU became the most abundant derivative.

On the cumulant analysis of EXAFS in crystalline solids.

The analysis of temperature-dependent EXAFS spectra based on the cumulant expansion is critically reviewed, seeking for accurate relations between EXAFS parameters and physical properties of crystals. The treatment is based on the distinction between the real and effective distribution of distances, and is divided into three logical steps. (a) The connection between lattice dynamics and cumulants C(n)* of the real distribution is studied and the extent of the usual approximations are numerically evaluated. Atomic vibrations perpendicular to the bond direction make the EXAFS thermal expansion larger than the crystallographic one; the difference is connected to a shift of the effective pair potential rather than to its asymmetry. Peculiar information on lattice dynamics of crystals can be obtained from accurate EXAFS measurements and their cumulant analysis. (b) The differences between cumulants of the real and effective distribution (C(n)* and C(n), respectively) are calculated for various physically realistic distributions. The largest discrepancy concerns the first cumulant: C(1)* measures the thermal expansion of the interatomic bond, while C(1) is a better estimate of the crystallographic thermal expansion. (c) The convergence properties of the cumulant series are discussed and some phenomenological procedures are suggested to monitor and possibly work out the connected failures of the cumulant method. Benefits and risks of the use of an effective pair potential are at last debated.