Description of two fatal cases of melioidosis in Mexican children with acute pneumonia: case report.

BACKGROUND: Melioidosis is an infectious disease caused by Burkholderia pseudomallei. In Mexico, the disease is rarely diagnosed in humans and there is no evidence of simultaneous environmental isolation of the pathogen. Here, we describe clinical profiles of fatal cases of melioidosis in two children, in a region without history of that disease. CASE PRESENTATION: About 48 h before onset of symptoms, patients swam in a natural body of water, and thereafter they rapidly developed fatal septicemic illness. Upon necropsy, samples from liver, spleen, lung, cerebrospinal fluid, and bronchial aspirate tissues contained Burkholderia pseudomallei. Environmental samples collected from the locations where the children swam also contained B. pseudomallei. All the clinical and environmental strains showed the same BOX-PCR pattern, suggesting that infection originated from the area where the patients were swimming. CONCLUSIONS: The identification of B. pseudomallei confirmed that melioidosis disease exists in Sonora, Mexico. The presence of B. pseudomallei in the environment may suggest endemicity of the pathogen in the region. This study highlights the importance of strengthening laboratory capacity to prevent and control future melioidosis cases.

Possible female philopatry of the smooth hammerhead shark Sphyrna zygaena revealed by genetic structure patterns.

We assessed the spatial pattern of genetic structure of smooth hammerhead shark Sphyrna zygaena in 10 localities from the Northern Mexican Pacific. A total of 35 haplotypes were identified in 129 sequences of the mtDNA control region. The results showed slight but significant genetic structure among localities (ΦST = 0.044, P < 0.001). In addition, the localities with highest number of juveniles were genetically different (ΦST = 0.058, P < 0.024), which may be representative of nursery areas. The genetic differentiation pattern can be associated to female philopatry and preference for particular birthing sites. Finally, historical demography shows that S. zygaena populations present a recent demographic expansion that occurred during glacial events in the late Pleistocene to early Holocene.

Keratocyst Capnocytophaga superinfection.

INTRODUCTION: Capnocytophaga spp are Gram-negative bacteria that cause severe infections in immunosuppressed patients. This situation is extremely rare in immunocompetent patients. CASE REPORT: This clinical report describes the unusual infection of an immunocompetent patient with Capnocytophaga spp. The imaging studies showed the existence of a cyst in the left jawbone. After treatment and a microbiological study of the content, it was found to be an outbreak of septicaemia. DISCUSSION: Capnocytophaga spp, commensal bacteria of the oral cavity, can lead to serious illness and that is why an empirical treatment is needed until a diagnostic confirmation can be obtained.

Explainable machine learning on baseline MRI predicts multiple sclerosis trajectory descriptors.

Multiple sclerosis (MS) is a multifaceted neurological condition characterized by challenges in timely diagnosis and personalized patient management. The application of Artificial Intelligence (AI) to MS holds promises for early detection, accurate diagnosis, and predictive modeling. The objectives of this study are: 1) to propose new MS trajectory descriptors that could be employed in Machine Learning (ML) regressors and classifiers to predict patient evolution; 2) to explore the contribution of ML models in discerning MS trajectory descriptors using only baseline Magnetic Resonance Imaging (MRI) studies. This study involved 446 MS patients who had a baseline MRI, at least two measurements of Expanded Disability Status Scale (EDSS), and a 1-year follow-up. Patients were divided into two groups: 1) for model development and 2) for evaluation. Three descriptors: ß1, ß2, and EDSS(t), were related to baseline MRI parameters using regression and classification XGBoost models. Shapley Additive Explanations (SHAP) analysis enhanced model transparency by identifying influential features. The results of this study demonstrate the potential of AI in predicting MS progression using the proposed patient trajectories and baseline MRI scans, outperforming classic Multiple Linear Regression (MLR) methods. In conclusion, MS trajectory descriptors are crucial; incorporating AI analysis into MRI assessments presents promising opportunities to advance predictive capabilities. SHAP analysis enhances model interpretation, revealing feature importance for clinical decisions.

Effect of aggressive vs conservative screening and confirmatory test on time to extubation among patients at low or intermediate risk: a randomized clinical trial.

PURPOSE: This study aimed to determine the best strategy to achieve fast and safe extubation. METHODS: This multicenter trial randomized patients with primary respiratory failure and low-to-intermediate risk for extubation failure with planned high-flow nasal cannula (HFNC) preventive therapy. It included four groups: (1) conservative screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and positive end-expiratory pressure (PEEP) ≤ 8 cmH2O plus conservative spontaneous breathing trial (SBT) with pressure support 5 cmH2O + PEEP 0 cmH2O); (2) screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and PEEP ≤ 8 plus aggressive SBT with pressure support 8 + PEEP 5; (3) aggressive screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 8 + PEEP 5; (4) screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 5 + PEEP 0. Primary outcomes were time-to-extubation and simple weaning rate. Secondary outcomes included reintubation within 7 days after extubation. RESULTS: Randomization to the aggressive-aggressive group was discontinued at the interim analysis for safety reasons. Thus, 884 patients who underwent at least 1 SBT were analyzed (conservative-conservative group, n = 256; conservative-aggressive group, n = 267; aggressive-conservative group, n = 261; aggressive-aggressive, n = 100). Median time to extubation was lower in the groups with aggressive screening (p < 0.001). Simple weaning rates were 45.7%, 76.78% (205 patients), 71.65%, and 91% (p < 0.001), respectively. Reintubation rates did not differ significantly (p = 0.431). CONCLUSION: Among patients at low or intermediate risk for extubation failure with planned HFNC, combining aggressive screening with preventive PEEP and a conservative SBT reduced the time to extubation without increasing the reintubation rate.

Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients.

BACKGROUND: Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1-4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. METHODS: To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population. RESULTS: Patients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T > G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C > T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T > G); and 11.11%, 8.82% and 9.00% for T (c.458C > T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33. CONCLUSIONS: The novel loss-of function mutation of CTSC gene (c.203 T > G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.

A Free-Market Environmentalist Enquiry on Spain's Energy Transition along with Its Recent Increasing Electricity Prices.

This paper analyzes the Spanish energy transition's general situation and its increasing electricity prices in recent years from a free-market environmentalist (FME) approach. We hypothesize and argue that high taxes, high government subsidies, and government industrial access restrictions breach private property rights, hindering Spain's renewable energy (RE) development. Our paper discovers that Spain's state-interventionist policies have increased the cost of the energy and power industries, leading to electricity prices remaining relatively high before and after the outbreak of the COVID-19 pandemic. After reviewing the literature on the FME approach and Spain's case, a Box-Jenkins (ARIMA) model is used to clarify the economic performance of the Spanish electricity industry with a proposal for forecasting electricity prices. It is observed that Spain fails the EU and its national goal of providing an affordable energy price as a part of the green energy transition. Finally, free-market environmental solutions and policy reforms are proposed to facilitate Spain's energy transition.

Rho-kinase in sea urchin eggs and embryos.

The activation of sea urchin eggs at fertilization provides an ideal system for studying the molecular events involved in cellular activation. Rho GTPases, which are key signaling enzymes in eukaryotes, are involved in sustaining the activation of sea urchin eggs; however, their downstream effectors have not yet been characterized. In somatic cells, RhoA regulates a serine/threonine kinase known as Rho-kinase (ROCK). The activity of ROCK in early sea urchin development has been inferred, but not tested directly. A ROCK gene was identified in the sea urchin (Strongylocentrotus purpuratus) genome and the sequence of its cDNA determined. The sea urchin ROCK (SpROCK) sequence predicts a protein of 158 kDa with >72% and 45% identities with different protein orthologues of the kinase catalytic domain and the complete protein sequence, respectively. SpROCK mRNA levels are high in unfertilized eggs and decrease to 35% after 15 min postfertilization and remain low up to the 4 cell stage. Antibodies to the human ROCK-I kinase domain revealed SpROCK to be concentrated in the cortex of eggs and early embryos. Co-immunoprecipitation assays indicate that RhoA and SpROCK are physically associated. This association is destroyed by treatment with the C3 exoenzyme and with the ROCK antagonist H-1152. H-1152 also inhibited DNA synthesis in embryos. We conclude that the Rho-dependent signaling pathway, via SpROCK, is essential for early embryonic development.

Concordance and interaction of guanine nucleotide dissociation inhibitor (RhoGDI) with RhoA in oogenesis and early development of the sea urchin.

Rho GTPases are Ras-related GTPases that regulate a variety of cellular processes. In the sea urchin Strongylocentrotus purpuratus, RhoA in the oocyte associates with the membrane of the cortical granules and directs their movement from the cytoplasm to the cell cortex during maturation to an egg. RhoA also plays an important role regulating the Na(+) -H(+) exchanger activity, which determines the internal pH of the cell during the first minutes of embryogenesis. We investigated how this activity may be regulated by a guanine-nucleotide dissociation inhibitor (RhoGDI). The sequence of this RhoA regulatory protein was identified in the genome on the basis of its similarity to other RhoGDI species, especially for key segments in the formation of the isoprenyl-binding pocket and in interactions with the Rho GTPase. We examined the expression and the subcellular localization of RhoGDI during oogenesis and in different developmental stages. We found that RhoGDI mRNA levels were high in eggs and during cleavage divisions until blastula, when it disappeared, only to reappear in gastrula stage. RhoGDI localization overlaps the presence of RhoA during oogenesis and in embryonic development, reinforcing the regulatory premise of the interaction. By use of recombinant protein interactions in vitro, we also find that these two proteins selectively interact. These results support the hypothesis of a functional relationship in vivo and now enable mechanistic insight for the cellular and organelle rearrangements that occur during oogenesis and embryonic development.

Rho1 and other GTP-binding proteins are associated with vesicles carrying glucose oxidase activity from Fusarium oxysporum f. sp. lycopersici.

In eucaryotic cells, the delivery of a secreted protein to the plasma membrane via vesicles must include transport, recognition, and fusion events. Proteins exposed on the cytoplasmic face of the secretory vesicles play a role in these events; these include the GTP-binding proteins, which are crucial components in this process. Fractions enriched with vesicles carrying glucose oxidase (GOX) activity from Fusarium oxysporum f. sp. lycopersici, a soilborne fungal pathogen causing vascular wilt on tomato plants, were obtained using two successive sucrose gradients, the first a linear-log and the second an isopycnic gradient. In this study, we used the following Fusarium strains: a wild-type and a strain carrying a Δrho1 loss-of-function mutation (presenting dramatically reduced virulence). By ADP-ribosylation with C3 exotoxin, and Western blot analysis with specific antibodies, we identified the small GTPases Rho1, Rho4, Cdc42 and Rab8, and a heterotrimeric Gα protein associated with vesicles carrying GOX activity. This was done for both strains, with the exception of Rho1, which was absent in the mutant strain; in addition, the levels of the Cdc42 protein were observed to be higher in the Δrho1 strain. These data indicate that three Rho proteins, Rho1, Rho4, and Cdc42, are present in secretory vesicles carrying GOX activity in F. oxysporum, and that Rho1 is not essential for the transport and secretion of, at least, cargo proteins carried in secretory vesicles, or Cdc42/Rho4 can fulfill its role in these events.

Interpositional collagenated cancellous bone blocks for nasal dorsum augmentation: A new technique for nasomaxillary hypoplasia treatment.

Nasomaxillary hypoplasia is a rare congenital malformation involving the middle third of the face. The present paper describes a novel technique for restoring the nasal projection in a patient with nasomaxillary hypoplasia, analyses its advantages and limitations, and discusses its potential applicability in other similar contexts. After orthognathic surgery, lateral osteotomies of the nasal bones were performed integrally with a piezoelectric device using a long cutting saw tip through the intraoral approach. The nasal bones were then projected by interpositioning two triangular-shaped collagenated cancellous bone graft blocks on each side in the osteotomies between the nasal and the frontal processes of the maxillary bones. Cone-beam computed tomography (CBCT) data was used to perform a morphometric analysis at one and 12 months of follow-up through image superimposition, which revealed a stable increased projection of the nasal dorsum and an anterior nasal spine (ANS) of 5.18 mm and 5.52 mm, respectively. The results of this case suggest that the technique affords satisfactory nasal dorsum augmentation while avoiding the use of permanent foreign materials, with minimal morbidity, no unsightly and visible scars, great patient satisfaction, and adequate stability at 12 months of follow-up.

Comparison between cultured and wild Pacific white shrimp (Penaeus vannamei) vitellogenesis: next-generation sequencing and relative expression of genes directly and indirectly related to reproduction.

Shrimp fisheries are among the most important fisheries worldwide, and shrimp culture has increased considerably in recent years. Most current studies on reproduction-related genes have been conducted on cultured shrimp. However, gene expression is intimately linked to physiological and environmental conditions, and therefore an organism's growth environment has a great influence on reproduction. Thus, gene expression profiling, should be applied in fisheries studies. Here, we identified the expression patterns of 76 reproduction-related genes in P. vannamei via the analysis of pooled transcriptomes from a time-series experiment encompassing a full circadian cycle. The expression patterns of genes associated both directly (Vtg, ODP, and ProR) and indirectly (FAMet, CruA1, and CruC1) with reproduction were evaluated, as these genes could be used as molecular markers of previtellogenic and vitellogenic maturation stages. The evaluated genes were prominently upregulated during vitellogenic stages, with specific expression patterns depending on the organism's environment, diet, and season. Vtg, ProR, ODP, and FaMet could serve as molecular markers for both wild and cultured organisms.

Engineering and directed evolution of a Ca2+ binding site A-deficient AprE mutant reveal an essential contribution of the loop Leu75-Leu82 to enzyme activity.

An aprE mutant from B. subtilis 168 lacking the connecting loop Leu(75)-Leu(82) which is predicted to encode a Ca(2+) binding site was constructed. Expression of the mutant gene (aprEDeltaLeu(75)-Leu(82)) produced B. subtilis colonies lacking protease activity. Intrinsic fluorescence analysis revealed spectral differences between wild-type AprE and AprEDeltaL(75)-L(82). An AprEDeltaL(75)-L(82) variant with reestablished enzyme activity was selected by directed evolution. The novel mutations Thr(66)Met/Gly(102)Asp located in positions which are predicted to be important for catalytic activity were identified in this variant. Although these mutations restored hydrolysis, they had no effect with respect to thermal inactivation of AprEDeltaL(75)-L(82) T(66)M G(102)D. These results support the proposal that in addition to function as a calcium binding site, the loop that connects beta-sheet e3 with alpha-helix c plays a structural role on enzyme activity of AprE from B. subtilis 168.

Crisis en urgencias: una vista a las características clínicas y terapéuticas a través de 122 pacientes / Seizures in the emergency service: the clinical and therapeutic characteristics of 122 patients

Introducción Las crisis epilépticas son un motivo frecuente de consulta en los servicios de urgencias hospitalarias. Llegar al diagnóstico correcto puede ser complejo, y es fundamental decidir cuándo y qué medicamento anticrisis (MAC) pautar. Nuestro objetivo es detallar las características de los pacientes que consultaron por este motivo en un hospital mediano. Pacientes y métodos Estudio observacional retrospectivo de todos los pacientes mayores de edad que consultaron en el servicio de urgencias del Hospital Universitario Lucus Augusti entre enero de 2022 y enero de 2023 con diagnóstico al alta de crisis epiléptica. Se registraron variables demográficas, los antecedentes, si era una primera crisis, el número de éstas, si se inició un MAC y cuál, el diagnóstico, qué pruebas se realizaron y si se interconsultó con la guardia de neurología. Resultados Se diagnosticó a 122 pacientes de crisis epilépticas en urgencias. El 50,8% eran mujeres. La media de edad fue de 69,8 años. Se solicitó valoración por neurología en un 47,6%. El 50,8% presentó una primera crisis. No se llegó al diagnóstico en un 46% de los casos, de los cuales sólo 10 fueron valorados por neurología. La etiología más frecuente fue la vascular. Se realizó un electroencefalograma en un 41,8%. El levetiracetam fue prácticamente el único fármaco utilizado cuando no se consultó con neurología. Conclusiones La valoración precoz de los pacientes con una primera crisis en urgencias por un especialista en neurología es determinante para el diagnóstico de epilepsia. Cuando no se interconsulta, casi siempre se pauta el mismo MAC. (AU)

INTRODUCTION Epileptic seizures are a common cause of admission in emergency services at hospitals. Performing the correct diagnosis can be difficult, and deciding when and which anti-seizure medication (ASM) to prescribe is critical. Our objective is to detail the characteristics of patients treated in a medium-sized hospital for this reason. PATIENTS AND METHODS A retrospective observational study was performed, including all the adult patients treated by the emergency service of the Lucus Augusti University Hospital between January 2022 and January 2023 with a diagnosis of epileptic seizure on discharge. The study recorded their demographic variables, history, whether it was their first seizure, the number of seizures, whether an anti-seizure medication was administered and which one, the diagnosis, the tests performed, and whether the patient was referred to the neurology service. RESULTS A total of 122 patients were diagnosed with epileptic seizures in the emergency service. 50.8% of the patients were women. The mean age was 69.8 years. Neurological assessment was requested for 47.6%. 50.8% presented their first seizure. No diagnosis was performed in 46% of the cases, of which only 10 were evaluated by the neurology service. The most common etiology was vascular. An electroencephalogram was performed on 41.8%. Levetiracetam was practically the only drug administered when the neurology department was not consulted. CONCLUSIONS Early evaluation of patients with their first seizure in the emergency service by a neurological specialist is crucial for the diagnosis of epilepsy. The same anti-seizure medication is almost always prescribed when no cross-consultation takes place. (AU)

Alargamiento estético de corona con planeación digital mediante el uso de guía quirúrgica / Esthetic crown lengthening with digital planning using a surgical guide

Introducción: el alargamiento de corona relacionado con la estética tiene como objetivo revelar una longitud adecuada de la corona y disminuir la exposición gingival. El procedimiento incluye gingivectomía y alveolectomía para restablecer el tejido gingival supracrestal requerido protésicamente según la dimensión fisiológica. Mediante un escaneo intraoral del maxilar, mandíbula y posición intercuspídea máxima y utilizando un software especializado, se diseña de manera digital la forma de los dientes y el contorno gingival. Este diseño genera una imagen de la restauración estética deseada para el prostodoncista y periodoncista. La fabricación física del diseño es asistida por computadora (CAD-CAM), creando una guía quirúrgica de resina acrílica moldeada al vacío para determinar la longitud de la corona clínica requerida en la cirugía. Objetivo: el caso interdisciplinario presentado describe una técnica innovadora empleando el flujo digital mediante un software que, a partir de un escaneo oral, diseña de manera digital un Mock-Up utilizado como guía para la cirugía periodontal. Presentación del caso: acude a clínica de la Maestría en Periodoncia de la Universidad Autónoma de Coahuila (UAdeC) paciente de 52 años, ASA I, para una cirugía periodontal con fines estéticos. Se procedió a la cirugía, colocando el Mock-Up en la región anterosuperior como guía para la gingivectomía. Luego, se realizó el levantamiento de colgajo antes de la alveolectomía, tomando en cuenta la longitud del tejido gingival supracrestal. Por último, se suturaron los tejidos blandos con técnica de colchonero horizontal. Resultados: siete días después, se retiran los puntos apreciando una cicatrización correcta y uniforme de los tejidos. Conclusiones: este abordaje digital ofrece una reducción significativa del tiempo quirúrgico, además de una estética satisfactoria y una precisa arquitectura gingival (AU)

Introduction: crown lengthening for aesthetic purposes aims to reveal an adequate crown length and reduce gingival exposure. The procedure includes gingivectomy and alveolectomy to restore the prosthetically required supracrestal gingival tissue according to physiological dimensions. Through an intraoral scan of the maxilla, mandible, and maximum intercuspidal position, and using specialized software, the shape of the teeth and the gingival contour are digitally designed. This design generates an image of the desired aesthetic restoration for the prosthodontist and periodontist. The physical fabrication of the design is computer-assisted (CAD-CAM), creating a vacuum-formed acrylic resin surgical guide to determine the clinical crown length required in surgery. Objective: the presented interdisciplinary case describes an innovative technique using digital workflow through software that, from an oral scan, digitally designs a Mock-Up used as a guide for periodontal surgery. Case presentation: a 52-year-old ASA I patient attended the Periodontics Master's clinic at Universidad Autónoma de Coahuila (UAdeC) for periodontal surgery with aesthetic purposes. The surgery was performed by placing the Mock-Up in the anterosuperior region as a guide for gingivectomy. Then, a flap was raised before the alveolectomy, considering the length of the supracrestal gingival tissue. Finally, the soft tissues were sutured with a horizontal mattress suture technique. Results: seven days later, the sutures were removed, showing correct and uniform tissue healing. Conclusions: this digital approach offers a significant reduction in surgical time, in addition to satisfactory esthetics and precise gingival architecture (AU)

Latino caregivers' beliefs about asthma: causes, symptoms, and practices.

BACKGROUND AND OBJECTIVE: This study examined belief systems of Latino caregivers who have children with asthma from Puerto Rican and Dominican backgrounds who resided on the Island of PR and the Mainland. The goal of this study was to document similarities and differences in beliefs about the causes, symptoms, and treatments of asthma across two sites and two Latino ethnic sub-groups of children who remain the most at risk for asthma morbidity. METHODS: Participants included 100 primary caregivers of a child with asthma; 50 caregivers from Island PR and 50 caregivers from mainland RI were interviewed (at each site; 25 caregivers were from Puerto Rican backgrounds and 25 caregivers were from Dominican backgrounds). The interview included an assessment of demographic information and beliefs about the causes and symptoms of asthma and asthma practices. RESULTS: Results indicated more similarities in beliefs about the causes and symptoms of asthma across site and ethnic group. The majority of differences were among beliefs about asthma practices by site and ethnic group. For example, a higher proportion of caregivers from Island PR, particularly those of Dominican descent, endorsed that a range of home and botanical remedies are effective for treating asthma. CONCLUSIONS: Results from this study point to several interesting directions for future research including larger samples of Latino caregivers with children who have asthma. A discussion of the importance of understanding cultural beliefs about asthma and asthma practices is also reviewed.

Postoperative chronic pain in arthroplasty papillon-lefèvre syndrome: 17-year dental follow-up: case report / Síndrome de papillon-lefèvre: seguimiento dental de 17 años: reporte de caso

Introduction: The present report describes the case of a 12-year-old patient with 17-year follow-up who was previously diagnosed with Papillon-Lefèvre Syndrome (PLS), which is a rare autosomal recessive irregularity in the cathepsin C gene (CTSC) characterized by palmoplantar hyperkeratosis and premature loss of primary and permanent teeth. Case Report: A specific mutation in the c.203 T > G gene inducing loss of function leading to PLS was detected, as was a mutation in the HLA-DRB1*11 allele, which is associated with this syndrome. There is no consanguinity of the parents, and the siblings are entirely healthy. Early identification of the main characteristics of this syndrome is imperative. Accurate diagnosis by genetic analysis allows differential diagnoses and timely comprehensive dental treatment. Conclusions: Additionally, it allows consultation with a dermatologist to maintain or improve the quality of life of patients with this condition due to progressive worsening and severity of the main physical manifestations. Keywords: Papillon-Lefevre Disease; Keratoderma, Palmo-plantar; Cathepsin C; Periodontitis; Skin Diseases, Genetic; Case reports

Introducción: El presente reporte describe el caso de un paciente de 12 años de edad con 17 años de seguimiento a quien previamente se le diagnosticó Síndrome de Papillon-Lefèvre (PLS), el cual es una rara irregularidad autosómica recesiva en el gen de la catepsina C (CTSC) caracterizada por hiperqueratosis palmoplantar y pérdida prematura de dientes primarios y permanentes. Reporte de Caso: Se detectó una mutación específica en el gen c.203 T > G que induce pérdida de función que conduce a PLS, así como una mutación en el alelo HLA-DRB1*11, que se asocia a este síndrome. No presenta consanguinidad de los padres, padres y hermanos totalmente sanos. La identificación temprana de las principales características de este síndrome es imperativa. El diagnóstico certero por análisis genético permite diagnósticos diferenciales y tratamientos odontológicos integrales oportunos. Conclusiones: Adicionalmente, permite la consulta con un dermatólogo para mantener o mejorar la calidad de vida de los pacientes con esta condición debido al progresivo empeoramiento y severidad de las principales manifestaciones físicas.

Rho-kinase (ROCK) in sea urchin sperm: its role in regulating the intracellular pH during the acrosome reaction.

Sperm must undergo the acrosome reaction (AR) in order to fertilize the egg. In sea urchins, this reaction is triggered by the egg jelly (EJ) which, upon binding to its sperm receptor, induces increases in the ion permeability of the plasma membrane and changes in protein phosphorylation. Here, we demonstrated that the sperm expresses ROCK (approximately 135kDa), which is a serine/threonine protein kinase. ROCK localized, as RhoGTPase (Rho), in the acrosomal region, midpiece and flagellum. H-1152, a ROCK antagonist, inhibited the two cellular processes defining the AR: the acrosomal exocytosis and the actin polymerization. The ionophores nigericin and A23187 reversed the AR inhibition induced by H-1152, suggesting that ROCK functions at the level of the EJ-induced ion fluxes. Accordingly, H-1152 blocked 70% the intracellular alkalinization induced by EJ. These results indicate that EJ activates a Na+-H+ exchanger (NHE) in the sperm through a Rho/ROCK-dependent signaling pathway that culminates in the AR.

Eficacia de la tomografía en el seguimiento del cáncer de pulmón tratado con inmunoterapia cubana

RESUMEN Introducción: el cáncer de pulmón representa en el mundo la primera causa de muerte oncológica. La tomografía computarizada es el medio diagnóstico más utilizado para clasificar esta enfermedad por estadios. Objetivo: determinar la eficacia de la tomografía computarizada en la evaluación de la pseudoprogresión de la enfermedad en pacientes con cáncer de pulmón de células no pequeñas, tratados con inmunoterapia cubana. Materiales y métodos: se realizó un estudio de evaluación, longitudinal, retrospectivo, analítico, en pacientes con cáncer de pulmón de células no pequeñas en estadio avanzado, tratados con inmunoterapia activa cubana, después de la primera línea de tratamiento con quimioterapia o quimiorradioterapia, entre el 1 de enero de 2013 y el 31 de diciembre de 2017. El universo lo constituyeron 91 pacientes tratados con Racotumomab y CIMAvax-EGF. Los datos se obtuvieron de las historias clínicas individuales, se incorporaron en una base de datos en Excel y se analizaron estadísticamente con el paquete SPSS 23. Resultados: del total de pacientes, 28 recibieron la vacuna Racotumomab y 63 la CIMAvax-EGF: pseudoprogresó el 12,5 % de los tratados con Racotumomab y el 28 % de los que lo fueron con CIMAvax-EGF. Se observó que la mayor supervivencia fue en los pseudoprogresores. Conclusiones: es eficaz el estudio tomográfico en la evaluación de respuesta de la pseudoprogresión de la enfermedad en pacientes con cáncer de pulmón de células no pequeñas, tratados con inmunoterapia cubana.

ABSTRACT Introduction: lung cancer represents the first cause of oncological death in the world. Computed tomography is the most used diagnostic mean to classify the disease by stages. Objective: to determine the efficacy of computed tomography in the evaluation of the disease pseudo-progression in patients with non-small cells lung cancer, treated with Cuban immunotherapy. Materials and methods: a longitudinal, retrospective, analytical study was conducted in patients with non-small cells lung cancer in advanced stage, treated with Cuban active immunotherapy after the first line of treatment with chemotherapy and chemoradiotherapy, between January 1, 2013 and December 31, 2017. The universe were 91 patients treated with Racotumomab and CIMAvax-EGF. Data were collected from personal clinical records, incorporated in an Excel database and statistically analyzed with the SPSS 23 package. Results: 28 patients from the total received the Racotumomab vaccine and 63 received the CIMAvax-ECG vaccine. 12.5 % of those treated with Racotumomab and 28 % of those treated with CIMAvax-ECG pseudo progressed. The greatest survival was found in pseudo progressors. Conclusions: the computed tomographic studio is efficacious in evaluating the response of the disease pseudo progression in patients with non-small cells lung cancer, treated with Cuban immunotherapy.

Low doses of alpha particle irradiation modify the expression of genes regulating apoptosis in human MCF-7 breast cancer cells.

The possibility of modifying apoptosis-related genes in tumor cells is an interesting line of research that calls for multidisciplinary experimentation to describe its characteristics and the conditions required. In vitro low doses of alpha particle irradiation due to radon have an antiproliferative effect on the growth of MCF-7 cells and increase the sensibility of cancer cells to taxol, a chemotherapeutic agent that induces cellular apoptosis. The present study examines the in vitro effects of low doses of alpha particle irradiation from the gas radon on the expression of some bcl-2 family apoptosis-related genes. The analyzed genes were bax, bcl-2 and bcl-x, with known responses to genotoxic stress (bcl-2) or ionising radiation (bax and bcl-x) in MCF-7 human breast cancer cells. The results obtained indicate that the cell line studied expresses the mentioned genes and they demonstrate that irradiation with low radon doses of MCF-7 cells induces underexpression of both bax and bcl-2 genes. Interestingly, the mRNA levels of the full-length bcl-x gene (bcl-xL) were overexpressed after irradiation, and we found significant mRNA levels of an alternative mRNA splicing form of the same gene (bcl-xS), which enhances the apoptotic sensitivity of the cell. The increased sensitivity to apoptosis resulting from bcl-xS overexpression is important because it might improve the efficacy of chemotherapeutic agents used to treat cancers which act through induction of apoptosis. The finding that low radiation doses of alpha particles from the gas radon modulate the expression of apoptosis-related genes suggests a therapeutic utility for this naturally occurring agent.