Comprehensive genomic filtering algorithm to expose the cause of skewed X chromosome inactivation. The proof of concept in female haemophilia expression.

BACKGROUND: Exploring the expression of X linked disorders like haemophilia A (HA) in females involves understanding the balance achieved through X chromosome inactivation (XCI). Skewed XCI (SXCI) may be involved in symptomatic HA carriers. We aimed to develop an approach for dissecting the specific cause of SXCI and verify its value in HA. METHODS: A family involving three females (two symptomatic with severe/moderate HA: I.2, the mother, and II.1, the daughter; one asymptomatic: II.2) and two related affected males (I.1, the father and I.3, the maternal uncle) was studied. The genetic analysis included F8 mutational screening, multiplex ligation-dependent probe amplification, SNP microarray, whole exome sequencing (WES) and Sanger sequencing. XCI patterns were assessed in ectoderm/endoderm and mesoderm-derived tissues using AR-based and RP2-based systems. RESULTS: The comprehensive family analysis identifies I.2 female patient as a heterozygous carrier of F8:p.(Ser1414Ter) excluding copy number variations. A consistent XCI pattern of 99.5% across various tissues was observed. A comprehensive filtering algorithm for WES data was designed, developed and applied to I.2. A Gly58Arg missense variant in VMA21 was revealed as the cause for SXCI.Each step of the variant filtering system takes advantage of publicly available genomic databases, non-SXCI controls and case-specific molecular data, and aligns with established concepts in the theoretical background of SXCI. CONCLUSION: This study acts as a proof of concept for our genomic filtering algorithm's clinical utility in analysing X linked disorders. Our findings clarify the molecular aspects of SXCI and improve genetic diagnostics and counselling for families with X linked diseases like HA.

[Analysis of the diversity of Actinomyces/Actinotignum clinical isolates in a university hospital]. / Análisis de la diversidad de aislados clínicos de Actinomyces/Actinotignum en un hospital universitario.

Actinomyces and related genera are grampositive bacilli, opportunistic pathogens, which have been mainly involved in endogenous infections. However, due to the complexity in identifying them for most clinical laboratories, there is scant knowledge about their real clinical significance. In this work, 166 isolates of 13 different species of Actinomyces/Actinotignum species recovered from clinical samples of patients treated in a university hospital were studied. The identification was performed by MALDI-TOF MS and molecular identification. MALDI-TOF MS identified 91.57% of the isolates (152/166) at the species level using a score ≥ 1.7 and 3.61% (6/166) of the isolates were identified only at the gender level with a score ≥ 1.5. MALDI-TOF MS did not yield reliable identification results for 4.82% (8/166) of the isolates. Actinomyces/Actinotignum species were isolated from: soft tissue (n: 47), urine samples (n: 35), head / neck abscesses (n: 19), genital abscesses (n: 11), blood samples (n: 10), breast abscesses (n: 8), osteoarticular samples (n: 6), abdominal/ascitic fluids (n: 3), abdominal abscesses (n: 5), sputum/BAL (n: 4), brain abscesses (n: 3), and others (n: 15). The results obtained from the statistical analysis showed a high differential frequency (> 2) for the location/species association: urine/A. schaalii/sanguinis; brain abscesses/A. europaeus; osteoarticular samples/A. urogenitalis; abdominal abscesses/ A. turicensis; respiratory samples/A. naeslundii/viscosus. This information provides a greater understanding of the clinical and epidemiological relevance of these species. The pathogenic role of Actinomyces spp. will be increasingly revealed as these microorganisms could be recognized thanks to prolonged culture and the advances in identification technology facilitated by MALDI-TOF MS.

Discrimination of the chemotherapy resistance status of human leukemia and glioblastoma cell lines by MALDI-TOF-MS profiling.

Chemotherapy mistreatment is partially due to a lack of rapid and reliable tools to discriminate between sensitive and resistant phenotypes. In many cases, the resistance mechanism is not fully understood, contributing to the diagnostic tools' absence. This work aims to determine the capacity of MALDI-TOF-MS profiling to discriminate between chemotherapy-resistant and sensitive phenotypes in leukemia and glioblastoma cells. A multivariate analysis of two therapy-resistant leukemia cell lines (Ki562 and Kv562) and two TMZ-resistant glioblastoma cell lines (U251-R and LN229-R) and their sensitive counterparts was performed. In this work, we first show MALDI-TOF-MS patterns analysis ability to differentiate these cancer cell lines by their chemotherapy-resistant status. We present a rapid and inexpensive tool that would guide and complement the therapeutic decision.

Proteomic and Bioinformatic Tools to Identify Potential Hub Proteins in the Audiogenic Seizure-Prone Hamster GASH/Sal.

The GASH/Sal (Genetic Audiogenic Seizure Hamster, Salamanca) is a model of audiogenic seizures with the epileptogenic focus localized in the inferior colliculus (IC). The sound-induced seizures exhibit a short latency (7-9 s), which implies innate protein disturbances in the IC as a basis for seizure susceptibility and generation. Here, we aim to study the protein profile in the GASH/Sal IC in comparison to controls. Protein samples from the IC were processed for enzymatic digestion and then analyzed by mass spectrometry in Data-Independent Acquisition mode. After identifying the proteins using the UniProt database, we selected those with differential expression and performed ontological analyses, as well as gene-protein interaction studies using bioinformatics tools. We identified 5254 proteins; among them, 184 were differentially expressed proteins (DEPs), with 126 upregulated and 58 downregulated proteins, and 10 of the DEPs directly related to epilepsy. Moreover, 12 and 7 proteins were uniquely found in the GASH/Sal or the control. The results indicated a protein profile alteration in the epileptogenic nucleus that might underlie the inborn occurring audiogenic seizures in the GASH/Sal model. In summary, this study supports the use of bioinformatics methods in proteomics to delve into the relationship between molecular-level protein mechanisms and the pathobiology of rodent models of audiogenic seizures.

The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype.

Monocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing anti-inflammatory/pro-reparative phenotypes at later phases, with highly dynamic switching depending on the wound environment. Chronic wounds are often arrested in the inflammatory phase with hampered inflammatory/repair phenotype transition. Promoting the tissue repair program switching represents a promising strategy to revert chronic inflammatory wounds, one of the major public health loads. We found that the synthetic lipid C8-C1P primes human CD14+ monocytes, restraining the inflammatory activation markers (HLA-DR, CD44, and CD80) and IL-6 when challenged with LPS, and preventing apoptosis by inducing BCL-2. We also observed increased pseudo-tubule formation of human endothelial-colony-forming cells (ECFCs) when stimulated with the C1P-macrophages secretome. Moreover, C8-C1P-primed monocytes skew differentiation toward pro-resolutive-like macrophages, even in the presence of inflammatory PAMPs and DAMPs by increasing anti-inflammatory and pro-angiogenic gene expression patterns. All these results indicate that C8-C1P could restrain M1 skewing and promote the program of tissue repair and pro-angiogenic macrophage.

Peptidome profiling for the immunological stratification in sepsis: a proof of concept study.

Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.

High-Efficiency Magnon-Mediated Magnetization Switching in All-Oxide Heterostructures with Perpendicular Magnetic Anisotropy.

The search for efficient approaches to realize local switching of magnetic moments in spintronic devices has attracted extensive attention. One of the most promising approaches is the electrical manipulation of magnetization through electron-mediated spin torque. However, the Joule heat generated via electron motion unavoidably causes substantial energy dissipation and potential damage to spintronic devices. Here, all-oxide heterostructures of SrRuO3 /NiO/SrIrO3 are epitaxially grown on SrTiO3 single-crystal substrates following the order of the ferromagnetic transition metal oxide SrRuO3 with perpendicular magnetic anisotropy, insulating and antiferromagnetic NiO, and metallic transition metal oxide SrIrO3 with strong spin-orbit coupling. It is demonstrated that instead of the electron spin torques, the magnon torques present in the antiferromagnetic NiO layer can directly manipulate the perpendicular magnetization of the ferromagnetic layer. This magnon mechanism may significantly reduce the electron motion-related energy dissipation from electron-mediated spin currents. Interestingly, the threshold current density to generate a sufficient magnon current to manipulate the magnetization is one order of magnitude smaller than that in conventional metallic systems. These findings suggest a route for developing highly efficient all-oxide spintronic devices operated by magnon current.

Growth conditions affect biofilms of Staphylococcus aureus producing mastitis: Contribution of MALDI-TOF-MS to strain characterization.

Bovine mastitis is a disease of dairy cattle prevalent throughout the world that causes alterations in the quality and composition of milk, compromising technological performance. Staphylococcus aureus is one of the most important pathogens that produce clinical, subclinical, and chronic mastitis. Biofilms are considered a virulence factor necessary for the survival of S. aureus in the mammary gland. Its zoonotic potential is important not only for the dairy industry sector but also for public health. This study aimed to evaluate the effect of different growing culture conditions on the biofilm formation of S. aureus isolated from mastitis and to test the MALDI-TOF-MS's ability to discriminate among different biofilm formation levels. Fluids commonly found in the dairy environment were incorporated to approach the pathogen's behavior in natural surroundings. PIA production was also evaluated. All strains were able to form high biofilms in TSB, TSBg, and milk. Milk changed the behavior of some strains which formed more biofilms in this medium than in TSBg. The free iron medium CTSBg and milk whey inhibited the biofilm formation of the most strains. MALDI-TOF-MS performance was an excellent tool to discriminate between high, moderate, and low biofilm producers strains of S. aureus in each media, confirming the results of crystal violet assay. PIA production was variable among the strains and showed a media-dependent behavior. Our data highlights the importance of considering the growing conditions that mimic the natural ones to the study of biofilm formation in vitro.

Salicylic acid stabilizes Staphylococcus aureus biofilm by impairing the agr quorum-sensing system.

Salicylic acid (SAL) has recently been shown to induce biofilm formation in Staphylococcus aureus and to affect the expression of virulence factors. This study was aimed to investigate the effect of SAL on the regulatory agr system and its impact on S. aureus biofilm formation. The agr quorum-sensing system, which is a central regulator in S. aureus pathogenicity, plays a pivotal role in the dispersal of S. aureus mature biofilms and contributes to the creation of new colonization sites. Here, we demonstrate that SAL impairs biofilm dispersal by interfering with agr expression. As revealed by our work, protease and surfactant molecule production is diminished, and bacterial cell autolysis is also negatively affected by SAL. Furthermore, as a consequence of SAL treatment, the S. aureus biofilm matrix revealed the lack of extracellular DNA. In silico docking and simulation of molecular dynamics provided evidence for a potential interaction of AgrA and SAL, resulting in reduced activity of the agr system. In conclusion, SAL stabilized the mature S. aureus biofilms, which may prevent bacterial cell dissemination. However, it may foster the establishment of infections locally and consequently increase bacterial persistence leading to therapeutic failure.

A combined approach of MALDI-TOF mass spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs.

Coronavirus disease 2019, known as COVID-19, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The early, sensitive and specific detection of SARS-CoV-2 virus is widely recognized as the critical point in responding to the ongoing outbreak. Currently, the diagnosis is based on molecular real time RT-PCR techniques, although their implementation is being threatened due to the extraordinary demand for supplies worldwide. That is why the development of alternative and / or complementary tests becomes so relevant. Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms, for the detection of COVID-19 positive and negative protein profiles directly from nasopharyngeal swabs samples. According to the preliminary results obtained, accuracy = 67.66 %, sensitivity = 61.76 %, specificity = 71.72 %, and although these parameters still need to be improved to be used as a screening technique, mass spectrometry-based methods coupled with multivariate analysis showed that it is an interesting tool that deserves to be explored as a complementary diagnostic approach due to the low cost and fast performance. However, further steps, such as the analysis of a large number of samples, should be taken in consideration to determine the applicability of the method developed.

MALDI-TOF-MS y machine learning como herramientas para la investigación traslacional en Argentina / MALDI-TOF-MS and machine learning as tools for translational research in Argentina

[RESUMEN]. La espectrometría de masas MALDI-TOF (Matrix Assisted Laser DesorptionIonization ­ Time of Flight) ha emergido como una técnica sobresaliente en el ámbito de la microbiología clínica; con una metodología simple y capacidad para ofrecer resultados precisos en un lapso breve. Esta tecnología mostró un éxito notorio, estableciéndose como una herramienta fundamental en la caracterización de microorganismos y en la investigación traslacional.La combinación de sus características con el potencial de análisis poraprendizaje automatizado ha demostrado ser de gran valor, acelerado el diagnóstico de la resistencia a antimicrobianos en bacterias. A su vez, ha abierto nuevas perspectivas en campos críticos de la medicina, como sepsis y la oncología. En Argentina, varios grupos contribuyen activamente a su expansión y aplicación en la lucha contra enfermedades infecciosas, incluida la pandemia de COVID-19. Estos esfuerzos prometen continuar impulsando la investigación y el diagnóstico clínico tanto en el país como en todo el mundo.

[ABSTRACT]. Matrix Assisted Laser DesorptionIonization ­ Time of Flight ­ MassSpectrometry (MALDI-TOF-MS) has emerged as anoutstandingtechnique in the field of clinical microbiology, with a simple methodology and deliveryof precise results in anexceptionally short timeframe. Thistechnology has garnered notable success in recentyears, establishing as a fundamental toolboth in the characterization of microorganisms and translational research. The combination of the inherent features of this technique with the potential of machine learning analysis has provento be of greatvalue in clinical microbiology, particularly in the antibiotic resistance field. Its application has accelerated bacterial diagnosis and opened new perspectives in critical areas of medicine, such sepsis and oncology. In Argentina, several research groups actively contributing to its expansión, applying MALDI-TOF-MS in the fight against infectious diseases, including the COVID-19 pandemic. Theseeffortspromiseto continue drivingresearch and clinical diagnosis in the country and worldwide.

Estudio exploratorio de eficacia de ivermectina combinada a α- PD-1 en cáncer colorrectal resistente a quimioinmunoterapia / EXPLORATORY EFFECTIVENESS STUDY OF IVERMECTIN COMBINED WITH α-PD-1 IN CHEMOTHERAPY RESISTANT COLORRECTAL CANCER

[RESUMEN]. Las terapias inmunológicas con inhibidores de checkpoints (ICIs) han revolucionado el abordaje del cáncer colorrectal (CCR), pero su efectividad se restringe a tumores inmunorreactivos con deficiencia en la reparación de errores tipo mismatch (dMMR). La ivermectina (IVM), un agente antiparasitario, se propone como posible estrategia terapéutica debido a su impacto en la muerte celular inmunogénica (MCI) y la reversión de resistencia a medicamentos. La investigación evaluó el efecto antineoplásico de IVM combinado con α-PD-1 empleando el modelo murino CT-26, una línea de CCR KRAS-mutada y competentes para MMR. El análisis bioinformático mediante la plataforma GEPIA2 empleandola base TCGA confirmó la expresión diferencial de blancos moleculares de IVM en tejido tumoral versus normal, siendo más alta en tumores con inestabilidad microsatelital baja (MSI-L)/microsatelital estable (MSS) que en inestabilidad microsatelital alta (MSI-H). En experimentos in vitro, CT-26 mostró alta sensibilidad a IVM (IC50: 11 µM, luego de exposición por 72 horas), alterando el metabolismo y aumentando la secreción de IL-6. El análisis proteómico identificó 17 proteínas sobreexpresadas y 8 inhibidas, relacionadas con evasión inmunológica y proliferación celular. En ratones BALB/c portadores de tumores CT-26, la terapia combinada de IVM y α-PD-1 redujo significativamente el crecimiento tumoral y la progresión metastásica. La preinmunización con células CT-26 tratadas con IVM disminuyó la incidencia y la progresión tumoral. IVM podría potenciar la respuesta a ICIs en tumores "fríos". Estos hallazgos sugieren que la combinación de IVM y α-PD-1 puede mejorar la inmunorreactividad y respuesta terapéutica en CCR.

[ABSTRACT]. Matrix Assisted Laser DesorptionIonization ­ Time of Flight ­ MassSpectrometry (MALDI-TOF-MS) has emerged as anoutstandingtechnique in thefieldofclinicalmicrobiology, with a simple methodology and deliveryof precise results in anexceptionally short timeframe. Thistechnology has garnered notable success in recentyears, establishing as a fundamental toolboth in thecharacterizationofmicroorganisms and translationalresearch.Thecombinationoftheinherentfeaturesofthistechniquewiththepotentialof machine learninganalysis has provento be ofgreatvalue in clinicalmicrobiology, particularly in theantibioticresistancefield. Itsapplication has acceleratedbacterial diagnosis and opened new perspectives in criticalareasof medicine, such sepsis and oncology. In Argentina, several research groups actively contributing to its expansión, applying MALDI-TOF-MS in the fight against infectious diseases, including the COVID-19 pandemic. Theseeffortspromiseto continue drivingresearch and clinical diagnosis in the country and worldwide.

Identification of Lama glama as Reservoirs for Acinetobacter lwoffii.

South American Camelids have an increasing relevance in local economies, worldwide. These animals are bred for their meat, fur and as companion and therapy animals. Thus, their sanitary status should be well-established. According to the OIE (World Organization for Animal Health), respiratory infections mainly produced by Pasteurella spp. have been reported for camelids. It has been stated that this microorganism causes a mild disease, although many authors report it is an important cause of mortality among alpacas. Nevertheless, the incidence of infection by Pasteurella spp. in camelids still needs to be investigated. The aim of the present study was to analyze the occurrence of nasopharyngeal colonization of Lama glama by respiratory bacteria, and to assess the usefulness of serological tests for clinical diagnosis. The colonization was studied by culture techniques carried out with material taken by nasopharyngeal swabs. Bacterial isolates were first phenotypically characterized and then identified by MALDI/TOF-MS. The presence of specific serum antibodies was studied by ELISA and Western blot. In the present work Pasteurella spp. was not found. Nevertheless, we report for the first time, the colonization of L. glama by bacteria of the Acinetobacter lwoffii, at a reliable level in 19.4% of the animals. Acinetobacter species are found in different environmental sources, as well as vegetables, animals, and humans, and their role in infections has recently gained relevance. The results presented herein contribute to a better understanding of the respiratory microbiota in camelids, and increase the knowledge about environmental distribution of Acinetobacter non-baumanii species. Given that these respiratory bacteria might be the cause of infection among cattle, and even humans, this report highlights the need for further research.

Prevalencia, distribución y diagnóstico histopatológico de hallazgos de imágenes radiolúcidas en los maxilares / Prevalence, distribution and histopathologic diagnosis of radiolucid images findings in the jaws

RESUMENObjetivo: el objetivo de este estudio fue identificar la prevalencia, ubicación y diagnóstico histopatológico de las lesiones radiolúcidas presentes en las radiografías panorámicas de pacientes que concurrieron a la cátedra de Cirugía y Traumatología Bucomaxilofacial I de la Facultad de Odontología de la Universidad de Buenos Aires, cuando el motivo de consulta no coincidió con el hallazgo radiográfico.Métodos: se realizó un análisis retrospectivo, observacional y descriptivo que consistió en identificar las imágenes radiolúcidas mayores a 1 cm de diámetro y presentes en radiografías panorámicas a partir de la revisión de historias clínicas de pacientes que concurrieron y fueron tratados quirúrgicamente en la cátedra de Cirugía y Traumatología Bucomaxilofacial I desde marzo de 2014 a diciembre de 2019. A partir de dichas historias clínicas, se registró edad y género del paciente, ubicación de la lesión en el maxilar, asociación o no a una pieza dentaria y resultado anatomopatológico.Resultados: los resultados AP se asociaron significativamente con los rangos etarios, no así con los sectores de piezas, ni con el sexo (AU)

Objective: the objective of this study was to identify the prevalence, location and histopathological diagnosis of radiolucent lesions present in the panoramic radiographs of patients who attended the chair of Bucomaxillofacial Surgery and Traumatology I, when the reason for consultation did not coincide with the radiographic finding.Methods: a retrospective, observational and descriptive analysis was carried out that consisted of identifying radiolucent images larger than 1 cm diameter present in panoramic radiographs from the review of medical records of patients who attended and were treated surgically in the chair of Bucomaxillofacial Surgery and Traumatology I from March 2014 to December 2019. From these medical records, the age and gender of the patient, location of the lesion in the maxilla, its association or not with a tooth, and pathological results were recorded.Results: the anatomopathological results were significantly associated with the age ranges, not with the sectors of pieces or with sex.

Production of a monoclonal antibody against serum immunoglobulin M of South American camelids and assessment of its suitability in two immunoassays.

A monoclonal antibody (mAb) was produced against immunoglobulin M (IgM) of South American camelids. A single radial immunodiffusion (SRID) assay and a competitive enzyme-linked immunosorbent assay (ELISA) were developed to measure IgM in serum samples. Isotype and specificity of the mAb were assessed. The performance of the SRID assay was preliminarily evaluated in terms of working range, plate stability over a 4-week period, and initial intra- and interassay variation. The concentration of IgM was determined in 55 samples by SRID assay and ELISA, and results were not significantly different by t-test (0.64 ± 0.19 mg/ml for the SRID assay, and 0.58 ± 0.24 mg/ml for ELISA; P = 0.1489). The mAb was shown to be stable over the 4-week evaluation period, and the SRID assay was reproducible when tested in triplicate for intra-assay variability and in quadruplicate for interassay variability, with a percentage coefficient of variation of less than or equal to 5%. Also, the SRID assay proved to be sensitive enough to measure IgM levels in undiluted serum samples, and had a good correlation with ELISA. The current study is intended to submit a preliminary report of a mAb against IgM of South American camelids, and suggest the future potential of the mAb developed for diagnostic application, including use in the SRID assay.

[The active and passive voice in the medical literature in Spain and in the United States. A comparative study]. / Las voces activa y pasiva en la literatura médica en España y en Estados Unidos. Estudio comparativo.

The majority of the manuals on style and scientific writing recommend limiting the use of the passive, preferring the active forms. In order to know the degree of monitoring of this recommendation we have carried out an analysis of a sample of articles of Spanish and United States journals in two different times (1989 and 2001). The use of the active voice is declining in Spain even being almost anecdotal, while in increases in the United States. In both times evaluated the American authors use the active voice more than the Spanish. The possible reasons of this situation are discussed and solutions are suggested.

Reproducción en parejas serodiscordantes para el VIH.Aproximación a la situación actual / Reproductive assitance to HIV-discordant couples. An actual approach

En los últimos años hemos asistido a multitud de cambios en torno al SIDA. La elevada incidencia del VIH en pacientes en edad fértil, unida al aumento en la expectativa y calidad de vida proporcionados por la introducción de los tratamientos antirretrovirales de gran actividad (TARGA) han hecho que cada vez más parejas en las que sólo uno de sus miembros es seropositivo (parejas serodiscordantes) deseen tener hijos El objetivo de este artículo es realizar una aproximación a las distintas opciones reproductivas que pueden llevarse a cabo en estas parejas para minimizar el riesgo de transmisión, incluyendo técnicas de reproducción asistida y lavado espermático, abordando su seguridad, eficacia y los problemas más frecuentemente asociados a las mismas (AU)

Actualización en el tratamiento del paciente infectado por el virus de la inmunodeficiencia humana (VIH). 2002 / The treatment update from the human immunodeficiency virus (HIV) infected patients. 2002

Hace 20 años que comenzó la pandemia producida por el virus de la inmunodeficiencia humana (VIH). Dado el impacto social y económico de la infección y su intensa extensión en los países industrializados, se ha producido un desarrollo de conocimiento científico sin precedentes. No obstante, con los tratamientos actuales sabemos que no es posible erradicar el virus, aunque gracias a ellos las infecciones oportunistas casi han desaparecido y la calidad de vida ha mejorado considerablemente. Esta mejoría evidenciada con terapia combinada antirretroviral, el coste de los medicamentos y -ante todo- los importantes efectos ad versos de la medicación, han motivado que cada vez se recomiende comenzar más tarde el tratamiento. Asumiendo que es preciso seguir a los pacientes asintomáticos durante años antes de comenzar con el tratamiento antirretroviral, si gran parte de los enfermos ya en tratamiento sólo precisan controles periódicos, ajustes de terapia y revisión de interacciones y efectos adversos, ¿podríamos plantear que dicho seguimiento se realizara fuera de los núcleos hospitalarios? (AU)

Diagnóstico diferencial entre nevus y melanoma en Atención Primaria, ¿cuándo biopsiar? / Differential diagnosis between nevi and melanoma in Primary Health Care, when a biopsy is in dicated?

No se han descubierto evidencias consistentes a favor de las reglas de valoración clínica del ABCD y de los 7 puntos, como herramientas útiles para decidir si se debe hacer una biopsia de lesiones compatibles con nevus o melanoma (AU)