Recommendations for the prevention of healthcare-associated infections in nursing homes / Recomendaciones para la prevención de infecciones en residencias para mayores

Nursing homes (NH) conceptually should look as much like a home as possible. However NH have unquestionable similar ities with a nosocomium as they are places where many pa tients with underlying diseases and comorbidities accumulate. There is evidence of transmission of microorganisms between residents and between residents and caregivers. We have not found any recommendations specifically aimed at the prevention of nosocomial infections in NH by the major Public Health Agencies and, therefore, the Health Sciences Foundation (Fundación de Ciencias de la Salud) has convened a series of experts and 14 Spanish scientific societies to discuss recommendations that could guide NH personnel in establishing written programs for the control and reduction of these infections. The present document is the result of these deliberations and contains suggestions for establishing such control programs on a voluntary and flexible basis in NH. We also hope that the document can help the health authorities to encourage this control activity in the different territorial areas of Spain. In our opinion, it is necessary to draw up a written plan and establish the figure of a coordinator or person respon sible for implementing these projects. The document includes measures to be implemented and ways of quantifying the real ity of different problems and of monitoring the impact of the measures established (AU)

Las residencias de ancianos (NH) aunque conceptualmente deberían parecerse lo más posible a un hogar, tienen induda bles similitudes con un nosocomio ya que son lugares donde se acumulan muchos pacientes con enfermedades de base y comorbilidades y donde la transmisión de microorganismos en tre residentes y entre residentes y cuidadores es frecuente. No hemos encontrado recomendaciones específicamente dirigidas a la prevención de las infecciones nosocomiales en NH por parte de las principales Agencias de Salud Pública y, por ello, la Fundación de Ciencias de la Salud ha convocado a una serie de expertos y a 14 sociedades científicas españolas para de batir recomendaciones que puedan orientar al personal de las NH en el establecimiento de programas escritos para el control y reducción de estas infecciones. El presente documento es el resultado de estas deliberaciones y contiene sugerencias para establecer dichos programas de control de forma voluntaria y flexible. También esperamos que el documento pueda ayudar a las autoridades sanitarias a fomentar esta actividad de control en los distintos ámbitos territoriales de España. En nuestra opi nión, es necesario elaborar un plan por escrito y establecer la figura de un coordinador o responsable de la ejecución de estos proyectos. El documento incluye las medidas a implantar y las formas de cuantificar la realidad de los diferentes problemas y de monitorizar el impacto de las medidas establecidas (AU)

Demographics, clinical findings and diagnoses of cranial thoracic myelopathies (T1-T6 vertebrae) in cats.

OBJECTIVES: The aim of the study was to describe the patient demographics, clinicopathological features and presumptive or final diagnoses in cats with myelopathies between the T1 and T6 vertebrae. METHODS: This retrospective multicentre case study enrolled cases between 2015 and 2022 that were diagnosed with myelopathies between the T1 and T6 vertebrae as the primary cause for the presenting clinical signs. RESULTS: A total of 21 cases matched the inclusion criteria, 13 males (11 castrated and 2 entire) and 8 spayed females (median age 93 months; range 5-192). Most of the cases presented with a chronic and progressive history (76% and 86%, respectively), with a median duration of 29 days (range 1-2880). At the time of presentation, 90% of the cases were localised to the T3-L3 spinal cord segments based on neurological examination. The most common underlying pathology was neoplasia (42.9%), followed by inflammatory (24%), anomalous (19%), degenerative (9.5%) and vascular (4.8%) disorders. The most common location was T3-T4 (29%), followed by T2-T3 and T5-T6 (19% each). The cutaneous trunci reflex was normal in 86% of the cases and most of the cases (71%) did not show spinal discomfort upon admission. CONCLUSIONS AND RELEVANCE: Neoplasia was the most common cause of cranial thoracic myelopathy in this study. The lack of pathognomonic clinical signs for this specific region highlights the importance of assessing the entire thoracolumbar region up to and including at least the T1 vertebra when investigating cases with signs consistent with a T3-L3 myelopathy.

MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange.

Presentation of antigenic peptides by major histocompatibility complex class II (MHC-II) proteins determines T helper cell reactivity. The MHC-II genetic locus displays a large degree of allelic polymorphism influencing the peptide repertoire presented by the resulting MHC-II protein allotypes. During antigen processing, the human leukocyte antigen (HLA) molecule HLA-DM (DM) encounters these distinct allotypes and catalyzes exchange of the placeholder peptide CLIP by exploiting dynamic features of MHC-II. Here, we investigate 12 highly abundant CLIP-bound HLA-DRB1 allotypes and correlate dynamics to catalysis by DM. Despite large differences in thermodynamic stability, peptide exchange rates fall into a target range that maintains DM responsiveness. A DM-susceptible conformation is conserved in MHC-II molecules, and allosteric coupling between polymorphic sites affects dynamic states that influence DM catalysis. As exemplified for rheumatoid arthritis, we postulate that intrinsic dynamic features of peptide-MHC-II complexes contribute to the association of individual MHC-II allotypes with autoimmune disease.

CD4+ T Cell Epitope Identification from Complex Parasite Antigen Mixtures.

Antigen complexity represents a major challenge for scoring CD4+ T cell immunogenicity, a key hallmark of immunity and with great potential to improve vaccine development. In this chapter, we provide a comprehensive picture of a pipeline that can be applied to virtually any complex antigen to overcome different limitations. Antigens are characterized by Mass Spectrometry to determine the available protein sources and their abundances. A reconstituted in vitro antigen processing system is applied along with bioinformatics tools to prioritize the list of candidates. Finally, the immunogenicity of candidate peptides is validated ex vivo using PBMCs from HLA-typed individuals. This protocol compiles the essential information for executing the whole pipeline while focusing on the candidate epitope prioritizing scheme.

Atención Primaria y personas mayores en las residencias: propuestas de mejora tras la experiencia durante la pandemia / Primary Care and the elderly in nursing homes: proposals for improvement after the experience during the pandemic

Con este artículo hemos querido acercarnos a la visión que desde la Atención Primaria (AP) tenemos sobre lo que ha supuesto la pandemia de la COVID-19 en la población mayor y particularmente en las personas ancianas que viven en residencias. La situación previa de los centros residenciales ha influido durante la pandemia en un elevado número de fallecimientos, aislamiento social y problemas de salud derivados. Las personas de estos centros son generalmente más vulnerables, frágiles, dependientes y longevas, pero estos condicionantes no justifican el nivel de contagios y mortalidad por sí mismos. En los momentos de mayor dureza de la crisis sanitaria, se activaron una serie de respuestas sociales y sanitarias variadas y diversas en cada comunidad autónoma. Algunas de estas tuvieron carácter urgente y terminaron por originar diferentes estrategias y/o nuevos modelos de atención y gestión de las residencias. En algunos casos, estos cambios se siguen manteniendo. El objetivo de este artículo es analizar algunas de las principales medidas que se llevaron a cabo, los cambios que se implementaron, los puntos en común, el consenso en la toma de decisiones, la evidencia sobre la que se basaron, los aspectos éticos y legales que inspiraron estas estrategias y los resultados en salud obtenidos. Atendiendo a lo comentado, el grupo hace una serie de propuestas de mejora de cara al futuro.(AU)

This article aims to get closer to the vision from the perspective of primary care about what the COVID 19 pandemic has entailed in the elderly population and especially in those who live in nursing homes. During the pandemic, the previous situation of residential centres has led to a high number of deaths, social isolation and derived health problems. People in these centres are in general more vulnerable, frail, dependent and long-lived. However, these conditions do not in themselves justify the level of infections and mortality. In the most difficult moments of the health crisis, a series of varied and diverse social and health responses were activated according to the different Autonomous Communities. Some were urgent in nature and ended up giving rise to different strategies and/or new care and management models for nursing homes. In some cases, these changes are still maintained. The aim of the article is to analyze some of the main measures that were performed; the changes implemented, the points in common, the consensus in decision-making, the evidence on which they were based, the ethics and legal aspects that inspired these strategies and the health outcomes obtained. In response to what has been said, the group makes a series of proposals for improvement in the future.(AU)

[PAPPS update on older people 2022]. / Actividades preventivas en el mayor. Actualización PAPPS 2022.

This article examines the latest available evidence on preventive activities in the elderly, including sleep disorders, physical exercise, deprescription, cognitive disorders and dementias, nutrition, social isolation and frailty.

Fragilidad en atención primaria: diagnóstico y manejo multidisciplinar / Frailty in primary care: Diagnosis and multidisciplinary management

El envejecimiento poblacional se asocia a un mayor uso de recursos sociales sanitarios, asociados a la mayor morbimortalidad y discapacidad de este grupo etario. La fragilidad es un síndrome geriátrico previo a la aparición de la dependencia funcional, que permite la identificación de individuos de mayor riesgo de dependencia, institucionalización, efectos adversos de fármacos, mortalidad y otros eventos negativos de salud. Este síndrome es potencialmente reversible con una intervención multicomponente. La atención primaria de salud es el lugar preferente para el diagnóstico y seguimiento de la fragilidad, a través de escalas como la FRAIL scale, el fenotipo de Fried o modelos de acumulación de déficits. Para el seguimiento se precisa la intervención multidimensional y coordinada de diferentes profesionales sanitarios y sociales, con la implicación del paciente y su familia. Se debe fomentar la investigación para determinar las intervenciones más eficaces y los cursos clínicos más frecuentes.(AU)

Population aging is associated with a greater use of social and health resources, associated with greater morbidity, mortality and disability in the elderly. Frailty is a geriatric syndrome prior to the onset of functional decline, which allows the identification of individuals at higher risk of dependency, institutionalization, adverse effects of drugs, mortality and other negative health events. This syndrome is potentially reversible with a multicomponent intervention. Primary health care is the preferred place for the diagnosis and follow-up of frailty, through scales such as the FRAIL scale, the Fried phenotype or deficit accumulation models. Follow-up requires the multidimensional and coordinated intervention of different health and social professionals, with the involvement of the patient and their family. Research should be encouraged to determine the most effective interventions and the most common clinical courses.(AU)

Deprescripción en personas mayores: es el momento de pasar a la acción / Deprescription in old people: It's time to take action

El uso de fármacos conlleva innegables beneficios en las personas mayores, pero no está exento de efectos indeseables. La deprescripción es el proceso de revisión sistemática de la medicación con el objetivo de lograr la mejor relación riesgo-beneficio en base a la mejor evidencia disponible. Este proceso es especialmente importante en mayores polimedicados, sobretratados, frágiles, con enfermedades terminales y en el final de la vida.La deprescripción debe hacerse de forma escalonada, estableciendo un seguimiento estrecho por si aparecen problemas tras la retirada. En la toma de decisiones es muy importante contar con la opinión del paciente y de los cuidadores, valorando los objetivos del tratamiento según la situación clínica, funcional y social del enfermo.Existen múltiples herramientas para facilitar a los clínicos la tarea de seleccionar qué fármacos deprescribir (criterios Beers, STOPP-START…). Los grupos farmacológicos más susceptibles de intervención son: antihipertensivos, antidiabéticos, estatinas, benzodiacepinas, antidepresivos, anticolinérgicos, anticolinesterásicos y neurolépticos.(AU)

The use of drugs has undeniable benefits to the elderly, but it is not exempt from undesirable effects. Deprescription is the process of systematic medication review with the target of achieving the best risk-benefit ratio based on the best available evidence. This process is especially important for polymedicated elderly patients as well as those overtreated, frail, terminally ill and at the end of life.The deprescription must be done in stages, establishing a close follow-up in case problems appear after withdrawal. In the decision-making process, it is very important to consider the patient and caregivers opinion, assessing the objectives of the treatment according to the clinical, functional and social situation of the patient.There are multiple tools to make it easier for clinicians to select which drugs to deprescribe (Beers criteria, STOPP-START…). The most susceptible to intervention pharmacological groups are: antihypertensives, antidiabetics, statins, benzodiazepines, antidepressants, anticholinergics, anticholinesterase agents, and neuroleptics.(AU)

[Deprescription in old people: It's time to take action]. / Deprescripción en personas mayores: es el momento de pasar a la acción.

The use of drugs has undeniable benefits to the elderly, but it is not exempt from undesirable effects. Deprescription is the process of systematic medication review with the target of achieving the best risk-benefit ratio based on the best available evidence. This process is especially important for polymedicated elderly patients as well as those overtreated, frail, terminally ill and at the end of life. The deprescription must be done in stages, establishing a close follow-up in case problems appear after withdrawal. In the decision-making process, it is very important to consider the patient and caregivers opinion, assessing the objectives of the treatment according to the clinical, functional and social situation of the patient. There are multiple tools to make it easier for clinicians to select which drugs to deprescribe (Beers criteria, STOPP-START…). The most susceptible to intervention pharmacological groups are: antihypertensives, antidiabetics, statins, benzodiazepines, antidepressants, anticholinergics, anticholinesterase agents, and neuroleptics.

[Frailty in primary care: Diagnosis and multidisciplinary management]. / Fragilidad en atención primaria: diagnóstico y manejo multidisciplinar.

Population aging is associated with a greater use of social and health resources, associated with greater morbidity, mortality and disability in the elderly. Frailty is a geriatric syndrome prior to the onset of functional decline, which allows the identification of individuals at higher risk of dependency, institutionalization, adverse effects of drugs, mortality and other negative health events. This syndrome is potentially reversible with a multicomponent intervention. Primary health care is the preferred place for the diagnosis and follow-up of frailty, through scales such as the FRAIL scale, the Fried phenotype or deficit accumulation models. Follow-up requires the multidimensional and coordinated intervention of different health and social professionals, with the involvement of the patient and their family. Research should be encouraged to determine the most effective interventions and the most common clinical courses.

Health Problems Encountered by Short-Term European Volunteers in a Nongovernmental Organization in Cambodia.

Short-term volunteers are susceptible to a wide spectrum of morbidities, mostly infectious diseases preventable with general hygiene and preventive measures. This study aimed to identify the health problems encountered by European short-term volunteers collaborating for 1 month with a nongovernmental organization (NGO) in Cambodia and to describe their characteristics. A prospective, descriptive observational study was conducted on short-term volunteers who collaborated with an NGO in Cambodia during August 2018. Informed consent and sociodemographic, clinical, and preventative health-related questionnaire data were provided by 198 volunteers. The health problems encountered were confirmed in a primary care consultation with healthcare professionals. Univariate and bivariate analyses were performed. The median age of the volunteers was 22 years (interquartile range = 21-24), and 64% were women. Some (18.2%) had allergies, 8.6% had preexisting health conditions, and 10.6% were under regular treatment. A total of 77.3% visited a pretravel consultation clinic, 39.9% completed a specific pretravel health course, 21.7% took malaria prophylaxis, 92.4% received hepatitis A vaccination, and 82.3% received typhoid fever vaccination. Medical assistance was sought by 112 (57.3%) of the volunteers. The average number of health problems was 2.5 (standard deviation = 1.5), and the total number of health problems attended by the medical team was 279. The most common health problems were upper respiratory infections (12.2 per 1,000 person/days), wounds (10.8 per 1,000 person/days), and diarrhea (6.3 per 1,000 person/days). Short-term volunteers experienced a high rate of health problems during their stay in Cambodia, but most of the problems were mild and preventable and resolved quickly. Pretravel consultation and specific pretravel health training seemed to increase disease awareness.

Sortase-Mediated Multi-Fragment Assemblies by Ligation Site Switching.

Sortase-mediated ligation (SML) is a powerful tool of protein chemistry allowing the ligation of peptides containing LPxTG sorting motifs and N-terminal glycine nucleophiles. The installation of a sorting motif into the product prohibits the assembly of multiple fragments by SML. Here we report multi-fragment SML based on switchable sortase substrates. Substitution of the Leu residue by disulfide-containing Cys(StBu) results in active sorting motifs, which are inactivatable by reduction. In combination with a photo-protected N-Gly nucleophile, multi-fragment SML is enabled by repetitive cycles of SML and ligation site switching. The feasibility of this approach was demonstrated by a proof-of-concept four-fragment ligation, the assembly of peptide probes for bivalent chromatin binding proteins and oligomerization of peptide antigens. Biochemical and immuno-assays demonstrated functionality of these probes rendering them promising tools for immunology and chromatin biochemistry.

Synthesis and functionalization of dendritic polyglycerol-based nanogels: application in T cell activation.

The concept of multivalency finds various applications in the fields of chemistry and biology, relying on the principle that multiple weak interactions can lead to strong adhesive forces. Polymeric carriers are promising tools to translate these properties into the field of biomedicine, especially upon functionalization by active biomolecules, such as antibodies. In this study we report on the synthesis of dendritic polyglycerol (dPG) and dPG-based nanogels (NGs) as platforms for the multivalent display of molecules and their potential application as carrier units. Macromolecules based on dPG were synthesized and NGs were generated by strain-promoted azide-alkyne cycloaddition (SPAAC) by inverse nanoprecipitation under mild conditions. Scale-up screening rendered a reproducible method for a batch size of up to 50 mg for the formation of NGs in a size range of 150 nm with narrow dispersity. Dye-labelled bovine serum albumin (FITC-BSA) was chosen as a model protein and showed successful conjugation to the carriers, while the protein's secondary structure was not affected. Consequently, cyanine-5-amine (Cy5-NH2) and avidin (Av) were conjugated in order to exploit the strong avidin-biotin interaction, facilitating the directed attachment of a myriad of biotinylated (bio)molecules. As a proof-of-concept, the biotinylated monoclonal antibodies (mAbs) α-CD3 and α-CD28 were attached to the platforms and their capability to activate T cells was assessed. Experiments were performed with a Jurkat reporter cell line which expresses green fluorescent protein (GFP) upon activation, providing a rapid and reliable readout by flow cytometry. Carriers clearly outperformed conventional compounds for activation (i.e. antibodies crosslinked with anti-IgG antibody) at significantly lower dosages. These findings could be confirmed by confocal laser scanning microscopy (CLSM), showing accumulation of the functional nanoplatforms at the cell surface and cytoplasmic GFP expression (>95% activation of cells for the multivalent conjugates at 10 µg mL-1 compared to 37% activation with conventionally crosslinked mAbs at 25 µg mL-1), whereas carriers without mAbs could not activate cells. As the attachment of biotinylated molecules to the functional nanoplatforms is straightforward, the results obtained show the great potential of our platforms for a broad range of applications.

[Vision of the management of frailty in Primary Health Care.] / Visión del manejo de la fragilidad en Atención Primaria.

Primary Care (PC) and community are the priority health sites for the detection and management of frailty. There are good guidelines (Strategy and consensus of the National Health Service, ADVANTAGE European Joint Action, recommendations of the Program of Prevention and Health Promotion Activities of the Spanish Society of Family and Community Medicine PAPPS-semFYC, Fisterra guideline); however, its implementation is not taking place with the expected magnitude or speed, also considering the influence of the COVID-19 pandemic. The detection and management of frailty requires multidisciplinary work by professionals who usually carry out their activity at the first level of care (physicians, nurses, social workers), with others whose integration is advisable (nutritionists, physiotherapists, etc.); and counting on others of reference (geriatricians). On the other hand, it is necessary to work with comprehensive approaches based on good coordination between PC and the Community, with various experiences in this regard. The support by the Information and Communication Technologies (ICT) can be very interesting, with tools for both users and careers (e.g., VIVIFRAIL), as well as for social and health professionals (e.g., VALINTAN or WHO ICOPE-Handbook App). Strategies to intervene in fragility in a more effective and systematic way must be consolidated: with an adequate professional training, establishment of campaigns and dissemination ways for visualizing its relevance and extend their intervention, prioritization of the most effective programmed assistance activities (highlighting fragility), multidisciplinary work with coordination and participation of the different healthcare and community levels and of the patients themselves, and providing the PC with adequate resources.

La Atención Primaria (AP) y la comunidad constituyen el medio asistencial primordial para el manejo de la fragilidad. Se cuenta con buenas directrices (Estrategia y Consenso del Sistema Nacional de Salud, Acción Conjunta Europea ADVANTAGE, recomendaciones del Programa de Actividades de Prevención y de Promoción de la Salud de la Sociedad Española de Medicina familiar y Comunitaria: PAPPS-semFYC, guía Fisterra...); no obstante, su implantación no se está dando con la magnitud ni rapidez esperada, considerando también la influencia de la pandemia por la COVID-19. La detección y manejo de la fragilidad exige un trabajo multidisciplinar de profesionales que habitualmente desarrollan su actividad en el primer nivel asistencial (profesionales de medicina, enfermería y trabajo social), junto con otros cuya integración es aconsejable (nutricionistas, fisioterapeutas, etc...) y contando con otros profesionales de referencia (geriatras). Por otro lado, es necesario trabajar con enfoques integrales basados en una buena coordinación entre AP y la Comunidad, existiendo diversas experiencias en este sentido. El apoyo de las Tecnologías de la Información y Comunicación (TIC) puede ser muy interesante, existiendo herramientas tanto para usuarios y personas cuidadoras (por ej. VIVIFRAIL), como para profesionales sociosanitarios (por ej. VALINTAN o WHO ICOPE-Handbook App). Deben consolidarse las estrategias para intervenir en fragilidad de una manera más efectiva y sistemática: con la formación adecuada de los profesionales, establecimiento de campañas y difusión que hagan visualizar la relevancia y extender su intervención, priorizando las actividades asistenciales programadas más efectivas (destacando la fragilidad), a través del trabajo multidisciplinar con coordinación y participación de los diferentes niveles asistenciales y comunitarios y de los propios pacientes, y dotando de medios y recursos a la AP.

Single Anastomosis Duodeno-ileal Bypass As a Revisional Procedure Following Sleeve Gastrectomy: Review of the Literature.

Laparoscopic sleeve gastrectomies (LSGs) can experience weight-loss failure and conversion to another bariatric procedure. An analysis of the bariatric literature concerning the single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as revisional surgery after LSG in terms of safety and efficacy identified 607 studies. Fifty-nine studies were analyzed for full content review and 9 primary studies (398 patients) were included. Revisional single anastomosis duodeno-ileal bypass (SADI) was performed in 294 patients at a mean interval of 37.7 months (range 11-179). Total weight loss (%) varies from 20.5% to 46.2%. Early complications after surgery occurred in 4.1% surgeries including leak (7 cases -1.9%). Mortality was nil. SADI after LSG, after failed sleeve gastrectomy or as a sequential procedure, offers a satisfactory weight loss result. Both early and late term complications are acceptable.

Type 1 Diabetes and the HLA Region: Genetic Association Besides Classical HLA Class II Genes.

Type 1 diabetes is an autoimmune disease with rising incidence in high-income countries. Genetic and environmental predisposing factors contribute to the etiology of the disease, although their interaction is not sufficiently understood to allow for preventive action. Strongest known associations with genetic variation map to classical HLA class II genes. Because of its genetic complexity, the HLA region has been under-represented in genome-wide association studies, having potentially hindered the identification of relevant associations underlying the etiology of the disease. Here, we performed a comprehensive HLA-wide genetic association analysis of type 1 diabetes including multi-allelic and rare variants. We used high-density whole-exome sequencing data of the HLA region in the large UK Biobank dataset to apply gene-based association tests with a carefully defined type 1 diabetes phenotype (97 cases and 48,700 controls). Exon-based and single-variant association tests were used to complement the analysis. We replicated the known association of type 1 diabetes with the classical HLA-DQ gene. Tailoring the analysis toward rare variants, we additionally identified the lysine methyl transferase EHMT2 as associated. Deeper insight into genetic variation associated with disease as presented and discussed in detail here can help unraveling mechanistic details of the etiology of type 1 diabetes. More specifically, we hypothesize that genetic variation in EHMT2 could impact autoimmunity in type 1 diabetes development.

Role of Leishmania infantum in Meningoencephalitis of Unknown Origin in Dogs from a Canine Leishmaniosis Endemic Area.

The main hypothesis for the aetiology of meningoencephalitis of unknown origin (MUO) in dogs is an autoimmune or genetic cause that is associated with a triggering event (environmental factors/infectious agents). The aim of this ambispective cohort study was to test for Leishmania infantum infection in the blood and cerebrospinal fluid (CSF) of dogs with MUO in an endemic area of canine leishmaniosis. Dogs with MUO were selected amongst all dogs undergoing blood anti-L. infantum antibody testing (control group). The blood plasma or serum samples from all dogs were analysed for anti- L. infantum antibodies by a quantitative indirect fluorescent assay (IFAT). In dogs with MUO, CSF samples were obtained for analysed by PCR detection of L. infantum DNA. Forty-four percent and 22% of the dogs in the MUO group featured magnetic resonance imaging (MRI) findings and CSF cytology respectively, consistent with L. infantum infection. IFAT, PCR, and histological findings were negative for L. infantum. A significant difference in L. infantum infection prevalence was found between the control and MUO group (p = 0.0022). While it seems unlikely that L. infantum plays a role in the aetiology of MUO, in endemic areas, this pathogen should be included in the differential diagnosis of this neurological disorder.

Revisiting nonclassical HLA II functions in antigen presentation: Peptide editing and its modulation.

The nonclassical major histocompatibility complex of class II molecules (ncMHCII) HLA-DM (DM) and HLA-DO (DO) feature essential functions for the selection of the peptides that are displayed by classical MHCII proteins (MHCII) for CD4+ Th cell surveillance. Thus, although the binding groove of classical MHCII dictates the main features of the peptides displayed, ncMHCII function defines the preferential loading of peptides from specific cellular compartments and the extent to which they are presented. DM acts as a chaperone for classical MHCII molecules facilitating peptide exchange and thereby favoring the binding of peptide-MHCII complexes of high kinetic stability mostly in late endosomal compartments. DO on the other hand binds to DM blocking its peptide-editing function in B cells and thymic epithelial cells, limiting DM activity in these cellular subsets. DM and DO distinct expression patterns therefore define specific antigen presentation profiles that select unique peptide pools for each set of antigen presenting cell. We have come a long way understanding the mechanistic underpinnings of such distinct editing profiles and start to grasp the implications for ncMHCII biological function. DM acts as filter for the selection of immunodominant, pathogen-derived epitopes while DO blocks DM activity under certain physiological conditions to promote tolerance to self. Interestingly, recent findings have shown that the unexplored and neglected ncMHCII genetic diversity modulates retroviral infection in mouse, and affects human ncMHCII function. This review aims at highlighting the importance of ncMHCII function for CD4+ Th cell responses while integrating and evaluating what could be the impact of distinct editing profiles because of natural genetic variations.