Brief cognitive tests as a decision-making tool in primary care. A population and validation study.

INTRODUCTION AND OBJECTIVES: Brief cognitive tests (BCT) are used in primary care (PC) for the detection of cognitive impairment (CI). Still, there are little data on their diagnostic utility (DU) in a community setting. This work evaluates the DU at the population level of Fototest, T@M, AD8 questionnaire and MMSE. It provides new cut-off points (CoP) validated in a CI early detection program. MATERIAL AND METHODS: In the population and validation samples, the evaluation was carried out in two phases, a first of screening and administration of BCT and a second of clinical diagnosis, blinded to the results of the BCT, applying the current NIA-AA criteria. The DU of BCT in the population sample was evaluated with the area under the ROC curve (aROC). Youden index and the CoP with the best specificity that ensured a sensitivity of 80% were used to decide on the most appropriate CoP. The sensitivity, specificity, and predictive values for these CoP were calculated in the validation sample. RESULTS: 260 participants (23.1% with CI) from the population sample and 177 (42.4% with CI) from the validation sample were included. The Fototest has the best UD at the population level (aROC 0.851), which improves with the combination of Fototest and AD8 (aROC 0.875). The proposed CoP are AD8 ≥ 1, Fototest ≤ 35, T@M ≤ 40, and MMSE ≤ 26. CONCLUSION: BCT are helpful in detecting CI in PC. This work supports the use of more demanding PoC.

Technology Readiness Levels for vaccine and drug development in animal health: From discovery to life cycle management.

Public research and innovation initiatives in animal health aim to deliver key knowledge, services and products that improve the control of animal infectious diseases and animal welfare to deliver on global challenges including public health threats, environmental concerns and food security. The Technology Readiness Level (TRL) is a popular innovation policy instrument to monitor the maturity of upcoming new technologies in publicly funded research projects. However, while general definition of the 9 levels on the TRL-scale enable uniform discussions of technical maturity across different types of technology, these definitions are very generic which hampers concrete interpretation and application. Here, we aligned innovation pipeline stages as used in the animal health industry for the development of new vaccines or drugs with the TRL scale, resulting in TRL for animal health (TRLAH). This more bespoke scale can help to rationally allocate funding for animal health research from basic to applied research, map innovation processes, monitor progress and develop realistic progress expectations across the time span of a research and innovation project. The TRLAH thus become an interesting instrument to enhance the translation of public research results into industrial and societal innovation and foster public-private partnerships in animal health.

Characterisation of Bergeyella spp. isolated from the nasal cavities of piglets.

The aim of this study was to characterise bacteria in the genus Bergeyella isolated from the nasal passages of healthy piglets. Nasal swabs from 3 to 4 week-old piglets from eight commercial domestic pig farms and one wild boar farm were cultured under aerobic conditions. Twenty-nine Bergeyella spp. isolates were identified by partial 16S rRNA gene sequencing and 11 genotypes were discriminated by enterobacterial repetitive intergenic consensus (ERIC)-PCR. Bergeyella zoohelcum and Bergeyella porcorum were identified within the 11 genotypes. Bergeyella spp. isolates exhibited resistance to serum complement and phagocytosis, poor capacity to form biofilms and were able to adhere to epithelial cells. Maneval staining was consistent with the presence of a capsule. Multiple drug resistance (resistance to three or more classes of antimicrobial agents) was present in 9/11 genotypes, including one genotype isolated from wild boar with no history of antimicrobial use. In conclusion, Bergeyella spp. isolates from the nasal cavities of piglets showed some in vitro features indicative of a potential for virulence. Further studies are necessary to identify the role of Bergeyella spp. in disease and within the nasal microbiota of pigs.

Réplica a "Melanoma dérmico solitario y estadio IIIC" / Response to ‘‘Stage IIIC Solitary Dermal Melanoma’’

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Melanoma dérmico primario: presentación de un caso y revisión de la literatura / Primary Dermal Melanoma: A Case Report and a Review of the Literature

La supervivencia de pacientes con metástasis cutánea de melanoma de origen primario desconocido, clasificados como estadio IV (M1a) por el American Joint Comittee on Cancer para melanoma, se estima en un 5-17,9% a los 5 años, con una mediana de 6 meses. Es conocida la existencia de pacientes así clasificados que presentan una supervivencia mucho mayor, lo que ha llevado a utilizar el término de «melanoma dérmico primario» (MDP). Presentamos un caso compatible con MDP, así como una revisión de los principales artículos publicados. El diagnóstico está sujeto a una correcta correlación clínico-patológica y debe ser considerado en todos los pacientes con melanoma solitario confinado en la dermis y en el tejido celular subcutáneo, en los que no se encuentre un origen primario ni evidencia de enfermedad tras un adecuado estudio de extensión. Creemos necesario el conocimiento de esta posibilidad para un correcto manejo e información pronóstica de los pacientes (AU)

Patients with cutaneous metastatic melanoma of unknown primary origin (stage IVM1a disease according to the American Joint Committee on Cancer melanoma staging system) have an estimated 5-year survival rate of between 5% and 17.9% and a median survival of 6 months. However, certain patients with stage IV M1 a disease have much higher survival rates. The existence of this subpopulation has given rise to the term primary dermal melanoma to describe such cases. We report a case of melanoma with characteristics consistent with primary dermal melanoma and review the relevant literature. A diagnosis of primary dermal melanoma requires careful clinical and pathologic correlation and should be considered in all patients with a solitary melanoma confined to the dermis and subcutaneous tissue when there is no evidence of a primary tumor or disease at other sites following appropriate staging studies. We believe that familiarity with this subtype of melanoma is essential in order to provide patients with optimal care and better prognostic information (AU)

Primary dermal melanoma: a case report and a review of the literature.

Patients with cutaneous metastatic melanoma of unknown primary origin (stage IV M1a disease according to the American Joint Committee on Cancer melanoma staging system) have an estimated 5-year survival rate of between 5% and 17.9% and a median survival of 6 months. However, certain patients with stage IV M1a disease have much higher survival rates. The existence of this subpopulation has given rise to the term primary dermal melanoma to describe such cases. We report a case of melanoma with characteristics consistent with primary dermal melanoma and review the relevant literature. A diagnosis of primary dermal melanoma requires careful clinical and pathologic correlation and should be considered in all patients with a solitary melanoma confined to the dermis and subcutaneous tissue when there is no evidence of a primary tumor or disease at other sites following appropriate staging studies. We believe that familiarity with this subtype of melanoma is essential in order to provide patients with optimal care and better prognostic information.

[Granular parakeratosis]. / Paraqueratosis granular.

Granular parakeratosis is a rare entity that results from an acquired disorder of keratinization. Clinically presents as dark erythematous plaques, occasionally pruritic, that usually involve the axilla and other intertriginous areas. The pathology is characteristic and consists of thickening of the stratum corneum with compact parakeratosis and retention of keratohyaline granules, whereas the stratum granulosum is preserved. The etiology is unknown although some factors such as irritating physical or chemical agents have been implicated. Treatment response is variable. We report a new case in a 50-year-old woman with brownish and hyperkeratotic plaques on both axillae, of two years duration, with a compatible pathology that showed a favorable response to tacalcitol.

Paraqueratosis granular / Granular parakeratosis

La paraqueratosis granular es una entidad poco frecuente que se caracteriza por ser una alteración adquirida de la queratinización. Clínicamente se presenta como placas eritematoparduscas, ocasionalmente pruriginosas, que clásicamente aparecen en la axila y áreas intertriginosas. La histología es característica, donde se observa un engrosamiento de la capa córnea con una paraqueratosis compacta y persistencia de gránulos de queratohialina, mientras que el estrato granuloso se encuentra preservado. La etiología es desconocida, se postula la acción de factores irritantes físicos o químicos. La respuesta al tratamiento es variable. Presentamos un nuevo caso en una mujer de 50 años, con placas marronáceas abollonadas e hiperqueratósicas en ambas axilas, de dos años de evolución y con histología compatible, que presentó una buena respuesta al tratamiento con tacalcitol

Granular parakeratosis is a rare entity that results from an acquired disorder of keratinization.Clinically presents as dark erythematous plaques, occasionally pruritic, that usually involve the axilla and other intertriginous areas. The pathology is characteristic and consists of thickening of the stratum corneum with compact parakeratosis and retention of keratohyaline granules, whereas the stratum granulosum is preserved. The etiology is unknown although some factors such as irritating physical or chemical agents have been implicated. Treatment response is variable. We report a new case in a 50-year-old woman with brownish and hyperkeratotic plaques on both axillae, of two years duration, with a compatible pathology that showed a favorable response to tacalcitol

Developmental changes of the GABA-immunoreactive fibers in the lamprey spinal cord.

The changes in distribution and number of GABA immunoreactive (GABA-ir) fibers from postembryonic stages to adulthood in the lamprey spinal cord white matter were studied by using immunocytochemical techniques. From prolarvae to adult spawning animals there was an increase of the number of GABA-ir fibers. Three phases can be distinguished: (a) from prolarvae to middle size larvae (around 50 mm in body length) an increase in the number of GABA-ir fibers per section is observed. Furthermore, an adult-like pattern of GABA-ir fibers distribution is established during this phase. (b) Then, the number of GABA-ir fibers remains stable until metamorphosis, the end of the larval period. (c) Finally, in young postmetamorphic and adult animals the number of GABA-ir fibers is higher than in larvae. These observations, joined to the changes previously reported in the GABA-ir neurons, indicate that at least parts of the GABA inhibitory component of the spinal locomotor network is reorganized during the lamprey life cycle and it may indicate different inhibitory requirements in the locomotor network.

Lymphoproliferative responses and protection in conventional piglets inoculated orally with virulent or attenuated porcine epidemic diarrhoea virus.

Lymphocyte proliferative responses were evaluated in mucosal (mesenteric lymph nodes) and systemic (spleen and blood) lymphoid tissues of conventional piglets inoculated with the virulent or attenuated isolates of porcine epidemic diarrhoea virus (PEDV) strain CV-777 and challenged 21 days later with the virulent isolate of the same virus. A lymphoproliferative assay was developed in which mononuclear cells isolated from lymphoid tissues at different postinoculation and postchallenge days underwent a secondary in vitro stimulation with semipurified antigen obtained from PEDV-infected cell cultures. Vigorous lymphocyte proliferative responses were detected in the pigs inoculated with the virulent PEDV at postinoculation days 4-21, especially in the mesenteric lymph nodes and the blood; however, in the spleen this response was lower and less regular. The pigs inoculated with the attenuated virus showed a less intense response, the higher lymphocyte proliferation also corresponded to the mononuclear cells from mesenteric lymph nodes. Lymphocyte proliferation responses showed high correlations with protection against homologous challenge with virulent PEDV, and this correlation was higher in the gut associated lymphoid tissues (mesenteric lymph nodes). The cell proliferation response detected in blood mirrored that detected in the mesenteric lymph nodes, and showed also good correlation with protection. The results confirm that T-cell-helper function, assessed by lymphocyte proliferation responses, contributes to establishing a protective immune response against PEDV infections.

Immunocytochemical localization of calretinin in the olfactory system of the adult lamprey, Lampetra fluviatilis.

The distribution of calretinin immunoreactive (CR-ir) structures in the adult lamprey (Lampetra fluviatilis) olfactory system was studied by using immunocytochemical techniques. In the olfactory epithelium, a subpopulation of olfactory receptor cells was CR-ir. In the olfactory bulbs, three different cell populations were observed. Large CR-ir cells (mitral cells) were located medially to the olfactory glomeruli and occasionally between them. In the inner cellular layer, two types of CR-ir perikarya were found: numerous small CR-ir cells (granule cells) and some medium-sized CR-ir cells (putative displaced periglomerular cells). In addition, different intensities of CR-ir fibers were present in particular rootlets of the olfactory nerves, as well as in particular glomeruli. The presence of CR-ir cells and fibers in all layers of the lamprey olfactory bulbs supports the idea that this protein is present in pathways underlying the processing of sensory information throughout evolution.

Mucosal and systemic isotype-specific antibody responses and protection in conventional pigs exposed to virulent or attenuated porcine epidemic diarrhoea virus.

Eleven-day-old conventionally reared piglets were inoculated orally with two different doses of the cell-culture adapted strain CV-777 of the porcine epidemic diarrhoea virus (PEDV) or the virulent isolate of the same strain and challenged with the same virulent PEDV 3 weeks later. Pigs inoculated with the two doses of the attenuated virus did not show any typical sign of the disease, and virus shedding was not frequent. In contrast, 31% of pigs exposed to the virulent PEDV developed diarrhoea and virus shedding was demonstrated in 100%. At different postinoculation day (PID) and postchallenge day (PCD) virus-specific antibody-secreting cells (ASC) in gut associated lymphoid tissues (duodenum and ileum lamina propria and mesenteric lymph nodes) and systemic locations (blood and spleen) were assessed by enzyme-linked immunospot (ELISPOT). Only a small response was detected in the groups inoculated with attenuated PEDV, whereas in the group previously exposed to the virulent virus on PID 21 a large number of IgG and IgA ASC was detected. Isotype-specific antibody responses in serum were investigated by ELISA. IgG responses were detected in all groups, although the highest response corresponded to the group inoculated with virulent virus and only this group showed an IgA response. The pigs exposed to virulent PEDV were completely protected against the challenge with a higher dose of the same virulent virus on PID 21 and none of them shed the virus. The pigs inoculated with the attenuated strain were partially protected against the challenge, and 25% of the low dose- and 50% of the high dose-exposed pigs did not shed virus after challenge. All the pigs from a control group, not previously exposed to the virus, excreted the virus in faeces. A strong positive correlation was established between protection and the ASC responses detected in gut associated lymphoid tissues and blood at the challenge day and also between protection and serum isotype-specific antibody titers on that day. In addition, the IgA and IgG ASC responses detected in the blood on PID 21 also correlated with the responses found in the gut associated lymphoid tissues. The ASC and serum antibody responses after the challenge corresponded to a secondary immune response in the groups inoculated with attenuated virus, whereas a primary response was evident in the control group. No increase was seen in any of the parameters studied in the pigs inoculated with virulent PEDV.

Isotype-specific antibody-secreting cells in systemic and mucosal associated lymphoid tissues and antibody responses in serum of conventional pigs inoculated with PEDV.

An enzyme-linked immunospot (ELISPOT) has been developed to detect porcine epidemic diarrhea virus (PEDV)-specific antibody secreting cells (ASC) in gut associated lymphoid tissues (duodenum and ileum lamina propria and mesenteric lymph nodes) and systemic locations (spleen and blood) of conventional pigs so as to characterise the mucosal and systemic antibody response generated by the infection with PEDV. A total number of 28 eleven-day-old conventional pigs were orally inoculated with the field isolate of the PEDV strain CV-777. Diarrhea was observed in 32% of the pigs and virus shedding was demonstrated in 100% between postinoculation day (PID) 1 and 8. Serum IgG and IgA antibodies to PEDV were detected by isotype ELISA from PID 12 and 15, respectively, reaching maximum values at PID 32 (IgG) and 21 (IgA). PEDV specific IgM ASC occurred in all the tissues between PID 4 and 7, with the strongest response in the intestinal lamina propria. IgA and IgG ASC responses were evident in the intestinal lymphoid tissues from PID 21, the highest number of specific ASC corresponded to the duodenum lamina propria. In the systemic lymphoid tissues the number of IgG and IgA ASC detected were lower than in the mucosal tissues, however, in the blood, presence of IgA ASC was constantly detected from PID 14 until the end of the experiment. Memory antibody response to the PEDV was also studied by secondary in vitro stimulation of the mononuclear cells (MNC) isolated from mesenteric lymph nodes, spleen and blood. The memory B cell response was prominent at PID 21 and 25 and consisted in IgG and IgA ASC. To our knowledge, this is the first report to research into the presence and distribution of specific ASC in different locations of the systemic and the gut associated lymphoid tissues after a PEDV infection as well as the presence of memory B cells.

Granulomatous enteritis and lymphadenitis in Iberian pigs naturally infected with Lawsonia intracellularis.

Intestinal samples and/or lymph nodes of two Iberian pigs from two different farms were submitted for histopathologic examination. Both pigs had proliferation of ileal and/or cecal crypts with almost complete absence of goblet cells. Infection by Lawsonia intracellularis was demonstrated by immunohistochemistry and polymerase chain reaction assay. The mesenteric lymph node of one pig had moderate lymphocyte depletion with granulomatous inflammation of the lymph node parenchyma. Histiocytes and multinucleated giant cells from the lymph node of one pig contained L. intracellularis antigen within the cytoplasm. This pig had also porcine circovirus type 2 (PCV-2) infection, but nucleic acid and antigen of this virus were not demonstrated in the lymph node. The second pig had lymphocyte depletion and marked granulomatous inflammation in Peyer's patches. Histiocytes and multinucleated giant cells in areas of granulomatous inflammation contained L. intracellularis antigen; no PCV-2 nucleic acid or antigen was detected in the tissues of this pig. This is the first description of granulomatous ileitis and lymphadenitis associated with L. intracellularis infection.