'Value-based methodology for person-centred, integrated care supported by Information and Communication Technologies' (ValueCare) for older people in Europe: study protocol for a pre-post controlled trial.

BACKGROUND: Older people receive care from multiple providers which often results in a lack of coordination. The Information and Communication Technology (ICT) enabled value-based methodology for integrated care (ValueCare) project aims to develop and implement efficient outcome-based, integrated health and social care for older people with multimorbidity, and/or frailty, and/or mild to moderate cognitive impairment in seven sites (Athens, Greece; Coimbra, Portugal; Cork/Kerry, Ireland; Rijeka, Croatia; Rotterdam, the Netherlands; Treviso, Italy; and Valencia, Spain). We will evaluate the implementation and the outcomes of the ValueCare approach. This paper presents the study protocol of the ValueCare project; a protocol for a pre-post controlled study in seven large-scale sites in Europe over the period between 2021 and 2023. METHODS: A pre-post controlled study design including three time points (baseline, post-intervention after 12 months, and follow-up after 18 months) and two groups (intervention and control group) will be utilised. In each site, (net) 240 older people (120 in the intervention group and 120 in the control group), 50-70 informal caregivers (e.g. relatives, friends), and 30-40 health and social care practitioners will be invited to participate and provide informed consent. Self-reported outcomes will be measured in multiple domains; for older people: health, wellbeing, quality of life, lifestyle behaviour, and health and social care use; for informal caregivers and health and social care practitioners: wellbeing, perceived burden and (job) satisfaction. In addition, implementation outcomes will be measured in terms of acceptability, appropriateness, feasibility, fidelity, and costs. To evaluate differences in outcomes between the intervention and control group (multilevel) logistic and linear regression analyses will be used. Qualitative analysis will be performed on the focus group data. DISCUSSION: This study will provide new insights into the feasibility and effectiveness of a value-based methodology for integrated care supported by ICT for older people, their informal caregivers, and health and social care practitioners in seven different European settings. TRIAL REGISTRATION: ISRCTN registry number is 25089186 . Date of trial registration is 16/11/2021.

¿Qué haría usted ante un paciente adulto que consulta por una tumoración cervical? / What would you do with an adult patient who complains of a neck mass?

Las tumoraciones cervicales son un motivo de consulta frecuente en Atención Primaria. La etiología de estas tumoraciones es muy diversa y engloba patología maligna. El reto fundamental para el médico de Atención Primaria es identificar los casos que son secundarios a tumores malignos o enfermedades graves. Un buen conocimiento de la anatomía del cuello, asociado a una buena anamnesis y a exploración física, nos permitirán llegar a una correcta orientación diagnóstica en la mayoría de los casos y, si es necesario, a seleccionar las pruebas complementarias adecuadas o a derivar al siguiente nivel asistencial, y con qué grado de prioridad, en función de la sospecha diagnóstica. El linfoma debuta con frecuencia con adenopatías cervicales como primera manifestación clínica, como es el caso de nuestro paciente. Tras la revisión del tema, aportamos un algoritmo de ayuda para el abordaje clínico (U)

Family physicians frequently encounter patients with neck mass. There are multiple causes that range from no clinical importance to malignant tumours. The critical challenge for the primary care physician is to identify which cases are secondary to malignancies or other serious conditions. With a good knowledge of the complex anatomy of the neck and a careful clinical history, including a complete physical examination, the different causes can be narrowed down, as well as to differentiate between significant and non-significant neck masses and select the appropriate studies. Lymphoma commonly presents as a painless enlarged lump in the neck, as in the case of the patient presented. An algorithm is provided to help practioners (AU)

[What would you do with an adult patient who complains of a neck mass?]. / ¿Qué haría usted ante un paciente adulto que consulta por una tumoración cervical?

Family physicians frequently encounter patients with neck mass. There are multiple causes that range from no clinical importance to malignant tumours. The critical challenge for the primary care physician is to identify which cases are secondary to malignancies or other serious conditions. With a good knowledge of the complex anatomy of the neck and a careful clinical history, including a complete physical examination, the different causes can be narrowed down, as well as to differentiate between significant and non-significant neck masses and select the appropriate studies. Lymphoma commonly presents as a painless enlarged lump in the neck, as in the case of the patient presented. An algorithm is provided to help practioners.

Informe alta enfermería: historia clínica integral / No disponible

Mediante la elaboración de nuestro trabajo pretendemos unificar criterios de actuación, fomentar el desarrollo de nuestra profesión mediante la práctica de la enfermería basada en la evidencia, garantizando la comunicación entre profesionales de enfermería de diferentes niveles de salud, mejorando la calidad de los cuidados proporcionados, promoviendo el trabajo en equipo, siempre en beneficio del paciente (AU)

With our paper we aim to unify action criteria, promote the development of our job by means of nursing practice based on evidence, guarantying the communication among nurse professionals of different health roles, improving the quality of cares delivered, promoting teamwork, always for the patients interest (AU)

Cot/Tpl-2 protein kinase as a target for the treatment of inflammatory disease.

Cot/Tpl-2/MAP3K8 is a serine/threonine protein kinase that is essential for lipopolysaccharide (LPS)-induced activation of the MEK/ERK pathway in macrophages as demonstrated in Cot/Tpl-2-deficient mice. Cot/Tpl-2 kinase activation plays an integral role in the production of pro-inflammatory cytokines such as TNF and IL-1beta in this immune cell type. Elevated levels of these cytokines have been clinically implicated as mediators of a number of autoimmune diseases, in particular, the pain and joint destruction of rheumatoid arthritis. By inference, pharmaceutical agents that inhibit Cot/Tpl-2 kinase have the potential to be novel and effective therapies for the treatment of these diseases. This review will describe the physiological regulation and importance of Cot/Tpl-2 in inflammation as well as the landscape of small molecules that have been reported as Cot/Tpl-2 inhibitors.

Utility of helical computed tomography to evaluate the invasion of actinomycetoma; a report of 21 cases.

BACKGROUND: Actinomycetoma is a chronic infection caused by several aerobic actinomycetes; it is a relatively frequent condition in tropical countries like Mexico. It is important to be aware of the extension and depth of the disease (bone and visceral) to make the prognosis and select treatment. OBJECTIVES: Our objective was to evaluate actinomycetomas using helical computed tomography (HCT) as well as its three-dimensional (3D) reconstruction. MATERIAL AND METHODS: Prospective study of clinically and microbiologically proven cases of actinomycetomas, all of them recently diagnosed and untreated or unresponsive to various treatments. All patients underwent simple and contrast HCT with various helical slices of the involved zones. Then three-dimensional reconstructions on the sagittal and coronal planes were made. RESULTS: Twenty-one patients with actinomycetomas were included, 19 males and two females, with a mean age of 35.5 years and mean duration of disease of 4.1 years. The disease was located in the lower limbs in 81%, and in the upper limbs and trunk in 19%. Twenty of the 21 cases were caused by Nocardia brasiliensis and one by Actinomadura madurae. In all patients the disease was localized to the skin and subcutaneous tissue; 76.2% had muscular involvement; 23.8% visceral involvement; 9.5% had bone involvement and 9.5% vascular involvement. The affected area was determined in each case. CONCLUSIONS: HCT provides precise information about the grade of invasion at diverse levels such as visceral, muscular and vascular systems, and the calculation of the affected area.

Activity of tigecycline against clinical isolates of Staphylococcus aureus and extended-spectrum beta-lactamase-producing Escherichia coli in Granada, Spain.

We evaluated the in vitro activity of tigecycline using the Etest and disk diffusion method according to Clinical and Laboratory Standards Institute guidelines against clinical isolates of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) as well as for CTX-M-9 extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and SHV ESBL-producing E. coli. All isolates were susceptible to tigecycline according to US Food and Drug Administration cut-off points. There were no differences in the activity of tigecycline between MSSA and MRSA isolates or between the presence of either type of ESBL. For each type of microorganism studied, we established the equation relating the minimum inhibitory concentration to the diameter of the zone of inhibition.

Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis.

The p105 precursor protein of NF-kappaB1 acts as an NF-kappaB inhibitory protein, retaining associated Rel subunits in the cytoplasm of unstimulated cells. Tumor necrosis factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) stimulate p105 degradation, releasing associated Rel subunits to translocate into the nucleus. By using knockout embryonic fibroblasts, it was first established that the IkappaB kinase (IKK) complex is essential for these pro-inflammatory cytokines to trigger efficiently p105 degradation. The p105 PEST domain contains a motif (Asp-Ser(927)-Gly-Val-Glu-Thr), related to the IKK target sequence in IkappaBalpha, which is conserved between human, mouse, rat, and chicken p105. Analysis of a panel of human p105 mutants in which serine/threonine residues within and adjacent to this motif were individually changed to alanine established that only serine 927 is essential for p105 proteolysis triggered by IKK2 overexpression. This residue is also required for TNFalpha and IL-1alpha to stimulate p105 degradation. By using a specific anti-phosphopeptide antibody, it was confirmed that IKK2 overexpression induces serine 927 phosphorylation of co-transfected p105 and that endogenous p105 is also rapidly phosphorylated on this residue after TNFalpha or IL-1alpha stimulation. In vitro kinase assays with purified proteins demonstrated that both IKK1 and IKK2 can directly phosphorylate p105 on serine 927. Together these experiments indicate that the IKK complex regulates the signal-induced proteolysis of NF-kappaB1 p105 by direct phosphorylation of serine 927 in its PEST domain.

Los colegios de Enfermería, Médicos y Veterinarios de Barcelona se unen para ayudar a Venezuela / The nursing, medical, and veterinary schools of Barcelona join together to help Venezuela

No disponible

TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105.

The transcription factor NF-kappaB is composed of homodimeric and heterodimeric complexes of Rel/NF-kappaB-family polypeptides, which include Rel-A, c-Rel, Rel-B, NF-kappaB/p50 and NF-kappaB2/p52 . The NF-kappaB1 gene encodes a larger precursor protein, p105, from which p50 is produced constitutively by proteasome-mediated removal of the p105 carboxy terminus. The p105 precursor also acts as an NFkappaB-inhibitory protein, retaining associated p50, c-Rel and Rel-A proteins in the cytoplasm through its carboxy terminus. Following cell stimulation by agonists, p105 is proteolysed more rapidly and released Rel subunits translocate into the nucleus. Here we show that TPL-2 , which is homologous to MAP-kinase-kinase kinases in its catalytic domain, forms a complex with the carboxy terminus of p105. TPL-2 was originally identified, in a carboxy-terminal-deleted form, as an oncoprotein in rats and is more than 90% identical to the human oncoprotein COT. Expression of TPL-2 results in phosphorylation and increased degradation of p105 while maintaining p50 production. This releases associated Rel subunits or p50-Rel heterodimers to generate active nuclear NF-kappaB. Furthermore, kinase-inactive TPL-2 blocks the degradation of p105 induced by tumour-necrosis factor-alpha. TPL-2 is therefore a component of a new signalling pathway that controls proteolysis of NF-kappaB1 p105.

Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase.

The Tpl-2 protein serine/threonine kinase was originally identified, in a C-terminally deleted form, as the product of an oncogene associated with the progression of Moloney murine leukemia virus-induced T cell lymphomas in rats. The kinase domain of Tpl-2 is homologous to the Saccharomyces cerevisiae gene product, STE11, which encodes a MAP kinase kinase kinase. This suggested that Tpl-2 might have a similar activity. Consistent with this hypothesis, immunoprecipitated Tpl-2 and Tpl-2deltaC (a C-terminally truncated mutant) phosphorylated and activated recombinant fusion proteins of the mammalian MAP kinase kinases, MEK-1 and SEK-1, in vitro. Furthermore, transfection of Tpl-2 into COS-1 cells or Jurkat T cells. markedly activated the MAP kinases, ERK-1 and SAP kinase (JNK), which are substrates for MEK-1 and SEK-1, respectively. Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1.

Transferrin receptor induces tyrosine phosphorylation in T cells and is physically associated with the TCR zeta-chain.

In addition to being an iron transporter, the transferrin receptor (TfR) has been shown to play a role in T cell activation. Stimulation of the TfR with specific Abs results in T cell proliferation, IL-2 secretion, and protein kinase C activation. In this paper we have analyzed early events caused by activation of the TfR. We have found several protein substrates to be tyrosine phosphorylated upon TfR stimulation in the human Jurkat T cell line. Interestingly, the TfR induced tyrosine phosphorylation in cell lines expressing TCR but not in TCR-negative mutants. Restoration of the TCR surface expression in these mutants reestablished the ability of the TfR to induce tyrosine phosphorylation. This result suggests that activation through the TfR is functionally dependent upon the expression of the TCR. Moreover, the functional relationship of the TfR with the TCR complex is also supported by data showing that TfR stimulation resulted in the tyrosine phosphorylation of the TCR zeta-chain; conversely, stimulation of the TCR complex resulted in an increased tyrosine phosphorylation of the TfR. More importantly, the TfR is shown to associate physically with the TCR zeta-chain as well as with the zeta-binding ZAP70 tyrosine kinase. The TfR/zeta complex is expressed on the cell surface independent of the expression of the other subunits of the TCR complex. We suggest that the TfR/zeta complex is responsible for transducing the TfR-induced signals, and that it could serve to amplify signals delivered by Ag binding to the TCR.

Tyrosine kinase-dependent activation of human NK cell functions upon stimulation through a 58-kDa surface antigen selectively expressed on discrete subsets of NK cells and T lymphocytes.

We have raised a mAb, termed HP-3E4 (IgM), by immunizing BALB/c mice against human IL2-activated NK cells. The HP-3E4 mAb recognized in different donors variable proportions (< 2-70%) of either fresh or activated NK cells. A small population of T cells (alpha/beta and gamma/delta) appeared HP-3E4+ in PBL. No reactivity was detected on other leukocytes and a panel of cell lines from different lineages. By immunohistochemical staining of different tissues, few HP-3E4+ cells were detected only in lymphoid organs. Analysis of CD56+CD16+CD3- clones (n = 167) from unrelated donors (n = 6), showed that the Ag was stably expressed on 8 to 70%, moreover it was detected on some gamma/delta + T cell clones, whereas all CD3+ alpha/beta +(CD4+ and CD8+) clones analyzed (n = 90) were HP-3E4-. As assessed by SDS-PAGE analysis, the HP-3E4 mAb immunoprecipitated a 58-kDa surface structure. When compared with two mAbs (GL183 and EB6) previously reported to bind also a clonally distributed 54- to 58-kDa Ag, the HP-3E4 mAb appeared to recognize a distinct epitope, thus allowing to further define NK cell subsets. Stimulation of IL2-activated NK cells with the mAb triggered TNF-alpha and IFN-gamma production, which was enhanced by using the mAb attached to plastic or in the presence of suboptimal concentrations of phorbol esters. Although the HP-3E4 mAb did not significantly modify NK cell-mediated cytotoxicity against different targets, with the exception of the Hmy-C1R cell line, it activated BLT esterase secretion. Remarkably, the HP-3E4 mAb triggered phosphoinositide turnover and an early increase of [Ca2+]i, as well as tyrosine phosphorylation of several cellular substrates including CD3 zeta; inhibition of tyrosine kinase activity with genistein hampered the HP-3E4-mediated stimulation of cytokine production. Our data provide further support for the structural diversity of a 58-kDa surface Ag, whose expression is restricted to discrete NK and T cell subsets. Moreover, the results support the fact that the molecule plays an active role in regulating NK cell functions through signal transduction mechanisms comparable to those triggered via Fc gamma RIII.

A conformational epitope expressed upon association of CD3-epsilon with either CD3-delta or CD3-gamma is the main target for recognition by anti-CD3 monoclonal antibodies.

We have performed immunofluorescence analysis of COS cells transfected with human CD3 genes and detergent permeabilized to define the specificity of several anti-CD3 antibodies. We have found that the mAb OKT3, WT31, UCHT1, and Leu-4 did not stain COS cells singly transfected with the CD3-epsilon chain. However, these antibodies very strongly stained COS cells doubly transfected with a combination of CD3-epsilon plus either CD3-gamma or CD3-delta. By contrast, the antibodies SP34 and APA 1/1, which were raised against isolated SDS-denatured CD3-epsilon protein, gave a strong staining of COS cells singly transfected with CD3-epsilon as well as of the double transfectans. The recognition by this panel of anti-CD3 antibodies of CD3-gamma/epsilon and CD3-delta/epsilon complexes and not of CD3-epsilon alone was assessed by immunoprecipitation. These findings suggest that the most widely used mAb specific for the CD3 complex recognize conformational epitopes on CD3-epsilon, which are expressed when this chain is bound to either CD3-gamma or CD3-delta. It should also be highlighted that antibody WT31 clearly recognizes the CD3 moiety of the TCR/CD3 complex.

Osteosíntesis en cirugía maxilofacial / Osteosynthesis in maxillofacial surgery

Se revisan los diferentes métodos de fijación ósea en el tratamiento de las fracturas craneofaciales y de la cirugía de las deformidades craneo-maxilofaciales. Se analizan las diferencias entre la consolidación ósea primaria y secundaria y los mecanismos que permiten cada una de ellas. Se presentan las indicaciones y las técnicas quirúrgicas de los sistemas de osteosíntesis rígida con compresión dinámica (A.O.), el sistema no compresivo monocortical (Wurtzburg) y la fijación interna comprensiva con tornillos