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Catalonia (Spain) has a total population of 7.3 million citizens for whom the National Health Service (NHS) provides health care that is free at the point of access. The prevalence of terminally ill patients is between 30,100 and 39,600. Twenty years ago, the World Health Organization (WHO), in collaboration with the Catalan Department of Health and the Catalan Institute of Oncology, began a demonstration project (WHO Demonstration Project) in palliative care (PC) with the aim of implementing specialist PC services, generating experience in this field, identifying areas for improvement, and introducing educative procedures (clinical and nonclinical). Over the past 20 years, 237 PC clinical services (72 home care support teams, 49 hospital support teams, 60 units with 742 dedicated beds, 50 outpatient clinics, and six psychosocial support teams) have been implemented. In the five years since the previous evaluation, 57 new clinical services (15 new hospital support teams, 36 outpatient clinics, and six psychosocial support teams among others) and four nonclinical services (education, research, WHO Collaborating Center, and planning) have been implemented. During the year 2010, a total of 46,200 processes were undertaken for the care of 23,100 patients, of whom 12,100 (52%) had cancer and 11,000 (48%) had other chronic advanced diseases. The overall yearly costs are around 52,568,000, with an overall savings of 69,300,000 (2275 per patient, net savings to the NHS of 16,732,000). In the last five years, three qualitative evaluations and a benchmarking process have been performed to identify weak points and inequities in care provision among districts. Systematic assessments indicate high cost-effectiveness of care as well as high levels of satisfaction by patients and their relatives, thus reinforcing the principle that access to PC under the auspices of the NHS at the end of life is a basic human right. [ABSTRACT FROM AUTHOR]

The role of culture is significant in hospice palliative care (HPC). While mainstream HPC has been well described in many Western countries, there is no conceptual clarity regarding the meaning of HPC among minority cultures and ethnicities. In this article, we describe and critically appraise the findings of a literature synthesis of 15 qualitative studies regarding the conceptualization of HPC among culturally diverse populations. Three primary themes emerged regarding HPC. They highlight that (1) HPC should attend to the physical, psychosocial, and spiritual aspects of death and dying; (2) the ideal HPC provider demonstrates excellent knowledge and expertise about end-of-life care, and is respectful, genuine, and compassionate; and (3) HPC should include a range of resources that alleviate the potential burdens associated with end-of-life care. The synthesis of this knowledge suggests that expectations regarding the scope of HPC across ethnic and cultural groups have more similarities than differences to the goals of mainstream HPC. [ABSTRACT FROM AUTHOR]

Harnessing beneficial microorganisms is seen as a promising approach to enhance sustainable agriculture production. Synthetic communities (SynComs) are increasingly being used to study relevant microbial activities and interactions with the plant host. Yet, the lack of community standards limits the efficiency and progress in this important area of research. To address this gap, we recommend three actions: (1) defining reference SynComs; (2) establishing community standards, protocols and benchmark data for constructing and using SynComs; and (3) creating an infrastructure for sharing strains and data. We also outline opportunities to develop SynCom research through technical advances, linking to field studies, and filling taxonomic blind spots to move towards fully representative SynComs., (© 2024. Springer Nature Limited.)

Background and Purpose: Magnetically controlled motorized intramedullary lengthening nails (ILNs) can be employed for simultaneous correction of angular deformities of the distal femur and leg length discrepancy. This spares typical complications of external fixators but requires precise preoperative planning and exact intraoperative execution. To date, its results are insufficiently reported. We aimed to elucidate the following questions: (i) Is acute angular deformity correction and gradual femoral lengthening via a retrograde ILN a reliable and precise treatment option? (ii) What are the most common complications of treatment?, Methods: Acute angular deformity correction and subsequent gradual lengthening of the distal femur with retrograde ILN was retrospectively analyzed in 45 patients (median patient age: 15 years, interquartile range [IQR] 13-19 and median follow-up: 40 months, IQR 31-50). Outcome parameters were accuracy, precision, reliability, bone healing, and complications of treatment., Results: The median distraction was 46 mm (IQR 29-49), median distraction and consolidation index 0.9 mm/day (IQR 0.7-1.0) and 29 days/cm (IQR 24-43), respectively. The median preoperative mechanical axis deviation (MAD) was 30 mm (IQR 23-39) in the varus cohort and -25 mm (IQR -29 to -15) in the valgus cohort and reduced to a mean of 8 mm (standard deviation [SD] 8) and -3 (SD 10), respectively. Accuracy, precision, and reliability of lengthening were 94%, 95% and 96%, respectively. Accuracy and precision of deformity correction were 92% and 89%, respectively. In total, 40/45 of patients achieved distraction with a difference of less than 1 cm from the initial plan and a postoperative MAD ranging from -10 mm to +15 mm. In 13/45 patients unplanned additional surgeries were conducted to achieve treatment goal with nonunion being the most frequent (4/45) and knee subluxation (3/45) the most severe complication., Conclusion: Acute deformity correction and subsequent lengthening of the distal femur with retrograde ILN is a reliable and accurate treatment achieving treatment goal in 89% but unplanned additional surgeries in 29% of patients should be anticipated.

During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury. If unresolved, this process leads to sustained inflammation, which can cause life-threatening diseases and cancer. Here, we identify a role of double PHD fingers 2 (DPF2) in modulating inflammation. DPF2 is a defining subunit of the hematopoiesis-specific BAF (SWI/SNF) chromatin-remodeling complex, and it is mutated in multiple cancers and neurological disorders. We uncovered that hematopoiesis-specific Dpf2-KO mice developed leukopenia, severe anemia, and lethal systemic inflammation characterized by histiocytic and fibrotic tissue infiltration resembling a clinical hyperinflammatory state. Dpf2 loss impaired the polarization of macrophages responsible for tissue repair, induced the unrestrained activation of Th cells, and generated an emergency-like state of HSC hyperproliferation and myeloid cell-biased differentiation. Mechanistically, Dpf2 deficiency resulted in the loss of the BAF catalytic subunit BRG1 from nuclear factor erythroid 2-like 2-controlled (NRF2-controlled) enhancers, impairing the antioxidant and antiinflammatory transcriptional response needed to modulate inflammation. Finally, pharmacological reactivation of NRF2 suppressed the inflammation-mediated phenotypes and lethality of Dpf2Δ/Δ mice. Our work establishes an essential role of the DPF2-BAF complex in licensing NRF2-dependent gene expression in HSCs and immune effector cells to prevent chronic inflammation.

Purpose: We aimed to evaluate the effectiveness of a virtual community of practice (vCoP) in improving primary health care professionals' (HCPs') attitudes toward empowering patients with chronic disease., Methods: We conducted a cluster randomized controlled trial. Practices were units of randomization, and primary HCPs and patients were units of analysis. Sixty-three practices in Madrid, Catalonia, and the Canary Islands were randomly allocated to the intervention or control groups. Randominzation of practices was performed after HCP and patient recruitment. The patients and statistician were anonymized to group allocation; it was not possible to anonymize HCPs. The intervention was a 12-month multicomponent tailored vCoP built on the Web 2.0 concept and focused on skills toward patient empowerment. The primary outcome was Patient-Provider Orientation Scale (PPOS) score at baseline and at 12 months. The secondary outcome was the Patient Activation Measure (PAM) score., Results: A total of 321 HCPs and 1,921 patients were assessed. The intervention had a positive effect on PPOS total score (0.14 points higher in the vCoP arm; 95% CI, 0.03-0.25; P = .011) and the PPOS Sharing subscale (0.3 points higher in the vCoP arm; 95% CI, 0.15-0.44; P < .001). No effect was found for the PPOS Caring subscale, and no significant differences were found for PAM scores., Conclusions: A vCoP led to a minor increase in the PPOS Sharing component and the total score but not in the Caring component. However, considerable uncertainty remains, given the observed attrition and other limitations of the study. Further research is needed on the effectiveness of the vCoP model and on how to improve HCP engagement. VISUAL ABSTRACT ., (© 2022 Annals of Family Medicine, Inc.)

Background: Fibroblastic foci (FF) are characteristic features of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) and one cardinal feature thought to represent a key mechanism of pathogenesis. Hence, FF have a high impact on UIP/IPF diagnosis in current guidelines. However, although less frequent, these histomorphological hallmarks also occur in other fibrotic pulmonary diseases. Currently, there is therefore a gap in knowledge regarding the underlying molecular similarities and differences of FF in different disease entities., Methods: In this work, we analyzed the compartment-specific gene expression profiles of FF in IPF and sarcoidosis in order to elucidate similarities and differences as well as shared pathomechanisms. For this purpose, we used laser capture microdissection, mRNA and protein expression analysis. Biological pathway analysis was performed using two different gene expression databases. As control samples, we used healthy lung tissue that was donated but not used for lung transplantation., Results: Based on Holm Bonferroni corrected expression data, mRNA expression analysis revealed a significantly altered expression signature for 136 out of 760 genes compared to healthy controls while half of these showed a similar regulation in both groups. Immunostaining of selected markers from each group corroborated these results. However, when comparing all differentially expressed genes with the fdr -based expression data, only 2 of these genes were differentially expressed between sarcoidosis and IPF compared to controls, i.e., calcium transport protein 1 ( CAT1 ) and SMAD specific E3 ubiquitin protein ligase 1 ( SMURF1 ), both in the sarcoidosis group. Direct comparison of sarcoidosis and IPF did not show any differentially regulated genes independent from the statistical methodology. Biological pathway analysis revealed a number of fibrosis-related pathways pronounced in IPF without differences in the regulatory direction., Conclusions: These results demonstrate that FF of end-stage IPF and sarcoidosis lungs, although different in initiation, are similar in gene and protein expression, encouraging further studies on the use of antifibrotic agents in sarcoidosis.

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 - 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Aims: The cytoskeletal signaling protein four and-a-half LIM domains 1 (FHL-1) has recently been identified as a novel key player in pulmonary hypertension as well as in left heart diseases. In this regard, FHL-1 has been implicated in dysregulated hypertrophic signaling in pulmonary arterial smooth muscle cells leading to pulmonary hypertension. In mice, FHL-1-deficiency (FHL-1 -/- ) led to an attenuated hypertrophic signaling associated with a blunted hypertrophic response of the pressure-overloaded left ventricle (LV). However, the role of FHL-1 in right heart hypertrophy has not yet been addressed., Methods and Results: We investigated FHL-1 expression in C57Bl/6 mice subjected to chronic biomechanical stress and found it to be enhanced in the right ventricle (RV). Next, we subjected FHL-1 -/- and corresponding wild-type mice to pressure overload of the RV by pulmonary arterial banding for various time points. However, in contrast to the previously published study in LV-pressure overload, which was confirmed here, RV hypertrophy and hypertrophic signaling was not diminished in FHL-1 -/- mice. In detail, right ventricular pressure overload led to hypertrophy, dilatation and fibrosis of the RV from both FHL-1 -/- and wild-type mice. RV remodeling was associated with impaired RV function as evidenced by reduced tricuspid annular plane systolic excursion. Additionally, PAB induced upregulation of natriuretic peptides and slight downregulation of phospholamban and ryanodine receptor 2 in the RV. However, there was no difference between genotypes in the degree of expression change., Conclusion: FHL-1 pathway is not involved in the control of adverse remodeling in the pressure overloaded RV.

Background/aim: Head and neck squamous cell carcinomas (HNSCC) are characterized by aggressiveness, early recurrence and lymph node metastasis. Therefore, there is an urgent need to identify new biomarkers and drug targets., Materials and Methods: Neck dissection specimens from 11 patients diagnosed with hypopharyngeal cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and rich in cysteine (SPARC) using immunoblot analysis., Results: Compared to lymph node biopsies of healthy controIs, LVD was significantly increased in metastatic lymph nodes as well as in advanced primary tumors. Overexpression of eIF4E and SPARC was demonstrated in all hypopharyngeal cancer specimens. Notably, we observed that increased LVD significantly correlated with the expression of eIF4E as well as SPARC levels., Conclusion: eIF4E- and SPARC-associated signaling pathways may be associated with lymphangiogenesis and could be exploited to counteract the spread of hypopharyngeal cancer cells., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To find out the perception, attitudes and needs expressed by primary care professionals in the Girona (Spain) health area as regards the diagnosis and monitoring of patients with cognitive disorders., Design: Cross sectional study conducted in 26 primary healthcare areas (ABS) in Girona., Setting: Primary healthcare areas (ABS) in Girona., Participants: Physicians and primary nursing care (PNC). MAIN MEASURAMENTS: Self-administered questionnaire by the professionals in the centres. In the context of regular meetings of the teams., Results: A total 218 practitioners from 19 ABS (73% of total) responded to the questionnaire (108 physicians and 110 primary nursing care-PNC-). Almost all (98.6%) of participants thought they needed training in dementia, but 49.1% of physicians and 74.5% of PNC mentioned never having any specific training or not in the last 5 years. A total of 88.7% of doctors do not make a diagnosis of dementia on a regular basis, and only in 25.5% of cases do they make one in the mild stages of dementia. The main barriers reported by physicians in the diagnosis of dementia were the lack of confidence in diagnosis (32.6%) and lack of consultation time (31.4%). The great majority (87%) of physicians mentioned difficulties in monitoring and control of these patients., Conclusions: This study provides useful information for those involved in the care of dementia. It identifies priority training issues, and barriers and difficulties in the diagnosis, treatment and monitoring of these patients in the field of primary care., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Background: A wide range of palliative care services has been implemented in Catalonia over the past 20 years. Quantitative and qualitative differences in the organization of palliative care services between districts and settings can result in wide variability in the quality of these services, and their accessibility., Methods: We implemented a benchmark methodology to compare dimensions of care and organization, to identify aspects requiring improvement, and to establish indicators to measure progress. The overall aim was to generate a consensus document for submission to the Department of Health (DoH) of the Government of Catalonia., Results: A Steering Committee convoked a meeting in Barcelona (Catalonia, Spain) and representatives (n = 114) of all the 37 districts within our health care remit (rural, urban, intermediate, and metropolitan) and settings of the health care system (hospitals, social health centers, community, and nursing homes) attended and took part in plenary sessions and workshops to define areas that, in their experience, were considered weak. Twenty-one consensus recommendations achieving high levels of consensus were generated for submission to the DoH. These included the formal definition of the model of care and organization of palliative care services at all levels in the region, the implementation of measures for improvement in different settings and scenarios, systems for continuous care, and facilities for the continuing training of health care personnel. These proposals have since been implemented in a trial region and, depending on the outcomes, will be applied throughout our health service., Conclusion: We conclude that benchmark methodology is valuable in acquiring data for use in improving palliative care organization for patients' benefit.

Biologic therapy for the treatment of autoimmune diseases such as rheumatoid arthritis leads to a series of secondary effects and complications which are ever more frequent and increasingly complicate both the management as well as the associated comorbidity. We present the case of a patient who had one of theses associated complications., (Copyright © 2008 Elsevier España. Reumatología Clínica ® Sociedad Española de Reumatología and ® Colegio Mexicano de Reumatología. Published by Elsevier Espana. All rights reserved.)

Background and Objective: There is enough evidence about how physical activity decreases the risk of some chronic diseases; although there are few studies that value the effectiveness of clinical counseling on increase physical activity levels on the population. There is no information about the effectiveness of clinical counseling on decreasing other non-healthy habits, like smoking., Patients and Method: After measure the amount of physical activity on adult population, we selected the group with light level (< 143 Kcal/day), dividing them in two random groups: intervention, that received sanitary advice on increase physical activity on free time, and control, without this intervention. On both, we inquire about physical activity and healthy habits 12 months after the intervention., Results: After twelve months, in the intervention group we observed a mean increase of 1,766 cal/week (95% confidence interval [CI], 1,400-2,132) vs 488 (95% CI, 295-520) in control group (p < .001). 69% of patients from intervention group made intense physical activity vs 15% from controls (p < .001). Control group also improved health-self perception and had a significant reduction on cigarettes consumption., Conclusions: Sanitary counseling is efficient on improving physical activity on leisure. An added benefit is to gain better self-perception health and smoking cessation.

Objective: To evaluate the effectiveness of medical counselling in reducing alcohol consumption in male heavy drinkers., Design: A controlled, randomised, simple-blind intervention study., Setting: Four Primary Care teams in Area 10, Madrid., Patients: 152 men who attended for on-demand treatment from the four teams and whose alcohol consumption was over 21 International Units (IU) a week., Intervention: Brief medical counselling backed up by didactic material. Two questionnaires on alcohol consumption in IU, consumption habits and problems related to alcohol were administered, separated by an interval of between 6 and 18 months. Non-parametric tests for paired samples (McNemar) were applied., Results: 60% answered the second questionnaire. Neither sociodemographic nor health habit differences were found between those who responded and those who did not, except for social class. There were no appreciable differences between the intervention and control groups. The percentage of drinkers above 35 IU decreased significantly in the intervention group., Conclusions: The intervention was clearly effective in reducing the percentage of drinkers whose weekly consumption was over 35 IU.

Human granulocyte-colony stimulating factor (hG-CSF) can be efficiently synthesized in E. coli as a fusion to a quimeric signal peptide, but this fusion is only partially exported to the periplasm. We have studied the effects of supplementing the host content in chaperonins on the secretion of prehG-CSF in E. coli. We have found that the DnaK/DnaJ chaperonin system improves the secretion of this recombinant protein. This improvement correlates with an increase in the solubility of the precursor. Only a small fraction of the mature protein is released from the periplasm by an osmotic shock.