Psychological assessment of patients on the heart transplant waiting list: A single center experience.

OBJECTIVE: To analyze the data of the psychological assessment, focusing attention on the quality of life and the psychological status of patients who are listed for heart transplant. METHODS: All heart failure patients listed for heart transplant at the Cardiac Surgery Unit of Bari University, Italy, were evaluated from September to November 2023, by administering the Symptom Checklist-90-R (SCL-90-R) and the Short Form Health Survey 36 (SF-36). RESULTS: Overall, 27 patients were studied. Mean age was 60 years, 88% were males. One third of the patients showed a clinically significant overall mental distress. The symptoms leading to domains such as somatization (55.55%), anxiety (40.74%) and depression (33.33%) were frequently observed. The majority of the population studied (96.30%) showed low levels of perceived physical health status, while 59,62% of them presented levels of perceived physical health status below normal ranges. CONCLUSIONS: Heart transplant candidates show elements of overall mental distress and low quality of life related to physical health status.

The prognostic value of the NECPAL instrument, Palliative Prognostic Index, and PROFUND index in elderly residents of nursing homes with advanced chronic condition.

BACKGROUND: It is essential to assess the need for palliative care and the life prognosis of elderly nursing home residents with an advanced chronic condition, and the NECPAL ICO-CCOMS©4.0 prognostic instrument may be adequate for both purposes. The objective of this study was to examine the predictive capacity of NECPAL, the Palliative Prognosis Index, and the PROFUND index in elderly residents with advanced chronic condition with and without dementia, comparing their results at different time points. METHODS: This prospective observational study was undertaken in eight nursing homes, following the survival of 146 residents with advanced chronic condition (46.6% with dementia) at 3, 6, 12, and 24 months. The capacity of the three instruments to predict mortality was evaluated by calculating the area under the receiver operating characteristic curve (AUC), with 95% confidence interval, for the global population and separately for residents with and without dementia. RESULTS: The mean age of residents was 84.63 years (± 8.989 yrs); 67.8% were female. The highest predictive capacity was found for PROFUND at 3 months (95%CI: 0.526-0.756; p = 0.016), for PROFUND and NECPAL at 12 months (non-significant; AUC > 0.5), and NECPAL at 24 months (close-to-significant (AUC = 0.624; 95% CI: 0.499-0.750; p = 0.053). The highest capacity at 12 months was obtained using PROFUND in residents with dementia (AUC = 0.698; 95%CI: 0.566-0.829; p = 0.003) and NECPAL in residents without dementia (non-significant; AUC = 0.649; 95%CI: 0.432-0.867; p = 0.178). Significant differences in AUC values were observed between PROFUND at 12 (p = 0.017) and 24 (p = 0.028) months. CONCLUSIONS: PROFUND offers the most accurate prediction of survival in elderly care home residents with advanced chronic condition overall and in those with dementia, especially over the short term, whereas NECPAL ICO-CCOMS©4.0 appears to be the most useful to predict the long-term survival of residents without dementia. These results support early evaluation of the need for palliative care in elderly care home residents with advanced chronic condition.

Is caring for pressure ulcers in the intensive care unit in Spain still a challenge? A qualitative study on nurses' perceptions.

BACKGROUND: The incidence of pressure ulcers is an indicator of quality in intensive care units. Due to their frequency and severity, they are identified as a problem of great importance, where the well-being of patients and relatives is compromised, also generating a high healthcare cost. Nurses are primarily responsible for the care of pressure ulcers, however, the existing literature exposes a clear lack of knowledge regarding its prevention and treatment. OBJECTIVES: To explore the attitudes, knowledge and perceived barriers by intensive care nurses regarding pressure ulcers treatment and prevention in a critical care setting. DESIGN: A descriptive qualitative study has been carried out through semi-structured interviews with 22 intensive care nurses from two tertiary university hospitals in Spain. The consolidated criteria for reporting qualitative research (COREQ) guidelines were used to reinforce the methodological approach of the study. FINDINGS: From the collected data, 4 main themes emerged: "lack of specific knowledge about pressure ulcers in intensive care", "continuity of care: the main problem to solve", "teamwork and pressure ulcers: gasping for improvement" and "Skin care as another vital sign". CONCLUSION: Most intensive care nurses consider that they do not have sufficient knowledge regarding pressure ulcers. The nurses' attitudes are positive, however, an ineffective transmission of information and registration regarding ulcers is perceived. Regarding the treatment of pressure ulcers, the lack of continuity of care and updated knowledge/training have been the main barriers. In terms of prevention, the most mentioned barriers have been the clinical condition of the patient and the lack of personnel, despite the level of knowledge.

[COVID-19 pandemic impact on primary care emergency services activity: Comparative study between 2019 and 2020 periods]. / Impacto de la pandemia de la COVID-19 en la actividad de los servicios de urgencias de atención primaria: estudio comparativo entre periodos de 2019 y 2020.

OBJECTIVE: To compare the care provided by primary care emergency services during the COVID19 lockdown (March-June 2020) and the same period in 2019. DESIGN: Retrospective descriptive study. SETTING: Basic Health Area of Granada. POPULATION: 10.790 emergency reports, 3.319 in 2020 and 7.471 in 2019. OUTCOMES: Age, sex, service, shifts, referrals, priority levels, care times, previous processes, and reasons for consultation. T-Student and Chi Square were used for continuous and categorical variables. Effect size (Cohen's d) and OR along with 95% CI were calculated. RESULTS: The patients attended by primary care emergency services decreased in 2020 compared to 2019, but the percentage of Priority V cases (p<0.01), home discharges (p=0.01) and hospital transfers (p<0.01) increased, and referrals to family doctors (p<0.01) decreased. In 2020, the percentage of emergencies at night (p<0.01) and in low-income neighborhoods (p<0.01) increased. Waiting time for classification decreased (p<0.01), but total care time increased in 2020 (p<0.01). The patients seen in 2020 were older (p<.001), and with a greater number of previous processes (p<0.01), highlighting patients with anxiety, depression, or somatization (p<0.01) and diabetes (p=0.041). Consultations related to various symptoms of COVID19, mental health problems and chronic pathologies increased. CONCLUSIONS: Primary care emergency services offer additional advantages in situations such as the COVID19 pandemic, as they allow channeling part of the health demand.

Negative modulation of SA signaling components by the capsid protein of tobacco mosaic virus is required for viral long-distance movement.

An important aspect of plant-virus interaction is the way viruses dynamically move over long distances and how plant immunity modulates viral systemic movement. Salicylic acid (SA), a well-characterized hormone responsible for immune responses against virus, is activated through different transcription factors including TGA and WRKY. In tobamoviruses, evidence suggests that capsid protein (CP) is required for long-distance movement, although its precise role has not been fully characterized yet. Previously, we showed that the CP of Tobacco Mosaic Virus (TMV)-Cg negatively modulates the SA-mediated defense. In this study, we analyzed the impact of SA-defense mechanism on the long-distance transport of a truncated version of TMV (TMV ∆CP virus) that cannot move to systemic tissues. The study showed that the negative modulation of NPR1 and TGA10 factors allows the long-distance transport of TMV ∆CP virus. Moreover, we observed that the stabilization of DELLA proteins promotes TMV ∆CP systemic movement. We also characterized a group of genes, part of a network modulated by CP, involved in TMV ∆CP long-distance transport. Altogether, our results indicate that CP-mediated downregulation of SA signaling pathway is required for the virus systemic movement, and this role of CP may be linked to its ability to stabilize DELLA proteins.

Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus.

Anticoagulant protein S (PS) in platelets (PSplt) resembles plasma PS and is released on platelet activation, but its role in thrombosis has not been elucidated. Here we report that inactivation of PSplt expression using the Platelet factor 4 (Pf4)-Cre transgene (Pros1lox/loxPf4-Cre+) in mice promotes thrombus propensity in the vena cava, where shear rates are low, but not in the carotid artery, where shear rates are high. At a low shear rate, PSplt functions as a cofactor for both activated protein C and tissue factor pathway inhibitor, thereby limiting factor X activation and thrombin generation within the growing thrombus and ensuring that highly activated platelets and fibrin remain localized at the injury site. In the presence of high thrombin concentrations, clots from Pros1lox/loxPf4-Cre- mice contract, but not clots from Pros1lox/loxPf4-Cre+ mice, because of highly dense fibrin networks. Thus, PSplt controls platelet activation as well as coagulation in thrombi in large veins, but not in large arteries.

Metabolism of phenolics in coffee and plant-based foods by canonical pathways: an assessment of the role of fatty acid ß-oxidation to generate biologically-active and -inactive intermediates.

ω-Phenyl-alkenoic acids are abundant in coffee, fruits, and vegetables. Along with ω-phenyl-alkanoic acids, they are produced from numerous dietary (poly)phenols and aromatic amino acids in vivo. This review addresses how phenyl-ring substitution and flux modulates their gut microbiota and endogenous ß-oxidation. 3',5'-Dihydroxy-derivatives (from alkyl-resorcinols, flavanols, proanthocyanidins), and 4'-hydroxy-phenolic acids (from tyrosine, p-coumaric acid, naringenin) are ß-oxidation substrates yielding benzoic acids. In contrast, 3',4',5'-tri-substituted-derivatives, 3',4'-dihydroxy-derivatives and 3'-methoxy-4'-hydroxy-derivatives (from coffee, tea, cereals, many fruits and vegetables) are poor ß-oxidation substrates with metabolism diverted via gut microbiota dehydroxylation, phenylvalerolactone formation and phase-2 conjugation, possibly a strategy to conserve limited pools of coenzyme A. 4'-Methoxy-derivatives (citrus fruits) or 3',4'-dimethoxy-derivatives (coffee) are susceptible to hepatic "reverse" hydrogenation suggesting incompatibility with enoyl-CoA-hydratase. Gut microbiota-produced 3'-hydroxy-4'-methoxy-derivatives (citrus fruits) and 3'-hydroxy-derivatives (numerous (poly)phenols) are excreted as the phenyl-hydracrylic acid ß-oxidation intermediate suggesting incompatibility with hydroxy-acyl-CoA dehydrogenase, albeit with considerable inter-individual variation. Further investigation is required to explain inter-individual variation, factors determining the amino acid to which C6-C3 and C6-C1 metabolites are conjugated, the precise role(s) of l-carnitine, whether glycine might be limiting, and whether phenolic acid-modulation of ß-oxidation explains how phenolic acids affect key metabolic conditions, such as fatty liver, carbohydrate metabolism and insulin resistance.

A fungal protease named AsES triggers antiviral immune responses and effectively restricts virus infection in arabidopsis and Nicotiana benthamiana plants.

BACKGROUND AND AIMS: Plants have evolved complex mechanisms to fight against pathogens. Among these mechanisms, pattern-triggered immunity (PTI) relies on the recognition of conserved microbe- or pathogen-associated molecular patterns (MAMPs or PAMPs, respectively) by membrane-bound receptors. Indeed, PTI restricts virus infection in plants and, in addition, BRI1-associated kinase 1 (BAK1), a central regulator of PTI, plays a role in antiviral resistance. However, the compounds that trigger antiviral defences, along with their molecular mechanisms of action, remain mostly elusive. Herein, we explore the role of a fungal extracellular subtilase named AsES in its capacity to trigger antiviral responses. METHODS: In this study, we obtained AsES by recombinant expression, and evaluated and characterized its capacity to trigger antiviral responses against Tobacco mosaic virus (TMV) by performing time course experiments, analysing gene expression, virus movement and callose deposition. KEY RESULTS: The results of this study provide direct evidence that exogenous treatment with recombinant AsES increases a state of resistance against TMV infection, in both arabidopsis and Nicotiana benthamiana plants. Also, the antiviral PTI response exhibited by AsES in arabidopsis is mediated by the BAK1/SERK3 and BKK1/SERK4 co-receptors. Moreover, AsES requires a fully active salicylic acid (SA) signalling pathway to restrict the TMV movement by inducing callose deposition. Additionally, treatment with PSP1, a biostimulant based on AsES as the active compound, showed an increased resistance against TMV in N. benthamiana and tobacco plants. CONCLUSIONS: AsES is a fungal serine protease which triggers antiviral responses relying on a conserved mechanism by means of the SA signalling pathway and could be exploited as an effective and sustainable biotechnology strategy for viral disease management in plants.

Frommelt Attitude Toward Care of the Dying Scale Form B: Validation for Spanish health professionals.

OBJECTIVE: The aim of this study is to culturally adapt and validate the Frommelt Attitude Toward Care of the Dying Scale Form B (FATCOD-B) in Spanish health professionals. METHOD: A cultural adaptation and scale validation was carried out to evaluate the validity of appearance, content and construct, reliability and feasibility. The psychometric validation of the FATCOD-B was carried out on a sample of 2,446 Spanish physicians, nurses, psychologists, and social workers and students of these disciplines, between January 2017 and December 2018. This sample was selected by intentional sampling. Descriptive statistics were used to characterize the sample. An exploratory multi-group factor analysis was performed, internal consistency was evaluated by calculating Cronbach's α and stability by test-retest. RESULTS: A total of 2,446 people participated in the study, 1,134 students and 1,312 professionals. The exploratory multi-group factor analysis revealed a two-dimensional factor structure, with a total of 17 items retained in the model from the 30 of the original scale. The results showed that this version has adequate reliability (α = 0.79) and for each subscale, and stability (ICC = 0.843, p < 0.001). SIGNIFICANCE OF RESULTS: FATCOD has been used with physicians and nurses from different countries. However, no reports have been found in the literature of its use with psychologists and social workers. It is important to have an instrument that allows us to know the attitudes of these professionals since they are all directly involved in the care of patients at the end of their lives and their families. The Spanish version of FATCOD-B has proven to be a reliable and valid instrument for its use in Spanish health professionals while allowing comparisons between disciplines.

Effectiveness and safety of the Space GlucoseControl system for glycaemia control in caring for postoperative cardiac surgical patients.

BACKGROUND: Hyperglycaemia is a very common complication in post-cardiac surgical patients, and as such, it must be properly managed. For this purpose, the enhanced Model Predictive Control algorithm for glycaemia control has been implemented into a nurse-led device called Space GlucoseControl (SGC) that aims to achieve a safe and effective blood glucose control in a better way than the traditional "paper-based" protocols. PURPOSE: The aim of the study was to know the effectiveness and safety of the SGC in glycaemia control in cardiosurgical adult patients in the immediate postoperative period in the intensive care unit. METHODS: A prospective before-and-after intervention study was conducted. One hundred sixty cardiosurgical adult patients with hyperglycaemia were selected: 80 in the control group from May to November 2018 and 80 in the intervention group (use of the SGC device) from January to December 2019. The primary outcome was the percentage of time within the target range (140-180 mg/dL in the control group and 100-160 mg/dL in the intervention group). RESULTS: The percentage of time within the target range was significantly higher in the SGC group than in the control group (70.5% [58.25-80] vs 54.83% [36.09-75], p < 0.001). The range was also achieved earlier with the SGC (5 [3-6.875] hours vs 7 [4-11] hours; p < 0.05). The first blood glucose value after reaching the target range was higher in the control group, with statistical significance (p < 0.05). There were no hypoglycaemia episodes in the control group. However, during SGC treatment, six episodes of hypoglycaemia occurred, and all of them were nonsevere (mean value = 61 mg/dL). CONCLUSION: The SGC is useful to achieve a faster tight glycaemic control, with a higher percentage of time within the target range, although episodes of nonsevere hypoglycaemia could be observed.

NUrsing Homes End of Life care Program (NUHELP): developing a complex intervention.

BACKGROUND: Nursing homes are likely to become increasingly important as end-of-life care facilities. Previous studies indicate that individuals residing in these facilities have a high prevalence of end-of-life symptoms and a significant need for palliative care. The aim of this study was to develop an end-of-life care program for nursing homes in Spain based on previous models yet adapted to the specific context and the needs of staff in nursing homes in the country. METHODS: A descriptive study of a complex intervention procedure was developed. The study consisted of three phases. The first phase was a prospective study assessing self-efficacy in palliative care (using the SEPC scale) and attitudes towards end-of-life care (using the FATCOD-B scale) among nursing home staff before and after the completion of a basic palliative care training program. In the second phase, objectives were selected using the Delphi consensus technique, where nursing home and primary care professionals assessed the relevance, feasibility, and level of attainment of 42 quality standards. In phase 3, interventions were selected for these objectives through two focus group sessions involving nursing home, primary care, and palliative care professionals. RESULTS: As a result of the training, an improvement in self-efficacy and attitudes towards end-of-life care was observed. In phase 2, 14 standards were selected and grouped into 5 objectives: to conduct a comprehensive assessment and develop a personalized care plan adapted to the palliative needs detected; to provide information in a clear and accessible way; to request and record advance care directives; to provide early care with respect to loss and grief; to refer patients to a specialized palliative care unit if appropriate, depending on the complexity of the palliative care required. Based on these objectives, the participants in the focus group sessions designed the 22 interventions that make up the program. CONCLUSIONS: The objectives and interventions of the NUHELP program constitute an end-of-life care program which can be implemented in nursing homes to improve the quality of end-of-life care in these facilities by modifying their clinical practice, organization, and relationship with the health system as well as serving as an example of an effective health intervention program.

Intensive care nurses' experiences during the COVID-19 pandemic: A qualitative study.

BACKGROUND: Because of the COVID-19 pandemic, health care systems worldwide are working under challenging conditions. Patients, who are seriously ill, require intensive care admission. In fighting COVID-19, nurses are frontline health care workers and, as such, have a great responsibility providing needed specialized patient care in intensive care units (ICU). However, working conditions and emotional factors have an impact on the quality of the care provided. AIM: The purpose of the present study was to explore and describe the experiences and perceptions of nurses working in an ICU during the COVID-19 global pandemic. STUDY DESIGN: Qualitative research was undertaken, using an empirical approach and inductive content analysis techniques. METHODS: The selected population consisted of ICU nurses from a tertiary teaching hospital in Spain. Data were obtained via semi-structured videocall interviews from Apr 12th to Apr 30th, 2020. Subsequently, transcribed verbatims were analysed using the template analysis model of Brooks. FINDINGS: A total of 17 nurses comprised the final sample after data saturation. Four main themes emerged from the analysis and 13 subthemes: "providing nursing care," "psychosocial aspects and emotional lability," "resources management and safety" and "professional relationships and fellowship." CONCLUSION: Providing health care by intensive care nursing professionals, during the COVID-19 pandemic, has shown both strong and weak points in the health care system. Nursing care has been influenced by fear and isolation, making it hard to maintain the humanization of the health care. RELEVANCE TO CLINICAL PRACTICE: Implications for practice include optimizing resource management (human and material), providing psychological support, and adequate training for ICU nurses, as well as high-quality protocols for future emergency situations.

Frailty, Complexity, and Priorities in the Use of Advanced Palliative Care Resources in Nursing Homes.

Background and objectives: This study aimed to determine the frailty, prognosis, complexity, and palliative care complexity of nursing home residents with palliative care needs and define the characteristics of the cases eligible for receiving advanced palliative care according to the resources available at each nursing home. Materials and Methods: In this multi-centre, descriptive, and cross-sectional study, trained nurses from eight nursing homes in southern Spain selected 149 residents with palliative care needs. The following instruments were used: the Frail-VIG index, the case complexity index (CCI), the Diagnostic Instrument of Complexity in Palliative Care (IDC-Pal), the palliative prognosis index, the Barthel index (dependency), Pfeiffer's test (cognitive impairment), and the Charlson comorbidity index. A consensus was reached on the complexity criteria of the Diagnostic Instrument of Complexity in Palliative Care that could be addressed in the nursing home (no priority) and those that required a one-off (priority 2) or full (priority 1) intervention of advanced palliative care resources. Non-parametric tests were used to compare non-priority patients and patients with some kind of priority. Results: A high percentage of residents presented frailty (80.6%), clinical complexity (80.5%), and palliative care complexity (65.8%). A lower percentage of residents had a poor prognosis (10.1%) and an extremely poor prognosis (2%). Twelve priority 1 and 14 priority 2 elements were identified as not matching the palliative care complexity elements that had been previously identified. Of the studied cases, 20.1% had priority 1 status and 38.3% had priority 2 status. Residents with some kind of priority had greater levels of dependency (p < 0.001), cognitive impairment (p < 0.001), and poorer prognoses (p < 0.001). Priority 1 patients exhibited higher rates of refractory delirium (p = 0.003), skin ulcers (p = 0.041), and dyspnoea (p = 0.020). Conclusions: The results indicate that there are high levels of frailty, clinical complexity, and palliative care complexity in nursing homes. The resources available at each nursing home must be considered to determine when advanced palliative care resources are required.

Targeting anticoagulant protein S to improve hemostasis in hemophilia.

Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400 000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by rebalancing coagulation. Protein S (PS) is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI). This dual role makes PS a key regulator of thrombin generation. Here, we report that targeting PS rebalances coagulation in hemophilia. PS gene targeting in hemophilic mice protected them against bleeding, especially when intra-articular. Mechanistically, these mice displayed increased thrombin generation, resistance to activated protein C and TFPI, and improved fibrin network. Blocking PS in plasma of hemophilia patients normalized in vitro thrombin generation. Both PS and TFPIα were detected in hemophilic mice joints. PS and TFPI expression was stronger in the joints of hemophilia A patients than in those of hemophilia B patients when receiving on-demand therapy, for example, during a bleeding episode. In contrast, PS and TFPI expression was decreased in hemophilia A patients receiving prophylaxis with coagulation factor concentrates, comparable to osteoarthritis patients. These results establish PS inhibition as both controller of coagulation and potential therapeutic target in hemophilia. The murine PS silencing RNA approach that we successfully used in hemophilic mice might constitute a new therapeutic concept for hemophilic patients.

Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology.

The Nomo1 gene mediates a wide range of biological processes of importance in embryonic development. Accordingly, constitutive perturbation of Nomo1 function may result in myriad developmental defects that trigger embryonic lethality. To extend our understanding of Nomo1 function in postnatal stages and in a tissue-specific manner, we generated a conditional knockout mouse model of Nomo1. To achieve this, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology in C57Bl/6J mouse zygotes to generate a new mouse model in which exon 3 of the Nomo1 gene is specifically flanked (or floxed) by LoxP sites (Nomo1f/f). Nomo1f/f mouse embryonic fibroblasts were transduced with a Cre adenovirus and efficiently recombined between LoxP sites. Genomic and expression studies in Nomo1-transduced MEFs demonstrated that the Nomo1 exon 3 is ablated. Western blot assay showed that no protein or early truncated protein is produced. In vivo assay crossing Nomo1f/f mouse with a Msi1-CRE transgenic mouse corroborated the previous findings and it showed Nomo1 exon 3 deletion at msi1+ cell compartment. This short technical report demonstrates that CRISPR/Cas9 technology is a simple and easy method for creating conditional mouse models. The Nomo1f/f mouse will be useful to researchers who wish to explore the role of Nomo1 in any developmental stage or in a tissue-specific manner.

Prediction of high proliferative index in pituitary macroadenomas using MRI-based radiomics and machine learning.

PURPOSE: Pituitary adenomas are among the most frequent intracranial tumors. They may exhibit clinically aggressive behavior, with recurrent disease and resistance to multimodal therapy. The ki-67 labeling index represents a proliferative marker which correlates with pituitary adenoma aggressiveness. Aim of our study was to assess the accuracy of machine learning analysis of texture-derived parameters from pituitary adenomas preoperative MRI for the prediction of ki-67 proliferation index class. METHODS: A total of 89 patients who underwent an endoscopic endonasal procedure for pituitary adenoma removal with available ki-67 labeling index were included. From T2w MR images, 1128 quantitative imaging features were extracted. To select the most informative features, different supervised feature selection methods were employed. Subsequently, a k-nearest neighbors (k-NN) classifier was employed to predict macroadenoma high or low proliferation index. Algorithm validation was performed with a train-test approach. RESULTS: Of the 12 subsets derived from feature selection, the best performing one was constituted by the 4 highest correlating parameters at Pearson's test. These all showed very good (ICC ≥ 0.85) inter-observer reproducibility. The overall accuracy of the k-NN in the test group was of 91.67% (33/36) of correctly classified patients. CONCLUSIONS: Machine learning analysis of texture-derived parameters from preoperative T2 MRI has proven to be effective for the prediction of pituitary macroadenomas ki-67 proliferation index class. This might aid the surgical strategy making a more accurate preoperative lesion classification and allow for a more focused and cost-effective follow-up and long-term management.

Prognostic Models Associated with 6-Month Survival of Patients Admitted to Nursing Homes.

BACKGROUND: Health status and the needs presented by people admitted to nursing homes make it necessary to contemplate aspects such as prognosis to offer quality palliative care. OBJECTIVE: To compare the prognostic utility in nursing homes of two prognostic models of 6-month survival based on the Palliative Prognostic Index (PPI) or Palliative Performance Status (PPS) instruments and palliative needs indicators. METHODS: A longitudinal prospective observational and analytical cohort study of survival and prognostic models in 88 patients with palliative needs (assessed by the NECPAL-ICO-CCOMS©) from an Andalusian (Spain) nursing home was performed. Sociodemographic and clinical variables were assessed, and 6 months later, in September 2017, survival was checked. Multiple logistic regression analysis was performed using the R-Commander program (version 3.2.2). RESULTS: Two models of the logistic regression analysis met the fit criteria. The two models combined the Surprise Question, the presence of persistent symptoms, and the clinical indicators of severity from the NECPAL tool, in addition to the Charlson Comorbidity Index, and varied only in terms of the latter variable, including the PPI in the first model and the PPS in the second. In the first model, significant associations were identified between 6-month survival and the persistent symptoms variable (OR = 7.78, p = 0.025, 95% CI = 1.45-60.92) and PPI (OR = 1.94, p < 0.001, 95% CI = 1.21). In the second model, 6-month survival was also significantly associated with the persistent symptoms variable (OR = 4.57, p = 0.045, 95% CI = 1.07-22.41) and the PPS (OR = 0.93, p = 0.001, 95% CI = 0.88-0.96). CONCLUSIONS: Prognostic models such as ours that include variables commonly included in clinical assessments can help nursing home professionals prioritize and ensure adequate mobilization of palliative care resources, which are very limited in these institutions.

Microcalcifications Drive Breast Cancer Occurrence and Development by Macrophage-Mediated Epithelial to Mesenchymal Transition.

BACKGROUND: This study aims to investigate: (a) the putative association between the presence of microcalcifications and the expression of both epithelial-to-mesenchymal transition and bone biomarkers, (b) the role of microcalcifications in the breast osteoblast-like cells (BOLCs) formation, and (c) the association between microcalcification composition and breast cancer progression. METHODS: We collected 174 biopsies on which we performed immunohistochemical and ultrastructural analysis. In vitro experiments were performed to demonstrate the relationship among microcalcification, BOLCs development, and breast cancer occurrence. Ex vivo investigations demonstrated the significant increase of breast osteoblast-like cells in breast lesions with microcalcifications with respect to those without microcalcifications. RESULTS: In vitro data displayed that in the presence of calcium oxalate and activated monocytes, breast cancer cells undergo epithelial to mesenchymal transition. Also, in this condition, cells acquired an osteoblast phenotype, thus producing hydroxyapatite. To further confirm in vitro data, we studied 15 benign lesions with microcalcification from patients that developed a malignant condition in the same breast quadrant. Immunohistochemical analysis showed macrophages' polarization in benign lesions with calcium oxalate. CONCLUSIONS: Altogether, our data shed new light about the role of microcalcifications in breast cancer occurrence and progression.

Leber's hereditary optic neuropathy, intellectual disability and epilepsy presenting with variable penetrance associated to the m.3460G >A mutation and a heteroplasmic expansion of the microsatellite in MTRNR1 gene - case report.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) associated with mutations in mitochondrial DNA (mtDNA) typically manifests only optic nerve involvement but in some patients may develop additional neurological complications. The cause of this association is not clear. CASE PRESENTATION: We present a case of a 24-year-old male with a history of subacute, painless, and rapidly progressive bilateral vision loss. We performed ophthalmological, neurological and neuropsychological investigations in the proband and his LHON family. The proband showed optic neuropathy, epilepsy, migraine, and intellectual disability; all the maternal relatives did not manifest optic neuropathy but a moderate to severe intellectual disability. Genetic screening revealed a novel association of the LHON m.3460G > A primary mutation with the m.T961delT + C(n)ins within the mitochondrial encoded 12S RNA (MTRNR1) gene which segregates with the intellectual disability through the maternal branch of the family. We also found a significant increase of mtDNA content in all the unaffected homo/heteroplasmic mutation carriers with respect to either affected or control subjects. CONCLUSION: This is the first case reporting the co-segregation of a mutation in MTRNR1 gene with a LHON primary mutation, which may be a risk factor of the extraocular signs complicating LHON phenotype. In addition, the data herein reported, confirmed that the key factor modulating the penetrance of optic atrophy in the family is the amount of mtDNA.

Methylation differences reveal heterogeneity in preterm pathophysiology: results from bipartite network analyses.

BACKGROUND: Recent studies have shown that epigenetic differences can increase the risk of spontaneous preterm birth (PTB). However, little is known about heterogeneity underlying such epigenetic differences, which could lead to hypotheses for biological pathways in specific patient subgroups, and corresponding targeted interventions critical for precision medicine. Using bipartite network analysis of fetal DNA methylation data we demonstrate a novel method for classification of PTB. METHODS: The data consisted of DNA methylation across the genome (HumanMethylation450 BeadChip) in cord blood from 50 African-American subjects consisting of 22 cases of early spontaneous PTB (24-34 weeks of gestation) and 28 controls (>39 weeks of gestation). These data were analyzed using a combination of (1) a supervised method to select the top 10 significant methylation sites, (2) unsupervised "subject-variable" bipartite networks to visualize and quantitatively analyze how those 10 methylation sites co-occurred across all the subjects, and across only the cases with the goal of analyzing subgroups and their underlying pathways, and (3) a simple linear regression to test whether there was an association between the total methylation in the cases, and gestational age. RESULTS: The bipartite network analysis of all subjects and significant methylation sites revealed statistically significant clustering consisting of an inverse symmetrical relationship in the methylation profiles between a case-enriched subgroup and a control-enriched subgroup: the former was predominantly hypermethylated across seven methylation sites, and hypomethylated across three methylation sites, whereas the latter was predominantly hypomethylated across the above seven methylation sites and hypermethylated across the three methylation sites. Furthermore, the analysis of only cases revealed one subgroup that was predominantly hypomethylated across seven methylation sites, and another subgroup that was hypomethylated across all methylation sites suggesting the presence of heterogeneity in PTB pathophysiology. Finally, the analysis found a strong inverse linear relationship between total methylation and gestational age suggesting that methylation differences could be used as predictive markers for gestational length. CONCLUSIONS: The results demonstrate that unsupervised bipartite networks helped to identify a complex but comprehensible data-driven hypotheses related to patient subgroups and inferences about their underlying pathways, and therefore were an effective complement to supervised approaches currently used.