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Purpose Method Findings Conclusions Implications for nursing practice When submitted to mutilating surgery, patients with head and neck cancer may present profound physical and psychosocial changes, temporary or definitive, with an individual impact and family. The most frequent human responses to this health condition are subjective, particularly concerning body image and self‐esteem. Differential validation emerges to provide nurses with clinical indicators for clinical reasoning and planning of effective interventions, considering the specific defining characteristics of each diagnosis.This study aimed at conducting a differential clinical validation of the nursing diagnoses of disturbed body image and low situational self‐esteem in patients with head and neck cancer using Q methodology.We performed an observational cross‐sectional study using Q methodology.Thirty‐eight participants were included. Data were analyzed using Q methodology procedures. The research and ethics committee approved the study.Factor analysis was performed, and eight defining characteristics were identified for the diagnosis of disturbed body image and one for situational low self‐esteem: avoiding looking at one's body, avoiding touching one's body, the behavior of monitoring one's body, depersonalization of body part by use of impersonal pronouns, focus on past appearance, focus on past function, negative feeling about body, and refusal at acknowledging change and helplessness.The use of the Q methodology in this process of differential validation allowed the study of two diagnoses of a subjective nature, disclosing the most specific defining characteristics of each and contributing to increasing the knowledge of these human responses.This study contributes to a better understanding of the predominant defining characteristics of the diagnoses under study. In terms of the NANDA‐I taxonomy, it helps to raise the levels of evidence for diagnoses. Using a qualitative and quantitative methodology allows for maintaining a more holistic research approach and greater rigor and acceptance of the results. [ABSTRACT FROM AUTHOR]

Simple Summary: Attention deficit hyperactivity disorder (ADHD) is a relatively common neurodevelopmental disorder mainly affecting children and adolescents. ADHD is associated with significant social stigma, psychosocial adversities, and reduced working abilities. As with humans, dogs can suffer from ADHD-like behaviors, but to date, there are few studies on this condition in the canine species. Therefore, the present study analyzed the levels of serum serotonin and dopamine in dogs with signs that are similar to the ones presented in human patients with ADHD (compared to control dogs) that were assessed clinically and through different behavior scales. The results obtained indicate that both neurotransmitters have a tendency to be observed in lower concentrations in dogs presenting behavioral signs consistent with ADHD-like disorders. This finding may be useful for contributing to the study of the diagnosis and treatment of this disorder in dogs. ADHD-like associated behaviors can disrupt the normal coexistence of the dogs in their homes and contribute to abandonment, which continues to be a major social and animal welfare problem today. As with humans, dogs can suffer from attention deficit hyperactivity disorder-like (ADHD-like) behaviors naturally and exhibit high levels of hyperactivity/impulsivity and attention deficit problems, making the domestic dog a potential animal model for ADHD. ADHD has a very complex pathophysiology in which many neurotransmitters are involved, such as serotonin and dopamine. The aim of the study was to evaluate serum serotonin and dopamine levels in dogs with ADHD-like symptomatology. Fifty-eight dogs were studied, of which, thirty-six were classified as ADHD-like after physical and behavioral assessments. Additionally, the dogs' owners performed a series of scientifically validated questionnaires which included C-BARQ, the Dog Impulsivity Assessment Scale, and the Dog-ADHD rating scale. Serum from every animal was collected after the behavioral assessments and analyzed with commercial ELISA tests for serotonin and dopamine determination. Kruskal–Wallis tests and Lasso regressions were applied to assess the relationships between both neurotransmitters and the ADHD-like behaviors (as assessed by clinical evaluation and through the different questionnaires). The dogs clinically classified as ADHD-like showed lower serotonin and dopamine concentrations. Further, serotonin and dopamine levels were also linked to aggression, hyperactivity, and impulsivity. Decreased serotonin concentrations were also related to fear, attachment, and touch sensitivity. Finally, it must be noted that our data suggested a strong relationship between serotonin and dopamine and ADHD-like behaviors. [ABSTRACT FROM AUTHOR]

Purpose: This review aimed to analyze the use of differential validation of nursing diagnosis. Methods: Integrative literature review with search on international databases. The diagnoses, the type of the diagnosis differential validation, the sample, the method, main results, and the limitations were extracted. Ten studies were included. Findings: Differential diagnostic validation publication dates from 1994, and Brazil was the predominant country. Conclusions: This method seems helpful in improving diagnosis accuracy, particularly those related to subjective, behavioral, or complex human responses. Implications for nursing practice: Using this model may facilitate understanding the specificity of nursing diagnosis, which is critical for teaching clinical reasoning and for new opportunities to research. [ABSTRACT FROM AUTHOR]

This article describes how nurses can use the Q methodology to include head and neck cancer patients in research. These patients are often excluded from participating in research based on temporary or permanent voiceless, disfigurement, or impaired communication. Q methodology is defined as the method for the study of subjectivity and related procedures seem to facilitate the participation of head and neck cancer patients. As so, this inclusive dimension should be taken into consideration in research project design also as an ethical aspect of the study, in particular when involving these patients or others in similar conditions. [ABSTRACT FROM AUTHOR]

PURPOSE: This article explores the current structure of NANDA‐I nursing diagnoses (ND) labels. METHODS: Critical analysis of the ND labels, as categorized in the NANDA‐I terminology. FINDINGS: Most of the 244 ND labels are composed of terms from the focus and judgment axes. CONCLUSIONS: The specificity of the human responses toward health and life transitions may not be totally represented in the two most common axes, as categorized within taxonomy II. IMPLICATIONS FOR NURSING PRACTICE: Improvements in NANDA‐I diagnosis labels would contribute to an advanced terminology and to increased specificity and accuracy of the diagnostic process that is needed in clinical practice. Completeness of the ND labels would reflect clinical reasoning preciseness and help students and nurses in delivering more personalized, safe, and effective patient‐centered care. OBJETIVO: Este artigo explora os títulos dos diagnósticos de enfermagem da NANDA‐I. MÉTODOS: Análise crítica dos títulos dos diagnósticos de enfermagem da NANDA‐I. RESULTADOS: A maioria dos 244 diagnósticos de enfermagem classificados são compostos essencialmente por termos referentes ao foco e ao julgamento. CONCLUSÕES: A especificidade das respostas às transições de saúde e vida pode não estar totalmente representada nos dois eixos mais comuns, como apresentado na taxonomia II. IMPLICAÇÕES PARA A PRÁTICA: Melhorias nos diagnósticos da NANDA‐I em relação ao seu aspeto multiaxial contribuiriam no desenvolvimento da sua terminologia e poderiam melhorar a especificidade e acurácia do processo diagnóstico que é necessário à prática clínica. Complementar os títulos dos diagnósticos de enfermagem poderia refletir a acurácia do raciocínio clínico e ajudar os estudantes e enfermeiros em prestarem cuidados centrados no paciente mais personalizados, seguros e eficazes. [ABSTRACT FROM AUTHOR]

Backgroud: The person undergoing total laryngectomy suffers an abrupt loss of ability to communicate orally, as a consequence of the lack of voice to speak resulting from complete laryngeal ablation. In addition to having limited communication with others, which in itself has a profound impact, the person is limited in her capacity to communicate symptoms, express their needs and feelings, question or request care, which interferes, among other things, with the quality and safety of the care provided. Objective: To identify the scientific evidence available in the literature on the interventions that promote effective communication of the person undergoing Total Laryngectomy in the peri-operative period. Methodology: A Scoping Review was carried out following the protocol recommended by the Joanna Briggs Institute and based on the research question "Which nursing interventions promoting effective communication of the person with laryngeal cancer undergoing total laryngectomy in the period peri-operative? "A research was conducted in the electronic databases CINAHL' and MEDLINE' between the 1st and the 16th of February 2019. Articles from primary studies, case studies, theoretical and literature reviews in English, Spanish and Portuguese, published between 2000 and 2019 were included. Results: Between 2000 and 2019 were identified 20 published articles. Conclusions: This Scoping Review enabled us to respond to the initial research question by identifying a wide variety of interventions aimed at optimizing the laryngectomized person communication or that can be adapted to these people. The use of lip mimics; gestures; signals; facial expressions as well as writing were the most frequently mentioned strategies, followed by the use of simple questions and the use of speech generating devices. The environmental conditions; the skills of health professionals; family incorporation and emotional support emerged as conditions and resources for optimizing communication care. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This article describes the adequacy of the Q methodology as a new option for the validation of nursing diagnoses related to subjective foci. METHODS: Discussion paper about the characteristics of the Q methodology. FINDINGS: This method has been used in nursing research particularly related to subjective concepts and includes both a quantitative and qualitative dimension. CONCLUSIONS: The Q methodology seems to be an adequate and innovative method for the clinical validation of nursing diagnoses. IMPLICATIONS FOR PRACTICE: The validation of nursing diagnoses related to subjective foci using the Q methodology could improve the level of evidence and provide nurses with clinical indicators for clinical reasoning and for the planning of effective interventions. OBJETIVO: Descrever a adequação da metodologia Q como uma nova opção para a validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos. MÉTODOS: Artigo de discussão sobre as características da metodologia Q. RESULTADOS: Este método tem sido utilizado na pesquisa em enfermagem relacionada com conceitos subjetivos e inclui em simultâneo uma vertente qualitativa e quantitativa. CONCLUSÕES: A metodologia Q parece ser uma opção metodológica adequada para a validação clínica de diagnósticos de enfermagem. IMPLICAÇÕES PARA A PRÁTICA: A utilização da metodologia Q na validação clínica de diagnósticos de enfermagem relacionados com focos subjetivos pode melhorar o nível e evidência e facilitar o raciocínio clínico dos enfermeiros, ao providenciar indicadores clínicos também necessários ao desenvolvimento de intervenções efetivas. [ABSTRACT FROM AUTHOR]

Simple Summary: The Can de Palleiro or Galician shepherd is a canine breed that was in danger of extinction but is currently growing rapidly in popularity. In this study, different behavioural traits of the breed were evaluated in order to assess breeds, select the best breeding animals and identify behaviour problems. This is the first study carried out in the Can de Palleiro breed using different scientifically validated tests. Questionnaires filled by the owners (C_BARQ) were collected, and a behavioural test (SAB) was conducted to evaluate the response of the dogs to a specific stimulus at a certain time and in a certain environment. In addition, the results from the Can de Palleiro breed were compared with those obtained from the general canine population of Galicia. Thereby, the Can de Palleiro breed showed less owner-directed aggression, dog-directed fear, excitability, non-social fear and separation-related problems and better trainability. The Can de Palleiro (CP) is an autochthonous canine breed from Galicia (NW Spain). Interestingly, no previous research has been published about the behaviour of this breed. Thus, the aim of the present study was to obtain a deeper understanding of CP behavioural and temperamental traits and detect any potentially problematic behaviour by using the Canine Behavioural Assessment and Research Questionnaire (C-BARQ) and the Socially Acceptable Behaviour (SAB) test. Behavioural information was obtained from 377 dogs—177 CPs and 200 general population (GP) dogs—using the C-BARQ. Additionally, 32 dogs were enrolled to perform the SAB test (19 CPs and 13 GP dogs) in order to directly evaluate their temperament. Our results indicated that CP dogs had a lower tendency to show aggressiveness towards their owners (0.18 times lower, p = 0.033) and less fear of other dogs (by 0.43 times, p = 0.001), as well as higher trainability levels (2.56 times higher, p < 0.001) when compared to GP dogs. CP dogs also had increased odds of showing chasing behaviour (3.81 times higher, p < 0.001). Conversely, CPs had reduced odds of non-social fear, separation-related problems and excitability (by 0.42, 0.35 and 0.48 times, respectively; p < 0.001, p < 0.001 and p = 0.002). The current research represents a starting point for the study of the behaviour of CPs, which appear to be a working breed, with guarding and, especially, herding characteristics. [ABSTRACT FROM AUTHOR]

Chow J, Miguel SS. International Journal of Nursing Practice 2010; 16: 484-491 Evaluation of the implementation of Assistant in Nursing workforce in haemodialysis units The aim of this project was to evaluate the introduction of Assistant in Nursing (AINs) in the haemodialysis units at a major tertiary Area Health Service in Sydney, Australia. All nursing staff were asked to complete a baseline and follow-up survey to determine changes to their attitudes to the new skill mix model and their satisfaction with the new organization of care delivery in their dialysis units. Comparison of the baseline and follow-up surveys in the paired data was favourable with nurses acknowledging that they would cope well with the introduction of AINs, and they were more likely to disagree with the statement that their workload would increase after the introduction of AINs in the follow-up survey. There was little difference in (i) the workload of the dialysis units before and during the intervention; and (ii) the incidence of patient and nursed related adverse outcome events. [ABSTRACT FROM AUTHOR]

A recently discovered group of novel polymerases are characterized by significantly reduced fidelity of DNA synthesis in vitro. This feature is consistent with the relaxed fidelity required for the replicative bypass of various types of base damage that frequently block high fidelity replicative polymerases. The present studies demonstrate that the specialized DNA polymerase kappa (polκ) is uniquely and preferentially expressed in the adrenal cortex and testis of the mouse, as well as in a variety of other tissues. The adrenal cortex is the sole site of detectable expression of the Polκ gene in mouse embryos. This adrenal expression pattern is consistent with a requirement for polκ for the replicative bypass of DNA base damage generated during steroid biosynthesis. The expression pattern of polκ in the testis is specific for particular stages of spermatogenesis and is distinct from the expression pattern of several other low fidelity DNA polymerases that are also expressed during spermatogenesis. The mouse (but not the human) Polκ gene is primarily regulated by the p53 gene and is upregulated in response to exposure to various DNA-damaging agents in a p53-dependent manner. [Copyright &y& Elsevier]

Exposure of mammalian cells to hypoxia, radiation and certain chemotherapeutic agents promotes cell cycle arrest and/or apoptosis. Activation of p53 responsive genes is believed to play an important role in mediating such responses. In this study we identified a novel gene, PA26, which maps to chromosome 6q21 and encodes at least three transcript isoforms, of which two are differentially induced by genotoxic stress (UV, γ-irradiation and cytotoxic drugs) in a p53-dependent manner. A functional p53-responsive element was identified in the second intron of the PA26 gene, in consistence with a mechanism of transcriptional induction of the PA26 gene by p53. No clues to its functions were revealed by sequence analysis, although pronounced negative regulation by serum factors argues for a potential role of PA26 in growth regulation. Immunological analysis suggests that PA26 protein(s) is localized to the cell nucleus. Our results suggest that the PA26 gene is a novel p53 target gene with properties common to the GADD family of growth arrest and DNA damage-inducible stress-response genes, and, thus, a potential novel regulator of cellular growth. [ABSTRACT FROM AUTHOR]

Abstract: Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of DNA polymerase kappa (Polκ −/−) deficient mice. The spontaneous mutation rate in homozygous Polκ −/− males was significantly higher than in isogenic wild-type mice (Polκ +/+), but the ESTR mutation spectrum in Polκ −/− animals did not differ from that in Polκ +/+ males. We suggest that compromised translesion synthesis in Polκ −/− mice may result in replication fork pausing which, in turn, may affect ESTR mutation rate. [Copyright &y& Elsevier]

Background The perinatal period is of big changes and adaptations for pregnant woman, making them more susceptible to depression. Perinatal depression can have huge negative consequences for the pregnant woman, child, family and society. Thus, the objective of this work is to understand the family influence in the appearance of this pathology. Methods This is a cross-sectional observational study of a sample of pregnant women included for convenience, who answered a questionnaire with sociodemographic questions, pathological and physiological background and 4 scales: ERAP, EADS-21, FACES IV and ESSS. A descriptive analysis was carried out and then an inferential statistical analysis between the levels of depression, stress and anxiety and different variables. Results The sample includes 41 pregnant women who agreed to participate in the study. It was found that only the family variables related to 'Satisfaction with the family' (P = 0.024) and 'Intimacy' (P = 0.006) seem to have significant relationship with the levels of perinatal depression. As possible confounding variables influencing these levels, we have the fact that pregnancy is planned (P = 0.049), 'Satisfaction with friends' (P = 0.001) and 'Social activities' (P ≤0.001). Conclusions It was proven that high levels of satisfaction with family and intimacy are protective factors for the development of perinatal depression. These family-related risk factors can be easily addressed in the context of family's doctor appointments and help to detect pregnant women at risk of perinatal depression. Deepening this knowledge will make it possible to prevent and intervene earlier in these cases and, consequently, reduce the harmful effects of this pathology. [ABSTRACT FROM AUTHOR]

The identification of new pharmacological approaches to effectively prevent, treat, and cure the metabolic syndrome is of crucial importance. Excessive exposure to dietary lipids causes inflammatory responses, deranges the homeostasis of cellular metabolism, and is believed to constitute a key initiator of the metabolic syndrome. Mammalian Sirti is a protein deacetylase that has been involved in resveratrol-mediated protection from high-fat diet-induced metabolic damage, but direct proof for the implication of Sirt1 has remained elusive. Here, we report that mice with moderate overexpression of Sirt1 under the control of its natural promoter exhibit fat mass gain similar to wild-type controls when exposed to a high-fat diet. Higher energy expenditure appears to be compensated by a parallel increase in food intake. Interestingly, transgenic Sirt1 mice under a high-fat diet show lower lipid-induced inflammation along with better glucose tolerance, and are almost entirely protected from hepatic steatosis. We present data indicating that such beneficial effects of Sirt1 are due to at least two mechanisms: induction of antioxidant proteins MnSOD and Nrf1, possibly via stimulation of PGC1α, and lower activation of proinflammatory cytokines, such as TNFα and IL-6, via down-modulation of NFκB activity. Together, these results provide direct proof of the protective potential of Sirt1 against the metabolic consequences of chronic exposure to a high-fat diet. [ABSTRACT FROM AUTHOR]

Replication across unrepaired DNA lesions in mammalian cells is effected primarily by specialized, low fidelity DNA polymerases. We studied translesion DNA synthesis (TLS) across a benzo[a]pyrene-guanine (BP-G) adduct, a major mutagenic DNA lesion generated by tobacco smoke. This was done using a quantitative assay that measures TLS indirectly, by measuring the recovery of gapped plasmids transfected into cultured mammalian cells. Analysis of Polk+/+ mouse embryo fibroblasts (MEFs) showed that TLS across the BP-G adduct occurred with an efficiency of 48 ± 4%, which is an order of magnitude higher than in Escherichia coli. In Polk-/- MEFs, bypass was 16 ± 1%, suggesting that at least two-thirds of the BP-G adducts in MEFs were bypassed exclusively by polymerase κ (polκ). In contrast, polη was not required for bypass across BP-G in a human XP-V cell line. Analysis of misinsertion specificity across BP-G revealed that bypass was more error-prone in MEFs lacking polκ. Expression of polκ from a plasmid introduced into PolK-/- MEFs restored both the extent and fidelity of bypass across BP-G. Polκ was not required for bypass of a synthetic abasic site. In vitro analysis demonstrated efficient bypass across BP-G by both polκ and polη, suggesting that the biological role of polκ in TLS across BP-G is due to regulation of TLS and not due to an exclusive ability to bypass this lesion. These results indicate that BP-G is bypassed in mammalian cells with relatively high efficiency and that polκ bypasses BP-G in vivo with higher efficiency and higher accuracy than other DNA polymerases. [ABSTRACT FROM AUTHOR]

Aim: Of the few instruments available to measure the important, positive aspects of caring, the Caregiver Reaction Assessment is regarded as the most suitable, but there is no validated Spanish version. The aim of this study was to translate the Caregiver Reaction Assessment into Spanish and assess its psychometric properties. Methods: The Caregiver Reaction Assessment was translated into Spanish and then back translated. Validation included construct validity, criterion validity and reliability: 287 interviews were conducted with informal caregivers of patients with dementia between November 2010 and April 2012. Results: Principal component analysis confirmed the original instrument's five subscales. Criterion validity showed a moderate negative correlation between the impact on health and the EQ‐5D (r = −.43), that is, a greater impact on health correlated with lower health‐related quality of life. The Caregiver Reaction Assessment showed good internal consistency, with a Cronbach alpha of.804, and good temporal stability for the distinct subscales, with intraclass correlation coefficients varying from.683 to.729 (p <.001). Conclusion: The Caregiver Reaction Assessment is a reliable, valid instrument for the measurement of the reactions of informal caregivers of patients with dementia, with good psychometric properties. SUMMARY STATEMENT: What is already known about this topic? The Caregiver Reaction Assessment is one of the few instruments that measures positive reactions in caregivers.A validated Spanish version of the instrument is required for Spain and other Spanish‐speaking countries. What this paper adds? The Caregiver Reaction Assessment was shown to be a reliable, valid instrument for the measurement of the reactions of informal caregivers of people with dementia in Spain and has good psychometric properties. The implications of this paper: Once validation is complete, the Caregiver Reaction Assessment may be used in all Spanish‐speaking informal caregivers and is suitable for home care and long‐term care institutions.The Caregiver Reaction Assessment subscales allow healthcare professionals to identify and focus on the areas that could bring about the greatest improvements in the care of people with dementia.The Caregiver Reaction Assessment permits the caregiver's state to be viewed at any stage of dementia and offers healthcare professionals the opportunity to act to avoid physical and emotional overload in caregivers. [ABSTRACT FROM AUTHOR]

Presents a study that investigated the functional consequences of the mouse T to L amino acid substitution mutation when expressed either in mammalian cells or in the yeast Saccharomyces cerevisiae. Failure of mouse embryo fibroblasts and human Saos-2 cells to suppress growth; Transactivation levels of T to L amino acid substitution; Use of rheostatable p53 induction system in yeast.

Aims: We analyzed indirect costs related to loss of labor productivity (LLP) in informal caregivers (ICs) of people with dementia (PwD) and the associated caregiver burden and patients’ clinical variables. Methods: Multicenter cohort study of PwD and their ICs (n = 287) focused on two groups: (1) home care and (2) institutional long-term care. The costs of LLP were assessed using the Resource Utilization Dementia instrument and a human capital approach. Results: The cost for LLP was 378€/month or 4.536€/year. Greater disease severity increased the likelihood of reducing working hours and missing a working day. There was a significant association between partial absenteeism and burden in employed informal caregiver in both the home and institutional setting. Conclusion: Cognitive impairment contributes to the cost of LLP in IC especially in home-care. LLP has a negative impact on IC burden. [ABSTRACT FROM AUTHOR]

Risk factors associated with admission of people with dementia to long-term care institutions need to be identified to support health-care professionals in dementia care at home. An explorative study, combining quantitative and qualitative data collection methods, was performed in people with dementia in Spain. The sample, consisting of people with dementia receiving formal care from health-care professionals but at risk of institutionalisation, and their informal care-givers; and people with dementia recently admitted to a long-term care institution, and their informal care-givers, was interviewed between November 2010 and April 2012. Perceived reasons for admission were determined through an open-ended question put to both groups. Presumed risk factors were collected with validated questionnaires and analysed using bivariate analysis. A total of 287 people with dementia and informal care-givers were studied. Reasons given by the institutionalised group were mostly related to the level of dependency of the person with dementia. People recently admitted to a long-term care institution had more cognitive impairment, a greater degree of dependency and poorer quality of life than those still living at home. Home-care services in Spain need to develop or improve interventions based on the risk factors identified in this study: informal care-giver profile, high cognitive impairment, high level of dependency and the poor quality of life of the person with dementia. [ABSTRACT FROM AUTHOR]

Background Due to the high prevalence of dementia, health care needs are increasing beyond existing formal resources. In Spain, it is the family that takes care of this disease. Aims To analyze the direct (health and non-health) and indirect economic costs related to care of people with dementia living with their informal caregiver in the home care/community environment, from the perspective of illness severity, associated comorbidity and social impact. Design Multicentric, descriptive study. Setting Three primary care public health centers associated with Hospital Clínic, Barcelona (Spain). Participants Patients over 65 years old with a diagnosis of dementia, and included in a home care program. Inclusion criteria People with a diagnosis of dementia made by a specialist neurologist; aged 65 years or older; a score ≤24 on the Mini-Mental State Examination, and identification of an informal caregiver. Exclusion criteria Patients unable to identify an informal caregiver, and those with primary psychiatric pathology or Korsakoff's syndrome. Measurements Use of Resources in Dementia to assess costs; Mini-Mental State Examination to evaluate cognitive capacity; Katz-Index to measure functional capacity; Neuropsychiatric Index for neuropsychiatric symptoms, and the Charlson-Index for comorbidity. Data collection took place between November, 2010 and April, 2012. Results The average estimated monthly care costs for people with dementia in the home setting are 1956.2€ (SD 1463.9). Informal care was the major contributor to this with a mean estimated cost of 1214.86 (SD 902.68)€/month. Greater illness severity, dependency in activities of daily living, comorbidity and behavioral disturbance are associated with higher costs. Behavioral disturbance appeared as the only factor independently associated with cost in dementia care. The group of people with dementia with severe behavioral disturbance requires the most care resources with an average cost of 2545.2 (SD 1753.2)€/month. Conclusions There is a direct association between dementia severity and increased costs. In addition, informal caregivers looking after people with dementia in Spain represent an important social cost. The independent factor associated with an increase in the total costs of patient care was neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Chromosome 3p and 1p deletions are among the most frequent genetic changes in human lung cancer and although candidate tumor suppressor genes have been identified in these regions, no causative correlations have been drawn between deletion or mutation of these and lung carcinogenesis. We identify XPC and Gadd45a as genes within each of these regions involved in lung tumor initiation and progression, respectively. One hundred per- cent of XPC-/- mice develop multiple spontaneous lung tumors with a minority progressing to non-small cell lung adenocarcinoma, occasionally with metastasis to adjacent lymph nodes. Deletion of Gadd45a alone does not lead to increased lung tumors in mice, but coupled with an XPC deletion, it results in lung tumor progression. Analysis of published data indicated allelic loss of XPC in most human lung tumors and allelic loss of Gadd45a in some human lung and other cancer types. Because DNA repair capacity is compromised in XPC+/- cells, it is possible that the loss of a single XPC allele in the human lung might confer a mutator phenotype. Coupled with cigarette carcinogens, decreased DNA repair would lead to additional mutations in genes such as p53 that are frequent targets in lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: The Y-family of DNA polymerases are capable of translesion synthesis both in vitro and in vivo. The mouse/human gene (Polκ/POLK) that encodes the Y-family member Polk is highly expressed in mouse/human testis. Using RT-PCR to amplify the coding sequence of the PolK gene, 11 forms of mouse PolK and 5 forms of human POLK transcripts were identified from testis. This phenomenon is apparently specific to PolK since several other specialized DNA polymerases capable of TLS do not express functional alternative transcripts in the testis. The multiple mouse/human (PolK/POLK) transcripts may encode multiple Polκ isoforms in testis. [Copyright &y& Elsevier]

Mutational hot spots in the human p53 gene are well established in tumors in the human population and are frequently negative prognosticators of the clinical outcome. We previously developed a mouse model of skin cancer with mutations in the xeroderma pigmentosum group C gene (Xpc). UVB radiation-induced skin cancer is significantly enhanced in these mice when they also carry a mutation in one copy of the Trp53 gene (Xpc−/−Trp53+/−). Skin tumors in these mice often contain inactivating mutations in the remaining Trp53 allele and we have previously reported a novel mutational hot spot at a non-dipyrimidine site (ACG) in codon 122 of the Trp53 gene in the tumors. Here we show that this mutation is not a hot spot in Xpa or Csa mutant mice. Furthermore, the mutation in codon T122 can be identified in mouse skin DNA from (Xpc−/−Trp53+/−) mice as early as 2 weeks after exposure to UVB radiation, well before histological evidence of dysplastic or neoplastic changes. Since this mutational hot spot is not at a dipyrimidine site and is apparently Xpc-specific, we suggest that some form of non-dipyrimidine base damage is normally repaired in a manner that is distinct from conventional nucleotide excision repair, but that requires XPC protein. [Copyright &y& Elsevier]

Cockayne syndrome (CS) is an inherited photosensitive neurodevelopmental disorder caused by a specific defect in the transcription-coupled repair (TCR) sub-pathway of NER. Remarkably, despite their DNA repair deficiency, CS patients do not develop skin cancer. Here, we present a mouse model for CS complementation group A. Like cells from CS-A patients, Csa−/− mouse embryonic fibroblasts (MEFs): (i) are ultraviolet (UV)-sensitive; (ii) show normal unscheduled DNA synthesis (indicating that the global genome repair sub-pathway is unaffected); (iii) fail to resume RNA synthesis after UV-exposure and (iv) are unable to remove cyclobutane pyrimidine dimers (CPD) photolesions from the transcribed strand of active genes. CS-A mice exhibit UV-sensitivity and pronounced age-dependent loss of retinal photoreceptor cells but otherwise fail to show the severe developmental and neurological abnormalities of the human syndrome. In contrast to human CS, Csa−/− animals develop skin tumors after chronic exposure to UV light, indicating that TCR in mice protects from UV-induced skin cancer development. Strikingly, inactivation of one Xpc allele (encoding a component of the damage recognition complex involved in the global genome repair sub-pathway) in Csa−/− mice resulted in a strongly enhanced UV-mediated skin cancer sensitivity, indicating that in a TC repair defective background, the Xpc gene product may be a rate-limiting factor in the removal of UV-induced DNA lesions. [ABSTRACT FROM AUTHOR]

Prescription patterns of non–vitamin K antagonist oral anticoagulants (NOACs) are unknown among primary care physicians, where most patients with nonvalvular atrial fibrillation (NVAF) are diagnosed and followed up. The goal of this study was to evaluate overdosing and underdosing of NOACs in patients with NVAF followed up in primary care and determine their clinical predictors. This multicenter cross-sectional study included all patients with NVAF followed up in 13 primary care units in the center region of Portugal. Patients receiving antithrombotic regimens other than NOACs and patients with missing data were excluded. The study included 858 patients with NVAF on an NOAC regimen. Overall, 30.3% were prescribed an off-label dosage (25.4% with infratherapeutic dosing [ITD] and 4.9% with supratherapeutic dosing). Chronic kidney disease (odds ratio, 14.0; 95% CI, 5.4–36.5; P < 0.001) and female sex (odds ratio, 2.6; 95% CI, 1.2–5.7; P < 0.001) were independent predictors of supratherapeutic dosing. We also found a significant effect of chronic kidney disease on ITD (odds ratio, 0.22; 95% CI, 0.258–0.678; P < 0.001). In primary care, NOACs are frequently prescribed with unadjusted dosages, generally infratherapeutic. Attention should be paid to women and patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

The article reports that the key signal to p53 to trigger tumor suppression are provided by the oncogenes, rather than the damaged DNA. In the present study, the percentage of apoptotic thymocytes was evaluated after irradiation on mice. The studies reportedly suggest that the cancer-protective activity of p53 is curtailed in the absence of ARF. It also reveals the importance of the oncogenic signalling, and that the role of DNA damage is less important in the development of tumors.