Non-pharmacological solutions to sleep and circadian rhythm disruption: voiced bedside experiences of hospice and end-oflife staff caregivers

Background: Sleep disturbance is a significant issue, particularly for patients with advanced terminal illness. Currently, there are no practice-based recommended approaches for managing sleep and circadian disruptions in this population. To address this gap, a cross-sectional focus group study was performed engaging 32 staff members at four hospices/end-of-life programs in three demographically diverse counties in New York State. Methods: Participants responded to structured open-ended questions. Responses were transcribed and subjected to qualitative content analysis. The themes and recommendations for improved practice that emerged were tabulated using Atlas TI qualitative software. Results: This report details the experiences of hospice and end-of-life care staff in managing sleep and circadian disruptions affecting patients and analyzes their recommendations for improving care. Caregivers involved in the study described potential interventions that would improve sleep and reduce circadian disruptions. They particularly highlighted a need for improved evaluation and monitoring systems, as well as sleep education programs for both formal and informal caregivers. Conclusions: The voiced experiences of frontline hospice and end-of-life caregivers confirmed that disruption in sleep and circadian rhythms is a common issue for their patients and is not effectively addressed in current research and practice. The caregivers’ recommendations focused on management strategies and underscored the need for well-tested interventions to promote sleep in patients receiving end-of-life care. Additional research is needed to examine the effectiveness of systematic programs that can be easily integrated into the end-of-life care process to attenuate sleep disturbances

Objective dyspnea evaluation on COVID-19 patients learning from exertion-induced dyspnea scores

Objective: Dyspnea is one of the most common symptoms for many pulmonary diseases including COVID-19. Clinical assessment of dyspnea is mainly performed by subjective self-report, which has limited accuracy and is challenging for continuous monitoring. The objective of this research study is to determine if dyspnea progression in COVID patients can be assessed using a non-invasive wearable sensor and if the findings are comparable to a learning model of physiologically induced dyspnea on healthy subjects. Methods: Non-invasive wearable respiratory sensors were employed to retrieve continuous respiratory characteristics with user comfort and convenience. Overnight (~16h) respiratory waveforms were collected on 12 COVID-19 patients, and a benchmark on 13 healthy subjects with exertion-induced dyspnea were also performed for blind comparison. The learning model was built from the respiratory features with self report on 32 healthy subjects under exertion and airway blockage. Results: High similarity between dyspnea on COVID patients and physiologically induced dyspnea on healthy subjects was established. COVID patients have consistently high objective dyspnea scores in comparison with normal breathing of healthy subjects. We also exhibited continuous dyspnea scoring capability for 12-16 hours on patients. Conclusion: This paper validates the viability to use our objective dyspnea scoring for clinical dyspnea assessment on COVID patients. Significance: The proposed system can help the identification of dyspneic exacerbation in conditions such as COVID, leading to early intervention and possibly improving their outcome. This approach can be potentially applied to other pulmonary disorders such as asthma, emphysema, and pneumonia

Gene expression profile in experimental frozen-thawed ovarian grafts treated with scaffold-base delivery of adipose tissue-derived stem cells

Purpose: Gelfoam scaffold is a feasible and safe non-invasive technique for Adipose tissue-derived Stem Cell (ASC)-delivery in the treatment of frozen-thawed ovarian autografts. This study seeks to analyze the genes expression profile of rat frozen-thawed ovarian autografts treated with scaffold-based delivery of adipose tissue-derived stem cells. Methods: Eighteen adult Wistar rats were distributed into three groups: Control (frozen-thawed only); Group 1 (G1) and Group 2 (G2) (frozen-thawed ovaries treated with culture medium or ASC, respectively). Both treatments were performed immediately after autologous retroperitoneal transplant with scaffold-based delivery. The ovarian grafts were retrieved 30 days after transplantation. Quantitative gene expression (qPCR) for apoptosis, angiogenesis, and inflammatory cytokines (84 genes in each pathway) were evaluated by RT-PCR. Graft morphology (HE), apoptosis (cleaved-caspase-3), neoangiogenesis (VEGF), and cellular proliferation (Ki-67) were assessed. Results: In grafts treated with ASC, the apoptosis pathway showed the highest number of genes over-regulated – 49 genes – compared to inflammation cytokines and angiogenesis pathway – 36 and 23 genes respectively, compared to grafts treated with culture medium. Serpinb5 family was highlighted in the angiogenesis pathway and Cxcl6 in the inflammation cytokines pathway. In the apoptosis pathway, the most over-regulated gene was Capsase14. ASC treatment promoted the reduction of cleaved caspase-3 in the theca internal layer and increased cell proliferation by Ki-67 in the granulosa layer without altering VEGF. A mild inflammatory infiltrate was observed in both groups. Conclusion: ASC therapy in rat frozen-thawed ovarian autografts promoted an abundance of genes involved with apoptosis and inflammatory cytokines without compromising the ovary graft morphology and viability for short time. Further studies are necessary to evaluate the repercussion of apoptosis and inflammation on the graft in the long term

Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL), DSM-5 update: translation into Brazilian Portuguese

Brazilian governmental research funding agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Brazilian governmental research funding agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Brazilian governmental research funding agency Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)ShireNovartisEli LillyJanssen-CilagUniv Fed Rio Grande do Sul, Fac Med, Dept Psiquiatria, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Fac Med, Dept Pediat, Porto Alegre, RS, BrazilUniv Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilPontifica Univ Catolica Rio Grande do Sul, Dev Cognit Neurosci Res Grp GNCD, Porto Alegre, RS, BrazilInst Bairral Psiquiatria, Ctr Integrado Desenvolvimento Infancia & Adolesce, Itapira, BrazilUniv Fed Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilWeb of Scienc

Molecular Binding Mechanism of TtgR Repressor to Antibiotics and Antimicrobials

A disturbing phenomenon in contemporary medicine is the prevalence of multidrug-resistant pathogenic bacteria. Efflux pumps contribute strongly to this antimicrobial drug resistance, which leads to the subsequent failure of clinical treatments. The TtgR protein of Pseudomonas putida is a HTH-type transcriptional repressor that controls expression of the TtgABC efflux pump, which is the main contributor to resistance against several antimicrobials and toxic compounds in this microbe. One of the main strategies to modulate the bacterial resistance is the rational modification of the ligand binding target site. We report the design and characterization of four mutants-TtgRS77A, TtgRE78A, TtgRN110A and TtgRH114A - at the active ligand binding site. The biophysical characterization of the mutants, in the presence and in the absence of different antimicrobials, revealed that TtgRN110A is the variant with highest thermal stability, under any of the experimental conditions tested. EMSA experiments also showed a different dissociation pattern from the operator for TtgRN110A, in the presence of several antimicrobials, making it a key residue in the TtgR protein repression mechanism of the TtgABC efflux pump. We found that TtgRE78A stability is the most affected upon effector binding. We also probe that one mutation at the C-terminal half of helix-α4, TtgRS77A, provokes a severe protein structure distortion, demonstrating the important role of this residue in the overall protein structure and on the ligand binding site. The data provide new information and deepen the understanding of the TtgR-effector binding mechanism and consequently the TtgABC efflux pump regulation mechanism in Pseudomonas putida.This work was supported by Spanish Ministry of Economy and Competitiveness, National programme for Recruitment and Incorporation of Human Resources, Subprogramme: Ramon y Cajal RYC-2009-04570 and grant P11-CVI-7391 from Junta de Andalucía and EFDR (European Regional Development Fund)

The effect of perceived discrimination on the health of immigrant workers in Spain

Background: Discrimination is an important determinant of health inequalities, and immigrants may be more vulnerable to certain types of discrimination than the native-born. This study analyses the relationship between immigrants' perceived discrimination and various self-reported health indicators. Methods: A cross-sectional survey was conducted (2008) amongst a non-random sample of 2434 immigrants from Ecuador, Morocco, Romania and Colombia in four Spanish cities: Barcelona, Huelva, Madrid and Valencia. A factorial analysis of variables revealed three dimensions of perceived discrimination (due to immigrant status, due to physical appearance, and workplace-related). The association of these dimensions with self-rated health, mental health (GHQ-12), change in self-rated health between origin and host country, and other self-reported health outcomes was analysed. Logistic regression was used adjusting for potential confounders (aOR-95%CI). Subjects with worsening self-reported health status potentially attributable to perceived discrimination was estimated (population attributable proportion, PAP %). Results: 73.3% of men and 69.3% of women immigrants reported discrimination due to immigrant status. Moroccans showed the highest prevalence of perceived discrimination. Immigrants reporting discrimination were at significantly higher risk of reporting health problems than those not reporting discrimination. Workplace-related discrimination was associated with poor mental health (aOR 2.97 95%CI 2.45-3.60), and the worsening of self-rated health (aOR 2.20 95%CI 1.73- 2.80). 40% (95% CI 24-53) PAP of those reporting worse self-rated health could be attributable to discrimination due to immigrant status. Conclusions: Discrimination may constitute a risk factor for health in immigrant workers in Spain and could explain some health inequalities among immigrant populations in Spanish society.This work was supported by the following sources: Carolina Foundation (Spain), Healthcare Research Fund of the Spanish Ministry of Health and Consumption (references PI050497, PI052202, PI052334, PI061701, and PI0790470

Adipose tissue-derived stem cell therapy in rat cryopreserved ovarian grafts

Abstract\ud The preliminary results of ovarian transplantation in clinical practice are encouraging. However, the follicular depletion caused by ischemic injury is a main concern and is directly related to short-term graft survival. Cell therapy with adipose tissue-derived stem cells (ASCs) could be an alternative to induce early angiogenesis in the graft. This study aimed to evaluate ASCs therapy in rat cryopreserved ovarian grafts. A single dose of rat ASC (rASCs) or vehicle was injected into the bilateral cryopreserved ovaries of twelve adult female rats immediately after an autologous transplant. Daily vaginal smears were performed for estrous cycle evaluation until euthanasia on postoperative day 30. Follicle viability, graft morphology and apoptosis were assessed. No differences were found with respect to estrous cycle resumption and follicle viability (P > 0.05). However, compared with the vehicle-treated grafts, the morphology of the ASCs-treated grafts was impaired, with diffuse atrophy and increased apoptosis (P < 0.05). ASCs direct injected in the stroma of rat cryopreserved ovarian grafts impaired its morphology although may not interfere with the functional resumption on short-term. Further investigations are necessary to evaluated whether it could compromise their viability in the long-term.We thank: 1) São Paulo Research Foundation (FAPESP) for grant support\ud (Process numbers: 2010/17897-5 and 2012/09469-9) and Coordenação de\ud Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for post-doctoral\ud scholarship

Association between light exposure and metabolic syndrome in a rural Brazilian town

Context: Metabolic syndrome (MetS) is a complex condition comprising a ‘clustering’ of components representing cardiometabolic risk factors for heart disease and diabetes; its prevalence rate is high and consequences serious. Evidence suggests that light exposure patterns and misalignment of circadian rhythms might contribute to MetS etiology by impacting energy metabolism and glucose regulation. Objective: We hypothesised that individuals with MetS would show disrupted circadian and sleep parameters alongside differences in light exposure profiles. We investigated this using data from a cohort study in Brazil. Methods: Data from 103 individuals from the Baependi Heart Cohort Study aged between 50 and 70 were analysed. Motor activity and light exposure were measured using wrist-worn actigraphy devices. Cardiometabolic data were used to calculate the number of MetS components present in each participant, and participants grouped as MetS/non-MetS according to standard guidelines. Between-group comparisons were made for the actigraphy measures; additionally, correlation analyses were conducted. Results: Motor activity and circadian profiles showed no differences between groups. However, the MetS group presented lower light exposure during the day and higher light exposure at night. Correlation analyses, including all participants, showed that greater daytime light exposure and greater light exposure difference between day and night were associated with reduced MetS risk (a lower number of MetS components). Also, the light exposure difference between day and night correlated with body mass index across all participants. Conclusions: The observed results suggest a direct association between light exposure and MetS which appears to not be attributable to disruptions in circadian activity rhythm nor to sleep parameters. This link between light exposure patterns and MetS risk could inform possible prevention strategies