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We evaluated work intensity, exercise tolerance, and mental health among workers with heart disease and assessed the relationship between return to work (RTW) status and changes in mental health 3 months post-discharge.

Patients were enrolled from 2014 to 2019. Data were collected on admission and 3 months post-discharge. Mental health was assessed using the Hospital Anxiety and Depression Scale. Jobs were defined as "reasonable workload (RW)" or "over workload (OW)" based on metabolic equivalents.

Twenty-six patients responded (81.3%). RTW after 3 months was higher in the RW group (100%) than in the OW group (63.6%). Mental health in the OW group significantly deteriorated compared with baseline and was higher than that in the RW group.

Patients whose work intensity was higher than their exercise tolerance had worsened mental health 3 months post-discharge.

Patients whose work intensity was higher than their exercise tolerance had worsened mental health 3 months post-discharge.This study was carried out to investigate the effect of complementary and alternative therapy on physical activity and self-care power in individuals diagnosed with type 2 diabetes. The study was conducted on 63 individuals who had been diagnosed with type 2 diabetes for at least 6 months, and met the inclusion criteria. The Personal Information Form, International Physical Activity Questionnaire Short Form, and Diabetes Self-Care Scale were used to collect the data. Percentage, median, Mann-Whitney U tests, and Wilcoxon tests were used for data analysis. While 71.9% of the individuals were only on diabetic diet, 58% of the individuals were on diabetic diet together with complementary and alternative medicine (CAM) methods, and all those patients regularly measured their blood glucose levels; 19.4% of the individuals on both diabetic diet and CAM methods, and 21.9% of the individuals only on diabetic diet used more than one oral medication per day. The findings of this study revealed that 35.5% of the individuals both on diabetic diet and CAM methods and 40.6% of the individuals only on diabetic diet used insulin. The individuals who were both on diabetic diet and CAM methods stated that their health statuses improved in the previous month; however, the individuals who were only on diabetic diet did not report any improvement in that period. Physical activity levels and self-care behaviors of the individuals on diabetic diet and CAM methods together were found to be significantly better than those who were only on a diabetic diet. A positive relationship was found between physical activity level and self-care behaviors.Infertility care is often directed by a biomedical approach rather than a holistic approach, especially in African countries. This article explores the opinions of health care providers regarding holistic health care interventions in managing women with infertility in Ghana. Data were retrieved using a qualitative design and nominal group technique with a purposive sample of 12 health care providers in Ghana. Data were analyzed through thematic analysis. Health care providers explored various psychological, educational, spiritual, social, and medical interventions to ensure women diagnosed with infertility receive holistic treatment and attain optimal health.Fatigue is a complication of hemodialysis (HD). We examined the effect of aromatherapy on fatigue in 62 HD patients. Data were collected using a questionnaire and the Piper Fatigue Scale. It was found that fatigue decreased in the intervention group (P less then .05). Lavender aromatherapy is useful in reducing fatigue.Individuals with chronic conditions are susceptible to stress-related health complications. Left unattended, chronic stress exacerbates inflammation, diminishes quality of life (QOL), and increases all-cause mortality. Here, we suggest a theoretical framework promoting the use of mindfulness-based interventions (MBIs) in patients with chronic conditions and a conceptual model of how MBIs may influence stress and QOL.

This study aimed to determine the prevalence of withholding or withdrawal of life-sustaining therapy (WLST) decisions in trauma ICU patients, using a large registry. We hypothesised that this prevalence is similar to that of the general population admitted to an ICU. As secondary aims, it sought to describe the trauma patients for whom the decision was made for WLST and the factors associated with this decision.

This observational study assessed data from 14 French centres listed in the TraumaBaseTM registry. All trauma patients hospitalised for more than 48 h were pro-spectively included.

Data from 8569 trauma patients, obtained from January 2016 to December 2018, were included in this study. A WLST decision was made in 6% of all cases. In the WLST group, 67% of the patients were older men (age 62 versus 36, P  < 0.001); more often they had a prior medical history and higher median severity scores than the patients in the no WLST decision group; SAPS II 58 (46 to 69) versus 21 (13 to 35) and ISS 26 (22 to 24) versus 12 (5 to 22), P  < 0.001. Neurological status was strongly associated with WLST decisions. The geographic area of the ICUs affected the rate of the WLST decisions. The ICU mortality was 11% (n = 907) of which 47% (n = 422) were preceded by WLST decisions. Fourteen percent of WLST orders were not associated to the death.

Among 8569 patients, medical history, trauma severity criteria, notably neurological status and geographical areas were associated with WLST. These regional differences deserve to be investigated in future studies.

Among 8569 patients, medical history, trauma severity criteria, notably neurological status and geographical areas were associated with WLST. These regional differences deserve to be investigated in future studies.KRAS G12C inhibitors such as sotorasib and adagrasib are often effective in KRAS G12C-driven non-small cell lung cancer (NSCLC) patients. Fluorofurimazine mw However, acquired resistance limits long-term patient survival. In this issue of the JCI, Tsai et al. present a comprehensive genetic analysis of multiple tumors with acquired sotorasib resistance obtained through an autopsy of a patient with KRAS G12C-mutant NSCLC. This analysis of pre- and posttreatment tumors uncovered cancer cell-intrinsic and -extrinsic features of resistance, including reactivation of KRAS-mediated signaling, reprogramming of metabolism, epithelial-mesenchymal transition, and tumor microenvironment changes. This elegant study demonstrates the multifaceted nature of KRAS G12C inhibitor clinical resistance and potential avenues to overcome resistance.A challenge in cancer treatment is targeting cancer cells while sparing normal cells. Thus, identifying cancer-specific neoepitopes is an active research area. Neoepitopes are generated by the accumulation of mutations; however, deadly cancer types, including pancreatic cancer, have a low mutational burden and, consequently, a paucity of neoantigens. In this issue of the JCI, Lim, Zhou, and colleagues describe a neoepitope generated upon proteolytic cleavage of the transmembrane CUB domain containing protein 1 (CDCP1). CDCP1 is overexpressed in cancer and portends a worse prognosis; previous attempts to target CDCP1 reduced cancer growth, but adversely affected the host. Here, the authors generated an antibody that specifically targeted cleaved CDCP1 (c-CDCP1) and developed a drug conjugate, a vector for radioactive ions, and a mediator of T cell activation. The therapeutics inhibited pancreatic cancer cell growth in vitro and in vivo. Exploiting proteolytic cleavage-derived neoantigens opens an attractive way for specifically targeting cancer cells.The chromosomal t(4;14) (p16;q32) translocation drives high expression of histone methyltransferase nuclear SET domain-containing 2 (NSD2) and plays vital roles in multiple myeloma (MM) evolution and progression. However, the mechanisms of NSD2-driven epigenomic alterations in chemoresistance to proteasome inhibitors (PIs) are not fully understood. Using a CRISPR/Cas9 sgRNA library in a bone marrow-bearing MM model, we found that hepatoma-derived growth factor 2 (HRP2) was a suppressor of chemoresistance to PIs and that its downregulation correlated with a poor response and worse outcomes in the clinic. We observed suppression of HRP2 in bortezomib-resistant MM cells, and knockdown of HRP2 induced a marked tolerance to PIs. Moreover, knockdown of HRP2 augmented H3K27me3 levels, consequentially intensifying transcriptome alterations promoting cell survival and restriction of ER stress. Mechanistically, HRP2 recognized H3K36me2 and recruited the histone demethylase MYC-induced nuclear antigen (MINA) to remove H3K27me3. Tazemetostat, a highly selective epigenetic inhibitor that reduces H3K27me3 levels, synergistically sensitized the anti-MM effects of bortezomib both in vitro and in vivo. Collectively, these results provide a better understanding of the origin of chemoresistance in patients with MM with the t(4;14) translocation and a rationale for managing patients with MM who have different genomic backgrounds.Gastrointestinal motility disorders involve alterations to the structure and/or function of the enteric nervous system (ENS) but the causal mechanisms remain unresolved in most cases. Homeostasis and disease in the ENS are processes that are regulated by enteric glia. Signaling mediated through type I lysophosphatidic acid receptors (LPAR1) has recently emerged as an important mechanism that contributes to disease, in part, through effects on peripheral glial survival and function. Enteric glia express LPAR1 but its role in ENS function and motility disorders is unknown. We used a combination of genetic, immunohistochemical, calcium imaging, and in vivo pharmacological approaches to investigate the role of LPAR1 in enteric glia. LPAR1 was enriched in enteric glia in mice and humans and LPA stimulated intracellular calcium responses in enteric glia, subsequently recruiting activity in a subpopulation of myenteric neurons. Blocking LPAR1 in vivo with AM966 attenuated gastrointestinal motility in mice and produced marked enteric neuro- and gliopathy. Samples from humans with chronic intestinal pseudo-obstruction (CIPO), a severe motility disorder, showed reduced glial LPAR1 expression in the colon and ileum. These data suggest that enteric glial LPAR1 signaling regulates gastrointestinal motility through enteric glia and could contribute to severe motility disorders in humans such as CIPO.Extracellular proteolysis is frequently dysregulated in disease and can generate proteoforms with unique neoepitopes not found in healthy tissue. Here, we demonstrate that Abs that selectively recognize a proteolytic neoepitope on CUB domain containing protein 1 (CDCP1) could enable more effective and safer treatments for solid tumors. CDCP1 is highly overexpressed in RAS-driven cancers, and its ectodomain is cleaved by extracellular proteases. Biochemical, biophysical, and structural characterization revealed that the 2 cleaved fragments of CDCP1 remain tightly associated with minimal proteolysis-induced conformational change. Using differential phage display, we generated recombinant Abs that are exquisitely selective to cleaved CDCP1 with no detectable binding to the uncleaved form. These Abs potently targeted cleaved CDCP1-expressing cancer cells as an Ab-drug conjugate, an Ab-radionuclide conjugate, and a bispecific T cell engager. In a syngeneic pancreatic tumor model, these cleaved-specific Abs showed tumor-specific localization and antitumor activity with superior safety profiles compared with a pan-CDCP1 approach.