When should Home-visit nurses initiate end-of-life discussions for patients with Organ failure and family caregivers? A qualitative study.

BACKGROUND: End-of-life (EOL) discussions for organ-failure patients with family caregivers are important factors for successful EOL care. However, identifying the appropriate time to initiate these discussions is difficult owing to the unpredictability of the disease trajectory. No practical tools or clinical indicators currently exist that can help identify non-cancer patients receiving home care who need EOL discussions. METHODS: The survey was conducted from February 2020 to June 2021. To identify the appropriate time at which to initiate EOL discussions for patients with organ failure and their caregivers, we determined the time when home-visit nurses initiated EOL discussions. We interviewed 19 home-visit nurses (mean total home-visit nursing experience: 6.7 ± 5.9 years) and analyzed the data using Hsieh and Shannon's qualitative content approach. RESULTS: Three themes related to home-visit nurses' experiences of identifying the appropriate time to start EOL discussions were identified: symptomatic worsening, lack of patients' and family caregivers' EOL awareness, and decline in activities of daily living. CONCLUSIONS: It is necessary to develop a tool that will enable home-visit nurses to implement EOL discussions at the appropriate time.

Low plasma fibrinogen levels are associated with poor prognosis in cutaneous angiosarcoma of the head and neck.

Angiosarcoma of the head and neck (ASHN) is one of the most aggressive malignancies of the skin, but the prognostic factors are not well known because of its rarity. Recently, high plasma fibrinogen levels were reported to predict poor prognosis in several malignancies. In the present retrospective study, we suggest that low plasma fibrinogen levels predict poor prognosis for ASHN.

Global coordination in adaptation to gene rewiring.

Gene rewiring is a common evolutionary phenomenon in nature that may lead to extinction for living organisms. Recent studies on synthetic biology demonstrate that cells can survive genetic rewiring. This survival (adaptation) is often linked to the stochastic expression of rewired genes with random transcriptional changes. However, the probability of adaptation and the underlying common principles are not clear. We performed a systematic survey of an assortment of gene-rewired Escherichia coli strains to address these questions. Three different cell fates, designated good survivors, poor survivors and failures, were observed when the strains starved. Large fluctuations in the expression of the rewired gene were commonly observed with increasing cell size, but these changes were insufficient for adaptation. Cooperative reorganizations in the corresponding operon and genome-wide gene expression largely contributed to the final success. Transcriptome reorganizations that generally showed high-dimensional dynamic changes were restricted within a one-dimensional trajectory for adaptation to gene rewiring, indicating a general path directed toward cellular plasticity for a successful cell fate. This finding of global coordination supports a mechanism of stochastic adaptation and provides novel insights into the design and application of complex genetic or metabolic networks.

Functional specialization in regulation and quality control in thermal adaptive evolution.

Distinctive survival strategies, specialized in regulation and in quality control, were observed in thermal adaptive evolution with a laboratory Escherichia coli strain. The two specialists carried a single mutation either within rpoH or upstream of groESL, which led to the activated global regulation by sigma factor 32 or an increased amount of GroEL/ES chaperonins, respectively. Although both specialists succeeded in thermal adaptation, the common winner of the evolution was the specialist in quality control, that is, the strategy of chaperonin-mediated protein folding. To understand this evolutionary consequence, multilevel analyses of cellular status, for example, transcriptome, protein and growth fitness, were carried out. The specialist in quality control showed less change in transcriptional reorganization responding to temperature increase, which was consistent with the finding of that the two specialists showed the biased expression of molecular chaperones. Such repressed changes in gene expression seemed to be advantageous for long-term sustainability because a specific increase in chaperonins not only facilitated the folding of essential gene products but also saved cost in gene expression compared with the overall transcriptional increase induced by rpoH regulation. Functional specialization offered two strategies for successful thermal adaptation, whereas the evolutionary advantageous was more at the points of cost-saving in gene expression and the essentiality in protein folding.

Growth rate-coordinated transcriptome reorganization in bacteria.

BACKGROUND: Cell growth rate reflects an organism's physiological state and largely relies on the ability of gene expression to respond to the environment. The relationship between cellular growth rate and gene expression remains unknown. RESULTS: Growth rate-coordinated changes in gene expression were discovered by analyzing exponentially growing Escherichia coli cells cultured under multiple defined environments, in which osmotic pressure, temperature and starvation status were varied. Gene expression analyses showed that all 3,740 genes in the genome could be simply divided into three clusters (C1, C2 and C3), which were accompanied by a generic trend in the growth rate that was coordinated with transcriptional changes. The direction of transcriptional change in C1 indicated environmental specificity, whereas those in C2 and C3 were correlated negatively and positively with growth rates, respectively. The three clusters exhibited differentiated gene functions and gene regulation task division. CONCLUSIONS: We identified three gene clusters, exhibiting differential gene functions and distinct directions in their correlations with growth rates. Reverses in the direction of the growth rate correlated transcriptional changes and the distinguished duties of the three clusters indicated how transcriptome homeostasis is maintained to balance the total expression cost for sustaining life in new habitats.

Timely Identification of Patients With Cancer and Family Caregivers in Need of End-of-Life Discussions by Home-Visit Nurses in Japan: A Qualitative Descriptive Study.

End-of-life (EOL) discussions for patients with cancer are a key factor of successful EOL care; however, identifying the optimal timing for these discussions in Japanese home-care settings is difficult. To identify the time at which patients with cancer and their caregivers need EOL discussions, we explored when home-visit nurses start EOL discussions. We interviewed 23 home-visit nurses and analyzed the data using qualitative content analysis. Three themes were derived from the analysis. Participants identified the timing of EOL discussions as being sensitive to patients' changing health and care needs (increases in patient's total pain), changes in the family caregiver's physical or mental condition through daily care (increases in family caregiver distress), and the EOL process that patients follow (trajectory of disease). Developing a tool or in-service educational program that will enable inexperienced or new graduate home-visit nurses to implement EOL discussions at appropriate times is necessary.

Adaptation by stochastic switching of a monostable genetic circuit in Escherichia coli.

Stochastic switching is considered as a cost-saving strategy for adaptation to environmental challenges. We show here that stochastic switching of a monostable circuit can mediate the adaptation of the engineered OSU12-hisC Escherichia coli strain to histidine starvation. In this strain, the hisC gene was deleted from the His operon and placed under the control of a monostable foreign promoter. In response to histidine depletion, the OSU12-hisC population shifted to a higher HisC expression level, which is beneficial under starving conditions but is not favoured by the monostable circuit. The population shift was accompanied by growth recovery and was reversible upon histidine addition. A weak directionality in stochastic switching of hisC was observed in growing microcolonies under histidine-free conditions. Directionality and fate decision were in part dependent on the initial cellular status. Finally, microarray analysis indicated that OSU12-hisC reorganized its transcriptome to reach the appropriate physiological state upon starvation. These findings suggest that bacteria do not necessarily need to evolve signalling mechanisms to control gene expression appropriately, even for essential genes.

The Potential Role of Peer Support Interventions in Treating Depressive Symptoms in Cancer Patients.

Depressive symptoms are prevalent in cancer patients and are one of the most distressing symptoms in this population. Although mental health professionals such as psychiatrists and psychologists are now engaged in cancer care, the management of depressive symptoms in cancer patients needs further improvement. Peer support interventions (PSIs) in cancer care have attracted substantial attention and have several advantages over support by medical professionals, potentially improving depressive symptoms in cancer patients. However, there may be some potential risks. Several strategies using PSIs have been developed to improve depressive symptoms and have been evaluated in randomized controlled trials. The strategies include education on stress management skills, promoting emotional support, counseling on specific topics that are difficult to discuss with others, helping patients navigate the use of resources, and promoting health-related behaviors to decrease depressive symptoms. In this paper, we present recent findings on PSIs in cancer, focusing on randomized controlled trials.

Tulobuterol patch maintains diaphragm muscle contractility for over twenty-four hours in a mouse model of sepsis.

Tulobuterol, a sympathomimetic drug used as a transdermal patch, increases normal diaphragm muscle strength. Because diaphragm muscle weakness (i.e. decrease of contraction) is a feature of bronchial asthma and sepsis, we examined the in vitro and in vivo effects of tulobuterol on the contractility of diaphragm muscles prepared from mice treated with endotoxin. We measured contractile parameters of force-frequency curves and twitch kinetics using untreated or treated diaphragm muscles at 0 (E0) and 4 (E4) hours after E. coli endotoxin (20 mg/kg) administration. The force-frequency curve of E4 diaphragm muscle was decreased from that of E0 diaphragm muscle (p < 0.001). E4 diaphragm muscle was incubated in an organ buffer containing 10(-7) or 10(-5) M concentrations of tulobuterol for 1 h (in vitro). The force-frequency curves of both 10(-7) (p < 0.01) or 10(-5) M (p < 0.001) tulobuterol concentrations shifted significantly upward from those of no tulobuterol, indicating that tulobuterol can recover the diaphragm muscle contractility that was decreased by endotoxin. In the in vivo treatment, E0 and E4 diaphragm muscles were analyzed at 0, 12, and 24 h after transdermal tulobuterol treatment. The force-frequency curves of E0 and E4 diaphragm muscles at three time points were not significantly changed each other, indicating that tulobuterol patch restores the muscle contractility. Thus, diaphragm muscle contractility was maintained during 4 h of endotoxin administration with tulobuterol patch for over 24 h. We suggest that this treatment of bronchial asthma may protect against endotoxin contained in inhaled house dust.

Hypoglycemia-like symptoms after restorative proctocolectomy for UC: a preliminary study.

This study was conducted to explore the hypoglycemia-like symptoms sometimes noted after proctocolectomy for ulcerative colitis. Eighty-three patients who underwent restorative proctocolectomy at least 1 year before December 2001 (staged procedure, n = 50; one-staged procedure, n = 33) were requested to answer three questionnaires at the stage of temporary diverting ileostomy and/or after completion of the operation (after stoma closure). The questionnaires evaluated the presence of 18 items of hypoglycemia-like symptoms, subject recognition of the cause, and whether the symptoms were improved after eating or drinking. Seven subjects (14%) experienced at least one of the three items considered to be specific symptoms of hypoglycemia ("cold sweats," "trembling of hands," and "extreme desire for sweets") at the stage of temporary ileostomy. Ten (20%) and 9 (27.3%) subjects experienced those specific symptoms at the stage after completion of the operation by staged procedure and by one-staged procedure, respectively. There was no significant difference between the stages. Hypoglycemia-like symptoms were found to be experienced in a considerable number of patients after proctocolectomy for ulcerative colitis.

Dermoscopic features of endocrine mucin-producing sweat gland carcinoma.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is very rare, with only 61 cases reported to date. EMPSGC is considered to be a low-grade carcinoma of sweat gland origin. Dermoscopic findings of EMPSGC have not been previously reported. We report the first case of a man with EMPSGC, featuring dermoscopic findings. Dermoscopic examinations of the present EMPSGC lesion revealed tumor cell proliferation that appeared as pink ovoid nests and elongated epidermis that resembled a whitish-pink network. Another characteristic finding of the present lesion was the large red/blue globules in pink ovoid nests in the tumor. Those reflected lacunae containing secretory fluid with red blood cells. We think that the large red/blue globules in pink ovoid nests in our case could be a characteristic dermoscopic finding specific to EMPSGC. We dermatologists encounter many "pink nodules" at out-patient clinics. The present dermoscopic findings may be useful for the differential diagnosis of EMPSGC.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (Translated Version).

Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different management from sporadic colorectal cancer. While the diagnosis of familial adenomatous polyposis might be easy because usually 100 or more adenomas that develop in the colonic mucosa are in this condition, Lynch syndrome, which is the most commonly associated disease with hereditary colorectal cancer, is often missed in daily medical practice because of its relatively poorly defined clinical characteristics. In addition, the disease concept and diagnostic criteria for Lynch syndrome, which was once called hereditary non-polyposis colorectal cancer, have changed over time with continual research, thereby possibly creating confusion in clinical practice. Under these circumstances, the JSCCR Guideline Committee has developed the "JSCCR Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (HCRC)," to allow delivery of appropriate medical care in daily practice to patients with familial adenomatous polyposis, Lynch syndrome, or other related diseases. The JSCCR Guidelines 2016 for HCRC were prepared by consensus reached among members of the JSCCR Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR Guidelines 2016 for HCRC.

Liver Metastasis of a Triple-Negative Breast Cancer and Complete Remission for 5 Years After Treatment With Combined Bevacizumab/Paclitaxel/Carboplatin: Case Report and Review of the Literature.

Triple-negative breast cancer (TNBC) is aggressive, with high risk of visceral metastasis and death. A substantial proportion of patients with TNBC is associated with BRCA mutations, implying that these tumors are sensitive to DNA-damaging agents. We report successful treatment of a metastatic TNBC in a woman with a BRCA2 germline mutation using combined bevacizumab/paclitaxel/carboplatin (BPC) therapy. The patient was pregnant and had liver metastases, and a complete clinical response was sustained for approximately 5 years. Mastectomy was performed during the 29th week of pregnancy, and the baby was later delivered by caesarean section. Subsequently, multiple metastases in both liver lobes were detected using computed tomography and magnetic resonance imaging and the patient was treated with a BPC regimen, which led to complete disappearance of metastatic lesions in the liver. No additional treatment was provided, and after 5 years the patient consented to direct sequencing of BRCA2 and a 6781delG mutation was identified. At the most recent (5-year) follow-up, the patient was alive with good quality of life and no evidence of metastases.This finding suggests that BPC therapy might be considered a good therapeutic option for the treatment of metastatic TNBC in a woman with a BRCA2 germline mutation.

Prevalence and differentiation of hereditary breast and ovarian cancers in Japan.

BACKGROUND: We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan. MATERIALS AND METHODS: Our study of BRCA1/2 collected data at eight institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March 2012. RESULTS: Among 260 proband cases, 46 (17.7 %) were positive for BRCA1, and 35 (13.5 %) were BRCA2-positive. Therefore, the total pathological mutation rate was 30.7 %. Pathology data after breast surgery were obtained from 37 cases of BRCA1 mutation, 23 (62.2 %) of which were triple negative (TN). On the other hand, 29 cases (82.9 %) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found two cases of large deletion detected by multiplex ligation-dependent probe amplification. One was an entire deletion of exon 20 and the lacked exons 1-9. TN with a family history of ovarian cancer was 11/20 (55 %). TN under 40-year-old (y.o.) 15/23 (65.2 %) and TN with one or more breast cancers in family history 17/32 (53.1 %) showed higher incidences of BRCA1 mutation. CONCLUSION: Hereditary breast and ovarian cancer (HBOC) may have nearly the same prevalence in Japan as in the US or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to develop risk models for BRCA1/2 carriers in Japan.