Knowledge, fatigue, and cognitive factors as predictors of lymphoedema risk-reduction behaviours in women with cancer.

OBJECTIVE: To identify social-cognitive factors predicting lymphoedema risk-reduction behaviours (hereafter, self-care) after discharge among patients in Japan with breast or gynaecological cancers, using the extended model of the theory of planned behaviour. METHODS: A cross-sectional questionnaire study was conducted in an oncology hospital. Items measured were (1) knowledge about self-care; (2) the Cancer Fatigue Scale; (3) social-cognitive factors in the theory of planned behaviour (attitudes, subjective norms, and perceived behavioural control); (4) self-care (limb hygiene, observation, articular movement, recommended risk-reduction behaviours in daily life, and diet and weight control); and (5) demographics. Of 202 respondents, 147 who had not been diagnosed with lymphoedema were eligible for statistical analysis (65.3% with gynaecological cancer, 34.7% with breast cancer). RESULTS: Structural equation modelling was used to examine a hypothesised model based on the theory of planned behaviour. The results revealed that a longer time since surgery, higher levels of fatigue, less knowledge, higher expected efficacy of self-care, and lower perceived behavioural control directly and significantly predicted less self-care behaviour. CONCLUSIONS: Besides education about self-care behaviour, levels of fatigue and perceived behavioural control should be taken into account to encourage female patients with cancer to perform self-care after discharge. Continuous psycho-educational programmes after discharge may help to facilitate self-care behaviours among long-term female cancer survivors.

First report on USA300 outbreak in a neonatal intensive care unit detected by polymerase chain reaction-based open reading frame typing in Japan.

Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) in the neonatal intensive care unit (NICU) have been reported worldwide. Some outbreaks were caused by USA300, which is a community-associated MRSA clone. In 2011, polymerase chain reaction-based open reading frame typing (POT) for the initial MRSA isolates from all inpatients was started at the Tokyo Metropolitan Children's Medical Center. From March 2014 to April 2015, a total of 131 MRSA strains were isolated, 104 of which were analyzed as healthcare-associated MRSA. Thirteen stains (12.5%) had a POT number of 106-9-93, which strongly suggested USA300; these included 6 from nasal swabs, 6 from blood cultures and 1 from subcutaneous pus. All the MRSA strains were isolated from patients in the NICU; were typed as sequence type 8, spa type t008, and staphylococcal cassette chromosome type mec IVa; and possessed the lukS-lukF and arginine catabolic mobile element-arcA gene. Pulsed-field gel electrophoresis of all the strains, with USA300-0114 as a reference, showed indistinguishable banding pattern. Based on these results, POT was useful in recognizing this first MRSA outbreak of USA300 in a Japanese NICU and was advantageous in terms of swiftness, less cost and monitoring change of the epidemic MRSA lineage.

Information-seeking, information sources and ongoing support needs after discharge to prevent cancer-related lymphoedema.

OBJECTIVES: To compare gynaecological and breast cancer patients in their information-seeking behaviours, usefulness of information sources and ongoing care needs after discharge to prevent the onset of lymphoedema. METHODS: We conducted a consecutive cross-sectional survey in an oncology hospital. Adult patients with stage I, II or III gynaecological or breast cancer who had undergone lymph node dissection and had not been diagnosed with lymphoedema were eligible for inclusion. The survey explored physical health status, knowledge of self-care, information-seeking behaviours, information sources and need for ongoing care from an oncology hospital and/or community health centre. RESULTS: Among 254 patients recruited, 202 responded (79.5% response rate). In total, 147 patients were eligible for statistical analysis. Irrespective of cancer type, the most commonly sought information was lymph drainage. Information on preventing weight gain was sought more often by breast cancer patients than gynaecological cancer patients. Regardless of cancer type, the most common information sources were nurses at an oncology hospital. Gynaecological cancer patients perceived nurses at the oncology hospital as useful for understanding risks, symptoms and prevention of lymphoedema. Irrespective of cancer type, ongoing need for help with lymphoedema prevention was reported both from the oncology hospital and the community centre. Limb symptoms, poor health status and poor knowledge affected the ongoing needs of gynaecological cancer patients at the oncology hospital, whereas poor health status affected ongoing needs in community health centres among both types of cancer patients. CONCLUSIONS: Both gynaecological and breast cancer patients reported ongoing care needs, but that details of information-seeking behaviours differed.

Stromal Cell-Derived Factor-1α Plays a Crucial Role Based on Neuroprotective Role in Neonatal Brain Injury in Rats.

Owing to progress in perinatal medicine, the survival of preterm newborns has markedly increased. However, the incidence of cerebral palsy has risen in association with increased preterm birth. Cerebral palsy is largely caused by cerebral hypoxic ischemia (HI), for which there are no effective medical treatments. We evaluated the effects of stromal cell-derived factor-1α (SDF-1α) on neonatal brain damage in rats. Left common carotid (LCC) arteries of seven-day-old Wistar rat pups were ligated, and animals were exposed to hypoxic gas to cause cerebral HI. Behavioral tests revealed that the memory and spatial perception abilities were disturbed in HI animals, and that SDF-1α treatment improved these cognitive functions. Motor coordination was also impaired after HI but was unimproved by SDF-1α treatment. SDF-1α reduced intracranial inflammation and induced cerebral remyelination, as indicated by the immunohistochemistry results. These data suggest that SDF-1α specifically influences spatial perception abilities in neonatal HI encephalopathy.

A bioinspired bifunctional catalyst: an amphiphilic organometallic catalyst for ring-closing metathesis forming liquid droplets in aqueous media.

Inspired by phase-separated biopolymers with enzymatic activity, we developed an amphiphilic catalyst consisting of alternating hydrophilic oligo(ethylene glycol) and hydrophobic aromatic units bearing a Hoveyda-Grubbs catalyst center (MAHGII). MAHGII served as both a droplet-forming scaffold and a catalyst for ring-closing metathesis reactions, providing a new biomimetic system that promotes organic reactions in an aqueous environment.

Transient control of lytic activity via a non-equilibrium chemical reaction system.

The development of artificial non-equilibrium chemical reaction systems has recently attracted considerable attention as a new type of biomimetic. However, due to the lack of bioorthogonality, such reaction systems could not be linked to the regulation of any biological phenomena. Here, we have newly designed a non-equilibrium reaction system based on olefin metathesis to produce the Triton X-mimetic non-ionic amphiphile as a kinetic product. Using phospholipid vesicles encapsulating fluorescent dyes and red blood cells as cell models, we demonstrate that the developed chemical reaction system is applicable for transient control of the resulting lytic activity.

Climate change by any other name: Social representations and language practices of coastal inhabitants on Mayotte Island in the Indian Ocean.

As population-related climate change research increases, so does the need to nuance approaches to this complex phenomenon, including issues related to cultural and linguistic translations. To explore how climate change is understood in understudied societies, a case-study approach is taken to address social representations of climate change by inhabitants of a Maore village in the French island of Mayotte. The study explores how local fishers understand the issue when considering observed environmental changes. Based on analyses of 30 interviews, the study found that social representations and related climate change discourses are not well established, except for individuals in close contact with French institutions. Issues regarding local culture and language reveal the importance of understanding the different components of climate change. Climate change communication and awareness-raising on the island are explored, as well as considerations of culturally and linguistically complex settings with a Global North/Global South interface.

Incomplete activation of Alyref and Gabpb1 leads to preimplantation arrest in cloned mouse embryos.

Differentiated cell nuclei can be reprogrammed after nuclear transfer (NT) to oocytes and the produced NT embryos can give rise to cloned animals. However, development of NT embryos is often hampered by recurrent reprogramming failures, including the incomplete activation of developmental genes, yet specific genes responsible for the arrest of NT embryos are not well understood. Here, we searched for developmentally important genes among the reprogramming-resistant H3K9me3-repressed genes and identified Alyref and Gabpb1 by siRNA screening. Gene knockout of Alyref and Gabpb1 by the CRISPR/Cas9 system resulted in early developmental arrest in mice. Alyref was needed for the proper formation of inner cell mass by regulating Nanog, whereas Gabpb1 deficiency led to apoptosis. The supplement of Alyref and Gabpb1 mRNA supported efficient preimplantation development of cloned embryos. Alyref and Gabpb1 were silenced in NT embryos partially because of the repressed expression of Klf16 by H3K9me3. Thus, our study shows that the H3K9me3-repressed genes contain developmentally required genes, and the incomplete activation of such genes results in preimplantation arrest of cloned embryos.

COVID-19 Vaccination in Patients with Cancer.

Patients with cancer are concerned about the effects of the COVID-19 vaccination. We conducted an online survey on the COVID-19 vaccination status and side effects among patients with cancer in Japan between 8 and 14 August 2021. We included 1182 female patients with cancer aged 20-70 years and registered on an online patient website. Of the patients, 944 had breast cancer, 216 had gynecological cancer, 798 were undergoing drug/radiation therapy, and 370 were in follow-up. At the time of the survey, 885 patients had already received at least one dose. Of these, 580 had also received their second dose. The incidence rate of side effects was equivalent to previous reports. In patients with breast cancer, problems such as the onset or worsening of lymphedema or axillary lymphadenopathy metastasis requiring differential diagnosis were encountered following vaccination. A total of 768 patients were concerned about the vaccine at some point, and 726 consulted with their attending physicians about the timing or side effects of the vaccination. Of the 110 patients undergoing chemotherapy or radiation therapy, 75 adjusted the timing of the vaccination based on their therapy. The cross-analysis revealed that 81% of those who consulted their physician had received at least one dose of the COVID-19 vaccination compared with 65% of those who had not consulted their physician. Consulting with a physician about the COVID-19 vaccination was found to alleviate the concerns of patients with cancer and encourage them to get vaccinated.

Imidazolinium-based Multiblock Amphiphile as Transmembrane Anion Transporter.

Transmembrane anion transport is an important biological process in maintaining cellular functions. Thus, synthetic anion transporters are widely developed for their biological applications. Imidazolinium was introduced as anion recognition site to a multiblock amphiphilic structure that consists of octa(ethylene glycol) and aromatic units. Ion transport assay using halide-sensitive lucigenin and pH-sensitive 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) revealed that imidazolinium-based multiblock amphiphile (IMA) transports anions and showed high selectivity for nitrate, which plays crucial roles in many biological events. Temperature-dependent ion transport assay using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) indicated that IMA works as a mobile carrier. 1 H NMR titration experiments indicated that the C2 proton of the imidazolinium ring recognizes anions via a (C-H)+ ⋅⋅⋅X- hydrogen bond. Furthermore, all-atom molecular dynamics simulations revealed a dynamic feature of IMA within the membranes during ion transportation.

Genetic variations in triple-negative breast cancers undergoing neo-adjuvant chemotherapy.

Aim: Triple negative breast cancer (TNBC) is known as aggressive subtype and have no identified targeted therapies. We examined the relationship of neoadjuvant chemotherapy response to genetic variations of TNBC. Methods: The tumors used in this study were collected from Showa University Hospital, Japan. Thirteen formalin-fixed paraffin-embedded tumors from Japanese TNBC patients who underwent neoadjuvant chemotherapy were used for analysis. Of these, eight surgically resected tumors showed progressive disease and/or recurrence after treatment (PD/REC), and biopsy tissues from five patients showing pathological complete response (pCR) were analyzed. DNA extracted from tissue sample were analyzed. The Miseq system and Trusight Tumor Sequence panel kit were used to sequence 174 amplicons over 82 exons of 26 cancer-related genes to identify genetic mutations. Results: Seven somatic non-synonymous variants were detected in three genes (FOXL2, PIK3CA, and TP53) in all five pCR patients, and six somatic non-synonymous variants in two genes (PTEN and TP53) were detected in six of eight PD/REC patients. Eight of 13 TNBC tumors were found to have TP53 pathogenic variants, in both pCR and PD/REC cases. Conclusion: Although TP53 variation was detected in both pCR and PD/REC cases, each location and type of the variant were different. We could not identify genetic mutations associated with chemotherapy response and recurrence.

Mapping phospho-catalytic dependencies of therapy-resistant tumours reveals actionable vulnerabilities.

Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a practical high-throughput system to measure the enzymatic activity of kinases using biological peptide targets as phospho-sensors to reveal kinase dependencies in tumour biopsies and cell lines. A 228-peptide screen was developed to detect the activity of >60 kinases, including ABLs, AKTs, CDKs and MAPKs. Focusing on BRAFV600E tumours, we found mechanisms of intrinsic resistance to BRAFV600E-targeted therapy in colorectal cancer, including targetable parallel activation of PDPK1 and PRKCA. Furthermore, mapping the phospho-catalytic signatures of melanoma specimens identifies RPS6KB1 and PIM1 as emerging druggable vulnerabilities predictive of poor outcome in BRAFV600E patients. The results show that therapeutic resistance can be caused by the concerted upregulation of interdependent pathways. Our kinase activity-mapping system is a versatile strategy that innovates the exploration of actionable kinases for precision medicine.

MicroRNA (miRNA) cloning analysis reveals sex differences in miRNA expression profiles between adult mouse testis and ovary.

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that can regulate the expression of complementary mRNA targets. Identifying tissue-specific miRNAs is the first step toward understanding the biological functions of miRNAs, which include the regulation of tissue differentiation and the maintenance of tissue identity. In this study, we performed small RNA library sequencing in adult mouse testis and ovary to reveal their characteristic organ- and gender-specific profiles and to elucidate the characteristics of the miRNAs expressed in the reproductive system. We obtained 10,852 and 11 744 small RNA clones from mouse testis and ovary respectively (greater than 10,000 clones per organ), which included 6630 (159 genes) and 10,192 (154 genes) known miRNAs. A high level of efficiency of miRNA library sequencing was achieved: 61% (6630 miRNA clones/10,852 small RNA clones) and 87% (10,192/11,744) for adult mouse testis and ovary respectively. We obtained characteristic miRNA signatures in testis and ovary; 55 miRNAs were detected highly, exclusively, or predominantly in adult mouse testis and ovary, and discovered two novel miRNAs. Male-biased expression of miRNAs occurred on the X-chromosome. Our data provide important information on sex differences in miRNA expression that should facilitate studies of the reproductive organ-specific roles of miRNAs.

Community-based lymphedema risk reduction programs for cancer survivors: An Internet survey of public health nurses.

AIM: Currently, there is no provision for continuous care to monitor lymphedema risk-reduction behavior for survivors of cancer. The aim was to explore the possibility of community-based lymphedema education programs by investigating the knowledge, training needs, and intention to organize such programs and barriers among government-employed public health nurses. METHODS: A cross-sectional Internet survey was conducted among government-employed public health nurses in Japan. The participants were recruited from 2841 health center and community health centers. RESULTS: The final sample included 641 government-employed public health nurses. The participants' knowledge about lymphedema risk-reduction strategies was relatively good, especially on the importance of observation, detection of early signs, and referral to lymphedema clinics. A small proportion of participants indicated an intention to organize community-based lymphedema education programs. Three determinants for this intention were identified: a general interest in lymphedema education, past experience of undertaking training in lymphedema risk-reduction strategies, and the perceived difficulty in organizing community-based lymphedema education programs. The participants' perceptions of difficulty included not knowing the needs for lymphedema education in their community with survivors of cancer. CONCLUSIONS: The results suggest that working collaboratively with government-employed public health nurses to organize community-based lymphedema education programs is possible. Achieving this requires further investigation of the needs of survivors of cancer in the community, communicating these needs to governmental agencies, and organizing and delivering comprehensive training programs about lymphedema risk-reduction strategies for government-employed public health nurses.

Diagnostic accuracy of contrast-enhanced spectral mammography in comparison to conventional full-field digital mammography in a population of women with dense breasts.

BACKGROUND: Contrast-enhanced spectral mammography to compare clinical efficacy of contrast-enhanced spectral mammography (CESM) and conventional digital mammography (MMG) with histopathology as gold standard in dense breasts. PATIENTS AND METHODS: A total of 143 breasts of 72 women who underwent CESM and MMG between 2011 and 2014 at Showa University Hospital were analyzed. RESULTS: 129 (90.2 %) of 143 breasts revealed dense breasts on MMG. 58 (40.6 %) of 143 breasts were diagnosed with breast cancer at histopathology. The remaining 85 breasts were diagnosed with benign findings after image assessments and/or core needle biopsy. CESM revealed 8 false-negative cases among 58 breast cancer cases (sensitivity 86.2 %) and 5 false-positive cases (specificity 94.1 %). Accuracy was 90.9 %. Conventional MMG was assessed true positive in 31 of 58 breast cancer cases (sensitivity 53.4 %) and false positive in 12 cases (specificity 85.9 %). Accuracy was 72.7 %. Sensitivity (p < 0.001), specificity (p = 0.016) and accuracy (p < 0.001) were significantly higher on CESM compared to MMG. MMG missed malignancy in 27 breasts. Of these, 25 were dense breasts. Of these 25, 20 (80.0 %) breasts were positive on CESM. CONCLUSION: These findings suggest that CESM offers superior clinical performance compared to MMG. Use of CESM may decrease false negatives especially for women with dense breasts.

Frozen section is superior to imprint cytology for the intra-operative assessment of sentinel lymph node metastasis in stage I breast cancer patients.

BACKGROUND: A standard intra-operative procedure for assessing sentinel lymph node metastasis in breast cancer patients has not yet been established. PATIENTS AND METHODS: One hundred and thirty-eight patients with stage I breast cancer who underwent sentinel node biopsy using both imprint cytology and frozen section were analyzed. RESULTS: Seventeen of the 138 patients had sentinel node involvement. Results of imprint cytology included nine false negative cases (sensitivity, 47.1%). In contrast, only two cases of false negatives were found on frozen section (sensitivity, 88.2%). There were two false positive cases identified by imprint cytology (specificity, 98.3%). On the other hand, frozen section had 100% specificity. CONCLUSION: These findings suggest that frozen section is superior to imprint cytology for the intra-operative determination of sentinel lymph node metastasis in stage I breast cancer patients.

[Tutorial session using cross sections of upper and lower limbs in human gross anatomy course].

We performed tutorial education in gross anatomy using thick serial cross sections (3-4 cm) of one of the upper or lower limbs of a cadaver donated for use in the macroscopic dissection course. Group learning (four people) proceeded with the extraction of the point in question from an arbitrary section. Consequently students obtained a deeper understanding of the cross sectional structure of an upper or lower limb and further deepened their understanding of the three-dimensional structure of limbs. Each group collected clinical images of the part corresponding to the selected section to present, thus bringing together the relationship between the anatomical knowledge studied from the specimen and the related disease. A questionnaire survey after the practicum suggested that the practice of using serial cross sections and the presentation of relevant images using Microsoft PowerPoint were effective means of the study. Useful points on the student's understanding were collected with respect to the following three opinions: Fresh aspects, Grasp of the position, and Three-dimensional views. Moreover, the dissection program in gross anatomy combined with thick cross sections was thought to be helpful in that not only was observing the cross structure but also to dissect it if necessary, with the students obtaining a deeper understanding of the structure as a result. In our anatomy practice thereafter, the practicum was done with awareness of the issues faced by the students in mind. It was concluded that the practicum that uses the cross sections is an effective means in gross anatomy education.

[Student evaluation of faculty teaching in molecular anatomy course at Nippon Medical School: results of a questionnaire survey].

For the purpose of improving education, the lecture and practices employed in the Molecular Anatomy Course were evaluated by students. The survey was performed with personal computer connected to a local area network and the results were readily exhibited on our website the following day. The total number of answers was 528 and the reply percentage was 31.2%. The average score (from 1: very bad to 5: very good) was 3.9, with a range of 3.2 to 4.8. Faculty teaching got better grades in the latter half of the period compared to those in the first half, particularly on "preparation" and "understanding". The correlation analysis showed a strong relationship between the understanding of the lecture and the orientation of practice. These findings suggest that constant evaluation by students during the whole period of the instruction is useful for improving the quality of education of our Anatomy Course.

Immune activation during the implantation phase causes preeclampsia-like symptoms via the CD40-CD40 ligand pathway in pregnant mice.

The CD40 ligand (CD40L) is expressed by T cells and has a critical role in immune system regulation. Interventions targeting CD40L interactions following embryo implantation represent an approach to preventing preeclampsia (PE). To better understand the role of CD40L in PE, we developed a PE mouse model in which we examined how CD40L-induced immune activation affects embryo implantation. Blastocysts were incubated with CD40L-expressing adenovirus and then were transferred into the uterine horns of pseudopregnant ICR mice. Histology, biochemistry and flow cytometry experiments were performed to examine the characteristics of the mouse model. In early pregnancy, decidualization and spiral artery remodeling were reduced in CD40L-transfected mice (CD40L mice) compared with control mice. Hematoxylin-eosin (HE) staining revealed hemorrhaging and excess fibrin deposition at the labyrinth layer-junctional zone interface of the placenta, and PAS staining demonstrated prominent focal and segmental sclerosis with collapsed glomerular capillaries in the kidneys of the CD40L mice. Flow cytometry data showed that interferon-γ production derived from CD4(+) T cells was elevated in the splenic cells of CD40L mice. Blood pressure (measured by the tail-cuff method) and urine albumin concentrations were significantly increased in CD40L mice compared with control mice. Furthermore, the plasma concentrations of soluble Flt-1 and soluble endoglin were increased in CD40L mice, as occurs in human patients with PE. Thus, CD40L-induced T-helper cell type 1 differentiation during embryo implantation may have a critical role in the pathogenesis of a PE-like presentation in a novel mouse model of PE.