Conectar
by Souma Suzuki, Susumu Suzuki, Yuri Sato-Nagaoka, Chisaki Ito, Shinichiro Takahashi
Differentiation therapy using all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is well established. However, because the narrow application and tolerance development of ATRA need to be improved, we searched for another efficient myeloid differentiation inducer. Kinase activation is involved in leukemia biology and differentiation block. To identify novel myeloid differentiation inducers, we used a Kinase Inhibitor Screening Library. Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. We focused on TCN because it was reported to be well tolerated by patients with advanced hematological malignancies. Nuclear/cytoplasmic (N/C) ratio was significantly decreased, and myelomonocytic markers (CD11b and CD11c) were potently induced by TCN in both NB4 and acute myeloid leukemia (AML) M2 derived HL-60 cells. Western blot analysis using NB4 cells demonstrated that TCN promoted ERK1/2 phosphorylation, whereas p38 MAPK phosphorylation was not affected, suggesting that activation of the ERK pathway is involved in TCN-induced differentiation. We further examined that whether ATRA may affect phosphorylation of ERK and p38, and found that there was no obvious effect, suggesting that ATRA induced differentiation is different from TCN effect. To reveal the molecular mechanisms involved in TCN-induced differentiation, we performed microarray analysis. Pathway analysis using DAVID software indicated that “hematopoietic cell lineage” and “cytokine-cytokine receptor interaction” pathways were enriched with high significance. Real-time PCR analysis demonstrated that components of these pathways including IL1β, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future.Unintended teenage pregnancies have become a global public health challenge, particularly in sub-Saharan Africa. There is a notably high prevalence of unintended pregnancies among unmarried teenagers in Uganda. This study will develop an intervention programme using mobile money shops (vendors) as a platform to deliver sexual and reproductive health and rights (SRHR) services to teenagers and assess its effectiveness and scalability in Uganda.
This hybrid study comprises two integral components: an intervention study to assess the effectiveness of vendor-mediated intervention and implementation research to evaluate the implementation process. 30 vendors will be recruited for both intervention and control arms in 2 municipalities in Eastern Uganda, which have a high unintended pregnancy prevalence rate among unmarried teens aged 15–19 years. A preintervention and postintervention repeated survey involving 600 participants for each arm will be conducted over 4 months. The primary outcome is the rate of condom users among teenage vendor users. The secondary outcomes include the rate of preference for receiving SRHR services at vendors and knowledge regarding SRHR. A difference-in-differences analysis will be used to determine the effectiveness of the intervention. The Bowen model will be employed to evaluate the implementation design.
Ethical approval was obtained from the Ethics Review Committee of Uganda Christen University and JICA Ogata Sadako Research Institute for Peace and Development in Japan. The findings will be widely disseminated. This study was registered with the University Hospital Medical Information Network in Japan (UMIN000053332) on 12 January 2024.
UMIN000053332.
Although guidelines recommend antiviral therapy for outpatients with COVID-19 who are at high risk of progressing to severe conditions, such as older adults, many patients do not receive appropriate treatment. Little is known, however, about the physician factors associated with the prescription of guideline-recommended antiviral therapy for patients with COVID-19.
A cross-sectional study.
Data including outpatient visits in primary care clinics in Japan from April to August 2023.
We analysed 30 953 outpatients aged ≥65 years treated with COVID-19 (mean (SD) age, 75.0 (7.6) years; 17 652 women (57.0%)) in 1394 primary care clinics.
The primary outcome was the prescription of guideline-recommended antivirals (ie, nirmatrelvir–ritonavir or molnupiravir), adjusted for patient characteristics, months of visits and regions.
Antiviral prescriptions were concentrated among a small proportion of physicians; for example, the top 10% of physicians that had the largest number of nirmatrelvir–ritonavir prescriptions accounted for 92.4% of all nirmatrelvir–ritonavir prescriptions. After adjusting for potential confounders, physicians with higher patient volumes were more likely to prescribe guideline-recommended antivirals to their patients (adjusted OR (aOR) for high vs low volume, 1.76; 95% CI 1.31 to 2.38; adjusted p
Our findings suggest that provider-level factors, such as the clinical experience of treating the patients with COVID-19, play an important role in the appropriate prescription of antiviral medications for COVID-19 in the primary care setting.
To evaluate the association between urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) level—a marker of oxidative stress—and the incidence of preterm births (PTBs).
Prospective cohort study.
The Japan Environment and Children’s Study (JECS).
Data from 92 715 women with singleton pregnancies at and after 22 weeks of gestation who were enrolled in the JECS, a nationwide birth cohort study, between 2011 and 2014 were analysed. U8-OHdG levels were assessed once in the second/third trimester using liquid chromatography–tandem mass spectrometry. Participants were categorised into the following three or five groups: low (
Adjusted OR (aOR) for PTB before 37 and 34 weeks of gestation were calculated using a multivariable logistic regression model while adjusting for confounding factors; the moderate or lowest U8-OHdG group was used as the reference, respectively.
The aORs for PTB before 37 weeks of gestation in the high U8-OHdG group were 1.13 (95% CI 1.05 to 1.22) and 1.13 (95% CI 1.04 to 1.23) after stratification. The aOR for PTB before 37 weeks in the fourth group was 0.90 (95% CI 0.81 to 0.99). After stratification, the aORs for PTB before 37 and 34 weeks in the fifth group were 1.15 (95% CI 1.03 to 1.29) and 1.46 (95% CI 1.08 to 1.97), respectively.
High U8-OHdG levels were associated with increased PTB incidence, especially in participants without representative causes for artificial PTB. Our results can help identify the mechanisms leading to PTB, considering the variable aetiologies of this condition; further validation is needed to clarify clinical impacts.
by Marco Tomasetti, Federica Monaco, Corrado Rubini, Marzia Rossato, Concetta De Quattro, Cristina Beltrami, Giacomo Sollini, Ernesto Pasquini, Monica Amati, Gaia Goteri, Lory Santarelli, Massimo Re
Sinonasal tumours are heterogeneous malignancies, presenting different histological features and clinical behaviour. Many studies emphasize the role of specific miRNA in the development and progression of cancer, and their expression profiles could be used as prognostic biomarkers to predict the survival. Recently, using the next-generation sequencing (NGS)-based miRNome analysis the miR-34/miR-449 cluster was identified as miRNA superfamily involved in the pathogenesis of sinonasal cancers (SNCs). In the present study, we established an Argonaute-2 (AGO2): mRNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miR-34/miR-449 in SNCs. Using this approach, we identified direct target genes (targetome), which were involved in regulation of RNA-DNA metabolic, transcript and epigenetic processes. In particular, the STK3, C9orf78 and STRN3 genes were the direct targets of both miR-34c and miR-449a, and their regulation are predictive of tumour progression. This study provides the first evidence that miR-34/miR-449 and their targets are deregulated in SNCs and could be proposed as valuable prognostic biomarkers.by Satomi Mezuki, Ryu Matsuo, Fumi Irie, Yuji Shono, Takahiro Kuwashiro, Hiroshi Sugimori, Yoshinobu Wakisaka, Tetsuro Ago, Masahiro Kamouchi, Takanari Kitazono, on behalf of the Fukuoka Stroke Registry Investigators
BackgroundThis study aimed to examine whether post-stroke early body temperature is associated with neurological damage in the acute phase and functional outcomes at three months.
MethodsWe included 7,177 patients with acute ischemic stroke within 24 h of onset. Axillary temperature was measured daily in the morning for seven days. Mean body temperature was grouped into five quintiles (Q1: 35.1‒36.5°C, Q2: 36.5‒36.7°C, Q3: 36.7‒36.8°C, Q4: 36.8‒37.1°C, and Q5: 37.1‒39.1°C). Clinical outcomes included neurological improvement during hospitalization and poor functional outcome (modified Rankin scale score, 3–6) at three months. A logistic regression analysis was performed to evaluate the association between body temperature and clinical outcomes.
ResultsThe patient’s mean (SD) age was 70.6 (12.3) years, and 35.7% of patients were women. Mean body temperature was significantly associated with less neurological improvement from Q2 (odds ratios [95% confidence interval], 0.77 [0.65–0.99] vs. Q1) to Q5 (0.33 [0.28–0.40], P for trend 37.0°C.
ConclusionsPost-stroke early high body temperature is independently associated with unfavorable outcomes following acute ischemic stroke.
by Chun-Ting Hsu, Wataru Sato, Sakiko Yoshikawa
A close relationship between emotional contagion and spontaneous facial mimicry has been theoretically proposed and is supported by empirical data. Facial expressions are essential in terms of both emotional and motor synchrony. Previous studies have demonstrated that trait emotional empathy enhanced spontaneous facial mimicry, but the relationship between autistic traits and spontaneous mimicry remained controversial. Moreover, previous studies presented faces that were static or videotaped, which may lack the “liveliness” of real-life social interactions. We addressed this limitation by using an image relay system to present live performances and pre-recorded videos of smiling or frowning dynamic facial expressions to 94 healthy female participants. We assessed their subjective experiential valence and arousal ratings to infer the amplitude of emotional contagion. We measured the electromyographic activities of the zygomaticus major and corrugator supercilii muscles to estimate spontaneous facial mimicry. Individual differences measures included trait emotional empathy (empathic concern) and the autism-spectrum quotient. We did not find that live performances enhanced the modulatory effect of trait differences on emotional contagion or spontaneous facial mimicry. However, we found that a high trait empathic concern was associated with stronger emotional contagion and corrugator mimicry. We found no two-way interaction between the autism spectrum quotient and emotional condition, suggesting that autistic traits did not modulate emotional contagion or spontaneous facial mimicry. Our findings imply that previous findings regarding the relationship between emotional empathy and emotional contagion/spontaneous facial mimicry using videos and photos could be generalized to real-life interactions.by Masahiro Suiko, Satoshi Mizukami, Kazuhiko Arima, Hiroki Nakashima, Takayuki Nishimura, Yoshihito Tomita, Yasuyo Abe, Natsumi Tanaka, Yuzo Honda, Michiko Kojima, Tetsuji Okawachi, Maiko Hasegawa, Youko Sou, Ritsu Tsujimoto, Mitsuo Kanagae, Makoto Osaki, Kiyoshi Aoyagi
BackgroundLow bone mass is an independent risk factor for osteoporotic fractures. We examined the association between physical performance and bone mass using quantitative ultrasound in community-dwelling postmenopausal Japanese women.
MethodsWe conducted a cross-sectional study on 524 community-dwelling postmenopausal Japanese women who were not being administered osteoporosis medications. Physical performance was assessed on the basis of grip strength, chair stand time, and functional reach. The stiffness index was measured as a quantitative ultrasound parameter for heel bone mass.
ResultsPhysical performance, assessed by grip strength, chair stand time, and functional reach, and the stiffness index significantly decreased with age (both p Conclusions
Physical performance was significantly associated with heel bone mass in community-dwelling postmenopausal Japanese women.
by Shohei Kitahata, Kiyoko Gocho, Naohiro Motozawa, Satoshi Yokota, Midori Yamamoto, Akiko Maeda, Yasuhiko Hirami, Yasuo Kurimoto, Kazuaki Kadonosono, Masayo Takahashi
ObjectiveCystoid macular edema (CME) in retinitis pigmentosa (RP) is an important complication causing visual dysfunction. We investigated the effect of CME on photoreceptors in RP patients with previous or current CME, using an adaptive optics (AO) fundus camera.
MethodsWe retrospectively observed the CME and ellipsoid zone (EZ) length (average of horizontal and vertical sections) by optical coherence tomography. The density and regularity of the arrangement of photoreceptor cells (Voronoi analysis) were examined at four points around 1.5° from superior to inferior and temporal to nasal. We also performed a multivariate analysis using CME duration, central macular thickness and transversal length of CME.
ResultsWe evaluated 18 patients with previous or current CME (18 eyes; age, 48.7 ± 15.6 years) and 24 patients without previous or current CME (24 eyes; age, 46.0 ± 14.5 years). There were no significant differences in age, logMAR visual acuity, or EZ length. In groups with and without CME, cell density was 11967 ± 3148 and 16239 ± 2935 cells/mm2, and sequence regularity was 85.5 ± 3.4% and 88.5 ± 2.8%, respectively; both parameters were significantly different. The correlation between photoreceptor density and age was more negative in group with CME. The CME group tended toward greater reductions in duration of CME.
ConclusionComplications of CME in RP patients may lead to a decrease in photoreceptor density and regularity. Additionally, a longer duration of CME may result in a greater reduction in photoreceptor density.
by Hiroki Iwata, Takasumi Katoh, Sang Kien Truong, Tsunehisa Sato, Shingo Kawashima, Soichiro Mimuro, Yoshiki Nakajima
Cardiopulmonary bypass (CPB) causes systemic inflammation and endothelial glycocalyx damage. Hydrogen has anti-oxidant and anti-inflammatory properties; therefore, we hypothesized that hydrogen would alleviate endothelial glycocalyx damage caused by CPB. Twenty-eight male Sprague–Dawley rats were randomly divided into four groups (n = 7 per group), as follows: sham, control, 2% hydrogen, and 4% hydrogen. The rats were subjected to 90 minutes of partial CPB followed by 120 minutes of observation. In the hydrogen groups, hydrogen was administered via the ventilator and artificial lung during CPB, and via the ventilator for 60 minutes after CPB. After observation, blood collection, lung extraction, and perfusion fixation were performed, and the heart, lung, and brain endothelial glycocalyx thickness was measured by electron microscopy. The serum syndecan-1 concentration, a glycocalyx component, in the 4% hydrogen group (5.7 ± 4.4 pg/mL) was lower than in the control (19.5 ± 6.6 pg/mL) and 2% hydrogen (19.8 ± 5.0 pg/mL) groups (P P = 0.999). The endothelial glycocalyces of the heart and lung in the 4% hydrogen group were thicker than in the control group. The 4% hydrogen group had lower inflammatory cytokine concentrations (interleukin-1β and tumor necrosis factor-α) in serum and lung tissue, as well as a lower serum malondialdehyde concentration, than the control group. The 2% hydrogen group showed no significant difference in the serum syndecan-1 concentration compared with the control group. However, non-significant decreases in serum and lung tissue inflammatory cytokine concentrations, as well as in serum malondialdehyde concentration, were observed. Administration of 4% hydrogen via artificial and autologous lungs attenuated endothelial glycocalyx damage caused by partial CPB in rats, which might be mediated by the anti-inflammatory and anti-oxidant properties of hydrogen.To identify insights for supporting people at risk of suicide in the community based on primary healthcare workers' experiences.
Qualitative descriptive design.
Semi-structured interviews were conducted with fifteen primary healthcare workers employed by Japanese municipalities between August and October 2019. The data were subjected to qualitative descriptive analysis.
The analysis revealed eleven subthemes, clustered under the following three themes: (1) fostering ‘opportunities for discovery’ for people at risk of suicide by encompassing strategies such as increasing access to services and promoting a holistic understanding of the life cycle; (2) fostering ‘meaningful connections’ by searching for channels to reach the heart and taking approaches from different objectives; and (3) engaging in ‘risk management’, by understanding and coping with real-life struggles and implementing timely crisis intervention.
Not only direct care targeting suicide prevention but also holistic care that includes atypical perspectives such as ‘approaches from different objectives’ may provide important insights for supporting people with suicide risk.
Beyond the limitations of existing suicide risk screening methods, this study highlights the importance of a holistic approach that sees people at risk of suicide in the context of their daily lives and aims to alleviate the difficulties in their lives that have brought them to the point of considering suicide.
By describing support focused on the difficulties that people at risk of suicide face in their daily lives, this study identified insights for supporting people at risk of suicide in communities where screening and intervention are difficult. These findings will contribute to the relief of people at risk of suicide by stimulating suicide prevention measures in primary healthcare settings.
This study complied with the COREQ guidelines.
No patient or public contribution.
Objetivo: conocer la producción científica brasileña sobre el racismo
en la profesión de enfermería. Método: se realizó una revisión integradora
de literatura en las siguientes bases de datos: Scientific Electronic
Library Online, Literatura Latinoamericana y del Caribe en Ciencias de la
Salud, Portal de Revistas de la Comisión para el Perfeccionamiento del
Personal de Educación Superior y Google Scholar. Se utilizaron los siguientes
descriptores: racismo, enfermería, enfermeros y enfermeros, con
los booleanos AND y OR, y sin demarcación temporal. Resultados: se seleccionaron
18 artículos en portugués, publicados entre 1997 y 2018. El
racismo aparece en la profesión desde sus inicios, en su formación y en el
mercado profesional, siendo abordado a través de una perspectiva histórica,
capaz de señalar a la mujer negra como su principal objetivo. En los
últimos años ha habido una mayor producción académica sobre el tema, que se ha convertido en una forma de enfrentar el racismo. Consideraciones finales: la producción académica sobre el racismo en la profesión de enfermería es escasa. Hay un silencio sobre el tema que dificulta el debate, así como las formas de enfrentar este tipo de violencia en la profesión.
Urge la apropiación teórico-conceptual del tema por estudiantes y profesionales de enfermería para que ocupe un lugar relevante en la literatura científica.
by Nana Takahashi, Kota Sato, Naoki Kiyota, Mai Yamazaki, Eriko Kunikane, Toru Nakazawa
PurposeThe purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits.
MethodsA crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day’s first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point.
ResultsThere were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P Conclusion
BBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF.
Since May 2019, comprehensive genomic profiling (CGP) has been covered by Japan’s health insurance system for patients with solid tumours that have progressed on standard chemotherapy, rare tumours or tumours of unknown primary origin. Although CGP has the potential to identify actionable mutations that can guide the selection of genomically matched therapies for patients with advanced cancer and limited treatment options, less than 10% of patients benefit from CGP testing, which may have a negative impact on patients’ mental status. The aim of this study is to investigate the prevalence of psychological distress and associated factors among patients with advanced cancer who are undergoing CGP testing across Japan.
This multicentre, prospective cohort study will enrol a total of 700 patients with advanced cancer undergoing CGP testing. Participants will be asked to complete questionnaires at three timepoints: at the time of consenting to CGP testing (T1), at the time of receiving the CGP results (T2; 2–3 months after T1) and 4–5 months after T2 (T3). Primary outcome is the prevalence of depression as measured by the Patient Health Questionnaire-9 at the three timepoints. Secondary outcomes are the prevalence of anxiety and Quality of Life Score. Associated factors with psychological distress will also be examined, including knowledge about CGP, attitudes, values and preferences towards CGP, satisfaction with oncologists’ communication and patient characteristics as well as medical information including CGP test results and genomically matched therapies if provided. The prevalence of depression and anxiety will be estimated using the unadjusted raw rates observed in the total sample. Longitudinal changes in measures will be explored by calculating differences between the timepoints. Multivariate associations between variables will be examined using multiple or logistic regression analysis depending on the outcomes to adjust for confounders and to identify outcome predictors.
This study was approved by the Institutional Review Board of the National Cancer Center Japan on 5 January 2023 (ID: 2022-228). Study findings will be disseminated through peer-reviewed journals and conference presentations.
The study is currently recruiting participants and the enrolment period will end on 31 March 2025, with an expected follow-up date of 31 March 2026.
UMIN000049964.
by Noriko Kojimahara, Yasuto Sato, Yoko Sato, Fumihiro Kojimahara, Katsuyuki Takahashi, Eiji Nakatani
BackgroundLong-term cancer prognosis after initial surgical procedures is an unlikely endpoint for clinical trials. Medical claim databases may aid in addressing this issue regardless of limited information on disease and patient background. However, the long-term prognosis (especially regarding long-term care needs) following surgical procedures remains unclear. This study aimed to assess whether long-term outcomes, such as the exacerbation of long-term care needs and mortality, differ with surgical methods.
MethodsUsing a longitudinal study with linkage between medical claim and long-term care database, patients with primary colorectal cancer who underwent initial colonoscopies were identified through anonymized data in Japan (Shizuoka Kokuho Database, 2012–2018). Odds ratios (ORs) for long-term outcomes (long-term care needs and all-cause mortality during a 6.5-year follow-up period) were analyzed using logistic regression to compare laparoscopy and endoscopic surgery to laparotomy.
ResultsOverall, 3,744 primary colorectal cancer cases (822 laparotomies, 705 laparoscopies, and 2,217 endoscopic surgeries) were included. Compared to the laparotomy group, the crude OR for exacerbation of long-term care needs in the laparoscopic surgery group was 0.376 (95% confidence interval, 0.227, 0.624), while the OR for all-cause mortality was 0.22 (0.329, 0.532).
ConclusionThis is the first study to analyze long-term prognosis after surgery for patients with colorectal cancer to combine medical and long-term needs data. As the national health insurance claim database rarely includes information on cancer stage and comorbidities, better prognosis on endoscopic surgery may need careful interpretation. Therefore, laparoscopy has superior outcomes in terms of long-term care needs and mortality compared to those of laparotomy.
Finding out whether there are differences in the levels of stress and burnout between workers providing care to dependent adults and those caring for independent older adults would provide comparative information about two different models of care. During the COVID-19 pandemic, workers caring for older adults were subjected to maladaptive situations that produced stress and burnout.
A cross-sectional survey design using the STROBE checklist.
A total of 900 nursing home and égidas workers were assessed for stress and burnout. Data were collected online from October 2020 to February 2021, when Puerto Rico was experiencing the peak of the third wave of COVID-19. MANOVAs were performed to study the interactions between the workplace and having had COVID, the workplace and the size of institution and the workplace and position held.
October 2020 to February 2021.
All interactions were significant. Nursing homes showed higher levels of stress and burnout when workers had undergone COVID, when the size of the institution was larger and for technical staff other services; in égidas, having undergone COVID did not influence stress or burnout, which increased when the institution was smaller and for executive staff.
This study showed that the effects of the COVID-19 pandemic affected nursing home workers more significantly than those working in other types of residential models with independent older adults.
Applying preventive interventions aimed at reducing stress and burnout would facilitate the adaptation of workers caring for older adults and help to improve the quality of care.
This study analysed the impact of COVID-19 on the stress and burnout of workers providing services to older adults. Nursing home workers who have had COVID-19 have higher stress and burnout. The size of the institution has a different effect depending on whether older adults are dependent or independent. Workers in institutions dedicated to the care of the older adults.
This study has adhered to the relevant EQUATOR guidelines: STROBE.
During the different waves of the COVID-19 pandemic, it was difficult to establish direct contact with workers providing care to older adults; this reason made it necessary to apply online systems to obtain information. The workers appreciated the fact that the implications for stress and burnout of the situation experienced during this difficult process were investigated.
FreshRSS 