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Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation

by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Development of a prognostic risk score to predict early mortality in incident elderly Japanese hemodialysis patients

by Hirokazu Okada, Atsushi Ono, Koji Tomori, Tsutomu Inoue, Norio Hanafusa, Ken Sakai, Ichiei Narita, Toshiki Moriyama, Yoshitaka Isaka, Kei Fukami, Seiji Itano, Eiichiro Kanda, Naoki Kashihara

Background

Information of short-term prognosis after hemodialysis (HD) introduction is important for elderly patients with chronic kidney disease (CKD) and their families choosing a modality of renal replacement therapy. Therefore, we developed a risk score to predict early mortality in incident elderly Japanese hemodialysis patients.

Materials and methods

We analyzed data of incident elderly HD patients from a nationwide cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) to develop a prognostic risk score. Candidate risk factors for early death within 1 year was evaluated using multivariate logistic regression analysis. The risk score was developed by summing up points derived from parameter estimate values of independent risk factors. The association between risk score and early death was tested using Cox proportional hazards models. This risk score was validated twice by using an internal validation cohort derived from the JRDR and an external validation cohort collected for this study.

Results

Using the development cohort (n = 2,000), nine risk factors were retained in the risk score: older age (>85), yes = 2, no = 0; sex, male = 2, female = 0; lower body mass index (2.0 mg/dL), yes = 2, no = 0. In the internal and external validation cohorts (n = 739, 140, respectively), the medium- and high-risk groups (total score, 6 to 10 and 11 or more, respectively) showed significantly higher risk of early death than the low-risk group (total score, 0 to 5) (p Conclusion

We developed a prognostic risk score predicting early death within 1 year in incident elderly Japanese HD patients, which may help detect elderly patients with a high-risk of early death after HD introduction.

Rituximab-combined anthracycline-free chemotherapy in newly diagnosed paediatric and adolescent patients with non-high-risk aggressive mature B cell lymphoma: protocol for a single-arm, open-label, multicentre, phase II study (the Japan Childrens Cancer G

Por: Sekimizu · M. · Fukano · R. · Koga · Y. · Mitsui · T. · Fujita · N. · Mori · T. · Hori · D. · Tanaka · M. · Ohki · K. · Iwafuchi · H. · Nakazawa · A. · Mori · T. · Kobayashi · R. · Hashimoto · H. · M. Saito · A. · Kamei · M. · on behalf of Lymphoma Committee of Japan Childrens Cancer G
Introduction

Children and adolescents with mature B cell non-Hodgkin lymphoma (B-NHL) are treated with short-intensive chemotherapy. The burden of short-term and long-term toxicity is highly relative to its high cure rate in good-risk patients. Although the addition of rituximab to standard lymphome Malin B (LMB) chemotherapy markedly prolongs event-free survival and overall survival in high-risk patients, the benefit of rituximab in good-risk patients remains to be elucidated. This clinical trial will examine whether the addition of rituximab eliminates anthracyclines in good-risk patients without compromising treatment outcomes.

Methods and analysis

We will perform a single-arm, open-label, multicentre phase II study. Low-risk (stage I – completely resected, stage II abdominal) and intermediate-risk (stages I and II – incompletely resected; stage II – resected, other than abdominal; stage III with LDH x upper limit of normal) patients with newly diagnosed B-NHL are eligible. Low-risk patients receive two courses of R-COM1P (rituximab, cyclophosphamide, vincristine, methotrexate, prednisolone and intrathecal methotrexate with hydrocortisone), and intermediate-risk patients receive COP (cyclophosphamide, vincristine, prednisolone and intrathecal methotrexate with hydrocortisone) followed by two courses each of R-COM3P and R-CYM (rituximab, cytarabine, methotrexate and intrathecal methotrexate with hydrocortisone). The primary endpoint is a 3-year event-free survival rate in paediatric patients (

Ethics and dissemination

This research was approved by the Certified Review Board at NHO Nagoya Medical Center (Nagoya, Japan) on 21 September 2021. Written informed consent is obtained from all patients and/or their guardians. The results of this study will be disseminated through peer-reviewed publications and conference presentations.

Study registration

Japan Registry of Clinical Trials, jRCTs041210104.

Urinary 8-hydroxy-2'-deoxyguanosine levels and preterm births: a prospective cohort study from the Japan Environment and Childrens Study

Por: Murata · T. · Kyozuka · H. · Fukuda · T. · Imaizumi · K. · Isogami · H. · Kanno · A. · Yasuda · S. · Yamaguchi · A. · Sato · A. · Ogata · Y. · Shinoki · K. · Hosoya · M. · Yasumura · S. · Hashimoto · K. · Nishigori · H. · Fujimori · K. · The Japan Environment and Childrens Study (JECS)
Objectives

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).

Design

Prospective cohort study.

Setting

The Japan Environment and Children’s Study (JECS).

Participants

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 (

Primary and secondary outcome measures

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.

Results

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.

Conclusions

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.

What works for whom and why? Treatment effects and their moderators among forcibly displaced people receiving psychological and psychosocial interventions: study protocol for an individual patient data meta-analysis

Por: Kurath · J. · Akhtar · A. · Karyotaki · E. · Sijbrandij · M. · Cuijpers · P. · Bryant · R. · Morina · N.
Introduction

Forcibly displaced people (FDP) have a high risk of developing mental disorders such as post-traumatic stress (PTS) disorder. Providing adequate mental healthcare for FDP is crucial but despite overall efficacy of many existing interventions, a large proportion of FDP does not benefit from treatment, highlighting the necessity of further investigating factors contributing to individual differences in treatment outcome. Yet, the few studies that have explored moderators of treatment effects are often insufficiently powered. Therefore, the present Individual Patient Data meta-analysis (IPD-MA) will investigate treatment effects and their moderators—variables related to beneficiaries, providers, intervention and study characteristics in relation to PTS outcomes.

Methods and analysis

A systematic literature search will be conducted from database inception in the databases PsycINFO, Cochrane, Embase, PTSDpubs and Web of Science. Only studies published in English, German, French, Spanish, Portuguese, and Dutch will be considered. Retrieved records will be screened for eligibility. Randomised controlled trials on adult FDP receiving psychological and psychosocial interventions aimed at alleviating symptoms such as PTS compared with a control condition without intervention will be included in this IPD-MA. Subsequently, authors of eligible studies will be contacted to request individual patient data (IPD). All datasets obtained will be synthesised into one large dataset which will be analysed using a one-stage approach by conducting mixed-effects linear regression models (ie, primary analysis). Additionally, aggregate data meta-analyes will be run using a two-stage approach by conducting multivariate regression models including all IPD (transformed) and available meta-data from study reports (ie, secondary analysis). PTS will serve as primary outcome measure, while mental health outcomes other than PTS, attendance, attrition, treatment non-response and adverse outcomes will be examined as secondary outcomes.

Ethics and dissemination

This IPD-MA does not require ethical approval. The results will be published in international peer-reviewed journals.

PROSPERO registration number

CRD42022299510.

Enhancing knowledge management in nursing through documentation

Journal of Advanced Nursing, Volume 80, Issue 3, Page 848-850, March 2024.

Cohort profile: rationale and design of the Resource Center for Health Science (RECHS) project - a study of health hazards and medical cost burden among the Japanese population

Por: Morishita · T. · Takemura · M. · Hayashi · M. · Saito · K. · Yamamoto · Y. · Tsurumi · H. · Matsunami · H.
Purpose

The increased global burden of non-communicable diseases and mental disorders is an urgent health challenge for countries around the entire world, especially those experiencing super-ageing societies, where over 21% of the population is age 65 years or older. Japan is the world’s most rapidly ageing society, and as a result, medical costs are also rising dramatically. With the aims of establishing a foundational framework for future research efforts, primarily focusing on the development of a personal health record (PHR) system, and creating a long-term repository for bioresources integrated with PHRs, this study investigated potential health risks and future healthcare burdens based on a longitudinal analysis of health records.

Participants

The Resource Center for Health Science (RECHS) project is a long-term, prospective biobank project, population and health check-up-based cohort that primarily investigates the associations between lifestyle and environmental factors and some surrogate markers of non-communicable diseases, such as diabetes, hypertension, cardiovascular disease and cancer. Starting in 2010, we initiated an annual cohort study among voluntary participants recruited from health check-up programmes and collected data from the following sources: a self-administered baseline questionnaire that included items on dietary habits and stress, a Brief Self-Administered Diet History Questionnaire, the Centre for Epidemiologic Studies Depression Scale and the General Health Questionnaire-28.

Findings to date

For this prospective cohort study, we planned to enrol approximately 10 000 participants. We collected and stored serum samples from all participants for future analyses. The study participants who still were able to participate in these health check-ups and their outcomes were then obtained from the measurements and questionnaire responses.

Future plans

Insights emerging from the RECHS study can provide researchers and public health policy administrators with evidence to aid in the prevention of non-communicable diseases and clarify the most malleable status to implement preventive measures.

Body temperature in the acute phase and clinical outcomes after acute ischemic stroke

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

Background

This 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.

Methods

We 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.

Results

The 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.

Conclusions

Post-stroke early high body temperature is independently associated with unfavorable outcomes following acute ischemic stroke.

Non-fibril form but not fibril form of human islet amyloid polypeptide 8–20 changes brain functions in mice

by Hinaho Suginoma, Ryuji Owada, Akiko Katano-Toki, Ayaka Mori, Jun Fujioka, Kazuhiro Nakamura

Whether fibril formation increases or decreases cytotoxicity remains unclear. Aggregation of human islet amyloid polypeptide (hIAPP), a pivotal regulator of glucose homeostasis, impairs the function and viability of pancreatic β cells. Evidence suggests that low-order oligomers of hIAPP are more toxic to β cells than fibril. However, it remains unclear whether non-fibril form of hIAPP specifically alters brain functions. This study produced fibril and non-fibril forms from a single hIAPP 8–20 peptide. The non-fibril form-injected mice showed changes in spontaneous motor activities, preference for location in the open field and social behavior. In contrast, the fibril-injected mice showed no changes in these behavioral tests. In line with the behavioral changes, the non-fibril form led to impaired neurite outgrowth of cultured neuron-like cells and the loss of neurons in the mouse hippocampus. These findings suggest that non-fibril form but not fibril form of hIAPP changes brain functions.

Detection of CTLA-4 level and humeral immune response after the second dose of COVID-19 vaccine in certain Iraqi provinces participants

by Laith A. I. K. Al-Kaif, Hussain Al-Ameri, Wael Rasheed Obaead Alfatlawi, Ammar Eesa Mahdi, Younis A. K. Al-Khafaji, Mohammad Abd-Kadhum Al-Saadi, Alaa H. Al-Charrakh, Raheem T. Al-Mammori, Mohammed Ahmed Akkaif

Background

Evaluating immune responses following COVID-19 vaccination is paramount to understanding vaccine effectiveness and optimizing public health interventions. This study seeks to elucidate individuals’ immune status after administering a second dose of diverse COVID-19 vaccines. By analyzing immune responses through serological markers, we aim to contribute valuable insights into the uniformity of vaccine performance.

Methods

A total of 80 participants were enrolled in this study, with demographic and COVID-19 infection-related data collected for categorization. Serum samples were acquired within a specified timeframe, and SARS-CoV-2 IgM/IgG rapid tests were conducted. Moreover, CTLA-4 levels were measured through ELISA assays, allowing us to assess the immune responses comprehensively. The participants were divided into eight groups based on various factors, facilitating a multifaceted analysis.

Results

The outcomes of our investigation demonstrated consistent immune responses across the diverse types of COVID-19 vaccines administered in Iraq. Statistical analysis revealed no significant distinctions among the vaccine categories. In contrast, significant differences were observed in CTLA-4 among the control group (non-infected/non-vaccinated, infected/non-vaccinated) and infected/Pfizer, non-infected/Pfizer, and infected/Sinopharm, non-infected/sinopharm (P = 0.001, Conclusions

In conclusion, our study’s results underscore the lack of discriminatory variations between different COVID-19 vaccine types utilized in Iraq. The uniform immune responses observed signify the equitable efficacy and performance of these vaccines. Despite minor quantitative discrepancies, these variations do not hold statistical significance, reaffirming the notion that the various vaccines serve a similar purpose in conferring protection against COVID-19.

Differences in health literacy related to gestational weight gain and childrens birth weight according to maternal nativity status in the Japan Environment and Childrens Study (JECS): a longitudinal cohort study

Por: Kigawa · M. · Tsuchida · A. · Matsumura · K. · Ito · M. · Tanaka · T. · Hamazaki · K. · Adachi · Y. · Inadera · H. · The Japan Environment and Childrens Study (JECS) Group · Kamijima · Yamazaki · Ohya · Kishi · Yaegashi · Hashimoto · Mori · Ito · Yamagata · Nakayama · Sobue · Shima
Objectives

We examined literacy related to healthy gestational weight gain (GWG) in immigrant and native Japanese mothers and determined whether it is associated with children’s birth weight.

Design

Longitudinal cohort study.

Setting

As the baseline survey in the Japan Environment and Children’s Study (JECS), mothers completed self-administered questionnaires distributed by hand during pregnancy. The self-administered questionnaires used in this study were distributed by mail 6 months after delivery. Children’s birth weight, actual GWG and any complications during delivery were recorded by obstetricians collaborating with JECS.

Participants

Of 97 452 mothers who consented to participate in the JECS during pregnancy between January 2011 and March 2014, 67 953 were included in this study after exclusions for multiple births, multiple instances of consent by the same pregnant woman, miscarriages/stillbirths or withdrawal from the study within 3 years after participating. In total, 324 immigrant mothers and 963 native Japanese mothers were selected by propensity score matching for analysis.

Primary and secondary outcome measures

Data were collected on maternal literacy related to healthy GWG at the baseline survey, and data on actual GWG and children’s birth weight were collected by obstetricians. The associations of knowledge about healthy GWG and mothers’ actual GWG with maternal nativity status were examined using a 2 or Student’s t-test.

Results

More native Japanese mothers than immigrant mothers knew the appropriate GWG and reason the for needing to know this. Actual GWG was significantly higher among the immigrant mothers, but was within the recommended range. The low birthweight (LBW) incidence was significantly higher among the native mothers.

Conclusions

Immigrant mothers to Japan had less knowledge about appropriate GWG, but their actual GWG was appropriate and they delivered fewer LBW infants than native Japanese mothers. These findings may indicate the presence of other protective factors for pregnancy or delivery among immigrant mothers.

Suicide trends in Denmark—An ecological study exploring suicide methods from 1995 to 2019

by Agnieszka Konieczna, Christina Petrea Larsen, Sarah Grube Jakobsen, Taro Okuda, Karin Moriyama, Winibaldus Stefanus Mere, Erik Christiansen

Suicide is a major public health problem and complex phenomenon, affecting many people around the world. However, the incidence of suicide varies by sex and age, which includes differences in the means used. Therefore, to implement effective preventative interventions, it is important to study these differences to design effective, preventative interventions. This study investigates the trends in suicide rates in Denmark from 1995 to 2019 by analysing changes based on sex, age, and the means used for suicide. Data on all suicide deaths in the study period were extracted from the Danish Register of Causes of Death, and data on the background population were obtained from Statistics Denmark. We used negative binomial regression models to analyse the data, and the obtained estimates as a logarithm of the rate ratios allowed us to compare the results across groups and years. An overall decline in Danish suicide rates was observed during the study period, with the exception of young females aged 15–29 years. The demographic composition did not change significantly, and suicide rates are still highest for males and the elderly aged 60+. Hanging, self-poisoning and firearms remain the most prevalent means of suicide. Suicide prevention initiatives are required, especially interventions targeting males and the elderly. Restricting access to the means of suicide for these groups with high fatality rates may help reduce the overall suicide rate. Moreover, more research is needed to understand the factors that lead to suicide and affect the choice of means, which should also include studying the effects of different suicide prevention strategies on males and females from different age groups.

Persistence of gut dysbiosis in individuals with anorexia nervosa

by Yukiko Morisaki, Noriyuki Miyata, Megumi Nakashima, Tomokazu Hata, Shu Takakura, Kazufumi Yoshihara, Takafumi Suematsu, Koji Nomoto, Kouji Miyazaki, Hirokazu Tsuji, Nobuyuki Sudo

Recent evidence suggests a crucial role of the gut microbiota in the pathogenesis of anorexia nervosa (AN). In this study, we carried out a series of multiple analyses of the gut microbiota of hospitalized individuals with AN over three months using 16S or 23S rRNA-targeted reverse transcription–quantitative polymerase chain reaction (PCR) technology (YIF-SCAN®), which is highly sensitive and enables the precise quantification of viable microorganisms. Despite the weight gain and improvements in psychological features observed during treatment, individuals with AN exhibited persistent gut microbial dysbiosis over the three-month duration. Principal component analysis further underscored the distinct microbial profile of individuals with AN, compared with that of age-matched healthy women at all time points. Regarding the kinetics of bacterial detection, the detection rate of Lactiplantibacillus spp. significantly increased after inpatient treatment. Additionally, the elevation in the Bifidobacterium counts during inpatient treatment was significantly correlated with the subsequent body weight gain after one year. Collectively, these findings suggest that gut dysbiosis in individuals with AN may not be easily restored solely through weight gain, highlighting the potential of therapeutic interventions targeting microbiota via dietary modifications or live biotherapeutics.

A longitudinal investigation of structural empowerment profiles among healthcare employees

Abstract

Purpose

Research on structural empowerment has typically adopted a variable-centered perspective, which is not ideal to study the combined effects of structural empowerment components. This person-centered investigation aims to enhance our knowledge about the configurations, or profiles, of healthcare employees' perceptions of the structural empowerment dimensions present in their workplace (opportunity, information, support, and resources). Furthermore, this study considers the replicability and stability of these profiles over a period of 2 years, and their outcomes (perceived quality of care, and positive and negative affect).

Design

Participants completed the same self-reported questionnaires twice, 2 years apart.

Methods

A sample of 633 healthcare employees (including a majority of nurses and nursing assistants) participated. Latent transition analyses were performed.

Results

Five profiles were identified: Low Empowerment, High Information, Normative, Moderately High Empowerment, and High Empowerment. Membership into the Normative and Moderately High Empowerment profiles demonstrated a high level of stability over time (79.1% to 83.2%). Membership in the other profiles was either moderately stable (43.5% for the High Empowerment profile) or relatively unstable (19.7% to 20.4% for the Low Empowerment and High Information profiles) over time. More desirable outcomes (i.e., higher positive affect and quality of care, and lower negative affect) were observed in the High Empowerment profile.

Conclusions

These results highlight the benefits of high structural empowerment, in line with prior studies suggesting that structural empowerment can act as a strong organizational resource capable of enhancing the functioning of healthcare professionals. These findings additionally demonstrate that profiles characterized by the highest or lowest levels of structural empowerment were less stable over time than those characterized by more moderate levels.

Clinical Relevance

From an intervention perspective, organizations and managers should pay special attention to employees perceiving low levels of structural empowerment, as they experience the worst outcomes. In addition, they should try to maintain high levels of structural empowerment within the High Empowerment profile, as this profile is associated with the most desirable consequences. Such attention should be fruitful, considering the instability of the High Empowerment and Low Empowerment profiles over time.

Registration

NCT04010773 on ClinicalTrials.gov (4 July, 2019).

La configuración sociocultural de la enfermedad desde el lente de una comunidad rural en Colombia

El propósito del estudio fue comprender las configuraciones socioculturales sobre las enfermedades construidas por un grupo de campesinos en el Departamento de Córdoba, Colombia, mediante un diseño micro etnográfico y la aplicación de entrevistas semiestructuradas, conversaciones y observaciones a 20 miembros de la comunidad, entre octubre de 2020 y marzo de 2021. Las entrevistas fueron transcritas, organizadas en matrices y procesadas para su posterior organización, categorización y análisis con apoyo de la técnica de Bardin. Se develan dos construcciones para concebir la enfermedad: estar enfermo es no poder trabajar y estar enfermo es intranquilidad y angustia; ambas configuraciones se construyen a partir del vínculo con las oportunidades para trabajar y realizar acciones de la vida cotidiana, pero están permeadas por el déficit en la prestación del servicio de salud y las dificultades para acceder a este. Se concluye que la configuración sociocultural de las enfermedades supera la visión de desequilibrio físico del individuo al enunciarse en el ámbito de las prácticas cotidianas, los modos de vivir y las redes de solidaridad tejidas por los campesinos como estrategia de resistencia ante el olvido estatal y la ineficacia de los abordajes del sector salud en zonas rurales colombianas.

Study protocol for a prospective, multicentre, phase II trial on endoscopic treatment using two fully covered self-expandable metallic stents for benign strictures after hepaticojejunostomy

Por: Kawasaki · Y. · Hijioka · S. · Nagashio · Y. · Ohba · A. · Maruki · Y. · Takeshita · K. · Takasaki · T. · Yagi · S. · Agarie · D. · Hagiwara · Y. · Hara · H. · Okamoto · K. · Yamashige · D. · Fukuda · S. · Kuwada · M. · Kondo · S. · Morizane · C. · Ueno · H. · Okusaka · T.
Introduction

The current endoscopic treatment for postoperative benign hepaticojejunostomy anastomotic stricture (HJAS) has a high technical success rate and is highly effective in the short term. However, long-term results have shown a high rate of stenosis recurrence, which indicates an insufficient response to treatment. Three prospective studies on fully covered self-expandable metallic stent (FC-SEMS) treatment for benign HJAS used the stenosis resolution rate as the primary endpoint, and no study has yet used the long-term non-stenosis rate (at 12 months) as the primary endpoint.

Methods and analysis

We launched the ‘saddle-cross study’, which will be conducted as a multicentre, prospective intervention of endoscopic treatment using two modified FC-SEMSs (BONASTENT M-Intraductal) that have been improved for benign stenosis in patients with benign HJAS, with the long-term non-restenosis rate (at 12 months) as the primary endpoint. This study aims to evaluate the long-term non-restenosis rate (at 12 months) and safety of the saddle-cross technique for benign HJAS. We plan to enrol 50 participants.

Ethics and dissemination

This study has been approved by the Certified Review Board of the National Cancer Center, Japan (CRB3180009). The results will be reported at various conferences and published in international peer-reviewed journals.

Clarithromycin overcomes stromal cell-mediated drug resistance against proteasome inhibitors in myeloma cells via autophagy flux blockage leading to high NOXA expression

by Shota Moriya, Hiromi Kazama, Hirotsugu Hino, Naoharu Takano, Masaki Hiramoto, Shin Aizawa, Keisuke Miyazawa

We previously reported that macrolide antibiotics, such as clarithromycin (CAM), blocked autophagy flux, and simultaneous proteasome and autophagy inhibition by bortezomib (BTZ) plus CAM resulted in enhanced apoptosis induction in multiple myeloma (MM) cells via increased endoplasmic reticulum (ER) stress loading. However, in actual therapeutic settings, cell adhesion-mediated drug resistance between bone marrow stromal cells (BMSC) and MM cells has been known to be a barrier to treatment. To investigate whether CAM could enhance BTZ-induced cytotoxicity in MM cells under direct cell adhesion with BMSC, we established a co-culture system of EGFP-labeled MM cells with BMSC. The cytotoxic effect of BTZ on MM cells was diminished by its interaction with BMSC; however, the attenuated cytotoxicity was recovered by the co-administration of CAM, which upregulates ER stress loading and NOXA expression. Knockout of NOXA in MM cells canceled the enhanced cell death by CAM, indicating that NOXA is a key molecule for cell death induction by the co-administration of CAM. Since NOXA is degraded by autophagy as well as proteasomes, blocking autophagy with CAM resulted in the sustained upregulation of NOXA in MM cells co-cultured with BMSC in the presence of BTZ. Our data suggest that BMSC-associated BTZ resistance is mediated by the attenuation of ER stress loading. However, the addition of CAM overcomes BMSC-associated resistance via upregulation of NOXA by concomitantly blocking autophagy-mediated NOXA degradation and transcriptional activation of NOXA by ER stress loading.

Loss of Aspm causes increased apoptosis of developing neural cells during mouse cerebral corticogenesis

by Madoka Tonosaki, Akira Fujimori, Takeshi Yaoi, Kyoko Itoh

Abnormal spindle-like microcephaly associated (ASPM) is a causative gene of primary autosomal recessive microcephaly. Microcephaly is considered to be a consequence of a small brain, but the associated molecular mechanisms are not fully understood. In this study, we generated brain-specific Aspm knockout mice to evaluate the fetal brain phenotype and observed cortical reduction in the late stage of murine cortical development. It has been reported that the total number of neurons is regulated by the number of neural stem and progenitor cells. In the Aspm knockout mice, no apparent change was shown in the neural progenitor cell proliferation and there was no obvious effect on the number of newly generated neurons in the developing cortex. On the other hand, the knockout mice showed a constant increase in apoptosis in the cerebral cortex from the early through the late stages of cortical development. Furthermore, apoptosis occurred in the neural progenitor cells associated with DNA damage. Overall, these results suggest that apoptosis of the neural progenitor cells is involved in the thinning of the mouse cerebral cortex, due to the loss of the Aspm gene in neocortical development.

Association between oral condition and subjective psychological well-being among older adults attending a university hospital dental clinic: A cross-sectional study

by Noriko Takeuchi, Nanami Sawada, Daisuke Ekuni, Manabu Morita

Positive psychological well-being has a favorable impact on survival rates in both healthy and unhealthy populations. Oral health is also associated with psychological well-being, is multidimensional in nature, and includes physical, psychological, emotional, and social domains that are integral to overall health and well-being. This study aimed to identify the associations between individual and environmental characteristics, oral condition and nutritional status in relation to subjective well-being among older adults using the Wilson and Cleary conceptual model. The participants were older adults (age ≥ 60 years) attending a university hospital. Subjective well-being was assessed using the World Health Organization-5 Well-Being Index, oral condition was assessed based on the number of bacteria in the tongue coating, oral wettability, tongue pressure, occlusal force, oral diadochokinesis, and masticatory ability, and subjective swallowing function was assessed using the Eating Assessment Tool, number of remaining teeth, and number of functional teeth. In addition, factors related to well-being, including social networks, life–space mobility, nutritional status, smoking history, drinking history, and medical history were assessed. In the analysis, structural equation modeling was used to investigate the association between oral condition and subjective well-being. Confirmatory factor analysis revealed oral condition as a latent variable, including tongue pressure, oral diadochokinesis /pa/, /ta/, /ka/, occlusal force, masticatory ability, subjective swallowing function, and number of functional teeth. Structural Equation Modeling revealed that oral condition was positively correlated with nutritional status, and nutritional status was positively correlated with the World Health Organization-5 Well-Being Index. These findings suggest that oral condition may influence subjective well-being via nutritional status or social environmental factors.
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