Non-communicable diseases (NCDs) constitute approximately 74% of global mortality, with 77% of these deaths occurring in low-income and middle-income countries. Tanzania exemplifies this situation, as the percentage of total disability-adjusted life years attributed to NCDs has doubled over the past 30 years, from 18% to 36%. To mitigate the escalating burden of severe NCDs, the Tanzanian government, in collaboration with local and international partners, seeks to extend the integrated package of essential interventions for severe NCDs (PEN-Plus) to district-level facilities, thereby improving accessibility. This study aims to estimate the cost of initiating PEN-Plus for rheumatic heart disease, sickle cell disease and type 1 diabetes at Kondoa district hospital in Tanzania.
We will employ time-driven activity-based costing (TDABC) to quantify the capacity cost rates (CCR), and capital and recurrent costs associated with the implementation of PEN-Plus. Data on resource consumption will be collected through direct observations and interviews with nurses, the medical officer in charge and the heads of laboratory and pharmacy units/departments. Data on contact times for targeted NCDs will be collected by observing a sample of patients as they move through the care delivery pathway. Data cleaning and analysis will be done using Microsoft Excel.
Ethical approval to conduct the study has been waived by the Norwegian Regional Ethics Committee and was granted by the Tanzanian National Health Research Ethics Committee NIMR/HQ/R.8a/Vol.IX/4475. A written informed consent will be provided to the study participants. This protocol has been disseminated in the Bergen Centre for Ethics and Priority Setting International Symposium, Norway and the 11th Muhimbili University of Health and Allied Sciences Scientific Conference, Tanzania in 2023. The findings will be published in peer-reviewed journals for use by the academic community, researchers and health practitioners.
EndoTrac is a line-attached sheath-type traction device that enables us to control the direction and the force of traction during endoscopic submucosal dissection (ESD). The efficacy of EndoTrac for gastric ESD has not been fully verified.
The G-Trac study is a multicentre (nine general hospitals and two university hospitals in Japan) collaborative trial assessing the efficacy of EndoTrac for gastric ESDs. Patients with superficial gastric neoplasms will be enrolled and randomly assigned to undergo either conventional ESD or EndoTrac ESD. Allocation will be stratified according to tumour location, operator experience and tumour diameter at an allocation rate of 1:1. The type of endoknife used will be confirmed before randomisation. The primary outcome, procedure time, will be compared between the groups in both intention-to-treat and per-protocol analyses using the Wilcoxon rank sum test. The efficacy-related, safety-related and device-related outcomes will be assessed in the secondary analysis. The planned sample size of the 142 patients in the two groups will enable us to detect a difference with a power of 80% by using the Wilcoxon rank sum test, assuming an effect size of 0.54, asymptotic relative efficiency of 0.864 and a two-sided type 1 error rate of 5%.
This trial was approved by the certified review board of Kobe University (22 December 2022). The results from this trial will be disseminated through peer-review journals, presentations at national and international conferences, and data sharing with other researchers.
jRCT1052220166.
Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms.
We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients’ hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions.
The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings.
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.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
BackgroundInformation 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 methodsWe 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.
ResultsUsing 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.
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.
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 (
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.
Japan Registry of Clinical Trials, jRCTs041210104.
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.
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.
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.
This IPD-MA does not require ethical approval. The results will be published in international peer-reviewed journals.
CRD42022299510.
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.
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.
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.
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.
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 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.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
BackgroundEvaluating 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.
MethodsA 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.
ResultsThe 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.
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.
Longitudinal cohort study.
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.
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.
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.
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.
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.
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.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.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).
Participants completed the same self-reported questionnaires twice, 2 years apart.
A sample of 633 healthcare employees (including a majority of nurses and nursing assistants) participated. Latent transition analyses were performed.
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.
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.
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.
NCT04010773 on ClinicalTrials.gov (4 July, 2019).
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.
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.
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.
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.
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.