bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a school-based participatory intervention to improve school environments using the Consolidated Framework for Implementation Research
Authors: Wilhelm April K. , Schwedhelm Maria , Bigelow Martha , Bates Nicole , Hang Mikow , Ortega Luis , Pergament Shannon , Allen Michele L.
Published: September 2021

Background

Participatory research offers a promising approach to addressing health inequities and improving the social determinants of health for diverse populations of adolescents. However, little research has systematically explored factors influencing the implementation of participatory health interventions targeting health disparities.

Objective

This study examined the utility of the Consolidated Framework for Implementation Research (CFIR) in identifying and comparing barriers and facilitators influencing implementation of participatory research trials by employing an adaptation of the CFIR to assess the implementation of a multi-component, urban public school-based participatory health intervention.

Methods

We collected qualitative data over a one-year period through weekly team meeting observational field notes and regular semi-structured interviews with five community-based participatory researchers, one school-based partner, and four school principals involved in implementing a participatory intervention in five schools. Adapted CFIR constructs guided our largely deductive approach to thematic data analysis. We ranked each of the three intervention components as high or low implementation to create an overall implementation effectiveness score for all five schools. Cross-case comparison of constructs across high and low implementation schools identified constructs that most strongly influenced implementation.

Results

Ten of 30 assessed constructs consistently distinguished between high and low implementation schools in this participatory intervention, with five strongly distinguishing. Three additional constructs played influential, though non-distinguishing, roles within this participatory intervention implementation. Influential constructs spanned all five domains and fit within three broad themes: 1) leadership engagement, 2) alignment between the intervention and institutional goals, priorities, demographics, and existing systems, and 3) tensions between adaptability and complexity within participatory interventions. However, the dynamic and collaborative nature of participatory intervention implementation underscores the artificial distinction between inner and outer settings in participatory research and the individual behavior change focus does not consider how relationships between stakeholders at multiple levels of participatory interventions shape the implementation process.

Conclusions

The CFIR is a useful framework for the assessment of participatory research trial implementation. Our findings underscore how the framework can be readily adapted to further strengthen its fit as a tool to examine project implementation in this context.
Decreasing hospital burden of COVID-19 during the first wave in Regione Lombardia: an emergency measures context
Authors: Grosso Francesca Maria , Presanis Anne Margaret , Kunzmann Kevin , Jackson Chris , Corbella Alice , Grasselli Giacomo , Andreassi Aida , Bodina Annalisa , Gramegna Maria , Castaldi Silvana , Cereda Danilo , Angelis Daniela De ,   Covid-19 Lombardy Working Group, Castrofino Ambra , Del Castillo Gabriele , Crottogini Lucia , Tirani Marcello , Zanella Alberto , Salmoiraghi Marco
Published: September 2021

Background

The aim of this study is to quantify the hospital burden of COVID-19 during the first wave and how it changed over calendar time; to interpret the results in light of the emergency measures introduced to manage the strain on secondary healthcare.

Methods

This is a cohort study of hospitalised confirmed cases of COVID-19 admitted from February–June 2020 and followed up till 17th July 2020, analysed using a mixture multi-state model. All hospital patients with confirmed COVID-19 disease in Regione Lombardia were involved, admitted from February–June 2020, with non-missing hospital of admission and non-missing admission date.

Results

The cohort consists of 40,550 patients hospitalised during the first wave. These patients had a median age of 69 (interquartile range 56–80) and were more likely to be men (60%) than women (40%). The hospital-fatality risk, averaged over all pathways through hospital, was 27.5% (95% CI 27.1–28.0%); and steadily decreased from 34.6% (32.5–36.6%) in February to 7.6% (6.3–10.6%) in June. Among surviving patients, median length of stay in hospital was 11.8 (11.6–12.3) days, compared to 8.1 (7.8–8.5) days in non-survivors. Averaged over final outcomes, median length of stay in hospital decreased from 21.4 (20.5–22.8) days in February to 5.2 (4.7–5.8) days in June.

Conclusions

The hospital burden, in terms of both risks of poor outcomes and lengths of stay in hospital, has been demonstrated to have decreased over the months of the first wave, perhaps reflecting improved treatment and management of COVID-19 cases, as well as reduced burden as the first wave waned. The quantified burden allows for planning of hospital beds needed for current and future waves of SARS-CoV-2 i.
Differentiating migraine, cervicogenic headache and asymptomatic individuals based on physical examination findings: a systematic review and meta-analysis
Authors: Anarte-Lazo E. , Carvalho G. F. , Schwarz A. , Luedtke K. , Falla D.
Published: September 2021

Background

Migraine and cervicogenic headache (CGH) are common headache disorders, although the large overlap of symptoms between them makes differential diagnosis challenging. To strengthen differential diagnosis, physical testing has been used to examine for the presence of musculoskeletal impairments in both conditions. This review aimed to systematically evaluate differences in physical examination findings between people with migraine, CGH and asymptomatic individuals.

Methods

The databases MEDLINE, PubMed, CINAHL, Web of Science, Scopus, EMBASE were searched from inception until January 2020. Risk of bias was assessed with the Downs and Black Scale for non-randomized controlled trials, and with the Quality Assessment of Diagnostic Accuracy Studies tool for diagnostic accuracy studies. When possible, meta-analyses with random effect models was performed.

Results

From 19,682 articles, 62 studies were included in this review and 41 were included in the meta-analyses. The results revealed: a) decreased range of motion [°] (ROM) on the flexion-rotation test (FRT) (17.67, 95%CI:13.69,21.65) and reduced neck flexion strength [N] (23.81, 95%CI:8.78,38.85) in CGH compared to migraine; b) compared to controls, migraineurs exhibit reduced flexion ROM [°] (− 2.85, 95%CI:-5.12,-0.58), lateral flexion ROM [°] (− 2.17, 95% CI:-3.75,-0.59) and FRT [°] (− 8.96, 95%CI:-13.22,-4.69), reduced cervical lordosis angle [°] (− 0.89, 95%CI:-1.72,-0.07), reduced pressure pain thresholds over the cranio-cervical region [kg/cm2], reduced neck extension strength [N] (− 11.13, 95%CI:-16.66,-5.6) and increased activity [%] of the trapezius (6.18, 95%CI:2.65,9.71) and anterior scalene muscles (2.87, 95%CI:0.81,4.94) during performance of the cranio-cervical flexion test; c) compared to controls, CGH patients exhibit decreased neck flexion (− 33.70, 95%CI:-47.23,-20.16) and extension (− 55.78, 95%CI:-77.56,-34.00) strength [N].

Conclusion

The FRT and neck flexion strength could support the differential diagnosis of CGH from migraine. Several physical tests were found to differentiate both headache types from asymptomatic individuals. Nevertheless, additional high-quality studies are required to corroborate these findings.

Study registration

Following indications of Prisma-P guidelines, this protocol was registered in PROSPERO on 21/05/2019 with the number CRD42019135269. All amendments performed during the review were registered in PROSPERO, indicating the date and what and why was changed.
Differences in myoelectric activity of the lumbar muscles between recurrent and chronic low back pain: a cross-sectional study
Authors: Balasch-Bernat Mercè , Willems Tine , Danneels Lieven , Meeus Mira , Goubert Dorien
Published: September 2021

Background

Altered lower back muscle activity is proposed as a contributing factor to the reoccurrence and chronicity of low back pain (LBP). This study compared lumbar muscle activity during trunk extension in patients with continuous chronic LBP (CLBP), non-continuous CLBP, recurrent LBP (RLBP) and healthy subjects.

Methods

In 75 subjects (16 continuous CLBP, 15 non-continuous CLBP, 23 RLBP, 21 healthy controls), surface electromyographic (EMG) activity of the lumbar erector spinae (ES), multifidus (MF), latissimus dorsi (LD) and gluteus maximus (GM) was recorded during the concentric, holding and eccentric phase of a modified Biering Sorenson exercise.

Results

Continuous CLBP patients showed higher EMG activity in the ES and MF muscles compared to healthy controls in the concentric (p = 0.011; p = 0.009 respectively) and the holding phase (p = 0.015; p = 0.013). Higher EMG activity was observed in continuous CLBP compared to RLBP in the ES and MF muscles in the holding phase (p = 0.035; p = 0.037), and in the MF in the concentric phase (p = 0.046), but not in the ES (p = 0.062). No differences in muscle activity were established in either the concentric, holding, and eccentric phase for the LD and GM muscles. No differences were found between non-continuous CLBP and the other groups.

Conclusions

An enhanced muscle activity of the lumbar muscles during the concentric and holding phase was observed during trunk extension in patients with continuous CLBP compared to patients with RLBP and healthy subjects. No differences between groups are present in the GM and LD muscles during concentric and holding phases and for any muscle in the eccentric phase.
Hard bilateral syphilitic testes with vasculitis: a case report and literature review
Authors: Nepal Sat Prasad , Nakasato Takehiko , Fukagai Takashi , Shichijo Takeshi , Morita Jun , Maeda Yoshiko , Oshinomi Kazuhiko , Nakagami Yoshihiro , Unoki Tsutomu , Noguchi Tetsuo , Inoue Tatsuki , Kato Ryosuke , Amano Satoshi , Mizunuma Moyuru , Kurokawa Masahiro , Tsunokawa Yoshiki , Yasuda Sou , Ogawa Yoshio
Published: September 2021

Background

We report the case of a patient with syphilitic testicular gumma and vasculitis with adrenal failure due to chronic steroid use.

Case presentation

A 63-year-old male presented with hard right eye swelling and very firm bilateral testes on palpation, which he had for 2 years. Testicular tumor markers were negative; syphilis test was positive. Radiological examination suggested aortitis and bilateral testicular malignancy. The patient received ampicillin for the infection and prednisolone for vasculitis. Left orchidectomy was performed to confirm the presence of testicular tumor; histological examinations revealed granulomatous orchitis. The prednisolone doses were adjusted because of relapses and adverse effects of steroid use. Unfortunately, the patient died in the intensive care unit because of uncontrolled blood pressure and pneumonia.

Conclusions

This is a rare case of syphilis with testicular involvement and vasculitis. This report shows the importance of broadening the differential diagnoses of testicular firmness.
Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats
Authors: Tawinwung Supannikar , Junsaeng Dhirarin , Utthiya Supanut , Khemawoot Phisit
Published: September 2021

Background

ECa 233 is a standardized extract ofC. asiaticacontaining the triterpenoid glycosides, madecassoside to asiaticoside in the ratio of (1.5 ± 0.5):1. Anti-inflammatory activities of ECa 233 have been reported; however the immunomodulatory effects of ECa 233 on regulatory T cells, which have a pivotal role in immune regulation, has not been elucidated. Therefore, we investigated the effects of ECa 233 on regulatory T cells that may provide benefits in autoimmune and chronic inflammatory diseases.

Methods

ECa 233 was prepared as oral suspension in 0.5% carboxymethylcellulose and administered to male Wistar rats via oral gavage. The pharmacokinetics and toxicity of ECa 233 were evaluated. Splenic lymphocytes were isolated and analyzed by flow cytometry and qPCR to determine the immunomodulatory effects of ECa 233 on regulatory T cells.

Results

All rats had good tolerability to ECa 233 and other test preparations. The pharmacokinetic study showed low oral bioavailability for both triterpenoids, with the maximum plasma concentration reached at 4 h for asiaticoside and at 0.5 h for madecassoside. Multiple oral administration of ECa 233 reduced the frequency of T cells, particularly CD8 T cells in rats. ECa 233 enhanced the percentage of regulatory T cells, characterized by high expression of CD25+and upregulation of FoxP3 gene.

Conclusions

The present study demonstrated that ECa 233 possesses immunosuppressive properties by enhancing regulatory T cells.These results provide in vivo evidence for the anti-inflammatory action of ECa 233, in line with previously reports, and the potential uses of ECa 233 in the treatment of chronic inflammatory and autoimmune diseases.
Role of financial incentives in family planning services in India: a qualitative study
Authors: Lalchandani Kamlesh , Gupta Aditi , Srivastava Ashish , Usmanova Gulnoza , Maadam Ashwarya , Sood Bulbul
Published: September 2021

Background

In an effort to encourage Family Planning (FP) adoption, since 1952, the Government of India has been implementing various centrally sponsored schemes that offer financial incentives (FIs) to acceptors as well as service providers, for services related to certain FP methods. However, understanding of the role of FIs on uptake of FP services, and the quality of FP services provided, is limited and mixed.

Methods

A qualitative descriptive study was conducted in Chatra and Palamu districts of Jharkhand state. A total of 64 interviews involving multiple stakeholders were conducted. The stakeholders included recent FP acceptors or clients, FP service providers of public health facilities including Accredited Social Healthcare Activists (ASHAs), government health officials managing FP programs at the district and state level, and members of development partners supporting FP programs in Jharkhand. Data analysis included both inductive and deductive strategies. It was done using the software Atlas ti version 8.

Results

It has emerged that there is a strong felt need for FP among majority of the clients, and FIs may be a motivator for uptake of FP methods only among those belonging to the lower socio economic strata. For ASHAs, FI is the primary motivator for providing FP related services. There may be a tendency among them and the nurses to promote methods which have more financial incentives linked with them. There are mixed opinions on discontinuing FIs for clients or replacing them with non-financial incentives. Delays in payment of FIs to both clients and the ASHAs is a common issue and adversely effects the program.

Conclusion

FIs for clients have limited influence on their decision to take up a FP method while different amounts of FIs for ASHAs and nurses, linked with different FP methods, may be influencing their service provision. More research is needed to determine the effect of discontinuing FI for FP services.
“I’m outta here!”: a qualitative investigation into why Aboriginal and non-Aboriginal people self-discharge from hospital
Authors: Askew Deborah A. , Foley Wendy , Kirk Corey , Williamson Daniel
Published: September 2021

Background

Occasions of self-discharge from health services before being seen by a health profession or against medical advice are often used by health systems as an indicator of quality care. People self-discharge because of factors such as dissatisfaction with care, poor communication, long waiting times, and feeling better in addition to external factors such as family and employment responsibilities. These factors, plus a lack of cultural safety, and interpersonal and institutional racism contribute to the disproportionately higher rates of Indigenous people self-discharging from hospital. This qualitative study aimed to increase understanding about the causative and contextual factors that culminate in people self-discharging and identify opportunities to improve the hospital experience for all.

Methods

Semi-structured interviews with five Aboriginal and/or Torres Strait Islander (hereafter, respectfully, Indigenous) people and six non-Indigenous people who had self-discharged from a major tertiary hospital in Brisbane, Australia, were audio-recorded, transcribed and thematically analysed.

Results

Study participants all respected hospitals’ vital role of caring for the sick, but the cumulative impact of unmet needs created a tipping point whereby they concluded that remaining in hospital would compromise their health and wellbeing. Five key categories of unmet needs were identified – the need for information; confidence in the quality of care; respectful treatment; basic comforts; and peace of mind. Although Indigenous and non-Indigenous participants had similar unmet needs, for the former, the deleterious impact of unmet needs was compounded by racist and discriminatory behaviours they experienced while in hospital.

Conclusions

Respectful, empathetic, person-centred care is likely to result in patients’ needs being met, improve the hospital experience and reduce the risk of people self-discharging. For Indigenous people, the ongoing legacy of white colonisation is embodied in everyday lived experiences of interpersonal and institutional racism. Racist and discriminatory behaviours experienced whilst hospitalised are thus rendered both more visible and more traumatic, and exacerbate the deleterious effect of unmet needs. Decreasing self-discharge events requires a shift of thinking away from perceiving this as the behaviour of a deviant individual, but rather as a quality improvement opportunity to ensure that all patients are cared for in a respectful and person-centred manner.
Hypertension in Guatemala’s Public Primary Care System: A Needs Assessment Using the Health System Building Blocks Framework
Authors: Fort Meredith P. , Mundo William , Paniagua-Avila Alejandra , Cardona Sayra , Figueroa Juan Carlos , Hernández-Galdamez Diego , Mansilla Kristyne , Peralta-García Ana , Roche Dina , Palacios Eduardo Alberto , Glasgow Russell E. , Gulayin Pablo , Irazola Vilma , He Jiang , Ramirez-Zea Manuel
Published: September 2021

Background

Uncontrolled hypertension represents a substantial and growing burden in Guatemala and other low and middle-income countries. As a part of the formative phase of an implementation research study, we conducted a needs assessment to define short- and long-term needs and opportunities for hypertension services within the public health system.

Methods

We conducted a multi-method, multi-level assessment of needs related to hypertension within Guatemala’s public system using the World Health Organization’s health system building blocks framework. We conducted semi-structured interviews with stakeholders at national (n = 17), departmental (n = 7), district (n = 25), and community (n = 30) levels and focus groups with patients (3) and frontline auxiliary nurses (3). We visited and captured data about infrastructure, accessibility, human resources, reporting, medications and supplies at 124 health posts and 53 health centers in five departments of Guatemala. We conducted a thematic analysis of transcribed interviews and focus group discussions supported by matrix analysis. We summarized quantitative data observed during visits to health posts and centers.

Results

Major challenges for hypertension service delivery included: gaps in infrastructure, insufficient staffing and high turnover, limited training, inconsistent supply of medications, lack of reporting, low prioritization of hypertension, and a low level of funding in the public health system overall. Key opportunities included: prior experience caring for patients with chronic conditions, eagerness from providers to learn, and interest from patients to be involved in managing their health. The 5 departments differ in population served per health facility, accessibility, and staffing. All but 7 health posts had basic infrastructure in place. Enalapril was available in 74% of health posts whereas hydrochlorothiazide was available in only 1 of the 124 health posts. With the exception of one department, over 90% of health posts had a blood pressure monitor.

Conclusions

This multi-level multi-method needs assessment using the building blocks framework highlights contextual factors in Guatemala’s public health system that have been important in informing the implementation of a hypertension control trial. Long-term needs that are not addressed within the scope of this study will be important to address to enable sustained implementation and scale-up of the hypertension control approach.
Water, sanitation, and hygiene (WASH) facilities and infection control/prevention practices in traditional birth homes in Southwest Nigeria
Authors: Arowosegbe Adediwura Oladunni , Ojo David Ajiboye , Shittu Olufunke Bolatito , Iwaloye Opeoluwa , Ekpo Uwem Friday
Published: September 2021

Background

Poor environmental conditions and hygiene practices at the time of childbirth is linked to life-threatening infections and death in mothers and babies. Improvements in water, sanitation, and hygiene (WASH) have been identified as a means through which the lives of mothers and babies could be saved. This study was carried out to explore WASH conditions and infection prevention and control (IPC) practices in traditional birth homes/centers in Abeokuta, Southwest Nigeria. A total of 50 traditional birth centers and attendants (TBAs) were enrolled in the study. Sociodemographic characteristics of the TBAs and features of the birth centers were obtained using a semi-structured questionnaire. Assessment of WASH conditions and IPC practices was based on established protocols.

Results

Findings revealed that majority of the centers operated under poor WASH conditions and IPC practices; none met with the WHO minimum standards for environmental health.

Conclusions

Adequate WASH facilities and IPC practices remain a critical component of maternal and child health even in non-facility birth. As the transition to facility births continues in many countries, the large number of non-facility births demands their inclusion in WASH-related strategies, if global goals of reducing deaths of newborns and women deaths will be achieved.
The effect of an electronic medical record intervention on hydroxychloroquine prescribing habits and surveyed providers’ opinions of the 2016 American Academy of Ophthalmology guidelines in the rheumatology and dermatology practices of an academic institution
Authors: Overbury Rebecca S. , Stoddard Gregory J. , Pupaibool Jakrapun , Hansen Christopher B. , Lebiedz-Odrobina Dorota
Published: September 2021

Background

Retinal toxicity is a rare adverse event related to the use of hydroxychloroquine (HCQ). To address this, in 2016, the American Academy of Ophthalmology (AAO) issued guidelines recommending that HCQ not exceed 5 mg/kg/day. We analyzed HCQ prescribing habits at our institution, compared to these guidelines, and used surveys to determine the opinions on these guidelines. We then introduced, in a prospective and non-controlled study, a clinical decision support (CDS) tool into the electronic medical record (EMR) to study how this intervention might affect adherence with or opinions on these guidelines.

Methods

Data were collected pre-intervention (June 2017–January 2019) and post-intervention (March 2019–April 2020). In January 2019 we released our CDS tool. Results were analyzed using descriptive statistics for demographic data and Fisher’s exact tests for comparisons of proportions between groups.

Results

Pre-intervention, we reviewed 1128 rheumatology charts and 282 dermatology charts. 31.0 and 39.7% respectively (32.8% combined) were prescribed HCQ > 5 .0 mg/kg/day. Post-intervention, we reviewed 1161 rheumatology charts and 110 dermatology charts. 23.0 and 25.5% respectively (23.2% combined) were prescribed HCQ > 5.0 mg/kg/day. Post-intervention, 9.6% fewer patients were prescribed HCQ > 5 mg/kg/day (P < .001). Pre-intervention, we compiled 18 rheumatology surveys and 12 dermatology surveys. Post-intervention, we compiled 16 rheumatology surveys and 12 dermatology surveys. Post-intervention, fewer rheumatologists incorrectly described the AAO weight-based guidelines. Combined, there was an overall reduction but not of statistical significance (P = .47). The majority of providers surveyed believed that the CDS tool was useful (72.2%).

Conclusions

At our academic institution, there remains unfamiliarity with and hesitation to comply with the 2016 AAO guidelines. Prescribed doses often exceed what is recommended in these guidelines. A CDS tool can improve adherence with these guidelines and might improve providers’ familiarity with these guidelines.
Transcription-dependent confined diffusion of enzymes within subcellular spaces of the bacterial cytoplasm
Authors: Rotter Daniel A. O. , Heger Christoph , Oviedo-Bocanegra Luis M. , Graumann Peter L.
Published: September 2021

Background

Knowledge on the localization and mobility of enzymes inside bacterial cells is scarce, but important for understanding spatial regulation of metabolism. The four central enzymes (Rib enzymes) of the riboflavin (RF) biosynthesis pathway in the Gram positive model bacterium Bacillus subtilis have been studied extensively in vitro, especially the heavy RF synthase, a large protein complex with a capsid structure formed by RibH and an encapsulated RibE homotrimer, which mediates substrate-channeling. However, little is known about the behavior and mobility of these enzymes in vivo.

Results

We have investigated the localization and diffusion of the Rib enzymes in the cytoplasm of B. subtilis. By characterizing the diffusion of Rib enzymes in live cells using single particle tracking (SPT) we provide evidence for confined diffusion at the cell poles and otherwise Brownian motion. A majority of RibH particles showed clear nucleoid occlusion and a high degree of confined motion, which is largely abolished after treatment with Rifampicin, revealing that confinement is dependent on active transcription. Contrarily, RibE is mostly diffusive within the cell, showing only 14% encapsulation by RibH nanocompartments. By localizing different diffusive populations within single cells, we find that fast diffusion occurs mostly across the nucleoids located in the cell centers, while the slower, confined subdiffusion occurs at the crowded cell poles.

Conclusions

Our results provide evidence for locally different motion of active enzymes within the bacterial cytoplasm, setting up metabolic compartmentalization mostly at the poles of cells.
Development of models for cervical cancer screening: construction in a cross-sectional population and validation in two screening cohorts in China
Authors: Wu Zeni , Li Tingyuan , Han Yongli , Jiang Mingyue , Yu Yanqin , Xu Huifang , Yu Lulu , Cui Jianfeng , Liu Bin , Chen Feng , Yin Jian , Zhang Xun , Pan Qinjing , Qiao Youlin , Chen Wen
Published: September 2021

Background

Current methods for cervical cancer screening result in an increased number of referrals and unnecessary diagnostic procedures. This study aimed to develop and evaluate a more accurate model for cervical cancer screening.

Methods

Multiple predictors including age, cytology, high-risk human papillomavirus (hrHPV) DNA/mRNA, E6 oncoprotein, HPV genotyping, and p16/Ki-67 were used for model construction in a cross-sectional population including women with normal cervix (N = 1085), cervical intraepithelial neoplasia (CIN, N = 279), and cervical cancer (N = 551) to predict CIN2+ or CIN3+. A base model using age, cytology, and hrHPV was calculated, and extended versions with additional biomarkers were considered. External validations in two screening cohorts with 3-year follow-up were further conducted (NCohort-I = 3179, NCohort-II = 3082).

Results

The base model increased the area under the curve (AUC, 0.91, 95% confidence interval [CI] = 0.88–0.93) and reduced colposcopy referral rates (42.76%, 95% CI = 38.67–46.92) compared to hrHPV and cytology co-testing in the cross-sectional population (AUC 0.80, 95% CI = 0.79–0.82, referrals rates 61.62, 95% CI = 59.4–63.8) to predict CIN2+. The AUC further improved when HPV genotyping and/or E6 oncoprotein were included in the base model. External validation in two screening cohorts further demonstrated that our models had better clinical performances than routine screening methods, yielded AUCs of 0.92 (95% CI = 0.91–0.93) and 0.94 (95% CI = 0.91–0.97) to predict CIN2+ and referrals rates of 17.55% (95% CI = 16.24–18.92) and 7.40% (95% CI = 6.50–8.38) in screening cohort I and II, respectively. Similar results were observed for CIN3+ prediction.

Conclusions

Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates.
Genomic analysis of circulating tumor cells in adenosquamous carcinoma of the prostate: a case report
Authors: Kitamura Junji , Taguchi Satoru , Okegawa Takatsugu , Honda Kazuki , Kii Toshihiko , Tomida Yoshihiro , Matsumoto Ryuki , Ninomiya Naoki , Masuda Kazuki , Nakamura Yu , Yamaguchi Tsuyoshi , Kinjo Manami , Tambo Mitsuhiro , Isomura Aya , Hayashi Akimasa , Kamma Hiroshi , Higashihara Eiji , Shibahara Junji , Fukuhara Hiroshi
Published: September 2021

Background

Adenosquamous carcinoma of the prostate (ASCP) is an extremely rare and aggressive prostate cancer variant, whose genomic characteristics have not been elucidated. Although liquid biopsy of circulating tumor cells (CTCs) is an emerging topic in oncology, no study has assessed CTCs in patients with ASCP.

Case presentation.

A 76-year-old man presented with discomfort in his urethra. His prostate-specific antigen (PSA) level was 13.37 ng/mL. A computed tomography (CT) scan indicated a prostate mass with multiple lymph node and lung metastases. The patient underwent transurethral resection of the prostate and prostatic needle biopsy; both specimens demonstrated Gleason grade group 5 acinar adenocarcinoma of the prostate. Bone scintigraphy indicated bone metastasis in the ischium. Combined androgen blockade was implemented, and his serum PSA level rapidly decreased to 0.01 ng/mL. However, a CT scan 6 months after the initial diagnosis revealed worsening of the disease. The patient therefore underwent repeated prostatic needle biopsy; its specimen demonstrated prostatic adenocarcinoma together with squamous carcinoma components. As immunohistochemical analyses showed the tumor cells to be negative for CD56, chromogranin A, synaptophysin, and PSA, the definitive diagnosis was ASCP. Although the patient underwent chemotherapy (docetaxel and cabazitaxel), he died of the disease 3 months after the diagnosis of ASCP, or 13 months after the initial diagnosis of prostatic adenocarcinoma. His PSA values remained ≤ 0.2 ng/mL. CTCs from the patient’s blood (collected before starting docetaxel) were analyzed and genomically assessed. It showed 5 cytokeratin (CK)+CTCs, 14 CK−CTCs, and 8 CTC clusters, per 10 mL. Next-generation sequencing identified a total of 14 mutations in 8 oncogenes or tumor suppressor genes:PIK3CB,APC,CDKN2A,PTEN,BRCA2,RB1,TP53, andCDK12. Of 14 mutations, 9 (64%) were detected on CK−CTCs and 5 (36%) were detected on CK+CTCs.

Conclusions

This is the first report of CTC analysis and genomic assessment in ASCP. Although the prognosis of ASCP is dismal due to lack of effective treatment, genomic analysis of CTCs might lead to effective treatment options and improved survival.
Impact of prior cerebrovascular disease and glucose status on incident cerebrovascular disease in Japanese
Authors: Oe Momoko , Fujihara Kazuya , Harada-Yamada Mayuko , Osawa Taeko , Kitazawa Masaru , Matsubayashi Yasuhiro , Sato Takaaki , Yaguchi Yuta , Iwanaga Midori , Seida Hiroyasu , Yamada Takaho , Sone Hirohito
Published: September 2021

Background

Although both a history of cerebrovascular disease (CVD) and glucose abnormality are risk factors for CVD, few large studies have examined their association with subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose status, and their combinations on subsequent CVD using real-world data.

Methods

This is a retrospective cohort study including 363,627 men aged 18–72 years followed for ≥ 3 years between 2008 and 2016. Participants were classified as normoglycemia, borderline glycemia, or diabetes defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD (i.e. ischemic stroke, transient ischemic attack, and non-traumatic intracerebral hemorrhage) were identified according to claims using ICD-10 codes, medical procedures, and questionnaires.

Results

Participants’ mean age was 46.1 ± 9.3, and median follow up was 5.2 (4.2, 6.7) years. Cox regression analysis showed that prior CVD + conferred excess risk for CVD regardless of glucose status (normoglycemia: hazard ratio (HR), 8.77; 95% CI 6.96–11.05; borderline glycemia: HR, 7.40, 95% CI 5.97–9.17; diabetes: HR, 5.73, 95% CI 4.52–7.25). Compared with normoglycemia, borderline glycemia did not influence risk of CVD, whereas diabetes affected subsequent CVD in those with CVD- (HR, 1.50, 95% CI 1.34–1.68). In CVD-/diabetes, age, current smoking, systolic blood pressure, high-density lipoprotein cholesterol, and HbA1c were associated with risk of CVD, but only systolic blood pressure was related to CVD risk in CVD + /diabetes.

Conclusions

Prior CVD had a greater impact on the risk of CVD than glucose tolerance and glycemic control. In participants with diabetes and prior CVD, systolic blood pressure was a stronger risk factor than HbA1c. Individualized treatment strategies should consider glucose tolerance status and prior CVD.
An overview of genes and mutations associated with Chlamydiae species’ resistance to antibiotics
Authors: Benamri Ichrak , Azzouzi Maryame , Sanak Kholoud , Moussa Ahmed , Radouani Fouzia
Published: September 2021

Background

Chlamydiae are intracellular bacteria that cause various severe diseases in humans and animals. The common treatment for chlamydia infections are antibiotics. However, when antibiotics are misused (overuse or self-medication), this may lead to resistance of a number of chlamydia species, causing a real public health problem worldwide.

Materials and methods

In the present work, a comprehensive literature search was conducted in the following databases: PubMed, Google Scholar, Cochrane Library, Science direct and Web of Science. The primary purpose is to analyse a set of data describing the genes and mutations involved in Chlamydiae resistance to antibiotic mechanisms. In addition, we proceeded to a filtration process among 704 retrieved articles, then finished by focusing on 24 studies to extract data that met our requirements.

Results

The present study revealed that Chlamydia trachomatis may develop resistance to macrolides via mutations in the 23S rRNA, rplD, rplV genes, to rifamycins via mutations in the rpoB gene, to fluoroquinolones via mutations in the gyrA, parC and ygeD genes, to tetracyclines via mutations in the rpoB gene, to fosfomycin via mutations in the murA gene, to MDQA via mutations in the secY gene. Whereas, Chlamydia pneumoniae may develop resistance to rifamycins via mutations in the rpoB gene, to fluoroquinolones via mutations in the gyrA gene. Furthermore, the extracted data revealed that Chlamydia psittaci may develop resistance to aminoglycosides via mutations in the 16S rRNA and rpoB genes, to macrolides via mutations in the 23S rRNA gene. Moreover, Chlamydia suis can become resistance to tetracyclines via mutations in the tet(C) gene. In addition, Chlamydia caviae may develop resistance to macrolides via variations in the 23S rRNA gene. The associated mechanisms of resistance are generally: the inhibition of bacteria’s protein synthesis, the inhibition of bacterial enzymes’ action and the inhibition of bacterial transcription process.

Conclusion

This literature review revealed the existence of diverse mutations associated with resistance to antibiotics using molecular tools and targeting chlamydia species’ genes. Furthermore, these mutations were shown to be associated with different mechanisms that led to resistance. In that regards, more mutations and information can be shown by a deep investigation using the whole genome sequencing. Certainly, this can help improving to handle chlamydia infections and healthcare improvement by decreasing diseases complications and medical costs.
Analysis of allergen components and identification of bioactivity of HSP70 in pollen of Populus deltoides
Authors: Guo Wei , Zhan Xiaodong , Jiang Feng , Xi Yilong
Published: September 2021

Background

Allergies caused by pollen from Populus deltoides are common, but the allergic components are still unclear.

Methods

The total proteins in pollen of P. deltoides were analyzed by proteomics, and the potential allergens were identified via the WHO/IUIS database and the allergenOnline database retrieval. One target protein was screened by bioinformatics and expressed in Escherichia coli. The biological activity of the expressed product was verified by animal experiments.

Results

The total of 3929 proteins in pollen of P. deltoides were identified, and 46 potential allergens belonging to 10 protein families were recognized by database retrieval. B9N9W6 protein of Hsp70 family was screened by bioinformatics analysis and expressed successfully. ELISA showed that B9N9W6 can stimulate the immune system to produce specific IgE and promote the generation of IL-4. Flow cytometry showed that B9N9W6 can significantly stimulate the proliferation of CD4+ T cells and promote the polarization of Th2 cells. The pathological sections of mice lung tissues indicated that alveolar destruction was more severe in the B9N9W6 group than that of extract group, and there were more inflammatory cells infiltration, mucus exudation and bleeding.

Conclusion

B9N9W6 is an important antigenic substance in the pollen of P. deltoides. Due to the conserved structure of Hsp70 family, more attention should be paid to the possibility of sensitization when Hsp70 from any pathogenic species is administered.
Circ_0029803 serves as the sponge of miR-216b-5p to promote the progression of colorectal cancer by regulating SKIL expression
Authors: Huang Linfei , Zhu Lei , Pan Sheng , Xu Jing , Xie Miao , Wang Wei , Xia Ganlin
Published: September 2021

Background

Circular RNA 0029803 (circ_0029803) was found to be upregulated in colorectal cancer (CRC) tissues, but its function and underlying molecular mechanism are not studied in CRC.

Methods

The expression levels of circ_0029803, microRNA-216b-5p (miR-216b-5p), and ski-oncogene-like (SKIL) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to affirm the existence of circ_0029803. Cell proliferation, apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, and Transwell assays, respectively. A glucose and lactate assay kit was used to detect glucose consumption and lactate production. Western blot was applied to analyze the levels of all proteins. Dual-luciferase reporter assay was performed to assess the relationship between miR-216b-5p and circ_0029803 or SKIL. Tumor xenograft models were established to elucidate the effect of circ_0029803 in vivo.

Results

Circ_0029803 expression was enhanced in CRC tissues and cells, and the 5-year overall survival rate of patients with high circ_0029803 expression was substantially reduced. Circ_0029803 depletion retarded proliferation, migration, invasion, EMT and glycolysis of CRC cells in vitro as well as the tumor growth in vivo. Mechanically, circ_0029803 could serve as miR-216b-5p sponge to regulate its expression, and miR-216b-5p knockdown reversed the inhibition of si-circ_0029803 on the malignant behaviors of CRC cells. Additionally, as the target mRNA of miR-216b-5p, SKIL could counteract the inhibitory effect of miR-216b-5p on the development of CRC cells. Importantly, silencing circ_0029803 reduced SKIL expression via sponging miR-216b-5p.

Conclusion

Circ_0029803 knockdown hindered proliferation, migration, invasion, EMT, and glycolysis and promoted apoptosis in CRC cells by modulating the miR-216b-5p/SKIL axis.
TLR4 signaling in the development of colitis-associated cancer and its possible interplay with microRNA-155
Authors: Guo Jie , Liao Mengfan , Wang Jun
Published: September 2021

Ulcerative colitis (UC) has closely been associated with an increased risk of colorectal cancer. However, the exact mechanisms underlying colitis-associated cancer (CAC) development remain unclear. As a classic pattern-recognition receptor, Toll like receptor (TLR)4 is a canonical receptor for lipopolysaccharide of Gram-negative bacteria (including two CAC-associated pathogens Fusobacterium nucleatum and Salmonella), and functions as a key bridge molecule linking oncogenic infection to colonic inflammatory and malignant processes. Accumulating studies verified the overexpression of TLR4 in colitis and CAC, and the over-expressed TLR4 might promote colitis-associated tumorigenesis via facilitating cell proliferation, protecting malignant cells against apoptosis, accelerating invasion and metastasis, as well as contributing to the creation of tumor-favouring cellular microenvironment. In recent years, considerable attention has been focused on the regulation of TLR4 signaling in the context of colitis-associated tumorigenesis. MicroRNA (miR)-155 and TLR4 exhibited a similar dynamic expression change during CAC development and shared similar CAC-promoting properties. The available data demonstrated an interplay between TLR4 and miR-155 in the context of different disorders or cell lines. miR-155 could augment TLR4 signaling through targeting negative regulators SOCS1 and SHIP1; and TLR4 activation would induce miR-155 expression via transcriptional and post-transcriptional mechanisms. This possible TLR4-miR-155 positive feedback loop might result in the synergistic accelerating effect of TLR4 and miR-155 on CAC development.
Lifestyle-integrated functional exercise to prevent falls and promote physical activity: Results from the LiFE-is-LiFE randomized non-inferiority trial
Authors: Jansen Carl-Philipp , Nerz Corinna , Labudek Sarah , Gottschalk Sophie , Kramer-Gmeiner Franziska , Klenk Jochen , Dams Judith , König Hans-Helmut , Clemson Lindy , Becker Clemens , Schwenk Michael
Published: September 2021

Background

The ‘Lifestyle-integrated Functional Exercise’ (LiFE) program successfully reduced risk of falling via improvements in balance and strength, additionally increasing physical activity (PA) in older adults. Generally being delivered in an individual one-to-one format, downsides of LiFE are considerable human resources and costs which hamper large scale implementability. To address this, a group format (gLiFE) was developed and analyzed for its non-inferiority compared to LiFE in reducing activity-adjusted fall incidence and intervention costs. In addition, PA and further secondary outcomes were evaluated.

Methods

Older adults (70 + years) at risk of falling were included in this multi-center, single-blinded, randomized non-inferiority trial. Balance and strength activities and means to enhance PA were delivered in seven intervention sessions, either in a group (gLiFE) or individually at the participant’s home (LiFE), followed by two “booster” phone calls. Negative binomial regression was used to analyze non-inferiority of gLiFE compared to LiFE at 6-month follow-up; interventions costs were compared descriptively; secondary outcomes were analyzed using generalized linear models. Analyses were carried out per protocol and intention-to-treat.

Results

Three hundred nine persons were randomized into gLiFE (n = 153) and LiFE (n = 156). Non-inferiority of the incidence rate ratio of gLiFE was inconclusive after 6 months according to per protocol (mean = 1.27; 95% CI: 0.80; 2.03) and intention-to-treat analysis (mean = 1.18; 95% CI: 0.75; 1.84). Intervention costs were lower for gLiFE compared to LiFE (-€121 under study conditions; -€212€ under “real world” assumption). Falls were reduced between baseline and follow-up in both groups (gLiFE: -37%; LiFE: -55%); increases in PA were significantly higher in gLiFE (+ 880 steps; 95% CI 252; 1,509). Differences in other secondary outcomes were insignificant.

Conclusions

Although non-inferiority of gLiFE was inconclusive, gLiFE constitutes a less costly alternative to LiFE and it comes with a significantly larger enhancement of daily PA. The fact that no significant differences were found in any secondary outcome underlines that gLiFE addresses functional outcomes to a comparable degree as LiFE. Advantages of both formats should be evaluated in the light of individual needs and preferences before recommending either format.

Trial registration

The study was preregistered under clinicaltrials.gov (identifier: NCT03462654) on March 12th 2018
Immunomodulatory treatment and surgical management of idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children: a French survey practice
Authors: Molimard Julie , Pajot Christine , Olle Priscille , Belot Alexandre , Quartier Pierre , Uettwiller Florence , Couret Chloé , Coste Valentine , Costet Camille , Bodaghi Bahram , Dureau Pascal , Bailhache Marion , Pillet Pascal
Published: September 2021

Background

Surgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up.

Methods

We conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected.

Results

A total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections.

Conclusions

The results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses.