bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival
Authors: Chen Tianzeng , Ho Matthew , Briere Jenna , Moscvin Maria , Czarnecki Peter G. , Anderson Kenneth C. , Blackwell T. Keith , Bianchi Giada
Published: October 2021

Multiple myeloma (MM) cells suffer from baseline proteotoxicity as the result of an imbalance between the load of misfolded proteins awaiting proteolysis and the capacity of the ubiquitin-proteasome system to degrade them. This intrinsic vulnerability is at the base of MM sensitivity to agents that perturb proteostasis, such as proteasome inhibitors (PIs), the mainstay of modern-day myeloma therapy. De novo and acquired PI resistance are important clinical limitations that adversely affect prognosis. The molecular mechanisms underpinning PI resistance are only partially understood, limiting the development of drugs that can overcome it. The transcription factor NRF1 is activated by the aspartic protease DNA damage inducible 1 homolog 2 (DDI2) upon proteasome insufficiency and governs proteasome biogenesis. In this article, we show that MM cells exhibit baseline NRF1 activation and are dependent upon DDI2 for survival. DDI2 knockout (KO) is cytotoxic for MM cells, both in vitro and in vivo. Protein structure-function studies show that DDI2 KO blocks NRF1 cleavage and nuclear translocation, causing impaired proteasome activity recovery upon irreversible proteasome inhibition and, thereby, increasing sensitivity to PIs. Add-back of wild-type, but not of catalytically dead DDI2, fully rescues these phenotypes. We propose that DDI2 is an unexplored promising molecular target in MM by disrupting the proteasome stress response and exacerbating proteotoxicity.
Anti-glycoprotein antibodies and sequestration pattern of indium-labeled platelets in immune thrombocytopenia
Authors: Amini Sufia N. , Porcelijn Leendert , Sobels Annemieke , Kartachova Marina , de Haas Masja , Zwaginga Jaap Jan , Schipperus Martin R.
Published: October 2021

Antiglycoprotein (anti-GP) antibodies play an important role in the pathophysiology of immune thrombocytopenia (ITP). The sequestration pattern of platelets in the spleen and liver can be studied with 111In-labeled autologous platelet scans. No studies have investigated the role of anti-GP antibodies in sequestration patterns in ITP patients. In this study, we examined the association between antibodies and (1) platelet sequestration site and (2) clearance rate of platelets. All ITP patients receiving an 111In-labeled autologous platelet study between 2014 and 2018 were included. Antibodies were measured using the direct MAIPA method to determine the presence and titer of anti-GPIIb/IIIa, anti-GPIb/IX, and anti-GPV antibodies. Multivariate regression models were used to study the association between anti-GP antibodies, sequestration site, and clearance rate. Seventy-four patients were included, with a mean age of 36 years. Forty-seven percent of the patients showed a predominantly splenic sequestration pattern, 29% mixed, and 25% a hepatic pattern. In 53% of the patients, anti-GP antibodies were detected. Regression models showed a significant association between splenic sequestration and GPV autoantibodies. Furthermore, in patients where antibodies were present, the clearance rate was higher in patients with a splenic sequestration. Anti-GPV antibodies are associated with a splenic sequestration pattern in ITP patients. These associations provide insight into the possible pathophysiological mechanisms of ITP, which may lead to better detection and treatment of this partly idiopathic and prevalent disease.
Platelet binding to polymerizing fibrin is avidity driven and requires activated αIIbβ3 but not fibrin cross-linking
Authors: Buitrago Lorena , Lefkowitz Samuel , Bentur Ohad , Padovan Julio , Coller Barry
Published: October 2021

The molecular basis of platelet-fibrin interactions remains poorly understood despite the predominance of fibrin in thrombi. We have studied the interaction of platelets with polymerizing fibrin by adding thrombin to washed platelets in the presence of the peptide RGDW, which inhibits the initial platelet aggregation mediated by fibrinogen binding to αIIbβ3 but leaves intact a delayed increase in light transmission (delayed wave; DW) as platelets interact with the polymerizing fibrin. The DW was absent in platelets from a patient with Glanzmann thrombasthenia, indicating a requirement for αIIbβ3. The DW required αIIbb3 activation and it was inhibited by the αIIbβ3 antagonists eptifibatide and the monoclonal antibody (mAb) 7E3, but only at much higher concentrations than needed to inhibit platelet aggregation initiated by a thrombin receptor activating peptide (T6). Surface plasmon resonance and scanning electron microscopy studies both supported fibrin having greater avidity for αIIbβ3 than fibrinogen rather than greater affinity, consistent with fibrin’s multivalency. mAb 10E5, a potent inhibitor of T6-induced platelet aggregation, did not inhibit the DW, suggesting that fibrin differs from fibrinogen in its mechanism of binding. Inhibition of factor XIII–mediated fibrin cross-linking by >95% reduced the DW by only 32%. Clot retraction showed a pattern of inhibition similar to that of the DW. We conclude that activated αIIbβ3 is the primary mediator of platelet-fibrin interactions leading to clot retraction, and that the interaction is avidity driven, does not require fibrin cross-linking, and is mediated by a mechanism that differs subtly from that of the interaction of αIIbβ3 with fibrinogen.
Long noncoding RNA MAPKAPK5-AS1 promoted lipopolysaccharide-induced inflammatory damage in the myocardium by sponging microRNA-124-3p/E2F3
Authors: Chen Weiwei , Gao Guangyuan , Yan Mengjie , Yu Ming , Shi Kaiyao , Yang Ping
Published: October 2021

Background

Myocardial dysfunction caused by sepsis (SIMD) leads to high mortality in critically ill patients. We investigated the function and mechanism of long non-coding RNA MAPKAPK5-AS1 (lncRNA MAPKAPK-AS1) on lipopolysaccharide (LPS)-induced inflammation response in vivo and in vitro.

Method

Male SD rats were utilized for in vivo experiments. Rat cardiomyocytes (H9C2) were employed for in vitro experiments. Western blotting was employed to measure protein expression, and RT-PCR was performed to measure mRNA expression of inflammation factors. TUNEL and flow cytometry were carried out to evulate cell apoptosis.

Result

The results showed that the expression of MAPKAPK5-AS1 was increased, while the expression of miR-124-3p was decreased in the inflammatory damage induced by LPS in vivo and in vitro. Knockdown of MAPKAPK5-AS1 reduced LPS-induced cell apoptosis and inflammation response, while overexpression of miR-124-3p weakened the effects of MAPKAPK5-AS1 knockdown on LPS-induced cell apoptosis and inflammation response. Moreover, miR-124-3p was identified as a downstream miRNA of MAPKAPK5-AS1, and E2F3 was a target of miR-214-3p. MAPKAPK5-AS1 knockdown increased the expression of miR-124-3p, while miR-124-3p overexpression reduced the expression of MAPKAPK5-AS1. In addition, miR-124-3p was found to downregulate E2F3 expression in H9C2 cells.

Conclusion

MAPKAPK5-AS1/miR-124-3p/E2F3 axis regulates LPS-related H9C2 cell apoptosis and inflammatory response.
The ratio of HDL-C to apoA-I interacts with free triiodothyronine to modulate coronary artery disease risk
Authors: Li Li , Cai Gaojun , Lu Wei , Li Feng , Yu Lei , Xiao Jianqiang
Published: October 2021

Objective

In the present work, research was carried out to explore the correlation between the high-density lipoprotein cholesterol (HDL-C)/apolipoprotein A-I (apoA-I) ratio and serum free triiodothyronine (FT3) and their interaction on the risk of coronary artery disease (CAD).

Methods

A total of 1686 patients who underwent selective coronary angiography were enrolled in the present study, including 1279 patients with CAD and 407 controls. The subjects were divided into three groups according to tertiles of the HDL-C/apoA-I ratio. Binary logistic regression analysis was used to evaluate the interaction of the HDL-C/apoA-I ratio and FT3 level with the risk of CAD.

Results

The group with the highest HDL-C/apoA-I ratio had the lowest levels of FT3. Multiple linear regression analysis showed that the HDL-C/apoA-I ratio was negatively associated with FT3 after adjusting for age, sex, body mass index (BMI), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), FT4 and TSH. A logistic regression model showed that a high HDL-C/apoA-I ratio (> 0.89 mmol/g) and high FT3 levels (> 4.5 pmol/l) were protective factors for CAD. Patients with a lower HDL-C/apoA-I ratio (≤ 0.89 mmol/g) and lower FT3 level (≤ 4.5 pmol/l) had an increased risk of CAD (OR = 2.441, P = 0.000, S = 1.13, AP = 0.068, AP* = 0.116, RERI = 0.168).

Conclusions

The HDL-C/apoA-I ratio was negatively associated with FT3, and there was a significant interaction between the HDL-C/apoA-I ratio and FT3 with the risk of CAD.
Predictors of severe leptospirosis: a multicentre observational study from Central Malaysia
Authors: Philip Noraini , Lung Than Leslie Thian , Shah Anim Md , Yuhana Muhamad Yazli , Sekawi Zamberi , Neela Vasantha Kumari
Published: October 2021

Background

Leptospirosis is a re-emerging disease with vast clinical presentations, that ranges from subclinical or mild to severe and fatal outcomes. Leptospirosis can be managed well if diagnosed earlier, however, similar clinical presentations by several other febrile illnesses or co-infections, and laboratory diagnostic challenges due to the biphasic nature of the illness, often result in mis- or underdiagnosis, thereby lead to severe illness. Identification of clinical predictors for the severe form of the disease plays a crucial role in reducing disease complication and mortality. Therefore, we aimed to determine the clinical predictors associated with severe illness among leptospirosis patients from Central Malaysia through a prospective multicenter observational study.

Methods

A prospective multicenter observational study was performed on patients admitted for clinically suspected leptospirosis. Three hospitals namely Hospital Serdang, Hospital Tengku Ampuan Rahimah and Hospital Teluk Intan were included in the study. Among a total of 165 clinically suspected leptospirosis patients, 83 confirmed cases were investigated for clinical predictors for severe illness. Qualitative variables were performed using χ2 and the relationship between mild and severe cases was evaluated using logistic regression. Multivariable logistic regression was used to predict the independent variable for severity.

Results

Among the 83 patients, 50 showed mild disease and 33 developed severe illness. The mean age of the patients was 41.92 ± 17.99 and most were males (n = 54, 65.06%). We identified mechanical ventilation, acute kidney injury, septic shock, creatinine level of > 1.13 mg/dL, urea > 7 mmol/L, alanine aminotransferase > 50 IU, aspartate aminotransferase > 50 IU, and platelet < 150 × 109/L as factors associated with severe illness. Acute kidney injury, alanine aminotransferase > 50 IU and platelet < 150 × 109/L were defined as the independent factors for severity.

Conclusions

Lungs, liver and kidney involvement and septic shock were found as the prognostic factors for severe leptospirosis. Acute kidney injury, high level of alanine aminotransferase and low level of platelets were found to be independent predictors of severity.
Retraction Note: Mothers’ experiences of caring for preterm babies at home: qualitative insights from an urban setting in a middle-income country
Authors: Garti Isabella , Donkor Elorm , Musah Nafisatu , Appiah Evans Osei , Gyekye Sandra , Menlah Awube , Akuoko Cynthia Pomaa
Published: October 2021

This article has been retracted. Please see the Retraction Notice for more detail: 10.1186/s12884-021-04185-7
The implementation of colorectal cancer screening interventions in low-and middle-income countries: a scoping review
Authors: Schliemann Désirée , Ramanathan Kogila , Matovu Nicholas , O’Neill Ciaran , Kee Frank , Su Tin Tin , Donnelly Michael
Published: October 2021

Background

Low- and middle-income countries (LMICs) experienced increasing rates of colorectal cancer (CRC) incidence in the last decade and lower 5-year survival rates compared to high-income countries (HICs) where the implementation of screening and treatment services have advanced. This review scoped and mapped the literature regarding the content, implementation and uptake of CRC screening interventions as well as opportunities and challenges for the implementation of CRC screening interventions in LMICs.

Methods

We systematically followed a five-step scoping review framework to identify and review relevant literature about CRC screening in LMICs, written in the English language before February 2020. We searched Medline, Embase, Web of Science and Google Scholar for studies targeting the general, asymptomatic, at-risk adult population. The TIDieR tool and an implementation checklist were used to extract data from empirical studies; and we extracted data-informed insights from policy reviews and commentaries.

Results

CRC screening interventions (n = 24 studies) were implemented in nine middle-income countries. Population-based screening programmes (n = 11) as well as small-scale screening interventions (n = 13) utilised various recruitment strategies. Interventions that recruited participants face-to-face (alone or in combination with other recruitment strategies) (10/15), opportunistic clinic-based screening interventions (5/6) and educational interventions combined with screening (3/4), seemed to be the strategies that consistently achieved an uptake of > 65% in LMICs. FOBT/FIT and colonoscopy uptake ranged between 14 and 100%. The most commonly reported implementation indicator was ‘uptake/reach’. There was an absence of detail regarding implementation indicators and there is a need to improve reporting practice in order to disseminate learning about how to implement programmes.

Conclusion

Opportunities and challenges for the implementation of CRC screening programmes were related to the reporting of CRC cases and screening, cost-effective screening methods, knowledge about CRC and screening, staff resources and training, infrastructure of the health care system, financial resources, public health campaigns, policy commitment from governments, patient navigation, planning of screening programmes and quality assurance.
Diagnostic value of monocyte chemoattractant Protein-1, soluble mannose receptor, Presepsin, and Procalcitonin in critically ill children admitted with suspected sepsis
Authors: Hassuna Noha A. , Elgezawy Ebtesam , Mousa Suzan O. , AbdelAziz Reem A. , Ibrahem Reham A. , Wahed Wafaa Yousif Abdel , Nasif Khalid A. , Hefzy Enas M.
Published: October 2021

Introduction

The differentiation between systemic inflammatory response syndrome and sepsis is very important as it determines essential treatment decisions, such as selection, initiation, and duration of antibiotic therapy.

Objectives

We aimed to investigate the diagnostic value of Procalcitonin, Monocyte Chemoattractant Protein-1, soluble Mannose Receptor, Presepsin as early biomarkers of pediatric sepsis in comparison to systemic inflammatory response syndrome in severely ill children.

Patients and methods

This study included 58 children diagnosed as sepsis (group 1), 24 children with systemic inflammatory response syndrome without infection (group 2), and 50 healthy children as controls (group 3). All the plasma levels of the studied biomarkers were measured and ROC curves were created for all the tested parameters to discriminate between sepsis and SIRS.

Results

The area under the curve for Monocyte Chemoattractant Protein-1 was 0.926 (0.846-0.927) with sensitivity 100% and specificity 62.5%. The soluble Mannose Receptor had the highest sensitivity (100%), with AUC equals 1(.0.956-1.0) and specificity of 100%. The cut-off values for Procalcitonin, Presepsin, soluble Mannose Receptor, and Monocyte Chemoattractant Protein-1 and were: 0.62 ng/ml, 100 pg/ml, 13 ng/ml and 90 pg/ml, respectively. In septic cases, both soluble Mannose Receptor and Procalcitonin have positive correlations with the severity of sepsis, low Glasgow Coma Scale, ventilatory support, use of inotropic drugs and mortality rate (r = 0.950, 0.812, 0.795, 0.732 and 0.861respectively) for soluble Mannose Receptor and (0.536, 0.473, 0.422, 0.305 and 0.474 respectively) for Procalcitonin.

Conclusion

Soluble Mannose Receptor, Presepsin, and Monocyte Chemoattractant Protein-1 can be used to differentiate between sepsis and SIRS in critically ill children.
Psychometric properties of the dementia knowledge assessment scale-traditional Chinese among home care workers in Taiwan
Authors: Sung Huei-Chuan , Su Hsin-Feng , Wang Hsiu-Mei , Koo Malcolm , Lo Raymond Y.
Published: October 2021

Background

The Dementia Knowledge Assessment Scale (DKAS) is a reliable and valid measurement of dementia knowledge for diverse allied health professionals but its traditional Chinese version has not been formally validated yet. The purpose of this study was to translate the DKAS from English to traditional Chinese and evaluate its psychometric properties among home care workers in Taiwan.

Methods

The DKAS scale was translated into traditional Chinese through a forward translation and back translation process following the cross-cultural translation guideline. A total of 285 home care workers in eastern Taiwan were recruited using convenience sample. A total of 252 participants completed the questionnaires, giving a response rate of 88.4%. We tested the construct validity by confirmatory factor analysis (CFA) and evaluated the reliability by internal consistency.

Results

The results of the CFA supported the 25-item, four-factor model for the DKAS-TC. The DKAS-TC achieved a good overall Cronbach’s alpha of .93 and McDonald’s omega of 0.94 with acceptable subscales McDonald’s omega ranged from .77 to .82.

Conclusions

The DKAS-TC has adequate construct validity and reliability and can serve as an assessment tool to evaluate the knowledge level of home care workers in a dementia training program in Taiwan. The dementia knowledge level among home care workers in Taiwan was inadequate. There is a need for developing suitable dementia care training tailored to their learning needs and educational levels, and to improve their quality of care for those with dementia.
Explaining utilization of HIV prevention and testing services among university students in Mozambique: results from a mixed methods study
Authors: Hooft Anneka , Pfeil Sarah , Mussengue Josina , Jetha Eunice , He Feng , Jain Sonia , Manuel Sandra , Langa Patrício V. , Sundararajan Radhika
Published: October 2021

Background

In Mozambique, HIV infection disproportionately affects young adults, particularly women. Despite awareness and knowledge of HIV transmission, many university students have not received HIV testing and continue to engage in high-risk sexual behaviors, including inconsistent condom use. Further understanding of patterns of engagement with HIV prevention and testing is key to reducing HIV transmission in this at-risk population.

Methods

This study used a sequential mixed methods approach to examine patterns of engagement and perceptions of HIV prevention and testing services among higher education students in Mozambique. Survey data were collected from a representative sample of 501 students from Universidade Eduardo Mondlane (UEM) in Maputo, Mozambique to assess the primary outcomes of 1) HIV testing within the last 12 months; and 2) condom use during last sexual encounter. We employed univariate and multivariate regression models. The survey was followed by qualitative interviews with 70 survey participants which were analyzed using an inductive, content-focused analysis to further explain and contextualize survey findings.

Results

Over 85% of students reported to be sexually active, among these 74% reported condom use during their last sexual encounter, and 64.2% reported an HIV test within the past 12 months. Females were more likely to have had HIV testing in the past 12 months in comparison to their male peers (aOR 1.82, 95% CI 1.11, 2.99), but were half as likely to have used a condom with their last sexual encounter (aOR 0.52, 95% CI 0.33, 0.83), when controlling for other factors. Qualitative data suggests that these discrepancies may be explained by differential perceptions in risk and trust/mistrust, with women being more concerned about infidelity by their male partner(s) and assuming more responsibility for knowing their own serostatus. Women were also subject to negative stereotypes for possessing condoms in comparison to men, which could explain lower propensity for use.

Conclusion

Given gendered differences in uptake of condom use and HIV testing, and perceived HIV risk, interventions tailored specifically to male and female students may impact engagement with HIV prevention and testing and empower informed choices about sexual behaviors.
The trajectories of depressive symptoms among working adults during the COVID-19 pandemic: a longitudinal analysis of the InHamilton COVID-19 study
Authors: Joshi Divya , Gonzalez Andrea , Griffith Lauren , Duncan Laura , MacMillan Harriet , Kimber Melissa , Vrkljan Brenda , MacKillop James , Beauchamp Marla , Kates Nick , Raina Parminder
Published: October 2021

Background

Longitudinal studies examining the impact of changes in COVID-19 pandemic-related stressors and experiences, and coping styles on the mental health trajectory of employed individuals during the lockdown are limited. The study examined the mental health trajectories of a sample of employed adults in Hamilton, Ontario during the initial lockdown and after the re-opening following the first wave in Canada. Further, this study also identified the pandemic-related stressors and coping strategies associated with changes in depressive symptoms in employed adults during the COVID-19 pandemic.

Methods

The InHamilton COVID-19 longitudinal study involved 579 employees aged 22–88 years from a large public university in an urban area of Hamilton, Ontario at baseline (April 2020). Participants were followed monthly with 6 waves of data collected between April and November 2020. A growth mixture modeling approach was used to identify distinct groups of adults who followed a similar pattern of depressive symptoms over time and to describe the longitudinal change in the outcome within and among the identified sub-groups.

Results

Our results showed two distinct trajectories of change with 66.2% of participants displaying low-consistent patterns of depressive symptoms, and 33.8% of participants displaying high-increasing depressive symptom patterns. COVID-19 pandemic-related experiences including health concerns, caregiving burden, and lack of access to resources were associated with worsening of the depressive symptom trajectories. Frequent use of dysfunctional coping strategies and less frequent use of emotion-focused coping strategies were associated with the high and increasing depressive symptom pattern.

Conclusions

The negative mental health impacts of the COVID-19 pandemic are specific to subgroups within the population and stressors may persist and worsen over time. Providing access to evidence-informed approaches that foster adaptive coping, alleviate the depressive symptoms, and promote the mental health of working adults is critical.
Evaluating the effectiveness and cost effectiveness of the ‘strengthening families, strengthening communities’ group-based parenting programme: study protocol and initial insights
Authors: Lodder Annemarie , Mehay Anita , Pavlickova Hana , Hoare Zoe , Box Leandra , Butt Jabeer , Weaver Tim , Crawford Mike J. , Clutterbuck Donna , Westbrook Nicola , Manning Karlet , Karlsen Saffron , Morris Steve , Brand Andrew , Ramchandani Paul , Kelly Yvonne , Heilmann Anja , Watt Richard G.
Published: October 2021

Background

Up to 20% of UK children experience socio-emotional difficulties which can have serious implications for themselves, their families and society. Stark socioeconomic and ethnic inequalities in children’s well-being exist. Supporting parents to develop effective parenting skills is an important preventive strategy in reducing inequalities. Parenting interventions have been developed, which aim to reduce the severity and impact of these difficulties. However, most parenting interventions in the UK focus on early childhood (0–10 years) and often fail to engage families from ethnic minority groups and those living in poverty. Strengthening Families, Strengthening Communities (SFSC) is a parenting programme designed by the Race Equality Foundation, which aims to address this gap. Evidence from preliminary studies is encouraging, but no randomised controlled trials have been undertaken so far.

Methods/design

The TOGETHER study is a multi-centre, waiting list controlled, randomised trial, which aims to test the effectiveness of SFSC in families with children aged 3–18 across seven urban areas in England with ethnically and socially diverse populations. The primary outcome is parental mental well-being (assessed by the Warwick-Edinburgh Mental Well-Being Scale). Secondary outcomes include child socio-emotional well-being, parenting practices, family relationships, self-efficacy, quality of life, and community engagement. Outcomes are assessed at baseline, post intervention, three- and six-months post intervention. Cost effectiveness will be estimated using a cost-utility analysis and cost-consequences analysis. The study is conducted in two stages. Stage 1 comprised a 6-month internal pilot to determine the feasibility of the trial. A set of progression criteria were developed to determine whether the stage 2 main trial should proceed. An embedded process evaluation will assess the fidelity and acceptability of the intervention.

Discussion

In this paper we provide details of the study protocol for this trial. We also describe challenges to implementing the protocol and how these were addressed. Once completed, if beneficial effects on both parental and child outcomes are found, the impact, both immediate and longer term, are potentially significant. As the intervention focuses on supporting families living in poverty and those from minority ethnic communities, the intervention should also ultimately have a beneficial impact on reducing health inequalities.

Trial registration

Prospectively registered Randomised Controlled Trial ISRCTN15194500.
Impact of child’s migration on health status and health care utilization of older parents with chronic diseases left behind in China
Authors: Liu Yuxin , Wang Jia , Yan Ziqi , Huang Rui , Cao Yan , Song Hongxun , Feng Da
Published: October 2021

Background

Adult child are used to taking the responsibility of taking care of their older parents in Chinese culture. However, the migration of adult child is not uncommon now in the context of urbanization in China. The purpose of this study is to explore the impact of child’s migration on health status and health care utilization of older parents with chronic diseases left behind.

Methods

The data of the 2015 nationally representative longitudinal survey of the aged population in China were used in this study. Binary logistic regression was used to evaluate the impact of adult child’s migration on health status and health care utilization of older parents with chronic diseases left behind.

Results

About a quarter of the respondents (25.5%) had at least one migrant child. Most of the respondents (86.6%) rated their health as poor, and 42.0% of them suffered from physical limitations. Nearly half of the respondents (45.0%) had depressive symptoms, but the vast majority (88.2%) were generally satisfied with their lives. Only a quarter of the respondents received outpatient treatment in the past month while only one fifth of them received inpatient visits in the past year. After controlling for other demographic and socioeconomic variables, it was found in this study that those who with migrant child were more likely to report poor self-rated health (OR = 1.26; 95% CI 1.01–1.58), not satisfied with general life (OR = 1.28; 95% CI 1.03–1.59) and seek outpatient visits (OR = 1.22; 95% CI 1.03–1.43) than those who without migrant child.

Conclusion

Our study found that there is a negative association between migration of adult child and physical health, mental health and health care utilization of older parents with chronic diseases left behind, which means a comprehensive effect on their health status. Further health policies should focus on improving the well-being of older parents with chronic diseases left behind.
A secular trend in age at menarche in Yunnan Province, China: a multiethnic population study of 1,275,000 women
Authors: Liu Wen , Yan Xuejing , Li Chengyu , Shu Qi , Chen Meng , Cai Le , You Dingyun
Published: October 2021

Background

Age at menarche (AAM) has shown different trends in women from different ethnic and economic regions in recent decades. Data on AAM among multiethnic women living in developing areas are scarce.

Methods

Data on AAM from 1,275,000 women among 26 ethnicities in Yunnan Province, China, who were born from 1965 to 2001 were obtained from the National Free Preconception Health Examination Project from 2010 to 2018. The patterns of AAM trends were analysed according to ethnic group, area of residence, and socioeconomic status.

Results

The mean AAM was 13.7 ± 1.21 years (95% CI 13.697–13.701), with a decrease from 14.12 (±1.41) among women born before 1970 to 13.3 (±1.04) among those born after 2000. The decline was 0.36 years per 10-year birth cohort, and the plateau has not yet been reached in Yunnan. A secular trend of earlier AAM was observed in all 26 ethnic groups. The fastest rate of decline was observed for the Bai ethnicity (0.36 years per decade). Consistent declining trends in AAM appeared among extreme-, middling-, and nonpoverty economic patterns from 1965 to 2001, with reductions of 1.19, 1.44, and 1.5 years, respectively (P < 0.001). The peak reduction among middling poverty and extreme poverty occurred in the early 2000s (0.4 and 0.32 years). Multivariate analysis showed a significant difference in the declining trends in AAM along rural/urban lines (P < 0.001).

Conclusion

There was a secular trend towards a younger AAM during the twentieth century and early twenty-first century birth cohorts in the Yunnan population. Considering the difference in AAM trends due to ethnic and socioeconomic status in Yunnan, the health authority should utilize flexible adjusted health care strategies in different regions.
Safety and efficacy of a single intra-articular injection of a novel enhanced protein solution (JTA-004) compared to hylan G-F 20 in symptomatic knee osteoarthritis: a randomized, double-blind, controlled phase II/III study
Authors: Bettonville Marie , Léon Marc , Margaux Joëlle , Urbin-Choffray Didier , Theunissen Emilie , Besse-Hammer Tatiana , Fortems Yves , Verlinden Séverine , Godeaux Olivier , Delmarcelle Anne-Sophie , Kaux Jean-François
Published: October 2021

Background

New minimally invasive treatments are vital to delay joint replacement surgery in patients with knee osteoarthritis. This study was designed to select the most effective among three formulations of an enhanced protein solution containing clonidine, hyaluronic acid, and human plasma (JTA-004), and compare the safety and efficacy of intra-articular administration of the selected formulation with a reference treatment (hyaluronic acid) in symptomatic knee osteoarthritis patients.

Methods

In this two-stage, double-blind, phase II/III study conducted in 12 Belgian centers, 50–79-year-old patients with primary knee osteoarthritis were randomized (1:1:1:1) to receive one dose of one of three JTA-004 formulations (differing in clonidine concentration [50 or 100 μg/ml] and volume [2 or 4 ml]) or the reference treatment (hylan G-F 20). Patients were evaluated using Western Ontario McMaster Universities (WOMAC®) Scores and the Short-Form health survey up to 6 months post-injection (Month 6). Drug consumption and safety were evaluated.

Results

Among 164 treated patients, 147 completed the study. The JTA-004 formulation containing 200 μg clonidine and 20 mg hyaluronic acid in 2 ml (JTA-200/2) was selected based on interim results at Month 6. The difference in adjusted mean change in WOMAC Pain Subscale Score from baseline (JTA-200/2 minus reference group) at Month 6 was − 9.49 mm; statistical superiority of JTA-200/2 over the reference was not demonstrated. No statistically significant differences in adjusted mean changes from baseline between JTA-200/2 and reference groups were observed for Pain, Physical Function and Stiffness Subscales WOMAC Scores, Total WOMAC Score, and Well-being Score at any timepoint, although JTA-200/2 induced larger improvements in WOMAC Scores than the reference. Statistically significantly larger improvements in WOMAC Pain Subscale Scores for JTA-004 versus the reference were observed in post-hoc analyses on pooled data from all JTA-004 formulations at Month 6 (p = 0.030) and Month 3 (p = 0.014). All JTA-004 formulations had clinically acceptable safety profiles.

Conclusions

This study provided preliminary evidence of the safety of intra-articular injection of JTA-004 in knee osteoarthritis patients. Phase III randomized controlled trials with larger sample sizes are needed to evaluate the efficacy of JTA-004 in knee osteoarthritis.

Trial registration

Clinicaltrials.gov/identifier NCT02740231;  clinicaltrialsregister.eu/identifier 2015–002117-30. Retrospectively registered 13/4/2016.
Pumpkin seed oil (Cucurbita pepo) versus tamsulosin for benign prostatic hyperplasia symptom relief: a single-blind randomized clinical trial
Authors: Zerafatjou Nikan , Amirzargar Mohammadali , Biglarkhani Mahdi , Shobeirian Farzaneh , Zoghi Ghazal
Published: October 2021

Background

Benign prostatic hyperplasia (BPH) is very common in aging men. We aimed to compare the effects of tamsulosin and pumpkin (Cucurbita pepo) seed oil on BPH symptoms.

Methods

This single-blind randomized clinical trial included patients with BPH aged ≥ 50 years referred to the Urology Clinic of Shahid Beheshti Hospital, Hamadan, Iran, from August 23, 2019 to February 19, 2020. Patients were randomized into two groups. One group received 0.4 mg tamsulosin every night at bedtime and the other received 360 mg pumpkin seed oil twice a day. Patients’ age, weight, height, and body mass index (BMI) were recorded. The International Prostate Symptom Score (IPSS) was filled out by the patients at baseline and then 1 month and 3 months after the initiation of treatment. The BPH-associated quality of life (QoL), serum prostate-specific antigen, prostate and postvoid residual volume, and maximum urine flow were also assessed at baseline and 3 months later. Drug side effects were also noted.

Results

Of the 73 patients included in this study with a mean age of 63.59 ± 7.04 years, 34 were in the tamsulosin group and 39 in the pupkin seed oil group. Patients were comparable with respect to age, weight, height, BMI, and baseline principal variables in both groups. Also, there was no significant difference between groups in terms of principal variables at any time point. However, there was a significant decrease in IPSS and a significant improvement in QoL in both groups. Although the decrease in IPSS from baseline to 1 month and 3 months was significantly higher in the tamsulosin group compared to the pumpkin group (P = 0.048 and P = 0.020, respectively), the decrease in IPSS from 1 to 3 months was similar (P = 0.728). None of the patients in the pumpkin group experienced drug side effects, while dizziness (5.9%), headache (2.9%), retrograde ejaculation (2.9%), and erythema with pruritus occurred in the tamsulosin group.

Conclusions

Pumpkin (Cucurbita pepo) seed oil relieved BPH symptoms with no side effects, but was not as effective as tamsulosin. Further studies are required to confirm the role of pumpkin seed oil as an option for the treatment of BPH symptoms.

Trial registration Iranian Registry of Clinical Trials, IRCT20120215009014N340. Registered 19.02.2020. Retrospectively registered, https://en.irct.ir/trial/45335.
Contribution of clinical breast exam to cancer detection in women participating in a modern screening program
Authors: Menes Tehillah S. , Coster Dan , Coster Daniel , Shenhar-Tsarfaty Shani
Published: October 2021

Purpose

Despite the controversy surrounding the role of clinical breast exam (CBE) in modern breast cancer screening, it is widely practiced. We examined the contribution of CBE in women undergoing routine screening mammography and in women under the screening age.

Methods

A retrospective cohort study including all women participating in a voluntary health screening program between 2007 and 2016. All participants undergo CBE; Screening mammography is done selectively based on age, breast imaging history and insurance coverage. Data collected included demographics, risk factors, previous imaging, and findings on CBE and mammography. Cancer detection rates within 3 months of the visit were calculated separately for women undergoing routine screening mammography, and women under the screening age.

Results

There were 14,857 CBE completed in 8378; women; 7% were abnormal. Within 3 months of the visit, 35 breast cancers (2.4 per 1000 visits) were diagnosed. In women within the screening age who completed a mammogram less than one year prior to the visit (N = 1898), 4 cancers (2.1 cancers per 1000 visits) were diagnosed. Only one was diagnosed in a woman with an abnormal CBE, suggesting that the cancer detection rate of CBE in women undergoing regular screening is very low (0.5 per 1000 visits). In women under the screening age (45), 3 cancers (0.4 per 1000 visits) were diagnosed; all were visualized on mammography, one had an abnormal CBE.

Conclusions

The contribution of CBE to cancer detection in women undergoing routine screening and in women under the screening age is rare.
Assessment of quality of routine health information system data and associated factors among departments in public health facilities of Harari region, Ethiopia
Authors: Shama Adisu Tafari , Roba Hirbo Shore , Abaerei Admas Abera , Gebremeskel Teferi Gebru , Baraki Negga
Published: October 2021

Background

Despite the improvements in the knowledge and understanding of the role of health information in the global health system, the quality of data generated by a routine health information system is still very poor in low and middle-income countries. There is a paucity of studies as to what determines data quality in health facilities in the study area. Therefore, this study was aimed to assess the quality of routine health information system data and associated factors in public health facilities of Harari region, Ethiopia.

Methods

A cross-sectional study was conducted in all public health facilities in the Harari region of Ethiopia. The department-level data were collected from respective department heads through document reviews, interviews, and observation checklists. Descriptive statistics were used to data quality and multivariate logistic regression was run to identify factors influencing data quality. The level of significance was declared at P value < 0.05.

Result

The study found good quality data in 51.35% (95% CI 44.6–58.1) of the departments in public health facilities in the Harari Region. Departments found in the health centers were 2.5 times more likely to have good quality data as compared to those found in the health posts. The presence of trained staffs able to fill reporting formats (AOR = 2.474; 95% CI 1.124–5.445) and provisions of feedbacks (AOR = 3.083; 95% CI 1.549–6.135) were also significantly associated with data quality.

Conclusion

The level of good data quality in the public health facilities was less than the expected national level. Lack of trained personnel able to fill the reporting format and feedback were the factors that are found to be affecting data quality. Therefore, training should be provided to increase the knowledge and skills of the health workers. Regular supportive supervision and feedback should also be maintained.
Healthcare utilization and cost of cancer-related care prior to allogeneic hematopoietic cell transplantation for hematologic malignancies in the US: a retrospective real-world analysis
Authors: Bonafede Machaon , Anaissie Elias , Evans Kristin , Itzler Robbin
Published: October 2021

Background

Hematopoietic cell transplantation (HCT) is a potentially curative therapy as well as a costly procedure. Published studies have examined the cost of HCT in the US and the complications that follow but little is known about the cancer-related healthcare costs and resource utilization prior to the procedure and none of the studies have examined the variability in cost based on the type of hematologic malignancy involved. The aim of this study was to estimate mean cancer-related costs and resources incurred before the HCT is performed from the time the hematologic malignancy first develops.

Methods

The IBM® MarketScan® Research Databases were used to identify adult patients ≥18 years of age with commercial or Medicare supplemental insurance who had undergone allogeneic HCT for hematologic malignancies from January 1, 2008 to December 31, 2017. Healthcare utilization and costs were assessed during the 6 months prior to diagnosis (pre-diagnostic period) and the follow-up period from diagnosis just prior to the HCT (pre-HCT period). Multivariable regression models were constructed to estimate total all-cause costs and cancer-related costs as well as healthcare utilization by type in each time period.

Results

A total of 2663 commercially insured patients and 266 with Medicare supplemental insurance were included in the study population. The mean-adjusted incremental cancer-related costs for commercially insured patients was $399,011 in the overall observation period including the pre-diagnostic and pre-HCT periods combined, 9% of which was incurred in the pre-diagnostic period. The corresponding mean-adjusted incremental cancer-related costs for Medicare supplemental patients was $195,575 for the same time period but the patterns of healthcare utilization were similar to the commercially insured population. Inpatient care accounted for approximately one-half the cost in both patient populations. By type of hematologic malignancy, costs were lowest for myeloproliferative disorders ($211,561) and highest for acute lymphocytic leukemia ($462,072) in the commercially insured population.

Conclusion

This study demonstrates that overall patients with hematologic malignancies requiring HCT have considerable cancer-related healthcare resource utilization and costs leading up to HCT compared to the period of time prior to developing cancer.
Potentiation of long-acting β2-agonist and glucocorticoid responses in human airway epithelial cells by modulation of intracellular cAMP
Authors: Kim Yechan , Hou Vincent , Huff Ryan D. , Aguiar Jennifer A. , Revill Spencer , Tiessen Nicholas , Cao Quynh , Miller Matthew S. , Inman Mark D. , Ask Kjetil , Doxey Andrew C. , Hirota Jeremy A.
Published: October 2021

Introduction

Over 300 million people in the world live with asthma, resulting in 500,000 annual global deaths with future increases expected. It is estimated that around 50–80% of asthma exacerbations are due to viral infections. Currently, a combination of long-acting beta agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lung inflammation represent the dominant strategy for the management of asthma, however, it is still sub-optimal in 35–50% of moderate-severe asthmatics resulting in persistent lung inflammation, impairment of lung function, and risk of mortality. Mechanistically, LABA/GCS combination therapy results in synergistic efficacy mediated by intracellular cyclic adenosine monophosphate (cAMP).

Hypothesis

Increasing intracellular cAMP during LABA/GCS combination therapy via inhibiting phosphodiesterase 4 (PDE4) and/or blocking the export of cAMP by ATP Binding Cassette Transporter C4 (ABCC4), will potentiate anti-inflammatory responses of mainstay LABA/GCS therapy.

Methods

Expression and localization experiments were performed using in situ hybridization and immunohistochemistry in human lung tissue from healthy subjects, while confirmatory transcript and protein expression analyses were performed in primary human airway epithelial cells and cell lines. Intervention experiments were performed on the human airway epithelial cell line, HBEC-6KT, by pre-treatment with combinations of LABA/GCS with PDE4 and/or ABCC4 inhibitors followed by Poly I:C or imiquimod challenge as a model for viral stimuli. Cytokine readouts for IL-6, IL-8, CXCL10/IP-10, and CCL5/RANTES were quantified by ELISA.

Results

Using archived human lung and human airway epithelial cells, ABCC4 gene and protein expression were confirmed in vitro and in situ. LABA/GCS attenuation of Poly I:C or imiquimod-induced IL-6 and IL-8 were potentiated with ABCC4 and PDE4 inhibition, which was greater when ABCC4 and PDE4 inhibition was combined. Modulation of cAMP levels had no impact on LABA/GCS modulation of Poly I:C-induced CXCL10/IP-10 or CCL5/RANTES.

Conclusion

Modulation of intracellular cAMP levels by PDE4 or ABCC4 inhibition potentiates LABA/GCS efficacy in human airway epithelial cells challenged with viral stimuli. The data suggest further exploration of the value of adding cAMP modulators to mainstay LABA/GCS therapy in asthma for potentiated anti-inflammatory efficacy.
Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF
Authors: Decaris Martin L. , Schaub Johanna R. , Chen Chun , Cha Jacob , Lee Gail G. , Rexhepaj Megi , Ho Steve S. , Rao Vikram , Marlow Megan M. , Kotak Prerna , Budi Erine H. , Hooi Lisa , Wu Jianfeng , Fridlib Marina , Martin Shamra P. , Huang Shaoyi , Chen Ming , Muñoz Manuel , Hom Timothy F. , Wolters Paul J. , Desai Tushar J. , Rock Fernando , Leftheris Katerina , Morgans David J. , Lepist Eve-Irene , Andre Patrick , Lefebvre Eric A. , Turner Scott M.
Published: October 2021

Rationale

αv integrins, key regulators of transforming growth factor-β activation and fibrogenesis in in vivo models of pulmonary fibrosis, are expressed on abnormal epithelial cells (αvβ6) and fibroblasts (αvβ1) in fibrotic lungs.

Objectives

We evaluated multiple αv integrin inhibition strategies to assess which most effectively reduced fibrogenesis in explanted lung tissue from patients with idiopathic pulmonary fibrosis.

Methods

Selective αvβ6 and αvβ1, dual αvβ6/αvβ1, and multi-αv integrin inhibitors were characterized for potency, selectivity, and functional activity by ligand binding, cell adhesion, and transforming growth factor-β cell activation assays. Precision-cut lung slices generated from lung explants from patients with idiopathic pulmonary fibrosis or bleomycin-challenged mouse lungs were treated with integrin inhibitors or standard-of-care drugs (nintedanib or pirfenidone) and analyzed for changes in fibrotic gene expression or TGF-β signaling. Bleomycin-challenged mice treated with dual αvβ6/αvβ1 integrin inhibitor, PLN-74809, were assessed for changes in pulmonary collagen deposition and Smad3 phosphorylation.

Measurements and main results

Inhibition of integrins αvβ6 and αvβ1 was additive in reducing type I collagen gene expression in explanted lung tissue slices from patients with idiopathic pulmonary fibrosis. These data were replicated in fibrotic mouse lung tissue, with no added benefit observed from inhibition of additional αv integrins. Antifibrotic efficacy of dual αvβ6/αvβ1 integrin inhibitor PLN-74809 was confirmed in vivo, where dose-dependent inhibition of pulmonary Smad3 phosphorylation and collagen deposition was observed. PLN-74809 also, more potently, reduced collagen gene expression in fibrotic human and mouse lung slices than clinically relevant concentrations of nintedanib or pirfenidone.

Conclusions

In the fibrotic lung, dual inhibition of integrins αvβ6 and αvβ1 offers the optimal approach for blocking fibrogenesis resulting from integrin-mediated activation of transforming growth factor-β.