bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a theory-based HPV vaccine promotion comic book for East African adolescents in the US
Authors: Celentano Isabelle , Winer Rachel L. , Jang Sou Hyun , Ibrahim Anisa , Mohamed Farah Bille , Lin John , Amsalu Fanaye , Ali Ahmed A. , Taylor Victoria M. , Ko Linda K.
Published: June 2021

Background

Human Papillomavirus (HPV) vaccine uptake is low among East African adolescents in the US. Adolescents’ preferences influence HPV vaccine decisions, yet few interventions exist that address East African adolescents’ beliefs about HPV vaccines. We describe a multi-step process on how to create a theory-based comic book by integrating empirical findings, theory and focus group data from East African parents in the US.

Methods

Our multi-methods process included conducting focus groups with Somali, Ethiopian, and Eritrean mothers (n = 30) to understand mothers and adolescents socio-cultural beliefs and information needs about the HPV vaccine, creating comic book messages integrating the focus group findings, and assessing the acceptability of the finalized comic book among Somali, Ethiopian, and Eritrean adolescents (n = 134).

Results

We identified categories around socio-cultural beliefs (such ethnic representation and concerns about pork gelatin in vaccines), HPV vaccine information needs, and diffusion of information. We then mapped the categories to theoretical constructs and operationalized them into the comic book. Finally, we describe the overall acceptability of the comic book and specifics on comic book structure, appeal of characters, and message relevance.

Conclusions

A rigorous multi-step process that integrates theory and focus group data can help create culturally appropriate health messages that can educate and appeal to the community.
Dietary, physical exercises and mental stress in a Chinese population: a cross-sectional study
Authors: Li Xiaona , Tian Dan , Qin Pei , Guo Wen , Lu Jing , Zhu Wenfang , Zhang Qun , Wang Jianming
Published: June 2021

Background

Mental health is affected by both genetic and environmental factors. However, previous studies have showed conflict findings about the role of lifestyle and little is known about the situation of the Chinese population. The purpose of this study was to explore the relationship between the frequency of food consumption, physical exercise condition and mental health, as well as factors related to mental stress in Chinese.

Methods

We recruited 8160 residents who had health examinations in a public hospital during June 2016 to May 2018. Demographic characteristics, the frequency of food consumption, physical exercise condition and mental health status was collected by a questionnaire. We estimated the association using the odds ratio (OR) and 95% confidence interval (CI) based on Binary or ordinal logistic regression models. A classification and regression tree (CART) demonstrated the prediction of the value of a target variable based on other values.

Results

The logistic regression model and classification tree model both found that the frequency of fresh vegetables or fruit and fried foods consumption and the current state of drinking alcohol were related to mental stress. The degree of mental stress reduced significantly with increasing consumption of fish (OR = 0.80, 95% CI: 0.71–0.90) and regular exercise (OR = 0.55, 95% CI:0.48–0.64) in females and increased consumption of fish (OR = 0.55, 95% CI: 0.48–0.64) and cereal crop (OR = 0.77, 95% CI: 0.68–0.89), fish (OR = 0.87, 95%CI:0.77–0.96) and regular exercise (OR = 0.61, 95%CI:0.53–0.70) in males. On the contrary, the frequency of consumption of desserts (OR = 1.43, 95% CI: 1.26–1.62) and the current of drinking alcohol (OR = 1.47, 95%CI:1.21–1.79) in females and meat (OR = 1.47, 95%CI: 1.31–1.65), pickled and smoked food (OR = 1.18, 95%CI:1.05–1.32) and the current state of drinking alcohol (OR = 1.25, 95%CI:1.12–1.40) in males were related to an increased risk of mental health.

Conclusions

Our study showed that both the frequency of some food consumption and physical exercise condition were associated with mental health and affected the degree of stress, which provided novel insights into interventions.
Change in medical practice over time? A register based study of regional trends in hysterectomy in Finland in 2001–2018
Authors: Vikstedt Tiina , Arffman Martti , Heliövaara-Peippo Satu , Manderbacka Kristiina , Reissell Eeva , Keskimäki Ilmo
Published: June 2021

Background

A persistent research finding in Finland and elsewhere has been variation in medical practices both between and within countries. Variation seems to exist especially if medical decision making involves discretion and the best treatment cannot be identified unambiguously. This is true for hysterectomy when performed for benign causes. The aim of the current study was to investigate regional trends in hysterectomy in Finland and the potential convergence of rates over time.

Methods

We used hospital discharge register data on hysterectomies performed, diagnoses, age, and region of residence to examine hospital discharges for women undergoing hysterectomy in 2001–2018 among total female population aged 25 years or older in Finland. We examined hysterectomy rates among biannual cohorts by indication, calculated age-standardised rates and used multilevel models to analyse potential convergence over time.

Results

Altogether 131,695 hysterectomies were performed in Finland 2001–2018. We found a decreasing trend, with the age-adjusted overall hysterectomy rate decreasing from 553/100,000 person years in 2001–2002 to 289/100,000 py in 2017–2018. Large but converging regional differences were found. The correlations between hospital district intercepts and slopes in time ranged from − 0.71 to − 0.97 (p < 0.001) suggesting diminishing variation.

Conclusions

Our findings demonstrate that change in hysterectomy practices and more uniformity across regions are achievable goals. Regional variation still exists suggesting differences in medical practices.
Nurses in the lead: a qualitative study on the development of distinct nursing roles in daily nursing practice
Authors: van Schothorst–van Roekel Jannine , Weggelaar-Jansen Anne Marie J.W.M. , Hilders Carina C.G.J.M. , De Bont Antoinette A. , Wallenburg Iris
Published: June 2021

Background

Transitions in healthcare delivery, such as the rapidly growing numbers of older people and increasing social and healthcare needs, combined with nursing shortages has sparked renewed interest in differentiations in nursing staff and skill mix. Policy attempts to implement new competency frameworks and job profiles often fails for not serving existing nursing practices. This study is aimed to understand how licensed vocational nurses (VNs) and nurses with a Bachelor of Science degree (BNs) shape distinct nursing roles in daily practice.

Methods

A qualitative study was conducted in four wards (neurology, oncology, pneumatology and surgery) of a Dutch teaching hospital. Various ethnographic methods were used: shadowing nurses in daily practice (65h), observations and participation in relevant meetings (n=56), informal conversations (up to 15 h), 22 semi-structured interviews and member-checking with four focus groups (19 nurses in total). Data was analyzed using thematic analysis.

Results

Hospital nurses developed new role distinctions in a series of small-change experiments, based on action and appraisal. Our findings show that: (1) this developmental approach incorporated the nurses’ invisible work; (2) nurses’ roles evolved through the accumulation of small changes that included embedding the new routines in organizational structures; (3) the experimental approach supported the professionalization of nurses, enabling them to translate national legislation into hospital policies and supporting the nurses’ (bottom-up) evolution of practices. The new roles required the special knowledge and skills of Bachelor-trained nurses to support healthcare quality improvement and connect the patients’ needs to organizational capacity.

Conclusions

Conducting small-change experiments, anchored by action and appraisal rather than by design, clarified the distinctions between vocational and Bachelor-trained nurses. The process stimulated personal leadership and boosted the responsibility nurses feel for their own development and the nursing profession in general. This study indicates that experimental nursing role development provides opportunities for nursing professionalization and gives nurses, managers and policymakers the opportunity of a ‘two-way-window’ in nursing role development, aligning policy initiatives with daily nursing practices.
New familial cases of karyomegalic interstitial nephritis with mutations in the FAN1 gene
Authors: Rejeb Imen , Jerbi Mouna , Jilani Houweyda , Gaied Hanène , Elaribi Yasmina , Hizem Syrine , Aoudia Raja , Hedri Hafedh , Zaied Chiraz , Abid Salwa , Bacha Hassen , BenAbdallah Taieb , BenJemaa Lamia , Goucha Rim
Published: June 2021

Background

Karyomegalic interstitial nephritis (KIN) is a rare disease entity first described by Burry in 1974. The term KIN was introduced by Mihatsch et al. in 1979. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to a progressive decline of renal function. The prevalence of this disease is less than 1% of all biopsies, and its pathogenesis is unclear. KIN results from mutations in FAN1 (FANCD2/FANCI-Associated Nuclease 1), a gene involved in the DNA damage response pathway, particularly in the kidney. In this study, we report two Tunisian consanguineous families with KIN caused by mutations in the FAN1 gene.

Methods

Direct sequencing of the coding regions and flanking intronic sequences of the FAN1 gene was performed in three affected members. Three prediction programs (Polyphen-2 software, SIFT, and MutationTaster) were used to predict the functional effect of the detected variations.

Results

Two causative frameshift variants in the FAN1 gene were identified in each family: The previously described frameshift mutation c.2616delA (p.Asp873ThrfsTer17) and a novel mutation c.2603delT (p.Leu868ArgfsTer22) classified as "pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines.

Conclusion

To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations in the FAN1 gene. We hypothesize that these findings can expand the mutational spectrum of KIN and provide valuable information on the genetic cause of KIN.
SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells
Authors: Mo Yuqing , Ye Ling , Cai Hui , Zhu Guiping , Wang Jian , Zhu Mengchan , Song Xixi , Yang Chengyu , Jin Meiling
Published: June 2021

Background

Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells.

Methods

Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus.

Results

Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells.

Conclusion

Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.
Nanoconjugates to enhance PDT-mediated cancer
immunotherapy by targeting the indoleamine-2,3-dioxygenase pathway
Authors: Yang Xueyuan , Zhang Weizhong , Jiang Wen , Kumar Anil , Zhou Shiyi , Cao Zhengwei , Zhan Shuyue , Yang Wei , Liu Rui , Teng Yong , Xie Jin
Published: June 2021

Background

Photodynamic therapy (PDT) may elicit antitumor immune response in addition to killing cancer cells. However, PDT as a monotherapy often fails to induce a strong immunity. Immune checkpoint inhibitors, which selectively block regulatory axes, may be used in combination with PDT to improve treatment outcomes. Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme and an important meditator of tumor immune escape. Combination therapy with PDT and IDO-targeted immune checkpoint blockage is promising but has been seldom been explored.

Methods

Herein we report a composite nanoparticle that allows for simultaneous delivery of photosensitizer and IDO inhibitor. Briefly, we separately load ZnF16Pc, a photosensitizer, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, into ferritin and poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PEG-PLGA) nanoparticles; we then conjugate these two compartments to form a composite nanoparticle referred to as PPF NPs. We tested combination treatment with PPF NPs first in vitro and then in vivo in B16F10-tumor bearing C57/BL6 mice.

Results

Our results showed that PPF NPs can efficiently encapsulate both ZnF16Pc and NLG919. In vivo studies found that the combination treatment led to significantly improved tumor suppression and animal survival. Moreover, the treatment increased tumor infiltration of CD8+ T cells, while reducing frequencies of MDSCs and Tregs. 30% of the animals showed complete tumor eradication, and they successfully rejected a second tumor inoculation. Overall, our studies introduce a unique composite nanoplatform that allows for co-delivery of photosensitizer and IDO inhibitor with minimal inter-species interference, which is ideal for combination therapy.
Acute cardiovascular effects of controlled exposure to dilute Petrodiesel and biodiesel exhaust in healthy volunteers: a crossover study
Authors: Unosson Jon , Kabéle Mikael , Boman Christoffer , Nyström Robin , Sadiktsis Ioannis , Westerholm Roger , Mudway Ian S. , Purdie Esme , Raftis Jennifer , Miller Mark R. , Mills Nicholas L. , Newby David E. , Blomberg Anders , Sandström Thomas , Bosson Jenny A.
Published: June 2021

Background

Air pollution derived from combustion is associated with considerable cardiorespiratory morbidity and mortality in addition to environmental effects. Replacing petrodiesel with biodiesel may have ecological benefits, but impacts on human health remain unquantified.

The objective was to compare acute cardiovascular effects of blended and pure biodiesel exhaust exposure against known adverse effects of petrodiesel exhaust (PDE) exposure in human subjects.

In two randomized controlled double-blind crossover studies, healthy volunteers were exposed to PDE or biodiesel exhaust for one hour. In study one, 16 subjects were exposed, on separate occasions, to PDE and 30% rapeseed methyl ester biodiesel blend (RME30) exhaust, aiming at PM10 300 μg/m3. In study two, 19 male subjects were separately exposed to PDE and exhaust from a 100% RME fuel (RME100) using similar engine load and exhaust dilution. Generated exhaust was analyzed for physicochemical composition and oxidative potential. Following exposure, vascular endothelial function was assessed using forearm venous occlusion plethysmography and ex vivo thrombus formation was assessed using a Badimon chamber model of acute arterial injury. Biomarkers of inflammation, platelet activation and fibrinolysis were measured in the blood.

Results

In study 1, PDE and RME30 exposures were at comparable PM levels (314 ± 27 μg/m3; (PM10 ± SD) and 309 ± 30 μg/m3 respectively), whereas in study 2, the PDE exposure concentrations remained similar (310 ± 34 μg/m3), but RME100 levels were lower in PM (165 ± 16 μg/m3) and PAHs, but higher in particle number concentration. Compared to PDE, PM from RME had less oxidative potential. Forearm infusion of the vasodilators acetylcholine, bradykinin, sodium nitroprusside and verapamil resulted in dose-dependent increases in blood flow after all exposures. Vasodilatation and ex vivo thrombus formation were similar following exposure to exhaust from petrodiesel and the two biodiesel formulations (RME30 and RME100). There were no significant differences in blood biomarkers or exhaled nitric oxide levels between exposures.

Conclusions

Despite differences in PM composition and particle reactivity, controlled exposure to biodiesel exhaust was associated with similar cardiovascular effects to PDE. We suggest that the potential adverse health effects of biodiesel fuel emissions should be taken into account when evaluating future fuel policies.

Trial registration

ClinicalTrials.gov, NCT01337882/NCT01883466. Date of first enrollment March 11, 2011, registered April 19, 2011, i.e. retrospectively registered.
Breastfeeding and employed mothers in Ethiopia: legal protection, arrangement, and support
Authors: Kebede Ermiyas Mulu , Seifu Benyam
Published: June 2021

Background

Breastfeeding is the single, most cost-effective intervention to reduce worldwide child mortality. Women empowerment interventions have positive impacts on child and maternal nutritional, and health status. Women’s employment and economic participation in Ethiopia have shown progress over the past three decades. However, consistent evidence indicated that maternal employment is often negatively associated with optimal breastfeeding in Ethiopia. The existence and enforcement of breastfeeding law, arrangement, and support in the workplace have vital roles in protecting employed mothers’ ability and right to breastfeed upon return to work from maternity leave. This commentary compared the breastfeeding laws, policies, and arrangements in Ethiopia with international standards, recommendations, and evidence-based practices.

Workplace breastfeeding policies in Ethiopia

Public legislations of Ethiopia poorly protect the breastfeeding right of most new mothers. Ethiopian revised Labor Proclamation (No.1156/2019) incorporates most of the International Labour Organization maternity protection recommendations. However, it poorly safeguards breastfeeding rights and abilities of employed women. The provided maternity leave period is also shorter than the recommended exclusive breastfeeding duration. The revised Federal Civil Servant Proclamation of Ethiopia (NO.1064/2017) mandates the establishment of a nursery in government institutions where female civil servants could breastfeed and take care of their babies in a private room. Though, it protects only a small proportion of working mothers in Ethiopia, as majority women employed in the agriculture and informal economy sectors. So far, there are no notable workplace breastfeeding arrangements and support for employed mothers by employers and other initiatives. The ILO recommendation and experience of other middle income and low-income countries can be legal and practical grounds for establishment of breastfeeding-friendly workplace in Ethiopia.

Conclusions

The lack of workplace breastfeeding laws, arrangements, and supports in Ethiopia limits mothers’ right to practice optimal breastfeeding. Policymakers, the government, and all concerned bodies should give due attention to enacting and enforcing sound laws and arrangements that will enable employed mothers to practice optimal breastfeeding upon return to work.
Biportal endoscopic posterior lumbar decompression and vertebroplasty for extremely elderly patients affected by lower lumbar delayed vertebral collapse with lumbosacral radiculopathy
Authors: Kang Min-Seok , Heo Dong-Hwa , Chung Hoon-Jae , You Ki-Han , Kim Hyong-Nyun , Choi Jun-Young , Park Hyun-Jin
Published: June 2021

Background

Lower lumbar osteoporotic vertebral compression fracture in extremely elderly patients can often lead to lumbosacral radiculopathy (LSR) due to delayed vertebral collapse (DVC). Surgical intervention requires posterior instrumented lumbar fusion as well as vertebral augmentation or anterior column reconstruction depending on the cleft formation and intravertebral instability. However, it is necessary to decide on surgery in consideration of the patient’s frail status, surgical invasiveness, and rehabilitation. In the lower lumbar DVC without intravertebral instability, biportal endoscopic posterior lumbar decompression and vertebroplasty (BEPLD + VP) can be simultaneously attempted. This study aimed to assess the clinical outcomes of BEPLD + VP for the treatment of DVC-related LSR.

Methods

This retrospective case series enrolled 18 consecutive extremely elderly (aged ≥ 75-year-old) patients (6 men and 12 women) who had lower lumbar (at or below L3) DVC-related LSR. Patients who require anterior column reconstruction, such as cleft formation accompanied by intravertebral instability and patients who have not been followed for more than 6 months, were excluded from this study. All patients underwent BEPLD + VP under epidural anesthesia. Clinical results were evaluated by the visual analog scale (VAS) score and the modified Japanese Orthopedic Association (mJOA) scores.

Results

Most of the patients had DVC affecting level L4, with the deformation being a flat type or concave type rather than a wedge type. The VAS score (back and leg) significantly decreased from 7.78 ± 1.17 and 6.89 ± 1.13 preoperatively to 2.94 ± 0.64 and 2.67 ± 1.08 within 2 postoperative days (p < 0.001). The mJOA score significantly improved from 4.72 ± 1.27 preoperatively to 8.17 ± 1.15 in the final follow-up (p < 0.001). The mean recovery rate (RR) in the last follow-up was 56.07% ± 9.98. Incidental durotomy was reported in two patients and epidural hematomas in another two patients; however, all patients improved with conservative treatment, and no re-operation was required.

Conclusions

BELPD + VP was a type of salvage therapy that reduces surgical morbidity, requires major spine surgery under general anesthesia and provides good clinical outcomes in extremely elderly patients with DVC-related LSR.
Sleep and physical activity patterns in adults and children with Bardet–Biedl syndrome
Authors: Pomeroy Jeremy , VanWormer Jeffrey J. , Meilahn Jill R. , Maki Tara , Murali Hema R. , Haws Robert M.
Published: June 2021

Background

Overweight and obesity are common features of the rare disease Bardet–Biedl syndrome (BBS). Sleep and physical activity are behaviors that might impact overweight and obesity and thus may play a key role in the health and well-being of people with BBS. Objectively-measured sleep and physical activity patterns in people with BBS are not well known. We evaluated objectively-measured sleep and physical activity patterns in the largest cohort to date of people with BBS.

Results

Short sleep duration, assessed using wrist-worn accelerometers, was common in both children and adults with BBS. Only 7 (10%) of adults and 6 (8%) of children met age-specific sleep duration recommendations. Most adults 64 (90%) achieved recommended sleep efficiency. The majority of children 26 (67%) age 6–12 years achieved recommended sleep efficiency, but among children age 13–18, only 18 (47%). In both adults and children, sleep duration was significantly negatively correlated with duration of prolonged sedentary time. In children age 6–12 sleep duration was also significantly related to total activity score, children with lower sleep duration had lower total activity scores.

Conclusions

Insufficient sleep duration is very common in people with BBS. Prolonged sedentary time and short sleep duration are both potentially important health-related behaviors to target for intervention in people with BBS.
Sequential everolimus for angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study
Authors: Gu Liangyou , Peng Cheng , Zhang Fan , Fang Cunjin , Guo Gang
Published: June 2021

Background

To evaluate the efficacy, safety and health economics of sequential everolimus in treating angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC).

Methods

In this prospective cohort study, patients met the inclusion criteria received standard or sequential treatment according to their willingness. All patients received an initial dose of everolimus (10 mg oral, once a day) for 3 months. The standard treatment group maintained 10 mg QD for 12 months, while the sequential treatment group reduced the dose to 5 mg QD from the 4th month. The efficacy, serum everolimus concentration and safety were evaluated at 1, 3, 6, 9 and 12 months after treatment. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in the total volume of target AML relative to baseline.

Results

Between June 1, 2016 and June 1, 2017, a total of 53 patients were included. Twenty-three patients received standard treatment, 30 patients received sequential treatment. At 1, 3, 6, 9 and 12 months after treatment, the proportion of patients whose total target tumor volume decreased by ≥ 50% from baseline was 39.1% versus 36.7%, 43.5% versus 56.7%, 47.8% versus 50%, 47.8% versus 60% and 47.8% versus 23.3% respectively (P > 0.05 for all). The overall response rate of skin lesions in the two groups was 40.4%, and the response rates of skin lesions at different times were similar for two groups (P > 0.05 for all). Major adverse effects (AEs) included mouth ulceration, hypertriglyceridemia, hypercholesterolemia, menstrual disorders. There was no significant difference between the two groups in the incidence of AEs at 3 months after treatment. The incidence of overall and grade 3/4 AEs at 12 months after treatment were significantly lower in the sequential treatment group. The average direct cost of the two groups in 12 months was $15,466 and $11,120, respectively.

Conclusions

Compared to standard treatment, sequential treatment was equally effective, with a lower incidence of adverse events and a lower direct cost, suggesting that it may be an alternative treatment for AML associated with TSC.
Discordant structural chromosomal aberrations in chorionic villi and amniotic fluid leading to a formation of an isochromosome 21: a case report
Authors: Westenius Eini , Pettersson Maria , Björck Erik
Published: June 2021

Background

Fetoplacental discrepancies occur in approximately 1–2% of analyzed prenatal cases. They are typically due to confined placental mosaicism, where an aberration is observed in the placental cells but not found in the fetal cells. Confined placental mosaicism usually involves aneuploidies and more sparsely structural chromosomal aberrations. To the best of our knowledge, this is the first reported case of a discrepancy in the analyses of chorionic villus sampling and amniocentesis involving two different structural chromosomal aberrations of chromosome 21.

Case presentation

We report a 33-year-old woman who was referred for a non-invasive prenatal testing due to an increased risk of trisomy 21 gleaned from a combined ultrasound and blood test. The non-invasive prenatal testing showed an increased risk of trisomy 21 with a normalized coverage signal that did not match the fetal cell-free DNA fraction. Rapid aneuploidy detection performed on uncultured chorionic villi indicated mosaicism for trisomy 21. The follow-up analyses revealed discordant chromosomal aberrations: 46,XY,der(21)t(10;21)(p11.21;q10) in the analysis of the chorionic villus sampling and 46,XY, + 21,der(21;21)(q10;q10) in the analysis of the amniocentesis. Thus, the analyses indicated mosaicism for a cell line containing trisomy 21 and a cell line containing a partially duplicated short arm of chromosome 10 in the chorionic villi and complete trisomy 21 resulting from an isochromosome 21 in the amniotic fluid. The analyses of the lymphocytes and the fibroblasts of the woman were normal.

Conclusions

We propose a multiple-step mechanism as a possible theoretical explanation for the formation of these discordant structural chromosomal aberrations in the chorionic villi and amniotic fluid. With this case report, we want to highlight the importance of understanding the possible underlying embryological mechanisms when interpreting results from different prenatal analyses.
Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases
Authors: Pang Yu , Wang Chaohong , Tang Junxiang , Zhu Jiansheng
Published: June 2021

Objective

To assess the detection efficiency of noninvasive prenatal testing (NIPT) for fetal autosomal aneuploidy, sex chromosome aneuploidy (SCA), other chromosome aneuploidy, copy number variation (CNV), and to provide further data for clinical application of NIPT.

Materials and methods

25,517 pregnant women who underwent NIPT testing in Anhui Province Maternity and Child Health Hospital from September 2019 to September 2020 were selected, and samples with high-risk test results were subjected to karyotype analysis for comparison by using amniotic fluid, with some samples subjected to further validation by chromosomal microarray analysis, and followed up for pregnancy outcome.

Results

A total of 25,517 pregnant women who received NIPT, 25,502 cases were tested successfully, and 294 high-risk samples (1.15%) were detected, there were 96 true positive samples, 117 false positive samples and 81 cases were refused further diagnosis. Samples with high risk of autosomal aneuploidy were detected in 71 cases (0.28%), and 51 cases were confirmed, including: trisomy 21 (T21) in 44 cases, trisomy 18 (T18) in 5 cases, and trisomy 13 (T13) in 2 cases; the positive predictive value (PPV) was 91.67%, 45.45%, and 33.33%, respectively, and the negative predictive value was 100%, the false positive rate (FPR) was 0.02%, 0.02%, and 0.02%, respectively.13 samples with high risk of mosaic trisomies 21, 18, and 13 were detected, and 1 case of T21mos was confirmed with a PPV of 8.33%. Samples with high risk of SCA were detected in 72 cases (0.28%), and the diagnosis was confirmed in 23 cases, with a PPV of 41.07% and a FPR of 0.13%. These included 3 cases of 45,X, 6 cases of 47,XXY, 8 cases of 47,XXX and 6 cases of 47,XYY, with PPVs of 12.00%, 50.00%, 72.73%, and 75.00%, respectively, and false-positive rates of 0.09%, 0.02%, 0.01% and 0.01% respectively. Samples with high risk of CNV were detected in 104 cases (0.41%) and confirmed in 18 cases, with a PPV of 32.14% and a FPR of 0.15%. Samples with high risk of other chromosomal aneuploidy were detected in 34 cases (0.13%), and the diagnosis was confirmed in 3 cases, which were T2, T9, and T16 respectively. The overall PPV for other chromosome aneuploidy was 12.50%, with a FPR of 0.08%.

Conclusion

NIPT is indicated for trisomies 21, 18 and 13 screening, especially for T21. It also has some certain reference value for SCA and CNV, but is not recommended for screening of other chromosomal aneuploidy.
Molecular laterality encodes stress susceptibility in the medial prefrontal cortex
Authors: Chae Sujin , Hong Jiso , Kang Keunsoo , Shin Anna , Kim Dae-Gun , Lee Sinjeong , Kim Moo-young , Jung Inkyung , Kim Daesoo
Published: June 2021

Functional lateralization of the prefrontal cortex has been implicated in stress and emotional disorders, yet underlying gene expression changes remains unknown. Here, we report molecular signatures lateralized by chronic social defeats between the two medial prefrontal cortices (mPFCs). Stressed mice show 526 asymmetrically expressed genes between the mPFCs. This cortical asymmetry selectively occurs in stressed mice with depressed social activity, but not in resilient mice with normal behavior. We have isolated highly asymmetric genes including connective tissue growth factor (CTGF), a molecule that modulates wound healing at the periphery. Knockdown of CTGF gene in the right mPFC by shRNA led to a stress-resistant behavioral phenotype. Overexpression of CTGF in the right mPFC using viral transduction induces social avoidance while the left mPFC thereof prevent stress-induced social avoidance. Our study provides a molecular window into the mechanism of stress-induced socioemotional disorders, which can pave the way for new interventions by targeting cortical asymmetry.
The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia
Authors: Krüger Renata L. , Clark Cameron M. , Dyck Adrienna M. , Anderson Todd J. , Clement Fiona , Hanly Patrick J. , Hanson Heather M. , Hill Michael D. , Hogan David B. , Holroyd-Leduc Jayna , Longman R. Stewart , McDonough Meghan , Pike G. Bruce , Rawling Jean M. , Sajobi Tolulope , Poulin Marc J.
Published: June 2021

Background

There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months).

Methods

We will recruit 264 participants (aged 50–80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months).

Discussion

This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing.

Trial registration

ClinicalTrials.gov NCT03035851. Registered on 30 January 2017
Recruitment and retention rates in randomised controlled trials of exercise therapy in people with multimorbidity: a systematic review and meta-analysis
Authors: Harris Lasse K. , Skou Søren T. , Juhl Carsten B. , Jäger Madalina , Bricca Alessio
Published: June 2021

Aim

To quantify recruitment, retention and differential retention rates and associated trial, participant and intervention characteristics in randomised controlled trials (RCTs) evaluating the effect of exercise therapy in people with multimorbidity.

Data sources

MEDLINE, EMBASE, CINAHL and CENTRAL from 1990 to April 20, 2020.

Study selection

RCTs including people with multimorbidity comparing exercise therapy with a non-exposed comparator group reporting at least one of the following outcomes: physical function, health-related quality of life, depression symptoms, or anxiety symptoms.

Data extraction and synthesis

Recruitment rates (proportion of people randomised/proportion of people eligible), retention rates (proportion of people providing the outcomes of interest/proportion randomised) and differential retention rates (difference in proportion of people providing the outcomes in the intervention group and comparator group) were calculated. Meta-analysis using a random-effects model was used to estimate pooled proportions. Methodological quality was assessed using Cochrane ´Risk of Bias tool 2.0´ for individual studies, and the GRADE approach was used to assess the overall quality of the evidence.

Results

Twenty-three RCTs with 3363 people were included. The pooled prevalence for recruitment rate was 75% (95%CI 66 to 84%). The pooled prevalence for retention rate was 90% (95%CI 86 to 94%) at the end of the intervention (12 weeks; interquartile range (IQR) (12 to 12)). Meta-regression analyses showed that increasing age and including a higher proportion of people with hypertension was associated with lower retention rates. Retention rates did not differ between the intervention and comparator groups. The overall quality of the evidence was deemed very low.

Conclusion

Three in four eligible people with multimorbidity were randomised to RCTs using exercise therapy, of which nine out of 10 provided end of treatment outcomes with no difference seen between the intervention and comparison groups. However, the results must be interpreted with caution due to large differences between the included studies.

Trial registration

ClinicalTrials.govCRD42020161329. Registered on 28 April 2020.
The cerebral mechanism underlying the acupoints with specific effect for gallbladder stone disease: protocol for a randomized controlled task-fMRI trial
Authors: Sun Ning , Zhou Yuan-Fang , Zhou Jie , Zuo Wen-Wei , Ye Xiang-Yin , Deng Xiao-Dong , Li Zheng-Jie , Cheng Shi-Rui , Qu Yu-Zhu , Zhou Jun , Sun Rui-Rui , Liang Fan-Rong
Published: June 2021

Background

As it has been recorded in ancient Chinese classics, Yanglingquan (GB34) and Dannangxue (EX-LE6) are two important acupoints that can regulate the function of the gallbladder. Acupuncture at these two acupoints is considered particularly effective for gallbladder disease treatment, especially for alleviating gallbladder stone disease (GSD) symptoms that can be aggravated after intaking high-fat food. However, the superior effect between the two acupoints still needs to be further explored, as well as the underlying central mechanism has never been investigated to date.

Methods and design

Ninety participants diagnosed with GSD will be randomly divided into group A (acupuncture at GB34), group B (acupuncture at EX-LE6), and group C (acupuncture at non-acupoint) in a ratio of 1:1:1. All of them will receive a 30-min acupuncture treatment with fatty-food cues being presented before and after acupuncture. During the task, participants will be scanned by MRI and required to rate their desire for high-/low-fat food with an 11-point Likert scale. Additionally, the participants’ pain/discomfort sensation will be evaluated using the Numeric Rating Scale (NRS) at four timepoints, including before the 1st task fMRI scan, before and after acupuncture, and after the 2nd task fMRI scan. For both behavior and fMRI data, the ANOVA analysis will be conducted among three groups to testify the immediate effect of GB34 and EX-LE6. The post hoc t-test will be employed to further explore the superiority between acupuncture with GB34 and EX-LE6. Furthermore, correlation analyses will be conducted to investigate a possible correlation between neural changes and clinical data.

Discussion

In comparison to the non-acupoint, the results will firstly explore the superior effect between acupuncture with GB34 and EX-LE6 on GSD patients by observing their behavioral and neural response change to fatty-food cue, and then to investigate the underlying central mechanism.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000034368. Registered on 3 July 2020.
Correction to: Improvements in cholesterol efux capacity of HDL and adiponectin contribute to mitigation in cardiovascular disease risk after bariatric surgery in a cohort with morbid obesity
Authors: Thakkar Himani , Vincent Vinnyfred , Shukla Sakshi , Sra Manraj , Kanga Uma , Aggarwal Sandeep , Singh Archna
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Differential effects of risk factors on the cognitive trajectory of early- and late-onset Alzheimer’s disease
Authors: Kim Jaeho , Woo Sook-Young , Kim Seonwoo , Jang Hyemin , Kim Junpyo , Kim Jisun , Kang Sung Hoon , Na Duk L. , Chin Juhee , Apostolova Liana G. , Seo Sang Won , Kim Hee Jin
Published: June 2021

Background

Although few studies have shown that risk factors for Alzheimer’s disease (AD) are associated with cognitive decline in AD, not much is known whether the impact of risk factors differs between early-onset AD (EOAD, symptom onset < 65 years of age) versus late-onset AD (LOAD). Therefore, we evaluated whether the impact of Alzheimer’s disease (AD) risk factors on cognitive trajectories differ in EOAD and LOAD.

Methods

We followed-up 193 EOAD and 476 LOAD patients without known autosomal dominant AD mutation for 32.3 ± 23.2 months. Mixed-effects model analyses were performed to evaluate the effects ofAPOEε4, low education, hypertension, diabetes, dyslipidemia, and obesity on cognitive trajectories.

Results

APOEε4 carriers showed slower cognitive decline in general cognitive function, language, and memory domains thanAPOEε4 carriers in EOAD but not in LOAD. Although patients with low education showed slower cognitive decline than patients with high education in both EOAD and LOAD, the effect was stronger in EOAD, specifically in frontal-executive function. Patients with hypertension showed faster cognitive decline than did patients without hypertension in frontal-executive and general cognitive function in LOAD but not in EOAD. Patients with obesity showed slower decline in general cognitive function than non-obese patients in EOAD but not in LOAD.

Conclusions

Known risk factors for AD were associated with slower cognitive decline in EOAD but rapid cognitive decline in LOAD.
Electric signals counterbalanced posterior vs anterior PTEN signaling in directed migration of Dictyostelium
Authors: Song Bing , Gu Yu , Jiang Wenkai , Li Ying , Ayre Wayne Nishio , Liu Zhipeng , Yin Tao , Janetopoulos Christopher , Iijima Miho , Devreotes Peter , Zhao Min
Published: June 2021

Background

Cells show directed migration response to electric signals, namely electrotaxis or galvanotaxis. PI3K and PTEN jointly play counterbalancing roles in this event via a bilateral regulation of PIP3 signaling. PI3K has been proved essential in anterior signaling of electrotaxing cells, whilst the role of PTEN remains elusive.

Methods

Dictyostelium cells with different genetic backgrounds were treated with direct current electric signals to investigate the genetic regulation of electrotaxis.

Results

We demonstrated that electric signals promoted PTEN phosphatase activity and asymmetrical translocation to the posterior plasma membrane of the electrotaxing cells. Electric stimulation produced a similar but delayed rear redistribution of myosin II, immediately before electrotaxis started. Actin polymerization is required for the asymmetric membrane translocation of PTEN and myosin. PTEN signaling is also responsible for the asymmetric anterior redistribution of PIP3/F-actin, and a biased redistribution of pseudopod protrusion in the forwarding direction of electrotaxing cells.

Conclusions

PTEN controls electrotaxis by coordinately regulating asymmetric redistribution of myosin to the posterior, and PIP3/F-actin to the anterior region of the directed migration cells.
A systematic review on the effectiveness of implementation strategies to postpone elective caesarean sections to ≥ 39 + (0–6) weeks of gestation
Authors: Prediger Barbara , Heu-Parvaresch Anahieta , Polus Stephanie , Bühn Stefanie , Neugebauer Edmund A. M. , Dawid Pieper
Published: June 2021

Background

Caesarean sections often have no urgent indication and are electively planned. Research showed that elective caesarean section should not be performed until 39 + (0–6) weeks of gestation to ensure best neonatal and maternal health if there are no contraindications. This was recommended by various guidelines published in the last two decades. With this systematic review, we are looking for implementation strategies trying to implement these recommendations to reduce elective caesarean section before 39 + (0–6) weeks of gestation.

Methods

We performed a systematic literature search in MEDLINE, EMBASE, CENTRAL, and CINAHL on 3rd of March 2021. We included studies that assessed implementation strategies aiming to postpone elective caesarean section to ≥ 39 + (0–6) weeks of gestation. There were no restrictions regarding the type of implementation strategy or reasons for elective caesarean section. Our primary outcome was the rate of elective caesarean sections before 39 + (0–6) weeks of gestation. We used the ROBINS-I Tool for the assessment of risk of bias. We did a narrative analysis of the results.

Results

We included 10 studies, of which were 2 interrupted time series and 8 before-after studies, covering 205,954 elective caesarean births. All studies included various types of implementation strategies. All implementation strategies showed success in decreasing the rate of elective caesarean sections performed < 39 + (0–6) weeks of gestation. Risk difference differed from − 7 (95% CI − 8; − 7) to − 45 (95% CI − 51; − 31). Three studies reported the rate of neonatal intensive care unit admission and showed little reduction.

Conclusion

This systematic review shows that all presented implementation strategies to reduce elective caesarean section before 39 + (0–6) weeks of gestation are effective. Reduction rates differ widely and it remains unclear which strategy is most successful. Strategies used locally in one hospital seem a little more effective. Included studies are either before-after studies (8) or interrupted time series (2) and the overall quality of the evidence is rather low. However, most of the studies identified specific barriers in the implementation process. For planning an implementation strategy to reduce elective caesarean section before 39 + (0–6) weeks of gestation, it is necessary to consider specific barriers and facilitators and take all obstetric personal into account.

Systematic review registration

PROSPERO CRD42017078231