bluuebunny/crossref_metadata_2025 huggingface dataset:
“I want to really crack this nut”: an analysis of parent-perceived policy needs surrounding food allergy
Authors: Abrams Elissa M. , Simons Elinor , Gerdts Jennifer , Nazarko Orla , Povolo Beatrice , Protudjer Jennifer L. P.
Published: August 2020

Background

In Canada, anaphylaxis-level food allergy constitutes a legal disability. Yet, no nationwide policies exist to support families. We sought to understand what parents of children with food allergy perceive as the most pressing food allergy-related policy concerns in Canada.

Methods

Between March–June 2019, we interviewed 23 families whose food allergic children (N = 28mean age 7.9 years) attending an allergy clinic in Winnipeg, Canada. Interviews were audio-recorded, transcribed and analyzed using content analysis.

Results

Over 40% of children had multiple food allergies, representing most of Health Canada’s priority allergens. We identified four themes: (1) High prevalence. High priority?. (2) Food labels can be misleading, (3) Costs and creative ideas, and (4) Do we have to just deal with the status quo around allergies?

Conclusion

Food allergy ought to be a national policy priority, to improve the process for precautionary labelling, to improve funding, educational tools access to care, and knowledge of current allergy guidelines.
LncRNA SNHG9 is downregulated in osteoarthritis and inhibits chondrocyte apoptosis by downregulating miR-34a through methylation
Authors: Zhang Hongfei , Li Jinglian , Shao Weiguang , Shen Naipeng
Published: August 2020

Background

Our preliminary RNA-Seq data revealed altered expression of small nucleolar RNA host gene 9 (SNHG9) in osteoarthritis (OA) and its reverse correlation with miR-34a, which can regulate chondrocyte apoptosis in rat OA model. This study was therefore carried out to investigate the potential interaction between SNHG9 and miR-34a in OA.

Methods

A total of 60 healthy volunteers (Control group) as well as 60 OA patients (OA group) were enrolled in this study. Transfections, RT-qPCR, methylation-specific PCR (MSP) and cell apoptosis assay were performed.

Results

We found that SNHG9 was downregulated in OA and its expression was reversely correlated with the expression of miR-34a only across OA samples but not healthy control samples. In chondrocytes from OA patients, overexpression of SNHG9 led to downregulation of miR-34a and increased methylation of miR-34a gene. In contrast, in chondrocytes from healthy controls, overexpression of SNHG9 did not affect the expression of miR-34a and the methylation of miR-34a gene. Cell apoptosis analysis showed that overexpression of SNHG9 led to decreased apoptotic rate of chondrocytes from OA patients but not chondrocytes from the healthy controls through miR-34a.

Conclusion

In conclusion, SNHG9 is downregulated in OA and inhibits chondrocyte apoptosis by downregulating miR-34a through methylation.
How to get better TAD? Relationship between anteversion angle of nail and position of femoral neck guide pin during nailing of intertrochanteric fractures
Authors: Wang Zhe , Liu Yadong , Li Shenglong , Wang Xiuhui , Liu Changjian , Tang Xin
Published: August 2020

Background

To demonstrate the correlation between guide pin-shaft angle (PSA) at the anteroposterior film and anteversion angle of guide pin at the lateral film and investigate whether excellent tip–apex distance (TAD) can be obtained by changing the entry point via axial rotation of the main intramedullary nail.

Methods

Fifty patients with intertrochanteric femoral fractures (IFFs) undergoing internal fixation with intramedullary nails under 2D fluoroscopy were retrospectively enrolled. Both of the PSA at the anteroposterior film and anteversion angle at the lateral film before and after adjustment of the guide pin were collected. Pearson correlation analysis was performed to investigate their correlation. Intraoperative and postoperative outcomes were recorded. Furthermore, the software of Mimics 10.0 and Pro/E were used to establish the 3D models of the proximal femur and main intramedullary nail/guide pin, respectively. Surgery was simulated on the Pro/E software platform and solid geometry analysis was conducted to calculate the correlation between the PSA and the anteversion angle.

Results

Pearson correlation analysis indicated there was a positive correlation between PSA and anteversion angle, with the correlation coefficient of 0.902 (p < 0.01). By altering the PSA and anteversion angle, TAD was adjusted to be less than 25 mm in all patients. The mean operative time, fluoroscopy time and length of hospital stay were 65.82 ± 11.16 min, 2.03 ± 0.79 min and 6.66 ± 2.49 d. Thirty-one patients received blood transfusions (3.55 ± 1.95 U). Fracture reduction was considered to be good or acceptable in all patients. Complications occurred only in 6 patients (12.00%). At a 3-month follow-up, the mean Timed Up and Go was 31.54 ± 20.95 s and Harris Hip Score was 72.88 ± 8.79. The 3D surgery model also showed when the main intramedullary nail was externally rotated or internally rotated of 20° at the standard location, the PSA of guide pin at the anteroposterior position and anteversion angle of the guide pin at the lateral position were simultaneously increased or decreased.

Conclusion

Our findings suggest altering the PSA and anteversion angle may be beneficial for obtaining excellent TAD and achieving superior outcomes.
Short- versus long-segment posterior spinal fusion with vertebroplasty for osteoporotic vertebral collapse with neurological impairment in thoracolumbar spine: a multicenter study
Authors: Ishikawa Yuya , Watanabe Kei , Katsumi Keiichi , Ohashi Masayuki , Shibuya Yohei , Izumi Tomohiro , Hirano Toru , Endo Naoto , Kaito Takashi , Yamashita Tomoya , Fujiwara Hiroyasu , Nagamoto Yukitaka , Matsuoka Yuji , Suzuki Hidekazu , Nishimura Hirosuke , Terai Hidetomi , Tamai Koji , Tagami Atsushi , Yamada Shuta , Adachi Shinji , Yoshii Toshitaka , Ushio Shuta , Harimaya Katsumi , Kawaguchi Kenichi , Yokoyama Nobuhiko , Oishi Hidekazu , Doi Toshiro , Kimura Atsushi , Inoue Hirokazu , Inoue Gen , Miyagi Masayuki , Saito Wataru , Nakano Atsushi , Sakai Daisuke , Nukaga Tadashi , Ikegami Shota , Shimizu Masayuki , Futatsugi Toshimasa , Ohtori Seiji , Furuya Takeo , Orita Sumihisa , Imagama Shiro , Ando Kei , Kobayashi Kazuyoshi , Kiyasu Katsuhito , Murakami Hideki , Yoshioka Katsuhito , Seki Shoji , Hongo Michio , Kakutani Kenichiro , Yurube Takashi , Aoki Yasuchika , Oshima Masashi , Takahata Masahiko , Iwata Akira , Endo Hirooki , Abe Tetsuya , Tsukanishi Toshinori , Nakanishi Kazuyoshi , Watanabe Kota , Hikata Tomohiro , Suzuki Satoshi , Isogai Norihiro , Okada Eijiro , Funao Haruki , Ueda Seiji , Shiono Yuta , Nojiri Kenya , Hosogane Naobumi , Ishii Ken
Published: August 2020

Background

Vertebroplasty with posterior spinal fusion (VP + PSF) is one of the most widely accepted surgical techniques for treating osteoporotic vertebral collapse (OVC). Nevertheless, the effect of the extent of fusion on surgical outcomes remains to be established. This study aimed to evaluate the surgical outcomes of short- versus long-segment VP + PSF for OVC with neurological impairment in thoracolumbar spine.

Methods

We retrospectively collected data from 133 patients (median age, 77 years; 42 men and 91 women) from 27 university hospitals and their affiliated hospitals. We divided patients into two groups: a short-segment fusion group (S group) with 2- or 3-segment fusion (87 patients) and a long-segment fusion group (L group) with 4- through 6-segment fusion (46 patients). Surgical invasion, clinical outcomes, local kyphosis angle (LKA), and complications were evaluated.

Results

No significant differences between the two groups were observed in terms of neurological recovery, pain scale scores, and complications. Surgical time was shorter and blood loss was less in the S group, whereas LKA at the final follow-up and correction loss were superior in the L group.

Conclusion

Although less invasiveness and validity of pain and neurological relief are secured by short-segment VP + PSF, surgeons should be cautious regarding correction loss.
A Surgeon’s handedness in direct anterior approach-hip replacement
Authors: Kong Xiangpeng , Yang Minzhi , Ong Alvin , Guo Renwen , Chen Jiying , Wang Yan , Chai Wei
Published: August 2020

Background

The impact of handedness on clinical outcomes was easily overlooked in hip replacement. This study aimed to find whether the component positioning and hip function were affected by the handedness in total hip arthroplasty (THA) through direct anterior approach (DAA).

Methods

Total 102 patients who underwent bilateral DAA-THAs simultaneously between May 2016 and November 2018 in our institute were reviewed. All surgeries were operated by one right-handed surgeon. Their demographic, cup positioning, stem alignment, femoral stem fit, Harris hip score (HHS), intraoperative and postoperative complications were used to evaluate the role of handedness in DAA.

Results

The inclination of left cups was significantly larger than that of right cups (42.61 ± 7.32 vs 39.42 ± 7.19,p = 0.000). The stem fit of left femur was significantly larger than that of right femur (84.34 ± 4.83 vs 82.81 ± 6.07,p = 0.043). No significant differences in safe zone ratio, HHS and complications between bilateral hips were found.

Conclusions

A surgeon’s handedness had significant impact on cup’s inclination and femoral stem fit in DAA-THA. However, there were no significant differences of cup malpositioning, stem alignment, hip function scores and complications between bilateral DAA-THAs.
‘Flower of the body’: menstrual experiences and needs of young adolescent women with cerebral palsy in Bangladesh, and their mothers providing menstrual support
Authors: Power R. , Wiley K. , Muhit M. , Heanoy E. , Karim T. , Badawi N. , Khandaker G.
Published: August 2020

Background

This study offers voice to young adolescent women with cerebral palsy (CP) in Bangladesh as they describe their menstrual experiences and needs, and their mothers providing menstrual support.

Method

Semi-structured focus groups with adolescents with CP, and separately their mother. Data was analysed using a material discursive framework and drawing on feminist disability theory. Participants were recruited from the Bangladesh CP Register (BCPR); a population-based surveillance of children and adolescents with CP in rural Bangladesh.

Results

Participants were 45 women including 12 female adolescents with CP and 33 female caregivers. Participants reported a wide range of experiences and needs; menarche acted as a gateway to menstrual information although for some a discourse of silence prevailed due to exclusion from peer and familial networks. Menstruation was discursively constructed as a sign of ‘female maturation’ marked by an expectation of ‘independence’, required for acceptance into socially valued adult roles, and was positioned alongside increased vulnerability to sexual abuse. Young adolescent women with CP were expected to ‘quietly endure’ the material aspects of menstruation although unmanaged pain and distress were described. Mothers reported an imperative for meeting their adolescent’s menstrual needs however this role was discursively positioned as ‘painful’, ‘irritating’ and ‘shameful’, in part due to an absence of affordable, functional menstrual resources.

Conclusion

The findings of the present study provide motivation for disability services in Bangladesh to account for the menstrual needs of young adolescent women with CP within service delivery through strategies such as providing menstrual education and by embedding value in constructs such as ‘interdependence’. Moreover, interventions focused on alleviating menstrual pain among young adolescent women with CP as well as those targeted to alleviate distress among mothers providing menstrual care are required. Finally, policy responses are required to ensure that ‘inclusive development’ considers the needs of menstruating women with disability.
Role of HPV 16 variants among cervical carcinoma samples from Northeastern Brazil
Authors: da Silva Rodrigo Lopes , da Silva Batista Zulmira , Bastos Gerusinete Rodrigues , Cunha Ana Paula Almeida , Figueiredo Fábio Vidal , de Castro Lailson Oliveira , dos Anjos Pereira Liwerbeth , da Silva Marcos Antonio Custódio Neto , Vidal Flávia Castello Branco , Barros Maria Claudene , da Costa Fraga Elmary , Brito Luciane Maria Oliveira , do Carmo Lacerda Barbosa Maria , Moreira Miguel Ângelo Martins , do Desterro Soares Brandão Nascimen Maria
Published: August 2020

Background

Cervical cancer is the fourth most common type of cancer affecting women globally. In Brazil, it is the third most frequent type of cancer in women and HPV is present in approximately 90% of cases. Evidence suggests that variants of HPV 16 can interfere biologically and etiologically during the development of cervical cancer.

Methods

Cervix tumor fragments were collected, their DNA was extracted, and nested PCR was used to detect HPV. Positive samples were sequenced to determine the viral genotype. To characterize the HPV 16 strains, positive samples PCR was used to amplify the LCR and E6 regions of the HPV 16 virus.

Results

Data from 120 patients with cervical cancer were analyzed. Most women were between 41 and 54 years of age, had schooling until primary school, a family income between 1 and 2 times the minimum wage and were married/in a consensual union. There was no statistically significant association between HPV or socio-demographic variables and risk factors for cervical cancer (P <  0.05). HPV was present in 88 women (73%). The most prevalent types were HPV 16 (53.4%), HPV 18 (13.8%), HPV 35 (6.9%) and HPV 45 (5.7%). Of the 47 HPV 16 positive cases, variant A (49%) was present in 23 samples, followed by variant D in 20 cases (43%), and variants B and C in 2 cases each (4%). The most prevalent histological type of HPV 16 tumors was squamous cell carcinoma, followed by adenocarcinoma. There was a statistically significant association between HPV 16 variants and the tumors’ histological types (P <  0.001).

Conclusions

Knowledge of HPV 16 variants will provide data on their influence on the pathological and oncogenic aspects of cervical lesions.
Transcutaneous Neuromodulation improved inflammation and sympathovagal ratio in patients with primary biliary ssscholangitis and inadequate response to Ursodeoxycholic acid: a pilot study
Authors: Yang Hui , Yang Hang , Wang Lixia , Shi Honggang , Liu Bojia , Lin Xue , Chang Qingyong , Chen Jiande D. Z. , Duan Zhijun
Published: August 2020

Background

At present, ursodeoxycholic acid (UDCA) is internationally recognized as a therapeutic drug in clinic. However, about 40% Primary Biliary Cholangitis (PBC) patients are poor responders to UDCA. It has been demonstrated that Transcutaneous Neuromodulation (TN) can be involved in gut motility, metabolism of bile acids, immune inflammation, and autonomic nerve. Therefore, this study aimed to explore the effect of TN combined with UDCA on PBC and related mechanisms.

Methods

According to inclusion and exclusion criteria, 10 healthy volunteers and 15 PBC patients were recruited to control group and TN group, respectively. PBC patients were alternately but blindly assigned to group A (TN combined with UDCA) and group B (sham-TN combined with UDCA), and a crossover design was used. The TN treatment was performed via the posterior tibial nerve and acupoint ST36 (Zusanli) 1 h twice/day for 2 weeks. T test and nonparametric test were used to analyze the data.

Results

1. TN combined with UDCA improved the liver function of PBC patients shown by a significant decrease of alkaline phosphatase and gamma-glutamyltransferase (γ-GT) (P < 0.05). 2. The treatment also decreased serum IL-6 levels (P < 0.05), but not the level of Tumor Necrosis Factor-α, IL-1β or IL-10. 3. TN combined with UDCA regulated autonomic function, enhanced vagal activity, and decreased the sympathovagal ratio assessed by the spectral analysis of heart rate variability (P < 0.05). 4. There was no change in 13 bile acids in serum or stool after TN or sham-TN.

Conclusions

TN cssombined with UDCA can significantly improve the liver function of PBC patients. It is possibly via the cholinergic anti-inflammatory pathway. TN might be a new non-drug therapy for PBC. Further studies are required.

Trial registration

The study protocol was registered in Chinese Clinical Trial Registry (numberChiCTR1800014633) on 25 January 2018.
Usage of do-not-attempt-to-resuscitate orders in a Swedish community hospital – patient involvement, documentation and compliance
Authors: Bertilsson Emilie , Semark Birgitta , Schildmeijer Kristina , Bremer Anders , Carlsson Jörg
Published: August 2020

Background

To characterize patients dying in a community hospital with or without attempting cardiopulmonary resuscitation (CPR) and to describe patient involvement in, documentation of, and compliance with decisions on resuscitation (Do-not-attempt-to-resuscitate orders; DNAR).

Methods

All patients who died in Kalmar County Hospital during January 1, 2016 until December 31, 2016 were included. All information from the patients’ electronic chart was analysed.

Results

Of 660 patients (mean age 77.7 ± 12.1 years; range 21–101; median 79; 321 (48.6%) female), 30 (4.5%) were pronounced dead in the emergency department after out-of-hospital CPR. Of the remaining 630 patients a DNAR order had been documented in 558 patients (88.6%). Seventy had no DNAR order and 2 an explicit order to do CPR. In 43 of these 70 patients CPR was unsuccessfully attempted while the remaining 27 patients died without attempting CPR. In 2 of 558 (0.36%) patients CPR was attempted despite a DNAR order in place. In 412 patients (73.8%) the DNAR order had not been discussed with neither patient nor family/friends. Moreover, in 75 cases (13.4%) neither patient nor family/friends were even informed about the decision on code status.

Conclusions

In general, a large percentage of patients in our study had a DNAR order in place (88.6%). However, 27 patients (4.3%) died without CPR attempt or DNAR order. DNAR orders had not been discussed with the patient/surrogate in almost three fourths of the patients. Further work has to be done to elucidate the barriers to discussions of CPR decisions with the patient.
Engendering health systems in response to national rollout of dolutegravir-based regimens among women of childbearing potential: a qualitative study with stakeholders in South Africa and Uganda
Authors: Alhassan Yussif , Twimukye Adelline , Malaba Thoko , Orrell Catherine , Myer Landon , Waitt Catriona , Lamorde Mohammed , Kambugu Andrew , Reynolds Helen , Khoo Saye , Taegtmeyer Miriam
Published: August 2020

Background

In the era of rapid dolutegravir rollout, concerns about neural tube defects have complicated the health systems response among women of childbearing potential. This qualitative study, which was nested within the DolPHIN-2 clinical trial, examined the current and future health system opportunities and challenges associated with the transition to dolutegravir-based regimen as first line antiretroviral therapy among women of childbearing potential in South Africa and Uganda.

Method

Semi-structured in-depth interviews with members of antiretroviral therapy guideline development groups and affiliates were conducted. Thirty-one participants were purposively selected for the study, including senior officials from the Ministry of Health and National Drug Regulatory Authority in Uganda and South Africa as well as health-sector development partners, activists, researchers and health workers. A thematic approach was used to analyse the data.

Findings

Despite differences in health system contexts, several common challenges and opportunities were identified with the transition among women of childbearing potential in South Africa and Uganda. In both contexts national stakeholders identified challenges with ensuring gender equity in roll out due to the potential teratogenicity of dolutegravir, paucity of data on dolutegravir use in pregnancy, potential stock out of effective contraceptives, poorly integrated contraception services, and limited pharmacovigilance in pregnancy. Participants identified opportunities that could be harnessed to accelerate the transition, including high stakeholder interest and commitment to transition, national approval and licensure of a generic tenofovir/lamivudine/dolutegravir regimen, availability of a network of antiretroviral therapy providers, and strong desire among women for newer and more tolerable regimens.

Conclusion

The transition to dolutegravir-based regimens has the potential to strengthen health systems in low- and middle-income countries to engender equitable access to optimised antiretroviral regimen among women. There is the need for a multi-sectoral effort to harness the opportunities of the health systems to addresses the bottlenecks to the transition and initiate extensive community engagement alongside individual and institutional capacity strengthening. Improvements in pregnancy pharmacovigilance and counselling and family planning services are critical to ensuring a successful transition among women of childbearing potential.
A problem-oriented systems approach to primary care system development: development and initial testing of the problem-oriented primary care system development record
Authors: Shukor Ali Rafik , Barbazza Erica , Klazinga Niek , Kringos Dionne Sofia
Published: August 2020

Background

There is significant global policy interest related to enabling a data-driven approach for evidence-based primary care system development. This paper describes the development and initial testing of a prototype tool (the Problem-Oriented Primary Care System Development Record, or PCSDR) that enables a data-driven and contextualized approach to primary care system development.

Methods

The PCSDR is an electronic record that enables the systematic input, classification, structuring, storage, processing and analysis of different types of data related to the structure, function and performance of primary care systems over time. Data inputted into the PCSDR was coded using the WHO’s PHC-IMPACT framework and classification system. The PCSDR’s functionalities were tested by using a case study of primary care system development in Tajikistan.

Results

Tajikistan’s case study demonstrated that the PCSDR is a potentially effective and conceptually-sound tool for the input, classification, structuring and storage of different data types from myriad sources. The PCSDR is therefore a basic data entry and data management system that enables query and analytics functions for health services research and evidence-based primary care system development functions.

Conclusions

The PCSDR is a data system that enables a contextualized approach to evidence-based primary care system development. It represents a coherent and effective synthesis of the fields of primary care system development and performance assessment. The PCSDR enables analysts to leverage primary care performance assessment frameworks for a broad range of functions related to health systems analysis, improvement and the development of learning health systems.
Perspectives and practices of health workers around diagnosis of paediatric tuberculosis in hospitals in a resource-poor setting – modern diagnostics meet age-old challenges
Authors: Oliwa Jacquie Narotso , Odero Sabina Adhiambo , Nzinga Jacinta , van Hensbroek Michaël Boele , Jones Caroline , English Mike , van’t Hoog Anja
Published: August 2020

Background

Detection of tuberculosis (TB) in children in Kenya is sub-optimal. Xpert MTB/RIF® assay (Xpert®) has the potential to improve speed of TB diagnosis due to its sensitivity and fast turnaround for results. Significant effort and resources have been put into making the machines widely available in Kenya, but use remains low, especially in children. We set out to explore the reasons for the under-detection of TB and underuse of Xpert® in children, identifying challenges that may be relevant to other newer diagnostics in similar settings.

Methods

This was an exploratory qualitative study with an embedded case study approach. Data collection involved semi-structured interviews; small-group discussions; key informant interviews; observations of TB trainings, sensitisation meetings, policy meetings, hospital practices; desk review of guidelines, job aides and policy documents. The Capability, Opportunity and Motivation (COM-B) framework was used to interpret emerging themes.

Results

At individual level, knowledge, skill, competence and experience, as well as beliefs and fears impacted on capability (physical & psychological) as well as motivation (reflective) to diagnose TB in children and use diagnostic tests. Hospital level influencers included hospital norms, processes, patient flows and resources which affected how individual health workers attempted to diagnose TB in children by impacting on their capability (physical & psychological), motivation (reflective & automatic) and opportunity (physical & social). At the wider system level, community practices and beliefs, and implementation of TB programme directives impacted some of the decisions that health workers made through capability (psychological), motivation (reflective & automatic) and opportunity (physical).

Conclusion

We used comprehensive approaches to identify influencers of TB case detection and use of TB diagnostic tests in children in Kenya. These results are being used to design a contextually-appropriate intervention to improve TB diagnosis, which may be relevant to similar low-resource, high TB burden countries and can be feasibly implemented by the National TB programme.
Long term clinical impact of successful recanalization of chronic total occlusion in patients with and without type 2 diabetes mellitus
Authors: Tsai Chuan-Tsai , Huang Wei-Chieh , Teng Hsin-I , Tsai Yi-Lin , Lu Tse-Min
Published: August 2020

Background

Diabetes mellitus is one of the risk factors for coronary artery disease and frequently associated with multivessels disease and poor clinical outcomes. Long term outcome of successful revascularization of chronic total occlusions (CTO) in diabetes patients remains controversial.

Methods and results

From January 2005 to December 2015, 739 patients who underwent revascularization for CTO in Taipei Veterans General Hospital were included in this study, of which 313 (42%) patients were diabetes patients. Overall successful rate of revascularization was 619 (84%) patients whereas that in diabetics and non-diabetics were 265 (84%) and 354 (83%) respectively. Median follow up was 1095 days (median: 5 years, interquartile range: 1–10 years). During 3 years follow-up period, 59 (10%) in successful group and 18 (15%) patients in failure group died. Although successful revascularization of CTO was non-significantly associated with better outcome in total cohort (hazard ratio (HR): 0.593, 95% confidence interval (CI) 0.349–0.008, P: 0.054), it might be associated with lower risk of all-cause mortality (HR: 0.307, 95% CI 0.156–0.604, P: 0.001) and CV mortality (HR: 0.266, 95% CI 0.095–0.748, P: 0.012) in diabetics (P: 0.512). In contrast, successful CTO revascularization didn’t improve outcomes in non-diabetics (all P > 0.05). In multivariate cox regression analysis, successful CTO revascularization remained an independent predictor for 3-years survival in diabetic subgroup (HR: 0.289, 95% CI 0.125–0.667, P: 0.004). The multivariate analysis result was similar after propensity score matching (all-cause mortality, HR: 0.348, 95% CI 0.142–0.851, P: 0.021).

Conclusions

Successful CTO revascularization in diabetes may be related to better long term survival benefit but not in non-diabetic population.
Cyclodextrinase from Thermococcus sp expressed in Bacillus subtilis and its application in the preparation of maltoheptaose
Authors: Wang Lei , Wu Quan , Zhang Kang , Chen Sheng , Yan Zhengfei , Wu Jing
Published: August 2020

Background

Maltoheptaose as malto-oligosaccharides with specific degree of polymerization, has wide applications in food, medicine and cosmetics industries. Currently, cyclodextrinase have been applied as prepared enzyme to prepare maltoheptaose. However, the yield and proportion of maltoheptaose was lower, which is due to limited substrate and product specificity of cyclodextrinase (CDase). To achieve higher maltoheptaose yield, cyclodextrinase with high substrate and product specificity should be obtained.

Results

In this study, cyclodextrinase derived from Thermococcus sp B1001 (TsCDase) was successfully expressed and characterized in Bacillus subtilis for the first time. The specific activity of TsCDase was 637.95 U/mg under optimal conditions of 90 °C and pH 5.5, which exhibited high substrate specificity for cyclodextrins (CDs). When the concentration of β-CD was 8%, the yield of maltoheptaose achieved by TsCDase was 82.33% across all reaction products, which exceeded the yields of maltoheptaose in other recent reports. Among malto-oligosaccharides generated as reaction products, maltoheptaose was present in the highest proportion, about 94.55%.

Conclusions

This study provides high substrate and product specificity of TsCDase. TsCDase is able to prepare higher yield of maltoheptaose through conversion of β-CD in the food industry.
Transgelin interacts with PARP1 in human colon cancer cells
Authors: Lew Zhen-xian , Zhou Hui-min , Fang Yuan-yuan , Ye Zhen , Zhong Wa , Yang Xin-yi , Yu Zhong , Chen Dan-yu , Luo Si-min , Chen Li-fei , Lin Ying
Published: August 2020

Background

Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that transgelin was up-regulated in node-positive colorectal cancer (CRC) versus node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms through which transgelin participates in the metastasis of colon cancer cells.

Methods

Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with transgelin. The 256 downstream transcripts regulated by transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with transgelin. The interaction between transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence.

Results

Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven key genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1, which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with transgelin. The interaction between PARP1 and transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays.

Conclusions

Our results suggest that transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.
Dibutyl phthalate promotes juvenile Sertoli cell proliferation by decreasing the levels of the E3 ubiquitin ligase Pellino 2
Authors: Ma Tan , Hou Jiwei , Zhou Yuan , Chen Yusheng , Qiu Jiayin , Wu Jiang , Ding Jie , Han Xiaodong , Li Dongmei
Published: August 2020

Background

A previous study showed that dibutyl phthalate (DBP) exposure disrupted the growth of testicular Sertoli cells (SCs). In the present study, we aimed to investigate the potential mechanism by which DBP promotes juvenile SC proliferation in vivo and in vitro.

Methods

Timed pregnant BALB/c mice were exposed to vehicle, or DBP (50, 250, and 500 mg/kg/day) from 12.5 days of gestation until delivery. In vitro, CCK-8 and EdU incorporation assays were performed to determine the effect of monobutyl phthalate (MBP), the active metabolite of DBP, on the proliferation of TM4 cells, which are a juvenile testicular SC cell line. Western blotting analysis, quantitative PCR (q-PCR), and flow cytometry were performed to analyse the expression of genes and proteins related to the proliferation and apoptosis of TM4 cells. Coimmunoprecipitation was used to determine the relationship between the ubiquitination of interleukin 1 receptor-associated kinase 1 (IRAK1) and the effect of MBP on promoting the proliferation of TM4 cells.

Results

In the 50 mg/kg/day DBP-exposed male mice offspring, the number of SCs was significantly increased. Consistent with the in vivo results, in vitro experiments revealed that 0.1 mM MBP treatment promoted the proliferation of TM4 cells. Furthermore, the data showed that 0.1 mM MBP-mediated downregulation of the E3 ubiquitin ligase Pellino 2 (Peli2) increased ubiquitination of IRAK1 by K63, which activated MAPK/JNK signalling, leading to the proliferation of TM4 cells.

Conclusions

Prenatal exposure to DBP led to abnormal proliferation of SCs in prepubertal mice by affecting ubiquitination of the key proliferation-related protein IRAK1 via downregulation of Peli2.
Left atrial spontaneous echo contrast occurring in patients with low CHADS2 or CHA2DS2-VASc scores
Authors: Akamatsu Kanako , Ito Takahide , Ozeki Michishige , Miyamura Masatoshi , Sohmiya Koichi , Hoshiga Masaaki
Published: August 2020

Background

Left atrial spontaneous echo contrast (LASEC) is common in patients with atrial fibrillation (AF), although scarce information exists on LASEC occurring in nonvalvular AF patients who have low thromboembolic risk scores. We therefore examined prevalence and determinants of LASEC under low CHADS2 or CHA2DS2-VASc scores in these patients.

Methods

Among 713 patients who underwent transesophageal echocardiography, 349 with a CHADS2 score < 2 (CHADS2 group) (93 women, mean age 65 years) and 221 with a CHA2DS2-VASc score < 2 (CHA2DS2-VASc group) (39 women, mean age 62 years) were separately examined for clinical and echocardiographic findings.

Results

LASEC was found in 77 patients of CHADS2 group (22%) and in 41 of CHA2DS2-VASc group (19%). Multivariate logistic regression analysis, adjusted for several parameters including non-paroxysmal AF, LA enlargement (LA diameter ≥ 50 mm), left ventricular (LV) hypertrophy, and an elevated B-type natriuretic peptide (BNP) (BNP ≥200 pg/mL) revealed that for CHADS2 group, non-paroxysmal AF (Odds ratio 5.65, 95%CI 3.08–10.5, P < 0.001), BNP elevation (Odds ratio 3.42, 95%CI 1.29–9.06, P = 0.013), and LV hypertrophy (Odds ratio 2.26, 95%CI 1.19–4.28, P = 0.013) were significant independent determinants of LASEC, and that for CHA2DS2-VASc group, non-paroxysmal AF (Odds ratio 3.38, 95%CI 1.51–7.54, P = 0.003) and LV hypertrophy (Odds ratio 2.53, 95%CI 1.13–5.70, P = 0.025) were significant independent determinants of LASEC.

Conclusions

LASEC was present in a considerable proportion of patients with nonvalvular AF under low thromboembolic risk scores. Information on AF chronicity, BNP, and LV hypertrophy might help identify patients at risk for thromboembolism, although large-scale studies are necessary to confirm our observations.
Deciphering the immunogenic potential of wheat flour: a reference map of the salt-soluble proteome from the U.S. wheat Butte 86
Authors: Altenbach Susan B. , Chang Han-Chang , Simon-Buss Annamaria
Published: August 2020

Background

Within the complex wheat flour proteome, the gluten proteins have attracted most of the attention because of their importance in determining the functional properties of wheat flour doughs and their roles in human health conditions such as celiac disease and food allergies. However, certain non-gluten proteins also trigger immunological responses but may be present in flour in low amounts or obscured by the more abundant gluten proteins in two-dimensional gels of total protein preparations.

Methods

Non-gluten proteins were preferentially extracted from the flour with a dilute salt solution and separated by two-dimensional gel electrophoresis. Proteins in 173 gel spots were identified by tandem mass spectrometry after cleavage with trypsin or chymotrypsin. Transgenic wheat lines in which specific groups of gluten proteins were suppressed by RNA interference were used to estimate the amount of carry-over of gluten proteins in the salt-soluble protein fraction.

Results

Fifty-seven different types of non-gluten proteins were identified, including 14 types that are known or suspected immunogenic proteins. The predominant proteins in 18 gel spots were gluten proteins. Some of these also contained non-gluten proteins. Analysis of the salt-soluble proteins from a transgenic line in which omega-1,2 gliadins were eliminated by RNA interference indicated that certain omega-1,2 gliadins were present in large amounts in the salt-soluble fraction and obscured relatively small amounts of beta-amylase and protein disulfide isomerase. In comparison, analysis of a transgenic line in which alpha gliadins were absent revealed that glyceraldehyde-3 phosphate dehydrogenase was a moderately abundant protein that co-migrated with several alpha gliadins.

Conclusions

In this study, we constructed a proteomic map of the non-gluten protein fraction of wheat flour from the US wheat Butte 86 that complements a proteomic map of the total flour proteins developed previously for the same cultivar. Knowing the identities of low abundance proteins in the flour as well as proteins that are hidden by some of the major gluten proteins on two-dimensional gels is critical for studies aimed at assessing the immunogenic potential of wheat flour and determining which wheat proteins that should be targeted in future gene editing experiments to reduce the immunogenic potential of wheat flour.
Health-related quality of life of female patients with congenital adrenal hyperplasia in Malaysia
Authors: Zainuddin Ani Amelia , Grover Sonia Regina , Abdul Ghani Nur Azurah , Wu Loo Ling , Rasat Rahmah , Abdul Manaf Mohd. Rizal , Shamsuddin Khadijah , Abdullah Mahdy Zaleha
Published: August 2020

Background

This study investigates the health-related quality of life (HRQOL) of female patients with congenital adrenal hyperplasia (CAH) in Malaysia. The objectives were to attain socio-demographic and medical data on these Malaysian females with CAH and establish their health-related quality of life (HRQOL) in comparison to age matched diabetic controls.

Methods

A cross-sectional study was conducted over 6 months in the two main tertiary centres for CAH patients in Malaysia. Participants including 59 female-raised CAH patients (mean age ± SD = 16.3 ± 4.2 years, range 10–28 years) compared to 57 age-matched female diabetic patients (mean age ± SD = 16.5 ± 3.4 years, range 10–26 years). Socio-demographic and medical profiles was obtained through semi-structured interviews. HRQOL of participants were evaluated utilising validated, Malay translated questionnaires which were age appropriate: Pediatric Quality of Life Inventory (PedsQL v4.0) scales for Child (8–12) and Adolescent (13–18) and Medical Outcome Survey 36-item Short Form version. These were then compared to the diabetic controls.

Results

The CAH participants consisted of children (ages 10–12 years, n = 12), adolescents (ages 13–17 years, n = 29) and adults (≥ 18 years, n = 18). The majority were Malays (64.4%) and had salt-wasting CAH (67.8%). There were no significant differences between the total mean score of the HRQOL of the combined children and adolescents CAH group (total mean score ± SD = 81.6 ± 17.9, 95% CI = 75.6–87.6) when compared to age-matched diabetic patients (total mean score ± SD = 80.8 ± 11.0, 95% CI = 77.0–84.5, P = 0.81, effect size = 0.05); no significant difference between the adult CAH and diabetic controls in the physical [median score (IQR) CAH vs diabetics; 49.3 (11.4) vs. 50.2 (6.1), P = 0.60, effect size = 0.09] and the mental composite scores [median score (IQR) CAH vs. diabetics; 47.8 (14.1) vs. 50.0 (10.8), P = 0.93, effect size = 0.01].

Conclusions

The HRQOL of the Malaysian CAH cohort were comparable to the diabetic controls.
Longitudinal impact of changes in the residential built environment on physical activity: findings from the ENABLE London cohort study
Authors: Clary Christelle , Lewis Daniel , Limb Elizabeth , Nightingale Claire M. , Ram Bina , Page Angie S. , Cooper Ashley R. , Ellaway Anne , Giles-Corti Billie , Whincup Peter H. , Rudnicka Alicja R. , Cook Derek G. , Owen Christopher G. , Cummins Steven
Published: August 2020

Background

Previous research has reported associations between features of the residential built environment and physical activity but these studies have mainly been cross-sectional, limiting inference. This paper examines whether changes in a range of residential built environment features are associated with changes in measures of physical activity in adults. It also explores whether observed effects are moderated by socio-economic status.

Methods

Data from the Examining Neighbourhood Activity in Built Living Environments in London (ENABLE London) study were used. A cohort of 1278 adults seeking to move into social, intermediate, and market-rent East Village accommodation was recruited in 2013–2015, and followed up after 2 years. Accelerometer-derived steps (primary outcome), and GIS-derived measures of residential walkability, park proximity and public transport accessibility were obtained both at baseline and follow-up. Daily steps at follow-up were regressed on daily steps at baseline, change in built environment exposures and confounding variables using multilevel linear regression to assess if changes in neighbourhood walkability, park proximity and public transport accessibility were associated with changes in daily steps. We also explored whether observed effects were moderated by housing tenure as a marker of socio-economic status.

Results

Between baseline and follow-up, participants experienced a 1.4 unit (95%CI 1.2,1.6) increase in neighbourhood walkability; a 270 m (95%CI 232,307) decrease in distance to their nearest park; and a 0.7 point (95% CI 0.6,0.9) increase in accessibility to public transport. A 1 s.d. increase in neighbourhood walkability was associated with an increase of 302 (95%CI 110,494) daily steps. A 1 s.d. increase in accessibility to public transport was not associated with any change in steps overall, but was associated with a decrease in daily steps amongst social housing seekers (− 295 steps (95%CI − 595, 3), and an increase in daily steps for market-rent housing seekers (410 95%CI -191, 1010) (P-value for effect modification = 0.03).

Conclusion

Targeted changes in the residential built environment may result in increases in physical activity levels. However, the effect of improved accessibility to public transport may not be equitable, showing greater benefit to the more advantaged.
Patient specific circulating tumor DNA fingerprints to monitor treatment response across multiple tumors
Authors: Li Jiaping , Jiang Wei , Wei Jinwang , Zhang Jianwei , Cai Linbo , Luo Minjie , Wang Zhan , Sun Wending , Wang Shengzhou , Wang Chen , Dai Chun , Liu Jun , Wang Guan , Wang Jiping , Xu Qiang , Deng Yanhong
Published: August 2020

Background

Circulating tumor DNA (ctDNA) offers a convenient way to monitor tumor progression and treatment response. Because tumor mutational profiles are highly variable from person to person, a fixed content panel may be insufficient to track treatment response in all patients.

Methods

We design ctDNA fingerprint panels specific to individual patients which are based on whole exome sequencing and target to high frequency clonal population clusters in patients. We test the fingerprint panels in 313 patients who together have eight tumor types (colorectal, hepatocellular, gastric, breast, pancreatic, and esophageal carcinomas and lung cancer and cholangiocarcinoma) and exposed to multiple treatment methods (surgery, chemotherapy, radiotherapy, targeted-drug therapy, immunotherapy, and combinations of them). We also monitor drug-related mutations in the patients using a pre-designed panel with eight hotspot genes.

Results

291 (93.0%) designed fingerprint panels harbor less than ten previously known tumor genes. We detected 7475 ctDNA mutations in 238 (76%) patients and 6196 (96.0%) of the mutations are detected in only one test. Both the level of ctDNA content fraction (CCF) and fold change of CCF (between the definitive and proceeding tests) are highly correlated with clinical outcomes (p-values 1.36e-6 for level and 5.64e-10 for fold change, Kruskal–Wallis test). The CCFs of PD patients are an order of magnitude higher than the CCFs of SD and OR patients (median/mean 2.22%/8.96% for SD, 0.18/0.21% for PD, and 0.31/0.54% for OR; pairwise p-values 7.8e-6 for SD ~ PD, 2.7e-4 for OR ~ PD, and 7.0e-3 for SD ~ OR, Wilcoxon rank sum test). The fold change of CCF distinguishes the patient groups even better, which increases for PD, remains stable for SD, and decreases for OR patients (p-values 0.002, ~ 1, and 0.0001 respectively, Wilcoxon signed-rank test). Eleven drug-related mutations are identified from nine out of the 313 patients.

Conclusions

The ctDNA fingerprint method improves both specificity and sensitivity of monitoring treatment response across several tumor types. It can identify tumor relapse/recurrence potentially earlier than imaging-based diagnosis. When augmented with tumor hotspot genes, it can track acquired drug-related mutations in patients.
Etiological analysis of virus, mycoplasma pneumoniae and chlamydia pneumoniae in hospitalized children with acute respiratory infections in Huzhou
Authors: Gao Min , Yao Xing , Mao Wei , Shen Cuifen , Zhang Zongxin , Huang Qiuling , Cui Dawei , Sun Haiyan , Zou Weihua
Published: August 2020

Background

Acute respiratory infections are a common disease in children with high mortality and morbidity. Multiple pathogens can cause acute respiratory infections. A 2-year survey of hospitalized children was conducted to understand the epidemic situation, seasonal spread of pathogens and the improvement of clinical diagnosis, treatment and prevention of disease in Huzhou, China.

Methods

From September 2017 to August 2019, 3121 nasopharyngeal swabs from hospitalized children with acute respiratory infections were collected, and real-time PCR was used to detect various pathogens. Then, pathogen profiles, frequency and seasonality were analyzed.

Results

Of the 3121 specimens, 14.45% (451/3121) were positive for at least one pathogen. Of the single-pathogen infections, RSV (45.61%, 182/399) was the most frequent pathogen, followed by PIVs (14.79%, 59/399), ADV (14.54%, 58/399), MP (10.78%, 43/399), and IAV (5.26%, 21/399). Of the 52 coinfections, RSV + PIVs viruses were predominantly identified and accounted for 40.38% (21/52) of cases. RSV was the most frequent pathogen in all four groups. The highest positive rate of the pathogens occurred in the winter (21.26%), followed by autumn (14.98%), the summer (14.11%) and the spring (12.25%).

Conclusion

Viruses are the main pathogens in hospitalized children with acute respiratory infections in Huzhou city, Zhejiang Province, China. Among the pathogens, RSV had the highest detection rate, and MP is also a common pathogen among children with acute respiratory infections. This study provided a better understanding of the distribution of pathogens in children of different ages and seasons, which is conducive to the development of more reasonable treatment strategies and prevention and control measures.