bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Sphincter Augmentation for Hiatus Hernia and De Novo Gerd after Sleeve Gastrectomy
Authors: Asti Emanuele , Bernardi Daniele , Bonavina Luigi
Published: August 2021

Laparoscopic sleeve gastrectomy (LSG) has become the most popular bariatric surgical procedure owing to its safety, reproducibility and effectiveness. However, gastroesophageal reflux disease (GERD) with or without hiatal hernia is diagnosed at an alarming rate after LSG. Revisional surgery and conversion to Roux-en-Y gastric bypass (RYGB) does not guarantee total reflux control and is associated with morbidity. Magnetic sphincter augmentation (MSA) combined with crural repair is an alternative therapeutic option as a concurrent or remedial procedure in LSG, but current clinical evidence is still limited.
Characterization of genes associated with TGA7 during the floral transition
Authors: Xu Xiaorui , Xu Jingya , Yuan Chen , Hu Yikai , Liu Qinggang , Chen Qianqian , Zhang Pengcheng , Shi Nongnong , Qin Cheng
Published: August 2021

Background

The TGACG-binding (TGA) family has 10 members that play vital roles in Arabidopsis thaliana defense responses and development. However, their involvement in controlling flowering time remains largely unknown and requires further investigation.

Results

To study the role of TGA7 during floral transition, we first investigated the tga7 mutant, which displayed a delayed-flowering phenotype under both long-day and short-day conditions. We then performed a flowering genetic pathway analysis and found that both autonomous and thermosensory pathways may affect TGA7 expression. Furthermore, to reveal the differential gene expression profiles between wild-type (WT) and tga7, cDNA libraries were generated for WT and tga7 mutant seedlings at 9 days after germination. For each library, deep-sequencing produced approximately 6.67 Gb of high-quality sequences, with the majority (84.55 %) of mRNAs being between 500 and 3,000 nt. In total, 325 differentially expressed genes were identified between WT and tga7 mutant seedlings. Among them, four genes were associated with flowering time control. The differential expression of these four flowering-related genes was further validated by qRT-PCR.

Conclusions

Among these four differentially expressed genes associated with flowering time control, FLC and MAF5 may be mainly responsible for the delayed-flowering phenotype in tga7, as TGA7 expression was regulated by autonomous pathway genes. These results provide a framework for further studying the role of TGA7 in promoting flowering.
Identification of Brassica napus small RNAs responsive to infection by a necrotrophic pathogen
Authors: Regmi Roshan , Newman Toby E. , Kamphuis Lars G. , Derbyshire Mark C.
Published: August 2021

Background

Small RNAs are short non-coding RNAs that are key gene regulators controlling various biological processes in eukaryotes. Plants may regulate discrete sets of sRNAs in response to pathogen attack. Sclerotinia sclerotiorum is an economically important pathogen affecting hundreds of plant species, including the economically important oilseed B. napus. However, there are limited studies on how regulation of sRNAs occurs in the S. sclerotiorum and B. napus pathosystem.

Results

We identified different classes of sRNAs from B. napus using high throughput sequencing of replicated mock and infected samples at 24 h post-inoculation (HPI). Overall, 3999 sRNA loci were highly expressed, of which 730 were significantly upregulated during infection. These 730 up-regulated sRNAs targeted 64 genes, including disease resistance proteins and transcriptional regulators. A total of 73 conserved miRNA families were identified in our dataset. Degradome sequencing identified 2124 cleaved mRNA products from these miRNAs from combined mock and infected samples. Among these, 50 genes were specific to infection. Altogether, 20 conserved miRNAs were differentially expressed and 8 transcripts were cleaved by the differentially expressed miRNAs miR159, miR5139, and miR390, suggesting they may have a role in the S. sclerotiorum response. A miR1885-triggered disease resistance gene-derived secondary sRNA locus was also identified and verified with degradome sequencing. We also found further evidence for silencing of a plant immunity related ethylene response factor gene by a novel sRNA using 5′-RACE and RT-qPCR.

Conclusions

The findings in this study expand the framework for understanding the molecular mechanisms of the S. sclerotiorum and B. napus pathosystem at the sRNA level.
Optimizing the diagnosis and management of dementia within primary care: a systematic review of systematic reviews
Authors: Fernandes Brooklynn , Goodarzi Zahra , Holroyd-Leduc Jayna
Published: August 2021

Background

To understand how best to approach dementia care within primary care and its challenges, we examined the evidence related to diagnosing and managing dementia within primary care.

Methods

Databases searched include: MEDLINE, Embase, PsycINFO and The Cochrane Database of Systematic Reviews from inception to 11 May 2020. English-language systematic reviews, either quantitative or qualitative, were included if they described interventions involving the diagnosis, treatment and/or management of dementia within primary care/family medicine and outcome data was available. The risk of bias was assessed using AMSTAR 2. The review followed PRISMA guidelines and is registered with Open Science Framework.

Results

Twenty-one articles are included. The Mini-Cog and the MMSE were the most widely studied cognitive screening tools. The Abbreviated Mental Test Score (AMTS) achieved high sensitivity (100 %, 95 % CI: 70-100 %) and specificity (82 %, 95 % CI: 72-90 %) within the shortest amount of time (3.16 to 5 min) within primary care. Five of six studies found that family physicians had an increased likelihood of suspecting dementia after attending an educational seminar. Case management improved behavioural symptoms, while decreasing hospitalization and emergency visits. The primary care educational intervention, Enhancing Alzheimer’s Caregiver Health (Department of Veterans Affairs), was successful at increasing carer ability to manage problem behaviours and improving outcomes for caregivers.

Conclusions

There are clear tools to help identify cognitive impairment in primary care, but strategies for management require further research. The findings from this systematic review will inform family physicians on how to improve dementia diagnosis and management within their primary care practice.
Nocturnal blood pressure rise as a predictor of cognitive impairment among the elderly: a retrospective cohort study
Authors: Xing Yunli , Sun Ying , Wang Shan , Feng Feng , Zhang Deqiang , Li Hongwei
Published: August 2021

Background

This study investigated the different blood pressure patterns that were evaluated by ambulatory blood pressure monitoring (ABPM) among elderly patients and explored the effect of pressure patterns on cognitive impairment and mortality.

Methods

A total of 305 elderly participants aged ≥65 years were divided into the cognitive impairment group (CI, n = 130) and the non-cognitive impairment group (NCI, n = 175) according to the MMSE score. All participants underwent ABPM to evaluate possible hypertensive disorder and cerebral MRI for the evaluation of cerebral small vessel disease. Follow-up was performed by telephone or medical records. The primary outcome was all-cause mortality. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE).

Results

Among 305 participants, 130 (42.6%) were identified with cognitive impairment (CI), with average systolic blood pressure (BP) of 127 mmHg and diastolic BP of 66 mmHg. According to ABPM, only 13.1% had a dipper pattern, 45.6% had a nocturnal BP rise, while 41.3% had a non-dipper pattern. Compared with NCI patients, the CI group had significantly higher night-time systolic BP (130.0 ± 18.2 vs. 123.9 ± 15.1, p = 0.011), and more participants had nocturnal BP rise (52.3% vs. 40.6%, p = 0.042). Nocturnal BP rise was associated with greater white matter hyperintensities (WMH) (p = 0.013). After 2.03 years of follow-up, there were 35 all-cause deaths and 33 cases of major adverse cardiac and cerebrovascular events (MACCE). CI was independently associated with all-cause mortality during long-term observation (p < 0.01). Nocturnal BP rise had no significant predictive ability for all-cause mortality in elderly patients (p = 0.178).

Conclusions

Nocturnal BP rise contributed to greater cognitive impairment in elderly patients. Not nocturnal BP rise, but CI could significantly increase all-cause mortality. Controlling BP based on ABPM is critical for preventing the progression of cognitive dysfunction.
The role of surgical management of BCG vaccine-induced regional suppurative lymphadenitis in children: a 7 years' experience from one medical center
Authors: Liu Chen , Huang Minxiang , Liu Fang , Xu Xiaoliang , Feng Wenyu , Han Guoxiu , Liu Xijie , Zheng Bufeng , Geng Lei , Fu Tingliang
Published: August 2021

Background

The management strategy of Bacille Calmette-Guérin (BCG) vaccine-induced regional suppurative lymphadenitis in children is still controversial and more clinical studies are needed. We therefore present a surgical case series to explore the role of surgical management for this dilemma.

Methods

From January 2013 to June 2020, data from 65 patients diagnosed with BCG vaccine-induced regional suppurative lymphadenitis were retrospectively reviewed. Clinical characteristics, ultrasonographic findings, surgical procedures, perioperative management, and outcome were analyzed. The association between postoperative seroma and symptom duration, skin involvement, and postoperative hospital stay were compared using Yates's corrected Chi-square test and Student's t-test for statistical analysis. The follow-up period ranged from three to six months.

Results

Of the 65 cases, the median age at presentation was 3.4 months. All patients were full-term with normal range of birth weight and received a BCG vaccination in the first 24 h of life. All patients underwent surgical excision of the abscess with the involved lymph node(s). Postoperative seroma formation was found in 20 patients and fine needle aspiration was needed. There was no significant association between postoperative seroma formation with symptom duration, skin involvement, and postoperative hospital stay. No oral anti-tubercular agents were given postoperatively. The mean length of postoperative hospital stay was 6.02 ± 1.62 days. Sixty-four cases (98.46%) received only one procedure and recovered. One patient required a second procedure due to postoperative sinus.

Conclusions

The present study showed that surgical excision of the abscess with involved lymph node(s) is one of the choices for BCG vaccine-induced suppurative lymphadenitis, but special attention should be paid to controlling the surgical indications. Intraoperative meticulous manipulation and postoperative care are crucial to achieve a good outcome.
The association of minerals intake in three meals with cancer and all-cause mortality: the U.S. National Health and Nutrition Examination Survey, 2003–2014
Authors: Xu Xiaoqing , Wei Wei , Xu Jiaxu , Huang Jiaxin , Li Li , Han Tianshu , Qi Jiayue , Sun Changhao , Li Ying , Jiang Wenbo
Published: August 2021

Background

Intake time of diet has recently been demonstrated to be associated with the internal clock and circadian pattern. However, whether and how the intake time of minerals would influence the natural course of cancer was largely unknown.

Methods

This study aimed to assess the association of mineral intake at different periods with cancer and all-cause mortality. A total of 27,455 participants aged 18–85 years old in the National Health and Nutrition Examination Survey were recruited. The main exposures were the mineral intakes in the morning, afternoon and evening, which were categorized into quintiles, respectively. The main outcomes were mortality of cancer and all causes.

Results

During the 178,182 person-years of follow-up, 2680 deaths, including 601 deaths due to cancer, were documented. After adjusting for potential confounders, compared to the participants who were in the lowest quintile(quintile-1) of mineral intakes at dinner, the participants in the highest quintile intake(quintile-5) of dietary potassium, calcium and magnesium had lower mortality risks of cancer (HRpotassium = 0.72, 95% CI:0.55–0.94, P for trend = 0.023; HRcalcium = 0.74, 95% CI:0.57–0.98, P for trend = 0.05; HRmagnesium = 0.75, 95% CI:0.56–0.99, P for trend = 0.037) and all-cause (HRpotassium = 0.83, 95% CI:0.73–0.94, P for trend = 0.012; HRcalcium = 0.87, 95% CI:0.76–0.99, P for trend = 0.025; HRmagnesium = 0.85, 95% CI:0.74–0.97, P for trend = 0.011; HRcopper = 0.80, 95%CI: 0.68–0.94, P for trend = 0.012). Further, equivalently replacing 10% of dietary potassium, calcium and magnesium consumed in the morning with those in the evening were associated with lower mortality risk of cancer (HRpotassium = 0.94, 95%CI:0.91–0.97; HRcalcium = 0.95, 95%CI:0.92–0.98; HRmagnesium = 0.95, 95%CI: 0.92–0.98).

Conclusions

This study demonstrated that the optimal intake time of potassium, calcium and magnesium for reducing the risk of cancer and all-cause mortality was in the evening.
Antibiomania: a case report of clarithromycin and amoxicillin-clavulanic acid induced manic episodes separately
Authors: Meszaros Edith Paula , Stancu Catheline , Costanza Alessandra , Besson Marie , Sarasin François , Bondolfi Guido , Ambrosetti Julia
Published: August 2021

Background

Antibiomania is a rare but recognized side effect with yet unclear definite pathogenesis although multiple hypotheses have been proposed. The novelty of this case is the suspected pharmacodynamic drug-drug interaction between clarithromycin and amoxicillin-clavulanic acid.

Case presentation

We present the occurrence of a brief manic episode concerning a 50-year-old man with no psychiatric history, first started on amoxicillin-clavulanic acid therapy and then switched to clarithromycin for left basal pneumonia. Shortly after the antibiotic prescription, he presented psychiatric symptomatology (logorrhea, elevated mood, irritability, increase in physical activity and delusions). The antibiotic was stopped and the patient received lorazepam (2.5 mg p.o.) to treat psychomotor agitation. Approximately 12 h after clarithromycin cessation, amelioration was already observed, supporting the diagnosis of a clarithromycin-induced manic episode. Amoxicillin-clavulanic acid was then reintroduced because of the pneumonia and psychiatric symptoms reemerged. This second antibiotic was also stopped, and 1 week later, the patient was symptom-free.

Conclusion

The emergence of psychiatric side effects related to antibiotherapy, which is a common treatment, can greatly impact a patient’s quality of life. Early recognition and intervention could substantially influence the administered medical care and recovery. Moreover, given the widespread use of antibiotics including in combination, we thought our case report might be clinically useful as a clinical reminder relevant to the use of antibiotic combinations.
A new classification of talocalcaneal coalitions based on computed tomography for operative planning
Authors: Wang Anhong , Shi Weili , Gao Lixiang , Chen Linxin , Xie Xing , Zhao Feng , Pi Yanbin , Jiao Chen , Hu Yuelin , Jiang Dong , Guo Qinwei
Published: August 2021

Background

Current classifications emphasize the morphology of the coalition, however, subtalar joint facets involved should also be emphasized.

Objective

The objective of this study was to develop a new classification system based on the articular facets involved to cover all coalitions and guide operative planning.

Methods

Patients were diagnosed with talocalcaneal coalition using a CT scan, between January 2009 and February 2021. The coalition was classified into four main types according to the shape and nature of the coalition: I, inferiorly overgrown talus or superiorly overgrown calcaneus; II, both talus and calcaneus overgrew; III, coalition with an accessory ossicle; IV, complete osseous coalition (I-III types are non-osseous coalition). Then each type was further divided into three subtypes according to the articular facets involved. A, the coalition involving the anterior facets; M, the coalition involving the middle facets, and P, the coalition involving the posterior facets. Interobserver reliability was measured at the main type (based on nature and shape) and subtype (articular facet involved) using weighted Kappa.

Results There were 106 patients (108 ft) included in this study. Overall, 8 ft (7.5%) were classified as type I, 75 ft (69.4%) as type II, 7 ft (6.5%) as type III, and 18 ft (16.7%) as type IV. Twenty-nine coalitions (26.9%) involved the posterior facets only (subtype-P), 74 coalitions (68.5%) involved both the middle and posterior facets (subtype-MP), and five coalitions (4.6%) simultaneously involved the anterior, middle, and posterior facets (subtype-AMP). Type II-MP coalition was the most common. The value of weighted Kappa for the main type was 0.93 (95%CI 0.86–0.99) (p<0.001), and the value for the subtype was 0.78 (95%CI 0.66–0.91) (p<0.001).

Conclusion

A new classification system of the talocalcaneal coalition to facilitate operative planning was developed.
P2Y2 promotes fibroblasts activation and skeletal muscle fibrosis through AKT, ERK, and PKC
Authors: Chen Mengjie , Chen Haibing , Gu Yonggui , Sun Peng , Sun Jianxiong , Yu Haojun , Zheng Hongliang , Chen Donghui
Published: August 2021

Background

Skeletal muscle atrophy and fibrosis are pathological conditions that contribute to morbidity in numerous conditions including aging, cachexia, and denervation. Muscle atrophy is characterized as reduction of muscle fiber size and loss of muscle mass while muscle fibrosis is due to fibroblasts activation and excessive production of extracellular matrix. Purinergic receptor P2Y2 has been implicated in fibrosis. This study aims to elucidate the roles of P2Y2 in sleketal muscle atrophy and fibrosis.

Methods

Primary muscle fibroblasts were isolated from wild type and P2Y2 knockout (KO) mice and their proliferating and migrating abilities were assessed by CCK-8 and Transwell migration assays respectively. Fibroblasts were activated with TGF-β1 and assessed by western blot of myofibroblast markers including α-SMA, CTGF, and collagen I. Muscle atrophy and fibrosis were induced by transection of distal sciatic nerve and assessed using Masson staining.

Results

P2Y2 KO fibroblasts proliferated and migrated significantly slower than WT fibroblasts with or without TGF-β1.The proliferation and ECM production were enhanced by P2Y2 agonist PSB-1114 and inhibited by antagonist AR-C118925. TGF-β1 induced fibrotic activation was abolished by P2Y2 ablation and inhibited by AKT, ERK, and PKC inhibitors. Ablation of P2Y2 reduced denervation induced muscle atrophy and fibrosis.

Conclusions

P2Y2 is a promoter of skeletal muscle atrophy and activation of fibroblasts after muscle injury, which signaling through AKT, ERK and PKC. P2Y2 could be a potential intervention target after muscle injury.
Mortality following emergency laparotomy: a Swedish cohort study
Authors: Jansson Timan Terje , Hagberg Gustav , Sernert Ninni , Karlsson Ove , Prytz Mattias
Published: August 2021

Background

Emergency laparotomy (EL) is a central, high-risk procedure in emergency surgery. Patients in need of an EL present an acute pathology in the abdomen that must be operated on in order to save their lives. Usually, the underlying condition produces an affected physiology. The perioperative management of this critically ill patient group in need of high-risk surgery and anaesthesia is challenging and related to high mortality worldwide. However, outcomes in Sweden have yet to be studied. This retrospective cohort study explores the perioperative management and outcome after 710 ELs by investigating mortality, overall length of stay (LOS) in hospital, need for care at the intensive care unit (ICU), surgical complications and a general review of perioperative management.

Methods

Medical records after laparotomy was retrospectively analysed for a period of 38 months (2014–2017), the emergency cases were included. Children (< 18 years), aortic surgery, second look and other expected reoperations were excluded. Demographic, management and outcome data were collected after an extensive analysis of the cohort.

Results

A total of 710 consecutive operations, representing 663 patients, were included in the cohort (mean age 65.6 years). Mortality (30 days/1 year) after all operations was 14.2% and 26.6% respectively. The mean LOS in hospital was 12 days, while LOS in the ICU was five days. Of all operations, 23.8% patients were admitted at any time to the ICU postoperatively and the 30-day mortality seen among ICU patients was 37.9%. Mortality was strongly correlated to existing comorbidity, high ASA classification, ICU care and faecal peritonitis. The mean/median time from notification to operate until the first incision was 3:46/3:02 h and 87% of patients had their first incision within 6 h of notification.

Conclusions

In this present Swedish study, high mortality and morbidity were observed after emergency laparotomy, which is in agreement with other recent studies.

Trial registration: The study has been registered with ClinicalTrials.gov (NCT03549624, registered 8 June 2018).
Exploring the opinions of secondary school students on the strengths and weaknesses of the school dental service in Selangor, Malaysia: a qualitative study
Authors: Ab Mumin Nazirah , Yusof Zamros Yuzadi Mohd , Marhazlinda Jamaludin , Obaidellah Unaizah
Published: August 2021

Background

The Malaysian School Dental Service (SDS) was introduced to provide systematic and comprehensive dental care to school students. The service encompasses promotive, preventive, and, curative dental care. This study aimed to undertake a process evaluation of the SDS based on the perspectives of government secondary school students in Selangor, Malaysia.

Methods

The study adopted a qualitative approach to explore the opinions of secondary school students on the SDS implementation in their schools. Data from focus group discussions involving Form Two (14-year-olds) and Form Four (16-year-olds) students from the selected schools were transcribed verbatim and coded using the NVivo software before framework method analysis was conducted.

Results

Among the strengths of the SDS were the convenience for students to undergo annual oral examination and dental treatment without having to visit dental clinics outside the school. The SDS also reduced possible financial burdens resulting from dental treatment costs, especially among students from low-income families. Furthermore, SDS helped to improve oral health awareness. However, the oral health education provided by the SDS personnel was deemed infrequent while the content and method of delivery were perceived to be less interesting. The poor attitude of the SDS personnel was also reported by the students.

Conclusion

The SDS provides effective and affordable dental care to secondary school students. However, the oral health promotion and education activities need to be improved to keep up with the evolving needs of the target audience.
Cross-cultural adaptation and psychometric evaluation of the Slovenian version of the nurse professional competence scale
Authors: Prosen Mirko , Kvas Andreja , Bošković Sandra , Ličen Sabina
Published: August 2021

Background

The competency-based approach to the assessment of nursing practice has been adopted as a key policy in the developed world. The continual self-assessment of competence gives nurses the opportunity to reflect on their competencies and has a significant impact on the quality of nursing practice and patient safety. The study was designed to describe the process of cross-cultural adaptation and to assess the psychometric properties of the Slovenian version of a short form of the Nurse Professional Competence scale (NPC-SF) and to evaluate the efficacy of this instrument in a sample of registered nurses.

Methods

A cross-sectional and validation study was conducted in 425 registered nurses to test the psychometric properties of the Slovenian version of a short form of the scale and to evaluate nurses’ professional competence. A multilevel approach was used: Translation, back-translation, language validity, face and content validity, construct validity, and reliability of the Slovenian version of the scale were analysed respectively. Participants completed an online survey, with the data being collected between April and July 2020.

Results

Factor analysis showed that the Slovenian version of the scale could be used in four dimensions explained with 65 % of the variance. Cronbach’s α was 0.972. The four-factor model fit the data (RMSEA = 0.083, CFI = 0.731). Self-reported competence was high and rated higher by nurses employed at the tertiary level of healthcare, followed by nurses employed at the secondary and primary, and from social care institutions. Nurses with more years of experience assessed their competence higher.

Conclusions

The NPC-SF helps understand and identify nurses’ self-reported core competencies in clinical settings, thereby providing an important predictor of the professional development of nursing. The Slovenian version of the scale demonstrated acceptable psychometric properties and may be used in research and clinical practice to evaluate nurses’ professional competence.
Facility-level conditions leading to higher reach: a configurational analysis of national VA weight management programming
Authors: Miech Edward J. , Freitag Michelle B. , Evans Richard R. , Burns Jennifer A. , Wiitala Wyndy L. , Annis Ann , Raffa Susan D. , Spohr Stephanie A. , Damschroder Laura J.
Published: August 2021

Background

While the Veterans Health Administration (VHA) MOVE! weight management program is effective in helping patients lose weight and is available at every VHA medical center across the United States, reaching patients to engage them in treatment remains a challenge. Facility-based MOVE! programs vary in structures, processes of programming, and levels of reach, with no single factor explaining variation in reach. Configurational analysis, based on Boolean algebra and set theory, represents a mathematical approach to data analysis well-suited for discerning how conditions interact and identifying multiple pathways leading to the same outcome. We applied configurational analysis to identify facility-level obesity treatment program arrangements that directly linked to higher reach.

Methods

A national survey was fielded in March 2017 to elicit information about more than 75 different components of obesity treatment programming in all VHA medical centers. This survey data was linked to reach scores available through administrative data. Reach scores were calculated by dividing the total number of Veterans who are candidates for obesity treatment by the number of “new” MOVE! visits in 2017 for each program and then multiplied by 1000. Programs with the top 40 % highest reach scores (n = 51) were compared to those in the lowest 40 % (n = 51). Configurational analysis was applied to identify specific combinations of conditions linked to reach rates.

Results

One hundred twenty-seven MOVE! program representatives responded to the survey and had complete reach data. The final solution consisted of 5 distinct pathways comprising combinations of program components related to pharmacotherapy, bariatric surgery, and comprehensive lifestyle intervention; 3 of the 5 pathways depended on the size/complexity of medical center. The 5 pathways explained 78 % (40/51) of the facilities in the higher-reach group with 85 % consistency (40/47).

Conclusions

Specific combinations of facility-level conditions identified through configurational analysis uniquely distinguished facilities with higher reach from those with lower reach. Solutions demonstrated the importance of how local context plus specific program components linked together to account for a key implementation outcome. These findings will guide system recommendations about optimal program structures to maximize reach to patients who would benefit from obesity treatment such as the MOVE! program.
A novel homozygous variant of COL2A1 in a Chinese male with type II collagenopathy: a case report
Authors: Zhang Qianwen , Yao Ruen , Li Qun , Li Xin , Feng Biyun , Chang Guoying , Wang Jian , Wang Xiumin
Published: August 2021

Background

Type II collagenopathies are a spectrum of diseases and skeletal dysplasia is one of the prominent features of collagenopathies. Molecular defects of the COL2A1 gene cause type II collagenopathies that is mainly an autosomal dominant disease, whereas some rare cases with autosomal recessive inheritance of mode have also been identified.

Case presentation

The patient was a 5-year-old male with a short neck, flat face, epiphyseal dysplasia, irregular vertebral endplates, and osteochondritis. Sequencing result indicated NM_001844.4: c.3662C > T; p. (Ser1221Phe) a novel missense variant, leading to a serine-to-phenylalanine substitution. Sanger sequencing confirmed the variant compared to his parents and brother.

Conclusions

We identified a novel homozygous variant of the COL2A1 gene as the cause of type II collagenopathies in a Chinese male, enriching the spectrum of genotypes. This is the first case of type II collagenopathies inherited in an autosomal recessive manner in China and East Asia, and it is the first case that resulted from serine substitution in the world.
WRAP-based nanoparticles for siRNA delivery: a SAR study and a comparison with lipid-based transfection reagents
Authors: Konate Karidia , Josse Emilie , Tasic Milana , Redjatti Karima , Aldrian Gudrun , Deshayes Sébastien , Boisguérin Prisca , Vivès Eric
Published: August 2021

Recently, we designed novel amphipathic cell-penetrating peptides, called WRAP, able to transfer efficiently siRNA molecules into cells. In order to gain more information about the relationship between amino acid composition, nanoparticle formation and cellular internalization of these peptides composed of only three amino acids (leucine, arginine and tryptophan), we performed a structure–activity relationship (SAR) study. First, we compared our WRAP1 and WRAP5 peptides with the C6M1 peptide also composed of the same three amino acids and showing similar behaviors in siRNA transfection. Afterwards, to further define the main determinants in the WRAP activity, we synthesized 13 new WRAP analogues harboring different modifications like the number and location of leucine and arginine residues, the relative location of tryptophan residues, as well as the role of the α-helix formation upon proline insertions within the native WRAP sequence. After having compared the ability of these peptides to form peptide-based nanoparticles (PBNs) using different biophysical methods and to induce a targeted gene silencing in cells, we established the main sequential requirements of the amino acid composition of the WRAP peptide. In addition, upon measuring the WRAP-based siRNA transfection ability into cells compared to several non-peptide transfection agents available on the markets, we confirmed that WRAP peptides induced an equivalent level of targeted gene silencing but in most of the cases with lower cell toxicity as clearly shown in clonogenic assays.
Plasmonic photothermal release of docetaxel by gold nanoparticles incorporated onto halloysite nanotubes with conjugated 2D8-E3 antibodies for selective cancer therapy
Authors: Taheri-Ledari Reza , Zhang Wenjie , Radmanesh Maral , Cathcart Nicole , Maleki Ali , Kitaev Vladimir
Published: August 2021

Background

Applied nanomaterials in targeted drug delivery have received increased attention due to tangible advantages, including enhanced cell adhesion and internalization, controlled targeted release, convenient detection in the body, enhanced biodegradation, etc. Furthermore, conjugation of the biologically active ingredients with the drug-containing nanocarriers (nanobioconjugates) has realized impressive opportunities in targeted therapy. Among diverse nanostructures, halloysite nanotubes (NHTs) with a rolled multilayer structure offer great possibilities for drug encapsulation and controlled release. The presence of a strong hydrogen bond network between the rolled HNT layers enables the controlled release of the encapsulated drug molecules through the modulation of hydrogen bonding either in acidic conditions or at higher temperatures. The latter can be conveniently achieved through the photothermal effect via the incorporation of plasmonic nanoparticles.

Results

The developed nanotherapeutic integrated natural halloysite nanotubes (HNTs) as a carrier; gold nanoparticles (AuNPs) for selective release; docetaxel (DTX) as a cytotoxic anticancer agent; human IgG1 sortilin 2D8-E3 monoclonal antibody (SORT) for selective targeting; and 3-chloropropyltrimethoxysilane as a linker for antibody attachment that also enhances the hydrophobicity of DTX@HNT/Au-SORT and minimizes DTX leaching in body’s internal environment. HNTs efficiently store DTX at room temperature and release it at higher temperatures via disruption of interlayer hydrogen bonding. The role of the physical expansion and disruption of the interlayer hydrogen bonding in HNTs for the controlled DTX release has been studied by dynamic light scattering (DLS), electron microscopy (EM), and differential scanning calorimetry (DSC) at different pH conditions. HNT interlayer bond disruption has been confirmed to take place at a much lower temperature (44 °C) at low pH vs. 88 °C, at neutral pH thus enabling the effective drug release by DTX@HNT/Au-SORT through plasmonic photothermal therapy (PPTT) by light interaction with localized plasmon resonance (LSPR) of AuNPs incorporated into the HNT pores.

Conclusions

Selective ovarian tumor targeting was accomplished, demonstrating practical efficiency of the designed nanocomposite therapeutic, DTX@HNT/Au-SORT. The antitumor activity of DTX@HNT/Au-SORT (apoptosis of 90 ± 0.3%) was confirmed by in vitro experiments using a caov-4 (ATCC HTB76) cell line (sortilin expression > 70%) that was successfully targeted by the sortilin 2D8-E3 mAb, tagged on the DTX@HNT/Au.

Graphic abstract
Effect of the duration of the capecitabine regimen following colon cancer surgery in an elderly population: a retrospective cohort study
Authors: Chen Weiwei , Dong Hongmin , Wang Gang , Chen Juan , Wang Wenling
Published: August 2021

Background

Only 50–70% of elderly colon cancer patients could complete the recommended 6 months of postoperative chemotherapy. It is unknown whether a shorter duration of postoperative capecitabine-alone chemotherapy would compromise survival. We thus conducted this study to analyze the association between postoperative chemotherapy duration of a capecitabine-alone regimen and cancer-specific survival (CSS) and disease-free survival (DFS) of surgery-treated elderly colon cancer patients.

Methods

We performed a retrospective cohort study of surgically treated stage III and high-risk stage II colon cancer patients aged ≥ 70 treated at two medical centers. Cox proportional hazard regression models were utilized to calculate crude and adjusted hazard ratios (HRs). The nonlinear relationship between postoperative chemotherapy duration and survival was analyzed through restricted cubic spline regression analysis, and the threshold effect was calculated by the two-piecewise Cox proportional hazard model.

Results

A total of 1217 surgery-treated colon cancer patients between August 1, 2013, and September 1, 2019, were reviewed, and 257 stage III and high-risk stage II patients aged ≥ 70 were enrolled. Postoperative chemotherapy with capecitabine was administered to 114 patients, and 143 patients only received surgery. As the duration of chemotherapy increased by 1 week, the risk of cancer-specific death was reduced by 11% (HR = 0.89, 95% confidence interval (CI) 0.82–0.96), and the risk of recurrence was reduced by 10% (HR = 0.90, 0.82–0.96). Nonlinearity exploration suggested a threshold effect of capecitabine duration on CSS in stage III disease. The HR for death was 0.79 (95% CI, 0.68–0.92) with duration ≤ 16 weeks and 1.34 (95% CI, 0.91–1.97) with duration > 16 weeks.

Conclusions

The postoperative capecitabine duration was significantly associated with a decrease in death risk and recurrence risk in elderly colon cancer patients. However, the threshold effect of capecitabine duration on survival suggests that short-term chemotherapy may improve survival in elderly stage III colon cancer patients.
Comment on “Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma”
Authors: Sharma Gopal
Published: August 2021

This article is a commentary on an article published in World Journal of Surgical Oncology by Liu et al. With this study, authors evaluated diagnostic accuracy of Xpert bladder cancer monitor in detecting recurrences. With this article, we highlight the strengths and limitations of the study.
Tranexamic acid for the prevention and treatment of bleeding in surgery, trauma and bleeding disorders: a narrative review
Authors: Ockerman Anna , Vanassche Thomas , Garip Melisa , Vandenbriele Christophe , Engelen Matthias M , Martens Jeroen , Politis Constantinus , Jacobs Reinhilde , Verhamme Peter
Published: August 2021

Objectives

We review the evidence for tranexamic acid (TXA) for the treatment and prevention of bleeding caused by surgery, trauma and bleeding disorders. We highlight therapeutic areas where evidence is lacking and discuss safety issues, particularly the concern regarding thrombotic complications.

Methods

An electronic search was performed in PubMed and the Cochrane Library to identify clinical trials, safety reports and review articles.

Findings

TXA reduces bleeding in patients with menorrhagia, and in patients undergoing caesarian section, myomectomy, hysterectomy, orthopedic surgery, cardiac surgery, orthognathic surgery, rhinoplasty, and prostate surgery. For dental extractions in patients with bleeding disorders or taking antithrombotic drugs, as well as in cases of idiopathic epistaxis, tonsillectomy, liver transplantation and resection, nephrolithotomy, skin cancer surgery, burn wounds and skin grafting, there is moderate evidence that TXA is effective for reducing bleeding. TXA was not effective in reducing bleeding in traumatic brain injury and upper and lower gastrointestinal bleeding. TXA reduces mortality in patients suffering from trauma and postpartum hemorrhage. For many of these indications, there is no consensus about the optimal TXA dose. With certain dosages and with certain indications TXA can cause harm, such as an increased risk of seizures after high TXA doses with brain injury and cardiac surgery, and an increased mortality after delayed administration of TXA for trauma events or postpartum hemorrhage. Whereas most trials did not signal an increased risk for thrombotic events, some trials reported an increased rate of thrombotic complications with the use of TXA for gastro-intestinal bleeding and trauma.

Conclusions

TXA has well-documented beneficial effects in many clinical indications. Identifying these indications and the optimal dose and timing to minimize risk of seizures or thromboembolic events is work in progress.
Social media, vaccine hesitancy and trust deficit in immunization programs: a qualitative enquiry in Malappuram District of Kerala, India
Authors: Nair Anoop T. , Nayar Kesavan Rajasekharan , Koya Shaffi Fazaludeen , Abraham Minu , Lordson Jinbert , Grace Chitra , Sreekumar Sreekutty , Chembon Priya , Swarnam Kamala , Pillai A. Marthanda , Pandey Anant Kumar
Published: August 2021

Background

With increased penetration of the internet and social media, there are concerns regarding its negative role in influencing parents’ decisions regarding vaccination for their children. It is perceived that a mix of religious reasons and propaganda by anti-vaccination groups on social media are lowering the vaccination coverage in Malappuram district of Kerala. We undertook a qualitative study to understand the factors responsible for generating and perpetuating vaccine hesitancy, the pathways of trust deficit in immunization programs and the interaction between various social media actors.

Methods

In-depth interviews and focus group discussions were conducted among parents/caregivers, physicians, public sector health staff, alternative system medical practitioners, field healthcare workers and teachers in areas with highest and lowest vaccination coverage in the district, as well as with communication experts.

Results

The trust deficit between parents/caregivers and healthcare providers is created by multiple factors, such as providers’ lack of technical knowledge, existing patriarchal societal norms and critical views of vaccine by naturopaths and homeopaths. Anti-vaccine groups use social media to influence caregivers' perceptions and beliefs. Religion does not appear to play a major role in creating vaccine resistance in this setting.

Conclusions

A long-term, multipronged strategy should be adopted to address the trust deficit. In the short to medium term, the health sector can focus on appropriate and targeted vaccine-related communication strategies, including the use of infographics, soft skills training for healthcare workers, technical competency improvement through a mobile application-based repository of information and creation of a media cell to monitor vaccine-related conversations in social media and to intervene if needed.
Cross-cutting lessons from the Decision-Maker Led Implementation Research initiative
Authors: Mancuso Arielle , Ahmed Malm Shahira , Sharkey Alyssa , Shahabuddin A. S. M. , Shroff Zubin Cyrus
Published: August 2021

Background

Almost 20 million children under one year of age did not receive basic vaccines in 2019, and most of these children lived in low- and middle-income countries. Implementation research has been recognized as an emerging area that is critical to strengthen the implementation of interventions proven to be effective. As a component of strengthening implementation, WHO has called for greater embedding of research within decision-making processes. One strategy to facilitate the embedding of research is to engage decision-makers as Principal Investigators of the research. Since 2015, the Alliance for Health Policy and Systems Research within the WHO and the United Nations Children’s Fund have supported decision-maker led research by partnering with Gavi, the Vaccine Alliance, in an initiative called "Decision-Maker Led Implementation Research". This synthesis paper describes the cross-cutting lessons from the initiative to further understand and develop future use of the decision-maker led strategy.

Methods

This study used qualitative methods of data collection, including a document review and in-depth interviews with decision-makers and researchers engaged in the initiative. Document extraction and thematic content analysis were applied. The individual project was the unit of analysis and the results were summarized across projects.

Results

Research teams from 11 of the 14 projects participated in this study, for an overall response rate of 78.6%. Most projects were carried out in countries in Africa and conducted at the sub-state or sub-district level. Seven enablers and five barriers to the process of conducting the studies or bringing about changes were identified. Key enablers were the relevance, acceptability, and integration of the research, while key barriers included unclear results, limited planning and support, and the limited role of a single study in informing changes to strengthen implementation.

Conclusions

Decision-maker led research is a promising strategy to facilitate the embedding of research into decision-making processes and contribute to greater use of research to strengthen implementation of proven-effective interventions, such as immunization. We identified several lessons for consideration in the future design and use of the decision-maker led strategy.
A qualitative study of the development and utilization of health facility-based immunization microplans in Uganda
Authors: Mafigiri David Kaawa , Iradukunda Constance , Atumanya Catherine , Odie Michael , Mancuso Arielle , Tran Nhan , McGrath Janet , Luzze Henry
Published: August 2021

Background

In 2006, Uganda adopted the Reaching Every District strategy with the goal of attaining at least 80% coverage for routine immunizations in every district. The development and utilization of health facility/district immunization microplans is the key to the strategy. A number of reports have shown suboptimal development and use of microplans in Uganda. This study explores factors associated with suboptimal development and use of microplans in two districts in Uganda to pinpoint challenges encountered during the microplanning process.

Methods

A qualitative study was conducted comparing two districts: Kapchorwa, with low immunization coverage, and Luwero with high immunization coverage. Data were collected through multilevel observation of health facilities, planning sessions and planning meetings; records review of microplans, micromaps and meeting minutes; 57 interviews with health workers at the ministry level and lower-level health facility workers. Data were analysed using NVivo 8 qualitative text analysis software. Transcripts were coded, and memos and display matrices were developed to examine the process of developing and utilizing microplans, including experiences of health workers (implementers).

Results

Three key findings emerged from this study. First, there are significant knowledge gaps with regard to the microplanning process among health workers at all levels (community and district health facility and nationally). Limited knowledge about communities and programme catchment areas greatly hinders the planning process by limiting the ability to identify hard-to-reach areas and to prioritize areas according to need. Secondly, the microplanning tool is bulky and complex. Finally, microplanning is being implemented in the context of already overtasked health personnel who have to conduct several other activities as part of their daily routines.

Conclusions

In order to achieve quality improvement as outlined in the Reaching Every District campaign, the microplanning process should be revised. Health workers’ misunderstanding and limited knowledge about the microplanning process, especially at peripheral health facilities, coupled with the complex, bulky nature of the microplanning tool, reduces the effectiveness of microplanning in improving routine immunization in Uganda. This study reveals the need to reduce the complexity of the tool and to identify ways to train and support workers in the use of the revised tool, including support in incorporating the microplanning process into their busy schedules.