bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing the implementation of screening and brief interventions for alcohol use in primary care practices: a systematic review using the COM-B system and Theoretical Domains Framework
Authors: Rosário Frederico , Santos Maria Inês , Angus Kathryn , Pas Leo , Ribeiro Cristina , Fitzgerald Niamh
Published: January 2021

Background

Alcohol is a leading risk factor contributing to the global burden of disease. Several national and international agencies recommend that screening and brief interventions (SBI) should be routinely delivered in primary care settings to reducing patients’ alcohol consumption. However, evidence shows that such activities are seldom implemented in practice. A review of the barriers and facilitators mediating implementation, and how they fit with theoretical understandings of behaviour change, to inform the design of implementation interventions is lacking. This study aimed to conduct a theory-informed review of the factors influencing general practitioners’ and primary care nurses’ routine delivery of alcohol SBI in adults.

Methods

A systematic literature search was carried out in four electronic databases (Medline, CINAHL, CENTRAL, PsycINFO) using comprehensive search strategies. Both qualitative and quantitative studies were included. Two authors independently abstracted and thematically grouped the data extracted. The barriers and facilitators identified were mapped to the domains of the Capability-Opportunity-Motivation-Behaviour system/Theoretical Domains Framework (TDF).

Results

Eighty-four out of the 258 studies identified met the selection criteria. The majority of the studies reported data on the views of general practitioners (n = 60) and used a quantitative design (n = 49). A total of 660 data items pertaining to barriers and 253 data items pertaining to facilitators were extracted and thematically grouped into 46 themes. The themes mapped to at least one of the 14 domains of the TDF. The three TDF domains with the highest number of data units coded were ‘Environmental Context and Resources’ (n = 158, e.g. lack of time), ‘Beliefs about Capabilities’ (n = 134, e.g. beliefs about the ability to deliver screening and brief advice and in helping patients to cut down) and ‘Skills’ (n = 99, e.g. lack of training).

Conclusions

This study identified a range of potential barriers and facilitators to the implementation of alcohol SBI delivery in primary care and adds to the scarce body of literature that identifies the barriers and facilitators from a theoretical perspective. Given that alcohol SBI is seldom implemented, this review provides researchers with a tool for designing novel theory-oriented interventions to support the implementation of such activity.

Systematic review registration

PROSPERO CRD42016052681
Primary total hip arthroplasty using a short bone-conserving stem in young adult osteoporotic patients with Dorr type C femoral bone
Authors: Zhen Ping , Chang Yanfeng , Yue Heng , Chen Hui , Zhou Shenghu , Liu Jun , He Xiaole
Published: January 2021

Background

Dorr type C femoral bone exhibits a wide, stovepipe-shaped femoral canal, and thin cortices in the proximal femur. Dorr C bone combined with severe osteoporosis is an important challenge in primary hip arthroplasty. In this study, we assessed the effects of short metaphyseal fitting cementless stems on preformatted primary total hip arthroplasties in young adult osteoporotic patients with this femoral presentation.

Methods

A total of 42 hip arthroplasties were performed in 35 young patients (range 20 to 36 years) using a short Tri-lock bone preservation metaphyseal-fitting cementless femoral component between 2012 and 2017. The mean age at surgery of the 27 male (33 hips) and 8 female (9 hips) patients was 27.5 years (range 20.3 to 35.8 years). The mean body mass index (BMI) was 20.2 kg/m2(range, 16.8–23.2 kg/m2). According to Dorr’s criteria, all 42 femora were classified as type C bone and all femurs suffered from severe osteoporosis (Singh index ≤ 3).

Results

The mean follow-up period was 5.5 years (range 3.0 to 8.0 years). The clinical and functional results improved for the Harris hip score, WOMAC, and UCLA activity scores. The Harris Hip score improved from 48.0 ± 8.0 (range 38.0 to 61.0) preoperatively to 87.0 ± 9.0 (range 77.0 to 92.0) at 12 months after surgery and 91.0 ± 8.0 (range 85.0 to 98.0) at final follow-up. The preoperative UCLA activity score was 3.0 ± 0.5 points (range, 1.0–4.0 points), which significantly improved to 7.5 ± 0.7 points (range 6.0 to 8.0 points) at the final follow-up. No patient exhibited thigh pain at the final follow-up. The mean stem-to-canal fill percentages were 97% ± 2.1% (anteroposterior view at midstem). For stem alignment, 40 hips (95.2%) of the femoral stem were positioned neutrally to 3° of varus with reference to the femoral shaft axis. The remaining two were positioned at 4° varus to 4° valgus. Radiographic evaluation showed good osteointegration of the implants in follow-up.

Conclusions

Based on the tapered-wedge design and proximal porous coating, the shortened tapered conventional stem can achieve reliable stability through neck filling and metaphyseal fixation, which does not depend on the isthmus hoop stress. This stem was suitable in severe osteoporotic patients with type C bones in young adults who presented with a correspondingly straightened femoral canal with a wide isthmus and thin cortex.
Mid-term subsidence and periprosthetic radiolucency of the AMIStem: a 5-year EBRA-FCA analysis
Authors: Hasler Julian , Flury Andreas , Dimitriou Dimitris , Holweg Iris , Helmy Naeder , Finsterwald Michael
Published: January 2021

Background

There has been an evolution in cementless total hip arthroplasty (THA) with newer short stem designs aimed to preserve metaphyseal bone stock and facilitate implantation through minimally invasive approaches. While early subsidence has been correlated to aseptic loosening in conventional stems, there is a paucity of data regarding short stems. The current study aims to report on stem subsidence and mid-term clinical outcomes of a cementless, metaphyseal-anchored short femoral stem, specifically designed for the direct anterior approach (DAA).

Methods

Ninety-four consecutive patients (100 hips) with a minimum follow-up of 5 years following cementless THA were included in this single-center retrospective study. Subsidence was evaluated using the “Ein-Bild-Roentgen-Analyse” (EBRA). Periprosthetic radiolucency allocated to the zones of Charnley and Gruen was assessed. Additionally, demographic and implant-related factors potentially associated with increased subsidence and clinical outcomes were evaluated.

Results

At the last follow-up, the average stem subsidence was 1.98 ± 1.20 mm, with 48% of the implants demonstrating subsidence of > 2 mm. Periprosthetic radiolucency of > 2 mm was found in 26% of the implants in zone 1 and in 9% in zone 7, respectively. Neither the amount of subsidence nor proximal periprosthetic radiolucency was associated with aseptic loosening or worse clinical outcomes.

Conclusions

Comparable to other proximally fixed short stem designs, the highest subsidence was observed within the first 3 months following implantation. No demographic or implant-related factors were found to have a statistically significant influence on stem subsidence. Periprosthetic radiolucency and subsidence of the AMISstem is not correlated with worse clinical outcomes at 5-year follow-up.
Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative disc cells following hyperbaric oxygen treatment
Authors: Lin Song-Shu , Niu Chi-Chien , Yuan Li-Jen , Tsai Tsung-Ting , Lai Po-Liang , Chong Kowit-Yu , Wei Kuo-Chen , Huang Chiung-Yin , Lu Meng-Ling , Yang Chuen-Yung , Ueng Steve W. N.
Published: January 2021

Background

MicroRNA (miRNA) plays a vital role in the intervertebral disc (IVD) degeneration. The expression level of miR-573 was downregulated whereas Bax was upregulated notably in human degenerative nucleus pulposus cells. In this study, we aimed to investigate the role of miR-573 in human degenerative nucleus pulposus (NP) cells following hyperbaric oxygen (HBO) treatment.

Methods

NP cells were separated from human degenerated IVD tissues. The control cells were maintained in 5% CO2/95% air and the hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute. MiRNA expression profiling was performed via microarray and confirmed by real-time PCR, and miRNA target genes were identified using bioinformatics and luciferase reporter assays. The mRNA and protein levels of Bax were measured. The proliferation of NPCs was detected using MTT assay. The protein expression levels of Bax, cleaved caspase 9, cleaved caspase 3, pro-caspase 9, and pro-caspase 3 were examined.

Results

Bioinformatics analysis indicated that the 3′ untranslated region (UTR) of the Bax mRNA contained the “seed-matched-sequence” for hsa-miR-573, which was validated via reporter assays. MiR-573 was induced by HBO and simultaneous suppression of Bax was observed in NP cells. Knockdown of miR-573 resulted in upregulation of Bax expression in HBO-treated cells. In addition, overexpression of miR-573 by HBO increased cell proliferation and coupled with inhibition of cell apoptosis. The cleavage of pro-caspase 9 and pro-caspase 3 was suppressed while the levels of cleaved caspase 9 and caspase 3 were decreased in HBO-treated cells. Transfection with anti-miR-573 partly suppressed the effects of HBO.

Conclusion

Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative NP cells following HBO treatment.
Assessing responsiveness of the EQ-5D-3L, the Oxford Hip Score, and the Oxford Knee Score in the NHS patient-reported outcome measures
Authors: Kang Sujin
Published: January 2021

Background

The degree to which a validated instrument is able to detect clinically significant change over time is an important issue for the better management of hip or knee replacement surgery. This study examines the internal responsiveness of the EQ-5D-3L, the Oxford Hip Score (OHS), and the Oxford Knee Score (OKS) by various methods. Data from NHS patient-reported outcome measures (PROMs) linked to the Hospital Episodes Statistics (HES) dataset (2009–2015) was analysed for patients who underwent primary hip surgery (N = 181,424) and primary knee surgery (N = 191,379).

Methods

Paired data-specific univariate responsiveness was investigated using the standardized response mean (SRM), the standardized effect size (SES), and the responsiveness index (RI). Multivariate responsiveness was furthermore examined using the defined capacity of benefit score (i.e. paired data-specific MCID), adjusting baseline covariates such as age, gender, and comorbidities in the Box-Cox regression models. The observed and predicted percentages of patient improvement were examined both as a whole and by the patients' self-assessed transition level.

Results

The results showed that both the OHS and the OKS demonstrated great univariate and multivariate responsiveness. The percentages of the observed (predicted) total improvement were high: 51 (54)% in the OHS and 73 (58)% in OKS. The OHS and the OKS showed distinctive differences in improvement by the 3-level transition, i.e. a little better vs. about the same vs. a little worse. The univariate responsiveness of the EQ-5D-3L showed moderate effects in total by Cohen’s thresholds. The percentages of improvement in the EQ-5D-3L were moderate: 44 (48)% in the hip and 42 (44)% for the knee replacement population.

Conclusions

Distinctive percentage differences in patients’ perception of improvement were observed when the paired data-specific capacity of benefit score was applied to examine responsiveness. This is useful in clinical practice as rationale for access to surgery at the individual-patient level. This study shows the importance of analytic methods and instruments for investigation of the health status in hip and/or knee replacement surgery. The study finding also supports the idea of using a generic measure along with the disease-specific instruments in terms of cross-validation.
Extracorporeal shock wave therapy for bone marrow edema syndrome in patients with osteonecrosis of the femoral head: a retrospective cohort study
Authors: Zhao Wenyi , Gao Yuan , Zhang Shouxiang , Liu Zhang , He Lin , Zhang Dahong , Li Wei , Meng Qinggang
Published: January 2021

Background

There is now ample evidence suggesting that extracorporeal shock wave therapy (ESWT) can improve hip mobility and reduce pain in patients with osteonecrosis of the femoral head (ONFH). The ability of ESWT to cure bone marrow edema syndrome (BMES) in patients with ONFH, 12 weeks after the initial course of ESWT, needs to be verified further and more relevant clinical research-based evidence should be consolidated. This study aimed to evaluate the efficacy of ESWT for BMES caused by ONFH.

Methods

This retrospective cohort study included 67 patients with BMES caused by ONFH who were participating in a rehabilitation program as outpatients. Before and after ESWT, the area of femoral bone marrow edema was evaluated by magnetic resonance imaging (MRI), and the Harris score and Charnley score were evaluated as hip pain and function indicators.

Results

After ESWT, MRI revealed that the area of bone marrow edema decreased from 984.6 ± 433.2 mm2to 189.7 ± 214.4 mm2(P< 0.0001). The Harris score increased from 42.2 ± 9.1 to 77.7 ± 10.8 points (P< 0.0001). The Charnley score increased from 7.3 ± 1.4 to 12.0 ± 1.7 (P< 0.0001). ESWT was effective in treating BMES in 98.5% of the cases.

Conclusions

This study demonstrated that ESWT can effectively treat BMES caused by ONFH and can aid in pain relief and functional recovery in patients with ONFH. Thus, ESWT should be included in the classic physical therapy regimen for patients with ONFH and BMES.
Reconstruction of the medial patellofemoral ligament using two blind transverse semi-patella tunnels and an implant-free technique for patellar fixation: a technical note
Authors: Raoulis Vasileios , Zibis Aristeidis , Fyllos Apostolos , Malahias Michael-Alexander , Banios Konstantinos , Hantes Michael
Published: January 2021

Background

The double-bundle technique with two points of patellar fixation in the upper half of the patella replicating the broad attachment site of the native medial patellofemoral ligament (MPFL) is the most commonly performed procedure for MPFL reconstruction. Complete transverse patella tunnels pose a threat to the integrity of the patella. We present an implant-free, double-bundle technique for MPFL reconstruction with gracilis autograft, overcoming the problem of complete patella bone tunnels and over-drilling.

Methods

After standard gracilis graft harvesting, the anteromedial side of the patella is exposed. With the guidance of an anterior-cruciate-ligament (ACL) tibia-aiming device, two 2-mm parallel guide pins are inserted from medial to lateral at the upper half of the patella. The two guide pins are over-drilled with a cannulated 4.5-mm drill bit 2-cm deep, to create two transverse blind semi-patellar tunnels. For the femoral fixation, a 2.4-mm guide pin with an eyelet is drilled at the Schöttle point and over-reamed with a 6-mm cannulated reamer to a depth of 30 mm. The two free ends of the graft (with two running Krakow sutures placed) are pulled into the two patella tunnels and the graft sutures are tied together with tension for stable graft fixation at the lateral patella rim. With the help of a femoral suture loop (which is inserted in the femoral bone tunnel), the graft-loop is advanced into the femoral bone tunnel and the graft is finally fixed with a 7-mm interference screw at 30° of knee flexion.

Results

The utilization of blind transverse tunnels (not trans-patellar tunnels) offers the advantage of avoiding stress risers at the patella. Thanks to the ACL tibia aiming device, multiple drilling, and breaching of the anterior patellar cortex or articular surface of the patella is avoided.

Conclusions

This implant-free, and consequently affordable technique, isolated or combined with bony procedures, minimizes possibilities for perioperative bony complications at the patella fixation site.
A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients
Authors: Liang Lili , Shuai Ruixue , Yu Yue , Qiu Wenjuan , Shen Linghua , Wu Shengnan , Wei Haiyan , Chen Yongxing , Yang Chiju , Xu Peng , Chen Xigui , Zou Hui , Feng Jizhen , Niu Tingting , Hu Haili , Ye Jun , Zhang Huiwen , Lu Deyun , Gong Zhuwen , Zhan Xia , Ji Wenjun , Yu Yongguo , Gu Xuefan , Han Lianshu
Published: January 2021

Background

Methylmalonic acidemia is an inherited organic acid metabolic disease. It involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be a rare type, which is seen more frequently in Asian than other populations. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype.

Methods

Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant.

Results

Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. 100% of these patients (29/29) were responsive to Vitamin B12 administration. The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients.

Conclusion

Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.
Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin
Authors: Coldiron Matthew E. , Gutierrez Zamudio Ana Gabriela , Manuel Rolanda , Luciano Gilda , Rusch Barbara , Ciglenecki Iza , Telnov Alex , Grais Rebecca F. , Trellu Laurence Toutous , Molfino Lucas
Published: January 2021

Background

Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique.

Methods

We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment.

Results

At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2],p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4],p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD.

Discussion

PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.
Association between oncogenic human papillomavirus type 16 and Killian polyp
Authors: Oton-Gonzalez Lucia , Rotondo John Charles , Cerritelli Luca , Malagutti Nicola , Lanzillotti Carmen , Bononi Ilaria , Ciorba Andrea , Bianchini Chiara , Mazziotta Chiara , De Mattei Monica , Pelucchi Stefano , Tognon Mauro , Martini Fernanda
Published: January 2021

Background

Killian polyp (KP) is a benign lesion that arises from the maxillary sinus. The etiology of KP is unknown. The aim of this study was to investigate the potential involvement of human papilloma- (HPV) and polyoma-viruses (HPyV) infections in the onset of KP.

Methods

DNA from antral (n = 14) and nasal (n = 14) KP fractions were analyzed for HPV and HPyV sequences, genotypes, viral DNA load and physical status along with expression of viral proteins and p16 cellular protein.

Results

The oncogenic HPV16 was detected in 3/14 (21.4%) antral KPs, whilst nasal KPs tested HPV-negative (0/14). The mean HPV16 DNA load was 4.65 ± 2.64 copy/104 cell. The whole HPV16 episomal genome was detected in one KP sample, whereas HPV16 DNA integration in two KPs. P16 mRNA level was lower in the KP sample carrying HPV16 episome than in KPs carrying integrated HPV16 and HPV- negative KPs (p< 0.001). None of the antral and nasal KP samples tested positive for HPyV DNA (0/28).

Conclusions

A fraction of KP tested positive for the oncogenic HPV16. HPV16 detection in the KP antral portion may be consistent with HPV16 infection derived from the maxillary sinus. HPV16 DNA integration represents a novel finding. Altogether, these data improve our knowledge on the association between KP and HPV infection, whereas it indicates that the KP onset is heterogeneous.
Correction to: Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients
Authors: Rashid Muhammad Usman , Muhammad Noor , Khan Faiz Ali , Shehzad Umara , Naeemi Humaira , Malkani Naila , Hamann Ute
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Differential PD-1/LAG-3 expression and immune phenotypes in metastatic sites of breast cancer
Authors: Sobottka Bettina , Moch Holger , Varga Zsuzsanna
Published: January 2021

Background

A dual blockade against the novel immune checkpoint inhibitor lymphocyte activation gene-3 (LAG-3) and programmed cell death protein-1 (PD-1) is currently considered in advanced breast cancer. Nevertheless, PD-1 or LAG-3 expression within distant metastatic breast cancer tissue remains understudied.

Methods

To address this knowledge gap, we investigated the PD-1 and LAG-3 expression in combination with the CD8-based immune phenotype in intrapatient matched primary tumor distant metastases, representing 95 breast cancer patients with metastases occurring at four different anatomical locations. The immune phenotype was categorized into 2 categories: inflamed corresponding to the clinical category “hot” and exhausted or desert consistent with clinically “cold” tumors.

Results

Metastases of “cold” primary tumors always remained “cold” at their matched metastatic site. Expression of PD-1/LAG-3 was associated with a “hot” immune phenotype in both the primary tumors and metastases. We could not observe any association between the immune phenotype and the breast cancer molecular subtype. Brain and soft tissue metastases were more commonly inflamed with signs of exhaustion than other anatomical sites of metastases. Taken together, (i) the immune phenotype varied between sites of distant metastases, and (ii) PD-1+/LAG-3+ was strongly associated with a “hot” immune phenotype and (iii) was most prevalent in brain and soft tissue metastases among distant metastases.

Conclusions

Our data strongly support an integrated analysis of the immune phenotype together with the PD-1/LAG-3 expression in distant metastases to identify patients with inflamed but exhausted tumors. This may eventually improve the stratification and likelihood for advanced breast cancer patients to profit from immunotherapy.
Improving gait adaptability in patients with hereditary spastic paraplegia (Move-HSP): study protocol for a randomized controlled trial
Authors: van de Venis Lotte , van de Warrenburg Bart P. C. , Weerdesteyn Vivian , van Lith Bas J. H. , Geurts Alexander C. H. , Nonnekes Jorik
Published: January 2021

Background

People with hereditary spastic paraplegia (HSP) experience difficulties adapting their gait to meet environmental demands, a skill required for safe and independent ambulation. Gait adaptability training is possible on the C-Mill, a treadmill equipped with augmented reality, enabling visual projections to serve as stepping targets or obstacles. It is unknown whether gait adaptability can be trained in people with HSP.

Aim

The aim of Move-HSP is to study the effects of ten 1-h sessions of C-Mill training, compared with usual care, on gait adaptability in people with pure HSP. In addition, this study aims to identify key determinants of C-Mill training efficacy in people with pure HSP.

Method

Move-HSP is a 5-week, two-armed, open-label randomized controlled trial with a cross-over design for the control group. Thirty-six participants with pure HSP will be included. After signing informed consent, participants are randomized (1:1) to intervention or control group. All participants register (near) falls for 15 weeks, followed by the first assessment (week 16), and, thereafter, wear an Activ8 activity monitor for 7 days (week 16). The intervention group receives 10 sessions of C-Mill training (twice per week, 1-h sessions; weeks 17–21), whereas control group continues with usual care (weeks 17–21). Afterwards, both groups are re-assessed (week 22). Subsequently, the intervention group enter follow-up, whereas control group receives 10 sessions of C-Mill training (weeks 23–27), is re-assessed (week 28), and enters follow-up. During follow-up, both groups wear Activ8 activity monitors for 7 days (intervention group: week 23, control group: week 29) and register (near) falls for 15 weeks (intervention group: weeks 23–37, control group: weeks 29–43), before the final assessment (intervention group: week 38, control group: week 44). The primary outcome is the obstacle subtask of the Emory Functional Ambulation Profile. Secondary outcomes consist of clinical tests assessing balance and walking capacity, physical activity, and fall monitoring.

Discussion

Move-HSP will be the first RCT to assess the effects of C-Mill gait adaptability training in people with pure HSP. It will provide proof of concept for the efficacy of gait adaptability training in people with pure HSP.

Trial registration

Clinicaltrials.gov NCT04180098. Registered on November 27, 2019.
Acupuncture for persistent atrial fibrillation after catheter ablation: study protocol for a pilot randomized controlled trial
Authors: Lin Ying , Wang Xian , Li Xue-Bin , Wu Bang-Qi , Zhang Zhao-Hui , Guo Wei-Hua , Wu Cun-Cao , Chen Xin , Chen Ming-Long , Dai Zhong , Chen Fu-Yan , Zhu Rui , Liang Chu-Xi , Tian Yun-Peng , Yang Gang , Yan Chao-Qun , Lu Jing , Wang Hai-Ying , Li Jin-Ling , Tu Jian-Feng , Li He-Wen , Yang Dan-Dan , Yu Fang-Ting , Wang Yu , Yang Jing-Wen , Shi Guang-Xia , Yan Shi-Yan , Wang Li-Qiong , Liu Cun-Zhi
Published: January 2021

Background

Atrial fibrillation (AF) is a common arrhythmia, which is closely related to cardiovascular morbidity and mortality. Although acupuncture is used in the treatment of AF, the evidence is insufficient. The objective of this pilot trial is to evaluate the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after catheter ablation (CA).

Methods and design

This will be a multi-center, 3-arm, pilot randomized controlled trial in China. Sixty patients in total will be randomly assigned to the specific acupoints group, the non-specific acupoints group, or the non-acupoints group in a 1:1:1 ratio. The whole study period is 6 months, including a 3-month treatment period and a 3-month follow-up period. All patients will receive 18 sessions of acupuncture over 12 weeks after CA and appropriate post-ablation routine treatment. The primary outcome is AF burden at 6 months after CA measured by electrocardiography patch that can carry out a 7-day continuous ambulatory electrocardiographic monitoring. The secondary outcomes include AF burden at 3  months after CA, recurrence of AF, quality of life, etc. The adverse events will also be recorded.

Discussion

This pilot study will contribute to evaluating the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after CA. The results will be used for the sample size calculation of a subsequent large-scale trial.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000030576. Registered on 7 March 2020.
Effects of intraoperative goal-directed fluid therapy and restrictive fluid therapy combined with enhanced recovery after surgery protocol on complications after thoracoscopic lobectomy in high-risk patients: study protocol for a prospective randomized controlled trial
Authors: Guan Zheng , Gao Yanfeng , Qiao Qiao , Wang Qiang , Liu Jingjie
Published: January 2021

Background

Acute kidney injury (AKI) is a common complication after thoracoscopic lobectomy in high-risk patients due to insufficient intraoperative infusion. Goal-directed fluid therapy (GDFT) is an individualized fluid infusion strategy; the fluid infusion strategy is adjusted according to the patient’s fluid response. GDFT during operation can reduce the incidence of AKI after major surgery. Enhanced recovery after surgery (ERAS) protocol optimizes perioperative interventions to decrease the postoperative complications after surgery. In ERAS protocol of lobectomy, intraoperative restrictive fluid therapy is recommended. In this study, we will compare the effects of intraoperative GDFT with restrictive fluid therapy combined with an ERAS protocol on the incidence of AKI after thoracoscopic lobectomy in high-risk patients.

Methods/design

This is a prospective single-center single-blind randomized controlled trial. Two hundred seventy-six patients scheduled for thoracoscopic lobectomy are randomly allocated to receive either GDFT or restrictive fluid therapy combined with an ERAS protocol at a 1:1 ratio. The primary outcome is the incidence of AKI after operation. The secondary outcomes include (1) the incidence of renal replacement therapy, (2) the length of intensive care unit stay after operation, (3) the length of hospital stay after operation, and (4) the incidence of other complications including infection, acute lung injury, pneumonia, arrhythmia, heart failure, myocardial injury after noncardiac surgery, and cardiac infarction.

Discussion

This is the first study to compare intraoperative GDFT with restrictive fluid therapy combined with an ERAS protocol on the incidence of AKI after thoracoscopic lobectomy in high-risk patients. The hypothesis is that the restrictive fluid therapy is noninferior to GDFT in reducing the incidence of AKI, but restrictive fluid therapy is simpler to apply than GDFT.

Trial registration

ClinicalTrials.govNCT04302467. Registered on 26 February 2020
Antiplatelet therapy for the prevention of atherosclerosis in chronic kidney disease (ALTAS-CKD) patients: study protocol for a randomized clinical trial
Authors: Xiong Jiachuan , He Ting , Yu Zhikai , Yang Ke , Chen Feng , Cheng Jingbo , Shi Yu , Huang Yinghui , Qiao Yu , Li Haiyang , Shen Yunzhu , Zhao Jinghong
Published: January 2021

Background

Cardiovascular disease (CVD) is the most common complication and the leading cause of death in patients with chronic kidney disease (CKD). Accelerated atherosclerosis is a pathophysiological process that is vital to the occurrence of cardiovascular complications associated with CKD. Abnormal platelet activation is not only the leading cause of atherosclerosis but also plays a critical role in the occurrence of thrombotic events. Currently, antiplatelet drugs are commonly used as a secondary prevention strategy for high blood pressure, obesity, diabetes, and ischemic heart disease and can reduce the risk of CVD in the susceptible population. However, the benefits and evidence of using antiplatelet agents in patients with CKD remain controversial. This study aimed to determine whether antiplatelet therapy can safely prevent atherosclerosis in patients with CKD in the primary care setting.

Methods/design

The ALTAS-CKD study is a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 554 adult patients with stage 3–5 non-dialysis-dependent CKD recruited from 10 territory medical centers in China. A secured web-based computer randomization system will be used to administer aspirin 100 mg once daily or a matching inactive placebo for 36 months. The primary endpoint will be the occurrence of atherosclerosis, as measured by carotid ultrasonography. The secondary endpoints will be combined cardiovascular events, all-cause mortality, and 50% decrease in the estimated glomerular filtration rate.

Trial registration {2a}

Current controlled trials number: ChiCTR1900021393. Registered on 18 February 2019.
The role of astrocyte‐mediated plasticity in neural circuit development and function
Authors: Perez-Catalan Nelson A. , Doe Chris Q. , Ackerman Sarah D.
Published: January 2021

Neuronal networks are capable of undergoing rapid structural and functional changes called plasticity, which are essential for shaping circuit function during nervous system development. These changes range from short-term modifications on the order of milliseconds, to long-term rearrangement of neural architecture that could last for the lifetime of the organism. Neural plasticity is most prominent during development, yet also plays a critical role during memory formation, behavior, and disease. Therefore, it is essential to define and characterize the mechanisms underlying the onset, duration, and form of plasticity. Astrocytes, the most numerous glial cell type in the human nervous system, are integral elements of synapses and are components of a glial network that can coordinate neural activity at a circuit-wide level. Moreover, their arrival to the CNS during late embryogenesis correlates to the onset of sensory-evoked activity, making them an interesting target for circuit plasticity studies. Technological advancements in the last decade have uncovered astrocytes as prominent regulators of circuit assembly and function. Here, we provide a brief historical perspective on our understanding of astrocytes in the nervous system, and review the latest advances on the role of astroglia in regulating circuit plasticity and function during nervous system development and homeostasis.
A novel assay to isolate and quantify third-stage Dirofilaria immitis and Brugia malayi larvae emerging from individual Aedes aegypti
Authors: McCrea Abigail R. , Edgerton Elizabeth B. , Oliver Genevieve T. , O’Neill Fiona M. , Nolan Thomas J. , Lok James B. , Povelones Michael
Published: January 2021

Background

Mosquitoes transmit filarial nematodes to both human and animal hosts, with worldwide health and economic consequences. Transmission to a vertebrate host requires that ingested microfilariae develop into infective third-stage larvae capable of emerging from the mosquito proboscis onto the skin of the host during blood-feeding. Determining the number of microfilariae that successfully develop to infective third-stage larvae in the mosquito host is key to understanding parasite transmission potential and to developing new strategies to block these worms in their vector.

Methods

We developed a novel method to efficiently assess the number of infective third-stage filarial larvae that emerge from experimentally infected mosquitoes. Following infection, individual mosquitoes were placed in wells of a multi-well culture plate and warmed to 37 °C to stimulate parasite emergence. Aedes aegypti infected with Dirofilaria immitis were used to determine infection conditions and assay timing. The assay was also tested with Brugia malayi-infected Ae. aegypti.

Results

Approximately 30% of Ae. aegypti infected with D. immitis and 50% of those infected with B. malayi produced emerging third-stage larvae. Once D. immitis third-stage larvae emerged at 13 days post infection, the proportion of mosquitoes producing them and the number produced per mosquito remained stable until at least day 21. The prevalence and intensity of emerging third-stage B. malayi were similar on days 12–14 post infection. Increased uptake of D. immitis microfilariae increased the fitness cost to the mosquito but did not increase the number of emerging third-stage larvae.

Conclusions

We provide a new assay with an associated set of infection conditions that will facilitate assessment of the filarial transmission potential of mosquito vectors and promote preparation of uniformly infectious third-stage larvae for functional assays. The ability to quantify infection outcome will facilitate analyses of molecular interactions between vectors and filariae, ultimately allowing for the establishment of novel methods to block disease transmission.
Diagnosis and identification of Leishmania species in patients with cutaneous leishmaniasis in the state of Roraima, Brazil's Amazon Region
Authors: de Almeida Joseneide Viana , de Souza Cristian Ferreira , Fuzari Andressa Alencastre , Joya Christie A. , Valdivia Hugo O. , Bartholomeu Daniella Castanheira , Brazil Reginaldo Peçanha
Published: January 2021

Background

Cutaneous leishmaniasis (CL) is an endemic disease in Brazil that is highly prevalent in the northern region of the country. Although there is a continuous and growing number of cases registered in the state of Roraima, there is limited information regarding the species of Leishmania that affect the human population. In this study, we aimed to characterize which Leishmania species cause human disease in those presenting with cutaneous leishmaniasis in endemic areas of the State of Roraima.

Methods

We conducted a prospective surveillance study between 2016 to 2018 in health centers located in the State of Roraima, Brazil. Participants with clinical suspicion of CL were enrolled and provided lesion samples for parasitological detection by microscopy. A subset of the samples was tested by polymerase chain reaction and sequencing of the internal transcribed spacer 1 (ITS-1 PCR) for molecular species identification.

Results

A total of 262 participants were enrolled in this study. Of those, 129 (49.27%) were positive by parasitological examination. Most positive subjects (81.58%) were male, and most cases presented a single lesion (80.26%). ITS-1 PCR and sequencing on a subset of 76 samples allowed us to detect nine different species of Leishmania: L. (V.) braziliensis, L (V.) panamensis, L. (V.) guyanensis, L. (V.) naiffi, L. (V.) shawi, L.(V.) utingensis, L. (V.) lindenbergi, L. (L.) amazonensis and L. (L.) mexicana.

Conclusions

Our study provides the first assessment of circulating species of Leishmania in the State of Roraima, Brazil, and shows the high diversity in this region. This study opens the path for further research on the transmission of leishmaniasis in the northernmost Brazilian State including vector and reservoir surveillance as well as for intensification of investigation and control activities against CL in the region.

Graphical Abstract
Effect of position and exercise on measurement of muscle quantity and quality: towards a standardised pragmatic protocol for clinical practice
Authors: Welch Carly , Majid Zeinab , Andrews Isabelle , Hassan-Smith Zaki , Kamwa Vicky , Picton Hannah , Wilson Daisy , Jackson Thomas A.
Published: January 2021

Background

Ultrasonography is an emerging non-invasive bedside tool for muscle quantity/quality assessment; Bioelectrical Impedance Analysis (BIA) is an alternative non-invasive bedside measure of body composition, recommended for evaluation of sarcopenia in clinical practice. We set out to assess impact of position and exercise upon measures towards protocol standardisation.

Methods

Healthy volunteers aged 18–35 were recruited. Bilateral Anterior Thigh Thickness (BATT; rectus femoris and vastus intermedius), BATT: Subcutaneous Ratio (BATT:SCR), and rectus femoris echogenicity were measured using ultrasound and BIA was performed; 1) lying with upper body at 45° (Reclined), 2) lying fully supine at 180o (Supine), 3) sat in a chair with upper body at 90o (Sitting), and 4) after exercise Reclined. Variability of Skeletal Muscle Mass (SMM) by two different equations from BIA (SMM-Janssen, SMM-Sergi), phase angle, fat percentage, and total body (TBW), extracellular (ECW), and intracellular water (ICW) were assessed.

Results

Forty-four participants (52% female; mean 25.7 years-old (SD 5.0)) were recruited. BATT increased from Reclined to Sitting (+ 1.45 cm, 1.27–1.63), and after exercise (+ 0.51, 0.29–0.73). Echogenicity reduced from Reclined to Sitting (− 2.1, − 3.9 – -0.26). SMM-Sergi declined from Reclined to Supine (− 0.65 kg, − 1.08 – − 0.23) and after exercise (− 0.70 kg, − 1.27 – -0.14). ECW increased from Reclined to Sitting (+ 1.19 L, 0.04–2.35). There were no other statistically significant changes.

Conclusion

Standardisation of protocols is especially important for assessment of muscle quantity by ultrasonography; BIA measurements may also vary dependent on the equations used. Where possible, participants should be rested prior to muscle ultrasonography and BIA, and flexion of the knees should be avoided.
A solitary brain metastasis as the only site of recurrence of HR positive, HER2 negative breast cancer: a case report and review of the literature
Authors: Patel Sandipkumar H , Saito Yoshihito David , Li Zaibo , Ramaswamy Bhuvaneswari , Stiff Andrew , Kassem Mahmoud , Wesolowski Robert
Published: January 2021

Background

Breast cancer is one of the most common causes of brain metastases. However, the presence of isolated central nervous system (CNS) metastatic disease early in the course of disease relapse is a rare event in cases of hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer.

Case presentation

We summarize the clinical course of a pre-menopausal, 39-year old Caucasian female with history of operable, hormone receptor positive, HER2 negative breast cancer who was initially treated with curative-intend therapy but who unfortunately developed solitary metastatic lesion in the left thalamus. A biopsy of the lesion confirmed the presence of hormone receptor positive, HER2 negative metastatic breast cancer. Patient’s CNS metastases continued to progress without any evidence of metastatic disease outside of the central nervous system and she eventually passed away about 5 years after the date of her initial diagnosis and 18 months following the diagnosis with brain metastasis.

Conclusion

Based on our case, although rare, patients with treated, operable, hormone receptor positive, HER2 negative breast cancer can present with solitary brain metastasis as the only sign of disease recurrence.
Glucocorticoid guides mobilization of bone marrow stem/progenitor cells via FPR and CXCR4 coupling
Authors: Gao Wenting , Yang Xuetao , Du Juan , Wang Haiyan , Zhong Hejiang , Jiang Jianxin , Yang Ce
Published: January 2021

Background

Our previous studies have proved the efficient exogenous repairing responses via bone marrow stem and progenitor cells (BMSPCs). However, the trafficking of endogenous bone marrow stem and progenitor cells to and from the bone marrow (BM) is a highly regulated process that remains to be elucidated. We aimed to study the relative importance of the hypothalamic-pituitary-adrenal (HPA) axis in the glucocorticoid-induced BMSPC mobilization.

Methods

The circulating mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) were examined in Crh (+/+, −/−) mice after running stress or glucocorticoid mini-infusion. The MSCs and EPCs were investigated ex vivo after treatment with glucocorticoid and glucocorticoid receptor (GR) antagonist, RU486. The expression of chemotaxis receptors, N-formyl peptide receptor (FPR), and Cys-X-Cys receptor 4 (CXCR4) of MSCs and EPCs as well as their colocalization were investigated after treatment with glucocorticoid, glucocorticoid receptor (GR) antagonist (RU486), and FPR antagonist (Cyclosporin H).

Results

Forced running stress increased circulating MSCs and EPCs in mice, which was blunted when Crh was knocked out, and positively related to the levels of serum glucocorticoid. Prolonged glucocorticoid mini-infusion imitated the stress-induced increase in circulating MSCs and EPCs in Crh+/+mice and rescued the impaired mobilization in circulating MSCs and EPCs in Crh−/−mice. Meanwhile, glucocorticoid promoted the chemotaxis of MSCs and EPCs ex vivo via GR, inhibited by RU486 (10 μM). Concurrently, glucocorticoid increased the expression of FPR of MSCs and EPCs, but inhibited their expression of CXCR4, followed by their changing colocalization in the cytoplasm. The GC-induced colocalization of FPR and CXCR4 was blunted by Cyclosporin H (1 μM).

Conclusion

Glucocorticoid-induced CXCR4-FPR responsiveness selectively guides the mobilization of BMSPCs, which is essential to functional tissue repair.

Graphical abstract

Schematic view of the role of glucocorticoid on the mobilization of bone marrow-derived stem/progenitor cells subsets in the present study. The HPA axis activation promotes the release of glucocorticoid, which regulates the directional migration of MSCs and EPCs mainly via GR. The possible mechanisms refer to the signal coupling of FPR and CXCR4. Their two-sided changes regulated by glucocorticoid are involved in the egress of MSCs and EPCs from BM, which is helpful for wound healing. MSCs, mesenchymal stem cells; EPCs, endothelial progenitor cells.
The serine-48 residue of nucleolar phosphoprotein nucleophosmin-1 plays critical role in subcellular localization and interaction with porcine circovirus type 3 capsid protein
Authors: Zhou Jianwei , Li Juan , Li Haimin , Zhang Ying , Dong Weiren , Jin Yulan , Yan Yan , Gu Jinyan , Zhou Jiyong
Published: January 2021

The transport of circovirus capsid protein into nucleus is essential for viral replication in infected cell. However, the role of nucleolar shuttle proteins during porcine circovirus 3 capsid protein (PCV3 Cap) import is still not understood. Here, we report a previously unidentified nucleolar localization signal (NoLS) of PCV3 Cap, which hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate nucleolar localization of PCV3 Cap. The NoLS of PCV3 Cap and serine-48 residue of N-terminal oligomerization domain of NPM1 are essential for PCV3 Cap/NPM1 interaction. In addition, charge property of serine-48 residue of NPM1 is critical for nucleolar localization and interaction with PCV3 Cap. Taken together, our findings demonstrate for the first time that NPM1 interacts with PCV3 Cap and is responsible for its nucleolar localization.