bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the impact of adjunctive istradefylline on the cumulative dose of levodopa-containing medications in Parkinson’s disease: study protocol for the ISTRA ADJUST PD randomized, controlled study
Authors: Hatano Taku , Kano Osamu , Sengoku Renpei , Yoritaka Asako , Suzuki Keisuke , Nishikawa Noriko , Mukai Yohei , Nomura Kyoichi , Yoshida Norihito , Seki Morinobu , Matsukawa Miho Kawabe , Terashi Hiroo , Kimura Katsuo , Tashiro Jun , Hirano Shigeki , Murakami Hidetomo , Joki Hideto , Uchiyama Tsuyoshi , Shimura Hideki , Ogaki Kotaro , Fukae Jiro , Tsuboi Yoshio , Takahashi Kazushi , Yamamoto Toshimasa , Yanagisawa Naotake , Nagayama Hiroshi
Published: March 2022

Background

Levodopa remains the most effective symptomatic treatment for Parkinson’s disease (PD) more than 50 years after its clinical introduction. However, the onset of motor complications can limit pharmacological intervention with levodopa, which can be a challenge when treating PD patients. Clinical data suggest using the lowest possible levodopa dose to balance the risk/benefit. Istradefylline, an adenosine A2Areceptor antagonist indicated as an adjunctive treatment to levodopa-containing preparations in PD patients experiencing wearing off, is currently available in Japan and the US. Preclinical and preliminary clinical data suggested that adjunctive istradefylline may provide sustained antiparkinsonian benefits without a levodopa dose increase; however, available data on the impact of istradefylline on levodopa dose titration are limited. The ISTRA ADJUST PD study will evaluate the effect of adjunctive istradefylline on levodopa dosage titration in PD patients.

Methods

This 37-week, multicenter, randomized, open-label, parallel-group controlled study in PD patients aged 30–84 years who are experiencing the wearing-off phenomenon despite receiving levodopa-containing medications ≥ 3 times daily (daily dose 300–400 mg) began in February 2019 and will continue until February 2022. Enrollment is planned to attain 100 evaluable patients for the efficacy analyses. Patients will receive adjunctive istradefylline (20 mg/day, increasing to 40 mg/day) or the control in a 1:1 ratio, stratified by age, levodopa equivalent dose, and presence/absence of dyskinesia. During the study, the levodopa dose will be increased according to symptom severity. The primary study endpoint is the comparison of the cumulative additional dose of levodopa-containing medications during the treatment period between the adjunctive istradefylline and control groups. Secondary endpoints include changes in efficacy rating scales and safety outcomes.

Discussion

This study aims to clarify whether adjunctive istradefylline can reduce the cumulative additional dose of levodopa-containing medications in PD patients experiencing the wearing-off phenomenon, and lower the risk of levodopa-associated complications. It is anticipated that data from ISTRA ADJUST PD will help inform future clinical decision-making for patients with PD in the real-world setting.

Trial registration

Japan Registry of Clinical Trials,jRCTs031180248; registered 12 March 2019.
Physical therapists’ experiences and perceptions of antepartum and postpartum care
Authors: Lin Kuan-Yin , Tsai Yi-Ju , Yang Jeng-Feng , Wu Meng-Hsing
Published: March 2022

Background

Little is known about the physical therapists’ practice and perceptions toward management of pregnancy/postpartum-related disorders in Taiwan. The aim of this study was to document current practice of physical therapy in antepartum and postpartum care in Taiwan.

Methods

An exploratory, cross-sectional study was conducted in registered physical therapists living in Taiwan. An anonymized online survey was designed, piloted, and advertised widely from March 2020 to March 2021. Data were analyzed using descriptive statistics, Chi square analysis and multivariate logistic regression.

Results

Of the 364 respondents, 37.6% had experience of treating pregnant or postpartum women in clinical practice. The most commonly treated pregnancy/postpartum-related disorder in practice was low back pain (61.3%). All respondents reported little to moderate level of confidence in their ability to manage pregnancy/postpartum-related disorder. Being female (p < 0.01); working at a regional hospital (p = 0.01), district hospital or district teaching hospital (p < 0.01), clinic (p = 0.01) or physiotherapy clinic (p = 0.01); and having prior experience of treating antepartum or postpartum women (p < 0.01) were significantly associated with willingness to provide customer-oriented service or health education to patients/clients with pregnancy/postpartum-related disorder after controlling for other confounding variables. The most commonly reported barrier was “lack of available training” (81.3%).

Conclusion

The majority of participating physical therapists indicated a positive attitude to antepartum and postpartum care but were not confident in management of various pregnancy/postpartum-related disorder in practices. The findings of this study highlight the educational needs related to antepartum and postpartum care in clinical practice for physical therapists in Taiwan.
The blood pressure and use of tourniquet are related to local recurrence after intralesional curettage of primary benign bone tumors: a retrospective and hypothesis-generating study
Authors: Zhou Lenian , Lin Shanyi , Zhu Hongyi , Dong Yang , Yang Qingcheng , Yuan Ting
Published: March 2022

Aims

Intralesional curettage is a commonly used treatment for primary bone tumors. However, local recurrence of tumors after curettage remains a major challenge.

Questions

(1) Is blood pressure related to local recurrence after intralesional curettage for benign or intermediate bone tumors? (2) What’s the impact of tourniquet usage on the risk of recurrence from high blood pressure?

Methods

This retrospective study evaluated patients receiving intralesional curettage for primary bone tumors from January 2011 to January 2015. A total of 411 patients with a minimum five-year follow-up were included for analysis. Demographic and disease-related variables were first assessed in univariable analyses for local recurrence risk. When a yielded p-value was < 0.2, variables were included in multivariable analyses to identify independent risk factors for local recurrence. Patients were then stratified by tourniquet usage (use/non-use), and risk from high blood pressure was evaluated in both subgroups.

Results

At an average follow-up of 6.8 ± 1.0 years, 63 of 411 patients (15.3%) experienced local recurrence. In multivariable analyses, local recurrence was associated with age (OR, 0.96; 95% CI, 0.94–0.99; p = 0.005); tumor type; lesion size (> 5 cm: OR, 3.58; 95% CI, 1.38–9.33; p = 0.009); anatomical site (proximal femur: OR, 2.49; 95% CI, 1.21–5.15; p = 0.014; proximal humerus: OR, 3.34; 95% CI, 1.61–6.92; p = 0.001); and preoperative mean arterial pressure (> 110 mmHg: OR, 2.61; 95% CI, 1.20–5.67; P = 0.015). In subgroup analyses, after adjusting for age, tumor type, lesion size, and anatomical site, tourniquet use modified the preoperative mean arterial pressure - recurrence relationship: when tourniquet was not used, preoperative mean arterial pressure predicted local recurrence (95–110 mmHg, 4.13, 1.42–12.03, p = 0.009; > 110 mmHg, 28.06, 5.27–149.30, p < 0.001); when tourniquet was used, preoperative mean arterial pressure was not related to local recurrence (all p values > 0.05).

Conclusions

A high preoperative blood pressure was related to local recurrence after intralesional curettage for primary bone tumors in our study. Tourniquet usage and controlling blood pressure might be beneficial for reducing local recurrence in patients scheduled to receive intralesional curettage for primary bone tumor treatment.

Level of evidence

Level IV, hypothesis-generating study.
Preoperative neutrophil-to-lymphocyte ratio may contribute to the prediction of postoperative infectious complications in patients with acute appendicitis: a retrospective study
Authors: Mori Mikito , Narushima Kazuo , Hirano Atsushi , Kano Yoshihiko , Chiba Fumihiro , Edamoto Yoshihiro , Yoshida Masahiro
Published: March 2022

Background

Several studies have assessed various clinical variables to identify risk factors for postoperative complications in patients with acute appendicitis. However, few studies have focused on the relationships between systemic inflammatory variables and postoperative complications in patients with acute appendicitis. We investigated the relationships between postoperative complications and systemic inflammatory variables, and assessed the clinical utility of these variables as predictors of postoperative complications in patients with acute appendicitis.

Methods

We retrospectively reviewed 181 patients who underwent immediate appendectomy for acute appendicitis. All postoperative complications were classified as infectious or noninfectious, and we evaluated the relationships between postoperative complications and clinical factors including the preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

Results

In total, 28 patients (15.5%) had postoperative Clavien-Dindo grade II–IV complications; 17 patients (9.4%) and 11 patients (6.1%) were categorized as the infectious and noninfectious complication groups, respectively. The cutoff value of the preoperative neutrophil-to-lymphocyte ratio for all complications was 11.3, and multivariate analysis revealed that the preoperative neutrophil-to-lymphocyte ratio was an independent predictor of any postoperative complication (odds ratio: 4.223, 95% confidence interval: 1.335–13.352; P = 0.014). The cutoff value of the preoperative neutrophil-to-lymphocyte ratio for infectious complications was 11.4, and multivariate analysis revealed that the preoperative neutrophil-to-lymphocyte ratio was an independent predictor of infectious complications (odds ratio: 4.235, 95% confidence interval: 1.137–15.776; P = 0.031).

Conclusions

In patients with acute appendicitis, the preoperative neutrophil-to-lymphocyte ratio may be a useful predictor of all postoperative complications, especially infectious complications.
Anti-inflammatory effects of flavonoids and phenylethanoid glycosides from Hosta plantaginea flowers in LPS-stimulated RAW 264.7 macrophages through inhibition of the NF-κB signaling pathway
Authors: Yang Li , He Junwei
Published: March 2022

Background

The flower of Hosta plantaginea (Lam.) Aschers has traditionally been used in China as an important Mongolian medicine for the treatment of inflammatory diseases with limited scientific evidence. In previous studies, 16 flavonoids and 3 phenylethanoid glycosides (1–19) were isolated from the ethanolic extract of H. plantaginea flowers. Nevertheless, the anti-inflammatory effects of these constituents remain unclear. In the present study, the anti-inflammatory effects of these 19 constituents and their underlying mechanisms were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.

Methods

The viability of RAW 264.7 macrophages was detected by Cell Counting Kit-8 (CCK-8) assay. Meanwhile, nitric oxide (NO) production was measured by Griess assay, while the secretion of tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), interleukin 1β (IL-1β) and IL-6 in LPS-induced macrophages was determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, the protein expression of nuclear factor kappa B (NF-κB) p65 and phosphorylated NF-κB p65 was evaluated by Western blot analysis.

Results

All constituents effectively suppressed excessive NO production at a concentration of 40 μM with no toxicity to LPS-induced RAW 264.7 macrophages. Among them, five flavonoids (1, 4–6 and 15) and one phenylethanoid glycoside (17) remarkably prevented the overproduction of NO with median inhibitory concentration (IC50) values in the range of 12.20–19.91 μM. Moreover, compounds 1, 4–6, 15 and 17 potently inhibited the secretion of TNF-α, PGE2, IL-1β and IL-6, and had a prominent inhibitory effect on the down-regulation of the phosphorylated protein level of NF-κB p65.

Conclusion

Taken together, compounds 1, 4–6, 15 and 17 may be useful in managing inflammatory diseases by blocking the NF-κB signaling pathway and suppressing the overproduction of inflammatory mediators.
Basic life support, a necessary inclusion in the medical curriculum: a cross-sectional survey of knowledge and attitude in Uganda
Authors: Ssewante Nelson , Wekha Godfrey , Iradukunda Angelique , Musoke Phillip , Kanyike Andrew Marvin , Nabukeera Germinah , Wamala Nicholas Kisaakye , Zziwa Wilson , Kamuhangire Lauben , Kajjimu Jonathan , Luggya Tonny Stone , Tagg Andrew
Published: March 2022

Background

Uganda continues to depend on a health system without a well-defined emergency response system. This is in the face of the rising cases of out-of-hospital cardiac arrest contributed largely to the high incidence of road traffic accidents. Non-communicable diseases are also on the rise further increasing the incidence of cardiac arrest. Medical students are key players in the bid to strengthen the health system which warrants an assessment of their knowledge and attitude towards BLS inclusion in their study curriculum.

Methods

A descriptive cross-sectional study was conducted in 2021 among undergraduate medical students across eight public and private universities in Uganda. An online-based questionnaire was developed using Google forms and distributed via identified WhatsApp groups. Chi-square or Fisher’s exact test and logistic regression were performed in STATA 15 to assess the association between knowledge of BLS and demographics. P < 0.05 was considered statistically significant.

Results

Out of the total 354 entries obtained, 351 were analyzed after eligibility screening. Of these, (n = 250, 71.2%) were male less than 25 years (n = 273, 77.8%). Less than half (n = 150, 42.7%) participants had undergone formal BLS training.

Less than a third of participants (n = 103, 29.3%) had good knowledge (≥ 50%) with an overall score of 42.3 ± 12.4%. Age (p = 0.045), level of academic progress (p = 0.001), and prior BLS training (p = 0.033) were associated with good knowledge. Participants with prior training were more likely to have more BLS knowledge (aOR: 1.7, 95% CI: 1.1–2.7,p = 0.009).

The majority (n = 348, 99.1%) believed that BLS was necessary and would wish (n = 343, 97.7%) to have it included in their curriculum.

Conclusions

Undergraduate medical students have poor BLS knowledge but understand its importance. Institutions need to adopt practical teaching methods such as clinical exposures, field experience in collaboration with local implementers, and participating in community health promotion campaigns.
Voice-based control system for smart hospital wards: a pilot study of patient acceptance
Authors: Jian Wen-Shan , Wang Ju-Yu , Rahmanti Annisa Ristya , Chien Shuo-Chen , Hsu Chun-Kung , Chien Chia-Hui , Li Yu-Chuan , Chen Chun-You , Chin Yen-Po , Huang Chen-Ling
Published: March 2022

Background

The smart hospital's concept of using the Internet of Things (IoT) to reduce human resources demand has become more popular in the aging society.

Objective

To implement the voice smart care (VSC) system in hospital wards and explore patient acceptance via the Technology Acceptance Model (TAM).

Methods

A structured questionnaire based on TAM was developed and validated as a research tool. Only the patients hospitalized in the VSC wards and who used it for more than two days were invited to fill the questionnaire. Statistical variables were analyzed using SPSS version 24.0. A total of 30 valid questionnaires were finally obtained after excluding two incomplete questionnaires. Cronbach’s α values for all study constructs were above 0.84.

Result

We observed that perceived ease of use on perceived usefulness, perceived usefulness on user satisfaction and attitude toward using, and attitude toward using on behavioral intention to use had statistical significance (p < .01), respectively.

Conclusion

We have successfully developed the VSC system in a Taiwanese academic medical center. Our study indicated that perceived usefulness was a crucial factor, which means the system function should precisely meet the patients' demands. Additionally, a clever system design is important since perceived ease of use positively affects perceived usefulness. The insight generated from this study could be beneficial to hospitals when implementing similar systems to their wards.
Analysis of factors contributing to medication errors during self-management of medication in the rehabilitation ward: a case control study
Authors: Suzuki Ryohei , Uchiya Takako , Nakamura Ayumi , Okubo Naoki , Sakai Takamasa , Takahashi Masaaki , Kaneko Mariko , Aiba Ikuko , Ohtsu Fumiko
Published: March 2022

Background

In the rehabilitation ward, many elderly patients require continuous use of medication after a stroke or bone fracture, even after discharge. They are encouraged to self-manage their medications from the time of admission. Medication errors, such as a missed dose or incorrect administered medication can worsen conditions, resulting in recurrent strokes, fractures, or adverse effects. The study was aimed to identify risk factors, such as medication and prescription, contributing to errors in self-management of medication.

Methods

This study was conducted on patients who self-managed their medication in the rehabilitation ward of Higashinagoya National Hospital from April 2018 to March 2020. The patient background including age and sex were investigated. The medication factors examined include the number of medications and administrations per day, dosing frequency on indicated days, prescription and start date are the same, medications from multiple prescriptions, and one package or one tablet at each dosage. The group of medication error cases were defined as the medication error group and that of control cases as the no-medication error group. A logistic regression analysis was performed for factors related to medication errors.

Results

A total of 348 patients were included in the study, of which 154 patients made medication errors, with 374 total medication error cases. The median number of medications in the medication error group was six, and that in the no-medication error group was five. Statistically significant factors correlated with errors made during self-management of medication were the number of medications, number of administrations per day, dosing frequency on indicated days, and medication from multiple prescriptions.

Conclusions

When a patient is self-managing their medications, errors are likely to occur due to a high number of medicines they are taking and the complexity of the dosage regimen. Therefore, to prevent medication errors, reviewing the prescribed medications and devise ways to simplify the dosage regimens is crucial.
Supporting efficiency improvement in public health systems: a rapid evidence synthesis
Authors: Walters James Kenneth , Sharma Anurag , Malica Emma , Harrison Reema
Published: March 2022

Background

Public health systems internationally are under pressure to meet increasing demand for healthcare in the context of increasing financial resource constraint. There is therefore a need to maximise health outcomes achieved with public healthcare expenditure. This paper aims to establish and synthesize the contemporary evidence base for approaches taken at a system management level to improve efficiency.

Methods

Rapid Evidence Assessment (REA) methodology was employed. A search strategy was developed and applied (PUBMED, MEDLINE) returning 5,377 unique titles. 172 full-text articles were screened to determine relevance with 82 publications included in the final review. Data regarding country, study design, key findings and approaches to efficiency improvement were extracted and a narrative synthesis produced. Publications covering health systems from developed countries were included.

Results

Identified study designs included policy reviews, qualitative reviews, mixed methods reviews, systematic reviews, literature reviews, retrospective analyses, scoping reviews, narrative papers, regression analyses and opinion papers. While findings revealed no comprehensive frameworks for system-wide efficiency improvement, a range of specific centrally led improvement approaches were identified. Elements associated with success in current approaches included dedicated central functions to drive system-wide efficiency improvement, managing efficiency in tandem with quality and value, and inclusive stakeholder engagement.

Conclusions

The requirement for public health systems to improve efficiency is likely to continue to increase. Reactive cost-cutting measures and short-term initiatives aimed only at reducing expenditure are unlikely to deliver sustainable efficiency improvement. By providing dedicated central system-wide efficiency improvement support, public health system management entities can deliver improved financial, health service and stakeholder outcomes.
Role of raphe magnus 5-HT1A receptor in increased ventilatory responses induced by intermittent hypoxia in rats
Authors: Su Jiao , Meng Yang , Fang Yifei , Sun Linge , Wang Mengge , Liu Yanjun , Zhao Chunling , Dai Liping , Ouyang Songyun
Published: March 2022

Background

Intermittent hypoxia induces increased ventilatory responses in a 5-HT-dependent manner. This study aimed to explore that effect of raphe magnus serotonin 1A receptor (5-HT1A) receptor on the increased ventilatory responses induced by intermittent hypoxia.

Methods

Stereotaxic surgery was performed in adult male rats, and acute and chronic intermittent hypoxia models were established after recovery from surgery. The experimental group received microinjections of 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the raphe magnus nucleus (RMg). Meanwhile, the control group received microinjections of artificial cerebrospinal fluid instead of 8-OH-DPAT. Ventilatory responses were compared among the different groups of oxygen status. 5-HT expressions in the RMg region were assessed by immunohistochemistry after chronic intermittent hypoxia.

Results

Compared with the normoxia group, the acute intermittent hypoxia group exhibited higher ventilatory responses (e.g., shorter inspiratory time and higher tidal volume, frequency of breathing, minute ventilation, and mean inspiratory flow) (P < 0.05). 8-OH-DPAT microinjection partly weakened these changes in the acute intermittent hypoxia group. Further, compared with the acute intermittent hypoxia group, rats in chronic intermittent hypoxia group exhibited higher measures of ventilatory responses after 1 day of intermittent hypoxia (P < 0.05). These effects peaked after 3 days of intermittent hypoxia treatment and then decreased gradually. Moreover, these changes were diminished in the experimental group. 5-HT expression in the RMg region increased after chronic intermittent hypoxia, which was consistent with the changing trend of ventilatory responses. While activation of the 5-HT1A receptor in the RMg region alleviated this phenomenon.

Conclusions

The results indicate that RMg 5-HT1A receptor, via changing the expression level of 5-HT in the RMg region, is involved in the modulation of the increased ventilatory responses induced by intermittent hypoxia.
A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases
Authors: He Siqin , Gui Jiajia , Xiong Kun , Chen Meiwan , Gao Huile , Fu Yao
Published: March 2022

Pulmonary drug delivery is a highly attractive topic for the treatment of infectious lung diseases. Drug delivery via the pulmonary route offers unique advantages of no first-pass effect and high bioavailability, which provides an important means to deliver therapeutics directly to lung lesions. Starting from the structural characteristics of the lungs and the biological barriers for achieving efficient delivery, we aim to review literatures in the past decade regarding the pulmonary delivery strategies used to treat infectious lung diseases. Hopefully, this review article offers new insights into the future development of therapeutic strategies against pulmonary infectious diseases from a delivery point of view.

Graphical Abstract
LPL, FNDC5 and PPARγ gene polymorphisms related to body composition parameters and lipid metabolic profile in adolescents from Southern Italy
Authors: Perrone Benedetta , Ruffo Paola , Zelasco Samanta , Giordano Cinzia , Morelli Catia , Barone Ines , Catalano Stefania , Andò Sebastiano , Sisci Diego , Tripepi Giovanni , Mammì Corrado , Bonofiglio Daniela , Conforti Francesca Luisa
Published: March 2022

Background

Plasma lipid profile and anthropometric variables are known to be under strong genetic control and the identification of genetic variants associated with bioclinical parameters is of considerable public health importance. In this study, a young cohort of healthy individuals was genotyped for genes related to health and pathological conditions, to analyze the association of single nucleotide polymorphisms (SNPs) with different bioclinical parameters, adherence to the Mediterranean Diet (MD) and physical activity, studying the role of lifestyle and body composition parameters on biochemical metabolic profile.

Methods

Association analysis of single variants in the genes of lipoprotein lipase (LPL), fibronectin type III domain containing protein 5 (FNDC5), and peroxisome proliferator-activated receptor-gamma (PPARγ) and haplotype analyses were performed.

Results

Multiple (n = 14) common variants in the three genes demonstrated a significant effect on plasma lipoprotein-lipid levels and/or on biochemical parameters in our sample. Specifically, SNPs were related to lipid metabolism (rs3866471, rs4922115, rs11570892, rs248, rs316, rs1059507, rs1801282) or glycemic profile (rs3208305) or anthropometric parameters (rs3480, rs726344, rs1570569) for a total of 26 significant associations (P < 0.01 and/or P < 0.05) and two haplotypes, for the first time, were strongly associated with lipid and body composition parameters. Interestingly, we identified twenty-four new variants not previously described in the literature and a novel significant association between rs80143795 and body composition.

Conclusions

In this study we confirm the association between these SNPs on lipid metabolism and body parameters also in a young cohort, indicating the important role of these genetic factors as determinants of health.
The Effect of Intra-articular Injection of Hyaluronic Acid in Frozen Shoulder: a Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Mao BeiNi , Peng Run , Zhang Zhong , Zhang KaiBo , Li Jian , Fu WeiLi
Published: March 2022

Background

Frozen shoulder (FS) is a common progressive disorder that causes restricted motion and refractory pain undermining quality of life. Intra-articular hyaluronic acid (HA) injection is a widely adopted conservative therapy relieving symptomatic FS, whereas the effect of which were contradictory and unclear in current literatures. The aim of the present study is to investigate whether intra-articular HA administration facilitates symptomatic pain relief and functional improvements in patients diagnosed with shoulder FS.

Methods

The PubMed, Embase, Cochrane Library electronic databases and Google scholar were searched, from inception to 15th Jan 2022. Randomized controlled trials (RCTs) comparing intra-articular HA administration with any other non-surgical treatment in patients with FS were included. Risk of bias was evaluated using the Cochrane risk-of-bias tool and meta-analyses were undertaken to pool the data of visual analog scale for pain, range of motion (ROM) in external rotation, abduction, and flexion, as well as Shoulder Pain and Disability Index (SPADI), Constant score and American Shoulder and Elbow Surgeons (ASES).

Results

The present study included 7 RCTs involving 504 patients. The results provided no support for superior pain control in patients undergoing HA injection compared with any other treatment (p = 0.75). Furthermore, HA group failed to exert superior improvements to other treatments in ROM concerning abduction (p = 0.69) and flexion (p = 0.33). However, HA injection was observed to facilitate functional recovery in external rotation (p = 0.003). In addition, the pooled data showed a significant higher SPADI score in control group than in HA group (p = 0.01), while no statistical significance between two groups was observed in Constant score (p = 0.36) and ASES (p = 0.76).

Conclusions

The current meta-analysis suggested that HA is a beneficial treatment procedure in improving the ROM of the shoulder for patients with FS, whereas the effect in relieving pain may be equal to the existing therapy. In conclusion, Intra-articular HA injection is recommended for FS patients.
Association of COL5A1 gene polymorphisms and musculoskeletal soft tissue injuries: a meta-analysis based on 21 observational studies
Authors: Guo Rui , Ji Zhe , Gao Shutao , Aizezi Aihaiti , Fan Yong , Wang Zhigang , Ning Kai
Published: March 2022

Objective

Inconsistent findings existed on the correlation of collagen type V α1 (COL5A1) gene polymorphisms and musculoskeletal soft tissue injuries (MSTIs). The purpose of this study was to collect and combine the current evidences by a meta-analysis approach.

Methods

Six online databases were searched up to August, 2021. The methodological quality of each individual study was evaluated based upon Newcastle–Ottawa Scale (NOS). The strength of the effect size was presented by odds ratio (OR) with 95% confidence interval (95%CI) in five genetic models. The data were analyzed using Review Manager 5.3.

Results

Twenty-one studies were eligible to this meta-analysis. The study quality was deemed fair to excellent according to NOS. In the overall analyses, the merged data suggested that rs12722, rs71746744, and rs3196378 polymorphisms were correlated to an increased susceptibility to MSTIs. But the association was not established in rs13946 or rs11103544 polymorphism. For rs12722 polymorphism, stratified analyses by injury type and ethnicity identified the association mainly existed in ligament injury and among Caucasian population. For rs13946 polymorphism, subgroup analysis suggested the association existed in tendon and ligament injuries.

Conclusion

This study supports that rs12722 is associated with an elevated susceptibility to ligament injury, especially in the Caucasian population. Rs13946 polymorphism appears to increase the risk to tendon and ligament injuries. Rs71746744 and rs3196378 polymorphisms have a tendency to confer an elevated risk to MSTIs. However, no relevance is found between rs11103544 polymorphism and MSTIs.
Peri-prosthetic bone remodeling of hydroxyapatite-coated compaction short stem was not affected by stem alignment
Authors: Hayashi Shinya , Kuroda Yuichi , Nakano Naoki , Matsumoto Tomoyuki , Kamenaga Tomoyuki , Maeda Toshihisa , Niikura Takahiro , Kuroda Ryosuke
Published: March 2022

Background

To improve implant survival through accelerated early bone remodeling during total hip arthroplasty (THA), hydroxyapatite (HA) is widely used as a bioactive coating, which is believed to enhance initial fixation by osseointegration. We aimed to investigate the relationship between stem insertion alignment and postoperative bone mineral density (BMD) changes in patients with full hydroxyapatite-coated (HA) compaction short stem and short tapered-wedge stem.

Methods

This retrospective cohort study enrolled 115 consecutive patients (115 joints) undergoing THA using the full HA compaction short (n = 59) and short tapered-wedge (n = 56) stems. Stem alignment, including anteversion, valgus, and anterior tilt were measured by a three-dimensional template using computed tomography data. Post-operative peri-prosthetic BMD was measured by dual-energy X-ray absorptiometry. The relationship between stem alignment and BMD changes in the stems was analyzed.

Results

Patterns of peri-prosthetic BMD changes were similar in both groups. Stem insertion alignments of anteversion, valgus, and anterior tilt were different between the two stem types. Stem alignment of valgus and anterior tilt did not affect peri-prosthetic BMD in either of the stem type. An absolute anteversion difference between stem anteversion and original canal anteversion caused significant peri-prosthetic BMD loss in Gruen zones one and seven in the tapered-wedge stem. However, stem alignment of absolute anteversion difference did not affect BMD changes in the HA compaction stem.

Conclusions

Peri-prosthetic bone remodeling remained unaffected by stem alignment after THA with the new short full HA compaction stem.
An integrated study of Violae Herba (Viola philippica) and five adulterants by morphology, chemical compositions and chloroplast genomes: insights into its certified plant origin
Authors: Lu Gengyu , Qiao Juanjuan , Wang Long , Liu Hui , Wu Gang , Zhu Yan , Zhao Yucheng , Xie Guoyong , Qin Minjian
Published: March 2022

Background

Viola philippica Cav. is the only original plant for Violae Herba, as described in the Chinese Pharmacopoeia. The quality of this crude drug is affected by several adulterants from congeneric Viola species, and the authentic plant origin of Violae Herba is still controversial. Genome-based identification offers abundant genetic information and potential molecular markers that can be used for the authentication of closely related species. This study aims to investigate the certified origin of Violae Herba and to develop more effective markers for these easily confused species at the genetic level.

Methods

We compared the morphology and chemical composition of 18 batches of commercial samples and six widespread medicinal Viola plants used as Violae Herba or its substitutes by TLC and HPLC-Triple-TOF–MS/MS analyses. The complete chloroplast genomes of these species were sequenced and analyzed, including the general features, repeat sequences, mutational hotspots and phylogeny. The complete chloroplast genomes used as superbarcodes and some specific barcodes screened from mutational hotspots were tested for their ability to distinguish Viola species.

Results

A comparative study showed that Violae Herba is a multi-origin traditional Chinese medicine. Commercial decoction pieces and the standard reference drug were mainly derived from V. prionantha, clashing with the record in the Chinese Pharmacopoeia. Chloroplast genome analyses of V. philippica and five adulterants indicated that sequence divergence was relatively low within Viola species. By tree-based approaches, the complete chloroplast genomes showed a better discrimination ability and phylogenetic resolution for each Viola species. These results indicate that the whole chloroplast genomes can be used as superbarcodes to differentiate Viola medicinal plants. More specific DNA barcodes could be further developed from the Viola chloroplast genomes for more efficient and rapid identification of commercial Violae Herba and its adulterants.

Conclusions

This study has implications for chloroplast genome-based phylogenetic analysis and the authentication of multiple Viola species used as Violae Herba. The legal origin recorded in the Chinese Pharmacopoeia should be further revised to V. prionantha, in line with the commercial Violae Herba in the TCM markets.
Does m-health-based exercise (guidance plus education) improve efficacy in patients with chronic low-back pain? A preliminary report on the intervention’s significance
Authors: Zheng Fuming , Liu Shufeng , Zhang Shanshan , Yu Qiuhua , Lo Wai Leung Ambrose , Li Tingni , Wang Chu Huai
Published: March 2022

Background

The utilization of mobile health (m-health) has rapidly expanded during the COVID-19 pandemic, and there is still a lack of relevant clinical data pertaining to chronic low-back pain (CLBP) management. This study was designed to compare the effectiveness of m-health-based exercise (via guidance plus education) versus exercise (via guidance) during CLBP management.

Methods

Participants (n = 40) were randomly assigned to intervention and control groups. The intervention group received m-health-based exercise (via guidance plus education), whereas the control group received m-health-based exercise (via guidance). The exercise prescription video and educational content were sent to participants by the application (app), Ding Talk. Repeated-measures analysis of variance was used to test the baseline’s intervention effects, 6-week follow-up, and 18-week follow-up. We selected function (Roland and Morris Disability Questionnaire) and pain intensity (current, mean, and most severe Numeric Rating Scale in the last 2 weeks) as the primary outcomes, changes of negative emotion (depression, anxious), and quality of life as the secondary outcomes.

Results

Time’s significant effect was found in pain, function, and health-related quality of life in both groups, but time did not show significant interaction effects. Participants were able to use m-based education with their anxiety and depression after treatment, but the relief only lasted until week 6. No differences were found on the aspect of mental health-related quality of life.

Conclusion

Preliminary findings suggest that m-health-based exercise (via guidance) may be a convenient and effective method to treat CLBP. However, additional health education didn't help more. More rigorous controlled trials are needed to improve the therapeutic effect in future studies.

Trial registration

Chinese Clinical Trials Registry Number ChiCTR2000041459. Registered on December 26, 2020.
The effects of remifentanil-propofol combined with dexmedetomidine on cognitive dysfunction in elderly patients after ureteroscopic holmium laser lithotripsy: a double-blind randomized controlled trial
Authors: Wang Fangjun , Xie Dan , Xu Hongchun , Ye Qin , Wu Le , Gao Xiao Pei
Published: March 2022

Background

A clinical study indicated that infusion of dexmedetomidine without a loading dose administered intraoperatively provided a smooth and hemodynamically stable emergence and improved the quality of recovery with fewer postoperative side effects and reduced analgesic requirements. The objective was to determine whether administering remifentanil-propofol combined with dexmedetomidine during general anesthesia would decrease the incidence and severity of postoperative emergence agitation, anxiety, and depression without affecting cognitive dysfunction in elderly patients.

Methods

A total of 120 elderly patients scheduled for ureteroscopic holmium laser lithotripsy were randomly allocated to the PR group and administered normal saline, and the PRD group was administered dexmedetomidine 0.4 μg kg−1 h−1 intravenously after the induction of anesthesia and stopped 30 min before the end of surgery. The primary outcome was the Mini-Mental State Examination score. The secondary outcomes were the Richmond Agitation Sedation, the State-Trait Anxiety Inventory, and the Zung Self-Rating Depression Scale scores; the memory span for Arabic numerals; the duration of surgery; and the time to spontaneous respiration, recovery, and extubation.

Results

The MMSE scores were lower at T1–2 in the two groups (P < 0.001). The dosage of propofol and remifentanil decreased more significantly in the PRD group than in the PR group (P < 0.001). Both the RASS scores and the incidence of emergence agitation (EA) in the PRD group were significantly lower than those in the PR group at t1–3 (P < 0.001). Compared to the PR group, the ZSDS scores and STAI scores at T1–2 were lower in the PRD group (P < 0.005). The number of the Arabic numbers that were accurately recalled from memory was lower at T2 in the PR group than in the PRD group (P < 0.001).

Conclusion

Dexmedetomidine administration has no influence on postoperative cognitive dysfunction but could reduce both the dosage of remifentanil and propofol needed during ureteroscopic holmium laser lithotripsy and the incidence and severity of postoperative emergence agitation, anxiety, and depression in elderly patients.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900021254. Registered on 3 February 2019
Synthesis, characterization and antimicrobial properties of two derivatives of pyrrolidine-2,5-dione fused at positions-3,4 to a dibenzobarrelene backbone
Authors: Sopbué Fondjo Emmanuel , Njoya Abdou Salamou , Tamokou Jean-de-Dieu , Doungmo Giscard , Ndjakou Lenta Bruno , Simon Peter F. W. , Tsopmo Apollinaire , Kuiate Jules-Roger
Published: March 2022

A new diazo derivative of a pyrrolidine-2,5-dione (8) fused at position-3,4 to a dibenzobarrelene backbone has been prepared by coupling the previously reportedN-arylsuccinimid (5) precursor with aryldiazonium ion of aniline. The initial step of the reaction involved the preparation of the intermediate 9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic anhydride (3) through [4 + 2]-cycloaddition between anthracene and maleic anhydride in refluxing xylene which was then condensed with para-aminophenol to give compound5. Compounds5and8were characterized by their physical, elemental, and spectroscopic data. 2D-NMR (COSY, HSQC, and HMBC) techniques were used to confirm the structure of compound5. Compounds5(MIC = 32–128 μg/mL) and8(MIC = 16–256 μg/mL) along with the precursor3(MIC = 64–128 μg/mL) displayed moderate to low antimicrobial activities against selected bacterial and fungal species when compared with those of nystatin (MIC = 0.50–2 μg/mL) and ciprofloxacin (MIC = 0.50–16 μg/mL) used as reference drugs.

Graphical Abstract
Multisystem inflammatory syndrome in adults: a case report and review of the literature
Authors: Behzadi Fardad , Ulloa Nicolas A. , Danckers Mauricio
Published: March 2022

Background

The current coronavirus disease pandemic has brought recognition of multisystem inflammatory syndrome in adults as ade novoentity, temporally associated with severe acute respiratory syndrome coronavirus 2 viral infection in adults. Hypothesis about its true pathophysiology remains controversial.

Case report

The patient was a 22-year-old African American female presenting to the emergency department with fever, sore throat, and neck swelling for the past 3 days. During her initial emergency department visit, her blood pressure was stable at 110/57 mmHg, temperature of 39.4 °C, and heart rate of 150 beats per minute. While in the emergency department, she received broad-spectrum antibiotics (vancomycin and ceftriaxone) and 30 cc/kg bolus of normal saline. Originally, she was admitted to a telemetry floor. The following night, a rapid response code was called due to hypotension. At that time, her blood pressure was 80/57 mmHg. She appeared comfortable without signs of respiratory distress. She received intravenous fluids and vasopressors, and was transferred to the intensive care unit. The patient had reported a previous coronavirus disease infection a few weeks prior. She was diagnosed and treated for multisystem inflammatory syndrome in adults. Intravenous immunoglobulin infusion was initiated and completed on hospital day 5. She was weaned off vasopressors by day 6, and discharged home on day 11.

Conclusion

Our case report is an example of the presentation, diagnosis, and management of multisystem inflammatory syndrome. Our research into previous case reports illustrates the wide range of presentations, degree of end organ damage, and treatment modalities. This diagnosis needs to be considered in the presence of recent coronavirus disease infection with new-onset end organ failure, as prompt diagnosis and treatment is crucial for better outcomes.
Safety and efficacy of autologous, adipose-derived mesenchymal stem cells in patients with rheumatoid arthritis: a phase I/IIa, open-label, non-randomized pilot trial
Authors: Vij Ridhima , Stebbings Kevin A. , Kim Hosu , Park Hyeonggeun , Chang Donna
Published: March 2022

Objective

The present study is a phase I/IIa non-randomized, open-label study to evaluate safety and efficacy of a single, intravenous infusion of autologous, adipose-derived mesenchymal stem cells (adMSCs) over a period of 52 weeks, in patients with active rheumatoid arthritis (RA).

Methods

15 eligible RA patients aged 18–65 years were enrolled and followed up at weeks 4, 12, 26 and 52 after receiving a single intravenous dose of 2 × 108 adMSCs. Efficacy was examined using American College of Rheumatology (ACR66/68 score) criteria for swollen and tender joint counts (S/TJC), and serum TNF-α, IL-6, CRP, and ESR levels. Safety endpoints included measures of hematologic, hepatic, and renal function.

Results

ACR66/68 scores for both S/TJC showed significant improvements with large effect sizes (ES) at week 52 vs baseline (p < 0.01, ES = 0.83 and p < 0.001, ES = 0.93 respectively). Medium to large ES were also obvious for ACR66/68 scores measured at other timepoints. Levels of inflammatory markers, TNF-α, IL-6 and ESR remained unchanged compared to baseline. However, a difference in CRP levels with a small effect size was observed at week 4 (p = 0.229, ES = 0.33) with further improvement at week 52 (p = 0.183, ES = 0.37). Post-intervention, levels of hematologic, hepatic, and renal function remained largely unchanged (p > 0.05). No acute or long-term serious adverse events (AEs) occurred.

Conclusions

The results indicated that a single, intravenous administration of autologous adMSCs is safe and efficacious for improvement in joint function in patients with active RA. Data from the current study supports the exploration of ad-MSCs as a therapeutic intervention for RA.

Trial Registration Clinical trial registration number: NCT03691909. Registered September 27, 2018- Retrospectively registered (https://clinicaltrials.gov/show/NCT03691909).
Regulatory effects of Trichinella spiralis and a serine protease inhibitor on the endoplasmic reticulum stress response of intestinal epithelial cells
Authors: Xu Jingyun , Pang Zixuan , Zhang Jinpeng , Xia Shuang , Wang Ruibiao , Zhang Yuheng , Zhen Jingbo , Song Xuewei , Lin Lihao , Sun Feng , Xuan Xinxin , Lu Yixin
Published: March 2022

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum can cause an endoplasmic reticulum stress (ERS) response. If ERS continues or cannot be alleviated, it will cause the production of proapoptotic factors and eventually lead to apoptosis. Therefore, this study mainly explored whether Trichinella spiralis Kazal-type serine protease inhibitor (TsKaSPI) contributed to the invasion of intestinal epithelial cells during the infectious stage of T. spiralis by regulating ERS. First, in the T. spiralis infection model, H&E staining was used to analyse the damage to jejunum tissue, a TUNEL assay was used to examine cell apoptosis, and the expression of ERS-related and apoptosis-related molecules was also measured. The results showed that ERS occurred during the intestinal phase of T. spiralis infection, while remission began during the cyclic phase. Then, we selected TsKaSPI, one of the important components of T. spiralis ES antigens, for in vitro experiments. The results showed that TsKaSPI could induce apoptosis in a porcine small intestinal epithelial cell line (IPEC cells) by activating ERS and promote activation of the NF-κB signalling pathway. Inhibition experiments confirmed that the occurrence of ERS was accompanied by the activation of NF-κB, and the two processes regulated each other. Finally, we conducted in vivo experiments and administered TsKaSPI to mice. The results confirmed that TsKaSPI could activate ERS and lead to apoptosis in intestinal epithelial cells. In conclusion, T. spiralis infection and TsKaSPI can promote cell apoptosis by activating the ERS response in intestinal epithelial cells and activate the NF-κB signalling pathway to promote the occurrence and development of inflammation.