bluuebunny/crossref_metadata_2025 huggingface dataset:
Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation
Authors: Xu Lihua , Zhang Kaixiang , Ma Xing , Li Yingying , Jin Yajie , Liang Chenglin , Wang Yong , Duan Wendi , Zhang Hongling , Zhang Zhenzhong , Shi Jinjin , Liu Junjie , Wang Yunlong , Li Wentao
Published: September 2022

Despite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisplatin delivery of deeper tissue and increased DNA adducts formation. The nanomotor displayed a self‐propelled tumor penetration fueled by hydrogen peroxide (H2O2) in tumor tissues, which is catalytically decomposed into a large amount of oxygen bubbles by Ag nanoparticles (NPs). Notably, cisplatin could elevate the intracellular H2O2 level through cascade reactions, further promote the degradation of Ag NPs accompanied with the Ag+ release, which could downregulate intracellular Cl− through the formation of AgCl precipitate, thereby enhancing cisplatin dechlorination and Pt–DNA formation. Moreover, polymer can also inhibit the activity of ALKBH2 (a Fe2+-dependent DNA repair enzyme) by chelating intracellular Fe2+ to increase the proportion of irreparable Pt–DNA cross-links. It is found that deep tissue penetration, as well as the increased formation and maintenance of Pt–DNA adducts induced by the nanomotor afford 80% of tumor growth inhibition with negligible toxicity. This work provides an important perspective of resolving chemotherapeutic barriers for boosting cisplatin therapy.

Graphical Abstract
Value of different anastomoses in laparoscopic radical right hemicolectomy for right-sided colon cancer: retrospective study and literature review
Authors: Wang Xiaoming , Ni Hongyan , Jia Wangqiang , Wang Sen , Zhang Yangyang , Zhao Peng , Yuan Long
Published: September 2022

Background

This study aimed to analyze the safety of circular lateral anastomosis and cross-lateral anastomosis in laparoscopic radical resection of right-sided colon cancer.

Methods

From January 2018 to March 2021, 147 patients with right-sided colon cancer were admitted to the Department of General Surgery, Cancer Hospital, Zhengzhou University. The experimental group comprised patients with circular lateral anastomosis, whereas the control group comprised patients with cruciform lateral anastomosis. The general clinical data, intraoperative features, and postoperative results of the two groups were compared and analyzed.

Results

Both groups successfully underwent laparoscopic lateral ileocolic anastomosis, with significant differences in anastomotic leakage (χ2=4.520, P < 0.05). By contrast, body mass index (t = 1.568, P = 0.119), histological typing (χ2 = 2.067, P = 0.559), intraoperative bleeding (t = 0.418, P = 0.677), and intestinal obstruction (χ2 = 2.564, P = 0.109) were not significantly different between the groups (P > 0.05).

Conclusions

In laparoscopic-assisted radical hemicolectomy for right-sided colon cancer, the incidence of postoperative anastomotic leakage was lower with circular lateral anastomosis than with cross-lateral anastomosis, and circular lateral anastomosis was superior to cross-lateral anastomosis in terms of reducing the length of hospital stay and improving patients' postoperative quality of life.
Prognostic value of lymph node density on cancer staging system for gastric cancer without distal metastasis: a population-based analysis of SEER database
Authors: Liu Yuhua , Cui Hao , Xu Xinxin , Liang Wenquan
Published: September 2022

Background

Accurate tumor staging is the cornerstone of tumor treatment. Current tumor staging system for gastric cancer (GC) is based on regional positive lymph nodes while ignoring the total number of examined lymph nodes. We aim to assess the prognostic value of lymph node density (LND), the ratio of positive nodes to the total number examined nodes, in GC without distal metastasis.

Methods

Clinical information of patients with histologically confirmed GC and without distal metastasis was identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-Tile software was used to identify the ideal prognosis-related cutoff point for LND. The prognostic value of LND on cancer-specific survival (CSS) and overall survival (OS) was assessed in Cox regression models. Subgroup analysis stratified by LND was performed on current lymph node staging system to further explore the interaction between LND and current lymph node staging system.

Results

A total of 4281 participants were identified from the SEER database for the final analysis. The optimal prognosis-related cutoff values of LND were calculated as 0.1 and 0.4, and LND was divided into three levels: LND1 (< 0.1), LND2 (> = 0.1, < 0.4), and LND3 (> = 0.4). LND3 was associated with worse CSS and OS in GC patients. Compared to patients with LND1, those with LND2 and LND3 had 2.43 (HR = 2.43, 95% CI 2.09–2.84, P < 0.001) and 4.69 (HR = 4.69, 95% CI 4.02–5.48, P < 0.001) folds increase in mortality in CSS, respectively. Similar results were found in the evaluation of OS in GC patients. Subgroup analysis stratified by LND also found that patients in the same current lymph node stage still had different prognosis due to the different LND levels after adjustment for other prognosis-related covariates (all P values < 0.001).

Conclusion

LND is an independent prognostic factor for GC without distal metastasis. In the current lymph node staging system, LND has potential value in further accurately classifying GC patients without distal metastasis.
A theory-based evaluation of the Leadership for Universal Health Coverage Programme: insights for multisectoral leadership development in global health
Authors: Witter Sophie , Brikci Nouria , Scherer David
Published: September 2022

Background

Leadership to manage the complex political and technical challenges of moving towards universal health coverage (UHC) is widely recognized as critical, but there are few studies which evaluate how to expand capacities in this area. This article aims to fill some of this gap by presenting the methods and findings of an evaluation of the Leadership for UHC (L4UHC) programme in 2019–2020.

Methods

Given the complexity of the intervention and environment, we adopted a theory-driven evaluation approach that allowed us to understand the role of the programme, amongst other factors. Data from a range of sources and tools were compared with a programme theory of change, with analysis structured using an evaluation matrix organized according to the Organisation for Economic Co-operation and Development–Development Assistance Committee (OECD-DAC) criteria. Data sources included key informant (KI) interviews (89 in total); surveys of the 80 workshop participants; a range of secondary data sources; case studies in two countries; and observation of activities and modules by the evaluator.

Results

Participants and KIs at the global and country levels reported high relevance of the programme and a lack of alternatives aiming at similar goals. In relation to effectiveness, at the individual level, there was an increase in some competencies, particularly for those with less experience at the baseline. Less change was observed in commitment to UHC as that started at a relatively high level. Understanding of UHC complexity grew, particularly for those coming from a non-health background. Connections across institutional divides for team members in-country increased, although variably across the countries, but the programme has not as yet had a major impact on national coalitions for UHC. Impacts on health policy and practice outcomes were evident in two out of seven countries. We examined factors favouring success and explanatory factors. We identified positive but no negative unintended effects.

Conclusions

While noting methodological constraints, the theory-based evaluation approach is found suitable for assessing and learning lessons from complex global programmes. We conclude that L4UHC is an important addition to the global and national health ecosystem, addressing a relevant need with some strong results, and also highlight challenges which can inform other programmes with similar objectives.
Operative public values as a tool for healthcare decisions: the social value and clinical criteria of triage
Authors: Cordeiro-Rodrigues Luis
Published: September 2022

With the current pandemic, many scholars have contended that clinical criteria offer the best way to implement triage. Further, they dismiss the criteria of social value as a good one for triage. In this paper, I respond to refute this perspective. In particular, I present two sets of arguments. Firstly, I argue that the objections to the social value criteria they present apply to the clinical criteria they favor. Secondly, they exaggerate the negative aspects of the social value criteria, while I suggest it is reasonable to use this. I end the article by recommending how operative public values can be a good way to make triaging decisions.
Linac-based stereotactic radiosurgery for brain arteriovenous malformations
Authors: Gawish Ahmed , Röllich Burkard , Ochel Hans-Joachim , Brunner Thomas B.
Published: September 2022

Purpose

Linac stereotactic radiosurgery (SRS) is gaining popularity as a form of radiation treatment for cerebral arteriovenous malformations (AVMs) since the theory of combined radiosurgical and endovascular treatment poses much uncertainty and due to significant technical progress for SRS. This study focuses on how to evaluate obliteration and re-bleeding rates, and to determine factors and adverse effects influencing obliteration after linac-based SRS for cerebral AVMs.

Material and methods

From a statistical record of 71 patients, 31 had partial embolisation, five surgery and 29 had no prior treatment. Using Kaplan–Meier survival and life table analyses, actuarial obliteration and annual bleeding hazard rates were calculated after SRS.

Results

After a follow up of 1, 2 and 3 years the actual obliteration rates were 22, 59 and 66%, respectively whereby it was noted that prior embolization had no effect on the obliteration rate. Annual bleeding hazard rates were further analyzed after stereotactic radiosurgery to be 2.1% and 1.4% for the first and second year respectively. Asymptomatic abnormalities were detected after imaging in 33.9% of patients. A dose of less than 18 Gy significantly reduced the obliteration probability.

Conclusion

SRS is a therapeutic option for intracerebral AVM. In general, there is a low rate of morbidity and a high probability of nidus obliteration.
Analgesic efficacy of adding the IPACK block to multimodal analgesia protocol for primary total knee arthroplasty: a meta-analysis of randomized controlled trials
Authors: Tang Xiumei , Lai Yahao , Du Siwei , Ning Ning
Published: September 2022

Background

Total knee arthroplasty (TKA) is a standard treatment for end-stage degenerative knee disease. Most patients will experience moderate-to-severe postoperative knee pain, significantly affecting rehabilitation. However, controversy remains regarding the efficacy of adding the interspace between the popliteal artery and capsule of the knee (IPACK) into multimodal analgesia protocol.

Methods

PubMed, Medline, Embase, Cochrane Library, and other databases were searched from inception to February 1, 2021. Studies comparing patients receiving IPACK to patients not receiving IPACK were included. The primary outcome was the ambulation pain score on a visual analogue scale (VAS) of 0–10. Secondary outcomes included pain score at rest, morphine usage, functional recovery, clinical outcomes, and complications.

Results

Thirteen RCTs involving 1347 knees were included. IPACK was associated with lower ambulation pain scores (weight mean difference [WMD] − 0.49, 95% confidence interval [CI] − 0.72 to − 0.26). The benefits were observed from 2 to 4 h, 6 to 12 h, and beyond one week. IPACK also significantly reduced rest pain scores (WMD − 0.49, 95% CI − 0.74 to − 0.24), and the benefits were observed from 6 to 12 h and beyond one week. IPACK reduced the overall morphine consumption (WMD − 2.56, 95% CI − 4.63 to − 0.49). Subgroup analysis found reduced oral morphine consumption from 24 to 48 h (WMD − 2.98, 95% CI − 5.71 to − 0.24) and reduced rate of morphine requirement from 12 to 24 h (relative risk [RR] = 0.51, 95% CI 0.31 to 0.83). Functional recovery outcomes regarding ambulation distances (on the second postoperative day [POD2]) (WMD = 1.74, 95% CI 0.34 to 3.15) and quadriceps muscle strength (at 0 degree) (WMD = 0.41, 95% CI 0.04 to 0.77) favored IPACK. And IPACK reduced the rate of sleep disturbance (on POD 1) (RR = 0.39, 95% CI 0.19 to 0.81). There was no significant difference in the other outcomes.

Conclusions

Moderate-level evidence confirmed that IPACK was related to better results in pain scores, morphine usage, and functional recovery without increasing the risk of complications.

Registration

CRD42021252156.
Needle-based gastrocnemius lengthening: a novel ultrasound-guided noninvasive technique
Authors: Iborra Marcos Álvaro , Villanueva Martínez Manuel , Fahandezh-Saddi Díaz Homid
Published: September 2022

Background

Gastrocnemius tendon lengthening is performed to treat numerous conditions of the foot and ankle. Gastrocnemius shortening has been associated with more than 30 lower limb disorders, including plantar heel pain/plantar fasciitis, Achilles tendinosis, equinus foot, adult flat foot deformity, and metatarsalgia. Ultrasound-guided ultraminimally invasive lengthening of the gastrocnemius is a step forward in this type of surgery. It can be performed in both legs simultaneously without ischemia using only local anesthesia plus sedation and without the need for a cast or immobilization. The truly novel advantage of the procedure is that it can be performed in the office, without specific surgical instruments. The aim of our research was to prove the effectiveness and safety of a new closed needle-based ultrasound-guided surgical procedure for lengthening the gastrocnemius tendon.

Methods and results

We performed ultrasound-guided gastrocnemius tendon lengthening using a needle in eight fresh frozen specimens (3 left and 5 right). None of the specimens had been affected by disease or undergone previous surgery that could have affected the surgical technique. We used a linear transducer with an 8- to 17-MHz linear transducer and the beveled tip of an Abbocath as a surgical blade to perform the lengthening procedure. The gastrocnemius Achilles tendon recession was entirely transected in all eight specimens, with no damage to the sural nerve or vessels. The improvement in dorsal flexion was 15°.

Conclusion

Needle-based ultrasound-guided gastrocnemius tendon lengthening is safe, since the surgeon can see all structures clearly, thus minimizing the risk of damage. The absence of a wound obviates the need for stitches, and recovery seems to be faster. The procedure can be performed in a specialist's office, as no specific surgical instruments are required. This technique could be a valid option for gastrocnemius lengthening and may even be less traumatic than using a hook-knife, as in our previous description.
Nitidine chloride induces caspase 3/GSDME-dependent pyroptosis by inhibting PI3K/Akt pathway in lung cancer
Authors: Yu Fei , Tan Weidan , Chen Zhiquan , Shen Xiaoju , Mo Xiaoxiang , Mo Xiaocheng , He Jingchuan , Deng Zhihua , Wang Jie , Luo Zhuo , Yang Jie
Published: September 2022

Background

As the increasing mortality and incidence of lung cancer (LC), there is an urgent need to discover novel treatment agent. In this study, we aimed to investigate the anti-LC effects of nitidine chloride (NC), a small molecular compound extracted from Chinese herbal medicine, while detailing its underlying mechanisms.

Methods

Cell viability was detected by MTT assays and five cell death inhibitors, including ferrostatin-1 (Fer-1), Z-VAD-FMK, necrostatin-1 (Nec-1), disulfiram (DSF) and IM-54 were used to explore the type of cell death induced by NC. The microscopic features of NC-induced pyroptosis were assessed by transmission electron microscopy (TEM) and the pyroptotic-related proteins such as caspase and gasdermin family, were examined by western blot. Network pharmacology was employed to predict the potential mechanisms of NC in lung cancer treatment. CETSA and DARTs were used to determine the activity of NC binding to targeted protein. Xenograft mice model was established to further investigate the inhibitory effect and mechanism of NC against LC.

Results

The pyroptosis inhibitor (DSF) and apoptosis inhibitor (Z-VAD-FMK) but not IM-54, necrostatin-1, or Ferrostatin-1 rescued NC-induced cell death. Morphologically, H1688 and A549 cells treated with NC showed notably pyroptotic features, such as cell swelling and large bubbles emerging from the plasma membrane. Gasdermin E (GSDME) rather than GSDMC or GSDMD was cleaved in NC-treated H1688 and A549 cells with an increased cleavage of caspase 3. Combined with network pharmacology and molecule docking, PI3K/Akt signaling axis was predicted and was further verified by CETSA and DARTs assay. In addition, the activation of PI3K is able to rescue the pyroptosis induced by NC in vitro. In xenograft model of LC, NC significantly hindered the transduction of PI3K-AKT pathway, inducing pyroptosis of tumor.

Conclusion

Our data indicated that NC is a potential therapeutic agent for the treatment of LC via triggering GSDME-dependent pyroptosis.
Clinical characteristics, healthcare use, and annual costs among patients with dystrophic epidermolysis bullosa
Authors: Feinstein James A. , Bruckner Anna L. , Chastek Benjamin , Anderson Amy , Roman Juan
Published: September 2022

Background

Dystrophic epidermolysis bullosa (DEB) is a serious, ultra-rare, genetic blistering disease that requires a multidisciplinary care team and lifelong, proactive disease management. To organize and optimize care, we comprehensively examined diagnoses, healthcare use, and annual costs in patients with DEB across all healthcare settings.

Methods

A retrospective study was performed using electronic health record (EHR) data from Optum Clinical Database (January 1, 2016, through June 30, 2020). Patients with an epidermolysis bullosa (EB) diagnosis between July 1, 2016, and December 31, 2019, with ≥ 6 months of baseline and 12 months of follow-up activity were included. Patients were stratified by EB type: recessive DEB (RDEB), dominant DEB (DDEB), DEB (type unknown), and EB unspecified. Demographics, comorbid conditions, and healthcare resource utilization were identified from EHR data. Cost of bandages and total medical costs (US$) were identified from linked claims data.

Results

A total of 412 patients were included, classified as having DDEB (n = 17), RDEB (n = 85), DEB (type unknown; n = 45), and EB unspecified (n = 265). Mean age was 38.4 years, and 41.7% had commercial insurance coverage. The most common comorbidities were mental health disorders, malnutrition, and constipation. Rates of cutaneous squamous cell carcinoma ranged from 0% (DDEB) to 4.4% (RDEB). Prescriptions included antibiotics (56.6%), pain medications (48.3%), and itch medications (50.7%). On average, patients had 19.7 ambulatory visits during the 12-month follow-up, 22.8% had an emergency department visit, and 23.8% had an inpatient stay. Direct medical costs among patients with claims data (n = 92) ranged from $22,179 for EB unspecified to $48,419 for DEB (type unknown).

Conclusions

This study demonstrated the range of comorbidities, multiple healthcare visits and prescription medications, and treatment costs during 1 year of follow-up for patients with DEB. The results underscore that the clinical and economic burden of DEB is substantial and primarily driven by supportive and palliative strategies to manage sequelae of this disease, highlighting the unmet need for treatments that instead directly address the underlying pathology of this disease.
Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study
Authors: Demoule Alexandre , Deleris Robin , Bureau Côme , Lebbah Said , Decavèle Maxens , Dres Martin , Similowski Thomas , Dechartres Agnes
Published: September 2022

Background

Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score.

Methods

In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18–75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea.

Discussion

To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure.

Trial registration

ClinicalTrials.govNCT04358133. Registered on 24 April 2020.
Testing a very low-carbohydrate adaption of the Diabetes Prevention Program among adults with prediabetes: study protocol for the Lifestyle Education about prediabetes (LEAP) trial
Authors: Griauzde Dina H. , O’Brien Alison , Yancy William S. , Richardson Caroline R. , Krinock Jamie , DeJonckheere Melissa , Isaman Deanna J. M. , Vanias Kaitlyn , Shopinski Samuel , Saslow Laura R.
Published: September 2022

Background

The Center for Disease Control and Prevention’s National Diabetes Prevention Program (NDPP) aims to help individuals with prediabetes avoid progression to type 2 diabetes mellitus (T2DM) through weight loss. Specifically, the NDPP teaches individuals to follow a low-fat, calorie-restricted diet and to engage in regular physical activity to achieve ≥ 5% body weight loss. Most NDPP participants, however, do not achieve this weight loss goal, and glycemic control remains largely unchanged. One promising opportunity to augment the NDPP’s weight loss and glycemic effectiveness may be to teach participants to follow a very low-carbohydrate diet (VLCD), which can directly reduce post-prandial glycemia and facilitate weight loss by reducing circulating insulin and enabling lipolysis. To date, there have been no high-quality, randomized controlled trials to test whether a VLCD can prevent progression to T2DM among individuals with prediabetes. The aim of this study is to test the effectiveness of a VLCD version the NDPP (VLC-NDPP) versus the standard NDPP. We hypothesize the VLC-NDPP will demonstrate greater improvements in weight loss and glycemic control.

Methods

We propose to conduct a 12-month, 1:1, randomized controlled trial that will assign 300 adults with overweight or obesity and prediabetes to either the NDPP or VLC-NDPP. The primary outcome will be glycemic control as measured by change in hemoglobin A1c (HbA1c) from baseline to 12 months. Secondary outcomes will include percent body weight change and changes in glycemic variability, inflammatory markers, lipids, and interim HbA1c. We will evaluate progression to T2DM and initiation of anti-hyperglycemic agents. We will conduct qualitative interviews among a purposive sample of participants to explore barriers to and facilitators of dietary adherence. The principal quantitative analysis will be intent-to-treat using hierarchical linear mixed effects models to assess differences over time.

Discussion

The NDPP is the dominant public health strategy for T2DM prevention. Changing the program’s dietary advice to include a carbohydrate-restricted eating pattern as an alternative option may enhance the program’s effectiveness. If the VLC-NDPP shows promise, this trial would be a precursor to a multi-site trial with incident T2DM as the primary outcome.

Trial registration

NCT05235425. Registered February 11, 2022.
Effects of meditation on physiological and metabolic parameters in patients with type 2 diabetes mellitus “MindDM”: study protocol for a randomized controlled trial
Authors: Dalpatadu K. P. C. , Galappatthy P. , Katulanda P. , Jayasinghe S.
Published: September 2022

Background

Sri Lanka is faced with the challenge of managing a large population with diabetes mellitus by 2030. Psychological stress plays a major role in disease outcome by exerting physiological, psychological and social effects on individuals with chronic disorders.

Meditation-based interventions have positive effects on the management of stress and diabetes, which are mediated via modulation of neuro-humoral mechanisms and autonomic functions, among others. Mechanisms of bio-physiological effects of meditation are considered to be through reduction of stress hormones, improvement of insulin resistance and improvement of autonomic dysfunction.

Methods

This study will be conducted as an open-label, randomized controlled clinical trial in the Faculty of Medicine, University of Colombo. The aim is to investigate the effects of meditation on glycaemic control and possible mechanisms of how meditation affects glycaemic control in patients with type 2 diabetes. The study was approved by the Ethics Review Committee of the Faculty of Medicine, University of Colombo (ERC/2019/094). Patients who are attending the professorial unit medical clinic with type 2 diabetes (172 in total) will be recruited based on inclusion-exclusion criteria. Patients who have never meditated or rarely meditated (less than once every three months) will be randomized using block randomization to meditation and waitlisted arms (1:1 allocation ratio). The meditation arm will undergo a mindfulness meditation program (selected after studying several meditation methods) conducted by a qualified instructor weekly for a period of 12 weeks in addition to usual care, while the waitlisted arm will only receive usual care. Daily meditation practices will be recorded in a diary. The primary outcome measure is HbA1c. Secondary outcome measures are fasting blood sugar, fructosamine, insulin resistance (calculated using fasting serum insulin), 24-h urinary cortisol, body mass index, cardiac autonomic reflex testing (Ewing’s battery of tests) and orocecal transit time using hydrogen breath analysis. All these will be done prior to commencement of the intervention and after 3 months in both arms. Data will be analysed using SPSS V-23.

Discussion

This study aims to identify the effect of mindfulness meditation on glycaemic control and the possible mechanisms (neuro humoral and autonomic functions) by which beneficial effects are mediated.

Trial registration

Registered under Sri Lanka Clinical Trial Registry: SLCTR/2021/015

The Universal Trial Number (UTN) U1111-1266-8640
The effect of transcranial direct current stimulation combined with working memory training on working memory deficits in schizophrenic patients: study protocol for a randomized controlled trial
Authors: Zhu Xiaolin , Huang Chao , Fan Hongzhen , Fan Fengmei , Zhao Yanli , Xiu Meihong , Wang Yunhui , Li Yajun , Tan Yunlong , Wang Zhiren , Tan Shuping
Published: September 2022

Background

Working memory deficits are one of the core and most characteristic clinical features of cognitive impairment in schizophrenia. Cognitive training can improve the cognitive function of patients with schizophrenia. However, the overall and transfer effects of working memory treatment (WMT) require improvement. Numerous studies have confirmed that transcranial direct current stimulation (tDCS) enhances neuroplasticity in the brain, providing a new treatment approach for cognitive impairment in patients with schizophrenia. We hypothesize that a training mode combining “preheating” (tDCS, which changes the neural activity of working memory-related brain regions) and “ironing” (WMT) affords greater cognitive improvements than WMT alone. In addition, this study aims to examine the mechanisms underlying the superiority of tDCS combined with WMT in improving cognitive function in patients with schizophrenia.

Methods

This study will include 120 patients with schizophrenia aged 18–60 years. The patients will be randomized into four groups: the study group (tDCS + WMT), tDCS group (tDCS + simple response training, SRT), WMT group (sham tDCS + WMT), and control group (sham tDCS + SRT). Patients will receive 20-min, 2 mA sessions of active or sham tDCS twice a day on weekdays for 2 weeks. Each stimulation will be immediately followed by a 1 − 2-min rest and 40 min of WMT or SRT. The primary outcome is cognitive function, measured using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and some subscales of the MATRICS Consensus Cognitive Battery (MCCB). The secondary outcomes are other behavioral measures, variations in brain imaging, and serum levels of brain-derived neurotrophic factor (BDNF). All outcomes will be measured at baseline, post-treatment, and 3-month follow-up, except for brain imaging and BDNF levels, which will be measured at baseline and post-treatment only.

Discussion

If tDCS combined with WMT results in significant improvements and prolonged effects on working memory, this method could be considered as a first-line clinical treatment for schizophrenia. Moreover, these results could provide evidence-based support for the development of other approaches to improve cognitive function in patients with schizophrenia, especially by enhancing WMT effects.

Trial registration

Chictr.org.cn; ChiCTR2200063844. Registered on September 19, 2022.
NAVKIDS2 trial: a multi-centre, waitlisted randomised controlled trial of a patient navigator intervention in children with chronic kidney disease — statistical analysis plan and update to the protocol
Authors: van Zwieten Anita , Ryan Elizabeth G. , Caldwell Patrina , Howard Kirsten , Tong Allison , Craig Jonathan C. , Alexander Stephen I. , Howell Martin , Teixeira-Pinto Armando , Hawley Carmel M. , Jesudason Shilpanjali , Walker Amanda , Mackie Fiona , Kennedy Sean E. , McTaggart Steven , McCarthy Hugh J. , Carter Simon A. , Kim Siah , Woodleigh Reginald , Francis Anna , Mallard Alistair R. , Bernier-Jean Amélie , Johnson David W. , Hahn Deirdre , Reidlinger Donna , Pascoe Elaine , Varghese Julie , Kiriwandeniya Charani , Vergara Liza , Larkins Nicholas , Macauley Luke , Irving Michelle , Khalid Rabia , Guha Chandana , Wong Germaine
Published: September 2022

Background

This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published.

Methods/design

The original protocol was published in BMC Nephrology (https://doi.org/10.1186/s12882-019-1325-y) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1–2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0–16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213. Prospectively registered on 12 July 2018
Fleas from the Silk Road in Central Asia: identification of Ctenocephalides canis and Ctenocephalides orientis on owned dogs in Uzbekistan using molecular identification and geometric morphometrics
Authors: Deak Georgiana , Safarov Alisher , Xie Xi Carria , Wang Runting , Mihalca Andrei Daniel , Šlapeta Jan
Published: September 2022

Background

The Silk Road connected the East and West for over 1500 years. Countries in Central Asia are valuable in addressing the hypothesis that parasites on domestic animals were introduced along the Silk Road. Adult fleas are obligate parasites, having worldwide distribution. In dogs,Ctenocephalides canis,C. felisandC. orientisare the most common species identified. The distribution of the Oriental cat flea,C. orientis, is restricted to southeast Asia. The purpose of this study was to determine the diversity of dog fleas from Uzbekistan, a country in Central Asia, with particular reference toC. orientis.

Methods

Fleas were collected from 77 dogs from 5 locations in Uzbekistan. Thecox1gene sequences fromCtenocephalidesspp. were compared to global collection ofCtenocephalides cox1haplotypes. Landmark-based geometric morphometrics have been applied to the head and curvature to compareC. canisandC. canisusing canonical variate analysis and discriminant function analysis.

Results

Overall, 199 fleas were collected and identified asC. canis(n = 115, 58%),C. orientis(n = 53, 27%) andPulex irritans(n = 22, 11%). None of the fleas wereC. felis. AllCtenocephalidesspp. fleas were subject tocox1amplification and 95% (166/175) yielded DNA sequence. There were 25cox1haplotypes; 14 (22/25, 88%) wereC. canis cox1haplotypes and 3 (3/25, 12%) wereC. orientis cox1haplotypes. Molecular analysis confirmed the absence ofC. felis. Four (4/22) and one (1/3)cox1haplotypes were identical tocox1haplotypes belonging toC. canisandC. orientis cox1haplotypes identified elsewhere, respectively. Overall morphometric analysis confirmed significant differences between the head shape ofC. canisandC. orientisand improved four–fivefold the species identification compared to traditional morphological key.

Conclusion

We report for the first time the presence ofC. orientisin Uzbekistan. Differentiation ofC. orientisfromC. canisandC. felisremains difficult in regions where these species coexist. Studies in Central and Southeast Asia should confirm species identity usingcox1locus to enable retracing of the distribution of theCtenocephalidesin Asia. The presence ofC. orientissuggests that this species may have been introduced from the east along the ancient Silk Road.

Graphical Abstract
Whipworm secretions and their roles in host-parasite interactions
Authors: Shears Rebecca K. , Grencis Richard K.
Published: September 2022

Whipworm (Trichuris) is a genus of roundworms that causes gastrointestinal infections in humans and animals. Of particular interest are T. trichiura, the causative agent of human trichuriasis, a neglected tropical disease that affects 477 million people worldwide, and T. suis, the pig whipworm species, responsible for growth stunting and economic losses within the agricultural industry. The naturally occurring mouse whipworm, T. muris, has been used for decades as a model for trichuriasis, yielding knowledge on the biology of these parasites and the host response to infection. Ex vivo culture of T. muris (and to some extent, T. suis) has provided insight into the composition of the excretory/secretory (E/S) products released by worms, which include a myriad of proteins, RNAs, lipids, glycans, metabolites and extracellular vesicles. T. muris E/S has formed the basis of the search for whipworm vaccine candidates, while the immunomodulatory potential of T. suis and T. muris secretions has been investigated with the aim of improving our understanding of how these parasites modulate host immunity, as well as identifying immunomodulatory candidates with therapeutic potential in the context of inflammatory diseases. This article will review the various components found within Trichuris E/S, their potential as vaccine candidates and their immunomodulatory properties.

Graphical Abstract
Dorso-ventral osteophytes of interphalangeal joints correlate with cartilage damage and synovial inflammation in hand osteoarthritis: a histological/radiographical study
Authors: Sunk Ilse-Gerlinde , Amoyo-Minar Love , Niederreiter Birgit , Soleiman Afschin , Kainberger Franz , Smolen Josef S. , Aletaha Daniel , Bobacz Klaus
Published: September 2022

Objective

To detect dorsally located osteophytes (OP) on lateral x-ray views and to correlate their presence with the extent of structural joint damage, determined by histologic grading (cartilage damage and synovial inflammation) and radiographic scoring in hand osteoarthritis (HOA).

Methods

Distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints were obtained from post mortem specimens (n = 40). Multiplanar plain x-rays were taken (dorso/palmar (dp) and lateral views). Radiographic OA was determined by the Kellgren and Lawrence classification. Joint samples were prepared for histological analysis and cartilage damage was graded according to the Mankin scoring system. Inflammatory changes of the synovial membrane were scored using the general synovitis score (GSS). Spearman’s correlation was applied to examine the relationship between histological and radiographical changes. Differences between groups were determined by Mann-Whitney test.

Results

Bony proliferations that were only detectable on lateral views but reminiscent of OPs on dp images were termed dorso-ventral osteophytes (dvOPs). All joints displaying dvOPs were classified as OA and the presence of dvOPs in DIP and PIP joints correlated with the extent of histological and radiographic joint damage, as well as with patient age. Joint damage in osteoarthritic DIP and PIP joints without any dvOPs was less severe compared to joints with dvOPs. Synovial inflammation was mainly present in joints displaying dvOPs and correlated with joint damage.

Conclusion

dvOPs are associated with increasing structural alterations in DIP and PIP joints and can be seen as markers of advanced joint damage. Detecting dvOPs can facilitate the diagnosis process and improve damage estimation in HOA.
Panhypopituitarism as the first sign of paraneoplastic limbic encephalitis in a patient with cured testicular cancer: a case report
Authors: Lei Yvonne , Glaeser Alexandra Milin
Published: September 2022

Background

Paraneoplastic limbic encephalitis is a rare neurologic syndrome that affects patients with cancer and commonly presents with symptoms of personality changes, visual disturbances, seizures, vertigo, and memory loss. It has an immune-mediated pathophysiology and is associated with antibodies directed against both the tumor and limbic structures in the nervous system. Here, we report a case of paraneoplastic limbic encephalitis with an unusual presentation with initial symptoms of panhypopituitarism.

Case presentation

A 28-year-old Caucasian man with history of testicular cancer in remission for almost 2 years was admitted to our hospital for altered mental status, syncope, vertical gaze palsy, ataxia, and tremor. Three months prior to admission, he began to have initial symptoms of fatigue, weight gain, and hypogonadism. A few weeks before admission, he also developed worsening neurological symptoms that led him to present to the hospital. While hospitalized, he had an episode of syncope. Evaluation of his syncope revealed that he was hypovolemic due to polyuria, concerning for diabetes insipidus. While the patient did not meet criteria for diabetes insipidus, further endocrine laboratory testing to evaluate his central hormonal axes revealed panhypopituitarism. He also underwent a neurologic work-up with brain magnetic resonance imaging and lumbar puncture, with results consistent with encephalitis. He received high-dose steroids, plasmapheresis, and intravenous immunoglobulin, which did not significantly improve his physical examination or mental status. Extensive testing did not show any recurrence of his testicular cancer. Paraneoplastic antibodies were also ordered, with anti-Ma2 antibodies eventually returning positive, consistent with anti-Ma2 paraneoplastic limbic encephalitis.

Conclusion

Paraneoplastic limbic encephalitis is often a difficult diagnosis due to its variable presentation and timeline of presentation, leading to delays in both diagnosis and treatment. While paraneoplastic limbic encephalitis usually presents with neurological symptoms, it may also present with panhypopituitarism. A high index of suspicion is warranted for paraneoplastic syndromes in patients with history of malignancy, even if the malignancy is in remission.
Acute pancreatitis in pregnancy following COVID-19 vaccine: a case report
Authors: Dey Rajib Kumar , Ilango Hemamala , Bhatta Subash , Shaheed Ahmed , Dole Shanaz , Zooshan Ahmed , Faisham Mohamed , Murad Moosa
Published: September 2022

Background

Since the approval of the Pfizer–BioNTech (BNT162b2) mRNA vaccine for COVID-19 infection, a few adverse effects have been reported. Acute pancreatitis has been reported in a few patients. However, there is currently no research showing a direct relationship between the vaccine and acute pancreatitis. Here, we report a case of acute pancreatitis following Pfizer vaccination in a young healthy pregnant woman without any known risk factors. To our knowledge, this is the first case report of possible vaccine-induced pancreatitis in a pregnant woman.

Case presentation

The patient, a 24-year-old South-Asian female, at 31 weeks of gestation, presented with severe epigastric pain radiating to the back and worsening on lying supine, associated with nausea and vomiting. She was diagnosed with acute pancreatitis with a serum lipase level of 4376 U/L and an ultrasound showing features of pancreatitis. The patient received her first dose of the Pfizer vaccine 1 week prior to these symptoms. Detailed evaluation did not show any etiological cause of pancreatitis. The patient had a spontaneous vaginal delivery and the baby was shifted to the neonatal intensive care unit in a stable condition. A computed tomography scan postpartum (day 2) demonstrated acute interstitial edematous pancreatitis. The patient was managed conservatively in the intensive care unit and discharged home in a stable condition.

Conclusion

This report highlights the importance of a detailed history and evaluation, and the close monitoring of any patient presenting with abdominal pain after vaccination. Acute pancreatitis can be fatal if not picked up early.
Associations of habitual glucosamine supplementation with incident gout: a large population based cohort study
Authors: Liu Mengyi , Ye Ziliang , Zhang Yanjun , Yang Sisi , Wu Qimeng , Zhou Chun , He Panpan , Zhang Yuanyuan , Gan Xiaoqin , Qin Xianhui
Published: September 2022

Objectives

The association between habitual glucosamine use and incident gout has not been examined in previous studies. We aimed to evaluate the association of habitual use of glucosamine with the risk of gout in general population.

Methods

A total of 436,594 participants (55.4% female) without prior gout at baseline who completed a questionnaire on supplementation use, which included glucosamine, in the UK Biobank were enrolled. Incident gout was recorded from self-report, death register, primary care, and hospital admission data.

Results

At baseline, 53,433 (22.1%) females and 30,685 (15.8%) males reported habitual glucosamine use. During a median follow-up period of 12.1 years, 1718 (0.7%) females and 5685 (2.9%) males developed gout. After multivariable adjustment for major risk factors, glucosamine use was associated with a significantly lower risk of incident gout in females (hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.71–0.92), but not in males (HR, 1.05, 95% CI, 0.97–1.13), compared with non-use (P-interaction < 0.001). Among females, the inverse association between glucosamine use and gout was stronger in participants with diuretics use (HR, 0.64, 95% CI, 0.50–0.81) than those without diuretics use (HR, 0.89, 95% CI, 0.77–1.03) (P-interaction = 0.015). Moreover, gout genetic risk scores did not significantly modify the association between glucosamine use and the risk of incident gout in males (P-interaction = 0.548) or females (P-interaction = 0.183).

Conclusions

Habitual glucosamine use to relieve osteoarthritis pain was related to lower risk of gout in females, but not in males.
An inactivated novel chimeric FAdV-4 containing fiber of FAdV-8b provides full protection against hepatitis-hydropericardium syndrome and inclusion body hepatitis
Authors: Wang Baiyu , Song Mingzhen , Song Congcong , Zhao Shiyi , Yang Panpan , Qiao Qilong , Cong Yanfang , Wang Yanling , Wang Zeng , Zhao Jun
Published: September 2022

Fowl adenovirus serotype 4 (FAdV-4) and FAdV-8b are causative agents of hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH), respectively. HHS and IBH co-infections were often reported in clinical, yet there are no commercially available bivalent vaccines for prevention and control of both FAdV-4 and -8b. In the present study, a chimeric FAdV-4 was firstly generated by substituting fiber-1 of FAdV-4 with fiber of FAdV-8b. The chimeric virus, rFAdV-4-fiber/8b, exhibited similar replication ability in vitro and pathogenicity in vivo to the parental wild type FAdV-4. A single dosage of vaccination with the inactivated rFAdV-4-fiber/8b induced high antibody titers against fiber-2 of FAdV-4 and fiber of FAdV-8b and provided full protection against FAdV-4 and -8b challenge. These results demonstrated that fiber of FAdV-8b could replace the role of fiber-1 of FAdV-4 in the process of viral infection, and rFAdV-4-fiber/8b could be used to make a potential bivalent vaccine for the control and prevention of HHS and IBH.