bluuebunny/crossref_metadata_2025 huggingface dataset:
The timing of oesophageal dilatations in anastomotic stenosis after one-stage anastomosis for congenital oesophageal atresia
Authors: Gao Xue-Jie , Huang Jin-Xi , Chen Qiang , Hong Song-Ming , Hong Jun-Jie , Ye Hong
Published: October 2021

Background

In infants with congenital oesophageal atresia, anastomotic stenosis easily occurs after one-stage oesophageal anastomosis, leading to dysphagia. In severe cases, oesophageal dilatation is required. In this paper, the timing of oesophageal dilatation in infants with anastomotic stenosis was investigated through retrospective data analysis.

Methods

The clinical data of 107 infants with oesophageal atresia who underwent one-stage anastomosis in our hospital from January 2015 to December 2018 were retrospectively analysed. Data such as the timing and frequency of oesophageal dilatation under gastroscopy after surgery were collected to analyse the timing of oesophageal dilatation in infants with different risk factors.

Results

For infants with refractory stenosis, the average number of dilatations in the early dilatation group (the first dilatation was performed within 6 months after the surgery) was 5.75 ± 0.5, which was higher than the average of 7.40 ± 1.35 times in the normal dilatation group (the first dilatation was performed 6 months after the surgery), P = 0.038. For the infants with anastomotic fistula and anastomotic stenosis, the number of oesophageal dilatations in the early dilatation group was 2.58 ± 2.02 times, which was less than the 6.38 ± 2.06 times in the normal dilatation group, P = 0.001. For infants with non-anastomotic fistula stenosis, early oesophageal dilatation could not reduce the total number of oesophageal dilatations.

Conclusion

Starting to perform oesophageal dilatation within 6 months after one-stage anastomosis for congenital oesophageal atresia can reduce the required number of dilatations in infants with postoperative anastomotic fistula and refractory anastomotic stenosis.
Transthoracic minimally invasive closure for the treatment of arch penetrating aortic ulcer: a case report
Authors: Wang Shixiong , Liu Debin , Li Yongnan , Gao Bingren
Published: October 2021

Penetrating aortic ulcer (PAU) is one of the three subtypes of acute aortic syndrome. PAUs occur at any point throughout the aorta, most commonly in the descending thoracic aorta and less frequently in the aortic arch. Open surgical repair and total/hybrid endovascular repair are currently available to treat aortic arch PAUs. Herein, we present a patient with aortic arch PAU who underwent transthoracic minimally invasive closure, which is a novel method for the treatment of PAU. We describe a 52-year old Asian man who presented with sudden chest and back pain for 8 h. Computed tomography angiography showed that the PAU occurred in the aortic arch and had a diameter of 16 mm and a depth of 6 mm. The opening was successfully closed via transthoracic minimally invasive closure with an atrial septal defect occluder.
Antibiotic-loaded bone cement combined with vacuum sealing drainage to treat deep sternal wound infection following cardiac surgery: the first case report
Authors: Jiang Xia , Bu Fanyu , Xu Yong , Jing Zhaohui , Jiao Guoqing , Li Mingqiu , Rong Xiaosong
Published: October 2021

Background

Deep sternal wound infection (DSWI) is a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. Here we first present a case of a patient successfully treated for antibiotic-loaded bone cement (ALBC) combined with vacuum sealing drainage (VSD) of DSWI.

Case presentation

This case report presented a patient who underwent open heart surgery, and suffered postoperatively from a DSWI associated with enterococcus cloacae. Focus debridement combined with ALBC filling and VSD was conducted in stage I. Appropriate antibiotics were started according to sensitivity to be continued for 2 weeks until the inflammatory markers decreased to normal. One month after the surgery, patient’s wound was almost healed and was discharged from hospital with a drainage tube. Two months after the stage I surgery procedure, the major step was removing the previous ALBC, and extensive debridement in stage II. The patient fully recovered without further surgical treatment.

Conclusions

The results of this case suggest that ALBC combined with VSD may be a viable and safe option for deep sternal wound reconstruction.
Short-term and intermediate outcomes of cardiogenic shock and cardiac arrest patients supported by venoarterial extracorporeal membrane oxygenation
Authors: Vakil Deep , Soto Cassandra , D’Costa Zoee , Volk Lindsay , Kandasamy Sivaveera , Iyer Deepa , Ikegami Hirohisa , Russo Mark J. , Lee Leonard Y. , Lemaire Anthony
Published: October 2021

Background

Cardiogenic shock and cardiac arrest are life-threatening emergencies with high mortality rates. Veno-arterial extracorporeal membrane oxygenation (VA ECMO) and extracorporeal cardiopulmonary resuscitation (e-CPR) provide viable options for life sustaining measures when medical therapy fails. The purpose of this study is to determine the utilization and outcomes of VA ECMO and eCPR in patients that require emergent cardiac support at a single academic center.

Methods

A retrospective chart review of prospectively collected data was performed at an academic institution from January 1st, 2018 to June 30th, 2020. All consecutive patients who required VA ECMO were evaluated based on whether they underwent traditional VA ECMO or eCPR. The study variables include demographic data, duration on ECMO, length of stay, complications, and survival to discharge.

Results

A total of 90 patients were placed on VA ECMO for cardiac support with 44.4% (40) of these patients undergoing eCPR secondary to cardiac arrest and emergent placement on ECMO. A majority of the patients were male (n = 64, 71.1%) and the mean age was 58.8 ± 15.8 years. 44.4% of patients were transferred from outside hospitals for a higher level of care and 37.8% of patients required another primary therapy such as an Impella or IABP. The most common complication experienced by patients was bleeding (n = 41, 45.6%), which occurred less often in eCPR (n = 29, 58% vs. n = 12, 30%). Other complications included infections (n = 11, 12.2%), limb ischemia (n = 13, 14.4%), acute kidney injury (n = 17, 18.9%), and cerebral vascular accident (n = 4, 4.4%). The length of stay was longer for patients on VA ECMO (32.1 ± 40.7 days vs. 17.7 ± 18.2 days). Mean time on ECMO was 8.1 ± 8.3 days. Survival to discharge was higher in VA ECMO patients (n = 23, 46% vs. n = 8, 20%).

Conclusion

VA ECMO provided an effective rescue therapy in patients in acute cardiogenic shock with a survival greater than the expected ELSO guidelines of 40%. While the survival of eCPR was lower than expected, this may reflect the severity of patient’s condition and emphasizes the importance of careful patient selection and planning.
Risk factors analysis of hyperbilirubinemia after off-pump coronary artery bypass grafting: a retrospective observational study
Authors: Gao Yingdi , Li Dongjie , Dong Honghong , Guo Yulin , Peng Yuanshu , Liu Yan , Su Pixiong
Published: October 2021

Background

Hyperbilirubinemia is a common complication after off-pump coronary artery bypass grafting (OPCAB), but the incidence and the risk factors are unclear. This study aimed to analyze the incidence and risk factors of postoperative hyperbilirubinemia in patients undergoing OPCAB.

Methods

From December 2016 to March 2019, a total of 416 consecutive patients undergoing OPCAB were enrolled in this single-center retrospective study. Patients were divided into the normal serum total bilirubin group and the hyperbilirubinemia group based on the serum total bilirubin levels. Perioperative variables between the two groups were compared by univariate logistic regression analysis. Then, multivariate binary logistic regression analysis was used to analyze the independent risk factors of developing hyperbilirubinemia in patients underwent OPCAB. P < 0.05 was considered as statistically significant.

Results

Thirty two of 416 (7.7%) patients developed postoperative hyperbilirubinemia. Univariate regression analysis showed significant differences in gender (73.96% vs. 93.75%, P = 0.012), preoperative total bilirubin levels (11.92 ± 4.52 vs. 18.28 ± 7.57, P < 0.001), perioperative IABP implantation (22.66% vs. 43.75%, P = 0.008), perioperative blood transfusion (37.50% vs. 56.25%, P = 0.037) between the two groups. Multivariate logistic regression analysis revealed that elevated preoperative serum total bilirubin levels (OR = 1.225, 95% CI 1.145–1.310, P < 0.001), perioperative blood transfusion (OR = 4.488, 95% CI 1.876–10.737, P = 0.001) and perioperative IABP implantation (OR = 4.016, 95% CI 1.709–9.439, P = 0.001) were independent risk factors for hyperbilirubinemia after OPCAB.

Conclusions

Hyperbilirubinemia is also a common complication after OPCAB. Elevated preoperative serum total bilirubin levels, perioperative blood transfusion, and perioperative IABP implantation were independent risk factors for patients developing hyperbilirubinemia after OPCAB. Further studies need to be conducted to confirm the risk factors of hyperbilirubinemia after OPCAB procedure.
One hundred twelve cases of 46, XY DSD patients after initial gender assignment: a short-term survey of gender role and gender dysphoria
Authors: Hou Liping , Zhao Ming , Fan Lijun , Cao Bingyan , Chen Jiajia , Cui Yonghua , Polak Michel , Gong Chunxiu
Published: October 2021

Background

46, XY disorders of sex development (46, XY DSD) are congenital disorders with 46, XY chromosomal karyotype but inconsistent gonadal/phenotypic sex. One of the biggest concerns for parents and clinicians is the gender assignment. However, there is no standard uniform of care nor consensus at present. We sought to evaluate the current treatment's rationality and provide a reference basis for the gender reassignment in 46, XY DSD patients with a specific diagnosis.

Methods

We conducted a cross-sectional survey of gender role with the Pre-school Activities Inventory (PSAI), the Children's Sex Role Inventory (CSRI) in 46, XY DSD patients and set up control groups comparison. Psychiatrist assessed gender dysphoria in patients ≥ 8-year-old with the criteria of diagnostic and statistical manual of mental disorders, 5th edition (DSM-5).

Results

A total of 112 responders of 136 patients participated in this study (82.4%, aged 2–17.8 years, median age: 4-year-old). The follow-up period was from 6 months to 10 years (median: 2 years). Twenty-five females were reassigned to the male gender after a specific diagnosis (16/25 (64%) in 5 alfa-reductase-2 deficiency (5α-RD2), 5/25 (20%) in partial androgen insensitivity syndrome (PAIS), 4/25 (16%) in NR5A1gene mutation). Male gender assignment increased from 55.3 (n = 62) to 77.7% (n = 87). The median PSAI score was similar to the control males in 5α-RD2, PAIS, and NR5A1 gene mutation groups (p > 0.05); while identical to the control females in complete androgen insensitivity syndrome (CAIS) and CYP17A1 gene mutation groups (p > 0.05). PSAI score of children raised as male was higher than those of CAIS and CYP17A1 groups raised as female (p < 0.05). CSRI scale showed no statistical differences in the consistency of gender roles and reassigned gender between 46, XY DSD patients and control groups (p > 0.05). None of the patients over 8-year-old (n = 44) had gender dysphoria.

Conclusion

The reassigned gender in 46, XY DSD patients is consistent with their gender role during early childhood. None of them had gender dysphoria. The molecular diagnosis, gonadal function, and the gender reassignment are congruent within our Chinese cohort. Long-term follow-up and more evaluation are still required.
Prospective study of epigenetic alterations responsible for isolated hemihyperplasia/hemihypoplasia and their association with leg length discrepancy
Authors: Shin Chang Ho , Lim Chaemoon , Kim Hwa Young , Yoo Won Joon , Cho Tae-Joon , Choi In Ho , Ko Jung Min
Published: October 2021

Background

Hemihyperplasia and hemihypoplasia result in leg length discrepancy (LLD) by causing skeletal asymmetry. Beckwith–Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS) are opposite growth-affecting disorders caused by opposite epigenetic alterations at the same chromosomal locus, 11p15, to induce hemihyperplasia and hemihypoplasia, respectively. Because of their somatic mosaicism, BWS and SRS show a wide spectrum of clinical phenotypes. We evaluated the underlying epigenetic alterations and potential epigenotype-phenotype correlations, focusing on LLD, in a group of individuals with isolated hemihyperplasia/hemihypoplasia.

Results

We prospectively collected paired blood-tissue samples from 30 patients with isolated hemihyperplasia/hemihypoplasia who underwent surgery for LLD. Methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA) and bisulfite pyrosequencing for differentially methylated regions 1 and 2 (DMR1 and DMR2) on chromosome 11p15 were performed using the patient samples. Samples from patients showing no abnormalities in MS-MLPA or bisulfite pyrosequencing were analyzed by single nucleotide polymorphism (SNP) microarray andCDKN1CSanger sequencing. We introduced a metric named as the methylation difference, defined as the difference in DNA methylation levels between DMR1 and DMR2. The correlation between the methylation difference and the predicted LLD at skeletal maturity, calculated using a multiplier method, was evaluated. Predicted LLD was standardized for stature. Ten patients (33%) showed epigenetic alterations in MS-MLPA and bisulfite pyrosequencing. Of these, six and four patients had epigenetic alterations related to BWS and SRS, respectively. The clinical diagnosis of hemihyperplasia/hemihypoplasia was not compatible with the epigenetic alterations in four of these ten patients. No patients showed abnormalities in SNP array or theirCDKN1Csequences. The standardized predicted LLD was moderately correlated with the methylation difference using fat tissue (r = 0.53;p = 0.002) and skin tissue (r = 0.50;p = 0.005) in all patients.

Conclusions

Isolated hemihyperplasia and hemihypoplasia can occur as a spectrum of BWS and SRS. Although the accurate differentiation between isolated hemihyperplasia and isolated hemihypoplasia is important in tumor surveillance planning, it is often difficult to clinically differentiate these two diseases without epigenetic tests. Epigenetic tests may play a role in the prediction of LLD, which would aid in treatment planning.
The diagnostic odyssey of autism: a cross-sectional study of 3 age cohorts of children from the 2016–2018 National Survey of Children’s Health
Authors: Hanley Allison , Nguyen Quynh C. , Badawi Deborah Golant , Chen Jie , Ma Tianzhou , Slopen Natalie
Published: October 2021

Background

Autism prevalence has increased rapidly in recent years, however, nationally representative estimates on the ages of first identification and intervention are out of date. Objectives: (1) To estimate the ages at which children with autism receive their first diagnosis, intervention plan, and developmental services; and (2) To evaluate differences in ages at events by birth cohort and sociodemographic characteristics.

Methods

Using cross-sectional data from the 2016–2018 National Survey of Children’s Health (NSCH), we examined associations via linear regression among a sample of 2303 children aged 2–17 years old, who had ever been diagnosed with autism and either (1) ever had a plan for special education or early intervention, or (2) ever received special services to meet developmental needs. Exposures included age cohort, child, household and healthcare provider characteristics.

Results

Most children in the study sample (n = 2303) were over age 6 years, male, of non-Hispanic white race/ethnicity and had mild/moderate autism. Mean ages (years) at first diagnosis was 4.56 (SE = 0.13); first plan was 4.43 (SE = 0.11); and first services was 4.10 (SE = 0.11). After adjustment for exposures and survey year, the middle childhood cohort was 18 months older at first intervention (β = 1.49, 95% CI, 1.18–1.81), and adolescents were 38 months older at first diagnosis (β = 3.16, 95% CI, 2.72–3.60) compared to those in early childhood. Younger ages at events were observed among: Hispanic/Latinx as compared to white children, those with moderate or severe symptoms as compared to mild symptoms, and children who received their diagnosis from a specialist as compared to psychologists or psychiatrists.

Conclusions

Children with autism receive their first diagnosis, intervention plans and developmental services at younger ages than they had in the past. Future research is needed to identify the mechanisms for these improvements in early identification and intervention to accelerate additional progress.
Targeting MUS81 promotes the anticancer effect of WEE1 inhibitor and immune checkpoint blocking combination therapy via activating cGAS/STING signaling in gastric cancer cells
Authors: Li Chengguo , Shen Qian , Zhang Peng , Wang Tao , Liu Weizhen , Li Ruidong , Ma Xianxiong , Zeng Xiangyu , Yin Yuping , Tao Kaixiong
Published: October 2021

Background

Identification of genomic biomarkers to predict the anticancer effects of indicated drugs is considered a promising strategy for the development of precision medicine. DNA endonuclease MUS81 plays a pivotal role in various biological processes during malignant diseases, mainly in DNA damage repair and replication fork stability. Our previous study reported that MUS81 was highly expressed and linked to tumor metastasis in gastric cancer; however, its therapeutic value has not been fully elucidated.

Methods

Bioinformatics analysis was used to define MUS81-related differential genes, which were further validated in clinical tissue samples. Gain or loss of function MUS81 cell models were constructed to elucidate the effect and mechanism of MUS81 on WEE1 expression. Moreover, the antitumor effect of targeting MUS81 combined with WEE1 inhibitors was verified using in vivo and in vitro assays. Thereafter, the cGAS/STING pathway was evaluated, and the therapeutic value of MUS81 for immunotherapy of gastric cancer was determined.

Results

In this study, MUS81 negatively correlated with the expression of cell cycle checkpoint kinase WEE1. Furthermore, we identified that MUS81 regulated the ubiquitination of WEE1 via E-3 ligase β-TRCP in an enzymatic manner. In addition, MUS81 inhibition could sensitize the anticancer effect of the WEE1 inhibitor MK1775 in gastric cancer in vitro and in vivo. Interestingly, when MUS81 was targeted, it increased the accumulation of cytosolic DNA induced by MK1775 treatment and activated the DNA sensor STING-mediated innate immunity in the gastric cancer cells. Thus, the WEE1 inhibitor MK1775 specifically enhanced the anticancer effect of immune checkpoint blockade therapy in MUS81 deficient gastric cancer cells.

Conclusions

Our data provide rational evidence that targeting MUS81 could elevate the expression of WEE1 by regulating its ubiquitination and could activate the innate immune response, thereby enhancing the anticancer efficacy of WEE1 inhibitor and immune checkpoint blockade combination therapy in gastric cancer cells.
Association of exposure to hydrocarbon air pollution with the incidence of atopic dermatitis in children
Authors: Wang Chieh , Wei Chang-Ching , Wan Lei , Lin Cheng-Li , Tsai Jeng-Dau
Published: October 2021

Background

There is growing evidence suggesting that air pollution may act as an important environmental risk factor in the development and aggravation of childhood atopic dermatitis (AD).

Methods

We collected data from the Taiwan National Health Insurance (NHI) research database and linked the data to the Taiwan Air Quality-Monitoring Database. From January 1, 2000 to December 31, 2012; children aged below 18 years were selected from the database and followed longitudinally until the diagnosis of AD, withdrawal from the NHI, or December 31, 2012. Children with missing data or those diagnosed with AD before enrolment in this study were excluded. We measured the incidence rate and hazard ratios (HRs) for AD and stratified them by quartiles (Q1–Q4) of air pollutant concentration. Multivariable Cox proportional hazards models were also applied by adjusting for age, sex, monthly income, and level of urbanization.

Results

When compared with the concentrations of pollutants in the Q1 quartile, the adjusted HR for AD increased with an increase in the exposure concentrations of total hydrocarbons (THCs), non-methane hydrocarbons (NMHCs), and methane (CH4) from 1.65 (95% confidence interval [CI]: 1.47–1.84) to 10.6 (95% CI: 5.85–7.07), from 1.14 (95% CI: 1.06–1.24) to 2.47 (95% CI: 2.29–2.66), and from 1.70 (95% CI: 1.52–1.89) to 11.9 (95% CI: 10.8–13.1), respectively. Patients exposed to higher levels of THCs, NMHCs, and CH4 exhibited greater incidence rates of childhood AD.

Conclusions

The present study demonstrated that exposure to higher concentrations of THCs, NMHCs, and CH4 were associated with an increased risk of childhood AD.
Is there an optimal place to hold the endotracheal tube during direct laryngoscopy for patients undergoing surgery under general anesthesia? Protocol for a randomized controlled trial
Authors: Sahoo Manisha , Tripathy Swagata , Mishra Nitasha
Published: October 2021

Background

Endotracheal intubation by direct laryngoscopy is a widely performed lifesaving technique. Although there are guidelines for optimal size and depth of insertion of an endotracheal tube (ETT) for successful intubation, there is no consensus on the point at which it should be held along its length. This will arguably affect the time, ease, and success of the technique due to a difference in visualization and torque applied to the ETT after glottic visualization. We aim to compare the effect of 2 different sites of holding the ETT on time to intubation (TTI), intubation difficulty scale (IDS), and complications.

Methods

ASA 1–2 patients (>18 years) posted for surgery under general anesthesia, undergoing supervised intubation by anesthesia trainees (experience < 18 months), will be included. Patients with an anticipated difficult airway or unanticipated difficulty—CL grade 3 or 4 requiring the use of airway adjuncts—will be excluded. Patients will be randomized by a computer-generated number list, and allocation concealed with opaque sealed envelopes. The two sites for holding the ETT will be group 1 at 19 cm and group 2 at 24 cm. ETT marked at the selected site will be handed by the technician once the optimum position of the table, patient, and laryngoscopic view is confirmed by the intubator. The entire procedure will be video recorded. Two blinded assessors will independently review the videos to document the time to intubation and intubation difficulty score. A postoperative sore throat will be recorded.

Sample size

To detect a 20% difference in time to intubation between groups with a significance level of 5% and power of 85%, we will need a total of 298 patients. Accounting for data loss, we plan to recruit 180 patients in each group.

Discussion

This will be the first study to assess whether the site of holding the tube has any impact on the ease and time taken for intubation. The findings of this study will provide scientific evidence for suggesting an appropriate place for holding the ETT during direct laryngoscopy procedures.

Trial registration

Clinical Trials Registry India CTRI/2019/09/021201
Photodynamic therapy for synovial hyperplasia in patients with refractory rheumatoid arthritis: a study protocol for a randomized, double-blind, blank-controlled prospective trial
Authors: Zhao Xiaofeng , Zuo Fangfang , Chen Ensheng , Bi Yanan , Cao Yanyan , Yuan Yi , Li Kaiqin , Xuan Yanan , Li Libo , Wan Lijuan , Zhang Xiangqun , Yan Feifei , Zhou Jiyuan , Yin Kun , Xiao Changhong
Published: October 2021

Background

Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is one of the main pathogeneses of refractory rheumatoid arthritis (RRA). Photodynamic therapy (PDT) causes less trauma than steroid injections or arthroscopic synovectomy while providing stronger targeting and more durable curative effects. The aim of this trial was to evaluate the short-, medium-, and long-term clinical efficacy of PDT when applied as a treatment for RRA synovial hyperplasia and synovitis.

Methods and analysis

This protocol is for a single-center, randomized, double-blind, blank-controlled prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the “PDT once” group, and the “PDT twice” group, with 42 participants per group. The trial will be conducted by the Rheumatology and Immunology Department of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. The Ultrasound Compound Score of Synovitis (UCSS) has been selected as the primary outcome measure. The secondary outcome measures include knee joint clinical assessments, ratio of relapse, duration of remission, Disease Activity Score in 28 joints (DAS28), inflammation indexes, serum concentrations of specific antibodies, and changes in articular structures as detected by X-ray scans in the 48th week. The improvement ratios of the UCSS at the 8th, 24th, and 48th weeks (compared with baseline) reflect short-, medium-, and long-term time frames, respectively.

Ethics and dissemination

The protocol was approved by the Medical Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. granted by the ethics committee: NFZXYEC-2017-005) and then entered in the Chinese Clinical Trials Registry under registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures are in accordance with Chinese laws and regulations and with the Declaration of Helsinki by the World Medical Association (WMA). Any modifications of this protocol during execution will need additional approval from the Ethics Committee of our hospital.

Trial registration number

ChiCTR1800014918.
Efficiency of donepezil in elderly patients undergoing orthopaedic surgery due to underlying post-operative cognitive dysfunction: study protocol for a multicentre randomised controlled trial
Authors: Zhu Huichen , Cong Lu , Chen Yi , Chen Shaoyi , Chen Lingke , Huang Zhenling , Zhou Jie , Xiao Jie , Huang Yonglei , Su Diansan
Published: October 2021

Background

Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer’s disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery.

Methods

A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation.

Discussion

This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs.

Trial registration

ClinicalTrials.govNCT04423276. Registered on 14 June 2020
The potential risk of enzootic Trypanosoma cruzi transmission inside four training and re-training military battalions (BITER) in Colombia
Authors: Cantillo-Barraza Omar , Torres Jeffer , Hernández Carolina , Romero Yanira , Zuluaga Sara , Correa-Cárdenas Camilo A. , Herrera Giovanny , Rodríguez Omaira , Alvarado María Teresa , Ramírez Juan David , Méndez Claudia
Published: October 2021

Background

Colombia’s National Army is one of the largest military institutions in the country based on the number of serving members and its presence throughout the country. There have been reports of cases of acute or chronic cases of Chagas disease among active military personnel. These may be the result of military-associated activities performed in jungles and other endemic areas or the consequence of exposure to Trypanosoma cruzi inside military establishments/facilities located in endemic areas. The aim of the present study was to describe the circulation of T. cruzi inside facilities housing four training and re-training battalions [Battalions of Instruction, Training en Re-training (BITERs)] located in municipalities with historical reports of triatomine bugs and Chagas disease cases. An entomological and faunal survey of domestic and sylvatic environments was conducted inside each of these military facilities.

Methods

Infection in working and stray dogs present in each BITER location was determined using serological and molecular tools, and T. cruzi in mammal and triatomine bug samples was determined by PCR assay. The PCR products of the vertebrate 12S rRNA gene were also obtained and subjected to Sanger sequencing to identify blood-feeding sources. Finally, we performed a geospatial analysis to evaluate the coexistence of infected triatomines and mammals with the military personal inside of each BITER installation.

Results

In total, 86 specimens were collected: 82 Rhodnius pallescens, two Rhodnius prolixus, one Triatoma dimidiata and one Triatoma maculata. The overall T. cruzi infection rate for R. pallescens and R. prolixus was 56.1 and 100% respectively, while T. dimidiata and T. maculata were not infected. Eight feeding sources were found for the infected triatomines, with opossum and humans being the most frequent sources of feeding (85.7%). Infection was most common in the common opossum Didelphis marsupialis, with infection levels of 77.7%. Sylvatic TcI was the most frequent genotype, found in 80% of triatomines and 75% of D. marsupialis. Of the samples collected from dogs (n = 52), five (9.6%; 95% confidence interval: 3.20–21.03) were seropositive based on two independent tests. Four of these dogs were creole and one was a working dog. The spatial analysis revealed a sympatry between infected vectors and mammals with the military population.

Conclusions

We have shown a potential risk of spillover of sylvatic T. cruzi transmission to humans by oral and vectorial transmission in two BITER installations in Colombia. The results indicate that installations where 100,000 active military personnel carry out training activities should be prioritized for epidemiological surveillance of Chagas disease.

Graphical abstract
Effect of personal activity intelligence (PAI) monitoring in the maintenance phase of cardiac rehabilitation: a mixed methods evaluation
Authors: Hannan Amanda L. , Hing Wayne , Coombes Jeff S. , Gough Suzanne , Climstein Mike , Adsett Geoff , Jayasinghe Rohan , Furness James
Published: October 2021

Background

Personal activity intelligence (PAI) is a single physical activity metric based upon heart rate responses to physical activity. Maintaining 100 PAI/week is associated with a 25% risk reduction in cardiovascular disease mortality and 50 PAI/week provides 60% of the benefits. The effect of utilising this metric within a cardiac population has not been previously investigated. The aim of this study was to determine the effect of PAI monitoring on the amount and/or intensity of physical activity for people in the maintenance phase of cardiac rehabilitation and to explore participants’ perceptions of this approach.

Methods

A concurrent mixed methods approach was undertaken. Participants in the maintenance phase of cardiac rehabilitation monitored PAI for six weeks via a wearable physical activity monitoring device (WPAM). In the first three weeks participants were blinded to their PAI score. A quality-of-life questionnaire (EQ-5D-5L) was completed, and semi-structured interviews conducted to investigate attitudes to PAI monitoring. Daily PAI data was collected throughout the 6-week period.

Results

Twenty participants completed the trial. PAI earned/day was increased after participants could view their data (mean difference: 2.1 PAI/day (95% CI 0.3, 4.0), p = 0.027). The median change in percentage of days participants achieved a Total PAI score of 25 (p = 0.023) and 50 (p = 0.015) were also increased. The mean change in total scores for the EQ-5D-5L and EQVAS were improved after 6 weeks (0.6 ± 1.05; 95% CI (0.11–1.09); p = 0.019); (5.8/100; 95% CI (2.4–9.2); p = 0.002 respectively). Thematic framework analysis identified three global themes (perceptions on the WPAM, PAI and factors affecting exercise). Most participants stated motivation to exercise increased after they could view their PAI data. Many of the participants believed they would continue to use PAI long-term. Others were undecided; the latter primarily due to technical issues and/or preferring devices with greater functionality and attractiveness. All participants would recommend PAI.

Conclusion

This exploratory study showed monitoring PAI via a WPAM increased the amount and/or intensity of physical activity within the cardiac population. Participants found PAI interesting, beneficial, and motivating. If technical issues, aesthetics, and functionality of the WPAM were improved, participants may continue to use the approach long-term. PAI may be a viable strategy to assist people with cardiac disease maintain physical activity adherence.
De novo assembly and annotation of the mangrove cricket genome
Authors: Satoh Aya , Takasu Miwako , Yano Kentaro , Terai Yohey
Published: October 2021

Objectives

The mangrove cricket, Apteronemobius asahinai, shows endogenous activity rhythms that synchronize with the tidal cycle (i.e., a free-running rhythm with a period of ~ 12.4 h [the circatidal rhythm]). Little is known about the molecular mechanisms underlying the circatidal rhythm. We present the draft genome of the mangrove cricket to facilitate future molecular studies of the molecular mechanisms behind this rhythm.

Data description

The draft genome contains 151,060 scaffolds with a total length of 1.68 Gb (N50: 27 kb) and 92% BUSCO completeness. We obtained 28,831 predicted genes, of which 19,896 (69%) were successfully annotated using at least one of two databases (UniProtKB/SwissProt database and Pfam database).
Timing and duration of lipofection-mediated CRISPR/Cas9 delivery into porcine zygotes affect gene-editing events
Authors: Lin Qingyi , Le Quynh Anh , Takebayashi Koki , Thongkittidilok Chommanart , Wittayarat Manita , Hirata Maki , Tanihara Fuminori , Otoi Takeshige
Published: October 2021

Objective

Lipofection-mediated introduction of the CRISPR/Cas9 system in porcine zygotes provides a simple method for gene editing, without requiring micromanipulation. However, the gene editing efficiency is inadequate. The aim of this study was to improve the lipofection-mediated gene editing efficiency by optimizing the timing and duration of lipofection.

Results

Zona pellucida (ZP)-free zygotes collected at 5, 10, and 15 h from the start of in vitro fertilization (IVF) were incubated with lipofection reagent, guide RNA (gRNA) targeting GGTA1, and Cas9 for 5 h. Lipofection of zygotes collected at 10 and 15 h from the start of IVF yielded mutant blastocysts. Next, ZP-free zygotes collected at 10 h from the start of IVF were incubated with lipofection reagent, gRNA, and Cas9 for 2.5, 5, 10, or 20 h. The blastocyst formation rate of zygotes treated for 20 h was significantly lower (p < 0.05) than those of the other groups, and no mutant blastocysts were obtained. Moreover, the mutation rates of the resulting blastocysts decreased as the incubation time increased. In conclusion, a lipofection-mediated gene editing system using the CRISPR/Cas9 system in ZP-zygotes is feasible; however, further improvements in the gene editing efficiency are required.
Activation of PLCβ1 enhances endocannabinoid mobilization to restore hippocampal spike-timing-dependent potentiation and contextual fear memory impaired by Alzheimer’s amyloidosis
Authors: Lee Jaedong , Kwag Jeehyun
Published: October 2021

Background

Accumulation of amyloid beta oligomers (AβO) in Alzheimer’s disease (AD) impairs hippocampal long-term potentiation (LTP), leading to memory deficits. Thus, identifying the molecular targets of AβO involved in LTP inhibition is critical for developing therapeutics for AD. Endocannabinoid (eCB) synthesis and release, a process collectively called eCB mobilization by hippocampal CA1 pyramidal cells, is known to facilitate LTP induction. eCB can be mobilized either by postsynaptic depolarization in an intracellular Ca2+ concentration ([Ca2+]i)-dependent pathway or by group 1 metabotropic glutamate receptor (mGluR) activation in a phospholipase Cβ (PLCβ)-dependent pathway. Moreover, group 1 mGluR activation during postsynaptic depolarization, which is likely to occur in vivo during memory processing, can cause synergistic enhancement of eCB (S-eCB) mobilization in a PLCβ-dependent pathway. Although AβO has been shown to disrupt [Ca2+]i-dependent eCB mobilization, the effect of AβO on PLCβ-dependent S-eCB mobilization and its association with LTP and hippocampus-dependent memory impairments in AD is unknown.

Methods

We used in vitro whole-cell patch-clamp recordings and western blot analyses to investigate the effect of AβO on PLCβ protein levels, PLCβ-dependent S-eCB mobilization, and spike-timing-dependent potentiation (tLTP) in AβO-treated rat hippocampal slices in vitro. In addition, we assessed the relationship between PLCβ protein levels and hippocampus-dependent memory impairment by performing a contextual fear memory task in vivo in the 5XFAD mouse model of AD.

Results

We found that AβO treatment in rat hippocampal slices in vitro decreased hippocampal PLCβ1 protein levels and disrupted S-eCB mobilization, as measured by western blot analysis and in vitro whole-cell patch-clamp recordings. This consequently led to the impairment of NMDA receptor (NMDAR)-mediated tLTP at CA3-CA1 excitatory synapses in AβO-treated rat hippocampal slices in vitro. Application of the PLCβ activator, m-3M3FBS, in rat hippocampal slices reinstated PLCβ1 protein levels to fully restore S-eCB mobilization and NMDAR-mediated tLTP. In addition, direct hippocampal injection of m-3M3FBS in 5XFAD mice reinstated PLCβ1 protein levels to those observed in wild type control mice and fully restored hippocampus-dependent contextual fear memory in vivo in 5XFAD mice.

Conclusion

We suggest that these results might be the consequence of memory impairment in AD by disrupting S-eCB mobilization. Therefore, we propose that PLCβ-dependent S-eCB mobilization could provide a new therapeutic strategy for treating memory deficits in AD.
Characteristics of behavioral symptoms in right-sided predominant semantic dementia and their impact on caregiver burden: a cross-sectional study
Authors: Sato Shunsuke , Hashimoto Mamoru , Yoshiyama Kenji , Kanemoto Hideki , Hotta Maki , Azuma Shingo , Suehiro Takashi , Kakeda Kyosuke , Nakatani Yoshitaka , Umeda Sumiyo , Fukuhara Ryuji , Takebayashi Minoru , Ikeda Manabu
Published: October 2021

Background

This study aimed to clarify the neuropsychiatric symptoms of right-sided predominant semantic dementia (SD-R) by comparing them with those of behavioral variant frontotemporal dementia (bvFTD), left-sided predominant SD (SD-L), and Alzheimer’s disease (AD). This study also aimed to identify clinical factors related to caregiver burden for bvFTD, SD-R, and SD-L.

Methods

The neuropsychiatric symptoms of 28 patients with bvFTD, 14 patients with SD-R, 24 patients with SD-L, and 43 patients with AD were evaluated using the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Dementia severity was assessed using the Clinical Dementia Rating. Activities of daily living were assessed using the Lawton Instrument Activities of Daily Living (IADL) scale and the Physical Self-Maintenance Scale. We compared the NPI and SRI scores among the four groups using the Kruskal-Wallis test. In addition, clinical factors related to caregiver burden, represented by the Japanese version of the Zarit Burden Interview (J-ZBI), were analyzed using multiple regression analysis in the bvFTD, SD-R, and SD-L groups.

Results

The NPI total score and the NPI subscale scores of apathy and disinhibition were significantly higher in the bvFTD group than in the SD-L and AD groups. The SD-R group scores were closer to those of the bvFTD group than the SD-L group. The SRI total score and SRI subscale scores for eating and cooking and speaking were significantly higher in the bvFTD, SD-R, and SD-L groups than in the AD group. The NPI total score was significantly associated with the J-ZBI score in the bvFTD group. The NPI total score and Lawton IADL scale score were independently associated with the J-ZBI score in the SD-R group. Furthermore, the NPI total score and MMSE score were independently associated with the J-ZBI score in the SD-L group.

Conclusions

SD-R seemed to be a similar condition to bvFTD rather than SD-L regarding behavioral symptoms. Our results suggest that each frontotemporal dementia subgroup requires different approaches to reduce the caregiver burden.
Serum 14-3-3β protein: a new biomarker in asthmatic patients with acute exacerbation in an observational study
Authors: Wang Decai , Rao Lizong , Cui Yalan , Tang Guoting , Huang Haiming , Yuan Ting , Mo Biwen
Published: October 2021

Background

The determination of systemic inflammatory markers is one of the important directions to study the pathogenesis of asthma and improve the diagnosis of asthma. Current studies have found that the 14-3-3 protein family subtypes interact with target proteins to participate in the pathogenesis of a variety of immune inflammatory diseases. However, studies on serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) in asthma are scarce. This study aimed to assess the clinical significance of 14-3-3β in asthmatic patients.

Methods

We recruited 54 asthmatic patients with acute exacerbation and 50 asthmatic patients with chronic persistent. The normal control group included 54 healthy individuals. Clinical characteristics, clinical indicators [fractional expiratory nitric oxide (FeNO), eosinophil count, forced vital capacity (FVC), percent of predicted FVC (FVC% predicted), forced expiratory volume in one second (FEV1), percent of predicted FEV1 (FEV1% predicted), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and serum 14-3-3β levels were measured to compare among each group. Spearman’s rank correlation coefficient was used to evaluate the correlation between 14-3-3β and clinical indicators. Finally, Receiver-operating characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of 14-3-3β.

Results

Our results showed that median (interquartile range) of serum 14-3-3β concentration (ng/mL) in acute exacerbation group of asthma (41.18 [33.06–51.76]) was much higher than that in normal control group (24.99 [17.43–29.91]; P < 0.001) and chronic persistent group of asthma (25.88 [21.03–34.55]; P < 0.001). Spearman’s correlation coefficient shows that the serum 14-3-3β level was positively correlated with FeNO (r = − 0.292, P = 0.032) and peripheral blood eosinophil count (r = 0.328, P = 0.016), and was negatively related to FEV1/FVC (r = − 0.293, P = 0.031) in the acute exacerbation group of asthma. At the same time, the serum 14-3-3β level was also negatively associated with FEV1 (r = − 0.297, P = 0.036) in the chronic persistent group of asthma. ROC curve analysis comparing acute exacerbation group of asthma with normal control group demonstrated a significant (P < 0.001) AUC of 0.90 (95% CI 0.85–0.96).

Conclusion

The serum 14-3-3β protein may become a potential biomarker in asthmatic patients with acute exacerbation.
A relapsed Pseudomonas stutzeri prosthetic valve endocarditis: a case report and review of the literature
Authors: Alabdely Mayyadah , Alazmah Mohammed , Alamro Bandar , Alabdaljabar Mohamad S. , Halim Magid
Published: October 2021

Background

Pseudomonas stutzeri is a nonfluorescent denitrifying bacterium widely distributed in the environment, and it has also been isolated as an opportunistic pathogen from humans. It is a Gram-negative bacterium and a common inhabitant of soil and water.

Case presentation

We report the case of a 51-year-old arab gentleman who has systemic lupus erythematous complicated by lupus nephritis and underwent renal transplantation twice. He underwent mitral valve replacement and 4 years later was diagnosed with prosthetic valve endocarditis caused by Pseudomonas stutzeri.

Conclusions

Literature review was conducted and revealed that this pathogen may be of a particular medical relevance in immunocompromised patients. Our case proves that early infection and relapse despite optimal antibiotics course are possible outcomes of Pseudomonas stutzeri endocarditis. To the best of our knowledge, this is the second case of fulminant early prosthetic valve endocarditis occurring only 1 month post-cardiac surgery with relapse despite a complete antibiotics course.
Primary biliary cirrhosis associated with myasthenia gravis after postpartum: a case report
Authors: Zhang Lulu , Ding Dongxue , Yu Liqiang , Qi Huan , Han Chunru , Jiang Jianhua , Jiang Juean
Published: October 2021

Background

Autoimmune diseases refers to a class of diseases involving abnormal immune response of human body and tissue damage caused by the dysregulation of autoimmune balance or destruction of immune tolerance. Recent research has revealed that the occurrence of autoimmune diseases is influenced by genetic, hormonal, immunological, and environmental factors. As sex hormone levels change obviously during pregnancy and postpartum, the morbidity and recurrence rate of autoimmune diseases increase during this period.

Case presentation

A 31-year-old Asian woman was admitted to our hospital for myasthenia gravis and treated with methylprednisolone and pyridostigmine bromide 3 months postpartum. Physical examination and laboratory inspection after admission suggested that the patient had primary biliary cirrhosis. Subsequently, azathioprine was added to the treatment, and the symptoms of both diseases were successfully controlled.

Conclusions

This case exhibits a rare condition of myasthenia gravis combined with primary biliary cirrhosis postpartum. Given the fluctuation of the immune status during the postpartum period, combined autoimmune diseases need to be taken into account when patients develop clinical symptoms of an autoimmune disease. Therefore, detailed physical and laboratory examination can help to prevent the missed diagnosis of these diseases.