bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features and treatment of “Non-dislocated hyperextension tibial plateau fracture”
Authors: Liangjun Jiang , Qiang Zheng , Zhijun Pan , Hanxiao Zhu , Erman Chen
Published: July 2020

Background

To explore the epidemiological characteristics, clinical characteristics, treatment strategies, and clinical results of non-dislocated hyperextension tibial plateau fracture.

Method

A total of 25 cases of non-dislocated hyperextension tibial plateau fracture patients were collected (12 males and 13 females), aged 27–79 years. Preoperative tibial plateau posterior slope angle was − 10~0° (average − 5.2°). Preoperative MRI showed 5 cases of MCL injury, 3 cases of PLC complex injury, and 2 cases of PLC + PCL injury. The change of tibial plateau posterior slope angle was more than 10° in patients with ligament injury, and the patients with a tibial plateau posterior slope angle change less than 10° had no ligament injury; 6 patients with simple column fracture had a ligament injury, 2 patients with bilateral column fracture had a ligament injury, and 2 patients with three column fracture had a ligament injury.

Results

Patients were followed up for 12–24 months (average 16.4 months). The operative time was 65–180 min (average 124 min), and the blood loss was 20–200 ml (average 106 ml). The plate was placed on the anterior part of tibial plateau. Evaluation of postoperative fracture reduction was as follows: 20 cases reached anatomic reduction, 5 cases reached good reduction (between 2 and 5 mm articular surface collapse), and the excellent rate of fracture reduction was 100%. The fracture healing time was 3–6 months (average 3.3 months). The postoperative knee Rasmussen score was 18–29 (average 24.9), and the postoperative knee joint mobility was 90–130° (average 118°). Two patients suffered superficial infection.

Conclusions

The main imaging characteristic of “non-dislocated hyperextension tibial plateau fracture” is the change of tibial plateau posterior slope angle. The injury of single anteromedial column/anterolateral column fracture is easy to combine with “diagonal” injury, and when the tPSA changes more than 10°, it is easy to be combined with ligament injury. By reducing the joint articular surface and lower limb force line, repairing the soft tissue structure, and reconstructing the knee joint stability, we can get satisfactory results.

Trial registration

It was a retrospective study. This study was consistent with the ethical standards of the Second Affiliated Hospital of Zhejiang University Medical College and was approved by the hospital ethics committee and the trial registration number of our hospital was20180145.
Evaluation of risk factors of vertebral fracture in Japanese female patients with glucocorticoid-induced osteoporosis
Authors: Mori Yu , Izumiyama Takuya , Baba Kazuyoshi , Mori Naoko , Fujii Hiroshi , Ishii Tomonori , Itoi Eiji
Published: July 2020

Background

Glucocorticoid-induced osteoporosis and vertebral fracture are common complications in patients on glucocorticoid treatment for rheumatological diseases. The present study aimed to identify the risk factors of vertebral fracture in Japanese female patients with glucocorticoid-induced osteoporosis.

Methods

This study included 225 Japanese women with glucocorticoid-induced osteoporosis and 72 patients with postmenopausal osteoporosis. All participants were treated with bisphosphonate or denosumab for osteoporosis with active form of vitamin D for at least 3 years. The differences of clinical parameters, including age, disease duration, body mass index (BMI), bone mineral density (BMD), and the dose and treatment duration of glucocorticoid were assessed between patients with and without vertebral fracture. Multivariate logistic regression analysis was also performed to evaluate the association of vertebral fracture with clinical parameters.

Results

The significant differences related to age, BMD of the hip, disease duration, glucocorticoid treatment duration between patients with and without vertebral fractures were demonstrated. The present study indicated that disease duration, BMI, and the total hip BMD were independent risk factors for vertebral fractures in patients with glucocorticoid-induced osteoporosis.

Conclusions

Prolonged disease duration, low BMI, and low total hip BMD could be risk factors of vertebral fracture in patients on glucocorticoid treatment for rheumatological diseases.
Different driver gene mutations in patients with synchronous multiple primary lung cancers: a case report
Authors: Yang Yong , Xie Xiaofeng , Jiang Gening , Liu Hongcheng
Published: July 2020

Background

Routine clinical and pathological examinations usually cannot fully conclusively determine the relationship between different lesions of lung cancer. Detailed genetic analysis of tumor samples may supply important additional information and identify second primary lung cancers.

Case presentation

In the present study, we report a case of synchronous multiple primary lung cancer (MPLC) composed of two distinct pathological subtypes with epidermal growth factor receptor (EGFR) gene mutations L858R of the acinar adenocarcinoma subtype and EML4–ALK rearrangement of the squamous cell carcinoma.

Conclusion

The present report highlights the clinical importance of molecular cancer biomarkers detection to guide management decisions in MPLC cases.
Mediastinal tumor resection in a patient with spinocerebellar degeneration
Authors: Tsuboi Eiyu , Azuma Yoko , Makino Takashi , Terada Takashi , Otsuka Hajime , Sano Atsushi , Koezuka Satoshi , Sakai Takashi , Tochigi Naobumi , Iyoda Akira
Published: July 2020

Background

In spinocerebellar degeneration (SCD) patients, general and regional anesthesia may cause postoperative dysfunction of respiratory, nerve and muscle systems. We present the surgical case of thymoma developed in patient with SCD.

Case presentation

A 47-year-old woman with spinocerebellar degeneration was admitted because of a well-defined mass measuring 48 × 31 mm in anterior mediastinum. She showed limb, truncal, ocular, and speech ataxia; hypotonia; areflexia; sensory disturbances; and muscle weakness. Her eastern cooperative oncology group performance status was 4. Surgical resection was performed via video-assisted thoracic surgery and under general anesthesia only without epidural analgesia. The mass was diagnosed as type B1 thymoma without capsular invasion (Masaoka stage I). The patients got a good postoperative course by cooperation with anesthesiologists and neurologists in perioperative managements. She has been well over 3 years of follow-up.

Conclusions

In conclusion, careful surgical and anesthesia management is essential for providing an uneventful postoperative course in patients with SCD. Especially, selection of minimal invasive approach and avoid diaphragmatic nerve damage are the most important points in surgical procedures.
Influence of chronic kidney disease on early clinical outcomes after off-pump coronary artery bypass grafting
Authors: Li Xihui , Zhang Siyu , Xiao Feng
Published: July 2020

Background

Patients with chronic kidney disease (CKD) have a high incidence of coronary heart disease, which is the leading cause of death in these patients. Coronary artery bypass grafting (CABG) significantly increases short-term mortality and decreases long-term mortality in patients with CKD compared with percutaneous coronary intervention (PCI). The effect of CKD on the early outcomes of off-pump CABG is not well-studied. We aimed to investigate the effect of CKD on early postoperative mortality and complications following off-pump CABG.

Methods

We retrospectively analyzed preoperative baseline and surgery data for 1173 patients undergoing off-pump CABG from January 2010 to December 2017 in the Department of Cardiac Surgery, Peking University First Hospital. Outpatient follow-up was performed until 30 days postoperatively. Patients with estimated glomerular filtration rates calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation of ≥60 mL/min/1.73 m2 were assigned to the normal renal function group (normal group, n = 924), and those with a rate < 60 mL/min/1.73 m2 were assigned to the CKD group (CKD group, n = 249).

Results

Patients in the CKD group were seriously ill with multiple complications, and postoperative 30-day mortality and complication rates were significantly higher than those in the normal group. In the logistic regression analysis, after correcting for common confounding factors, namely sex, age, and left ventricular ejection fraction, preoperative CKD was a risk factor for postoperative acute kidney injury, perioperative myocardial infarction, gastrointestinal bleeding, secondary tracheal intubation, stroke, chest wound infection, prolonged mechanical ventilation (≥ 24 h), prolonged intensive care unit stay (≥ 72 h), prolonged length of stay (≥ 14 d), dialysis requirement, and postoperative death within 30 days.

Conclusions

Patients with CKD had more preoperative complications, and their postoperative 30-day mortality and complication rates after off-pump CABG were significantly higher than those of patients with normal renal function. For CABG patients with CKD, the risk of surgery should be assessed carefully, and comprehensive measures should be taken to strengthen perioperative management, with an aim to reduce complications and mortality and improve surgical outcomes.
BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology
Authors: Taga Mariko , Petyuk Vladislav A. , White Charles , Marsh Galina , Ma Yiyi , Klein Hans-Ulrich , Connor Sarah M. , Kroshilina Alexandra , Yung Christina J. , Khairallah Anthony , Olah Marta , Schneider Julie , Karhohs Kyle , Carpenter Anne E. , Ransohoff Richard , Bennett David A. , Crotti Andrea , Bradshaw Elizabeth M. , De Jager Philip L.
Published: July 2020

Background

Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear.

Methods

Utilizing antibodies targeting specific BIN1 epitopes in human post-mortem tissue and analyzing mRNA expression data from purified microglia, we identified three isoforms expressed in neurons and astrocytes (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed.

Results

Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with AD-related traits and, particularly, tau tangles. Decreased expression of BIN1 isoforms containing exon 7 is associated with greater accumulation of tangles and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant.

Conclusions

Exploring the molecular mechanisms of specific BIN1 isoforms expressed by astrocytes may open new avenues for modulating the accumulation of Tau pathology in AD.
Morbidities & outcomes of a neonatal intensive care unit in a complex humanitarian conflict setting, Hajjah Yemen: 2017-2018
Authors: Eze Paul , Al-Maktari Fatoum , Alshehari Ahmed Hamood , Lawani Lucky Osaheni
Published: July 2020

Background

The protracted conflict in Yemen has taken a massive toll on the health system, negatively impacting the health of children, especially the most vulnerable age group; the newborns.

Methods

A 2-year retrospective study of admissions into the Neonatal Intensive Care Unit (NICU) in Al-Gomhoury Hospital Hajjah, Northwest Yemen was conducted. Data was analyzed with IBM SPSS® version 25.0 statistical software using descriptive/inferential statistics.

Results

A total of 976 newborns were eligible and included in this study; 506 preterm newborns (51.8%) and 470 term newborns (48.2%). Over half, 549 (56.3%) newborns were admitted within 24 h after birth and 681 (69.8%) newborns travelled for over 60 min to arrive at the NICU. The most common admission diagnoses were complications of prematurity (341; 34.9%), perinatal asphyxia (336; 34.4%), neonatal jaundice (187; 18.8%), and neonatal sepsis (157, 16.1%). The median length of stay in the NICU was 4 days. There were 213 neonatal deaths (Facility neonatal mortality rate was 218 neonatal deaths per 1000 livebirths); 192 (90.1%) were preterm newborns, while 177 (83.1%) were amongst newborns that travelled for more 60 min to reach the NICU. Significant predictors of neonatal deaths are preterm birth (aOR = 3.09, 95% CI: 1.26–7.59, p = 0.014 for moderate preterm neonates; aOR = 6.18, 95% CI: 2.12–18.01, p = 0.001 for very preterm neonates; and aOR = 44.59, 95% CI: 9.18–216.61, p <  0.001 for extreme preterm neonates); low birth weight (aOR = 3.67, 95% CI: 1.16–12.07, p = 0.032 for very low birth weight neonates; and aOR = 17.42, 95% CI: 2.97–102.08, p = 0.002 for extreme low birth weight neonates); and traveling for more than 60 min to arrive at the NICU (aOR = 2.32, 95% CI: 1.07–5.04, p = 0.033). Neonates delivered by Caesarean section had lower odds of death (aOR = 0.38, 95% CI 0.20–0.73, p = 0.004) than those delivered by vaginal birth.

Conclusions

Preterm newborns bear disproportionate burden of neonatal morbidity and mortality in this setting which is aggravated by difficulties in accessing early neonatal care. Community-based model of providing basic obstetric and neonatal care could augment existing health system to improve neonatal survival in Yemen.
Development of mental healthcare in Cambodia: barriers and opportunities
Authors: Parry Sarah J. , Ean Nil , Sinclair Shirley P. , Wilkinson Ewan
Published: July 2020

Background

Despite the increasing recognition globally of the importance of mental health for sustainable development, significant barriers remain to developing mental health services in low- and middle-income countries. This study explored the particular barriers and opportunities for developing mental health services in Cambodia and how these compared with those described in other low- and middle-income countries.

Methods

For this qualitative study, 18 experienced mental health professionals from different disciplines were selected using purposive sampling. Semi-structured interviews were carried out in Phnom Penh and thematic analysis of the data was completed.

Results

Five key themes were identified: (1) Prioritising mental health in Cambodia, (2) Strengthening collaborations between mental health stakeholders, (3) Developing a mental healthcare model appropriate for the Cambodian culture and context, (4) Increasing the quantity and (5) Improving the quality of mental healthcare. All five themes were referred to by all 18 participants and the two most repeated themes were (2) Strengthening collaborations and (5) Improving the quality of mental healthcare.

Conclusions

The themes identified in this study both corroborate previous barriers identified to developing mental health services in low- and middle-income countries and shed new light on opportunities of particular importance in Cambodia. Strengthening collaborations between key stakeholders in mental health and prioritising the quality of mental health education, training and service provision were both cited as being significant opportunities for enhancing the development of mental health services in Cambodia. These have not been widely described before as being important factors.
Roadmap to strengthen global mental health systems to tackle the impact of the COVID-19 pandemic
Authors: Maulik Pallab K. , Thornicroft Graham , Saxena Shekhar
Published: July 2020

Background

The COVID pandemic has been devastating for not only its direct impact on lives, physical health, socio-economic status of individuals, but also for its impact on mental health. Some individuals are affected psychologically more severely and will need additional care. However, the current health system is so fragmented and focused on caring for those infected that management of mental illness has been neglected. An integrated approach is needed to strengthen the health system, service providers and research to not only manage the current mental health problems related to COVID but develop robust strategies to overcome more long-term impact of the pandemic. A series of recommendations are outlined in this paper to help policy makers, service providers and other stakeholders, and research and research funders to strengthen existing mental health systems, develop new ones, and at the same time advance research to mitigate the mental health impact of COVID19. The recommendations refer to low, middle and high resource settings as capabilities vary greatly between countries and within countries.

Discussion

The recommendations for policy makers are focused on strengthening leadership and governance, finance mechanisms, and developing programme and policies that especially include the most vulnerable populations. Service provision should focus on accessible and equitable evidence-based community care models commensurate with the existing mental health capacity to deliver care, train existing primary care staff to cater to increased mental health needs, implement prevention and promotion programmes tailored to local needs, and support civil societies and employers to address the increased burden of mental illness. Researchers and research funders should focus on research to develop robust information systems that can be enhanced further by linking with other data sources to run predictive models using artificial intelligence, understand neurobiological mechanisms and community-based interventions to address the pandemic driven mental health problems in an integrated manner and use innovative digital solutions.

Conclusion

Urgent action is needed to strengthen mental health system in all settings. The recommendations outlined can be used as a guide to develop these further or identify new ones in relation to local needs.
Symptoms and level of functioning related to comorbidity in children and adolescents with ADHD: a cross-sectional registry study
Authors: Elwin Marie , Elvin Tove , Larsson Jan-Olov
Published: July 2020

Background

It is well known that a wide range of psychiatric disorders co-occur with attention deficit hyperactivity disorder. In this study we aimed to examine the associations of psychiatric comorbidity in ADHD with symptom severity and level of functioning.

Methods

We used data from the Swedish National Quality Registry for ADHD Treatment Follow-up and identified comorbid diagnoses in a sample of 3246 Swedish children and adolescents with ADHD. We investigated the association of comorbidity with symptom severity and level of function by multiple linear regressions.

Results

Autism spectrum disorder, anxiety and affective disorders, oppositional defiant disorder or conduct disorder, learning disorders, and multiple comorbid disorders associate to lower levels of functioning compared to ADHD only. Multiple comorbidity, autism spectrum disorder, oppositional defiant or conduct disorders and tic disorders relate to ADHD symptom severity.

Conclusions

Comorbidity subgroups with ADHD differ in functional impairment and ADHD symptoms severity. Information on comorbidity profiles could be used for treatment planning more adapted to the individual. Especially those who have autism spectrum disorders and multiple comorbid disorders are at risk of severe ADHD symptoms and low level of functioning.
PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas
Authors: Noorani Imran , de la Rosa Jorge , Choi Yoon Ha , Strong Alexander , Ponstingl Hannes , Vijayabaskar M. S. , Lee Jusung , Lee Eunmin , Richard-Londt Angela , Friedrich Mathias , Furlanetto Federica , Fuente Rocio , Banerjee Ruby , Yang Fengtang , Law Frances , Watts Colin , Rad Roland , Vassiliou George , Kim Jong Kyoung , Santarius Thomas , Brandner Sebastian , Bradley Allan
Published: July 2020

Background

Glioma is the most common intrinsic brain tumor and also occurs in the spinal cord. Activating EGFR mutations are common in IDH1 wild-type gliomas. However, the cooperative partners of EGFR driving gliomagenesis remain poorly understood.

Results

We explore EGFR-mutant glioma evolution in conditional mutant mice by whole-exome sequencing, transposon mutagenesis forward genetic screening, and transcriptomics. We show mutant EGFR is sufficient to initiate gliomagenesis in vivo, both in the brain and spinal cord. We identify significantly recurrent somatic alterations in these gliomas including mutant EGFR amplifications and Sub1, Trp53, and Tead2 loss-of-function mutations. Comprehensive functional characterization of 96 gliomas by genome-wide piggyBac insertional mutagenesis in vivo identifies 281 known and novel EGFR-cooperating driver genes, including Cdkn2a, Nf1, Spred1, and Nav3. Transcriptomics confirms transposon-mediated effects on expression of these genes. We validate the clinical relevance of new putative tumor suppressors by showing these are frequently altered in patients’ gliomas, with prognostic implications. We discover shared and distinct driver mutations in brain and spinal gliomas and confirm in vivo differential tumor suppressive effects of Pten between these tumors. Functional validation with CRISPR-Cas9-induced mutations in novel genes Tead2, Spred1, and Nav3 demonstrates heightened EGFRvIII-glioma cell proliferation. Chemogenomic analysis of mutated glioma genes reveals potential drug targets, with several investigational drugs showing efficacy in vitro.

Conclusion

Our work elucidates functional driver landscapes of EGFR-mutant gliomas, uncovering potential therapeutic strategies, and provides new tools for functional interrogation of gliomagenesis.
Sanfu herbal patch applied at acupoints in patients with bronchial asthma: study protocol for a randomized controlled trial
Authors: Xie Xiaoyan , Xu Danghan , Zhuang Lixing , Liu Hui , Tan Sui , Lu Yanqing , Su Meiyi , Chen Jie , Pan Haihua , Lu Lu , Xu Yiming , Liao Muxi , Xu Zhanqiong , He Jun
Published: July 2020

Background

Bronchial asthma is one of the most common inflammatory airway disorders. As one of the main non-drug therapies, the Sanfu herbal patch (SHP) has been widely used to treat bronchial asthma, although the evidence for its efficacy and associated mechanism are inconclusive. The objective of this trial is to clarify the clinical efficacy and safety of the SHP in the treatment of bronchial asthma in the chronic persistent or clinical remission stage and to provide high-quality data for further research.

Methods

We propose a multicentre, double-blinded, parallel, randomized, placebo-controlled clinical trial involving 4 study hospitals in China. A total of 72 eligible participants will be randomized into an SHP group and a placebo group. They will receive an SHP for 3 treatment sessions. The primary outcome will be changes in forced expiratory volume in 1 s after 3 treatment sessions. Secondary outcomes will include the following: (1) the Asthma Quality of Life Questionnaire, Asthma Control Test, and Asthma Long-term Follow-up Scale; (2) levels of Metallothionein-2 and Transgelin-2 in blood and urine; and (3) levels of IL-5, IL-13, IL-23, IL-25, and thymic stromal lymphopoietin in blood. Analysis of the data will be performed at baseline, at the end of the 2nd and 3rd treatment sessions, and at the 24-week follow-up. The safety of the SHP will be evaluated at each treatment session.

Discussion

The aims of this trial are to determine whether the SHP is more effective than placebo in the treatment of patients with bronchial asthma, as well as whether the SHP works by reducing airway inflammation and reversing bronchoconstriction.

Trial registration

Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR1900024616. Registered on 19 July 2019.
High production of triterpenoids in Yarrowia lipolytica through manipulation of lipid components
Authors: Zhang Jin-Lai , Bai Qiu-Yan , Peng Yang-Zi , Fan Jie , Jin Cong-Cong , Cao Ying-Xiu , Yuan Ying-Jin
Published: July 2020

Background

Lupeol exhibits novel physiological and pharmacological activities, such as anticancer and immunity-enhancing activities. However, cytotoxicity remains a challenge for triterpenoid overproduction in microbial cell factories. As lipophilic and relatively small molecular compounds, triterpenes are generally secreted into the extracellular space. The effect of increasing triterpene efflux on the synthesis capacity remains unknown.

Results

In this study, we developed a strategy to enhance triterpene efflux through manipulation of lipid components in Y. lipolytica by overexpressing the enzyme Δ9-fatty acid desaturase (OLE1) and disturbing phosphatidic acid phosphatase (PAH1) and diacylglycerol kinase (DGK1). By this strategy combined with two-phase fermentation, the highest lupeol production reported to date was achieved, where the titer in the organic phase reached 381.67 mg/L and the total production was 411.72 mg/L in shake flasks, exhibiting a 33.20-fold improvement over the initial strain. Lipid manipulation led to a twofold increase in the unsaturated fatty acid (UFA) content, up to 61–73%, and an exceptionally elongated cell morphology, which might have been caused by enhanced membrane phospholipid biosynthesis flux. Both phenotypes accelerated the export of toxic products to the extracellular space and ultimately stimulated the capacity for triterpenoid synthesis, which was proven by the 5.11-fold higher ratio of extra/intracellular lupeol concentrations, 2.79-fold higher biomass accumulation and 2.56-fold higher lupeol productivity per unit OD in the modified strains. This strategy was also highly efficient for the biosynthesis of other triterpenes and sesquiterpenes, including α-amyrin, β-amyrin, longifolene, longipinene and longicyclene.

Conclusions

In conclusion, we successfully created a high-yield lupeol-producing strain via lipid manipulation. We demonstrated that the enhancement of lupeol efflux and synthesis capacity was induced by the increased UFA content and elongated cell morphology. Our study provides a novel strategy to promote the biosynthesis of valuable but toxic products in microbial cell factories.
Insights into the phylogenetic relationships and drug targets of Babesia isolates infective to small ruminants from the mitochondrial genomes
Authors: Wang Xiaoxing , Wang Jinming , Liu Junlong , Liu Aihong , He Xin , Xiang Quanjia , Li Youquan , Yin Hong , Luo Jianxun , Guan Guiquan
Published: July 2020

Background

Babesiosis, a tick-borne disease caused by protozoans of the genus Babesia, is widespread in subtropical and tropical countries. Mitochondria are essential organelles that are responsible for energy transduction and metabolism, calcium homeostasis and cell signaling. Mitochondrial genomes could provide new insights to help elucidate and investigate the biological features, genetic evolution and classification of the protozoans. Nevertheless, there are limited data on the mitochondrial genomes of ovine Babesia spp. in China.

Methods

Herein, we sequenced, assembled and annotated the mitochondrial genomes of six ovine Babesia isolates; analyzed the genome size, gene content, genome structure and cytochrome b (cytb) amino acid sequences and performed comparative mitochondrial genomics and phylogenomic analyses among apicomplexan parasites.

Results

The mitochondrial genomes range from 5767 to 5946 bp in length with a linear form and contain three protein-encoding genes, cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 3 (cox3) and cytb, six large subunit rRNA genes (LSU) and two terminal inverted repeats (TIR) on both ends. The cytb gene sequence analysis indicated the binding site of anti-Babesia drugs that targeted the cytochrome bc1 complex. Babesia microti and Babesia rodhaini have a dual flip-flop inversion of 184–1082 bp, whereas other Babesia spp. and Theileria spp. have one pair of TIRs, 25–1563 bp. Phylogenetic analysis indicated that the six ovine Babesia isolates were divided into two clades, Babesia sp. and Babesia motasi. Babesia motasi isolates were further separated into two small clades (B. motasi Hebei/Ningxian and B. motasi Tianzhu/Lintan).

Conclusions

The data provided new insights into the taxonomic relationships and drug targets of apicomplexan parasites.
Molecular analysis reveals a high diversity of Anopheles species in Karama, West Sulawesi, Indonesia
Authors: Davidson Jenna R. , Wahid Isra , Sudirman Rusdiyah , Small Scott T. , Hendershot Allison L. , Baskin Robert N. , Burton Timothy A. , Makuru Victoria , Xiao Honglin , Yu Xiaoyu , Troth Emma V. , Olivieri Daniel , Lizarraga Stephanny , Hasan Hajar , Arfah Andi , Yusuf Muhammad , Nur Nirwana , Syafruddin Din , Asih Puji , Lobo Neil F.
Published: July 2020

Background

Understanding local Anopheles species compositions and bionomic traits are vital for an effective malaria vector intervention strategy. Though eight malaria vectors, including species complexes, have been documented across the island of Sulawesi, Indonesia, a comprehensive survey linking morphological and molecular species identification has not been conducted in this global hotspot of biodiversity.

Results

Eighteen distinct species of Anopheles were molecularly identified in a 1 km2 area in Karama village, West Mamuju Province, Sulawesi. Known species included An. aconitus, An. karwari, An. peditaeniatus, An. vagus, An. barbirostris, An. tessellatus, An. nigerrimus, An. crawfordi, An. maculatus, An. flavirostris and An. kochi. Of the 18 distinct sequence groups identified through both ribosomal DNA internal transcribed spacer region 2, and mitochondrial DNA cytochrome c oxidase subunit 1 loci, 8 could not be identified to species through comparison to published sequences. The comparison of morphological and molecular identities determined that interpretations of local species compositions for primary and expected species in Karama (An. barbirostris and An. vagus) had the highest rate of accuracy (92.1% and 87.6%, respectively) when compared to molecular analysis. However, the remaining distinct sequences molecularly identified to species were identified correctly by morphological methods less frequently, from 0 to 83%.

Conclusions

Karama, Indonesia has a high diversity of Anopheles spp. The unexpected high number of Anopheles species in a small area points to possible complex transmission dynamics and limitations with vector control based on possible varying behaviors and interactions with both humans and interventions. Morphological identification of Anopheles spp. in this study was more accurate for primary and expected species than secondary or unexpected species. Finally, the inability to identify seven sequence groups to species with consensus sequences implies that future studies employing sequencing are required to clarify species compositions in the Nigerrimus Subgroup, among others, as well as their distribution and vector status. Use of molecular methods in conjunction with morphological investigations for analysis of species composition, population dynamics and bionomic characteristics is directly implicated in understanding drivers of malaria transmission, intervention effectiveness, and the pursuit of malaria elimination.
Identification and validation of a commercial cryopreservation medium for the practical preservation of Dirofilaria immitis microfilaria
Authors: Shirozu Takahiro , Soga Akira , Fukumoto Shinya
Published: July 2020

Background

Dirofilaria immitis is a parasitic nematode transmitted by mosquitoes and the cause of heartworm disease in dogs and dirofilariasis in humans and other mammals. The parasite is endemic worldwide. Vector stage research requires a reliable supply of D. immitis microfilariae (mf). It is believed that cryopreserved mf would retain viability and provide a powerful tool for vector stage research. However, reports on cryopreservation of D. immitis mf are limited. Therefore, this study aimed to validate commercial cryopreservation media to establish a practical, convenient and reproducible storage procedure for D. immitis mf.

Methods

Six different commercially available cryopreservation media were compared with the traditional polyvinylpyrrolidone-dimethyl sulfoxide (PVP-DMSO) preservation solution. In vitro viability of purified D. immitis mf and mf-infected total blood was analyzed using a motility assay and propidium iodide staining. In vivo infectivity of Aedes aegypti mosquitoes with cryopreserved mf was assessed using a mosquito survival test and quantifying the number of third-stage larvae (L3) after 13 days post-infection.

Results

Purified mf cryopreserved in CultureSure showed the best viability when compared to mf cryopreserved in the remaining five commercially available media and PVP-DMSO. Viability of mf in mf-infected total blood cryopreserved in CultureSure varied with the ratio of infected blood to CultureSure. Optimum results were obtained with 200 µl mf-infected blood:800 µl CultureSure. CultureSure was also the optimum medium for cryopreserving mf prior to infectivity of A. aegypti. The number of L3 was approximately the same for CultureSure cryopreserved mf (3× concentrated solution) and non-cryopreserved fresh mf.

Conclusions

CultureSure is an optimal commercial cryopreservation solution for the storage of D. immitis purified mf, mf-infected total blood, and mf used for in vivo mosquito experiments. Furthermore, this study describes an easy preservation method for clinical D. immitis-infected blood samples facilitating vector stage studies, as well as the study of macrocyclic lactone resistance in heartworms and the education of veterinarians.
Questing abundance of adult taiga ticks Ixodes persulcatus and their Borrelia prevalence at the north-western part of their distribution
Authors: Pakanen Veli-Matti , Sormunen Jani J. , Sippola Ella , Blomqvist Donald , Kallio Eva R.
Published: July 2020

Background

Because ixodid ticks are vectors of zoonotic pathogens, includingBorrelia, information of their abundance, seasonal variation in questing behaviour and pathogen prevalence is important for human health. As ticks are invading new areas northwards, information from these new areas are needed. Taiga tick (Ixodes persulcatus) populations have been recently found at Bothnian Bay, Finland. We assessed seasonal variation in questing abundance of ticks and their pathogen prevalence in coastal deciduous forests near the city of Oulu (latitudes 64–65°) in 2019.

Methods

We sampled ticks from May until September by cloth dragging 100 meters once a month at eight study sites. We calculated a density index (individuals/100 m2) to assess seasonal variation. Samples were screened forBorrelia burgdorferi(sensu lato) (includingB. afzelii,B. garinii,B. burgdorferi(sensu stricto) andB. valaisana),Borrelia miyamotoi,Anaplasma phagocytophilum,Rickettsiaspp.,Neoehrlichia mikurensis,Francisella tularensisandBartonella spp.,Babesiaspp. and for the tick-borne encephalitis virus.

Results

All except one nymph were identified asI. persulcatus.The number of questing adults showed a strong peak in May (median: 6.5 adults/100 m2), which is among the highest values reported in northern Europe, and potentially indicates a large population size. After May, the number of questing adults declined steadily with few adults still sampled in August. Nymphs were present from May until September. We found a striking prevalence ofBorreliaspp. in adults (62%) and nymphs (40%), withB. garinii(51%) andB. afzelii(63%) being the most common species. In addition, we found that 26% of infected adults were coinfected with at least twoBorreliagenospecies, mainlyB. gariniiandB. afzelii, which are associated with different host species.

Conclusions

The coastal forest environments at Bothnian Bay seem to provide favourable environments forI. persulcatusand the spread ofBorrelia. High tick abundance, a low diversity of the host community and similar host use among larvae and nymphs likely explain the highBorreliaprevalence and coinfection rate. Research on the infestation of the hosts that quantifies the temporal dynamics of immature life stages would reveal important aspects of pathogen circulation in these tick populations.
Mesenchymal stem cells inhibited the differentiation of MDSCs via COX2/PGE2 in experimental sialadenitis
Authors: Qi Jingjing , Tang Xiaojun , Li Wenchao , Chen Weiwei , Yao Genhong , Sun Lingyun
Published: July 2020

Background

Mesenchymal stem cells (MSCs) can regulate innate and adaptive immune systems through interacting with immune cells directly and secreting multiple soluble factors. Due to their immunosuppressive properties, MSC transplantation has been applied to treat many clinical and experimental autoimmune diseases. However, the therapeutic effects and mechanisms by which MSCs regulate myeloid cells in Sjögren’s syndrome (SS) still remain elusive.

Methods

The number and immune-suppressive activity of myeloid-derived suppressor cells (MDSCs), polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) were determined in non-obese diabetic (NOD) mice with sialadenitis and in NOD mice with human umbilical cord-derived MSC (UC-MSC) transplantation. Bone marrow cells were cultured with MSC-conditioned medium (MSC-CM) for 4 days. The number and immune-suppressive gene of MDSCs were detected by flow cytometry or qRT-PCR.

Results

The results showed that the number of MDSCs and PMN-MDSCs was higher and M-MDSCs were lower in NOD mice with sialadenitis. UC-MSCs ameliorated SS-like syndrome by reducing MDSCs, PMN-MDSCs, and M-MDSCs and promoting the suppressive ability of MDSCs significantly in NOD mice. UC-MSCs inhibited the differentiation of MDSCs. In addition, UC-MSCs enhanced the suppressive ability of MDSCs in vitro. Mechanistically, MSCs inhibited the differentiation of MDSCs and PMN-MDSCs via secreting prostaglandin E2 (PGE2) and inhibited the differentiation of M-MDSCs through secreting interferon-β (IFN-β).

Conclusions

Our findings suggested that MSCs alleviated SS-like symptoms by suppressing the aberrant accumulation and improving the suppressive function of MDSCs in NOD mice with sialadenitis.
The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells
Authors: Li Xiaoyu , Zhang Bowen , Wang Hong , Zhao Xiaolu , Zhang Zijie , Ding Gang , Wei Fulan
Published: July 2020

Background

Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear.

Methods

In this study, we compared PDLSCs isolated from young and adult individuals. PDLSC proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSC osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining, and related quantitative analysis. PDLSC immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs.

Results

Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation ofCCND3andRC3H2, and a downregulation ofRunx2,ALP,COL1A1,PPARγ2,CXCL12,FKBP1A,FKBP1B,NCSTN,P2RX7,PPP3CB,RIPK2,SLC11A1, andTP53in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, COL1A1, and PPARγ2 in the adult group were decreased, whereas that of CCND3 increased.

Conclusions

Taken together, aging influences the biological and immunological characteristics of PDLSCs, and thus, it is more appropriate to utilize PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation.
Severe recurrent Streptobacillus moniliformis endocarditis in a pregnant woman, and review of the literature
Authors: Crofton Kathryn R. , Ye Jiqing , Lesho Emil P.
Published: July 2020

Background

Rat bite fever is a systemic febrile illness caused by infection with the Gram-negative bacillus Streptobacillus moniliformis following a bite, scratch, or contact with excrement. Only 26 cases of native valve endocarditis have been reported to date. We could find no other reports of severe Streptobacillus endocarditis requiring valve replacement in a young, pregnant patient.

Case presentation

A pregnant patient sought care for right leg pain, fevers, left upper quadrant pain, generalized weakness, fatigue, and inability to bear weight on her right leg. She had a syncopal episode 9 months earlier, resulting in a mandibular fracture and internal fixation hardware. Her pregnancy was complicated by hyperemesis and weight loss. Her pets included a rescued wild bird, a cat, and four rats. Her parents rescued stray cats, and she recalled multiple cat bites and scratches since childhood. She denied injection drug use. Ultrasound indicated a right popliteal artery thrombus. Transesophageal echocardiogram revealed a 2 cm × 0.7 cm vegetation. Angiography demonstrated multiple splenic infarcts and bilateral renal infarcts. She underwent mitral valve repair. The mitral valve Gram stain demonstrated 2+ Gram-negative rods, rare Gram-positive rods, and moderate white blood cells. Propionibacterium spp. was isolated from the mitral valve tissue on Columbia agar incubated anaerobically. Anaerobic and aerobic cultures of the valve tissue on all other broths and agars remained negative at 14 days. Hematoxylin and eosin stains showed a fibro-inflammatory vegetation. Aggregates of rod-shaped bacteria were identified on Warthin Starry/Steiner stain. Bartonella titers were positive for B. henselae IgG 1:256, IgM < 1:20. Brown-Hopps Gram stain, AFB, and GMS stains for bacterial and fungal microorganisms were negative. Broad range bacterial PCR and sequencing of a segment of 16 s rRNA gene of the valve tissue matched to Streptobacillus sp. (genus level) and most closely related to Streptobacillus moniliformis.

Conclusion

This case demonstrates diagnostic and therapeutic challenges associated with a relatively uncommon cause of endocarditis. The diagnosis of rat bite fever was delayed due to symptoms of a concomitant pregnancy. Other confounders included possible alternative sources or co-infections with another zoonosis from multiple pets, and an odontogenic source due to presence of exposed jaw hardware.
Recommendations from the Canadian Association of Head and Neck Surgical Oncology for the Management of Head and Neck Cancers during the COVID-19 pandemic
Authors: O'Connell Daniel A. , Seikaly Hadi , Isaac Andre , Pyne Justin , Hart Robert D. , Goldstein David , Yoo John ,   Canadian Association of Head and Neck Surgical Oncology
Published: July 2020

Introduction

The SARS-CoV-2 virus (COVID19) pandemic has placed extreme pressures on the Canadian Healthcare system. Many health care regions in Canada have cancelled or limited surgical and non-surgical interventions on patients to preserve healthcare resources for a predicted increase in COVID19 related hospital admissions. Also reduced health interventions may limit the risk of possible transmission of COVID19 to other patients and health care workers during this pandemic. The majority of institutions in Canada have developed their own operational mandates regarding access to surgical resources for patients suffering from Head and Neck Cancers during this pandemic. There is a large degree of individual practitioner judgement in deciding access to care as well as resource allocation during these challenging times. The Canadian Association of Head and Neck Surgical Oncology (CAHNSO) convened a task force to develop a set of guidelines based on the best current available evidence to help Head and Neck Surgical Oncologists and all practitioners involved in the care of these patients to help guide individual practice decisions.

Main body

The majority of head and neck surgical oncology from initial diagnosis and work up to surgical treatment and then follow-up involves aerosol generating medical procedures (AGMPs) which inherently put head and neck surgeons and practitioners at high risk for transmission of COVID19. The aggressive nature of the majority of head and neck cancer negates the ability for deferring surgical treatment for a prolonged period of time. The included guidelines provide recommendations for resource allocation for patients, use of personal protective equipment for practitioners as well as recommendations for modification of practice during the current pandemic.

Conclusion

Enhanced triaging should be used to identify patients with aggressive malignancies. These patients should be prioritized to reduce risk of significant disease progression in the reduced resource environment of COVID19 era. Enhanced triaging including aggressive pre-treatment COVID19 testing should be used to identify patients with high risk of COVID19 transmission. Enhanced personal protective equipment (PPE) including N95 masks and full eye protection should be used for any AGMPs performed even in asymptomatic patients. Enhanced PPE including full eye protection, N95 masks and/or powered air purifying respirators (PAPRs) should be used for any AGMPs in symptomatic or presumptive positive COVID 19 patients.
Novel technique to repair a bronchopleural fistula after esophagectomy using wide intercostal muscle flap fixed by azygos vein and bronchus: a case report
Authors: Honda Yohei , Taira Akihiro , Hirai Ayako , Kuroda Koji , Ichiki Yoshinobu , Tanaka Fumihiro
Published: July 2020

Background

Post-esophagectomy bronchopleural fistulas can be life-threatening in patients who are exhausted, for example, by surgical stress and pleural infection; therefore, establishment of a reliable surgical procedure is extremely important. We here report a novel procedure entailing muscle flap closure for bronchopleural fistula.

Case presentation

A 64-year-old man developed a right bronchopleural fistula after esophagectomy. Because he was exhausted by surgical stress and malnourished, we considered reliable surgical closure of the fistula essential. Intraoperatively, it was found to connect with the membranous portion of the right main bronchus. We decided to close the fistula with a pedicled fourth and fifth intercostal muscle flap. After separating the intercostal muscles near the angle of the rib, we passed a muscle flap between the azygos vein and bronchus and sutured it securely to the fistula. The postoperative course was uneventful, and there was no thoracic infection. Postoperative bronchoscopy confirmed the muscle flap had securely closed the fistula.

Conclusions

The route and suturing technique of the intercostal muscle flap to a fistula are important, especially in exhausted patients.