bluuebunny/crossref_metadata_2025 huggingface dataset:
Which anatomic structures are responsible for the reduction loss after hybrid stabilization of osteoporotic fractures of the thoracolumbar spine?
Authors: Spiegl Ulrich J. , Ahrberg Annette B. , Anemüller Christine , Jarvers Jan-Sven , Glasmacher Stefan , von der Höh Nicolaus , Josten Christoph , Heyde Christoph-Eckhard
Published: January 2020

Introduction

Hybrid stabilization is an accepted therapy strategy for unstable osteoporotic thoracolumbar fractures. However, a moderate reduction loss has been reported and it remains unclear which anatomic structure is responsible for the reduction loss.

Methods

This retrospective study was performed at a level I trauma center. Patients aged 61 and older were stabilized using hybrid stabilization after suffering acute and unstable osteoporotic vertebral body fractures at the thoracolumbar spine. Posterior stabilization was done short-segmental and minimal invasive with cement-augmentation of all pedicle screws. The minimum follow-up has been 2 years. The outcome parameters were the reduction loss and the relative loss of height of both intervertebral discs adjacent to the fractured vertebral body, the fractured vertebral body and a reference disc (intervertebral disc superior of the stabilization) between the postoperative and latest lateral radiographs. Additionally, implant positioning and loosening was analyzed.

Results

29 mainly female (72%) patients (73.3 ± 6.0 years) were included. Fractures consisted of 26 incomplete burst fractures and 3 complete burst fractures of the thoracolumbar junction (Th11 – L2: 86%) and the midlumbar spine. The mean follow-up time was 36 months (range: 24–58 months). The mean reduction loss was 7.7° (range: 1–25). The relative loss of heights of both intervertebral discs adjacent to the fractured vertebral body, the reference disc, and the central vertebral body were significant. Thereby, the relative loss of the superior disc height was significant higher compared to the reference disc. Additionally, only the relative loss of central vertebral body height and reduction loss correlated significantly. There were no signs of implant loosening in any patient.

Conclusions

The mean reduction loss was moderate 3 years after hybrid stabilization of unstable osteoporotic vertebral fractures of the thoracolumbar spine. A significant loss of both adjacent disc heights and the central vertebral body was seen, with the highest loss in the superior adjacent disc significantly outranging the reference disc. The superior adjacent intervertebral disc and the central part of the fractured vertebral body seem to be responsible for the majority of reduction loss.
Popliteal artery transection associated with a minimally displaced tibial plateau fracture: a case report and review of the literature
Authors: Liu Yan-Wei , Li Yan-Hui , Yu Tiecheng , Yang Tianye , Li Yuying , Tan Lei
Published: January 2020

Background

Poplital artery transection injury is potentially catastrophic, or even life-threatening. Severe traumas, including open fracture, gunshot, stabs, and knee dislocation and complex fracture of proximal tibia or distal femur, are the common causes of high rate of amputation due to popliteal artery trauma. No report mentions vascular injury associated with minimally displaced tibial plateau fracture in adult.

Case presentation

A 30-year-old male presented with popliteal artery transection injury associated with minimally displaced tibial plateau fracture. He presented to emergency department, 6 h after fall from ground into a 1-m height hole. Physical examination suggested acute ischemia, with signs of paleness, coldness, anesthesia, hemorrhagic bullae below the right knee level. There was severe swelling and ecchymosis in popliteal fossa and around the leg with significant calf tenderness and pedal edema. Tibialis posterior, dorsalis pedis, and popliteal arterial pulses were not palpable. Radiograph suggested minimally displaced tibial plateau fracture with no evidence of knee dislocation. The patient was taken up for emergency surgery after consultation with vascular surgeon. During the closed reduction external fixation and compartment decompression, popliteal artery trunk was found transected and end-to-end repair was performed. During the post-operational period, no complication was developed and the patient was followed-up for 1 year. At the one-year follow-up, he acquired good stability of his right knee with full range of motion.

Conclusion

Significant swelling and ecchymosis should alert the surgeons to the possibility of vascular injury in knee joint injury, even if there is no fracture or dislocation, or fracture is minimally displaced.
Determinants of surgeons’ adherence to preventive intraoperative measures of surgical site infection in Gaza Strip hospitals: a multi-centre cross-sectional study
Authors: Elshami Mohamedraed , Bottcher Bettina , Awadallah Issam , Alnaji Ahmed , Aljedaili Basel , Abu Sulttan Haytham , Hwaihi Mohamed
Published: January 2020

Background

Surgical site infection (SSI) is one of the most common hospital-acquired infections and is associated with serious impact on the rates of morbidity, mortality as well as healthcare costs. This study examined factors influencing the application of several intraoperative preventive measures of SSI by surgeons and surgical residents in the Gaza Strip.

Methods

A cross-sectional study was conducted from December 2016 to February 2017 at the operation rooms of the three major hospitals located in the Gaza-Strip, Palestine. Inclusion criteria for patients were being adult (aged ≥18 years), no history of wound infection at time of operation and surgical procedure under general anaesthesia with endotracheal intubation. The association between different patient- and procedure-related SSI risk factors and adherence to several intraoperative SSI preventive measures was tested.

Results

In total, 281 operations were observed. The mean patient age ± standard deviation (SD) was 38.4 ± 14.6 years and the mean duration of surgery ± SD was 58.2 ± 32.1 minutes. A hundred-thirty-two patients (47.0%) were male. Location and time of the operation were found to have significant associations with adherence to all SSI preventive measures except for antibiotic prophylaxis. Type of operation had a significant association with performing all measures except changing surgical instruments. Patient age did not have a statistically significant association with adherence to any measure.

Conclusion

The results suggest that the surgeon could be a major factor that can lead to a better outcome of surgical procedures by reducing postoperative complications of SSI. Operating department professionals would benefit from clinical guidance and continuous training, highlighting the importance of persistent implementation of SSI preventive measures in everyday practice to improve the quality of care provided to surgical patients.
Pancreatic abscess within hepato-gastric ligament: case report of an extremely rare disease
Authors: Bakshi Sabyasachi
Published: January 2020

Background

Pancreatic pseudocyst is a very common benign cystic lesion of the pancreas. It develops in 5–15% of patients with peri-pancreatic fluid collection following acute pancreatitis. Collection usually occurs within the lesser sac of the omentum (near the pancreatic head and body region). But in 20–22% cases, that may be extra-pancreatic like in the mediastinum, pleura, in the peritoneal cavity including the pelvis. The pancreatic pseudocyst typically contains brownish fluid with necrotic tissue sludge which may get infected giving rise to infected pseudocyst or pancreatic abscess. The present case is an unusual condition of a young alcoholic subject who was finally diagnosed as a case of a pancreatic abscess within hepato-gastric ligament and was managed with operative intervention.

To the best of the author’s knowledge, it is the first-ever reported case of a pancreatic abscess within the hepato-gastric ligament in the world. Literature was reviewed to explore potential etiopathogenesis and therapeutic strategies of this extremely rare condition.

Case presentation

A 38 years old gentleman, chronic alcoholic, having a previous history of acute pancreatitis 3 months back, presented with fever (102 degrees Fahrenheit) and a huge [20 cm (horizontal) X 15 cm (vertical)] severely painful swelling in the epigastric region. The swelling was round-shaped, intra-abdominal, fixed to deeper tissue, tense-cystic, poorly trans-illuminant, non-pulsatile and irreducible. Routine blood tests showed leucocytosis (14,500/mm3) with neutrophilia and elevated plasma pancreatic amylase and lipase levels. USG and MDCT scan of the whole abdomen revealed a thick-walled echogenic cystic swelling of size 18 cm × 12 cm in the epigastric region. USG guided aspiration of the cyst revealed mixed purulent brownish fluid. The cyst fluid was negative for mucin stain and contained high amylase level with low CEA level, suggesting infected pancreatic pseudocyst.

An open drainage procedure was considered through an upper midline laparotomy. Aspiration of the pus mixed cyst fluid along with tissue debris was done. Through irrigation of the cyst was done with normal saline. The cyst wall was de-roofed leaving a small part adherent to the inferior surface of the left lobe of the liver. Later the cyst fluid culture showed significant growth of Escherichia coli. He was put on IV antibiotics. The patient was discharged in a stable condition after 5 days. The histopathological examination confirmed pancreatic abscess.

Six months after the operation, the patient is doing well, remaining asymptomatic and there is no sign of recurrence.

Conclusions

Due to extreme rarity, pancreatic abscess formation within hepato-gastric ligament may be a diagnostic dilemma and requires a high index of suspicion. Surgeons should be aware of this rare clinical entity for prompt management of potential morbidity.
Vitamin D receptor genetic polymorphisms are associated with oral lichen planus susceptibility in a Chinese Han population
Authors: Shen Hong , Liu Qinglan , Huang Peng , Fan Haozhi , Zang Feng , Liu Mei , Zhuo Lingyun , Wu Jingjing , Wu Guoying , Yu Rongbin , Yang Jianrong
Published: January 2020

Background

Vitamin D receptor (VDR) is involved in multiple immune-mediated disorders including oral lichen planus (OLP). This study investigated the association between VDR gene polymorphisms and the risk of OLP.

Methods

In total, 177 OLP patients and 207 healthy participants were recruited from the Affiliated Hospital of Stomatology, Nanjing Medical University. Eight single nucleotide polymorphisms (SNPs: rs731236, rs739837, rs757343, rs2107301, rs2239185, rs7975232, rs11574129 and rs11568820) in the VDR gene were selected and genotyped.

Results

The results showed that OLP risk was increased in subjects with the rs2239185 TT genotype (Recessive model: adjusted Odd ratio(OR) = 2.68, 95% Confidence interval(CI) = 1.28–5.62, P = 0.009) and rs7975232 CC genotype (Recessive model: adjusted OR = 2.25, 95% CI = 1.10–4.58, P = 0.026). Moreover, rs2239185 and rs7975232 (P < 0.01) showed significant cumulative effects on OLP risk.Haplotype analysis showed that the CC haplotype (rs2239185-rs7975232) was associated with an increased risk of OLP (OR = 3.11, 95% CI = 1.42–6.83, P = 0.005), compared with the AC haplotype.

Conclusion: The rs2239185 and rs7975232 variants of VDR may influence OLP susceptibility, and VDR gene polymorphisms may be candidate susceptibility regions for OLP in a Chinese Han population.
Treatment of peri-invagination lesion and vitality preservation in an immature type III dens invaginatus: a case report
Authors: Lee Ju-Kyung , Hwang Jae Joon , Kim Hyeon-Cheol
Published: January 2020

Background

To report a case of type III dens invaginatus associated with peri-invagination periodontitis in an immature permanent mandibular central incisor with open apex, in which only the invagination area was treated and vitality was preserved.

Case presentation

A 9-year-old boy was referred complaining of pain in the mandibular left central incisor. After radiographic examination, an invagination into the pulp chamber of the tooth associated with periapical radiolucency was detected. Endodontic access was performed and the orifice was identified under a dental operating microscope. The invagination area was chemo-mechanically cleaned. After 1 week, the invagination was obturated with mineral trioxide aggregate. During the 2-year follow up period, the tooth was asymptomatic. Radiographic examination revealed significant progression of periapical healing and root development in the main root canal of the tooth.

Conclusion

Non-surgical root canal treatment of the invagination may preserve pulp vitality, and continuous root development of the tooth.
Substance P participates in periodontitis by upregulating HIF-1α and RANKL/OPG ratio
Authors: Yan Kaixian , Lin Qin , Tang Kailiang , Liu Shuang , Du Yi , Yu Xijiao , Li Shu
Published: January 2020

Background

Both substance P and hypoxia-inducible factor 1 alpha (HIF-1α) are involved in inflammation and angiogenesis. However, the relationship between substance P and HIF-1α in rat periodontitis is still unknown.

Methods

Ligation-induced rat periodontitis was established to observe the distribution and expression of substance P and HIF-1α by immunohistochemistry. Rat gingival fibroblasts were cultured and stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Recombinant substance P was applied to elaborate the relationship between substance P and HIF-1α in gingival fibroblasts in vitro. Primary mouse bone marrow-derived macrophages (BMMs) were isolated and cultured to observe the effect of substance P on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis by TRAP staining. Western blotting was used to investigate the expression of HIF-1α, osteoprotegerin (OPG) and RANKL.

Results

Rat experimental periodontitis was successfully established 6 weeks after ligation. Gingival inflammatory infiltration and alveolar bone loss were observed. Positive expression of substance P was found in the infiltrating cells. Higher HIF-1α levels were observed in periodontitis compared to that of normal tissues. Substance P upregulated the level of HIF-1α in gingival fibroblasts with or without 1 μg/ml LPS in vitro (*P < 0.05). Substance P upregulated the expression of HIF-1α in RANKL-stimulated BMMs in vitro. Substance P also increased the RANKL/OPG ratio in gingival fibroblasts (*P < 0.05). Both 10 nM and 50 nM substance P promoted RANKL-induced osteoclast differentiation (*P < 0.05).

Conclusion

Substance P participates in periodontitis by upregulating HIF-1α and the RANKL/OPG ratio.
Effects of lemon decoction on malaria parasite clearance and selected hematological parameters in Plasmodium berghei ANKA infected mice
Authors: Shija Kelvin M. , Nondo Ramadhani S. O. , Mloka Doreen , Sangeda Raphael Z. , Bwire George M.
Published: January 2020

Background

Citrus plants particularly lemon (Citrus limon L.) concoctions are ethno-medically used for treatment of infectious diseases including malaria. Therefore, we set an experiment to investigate the effects of lemon decoction in mice infected with Plasmodium berghei ANKA parasites.

Methods

Antimalarial activity was determined using Rane’s curative test on 25 Theiler’s albino mice. Twenty mice were each injected with 2 × 107 infected red blood cells (iRBCs). The mice were divided into four groups, consisting of five mice per group. Each group received an oral dose of either 5% carboxymethyl cellulose/placebo (negative infected control), lemon decoction (Citrus limon [CILI extract]) alone or a combination of artemether/lumefantrine (A/LU, 28 mg/kg) and CILI extract and A/LU alone. A fifth group of mice consisted of uninfected mice as parasite-negative control.

Results

Within 72 hours after initiation of treatment, the mean percentage parasitemia ± standard deviation of the CILI extract group (24.2% ± 9.83%) was lower compared to placebo group (40.0% ± 14.78%), p = 0.037. CILI extract group was found to have an increased survival rate (11 days ± 1.6 days) as compared to placebo group (8.6 days ± 3.4 days), p = 0.226. Mice in the combination group (A/LU + CILI extract) had the highest mean counts in terms of hemato-immunological parameters, whereas those in the CILI extract alone had the lowest hematocrit levels. The study also found that mice that received a combination of CILI extract and A/LU exhibited a decreased lag time with regards to time required to clear 99% of parasites (58.8 h vs. 64.2 h, p = 0.681) as compared to the A/LU alone group.

Conclusion

Lemon decoction demonstrated antimalarial activity in mice infected with P. berghei ANKA through parasites suppression by 39% as compared to those received placebo. However, when used alone, lemons did not suffice as a cure but in combination with standard antimalarials, lemons promoted early parasite clearance with an improved hematological parameters.
Assessment of medical professionalism: preliminary results of a qualitative study
Authors: Fong Warren , Kwan Yu Heng , Yoon Sungwon , Phang Jie Kie , Thumboo Julian , Leung Ying Ying , Ng Swee Cheng
Published: January 2020

Background

The importance of medical professionalism has been well documented in the literature. Cultural background affects the constituents of professionalism. However, few studies have explored the domains of medical professionalism in an Asian context. We aim to describe the views and experiences of both patients and faculty on medical professionalism in an urban Asian city state.

Methods

Data for this qualitative study were collected through focus group discussions (FGDs) with patients and in-depth interviews (IDIs) with faculty members. The IDIs and FGDs were audio-recorded and transcribed verbatim. Thematic analysis was conducted by two independent coders using a priori framework derived from Professionalism Mini Evaluation Exercise (P-MEX). Sociodemographic data of faculty members and patients were obtained through brief questionnaires.

Results

A total of 31 patients (58.1% male, all had visited healthcare facilities within the past year) and 26 faculty members (42.3% male, 38.5% from medical disciplines, median years as faculty is 11) participated in this study. The results supported the four domains of medical professionalism - Doctor-patient relationship skills, Reflective skills, Time management and Inter-professional relationship skills. Two new sub-domains which emerged from data were (1) communicated effectively with patient and (2) demonstrated collegiality.

Conclusions

The domains of professionalism in Singapore were similar to previous studies. This study allows a better understanding of medical professionalism to enhance the assessment and ultimately, the teaching of medical professionalism in an urban multi-ethnic Asian city.
Addressing harm in moral case deliberation: the views and experiences of facilitators
Authors: Spronk Benita , Widdershoven Guy , Alma Hans
Published: January 2020

Background

In healthcare practice, care providers are confronted with decisions they have to make, directly affecting patients and inevitably harmful. These decisions are tragic by nature. This study investigates the role of Moral Case Deliberation (MCD) in dealing with tragic situations. In MCD, caregivers reflect on real-life dilemmas, involving a choice between two ethical claims, both resulting in moral damage and harm. One element of the reflection process is making explicit the harm involved in the choice. How harmful are our decisions? We investigated how facilitators of MCD experience the importance of addressing harm in MCD and what participants learn from reflecting on harm.

Methods

The study was qualitative, focusing on the views and experiences of the facilitators of MCD. Semi-structured interviews (N = 12) were conducted with facilitators of MCD. The research focuses on the subjective experiences of facilitators. Grounded Theory was used for analysis.

Results

The results show two main categories. The first concerns the awareness of tragedy. Within this category, five themes were discerned: making explicit that there is no solution, visualizing consequences, uncovering pain, focusing on emotion, and exploring perspectives on harm. The second category concerns the support for healthcare professionals in dealing with the tragedy of the choices they face. In this category, five themes came forward: acknowledging, offering comfort, managing harm, consideration through dialogue and repairing harm.

Conclusion

Our study shows that addressing harm in MCD in tragic situations provides an important moral learning opportunity for participants. By formulating and becoming aware of harm, MCD aids healthcare professionals in the task they are faced with, namely making difficult and painful choices. MCD helps healthcare professionals to repair moral damage, making clear at the same time that harm cannot be undone.
Barriers and facilitators to the implementation of a community-based hypertension improvement project in Ghana: a qualitative study of ComHIP
Authors: Adler Alma J. , Laar Amos K. , Kotoh Agnes M. , Legido-Quigley Helena , Perel Pablo , Lamptey Peter , Lange Isabelle L.
Published: January 2020

Background

Globally, hypertension is a leading cause of cardiovascular disease and mortality, with the majority of deaths occurring in low- and middle-income countries. Because the burden of hypertension is increasing in low resource settings with restricted infrastructure, it is imperative that new models for hypertension care are realised. One such model is the Community-based Hypertension Improvement Project (ComHIP) which employs a community-based method of task-shifting for managing hypertension. This study is a qualitative analysis of the barriers and facilitators of the main components of ComHIP.

Methods

We purposively selected 55 informants for semi-structured interviews or focus group discussions, which were carried out bythree trained local researchers in Krobo, Twi or English. Informants included patients enrolled in ComHIP, health care providers and Licensed Chemical Sellers trained by ComHIP, and Ghana Health Service employees. Data were analysed using a multi-step thematic analysis.

Results

While results of the effectiveness of the intervention are pending, overall, patients and nurses reported positive experiences within ComHIP, and found that it helped enable them to manage their hypertension. Healthcare providers appreciated the additional training, but had some gaps in their knowledge. Ghana Health Service employees were cautiously optimistic about the programme, but expressed some worries about the sustainability of the programme. Many informants expressed concerns over the inability of community nurses and workers to dispense anti-hypertensives, due to legal restrictions.

Conclusions

The WHO recommends task-sharing as a technique for managing chronic conditions such as hypertension in resource constrained settings. ComHIP presents an example of a task-sharing programme with a high level of acceptability to all participants. Going forward, we recommend greater levels of communication and dialogue to allow community-based health workers to be allowed to dispense anti-hypertensives.
Frequency of thyroid function tests and examinations in participants of a population-based study
Authors: Kiel Simone , Ittermann Till , Völzke Henry , Chenot Jean-François , Angelow Aniela
Published: January 2020

Background

Thyroid disorders are common in the adult German population. Little is known about guideline implementation in clinical practice and the prevalence of diagnostic procedures in ambulatory care. The study aims to investigate the use of thyroid hormone measurements, thyroid ultrasound, thyroid scintiscan and associated costs in ambulatory care at population level.

Methods

Data were derived from two independent population-based cohorts of the Study of Health In Pomerania (SHIP). Ambulatory billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were individually linked for the period 2002–2016 with SHIP data. The main outcomes were the frequency of outpatient ultrasound, scintiscan, serum TSH level measurement, free triiodothyronine (fT3) and free thyroxine (fT4) measurement, TSH-receptor-antibodies and microsomal antibodies measurement within 1 year and 3 years prior to the study entrance of the participants. Multinomial logistic regression models were used to assess the association of age, sex, thyroid medication intake and Charlson-Comorbidity-Index with frequency of TSH measurements and ultrasound examinations.

Results

A total of 5552 participants (47% male, median age 55) were included in the analysis. 25% (1409/5552) had a diagnosed thyroid disorder or treatment, 40% (2191/5552) had clinical findings based on ultrasound or laboratory testing in SHIP only and 35% (1952/5552) neither a coded thyroid disorder or clinical finding nor thyroid medication. In the total study population 30% (1626/5552) received at least one TSH measurement, 6.8% (378/5552) at least one thyroid ultrasound and 2.6% (146/5552) at least one scintiscan within the past year before the study examination. Tests were performed more frequently in patients with thyroid medication and coded thyroid disorders. Hence, this group caused the highest expenditures.

Conclusions

Given the high prevalence of thyroid disorders, diagnostic and monitoring tests should be used rationally with regard to costs. TSH levels should be monitored regularly in patients on thyroid medication. A consensus on monitoring frequency and iteration of monitoring of morphological thyroid disorders with TSH and ultrasound and specific guideline recommendations are needed.

Trial registration

Versorgungsforschung Deutschland (VfD_17_003880).
Evaluation and facilitation of intervention fidelity in community exercise programs through an adaptation of the TIDier framework
Authors: Bird Marie-Louise , Mortenson William B. , Eng Janice J.
Published: January 2020

Background

Despite high quality evidence supporting multiple physical and cognitive benefits of community-based exercise for people after stroke, there is little understanding on how to facilitate uptake of these research findings to real-world programs. A common barrier is a lack of standardised training for community fitness instructors, which hampers the ability to train more instructors to deliver the program as it was designed. Scaling up program delivery, while maintaining program fidelity, is complex. The objective of this research is to explore novel use of the Template for Intervention Description and Replication (TIDier) framework to evaluate and support implementation fidelity of a community exercise program.

Methods

We embedded intervention fidelity evaluation into an inaugural training program for fitness instructors who were to deliver the Fitness and Mobility Exercise Program for stroke, which has established efficacy. The training program consisted of a face-to-face workshop followed by 3 worksite ‘audit and feedback coaching cycles’ provided over 3 iterations of the 12-week program offered over 1 year. A modified TIDIER checklist (with 2 additional criteria) was used within the training workshop to clarify the key ‘active ingredients’ that were required for program fidelity, and secondly as a basis for the audit and feedback process enabling the quantitative measurement of fidelity. Data were collected from audits of observed classes and from a survey provided by fitness instructors who implemented the program.

Results

We demonstrated the feasibility of the TIDier checklist to capture 14 essential items for implementation evaluation of a complex exercise intervention for people with chronic health conditions over 3 iterations of the program. Based on the audit tool, program fidelity was high and improved over time. Three content areas for workplace coaching (intensity monitoring, space, and educational tips) were identified from the audit tool and were addressed.

Conclusion

Training of staff to deliver exercises to high need populations utilising workshops and workplace coaching that used the TIDier framework for training, onsite audit and feedback resulted in a high level of fidelity to the program principles. A novel checklist based on the TIDier framework was useful for embedding implementation fidelity in complex community-based interventions.
Antioxidant defence and oxidative stress markers in cats with asymptomatic and symptomatic hypertrophic cardiomyopathy: a pilot study
Authors: Michałek Marcin , Tabiś Aleksandra , Pasławska Urszula , Noszczyk-Nowak Agnieszka
Published: January 2020

Background

Hypertrophic cardiomyopathy is the most common cardiovascular cause of death in cats. Although the majority of cats remain asymptomatic, some may develop signs of chronic heart failure due to diastolic failure, arterial thromboembolism (ATE) or sudden cardiac death. Therefore, it is crucial to identify individuals that are in high risk of developing cardiac complications before the onset of life-threatening signs. Oxidative stress is the imbalance between the production and neutralisation of reactive oxygen species. Uncontrolled reactive oxygen species overproduction leads to protein and lipid peroxidation and damages the DNA strands, injuring the cells and leading to their death. The aim of the study was to evaluate the oxidative state in cats with hypertrophic cardiomyopathy and healthy controls.

Results

In total, 30 cats divided into three groups were assessed: animals with clinically evident hypertrophic cardiomyopathy (HCM;n = 8), subclinical hypertrophic cardiomyopathy (SUB-HCM;n = 11) and healthy controls (n = 11). The activity of superoxide dismutase was statistically significantly lower in animals with symptomatic and asymptomatic hypertrophic cardiomyopathy (HCM 0.99 ± 0.35 U/mL; SUB-HCM 1.39 ± 0.4 U/mL) compared to healthy cats (2.07 ± 0.76 U/mL,p < 0.01). The activity of catalase was significantly lower in the SUB-HCM group (19.4 ± 4.2 nmol/min/mL) compared to the HCM (23.6 ± 5.9 nmol/min/mL) and the control (30 ± 7.5 nmol/min/mL,p < 0.01) group. The activity of glutathione peroxidase was 4196 ± 353 nmol/min/mL in the HCM group, 4331 ± 451 nmol/min/mL in the SUB-HCM group and 4037 ± 341 nmol/min/mL in the control group and did not differ significantly between groups. The total antioxidant capacity of plasma was 602 ± 65.5 copper reducing equivalents (CRE) in the HCM group, 605.9 ± 39.9 CRE in the SUB-HCM group and 629 ± 77.5 CRE in the healthy cats and did not differ significantly between the groups.

Conclusions

Activities of superoxide dismutase and catalase differed in cats with hypertrophic cardiomyopathy, however the activity of the latter was only significantly lower in asymptomatic stage of the disease. The potentially beneficial effect of antioxidative substances on the disease progression in the asymptomatic and symptomatic stage of this disease should also be examined.
Periostin plays a critical role in the cell cycle in lung fibroblasts
Authors: Yoshihara Tomohito , Nanri Yasuhiro , Nunomura Satoshi , Yamaguchi Yukie , Feghali-Bostwick Carol , Ajito Keiichi , Murakami Shoichi , Mawatari Masaaki , Izuhara Kenji
Published: January 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a median survival of only three to 5 years. Fibroblast proliferation is a hallmark of IPF as is secretion of extracellular matrix proteins from fibroblasts. However, it is still uncertain how IPF fibroblasts acquire the ability to progressively proliferate. Periostin is a matricellular protein highly expressed in the lung tissues of IPF patients, playing a critical role in the pathogenesis of pulmonary fibrosis. However, it remains undetermined whether periostin affects lung fibroblast proliferation.

Methods

In this study, we first aimed at identifying periostin-dependently expressed genes in lung fibroblasts using DNA microarrays. We then examined whether expression of cyclins and CDKs controlling cell cycle progression occur in a periostin-dependent manner. We next examined whether downregulation of cell proliferation-promoting genes by knockdown of periostin or integrin, a periostin receptor, using siRNA, is reflected in the cell proliferation of lung fibroblasts. We then looked at whether lung fibroblasts derived from IPF patients also require periostin for maximum proliferation. We finally investigated whether CP4715, a potent inhibitor against integrin αVβ3(a periostin receptor), which we have recently found blocks TGF-β signaling, followed by reduced BLM-induced pulmonary fibrosis in mice, can block proliferation of lung fibroblasts derived from IPF patients.

Results

Many cell-cycle–related genes are involved in the upregulated or downregulated genes by periostin knockdown. We confirmed that in lung fibroblasts, periostin silencing downregulates expression of several cell-cycle–related molecules, including the cyclin, CDK, and, E2F families, as well as transcription factors such as B-MYB and FOXM1. Periostin or integrin silencing slowed proliferation of lung fibroblasts and periostin silencing increased the distribution of the G0/G1 phase, whereas the distribution of the G2/M phase was decreased. Lung fibroblasts derived from IPF patients also required periostin for maximum proliferation. Moreover, CP4715 downregulated proliferation along with expression of cell-cycle–related genes in IPF lung fibroblasts as well as in normal lung fibroblasts.

Conclusions

Periostin plays a critical role in the proliferation of lung fibroblasts and the present results provide us a solid basis for considering inhibitors of the periostin/integrin αVβ3interaction for the treatment of IPF patients.
Polygenic risk for coronary heart disease acts through atherosclerosis in type 2 diabetes
Authors: Lu Tianyuan , Forgetta Vincenzo , Yu Oriana H. Y. , Mokry Lauren , Gregory Madeline , Thanassoulis George , Greenwood Celia M. T. , Richards J. Brent
Published: January 2020

Background

Type 2 diabetes increases the risk of coronary heart disease (CHD), yet the mechanisms involved remain poorly described. Polygenic risk scores (PRS) provide an opportunity to understand risk factors since they reflect etiologic pathways from the entire genome. We therefore tested whether a PRS for CHD influenced risk of CHD in individuals with type 2 diabetes and which risk factors were associated with this PRS.

Methods

We tested the association of a CHD PRS with CHD and its traditional clinical risk factors amongst individuals with type 2 diabetes in UK Biobank (N = 21,102). We next tested the association of the CHD PRS with atherosclerotic burden in a cohort of 352 genome-wide genotyped participants with type 2 diabetes who had undergone coronary angiograms.

Results

In the UK Biobank we found that the CHD PRS was strongly associated with CHD amongst individuals with type 2 diabetes (OR per standard deviation increase = 1.50; p = 1.5 × 10− 59). But this CHD PRS was, at best, only weakly associated with traditional clinical risk factors, such as hypertension, hyperlipidemia, glycemic control, obesity and smoking. Conversely, in the angiographic cohort, the CHD PRS was strongly associated with multivessel stenosis (OR = 1.65; p = 4.9 × 10− 4) and increased number of major stenotic lesions (OR = 1.35; p = 9.4 × 10− 3).

Conclusions

Polygenic predisposition to CHD is strongly associated with atherosclerotic burden in individuals with type 2 diabetes and this effect is largely independent of traditional clinical risk factors. This suggests that genetic risk for CHD acts through atherosclerosis with little effect on most traditional risk factors, providing the opportunity to explore new biological pathways.
The effects of external Mn2+ concentration on hyphal morphology and citric acid production are mediated primarily by the NRAMP-family transporter DmtA in Aspergillus niger
Authors: Fejes Balázs , Ouedraogo Jean-Paul , Fekete Erzsébet , Sándor Erzsébet , Flipphi Michel , Soós Áron , Molnár Ákos P. , Kovács Béla , Kubicek Christian P. , Tsang Adrian , Karaffa Levente
Published: January 2020

Background

Citric acid, a commodity product of industrial biotechnology, is produced by fermentation of the filamentous fungus Aspergillus niger. A requirement for high-yield citric acid production is keeping the concentration of Mn2+ ions in the medium at or below 5 µg L−1. Understanding manganese metabolism in A. niger is therefore of critical importance to citric acid production. To this end, we investigated transport of Mn2+ ions in A. niger NRRL2270.

Results

we identified an A. niger gene (dmtA; NRRL3_07789), predicted to encode a transmembrane protein, with high sequence identity to the yeast manganese transporters Smf1p and Smf2p. Deletion of dmtA in A. niger eliminated the intake of Mn2+ at low (5 µg L−1) external Mn2+ concentration, and reduced the intake of Mn2+ at high (> 100 µg L−1) external Mn2+ concentration. Compared to the parent strain, overexpression of dmtA increased Mn2+ intake at both low and high external Mn2+ concentrations. Cultivation of the parent strain under Mn2+ ions limitation conditions (5 µg L−1) reduced germination and led to the formation of stubby, swollen hyphae that formed compact pellets. Deletion of dmtA caused defects in germination and hyphal morphology even in the presence of 100 µg L−1 Mn2+, while overexpression of dmtA led to enhanced germination and normal hyphal morphology at limiting Mn2+ concentration. Growth of both the parent and the deletion strains under citric acid producing conditions resulted in molar yields (Yp/s) of citric acid of > 0.8, although the deletion strain produced ~ 30% less biomass. This yield was reduced only by 20% in the presence of 100 µg L−1 Mn2+, whereas production by the parent strain was reduced by 60%. The Yp/s of the overexpressing strain was 17% of that of the parent strain, irrespective of the concentrations of external Mn2+.

Conclusions

Our results demonstrate that dmtA is physiologically important in the transport of Mn2+ ions in A. niger, and manipulation of its expression modulates citric acid overflow.
ALKBH5-mediated m6A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma
Authors: Chen Shuo , Zhou Liwu , Wang Yang
Published: January 2020

Background

Osteosarcoma (OS) is one of the most common malignant bone tumors. Plasmacytoma variant translocation 1 (PVT1) is a well-known oncogenic long noncoding RNA (lncRNA). However, to date, the regulatory mechanism of PVT1 upregulation in OS remains unknown.

Methods

qRT-PCR was carried out to test the expression level of PVT1 and ALKBH5. RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to detect the interaction of PVT1 with ALKBH5 and YTHDF2. Methylated RNA immune-precipitation (MeRIP) was used to examine the N6-methyladenosine (m6A) modification of PVT1 transcript.

Results

In this study, we found that PVT1 expression was upregulated in OS tissues and cells and significantly related with clinical stage, tumor size, and prognosis of patients with OS. Further investigation revealed that N6-methyladenosine (m6A) demethylase ALKBH5 could associate with PVT1 and suppress its degradation. ALKBH5 decreased the m6A modification of PVT1, thus inhibiting the binding of reader protein YTHDF2 in PVT1. Functionally, ALKBH5-mediated PVT1 upregulation promoted the OS cell proliferation in vitro and tumor growth in vivo.

Conclusions

Our study suggests that ALKBH5-mediated m6A modification of PVT1 contributes to OS tumorigenesis.
Baicalin reverses radioresistance in nasopharyngeal carcinoma by downregulating autophagy
Authors: Wang Cong , Yang Yinli , Sun Lining , Wang Jing , Jiang Zhansheng , Li Yanwei , Liu Dongying , Sun Haiyan , Pan Zhanyu
Published: January 2020

Background

Radiation resistance is the main cause of recurrence after radiotherapy, and increased autophagy after radiotherapy is related to radiotherapy resistance. This study aims to investigate the reversal effect of baicalin on radioresistance and its related mechanism.

Methods

CCK-8 and flow cytometry were used to detect the effect of proliferation and apoptosis by baicalin. Clone formation test was used to verify the effect of baicalin radiosensitization. Western blot analysis and electron microscopy were employed to observe the effect of baicalin on autophagy.

Results

Compared with the radiation therapy (RT) group, the RT combined baicalin (RT + BA) group showed a significantly low 2 Gy survival fraction of radiation therapy (P < 0.05). LC3-II protein expression in the RT group was significantly higher than which in the RT + BA group (P < 0.05). Electron microscopy showed that more autophagic vacuoles were observed in the RT group than those in the RT + BA group.

Conclusions

Overall, baicalin can reverse the radioresistance of human nasopharyngeal carcinoma CNE-2R cells by downregulating RT-enhanced autophagy.
A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products
Authors: Li Keke , Zhao Shuang , Long Jing , Su Juan , Wu Lisha , Tao Juan , Zhou Jianda , Zhang JiangLin , Chen Xiang , Peng Cong
Published: January 2020

Background

Melanoma is one of the most aggressive tumors with the remarkable characteristic of resistance to traditional chemotherapy and radiotherapy. Although targeted therapy and immunotherapy benefit advanced melanoma patient treatment, BRAFi (BRAF inhibitor) resistance and the lower response rates or severe side effects of immunotherapy have been observed, therefore, it is necessary to develop novel inhibitors for melanoma treatment.

Methods

We detected the cell proliferation of lj-1-59 in different melanoma cells by CCK 8 and colony formation assay. To further explore the mechanisms of lj-1-59 in melanoma, we performed RNA sequencing to discover the pathway of differential gene enrichment. Western blot and Q-RT-PCR were confirmed to study the function of lj-1-59 in melanoma.

Results

We found that lj-1-59 inhibits melanoma cell proliferation in vitro and in vivo, induces cell cycle arrest at the G2/M phase and promotes apoptosis in melanoma cell lines. Furthermore, RNA-Seq was performed to study alterations in gene expression profiles after treatment with lj-1-59 in melanoma cells, revealing that this compound regulates various pathways, such as DNA replication, P53, apoptosis and the cell cycle. Additionally, we validated the effect of lj-1-59 on key gene expression alterations by Q-RT-PCR. Our findings showed that lj-1-59 significantly increases ROS (reactive oxygen species) products, leading to DNA toxicity in melanoma cell lines. Moreover, lj-1-59 increases ROS levels in BRAFi -resistant melanoma cells, leading to DNA damage, which caused G2/M phase arrest and apoptosis.

Conclusions

Taken together, we found that lj-1-59 treatment inhibits melanoma cell growth by inducing apoptosis and DNA damage through increased ROS levels, suggesting that this compound is a potential therapeutic drug for melanoma treatment.
Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy
Authors: Ren Daixi , Hua Yuze , Yu Boyao , Ye Xin , He Ziheng , Li Chunwei , Wang Jie , Mo Yongzhen , Wei Xiaoxu , Chen Yunhua , Zhou Yujuan , Liao Qianjin , Wang Hui , Xiang Bo , Zhou Ming , Li Xiaoling , Li Guiyuan , Li Yong , Zeng Zhaoyang , Xiong Wei
Published: January 2020

Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.
Application of antigen presenting cell-targeted nanovaccine delivery system in rhabdovirus disease prophylactics using fish as a model organism
Authors: Zhang Chen , Wang Gao-Xue , Zhu Bin
Published: January 2020

Background

Targeted delivery of virus-associated antigens to professional antigen-presenting cells (APCs) is considered as an efficient strategy to enhance the pyrophytic effect of vaccines against rhabdovirus disease.

Materials and methods

In this study, we constructed a targeted carbon nanotubes-based vaccine deliver system (SWCNTs-MG) which can recognize the signature receptor (mannose) of APCs. An environmentally and economically important disease called spring viremia of carp (SVC) was studied as a model to evaluate the feasibility of single-walled carbon nanotubes (SWCNTs) conjugated with mannosylated antigen for rhabdovirus prevention.

Results

Results showed that SWCNTs-MG could cross into fish body and present to internal immune-related tissues through gill, muscle and intestine within 6 h immersed vaccination. With further modification of mannose moiety, the obtained nanovaccine showed enhanced uptake by carp macrophages and immune-related tissues, which would then trigger strong immune responses against spring viremia of carp virus (SVCV) infection. Moreover, the survival rate of fish vaccinated with SWCNTs-MG (30 mg/L) was 63.5% after SVCV infection, whereas it was 0% for the control group.

Conclusion

This study not only provide a theoretical basis and research template for the application of targeted nanovaccine system in aquatic animals, but also play an important role in supporting development of healthy aquaculture and ensuring the safety of aquatic products and ecology.