bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors of recurrent erysipelas in adult Chinese patients: a prospective cohort study
Authors: Li Ang , Wang Ni , Ge Lingzhi , Xin Hongyan , Li Wenfei
Published: January 2021

Background

Erysipelas is a common skin infection that is prone to recur. Recurrent erysipelas has a severe effect on the quality of life of patients. The present study aimed to investigate the risk factors of recurrent erysipelas in adult Chinese patients.

Methods

A total of 428 Chinese patients with erysipelas who met the inclusion criteria were studied. The patients were divided into the nonrecurrent erysipelas group and the recurrent erysipelas group. Clinical data were collected on the first episode and relapse of erysipelas. The patients were followed up every 3 months. Statistical analysis was performed to analyze and determine the risk factors of erysipelas relapse.

Results

Univariate analysis was performed to analyze the data, including surgery, types of antibiotics administered in the first episode, obesity, diabetes mellitus, venous insufficiency, lymphedema, and malignancy. The differences between the groups were statistically significant (p < 0.05). The Cox proportional hazards regression model analysis showed that the final risk factors included surgery, obesity, diabetes mellitus, venous insufficiency, and lymphedema.

Conclusions

Surgery, obesity, diabetes mellitus, venous insufficiency, and lymphedema are considered as risk factors for recurrent erysipelas.
Septic shock due to Yersinia pseudotuberculosis infection in an adult immunocompetent patient: a case report and literature review
Authors: Hashimoto Takehiro , Takenaka Ryuichi , Fukuda Haruka , Hashinaga Kazuhiko , Nureki Shin-ichi , Hayashidani Hideki , Sakamoto Teruo , Shigemitsu Osamu
Published: January 2021

Background

Yersinia pseudotuberculosis infection can occur in an immunocompromised host. Although rare, bacteremia due to Y. pseudotuberculosis may also occur in immunocompetent hosts. The prognosis and therapeutic strategy, especially for immunocompetent patients with Y. pseudotuberculosis bacteremia, however, remains unknown.

Case presentation

A 38-year-old Japanese man with a mood disorder presented to our hospital with fever and diarrhea. Chest computed tomography revealed consolidation in the right upper lobe with air bronchograms. He was diagnosed with pneumonia, and treatment with intravenous ceftriaxone and azithromycin was initiated. The ceftriaxone was replaced with doripenem and the azithromycin was discontinued following the detection of Gram-negative rod bacteria in 2 sets of blood culture tests. The isolated Gram-negative rod bacteria were confirmed to be Y. pseudotuberculosis. Thereafter, he developed septic shock. Doripenem was switched to cefmetazole, which was continued for 14 days. He recovered without relapse.

Conclusions

We herein report a case of septic shock due to Y. pseudotuberculosis infection in an adult immunocompetent patient. The appropriate microorganism tests and antibiotic therapy are necessary to treat patients with Y. pseudotuberculosis bacteremia.
Non-surgical treatment of tetanus infection associated with breast cancer skin ulcer: a case report and literature review
Authors: Nomura Kazuhito , Sakawaki Eiji , Sakawaki Sonoko , Yamaoka Ayumu , Aisaka Wakiko , Okamoto Hiroyuki , Takeyama Yoshihiro , Uemura Shuji , Narimatsu Eichi
Published: January 2021

Background

Previous studies have reported poor prognosis in cases of tetanus that develops after bacteria enters via breast cancer-related skin ulcers that are not treated with surgical debridement. Herein, we review the literature concerning this presentation and report the first case of complete remission from tetanus without surgical debridement of the skin ulcer.

Case presentation

An Asian woman aged over 60 years had a history of skin ulcer caused by breast cancer. She was diagnosed with tetanus due to trismus and opisthotonus. Based on the suspicion that the skin ulcer was the portal of entry for tetanus bacteria, we considered several debridement and thoracic surgical options for tetanus treatment. However, debridement was not performed as the surgery was considered high risk and the patient did not consent to it. The patient received treatment with anti-tetanus globulin and metronidazole; sound insulation and shielding were also performed in a dark room. Subsequently, the patient’s symptoms improved, and sound insulation and deep sedation management were completed on 19th day of hospitalization. With no symptom recurrence, the patient was discharged on Day 54. To date, over 3 years after treatment, no evidence of tetanus recurrence has been observed. The case was characterized by a lack of autonomic hyperactivity. The tetanus severity was likely representative of the low amount of toxin that the patient was exposed to.

Conclusion

This case involved moderate severity tetanus originating from a chronic skin ulcer related to breast cancer. The patient survived without undergoing extensive debridement. No evidence of tetanus relapse was observed during the follow-up period, likely due to vaccination that might have restored the patient’s active immunity. Debridement is not always necessary for tetanus complicated by breast cancer skin ulcers. Furthermore, appropriate toxoid vaccination is critical for preventing the onset and recurrence of tetanus in these patients.
Association between colic and sleep problems in infancy and subsequent development, emotional and behavioral problems: a longitudinal study
Authors: Valla Lisbeth , Småstuen Milada Cvancarova , Andenæs Randi , Misvær Nina , Olbjørn Christine , Helseth Sølvi
Published: January 2021

Background

Sleep and colic problems in infancy have been linked to adverse health outcome, but there is limited knowledge of the association between sleep and colic problems in infancy and subsequent development, emotional and behavior problems in young children. The aim of the present study was to examine whether there is an associations between infants’ crying and sleep problems at 6 months and behavioral and development problems at 18 months, 3 and 5 years.

Methods

This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa), conducted at the Norwegian Institute of Public Health from June 1999 to December 2008. A total of 86,724 children were included. Colic and sleep (sleep duration, nocturnal awakenings and easy to put to bed) was assessed by mother-reports. Z-scores were used to assess differences between groups of children (e.g. having colic or not, having a sleep problem or not). Emotional and behavioral problems were measured with items from the Child Behavior Checklist. Development problems were measured with items from The Ages and Stages Questionnaire.

Results

Infants with colic scored significantly lower on development at 5 years (B=-0.10, CI [− 0.14 to - 0.06]) and higher on internalizing problems both at 3 years (B=0.15. CI [0.11 to 0.18]) and 5 years (B=0.17. CI [0.12 to 0.21]) than the reference population. Children who awoke frequently and were more difficult to put to bed at 6 months scored significantly lower on development at 18 months and 3 and 5 years, and higher on internalizing behavior problems at 3 and 5 years (B=0.18 and B=0.16). Children with shorter sleep duration at 6 months had more internalizing behavior problems at 3 years (B=0.14. CI [0.07 to 0.21]) and 5 years (B=0.15. CI [0.05 to 0.25]) than the reference population.

Conclusions

Colic and sleep problems early in life should be taken into account as risk factors for development and behavioral problems within the first 5 years of a child’s life.
Self-reported sleep bruxism is associated with vitamin D deficiency and low dietary calcium intake: a case-control study
Authors: Alkhatatbeh Mohammad J. , Hmoud Zainab L. , Abdul-Razzak Khalid K. , Alem Esam M.
Published: January 2021

Background

Sleep bruxism may result in deleterious effects including loss of tooth enamel,
fracture of teeth or restorations, teeth hypersensitivity or pain, and headache. The aim was to study the link between sleep bruxism, low serum vitamin D, low consumption of dietary calcium, psychological symptoms, and frequent headache.

Methods

This case-controlled study included 50 individuals with sleep bruxism and 50 age and gender matched controls. 25-hydroxyvitamin D was measured in serum. Hospital Anxiety and Depression Scale was used to measure anxiety and depression. Data about dietary calcium and frequent headache were self-reported.

Results

Participants with sleep bruxism had lower 25-hydroxyvitamin D and higher scores of anxiety and depression compared to controls (p < 0.05). Vitamin D deficiency, abnormal scores of anxiety and depression, low calcium consumption (< 323 mg/day), and frequent headache were reported in higher % of individuals with sleep bruxism compared to controls (p < 0.05). Binary logistic regression showed that sleep bruxism was significantly associated with vitamin D deficiency (OR = 6.66, p = 0.02), low consumption of dietary calcium (OR = 5.94, p = 0.01), and frequent headache (OR = 9.24, p < 0.001). Multiple linear regression showed that anxiety was significantly associated with decreased 25-hydroxyvitamin D (p = 0.03), increased scores of depression (p < 0.001) and female sex (p = 0.01). Binary logistic regression also showed that frequent headache was significantly associated with sleep bruxism (OR = 5.51, p < 0.01).

Conclusions

Sleep bruxism was associated with vitamin D deficiency and low consumption of calcium and was also associated with increased scores of anxiety and depression. Further investigations should be performed to check if vitamin D and calcium supplementation could relieve sleep bruxism.
Anti-inflammatory and antitumor activities of the chloroform extract and anti-inflammatory effect of the three diterpenes isolated from Salvia ballotiflora Benth
Authors: Campos-Xolalpa Nimsi , Alonso-Castro Ángel Josabad , Ortíz-Sanchez Elizabeth , Zapata-Morales Juan Ramon , González-Chávez Marco Martin , Pérez Salud
Published: January 2021

Background

Drugs used for the treatment of diseases associated with chronic inflammation, such as cancer and rheumatoid arthritis have the potential to cause undesirable side-effects, which might result in patients ending treatment prematurely. However, plants are a viable option for the treatment of inflammatory diseases. In this study, we assessed the in vivo and in vitro anti-inflammatory activity, and the antitumor effects of the chloroform extract of Salvia ballotiflora (ECL). The pro-apoptotic effects of ECL in CT26 cells were also determined.

Methods

The chloroform extract of Salvia ballotiflora (ECL) was standardized using 19-deoxyicetexone (DEOX) as a phytochemical marker. The anti-inflammatory activity of ECL was determined on acute and chronic inflammatory models using the TPA-induced mouse ear edema assay. The antitumor activity of ECL was evaluated by the subcutaneous inoculation of CT26 cells on the back of Balb/c mice. In vitro CT26 cell death induced by ECL was determined by Annexin V/propidium iodide staining assay using flow cytometry. ECL and the diterpenes isolated from the chloroform extract included 19-deoxyicetexone (DEOX), icetexone (ICT), and 7,20-dihydroanastomosine (DAM), which were tested in LPS-stimulated J774A.1 macrophages to quantify pro-inflammatory cytokine levels. The in vitro anti-arthritic activity of ECL was determined using the bovine serum protein (BSP) denaturation assay.

Results

ECL exerted anti-inflammatory activities in acute (84% of inhibition, 2 mg/ear) and chronic models (62.71%, at 100 mg/kg). ECL showed antitumor activity at 200 mg/kg and 300 mg/kg, reducing tumor volume by 30 and 40%, respectively. ECL (9.5 μg/mL) induced in vitro apoptosis in CT26 cells by 29.1% (48 h of treatment) and 93.9% (72 h of treatment). ECL (10 μg/ml) decreased levels of NO (53.7%), pro-inflammatory cytokines IL-6 (44.9%), IL-1β (71.9%), and TNF-α (40.1%), but increased the production of the anti-inflammatory cytokine IL-10 (44%). The diterpenes DEOX, ICT, and DAM decreased levels of NO (38.34, 47.63, 67.15%), IL-6 (57.84, 60.45, 44.26%), and TNF-α (38.90, 31.30, 32.83%), respectively. ECL showed in vitro antiarthritic activity (IC50 = 482.65 μg/mL).

Conclusions

ECL exhibited anti-inflammatory and anti-tumor activities. Furthermore, the diterpenes DEOX, DAM, and ICT showed anti-inflammatory activity by reducing levels of NO, TNF-α, and IL-6.
Vochysia tucanorum Mart. butanol fraction presents antitumoral activity in vivo and prevents the installation of cachexia in solid Ehrlich tumor model
Authors: Morgan Henrique Jorge Novaes , Delgado Aislan Quintiliano , Saldanha Luiz Leonardo , Camaforte Nathalia Aparecida De Paula , Dokkedal Anne Lígia , Bosqueiro José Roberto
Published: January 2021

Background

Cancer is a multifactorial disease caused by uncontrolled proliferation of cells. About 50–80% of cancer patients develop cachexia, a complex metabolic syndrome associated with an increase of mortality and morbidity. However, there are no effective therapies in medical clinic for cancer cachexia. Vochysia tucanorum Mart. is a common three of the Brazilian “Cerrado”. The butanolic fraction of V. tucanorum (Fr-BuVt), very rich in triterpenes with various biological activities, might be interesting in being tested in cancer cachexia syndrome. Hence, the present study was undertaken to investigate the antitumoral activity of Fr-BuVt and its potential against cachexia development.

Methods

Ehrlich tumor was used as model of cancer cachexia. Ascitic Ehrlich tumor cells were collected, processed and inoculated subcutaneously in saline solution (1 × 107/100 μl; ≥95% viability) for the obtention of solid Ehrlich carcinoma. After inoculation, solid Ehrlich carcinoma-bearing mice were treated by 14 consecutive days by gavage with Fr-BuVt (200 mg/kg). Body weight and tumor volume were measure during the treatment period. Tumors were removed, weighed and properly processed to measure the content and phosphorylation levels of key-proteins involved to apoptotic and proliferation process by Western Blot. Muscles and adipose tissues were removed for weighed. Serum was collected to cytokines levels and energetic blood markers measurements.

Results

The treatment with the Fr-BuVt (200 mg/kg, 14 days) decreased the solid Ehrlich tumor volume and weight besides increased the expression of the pro-apoptotic proteins caspase-3 and BAX, but also decreased the expression of the proteins involved in proliferation NFκB, mTOR and ERK. In addition, our data shows that the administration of Fr-BuVt was able to prevent the installation of cancer cachexia in Ehrlich carcinoma-bearing mice, since prevented the loss of body weight, as well as the loss of muscle and adipose tissue. Moreover, an improvement in some blood parameters such as decrease in cytokines TNF-α and IL-6 levels is observed.

Conclusions

The study revealed that Fr-BuVt has antitumoral activity and prevent installation of cancer cachexia in Ehrlich model. Therefore, Fr-BuVt may represent an alternative treatment for cancer cachexia.
Using Lean Six Sigma techniques to improve efficiency in outpatient ophthalmology clinics
Authors: Kam Andrew W. , Collins Scott , Park Tae , Mihail Michael , Stanaway Fiona F. , Lewis Noni L. , Polya Daniel , Fraser-Bell Samantha , Roberts Timothy V. , Smith James E.H.
Published: January 2021

Background

Increasing patient numbers, complexity of patient management, and healthcare resource limitations have resulted in prolonged patient wait times, decreased quality of service, and decreased patient satisfaction in many outpatient services worldwide. This study investigated the impact of Lean Six Sigma, a service improvement methodology originally from manufacturing, in reducing patient wait times and increasing service capacity in a publicly-funded, tertiary referral outpatient ophthalmology clinic.

Methods

This quality improvement study compared results from two five-months audits of operational data pre- and post-implementation of Lean Six Sigma. A baseline audit was conducted to determine duration and variability of patient in-clinic time and number of patients seen per clinic session. Staff interviews and a time-in-motion study were conducted to identify issues reducing clinic service efficiency. Solutions were developed to address these root causes including: clinic schedule amendments, creation of dedicated postoperative clinics, and clear documentation templates. A post-implementation audit was conducted, and the results compared with baseline audit data. Significant differences in patient in-clinic time pre- and post-solution implementation were assessed using Mann-Whitney test. Differences in variability of patient in-clinic times were assessed using Brown-Forsythe test. Differences in numbers of patients seen per clinic session were assessed using Student’s t-test.

Results

During the baseline audit period, 19.4 patients were seen per 240-minute clinic session. Median patient in-clinic time was 131 minutes with an interquartile range of 133 minutes (84–217 minutes, quartile 1- quartile 3). Targeted low/negligible cost solutions were implemented to reduce in-clinic times. During the post-implementation audit period, the number of patients seen per session increased 9% to 21.1 (p = 0.016). There was significant reduction in duration (p < 0.001) and variability (p < 0.001) of patient in-clinic time (median 107 minutes, interquartile range 91 minutes [71–162 minutes]).

Conclusions

Lean Six Sigma techniques may be used to reduce duration and variability of patient in-clinic time and increase service capacity in outpatient ophthalmology clinics without additional resource input.
Gastrointestinal ultrasonographic findings in cats with Feline panleukopenia: a case series
Authors: Isaya Rosaria , Ciccarelli Stefano , Enache Daniela , Specchi Swan , Pesaresi Marco , Ferri Filippo , Porporato Federico , Auriemma Edoardo , Contiero Barbara , Coppola Luigi M , Zini Eric
Published: January 2021

Background

Feline panleukopenia virus (FPV) is very resistant and highly contagious and infects domestic cats and other felids. FPV is particularly widespread among sheltered cats, and is associated with high morbidity and mortality, causing severe gastroenteritis characterized by anorexia, lethargy, fever, dehydration, hemorrhagic diarrhea, and vomiting. There is currently no data on the ultrasonographic features of cats affected with FPV. This case series describes abdominal ultrasonographic findings in shelter cats with naturally-occurring FPV, and assesses whether are associated with clinical and laboratory findings. Cats affected by FPV were enrolled in the study if an abdominal ultrasound was performed within 12 hours of diagnosis. Clinical, laboratory and survival data were collected from medical records. Ultrasonographic examinations were reviewed for gastrointestinal abnormalities and their associations with the above data were explored.

Results

Twenty-one cats were included. Nine cats (42.9%) died and 12 (57.1%) recovered. Based on ultrasonography, the duodenum and jejunum showed thinning of the mucosal layer in 70.6% and 66.6% of cats, thickening of the muscular layer in 52.9% and 57.1% of cats, and hyperechogenicity of the mucosa in 41.2% and 33.3%. Jejunal hyperechoic mucosal band paralleling the submucosa and irregular luminal surface were both observed in 33.3% of the cats. Survival was positively associated with increased jejunal mucosal echogenicity (P = 0.003) and hyperechoic mucosal band (P = 0.003). Peritoneal free fluid was positively associated with vomiting (P = 0.002).

Conclusions

This study provides ultrasonographic features of naturally-occurring FPV in cats, which, as expected, are compatible with gastroenteropathy. The most frequent findings were diffuse small intestine mucosal layer thinning, muscular layer thickening and mucosal hyperechogenicity, jejunal hyperechoic mucosal band and irregular luminal surface. Ultrasonographic features may be useful to complete the clinical picture and assess the severity of the gastroenteropathy in FPV cats. Prospective studies are needed to confirm ultrasonographic prognostic factors.
Effect of host breeds on gut microbiome and serum metabolome in meat rabbits
Authors: Ye Xiaoxing , Zhou Liwen , Zhang Yao , Xue Shuaishuai , Gan Qian Fu , Fang Shaoming
Published: January 2021

Background

Gut microbial compositional and functional variation can affect health and production performance of farm animals. Analysing metabolites in biological samples provides information on the basic mechanisms that affect the well-being and production traits in farm animals. However, the extent to which host breeds affect the gut microbiome and serum metabolome in meat rabbits is still unknown. In this study, the differences in phylogenetic composition and functional capacities of gut microbiota in two commercial rabbit breeds Elco and Ira were determined by 16S rRNA gene and metagenomic sequencing. The alternations in serum metabolome in the two rabbit breeds were detected using ultra-performance liquid chromatography system coupled with quadrupole time of flight mass spectrometry (UPLC-QTOFMS).

Results

Sequencing results revealed that there were significant differences in the gut microbiota of the two breeds studied, suggesting that host breeds affect structure and diversity of gut microbiota. Numerous breed-associated microorganisms were identified at different taxonomic levels and most microbial taxa belonged to the families Lachnospiraceae and Ruminococcaceae. In particular, several short-chain fatty acids (SCFAs) producing species including Coprococcus comes, Ruminococcus faecis, Ruminococcus callidus, and Lachnospiraceae bacterium NK4A136 could be considered as biomarkers for improving the health and production performance in meat rabbits. Additionally, gut microbial functional capacities related to bacterial chemotaxis, ABC transporters, and metabolism of different carbohydrates, amino acids, and lipids varied greatly between rabbit breeds. Several fatty acids, amino acids, and organic acids in the serum were identified as breed-associated, where certain metabolites could be regarded as biomarkers correlated with the well-being and production traits of meat rabbits. Correlation analysis between breed-associated microbial species and serum metabolites revealed significant co-variations, indicating the existence of cross-talk among host-gut microbiome-serum metabolome.

Conclusions

Our study provides insight into how gut microbiome and serum metabolome of meat rabbits are affected by host breeds and uncovers potential biomarkers important for breed improvement of meat rabbits.
Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study
Authors:   the BETonMACE Investigators, Nicholls Stephen J. , Schwartz Gregory G. , Buhr Kevin A. , Ginsberg Henry N. , Johansson Jan O. , Kalantar-Zadeh Kamyar , Kulikowski Ewelina , Toth Peter P. , Wong Norman , Sweeney Michael , Ray Kausik K.
Published: January 2021

Background

Patients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known.

Methods

The phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied.

Results

Patients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38–0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27–0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53–0.98], P = 0.04).

Conclusion

Apabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS.
A minimal 3D model of mosquito flight behaviour around the human baited bed net
Authors: Jones Jeff , Murray Gregory P D , McCall Philip J
Published: January 2021

Background

Advances in digitized video-tracking and behavioural analysis have enabled accurate recording and quantification of mosquito flight and host-seeking behaviours, facilitating development of individual (agent) based models at much finer spatial scales than previously possible.

Methods

Quantified behavioural parameters were used to create a novel virtual testing model, capable of accurately simulating indoor flight behaviour by a virtual population of host-seeking mosquitoes as they interact with and respond to simulated stimuli from a human-occupied bed net. The model is described, including base mosquito behaviour, state transitions, environmental representation and host stimulus representation.

Results

In the absence of a bed net and human host bait, flight distribution of the model population was relatively uniform throughout the arena. Introducing an unbaited untreated bed net induced a change in distribution with an increase in landing events on the net surface, predominantly on the sides of the net. Adding the presence of a simulated human bait dramatically impacted flight distribution patterns, exploratory foraging and, the number and distribution of landing positions on the net, which were determined largely by the orientation of the human within. The model replicates experimental results with free-flying living mosquitoes at human-occupied bed nets, where contact occurs predominantly on the top surface of the net. This accuracy is important as it quantifies exposure to the lethal insecticide residues that may be unique to the net roof (or theoretically any other surface). Number of net contacts and height of contacts decreased with increasing attractant dispersal noise.

Conclusions

Results generated by the model are an accurate representation of actual mosquito behaviour recorded at and around a human-occupied bed net in untreated and insecticide-treated nets. This fine-grained model is highly flexible and has significant potential for in silico screening of novel bed net designs, potentially reducing time and cost and accelerating the deployment of new and more effective tools for protecting against malaria in sub-Saharan Africa.
FAK displacement from focal adhesions: a promising strategy to target processes implicated in cancer progression and metastasis
Authors: Antoniades Ioanna , Kyriakou Maria , Charalambous Anna , Kalalidou Katerina , Christodoulou Andri , Christoforou Maria , Skourides Paris A.
Published: January 2021

Background

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed or activated in several advanced-stage solid cancers. It is known to play both kinase-dependent and -independent roles in promoting tumor progression and metastasis. Numerous inhibitors, targeting either the enzymatic or scaffolding activities of FAK have been generated, with varying degree of success. Here, we describe a novel approach to site-specifically target both kinase-dependent and -independent FAK functions at focal adhesions (FAs), the primary sites at which the kinase exerts its activity.

Methods

We took advantage of the well-characterized interactions between the paxillin LD motifs and the FAK FAT domain and generated a polypeptide (LD2-LD3-LD4) expected to compete with interactions with paxillin. Co-immunoprecipitation experiments were performed to examine the interaction between the LD2-LD3-LD4 polypeptide and FAK. The effects of LD2-LD3-LD4 in the localization and functions of FAK, as well as FA composition, were evaluated using quantitative immunofluorescence, cell fractionation, FA isolation and Western Blot analysis. Live cell imaging, as well as 2-D migration and cell invasion assays were used to examine the effects on FA turnover and tumor cell migration and invasion.

Results

Expression of the LD2-LD3-LD4 polypeptide prevents FAK localization at FAs, in a controlled and dose-dependent manner, by competing with endogenous paxillin for FAK binding. Importantly, the LD2-LD3-LD4 peptide did not otherwise affect FA composition or integrin activation. LD2-LD3-LD4 inhibited FAK-dependent downstream integrin signaling and, unlike existing inhibitors, also blocked FAK’s scaffolding functions. We further show that LD2-LD3-LD4 expression markedly reduces FA turnover and inhibits tumor cell migration and invasion. Finally, we show that dimers of a single motif, linked through a flexible linker of the proper size, are sufficient for the displacement of FAK from FAs and for inhibition of tumor cell migration. This work raises the possibility of using a synthetic peptide as an antimetastatic agent, given that effective displacement of FAK from FAs only requires dimers of a single LD motif linked by a short flexible linker.

Conclusion

In conclusion, these results suggest that FAK displacement from FAs is a promising new strategy to target critical processes implicated in cancer progression and metastasis.

Graphical abstract
Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients
Authors: Liu Jungang , Huang Xiaoliang , Liu Haizhou , Wei Chunyin , Ru Haiming , Qin Haiquan , Lai Hao , Meng Yongsheng , Wu Guo , Xie Weishun , Mo Xianwei , Johnson Caroline H. , Zhang Yawei , Tang Weizhong
Published: January 2021

Background

KRASgene is the most common type of mutation reported in colorectal cancer (CRC).KRASmutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated.

Methods

535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment betweenKRAS-mutant andKRASwild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence ofKRASmutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction inKRAS-mutant CRC patients was established and validated.

Results

NF-κB and T-cell receptor signaling pathways were significantly inhibited inKRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased inKRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased inKRAS-mutant compared toKRASwild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes.

Conclusions

KRASmutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments inKRAS-mutant CRC patients.
Rutting vocal display in male impala (Aepyceros melampus) and overlap with alarm context
Authors: Volodin Ilya A. , Volodina Elena V. , Frey Roland
Published: January 2021

Background

The rutting vocal display of male impalaAepyceros melampusis unique for its complexity among ruminants. This study investigates bouts of rutting calls produced towards potential mates and rival males by free-ranging male impala in Namibia. In particular, a comparison of male rutting and alarm snorts is conducted, inspired by earlier findings of mate guarding by using alarm snorts in male topiDamaliscus lunatus.

Results

Rutting male impala produced 4–38 (13.5 ± 6.5) rutting calls per bout. We analyzed 201 bouts, containing in total 2709 rutting calls of five types: continuous roars produced within a single exhalation-inhalation cycle; interrupted roars including few exhalation-inhalation cycles; pant-roars distinctive by a pant-phase with rapidly alternating inhalations and exhalations; usual snorts lacking any roar part; and roar-snorts starting with a short roar part. Bouts mostly started and ended with usual snorts. Continuous roars were the shortest roars. The average duration of the exhalatory phase was longest in the continuous roars and shortest in the pant-roars. The average fundamental frequency (49.7–51.4 Hz) did not differ between roar types. Vocal tract length, calculated by using measurements of the first four vocal tract resonances (formants), ranged within 381–382 mm in all roar types. In the studied male impala, rutting snorts within bouts of rutting calls were longer and had higher values of the upper quartile in the call spectra than alarm snorts produced towards potential danger.

Conclusions

Additional inhalations during the emission of the interrupted and pant-roars prolong their duration compared to the continuous roars but do not affect the fundamental frequency or the degree of larynx retraction while roaring. Alarm snorts are separated from one another by large intervals, whereas the intervals between rutting snorts within bouts are short. Sometimes, rutting snorts alternate with roars, whereas alarm snorts do not. Therefore, it is not the acoustic structure of individual snorts but the temporal sequence and the occasional association with another call type that defines snorts as either rutting or alarm snorts. The rutting snorts of male impala may function to attract the attention of receptive females and delay their departure from a male’s harem or territory.
Higher expression of monocyte chemotactic protein 1 in mild COVID-19 patients might be correlated with inhibition of Type I IFN signaling
Authors: Xi Xueyan , Guo Yang , Zhu Min , Wei Yuhui , Li Gang , Du Boyu , Wang Yunfu
Published: January 2021

Background

Chemokine levels in severe coronavirus disease 2019 (COVID-19) patients have been shown to be markedly elevated. But the role of chemokines in mild COVID-19 has not yet been established. According to the epidemiological statistics, most of the COVID-19 cases in Shiyan City, China, have been mild. The purpose of this study was to evaluate the level of chemokines in mild COVID-19 patients and explore the correlation between chemokines and host immune response.

Methods

In this study, we used an enzyme-linked immunosorbent assay to detect serum levels of chemokines in COVID-19 patients in Shiyan City. Expression of chemokine receptors and of other signaling molecules was measured by real-time polymerase chain reaction.

Results

We first demonstrated that COVID-19 patients, both sever and mild cases, are characterized by higher level of chemokines. Specifically, monocyte chemotactic protein 1 (MCP-1) is expressed at higher levels both in severe and mild cases of COVID-19. The receptor of MCP-1, C-C chemokine receptor type 2, was expressed at higher levels in mild COVID-19 patients. Finally, we observed a significant negative correlation between expression levels of interferon (IFN) regulatory factor 3 (IRF3) and serum levels of MCP-1 in mild COVID-19 patients.

Conclusion

Higher expression of MCP-1 in mild COVID-19 patients might be correlated with inhibition of IFN signaling. The finding adds to our understanding of the immunopathological mechanisms of severe acute respiratory syndrome coronavirus 2 infection and provides potential therapeutic targets and strategies.
The relationship between severity of drug problems and perceived interdependence of drug use and sexual intercourse among adult males in drug addiction rehabilitation centers in Japan
Authors: Yamada Risa , Shimane Takuya , Kondo Ayumi , Yonezawa Masako , Matsumoto Toshihiko
Published: January 2021

Background

Consuming drugs in conjunction with sexual intercourse may shape the perceived interdependence of drug use and sexual intercourse (PIDS). Additionally, the severity of drug problems may have a significant impact on PIDS. However, this relationship remains unverified. Therefore, this study investigates whether the severity of drug problems is associated with PIDS among adult males in drug addiction rehabilitation centers (DARC) in Japan.

Methods

This study was a secondary analysis of the “DARC Follow-Up Study in Japan” conducted by the National Center of Neurology and Psychiatry in 2016, in which participants from 46 facilities completed a self-report questionnaire. A total of 440 males with drug dependence were included in the analysis. We analyzed participants’ demographic characteristics, history of sexually transmitted disease diagnoses, and responses to questions related to drug use (e.g., primary drug use and PIDS). Additionally, we measured the severity of drug problems using the Japanese version of the Drug Abuse Screening Test-20 (DAST-20).

Results

The median age of the participants was 42 years. The median DAST-20 score was 14.0, the primary drug was methamphetamine (61.4%) and new psychoactive substances (NPS: 13.6%). Multivariate analysis indicated that participants’ experiences with unprotected sexual intercourse (“mostly a non-condom user”: adjusted odds ratio (AOR) = 4.410), methamphetamine use (AOR = 3.220), new psychoactive substances use (AOR = 2.744), and the DAST-20 score (AOR = 1.093) were associated with PIDS.

Conclusions

This study indicated that the frequency of unprotected sexual intercourse under the influence of drugs, methamphetamine and NPS use were strongly associated with PIDS. The severity of drug problems was also significantly associated with PIDS. It is necessary to develop culturally appropriate treatment programs adapted to the needs of patients who experience strong PIDS.
A facilitation model for implementing quality improvement practices to enhance outpatient substance use disorder treatment outcomes: a stepped-wedge randomized controlled trial study protocol
Authors: O’Grady Megan A. , Lincourt Patricia , Greenfield Belinda , Manseau Marc W. , Hussain Shazia , Genece Kamala Greene , Neighbors Charles J.
Published: January 2021

Background

The misuse of and addiction to opioids is a national crisis that affects public health as well as social and economic welfare. There is an urgent need for strategies to improve opioid use disorder treatment quality (e.g., 6-month retention). Substance use disorder treatment programs are challenged by limited resources and a workforce that does not have the requisite experience or education in quality improvement methods. The purpose of this study is to test a multicomponent clinic-level intervention designed to aid substance use disorder treatment clinics in implementing quality improvement processes to improve high-priority indicators of treatment quality for opioid use disorder.

Methods

A stepped-wedge randomized controlled trial with 30 outpatient treatment clinics serving approximately 2000 clients with opioid use disorder each year will test whether a clinic-level measurement-driven, quality improvement intervention, called Coaching for Addiction Recovery Enhancement (CARE), improves (a) treatment process quality measures (use of medications for opioid use disorder, in-treatment symptom and therapeutic progress, treatment retention) and (b) recovery outcomes (substance use, health, and healthcare utilization). The CARE intervention will have the following components: (1) staff clinical training and tools, (2) quality improvement and change management training, (3) external facilitation to support implementation and sustainability of quality improvement processes, and (4) an electronic client-reported treatment progress tool to support data-driven decision making and clinic-level quality measurement. The study will utilize multiple sources of data to test study aims, including state administrative data, client-reported survey and treatment progress data, and staff interview and survey data.

Discussion

This study will provide the field with a strong test of a multicomponent intervention to improve providers’ capacity to make systematic changes tied to quality metrics. The study will also result in training and materials that can be shared widely to increase quality improvement implementation and enhance clinical practice in the substance use disorder treatment system.

Trial registration

Trial #NCT04632238NCT04632238registered at clinicaltrials.gov on 17 November 2020
The treatment of the atrophic clavicular nonunion by double-plate fixation with autogenous cancellous bone graft: a prospective study
Authors: Zhang Jun , Yin Peng , Han Bo , Zhao Jianmin , Yin Bo
Published: January 2021

Background

The objective of this study is to assess prospectively the effectiveness of double-plate fixation combined with autogenous cancellous bone graft in the treatment for the atrophic clavicular nonunion.

Methods

Between February 2013 and November 2017, a total of 12 patients with atrophic clavicular nonunion (mean age, 40.4 ± 9.0 years, range, 27–60 years) were treated by double-plate fixation with autogenous cancellous bone graft in our institute. The Constant Score System was used to evaluate the preoperative and final outcomes. The Short Form-36 (SF-36) outcome questionnaire was used to assess the final clinical results.

Results

All patients were followed-up, with the average follow-up of 34.7 ± 6.7 months (range, 24–48 months). The healing rate was 100% in our study. The mean time of bony union was 9 weeks (range, 8–10 weeks). One patient had a postoperative superficial infection, and the patient was cured by oral antibiotics and wound dressing. No implant-related complications (plate-screw loosening or breakage) were observed postoperatively. No vascular injury, neural impairment, or thoracic outlet syndrome was discovered preoperatively or postoperatively. There is a statistical significance between the preoperative and the postoperative constant scores (P< 0.05). All the patients were satisfied with their final clinical results by SF-36 outcome questionnaire. Average scores of the physical function and bodily pain components of the SF-36 were 94.2 ± 7.3 and 92.5 ± 5.8, respectively.

Conclusion

Our results presented that double-plate fixation with autogenous cancellous bone graft is an effective treatment for atrophic clavicular nonunion, especially for those with a significant bone defect.
Implants for trochanteric fractures in Norway: the role of the trochanteric stabilizing plate—a study on 20,902 fractures from the Norwegian hip fracture register 2011–2017
Authors: Alm Carl Erik , Frihagen Frede , Dybvik Eva , Matre Kjell , Madsen Jan Erik , Gjertsen Jan-Erik
Published: January 2021

Background

The trochanteric stabilizing plate (TSP) is used as an adjunct to the sliding hip screw (SHS) in unstable trochanteric and subtrochanteric fractures. We wanted to describe the choice of implant for trochanteric fractures with a focus on the TSP in Norway.

Methods

A total of 20,902 fractures from the Norwegian Hip Fracture Register treated surgically in 43 hospitals from 2011 to 2017 were included. Logistic regression analyses were performed to detect factors potentially influencing implant choice.

Results

The mean age was 83 years, and 15,137 (72%) were women. An SHS was used in 13,273 (63%) fractures, of them 4407 (33%) with a TSP. Fracture classification was the most important determinant of TSP. In cases where an SHS was used, the odds ratio (OR) for using a TSP was 14 for AO/OTA 31A2 fractures and 71 for AO/OTA 31A3 and subtrochanteric fractures, compared to AO/OTA 31A1 fractures. The probability of receiving a TSP was higher in urban, academic, and high-volume hospitals (OR 1.2 to 1.3) and lower in Central and Northern Norway (OR 0.3 to 0.7). The use of an intramedullary nail (IMN) (n = 7629 (36%)) was also to a degree decided by fracture classification (OR 1.8 to 5.3). However, hospital factors, with OR 0.1 to 0.4 for IMN in academic, urban, and high-volume hospitals and OR 1.5 to 2.6 outside South-Eastern Norway (all p < 0.001), were also important.

Conclusions

Fracture classification was the main determinant for TSP use. Any additional benefit from a TSP on postoperative fracture stability or clinical outcome needs to be clarified.
Improvement of intestinal flora: accompany with the antihypertensive effect of electroacupuncture on stage 1 hypertension
Authors: Wang Jun-meng , Yang Ming-xiao , Wu Qiao-feng , Chen Ji , Deng Shu-fang , Chen Lin , Wei Da-neng , Liang Fan-rong
Published: January 2021

Background

Increasing evidence have indicated the relationship between intestinal dysbiosis and hypertension. We aimed to evaluate the effect of the electroacupuncture (EA) on intestinal microbiota in patients with stage 1 hypertension.

Methods

93 hypertensive patients and 15 healthy subjects were enrolled in this study. Applying a highly accurate oscillometric device to evaluate the antihypertensive effect of EA. 16S rRNA sequencing was used to profile stool microbial communities from Healthy group, Before treatment (BT) group and After treatment (AT) group, and various multivariate analysis approaches were used to assess diversity, composition and abundance of intestinal microbiota.

Results

In this study, EA significantly decreased the blood pressure (BP) of hypertensive patients. Higher abundance of Firmicutes and lower Bacteroidetes abundance were observed in the BT group compared to the Healthy group. And EA treatment significantly decreased the Firmicutes/Bacteroidetes ratio compared to the BT group. Moreover, at the genus level, there was an increased abundance of Escherichia-Shigella in patients with hypertension, while Blautia were decreased, and EA reversed these changes.

Conclusions

Our study indicates that EA can effectively lower BP and improve the structure of intestinal microbiota which are correlate with the alteration of blood pressure by electroacupuncture.

Trial registration: Clinicaltrial.gov, NCT01701726. Registered 5 October 2012, https://clinicaltrials.gov/ct2/show/study/NCT01701726