bluuebunny/crossref_metadata_2025 huggingface dataset:
LcMYB4, an unknown function transcription factor gene from sheepgrass, as a positive regulator of chilling and freezing tolerance in transgenic Arabidopsis
Authors: Li Xiaoxia , Jia Junting , Zhao Pincang , Guo Xiufang , Chen Shuangyan , Qi Dongmei , Cheng Liqin , Liu Gongshe
Published: May 2020

Background

Sheepgrass (Leymus chinensis (Trin.) Tzvel) is a perennial forage grass that can survive extreme freezing winters (− 47.5 °C) in China. In this study, we isolated an unknown function MYB transcription factor gene, LcMYB4, from sheepgrass. However, the function of LcMYB4 and its homologous genes has not been studied in other plants.

Results

The expression of the LcMYB4 gene was upregulated in response to cold induction, and the LcMYB4 fusion protein was localized in the nucleus, with transcriptional activation activity. Biological function analysis showed that compared with WT plants, LcMYB4-overexpressing Arabidopsis presented significantly increased chilling and freezing tolerance as evidenced by increased germination rate, survival rate, and seed setting rate under conditions of low temperature stress. Furthermore, LcMYB4-overexpressing plants showed increased soluble sugar content, leaf chlorophyll content and superoxide dismutase activity but decreased malondialdehyde (MDA) under chilling stress. Moreover, the expression of the CBF1, KIN1, KIN2 and RCI2A genes were significantly upregulated in transgenic plants with chilling treatment. These results suggest that LcMYB4 overexpression increased the soluble sugar content and cold-inducible gene expression and alleviated oxidative damage and membrane damage, resulting in enhanced cold resistance in transgenic plants. Interestingly, our results showed that the LcMYB4 protein interacts with fructose-1,6-bisphosphate aldolase protein1 (LcFBA1) and that the expression of the LcFBA1 gene was also upregulated during cold induction in sheepgrass, similar to LcMYB4.

Conclusion

Our findings suggest that LcMYB4 encodes MYB transcription factor that plays a positive regulatory role in cold stress.
A case report of iatrogenic gas gangrene post colonoscopy successfully treated with conservative management- is surgery always necessary?
Authors: Fairley Lachlan J. , Smith Samuel L. , Fairley Stephen K.
Published: May 2020

Background

Colonoscopy is a routine procedure in diagnosis and treatment of colonic disease. While generally regarded as a safe procedure, potentially fatal complications can occur. Gas gangrene is one such complication, with very high mortality. There are few cases of gas gangrene occurring after colonoscopy, making it one of the rarer complications of this procedure. There have been no previously reported cases of a patient surviving such an infection and the optimal treatment strategy is contentious. This report describes a case of intramural gas gangrene of the colon, treated conservatively with antibiotic therapy in which the patient survived with full recovery.

Case presentation

A 71-year-old, previously healthy male presented 6 h post apparently uncomplicated colonoscopic polypectomy with rigors, nausea, vomiting and right upper quadrant pain. At presentation he was febrile at 40.1 °C but hemodynamically stable. Abdominal computed tomography revealed substantial colonic thickening and several focal intramural gas bubbles (pneumatosis intestinalis) surrounding the polypectomy site. Within 24 h post procedure he became hypotensive and was admitted to ICU in frank septic shock requiring inotropes, and with demonstrable septic myocardial depression. Bloods showed multi-organ derangement with leukocytosis, lactic acidosis, haemolytic anaemia and hyperbilirubinemia. A diagnosis of presumed Clostridial gas gangrene was made, and treatment was initiated with benzylpenicillin, clindamycin, metronidazole and vancomycin. After 4 days in ICU he was stepped down, and discharged after a further 10 days with no surgical or endoscopic interventions. At three-month review he reported being back to full health.

Conclusions

This case demonstrates that gas gangrene infection is a possible complication of colonoscopic polypectomy. This is a cause of rapid deterioration in post-colonoscopy patients and has been misdiagnosed as colonic perforation in previously reported cases of retroperitoneal gas gangrene. Such misdiagnosis delays antibiotic therapy, which likely plays a role in the high mortality of this condition. Early diagnosis and initiation of antibiotic therapy with benzylpenicillin and clindamycin as seen in this case is essential for patient survival. While surgery is typically performed, non-operative management of pneumatosis intestinalis, and potentially gas gangrene is becoming more common and was utilized effectively in this patient.
The association between genetic variants in lactotransferrin and dental caries: a meta- and gene-based analysis
Authors: Li Xueyan , Su Yi , Liu Di , Yang Jingyun
Published: May 2020

Background

The pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in lactotransferrin (LTF) and the risk of dental caries with inconsistent results.

Methods

A systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases was performed by two authors independently for papers published before December 5, 2019 on the association between genetic variants inLTFand the risk of dental caries. We adopted the subsequent inclusion criteria to assess study eligibility: 1) The studies were based on human subjects; 2) the presence of dental caries should be screened for in both the case group and the control group; and 3) genotype data on variants inLTFwere available in both the case group and the control group. We calculated odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by using random-effects models to assess the association of genetic variants inLTFwith the risk of dental caries. We also performed a gene-based analysis to explore the joint association of multiple genetic variants inLTFwith the risk of dental caries.

Results

Our systematic literature search identified six relevant papers for analysis. We found no significant association between rs1126478 and the risk of dental caries when meta-analysing the genotype distribution between subjects with dental caries and those without dental caries (additive model: OR = 1.41; 95% CI = 0.98–2.02;P = 0.065). However, further analysis indicated that rs1126478 was associated with dental risk in subjects who had moderate or severe dental caries compared to those without dental caries (P < 0.0001). The gene-based analysis indicated that multiple genetic variants inLTFwere jointly associated with the risk of dental caries (P = 0.002).

Conclusions

The present meta-analysis revealed some evidence of the association between rs1126478 and dental caries and that multiple genetic variants inLTFare jointly associated with the risk of dental caries. Our findings need to be validated by larger studies that adjust for important confounding factors for the risk of dental caries.
Application of combined cerebrospinal fluid physicochemical parameters to detect intracranial infection in neurosurgery patients
Authors: Zhai Tiantian , Fu Zhong lian , Qiu Yan bing , Chen Qiang , Luo Dong , Chen Kaisen
Published: May 2020

Routine test of cerebrospinal fluid (CSF), such as glucose concentrations, chloride ion, protein and leukocyte, as well as color, turbidity and clot, were important indicators for intracranial infection. However, there were no models to predict the intracranial infection with these parameters. We collected data of 221 cases with CSF positive-culture and 50 cases with CSF negative culture from January 1, 2016 to December 31, 2018 in the First Affiliated Hospital of Nanchang University, China. SPSS17.0 software was used to establish the model by adopting seven described indicators, and P < 0.05 was considered as statistically significant. Meanwhile, 40 cases with positive-culture and 10 cases with negative-culture were selected to verify the sensitivity and specificity of the model. The results showed that each parameter was significant in the model establishment (P < 0.05). To extract the above seven parameters, the interpretation model C was established, and C = 0.952–0.183 × glucose value (mmol/L) - 0.024 × chloride ion value (mmol/L)- 0.000122 × protein value (mg/L) - 0.0000859 × number of leukocytes per microliter (× 106/L) + 1.354 × color number code + 0.236 × turbidity number code + 0.691 × clot number code. In addition, the diagnostic sensitivity and specificity of the model were 85.0 and 100%, respectively. The combining application of seven physicochemical parameters of CSF might be of great value in the diagnosis of intracranial infection for adult patients.
Clinical features of Guillain–Barré syndrome patients with elevated serum creatine kinase levels
Authors: Hosokawa Takafumi , Nakajima Hideto , Sawai Taiki , Nakamura Yoshitsugu , Sano Eri , Tsukahara Akihiro , Unoda Kiichi , Ishida Shimon , Sakane Sadaki , Kimura Fumiharu , Arawaka Shigeki
Published: May 2020

Background

It is not well defined whether Guillain–Barré syndrome (GBS) patients with elevated serum creatine kinase (CK) levels have characteristic clinical features and are related to the subgroups of GBS.

Methods

We retrospectively studied 51 consecutive patients with GBS, who visited our hospital, and compared clinical, laboratory and electrophysiological findings between patients with and without elevated CK levels.

Results

Of 51 patients, 14 patients (27%) showed an elevation of serum CK levels. When compared with patients with the normal CK levels, the ratios of male, antecedent infections, and anti-GM1 antibody positivity were significantly higher in patients with elevated CK levels. The ratios of hypoesthesia, cranial nerve involvement, and urinary retention were significantly less in patients with elevated CK levels. There were no significant differences in disability at peak between two groups. In the electrophysiological examination, sensory nerve abnormalities were not observed. Although some patients with elevated CK levels showed prolongation of distal motor latencies (DMLs) and increase of durations in the initial examination, development of the prolongation of DMLs and increase of durations was not observed in the follow-up examinations. The findings were consistent with acute motor axonal neuropathy (AMAN) with reversible conduction failure (RCF) but not acute inflammatory demyelinating polyneuropathy (AIDP).

Conclusions

The results suggest that the GBS patients with elevated CK levels represent not a group of AIDP but a group of AMAN with axonal degeneration or RCF even though the initial electrophysiological examination shows AIDP pattern.
CYP19A1 gene expression in the peripheral blood of Brazilian women with breast cancer relapse
Authors: Barros-Oliveira Maria da Conceição , Costa-Silva Danylo Rafhael , Campos-Verdes Larysse Cardoso , Pereira Renato de Oliveira , Silva Rozirene Araújo , Moura-Borges Paulo de Tarso , Sousa Emerson Brandão , Pinho-Sobral André Luiz , Lopes-Costa Pedro Vitor , dos Santos Alesse Ribeiro , Soares-Lopes Ione Maria Ribeiro , Viana Jackeline Lopes , Melo Mariella de Almeida , Manes Neto Fidelis , Coelho Eid Gonçalves , Pires e Cruz Maria do Socorro , Costa-Silva Vladimir , Gebrim Luiz Henrique , Da Silva Benedito Borges
Published: May 2020

Background

The CYP19A1 gene, which encodes the enzyme responsible for androgen aromatization into estrogens, may play an important role in breast cancer aggressiveness. However, no study has evaluated CYP19A1 gene expression in the peripheral blood of women with relapsed breast cancer.

Methods

In this cross-sectional study, CYP19A1 gene expression was quantified by RT-PCR in the peripheral blood of 146 women with breast cancer who were first divided into two groups according to the expression of CYP19A1 (low and high); each group had 73 patients. Subsequently, women were divided into two groups: those without recurrence (control, n = 85) and those with recurrence (study, n = 61). Statistical analysis of the data was performed using ANOVA, the Mann-Whitney, Chi-square or Fisher’s exact test (p <  0.05).

Results

There were no significant differences between the relative expression of CYP19A1 mRNA in the low expression group and the high expression group according to the variables studied. There were no significant differences in CYP19A1 gene expression in the study and control groups (p = 0.8461). In the relapse group, CYP19A1 gene expression was significantly higher in the hybrid luminal subtype than in the triple-negative subtype (p = 0.0321), whereas it was significantly lower in HER2-negative cases than in HER2-positive cases (p <  0.0376). Women with locoregional recurrence showed higher expression than women with distant recurrence (p <  0.0001).

Conclusions

The present study found no significant differences between women with high and low expression of the CYP19A1 gene mRNA or between those in the study group and the control group. However, in women with recurrence, there was increased expression of CYP19A1 mRNA in those who had the luminal hybrid subtype and locoregional relapse and decreased expression in those negative for HER2.
A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods
Authors: Bosch Annick , Bierens Margreet , de Wit Ardine G. , Ly Verena , van der Velde Jessica , de Boer Heleen , van Beek Gerry , Appelman Danielle , Visser Sacha , Bos Lisa , van der Meer Jolanda , Kamphuis Niki , Draaisma Jos M. T. , Donders Rogier , van de Loo-Neus Gigi H. H. , Hoekstra Pieter J. , Bottelier Marco , Arias-Vasquez Alejandro , Klip Helen , Buitelaar Jan K. , van den Berg Saskia W. , Rommelse Nanda N.
Published: May 2020

Background

Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD.

Methods

A total ofN = 162 children (5–12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm includingN = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only.

Discussion

This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD.

Trial registration

www.trialregister.nl,NTR5434. Registered at October 11th, 2015.
Relationship between Toxoplasma gondii seropositivity and schizophrenia in the Lebanese population: potential implication of genetic polymorphism of MMP-9
Authors: El Mouhawess Amata , Hammoud Amal , Zoghbi Marouan , Hallit Souheil , Haddad Chadia , El Haddad Kinda , El Khoury Saydeh , Tannous Jennifer , Obeid Sahar , Halabi Mohamad Adnan , Mammari Nour
Published: May 2020

Background

Toxoplasmamultiplication and its persistence into the brain cause a local neuroinflammatory reaction, resulting synthesis of neurotransmitters involved in neurological disorders, especially schizophrenia. The Matrix metallopeptidase 9 (MMP-9) protein can play a major role in this neuroinflammation. It can promote extravasation and migration of infected immune cells into the brain. The objectives of this study are to determine the possible association between schizophrenia and toxoplasmosis and highlight the existence of gene polymorphism encoding MMP-9 protein’s in patients presented both schizophrenia and toxoplasmosis.

Methods

A case-control study was conducted on 150 patients with schizophrenia (case group), and 150 healthy persons (control group). Groups were matched with age, gender, and place of residence. The survey was conducted using a questionnaire and a serological profile assay for specific IgG and IgM antibodies againstT. gondii. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) of gene polymorphism encoding MMP-9 was performed on 83 cases selected randomly.

Results

Data show a significant association between toxoplasmosis (IgM+/IgG+ serological profile) and schizophrenia. Significant effects of raw meat consumption and contact with cats have been associated with the occurrence of schizophrenia. PCR-RFLP shows the presence of muted allele of MMP-9 gene in selected cases whose present T. gondii serological profile IgM+/IgG+ and IgM-/IgG+ respectively.

Conclusion

Toxoplasmosis may be one of the etiological causes of schizophrenia, andMMP-9gene polymorphism could be involved in the occurrence mechanism of this pathology followingToxoplasmainfection.
A new sequential animal model for infection-related non-unions with segmental bone defect
Authors: Helbig Lars , Guehring Thorsten , Titze Nadine , Nurjadi Dennis , Sonntag Robert , Armbruster Jonas , Wildemann Britt , Schmidmaier Gerhard , Gruetzner Alfred Paul , Freischmidt Holger
Published: May 2020

Background

The treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects.

Methods

After randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 103 CFUStaphylococcus aureus(infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis.

Results

We developed and presented a new two-stage non-union animal model through a targetedS. aureusinfection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and non-infected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculatedS. aureusstrain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the μ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001).

Conclusions

We were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.
A prospective observational cohort study of posterior tibial nerve stimulation in patients with multiple sclerosis: design and methods
Authors: Lane Giulia I. , Mao-Draayer Yang , Barboglio-Romo Paholo , Clemens J. Quentin , Gupta Priyanka , Dunn Rod , Qin Yongmei , Cameron Anne P. , Stoffel John T.
Published: May 2020

Background

Posterior tibial nerve stimulation (PTNS) is a promising treatment for lower urinary tract symptoms (LUTS) in patients with MS. However, long term data focusing on PTNS impact on health-related quality of life (HRQOL), bowel and bladder symptoms are lacking. This paper describes a study protocol that examines the extended efficacy of PTNS on MS related bladder and bowel symptoms and resulting HRQOL.

Methods/Design

This is a single-centered, prospective, longitudinal, observational cohort study of patients with MS who suffer from LUTS and are refractory to two prior treatment modalities. Participants who have elected to pursue PTNS therapy for LUTS will be eligible. The primary outcome is the median number of urinary frequency and incontinence episodes on a 3-day voiding diary at 3, 12 and 24 months compared to baseline. Secondary outcome measures will include change in total AUA-SS, M-ISI, NBSS, SF-12, SSS and BCS scores from baseline The Expanded Disability Status Scale and magnetic resonance imaging will be evaluated at baseline and annually throughout the study.

Discussion

This research protocol aims to expand on the existing literature regarding outcomes of PTNS in MS. Specifically, it will provide long term follow-up data on bladder, bowel, sexual and HRQOL outcomes. The completion of this study will provide longitudinal efficacy data of the impact of PTNS in MS patients.

Trial registration

NCT04063852.
Report: central diabetes insipidus and schwannoma in a male with X-linked congenital adrenal hypoplasia
Authors: Seo Boo Kyeong , Jeong Seul Ah. , Cho Jae Young , Park Ji Sook , Seo Ji-Hyun , Park Eun Sil , Lim Jae-Young , Woo Hyang-Ok , Youn Hee-Shang
Published: May 2020

Background

DAX1 mutations are related to the X-linked form of adrenal hypoplasia congenita (AHC) in infancy and to hypogonadotropic hypogonadism (HH) in puberty. We report a male patient affected by X-linked AHC who presented with central diabetes insipidus and schwannoma in adulthood, which has not been described in association with AHC.

Case presentation

A 36-day-old male infant who presented with severe dehydration was admitted to the intensive care unit. His laboratory findings showed hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis. After hormonal evaluation, he was diagnosed with adrenal insufficiency, and he recovered after treatment with hydrocortisone and a mineralocorticoid. He continued to take hydrocortisone and the mineralocorticoid after discharge. At the age of 17, he did not show any signs of puberty. On the basis of a GnRH test, a diagnosis of HH was made. At the age of 24, he was hospitalized with thirst, polydipsia and polyuria. He underwent a water deprivation test for polydipsia and was diagnosed with central diabetes insipidus. By quantitative polymerase chain reaction analysis, we identified a hemizygous frameshift mutation in DAX1 (c.543delA).

Conclusions

We suggest that DAX1 mutations affect a wider variety of endocrine organs than previously known, including the posterior pituitary gland.
A combined individual and group-based stabilization and skill training intervention versus treatment as usual for patients with long lasting posttraumatic reactions receiving outpatient treatment in specialized mental health care – a study protocol for a randomized controlled trial
Authors: Holgersen K. H. , Brønstad I. , Jensen M. , Brattland H. , Reitan S. K. , Hassel A. M. , Arentz M. , Lara-Cabrera M. , Skjervold A. E.
Published: May 2020

Background

Suffering linked to previous interpersonal trauma is common among patients in mental health care. Diagnostic labels may vary, but the clinical picture is often characterized by long-lasting and complex psychological and somatic symptoms, subjective distress and reduced quality of health and life. A substantial proportion of patients do not recover after individual treatment in ordinary specialized mental healthcare settings, despite the proven usefulness of individual trauma-specific treatments. The therapeutic factors that arise in group settings, such as normalization, shame reduction and corrective relational experiences, may be particularly useful for trauma survivors. However, evidence in support of group treatment for trauma survivors is scarce. This study aims to test whether combining a novel group intervention to individual treatment is superior to conventional individual out-patient treatment in an ordinary community mental health hospital.

Methods

In a single-site, non-blinded, randomized controlled trial (RCT), the effect of a combined group-based stabilization and skill-training (SST) intervention added to individual treatment will be compared to conventional treatment (treatment as usual, TAU) alone. Participants (N = 160) with ongoing and long-lasting reactions related to known adverse life events from the past will be recruited among patients at general outpatient clinics in a community mental health centre at St. Olav’s University Hospital, Trondheim, Norway. Following baseline assessment and randomization, participants will complete follow-up measures at 4, 8, 13 and 19 months post-baseline. The primary outcome is personal recovery (The questionnaire about the process of recovery , QPR). Secondary outcomes include (1) self-reported symptoms of posttraumatic stress, general mental and somatic health symptoms, well-being, functional impairment and client satisfaction, (2) immunological and endocrine response measured in blood samples and (3) national registry data on occupational status, use of mental health services and pharmacological treatment. Additionally, mechanisms of change via posttraumatic cognitions will be examined.

Discussion

The addition of a group-based intervention to individual treatment for trauma survivors might prove to be an efficient way to meet the need of long-lasting high-intensity treatment in a large group of patients in mental health care, thereby reducing their suffering and increasing their psychosocial functioning.

Trial registration

ClinicalTrials.gov: NCT03887559. Registered on 25 March 2019.
The Medical Genome Initiative: moving whole-genome sequencing for rare disease diagnosis to the clinic
Authors:   on behalf of the Medical Genome Initiative, Marshall Christian R. , Bick David , Belmont John W. , Taylor Stacie L. , Ashley Euan , Dimmock David , Jobanputra Vaidehi , Kearney Hutton M. , Kulkarni Shashikant , Rehm Heidi
Published: May 2020

Clinical whole-genome sequencing (WGS) offers clear diagnostic benefits for patients with rare disease. However, there are barriers to its widespread adoption, including a lack of standards for clinical practice. The Medical Genome Initiative consortium was formed to provide practical guidance and support the development of standards for the use of clinical WGS.
Epidermal growth factor upregulates expression of MUC5AC via TMEM16A, in chronic rhinosinusitis with nasal polyps
Authors: Jiao Jian , Zhang Tao , Zhang Yu , Li Jingyun , Wang Min , Wang Ming , Li Ying , Wang Xiangdong , Zhang Luo
Published: May 2020

Background

Mucus hypersecretion and goblet cell upregulation are common features of chronic rhinosinusitis with nasal polyps (CRSwNP). Although epidermal growth factor (EGF) has been reported to stimulate the expression of MUC5AC, the major macro-molecular constituent of airway mucus, the precise mechanisms underlying the regulation of MUC5AC expression are still not fully understood. The aim of this study therefore was to investigate the role of EGF in regulation of mucin MUC5AC expression and define the involvement of transmembrane protein 16A (TMEM16A) in mediating the EGF-induced mucus overexpression.

Methods

Human nasal epithelial cells (HNECs) derived from tissue of patients with CRSwNP and control subjects were established as air–liquid interface (ALI) cultures. Differentiated cultures were treated with different concentrations of EGF for 4–24 h, and assessed for the expression of TMEM16A and MUC5AC by real-time RT-PCR, Western blotting, ELISA and immunofluorescence. Cultures pretreated for 30 min with T16Ainh-A01 (a specific TMEM16A inhibitor) or LY294002 (a phosphoinositide 3-kinase (PI3K) inhibitor) were also assessed similarly following EGF treatment.

Results

EGF treatment (10–100 ng/ml for 4–24 h) significantly increased the expression of both TMEM16A and MUC5AC mRNA and protein, as well as the percentage of TMEM16A-positive cells, MUC5AC-positive cells and cells coexpressing TMEM16A and MUC5AC in HNECs compared to control non-EGF-treated HNECs. Pretreatment of the HNECs with T16Ainh-A01 and LY294002 attenuated these EGF-induced effects.

Conclusions

This study demonstrated that EGF upregulates the expression of MUC5AC in HNECs from CRSwNP patients. Furthermore, the EGF-mediated regulation of MUC5AC expression is likely to involve a PI3K-TMEM16A signalling pathway in CRSwNP.
Dysregulation of protein synthesis and dendritic spine morphogenesis in ASD: studies in human pluripotent stem cells
Authors: Lo Louisa Hoi-Ying , Lai Kwok-On
Published: May 2020

Autism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has been observed in ASD patients and transgenic mice that model different monogenetic causes of ASD. A number of ASD-associated genetic variants are known to disrupt dendritic local protein synthesis, which is essential for spine morphogenesis, synaptic transmission, and plasticity. Most of our understanding on the molecular mechanism underlying ASD depends on studies using rodents. However, recent advance in human pluripotent stem cells and their neural differentiation provides a powerful alternative tool to understand the cellular aspects of human neurological disorders. In this review, we summarize recent progress on studying mRNA targeting and local protein synthesis in stem cell-derived neurons, and discuss how perturbation of these processes may impact synapse development and functions that are relevant to cognitive deficits in ASD.
Correction to: Effects of dietary hemp seed oil to sows on fatty acid profiles, nutritional and immune status of piglets
Authors: Vodolazska D. , Lauridsen C.
Published: May 2020

In the original publication of this article [1], a figure of gene expression of Cox-2 in the Appendix 1 is missing. The correct Appendix is attached.
International Hip Outcome Tool (12-items) as health-related quality-of-life measure in osteoarthritis: validation of Greek version
Authors: Stasi Sophia , Stamou Magdalini , Papathanasiou George , Frantzeskaki Paraskevi , Kanavas Emmanouil , Evaggelou-Sossidis George , Gouskos Adamantios , Palantzas Andreas , Poursanidis Kyriakos , Macheras George A.
Published: May 2020

Background

The 12-item International Hip Outcome Tool (iHOT12) is a patient-reported outcome (PRO) designed to evaluate quality of life. We assessed the psychometric properties of the Greek version (iHOT12-Gr) in hip osteoarthritic patients.

Methods

Data from 124 patients aged > 50 years were used for factor analysis. Reliability evaluation included internal consistency, test-retest reliability, and interpretability. Content validity was examined by calculating the item-level content validity indices (I-CVI) and the scale-level content validity indices (S-CVI), using two methods: S-CVI Average (S-CVI/Ave), and the S-CVI Universal Agreement among experts (S-CVI/UA). Construct validity was tested against Greek versions of the Lower Extremity Functional Scale (LEFS-Greek), Modified Harris Hip Score (MHHS-Gr), and the 30 s chair-to-stand, Timed Up & Go (TUG), and 9-stairs-ascend/descend (9S-A/D) tests. Known-groups validity was examined using LEFS-Greek (cut-off = 53 points) as estimate variable. Responsiveness was examined pre and post total hip arthroplasty (4 and 8 weeks).

Results

Factor analysis revealed a two-factor model. Factor-1 (items 1–9) reflects “Symptoms and functionality”, while Factor-2 (items 10–12) reflects “Hip disorder-related concerns”. Reliability: Internal consistency and test-retest reliability of iHOT12-Gr-total were excellent: Cronbach’s alpha > 0.92 and ICC(95% CI) > 0.976(0.96–0.99)(p < 0.001). Interpretability: There was no floor or ceiling effect; measurement error: 3.72 (Factor-1), 3.64 (Factor-2), and 3.22 (iHOT12-Gr-total); minimal detectable change: 10.3 (Factor-1), 10.1 (Factor-2), and 8.92 (iHOT12-Gr-total). Validity: Content validity: The I-CVI value of the 12 items ranged from 1.00 to 0.83, the S-CVI/Ave was 0.97 and the S-CVI/UA was 0.83. Construct validity: iHOT12-Gr correlated strongly with both LEFS-Greek and MHHS-Gr, and weakly but significantly with 30s chair-to-stand, TUG and 9S-A/D (p < 0.001). Known-groups validity showed that iHOT12-Gr well discriminated subgroups of patients (p < 0.001). ROC analysis cut-off points were 51.9 (Factor-1), 25 (Factor-2) and 45.2 (iHOT12-Gr-total) (p < 0.001). Responsiveness: Four and 8 weeks postoperatively, standardized response means of Factor-1, Factor-2, and iHOT12-Gr-total were > 0.8.

Conclusion

iHOT12-Gr showed excellent reliability properties. The content validity was excellent and significant weak-to-strong correlations were found regarding construct validity. The known-group validity was also significant, while the responsiveness was excellent. iHOT12-Gr could be a reliable and valid PRO for assessing quality of life in patients with hip osteoarthritis.
The role of advanced MRI in the development of treat-to-target therapeutic strategies, patient stratification and phenotyping in rheumatoid arthritis
Authors: Mobasheri Ali , Hinton Mark , Shaikh Faiq , Kubassova Olga
Published: May 2020

In this commentary, we discuss the potential of advanced imaging, particularly Dynamic Contrast Enhanced (DCE) magnetic resonance imaging (MRI) for the objective assessment of the inflammatory process in rheumatoid arthritis (RA). We emphasise the potential of DCE-MRI in advancing the field and exploring new areas of research and development in RA. We hypothesize that different grades of bone marrow edema (BME) and synovitis in RA can be examined and monitored in a more sensitive manner with DCE-MRI. Future treatments for RA may benefit from the application of enhanced imaging of BMEs and synovitis. DCE-MRI may also facilitate enhanced stratification and phenotyping of patients enrolled in clinical trials.
Learning to rebel
Authors: Luna Elsie , Mearman Andrew
Published: May 2020

Background

As a response to collective failure to move adequately towards sustainability, youth movements have grown. This article explores the experiences of one young climate activist, Elsie Luna. The article is the product of conversations between the co-authors, augmented by written material by Elsie Luna. The article seeks to avoid adultism, that is, the power that adults have over children; hence it is written principally using Elsie’s own words, with minimal translation or interpretation. The article reflects on three key recent events in Elsie Luna’s activism: her approach to the London headquarters of several oil companies; her ‘dying’ symbolically at the BBC in Berlin; and her recent involvement in the large Extinction Rebellion actions in London.

Findings

The article suggests that these events offer insights on learning. Specifically, she is formulating views on sustainability, on system change and associated strategies, and developing a moral position on these matters. She has learned socially, from family and other immediate influences, and from activism. Thus, further, she has learned from experience, but has done so in her own self-managed way.
Rapid guide to the management of cardiac patients during the COVID-19 pandemic in Egypt: “a position statement of the Egyptian Society of Cardiology”
Authors: Shaheen Sameh , Awwad Omar , Shokry Khalid , Abdel-Hamid Magdy , El-Etriby Adel , Hasan-Ali Hosam , Shawky Islam , Magdy Ahmad , Nasr Gamila , Kabil Hamza , Elhadidy Amr , Zaki Mohamad , Hegab Ahmad
Published: May 2020

COVID-19 pandemic poses an enormous challenge to healthcare system in Egypt. This document is a position statement from the Egyptian Society of Cardiology. It aims to provide information to cardiovascular healthcare providers in Egypt to guarantee delivery of qualitypatient careand ensure adequate levels ofprotectionagainst infection during the COVID-19 pandemic. Older patients and those with cardiovascular disease are at higher risk of mortality. The current situation requires unusual allocation of resources which may negatively impact the care of patients with cardiovascular disease. Cardiologists should be prepared in the COVID-19 pandemic. The challenge is in providing the best quality of care despite limited resources while keeping all medical staff as safe as possible. Consider deferring elective procedures whenever possible. All medical staff should undergo rigorous training on infection control and the use of high-quality personal protection equipment. Cardiologists should promote telemedicine in the outpatient setting, prioritize outpatient contacts, and avoid nosocomial dissemination of the virus to patients and healthcare providers. A much conservative approach for emergent cardiac patients is recommended, and invasive interventions are reserved for high risk hemodynamically unstable patients. During the pandemic, the most important principles of treatment should be controlling the spread of infection as the first priority, prompt assessment of patient risk, recommending conservative medical therapy rather than invasive interventions, and strict infection control measures to limit infection spread within the hospital and to healthcare workers.
Atypical central neurocytoma with leptomeningeal dissemination: a case report
Authors: Goyal Shikha , Kataria Tejinder , Gupta Deepak , Dhyani Aruj , Mohapatra Ishani , Narang Karanjit Singh
Published: May 2020

Background

Central neurocytomas represent 0.25–0.5% of all intracranial tumors in adults. Leptomeningeal spread is uncommon, and the exact incidence of meningeal spread is unknown due to sparse literature. We present the clinical course and management outcome of a case of atypical central neurocytoma with leptomeningeal spread.

Case presentation

A young gentleman, who initially presented with memory loss, was found to have a right intra-axial periventricular mass on imaging. He underwent subtotal resection, and operative histopathology suggested a periventricular atypical neurocytoma. In view of subtotal resection, adjuvant focal radiation therapy was recommended, but he developed headache and blurring of vision 10 days postoperatively. Contrast enhanced craniospinal magnetic resonance imaging (MRI) showed residual primary tumor as well as diffuse leptomeningeal spread. Cerebrospinal fluid cytology also showed malignant cells. After tumor board discussion, craniospinal axis irradiation was advised and delivered. He remained disease-free for 10 months after radiation therapy, but then developed local and spinal recurrence, and offered salvage chemotherapy. His general condition deteriorated following chemotherapy with disease progression, and he was subsequently advised best supportive care.

Conclusion

Leptomeningeal dissemination in atypical neurocytomas portends an aggressive course and adverse prognosis; management decisions may need tailoring as per individual presentation.
Association of polymorphisms in metastasis suppressor genes NME1 and KISS1 with breast cancer development and metastasis
Authors: Antar Sarah , Mokhtar Naglaa , Abd elghaffar Mahmoud Adel , Seleem Amal K.
Published: May 2020

Background

NME1 and KISS1 genes are two tumor metastasis suppressor genes, mapped to chromosomes 17q21.3 and 1q32 respectively. Here, we analyzed the association of EcoR1 (rs34214448—G/T) polymorphism in NME1 gene and 9 del T (rs5780218—A/-) polymorphism in KISS1 gene with breast cancer development and metastasis.

Results

The study included 75 women newly diagnosed with breast cancer recruited from Oncology Center at Mansoura University Hospitals and 37 age-matched healthy female volunteers as a control group. DNA was extracted from peripheral blood samples and genotyping of rs34214448 and rs5780218 SNPs was carried out by PCR-RFLP technique. NME1 EcoR1 (rs34214448) polymorphism has a statistically significant association with breast cancer risk (P < 0.001). Most of breast cancer group (55%) had heterozygous (G/T) genotype while most of control group (95%) had homozygous wild (G/G) genotype (P < 0.0005). Also, KISS1 rs5780218 polymorphism has a statistically significant association with breast cancer risk. The wild (A/A) genotype was associated with lower risk of breast cancer (A/- + -/- vs. A/A: OR = 3.1, 95% CI = 1.15–8.36, P = 0.025). EcoR1 (rs34214448) polymorphism revealed a significant association with tumor stage and distant metastasis as patients. Carriers of the wild (G/G) genotype were more likely to present with advanced disease stages and distant metastasis.

Conclusions

Both EcoR1 (rs34214448) polymorphism of NME1 gene and rs5780218 polymorphism of KISS1 gene revealed significant association with increased risk of breast cancer development. The (G/G) genotype of EcoR1 polymorphism was associated with higher risk of breast cancer metastasis.
Role of fetal echocardiography in morphologic and functional assessment of fetal heart in diabetic mothers
Authors: Raafat Mariam , Aborizk Sameh , Saraya Mahmoud , Soliman Hazem Hamed
Published: May 2020

Background

Diabetes mellitus (DM) is the commonest medical disorder faced during pregnancy and it includes type I, type II, and gestational diabetes. It may predispose to various complications including fetus malformation, macrosomia, spontaneous abortion, stillbirth, neonatal death, and intrauterine growth retardation. Hypertrophic cardiomyopathy (HCM) is one of the common anomalies depicted with diabetes. Fetal cardiac function analysis might provide important information on the hemodynamic status and cardiac adaptation to different perinatal complications.

Results

The mean septal thickness in the diabetic group was 0.7163 ± 0.1746 cm and 0.4989 ± 0.08068 cm in the control group. The mean myocardial thickness of the right ventricular free wall in the diabetic group was 0.6532 ± 0.13792 cm and 0.4874 ± 0.07482 cm in the control group. The mean myocardial thickness of the left ventricular free wall in the diabetic group was 0.6437 ± 0.13421 cm and 0.4737 ± 0.07573 cm in the control group. The mean value of myocardial performance index (Tie Index) in the diabetic group was 0.6232 ± 0.15606 and 0.4626 ± 0.04357 in the control group.

Conclusion

From our study, we can conclude that prenatal complete echocardiographic study should be mandatory in fetuses of diabetic mothers due to high risk of congenital heart defects and onset of hypertrophic cardiomyopathy with fetal cardiac function impairment in the third trimester.

Early diagnosis of congenital heart defects as well as evidence of hypertrophic cardiomyopathy and fetal cardiac function impairment that occurs in fetuses of maternal diabetes will definitely guide prompt postnatal therapy and care for those neonates.
Visualizing implementation: contextual and organizational support mapping of stakeholders (COSMOS)
Authors: Bernstein Steven L. , Weiss June , Curry Leslie
Published: May 2020

Background

While stakeholder mapping is common in public policy, social sciences, and business management, this tool has not often been used in healthcare settings. We developed a new method of healthcare stakeholder mapping, which we call Contextual and Organizational Support Mapping of Stakeholders (COSMOS), to identify and assess key stakeholders in an implementation project. Stakeholder mapping allows the implementation team to assess and visually display all relevant stakeholders, their support for the project, and their ability to facilitate—or hinder—project implementation.

Methods

The COSMOS model was developed to visualize the stakeholders involved in a hospital-based study conducted from 2013–2016. In this study, a new screen prompt and order set were embedded in the electronic health record to facilitate the identification and treatment of adult smokers admitted to the hospital. Physicians were the unit of randomization; physician behavior and tobacco quit rates among patients were followed for 1 year. Qualitative interviews with hospital administration, physicians, and information technology (IT) personnel (n=24) were conducted to identify the components and characteristics of the COSMOS.

Results

The COSMOS consists of an organizational chart identifying all key stakeholders, with manipulation of colors and borders of the component boxes to indicate stakeholder support for the implementation project, and degree of criticality to its success. The COSMOS visualization informed the team’s subsequent work by identifying potential impediments that might require additional attention to garner and maintain support throughout the project. In addition, the approach has proved to be a useful tool to explain these concepts to trainees in implementation science.

Conclusion

The COSMOS schematic provides a visually rich means of identifying stakeholders, understanding their relationships to each other, displaying their level of support for the proposed implementation, and noting their criticality to the effort. The COSMOS can support researchers, project teams, administrators, and others engaged with implementation science-related work in healthcare, as well as other fields such as education, government, and industry.