bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptability and feasibility of short message service to improve ART medication adherence among people living with HIV/AIDS receiving antiretroviral treatment at Adama hospital medical college, Central Ethiopia
Authors: Endebu Tamrat , Deksisa Alem , Dugasa Warku , Mulu Ermiyas , Bogale Tilahun
Published: October 2019

Background

People living with HIV/AIDS are facing sub-optimal adherence to antiretroviral therapy. Short message service innovative strategies have been recommended by the national strategy to support medication adherence among HIV positive people. Thus, this study was conducted to examine the feasibility and acceptability of a short message service to improve medication adherence among people living with HIV/AIDS receiving Antiretroviral Treatment.

Methods

We conducted a cross-sectional survey, from February 5 to 30, 2018, among 422 randomly selected adults living with HIV/AIDS receiving antiretroviral treatment at Adama Hospital. Interviewer administered structured questionnaire was used to collect quantitative data on the feasibility and acceptability of short message services, socio-demographic and clinical characteristics of participants. Qualitative data were also collected from two focus groups to supplement the quantitative findings. Logistic regression analysis was performed to identify factors associated with the feasibility and acceptability of short message services.

Results

Of 420 participants responded to our questionnaire, about nine of ten patients (93.8%) possessed had a mobile phone. Most of the patients (90.9%) were willing to accept SMS to improve their medication adherence. Patients who were in young age, early adult, disclosed their HIV status, having cell phone always and believe short message service aid adherence were more likely to accept short messages on adherence. On the other hand, frequent ART Clinic visit and perceived low confidentiality of short message service were negatively associated with acceptability of short message service.

Conclusion

The acceptability of short message service on adherence to antiretroviral therapy was high among people living with HIV/AIDS central Ethiopia. Authors recommend further studies, piloting or experimenting, that validate the acceptability, feasibility, effectiveness, and scalability of the intervention.
Kikuchi-Fujimoto disease: a case report and the evaluation of diagnostic procedures
Authors: Xu Shenjie , Sun Weilian , Liu Jiamei
Published: October 2019

Background

Kikuchi-Fujimoto disease, known as histiocytic necrotizing lymphadenitis, is a benign, self-limiting and systemic disorder involving lymph nodes with unknown aetiology. First reported in Japan, there has been an increase in its incidence globally. Because of its non-specific clinical features, the disease can be easily mistaken for other forms of lymphadenitis with a high rate of misdiagnosis and mistreatment, posing a considerable challenge.

Case presentation

A case of young Chinese woman with fever and cervical lymphadenopathy is presented. Physical examinations and imaging techniques were used to rule out common forms of lymphadenitis (e.g. cat-scratch disease and tuberculous lymphadenitis). Laboratory tests were then conducted to exclude others such as systemic lupus erythematosus and non-Hodgkin lymphoma. After Kikuchi-Fujimoto disease was identified, the patient was managed with symptomatic treatments. Our case was compared with relevant cases in the literature. A diagnostic flow chart was proposed to facilitate the diagnosis and treatment.

Conclusions

With its shared clinical features, Kikuchi-Fujimoto disease can be mistaken for other forms of lymphadenitis. A combined use of medical imaging and laboratory tests is the effective way to avoid misdiagnosis.
Antioxidant and Cytoprotective effects of Pyrola decorata H. Andres and its five phenolic components
Authors: Chen Ban , Li Xican , Liu Jie , Qin Wei , Liang Minshi , Liu Qianru , Chen Dongfeng
Published: October 2019

Background

Pyrola decorata H. Andres, is exclusively distributed in China and a source of traditional Chinese herbal medicine Luxiancao for more than 2000 years. Here, we evaluated the antioxidant and cytoprotective effects of P. decorata and its five phenolic components (protocatechuic acid, gallic acid, hyperoside, 2′′-O-galloylhyperin, and quercetin), and discussed their antioxidant chemistry.

Methods

A lyophilized aqueous extract of P. decorata (LAEP) was prepared and analyzed with high-performance liquid chromatography (HPLC). LAEP and its five phenolic components were comparatively investigated using five antioxidant assays, including ferric-reducing antioxidant power, cupric ion-reducing antioxidant capacity, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical (PTIO•)-scavenging, 1,1-diphenyl-2-picryl-hydrazl radical (DPPH•)-scavenging, and 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical (ABTS+•)-scavenging activities. The reaction products of the five phenolic components with 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl radical (4-methoxy-TEMPO•) were determined with ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis. LAEP and its five phenolic components were incubated with bone marrow-derived mesenchymal stem cells (bmMSCs) subjected to oxidative stress to demonstrate their cytoprotective effects with a flow cytometry assay.

Results

In the five antioxidant assays, LAEP and its five phenolic components dose-dependently increased the radical-scavenging (or reducing power) activities. However, the IC50 values of hyperoside were consistently higher than those of 2′′-O-galloylhyperin. UPLC-ESI-Q-TOF-MS/MS analysis results indicated that the five phenolics could yield dimer products in the presence of 4-methoxy-TEMPO• via the radical adduct formation (RAF) pathway. Flow cytometry assay results confirmed the cytoprotective activity of LAEP and its five phenolic components toward stressed bmMSCs. In particular, 2′′-O-galloylhyperin could more effectively reduce the percentage of damaged bmMSCs than hyperoside.

Conclusion

LAEP and its five phenolic components may undergo redox-based pathways (such as electron transfer and H+ transfer) and covalent-based pathway (i.e., RAF) to exhibit antioxidant activity. One consequence of RAF is the generation of phenolic-phenolic dimer. In both organic and aqueous media, 2′′-O-galloylhyperin exhibited higher redox-based antioxidant levels (or cytoprotective levels) than those with hyperoside. The differences could be attributed to 2′′-O-galloylation reaction.
Methods for a similarity measure for clinical attributes based on survival data analysis
Authors: Karmen Christian , Gietzelt Matthias , Knaup-Gregori Petra , Ganzinger Matthias
Published: October 2019

Background

Case-based reasoning is a proven method that relies on learned cases from the past for decision support of a new case. The accuracy of such a system depends on the applied similarity measure, which quantifies the similarity between two cases. This work proposes a collection of methods for similarity measures especially for comparison of clinical cases based on survival data, as they are available for example from clinical trials.

Methods

Our approach is intended to be used in scenarios, where it is of interest to use longitudinal data, such as survival data, for a case-based reasoning approach. This might be especially important, where uncertainty about the ideal therapy decision exists. The collection of methods consists of definitions of the local similarity of nominal as well as numeric attributes, a calculation of attribute weights, a feature selection method and finally a global similarity measure. All of them use survival time (consisting of survival status and overall survival) as a reference of similarity. As a baseline, we calculate a survival function for each value of any given clinical attribute.

Results

We define the similarity between values of the same attribute by putting the estimated survival functions in relation to each other. Finally, we quantify the similarity by determining the area between corresponding curves of survival functions. The proposed global similarity measure is designed especially for cases from randomized clinical trials or other collections of clinical data with survival information. Overall survival can be considered as an eligible and alternative solution for similarity calculations. It is especially useful, when similarity measures that depend on the classic solution-describing attribute “applied therapy” are not applicable. This is often the case for data from clinical trials containing randomized arms.

Conclusions

In silico evaluation scenarios showed that the mean accuracy of biomarker detection in k = 10 most similar cases is higher (0.909–0.998) than for competing similarity measures, such as Heterogeneous Euclidian-Overlap Metric (0.657–0.831) and Discretized Value Difference Metric (0.535–0.671). The weight calculation method showed a more than six times (6.59–6.95) higher weight for biomarker attributes over non-biomarker attributes. These results suggest that the similarity measure described here is suitable for applications based on survival data.
Stroke survivors’ experiences of team support along their recovery continuum
Authors: Hartford W. , Lear S. , Nimmon L.
Published: October 2019

Background

A coordinated stroke rehabilitation care team is considered optimal for supporting stroke survivors from diagnosis to recovery. Despite this recognition, many stroke survivors cannot access essential rehabilitation services. Furthermore, there is a lack of understanding of stroke patients’ and their caregivers’ rehabilitation needs and wishes. We sought to gain insight into healthcare and social structures from the perspective of patients and caregivers that can better support long-term stroke recovery.

Methods

We conducted individual interviews with 24 participants comprised of stroke survivors, spousal caregivers, stroke support group coordinators, and speech pathologist. Participants were recruited through three stroke survivor support groups. An empowerment lens was integrated into data analysis and data interpretation.

Results

Two dominant themes captured participants’ experiences through stroke survivors’ trajectory of care. 1) Experiences of managing stroke. This theme identified stroke survivors and spousal caregivers’ experiences with stroke recovery, rehabilitation, and fulfilling unmet needs. 2) Resources of support. This theme described the social and financial support structures drawn upon to assist with stroke rehabilitation.

Conclusions

The study highlighted a lack of teamwork between stroke survivors, spousal caregivers, and health professionals. This fragmented care was compounded by inequities in rehabilitation programs and health services resulting in what appeared to be a disempowering rehabilitation process. Although stroke recovery groups were a significant source of support for stroke survivors and spousal caregivers, participants perceived they were overlooked, by stroke recovery healthcare providers, as a site for stroke recovery healthcare services. An empowerment approach to stroke rehabilitation involves collaboration between stroke survivors, caregivers, healthcare providers, health services, and existing community stroke support structures. Framing stroke based care through an empowerment lens may serve to address stroke rehabilitation inadequacies and inequities.
Modular service provision for heterogeneous patient groups: a single case study in chronic Down syndrome care
Authors: Fransen L. , Peters V. J. T. , Meijboom B. R. , de Vries E.
Published: October 2019

Background

Service modularity could be promising for organizing healthcare delivery to heterogeneous patient groups because it enables cost reductions while also being responsive towards individual patients’ needs. However, no research on the applicability of modularity in this context exists. To this end, we conducted a qualitative single-case study on chronic healthcare provision for Down syndrome patients, delivered by multidisciplinary pediatric Downteams in the Netherlands, from a modular perspective.

Methods

We conducted six semi-structured interviews with coordinators of multidisciplinary Downteams in six hospitals. In addition, we gathered data by means of observations and analysis of relevant documentation. We transcribed, coded, and analyzed the interviews utilizing the Miles and Huberman approach. The consolidated criteria for reporting qualitative research (COREQ) were applied in this study.

Results

In all six Downteams studied, the modular package for Down syndrome patients (i.e. the visit to the Downteams) could clearly be divided into modules (i.e. the separate consultations with the various professionals), and into different components (i.e. sub-elements of these consultations). These modules and components were linked by different types of customer-flow and information-flow interfaces. These interfaces allowed patients to flow smoothly through the system and allowed for information transfer, respectively.

Conclusion

Our study shows a modular perspective is applicable to analyzing chronic healthcare for a heterogeneous patient group like children with Down syndrome. The decomposition of the various Downteams into modules and components led to mutual insight into each other’s professional practices, both within and across the various Downteams studied. It could be used to increase transparency of delivered care for patients and family. Moreover, it could be used to customize care provision by mixing-and-matching components. More detailed research on chronic modular care provision for patients with DS is needed to explore this.
Feasibility and long-term efficacy of a proactive health program in the treatment of chronic back pain: a randomized controlled trial
Authors: Hüppe A. , Zeuner C. , Karstens S. , Hochheim M. , Wunderlich M. , Raspe H.
Published: October 2019

Background

To facilitate access to evidence-based care for back pain, a German private medical insurance offered a health program proactively to their members. Feasibility and long-term efficacy of this approach were evaluated.

Methods

Using Zelen’s design, adult members of the health insurance with chronic back pain according to billing data were randomized to the intervention (IG) or the control group (CG). Participants allocated to the IG were invited to participate in the comprehensive health program comprising medical exercise therapy and life style coaching, and those allocated to the CG to a longitudinal back pain survey. Primary outcomes were back pain severity (Korff’s Chronic Pain Grade Questionnaire) as well as health-related quality of life (SF-12) assessed by identical online questionnaires at baseline and 2-year follow-up in both study arms. In addition to analyses of covariance, a subgroup analysis explored the heterogeneity of treatment effects among different risks of back pain chronification (STarT Back Tool).

Results

Out of 3462 persons selected, randomized and thereafter contacted, 552 agreed to participate. At the 24-month follow-up, data on 189 of 258 (73.3%) of the IG were available, in the CG on 255 of 294 (86.7%). Significant, small beneficial effects were seen in primary outcomes: Compared to the CG, the IG reported less disability (1.6 vs 2.0; p = 0.025; d = 0.24) and scored better at the SF-12 physical health scale (43.3 vs 41.0; p < 0.007; d = 0.26). No effect was seen in back pain intensity and in the SF-12 mental health scale. Persons with medium or high risk of back pain chronification at baseline responded better to the health program in all primary outcomes than the subgroup with low risk at baseline.

Conclusions

After 2 years, the proactive health program resulted in small positive long-term improvements. Using risk screening prior to inclusion in the health program might increase the percentage of participants deriving benefits from it.

Trial registration

The trial was registered at the German Clinical Trials Register under DRKS00015463 retrospectively (dated 4 Sept 2018).
Knowledge, attitude and practices of medical and health science students on the antiretroviral based HIV post-exposure prophylaxis in an Ethiopian hospital: an institutional based cross-sectional study
Authors: Anteneh Betelhem , Belachew Sewunet Admasu , Endeshaw Alem , Wubneh Zewdu Birhanu , Sarkar Barun Ranjan
Published: October 2019

Background

HIV/AIDS in resource-limited settings poses a high risk of occupational exposure to healthcare workers due to higher number of HIV infected patients. Hence, antiretroviral based post-exposure prophylaxis (PEP) for HIV is very crucial. The aim of the study was to determine the knowledge, attitudes, and practices of medical and Health science students on antiretroviral based HIV PEP in University of Gondar comprehensive specialized hospital (UOGCSH), Northwestern Ethiopia.

Methods

An institutional-based cross-sectional study was conducted among 220 medical and health science graduating students in UOGCSH from May to July 2015. Data were collected using a self-administered pretested questionnaire. The collected data were analyzed using SPSS software version 22. Results were summarized in frequencies, percentages, and means with standard deviations and presented using tables or figures.

Results

Among the respondents, only sixty-six (30%) of the 220 study participants has had adequate knowledge about HIV PEP. Furthermore, over 90 % of the students had positive attitude towards HIV PEP f. Out of the total respondents, 37/220 (16.8%) were in need of HIV PEP and of these students only 18/37 (48.6%) took PEP. On the other hand, merely 50% of the study subjects completed the full course of HIV PEP, while the rest 50% failed to finish. As to the respondents self-report, the sole reason for starting but failing to complete the full course of HIV PEP was intolerance to the side effects of antiretroviral.

Conclusions

Although majority of the respondents had poor knowledge and practice, they owned a good attitude towards HIV PEP. Therefore, a pre-service intensive training for all students regarding HIV PEP prior to their clinical attachments is mandatory. In addition, potential side effects of ARTs and its managements should be priory informed to the students so as to prevent the associated non-adherence to ultimately reduce the incidence of drug resistance. Moreover, the habit of needle stick injury reporting was found to be poor that needs due improvement and there has been also a pressing need to supply sufficient protective barriers to the students while planning and rendering services.
Should there be a World Health Assembly resolution for malaria eradication? Opinion against
Authors: John T. Jacob
Published: October 2019

A resolution for eradicating malaria, if passed by the World Health Assembly (WHA), will have a distracting effect on all countries with malaria. The continued prevalence of malaria is indicative of weak public health infrastructure. True, smallpox was eradicated by international efforts following WHA resolution: the success factor was primary prevention using a safe and effective vaccine. A resolution to eradicate polio was passed in 1988, with a target year of 2000, but even in 2019 success is not within reach. Public health experts are hesitant to move forward with measles eradication before polio is eradicated. Country by country elimination of malaria is a better way, ensuring the strengthening of public health infrastructure, with many other health benefits.
Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis
Authors: Yang Rui-Xu , Pan Qin , Liu Xiao-Lin , Zhou Da , Xin Feng-Zhi , Zhao Ze-Hua , Zhang Rui-Nan , Zeng Jing , Qiao Liang , Hu Chun-Xiu , Xu Guo-Wang , Fan Jian-Gao
Published: October 2019

Background

Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy.

Methods

Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB).

Results

Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Pparα, Cpt-1α and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB.

Conclusions

Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH.

Trial registration

Registration ID: ChiCTR-DDT-13003983. Data of registration: 13 May, 2013, retrospectively registered.
Correction to: MIIP inhibits the growth of prostate cancer via interaction with PP1α and negative modulation of AKT signaling
Authors: Yan Guang , Ru Yi , Yan Fengqi , Xiong Xin , Hu Wei , Pan Tao , Sun Jianming , Zhang Chi , Wang Qinhao , Li Xia
Published: October 2019

Following publication of the original article [1], the authors reported that the given name of Qinhao Wang was incorrectly published as Qinghao Wang. The original article has been corrected.
Plasmacytoid urothelial carcinoma: a rapid autopsy case report with unique clinicopathologic and genomic profile
Authors: Simon Caroline T. , Skala Stephanie L. , Killen Paul D. , Siddiqui Javed , Cao Xuhong , Qiao Yuanyuan , Al-Ahmadie Hikmat , Camelo-Piragua Sandra I. , Jentzen Jeffrey , Chinnaiyan Arul M. , Dhanasekaran Saravana M. , Reichert Zachery R. , Mehra Rohit
Published: October 2019

Background

Rapid (“warm”) autopsies of patients with advanced metastatic cancer provide important insight into the natural history, pathobiology and histomorphology of disease in treatment-resistant tumors. Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma characterized by neoplastic cells morphologically resembling plasma cells. PUC is typically aggressive, high-stage at presentation, and associated with poor outcomes. Recurrence is common in PUC, with the majority of recurrences occurring in the peritoneum.

Case presentation

Here, we report rapid autopsy findings from a patient with recurrent PUC. The patient had persistent pain after cystoprostatectomy, although initial post-operative imaging showed no evidence of disease. Imaging obtained shortly before his death showed only subtle growth along vascular tissue planes; however, extensive disease was seen on autopsy. Plasmacytoid tumor cells formed sheets involving many serosal surfaces. Molecular interrogation confirmed a mutation in CDH1 exon 12 leading to early truncation of the CDH1 protein in the tumor cells.

Conclusions

The sheet-like growth pattern of PUC makes early phases of disease spread much more difficult to capture on cross-sectional imaging. Alternative forms of surveillance may be required for detection of recurrent PUC, and providers may need to treat based on symptoms and clinical suspicion.
The Chk1 inhibitor SAR-020106 sensitizes human glioblastoma cells to irradiation, to temozolomide, and to decitabine treatment
Authors: Patties Ina , Kallendrusch Sonja , Böhme Lisa , Kendzia Eva , Oppermann Henry , Gaunitz Frank , Kortmann Rolf-Dieter , Glasow Annegret
Published: October 2019

Background

Glioblastoma is the most common and aggressive brain tumour in adults with a median overall survival of only 14 months after standard therapy with radiation therapy (IR) and temozolomide (TMZ). In a novel multimodal treatment approach we combined the checkpoint kinase 1 (Chk1) inhibitor SAR-020106 (SAR), disrupting homologue recombination, with standard DNA damage inducers (IR, TMZ) and the epigenetic/cytotoxic drug decitabine (5-aza-2′-deoxycitidine, 5-aza-dC). Different in vitro glioblastoma models are monitored to evaluate if the impaired DNA damage repair may chemo/radiosensitize the tumour cells.

Methods

Human p53-mutated (p53-mut) and -wildtype (p53-wt) glioblastoma cell lines (p53-mut: LN405, T98G; p53-wt: A172, DBTRG) and primary glioblastoma cells (p53-mut: P0297; p53-wt: P0306) were treated with SAR combined with TMZ, 5-aza-dC, and/or IR and analysed for induction of apoptosis (AnnexinV and sub-G1 assay), cell cycle distribution (nuclear PI staining), DNA damage (alkaline comet or gH2A.X assay), proliferation inhibition (BrdU assay), reproductive survival (clonogenic assay), and potential tumour stem cells (nestinpos/GFAPneg fluorescence staining). Potential treatment-induced neurotoxicity was evaluated on nestin-positive neural progenitor cells in a murine entorhinal-hippocampal slice culture model.

Results

SAR showed radiosensitizing effects on the induction of apoptosis and on the reduction of long-term survival in p53-mut and p53-wt glioblastoma cell lines and primary cells. In p53-mut cells, this effect was accompanied by an abrogation of the IR-induced G2/M arrest and an enhancement of IR-induced DNA damage by SAR treatment. Also TMZ and 5-aza-dC acted radioadditively albeit to a lesser extent. The multimodal treatment achieved the most effective reduction of clonogenicity in all tested cell lines and did not affect the ratio of nestinpos/GFAPneg cells. No neurotoxic effects were detected when the number of nestin-positive neural progenitor cells remained unchanged after multimodal treatment.

Conclusion

The Chk1 inhibitor SAR-020106 is a potent sensitizer for DNA damage-induced cell death in glioblastoma therapy strongly reducing clonogenicity of tumour cells. Selectively enhanced p53-mut cell death may provide stronger responses in tumours defective of non-homologous end joining (NHEJ). Our results suggest that a multimodal therapy involving DNA damage inducers and DNA repair inhibitors might be an effective anti-tumour strategy with a low risk of neurotoxicity.
Infants and young children feeding practice and associated factors among HIV positive mothers of children 0–23 months in health centers of Gulele sub-city, Addis Ababa, Ethiopia
Authors: Negash Samuel , Mesfin Firehiwot , Egata Gudina
Published: October 2019

Objective

A health facility based cross sectional study design was conducted among 358 randomly selected HIV positive mothers attending at four health centers from February 1 to 28, 2018. Magnitude of HIV positive mothers’ child feeding practice and associated factors was assessed according to WHO recommendation. Data were collected using structured pretested questionnaire and entered into EPI data version 3.1 and exported to SPSS version 20 computer software for analysis.

Result

The magnitude of recommended way of infant feeding practice among HIV positive mothers attending public health centers in Gulele sub-city is 37.4%, 95% CI (32.26–42.67). Statistically significant correlates of HIV exposed infant feeding practice of mothers in this study were knowledge of mother on HIV exposed infant feeding practice (AOR = 1.80 (95% CI 1.04–3.01)), head of family being father (AOR = 0.17 (95% CI 0.03–0.87)), having family (relatives) support (AOR = 2.05 (95% CI 1.00–4.18)) and information on HIV exposed infant feeding, practice (AOR = 1.77 (95% CI 1.07–2.93)).
Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy
Authors: Wang Yi , Guo Zhiheng , Gao Yongmei , Liang Ping , Shan Yanhong , He Jin
Published: October 2019

Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy.
Patients’ experiences from basic body awareness therapy in the treatment of binge eating disorder -movement toward health: a phenomenological study
Authors: Albertsen Marit Nilsen , Natvik Eli , Råheim Målfrid
Published: October 2019

Background

Binge Eating Disorder (BED) is the most common eating disorder. Patients with BED are often not diagnosed, nor offered adequate specific treatment. A great number of those who receive recommended treatment do not recover over time. More knowledge about central aspects of BED, and treatments that specifically target such aspects is needed. Previous research has linked body experience to the development and maintenance of eating disorders, as well as influencing treatment results and the risk of relapse. The aim of this study was to explore how patients with BED experience Basic Body Awareness Therapy (BBAT), which is a psychomotor physiotherapy treatment addressing body experience.

Method

In this phenomenological study, we interviewed two patients with BED in depth during and after treatment. Video observations of treatment sessions and logs written by the patients were used as supporting data. The analysis was guided by Van Manen’s hermeneutic phenomenology.

Results

A meaning structure was identified: “On the way from the body as a problem to the body as a possibility.” The two participants that besides BED also had a history of childhood trauma, perceived BBAT as a process of getting to know their own bodies in new ways, and described that the way they related to their own body changed as did aspects of their way of being. These changes were prominent when the participants described emotions, movement, pain, calmness, and self-experience, and interwoven with relational aspects as well as practices in everyday life.

Conclusion

The present results indicate that BBAT stimulated body experience in a way that opened new possibilities for two participants with BED, and hence that BBAT can improve the health status of BED patients also suffering from childhood trauma.
Comparison of a tridimensional cephalometric analysis performed on 3T-MRI compared with CBCT: a pilot study in adults
Authors: Maspero Cinzia , Abate Andrea , Bellincioni Francesca , Cavagnetto Davide , Lanteri Valentina , Costa Antonella , Farronato Marco
Published: October 2019

Objective

Since the introduction of cone-beam computed tomography (CBCT) in dentistry, this technology has enabled distortion-free three-dimensional cephalometric analysis for orthodontic and orthognathic surgery diagnosis. However, CBCT is associated with significantly higher radiation exposure than traditional routine bidimensional examinations for orthodontic diagnosis, although low-dose protocols have markedly reduced radiation exposure over time.

The objective of this preliminary feasibility study is to compare the accuracy and diagnostic capabilities of an already-validated three-dimensional cephalometric analysis on CBCT to those of an analysis on 3-T magnetic resonance imaging (3T-MRI) to assess whether the latter can deliver a comparable quality of information while avoiding radiation exposure.

Materials and methods

In order to test the feasibility of three-dimensional cephalometry on 3T-MRI, 18 subjects (4 male; 14 female) with mean age 37.8 ± SD 10.2, who had undergone both maxillofacial CBCT and maxillofacial 3T-MRI for various purposes within 1 month, were selected from the archive of the Department of Dentistry and Maxillofacial Surgery of Fondazione Ospedale Policlinico Maggiore, IRCCS, Milano, Italy.

A three-dimensional cephalometric analysis composed of ten midsagittal and four bilateral landmarks and 24 measurements (11 angular, 13 linear) was performed on both scans using Mimics Research® v. 17.0 (NV, Technologielaan 15, 3001 Leuven, Belgium). Cephalometric analysis was performed twice by two independent orthodontists for each scan, and each orthodontist repeated the measurements 3 weeks later. Statistical analysis was performed with SPSS® 20.00 for Windows (IBM® Corporation, Sommers, NY, USA). A Bland-Altman test for each cephalometric value was performed to assess the agreement between the procedures. The intraclass correlation coefficient (ICC) was used to assess interobserver and intraobserver reliability. The coefficient of variation was used to evaluate precision.

Results

Both procedures showed good reliability, with mean intraobserver ICCs of 0.977/0.971 for CBCT and 0.881/0.912 for MRI. The average interobserver ICCs were 0.965 for CBCT and 0.833 for MRI. A Bland-Altman analysis for the cephalometric tracing revealed a similar range of agreement between the two modalities; the bias range (mean ± SD) was − 0.25–0.66 mm (0.174 ± 0.31) for distances and − 0.41–0.54° (0.12 ± 0.33) for angles.

Conclusions

Within the main limitation of this pilot study, that is, the small sample, it is possible to state that cephalometric measurements on 3T-MRI seem to possess adequate reliability and repeatability and that they show satisfying agreement with values measured on CBCTs. An MRI examination does not expose patients to ionizing radiation and could provide an alternative to CBCT for three-dimensional cephalometrics in the future.
Electronic nicotine delivery system (ENDS) liquid nicotine exposure in young children presenting to US emergency departments, 2018
Authors: Chang Joanne T. , Rostron Brian L.
Published: October 2019

Background

Increased use of electronic nicotine delivery systems (ENDS) in the United States (U.S.) has been related to acute adverse events from liquid nicotine exposure. Previous studies have reported on these events through 2017.

Findings

We used 2018 National Emergency Injury Surveillance System data to generate national estimates with 95% confidence intervals (CIs) of ENDS liquid nicotine-related poisonings among children under age 5 treated in U.S. hospital emergency departments (EDs). In 2018, an estimated 885 (95% CI: 397–1374) poisoning cases related to liquid nicotine among children under 5 were treated in U.S. EDs, which was a non-statistically signficant increase from 2017 (411 poisoning cases, 95% CI: 84–738). The most common route of exposure was through ingestion (99.4%). The majority of cases were treated and released from the hospital (90.0%), 8.9% of the cases left the hospital without being seen, and 1.1% of the cases were treated and admitted to the hospital.

Conclusions

This study provides updated national estimates of poisoning events related to liquid nicotine exposure that occurred in 2018 among children under age 5. Updated information from this study may complement public education efforts and prevent liquid nicotine exposure among children.
Temporary loss of consciousness during cetuximab treatment of a patient with metastatic colon cancer: a case report
Authors: Fukui Taro , Suzuki Koichi , Tamaki Sawako , Abe Iku , Endo Yuhei , Ishikawa Hideki , Kakizawa Nao , Watanabe Fumiaki , Saito Masaaki , Tsujinaka Shingo , Futsuhara Kazushige , Miyakura Yasuyuki , Noda Hiroshi , Rikiyama Toshiki
Published: October 2019

Background

Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed.

Case presentation

A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment.

Conclusions

This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.
A pathological complete response by chemotherapy with S-1 and oxaliplatin for a locally advanced duodenal adenocarcinoma in Lynch syndrome: a case report
Authors: Yasuda Satoshi , Harada Suzuka , Tsujimoto Akinori , Aoki Satoko , Takei Takeshi , Migita Kazuhiro , Ueno Masato , Tatsumi Mitsutoshi , Watanabe Akihiko
Published: October 2019

Background

Although primary duodenal adenocarcinoma (DA) is a rare malignancy representing ~ 0.5% of all gastrointestinal cancers, the incidence of DA is more frequent in Lynch syndrome. Because of its rarity, treatment strategies or optimal chemotherapeutic regimens have not been clearly defined for advanced DA.

Case presentation

A 72-year-old woman with Lynch syndrome visited our hospital with a right upper abdominal pain. Computed tomography (CT) showed wall thickness with enhancement in the second portion of the duodenum and adjacent abdominal wall, which suggested direct tumor invasion to the abdominal wall. Upper gastrointestinal endoscopy (UGE) showed a large ulcerative tumor in the second portion of the duodenum, and histological analysis revealed a poorly differentiated adenocarcinoma. A cT4N0M0, cStage IIB (Union for International Control Cancer TNM staging) DA was diagnosed. After three courses of chemotherapy with S-1 and oxaliplatin (SOX), follow-up CT and UGE showed shrinkage of the duodenal tumor. Therefore, the patient underwent pancreaticoduodenectomy with lymph node dissection with curative intent. Histological examination showed a pathological complete response to SOX therapy. The postoperative course was uneventful, and the patient was discharged on postoperative day 29. The patient received no adjuvant chemotherapy, and there has been no evidence of recurrence 6 months after the operation.

Conclusions

SOX therapy provided a remarkable response and can be an optimal chemotherapeutic regimen for advanced DA in Lynch syndrome.
Prognosis of lymphotropic invasive micropapillary breast carcinoma analyzed by using data from the National Cancer Database
Authors: Lewis Gary D. , Xing Yan , Haque Waqar , Patel Tejal , Schwartz Mary , Chen Albert , Farach Andrew , Hatch Sandra S. , Butler E. Brian , Chang Jenny , Teh Bin S.
Published: October 2019

Background

Invasive micropapillary carcinoma (IMPC) is an uncommon subtype of breast cancer. Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carcinoma (IDC). The purpose of the present study was to determine the clinical characteristics, outcomes, and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database (NCDB).

Methods

Records of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB. Log‐rank test was performed to evaluate associations of clinical characteristics with overall survival (OS). Cox proportional hazards model was used to determine variables associated with OS.

Results

Overall, 2660 patients with IMPC met the selection criteria; the 5‐year OS rate was 87.5% and 24.9% of patients had nodal involvement at presentation. Patients with ≥ 4 positive lymph nodes had shorter OS than node‐negative patients, whereas patients with 1–3 positive nodes had similar OS to node‐negative patients. Age < 65 years, receipt of radiotherapy, and estrogen receptor positivity were also associated with prolonged OS. The benefit of radiotherapy was limited to IMPC patients undergoing lumpectomy; there was no benefit for the patients undergoing mastectomy (regardless of nodal positivity/negativity).

Conclusions

Favorable prognostic factors of IMPC patients included age < 65 years, < 4 positive lymph nodes, receipt of radiotherapy, and estrogen receptor positivity. The results presented herein suggest a survival benefit associated with radiotherapy in IMPC treatment, though this may be limited to the patients treated with lumpectomy.
Planting and harvesting innovation - an analysis of Samsung Electronics
Authors: Jang Seung Hoon , Lee Sang M. , Kim Taewan , Choi Donghyun
Published: October 2019

This study explores how firms manage the entire life cycle of innovation projects based on the framework of harvesting and planting innovation. While harvesting innovation seeks new products in the expectation of financial performance in the short term, planting innovation pursues creating value over a long time period. Without proper management of the process of planting and harvesting innovation, firms with limited resources may not be successful in launching innovative new products to seize a momentum in high tech industries. To examine this issue, the case of Samsung Electronics (SE), now an electronics giant originated from a former developing country, is analyzed. SE has shown to effectively utilize co-innovation to maintain numerous planting and harvesting innovation projects. Both researchers and practitioners would be interested in learning about how SE shared risks of innovation investment with external partners at the early stage of innovation cycles.
In vitro differentiation of cGMP-grade retinal pigmented epithelium from human embryonic stem cells
Authors: Lojudice Fernando H. , Fernandes Rodrigo A. Brant , Innocenti Francesco , Franciozi Carlos E. , Cristovam Priscila , Maia Maurício , Sogayar Mari C. , Belfort Rubens
Published: October 2019

Background

The World Health Organization (WHO) estimates that the number of individuals who lose their vision due to retinal degeneration is expected to reach 6 million annually in 2020. The retinal degenerative diseases affect the macula, which is responsible for central and detailed vision. Most macular degeneration, i.e., age-related macular degeneration (AMD) develops in the elderly; however, certain hereditary diseases, such as the Stargardt disease, also affect young people. This degeneration begins with loss of retinal pigmented epithelium (RPE) due to formation of drusen (atrophic) or abnormal vessels (exudative). In wet AMD, numerous drugs are available to successful treat the disease; however, no proven therapy currently is available to treat dry AMD or Stargardt. Since its discovery, human embryonic stem cells (hESCs) have been considered a valuable therapeutic tool. Some evidence has shown that transplantation of RPEs differentiated from hESCs cells can result in recovery of both RPE and photoreceptors and prevent visual loss.

Methods

The human embryonic WA-09 stem cell lineage was cultured under current Good Manufacturing Practices (cGMP) conditions using serum-free media and supplements. The colonies were isolated manually and allowed to spontaneously differentiate into RPE cells.

Results

This simple and effective protocol required minimal manipulation and yielded more than 10e8 RPE cells by the end of the differentiation and enrichment processes, with cells exhibiting a cobblestone morphology and displaying cellular markers and a gene expression profile typical of mature RPE cells. Moreover, the differentiated cells displayed phagocytic activity and only a small percentage of the total cells remained positive for the Octamer-binding transcriptions factor 4 (OCT-4) pluripotency cell marker.

Conclusions

These results showed that functional RPE cells can be produced efficiently and suggested the possibility of scaling-up to aim at therapeutic protocols for retinal diseases associated with RPE degeneration.