bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosafety and biosecurity requirements for Orientia spp. diagnosis and research: recommendations for risk-based biocontainment, work practices and the case for reclassification to risk group 2
Authors: Blacksell Stuart D. , Robinson Matthew T. , Newton Paul N. , Ruanchaimun Soiratchaneekorn , Salje Jeanne , Wangrangsimakul Tri , Wegner Matthew D. , Abdad Mohammad Yazid , Bennett Allan M. , Richards Allen L. , Stenos John , Day Nicholas P. J.
Published: December 2019

Scrub typhus is an important arthropod-borne disease causing significant acute febrile illness by infection with Orientia spp.

Using a risk-based approach, this review examines current practice, the evidence base and regulatory requirements regarding matters of biosafety and biosecurity, and presents the case for reclassification from Risk Group 3 to Risk Group 2 along with recommendations for safe working practices of risk-based activities during the manipulation of Orientia spp. in the laboratory.

We recommend to reclassify Orientia spp. to Risk Group 2 based on the classification for RG2 pathogens as being moderate individual risk, low community risk. We recommend that low risk activities, can be performed within a biological safety cabinet located in a Biosafety Level (BSL) 2 core laboratory using standard personal protective equipment. But when the risk assessment indicates, such as high concentration and volume, or aerosol generation, then a higher biocontainment level is warranted. For, the majority of animal activities involving Orientia spp., Animal BSL 2 (ABSL2) is recommended however where high risk activities are performed including necropsies, Animal BSL (ABSL3) is recommended.
Prognostic implications of forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) in epithelial ovarian cancer
Authors: Han Gwan Hee , Chay Doo Byung , Nam Sanghee , Cho Hanbyoul , Chung Joon-Yong , Kim Jae-Hoon
Published: December 2019

Background

Transcription factors forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) have been reported to play important roles in various cancers. However, their role in epithelial ovarian cancer (EOC) has not been elucidated yet. Therefore, we evaluated the expression and clinical significance of FOXO1 and PAX3 in EOC.

Methods

Immunohistochemical analyses of FOXO1 and PAX3 in 212 EOCs, 57 borderline ovarian tumors, 153 benign epithelial ovarian tumors, and 79 nonadjacent normal epithelial tissues were performed using tissue microarray. Various clinicopathological variables, including the survival of EOC patients, were compared. In addition, the effect of FOXO1 on cell growth was assessed in EOC cell lines.

Results

FOXO1 and PAX3 protein expression levels were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues, and borderline tumors (allp < 0.001). In EOC tissues, FOXO1 expression was positively correlated with PAX3 expression (Spearman’s rho = 0.118,p = 0.149). Multivariate survival analysis revealed that high FOXO1 expression (hazard ratio = 2.77 [95% CI, 1.48–5.18],p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed a high hazard ratio (4.60 [95% CI, 2.00–10.55],p < 0.001) for overall survival. Also in vitro results demonstrated that knockdown of FOXO1 was associated with decreased cell viability, migration, and colony formation.

Conclusions

This study revealed that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results suggest the promising potential of FOXO1 and PAX3 as prognostic and therapeutic markers. The possible link between biological functions of FOXO1 and PAX3 in EOC warrants further studies.
Autophagy activated via GRP78 to alleviate endoplasmic reticulum stress for cell survival in blue light-mediated damage of A2E-laden RPEs
Authors: Feng Jingyang , Chen Yuhong , Lu Bing , Sun Xiangjun , Zhu Hong , Sun Xiaodong
Published: December 2019

Background

Retinal pigment epithelium cells (RPEs) are critical for maintaining retinal homeostasis. Accumulation of age-related lipofuscin, N-retinylidene-N-retinylethanolamine (A2E), makes RPEs vulnerable to blue light-mediated damage, which represents an initial cause of some retinal degenerative diseases. This study investigated the activation of autophagy and the signaling pathway involved in glucose-related protein 78 (GRP78) induced autophagy in blue light-mediated damage of A2E-laden RPEs. In addition, we explored whether autophagy could play a protective role by alleviating endoplasmic reticulum (ER) stress to promote RPEs survival.

Methods

RPEs were incubated with 25 μM A2E for 2 h and exposed to blue light for 20 min. The expression of ER stress-related apoptotic proteins, CHOP and caspase-12, as well as autophagy marker LC3 were measured by western blot analysis. Autophagosomes were observed by both transmission electron microscopy and immunofluorescence assays. GRP78 interference performed by short hairpin RNA (shRNA) was used to identify the signaling pathway involved in GRP78 induced autophagy. Cell death was assessed using TUNEL analysis.

Results

Treatment with A2E and blue light markedly increased the expression of ER stress-related apoptotic molecules CHOP and caspase-12. The activation of autophagy was recognized by observing autophagosomes at ultrastructural level. Additionally, punctate distributions of LC3 immunofluorescence and enhanced conversions of LC3-I to LC3-II were found in A2E and blue light-treated RPEs. Moreover, GRP78 interference reduced AMPK phosphorylation and promoted mTOR activity, thereby downregulating autophagy. In addition, the inhibition of autophagy made RPEs vulnerable to A2E and blue light damage. In contrast, the autophagy inducer rapamycin alleviated ER stress to promote RPEs survival.

Conclusions

GRP78 activates autophagy via AMPK/mTOR in blue light-mediated damage of A2E-laden RPEs in vitro. Autophagy may be a vital endogenous cytoprotective process to alleviate stress for RPEs survival in retinal degenerative diseases.
The effect of oral contraceptive pills on the macula, the retinal nerve fiber layer, the ganglion cell layer and the choroidal thickness
Authors: Shaaban Yasmine Maher , Badran Tamer Abdel Fattah
Published: December 2019

Backgroun

To evaluate the effect of oral contraceptive pills (OCP) on the macula, the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the choroidal thickness (CT).

Methods

In this prospective observational cross-sectional study, 60 eyes of 30 healthy women taking monophasic OCP (0.03 mg ethinylestradiol and 0.15 mg levonorgestrel) for contraception for at least 1 year were compared with 60 eyes of a control group of 30 healthy women who were not taking any OCP. Spectral-Domain Optical Coherence Tomography (SD-OCT) was used to evaluate the macula, the RNFL, the GCL, and the CT. Measurements were taken in the follicular phase (day 3) of the last menstrual cycle in all women. The body mass index (BMI) scores of all participants were also recorded.

Results

No disparity in terms of age and BMI between both groups was observed (p = 0.444, p = 0.074, respectively). All the macular parameters measurements were considerably lower in the OCP group compared to the control group (p < 0.001). Also, the RNFL thickness, the GCL thickness, and the CT were all significantly thinner in the OCP group (p < 0.001).

Conclusions

The use of OCP can cause significant changes in the retina and choroid thickness over 1 year period. The women who are using OCP for a longer duration could have some eye problems. OCT should be routinely done for follow up. Further long term studies are required, using different preparations of OCP. It is important to find out when this thickness alterations can be clinically significant or symptomatic and if these changes are reversible or not.
A new method for quantitative detection of Lactobacillus casei based on casx gene and its application
Authors: Pang Xiaoyang , Jia Ziyang , Lu Jing , Zhang Shuwen , Zhang Cai , Zhang Min , Lv Jiaping
Published: December 2019

Background

The traditional method of bacterial identification based on 16S rRNA is a widely used and very effective detection method, but this method still has some deficiencies, especially in the identification of closely related strains. A high homology with little differences is mostly observed in the 16S sequence of closely related bacteria, which results in difficulty to distinguish them by 16S rRNA-based detection method. In order to develop a rapid and accurate method of bacterial identification, we studied the possibility of identifying bacteria with other characteristic fragments without the use of 16S rRNA as detection targets.

Results

We analyzed the potential of using cas (CRISPR-associated proteins) gene as a target for bacteria detection. We found that certain fragment located in the casx gene was species-specific and could be used as a specific target gene. Based on these fragments, we established a TaqMan MGB Real-time PCR method for detecting bacteria. We found that the method used in this study had the advantages of high sensitivity and good specificity.

Conclusions

The casx gene-based method of bacterial identification could be used as a supplement to the conventional 16 s rRNA-based detection method. This method has an advantage over the 16 s rRNA-based detection method in distinguishing the genetic relationship between closely-related bacteria, such as subgroup bacteria, and can be used as a supplement to the 16 s rRNA-based detection method.
Abiraterone and MDV3100 inhibits the proliferation and promotes the apoptosis of prostate cancer cells through mitophagy
Authors: Han Jingli , Zhang Junhua , Zhang Wei , Zhang Dalei , Li Ying , Zhang Jinsong , Zhang Yaqun , Diao Tongxiang , Cui Luwei , Li Wenqing , Xiao Fei , Liu Ming , Zou Lihui
Published: December 2019

Background

Abiraterone and MDV3100 are two effective anticancer agents for prostate cancer, however, the mechanism of their downstream action remains undefined.

Methods

A dual fluorescent biosensor plasmid was transfected in LNCaP cells to measure mitophagy. The DNA of LNCaP cells was extracted and performed with quantitative real-time PCR to detect mitochondrial DNA copy number. JC-1 staining was utilized to detect the mitochondrial membrane potential and electron microscope was performed to analyze mitochondrial morphology. Moreover, the protein levels of mitochondrial markers and apoptotic markers were detected by western blot. At last, the proliferation and apoptosis of LNCaP cells were analyzed with CCK-8 assay and flow cytometry after abiraterone or MDV3100 treatment.

Results

Mitophagy was induced by abiraterone and MDV3100 in LNCaP cells. The low expression level of mitochondrial DNA copy number and mitochondrial depolarization were further identified in the abiraterone or MDV3100 treatment groups compared with the control group. Besides, severe mitochondria swelling and substantial autophagy-lysosomes were observed in abiraterone- and MDV3100-treated LNCaP cells. The expression of mitochondria-related proteins, frataxin, ACO2 and Tom20 were significantly downregulated in abiraterone and MDV3100 treated LNCaP cells, whereas the expression level of inner membrane protein of mitochondria (Tim23) was significantly upregulated in the same condition. Moreover, the proliferation of LNCaP cells were drastically inhibited, and the apoptosis of LNCaP cells was increased in abiraterone or MDV3100 treatment groups. Meanwhile, the addition of mitophagy inhibitor Mdivi-1 (mitochondrial division inhibitor 1) could conversely elevate proliferation and constrain apoptosis of LNCaP cells.

Conclusions

Our results prove that both abiraterone and MDV3100 inhibit the proliferation, promote the apoptosis of prostate cancer cells through regulating mitophagy. The promotion of mitophagy might enhance the efficacy of abiraterone and MDV3100, which could be a potential strategy to improve chemotherapy with these two reagents.
Genotypes and phenotypes of resistance in Ecuadorian Plasmodium falciparum
Authors: Valenzuela Gabriela , Castro L. Enrique , Valencia-Zamora Julio , Vera-Arias Claudia A. , Rohrbach Petra , Sáenz Fabián E.
Published: December 2019

Background

Malaria continues to be endemic in the coast and Amazon regions of Ecuador. Clarifying current Plasmodium falciparum resistance in the country will support malaria elimination efforts. In this study, Ecuadorian P. falciparum parasites were analysed to determine their drug resistance genotypes and phenotypes.

Methods

Molecular analyses were performed to search for mutations in known resistance markers (Pfcrt, Pfdhfr, Pfdhps, Pfmdr1, k13). Pfmdr1 copy number was determined by qPCR. PFMDR1 transporter activity was characterized in live parasites using live cell imaging in combination with the Fluo-4 transport assay. Chloroquine, quinine, lumefantrine, mefloquine, dihydroartemisinin, and artemether sensitivities were measured by in vitro assays.

Results

The majority of samples from this study presented the CVMNT genotype for Pfcrt (72–26), NEDF SDFD mutations in Pfmdr1 and wild type genotypes for Pfdhfr, Pfdhps and k13. The Ecuadorian P. falciparum strain ESM-2013 showed in vitro resistance to chloroquine, but sensitivity to quinine, lumefantrine, mefloquine, dihydroartemisinin and artemether. In addition, transport of the fluorochrome Fluo-4 from the cytosol into the digestive vacuole (DV) of the ESM-2013 strain was minimally detected in the DV. All analysed samples revealed one copy of Pfmdr1.

Conclusion

This study indicates that Ecuadorian parasites presented the genotype and phenotype for chloroquine resistance and were found to be sensitive to SP, artemether-lumefantrine, quinine, mefloquine, and dihydroartemisinin. The results suggest that the current malaria treatment employed in the country remains effective. This study clarifies the status of anti-malarial resistance in Ecuador and informs the P. falciparum elimination campaigns in the country.
Households forgoing healthcare as a measure of financial risk protection: an application to Liberia
Authors: Gabani Jacopo , Guinness Lorna
Published: December 2019

Introduction

Access to Liberia’s health system is reliant on out-of-pocket (OOP) health expenditures which may prevent people from seeking care or result in catastrophic health expenditure (CHE). CHE and impoverishment due to OOP, which are used by the World Bank and World Health Organization as the sole measures of financial risk protection, are limited: they do not consider households who, following a health shock, do not incur expenditure because they cannot access the healthcare services they need (i.e., households forgoing healthcare (HFH) services). This paper attempts to overcome this limitation and improve financial risk protection by measuring HFH incidence and comparing it with CHE standard measures using household survey data from Liberia.

Methods

Data from the Liberia Household Income and Expenditure Survey 2014 were analysed. An OOP health expenditure is catastrophic when it exceeds a total or non-food household expenditure threshold. A CHE incidence curve, representing CHE incidence at different thresholds, was developed. To overcome CHE limitations, an HFH incidence measure was developed based on CHE, OOP and health shocks data: households incurring health shocks and having negligible OOP were considered to have forgone healthcare. HFH incidence was compared with standard CHE measures.

Results

CHE incidence and intensity levels depend on the threshold used. Using a 30% non-food expenditure threshold, CHE incidence is 2.1% (95% CI: 1.7–2.5%) and CHE intensity is 37.4% (95% CI: 22.7–52.0%). CHE incidence is approximately in line with other countries, while CHE intensity is higher than in other countries. CHE pushed 1.6% of households below the food poverty line in 2014. HFH incidence is approximately 4 times higher than CHE (8.0, 95% CI, 7.2–8.9%).

Conclusion

Lack of financial risk protection is a significant problem in Liberia and it may be underestimated by CHE: this study confirms that HFH incidence can complement CHE measures in providing a complete picture of financial risk protection and demonstrates a simple method that includes measures of healthcare forgone as part of standard CHE analyses. This paper provides a new methodology to measure HFH incidence and highlights the need to consider healthcare forgone in analyses of financial risk protection, as well as the need for further development of these measures.
CPT1a gene expression reverses the inflammatory and anti-phagocytic effect of 7-ketocholesterol in RAW264.7 macrophages
Authors: Calle Priscila , Muñoz Angeles , Sola Anna , Hotter Georgina
Published: December 2019

Background

Macrophage are specialized cells that contributes to the removal of detrimental contents via phagocytosis. Lipid accumulation in macrophages, whether from phagocytosis of dying cells or from circulating oxidized low-density lipoproteins, alters macrophage biology and functionality. It is known that carnitine palmitoyl transferase 1-a (CPT1a) gene encodes an enzyme involved in fatty acid oxidation and, therefore, lipid content. However, the potential of CPT1a to activate macrophage phagocytic function have not been elucidated.

Methods

Using a murine macrophage cell line, RAW264.7, we determine if intracellular accumulation of 7-ketocholesterol (7-KC) modulates macrophage phagocytic function through CPT1a gene expression. In addition, the effects of CPT1a genetic modification on macrophage phenotype and phagocytosis has been studied.

Results

Our results revealed that CPT1a gene expression decreased by the accumulation of 7-KC at the higher dose of 7-KC. This was concomitant with an impair ability to phagocytize bioparticles and an inflammatory phenotype. GW3965 treatment, which have shown to facilitate the efflux of cholesterol, eliminated the intracellular lipid droplets of 7-KC-laden macrophages, increased the gene expression of CPT1a, diminished the gene expression of the inflammatory marker iNOS and restored macrophage phagocytosis. Furthermore, CPT1a Knockdown per se was detrimental for macrophage phagocytosis whereas transcriptional activation of CPT1a heightened the uptake of bioparticles.

Conclusions

Altogether, our findings indicate that downregulation of CPT1a by lipid content modulates macrophage phagocytosis and inflammatory phenotype.
Penalty algorithm adapted for the spectral element discretization of the Darcy equations
Authors: Abdelwahed Mohamed , Chorfi Nejmeddine
Published: December 2019

Any spectral element discretization of the Darcy problem can be efficiently solved by applying the penalty method. This method leads to a system of equations with uncoupled unknowns. We prove a posteriori error estimates for a spectral element discretization of the Darcy problem. The proposed algorithm permits the optimization of the penalty parameter as a function of the error indicators.
Protecting the psychological wellbeing of staff exposed to disaster or emergency at work: a qualitative study
Authors: Brooks Samantha K. , Dunn Rebecca , Amlôt Richard , Rubin G. James , Greenberg Neil
Published: December 2019

Background

Disasters are becoming more prevalent across the world and people are frequently exposed to them as part of their occupational groups. It is important for organisations to understand how best to support employees who have experienced a trauma such as a disaster. The purpose of this study was to explore employees’ perceptions of workplace support and help-seeking in the context of a disaster.

Methods

Forty employees in England took part in semi-structured interviews. Thematic analysis was used to extract recurring themes from the data.

Results

Participants reported both positive and negative psychological outcomes of experiencing a disaster or emergency at work. Most had little training in how to prepare for, and cope with, the psychological impact. They perceived stigma around mental health and treatment for psychological issues which often made them reluctant to seek help. Many reported that the psychological support available in the workplace was insufficient and tended to be reactive rather than proactive. Interpersonal relationships at work were viewed as being important sources of support, particularly support from managers. Participants suggested that psychosocial training in the workplace could be beneficial in providing education about mental health, encouraging supportive workplace relationships, and developing listening skills and empathy.

Conclusions

Organisations can take steps to reduce the psychological impact of disasters on employees. This could be done through provision of training workshops incorporating mental health education to reduce stigma, and team-building exercises to encourage supportive workplace relationships.
Ethical considerations about artificial intelligence for prognostication in intensive care
Authors: Beil Michael , Proft Ingo , van Heerden Daniel , Sviri Sigal , van Heerden Peter Vernon
Published: December 2019

Background

Prognosticating the course of diseases to inform decision-making is a key component of intensive care medicine. For several applications in medicine, new methods from the field of artificial intelligence (AI) and machine learning have already outperformed conventional prediction models. Due to their technical characteristics, these methods will present new ethical challenges to the intensivist.

Results

In addition to the standards of data stewardship in medicine, the selection of datasets and algorithms to create AI prognostication models must involve extensive scrutiny to avoid biases and, consequently, injustice against individuals or groups of patients. Assessment of these models for compliance with the ethical principles of beneficence and non-maleficence should also include quantification of predictive uncertainty. Respect for patients’ autonomy during decision-making requires transparency of the data processing by AI models to explain the predictions derived from these models. Moreover, a system of continuous oversight can help to maintain public trust in this technology. Based on these considerations as well as recent guidelines, we propose a pathway to an ethical implementation of AI-based prognostication. It includes a checklist for new AI models that deals with medical and technical topics as well as patient- and system-centered issues.

Conclusion

AI models for prognostication will become valuable tools in intensive care. However, they require technical refinement and a careful implementation according to the standards of medical ethics.
“Volcanism in the Chugoku region: a review for the first UNESCO field school on Geoenvironmental disaster reduction”
Authors: Auer Andreas
Published: December 2019

Field studies related to natural hazards are an integral part of any disaster mitigation effort, because geological samples and field records must initially be obtained from the context in which they occur. A sound fieldwork and careful observation and documentation of field relations is crucial for meaningful subsequent laboratory work, further data analysis and modelling. Teaching the necessary practical skills that enable students to recognize natural disaster events in the geological records and to understand circumstances under which they occur is not a trivial task. Some barriers to fieldwork usually exist, especially when the teaching subject focusses on natural disasters. Beside cost and logistics it is often the lack of suitable sites, that serve as instructive examples, displaying the deposits, structures and preserved evidence of natural hazards in the geological record. To students of volcanology, southwest Japan offers an almost unparalleled variety of interesting volcanic successions, including a broad range of different volcanic landforms and deposits that illustrate the various hazards associated with volcanic eruptions. This review will provide a brief overview of the geology of southwest Japan with special emphasis on the igneous and volcanic evolution. It will give participants of the field school a minimum of required background and anybody beyond a quick introduction into one of the most diverse and interesting volcanic field areas in the world.
The Frailty Risk Score predicts length of stay and need for rehospitalization after kidney transplantation in a retrospective cohort: a pilot study
Authors: Schaenman Joanna , Castellon Loren , Liang Emily C. , Nanayakkara Deepa , Abdalla Basmah , Sarkisian Catherine , Goldwater Deena
Published: December 2019

Background

Frailty is a widely used measure in older patients as a predictor of poor outcomes after hospitalization and surgery. There is a growing body of data in kidney transplantation suggesting frailty can predict adverse outcomes. There is interest in using chart review measures of frailty and multimorbidity, as they may be equally predictive as physical measurement. This approach holds promise for patient evaluation, identifying candidates for prehabilitation, and targeting resources towards those anticipated to have an increased rate of clinical challenges after kidney transplantation. Frail patients who are often older may place a large resource and economic burden on transplant programs.

Methods

We applied a previously published chart review–based approach in a retrospective, pilot study to calculate the Frailty Risk Score (FRS) utilizing a cohort of kidney transplant patients. We reviewed concurrent comorbidities using the Charlson comorbidity (CM) score to determine the feasibility and utility of applying this approach in transplant patients to predict post-transplant outcomes such as length of hospitalization and the need for rehospitalization.

Results

Sixty kidney transplant recipients were evaluated by chart review, 23 characterized as older (> = 60) and 37 younger (ages 30–59). Median FRS score was 3 (range 1–7). Higher FRS was significantly associated with increased patient age (high FRS 19% in younger patients, 43% in older patients). Increased CM score was also associated with increased patient age. Patients with a high FRS stayed in the hospital for an average of 8 days, compared with 5.7 days for a low FRS. Patients with high FRS were readmitted an average of 2.9 times compared with an average of 1.1 for those with a low FRS. FRS score remained significant for predicting outcomes after adjustment for patient age.

Conclusion

Elevated FRS prior to transplantation was associated with increased hospital stay and the need for readmission in kidney transplant recipients. This analysis demonstrates the potential strength of chart review in evaluating frailty prior to transplantation, permitting risk stratification and targeting of resources for rehabilitation and close post-transplant monitoring. Frail patients may benefit from targeted “prehabilitation” to attenuate the associated adverse clinical outcomes.
Placement of a single anterior odontoid screw for type II odontoid fractures in a setting with limited resources
Authors: Ashry Ahmed Hamdy , Aboul-Ela Hashem Mohamed
Published: December 2019

Background

Treatment of odontoid fractures with odontoid screws is an established method for fusion. However, it is facilitated by using advanced equipment in the operating theatre not always available as in developing countries.

Objectives

In this study we aim to outline the important key points for successful placement of odontoid screw in the absence of advanced tools, e.g. navigation or O-arm.

Materials and methods

Fifteen patients suffering from type II odontoid fractures were managed with single odontoid screw. Reduction of the fractures was achieved. A simple instrument set was used with the help of a single plane image intensifier. Longitudinal incision was used in 4 cases, and transverse incision was used in the remaining eleven cases. Anatomical identification of the midline helped to mark the entry point. The entry point used was millimetres below the anteroinferior edge of the axis vertebra. A short-headed screw was used.

Results

Road traffic accident was the only mechanism of trauma reported in our study. All of the patients were neurologically intact. All of the patients remained neurologically intact after the procedure. There were no instances of wrong trajectory of the screw in our study. During follow-up, we found good union of all the fractures. Only 2 cases suffered from mild dysphagia.

Conclusion

Fixation of odontoid fractures by anterior odontoid screws appears to be a safe and feasible procedure even in underequipped theatres. Anatomical knowledge helps in determining midline. Various modifications can help in overcoming shortcomings.
CYP2D6 Genotype–Guided Tamoxifen Dosing in Hormone Receptor–Positive Metastatic Breast Cancer (TARGET-1): A Randomized, Open-Label, Phase II Study
Authors: Tamura Kenji , Imamura Chiyo K. , Takano Toshimi , Saji Shigehira , Yamanaka Takeharu , Yonemori Kan , Takahashi Masato , Tsurutani Junji , Nishimura Reiki , Sato Kazuhiko , Kitani Akira , Ueno Naoto T. , Mushiroda Taisei , Kubo Michiaki , Fujiwara Yasuhiro , Tanigawara Yusuke
Published: December 2019

PURPOSE

In patients taking tamoxifen, the CYP2D6 genotype causes different exposure of active metabolite endoxifen. The objective of this randomized, open-label, multicenter, phase II study was to prospectively evaluate whether CYP2D6 genotype–guided tamoxifen dosing in patients with hormone receptor–positive metastatic breast cancer could have an impact on the clinical outcome.

METHODS

Patients who needed first-line tamoxifen therapy were enrolled. Based on individual CYP2D6 genotype, patients heterozygous (wild type [wt]/variant [V]) or homozygous (V/V) for variant alleles of decreased or no function were randomly assigned to receive tamoxifen at an increased dose (ID arm; 40 mg daily) or regular dose (RD arm; 20 mg daily), and patients homozygous for wild-type alleles (wt/wt) received tamoxifen at 20 mg daily. The primary endpoint was the progression-free survival (PFS) rate at 6 months. The secondary endpoints included PFS and correlation of Z-endoxifen concentration with clinical outcomes.

RESULTS

Between December 2012 and July 2016, 186 patients were enrolled in Japan. Of 184 evaluable patients, 136 carried wt/V or V/V (ID arm, 70; RD arm, 66), and 48 carried wt/wt. PFS rates at 6 months were not significantly different between the ID and RD arms (67.6% v 66.7%). The serum trough concentrations of Z-endoxifen in the ID arm were significantly higher than those in the RD arm (median, 89.2 nM v 51.1 nM; P < .0001) and were also higher compared with wt/wt patients (72.0 nM; P = .045). No significant difference in Z-endoxifen concentrations was observed between patients with disease progression and those who were progression free at 6 months ( P = .43).

CONCLUSION

In patients with CYP2D6-variant alleles, increasing tamoxifen dosing did not achieve a higher PFS rate at 6 months. The CYP2D6 genotype solely cannot explain individual variability in the efficacy of tamoxifen.
Increased Serum Sclerostin Levels in Patients With Active Acromegaly
Authors: Pekkolay Zafer , Kılınç Faruk , Gozel Nevzat , Önalan Ebru , Tuzcu Alpaslan Kemal
Published: December 2019

Context

Bone mineral density is normal in acromegalic patients and the cause of increased fracture risk that characterizes active acromegaly is unknown.

Objective

This study compared serum sclerostin levels between patients with active acromegaly and healthy individuals.

Design, Setting, and Participants

The serum sclerostin levels of patients with active acromegaly were compared with those of healthy volunteers in a cross-sectional study. The mean age of the 30 acromegaly patients (male/female: 14/16) was 47.26 ± 12.52 years (range, 18–64 years) and that of the healthy volunteers (male/female: 17/13) was 44.56 ± 10.74 years (range, 19–62 years). IGF-1 and GH levels were measured using an electrochemiluminescence method, and serum sclerostin levels using an ELISA. The Mann-Whitney U test was used to compare sclerostin levels between the 2 groups. The correlations of sclerostin level with IGF-1 and GH were determined using Spearman’s test.

Results

The 2 groups did not differ in age or sex (P > 0.05). The median GH and IGF-1 levels in the patient group were 2.49 ng/mL (range, 0.22–70.00 ng/mL) (interquartile range [IQR], 1.3–4.52) and 338.5 ng/mL (range, 147–911 ng/mL) (IQR, 250–426), respectively. The median GH and IGF-1 levels in the control group were 0.95 ng/mL (range, 0.3-2.3) and 144 ng/mL (range, 98–198), respectively. The median sclerostin level was 29.95 ng/mL (range, 7.5–78.1 ng/mL) (IQR, 14.37–37.47) in the acromegaly group and 22.44 ng/mL (range, 8.45–36.44 ng/mL) (IQR, 13.71–27.52) in the control group (P < 0.05). There was a moderate positive correlation between the sclerostin and IGF-1 levels (rho = 0.54; P < 0.01), and between the sclerostin and GH levels (rho = 0.41; P < 0.05).

Conclusions

High sclerostin levels may contribute to the increased fracture risk seen in patients with acromegaly.
Examination of new parameters for sex determination of mandible using Japanese computer tomography data
Authors: Suzuki Kei , Nakano Hiroyuki , Inoue Kazuya , Nakajima Yoichiro , Mizobuchi Sho , Omori Michi , Kato-Kogoe Nahoko , Mishima Katsuaki , Ueno Takaaki
Published: December 2019

Objective:

In the field of forensic science, sex discrimination of skeletons is an important identification item for personal identification. The individual sex discrimination method using skeletons includes a determination method using measurement values and a macroscopic form observation method. Both methods have advantage and disadvantage. In this study, we used the homologous model technique and principal component (PC) analysis to determine gender difference from morphology of the mandible.

Methods and materials:

45 patients (23 males and 22 females) of CT imaging for tooth extraction from January 2018 to March 2019 at department of oral surgery, Osaka Medical College. The mean age was 43.1 ± 14.6. Patients with less than 14 remaining teeth were excluded because the number of remaining teeth may affect the shape of the mandible. 3D images were constructed, and 20 landmarks plotting on the 3D model surfaces. We generated template models of the mandible consisting of approximately 8434 polygons. The template model automatically fitted into the individually scanned point cloud of the mandible by minimising external and internal energy functions. As described above, the mandibles were constructed for each sample by using the Homologous Body Modeling software (HBM, Digital Human Technology, Inc.) and the mHBM-Rugle (Medic Engineering Corporation). The mandibles were analysed using the PCA.

Results:

The contribution of the most important PC was found to be 27.2%. 12 PCs explained over 75% of the total variance. That is, it was able to express 75% or more of the mandible expression with 12 PCs. A significant difference between male and female was observed in the first PCs (Wilcoxon test, p < 0.05). Visualising the result of the first PC showed that the mandibular branch of male was larger than that of female, and the mandible angle was overhanging outside.

Conclusion:

This method is a combination of the determination method using the previous measurement values and the determination using macroscopic observation, and is considered to be innovative method.
Challenges in multidisciplinary medical rehabilitation - Swyer-James-MacLeod Syndrome: case presentation and short literature review
Authors: ANTON Adelina , GHERGHISAN Ioana Sinziana , OMER (Gheorghe) Angela , IONESCU Elena Valentina , ILIESCU Madalina Gabriela , BAZ Radu
Published: December 2019

Introduction. Swyer-James-MacLeod syndrome (SJMS) or unilateral hyperlucent lung syndrome is a rare disorder caused by infectious bronchiolitis obliterans and pneumonitis occurring in childhood. It is characterized by hypoplasia and/or agenesis of the pulmonary arteries resulting in pulmonary parenchyma hypoperfusion. Materials and methods. We report the case of a 27 years-old female patient who presented with progressive dyspnea, productive cough, fever and chills. Results and discussion. Chest radiography showed unilateral loss of left lung volume with hyperlucency. Unilateral reduction in vascularity with reduced caliber of the left pulmonary artery was revealed on CT scan of the chest, final diagnosis of SJMS being confirmed by angiography. Conclusions. This case strongly supports the recommendation of considering SJMS within the differential diagnosis workup of bronchiectasis, the syndrome being usually underdiagnosed.
Pulsed short waves in the remineralization of alveolar bone structures of the jaw in patients with diabetes mellitus – a series of cases
Authors: ALEXANDRU Bogdan-Cătălin , POPA Monica , DOGARU Gabriela , CONSTANTIN Anne-Marie , GEORGIU Carmen , ȘOVREA Alina Simona
Published: December 2019

This clinical study included three patients aged between 50 and 78 years who had chronic marginal periodontitis and type 2 diabetes mellitus, diseases that are frequently associated due to changes occurring in polymorphonuclear cells, as well as to alterations of microcirculation. No bone augmentation therapies were performed. Bone regeneration was strictly influenced by conventional periodontal therapy, supplemented with ten pulsed short wave sessions applied to the lower face shortly after closed periodontal curettage. The allocated time was ten minutes for the first two sessions, and 15 minutes for the following 8 sessions. Clinical and radiological evaluations were performed at the time of presentation, as well as after initiation of pulsed short wave therapy: in the first case, three weeks after initiation of therapy and three years after the end of complex oral rehabilitation; in the second case, eight weeks after the onset of pulsed short wave therapy and in the third case, five weeks after the onset of pulsed short wave therapy. The results were significant in all three cases, demonstrated radiologically by the same type of radiological examination at identical scales. Bone remineralization was obvious in the alveolar processes of the jaw. Although further studies in this direction are necessary, the results are both clinically and radiologically significant.

Key words: pulsed short waves, alveolar bone resorption, periodontal disease, diabetes,
Diagnostic particularities and multimodal therapeutic and rehabilitation approches to a complex case of post ischemic stroke with dyshphagia and dysphonia, associating Millard-Gubler and Wallenberg syndromes- case report
Authors: NIRLU Luminița , POPESCU Laura Georgiana , ALBEȘTEANU Ana Carmen , SAGLAM Ali-Osman , STAVRICĂ Alexandru G. , ONOSE Gelu
Published: December 2019

Introduction. Millard-Gubler syndrome (MGS), also known as the ventral pontine syndrome or hemiplegic syndrome, is one of the classical crossed syndromes characterized by a unilateral lesion of the basal portion of the caudal part of the pons. MGS manifests as ipsilateral palsy of CN VI and VII with contralateral hemiplegia. Wallenberg syndrome or lateral medullary syndrome, is characterized by the triad of Horner's syndrome, ipsilateral ataxia and contralateral hypoalgesia. Other clinical symptoms may include difficult swallowing, slurred speech, vertigo, nausea, vomiting, dyspnea, tachycardia, headaches and muscular hypertonia. Materials and Methods Having the patient’s consent and The Teaching Emergency Hospital “Bagdasar-Arseni” Ethics Committee N.O 20270 from the 26th of June 2019, the current case report presents a 67-year-old male patient from rural area with left hemiplegia (complete brachial and crural motor deficit), right eye abduction paresis, dysphagia, dysphonia, central facial palsy - all post acute ischemic stroke. The patient was also diagnosed with ischemic cardiomyopathy, atherosclerosis, alcoholism, type 2 diabetes with Insulin therapy and oral antidiabetic agent. The patient was admitted in the Neurorehabilitation Clinic of the Teaching Emergency Hospital „Bagdasar-Arseni” (TEHBA) Bucharest, Romania, associating severe alteration in self-care abilities, locomotor dysfunction, memory disorders, slurred speech, for specialized rehabilitation treatment and nursing. Results. A case of rare pathology for which, unfortunately, there is a discrepancy between functional improvement and the poor motor control in the in the lower limbs (muscle force was 0-1 out of 5 on the Medicale Research Council scale), within an overall favorable evolution, including elements of the clinical status afferent to the two above mentioned syndromes. Conclusions. Approaching such a clinical case has been a complex and extensive challenge for the entire neuromuscular recovery team and remains similar for any other squad. This pathology remains an issue that demands our earnest attention. Key words: Millard-Gubler syndrome (MGS), Wallenberg syndrome, crossed syndromes, hemiplegia, neurorehabilitation, stroke
Spinal nephroblastoma in a dog: a case report
Authors: KAMPOURI P. , KARIKI A. , BAKA R.D. , PATSIKAS M.N. , POLIZOPOULOU Z.S.
Published: December 2019

The case report presents the clinical, clinicopathological, diagnostic imaging and histopathological findings of spinal cord nephroblastoma in a dog. It was admitted with a 2-week history of a “weight-bearing” lameness of the left posterior limb that evolved to paraplegia within hours. Neurological examination showed spastic paraplegia compatible with a T3-L3 spinal cord lesion. Differential diagnosis included ischemic myelopathy, myelitis and acute spinal cord compression. The spinal radiographs and cerebrospinal fluid analysis were unremarkable. Cisternal myelography indicated a focal intradural-extramedullary lesion at the level of T12 vertebra. Further diagnostic investigation was not performed because the owner decided to proceed to euthanasia. Histopathological examination of the spinal cord confirmed the diagnosis of intraspinal nephroblastoma.
Water quality of Kahta Stream (Adıyaman) discharging into Atatürk Dam Lake
Authors: Gölbaşı Selami , Şen Bülent
Published: December 2019

In this study, it is aimed to determine the water quality of Kahta Stream which is poured into Atatürk Dam Lake by following some hydrological and physico-chemical characteristics between April 2012 and March 2013. For this purpose, monthly measurements were made at five stations from the source to the downstream and water samples were taken. During the monitoring period, water temperature 5.0-25.2 °C; electrical conductivity 216-359 μS/cm; total dissolved solids 147-244 mg/L; dissolved oxygen 8.67-13.36 mg/L and pH were measured in range of 7.08-8.76. Suspended solid 2-138 mg/L; turbidity 0.92-96.70 NTU; total alkalinity 102-200 mg/L; chloride 0.71-5.02 mg/L; ammonium nitrogen 0.007-0.400 mg/L; nitrite nitrogen 0.003-0.060 mg/L; nitrate nitrogen 0.12-1.19 mg/L; dissolved reactive phosphorus 0.007-0.033 mg/L; silica 5-23 mg/L; sulphate 8-33 mg/L and chemical oxygen demand were determined betwen 0.63-9.18 mg/L.

Kahta Stream with slightly alkaline character, in terms of the parameters monitored, it is determined that the Surface Water Quality Regulation has the characteristics of Class I (high quality water) according to the Environmental Quality Standards. With this characteristic, it has been determined that Kahta Stream has a high potential to be used for drinking water supply, it can be used for re-use, trout farming, animal production and other farm needs. In addition, when the temporal relationship of variables was analyzed statistically, a significant difference was found among all variables except SiO2 (p <0.05). This result shows that the variables are affected by seasonal changes.
Assessment of environmental applicability of TiO2 coated self-cleaning glass for photocatalytic degradation of estrone, 17β-estradiol and their byproducts
Authors: Matin Golnar , Amani-Ghadim Ali Reza , Matin Amir Abbas , Kargar Navid , Buyukışık Hasan Baha
Published: December 2019

Optimization of photocatalytic degradation of two natural estrogenic compounds, estrone (E1) and 17β-estradiol (17β-E2) in aqueous medium was performed on TiO2 coated Pilkington ActivTM self-cleaning glass as a novel approach to eliminate free nano-TiO2 releasing to the intended environment after treatment. The active glass was characterized by Atomic Force Microscopy (AFM), X-ray diffraction (XRD), and Raman spectroscopy to characterize the TiO2 nanoparticles. The main purposes were mineralization of target compounds in the treated water during the photocatalytic reaction and also to investigate the oxidation by products. Response Surface Methodology (RSM) has been applied to optimize the photocatalytic degradation by changing time, pH, and light intensity as effective factors. According to the results, time was the more effective parameter. The maximum efficiency degradation was achieved in alkaline media. Due to interactive effects between variable factors, 1 mg/L aqueous solution of E1 and 17β-E2 in water was totally decomposed by TiO2 photocatalyzed reactions under UV-C irradiation of 10.08 W/m2 for 52.49 min at pH 9.42. Results of GC-MS analysis were introduced 17-deoxy Estrone and 2-Hydroxyestradiol as intermediate products for E1 and 17β-E2, respectively. All of the peaks finally disappeared after 170 min. Optimized conditions were applied for real sample of wastewater, presenting 30.40% and 56.84% in the efficiency degradation of E1 and 17β-E2, respectively.
Effects of various antioxidants on oxidative stability of anchovy (Engraulis encrasicolus) oil
Authors: Soydan Mehmet Gökhan , Erdoğan Fatime
Published: December 2019

The aim of study was to investigate four commercial available antioxidants (groups A (300 mg propyl gallate (PG)+10 mg rosemary extract (RE)/1000 mg), B (240 mg butylated hydroxy anisole (BHA)+80 mg PG+80 mg citric acid (CA)/1000 mg), C (120 mg BHA+120 mg PG+50 mg CA)/1000 mg), D (150 mg butylated hydroxytoluene (BHT)+100 mg BHA+10 mg PG)/1000 mg) used to evaluate oxidation during the storage in fish oil. Antioxidants were added to the fish oil to determine which ones were most effective in preventing oxidation, and fish oil was stored in the amber bottles at room temperature (20 °C) for 90 days. The control group samples were stored under the same conditions and antioxidant was not added. To determine the effect of antioxidants, the recommended by the manufacturer dose of commercial antioxidant (1000 mg kg-1 fish oil) was used in the experimental groups. The formation of the primary and secondary oxidation products in fish oil storage trial was examined by conducting the peroxide value (PV) and p-anisidine value (AV) analyses. The total oxidation value (TOTOX) was calculated based on the PV and AV measurements. Minor changes were observed in the PV of the fish oil during the first 30 days. In the study, antioxidant added samples (groups B, C, D > 5 meq kg-1) were oxidized on the 45th day; on the other hand both control and group A oxidized on the 75th day. A possible prooxidative effect was seen for some of the antioxidants. There was a very little change secondary oxidation of fish oil and no significant effects of all four antioxidant groups on the changes of AV (<20) during the storage period (P>0.05). In addition TOTOX was calculated under GOED (<26) limit during the storage for 90 days. At the end of the study, control samples were not significantly different from the other samples with antioxidant-added. Due to the results obtained at the end of the 90-day study, it was found that none of the antioxidants were used efficiently in this study.
First record of the Guppy (Poecilia reticulata Peters, 1859) in inlandwaters of Turkey
Authors: Türkmen Gürel
Published: December 2019

The ever-increasing global trade of ornamental aquarium fishes is one of the most important pathways for aquatic invasion. Occurrence of ornamental freshwater fishes in natural freshwaters has been increasing in recent years. The ornamental trade accounts for a limited but steadily growing proportion of fish introductions to Turkish inlandwaters. In this study, Guppy, Peocilia reticulata, is recorded for the first time from natural inlandwaters of Turkey. P. reticulata was probably released into the wild, but is now established in aquifer of Çeşme-Ildır (İzmir).