bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Method Development for Sodium Valproate through Chemical Derivatization
Authors: Abualhasan Murad , Odeh Nihaya Wasif , Younis Ghadeer Naser , Zeidan Oyoun Fadel
Published: January 2020

Background. Sodium valproate has anticonvulsant activity and is structurally different to conventional antiepileptic drugs. The problem with valproic acid is the lack of a chromophore, which means that gas chromatography is the sole assay methodology. The introduction of benzoyl and phenyl groups to the molecule is a useful derivatisation, which enables the creation of detectable chromophores for HPLC analysis for pharmaceutical dosages as well as biological systems. Methodology. Sodium valproate was derivatised by the addition of a chromophore to its structure by introducing a methyl benzoyl or a phenyl group. Trichlorophenol and 2-hydroxyacetophenone were used to introduce phenyl and benzoyl groups to valproic acid, respectively. The reaction used was estrification reaction using coupling agents. An analytical method was then developed and validated using reverse-phase HPLC. The method was validated for parameters like linearity, range, accuracy precision, and robustness. Results. The developed method was easy and feasible and can be applied to both routine analysis and bioanalysis. The method was very sensitive and could quantify valproic acid at a very low concentration of 0.75 × 10−5 mg/ml. The developed method was found to be linear (R2 = 0.997), accurate, precise, and robust. Conclusion. The proposed chemical derivatisation and the developed analytical method are novel. The developed analytical procedure is the first of its kind; it is easy and feasible and can be used to quantify and detect sodium valproate at very low concentrations compared to other available methods in the literature.
Neurotrophic Receptor Tyrosine Kinase 2 (NTRK2) Alterations in Low-Grade Gliomas: Report of a Novel Gene Fusion Partner in a Pilocytic Astrocytoma and Review of the Literature
Authors: Pattwell Siobhan S. , Konnick Eric Q. , Liu Yajuan J. , Yoda Rebecca A. , Sekhar Laligam N. , Cimino Patrick J.
Published: January 2020

Pilocytic astrocytoma is a low-grade glial neoplasm of the central nervous system (CNS) that tends to occur in the pediatric population and less commonly presents in adults. Hereditary pilocytic astrocytoma is often associated with germline genetic alterations in the tumor suppressor NF1, the gene responsible for the syndrome neurofibromatosis type 1. Sporadic pilocytic astrocytoma frequently harbors somatic alterations in BRAF, with rare pilocytic astrocytomas containing alterations in FGFR1 and NTRK2. NTRK2 encodes for the protein tropomyosin receptor kinase B (TrkB), which is a neurotrophin receptor with high affinity for Brain-Derived Neurotrophic Factor (BDNF), and plays a role in several physiological functions of neurons, including cell survival and differentiation. In this report, we describe a novel PML-NTRK2 gene fusion occurring in an adult sporadic pilocytic astrocytoma and review the biology and implications of specific NTRK2 mutations occurring in CNS neoplasms.
IVIG and under Burn Unit Care Yield Favorable Outcomes in Pediatric Patients with Toxic Epidermal Necrolysis: A Case Report and Literature Review
Authors: Alzughayyar Tareq Z. , Hamad Wasim Noureddin Ibrahim , Abuqweider Eman A. S. , Alqam Bilal Nabeel Mohammad , Abukhalaf Sadi A. , Misk Rami A. , Abunejma Fawzy M. , Zalloum Jihad Samer , Saleh Mohanad , Abumunshar Ali A. , Zatari Yousef I. M.
Published: January 2020

Body reactions to drugs can manifest as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). TEN is the most severe form of cutaneous reactions with an incidence rate of 1-2 per million cases per year. Despite TEN being a critical and life-threatening condition, there is little to no evidence of clear management protocol. We reported a 5-year-old male child who presented with lamotrigine-induced TEN and was successfully treated with intravenous immune globulin (IVIG) with a burn unit care level, while TEN treatment with IVIG is an appropriate approach with predictable good outcomes, burn unit care is also effective in creating highly favorable effects. Upon reviewing the literature, several studies indicate that TEN patients treated with the combination of IVIG and burn unit care lead to decreased levels of morbidity and mortality than when treated with IVIG or burn unit care alone. Therefore, treatment involving both IVIG and burn unit care should be considered for TEN patients.
Nonfatal Occupational Injuries among Workers in Microscale and Small-Scale Woodworking Enterprise in Addis Ababa, Ethiopia
Authors: Mulugeta Hailemichael , Tefera Yifokire , Gezu Meaza
Published: January 2020

Background. Microscale and small-scale industries have been widely expanded in low-income countries, including Ethiopia, as a job opportunity for young workers, which makes workers vulnerable to injury. Woodworking is one of the high-risk jobs in this sector due to the use of hazardous tools and machineries. Therefore, the aim of this study was to estimate the prevalence of injury and associated contributing factors of this sector. Methods. A cross-sectional study design was conducted among 634 workers selected from 194 microscale and small-scale woodworking enterprises in Addis Ababa. Data were collected using a structured interview questionnaire and observation checklist from February to March 2016. Occupational injuries were documented according to the ILO operational definition. Descriptive statistics and multivariable analyses were used to characterize the data and to identify the factors associated with injury at a p value <0.05, respectively. Result. A total of 625 (98.6%) workers were interviewed. The prevalence of occupational injury was 92 (14.7%) in the past 12 months. Workers with khat chewing behavior (AOR: 2.25, 95% CI (1.04, 4.85)), job dissatisfaction (AOR: 2.89, 95% CI (1.75, 4.76)), work-related stress (AOR: 4.79, 95% CI (1.69–13.58)), job categories (AOR: 3.52, 95% CI (1.08, 11.41)) and workplace characteristics such as unguarded machines (AOR: 3.32 (1.21, 9.11)), and inadequate work space (AOR: 3.85 (1.14, 13.04)) were significantly associated with occupational injury. Conclusion. The prevalence of nonfatal occupational injuries among workers in this study was substantially high. Workers’ behavior, psychosocial issues, and work-related characteristics played a causal role in the occurrence of occupational injury. Therefore, workers' safety protection and behavioral intervention should be initiated.
All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling
Authors: Xie Linjun , Zou Liying , Chen Jie , Liu Youxue
Published: January 2020

Obesity, caused by an increased number and volume of adipocytes, is a global epidemic that seriously threatens human health. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into adipocytes. All-trans retinoic acid (atRA, the active form of vitamin A) inhibits the adipogenic differentiation of BMSCs through its receptor RARG. The expression level of FRA1 (FOS like 1, AP-1 transcription factor subunit) in atRA-treated BMSCs increased, suggesting that atRA-mediated inhibition of BMSCs adipogenesis involves FRA1. BMSCs were transfected with adenovirus overexpressing Fra1 (ad-fra1) or silenced for Fra1 (si-fra1) and then treated with atRA. BMSCs treated with atRA and treated with ad-fra1 showed decreased mRNA and protein levels of key adipogenic genes (Pparg2, Cebpa) and adipogenesis-associated genes (Cd36, Fabp, Lpl, and Plin); atRA had a stronger inhibitory effect on adipogenesis compared with that in the ad-fra1 group. Adipogenic gene expression in Fra1-silenced BMSCs was significantly upregulated. Compared with that in the atRA group, the si-fra1 + atRA also upregulated adipogenic gene expression. However, compared with si-fra1, si-fra1 + atRA significantly inhibited adipogenic differentiation. Chromatin immunoprecipitation showed that RARG directly regulates Fra1 and FRA1 directly regulates Pparg2 and Cebpa. The results supported the conclusion that atRA inhibits BMSC adipogenesis partially through the RARG-FRA1-PPARG2 or the CEBPA axis or both. Thus, vitamin A might be used to treat obesity and its related diseases.
Verrucous Carcinoma in a Giant Cutaneous Horn: A Case Report and Literature Review
Authors: Shahi Sudha , Bhandari Tika Ram , Pantha Tridip
Published: January 2020

Background. A cutaneous horn is a common clinical entity which usually presents as a cutaneous lesion. Because of its subtle nature, patients usually tend to present late unless the lesion is big or complications develop. Because of its resemblance to animal horn, it has been given the term “horn.” Cutaneous horn seems to have a remarkable history. Though cutaneous horn is benign most of the times, chances of malignancy (20–25%) should be kept in mind. Old age, giant cutaneous horn carries more chances of transformation into malignancy like in our case. Thus, early diagnosis and treatment is required in all cases. Case Presentation. We report a case of a 74-year-old farmer with a cutaneous projection measuring ∼8 × 5 × 3 cm3 over the medial surface of the right pinna for 1 year. It started as a small projection which was progressively enlarging. The primary reason behind him presenting to us was cosmetic reason since it resembled an animal horn. The projection was not associated with pain or similar lesions anywhere else in body. Understanding the malignancy risks and the cosmetic benefits, he was planned for excision biopsy of the horn. He had no systemic signs of malignancy. Histopathological reports were consistent with malignancy. Conclusions. Cutaneous horns are usually benign lesions and mostly found in the head and neck region. Because of the chances of malignancy, cutaneous horns should undergo surgical removal and biopsy for early and definitive diagnosis and management.
Primary versus Redo Urethroplasty: Results from a Single‐Center Comparative Analysis
Authors: Verla Wesley , Waterloos Marjan , Spinoit Anne-Françoise , Buelens Sarah , De Bleser Elise , Oosterlinck Willem , Martins Francisco , Palminteri Enzo , Ploumidis Achilles , Lumen Nicolaas
Published: January 2020

Objectives. To explore the differences between primary and redo urethroplasty and to directly compare according stricture‐free survival (SFS). Materials and Methods. Data of all male patients who underwent urethroplasty at Ghent University Hospital were collected between 2000 and 2018. Exclusion criteria for this analysis were age <18 years and follow‐up <1 year. Two patient groups were created for further comparison: the primary urethroplasty (PU) group (no previous urethroplasty) and redo urethroplasty (RU) group (≥1 previous urethroplasty), irrespective of prior endoscopic treatments. A comparison between groups was performed using the Mann–Whitney U test and Fisher’s Exact test. SFS was calculated using Kaplan–Meier statistics. A functional definition of failure, being the need for further urethral manipulation, was used. Uni‐ and multivariate Cox regression analyses were performed on the entire patient cohort. Results. 805 patients were included. Median (IQR) follow‐up of the PU (n = 556) and RU (n = 249) groups was 87 (50–136) and 76 (40–133) months, respectively (p = 0.1). The RU group involved more penile strictures (p < 0.001), Lichen Sclerosus (p = 0.016), failed hypospadias repair (p = 0.004), multistage procedures (p < 0.001), and definitive perineostomies (p = 0.001). The 5‐ and estimated 10‐year SFS was, respectively, 86% and 79% for the PU group and, respectively, 75% and 63% for the RU group (p < 0.001). Prior urethroplasty (HR: 1.52; p = 0.01) and diabetes (HR: 1.83; p = 0.03) remained statistically significant in the multivariate Cox regression analysis. Conclusions. Several differences between primary and redo urethroplasties exist. Redo urethroplasty entails a distinct patient population to treat and is, in general, associated with lower stricture‐free survival than primary urethroplasty, although more homogeneous series are required to corroborate these results. Prior urethroplasty and diabetes are independent risk factors for urethroplasty failure.
Comparative Evaluation of Combinatory Interaction between Endocannabinoid System Compounds and Poly‐L‐lysine against Streptococcus mutans Growth and Biofilm Formation
Authors: Feldman Mark , Sionov Ronit , Smoum Reem , Mechoulam Raphael , Ginsburg Isaac , Steinberg Doron
Published: January 2020

Endocannabinoid/endocannabinoid‐like (EC/EC‐like) are natural endogenous compounds which have been found to affect MRSA pathogenicity. Our previous studies showed that EC/EC‐like was able to impair staphylococcal biofilm formation and maintenance as well as to alter biofilm‐associated virulence factors. In the present study, we investigated the combinatory effect of the selected EC/EC‐like with a natural antimicrobial agent, poly‐L‐lysine, on cariogenic bacteria Streptococcus mutans growth and biofilm formation. Among four tested EC/EC‐like, only two, anandamide (AEA) and oleoylethanolamide (OEA), exhibited synergistic combinatory effect with poly‐L‐lysine against S. mutans. We attribute this distinct effect to differences in the fatty acid chain structure of the selected EC/EC‐like compounds. Moreover, AEA exerted a specific antibiofilm mode of action against S. mutans by effecting total inhibition of biofilm formation while still allowing bacteria viability. Finally, we postulate that the presence of EC/EC‐like and poly‐L‐lysine could enhance the permeability and efficacy of each other via hydrophobic and electrostatic interactions with the S. mutans membrane. In conclusion, we assume that a combination of endogenous natural compounds such as EC/EC‐like and poly‐L‐lysine may benefit oral hygiene by preventing dental plaque.
Working Load Characteristics of the PDC-Cone Composite Bit under Impact and Scraping
Authors: Huang Kuilin , Zhou Chunxiao , Yang Yingxin , Ren Haitao , Niu Qingzhi
Published: January 2020

The PDC-roller hybrid bit combines the cutting structure of a tricone bit with a PDC bit. It can achieve good results, breaking rock in directional drilling, drilling in inhomogeneous formations, and drilling in formations with high levels of hardness, and it can achieve the engineering goals of increasing speed and efficiency. First, we analyzed the rock-breaking mechanism of the composite bit and the principles of cushioning, torsion reduction, and prebreaking of the cone teeth during the breaking of rock. Second, cutting load models of the cone teeth and PDC teeth were established through unit experiments and through the calculation methods of the axial force, lateral force and torque, and lateral bending moment of the composite bit. Third, the digital simulation and analysis system was improved to include the function of calculating the working load of the composite bit. Taking an 8-1/2 inch, 2 + 4 type composite bit as an example, the working load characteristics of three cutting structures (cone, blade, and composite) were analyzed and compared. The analysis shows that the composite bit has high drilling efficiency, obvious deviation advantages, and good working stability under specific formation conditions. This paper provides technical support for the performance analysis, formation adaptability evaluation, and cutting structure design optimization of the PDC-cone bit.
Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications
Authors: El Moshy Sara , Radwan Israa Ahmed , Rady Dina , Abbass Marwa M. S. , El-Rashidy Aiah A. , Sadek Khadiga M. , Dörfer Christof E. , Fawzy El-Sayed Karim M.
Published: January 2020

Regenerative medicine literature has proposed mesenchymal stem/progenitor cell- (MSC-) mediated therapeutic approaches for their great potential in managing various diseases and tissue defects. Dental MSCs represent promising alternatives to nondental MSCs, owing to their ease of harvesting with minimally invasive procedures. Their mechanism of action has been attributed to their cell-to-cell contacts as well as to the paracrine effect of their secreted factors, namely, secretome. In this context, dental MSC-derived secretome/conditioned medium could represent a unique cell-free regenerative and therapeutic approach, with fascinating advantages over parent cells. This article reviews the application of different populations of dental MSC secretome/conditioned medium in in vitro and in vivo animal models, highlights their significant implementation in treating different tissue’ diseases, and clarifies the significant bioactive molecules involved in their regenerative potential. The analysis of these recent studies clearly indicate that dental MSCs’ secretome/conditioned medium could be effective in treating neural injuries, for dental tissue regeneration, in repairing bone defects, and in managing cardiovascular diseases, diabetes mellitus, hepatic regeneration, and skin injuries, through regulating anti-inflammatory, antiapoptotic, angiogenic, osteogenic, and neurogenic mediators.
Numerical Solution of Blood Flow and Mass Transport in an Elastic Tube with Multiple Stenoses
Authors: Alsemiry Reima D. , Sarifuddin  , Mandal Prashanta K. , Sayed Hamed M. , Amin Norsarahaida
Published: January 2020

The simultaneous effect of flexible wall and multiple stenoses on the flow and mass transfer of blood is investigated through numerical computation and simulations. The solution is obtained using the Marker and Cell technique on an axisymmetric model of Newtonian blood flow. The results compare favorably with physical observations where the pulsatile boundary condition and double stenoses result in a higher pressure drop across the stenoses. The streamlines, the iso‐concentration lines, the Sherwood number, and the mass concentration variations along the entire wall segment provide a comprehensive analysis of the mass transport characteristics. The double stenoses and pulsatile inlet conditions increase the number of recirculation regions and effect a higher mass transfer rate at the throat, whereby more mass is expected to accumulate and cause further stenosis.
Predicting Severe Enterovirus 71-Infected Hand, Foot, and Mouth Disease: Cytokines and Chemokines
Authors: Zhang Weijian , Huang Zhigang , Huang Mingyuan , Zeng Jincheng
Published: January 2020

Enterovirus 71 (EV71) is one of the most common intestinal virus that causes hand, foot, and mouth disease (HFMD) in infants and young children (mostly ≤5 years of age). Generally, children with EV71-infected HFMD have mild symptoms that resolve spontaneously within 7-14 days without complications. However, some EV71-infected HFMD cases lead to severe complications such as aseptic meningitis, encephalitis, acute flaccid paralysis, pulmonary edema, cardiorespiratory complication, circulatory disorders, poliomyelitis-like paralysis, myocarditis, meningoencephalitis, neonatal sepsis, and even death. The mechanism of EV71 pathogenesis has been studied extensively, and the regulation of host immune responses is suspected to aggravate EV71-induced severe complications. Recently, several cytokines or chemokines such as TNF-α, IFN-γ, IL-1β, IL-18, IL-33, IL-37, IL-4, IL-13, IL-6, IL-12, IL-23, IL-27, IL-35, IL-10, IL-22, IL-17F, IL-8, IP-10, MCP-1, G-CSF, and HMGB1 have been reported to be associated with severe EV71 infection by numerous research teams, including our own. This review is aimed at summarizing the pathophysiology of the cytokines and chemokines with severe EV71 infection.
Productivity Evaluation of Vertical Wells Incorporating Fracture Closure and Reservoir Pressure Drop in Fractured Reservoirs
Authors: Zhao Lun , Fan Zifei , Wang Mingxian , Xing Guoqiang , Zhao Wenqi , Tan Chengqian , Cheng Youyou
Published: January 2020

In most oilfields, many wells produce in pseudo-steady-state period for a long time. Because of large reservoir pressure drop in this period, fractured reservoirs always show strong stress sensitivity and fracture closure is likely to occur near wellbores. The primary goal of this study is to evaluate productivity of vertical wells incorporating fracture closure and reservoir pressure drop. Firstly, a new composite model was developed to deal with stress sensitivity and fracture closure existed in fractured reservoirs. Secondly, considering reservoir saturation condition, new pseudo-steady productivity equations for vertical wells were derived by using the proposed composite system. Thirdly, related inflow performance characteristics and influence of some factors on them were also discussed in detail. Results show that fracture closure has a great effect on vertical well inflow performance and fracture closure radius is negatively correlated with well productivity. In this composite model, the effects of stress sensitivity of the inner and outer zone on well productivity are rather different. The inner zone’s stress sensitivity affects well productivity significantly, but the outer zone’s stress sensitivity just has a weak effect on the productivity. Strong stress sensitivity in the inner zone leads to low well productivity, and both inflow performance and productivity index curves bend closer to the bottom-hole pressure axis with stress sensitivity intensifying. Meanwhile, both maximum productivity and optimal bottom-hole pressure can be achieved from inflow performance curves. In addition, reservoir pressure is positively correlated with vertical well productivity. These new productivity equations and inflow performance curves can directly provide quantitative reference for optimizing production system in fractured reservoirs.
Exploration of the Pressurization Condition for Killing Human Skin Cells and Skin Tumor Cells by High Hydrostatic Pressure
Authors: Mitsui Toshihito , Morimoto Naoki , Mahara Atsushi , Notodihardjo Sharon Claudia , Le Tien Minh , Munisso Maria Chiara , Moriyama Mariko , Moriyama Hiroyuki , Kakudo Natsuko , Yamaoka Tetsuji , Kusumoto Kenji
Published: January 2020

High hydrostatic pressure (HHP) is a physical method for inactivating cells or tissues without using chemicals such as detergents. We previously reported that HHP at 200 MPa for 10 min was able to inactivate all cells in skin and giant congenital melanocytic nevus (GCMN) without damaging the extracellular matrix. We also reported that HHP at 150 MPa for 10 min was not sufficient to inactivate them completely, while HHP at 200 MPa for 10 min was able to inactivate them completely. We intend to apply HHP to treat malignant skin tumor as the next step; however, the conditions necessary to kill each kind of cell have not been explored. In this work, we have performed a detailed experimental study on the critical pressure and pressurization time using five kinds of human skin cells and skin tumor cells, including keratinocytes (HEKas), dermal fibroblasts (HDFas), adipose tissue‐derived stem cells (ASCs), epidermal melanocytes (HEMa‐LPs), and malignant melanoma cells (MMs), using pressures between 150 and 200 MPa. We pressurized cells at 150, 160, 170, 180, or 190 MPa for 1 s, 2 min, and 10 min and evaluated the cellular activity using live/dead staining and proliferation assays. The proliferation assay revealed that HEKas were inactivated at a pressure higher than 150 MPa and a time period longer than 2 min, HDFas and MMs were inactivated at a pressure higher than 160 MPa and for 10 min, and ASCs and HEMa‐LPs were inactivated at a pressure higher than 150 MPa and for 10 min. However, some HEMa‐LPs were observed alive after HHP at 170 MPa for 10 min, so we concluded that HHP at a pressure higher than 180 MPa for 10 min was able to inactivate five kinds of cells completely.
Systematic Review and Meta: Analysis of Aortic Graft Infections following Abdominal Aortic Aneurysm Repair
Authors: Niaz O. S. , Rao A. , Carey D. , Refson J. R. , Abidia A. , Somaiya P.
Published: January 2020

Introduction. Aortic graft infection (AGI) is a rare complication following AAA repair and is associated with high morbidity and mortality. Management is variable, and there are no evidence-based guidelines. The aim of this study was to systematically review and analyse management options for AGI.Methods. Data was collected between July and August 2018. A full HDAS search was conducted on the following databases: MEDLINE, EMBASE, CINAHL, and PUBMED. Meta-analysis was conducted using RevMan 5 software.Results. 1,365 patient outcomes were assessed (10 cohort studies and 12 comparative studies). The most common treatment was in situ replacement of the graft (ISR) followed by extra-anatomical replacement (EAR). Various grafts were used for ISR, such as fresh/cryopreserved allograft, venous graft, and prosthetic grafts. No graft material was shown to be superior. Axillobifemoral graft was the commonest type of EAR used. In the majority of cohort studies, ISR was the main treatment for AGI. There was no significant difference in the overall mortality rate (ISRn=70/176vs. EARn=47/126, OR 0.93 [95% CI 0.36-2.36],P=0.87). Graft occlusion rate was significantly lower in the ISR group vs. the EAR group (n=14/115vs.n=29/60OR 0.16 [95% CI 0.07-0.36],P<0.001). There was no significant difference in the amputation rate between the surgical treatments (ISRn=9/141vs. EARn=8/82, OR 0.75 [95% CI 0.07-8.39],P=0.82).Discussion. In situ replacement is the preferred method of treatment as it had lower rates of occlusion. Further strong evidence is required, such as a multicentre trial to establish a management pathway for the condition.
Resultados después de la implementación del test de DNA fetal libre circulante en sangre materna (DNA-lc) para cribado de cromosomopatías fetales.
Authors: Soto Sánchez Eva María , López Carmen , Ibáñez Ana Belén , Lagarejos Sandra , Hernández Juan José
Published: January 2020

Objetivo: Evaluar la disminución de la tasa de técnicas invasivas de diagnóstico prenatal tras la introducción del cribado contingente de cromosomopatías con test de DNA fetal libre circulante (DNA-lc)y demostrar que este método de cribado es coste-efectivo. Método: estudio observacional prospectivo y estudio de coste efectividad. Primero se describen los resultados del cribado combinado en dos tiempos de primer trimestre desde febrero de 2008 a junio 2018 diez primeros años del hospital): 21744 cribados realizados de un total de 23000 partos.  En abril de 2016 se implementa un modelo de cribado contingente de cromosomopatías con test de DNAlc (se oferta el test a pacientes con resultado de riesgo intermedio en el cribado combinado). En segundo lugar se analizan los resultados tras la implementación del test y se comparan dos períodos de tiempo con y sin cribado contingente (año 2015 con el período abril 2016 hasta marzo de 2019). Resultados: disminución total de las técnicas invasivas del 54% por disminución de la tasa de amniocentesis, manteniéndose constante la tasa de biopsias coriales. La tasa de pérdidas fetales por técnica invasiva alcanza el 0%. Usamos seis  indicadores de calidad para evaluar el test. Se hanahorrado 70200 euros con la implementación del test de DNA-lc. Discusión: el test de DNAlc resulta útil en el cribado contingente de cromosomopatías porque reduce la tasa de amniocentesis por indicación de alto riesgo y además es coste efectivo. El cribado combinado de primer trimestre es la técnica de elección para el cribado de aneuploidias. El test de DNAlc no puede sustituir al cribado combinado porque es caro, pero resulta muy útil si se realiza cribado contingente a la población seleccionada de riesgo intermedio.
Reflexiones en torno a la extrema violencia que ha acompañado a la crisis social de Chile
Authors: Dorr Otto
Published: January 2020

Señor Editor, El 18 de octubre de este año 2019 se inició en Chile una severa crisis social, desencadenada por un alza marginal en el precio del Metro, pero que – según los dichos de los mismos manifestantes – era la expresión de un descontento por los “abusos” (no bien definidos), la desigualdad, las bajas pensiones, la mala salud, etc. En forma casi paralela, hemos visto manifestaciones violentas en contra de la autoridad en Ecuador, Bolivia y Colombia. En años anteriores se habían dado fenómenos semejantes en Inglaterra, Francia, España y Grecia, que se han repetido este año en Francia y en España. La crisis chilena ha sido, sin embargo, la más violenta de todas, porque a las marchas y gritos se han agregado incendios y profanaciones de iglesias, saqueos de supermercados y destrucción de monumentos a nuestros héroes.
Effects of Ultrasound Familiarization on Production and Perception of Nonnative Contrasts
Authors: Roon Kevin D. , Kang Jaekoo , Whalen D.H.
Published: January 2020

Background/Aims:We investigated the efficacy of ultrasound imaging of the tongue as a tool for familiarizing naïve learners with the production of a class of nonnative speech sounds: palatalized Russian consonants.Methods:Two learner groups were familiarized, one with ultrasound and one with audio only. Learners performed pre- and postfamiliarization production and discrimination tasks.Results:Ratings of productions of word-final palatalized consonants by learners from both groups improved after familiarization, as did discrimination of the palatalization contrast word-finally. There were no significant differences in the improvement between groups in either task. All learners were able to generalize to novel contexts in production and discrimination. The presence of palatalization interfered with discrimination of word-initial manner, and ultrasound learners were more successful in overcoming that interference.Conclusion:Ultrasound familiarization resulted in improvements in production and discrimination comparable to audio only. Ultrasound familiarization additionally helped learners overcome difficulties in manner discrimination introduced by palatalization. When familiarizing learners with a novel, nonnative class of sounds, a small set of stimuli in different contexts may be more beneficial than using a larger set in one context. Although untrained production can disrupt discrimination training, we found that production familiarization was not disruptive to discrimination or production.
Hair Loss in Lichen Planopilaris and Frontal Fibrosing Alopecia: Not Always Irreversible
Authors: Batra Prag , Sukhdeo Kumar , Shapiro Jerry
Published: January 2020

Introduction: We present 2 cases in which typically irreversible lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) showed signs of reversal. Case Presentation: A 27-year-old Caucasian man presented with hair loss and intense pruritus on the vertex scalp for 4 years with biopsy-proven LPP and having failed multiple pharmacologic modalities. Six months after adding oral tofacitinib and later dapsone, he demonstrated reduced scalp visibility, evidence of crown and vertex hair regrowth, and elimination of itch. A 45-year-old premenopausal Hispanic woman presented with eyebrow loss for 3.75 years and hair loss for 9 months with biopsy-proven FFA. After beginning oral finasteride and hydroxychloroquine, triamcinolone injections, and topical minoxidil, she initially worsened over 11 months but subsequently improved over 6 months, demonstrating hair and eyebrow regrowth, reduction in glabella-hairline distance, and new absence of frontal hair line hyperkeratosis and inflammation. Discussion/Conclusion: Cicatricial alopecia involves inflammation with JAK-STAT upregulation. We report a positive clinical response in LPP to tofacitinib, a JAK1/3 inhibitor, and dapsone, an anti-neutrophilic agent. FFA is believed to involve autoimmune and/or hormonal processes. Here we report a positive clinical response to androgenic and immune modulators.
Lack of Association between Pretransplant Donor-Specific Antibodies and Posttransplant Kidney Outcomes in Simultaneous Liver-Kidney Transplant Recipients with Rabbit Anti-Thymocyte Globulin Induction and Steroid-Free Protocol
Authors: Yazawa Masahiko , Cseprekal Orsolya , Helmick Ryan A. , Talwar Manish , Balaraman Vasanthi , Podila Pradeep S.B. , Agbim Uchenna A. , Maliakkal Benedict , Fossey Sallyanne , Satapathy Sanjaya K. , Sumida Keiichi , Kovesdy Csaba P. , Nair Satheesh , Eason James D. , Molnar Miklos Z.
Published: January 2020

Introduction and Objective: The impact of pretransplant donor-specific antibodies (DSAs), especially class II DSAs, on kidney allograft outcomes remains unclear in simultaneous liver-kidney transplantation (SLKT) recipients. Methods: We examined 85 recipients who consecutively underwent SLKT between 2009 and 2018 in our center. Associations between pretransplant DSA and worsening kidney function (WKF), kidney allograft loss, composite kidney outcome (WKF and/or antibody-mediated rejection and/or death-censored kidney allograft loss), death with functioning graft, and overall mortality were examined in survival analysis. WKF was defined as an eGFR decrease of 30% or greater from baseline, or 2 or more episodes of proteinuria, at least 90 days apart from each other. Results: The mean age at SLKT was 56 ± 10 years, and 62% of the recipients were male. More than one quarter (26%) of our recipients were African American. The 2 major causes of end-stage liver disease were hepatitis C (28%) and alcoholic hepatitis (26%). Nineteen recipients (22%) had pretransplant DSAs at the time of SLKT. The DSA(+) group and DSA(−) group had similar risk of WKF (unadjusted model: hazard ratio [HR] = 0.77, 95% confidence interval [CI]: 0.29–2.05 and adjusted model: HR = 0.36, 95% CI: 0.12–1.08); similar risk of composite kidney outcome (unadjusted model: HR = 1.04, 95% CI: 0.45–2.43 and adjusted model: HR = 0.53, 95% CI: 0.20–1.39); and similar risk of overall death (unadjusted model: HR = 1.23, 95% CI: 0.45–3.36 and adjusted model: HR = 1.28, 95% CI: 0.42–3.87). We found similar results when comparing different DSA subclasses (class I and II DSAs) with recipients without DSAs. Conclusions: The presence of pretransplant DSAs was not associated with worse kidney allograft outcomes from our single-center experience. Further prospective larger studies are strongly warranted.
Diabetes Insipidus: New Concepts for Diagnosis
Authors: Christ-Crain Mirjam
Published: January 2020

Diabetes insipidus (DI), be it from central or from nephrogenic origin, has to be differentiated from primary polydipsia. This differentiation is crucial since wrong treatment can have dangerous consequences. For decades, the “gold standard” for differential diagnosis has been the standard water deprivation test. However, this test has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 h and is cumbersome for patients. Also clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. Direct measurement of arginine vasopressin (AVP) upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay. Copeptin is secreted in equimolar ratio to AVP, mirroring AVP concentrations in the circulation. We have shown that copeptin, without prior fluid deprivation, identifies patients with nephrogenic DI. For the more difficult differentiation between central DI and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these 2 entities with a high diagnostic accuracy and is superior to the water deprivation test. However, it is important to note that close and regular sodium monitoring every 30 min during the hypertonic saline test is a prerequisite, which is not possible in all hospitals. Furthermore, side effects are common. Therefore, a nonosmotic stimulation test would be advantageous. Arginine significantly stimulates copeptin and therefore is a novel, so far unknown stimulus of this peptide. Consequently, infusion of arginine with subsequent copeptin measurement was shown to be an even simpler and better tolerated test, but head to head comparison is still lacking.
Novel AHDC1 Gene Mutation in a Brazilian Individual: Implications of Xia-Gibbs Syndrome
Authors: Cardoso-dos-Santos Augusto C. , Oliveira Silva Thiago , Silveira Faccini Anderson , Woycinck Kowalski Thayne , Bertoli-Avella Aida , Morales Saute Jonas A. , Schuler-Faccini Lavinia , de Oliveira Poswar Fabiano
Published: January 2020

Xia-Gibbs syndrome (XGS) is a rare neurological disorder characterized by global developmental delay, hypotonia, intellectual disability, seizures, and sleep apnea. XGS is defined by monoallelic pathogenic variants in AHDC1. In this study, we identified a Brazilian patient carrying a likely de novo AHDC1 nonsense mutation (c.451C>T; p.Arg151*) which was absent in both parents. All disease-causative variants already associated with XGS have been reviewed and the mutation described here corresponds to the closest one to the N-terminal region. Our findings were discussed based on the suggested genotype-phenotype correlation of the disease.
Blood Harmane (1-Methyl-9H-Pyrido[3,4-b]indole) and Mercury in Essential Tremor: A Population-Based, Environmental Epidemiology Study in the Faroe Islands
Authors: Louis Elan D. , Eliasen Eina H. , Ferrer Monica , Iglesias Hernandez Daniella , Gaini Shahin , Jiang Wendy , Zheng Wei , Nielsen Flemming , Petersen Maria Skaalum
Published: January 2020

Background: Essential tremor (ET) is among the most prevalent neurological diseases. Its environmental determinants are poorly understood. Harmane (1-methyl-9H-pyrido[3, 4-b]indole), a dietary tremor-producing neurotoxin, has been linked to ET in a few studies in New York and Madrid. Mercury, also a tremor-producing neurotoxin, has not been studied in ET. The Faroe Islands have been the focus of epidemiological investigations of numerous neurological disorders. Objective: In this population-based, case-control study, we directly measured blood harmane concentrations (HA) and blood mercury concentrations (Hg) in ET cases and controls. Methods: In total, 1,328 Faroese adults were screened; 26 ET cases were identified whose (HA) and (Hg) were compared to 197 controls. Results: Although there were no statistically significant differences between diagnostic groups, median (HA) was 2.7× higher in definite ET (4.13 g–10/mL) and 1.5× higher in probable ET (2.28 g–10/mL) than controls (1.53 g–10/mL). Small sample size was a limitation. For definite ET versus controls, p = 0.126. (Hg) were similar between groups. Conclusions: We demonstrated marginally elevated (HA) in definite and probable ET. These data are similar to those previously published and possibly extend etiological links between this neurotoxin and ET to a third locale. The study did not support a link between mercury and ET.
Syndecan‐4 Protects the Heart From the Profibrotic Effects of Thrombin‐Cleaved Osteopontin
Authors: Herum Kate M. , Romaine Andreas , Wang Ariel , Melleby Arne Olav , Strand Mari E. , Pacheco Julian , Braathen Bjørn , Dunér Pontus , Tønnessen Theis , Lunde Ida G. , Sjaastad Ivar , Brakebusch Cord , McCulloch Andrew D. , Gomez Maria F. , Carlson Cathrine R. , Christensen Geir
Published: January 2020

Background

Pressure overload of the heart occurs in patients with hypertension or valvular stenosis and induces cardiac fibrosis because of excessive production of extracellular matrix by activated cardiac fibroblasts. This initially provides essential mechanical support to the heart, but eventually compromises function. Osteopontin is associated with fibrosis; however, the underlying signaling mechanisms are not well understood. Herein, we examine the effect of thrombin‐cleaved osteopontin on fibrosis in the heart and explore the role of syndecan‐4 in regulating cleavage of osteopontin.

Methods and Results

Osteopontin was upregulated and cleaved by thrombin in the pressure‐overloaded heart of mice subjected to aortic banding. Cleaved osteopontin was higher in plasma from patients with aortic stenosis receiving crystalloid compared with blood cardioplegia, likely because of less heparin‐induced inhibition of thrombin. Cleaved osteopontin and the specific osteopontin peptide sequence
RGDSLAYGLR
that is exposed after thrombin cleavage both induced collagen production in cardiac fibroblasts. Like osteopontin, the heparan sulfate proteoglycan syndecan‐4 was upregulated after aortic banding. Consistent with a heparan sulfate binding domain in the osteopontin cleavage site, syndecan‐4 was found to bind to osteopontin in left ventricles and cardiac fibroblasts and protected osteopontin from cleavage by thrombin. Shedding of the extracellular part of syndecan‐4 was more prominent at later remodeling phases, at which time levels of cleaved osteopontin were increased.

Conclusions

Thrombin‐cleaved osteopontin induces collagen production by cardiac fibroblasts. Syndecan‐4 protects osteopontin from cleavage by thrombin, but this protection is lost when syndecan‐4 is shed in later phases of remodeling, contributing to progression of cardiac fibrosis.
Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study
Authors: Lapinskas Tomas , Kelle Sebastian , Grune Jana , Foryst‐Ludwig Anna , Meyborg Heike , Jeuthe Sarah , Wellnhofer Ernst , Elsanhoury Ahmed , Pieske Burkert , Gebker Rolf , Kintscher Ulrich , Stawowy Philipp
Published: January 2020

Background

Animal studies demonstrated that serelaxin lessens fibrosis in heart failure. This study assessed its effect on myocardial deformation using cardiac magnetic resonance and elucidated its relationship to gene regulation and histology in a mouse heart failure model.

Methods and Results

C57
BL
/6J mice were subjected to
SHAM
(n=4) or transverse aortic constriction (
TAC
). At week 10,
TAC
mice were randomized to receive either serelaxin (0.5 mg/kg per day; n=11) or vehicle (n=13) for 4 weeks. Cardiac magnetic resonance imaging was performed at baseline and repeated at the end of the study (week 14). Cine images were used to calculate left ventricular (
LV
) global longitudinal, circumferential, and radial strain. Hearts were examined for histology and gene expression. Compared with
SHAM
, mice 10 weeks after
TAC
showed increased
LV
mass with significant decreases in
LV
deformation parameters, indicating subclinical deterioration of myocardial function. At week 14,
TAC
mice given serelaxin demonstrated significant improvements in all
LV
strain parameters and no decrease in
LV
stroke volume and ejection fraction compared with TAC mice given vehicle. A significant positive correlation between global circumferential strain and the extent of myocardial fibrosis was found, and global circumferential strain correlated significantly with the expression of heart failure genes in serelaxin‐treated mice.

Conclusions

Serelaxin improved cardiac magnetic resonance–derived myocardial deformation parameters as well as histomorphometric and gene expression findings in mice with heart failure. Cardiac magnetic resonance–derived myocardial mechanics correlate with histology and gene expression, stressing its utilization in myocardial remodeling.
Old and new challenges in taxonomy: what are taxonomists up against?
Authors: DUPÉRRÉ NADINE
Published: January 2020

Old and new challenges in taxonomy: 1. How is alpha taxonomy coping with Natural History Museum staff and funding shortages? 2. Is alpha taxonomy being falsely portrayed as: the tedious, painstaking, time-consuming labour, the none-accessible, old-fashioned science? 3. How will taxonomists face the trend of naming species based on DNA without morphological diagnosis or description?
Australasian genus Crasilogia Warren (Lepidoptera: Geometridae: Larentiinae)
Authors: SCHMIDT OLGA
Published: January 2020

The Australasian genus Crasilogia Warren comprising the species C. dispar Warren, C. flavipennis Warren, C. fulvitincta Joicey & Talbo, C. fumipennis Warren, C. gressitti Holloway, C. simplex (Prout), C. parasimplex, sp. nov., and C. diversisimplex, sp. nov. is reviewed based on the museum specimens, including primary types. Lectotype is designated for C. simplex.
Value of Ultrasonic Cardiogram Combined with Flash CT in Diagnosis of Conotruncal Defects
Authors: Zhou Pingan
Published: January 2020

The paper aims at exploring the value of ultrasonic cardiogram (UCG) combined with Flash CT in the diagnosis of conotruncal defects (CTD). This complex cyanotic congenital heart disease is divided into several types by using UCG and Flash dual source CT imaging. The results show that
the detection method of UCG is simple and fast, but it has some deficiencies in the display of extracardiac vessels. Flash CT technology has a strong image post-processing function, which makes up for the shortcomings of UCG and is an important supplementary means for patients after echocardiographic
examination. Therefore, UCG combined with Flash CT technology can detect the patient's disease more accurately and quickly, avoid the traumatic detection of angiography, and is more convenient. It is hopeful to replace angiography as the gold standard for the diagnosis of congenital heart
disease.
Enhancement of Lesions in CT Images of Lung Cancer Based on MIMICS Software
Authors: Zhou Hongsuo , Pan Hongtao , Dong Mo , Zhou Zhizun , Zhao Xiangkun
Published: January 2020

In order to explore the three-dimensional reconstruction of lung cancer CT images by MIMICS software, the purpose of enhancing the effect of the lesion area is realized, and the visualization model can be realized, which can effectively assist the early diagnosis of lung cancer and
the surgical treatment of lung cancer. Using lung CT scan data from lung cancer patients, semi-automated segmentation methods are used to segment the lung tumors in MIMICS software to create an individualized lung cancer model. MIMICS software accurately and efficiently distributes the model
according to the gray values of different tissues, and successfully establishes a human body chest finite element model with realistic shape and accurate structure. The model includes chest skin, bones, lungs, pulmonary arteries, pulmonary veins, and tracheobronchial trees, providing precise
model support for finite element analysis. This study successfully constructs a three-dimensional digital model of individualized lung cancer. The model has high geometric similarity and strong stereoscopic effect. It truly reflects the morphological characteristics of lung cancer and the
spatial relationship between adjacent structures, which makes the imaging effect of lung cancer lesions more prominent. By moving, separating, combining, and revealing the model, multi-angle observation and measurement can be performed, which facilitates preoperative planning and shortens
the operation time.