bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermodynamics in f(G,T) Gravity
Authors: Sharif M. , Ikram Ayesha
Published: March 2018

This paper explores the nonequilibrium behavior of thermodynamics at the apparent horizon of isotropic and homogeneous universe model in f(G,T) gravity (G and T represent the Gauss-Bonnet invariant and trace of the energy-momentum tensor, resp.). We construct the corresponding field equations and analyze the first as well as generalized second law of thermodynamics in this scenario. It is found that an auxiliary term corresponding to entropy production appears due to the nonequilibrium picture of thermodynamics in first law. The universal condition for the validity of generalized second law of thermodynamics is also obtained. Finally, we check the validity of generalized second law of thermodynamics for the reconstructed f(G,T) models (de Sitter and power-law solutions). We conclude that this law holds for suitable choices of free parameters.
Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic Melanoma, Psoriasis, and a Previous Guillain–Barré Syndrome
Authors: Cortellini Alessio , Parisi Alessandro , Fargnoli Maria Concetta , Cannita Katia , Irelli Azzurra , Porzio Giampiero , Martinazzo Claudio , Ficorella Corrado
Published: March 2018

Background. Patients with autoimmune diseases were not evaluated in clinical trials with immune checkpoint inhibitors (ICIs), since a history of immune disorders, such as Guillain–Barré syndrome (GBS) and psoriasis, is one of the major risk factors for the development of immune-related adverse events (irAEs). This risk cannot be defined; therefore, physicians are called to manage these patients in clinical practice. Case Report. We report the case of a 62-year-old male patient affected by metastatic melanoma, with a history of GBS and psoriasis, and treated with sequential ipilimumab, pembrolizumab, and nivolumab, without significant toxicities. Conclusion. This case report supports that although a history of immune disorders is one of the major risk factors for development of irAEs, in some patients, it could be possible to safely administer sequential treatments with ICIs. A proper decision should be made, considering therapeutic options, disease-related risks, and those related to a recurrence of preexisting autoimmune disorders.
Rooming-in Reduces Salivary Cortisol Level of Newborn
Authors: De Bernardo Giuseppe , Riccitelli Marina , Giordano Maurizio , Proietti Fabrizio , Sordino Desiree , Longini Mariangela , Buonocore Giuseppe , Perrone Serafina
Published: March 2018

Background. Rooming-in practice improves breastfeeding and reduces newborn stress reactivity. When this modality is not available, partial rooming-in after birth can be considered. Salivary cortisol levels (SCLs) are considered reliable biomarkers to indicate stress. Objective. To test the hypothesis that rooming-in duration impacts neonatal stress response in hospitalized newborns. Design/methods. Forty term newborns, enrolled in the Neonatology and Obstetrics Nursing, C.G. Ruesch, Naples, Italy, were divided, according to the mother’s choice, into the study (SG; n=20) and control (CG; n=20) groups if they received full (24 hs) or partial (14 hs) rooming-in care, respectively. Saliva samples were collected from all babies between 7:00 a.m. and 8:00 a.m. of the 3rd day of life by using oral swab. Salivary cortisol levels were measured using an enzyme immunoassay kit (Salimetrics LLC, PA, USA). Results. A statistically significant difference in the SCLs between SG and CG was found (median: 258 ng/dl versus 488.5 ng/dl; p=0.048). Conclusions. Data support the practice of full rooming-in care compared with partial rooming-in. The rooming-in duration clearly reduces SCLs and likely neonatal stress. These lower SCLs may have long-term positive effects reducing the risk of metabolic syndrome, high blood pressure, and cognitive and behavioural changes.
Current Concepts of Neurodegenerative Mechanisms in Alzheimer’s Disease
Authors: Magalingam Kasthuri Bai , Radhakrishnan Ammu , Ping Ng Shee , Haleagrahara Nagaraja
Published: March 2018

Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer’s disease is characterized by the abnormal accumulation of extracellular amyloid-βplaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.
An Efficient and Privacy-Preserving Multiuser Cloud-Based LBS Query Scheme
Authors: Ou Lu , Yin Hui , Qin Zheng , Xiao Sheng , Yang Guangyi , Hu Yupeng
Published: March 2018

Location-based services (LBSs) are increasingly popular in today’s society. People reveal their location information to LBS providers to obtain personalized services such as map directions, restaurant recommendations, and taxi reservations. Usually, LBS providers offer user privacy protection statement to assure users that their private location information would not be given away. However, many LBSs run on third-party cloud infrastructures. It is challenging to guarantee user location privacy against curious cloud operators while still permitting users to query their own location information data. In this paper, we propose an efficient privacy-preserving cloud-based LBS query scheme for the multiuser setting. We encrypt LBS data and LBS queries with a hybrid encryption mechanism, which can efficiently implement privacy-preserving search over encrypted LBS data and is very suitable for the multiuser setting with secure and effective user enrollment and user revocation. This paper contains security analysis and performance experiments to demonstrate the privacy-preserving properties and efficiency of our proposed scheme.
NIRF Optical/PET Dual-Modal Imaging of Hepatocellular Carcinoma Using Heptamethine Carbocyanine Dye
Authors: Zhang Caiqin , Zhao Yong , Zhao Ningning , Tan Dengxu , Zhang He , Chen Xue , Zhang Hai , An Jiaze , Shi Changhong , Li Mengbin
Published: March 2018

Combining near-infrared fluorescence (NIRF) and nuclear imaging techniques provides a novel approach for hepatocellular carcinoma (HCC) diagnosis. Here, we report the synthesis and characteristics of a dual-modality NIRF optical/positron emission tomography (PET) imaging probe using heptamethine carbocyanine dye and verify its feasibility in both nude mice and rabbits with orthotopic xenograft liver cancer. This dye, MHI-148, is an effective cancer-specific NIRF imaging agent and shows preferential uptake and retention in liver cancer. The corresponding NIRF imaging intensity reaches 109/cm2tumor area at 24 h after injection in mice with HCC subcutaneous tumors. The dye can be further conjugated with radionuclide68Ga (68Ga-MHI-148) for PET tracing. We applied the dual-modality methodology toward the detection of HCC in both patient-derived orthotopic xenograft (PDX) models and rabbit orthotopic transplantation models. NIRF/PET images showed clear tumor delineation after probe injection (MHI-148 and68Ga-MHI-148). The tumor-to-muscle (T/M) standardized uptake value (SUV) ratios were obtained from PET at 1 h after injection of68Ga-MHI-148, which was helpful for effectively capturing small tumors in mice (0.5 cm × 0.3 cm) and rabbits (1.2 cm × 1.8 cm). This cancer-targeting NIRF/PET dual-modality imaging probe provides a proof of principle for noninvasive detection of deep-tissue tumors in mouse and rabbit and is a promising technique for more accurate and early detection of HCC.
Multifrequency Piezoelectric Energy Harvester Based on Polygon‐Shaped Cantilever Array
Authors: Mažeika Dalius , Čeponis Andrius , Yang Ying
Published: March 2018

This paper focuses on numerical and experimental investigations of a novel design piezoelectric energy harvester. Investigated harvester is based on polygon‐shaped cantilever array and employs multifrequency operating principle. It consists of eight cantilevers with irregular design of cross‐sectional area. Cantilevers are connected to each other by specific angle to form polygon‐shaped structure. Moreover, seven seismic masses with additional lever arms are added in order to create additional rotation moment. Numerical investigation showed that piezoelectric polygon‐shaped energy harvester has five natural frequencies in the frequency range from 10 Hz to 240 Hz, where the first and the second bending modes of the cantilevers are dominating. Maximum output voltage density and energy density equal to 50.03 mV/mm3 and 604 μJ/mm3, respectively, were obtained during numerical simulation. Prototype of piezoelectric harvester was made and experimental investigation was performed. Experimental measurements of the electrical characteristics showed that maximum output voltage density, energy density, and output power are 37.5 mV/mm3, 815.16 μJ/mm3, and 65.24 μW, respectively.
Engineering Tissues without the Use of a Synthetic Scaffold: A Twenty-Year History of the Self-Assembly Method
Authors: Saba Ingrid , Jakubowska Weronika , Bolduc Stéphane , Chabaud Stéphane
Published: March 2018

Twenty years ago, Dr. François A. Auger, the founder of the Laboratory of Experimental Organogenesis (LOEX), introduced the self-assembly technique. This innovative technique relies on the ability of dermal fibroblasts to produce and assemble their own extracellular matrix, differing from all other tissue-engineering techniques that use preformed synthetic scaffolds. Nevertheless, the use of the self-assembly technique was limited for a long time due to its main drawbacks: time and cost. Recent scientific breakthroughs have addressed these limitations. New protocol modifications that aim at increasing the rate of extracellular matrix formation have been proposed to reduce the production costs and laboratory handling time of engineered tissues. Moreover, the introduction of vascularization strategies in vitro permits the formation of capillary-like networks within reconstructed tissues. These optimization strategies enable the large-scale production of inexpensive native-like substitutes using the self-assembly technique. These substitutes can be used to reconstruct three-dimensional models free of exogenous materials for clinical and fundamental applications.
Adolescent Internet Abuse: A Study on the Role of Attachment to Parents and Peers in a Large Community Sample
Authors: Ballarotto Giulia , Volpi Barbara , Marzilli Eleonora , Tambelli Renata
Published: March 2018

Adolescents are the main users of new technologies and their main purpose of use is social interaction. Although new technologies are useful to teenagers, in addressing their developmental tasks, recent studies have shown that they may be an obstacle in their growth. Research shows that teenagers with Internet addiction experience lower quality in their relationships with parents and more individual difficulties. However, limited research is available on the role played by adolescents’ attachment to parents and peers, considering their psychological profiles. We evaluated in a large community sample of adolescents (N=1105) the Internet use/abuse, the adolescents’ attachment to parents and peers, and their psychological profiles. Hierarchical regression analyses were conducted to verify the influence of parental and peer attachment on Internet use/abuse, considering the moderating effect of adolescents’ psychopathological risk. Results showed that adolescents’ attachment to parents had a significant effect on Internet use. Adolescents’ psychopathological risk had a moderating effect on the relationship between attachment to mothers and Internet use. Our study shows that further research is needed, taking into account both individual and family variables.
Analysis of Managing Safety in Small Enterprises: Dual-Effects of Employee Prosocial Safety Behavior and Government Inspection
Authors: Wang Qiwei , Mei Qiang , Liu Suxia , Zhang Jingjing
Published: March 2018

This paper aims to promote a national and international occupational health and safety (OHS) intervention for small and medium enterprises (SMEs) within internal and external resources. Based on the characteristics of small SME management, the work environment and occupational health may be positively affected by the dual-effects of employees and government. Evolutionary game theory is utilized to identify relevant interactions among the government, small enterprises, and employees. Furthermore, dynamic simulations of the evolutionary game model are used to explore stability strategies and to identify modes of equilibrium.
Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome
Authors: Zhang Bingjie , Wang Jing , Shen Shanmei , Liu Jiayi , Sun Jie , Gu Tianwei , Ye Xiao , Zhu Dalong , Bi Yan
Published: March 2018

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p<0.001). Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.
A Rare but Fascinating Disorder: Case Collection of Patients with Schnitzler Syndrome
Authors: Bashir Maaman , Bettendorf Brittany , Hariman Richard
Published: March 2018

Background. Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash and monoclonal gammopathy (IgM in more than 90% of the cases). It is difficult to distinguish from other neutrophilic urticarial dermatoses, and diagnosis is based on the Strasbourg criteria. Interleukin-1 is considered the key mediator, and interleukin-1 inhibitors are considered first line treatment. Here, we present two cases of Schnitzler syndrome, both successfully treated with anakinra. Objectives. To increase awareness regarding clinical presentation, diagnosis, and treatment of this rare disorder. Cases. We describe the clinical features and disease course of two patients with Schnitzler syndrome, diagnosed using the Strasbourg criteria. Both were treated with anakinra with remarkable response to therapy. Conclusion. Schnitzler syndrome is a rare and underdiagnosed disorder. High suspicion should be maintained in patients with chronic urticaria-like dermatoses, intermittent fevers, and arthralgias. A serum protein electrophoresis and immunofixation should be performed in these patients. The diagnosis is important to recognize as Schnitzler syndrome is associated with malignancy. A lymphoproliferative disorder develops in about 20% of patients at an average of 7.6 years after onset of symptoms. Thus, patients warrant long-term follow-up. IL-1 inhibitors are extremely effective in relieving symptoms and are considered first line therapy.
Physical Activity and Sedentary Patterns among Metabolically Healthy Individuals Living with Obesity
Authors: de Winter Marika , Rioux Brittany V. , Boudreau Jonathan G. , Bouchard Danielle R. , Sénéchal Martin
Published: March 2018

Background. Some individuals living with obesity are free from typical cardiometabolic risk factors and are termed metabolically healthy obese (MHO). The patterns of physical activity and sedentary behaviors among MHO are currently unknown. Methods. This study includes 414 youth (12–18 years old), 802 adults (19–44 years old), and 1230 older adults (45–85 years old) living with obesity from the 2003-2004 or 2005-2006 NHANES cycles. Time spent in bouts of 1, 5, 10, 30, and 60 minutes for moderate-to-vigorous physical activity (MVPA) and sedentary time was measured objectively using accelerometers. Participants were categorized as MHO if they had no cardiometabolic risk factors above the identified thresholds (triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, and glucose). Results. The proportion of MHO was 19%, 14%, and 12% in youth, adults, and older adults, respectively. MHO adults displayed a higher 1-minute bout of MVPA per day compared to non-MHO (p=0.02), but no difference was observed for MVPA and sedentary behavior patterns for youth and older adults. When adjusted for confounders, all bouts of sedentary behavior patterns in youth were significantly associated with being classified as MHO. Conclusion. This study suggests that greater sedentary time is associated with cardiometabolic risk factors in youth even if they are physically active.
Determination of Pyrethroids in Tea Brew by GC-MS Combined with SPME with Multiwalled Carbon Nanotube Coated Fiber
Authors: Ren Dongxia , Sun Chengjun , Ma Guanqun , Yang Danni , Zhou Chen , Xie Jiayu , Li Yongxin
Published: March 2018

A new method has been developed to simultaneously determine 7 pyrethroid residues in tea brew using gas chromatography-mass spectrometry (GC-MS) combined with solid phase microextraction (SPME) with multiwalled carbon nanotubes (MWCNTs) coated fiber. The MWCNTs coated fiber of SPME was homemade by using stainless steel wire as coating carrier and polyacrylonitrile (PAN) solution as adhesive glue. Under the optimized conditions, a good linearity was shown for bifenthrin, fenpropathrin, permethrin, and cyfluthrin in 1–50 ng mL−1 and for cypermethrin, fenvalerate, and deltamethrin in 5–50 ng mL−1. The correlation coefficients were in the range of 0.9948–0.9999. The average recoveries of 7 pyrethroids were 94.2%–107.3% and the relative standard deviations (RSDs) were less than 15%. The detection limit of the method ranged from 0.12 to 1.65 ng mL−1. The tea brew samples made from some commercial tea samples were analyzed. Among them, bifenthrin, fenpropathrin, and permethrin were found. The results show that the method is rapid and sensitive and requires low organic reagent consumption, which can be well used for the detection of the pyrethroids in tea brew.
Automated Analysis of Facial Cues from Videos as a Potential Method for Differentiating Stress and Boredom of Players in Games
Authors: Bevilacqua Fernando , Engström Henrik , Backlund Per
Published: March 2018

Facial analysis is a promising approach to detect emotions of players unobtrusively; however approaches are commonly evaluated in contexts not related to games or facial cues are derived from models not designed for analysis of emotions during interactions with games. We present a method for automated analysis of facial cues from videos as a potential tool for detecting stress and boredom of players behaving naturally while playing games. Computer vision is used to automatically and unobtrusively extract 7 facial features aimed at detecting the activity of a set of facial muscles. Features are mainly based on the Euclidean distance of facial landmarks and do not rely on predefined facial expressions, training of a model, or the use of facial standards. An empirical evaluation was conducted on video recordings of an experiment involving games as emotion elicitation sources. Results show statistically significant differences in the values of facial features during boring and stressful periods of gameplay for 5 of the 7 features. We believe our approach is more user-tailored, convenient, and better suited for contexts involving games.
CD16A Activation of NK Cells Promotes NK Cell Proliferation and Memory-Like Cytotoxicity against Cancer Cells
Authors: Pahl Jens H.W. , Koch Joachim , Götz Jana-Julia , Arnold Annette , Reusch Uwe , Gantke Thorsten , Rajkovic Erich , Treder Martin , Cerwenka Adelheid
Published: March 2018

CD16A is a potent cytotoxicity receptor on human natural killer (NK) cells, which can be exploited by therapeutic bispecific antibodies. So far, the effects of CD16A-mediated activation on NK cell effector functions beyond classical antibody-dependent cytotoxicity have remained poorly elucidated. Here, we investigated NK cell responses after exposure to therapeutic antibodies such as the tetravalent bispecific antibody AFM13 (CD30/CD16A), designed for the treatment of Hodgkin lymphoma and other CD30+ lymphomas. Our results reveal that CD16A engagement enhanced subsequent IL2- and IL15-driven NK cell proliferation and expansion. This effect involved the upregulation of CD25 (IL2Rα) and CD132 (γc) on NK cells, resulting in increased sensitivity to low-dose IL2 or to IL15. CD16A engagement initially induced NK cell cytotoxicity. The lower NK cell reactivity observed 1 day after CD16A engagement could be recovered by reculture in IL2 or IL15. After reculture in IL2 or IL15, these CD16A-experienced NK cells exerted more vigorous IFNγ production upon restimulation with tumor cells or cytokines. Importantly, after reculture, CD16A-experienced NK cells also exerted increased cytotoxicity toward different tumor targets, mainly through the activating NK cell receptor NKG2D. Our findings uncover a role for CD16A engagement in priming NK cell responses to restimulation by cytokines and tumor cells, indicative of a memory-like functionality. Our study suggests that combination of AFM13 with IL2 or IL15 may boost NK cell antitumor activity in patients by expanding tumor-reactive NK cells and enhancing NK cell reactivity, even upon repeated tumor encounters. Cancer Immunol Res; 6(5); 517–27. ©2018 AACR.
Evaluation of the New Lateral Flow Card MDmulticard® Basic Extended Phenotype in Routine Clinical Practice
Authors: Mayer Beate , Müller Julia , Candela-García María-José , Manteau Annie-Claude , Weinstock Christof , Pruß Axel
Published: March 2018

Background: Transfusion emergencies and critical situations require specifically designed devices to simplify and optimize the standard procedures. In addition, matching antigens over and above ABO-Rh-K would be beneficial. Methods: Routine blood samples were collected in four immunohematology centers and tested with the new MDmulticard Basic Extended Phenotype for the simultaneous detection of the Duffy, Kidd, and Ss antigens, according to the principle of the lateral flow. Results were compared with those obtained using routine serology methods. Discrepancies were analyzed by molecular techniques/genotyping. Results: 310 samples were tested (167 donors; 75 patients; 28 subjects with positive direct antiglobulin test (DAT); 15 newborns; 25 previously transfused patients). The 285 samples with non-mixed-field reaction yielded 1,710 antigen results with 8 discrepancies (0.47%) six of which in DAT-positive subjects: three false-positive (Fya) for MDmulticard, and two false-positive (Fya) plus three false-negative (Fyb) for the reference methods (MDmulticard PPA for donors/patients/newborns: 99.82%; negative percent agreement: 100%; sensitivity: 100%; specificity: 99.39%, positive predictive value: 99.75%; negative predictive value: 100%). The MDmulticard detected mixed-field in 15 antigen reactions from 13 transfused patients, undetected by the comparative method, with the opposite result in 8 antigens (5 patients). Conclusion: The MDmulticard Basic Extended Phenotype met the criteria prescribed for the testing of donor, patient, DAT-positive, and newborn samples in transfusion laboratory routine.
Complement Deposition and IgG Binding on Stored Red Blood Cells Are Independent of Storage Time
Authors: Thielen Astrid J.F. , Meulenbroek Elisabeth M. , Baas Inge , Bruggen Robin , Zeerleder Sacha S. , Wouters Diana
Published: March 2018

Background: In the Netherlands, red blood cells (RBCs) are allowed to be stored up to 35 days at 2-6 °C in saline-adenine-glucose-mannitol (SAGM). During storage, RBCs undergo several changes that are collectively known as storage lesion. We investigated to what extent complement deposition and antibody binding occurred during RBC storage and investigated phagocytic uptake in vitro. Methods: RBCs were stored for different lengths of time at 2-6 °C in SAGM. Complement deposition and antibody binding were assessed upon storage and after incubation with serum. M1- and M2-type macrophages were generated from blood monocytes to investigate RBC phagocytosis. Results: No complement deposition was directly observed on stored RBCs, while incubation of RBCs with serum resulted in variable donor-dependent C3 deposition and IgG binding, both independent of storage time. Only 1-4% phagocytosis of stored RBCs by macrophages was observed. Conclusion: RBCs are susceptible to complement deposition and antibody binding independent of storage time. Limited phagocytic uptake by macrophages was observed in vitro.
Does Ramadan Fasting Affect Hydration Status and Kidney Function in CKD Patients?
Authors: Hassan Shadia , Hassan Fadi , Abbas Nur , Hassan Kamal , Khatib Nihal , Edgim Rabia , Fadol Rawia , Khazim Khaled
Published: March 2018

Background/Aims: This study is the first of its kind to examine the impact of the Ramadan fasting on hydration status, plasma brain natriuretic peptide (BNP) levels, and kidney function in chronic kidney disease (CKD) patient. Methods: This prospective cohort study included 2 groups of patients with CKD grades 2–4: thirty-one Muslim patients who fasted the month of Ramadan (fasting group) and 26 Muslim patients who did not fast (control group). One week before the Ramadan fast, in the last week of the month of Ramadan (4 weeks), and 4 weeks after the end of the Ramadan month (8 weeks), hydration status and blood analysis of urea, creatinine and BNP levels were measured. Results: Among fasting patients, serum urea levels increased significantly (p = 0.024) during the last week of fasting and returned to basal levels at 4 weeks after the end of the Ramadan month, the estimated glomerular filtration rate did not change significantly at the end of fasting (p = 0.411), the hydration status indices and plasma BNP levels were significantly decreased after fasting (p ≤ 0.021) but returned to basal values 4 weeks thereafter. Conclusions: Patients with CKD grades 2–4 can fast throughout the month of Ramadan with no significant deterioration of renal functions and with a reasonable degree of safety.
Dietary Docosahexaenoic Acid and Arachidonic Acid in Early Life: What Is the Best Evidence for Policymakers?
Authors: Forsyth Stewart , Calder Philip C. , Zotor Francis , Amuna Paul , Meyer Barbara , Holub Bruce
Published: March 2018

Background: A wealth of information on the functional roles of docosahexaenoic acid (DHA) and arachidonic acid (ARA) from cellular, animal, and human studies is available. Yet, there remains a lack of cohesion in policymaking for recommended dietary intakes of DHA and ARA in early life. This is predominantly driven by inconsistent findings from a relatively small number of randomised clinical trials (RCTs), which vary in design, methodology, and outcome measures, all of which were conducted in high-income countries. It is proposed that this selective evidence base may not fully represent the biological importance of DHA and ARA during early and later life and the aim of this paper is to consider a more inclusive and pragmatic approach to evidence assessment of DHA and ARA requirements in infants and young children, which will allow policymaking to reflect the marked diversity of need worldwide. Summary: Data from clinical RCTs is considered in the context of the extensive evidence from experimental, animal and human observational studies. Although the RCT data shows evidence of beneficial effects on visual function and in specific cognitive domains, early methodological approaches do not reflect current thinking and this undermines the strength of evidence. An outline of a framework for an inclusive and pragmatic approach to policy development on dietary DHA and ARA in early life is described. Conclusion: High-quality RCTs that will determine long-term health outcomes in appropriate real-world settings need to be undertaken. In the meantime, a collective pragmatic approach to evidence assessment, may allow public health policymakers to make comprehensive reasoned judgements on the merits, costs, and expediency of dietary DHA and ARA interventions.
From Treating Childhood Malnutrition to Public Health Nutrition
Authors: James W. Philip T.
Published: March 2018

Background: This analysis sets out an overview of an IUNS presentation of a European clinician’s assessment of the challenges of coping with immediate critical clinical problems and how to use metabolic and a mechanistic understanding of disease when developing nutritional policies. Summary: Critically ill malnourished children prove very sensitive to both mineral and general nutritional overload, but after careful metabolic control they can cope with a high-quality, energy-rich diet provided their initial lactase deficiency and intestinal atrophy are taken into account. Detailed intestinal perfusion studies also showed that gastroenteritis can be combatted by multiple frequent glucose/saline feeds, which has saved millions of lives. However, persisting pancreatic islet cell damage may explain our findings of pandemic rates of adult diabetes in Asia, the Middle East and Mexico and perhaps elsewhere including Africa and Latin America. These handicaps together with the magnitude of epigenetic changes emphasized the importance of a whole life course approach to nutritional policy making. Whole body calorimetric analyses of energy requirements allowed a complete revision of estimates for world food needs and detailed clinical experience showed the value of redefining stunting and wasting in childhood and the value of BMI for classifying appropriate adult weights, underweight and obesity. Lithium tracer studies of dietary salt sources should also dictate priorities in population salt-reduction strategies. Metabolic and clinical studies combined with meticulous measures of population dietary intakes now suggest the need for far more radical steps to lower the dietary goals for both free sugars and total dietary fat unencumbered by flawed cohort studies that neglect not only dietary errors but also the intrinsic inter-individual differences in metabolic responses to most nutrients. Key Messages: Detailed clinical and metabolic analyses of physiological responses combined with rigorous dietary and preferably biomarker of mechanistic pathways should underpin a new approach not only to clinical care but also to the development of more radical nutritional policies.
Elevated Plasma Haptoglobin Level as a Potential Marker for Poor Prognosis in Acute Cerebral Infarction
Authors: Zhang Tao , Xiang Lei
Published: March 2018

Background: Relationship between peripheral circulation concentration of haptoglobin (Hp) and risk of cerebrovascular disease has not been well investigated so far. The aim of the study was to reveal the prognostic significance of Hp on acute cerebral infarction. Methods: A total of 200 patients with acute cerebral infarction and 200 controls were included. Research data were collected from their medical records. Blood samples were obtained on admission. Hp phenotyping was performed using a native polyacrylamide gel electrophoresis. Plasma Hp levels were determined using enzyme-linked immunosorbent assays. The patients were followed up yearly, and endpoint was overall death. Results: Plasma levels of Hp were significantly elevated in the patients than in the controls (p < 0.001). Three-year overall death in the follow-up period was associated with the high plasma level of Hp (Hazard ratio [HR] 2.33, 95% CI 1.74–3.12). But, 3-year overall death was not related to Hp phenotyping (Hp 2–1 vs. 1–1: HR 1.07, 95% CI 0.66–1.73; Hp 2–2 vs. 1–1: HR 1.08, 95% CI 0.67–1.74). Conclusion: Peripheral circulation concentration of Hp might be an independent prognostic factor for acute cerebral infarction. But there was no relationship between Hp phenotyping and prognosis in this disease.
Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways
Authors: Li Xuelian , Wang GuoYuan , QiLi MuGe , Liang HaiHai , Li TianShi , E XiaoQiang , Feng Ying , Zhang Ying , Liu Xiao , Qian Ming , Xu BoZhi , Shen ZhiHang , Gitau Samuel Chege , Zhao DanDan , Shan HongLi
Published: March 2018

Background/Aims: Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload–induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. Methods: C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Results: Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Conclusions: Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways.
A coroa de Cristo x O beijo de Judas: "Batismo de sangue" e a denúncia da violência
Authors: Souza Táscia Oliveira , Noronha Jovita Maria Gerheim
Published: March 2018

Este artigo busca mostrar, com base na relação entre memória e testemunho, como Batismo de sangue, escrito por Frei Betto sobre o envolvimento de frades dominicanos brasileiros no caso Carlos Marighella, denuncia a violência da ditadura militar e se apresenta como peça de defesa, desconstruindo a narrativa oficial.
Memória do desaparecimento: a ditadura no romance "K. Relato de uma busca", de Bernardo Kucinski
Authors: Michael Joachim
Published: March 2018

O presente estudo mostra que o desaparecimento forçado se encontra no centro do debate literário contemporâneo da ditadura militar (1964-1985) no Brasil. K. Relato de uma busca de (2011) Bernardo Kucinski evidencia que o desaparecimento forçado não é um crime de Estado cuja gravidade possa ser descrita em termos quantitativos. Ao contrário, o livro demonstra que se trata de uma estratégia de extermínio que destrói não só a vítima mas também as pessoas a seu redor e que não se detém no tempo (passado). O romance expõe a destruição humana sem superá-la com a reconstrução daquilo que aconteceu. A memória aqui é a consciência da perda e da incerteza. Nesse sentido, o desaparecimento continua e a destruição também.
MicroRNA-21 Knockout Exacerbates Angiotensin II–Induced Thoracic Aortic Aneurysm and Dissection in Mice With Abnormal Transforming Growth Factor-β–SMAD3 Signaling
Authors: Huang Xiaofan , Yue Zhang , Wu Jia , Chen Jiuling , Wang Sihua , Wu Jie , Ren Linyun , Zhang Anchen , Deng Peng , Wang Ke , Wu Chuangyan , Ding Xiangchao , Ye Ping , Xia Jiahong
Published: March 2018

Objective—

Thoracic aortic aneurysm and dissection (TAAD) are severe vascular conditions. Dysfunctional transforming growth factor-β (TGF-β) signaling in vascular smooth muscle cells and elevated angiotensin II (AngII) levels are implicated in the development of TAAD. In this study, we investigated whether these 2 factors lead to TAAD in a mouse model and explored the possibility of using microRNA-21 (
miR-21
) for the treatment of TAAD.

Approach and Results—

TAAD was developed in
Smad3
(mothers against decapentaplegic homolog 3) heterozygous (S3
+/−
) mice infused with AngII. We found that p-ERK (phosphorylated extracellular regulated protein kinases)– and p-JNK (phosphorylated c-Jun N-terminal kinase)–associated
miR-21
was higher in TAAD lesions. We hypothesize that downregulation of
miR-21
mitigate TAAD formation. However,
Smad3
+/−
:miR-21
−/−
(S3
+/−
21
−/−
) mice exhibited conspicuous TAAD formation after AngII infusion. The vascular wall was dilated, and aortic rupture occurred within 23 days during AngII infusion. We then examined canonical and noncanonical TGF-β signaling and found that
miR-21
knockout in S3
+/−
mice increased SMAD7 and suppressed canonical TGF-β signaling. Vascular smooth muscle cells lacking TGF-β signals tended to switch from a contractile to a synthetic phenotype. The silencing of
Smad7
with lentivirus prevented AngII-induced TAAD formation in S3
+/−
21
−/−
mice.

Conclusions—

Our study demonstrated that
miR-21
knockout exacerbated AngII-induced TAAD formation in mice, which was associated with TGF-β signaling dysfunction. Therapeutic strategies targeting TAAD should consider unexpected side effects associated with alterations in TGF-β signaling.
The Nature of Schizophrenia: Signposts to Prevention
Authors: McGorry Patrick D.
Published: March 2018

Objective

To describe the characteristics of schizophrenia relevant to conducting indicated preventive interventions.

Method

A systematic review of the literature informed by experiences at the Personal Assistance and Crisis Evaluation (PACE) clinic.

Results

Primary prevention requires a sophisticated knowledge of key causal risk factors relevant to the expression of a disorder. The causal risk factors most useful from an intervention standpoint may turn out to be somewhat removed from the neurobiology of the disorder and may even be relatively non-specific, so that tackling them could reduce the risks for a range of mental disorders. The frontier for more specific prevention in schizophrenia and related psychosis is currently represented by indicated preventive interventions for subthreshold symptoms. Again, these may be relatively broad spectrum early in the prepsychotic phase but more proximal to onset, greater treatment specificity can be explored. However, this can be viewed more as preventively orientated treatment rather than primary prevention per se. Early detection of first episode psychosis and optimal intensive treatment of first episodes and the critical early years after diagnosis also represent increasingly attractive preventive foci in psychotic disorders.

Conclusion

As evidence accumulates, implementation of evidence-based practice in real work settings is a major challenge as it is throughout the mental health service system. The momentum of preventively orientated treatment must be maintained through the 2nd National Mental Health Strategy and in the face of recent misleading polemic regarding the treatability of psychotic disorders, especially schizophrenia. The evidence demonstrates that schizophrenia and related disorders have never been more treatable.
Should we Ignore Dimensional Risk Factors in Prevention of Schizophrenia? Signposts to Prevention
Authors: McConaghy Nathaniel
Published: March 2018

Objective

The objective was to outline the development of the concept of allusive thinking as a genetic marker of predisposition to schizophrenia and relate this to other cognitive markers of this predisposition.

Method

Publications were reviewed which were considered relevant to the objective.

Results

Allusive thinking as detected clinically could be measured objectively from subjects' performance on an Object Sorting Test. Using this test it was shown that parents, both of patients with schizophrenia and of university students with allusive thinking, themselves showed allusive thinking, indicating it was familially transmitted. Subjects with allusive thinking showed reduced cortical evoked brain P300 potentials, suggesting the transmission was genetic. The hypothesis that allusive thinking was associated with weaker cortical inhibitory processes was supported by the finding that subjects with such thinking chose more remote word associations. It was suggested that reasons allusive thinking has not been used as a marker in intervention studies is that as a dimension of abstract thinking, marked allusive thinking is not associated with a high risk of developing schizophrenia, and that administration of the Object Sorting Test is time-consuming. Other dimensional cognitive factors, such as psychoticism and perceptual anhedonia and aberration, are independent of allusive thinking and are also associated with a low risk of developing schizophrenia. Genetic transmission of schizophrenia would appear to involve a number of predisposing factors distributed dimensionally in the population with the contribution of each factor being small.

Conclusions

As they are associated with only a low risk of predisposition to schizophrenia, cognitive markers may not be of immediate value in the prevention of schizophrenia when compared with the less specific markers used for this purpose. However, it would seem that their study will be necessary if the nature of the genetic transmission of the illness is to be understood. This understanding could be expected to ultimately lead to more effective prevention.
Phenotypic Markers as Risk Factors in Schizophrenia: Neurocognitive Functions
Authors: Michie Patricia T. , Kent Aaron , Stienstra Renee , Castine Rochelle , Johnston Julie , Dedman Kellie , Wichmann Helen , Box Juliette , Rock Daniel , Rutherford Elizabeth , Jablensky Assen
Published: March 2018

Objective

To review the literature on neurocognitive measures as risk markers for schizophrenia and to present data from the Perth family study of schizophrenia. Of all the risk markers that have been identified, the most promising are deficits in sustained attention.

Method

Inclusion in the review was determined by whether the research addressed a number of key questions: methods of assessing sustained attention; evidence of sustained attention deficits in patients and first-degree relatives including children; the importance of attentional dysfunction in the schizophrenic process and functional outcome; and the biological basis of sustained attention deficits.

Results

Sustained attention deficits are evident in both patients and a proportion of their first-degree relatives, a finding replicated in preliminary data from the Perth family study. The literature suggests that the attention deficit is a stable enduring trait that is independent of clinical state. The neural basis of the deficit may be a functional disconnection between prefrontal and parietal cortex. Attention impairment is an important predictor of functional outcome in patients and the development of social dysfunction in adulthood in the at-risk offspring of patients. However, sustained attention deficits that are measured in childhood results in an unacceptable high false-positive rate (21%) when predicting which at-risk offspring of parents with schizophrenia will develop a schizophrenia spectrum disorder, although the overall classification accuracy (78%) is impressive.

Conclusions

The main findings are that sustained attention deficits are important risk markers for schizophrenia but need to be supplemented by other neurocognitive risk markers to improve predictive accuracy.
Neuromotor Markers of Risk for Schizophrenia
Authors: McNeil Thomas F. , Cantor-Graae Elizabeth
Published: March 2018

Objective

To evaluate the possibility of using neuromotor deviation (NMD) as an individual-orientated, early life marker for increased risk for schizophrenia.

Method

Previous findings based on systematic examination of NMD are summarised concerning schizophrenia patients and individuals at heightened genetic risk for schizophrenia.

Results

Significantly increased rates of NMD are found in patients with schizophrenia, both after and long before disease onset. Neuromotor deviation can be efficiently studied at all ages from infancy to adulthood, and is typically not in itself stigmatising. Neuromotor deviation may represent an unstable characteristic of individuals from infancy to middle-to-late childhood, possibly attaining greater stability thereafter. Neuromotor deviation may also be more stable over time in the high-risk offspring of parents with schizophrenia than in other children. Neuromotor deviation in childhood predicts subsequent serious mental disturbance in genetic high-risk children. The efficiency of NMD for predicting schizophrenia in unselected samples is unknown, as is the optimal age(s) for assessing NMD to predict schizophrenia in high-risk and normal-risk groups. Neuromotor deviation is also found in the well relatives of schizophrenia patients, individuals developing a broad range of mental and physical disorders, and mentally normal individuals in the general population.

Conclusions

Neuromotor deviation should definitely be included in batteries of methods for identifying individuals with notably heightened risk of schizophrenia. However, NMD is not pathognomonic for schizophrenia, and the investigation of NMD during childhood and adolescence must thus be used judiciously in order to avoid possible stigmatisation. Further research should be done concerning the specific forms and developmental timing of NMD as related to schizophrenia.