bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in High-Resolution Microscale Impedance Sensors
Authors: Carminati Marco
Published: March 2017

Sensors based on impedance transduction have been well consolidated in the industry for decades. Today, the downscaling of the size of sensing elements to micrometric and submicrometric dimensions is enabled by the diffusion of lithographic processes and fostered by the convergence of complementary disciplines such as microelectronics, photonics, biology, electrochemistry, and material science, all focusing on energy and information manipulation at the micro- and nanoscale. Although such a miniaturization trend is pivotal in supporting the pervasiveness of sensors (in the context of mass deployment paradigms such as smart city, home and body monitoring networks, and Internet of Things), it also presents new challenges for the detection electronics, reaching the zeptoFarad domain. In this tutorial review, a selection of examples is illustrated with the purpose of distilling key indications and guidelines for the design of high-resolution impedance readout circuits and sensors. The applications span from biological cells to inertial and ultrasonic MEMS sensors, environmental monitoring, and integrated photonics.
A Retrospective Study on Clinical Features and Visual Outcome of Patients Hospitalized for Ocular Trauma in Cangzhou, China
Authors: Zhang Xi , Liu Yuqing , Ji Xiangning , Zou Yuanyuan
Published: March 2017

Purpose. To describe clinical features and to analyze visual outcome of ocular trauma in Cangzhou in 2012–2015, China.Methods. A retrospective study of ocular trauma cases admitted to Cangzhou Central Hospital from January 2012 till December 2015 was performed.Results. This study included a total of 507 eyes from 478 patients. Four hundred (83.7%) patients were male, with a male-to-female ratio of 5.1 : 1. Mean age was43.6±18.3years (5–95 years). The largest age group was 45–59 years old, followed by 30–44 years old, presenting two peaks of the age distribution and accounting for 28.5% and 27.2%, respectively. The most frequent type of injuries was work-related (194, 40.6%) followed by home-related (123, 25.7%). Initial visual acuity (VA) correlated with final VA (Spearman’s test,r=0.703,p=0.001). The Ocular Trauma Score also correlated with the final VA significantly (Spearman’s test,r=0.802,p=0.001).Conclusions. Susceptible population of eye injuries were middle- and young-aged working groups, and the proportion of males was higher. The leading two types of ocular trauma were work-related and home-related. Initial VA was a significant predictor of the final VA and the OTS possibly had predictive value in the final VA.
Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline
Authors: Kang Yunxiao , Yan Wensheng , Fang Hui , Zhang Guoliang , Du Yakun , Wang Lei , Cui Huixian , Shi Geming
Published: March 2017

The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium‐pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2‐related factor 2‐ (Nrf2‐) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats. The transient activation of Nrf2 in SE rats was enhanced by Ptx pretreatment, which was followed by the upregulation of heme oxygenase‐1 and NAD(P)H:quinone oxidoreductase‐1. Ptx pretreatment to SE rats significantly suppressed the epileptic seizures, decreased the levels of lipid peroxide and malondialdehyde, and elevated the ratio of reduced glutathione/oxidized glutathione. Compared with intraperitoneal injection, intranasal Ptx delivery completely restored the visuospatial memory and the activity of mesodopaminergic system in SE rats. Intranasal administration of Ptx may hopefully become a noninvasive, painless, and easily administered option for epileptic patients.
Cholesterol Synthesis Increased in the MMI-Induced Subclinical Hypothyroidism Mice Model
Authors: Song Yongfeng , Zhang Xiujuan , Chen Wenbin , Gao Ling
Published: March 2017

Subclinical hypothyroidism (SCH) is defined as increased serum thyroid-stimulating hormone (TSH) concentrations and normal serum thyroid hormone (TH) levels as well as an increased serum cholesterol level, which is an important cause of secondary hypercholesterolemia and cardiovascular diseases. Some studies have demonstrated a direct effect of TSH on cholesterol metabolism via in vivo and in vitro experiments. However, because no suitable SCH model has been established until now, the changes in cholesterol synthesis that occur in SCH patients remain unknown. Here, we establish an SCH mouse model by using long-term low-dose MMI administered in drinking water. Compared with the control group, the MMI-treated mice had elevated circulating TSH levels, but the serum FT3 levels in these mice did not change. Additionally, the TC levels increased in both the serum and liver of the experimental mice. Both the protein expression and activity of hepatic HMGCR, the rate-limiting enzyme for cholesterol synthesis in the liver, increased in these mice. We also found that the SCH mice had decreased phospho-HMGCR and phospho-AMPK expression, while the expression of AMPK showed no change. In conclusion, we established a suitable SCH model in which cholesterol synthesis is increased.
A 10-Year Follow-Up of Two-Incision and Modified Watson-Jones Total Hip Arthroplasty in Patients with Osteonecrosis of the Femoral Head
Authors: Lin Shih-Jie , Huang Tsan-Wen , Lin Po-Chun , Kuo Feng-Chih , Peng Kuo-Ti , Huang Kuo-Chin , Lee Mel S.
Published: March 2017

Long-term data and information indicating whether minimally invasive surgery (MIS) approaches are safe and effective with total hip arthroplasty (THA) are lacking. Between 2004 and 2006, 75 patients with alcohol-related osteonecrosis of the femoral head (ONFH) who underwent 75 THAs with the two-incision approach were studied. The medical records, radiographic parameters, and functional outcomes were collected prospectively. All data were compared with those for matched patients who underwent a modified Watson-Jones (WJ) approach. THA using the two-incision approach was associated with longer operation time, more blood loss, more lateral femoral cutaneous nerve injury, and more periprosthetic femoral fractures (p<0.05for all four) than the modified WJ approach. The Harris Hip Score (HHS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) increased significantly from the period preoperatively to 6 weeks postoperatively and thereafter up to the last follow-up in both groups. However, there were no significant differences in terms of radiographic parameters and functional outcomes between the two groups throughout the study period. Both the two-incision and the modified WJ approach provided satisfactory results and survival rates at a mean follow-up of 10.8 years. A prospective, randomized, large-scale cohort study is still warranted for evidence-based recommendations.
Investigating the Temporal Effect of User Preferences with Application in Movie Recommendation
Authors: Li Wen-Jun , Dong Qiang , Fu Yan
Published: March 2017

As the rapid development of mobile Internet and smart devices, more and more online content providers begin to collect the preferences of their customers through various apps on mobile devices. These preferences could be largely reflected by the ratings on the online items with explicit scores. Both of positive and negative ratings are helpful for recommender systems to provide relevant items to a target user. Based on the empirical analysis of three real-world movie-rating data sets, we observe that users’ rating criterions change over time, and past positive and negative ratings have different influences on users’ future preferences. Given this, we propose a recommendation model on a session-based temporal graph, considering the difference of long- and short-term preferences, and the different temporal effect of positive and negative ratings. The extensive experiment results validate the significant accuracy improvement of our proposed model compared with the state-of-the-art methods.
Bacterial Isolates and Their Antimicrobial Susceptibility Patterns of Wound Infections among Inpatients and Outpatients Attending the University of Gondar Referral Hospital, Northwest Ethiopia
Authors: Mohammed Aynalem , Seid Mengistu Endris , Gebrecherkos Teklay , Tiruneh Moges , Moges Feleke
Published: March 2017

Background.The widespread uses of antibiotics, together with the length of time over which they have been available, have led to the emergence of resistant bacterial pathogens contributing to morbidity and mortality. This study was aimed to assess bacterial isolates and their drug susceptibility patterns from inpatients and outpatients with pus and/or wound discharge.Methods.A cross-sectional study was conducted at the University of Gondar Referral Hospital from March to May, 2014. Wound swab samples were collected from each study participant and inoculated into appropriate media. The bacterial pathogens were identified using standard microbiological methods. Antimicrobial susceptibility tests were performed using disk diffusion technique following Kirby-Bauer method.Results.A total of 137 study subjects were included in the study with bacterial isolation rate of 115 (83.9%). Of all, 81 (59.1%) were males. Seventy-seven (57%) of the isolates were Gram-negative and 59 (43%) were Gram-positive. From the total isolates,Staphylococcus aureuswas the most predominant isolate 39/115 (34%) followed by Klebsiella species (13%), coagulase negative staphylococci spp. (12%) andPseudomonas aeruginosa. Gram-positive isolates were resistant to ampicillin (86.4%), amoxicillin (83%), penicillin (81.3%), oxacillin (74.6%), and tetracycline (59.4%), while Gram-negative isolates were resistant to amoxicillin (97.4%), ampicillin (94.8%), tetracycline (72.7%), trimethoprim/sulfamethoxazole (66%), and chloramphenicol (54.5%).Conclusion. High prevalence of bacterial isolates was found,Staphylococcus aureusbeing the most dominant. High rates of multiple drug resistance pathogens to the commonly used antimicrobial agents were isolated. Therefore, concerned bodies should properly monitor the choice of antibiotics to be used as prophylaxis and empiric treatment in the study area.
Drip Loss Assessment by Different Analytical Methods and Their Relationships with Pork Quality Classification
Authors: Torres Filho Robledo de Almeida , Cazedey Henrique Pereira , Fontes Paulo Rogério , Ramos Alcinéia de Lemos Souza , Ramos Eduardo Mendes
Published: March 2017

We analyzed drip loss in pork by comparing the standard bag (DL), filter-paper wetness (FPW), and EZ-DripLoss methods by weighing the meat juice container and dabbed sample after 24 h and 48 h. Samples were classified into quality categories based on pH, color, and drip loss. The relationship between DL and FPW revealed the cut-off of 5% DL as corresponding to FPW of 139 mg; 1.89% when analyzed by weighing meat juice container or dabbed sample after 24 h; and 3.18% and 3.74% for those analyzed by weighing both meat juice container and dabbed sample after 48 h, respectively. Highest correlations were observed between DL and EZ when the meat juice container was weighed after 48 h (r=0.86). The EZ-DripLoss method in which the meat juice container was weighed after 24 h was able to distinguish drip loss into meat-quality categories in accordance with the bag method. Therefore, this method is recommended for meat categorization because of its greater standardization and ease of application.
In Vitro Study of Adsorption Kinetics of Dextromethorphan Syrup onto Activated Charcoal in Simulated Gastric and Intestinal Fluids
Authors: Regmi Shobha , Regmi Balmukunda , Shyaula Sajan Lal , Pathak Shiva , Bhattarai Bishnu Prasad , Sah Saroj Kumar
Published: March 2017

Adsorption kinetics of dextromethorphan (DXM) syrup in simulated gastric and intestinal fluids onto activated charcoal (AC) were investigated in an in vitro model. The adsorption studies were performed as a function of time, initial concentration, and temperature. The quantification of DXM adsorbed onto AC was obtained from the Langmuir adsorption isotherms using HPLC. The maximum adsorption capacities (at 95% confidence limits) of AC for DXM were 111.615 [106.38; 126.85] mg in simulated intestinal environment (pH 6.8) and 78.314 [86.206; 70.422] mg in simulated gastric environment (pH 1.2). The adsorption capacity of AC for DXM in simulated gastric fluid (pH 1.2) was not significantly different from the adoption capacity of AC for DXM in simulated intestinal fluid (pH 6.8). Moreover, the adsorption kinetics behavior of dextromethorphan onto AC followed pseudo-second-order kinetics. Our results show that AC in therapeutically acceptable doses can be beneficial in the majority of oral overdose of DXM.
Total Knee Arthroplasty in Severe Valgus Osteoarthritis Excellent Early Results in a 90-Year-Old Patient with a Valgus Deformity of 47°
Authors: Ismailidis Petros , Kernen Rolf , Mueller Sebastian Andreas
Published: March 2017

Grade III valgus deformity (tibiofemoral alignment > 20°) is present in only 0.5% of patients receiving total knee arthroplasty. Furthermore, cases with a valgus deformity exceeding 40° are even rarer. Since they mostly affect elderly, polymorbid patients, successful outcome means a great challenge. We report on a case of a 90-year-old patient with a valgus deformity of 47°. The patient was preoperatively restricted to a wheel chair, unable to walk, and only able to stand for a few seconds. The maximal knee flexion was 100°, and there was an extension deficit of 15°. The WOMAC score was 91; the EQ-5D-5L Index was 0.048. She was treated with a constrained hinged prosthesis. Postoperatively, the axis was 6° valgus. After 3 months of rehabilitation, she was independent using a wheeled walker. The maximal flexion of the knee was 110° and there was no extension deficit. The WOMAC score was 45; the EQ-5D-5L Index was 0.813. This case demonstrates the possibility of a satisfactory result and an improvement in quality of life and mobility with a plausible timetable and with reasonable use of resources even in advanced age and severe valgus deformity.
Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer
Authors: Cao Yue , Gang Xiaokun , Sun Chenglin , Wang Guixia
Published: March 2017

Mesenchymal stem cells (MSCs), an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU). Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs), compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation.
The Citrus Flavanone Naringenin Protects Myocardial Cells against Age‐Associated Damage
Authors: Da Pozzo Eleonora , Costa Barbara , Cavallini Chiara , Testai Lara , Martelli Alma , Calderone Vincenzo , Martini Claudia
Published: March 2017

In recent years, the health‐promoting effects of the citrus flavanone naringenin have been examined. The results have provided evidence for the modulation of some key mechanisms involved in cellular damage by this compound. In particular, naringenin has been revealed to have protective properties such as an antioxidant effect in cardiometabolic disorders. Very recently, beneficial effects of naringenin have been demonstrated in old rats. Because aging has been demonstrated to be directly related to the occurrence of cardiac disorders, in the present study, the ability of naringenin to prevent cardiac cell senescence was investigated. For this purpose, a cellular model of senescent myocardial cells was set up and evaluated using colorimetric, fluorimetric, and immunometric techniques. Relevant cellular senescence markers, such as X‐gal staining, cell cycle regulator levels, and the percentage of cell cycle‐arrested cells, were found to be reduced in the presence of naringenin. In addition, cardiac markers of aging‐induced damage, including radical oxidative species levels, mitochondrial metabolic activity, mitochondrial calcium buffer capacity, and estrogenic signaling functions, were also modulated by the compound. These results suggested that naringenin has antiaging effects on myocardial cells.
An Efficient Quality-Related Fault Diagnosis Method for Real-Time Multimode Industrial Process
Authors: Peng Kaixiang , Wang Bingzheng , Dong Jie
Published: March 2017

Focusing on quality-related complex industrial process performance monitoring, a novel multimode process monitoring method is proposed in this paper. Firstly, principal component space clustering is implemented under the guidance of quality variables. Through extraction of model tags, clustering information of original training data can be acquired. Secondly, according to multimode characteristics of process data, the monitoring model integrated Gaussian mixture model with total projection to latent structures is effective after building the covariance description form. The multimode total projection to latent structures (MTPLS) model is the foundation of problem solving about quality-related monitoring for multimode processes. Then, a comprehensive statistics index is defined which is based on the posterior probability of the monitored samples belonging to each Gaussian component in the Bayesian theory. After that, a combined index is constructed for process monitoring. Finally, motivated by the application of traditional contribution plot in fault diagnosis, a gradient contribution rate is applied for analyzing the variation of variable contribution rate along samples. Our method can ensure the implementation of online fault monitoring and diagnosis for multimode processes. Performances of the whole proposed scheme are verified in a real industrial, hot strip mill process (HSMP) compared with some existing methods.
Acute Colonic Pseudo-Obstruction with Feeding Intolerance in Critically Ill Patients: A Study according to Gut Wall Analysis
Authors: Zhao Chenyan , Xie Tingbin , Li Jun , Cheng Minhua , Shi Jialiang , Gao Tao , Xi Fengchan , Shen Juanhong , Cao Chun , Yu Wenkui
Published: March 2017

Objective. To compare the differences between acute colonic pseudo-obstruction (ACPO) with and without acute gut wall thickening.Methods. ACPO patients with feeding tolerance were divided into ACPO with no obvious gut wall thickening (ACPO-NT) group and ACPO with obvious acute gut wall thickening (ACPO-T) group according to computed tomography and abdominal radiographs. Patients’ condition, responses to supportive measures, pharmacologic therapy, endoscopic decompression, and surgeries and outcomes were compared.Results. Patients in ACPO-T group had a significantly higher APACHE II (11.82 versus 8.25,p=0.008) and SOFA scores (6.47 versus 3.54,p<0.001) and a significantly higher 28-day mortality (17.78% versus 4.16%,p=0.032) and longer intensive care unit stage (4 versus 16 d,p<0.001). Patients in ACPO-NT group were more likely to be responsive to supportive treatment (62.50% versus 24.44%,p<0.001), neostigmine (77.78% versus 17.64%,p<0.001), and colonoscopic decompression (75% versus 42.86%,p=0.318) than those in ACPO-T group. Of the patients who underwent ileostomy, 81.25% gained benefits.Conclusions. ACPO patients with gut wall thickening are more severe and are less likely to be responsive to nonsurgical treatment. Ileostomy may be a good option for ACPO patients with gut wall thickening who are irresponsive to nonsurgical treatment.
Impact of Delayed Admission to the Intensive Care Unit from the Emergency Department upon Sepsis Outcomes and Sepsis Protocol Compliance
Authors: Agustin Michael , Price Lori Lyn , Andoh-Duku Augustine , LaCamera Peter
Published: March 2017

Rationale. The impact of emergency department length of stay (EDLOS) upon sepsis outcomes needs clarification. We sought to better understand the relationship between EDLOS and both outcomes and protocol compliance in sepsis. Methods. We performed a retrospective observational study of septic patients admitted to the ICU from the ED between January 2012 and December 2015 in a single tertiary care teaching hospital. 287 patients with severe sepsis and septic shock were included. Study population was divided into patients with EDLOS < 6 hrs (early admission) versus ≥6 hours (delayed admission). We assessed the impact of EDLOS on hospital mortality, compliance with sepsis protocol, and resuscitation. Statistical significance was determined by chi-square test. Results. Of the 287 septic ED patients, 137 (47%) were admitted to the ICU in <6 hours. There was no significant in-hospital mortality difference between early and delayed admissions (p=0.68). Both groups have similar compliance with the 3-hour protocol (p=0.77). There was no significant difference in achieving optimal resuscitation within 12 hours (p=0.35). Conclusion. We found that clinical outcomes were not significantly different between early and delayed ICU admissions. Additionally, EDLOS did not impact compliance with the sepsis protocol with the exception of repeat lactate draw.
A Traffic Restriction Scheme for Enhancing Carpooling
Authors: Ding Dong , Shuai Bin
Published: March 2017

For the purpose of alleviating traffic congestion, this paper proposes a scheme to encourage travelers to carpool by traffic restriction. By a variational inequity we describe travelers’ mode (solo driving and carpooling) and route choice under user equilibrium principle in the context of fixed demand and detect the performance of a simple network with various restriction links, restriction proportions, and carpooling costs. Then the optimal traffic restriction scheme aiming at minimal total travel cost is designed through a bilevel program and applied to a Sioux Fall network example with genetic algorithm. According to various requirements, optimal restriction regions and proportions for restricted automobiles are captured. From the results it is found that traffic restriction scheme is possible to enhance carpooling and alleviate congestion. However, higher carpooling demand is not always helpful to the whole network. The topology of network, OD demand, and carpooling cost are included in the factors influencing the performance of the traffic system.
Malliavin Differentiability of Solutions of SPDEs with Lévy White Noise
Authors: Balan Raluca M. , Ndongo Cheikh B.
Published: March 2017

We consider a stochastic partial differential equation (SPDE) driven by a Lévy white noise, with Lipschitz multiplicative term σ. We prove that, under some conditions, this equation has a unique random field solution. These conditions are verified by the stochastic heat and wave equations. We introduce the basic elements of Malliavin calculus with respect to the compensated Poisson random measure associated with the Lévy white noise. If σ is affine, we prove that the solution is Malliavin differentiable and its Malliavin derivative satisfies a stochastic integral equation.
A Robust Method to Suppress Jamming for GNSS Array Antenna Based on Reconstruction of Sample Covariance Matrix
Authors: Gong Yanyun , Wang Ling , Yao Rugui , Zhang Zhaolin
Published: March 2017

The Global Navigation Satellite System (GNSS) receiver is vulnerable to active jamming, which results in imprecise positioning. Therefore, antijamming performance of the receiver is always the key to studies of satellite navigation system. In antijamming application of satellite navigation system, if active jamming is received from array antenna main-lobe, main-lobe distortion happens when the adaptive filtering algorithm forms main-lobe nulling. A robust method to suppress jamming for satellite navigation by reconstructing sample covariance matrix without main-lobe nulling is proposed in this paper. No nulling is formed while suppressing the main-lobe jamming, which avoids main-lobe direction distortion. Meanwhile, along with adaptive pattern control (APC), the adaptive pattern of array antenna approaches the pattern without jamming so as to receive the matching navigation signal. Theoretical analysis and numerical simulation prove that this method suppresses jamming without main-beam distortion. Furthermore, the output SINR will not decrease with the main-lobe distortion by this method, which improves the antijamming performance.
Comprehensive Histological and Immunochemical Forensic Studies in Deaths Occurring in Custody
Authors: Nugent Kenneth , Orellana-Barrios Menfil A. , Buscemi Dolores
Published: March 2017

In-custody deaths have several causes, and these include homicide, suicide, natural death from chronic diseases, and unexplained death possibly related to acute stress, asphyxia, excited delirium, and drug intoxication. In some instances, these deaths are attributed to undefined accidents and natural causes even though there is no obvious natural cause apparent after investigation. Understanding these deaths requires a comprehensive investigation, including documentation of circumstances surrounding the death, review of past medical history, drug and toxicology screens, and a forensic autopsy. These autopsies may not always clearly explain the death and reveal only nonspecific terminal events, such as pulmonary edema or cerebral edema. There are useful histologic and biochemical signatures which identify asphyxia, stress cardiomyopathy, and excited delirium. Identifying these causes of death requires semiquantitative morphologic and biochemical studies. We have reviewed recent Bureau of Justice Statistics on in-custody death, case series, and morphological and biochemical studies relevant to asphyxia, stress cardiomyopathy, and excited delirium and have summarized this information. We suggest that regional centers should manage the investigation of these deaths to provide more comprehensive studies and to enhance the expertise of forensic pathologists who would routinely manage potentially complex and difficult cases.
Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex
Authors: Palavra Filipe , Robalo Conceição , Reis Flávio
Published: March 2017

Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of benign, noninvasive, and tumor‐like lesions called hamartomas that can affect multiple organ systems and are responsible for the clinical features of the disease. In the majority of cases, TSC results from mutations in the TSC1 and TSC2 genes, leading to the overactivation of the mammalian target of rapamycin (mTOR) signalling pathway, which controls several cell functions, including cell growth, proliferation, and survival. The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC‐associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. However, the intrinsic characteristics of these drugs and their systemic effects in such a heterogeneous condition pose many challenges in clinical practice, so that some questions remain unanswered. This article provides an overview of the pharmacological aspects of mTOR inhibitors about the clinical trials leading to their approval in TSC‐related conditions and exposes current challenges and future directions associated with this promising therapeutic line.
Antibody–Drug Conjugates Bearing Pyrrolobenzodiazepine or Tubulysin Payloads Are Immunomodulatory and Synergize with Multiple Immunotherapies
Authors: Rios-Doria Jonathan , Harper Jay , Rothstein Raymond , Wetzel Leslie , Chesebrough Jon , Marrero Allison , Chen Cui , Strout Patrick , Mulgrew Kathy , McGlinchey Kelly , Fleming Ryan , Bezabeh Binyam , Meekin John , Stewart David , Kennedy Maureen , Martin Philip , Buchanan Andrew , Dimasi Nazzareno , Michelotti Emil , Hollingsworth Robert
Published: March 2017

Immunogenic cell death (ICD) is the process by which certain cytotoxic drugs induce apoptosis of tumor cells in a manner that stimulates the immune system. In this study, we investigated whether antibody–drug conjugates (ADCS) conjugated with pyrrolobenzodiazepine dimer (PBD) or tubulysin payloads induce ICD, modulate the immune microenvironment, and could combine with immuno-oncology drugs to enhance antitumor activity. We show that these payloads on their own induced an immune response that prevented the growth of tumors following subsequent tumor cell challenge. ADCs had greater antitumor activity in immunocompetent versus immunodeficient mice, demonstrating a contribution of the immune system to the antitumor activity of these ADCs. ADCs also induced immunologic memory. In the CT26 model, depletion of CD8+ T cells abrogated the activity of ADCs when used alone or in combination with a PD-L1 antibody, confirming a role for T cells in antitumor activity. Combinations of ADCs with immuno-oncology drugs, including PD-1 or PD-L1 antibodies, OX40 ligand, or GITR ligand fusion proteins, produced synergistic antitumor responses. Importantly, synergy was observed in some cases with suboptimal doses of ADCs, potentially providing an approach to achieve potent antitumor responses while minimizing ADC-induced toxicity. Immunophenotyping studies in different tumor models revealed broad immunomodulation of lymphoid and myeloid cells by ADC and ADC/immuno-oncology combinations. These results suggest that it may be possible to develop novel combinatorial therapies with PBD- and tubulysin-based ADC and immuno-oncology drugs that may increase clinical responses. Cancer Res; 77(10); 2686–98. ©2017 AACR.
Responsiveness of Brca1 and Trp53 Deficiency–Induced Mammary Preneoplasia to Selective Estrogen Modulators versus an Aromatase Inhibitor in Mus musculus
Authors: Alothman Sahar J. , Wang Weisheng , Goerlitz David S. , Islam Md , Zhong Xiaogang , Kishore Archana , Azhar Redha I. , Kallakury Bhaskar V. , Furth Priscilla A.
Published: March 2017

An intervention study initiated at age 4 months compared the impact of tamoxifen (25 mg), raloxifene (22.5 mg), and letrozole (2.5 mg) administered by 60-day release subcutaneous pellet on mammary preneoplasia prevalence at age 6 months in conditional genetically engineered mouse models with different Breast cancer 1 (Brca1) gene dosages targeted to mammary epithelial cells and germline Tumor protein P53 (Trp53) haploinsufficiency (10–16/cohort). The proportion of unexposed control mice demonstrating mammary preneoplasia at age 6 months was highest in Brca1fl11/fl11/Cre/p53−/+ (54%) mice followed by Brca1WT/fl11/Cre/p53−/+ mice (30%). By age 12 months, invasive mammary cancers appeared in 80% of Brca1fl11/fl11/Cre/p53−/+and 42% of Brca1WT/fl11/Cre/p53−/+control unexposed mice. The spectrum of cancer histology was similar in both models without somatic mutation of the nongenetically engineered Brca1, Trp53, Brca2, or Death-associated protein kinase 3 (Dapk3) alleles. Two-month exposure to tamoxifen, raloxifene, and letrozole significantly reduced estrogen-mediated tertiary branching by 65%, 71%, and 78%, respectively, in Brca1fl11/fl11/Cre/p53−/+mice at age 6 months. However, only letrozole significantly reduced hyperplastic alveolar nodules (HAN) prevalence (by 52%) and number (by 30%) and invasive cancer appeared despite tamoxifen exposure. In contrast, tamoxifen significantly reduced HAN number by 95% in Brca1WT/fl11/Cre/p53−/+ mice. Control mice with varying combinations of the different genetically modified alleles and MMTV-Cre transgene demonstrated that the combination of Brca1 insufficiency and Trp53 haploinsufficiency was required for appearance of preneoplasia and no individual genetic alteration confounded the response to tamoxifen. In summary, although specific antihormonal approaches showed effectiveness, with Brca1 gene dosage implicated as a possible modifying variable, more effective chemopreventive approaches for Brca1 mutation–induced cancer may require alternative and/or additional agents. Cancer Prev Res; 10(4); 244–54. ©2017 AACR.
Unemployment and the Division of Housework in Europe
Authors: van der Lippe Tanja , Treas Judith , Norbutas Lukas
Published: March 2017

Unemployment, especially in insecure times, has devastating effects on families, but it is not clear what happens to domestic work. On the one hand, unemployment frees up time for more housework by both men and women. On the other hand, once unemployed, women may take on more additional housework than men do, either because they capitalize on their time to act out traditional gender roles or because unemployment compounds women’s general disadvantage in household bargaining. Multi-level analyses based on the European Social Survey show that both men and women perform more housework when unemployed. However, the extra domestic work for unemployed women is greater than for unemployed men. They also spend more time on housework when their husband is unemployed. Compared to their employed counterparts, unemployed women, but not men, perform even more housework in a country where the unemployment rate is higher.
The UK EU referendum and the move towards Brexit
Authors: Raitio Juha , Raulus Helena
Published: March 2017

After the referendum in June 2016, both the EU and the UK were plunged into political turmoil. The withdrawal procedure must be triggered by the UK government, in accordance with the UK’s constitutional requirements. The judiciary has consequently faced questions whether the government could use the royal prerogative and the status of the devolved legislatures in the context of triggering Brexit. The Supreme Court confirmed that the UK government cannot trigger Article 50 TEU without an authorizing Act of Parliament. On the role of the devolved legislatures, the Supreme Court ruled that these do not have a veto on the UK’s decision to withdraw from the EU. The UK now needs to decide what it wants to achieve in the negotiations for its future relationship with the EU. In this article, a few models are explored. Although it currently seems that the UK government is leaning towards a ‘hard’ or ‘clean’ Brexit, a deeper analysis of the options reveals that there is no easy answer to the question of what the new EU–UK relationship will be like. The purpose of this article is to analyse the options available to the UK rather than to advocate any one particular model.
A high‐yield isolation and enrichment strategy for human lung microvascular endothelial cells
Authors: Gaskill Christa , Majka Susan M.
Published: March 2017

Vasculopathies, characterized by the formation of fragile and abnormal microvessels, are associated with the severity of many chronic lung diseases, including pulmonary fibrosis, emphysema/chronic obstructive pulmonary disease, systemic sclerosis, and hypertension. However, the study of human lung vasculature has been limited by the ability to isolate generous quantities of microvascular endothelial cells (MVEC) free from mesenchymal contamination. Expansion and passaging of primary human MVEC in vitro typically results in loss of a traditional phenotype in favor of an intermediate mesenchymal one, as early as passage five. Here we provide a detailed protocol for the selection of large quantities of enriched primary human lung MVEC based upon differential adherence from mesenchyme and simple magnetic separation, which decreases the need for excessive passaging, in order to obtain sufficient cell numbers to successfully freeze stock cultures. Additional protocols are provided for Ac‐di‐LDL selection, characterization, and a sandwich angiogenesis method of functional tube formation. The complete protocol including cell isolation and characterization takes approximately six weeks to complete.
Understanding Interpersonal Dysfunction in Borderline Personality Disorder
Authors: Miano Annemarie , Dziobek Isabel , Roepke Stefan
Published: March 2017

The core interpersonal dysfunction in borderline personality disorder (BPD) has not yet been conclusively explained. We used a naturalistic dyadic paradigm to test for the presence of functional empathic inaccuracy in BPD, which is a reduced understanding of the partner’s feelings in relationship-threatening situations. A total of 64 heterosexual couples ( N = 128) were videotaped while engaging in (a) neutral (favorite films), (b) personally threatening (personal fears), and (c) relationship-threatening (separation from partner) conversations. Females were either diagnosed with BPD or healthy controls. Empathic accuracy (EA) was measured from the recorded interactions. Healthy couples’ EA was lower during relationship-threatening compared with personally threatening situations. In contrast, women with BPD showed increased EA, relative to the controls, for relationship- versus personally threatening situations. Reduced EA in response to relationship-threatening situations is likely to be relationship protective. This mechanism appears to be defective in women with BPD, which might explain the interpersonal difficulties experienced by BPD individuals.
3‐D computer modelling of malunited posterior malleolar fractures: effect of fragment size and offset on ankle stability, contact pressure and pattern
Authors: Alonso‐Rasgado Teresa , Jimenez‐Cruz David , Karski Michael
Published: March 2017

Background

The positioning of the fracture fragment of a posterior malleolus fracture is critical to healing and a successful outcome as malunion of a posterior malleolar fracture, a condition seen in clinical practice, can affect the dynamics of the ankle joint, cause posterolateral rotational subluxation of the talus and ultimately lead to destruction of the joint. Current consensus is to employ anatomic reduction with internal fixation when the fragment size is larger than 25 to 33% of the tibial plafond.

Methods

A 3‐dimensional finite element (FE) model of ankle was developed in order to investigate the effect of fragment size (6–15 mm) and offset (1–4 mm) of a malunited posterior malleolus on tibiotalar joint contact area, pressure, motion of joint and ligament forces. Three positions of the joint were simulated; neutral position, 20° dorsiflexion and 30° plantarflexion.

Results

Compared to the intact joint our model predicted that contact area was greater in all malunion scenarios considered. In general, the joint contact area was affected more by section length than section offset. In addition fibula contact area played a role in all the malunion cases.

Conclusions

We found no evidence to support the current consensus of fixing posterior malleolus fractures of greater than 25% of the tibial plafond. Our model predicted joint instability only with the highest level of fracture in a loaded limb at an extreme position of dorsiflexion. No increase of peak contact pressure as a result of malunion was predicted but contact pattern was modified. The results of our study support the view that in cases of posterior malleolar fracture, posttraumatic osteoarthritis occurs as a result of load on areas of cartilage not used to loading rather than an increase in contact pressure. Ankle repositioning resulted in increased force in two ankle ligaments. Our finding could explain commonly reported clinical observations.
MacroH2A histone variants maintain nuclear organization and heterochromatin architecture
Authors: Douet Julien , Corujo David , Malinverni Roberto , Renauld Justine , Sansoni Viola , Posavec Marjanović Melanija , Cantariño Neus , Valero Vanesa , Mongelard Fabien , Bouvet Philippe , Imhof Axel , Thiry Marc , Buschbeck Marcus
Published: March 2017

Genetic loss-of-function studies on development, cancer and somatic cell reprogramming have suggested that the group of macroH2A histone variants might function through stabilizing the differentiated state by a yet unknown mechanism. Here, we present results demonstrating that macroH2A variants have a major function in maintaining nuclear organization and heterochromatin architecture. Specifically, we find that a substantial amount of macroH2A is associated with heterochromatic repeat sequences. We further identify macroH2A on sites of interstitial heterochromatin decorated by histone H3 trimethylated on K9 (H3K9me3). Loss of macroH2A leads to major defects in nuclear organization, including reduced nuclear circularity, disruption of nucleoli and a global loss of dense heterochromatin. Domains formed by DNA repeat sequences are disorganized, expanded and fragmented, and mildly re-expressed when depleted of macroH2A. At the molecular level, we find that macroH2A is required for the interaction of repeat sequences with the nucleostructural protein lamin B1. Taken together, our results argue that a major function of macroH2A histone variants is to link nucleosome composition to higher-order chromatin architecture.
Exertional Heat Injury: Effects of Adding Cold (4°C) Intravenous Saline to Prehospital Protocol
Authors: Mok Gordon , DeGroot David , Hathaway Nathanael E. , Bigley Daniel P. , McGuire Christopher S.
Published: March 2017

This article reviews current prehospital treatment for heat casualties and introduces a retrospective study on the addition of cold (4 °C) intravenous (IV) saline to prehospital treatment and its effect on morbidity. The study is a retrospective cohort reviewing electronic medical records of 290 heat casualties admitted to Martin Army Community Hospital, Ft. Benning, GA, comparing two treatment groups; U.S. Army Training and Doctrine Command (ice-sheeting and ambient temperature IV saline) versus Benning (ice-sheeting and cold IV saline). U.S. Army Training and Doctrine Command group significantly differed from Benning group on a number of measures, the median length of stay in the hospital was 3 and 2 d, respectively (P < 0.0001); pCr were 1.8 to 1.4 mg·dL−1, respectively (difference of 0.4 mg·dL−1 pCr, P < 0.0001). However, creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase were not significantly different across groups. Findings demonstrate that adding cold IV saline to ice-sheeting as a protocol reduces the length of hospitalization of heat casualties and lowers their peak creatinine values.
Zany Over Zika Virus: An Overview of Diagnosis and Treatment Modalities
Authors: Pyzocha Natasha J. , Chinchen Stephanie E. , Maurer Douglas M.
Published: March 2017

Zika virus has been a recent international public health concern with outbreaks occurring in the Americas, Caribbean, and Pacific. The zoonotic infection is primarily spread to humans by the bite of an infected Aedes mosquito. The virus also can be transmitted via bodily fluids, sexual intercourse, and maternal-fetal vertical transmission. Asymptomatic presentation is common. If symptoms do occur, individuals display a low-grade fever, maculopapular rash, arthralgia, or conjunctivitis 2 to 7 d after infection. Infection is concerning due to its associated fetal effects in pregnant women and relationship with Guillain-Barre syndrome. Diagnosis should be suspected in individuals with the appropriate symptomatology and exposure history. Diagnostic tests for the Zika virus are available and vary based on symptom duration. Treatment is supportive, and surveillance is suggested for all pregnant women. Prior infection is thought to provide immunity toward future exposures. Prevention and education is key in decreasing the spread of disease.
Ανάλυση περιεχομένου των σχολικών εγχειριδίων της Γλώσσας Δ΄ Δημοτικού σχετικά με την ανάδειξη των Δικαιωμάτων του Παιδιού και την ευαισθητοποίηση των μαθητών απέναντι σε αυτά
Authors: Στεφανοπούλου (Stefanopoulou) Σοφία (Sofia) Χρήστος , Τσατήρη (Tsatiri) Μαρία (Maria) Λουκάς , Κουμζής (Koumzis) Ιωάννης (Ioannis) Ευάγγελος
Published: March 2017

Η παρούσα εργασία πραγματεύεται την προβολή και ανάδειξη των Δικαιωμάτων του Παιδιού έχοντας ως οδηγό τα άρθρα της Διεθνούς Σύμβασης για τα Δικαιώματα του Παιδιού στα εν χρήσει σχολικά εγχειρίδια της Γλώσσας Δ΄ Δημοτικού. Σκοπός της έρευνας είναι να διερευνήσει την προβολή των Δικαιωμάτων του Παιδιού στα εν λόγω σχολικά βιβλία -συμπεριλαμβανομένου του βιβλίου για τον δάσκαλο- εστιάζοντας στην πληροφόρηση και ευαισθητοποίηση των μαθητών για τα κατοχυρωμένα δικαιώματά τους. Η μέθοδος που χρησιμοποιήθηκε είναι η ποσοτική ανάλυση περιεχομένου σε συνδυασμό με την ερμηνευτική προσέγγιση από τις μεθόδους ποιοτικής ανάλυσης περιεχομένου. Η ανάλυση αναδεικνύει ότι δεν προβάλλονται σε μεγάλο βαθμό όλα τα Δικαιώματα του Παιδιού στα υπό μελέτη σχολικά βιβλία. Ειδικότερα, 24 άρθρα από τα 54 που περιέχει η Διεθνής Σύμβαση για τα Δικαιώματα του Παιδιού δεν προβάλλονται καθόλου. Επιπλέον, διαπιστώθηκε ότι μόνο 6 άρθρα εμφανίζονται με μεγάλη συχνότητα σε σχέση με τα υπόλοιπα. Επιπροσθέτως, στο βιβλίο του δασκάλου βρέθηκε ότι αναδεικνύονται μόνο 12 από τα 54 άρθρα της Διεθνούς Σύμβασης για τα Δικαιώματα του Παιδιού. Ως συμπέρασμα προκύπτει τόσο η έλλειψη ενημέρωσης και ενεργοποίησης των μαθητών/ριών μέσα από την επίδραση που ασκούν τα εγχειρίδια στη συνειδητοποίηση των δικαιωμάτων τους όσο και η άνιση κατανομή της ανάδειξης των άρθρων της Διεθνούς Σύμβασης στα σχολικά εγχειρίδια. Τέλος, προτείνονται δραστηριότητες, που ενισχύουν την προβολή των Δικαιωμάτων του Παιδιού στα σχολικά εγχειρίδια της Γλώσσας Δ΄ Δημοτικού και ευαισθητοποιούν τους μαθητές και τις μαθήτριες σχετικά με αυτά.
Dr. Karol de Beaurain – a psychiatrist’s profile. Part 2
Authors: Rutkowski Krzysztof , Dembińska Edyta
Published: March 2017

Artykuł przypomina postać doktora Karola de Beaurain psychiatry, jednego z pierwszych Polaków leczących psychoanalizą, dotychczas znanego przede wszystkim z przeprowadzenia psychoanalizy Witkacego. Stanisław Ignacy Witkiewicz i Eugenia Dunin-Borkowska są pierwszymi znanymi z nazwisk pacjentami leczonymi psychoanalizą w historii polskiej medycyny. Źródło informacji dotyczących psychoanalizy Stanisława Ignacego Witkiewicza stanowiły jego listy oraz rysunki pochodzące z okresu analizy. Odtworzono losy dr Beaurian podczas I wojny światowej, najpierw jako lekarza wojskowego w Skoczowie, a następnie asystenta Klinice Neurologiczno-Psychiatrycznej prof. Piltza w Krakowie biorącego czynny udział w tworzeniu wielowymiarowego programu leczenia nerwic wojennych. Po zakończeniu wojny Beaurain początkowo pozostał asystentem Kliniki Psychiatrii w Krakowie. Jednak już w 1921 roku przeniósł się do Krajowego Zakładu Psychiatrycznego w Dziekance pod Poznaniem, wspomagając swoim doświadczeniem zawodowym wielkopolską psychiatrię, która po odejściu niemieckiego wykwalifikowanego personelu cierpiała na ogromnie niedobory kadrowe. Wzrastająca liczba pacjentów i przeciążenie obowiązkami zawodowymi najprawdopodobniej doprowadziły do przedwczesnej śmierci dr Karola de Beuarain w trakcie pełnienia funkcji ordynatora Krajowego Zakładu Psychiatrycznego w Owińskach w lutym 1927 roku.
Helping older people with a stoma recover with dignity
Authors: Burch Jennie
Published: March 2017

Nurses and care assistants must make dignity a priority when caring for residents with a stoma. In this article, Jennie Burch explores how understanding the physical recovery, emotional concerns and practical care of these residents can promote dignity in care