bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of culture in early interventions
Authors: Ventriglio Antonio , Bhugra Dinesh
Published: May 2019

Cultures play a major role in shaping people’s behaviours and attitudes. They also shape individuals’ social and cognitive development, and the idioms of distress they use and the pathways into care they take. In addition, cultures shape the causation, precipitation, and perpetuation of psychiatric symptoms which may not always fit neatly into diagnostic categories. Cultures define what is normal and what is abnormal or deviant. This, in turn, will influence how diseases are recognized and what early intervention strategies are put into place. For psychoses, the untreated duration of mental illness can last for years depending upon the resources available and the models of illness. The preclinical state is often a non-state and offers a critical threshold, and, according to resources, cultures will often dictate, in subtle ways, what the threshold is in order to develop psychiatric services. In many cultures—depending upon the available services and the personality of individuals, as well as the level of family support—a risk assessment may well contribute to stress and may also affect the likelihood of getting health or other insurance. It may also lead to personal difficulties, such as marriage problems. Clinicians need to remember that cultural differences in communication between doctors and patients may well contribute to tensions and poor therapeutic engagement if the patients’ or their carers’ views and explanatory models are not taken into account.
Early psychosis initiative in Japan
Authors: Mizuno Masafumi , Inoue Naomi , Nemoto Takahiro , Tsujino Naohisa , Katagiri Naoyuki , Funatogawa Tomoyuki
Published: May 2019

Psychiatric services in Japan have been dominantly hospital-based, and the largest task for psychiatry in Japan today remains the deinstitutionalization of patients, rather than early intervention. Individuals with mental health problems and their families are often reluctant to seek help for various reasons, including a lack of knowledge regarding the features and treatability of mental disorders. These obstacles may explain the long duration of untreated psychosis (DUP) and the social stigma of mental disorders in Japan. The concept of an at-risk mental state (ARMS)/prodromal state might not yet be widely recognized among Japanese psychiatrists. Competency in treating and diagnosing mild and moderate disorders should be integrated into training for the primary care specialty, and building the community-based network for early detection is the key strategy in Japan.
Early intervention in underage drinking
Authors: de Andrade Arthur Guerra , Siu Erica Rosanna , Dalbosco Carla , Diniz Gomes Telma Tiemi Schwindt , do Carmo Paulina , Duarte Arruda Vieira
Published: May 2019

The implementation of early interventions stands out as an interesting approach to reduce harmful use of alcohol by focusing on the early recognition, diagnosis, and treatment across the full trajectory of alcohol use before more severe consequences occur. This chapter provides a brief overview of the literature on early intervention in harmful use of alcohol in Brazil—the largest middle-income country in Latin America, where alcohol use represents a significant burden. Though the scenario is rather worrisome, advances have been made in the past years: more research has been developed and public policies have been carried out to reduce such a burden. Early interventions focused on young people (underage and college students) should be given primarily, with a particularly growing concern on girls. There is robust evidence that screening and brief interventions (SBIs) can, in the short term, reduce problems related to alcohol use, at lower costs than more intensive treatments worldwide. In Brazil, the barriers for its implementation in primary care services seem to be related to integration and intersectional healthcare settings, and to training of professionals, the latter of which could initially be tackled through distance-learning approaches. Further research is still necessary to develop and evaluate SBI approaches addressing vulnerable populations. Finally, the reduction of harmful alcohol-use related consequences requires the joint effort of civil society, government, and the private sector, with special engagement of public health and research institutes to consolidate evidence-based strategies and measures.
Cancer-related Breakthrough Pain
Authors: Davies Andrew
Published: May 2019

This volume contains chapters detailing strategies for the assessment, management, and treatment of breakthrough pain. The use of opioids for the treatment of breakthrough pain is thoroughly explored, with material covering oral, nasal, and other routes for opioid administration. Furthermore, the book includes chapters on non-opioid pharmacological treatments, as well as non-pharmacological interventions.
Intranasal and intrapulmonary opioids
Authors: Davies Andrew
Published: May 2019

The intranasal and intrapulmonary routes are simple, do not necessarily require any specialized equipment, and can be used by both patients and their non-professional caregivers. Intranasal administration may be associated with rapid onset of analgesia. A number of fentanyl-based formulations are commercially available to manage breakthrough cancer pain. Intranasal opioids can be delivered by traditional spray bottles, and also by syringes fitted with atomisers. The intrapulmonary route has the potential for rapid onset of analgesia. and can be delivered by traditional nebulizers, and other inhalation devices (e.g. metered dose inhalers, dry powder inhalers). The transdermal route has less potential for rapid onset of analgesia. However, new patch technology (iontophoretic technology) may alter the current position.
The nature of strong H i absorbers probed by cosmological simulations: satellite accretion and outflows
Authors: Rhodin N H P , Agertz O , Christensen L , Renaud F , Fynbo J P U
Published: May 2019

We use cosmological hydrodynamic zoom simulations to study the neutral gas distribution in and around galaxies that gives rise to high column density H i Ly α absorption (damped Ly α systems (DLAs) and sub-DLAs) in background quasar spectra. Such simulations often sacrifice numerical resolution for volume that affects the lower density galaxy halo gas, and simulations have difficulties reproducing the span of projected separations (b) between absorbing clouds and their hosts. Our simulations produce (sub-)DLAs over the entire probed parameter space ($b\lesssim 50\, \mathrm{kpc}$ and metallicity −4 ≲[M/H]≲ 0.5) at all redshifts (z ∼ 0.4 − 3.0), enclosing spectroscopically confirmed absorber-galaxy pairs. Recovering (sub-)DLAs at b ≳ 20 − 30 kpc from a massive host galaxy requires high numerical resolution and efficient feedback, and we show that these lines-of-sight are associated with dwarf satellites in the main halo, stripped metal-rich gas, and outflows. H i disc- and halo gas significantly contributes to (sub-)DLAs around galaxies. At large redshifts the halo plays an increasingly important role, while at 0.4 < z < 1 the disc and halo contribute with ∼60(80) and ∼40(20) per cent to column densities above the sub-DLA(DLA) lower limits. The distribution of b for sub-DLAs and DLAs overlap at z ∼ 2 − 3, but evolves so that sub-DLAs on average are located at twice larger b by z ∼ 0.5. A weak correlation suggests that sub-DLA covering fractions increase with stellar mass more rapidly than those of DLA. This can explain why sub-DLAs are preferentially selected in more massive galaxies in the low-z Universe.
Characterization of the stimulators of protein-directed ribosomal frameshifting in Theiler's murine encephalomyelitis virus
Authors: Napthine Sawsan , Bell Susanne , Hill Chris H , Brierley Ian , Firth Andrew E
Published: May 2019

Many viruses utilize programmed –1 ribosomal frameshifting (–1 PRF) to express additional proteins or to produce frameshift and non-frameshift protein products at a fixed stoichiometric ratio. PRF is also utilized in the expression of a small number of cellular genes. Frameshifting is typically stimulated by signals contained within the mRNA: a ‘slippery’ sequence and a 3′-adjacent RNA structure. Recently, we showed that −1 PRF in encephalomyocarditis virus (EMCV) is trans-activated by the viral 2A protein, leading to a temporal change in PRF efficiency from 0% to 70% during virus infection. Here we analyzed PRF in the related Theiler's murine encephalomyelitis virus (TMEV). We show that 2A is also required for PRF in TMEV and can stimulate PRF to levels as high as 58% in rabbit reticulocyte cell-free translations and 81% during virus infection. We also show that TMEV 2A trans-activates PRF on the EMCV signal but not vice versa. We present an extensive mutational analysis of the frameshift stimulators (mRNA signals and 2A protein) analysing activity in in vitro translation, electrophoretic mobility shift and in vitro ribosome pausing assays. We also investigate the PRF mRNA signal with RNA structure probing. Our results substantially extend previous characterization of protein-stimulated PRF.
Proteomic characterization of chromosomal common fragile site (CFS)-associated proteins uncovers ATRX as a regulator of CFS stability
Authors: Pladevall-Morera David , Munk Stephanie , Ingham Andreas , Garribba Lorenza , Albers Eliene , Liu Ying , Olsen Jesper V , Lopez-Contreras Andres J
Published: May 2019

Common fragile sites (CFSs) are conserved genomic regions prone to break under conditions of replication stress (RS). Thus, CFSs are hotspots for rearrangements in cancer and contribute to its chromosomal instability. Here, we have performed a global analysis of proteins that recruit to CFSs upon mild RS to identify novel players in CFS stability. To this end, we performed Chromatin Immunoprecipitation (ChIP) of FANCD2, a protein that localizes specifically to CFSs in G2/M, coupled to mass spectrometry to acquire a CFS interactome. Our strategy was validated by the enrichment of many known regulators of CFS maintenance, including Fanconi Anemia, DNA repair and replication proteins. Among the proteins identified with unknown functions at CFSs was the chromatin remodeler ATRX. Here we demonstrate that ATRX forms foci at a fraction of CFSs upon RS, and that ATRX depletion increases the occurrence of chromosomal breaks, a phenotype further exacerbated under mild RS conditions. Accordingly, ATRX depletion increases the number of 53BP1 bodies and micronuclei, overall indicating that ATRX is required for CFS stability. Overall, our study provides the first proteomic characterization of CFSs as a valuable resource for the identification of novel regulators of CFS stability.
Third Party Policing
Authors: Ransley Janet
Published: May 2019

The major premise of third party policing is that police on their own cannot succeed in reducing many crime and disorder problems. Instead, they need to draw on the social control mechanisms held by other government and community actors. Third party policing occurs when police leverage the powers or legal levers held by those other actors or partners to help control or reduce crime or disorder. The move for police to work through partners has accelerated due to trends in governance, the increasing scope of government regulation, and the expectation that communities will help co-produce public safety. At a time when many police agencies face budget restrictions, encouraging others to assume some crime control responsibility becomes especially important. These trends have expanded how crime can be regulated and prevented in ways that do not rest only on traditional criminal law or justice processes. Typical police partners include regulators, businesses, property owners, and schools. Legal levers include property or fire codes, liquor regulation, rental contracts, and school suspension or discipline powers. Police seek to activate or escalate their partners’ use of these non-criminal powers, either cooperatively or coercively, so as to extend the range of policing influence over problem places, people, or situations. Therefore, third party policing is both proactive, in that it is focused on addressing and reducing the causes of crime and disorder, and problem-oriented, in that it seeks to do so by analyzing and resolving recurrent, underlying problems. The focus on places, people, and situations also aligns with situational crime prevention techniques, such as hots spots policing and focused deterrence. But third party policing is differentiated from these other approaches through its reliance on the legal levers of partners. The first section in this entry outlines how third party policing has developed over the past twenty years. There are also sections on the role and use of regulation in policing, the contribution of civil remedies to crime prevention, descriptions of the multiple contexts in which third party policing has been adopted, factors that promote successful partnerships, assessments of outcomes and effectiveness, and issues to do with ethics and accountability.
Quilombos
Authors: Helena P. T. Machado Maria , dos S. Gomes Flávio , B. A. Ariza Marília
Published: May 2019

Between the 16th and 19th centuries, great numbers of men and women in the Americas escaped slavery by joining communities of fugitives. In Brazil, these communities were called mocambos, at first, and they were later referred to as quilombos, both of which were African terms that designated camps in several small societies in Central West Africa. It remains unclear to researchers what terms fugitives used to name themselves. As far as is known, the Portuguese colonial administration was responsible for disseminating the terms mocambos and quilombos. Colonial authorities moved around the Portuguese Empire and frequently took up posts in Africa and Asia prior to their arrival in South America. The term quilombo originally designated both Portuguese military strategies in precolonial Africa and forms of resistance to slavery in Portuguese America. Therefore, by using the term, colonial authorities could be referring to two different entities: war and prisoner camps in Central Africa or communities of runaway slaves in Brazil. Apart from that fact, several military officials who served in Africa had previous experiences in military campaigns against Dutch attacks in the 17th century in Portuguese America as well as in expeditions to dismantle mocambos and capture indigenous slaves. In any case, the term quilombo emerges only in the colony’s historical documentation by the end of the 17th century. Before that time, runaway communities were most commonly referred to by the name mocambos. Found in documents of colonial administration of the Captaincy of Bahia, the earliest reference to mocambos in Portuguese America dates from 1757. By the late 16th century, records point to the existence of Quilombo dos Palmares in the Captaincy of Pernambuco. Colonial authorities did not consider it completely destroyed until the beginning of the 18th century. Other large quilombos emerged during the 18th century in mining areas of Goiás, Mato Grosso, and Minas Gerais. Throughout the 19th century, quilombo communities proliferated in various locations: they could be found close to mining areas, plantations, or smaller farms; in vacant lands on economic frontiers and backlands inhabited by indigenous peoples; and in border areas such as those between Brazil and the Guianas. They also became part of urban landscapes, especially in the last decades of the 19th century. However, these communities were smaller, the modest dimensions of which enabled their longevity. Defined by specific cultural, social, and economic lifestyles and worldviews, quilombo communities survived post-abolition and they exist up to today.
Community Health Interventions
Authors: Galer-Unti Regina A. , Tappe Marlene
Published: May 2019

The term “community health intervention” refers to the community-wide approach to health behavior change. While there are shared terms and differences among community health interventions, community-based participatory research, and social epidemiology, they remain different approaches to improving community health. Rather than focusing primarily on the individual as change agent, community interventionists recognize a host of other factors that contribute to an individual’s capacity to achieve optimal health. This approach recommends that a multisectoral strategy be undertaken in order to make changes to create an environment or foundation of a healthy community. These modifications can be environmental, political, economic, and/or sociocultural. Community health interventions have deep roots in the theories of not only health behavior, but also in those of social change. Increasingly, this tactic of community intervention has been adopted by public health researchers and practitioners in many countries. This article provides a collection of articles, books, and monograms illustrative of the history and theoretical foundations of community health interventions. This article also provides examples of community health intervention in practice, strategies, and techniques for interventions and evaluation literature on the topic.
The Spiritual Conquest of Latin America
Authors: Tavárez David
Published: May 2019

The notion of a “spiritual conquest,” as opposed to a military conquest by Spanish forces and indigenous allies, was developed in detail in Robert Ricard’s eponymous 1933 work. While the metaphor of a “spiritual conquest” is broadly understood and used, many recent historical works eventually turned their attention to a close analysis of distinct processes and tendencies in terms of the methods, practices, and dynamics of colonial evangelization in Spanish and Portuguese America. The topical sections below address important work in this area of inquiry published in the last twenty-five years, with occasional references to earlier foundational works.
Knowledge Sharing and Collaboration within and across Firms
Authors: Kim Sang-Joon
Published: May 2019

Knowledge sharing is an interdependent process in which one gives something of value to the other and receives something of value from the other. It ranges from exploring new knowledge from outside to combining existing knowledge with others’ knowledge. Studies on knowledge sharing deal with the transfer of knowledge among social actors (whether individuals or organizations) or even among different fields. Capturing the activities on knowledge flow between social actors has also been widely studied in terms of knowledge transfer. In this sense, the terms of knowledge sharing and knowledge transfer have been used interchangeably. Yet, studies on knowledge sharing have focused on the activities that make knowledge accessible to various social actors. Accordingly, knowledge sharing includes a variety of social interactions between various social actors (within, between, and across organizations), and it doesn’t specify the direction of knowledge flow, including unidirectional, bidirectional, and multidirectional flow of knowledge. This implies that studies on knowledge sharing, as a combinatory term between an object (i.e., knowledge) and an action for it (i.e., sharing), revolve around which knowledge is shared or how a certain knowledge is shared. These two aspects of knowledge sharing can be further elaborated in terms of who takes the initiatives for this. That is, intraorganizational knowledge sharing (i.e., knowledge sharing between or among individuals within an organization) shows differentiated understandings from those of interorganizational knowledge sharing (i.e., knowledge sharing between organizations) or from those of population-level knowledge sharing (i.e., knowledge sharing across populations, industries, fields, or communities). Hence, we can further deepen our knowledge on knowledge sharing by specifying levels of analysis.
Krill spatial distribution in the Spanish Mediterranean Sea in summer time
Authors: Ventero Ana , Iglesias Magdalena , Córdoba Pilar
Published: May 2019

We documented krill distribution in the Spanish Mediterranean Sea for the first time using acoustic methods, highlighting the method’s suitability to study marine communities restricted to specific areas with patchy aggregation behavior. The 2009–2017 acoustic time series analysis revealed that krill distribution, mainly located on the continental shelf edge, was driven by the presence of fronts and submarine canyons. On the other hand, areas of persistent krill distribution included from Cape La Nao to the eastern part of Almeria Bay, although an interannual northwards increase of krill presence had been detected in 2015–2017 likely related to the position of the Balearic front. We provide information on the aggregation characteristics and biological parameters of three krill species, Nyctiphanes couchii, Nematoscelis megalops and Meganyctiphanes norvegica. N. couchii and N. megalops formed patchy pelagic aggregations in the neritic and oceanic zone, respectively, and they were the most common species in the net tows. By contrast, M. norvegica formed a large demersal aggregation on the continental shelf edge and was only found in 2017; nevertheless, its 861-kg catch represented a unique milestone in the Mediterranean. Finally, krill species shared distribution area with Maurolicus muelleri; thus, coexistence between them are also described.
Why Thomas Reid Matters to the Epistemology of the Social Sciences
Authors: Jaffro Laurent , Freitas Vinícius França
Published: May 2019

Little attention has been paid to the fact that Thomas Reid's epistemology applies to ‘political reasoning’ as well as to various operations of the mind. Reid was interested in identifying the ‘first principles’ of political science as he did with other domains of human knowledge. This raises the question of the extent to which the study of human action falls within the competence of ‘common sense’. Our aim is to reconstruct and assess Reid's epistemology of the sciences of social action and to determine how it connects with the fundamental tenets of his general epistemology. In the first part, we portray Reid as a methodological individualist and focus on the status of the first principles of political reasoning. The second part examines Reid's views on the explanatory power of the principles of human action. Finally, we draw a parallel between Reid's epistemology and the methodology of Weberian sociology.
Characterization and Pathogenicity of Pestalotiopsis-Like Species Associated With Gray Blight Disease on Camellia sinensis in Anhui Province, China
Authors: Wang Shuangshuang , Mi Xiaozeng , Wu Zhiran , Zhang Lixin , Wei Chaoling
Published: May 2019

Gray blight disease, caused by Pestalotiopsis-like fungi, is one of the deadliest threats to tea (Camellia sinensis) production. However, little information is known about the traits and characteristics of this pathogen. Here, a systematic survey was performed, and a total of 20 representative isolates were obtained from the leaves of tea plants affected by gray blight in two main tea plantations located in Anhui Province, China. Further analyses showed that two isolates were identified as Neopestalotiopsis ellipsospora, three isolates were regarded as Pseudopestalotiopsis chinensis, one isolate was considered as Pseudopestalotiopsis camelliae-sinensis, and the remaining isolates belonged to Pseudopestalotiopsis spp., on the basis of morphological characteristics and multigene phylogenetic analyses of the internal transcribed spacer, β-tubulin, and translation elongation factor 1-α. Pathogenicity tests indicated that there were significant differences in virulence among the Neopestalotiopsis and Pseudopestalotiopsis isolates when inoculated on the leaves of the tea plant (C. sinensis ‘Shuchazao’). Furthermore, varied pathogenicity was also observed for the same isolate when inoculated on different varieties of tea plants. To our knowledge, this is the first record of Neopestalotiopsis ellipsospora and Pseudopestalotiopsis chinensis causing gray blight disease of tea plants in China.
A Quantitative Synthesis of the Efficacy and Profitability of Conventional and Biological Fungicides for Botrytis Fruit Rot Management on Strawberry in Florida
Authors: Cordova Leandro G. , Dalla Lana Felipe , Paul Pierce A. , Peres Natalia A.
Published: May 2019

Botrytis fruit rot (BFR) is a major disease that affects strawberry production in Florida and worldwide. BFR management relies on frequent fungicide applications. A meta-analysis was conducted on the outcomes from nine field trials to evaluate the efficacy and profitability of conventional and biological fungicides compared with a nontreated control (NTC). All trials were conducted in Florida between the 2005/06 and 2016/17 growing seasons. Fungicide treatments were applied weekly, and plots were harvested twice a week for yield and BFR incidence quantification. Treatments were grouped into four categories: NTC, multisite only (Thiram), Standard (captan alternated with fludioxonil + cyprodinil), and Bacillus. Following primary analyses, a random effects network meta-analytical model was fitted to estimate the mean yield and BFR incidence responses for each treatment group and to compare means between pairs of groups. The Thiram and the Standard treatment groups increased yield by 378.8 and 502.2 kg/ha/week, respectively, compared with the NTC. The yield difference between Bacillus and NTC was not statistically significant. Besides increasing yield, Thiram and Standard also reduced BFR incidence by approximately 10% compared with the NTC. The mean yield responses and among-study variability from the meta-analysis were used to estimate the probability of a given yield response in a new future trial. The Standard and Thiram treatment groups showed higher estimated probabilities of increasing yield and resulting in a profitable return on application investments than the Bacillus group of treatments. The results from this study provide growers with information that will aid their decision-making process regarding BFR management.
Poverty and Excess Length of Hospital Stay in Neonatal Opioid Withdrawal Syndrome
Authors: Vesoulis Zachary A. , Lust Christopher E. , Cohlan Barbara A. , Liao Steve M. , Mathur Amit M.
Published: May 2019

Objectives:

To study the impact of sociodemographic factors on length of stay (LOS) for infants with neonatal opioid withdrawal syndrome (NOWS) secondary to fetal opioid exposure.

Methods:

In this retrospective cohort study, we included term infants with NOWS, excluding those with other significant medical issues. Comprehensive clinical and sociodemographic data were collected. Multivariate regression modeling was used to identify factors which contributed to excess LOS, which was defined as the number of days beyond the standard monitoring and/or treatment protocol.

Results:

In all, 129 infants were identified; mean gestational age of 37.9 ± 1.3 weeks and mean body weight of 2880 ± 496 g. Among them, 68% of infants were exposed to opioids; 27% were exposed to methadone; and 67% required pharmacologic treatment. The degree of poverty was assessed using the Area Deprivation Index (ADI) based on the mother's address at the time of birth. Median LOS for treated infants was 23 days versus 8 days for those who did not need pharmacologic treatment. The median excess LOS was 4 days (range 0–24).

Excess hospital days were strongly correlated with degree of deprivation in the mother's community (r = 0.55, P < 0.01). ADI remained a strong predictor of excess LOS, even when controlling for pharmacologic treatment, placement in state's custody, race, and gestational age at birth.

Conclusions:

These results suggest poverty is associated with excess LOS and that early allocation of resources for at-risk families may help to reduce overall length of hospital stay.
The role of epigenetics in paediatric rheumatic disease
Authors: Charras Amandine , Hedrich Christian M.
Published: May 2019

Purpose of review

Autoimmune/inflammatory disorders can be stratified along a spectrum based on the primary involvement of innate vs. adaptive mechanisms. Stratifying patients based on molecular mechanisms rather than clinical phenotypes may allow for target-directed and individualized treatment.

Recent findings

Epigenetic events are gene regulatory mechanisms that contribute to inflammation across inflammatory diseases and resemble shared mechanisms that may be used as disease biomarkers and treatment targets. Significant progress has been made dissecting the epigenome in paediatric rheumatic diseases and identifies associations with clinical phenotypes, treatment responses and disease outcomes. Here, we will summarize and discuss epigenetic patterns in autoimmune/inflammatory disorders, underlying molecular alterations and their effects on gene expression and immune phenotypes.

Structured investigation of epigenetic events, their causes and effects on immune phenotypes in autoimmune/inflammatory, will improve our understanding of disease, deliver new diagnostic tools and treatment options.
Exploring the potential carcinogenic role of arsenic in gallbladder cancer
Authors: Ganesan Nivetha , Bambino Kathryn , Boffetta Paolo , Labgaa Ismail
Published: May 2019

Gallbladder cancer (GBC) is an aggressive malignancy, associated with dismal outcomes. Although several risk factors including age, sex, and gallstones have been postulated, epidemiologic determinants of the disease remain largely uncovered. Moreover, the implication of environmental toxicants as possible risk factors is increasingly suspected. Arsenic (As), an established human carcinogen, is a natural contaminant of groundwater and has a geographic distribution similar to GBC incidence. This, combined with As metabolites being partially excreted in bile, raised the hypothesis that As may represent a carcinogenic hazard for the gallbladder. We conducted an analysis of the association between As concentration in groundwater and incidence rates of GBC worldwide in 52 countries. The USA, India, and Taiwan were selected on the basis of availability and quality of data for further investigation at a county-level. Relationships between As levels and GBC incidence were assessed using multivariable linear regression analyses. Analyses revealed significant associations between high As concentrations in groundwater and increased GBC incidences. Among women, correlations were observed worldwide (Spearman = 0.31, P = 0.028), in Taiwan (Spearman = 0.57, P = 0.005) and in India (R
2 = 0.23, P = 0.006). In men, a correlation was observed in India (R
2 = 0.26, P = 0.009) and a modest correlation was identified in the USA (Spearman = 0.14, P = 0.026). These results provide some support to the hypothesis of an association between high exposures to As-contaminated water on GBC, which appeared more prominent in women. Further observational and molecular studies, conducted at the individual level, are required to confirm this association and decipher its nature.
Prognostic Significance of Hematological Indices in Malignant Melanoma Treated With Immune Checkpoint Inhibitors
Authors: Afzal Muhammad Z. , Sarwar Tayyaba , Shirai Keisuke
Published: May 2019

Local and systemic inflammation significantly effects tumor progression and its response to therapy. We aim to evaluate the prognostic significance of inflammatory cells, their ratios, and a change in these indices while patients are receiving immune checkpoint inhibitors (ICIs). We retrospectively reviewed 120 malignant melanoma patients who had received any ICIs from 2011 until December 2017 and evaluated the effect of hematological indices on survival and radiographic responses. We followed the trends of these indices at 0, 6, and 12 weeks while on ICIs. Univariate and multivariate survival analyses were performed. The Student t tests and logistic regression were performed as well. Patients with neutrophil to lymphocyte ratio (NLR) <5 and derived neutrophil to lymphocyte ratio (dNLR) <3 had better overall survival and progression-free survival. The objective response rate was significantly higher in patients with absolute neutrophil count (ANC) <5 and dNLR<3 at baseline. Responder to ICIs had downtrending median ANC, NLR, dNLR, and an uptrending median lymphocyte to monocyte ratio compared with those of nonresponders. Moreover, in responders, the decrease in mean ANC, NLR, and dNLR were statistically significant compared with that of nonresponders at 6 and 12 weeks while on ICIs. Hematological indices can predict the response to ICIs and prognosis in malignant melanoma. Besides, the changes in these indices from their baseline values could be monitored in real-time to predict an earlier response even before a radiographic evaluation. However, the prospective and validation studies are needed before these models can be used in routine clinical practices.
Anthropometric Changes in a Prospective Study of 100 Patients Requesting Breast Reduction
Authors: Hudson Donald A. , Lelala Ngoato B.
Published: May 2019

Background:

The anthropomometry of the “ideal” breast is well described, but changes that occur with enlarged breasts are not. The aim of this study was to assess the prevalence of nipple asymmetry in the horizontal plane and changes in the inframammary fold (IMF) in patients presenting with macromastia (defined as excessive development of the mammary glands by Merriam-Webster dictionary).

Methods:

One hundred patients (200 breasts) presenting to the Plastic Surgery Clinic for bilateral breast reduction were enrolled in this study. Patients’ characteristics captured for this study included age, body mass index (BMI), and breast anthropometric measurements, such as suprasternal notch to nipple, nipple to IMF, IMF projected to cubital fossa, midhumeral point, and nipple measurement from meridian. Basic univariate statistical analyses were performed to evaluate the impact of nipple asymmetry.

Results:

The average age was 37 years (SD 12 years), and the median BMI was 33 (IQR 28–37). More patients presented with nipple asymmetry, of whom 45% were classified as lateral to the meridian, 19% were classified as medial to the meridian, and 36% were classified as central to the meridian. Patients with lateral asymmetry and medial asymmetry had a significantly higher BMI (median BMI 35) compared with patients with central positioning (median BMI 30). Increasing breast size was positively associated with nipple asymmetry, whereas BMI (R = −0.30, P = 0.003) and macromastia correlated negatively with IMF position (R = −0.38, P = 0.0001).

Conclusion:

In macromastia, nipple displacement from the breast meridian, especially lateral displacement, is common and is aggravated by an increase in BMI. The IMF also descends, and this is also more common in patients with a raised BMI. These changes have clinical implications.
Peripherally Inserted Central Catheters as Potential Risk Factors for Failure in Pedicled Latissimus Dorsi Flaps
Authors: Efanov Johnny Ionut , Bouhadana Gabriel , Danino Michel A.
Published: May 2019

Pedicled latissimus dorsi musculocutaneous flaps are reliable options for reconstruction of torso and head and neck defects. After ensuring that no kink or external compression occurs on the pedicle, the survival rate exceeds 99%. However, we experienced a complete necrosis of the flap after insertion of a peripherally inserted central catheter line. Intraoperative findings demonstrated thrombosis of the subclavian vein over a large segment, which was found to be the cause of flap failure. The clinical significance of this case report is aimed at raising awareness against insertion of peripherally inserted central catheter lines on the ipsilateral arm of a pedicled latissimus dorsi flap.
Lag Screw in Mandibular Plate Technique for Sagittal Splitting Mandibular Fractures
Authors: Reyad Khaled A , Al Mahmoudy Niveen F
Published: May 2019

Mandibular fractures with sagittal splitting and splaying of both the near and far cortices pose a challenge in their fixation as screws may push the far cortex during screw tightening, resulting in more widening. Screw lagging inside the lower mandibular plate technique may help approximation of the near and far cortices during screw tightening, and this was applied for 4 cases with mandibular fractures. The splaying improved using this technique. Using the screw lagging inside the plate technique may be a safe technique used in mandibular fractures that have cortical splaying.
Sensory profiles and immune-related expression patterns of patients with and without neuropathic pain after peripheral nerve lesion
Authors: Held Melissa , Karl Franziska , Vlckova Eva , Rajdova Aneta , Escolano-Lozano Fabiola , Stetter Christian , Bharti Richa , Förstner Konrad U. , Leinders Mathias , Dušek Ladislav , Birklein Frank , Bednarik Josef , Sommer Claudia , Üçeyler Nurcan
Published: May 2019

In this multicenter cross-sectional study, we determined sensory profiles of patients with (NL-1) and without neuropathic pain (NL-0) after nerve lesion and assessed immune-related systemic gene expression. Patients and matched healthy controls filled in questionnaires and underwent neurological examination, neurophysiological studies, quantitative sensory testing, and blood withdrawal. Neuropathic pain was present in 67/95 (71%) patients (NL-1). Tactile hyperalgesia was the most prominent clinical sign in NL-1 patients (P< 0.05). Questionnaires showed an association between neuropathic pain and the presence of depression, anxiety, and catastrophizing (P< 0.05 toP< 0.01). Neuropathic pain was frequently accompanied by other chronic pain (P< 0.05). Quantitative sensory testing showed ipsilateral signs of small and large fiber impairment compared to the respective contralateral side, with elevated thermal and mechanical detection thresholds (P< 0.001 toP< 0.05) and lowered pressure pain threshold (P< 0.05). Also, more loss of function was found in patients with NL-1 compared to NL-0. Pain intensity was associated with mechanical hyperalgesia (P< 0.05 toP< 0.01). However, quantitative sensory testing did not detect or predict neuropathic pain. Gene expression of peptidylglycine α-amidating monooxygenase was higher in NL patients compared with healthy controls (NL-1,P< 0.01; NL-0,P< 0.001). Also, gene expression of tumor necrosis factor-α was higher in NL-1 patients compared with NL-0 (P< 0.05), and interleukin-1ß was higher, but IL-10 was lower in NL-1 patients compared with healthy controls (P< 0.05 each). Our study reveals that nerve lesion presents with small and large nerve fiber dysfunction, which may contribute to the presence and intensity of neuropathic pain and which is associated with a systemic proinflammatory pattern.
Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: results from 2 randomized, placebo-controlled, phase 3 trials
Authors: Wild James , Yamada Tadaaki , Arjona Ferreira Juan Camilo , Hale Martin
Published: May 2019

Opioid-induced constipation (OIC) is a common side effect of chronic opioid therapy. Previously, naldemedine, a peripherally acting μ-opioid receptor antagonist demonstrated efficacy in the treatment of OIC. In this exploratory analysis, the onset of action of naldemedine was evaluated in 2 identically designed phase 3, randomized, placebo-controlled trials. Proportion of patients experiencing a spontaneous bowel movement (SBM) within 24 hours of treatment initiation, time from initial dose to first SBM and weekly SBM frequency were assessed. Naldemedine was associated with significant increases in the proportion of patients experiencing an SBM at 4, 8, 12, and 24 hours after the initial dose compared with placebo (all P < 0.0001). Within 24 hours in both studies, statistically significantly (P < 0.0001) more patients treated with naldemedine compared with placebo experienced an SBM (61.2% vs 28.3% and 56.5% vs 33.6%, respectively). Median times to first SBM were significantly shorter in the naldemedine group vs placebo (COMPOSE-1, 16.1 vs 46.7 hours; COMPOSE-2, 18.3 vs 45.9 hours; P < 0.0001). Naldemedine was also associated with significant increases in weekly SBM frequency vs placebo within 1 week (P < 0.001). Most common treatment-emergent adverse events were gastrointestinal-related (abdominal pain, diarrhea, and nausea). Treatment-emergent adverse events were reported most frequently on day 1, followed by a decrease from days 2 to 7. Naldemedine had a timely onset of effect, and gastrointestinal adverse events largely resolved within the first week. These findings should assist clinicians counseling patients with chronic noncancer pain on expectations when initiating naldemedine for OIC.
Elevated neutrophil gelatinase-associated lipocalin levels before contrast media administration among ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention
Authors: Rozenfeld Keren-Lee , Zahler David , Shtark Moshe , Goldiner Ilana , Keren Gad , Shacham Yacov
Published: May 2019

Background

Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released by renal tubular cells upon nephrotoxic or ischemic events and is considered an early marker of tubular damage. We aimed to demonstrate the presence of early renal injury detected by elevated NGAL levels taken before contrast administration in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI).

Patients and methods

We prospectively included 88 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (baseline NGAL; NGAL1) and 24 h after PCI (NGAL2). Abnormal elevations in NGAL levels were defined using the cardiac surgery associated NGAL score (NGAL score) with NGAL levels at least 100 ng/ml, suggesting renal tubular damage. Patients were also assessed for the dynamics between NGAL2 and NGAL1 levels.

Results

The mean age of the patients was 62 ± 13 years and 78% were men. A total of 50/88 (56%) patients had baseline NGAL level of at least 100, suggesting possible tubular damage before PCI. Only 10 patients progressed to clinical acute kidney injury during hospitalization, all of whom had baseline NGAL level of at least 100 (P < 0.001). Among patients with baseline NGAL at least 100, 28/50 (56%) showed a decrease in the NGAL level within 24 h, whereas only 9/50 (18%) showed an elevation in the NGAL level. In contrast, only 7/38 (19%) patients with baseline NGAL level less than 100 showed an elevation in NGAL levels within 24 h.

Conclusion

Elevated NGAL levels before primary PCI suggesting renal tubular damage are common among STEMI patients. Further trials are needed to assess the complex cardio–renal interactions.
CD4+CD25+Foxp3+ regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood
Authors: Geng Xu , Li Ming , Cui Bin , Lu Chao , Liu Xiaowen , Zhang Peng , Liu Bin , Ma Chunyan , Shen Yajuan , Lu Zhiming
Published: May 2019

Background:

Studies have shown that CD4+CD25+Foxp3+Treg cells suppress NKG2D expression on NK cells via a cell contact-dependent mechanism and increased TGF-β and IL-10 production in some cancer models. We herein aimed to explore whether CD4+CD25+Foxp3+Tregs suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood and elucidate the exact mechanism underlying this phenomenon.

Methods:

To explore the function of NKG2D, NK cell cultures were treated with an NKG2D-blocking antibody to block these receptors. Additionally, TGF-β- and IL-10-blocking antibodies were added to NK and CD4+CD25+Foxp3+Treg cell cocultures to evaluate whether the latter cells suppress NKG2D expression of NK cells via increasing the production of TGF-β and IL-10. The expression of NKG2D on NK cells was detected by 3-color flow cytometry, and NK cell activity was assessed by 3 assays: a nonradioactive cytotoxicity assay, an ELISA measuring IFN-γ production and a flow cytometry assay to evaluate CD107a expression.

Results:

Blocking NKG2D decreased NK cell cytotoxicity, IFN-γ production and CD107a expression. Moreover, blocking TGF-β and IL-10 substantially increased the NKG2D expression in NK and CD4+CD25+Foxp3+Treg cell cocultures. Similarly, blocking TGF-β and IL-10 enhanced NK cell cytotoxicity, IFN-γ production and CD107a expression; Transwell insert assays also revealed increased IFN-γ production and CD107a and NKG2D expression.

Conclusion:

CD4+CD25+Foxp3+Tregs suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood via a cell contact-dependent mechanism and increased TGF-β and IL-10 production.
Robot-assisted and laparoscopic vs open radical prostatectomy in clinically localized prostate cancer: perioperative, functional, and oncological outcomes
Authors: Cao Lan , Yang Zhenyu , Qi Lin , Chen Minfeng
Published: May 2019

Background:

To perform a systematic review and meta-analysis evaluating the perioperative, functional, and oncological outcomes and cost of robot-assisted radical prostatectomy (RARP), or laparoscopic radical prostatectomy (LRP) comparing with open radical prostatectomy (ORP) in men with clinically localized prostate cancer through all prospective comparative studies.

Methods:

A comprehensive literature search was performed in August 2018 using the Pubmed, Medline, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) and prospective studies including patients with clinically localized prostate cancer were eligible for study inclusion. Cumulative analysis was conducted using Review Manager v. 5.3 software.

Results:

Two RCTs and 9 prospective studies were included in this systematic review. There were no significant differences between RARP/LRP and ORP in overall complication rate, major complication rate, overall positive surgical margin (PSM) rate, ≤pT2 tumor PSM rate, ≥pT3 tumor PSM rate. Moreover, RARP/LRP and ORP showed similarity in biochemical recurrence (BCR) rate at 3, 12, 24 months postoperatively. Urinary continence and erectile function at 12 months postoperatively between RARP and ORP are also comparable. RARP/LRP were associated with significantly lower estimated blood loss [mean difference (MD) −749.67, 95% CI −1038.52 to −460.82, P = .001], lower transfusion rate (OR 0.17, 95% CI 0.10 to 0.30, P < .001) and less hospitalization duration (MD −1.18, 95% CI −2.18 to −0.19, P = .02). And RARP/LRP required more operative time (MD 50.02, 95% CI 6.50 to 93.55, P = .02) and cost.

Conclusion:

RARP/LRP is associated with lower blood loss, transfusion rate and less hospitalization duration. The available data were insufficient to prove the superiority of any surgical approach in terms of postoperative complications, functional and oncologic outcomes.
Decreased let-7b is associated with poor prognosis in glioma
Authors: Zhang Wanzeng , Zhao Wangmiao , Ge Chunyan , Li Xiaowei , Yang Xuehui , Xiang Yi , Sun Zhaosheng
Published: May 2019

Abnormal expression of let-7b has been observed in many tumors, including glioma. However, the clinical significance of let-7b in glioma remained unclear. The aim of the study was to explore the correlation of let-7b expression with clinicopathological factors and prognosis in human glioma.

Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to detect the relative expression of let-7b in glioma tissues. The association of let-7b expression with clinicopatholoigcal features of glioma patients was estimated using chi-square test. Overall survival curves were plotted using Kaplan–Meier method with log rank test. The prognosis analysis was performed using Cox regression model, and the results were shown as hazard ration (HR) with 95% confidence interval (CI).

The relative expression of let-7b was significantly lower in glioma tissues than that in normal brain tissues (P < .001). Furthermore, let-7b level was closely correlated with World Health Organization (WHO) grade (P = .027) and Karnofsky performance score (KPS) (P = .018). Survival analysis indicated that glioma patients with low let-7b expression had significantly shorter overall survival time than those with high expression (log rank test, P < .001). Let-7b might be an independent prognostic biomarker for glioma (P < .001, HR = 2.415; 95% CI: 1.531–3.808).

Let-7b may be a promising prognostic factor in glioma.