bluuebunny/crossref_metadata_2025 huggingface dataset:
Disconnected: a survey of users and nonusers of telehealth and their use of primary care
Authors: Liaw Winston R , Jetty Anuradha , Coffman Megan , Petterson Stephen , Moore Miranda A , Sridhar Gayathri , Gordon Aliza S , Stephenson Judith J , Adamson Wallace , Bazemore Andrew W
Published: December 2018

Objective

The study sought to assess awareness, perceptions, and value of telehealth in primary care from the perspective of patients.

Materials and Methods

We conducted a cross-sectional, Web-based survey of adults with access to telehealth services who visited healthcare providers for any of the 20 most-commonly seen diagnoses during telehealth visits. Three groups were studied: registered users (RUs) of telehealth had completed a LiveHealth Online (a health plan telehealth service provider) visit, registered nonusers (RNUs) registered for LiveHealth Online but had not conducted a visit, and nonregistered nonusers (NRNUs) completed neither step.

Results

Of 32 831 patients invited, 3219 (9.8%) responded and 766 met eligibility criteria and completed surveys: 390 (51%) RUs, 117 (15%) RNUs, and 259 (34%) NRNUs. RUs were least likely to have a primary care usual source of care (65.6% vs 78.6% for RNUs vs 80.0% for NRNUs; P < .001). Nearly half (46.8%) of RUs were unable to get an appointment with their doctor, and 34.8% indicated that their doctor’s office was closed. Among the 3 groups, RUs were most likely to be employed (89.5% vs 88.9% vs 82.2%; P = .007), have post–high school education (94.4% vs 93.2% vs 86.5%; P = .003), and live in urban areas (81.0% vs 69.2% vs 76.0%; P = .021).

Conclusions

Telehealth users reported that they relied on live video for enhanced access and were less connected to primary care than nonusers were. Telehealth may expand service access but risks further fragmentation of care and undermining of the primary care function absent better coordination and information sharing with usual sources of patients’ care.
The Gluten Free Diet: Assessing Adherence in a Pediatric Celiac Disease Population
Authors: Dowhaniuk Jenna K , Mileski Heather , Saab Joanne , Tutelman Perri , Thabane Lehana , Brill Herbert
Published: December 2018

Background

A strict, lifelong, gluten-free diet (GFD) remains the sole treatment for celiac disease (CD). The assessment of adherence to the GFD in pediatric studies is often based on self-report and visual analogue scales which lack proven validity. We sought to compare parental-report of GFD adherence to expert registered dietitian (RD) assessments, the best available standard.

Methods

Parents of children with biopsy-proven CD scored their adherence to the GFD on a five-point Likert scale similar to that used in previous pediatric CD studies. Each family was then evaluated by an RD expert in CD management who conducted a comprehensive and standardized assessment and scored the family’s adherence. The agreement between parents and the RD was assessed using paired t test and intraclass correlation coefficient (ICC) based on their scores.

Results

One hundred twenty-two children and their families participated in the study, with a median of 32 months on a GFD. Excellent adherence (score 5 out of 5) was attributed to 60.5% of the sample by the RD. The parents scored adherence higher than the RD by an average difference of 0.41 scale points (95% CI, 0.28–0.54; P < 0.001). The agreement between parents and the registered dietitian was poor (ICC = 0.21).

Conclusion

Reliance on self-report through Likert scales for GFD adherence overestimates adherence and misses opportunities for patient and family education. Approximately 40% of children with CD have ongoing gluten exposure, highlighting the need for regular assessment by an RD expert in the GFD to identify education and counselling needs for children with CD.
Tumor Variant Identification That Accounts for the Unique Molecular Landscape of Pediatric Malignancies
Authors: Lorentzian Amanda , Biegel Jaclyn A , Ostrow D Gigi , Rolf Nina , Liu Chi-Chao , Rassekh S Rod , Deyell Rebecca J , Triche Timothy , Schultz Kirk R , Rozmus Jacob , Reid Gregor S D , Lim C James , Lange Philipp F , Maxwell Christopher A
Published: November 2018

Precision oncology trials for pediatric cancers require rapid and accurate detection of genetic alterations. Tumor variant identification should interrogate the distinctive driver genes and more frequent copy number variants and gene fusions that are characteristics of pediatric tumors. Here, we evaluate tumor variant identification using whole genome sequencing (n = 12 samples) and two amplification-based next-generation sequencing assays (n = 28 samples), including one assay designed to rapidly assess common diagnostic, prognostic, and therapeutic biomarkers found in pediatric tumors. Variant identification by the three modalities was comparable when filtered for 151 pediatric driver genes. Across the 28 samples, the pediatric cancer-focused assay detected more tumor variants per sample (two-sided, P < .05), which improved the identification of potentially druggable events and matched pathway inhibitors. Overall, our data indicate that an assay designed to evaluate pediatric cancer-specific variants, including gene fusions, may improve the detection of target-agent pairs for precision oncology.
Investigating the Sleep–Pain Relationship in Youth with Sickle Cell Utilizing mHealth Technology
Authors: Valrie Cecelia R , Kilpatrick Rebecca L , Alston Kristen , Trout Krystal , Redding-Lallinger Rupa , Sisler India , Fuh Beng
Published: December 2018

Objectives

The current study utilized mHealth technologies that were objective (e.g., sleep actigraphy and pulse oximetry) and time-sensitive (e.g., ecological momentary assessments [EMAs]) to characterize sleep in youth with sickle cell disease (SCD) and investigate the relationships between sleep variables and pain. It also investigated the influence of age on sleep and the sleep–pain relationship.

Methods

Eighty-eight youth with SCD (aged 8–17 years) were recruited from three regional pediatric SCD clinics. Youth completed twice daily EMAs for up to 4 weeks to assess nighttime subjective sleep quality and daily pain. They also wore a sleep actigraph for 2 weeks to assess sleep duration, sleep efficiency, and sleep latency, and a wrist-worn pulse oximeter for two nights to assess whether they had sleep apnea. Multilevel models were calculated predicting daily SCD pain using the sleep variables, age, and the interaction between age and the sleep variables.

Results

None of the sleep variables were related to one another. Poor subjective sleep quality during the night was related to high pain severity the next day, and high pain was related to poor subjective sleep quality that night. Older age was associated with poorer subjective sleep quality, shorter duration of nighttime sleep, and high sleep latency. Also, findings indicated that as age increased, the strength of the relationship between poor continuous subjective sleep quality and high pain severity increased.

Conclusions

Future research is needed to examine possible mechanisms connecting subjective sleep quality to high pain.
Incidence and Outcome of Severe and Nonsevere Thrombocytopenia Associated With Zika Virus Infection—Puerto Rico, 2016
Authors: Van Dyne Elizabeth A , Neaterour Paige , Rivera Aidsa , Bello-Pagan Melissa , Adams Laura , Munoz-Jordan Jorge , Baez Priscilla , Garcia Myriam , Waterman Stephen H , Reyes Nimia , Richardson Lisa C , Rivera-Garcia Brenda , Sharp Tyler M
Published: December 2018

Background

Zika virus (ZIKV) infection has been associated with severe thrombocytopenia. We describe the incidence, clinical manifestations, and outcomes of patients with ZIKV infection and thrombocytopenia.

Methods

We reviewed medical records of patients with ZIKV infection and thrombocytopenia (platelet count <100 ×109 cells/L) in Puerto Rico during 2016. Severe thrombocytopenia was defined by platelet count <20 ×109/L or a platelet count <50 ×109/L and treatment for immune thrombocytopenia (ITP).

Results

Of 37 878 patients with ZIKV infection, 47 (0.1%) had thrombocytopenia in the absence of an alternative etiology (1.4 cases/100 000 population), including 12 with severe thrombocytopenia. Most patients with thrombocytopenia were adult (77%) and male (53%). Platelet nadir occurred a median (range) of 6 (1–16) and 5 (0–34) days after symptom onset for patients with severe and nonsevere thrombocytopenia, respectively. Among patients with severe thrombocytopenia, all had bleeding, 33% were admitted to the intensive care unit, and 8% died; 50% were treated for ITP. Among 5 patients with severe thrombocytopenia who received intravenous immunoglobulin, the median platelet count increase (range) was 112 (65–202) ×109/L. In contrast, among 4 patients who received platelet transfusion, the median increase in platelet count (range) was 8.5 (–6 to 52) ×109/L.

Conclusions

Patients with severe thrombocytopenia and ZIKV infection experienced prominent acute morbidity. Consistent with recommended management, administration of ITP treatments to such patients may be more efficacious than platelet transfusion in resolving thrombocytopenia. Severe thrombocytopenia should be considered a rare outcome of ZIKV infection.
INITIAL EVALUATION OF INDIVIDUAL DOSES IN THE EARLY PHASE OF A NUCLEAR REACTOR ACCIDENT BASED ON IN-VIVO MONITORING DATA AND SIMULATED RADIOLOGICAL CONSEQUENCES
Authors: Challeton-de Vathaire Cécile , Quentric Emmanuel , Didier Damien , Blanchardon Eric , Davesne Estelle , Rannou Alain , Agarande Michelle , Renaud-Salis Valérie , Franck Didier
Published: November 2018

In the early phase of a nuclear reactor accident, in-vivo monitoring of impacted population would be highly useful to detect potential contamination during the passage of the cloud and to estimate the dose from inhalation of measured radionuclides. However, it would be important to take into account other exposure components: (1) inhalation of unmeasured radionuclides and (2) external irradiation from the plume and from the radionuclides deposited on the soil. This article presents a methodology to calculate coefficients used to convert in-vivo measurement results directly into doses, not only from the measured radionuclides but from all sources of exposure according to model-based projected doses. This early interpretation of in-vivo measurements will provide an initial indication of individual exposure levels. As an illustration, the methodology is applied to two scenarios of accidents affecting a nuclear power plant: a loss-of-coolant accident leading to core meltdown and a steam generator tube rupture accident.
CAPABILITIES OF THE ARADOS-WG03 REGIONAL NETWORK FOR LARGE-SCALE RADIOLOGICAL AND NUCLEAR EMERGENCY SITUATIONS IN ASIA
Authors: Jang S , Suto Y , Liu J , Liu Q , Zuo Y , Duy P N , Miura T , Abe Y , Hamasaki K , Suzuki K , Kodama S
Published: December 2018

In 2015, the Asian Radiation Dosimetry Group established a regional network of biological dosimetry laboratories known as the ARADOS-WG03 (Working Group 03; Biological Dosimetry). A survey was conducted in 2017 to evaluate the capabilities and capacities of the participating laboratories for emergency preparedness and responses in large-scale nuclear and/or radiological incidents. The results of this survey were identified and assessed. The data provide important information on the current state of emergency cytogenetic biological dosimetry capabilities in the Asian region.
Potent Dopamine D2 Antagonists Block the Reward-Enhancing Effects of Nicotine in Smokers With Schizophrenia
Authors: Whitton Alexis E , Green Alan I , Pizzagalli Diego A , Roth Robert M , Williams Jill M , Brunette Mary F
Published: December 2018

Antipsychotics that are potent dopamine (DA) D2 receptor antagonists have been linked to elevated levels of nicotine dependence in smokers with schizophrenia. Because activation of D2 receptors mediates motivation for nicotine, we examined whether potent D2 antagonists would diminish nicotine’s ability to stimulate reward processing—a mechanism that may drive compensatory increases in smoking. Smokers with schizophrenia (n = 184) were recruited and stratified into medication groups based on D2 receptor antagonist potency. The effects of smoking on reward function were assessed using a probabilistic reward task (PRT), administered pre- and post-smoking. The PRT used an asymmetrical reinforcement schedule to produce a behavioral response bias, previously found to increase under conditions (including smoking) that enhance mesolimbic DA signaling. Among the 98 participants with valid PRT data and pharmacotherapy that could be stratified into D2 receptor antagonism potency, a medication × smoking × block interaction emerged (P = .005). Post-hoc tests revealed a smoking × block interaction only for those not taking potent D2 antagonists (P = .007). This group exhibited smoking-related increases in response bias (P < .001) that were absent in those taking potent D2 antagonists (P > .05). Our findings suggest that potent D2 antagonists diminish the reward-enhancing effects of nicotine in smokers with schizophrenia. This may be a mechanism implicated in the increased rate of smoking often observed in patients prescribed these medications. These findings have important clinical implications for the treatment of nicotine dependence in schizophrenia.
Dynamic Insertion of Pot3 in AvrPib Prevailing in a Field Rice Blast Population in the Philippines Led to the High Virulence Frequency Against the Resistance Gene Pib in Rice
Authors: Olukayode Toluwase , Quime Berlaine , Shen Yin-Chi , Yanoria Mary Jeannie , Zhang Suobing , Yang Jianyuan , Zhu Xiaoyuan , Shen Wei-Chiang , von Tiedemann Andreas , Zhou Bo
Published: December 2018

The Magnaporthe oryzae avirulence gene AvrPib is required for the resistance mediated by its cognate resistance gene Pib, which has been intensively used in indica rice breeding programs in many Asian countries. However, the sequence diversity of AvrPib among geographically distinct M. oryzae populations was recently shown to be increasing. Here, we selected a field population consisting of 248 rice blast isolates collected from a disease hotspot in Philippine for the analysis of AvrPib haplotypes and their pathogenicity against Pib. We found that all of the isolates were virulent to Pib and each of them contained an insertion of Pot3 transposon in AvrPib. Moreover, Pot3 insertion was detected in different genomic positions, resulting in three different AvrPib haplotypes, designated avrPib-H1 to H3. We further conducted a genome-wide Pot2 fingerprinting analysis by repetitive element palindromic polymerase chain reaction (PCR) and identified seven different lineages out of 47 representative isolates. The isolates belonging to the same lineage often had the same AvrPib haplotype. In contrast, the isolates having the same AvrPib haplotypes did not always belong to the same lineages. Both mating types MAT1-1 and MAT1-2 were identified in the population in Bohol and the latter appeared dominant. On the host side, we found that 32 of 52 released rice varieties in the Philippines contained Pib diagnosed by PCR gene-specific primers and DNA sequencing of gene amplicons, suggesting that it was widely incorporated in different rice varieties. Our study highlights the genetic dynamics of rice blast population at both the AvrPib locus and the genome-wide levels, providing insight into the mechanisms of the mutations in AvrPib leading to the breakdown of Pib-mediated resistance in rice.
Genetic evaluation of disorders of sex development: current practice and novel gene discovery
Authors: Kremen Jessica , Chan Yee-Ming
Published: November 2018

Purpose of review

As the pace of genetic discovery accelerates, genetic sequencing is increasingly applied to rare disease such as DSD (differences or disorders of sex development,) which has led to an increase in the number of novel variant-containing candidate genes identified. In this review, we will discuss several candidate genes which have recently been proposed as causative of DSD, as well as novel work in understanding gene regulation in the mouse gonad that may have implications for the DSD phenotype in humans.

Recent findings

We performed a comprehensive search of PubMed through August 2018 to identify relevant peer-reviewed publications from 2017 to 2018 on DSD genetics.

Seminal work has identified a critical gonadal enhancer of Sox9 in a mouse model. This enhancer is located in a region which had previously been implicated in both XX and XY DSD, though the specific enhancer and its role in Sox9 gene expression had not been defined. Novel candidate genes in XY gonadal dysgenesis (SOX8, ESR2) and XX ovotesticular DSD (NR2F2) have been described.
Short article: Sequence variations of PKHD1 underlie congenital hepatic fibrosis in a Chinese family
Authors: Yang Ni , Leng Yunji , Dai Shundong , Chen Chen , Liu Chunfeng , Cao Lihua
Published: November 2018

Objective

Congenital hepatic fibrosis (CHF) is a developmental disorder of the portobiliary system characterized by hepatic fibrosis, portal hypertension, and renal cystic disease. The aim of our study was to identify the disease-causing gene of a Chinese family with CHF.

Patients and methods

Whole-exome sequencing was performed in the family with CHF and variants were confirmed by Sanger sequencing. Online bioinformatics tools were used to evaluate the pathogenicity of the missense variants. Liver specimens were reviewed to confirm the histopathological diagnosis.

Results

The compound heterozygous variants c.7994T>C, p.(Leu2665Pro) and c.8518C>T, p.(Arg2840Cys) in PKHD1 were identified in a Chinese family with CHF by whole-exome sequencing. Liver histomorphology was reviewed to confirm the diagnosis of CHF.

Conclusion

We have identified variations in PKHD1 in a Chinese family with CHF. Our study extends the mutation spectrum of CHF and provides information for genetic counseling of patients’ family members.
Advances in Anti-GD2 Immunotherapy for Treatment of High-risk Neuroblastoma
Authors: Voeller Julie , Sondel Paul M.
Published: November 2018

Neuroblastoma (NBL) is the most common extracranial solid tumor in pediatrics, yet overall survival is poor for high-risk cases. Immunotherapy regimens using a tumor-selective antidisialoganglioside (anti-GD2) monoclonal antibody (mAb) have been studied for several decades now, but have only recently been incorporated into standard of care treatment for patients with high-risk NBL with clear benefit. Here we review a brief history of anti-GD2-based immunotherapy, current areas of neuroblastoma research targeting GD2, and potential diagnostic and therapeutic uses targeting GD2.
Using Immunohistochemistry Without Linkers to Determine the Optimum Concentrations of Primary Antibodies for Immunofluorescence Staining of Formalin-fixed Paraffin-embedded Tissue Sections
Authors: Lugos Moses D. , Davou Gwom I. , Choji Tobias P.P. , Jugu Kizito P. , Ashi Robert R. , Oyero Steve K. , Perikala Venkateswarlu
Published: November 2018

The use of immunofluorescence (IF) technique to detect and evaluate expression levels and localization of cellular proteins and other antigens of interest through the antibodies in their cellular or tissue context has become a standard approach among researchers. Optimizing primary antibody concentrations/dilutions is an essential step in the fluorescent antibody staining protocol. The steps in IF staining are similar to those of the immunohistochemistry (IHC) technique. The use of IHC technique to determine the optimal working dilutions of primary antibodies for IF staining of formalin-fixed paraffin-embedded (FFPE) tissues sections can minimize time wasting and cumbersome approach of using direct IF single labeling using variable dilutions of both primary and secondary antibodies. We used IHC staining technique to determine the working dilutions of the respective primary antibodies by staining 3-µm sections of recommended positive FFPE tissue sections using 3 different dilutions of the primary antibodies and an isotype control (used at the highest concentration). Digital images of sections stained were reviewed in ImageScope by a Consultant Pathologist for positivity, intensity, and histologic distribution. We adopted the IHC predetermined optimal dilutions of primary antibodies to CD4, CD8, CD16, CD21, CD56, CD68, CD163, FOXP3, and PD1 to carry out IF staining of FFPE tissue sections. This approach has helped to remove the complexities associated with grappling with 2 unknown to optimize for both the primary and secondary antibodies using IF technique.
Papillary Renal Cell Carcinoma (PRCC): An Update
Authors: Akhtar Mohammed , Al-Bozom Issam A. , Al Hussain Turki
Published: November 2018

Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma. Papillary renal cell carcinoma is usually divided histologically into 2 types namely, type 1 and type 2. This classification, however, is unsatisfactory as many of papillary carcinoma are unclassifiable by the existing criteria. In recent years there has been a remarkable progress in our understanding of the molecular basis of PRCC. These studies have revealed that type 2 PRCCs represent a heterogenous group which may be subdivided into additional subtypes based on the genetic and molecular make up of these tumors and reflecting different clinical course and prognosis. Some of the molecular features such a hypermethylation of CPG islands in the promotor regions of genes and over expression of the antioxidant pathways within tumor cells have been recognized as markers of poor prognosis. Targeted therapies for papillary carcinoma in the past have been unsuccessful because of lack of clear understanding of the molecular basis of these tumors. It is hoped that recent progress in our understanding of the pathogenesis of various subtypes of PRCC, effective targeted therapies will eventually emerge in due course.
Diaper Use Increases the Risk of Buttock and Perineal Abscesses
Authors: Pappano Dante , Radu Heather , Sexton Michelle
Published: November 2018

Objectives

Over the last decade, there has been a notable increase in the incidence of abscesses. Children in the diaper-wearing age group are disproportionately affected, and most of these abscesses occur in the buttock and perineal region. Using case-control methodology, we sought to determine if diaper use itself is an independent risk factor for abscess formation.

Methods

Cases were patients, at least 2 years of age but less than 4 years, who presented to the emergency department with a complaint of a buttock or perineal abscess. Age-matched controls presented to the emergency department for unrelated reasons. Caregivers of subjects responded to a survey regarding diaper use (toilet trained, for sleep only, or all day), type and brand of diaper, and diaper hygiene-related factors.

Results

We enrolled 465 patients (93 cases, 372 controls). Fully toilet trained children were less likely to have buttock and perineal abscess than their sleep-only and all-day diaper-wearing peers. Limiting diaper use to naptime and overnights (sleep only) did not confer protection against abscesses. Diaper hygiene–related factors did not affect the risk of abscess formation. Female sex was also identified as a strong risk factor for buttock and perineal abscess formation.

Conclusions

Diaper use is a potentially modifiable risk factor for buttock and perineal abscess formation in young children.
A Lodged Barramundi Fish-Bone Stabbing the Piriform Fossa in a Child
Authors: Goldman Ran D. , Gurberg Joshua , Paul Moxham J.
Published: November 2018

Unintentional ingestion of a fish bone is common in children, especially among families with high consumption of seafood. Complications in children are extremely rare. We describe a 3-year-old healthy boy who had a large bone of Barramundi fish lodged in his upper esophagus causing significant distress. Soft tissue neck radiograph revealed a mildly thickened epiglottis and bulbous and hypertrophied adenoid soft tissue. A 21-mm foreign body was noticed. A flexible fiberoptic laryngoscopy revealed a large fish bone emerging from the left piriform fossa and arcing over the left arytenoid to hover over the posterior glottis. The bone was removed during anesthesia induction before a rigid esophagoscopy. The fish-bone entry point was seen stabbing through the edge of the piriform fossa and running down alongside the esophagus, without causing a through and through perforation. Fish bone ingestion can cause significant complications including perforation of the esophagus. Early suspicion of ingestion, radiological investigation, and swift management are important to ensure reduced complication rate in children.
An Update on End-Tidal CO2 Monitoring
Authors: Selby Samuel T. , Abramo Thomas , Hobart-Porter Nicholas
Published: November 2018

End-tidal CO2 (etCO2) monitoring is not a new modality in the pediatric emergency department (PED) and emergency department. It is the standard of care during certain procedures such as intubations and sedations and can be used in variety of clinical situations. However, etCO2 may be underused in the PED setting. The implementation of etCO2 monitoring may be accomplished many ways, but a foundation of capnography principles specifically in ventilation, cardiac output, and current literature regarding its application is essential to successful implementation. It is the intention of this article to briefly review the principles of etCO2 monitoring and its clinical applications in the PED setting.
Integrating Childhood and Adult Blood Lead Surveillance to Improve Identification and Intervention Efforts
Authors: Egan Kathryn B. , Tsai Rebecca J. , Chuke Stella O.
Published: November 2018

The Centers for Disease Control and Prevention (CDC) collects information on blood lead levels (BLLs) in the United States through the Childhood Blood Lead Surveillance (CBLS) system (<16 years of age) and the Adult Blood Lead Epidemiology and Surveillance (ABLES) program (≥16 years of age). While both of these state-based national programs share the mutual goal of monitoring and reducing lead exposure in the US population, blood lead data for children and adults are maintained in separate data collection systems. This limits the ability to fully describe lead exposure in the US population across these 2 distinct population groups from sources such as take-home and maternal-child lead exposure. In addition, at the state level, having a unified system to collect, maintain, and analyze child and adult blood lead data provides a more efficient use of limited resources. Based on feedback from state partners, CDC is working to integrate CBLS and ABLES data collection systems at the national level. Several states have developed or are developing an integrated child and adult blood lead data collection system. We highlight efforts undertaken in Wisconsin, Minnesota, North Carolina, Iowa, and Oregon to investigate workplace and take-home lead exposure. Integrating blood lead surveillance data at the national level will enhance CDC's ability to monitor sources of lead exposure from both the home and work environments including paint, water, soil, dust, consumer products, and lead-related industries. Together, an integrated child and adult blood lead surveillance system will offer a coordinated, comprehensive, and systematic public health approach to the surveillance and monitoring of reported BLLs across the US population.
The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment: 2018 update
Authors: Verstraelen Hans , Swidsinski Alexander
Published: November 2018

Purpose of review

Bacterial vaginosis is conventionally appreciated as a temporary community disturbance of the vaginal microbiota, though really involving self-organization as a resilient biofilm community. We will briefly review here how recent findings on this matter may affect practice and research in this field.

Recent findings

The rapidly expanding literature base on the vaginal microbiome is largely based on 16S ribosomal ribonucleic acid (rRNA) and cpn60 gene sequencing, with few studies accounting thus far for spatial microbiota organization. The putative sexually transmitted disease profile of bacterial vaginosis inferred from epidemiologic research, may concur with its biofilm nature, notably involving spread of dispersed cells or cell aggregates between hosts. De novo biofilm formation in response to prolonged vaginal ecosystem pressure should be considered a pathogenetic model as well. Biofilm assays may not only aid epidemiologic research, but also add to monitoring therapeutic efficacy of novel treatments. Therapeutic research thus far is largely confined to inhibition of in-vitro biofilm formation, though a recent innovative clinical trial involved a combinational approach of metronidazole and a surfactant, specifically aiming for the biofilm.

Bacterial vaginosis research will further benefit from biofilm assays complementing taxonomy-based data, and this already translates in a novel treatment paradigm.
Lymphoganuloma venereum in the Western world, 15 years after its re-emergence: new perspectives and research priorities
Authors: de Vries Henry J.C.
Published: November 2018

Purpose of review

Lymphogranuloma venereum (LGV) is a serious sexually transmitted infection caused by Chlamydia trachomatis. If left untreated LGV can cause irreversible late sequelae. LGV is endemic among a high-risk population of men who have sex with men (MSM), and largely reported in Western metropoles.

Recent findings

Although the majority of LGV patients are HIV positive, in recent years the proportion of HIV-negative MSM with LGV is rising. This could indicate a shift toward lower risk populations. Apart from a few European countries, no proper LGV surveillance efforts have been implemented so far. Moreover, a considerable proportion of the infections are asymptomatic. As a result, the true magnitude of the LGV epidemic is underestimated.

Depending on the stage and location of infection, LGV manifests in a variety of clinical presentations. Among MSM, anorectal infections are overreported as opposed to genital LGV infections in a ratio of 15 to 1, respectively. Therefore, other modes of transmission apart from anal sex are here discussed.

To improve surveillance, cheaper and more practical screening methods are needed. Moreover, randomized clinical trials are needed to evaluate more simple treatment modalities as opposed to the currently recommended 3-week course of doxycycline.
Can a complex adaptive systems perspective support the resiliency of the heart failure patient – informal caregiver dyad?
Authors: Nimmon Laura , Kimel Gil , Lingard Lorelei , Bates Joanna
Published: November 2018

Purpose of review

A holistic palliative approach for heart failure care emphasizes supporting nonprofessional informal caregivers. Informal caregivers play a vital role caring for heart failure patients. However, caregiving negatively affects informal caregivers’ well being, and in turn heart failure patients’ health outcomes. This opinion article proposes that complex adaptive systems (CAS) theory applied to heart failure models of care can support the resiliency of the heart failure patient – informal caregiver dyad.

Recent findings

Heart failure care is enacted within a complex system composed of patients, their informal caregivers and a variety of health professionals. In a national study, we employed a CAS perspective to explore how all parts of the heart failure team function interdependently in emergent and adaptive ways. Salient in our data were the severe vulnerability of elderly heart failure patients and their long-term partners who suffered from a chronic illness. Novel approaches are needed that can quickly adapt and reorganize care when unpredictable disturbances occur in the couples’ functional capacity.

The linear protocol-driven care models that shape heart failure guidelines, training and care delivery initiatives do not adequately capture heart failure patients’ social environment. CAS is a powerful theoretical tool that can render visible the most vulnerable members of the heart failure team, and incite robust specialized holistic palliative heart failure care models.
Salt in freshwaters: causes, effects and prospects - introduction to the theme issue
Authors: Cañedo-Argüelles Miguel , Kefford Ben , Schäfer Ralf
Published: December 2018

Humans are globally increasing the salt concentration of freshwaters (i.e. freshwater salinization), leading to significant effects at the population, community and ecosystem level. The present theme issue focuses on priority research questions and delivers results that contribute to shaping the future research agenda on freshwater salinization as well as fostering our capacity to manage salinization. The issue is structured along five topics: (i) the estimation of future salinity and evaluation of the relative contribution of the different drivers; (ii) the physiological responses of organisms to alterations in ion concentrations with a specific focus on the osmophysiology of freshwater insects and the responses of different organisims to seawater intrusion; (iii) the impact of salinization on ecosystem functioning, also considering the connections between riparian and stream ecosystems; (iv) the role of context in moderating the response to salinization. The contributions scrutinise the role of additional stressors, biotic interactions, the identify of the ions and their ratios, as well as of the biogeographic and evolutionary context; and (v) the public discourse on salinization and recommendations for management and regulation. In this paper we introduce the general background of salinization, outline research gaps and report key findings from the contributions to this theme issue.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Predicting current and future background ion concentrations in German surface water under climate change
Authors: Le Trong Dieu Hien , Kattwinkel Mira , Schützenmeister Klaus , Olson John R. , Hawkins Charles P. , Schäfer Ralf B.
Published: December 2018

Salinization of surface waters is a global environmental issue that can pose a regional risk to freshwater organisms, potentially leading to high environmental and economic costs. Global environmental change including climate and land use change can increase the transport of ions into surface waters. We fit both multiple linear regression (LR) and random forest (RF) models on a large spatial dataset to predict Ca2+(266 sites), Mg2+(266 sites), and(357 sites) ion concentrations as well as electrical conductivity (EC—a proxy for total dissolved solids with 410 sites) in German running water bodies. Predictions in both types of models were driven by the major factors controlling salinity including geologic and soil properties, climate, vegetation and topography. The predictive power of the two types of models was very similar, with RF explaining 71–76% of the spatial variation in ion concentrations and LR explaining 70–75% of the variance. Mean squared errors for predictions were all smaller than 0.06. The factors most strongly associated with stream ion concentrations varied among models but rock chemistry and climate were the most dominant. The RF model was subsequently used to forecast the changes in EC that were likely to occur for the period of 2070 to 2100 in response to just climate change—i.e. no additional effects of other anthropogenic activities. The future forecasting shows approximately 10% and 15% increases in mean EC for representative concentration pathways 2.6 and 8.5 (RCP2.6 and RCP8.5) scenarios, respectively.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Predicting combined effects of land use and climate change on river and stream salinity
Authors: Olson John R.
Published: December 2018

Agricultural, industrial and urban development have all contributed to increased salinity in streams and rivers, but the likely effects of future development and climate change are unknown. I developed two empirical models to estimate how these combined effects might affect salinity by the end of this century (measured as electrical conductivity, EC). The first model predicts natural background from static (e.g. geology and soils) and dynamic (i.e. climate and vegetation) environmental factors and explained 78% of the variation in EC. I then compared the estimated background EC with current measurements at 2001 sites chosen probabilistically from all conterminous USA streams. EC was more than 50% greater at 34% of these sites. The second model predicts deviation of EC from background as a function of human land use and environmental factors and explained 60% of the variation in alteration from background. I then predicted the effects of climate and land use change on EC at the end of the century by replacing dynamic variables with published projections of future conditions based on the A2 emissions scenario. By the end of the century, the median EC is predicted to increase from 0.319 mS cm
−1
to 0.524 mS cm
−1
with over 50% of streams having greater than 50% increases in EC and 35% more than doubling their EC. Most of the change is related to increases in human land use, with climate change accounting for only 12% of the increase. In extreme cases, increased salinity may make water unsuitable for human use, but widespread moderate increases are likely a greater threat to stream ecosystems owing to the elimination of low EC habitats.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Lost in translation: the German literature on freshwater salinization
Authors: Schulz Claus-Jürgen , Cañedo-Argüelles Miguel
Published: December 2018

Human activities have globally increased and altered the ion concentration of freshwater ecosystems. The proliferation of potash mines in Germany (especially intense in the early 1900s) constitutes a good example of it. The effluents and runoff coming from potash mines led to extreme salt concentrations (e.g. 72 g l
–1
of total salt content, approx. 149 mS cm
–1
) in surrounding rivers and streams, causing ecosystem degradation (e.g. massive algal blooms and fish kills). This promoted scientific research that was mostly published in German, thereby being neglected by the wide scientific community. Here, the findings of the German literature on freshwater salinization are discussed in the light of current knowledge. German studies revealed that at similar ion concentrations potassium (K
+
) can be the most toxic ion to freshwater organisms, whereas calcium (Ca
2+
) could have a toxicity ameliorating effect. Also, they showed that salinization could lead to biodiversity loss, major shifts in the composition of aquatic communities (e.g. dominance of salt-tolerant algae, proliferation of invasive species) and alter organic matter processing. The biological degradation caused by freshwater salinization related to potash mining has important management implications, e.g. it could prevent many European rivers and streams from reaching the good ecological status demanded by the Water Framework Directive. Within this context, German publications show several examples of salinity thresholds and biological indices that could be useful to monitor and regulate salinization (i.e. developing legally enforced salinity and ion-specific standards). They also provide potential management techniques (i.e. brine collection and disposal) and some estimates of the economic costs of freshwater salinization. Overall, the German literature on freshwater salinization provides internationally relevant information that has rarely been cited by the English literature. We suggest that the global editorial and scientific community should take action to make important findings published in non-English literature more widely available.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Effects of salinity changes on aquatic organisms in a multiple stressor context
Authors: Velasco Josefa , Gutiérrez-Cánovas Cayetano , Botella-Cruz María , Sánchez-Fernández David , Arribas Paula , Carbonell José Antonio , Millán Andrés , Pallarés Susana
Published: December 2018

Under global change, the ion concentration of aquatic ecosystems is changing worldwide. Many freshwater ecosystems are being salinized by anthropogenic salt inputs, whereas many naturally saline ones are being diluted by agricultural drainages. This occurs concomitantly with changes in other stressors, which can result in additive, antagonistic or synergistic effects on organisms. We reviewed experimental studies that manipulated salinity and other abiotic stressors, on inland and transitional aquatic habitats, to (i) synthesize their main effects on organisms' performance, (ii) quantify the frequency of joint effect types across studies and (iii) determine the overall individual and joint effects and their variation among salinity–stressor pairs and organism groups using meta-analyses. Additive effects were slightly more frequent (54%) than non-additive ones (46%) across all the studies (
n
= 105 responses). However, antagonistic effects were dominant for the stressor pair salinity and toxicants (44%,
n
= 43), transitional habitats (48%,
n
= 31) and vertebrates (71%,
n
= 21). Meta-analyses showed detrimental additive joint effects of salinity and other stressors on organism performance and a greater individual impact of salinity than the other stressors. These results were consistent across stressor pairs and organism types. These findings suggest that strategies to mitigate multiple stressor impacts on aquatic ecosystems should prioritize restoring natural salinity concentrations.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Evolved tolerance to freshwater salinization in zooplankton: life-history trade-offs, cross-tolerance and reducing cascading effects
Authors: Hintz William D. , Jones Devin K. , Relyea Rick A.
Published: December 2018

Recent discoveries have documented evolutionary responses to freshwater salinization. We investigated if evolutionary responses to salinization exhibit life-history trade-offs or if they can mitigate ecological impacts such as cascading effects through mechanisms of tolerance and cross-tolerance. We conducted an outdoor mesocosm experiment using populations of
Daphnia pulex
—a ubiquitous algal grazer—that were either naive or had previously experienced selection to become more tolerant to sodium chloride (NaCl). During the initial phase of population growth, we discovered that evolved tolerance comes at the cost of slower population growth in the absence of salt. We found evolved
Daphnia
populations maintained a tolerance to NaCl approximately 30 generations after the initial discovery. Evolved tolerance to NaCl also conferred cross-tolerance to a high concentration of CaCl
2
(3559 µS cm
−1
) and a moderate concentration of MgCl
2
(967 µS cm
−1
). A higher concentration of MgCl
2
(2188 µS cm
−1
) overwhelmed the cross-tolerance and killed all
Daphnia
. Tolerance to NaCl did not mitigate NaCl-induced cascades leading to phytoplankton blooms, but cross-tolerance at moderate concentrations of MgCl
2
and high concentrations of CaCl
2
mitigated such cascading effects caused by these two salts. These discoveries highlight the important interplay between ecology and evolution in understanding the full impacts of freshwater salinization.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Biological interactions mediate context and species-specific sensitivities to salinity
Authors: Bray J. P. , Reich J. , Nichols S. J. , Kon Kam King G. , Mac Nally R. , Thompson R. , O'Reilly-Nugent A. , Kefford B. J.
Published: December 2018

Toxicants have both sub-lethal and lethal effects on aquatic biota, influencing organism fitness and community composition. However, toxicant effects within ecosystems may be altered by interactions with abiotic and biotic ecosystem components, including biological interactions. Collectively, this generates the potential for toxicant sensitivity to be highly context dependent, with significantly different outcomes in ecosystems than laboratory toxicity tests predict. We experimentally manipulated stream macroinvertebrate communities in 32 mesocosms to examine how communities from a low-salinity site were influenced by interactions with those from a high-salinity site along a gradient of salinity. Relative to those from the low-salinity site, organisms from the high-salinity site were expected to have greater tolerance and fitness at higher salinities. This created the potential for both salinity and tolerant-sensitive organism interactions to influence communities. We found that community composition was influenced by both direct toxicity and tolerant-sensitive organism interactions. Taxon and context-dependent responses included: (i) direct toxicity effects, irrespective of biotic interactions; (ii) effects that were owing to the addition of tolerant taxa, irrespective of salinity; (iii) toxicity dependent on sensitive-tolerant taxa interactions; and (iv) toxic effects that were increased by interactions. Our results reinforce that ecological processes require consideration when examining toxicant effects within ecosystems.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Temperature affects acute mayfly responses to elevated salinity: implications for toxicity of road de-icing salts
Authors: Jackson John K. , Funk David H.
Published: December 2018

Salinity in freshwater ecosystems has increased significantly at numerous locations throughout the world, and this increase often reflects the use or production of salts from road de-icing, mining/oil and gas drilling activities, or agricultural production. When related to de-icing salts, highest salinity often occurs in winter when water temperature is often low relative to mean annual temperature at a site. Our study examined acute (96 h) responses to elevated salinity (NaCl) concentrations at five to seven temperature treatments (5–25°C) for four mayfly species (Baetidae:Neocloeon triangulifer,Procloeon fragile; Heptageniidae:Maccaffertium modestum; Leptophlebiidae:Leptophlebia cupida) that are widely distributed across eastern North America. Based on acute LC50s at 20°C,P. fragilewas most sensitive (LC50 = 767 mg l−1, 1447 µS cm−1), followed byN. triangulifer(2755 mg l−1, 5104 µS cm−1),M. modestum(2760 mg l−1, 5118 µS cm−1) andL. cupida(4588 mg l−1, 8485 µS cm−1). Acute LC50s decreased as temperature increased for all four species (n= 5–7,R2= 0.65–0.88,p= 0.052–0.002). Thus, acute salt toxicity is strongly temperature dependent for the mayfly species we tested, which suggests that brief periods of elevated salinity during cold seasons or in colder locations may be ecologically less toxic than predicted by standard 20 or 25°C laboratory bioassays.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.