bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of blockchain technologies and smart contracts on dispute resolution: arbitration and court litigation at the crossroads
Authors: Ortolani Pietro
Published: May 2019

This article investigates the twofold impact that blockchain technologies and smart contracts have on dispute resolution. On the one hand, these technologies enable private parties to devise arbitral systems that are self-enforcing and, therefore, largely bypass the recognition and enforcement procedures through which State courts traditionally exert a certain control over arbitration. This phenomenon may in the future allow arbitration to become entirely self-sufficient, thus leading to the marginalization of State courts. On the other hand, however, such a marginalization has not taken place yet; to the contrary, the recent blockchain-related phenomenon of initial coin offerings has given rise to some prominent court cases. These cases raise particularly interesting jurisdictional questions, especially in light of the difficulty of reconciling the decentralized nature of the blockchain with the territorial approach whereby jurisdiction is typically allocated among national courts.
Student-Novice Nurse Preparation: Addressing Barriers in Discharge Teaching
Authors: Chidume Tiffani , Pass-Ivy Sherry
Published: May 2019

AIM

The aim of this article was to assess how and to what degree nursing students are prepared for patient discharge teaching (DT).

BACKGROUND

The process of discharging patients has become more complex. Despite the expectation that nursing students will be competent in providing effective DT upon graduation, the preparation of new graduates is a problem for hospitals.

METHOD

A review of the literature was conducted.

REVIEW

The review showed that novice nurses enter the workforce unprepared to provide adequate DT due to limited communication and limited time during their education, which led to low confidence and limited knowledge.

CONCLUSION

Methods to overcome current barriers in DT, including simulation practices, the teach-back method, dedicated education units, collaborative efforts, discharge checklists, and health literacy identification, are presented as recommendations for nursing education.
New phenotypes in hypersensitivity reactions to nonsteroidal anti-inflammatory drugs
Authors: Lee Youngsoo , Shin Yoo Seob , Park Hae-Sim
Published: May 2019

Purpose of review

Nonsteroidal anti-inflammatory drug (NSAID) is one of the most frequently prescribed medications in the medical field, and hypersensitivity to NSAID is a common adverse drug reaction encountered. However, NSAID hypersensitivity presents a variety of symptoms caused by diverse pharmacological and immunological mechanisms.

Recent findings

Owing to the heterogeneity of the disease, a new concept for the classification of NSAID hypersensitivity has recently been proposed to diagnose and manage NSAID hypersensitivity for personalized treatment. Acute and delayed reactions were distinguished in this classification, and identification of symptoms and speculation of putative mechanisms help physicians make the right diagnosis. NSAID-exacerbated respiratory disease is a noticeable phenotype of NSAID hypersensitivity that involves upper airway comorbidities (chronic rhinosinusitis with nasal polyps) as well as asthmatic features. The cutaneous phenotypes of NSAID hypersensitivity occur, and cross-reactivity with other types of NSAID should be considered in establishing a proper diagnosis. Hypersensitivity to a single NSAID can present urticaria/angioedema and anaphylaxis, in which an IgE-mediated immune response is suggested to be a prime mechanism. Management of NSAID hypersensitivity reactions includes avoidance, pharmacological treatment following standard guidelines, and aspirin desensitization.

The classification, diagnosis, and management of NSAID hypersensitivity should be individually reached by identifying its phenotype.
Microbiome and skin biology
Authors: Lunjani Nonhlanhla , Hlela Carol , O’Mahony Liam
Published: May 2019

Purpose of review

The skin is home to a diverse milieu of bacteria, fungi, viruses, bacteriophages, and archaeal communities. The application of culture-independent approaches has revolutionized the characterization of the skin microbiome and have revealed a previously underappreciated phylogenetic and functional granularity of skin-associated microbes in both health and disease states.

Recent findings

The physiology of a given skin-niche drives the site-specific differences in bacterial phyla composition of healthy skin. Changes in the skin microbiome have consistently been associated with atopic dermatitis. In particular, Staphylococcus aureus overgrowth with concomitant decline in Staphylococcus epidermidis is a general feature associated with atopic dermatitis and is not restricted to eczematous lesions. Changes in fungal species are now also being described. Changes in the composition and metabolic activity of the gut microbiota are associated with skin health.

We are now beginning to appreciate the intimate and intricate interactions between microbes and skin health. Multiple studies are currently focused on the manipulation of the skin or gut microbiome to explore their therapeutic potential in the prevention and treatment of skin inflammation.
Association Between Critical Care Admissions and Cognitive Trajectories in Older Adults*
Authors: Schulte Phillip J. , Warner David O. , Martin David P. , Deljou Atousa , Mielke Michelle M. , Knopman David S. , Petersen Ronald C. , Weingarten Toby N. , Warner Matthew A. , Rabinstein Alejandro A. , Hanson Andrew C. , Schroeder Darrell R. , Sprung Juraj
Published: May 2019

Objectives:

Patients requiring admission to an ICU may subsequently experience cognitive decline. Our objective was to investigate longitudinal cognitive trajectories in older adults hospitalized in ICUs. We hypothesized that individuals hospitalized for critical illness develop greater cognitive decline compared with those who do not require ICU admission.

Design:

A retrospective cohort study using prospectively collected cognitive scores of participants enrolled in the Mayo Clinic Study of Aging and ICU admissions retrospectively ascertained from electronic medical records. A covariate-adjusted linear mixed effects model with random intercepts and slopes assessed the relationship between ICU admissions and the slope of global cognitive z scores and domains scores (memory, attention/executive, visuospatial, and language).

Setting:

ICU admissions and cognitive scores in the Mayo Clinic Study of Aging from October 1, 2004, to September 11, 2017.

Patients:

Nondemented participants age 50 through 91 at enrollment in the Mayo Clinic Study of Aging with an initial cognitive assessment and at least one follow-up visit.

Interventions:

None.

Measurements and Main Results:

Of 3,673 participants, 372 had at least one ICU admission with median (25–75th percentile) follow-up after first ICU admission of 2.5 years (1.2–4.4 yr). For global cognitive z score, admission to an ICU was associated with greater decline in scores over time compared with participants not requiring ICU admission (difference in annual slope = –0.028; 95% CI, –0.044 to –0.012; p < 0.001). ICU admission was associated with greater declines in memory (–0.029; 95% CI, –0.047 to –0.011; p = 0.002), attention/executive (–0.020; 95% CI, –0.037 to –0.004; p = 0.016), and visuospatial (–0.013; 95% CI, –0.026 to –0.001; p = 0.041) domains. ICU admissions with delirium were associated with greater declines in memory (interaction p = 0.006) and language (interaction p = 0.002) domains than ICU admissions without delirium.

Conclusions:

In older adults, ICU admission was associated with greater long-term cognitive decline compared with patients without ICU admission. These findings were more pronounced in those who develop delirium while in the ICU.
Corneal Perforation After Corneal Cross-Linking in Keratoconus Associated With Potentially Pathogenic ZNF469 Mutations
Authors: Zhang Wenlin , Margines J. Ben , Jacobs Deborah S. , Rabinowitz Yaron S. , Hanser Evelyn Maryam , Chauhan Tulika , Chung Doug , Bykhovskaya Yelena , Gaster Ronald N. , Aldave Anthony J.
Published: May 2019

Purpose:

To report a case of bilateral and repetitive corneal perforations after corneal cross-linking (CXL) for keratoconus in a woman harboring potentially pathogenic variants in the ZNF469 gene and to characterize the keratoconus phenotype in this woman and her daughter who shared the same ZNF469 mutations.

Methods:

Clinical characterization of the proband and her daughter followed by sequencing of the genes associated with brittle cornea syndrome, ZNF469 and PRDM5, in both individuals.

Results:

An Ashkenazi Jewish woman in her sixth decade presented with diffuse corneal thinning and progressive steepening consistent with keratoconus. After CXL, epithelium-off in the first eye and epithelium-on in the second, she developed spontaneous corneal perforations in each eye. Her daughter in her fourth decade demonstrated a similar pattern of diffuse corneal thinning and progressive corneal steepening but did not undergo CXL and did not develop corneal perforation. Screening of the ZNF469 and PRDM5 genes revealed 3 missense ZNF469 variants (c.2035G>A, c.10244G>C, and c.11119A>G) in cis arrangement on 1 allele of ZNF469 in both proband and her daughter. Although the 3 variants share low (<0.01) global minor allele frequencies, each has significantly higher minor allele frequencies (0.01–0.03) in the Ashkenazi Jewish population, leading to uncertainty regarding a pathogenic role for the identified variants.

Conclusions:

CXL may be associated with the development of corneal perforation in particular at-risk individuals with keratoconus. Identifying clinical and genetic risk factors, including screening of ZNF469 and PRDM5, may be useful in the prevention of significant complications after CXL.
Listeria Meningitis in Danish Children 2000–2017
Authors: Vissing Nadja Hawwa , Kristensen Kim , Mønster Mette Bondo , Møller Frederik Trier , Knudsen Jenny Dahl , Poulsen Anja , Ethelberg Steen , Nygaard Ulrikka
Published: May 2019

Listeria monocytogenes meningitis in Danish children 1 month to 17 years from 2000 to 2017 was identified and patient files reviewed. There were 5 cases, equaling an annual incidence of 0.024 per 100,000 children or 0.014 when excluding 2 immunodeficient children. Even in a country with a high general incidence of listeriosis, Listeria meningitis is a rare event in healthy children.
Pain or nociception? Subjective experience mediates the effects of acute noxious heat on autonomic responses - corrected and republished
Authors: Mischkowski Dominik , Palacios-Barrios Esther E. , Banker Lauren , Dildine Troy C. , Atlas Lauren Y.
Published: May 2019

Nociception reliably elicits an autonomic nervous system (ANS) response. Because pain and ANS circuitry interact on multiple spinal, subcortical, and cortical levels, it remains unclear whether autonomic responses are simply a reflexive product of noxious stimulation regardless of how stimulation is consciously perceived or whether the experience of pain mediates ANS responses to noxious stimulation. To test these alternative predictions, we examined the relative contribution of noxious stimulation and individual pain experience to ANS responses in healthy volunteers who underwent 1 or 2 pain assessment tasks. Participants received 8 seconds of thermal stimulation of varied temperatures and judged pain intensity on every trial. Skin conductance responses and pupil dilation responses to stimulation served as measures of the heat-evoked autonomic response. We used multilevel modelling to examine trial-by-trial relationships between heat, pain, and ANS response. Although both pain and noxious heat stimulation predicted skin conductance response and pupil dilation response in separate analyses, the individual pain experience statistically mediated effects of noxious heat on both outcomes. Furthermore, moderated mediation revealed that evidence for this process was stronger when stimulation was perceived as painful compared with when stimulation was perceived as nonpainful, although this difference emerged late, in the 4-second period after thermal stimulation. These findings suggest that pain appraisal regulates the heat-evoked autonomic response to noxious stimulation, documenting the flexibility of the autonomic pain response to adjust to perceived or actual changes in environmental affordances above and beyond nociceptive input.
Testing a positive-affect induction to reduce verbally induced nocebo hyperalgesia in an experimental pain paradigm
Authors: Geers Andrew L. , Close Shane , Caplandies Fawn C. , Vogel Charles L. , Murray Ashley B. , Pertiwi Yopina , Handley Ian M. , Vase Lene
Published: May 2019

There is an ethical obligation to notify individuals about potential pain associated with diagnoses, treatments, and procedures; however, supplying this information risks inducing nocebo hyperalgesia. Currently, there are few empirically derived strategies for reducing nocebo hyperalgesia. Because nocebo effects are linked to negative affectivity, we tested the hypothesis that a positive-affect induction can disrupt nocebo hyperalgesia from verbal suggestion. Healthy volunteers (N = 147) were randomly assigned to conditions in a 2 (affect induction: positive vs neutral) by 2 (verbal suggestion: no suggestion vs suggestion of pain increase) between-subjects design. Participants were induced to experience positive or neutral affect by watching movie clips for 15 minutes. Next, participants had an inert cream applied to their nondominant hand, and suggestion was manipulated by telling only half the participants the cream could increase the pain of the upcoming cold pressor test. Subsequently, all participants underwent the cold pressor test (8 ± 0.04°C), wherein they submerged the nondominant hand and rated pain intensity on numerical rating scales every 20 seconds up to 2 minutes. In the neutral-affect conditions, there was evidence for the nocebo hyperalgesia effect: participants given the suggestion of pain displayed greater pain than participants not receiving this suggestion, P's < 0.05. Demonstrating a blockage effect, nocebo hyperalgesia did not occur in the positive-affect conditions, P's > 0.5. This is the first study to show that positive affect may disrupt nocebo hyperalgesia thereby pointing to a novel strategy for decreasing nocebo effects without compromising the communication of medical information to patients in clinical settings.
A Model of Pediatric End-Stage Lung Failure in Small Lambs <20 kg
Authors: Carr Benjamin D. , Poling Clinton J. , Hala Pavel , Caceres Quinones Matias , Prater Aaron R. , McLeod Jennifer S. , Bartlett Robert H. , Rojas-Pena Alvaro , Hirschl Ronald B.
Published: May 2019

One in five children with end-stage lung failure (ESLF) die while awaiting lung transplant. No suitable animal model of ESLF exists for the development of artificial lung devices for bridging to transplant. Small lambs weighing 15.7 ± 3.1 kg (n = 5) underwent ligation of the left anterior pulmonary artery (PA) branch, and gradual occlusion of the right main PA over 48 hours. All animals remained hemodynamically stable. Over seven days of disease model conditions, they developed pulmonary hypertension (mean PA pressure 20 ± 5 vs. 33 ± 4 mm Hg), decreased perfusion (SvO2 66 ± 3 vs. 55 ± 8%) with supplemental oxygen requirement, and severe tachypneic response (45 ± 9 vs. 82 ± 23 breaths/min) (all p < 0.05). Severe right heart dysfunction developed (tricuspid annular plane systolic excursion 13 ± 3 vs. 7 ± 2 mm, fractional area change 36 ± 6 vs. 22 ± 10 mm, ejection fraction 51 ± 9 vs. 27 ± 17%, all p < 0.05) with severe tricuspid regurgitation and balloon-shaped dilation of the right ventricle. This model of pediatric ESLF reliably produces pulmonary hypertension, right heart strain, and impaired gas exchange, and will be used to develop a pediatric artificial lung.
Enteral vs. parenteral nutrition in septic shock: are they equivalent?
Authors: Kott Matthias , Hartl Wolfgang H. , Elke Gunnar
Published: May 2019

Purpose of review

The current review focuses on recent clinical evidence and updated guideline recommendations on the effects of enteral vs. parenteral nutrition in adult critically ill patients with (septic) shock.

Recent findigs

The largest multicenter randomized-controlled trial showed that the route of nutrient supply was unimportant for 28-day and 90-day mortality, infectious morbidity and length of stay in mechanically ventilated patients with shock. The enteral route, however, was associated with lower macronutrient intake and significantly higher frequency of hypoglycemia and moderate-to-severe gastrointestinal complications. Integrating these findings into recent meta-analyses confirmed that the route per se has no effect on mortality and that interactions with (infectious) morbidity are inconsistent or questionable.

The strong paradigm of favoring the enteral over the parenteral route in critically ill patients has been challenged. As a consequence, updated guidelines recommend withholding enteral nutrition in patients with uncontrolled shock. It is still unclear, however, whether parenteral nutrition is advantageous in patients with shock although benefits are conceivable in light of less gastrointestinal complications. Thus far, no guideline has addressed indications for parenteral nutrition in these patients. By considering recent scientific evidence, specific guideline recommendations, and expert opinions, we present a clinical algorithm that may facilitate decision-making when feeding critically ill patients with shock.
Translating the European Society for Clinical Nutrition and Metabolism 2019 guidelines into practice
Authors: Reintam Blaser Annika , Deane Adam M. , Starkopf Joel
Published: May 2019

Purpose of review

To present a pragmatic approach to facilitate clinician's implementing the recent European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines on clinical nutrition in the intensive care unit.

Recent findings

The ESPEN guidelines include 54 recommendations with a rationale for each recommendation. All data published since 1 January 2000 was reviewed and 31 meta-analyses were performed to inform these guidelines. An important aspect of the most recent ESPEN guidelines is an attempt to separate periods of critical illness into discrete – early acute, late acute and recovery – phases, with each exhibiting different metabolic profiles and requiring different strategies for nutritional and metabolic support.

A pragmatic approach to incorporate the recent ESPEN guidelines into everyday clinical practice is provided.
The Effects of Fortification and Refrigerated Storage on Bioactive Proteins in Holder‐pasteurized Donor Human Milk
Authors: Schlotterer Hannah R. , Parvez Boriana , Perrin Maryanne T.
Published: May 2019

Objective:

The aim of the study was to assess the total protein, lysozyme, and immunoglobulin A (IgA) content of unfortified and fortified Holder‐pasteurized donor human milk (HPDHM) during 96 hours of refrigerated storage.

Study Design:

HPDHM was prepared in a hospital feeding room and subjected to treatment with 3 different fortifiers: an acidic, bovine‐based (F‐ACID), a neutral, bovine‐based, and a human milk–derived (F‐HUM) fortifier. Unfortified HPDHM served as the control (CONTROL). Samples were stored at 4°C, and every 24 hours, a 1‐mL aliquot was removed for analysis.

Results:

At baseline, there was a significant difference in protein (mean, standard deviation) concentration (g/dL) between control (1.3, 0.1) and all other treatments (F‐ACID = 2.0, 0.2; neutral, bovine‐derived fortifier = 2.2, 0.1; F‐HUM = 2.5, 0.1; P < 0.001). Lysozyme and IgA were significantly lower in the F‐ACID group (P < 0.001). Lysozyme and IgA were significantly higher in the F‐HUM group (P < 0.001). There was no significant effect of storage time (P > 0.9) for all dependent variables.

Conclusion:

The type of fortifier has a more significant impact on bioactive components in fortified HPDHM than does storage time. Our findings of lack of negative impact of refrigeration storage time on the protein and bioactive components of donor milk strengthen the recent recommendations to extend storage time to 48 hours.
Electronically augmented gait abnormality assessment following lower extremity trauma
Authors: Swart Eric , Peindl Richard , Zheng Nigel , Habet Nahir , Churchill Christine , Ruder John Adam , Seymour Rachel , Karunakar Madhav , Kellam James , Sims Stephen
Published: May 2019

Background:

Objective evaluation of patient outcomes has become an essential component of patient management. Along with patient-reported outcomes, performance-based measures (PBMs) such as gait analysis are an important part of this evaluation. The purpose of this study was to evaluate the validity of utilizing a wearable inertial measurement unit (IMU) in an outpatient clinic setting to assess its ability to provide clinically relevant data in patients with altered gait resulting from lower extremity trauma.

Methods:

Five orthopaedic trauma patients with varying degrees of gait pathologies were compared to 5 healthy control subjects. Kinematic data were simultaneously recorded by the IMU and a gold standard Vicon video motion analysis system (Vicon Motion Systems Ltd, Oxford, UK) during a modified 10-m walk test. Raw data captured by the IMU were directly compared to Vicon data. Additionally, 5 objective gait parameters were compared for controls and the 5 trauma patients.

Results:

The IMU data streams strongly correlated with Vicon data for measured variables used in the subsequent gait analysis: vertical acceleration, vertical displacement, pitch angular velocity, and roll angular velocity (Pearson r-value > 0.9 for all correlations). Quantitative kinematic data in post-trauma patients significantly differed from control data and correlated with observed gait pathology.

Conclusions:

When compared to the gold standard motion capture reference system (Vicon), an IMU can reliably and accurately measure clinically relevant gait parameters and differentiate between normal and pathologic gait patterns. This technology is easily integrated into clinical settings, requires minimal time, and represents a performance-based method for quantifiably assessing gait outcomes.

Level of Evidence:

Diagnostic Level 1.
The AOSpine thoracolumbar spine injury classification system: A comparative study with the thoracolumbar injury classification system and severity score in children
Authors: Mo Andrew Z. , Miller Patricia E. , Troy Michael J. , Rademacher Emily S. , Hedequist Daniel J.
Published: May 2019

Background:

There is no uniform classification in the pediatric population for thoracolumbar (TL) fractures, nor any operative guidelines. This study evaluates the AOSpine TL spine injury classification in the pediatric population and compares it to the thoracolumbar injury classification system (TLICS), which has previously been validated in pediatric spine trauma.

Methods:

Twenty-eight patients with operative TL injuries were identified from 2006 to 2016. Inclusion criteria included available imaging, operative records, age <18, and posterior approach. Each case was classified by AOSpine TL spine injury classification and TLICS. Each classification was compared to documented intraoperative posterior ligamentous complex (PLC) integrity as well as each other.

Results:

Utilizing the AOSpine TL spine injury classification, 7 patients had type A injuries, 15 patients had type B injuries, and 6 patients had type C injuries; 21 patients had injuries classified as involving the PLC. Using TLICS, 16 patients had burst fractures, 6 patients had distraction injuries, and 6 patients had translation injuries; 21 patients had injuries classified as involving the PLC. Spearman correlation analysis substantiated convergence of AOSpine TL spine injury classification scores to TLICS scores (r = 0.75; 95% confidence interval, CI = 0.51 to 0.98; P < .001). Concordance between PLC integrity by each classification and intraoperative evaluation was 96% (27/28) of cases (k = 0.91; 95% CI = 0.73 to 1.08). Neurologic status was 100% concordant between the AOSpine TL spine injury classification and TLICS.

Conclusion:

There is high statistical correlation between the AOSpine TL spine injury classification and TLICS, and to intraoperative evaluation of the PLC, suggesting that the AOSpine TL spine injury classification is applicable to the pediatric population.

Level of evidence:

III.
Virologic Failure Among People Living With HIV Initiating Dolutegravir-Based Versus Other Recommended Regimens in Real-World Clinical Care Settings
Authors: Nance Robin M. , Vannappagari Vani , Smith Kimberly , Johannes Catherine B. , Calingaert Brian , Saltus Catherine W. , Mayer Kenneth H. , Whitney Bridget M. , Rodriguez Benigno , Moore Richard D. , Eron Joseph J. , Geng Elvin , Mathews William Christopher , Mugavero Michael J. , Saag Michael S. , Kitahata Mari M. , Delaney Joseph A. C. , Crane Heidi M.
Published: May 2019

Background:

Guidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTIs) increasingly prominent. Research on virologic failure (VF) with INSTI therapy is predominantly from clinical trials not care settings, especially for recently approved medications including dolutegravir. We compared outcomes among people living with HIV (PLWH) who initiated recommended regimens in clinical care across the United States.

Setting:

We examined 2 groups of PLWH at 8 clinics who initiated ART regimens (August 1, 2013–March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced.

Methods:

The outcome in this longitudinal cohort study was VF, defined as a viral load of ≥400 copies/mL ≥6 months after ART initiation. We examined the proportion of individuals who remained on, switched, or discontinued the regimen. Associations between regimens and outcomes were examined with adjusted Cox proportional hazards models.

Results:

Among 5177 PLWH, a lower proportion experienced VF on dolutegravir- versus other INSTI- or darunavir-based regimens for previously treatment-naive (7% vs. 12% vs. 28%) and treatment-experienced PLWH (6% vs. 10% vs. 21%). In adjusted analyses, hazard ratios were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The hazard ratios for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95% CI: 0.2 to 0.6) among previously treatment-naive PLWH and was 0.60 (95% CI: 0.4 to 0.8) among treatment-experienced PLWH.

Conclusions:

The proportion of previously treatment-naive PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than darunavir-based regimens for previously treatment-naive and treatment-experienced PLWH.
Brief Report: Aging Attenuates the Association Between Coronary Artery Calcification and Bone Loss Among HIV-Infected Persons
Authors: Escota Gerome , Baker Jason , Bush Tim , Conley Lois , Brooks John T. , Patel Pragna , Powderly William , Presti Rachel , Overton Edgar T. ,   for the CDC (Centers for Disease Control and Prevention)-SUN (Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy) Investigators
Published: May 2019

Introduction:

Studies among HIV-uninfected persons (mostly in their sixth decade of life) show that detectable coronary artery calcium (CAC) is independently associated with low bone mineral density (BMD), suggesting a possible common pathogenic mechanism.

Aim:

We assessed the relationship between CAC and BMD, which has not been well described among younger to middle-aged HIV-infected persons.

Methods:

We studied participants with baseline CAC and BMD measures from a prospective cohort of HIV-infected persons enrolled in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) during 2004–2006. We used logistic regression to assess the association between detectable CAC (>0 Agatston score) and BMD (g/cm2, T-score), and adjusted for known traditional and HIV-related risk factors.

Results:

Among 472 participants (76% male, 30% non-Hispanic black, median age 41 years, and 71% with HIV RNA < 400 copies/mL), the majority had no detectable CAC (82%), but had baseline osteopenia (53%) or osteoporosis (10%). In univariate analysis, participants with detectable CAC had lower femoral neck/total hip T-scores, lower femoral neck/total hip/lumbar spine BMD, and higher rates of osteopenia/osteoporosis. After adjustment for age, all associations were no longer significant; adjustment for traditional risk factors excluding age and HIV-related variables failed to attenuate these associations.

Conclusions:

We found aging attenuates the association between detectable CAC and BMD in this cohort. Aging remains an important contributor to non–AIDS-defining illnesses. These data reinforce the importance of developing screening and prevention strategies for aging HIV-infected persons given their excess risk across a wide spectrum of end-organ complications.
Determinants of Liver Complications Among HIV/Hepatitis B Virus–Coinfected Patients
Authors: Lo Re Vincent , Newcomb Craig W. , Carbonari Dena M. , Roy Jason A. , Althoff Keri N. , Kitahata Mari M. , Reddy K. Rajender , Lim Joseph K. , Silverberg Michael J. , Mayor Angel M. , Horberg Michael A. , Cachay Edward R. , Kirk Gregory D. , Hull Mark , Gill John , Sterling Timothy R. , Kostman Jay R. , Peters Marion G. , Moore Richard D. , Klein Marina B. , Kim H. Nina ,   for the North American AIDS Cohort Collaboration on Research and Design of IeDEA
Published: May 2019

Background:

Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown.

Setting:

North American AIDS Cohort Collaboration on Research and Design.

Methods:

We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL).

Results:

Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13–2.74)], diabetes mellitus [aHR = 2.07 (1.20–3.57)], lower time-updated CD4 cell count [<200 cells/mm3: aHR = 2.59 (1.36–4.91); 201–499 cells/mm3: aHR = 1.75 (1.01–3.06) versus ≥500 cells/mm3], heavy alcohol use [aHR = 1.58 (1.04–2.39)], and higher FIB-4 at start of follow-up [>3.25: aHR = 9.79 (5.73–16.74); 1.45–3.25: aHR = 3.20 (1.87–5.47) versus FIB-4 <1.45]. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35–0.91)].

Conclusions:

Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.
Molecular diagnosis of Pneumocystis pneumonia in immunocompromised patients
Authors: Guegan Hélène , Robert-Gangneux Florence
Published: May 2019

Purpose of review

Pneumocystis pneumonia (PCP) is a frequent opportunistic infection associated with a high mortality rate. PCP is of increasing importance in non-HIV immunocompromised patients, who present with severe respiratory distress with low fungal loads. Molecular detection of Pneumocystis in broncho-alveolar lavage (BAL) has become an important diagnostic tool, but quantitative PCR (qPCR) needs standardization.

Recent findings

Despite a high negative predictive value, the positive predictive value of qPCR is moderate, as it also detects colonized patients. Attempts are made to set a cut-off value of qPCR to discriminate between PCP and colonization, or to use noninvasive samples or combined strategies to increase specificity.

It is easy to set a qPCR cut-off for HIV-infected patients. In non-HIV IC patients, a gain in specificity could be obtained by combining strategies, that is, qPCR on BAL and a noninvasive sample, or qPCR and serum beta-1,3-D-glucan dosage.
Neonatal Head Ultrasound: A Review and Update—Part 2
Authors: Maller Vijetha Vinod , Choudhri Asim Fiaz , Cohen Harris L.
Published: May 2019

Neonatal head ultrasound has a key role in triaging neonates with antenatal imaging or postnatal clinical concerns. This article will discuss key features of various intracranial pathologies of concern in term infants. It will also illustrate various congenital malformations.
Mammalian Skull Dimensions and the Golden Ratio (Φ)
Authors: Tamargo Rafael J. , Pindrik Jonathan A.
Published: May 2019

The Golden Ratio (Phi, or Φ = 1.618…) is a potentially unifying quantity of structure and function in nature, as best observed in phyllotactic patterns in plants. For centuries, Φ has been identified in human anatomy, and in recent decades, Φ has been identified in human physiology as well. The anatomy and evolution of the human skull have been the focus of intense study. Evolving over millenia, the human skull embodies an elegant harmonization of structure and function. The authors explored the dimensions of the neurocranium by focusing on the midline calvarial perimeter between the nasion and inion (nasioiniac arc) and its partition by bregma into 2 sub-arcs. The authors studied 100 human skulls and 70 skulls of 6 other mammalian species and calculated 2 ratios: 1) the nasioiniac arc divided by the parieto-occipital arc (between bregma and inion), and 2) the parieto-occipital arc divided by the frontal arc (between nasion and bregma). The authors report that in humans these 2 ratios coincide (1.64 ± 0.04 and 1.57 ± 0.10) and approximate Φ. In the other 6 mammalian species, these 2 ratios were not only different, but also unique to each species. The difference between the ratios showed a trend toward convergence on Φ correlating with species complexity. The partition of the nasioiniac arc by bregma into 2 unequal arcs is a situation analogous to that of the geometrical division of a line into Φ. The authors hypothesize that the Golden Ratio (Φ) principle, documented in other biological systems, may be present in the architecture and evolution of the human skull.
Controversy on the Age of Hypertelorism Correction
Authors: Medra Ahmed Mohamed , Hassanein Ahmed Gaber , Fadle Khalid Nasser
Published: May 2019

Introduction:

Orbital hypertelorism (HTO) is a challenging craniofacial problem seen in association with some congenital deformities. The age of HTO correction is a matter of debate.

The Aim of the work:

to evaluate the outcome of HTO correction and determine the optimal timing for intervention, striving for the earliest possible intervention with the lowest relapse.

Patients and methods:

A standard craniofacial approach with medial bone resection, 4 walls orbital box osteotomy and orbital medialization were done for all patients. Skeletal and soft tissue procedures were done as indicated.

Results:

there were 10 patients aging 6 to 19 years. Seven were associated with craniofacial clefts, and 3 with craniosynostosis syndromes. HTO was severe in 8 cases and moderate in 2 cases. It was asymmetric in 2 cases. Frontoorbital remodeling was done in 3 cases with craniosynostosis. Failed surgery was reported in 2 cases. A redo surgery was done for one of them with an excellent outcome, while refused by the other. Nine patients had an excellent outcome. The mean level of satisfaction was 93.37%. Three patients had ugly facial scars. No major complications were recorded.

Conclusion:

The time for surgical treatment of HTO is determined by the severity of the associated deformity. If there is an urgent factor indicating intervention, early correction can be performed exceptionally; otherwise, HTO correction should be performed after the age of 6 years.
Screening for Microscopic Hematuria in a Urogynecologic Population
Authors: Dune Tanaka J. , Kliethermes Stephanie , Mueller Elizabeth R. , Fitzgerald Colleen M. , Brubaker Linda , Brincat Cynthia A.
Published: May 2019

Objectives

The objectives of this were to determine the correlation of greater than or equal to 3 red blood cells per high-power field (RBCs/HPF) with a positive urine dipstick for blood and to identify clinically relevant factors than can influence this relationship.

Methods

The charts of women with positive blood urine dipsticks were reviewed from August 2012 to August 2013. The cohort of women was divided into 2 groups; those with urine with greater than or equal to 3 RBCs/HPF on microscopy and those without. Relevant clinical and demographic variables were extracted from the electronic medical record. Data analysis was conducted using SAS version 9.4 (SAS Institute, Cary, NC).

Results

Most of the 203 patients eligible for analysis were Caucasian, and the total cohort had a mean age of approximately 62.8 years. Microscopy confirmed greater than or equal to 3 RBCs/HPF in 25.6% of the urine samples. A dipstick finding of moderate or large blood was significantly more likely to have greater than or equal to 3 RBCs/HPF on univariate and multivariable analyses (P < 0.001). Factors significantly associated with greater than or equal to 3 RBCs/HPF were increasing age, recurrent urinary tract infections, and urinary specific gravity of greater than 1.010.

Conclusions

Lower urinary specific gravities appear to be associated with underestimating microhematuria, likely owing to the underrepresentation of the true number of red blood cells. Urine dipstick indicators of moderate or large blood increase the likelihood the microscopy samples demonstrated greater than or equal to 3 RBCs/HPF. These findings suggest that clarification of microhematuria detection and evaluation guidelines should be considered, given both important clinical and economic consequences.
Update on PET in neurodegenerative and neuroinflammatory disorders manifesting on a behavioural level: imaging for differential diagnosis
Authors: Hellwig Sabine , Domschke Katharina , Meyer Philipp T.
Published: May 2019

Purpose of review

To give an update on recent findings concerning the use of PET for differential diagnosis in neurodegenerative and neuroinflammatory disorders manifesting on a behavioural level.

Recent findings

Although accurate differential diagnosis of dementia can be achieved by imaging disease-specific patterns of cerebral glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG)-PET, the diagnostic impact of [18F]FDG-PET in primary psychiatric disorders is limited. Amyloid-beta PET provides an incremental value beyond [18F]FDG-PET in the differential diagnosis of dementia and was proposed as a biomarker defining the so-called Alzheimer continuum. Recently developed tau-specific tracers might also aid in the diagnostic process (biological definition of Alzheimer's disease together with amyloid-beta). Surpassing the diagnostic accuracy of other techniques, such as MRI, [18F]FDG-PET has also gained widespread clinical use for diagnosis and follow-up of paraneoplastic and autoimmune disorders of the central nervous system (CNS) as an important differential diagnosis for rapid progressive dementia and subacute onset of psychiatric syndromes.

Molecular neuroimaging with PET is an established method for the differential diagnosis of neurodegenerative and autoimmune CNS disorders manifesting on a behavioural level with significant therapeutic and prognostic impact. Future prospective studies are needed to define the value of tau imaging for diagnosis and prognosis in neurodegenerative disorders.
Evaluation of SNP calling methods for closely related bacterial isolates and a novel high-accuracy pipeline: BactSNP
Authors: Yoshimura Dai , Kajitani Rei , Gotoh Yasuhiro , Katahira Katsuyuki , Okuno Miki , Ogura Yoshitoshi , Hayashi Tetsuya , Itoh Takehiko
Published: May 2019

Bacteria are highly diverse, even within a species; thus, there have been many studies which classify a single species into multiple types and analyze the genetic differences between them. Recently, the use of whole-genome sequencing (WGS) has been popular for these analyses, and the identification of single-nucleotide polymorphisms (SNPs) between isolates is the most basic analysis performed following WGS. The performance of SNP-calling methods therefore has a significant effect on the accuracy of downstream analyses, such as phylogenetic tree inference. In particular, when closely related isolates are analyzed, e.g. in outbreak investigations, some SNP callers tend to detect a high number of false-positive SNPs compared with the limited number of true SNPs among isolates. However, the performances of various SNP callers in such a situation have not been validated sufficiently. Here, we show the results of realistic benchmarks of commonly used SNP callers, revealing that some of them exhibit markedly low accuracy when target isolates are closely related. As an alternative, we developed a novel pipeline BactSNP, which utilizes both assembly and mapping information and is capable of highly accurate and sensitive SNP calling in a single step. BactSNP is also able to call SNPs among isolates when the reference genome is a draft one or even when the user does not input the reference genome. BactSNP is available at https://github.com/IEkAdN/BactSNP.
Hemozoin produced by mammals confers heme tolerance
Authors: Pek Rini H. , Yuan Xiaojing , Rietzschel Nicole , Zhang Jianbing , Jackson Laurie K. , Nishibori Eiji , Ribeiro Ana , Simmons William R. , Jagadeesh Jaya , Sugimoto Hiroshi , Alam Md Zahidul , Garrett Lisa J. , Haldar Malay , Ralle Martina , Phillips John , Bodine David , Hamza Iqbal
Published: May 2019

Free heme is cytotoxic as exemplified by hemolytic diseases and genetic deficiencies in heme recycling and detoxifying pathways. Thus, intracellular accumulation of heme has not been observed in mammalian cells to date. Here we show that mice deficient for the heme transporter HRG1 accumulate over ten-fold excess heme in reticuloendothelial macrophage lysosomes that are 10 to 100 times larger than normal. Macrophages tolerate these high concentrations of heme by polymerizing them into crystalline hemozoin, which heretofore has only been found in blood-feeding parasites.HRG1deficiency results in impaired erythroid maturation and an inability to systemically respond to iron deficiency. Complete heme tolerance requires a fully-operational heme degradation pathway as haploinsufficiency ofHMOX1combined withHRG1inactivation causes perinatal lethality demonstrating synthetic lethal interactions between heme transport and degradation. Our studies establish the formation of hemozoin by mammals as a previously unsuspected heme tolerance pathway.
From morphogenesis to pathogenesis: A cellulose loosening protein is one of the most widely distributed tools in nature
Authors: Chase William R. , Zhaxybayeva Olga , Rocha Jorge , Cosgrove Daniel J. , Shapiro Lori R.
Published: May 2019

Plants must rearrange the network of complex carbohydrates in their cell walls during normal growth and development. To accomplish this, all plants depend on proteins called expansins that non-enzymatically loosen hydrogen bonds between cellulose microfibrils. Because of their key role in cell wall extension during growth, expansin genes are ubiquitous, diverse, and abundant throughout all land plants. Surprisingly, expansin genes have more recently been found in some bacteria and microbial eukaryotes, where their biological functions are largely unknown. Here, we reconstruct the phylogeny of microbial expansin genes. We find these genes in all eukaryotic microorganisms that have structural cellulose in their cell walls, suggesting expansins evolved in ancient marine microorganisms long before the evolution of land plants. We also find expansins in an unexpectedly high phylogenetic diversity of bacteria and fungi that do not have cellulosic cell walls. These bacteria and fungi with expansin genes inhabit varied ecological contexts mirroring the diversity of terrestrial and aquatic niches where plant and/or algal cellulosic cell walls are present. The microbial expansin phylogeny shows evidence of multiple horizontal gene transfer events within and between bacterial and eukaryotic microbial lineages, which may in part underlie their unusually broad phylogenetic distribution. Taken together, we find expansins to be unexpectedly widespread in both bacterial and eukaryotic genetic backgrounds, and that the contribution of these genes to bacterial and fungal ecological interactions with plants and algae has likely been underappreciated.

Importance

Cellulose is the most abundant biopolymer on earth. In plant cell walls, where most global cellulose biomass is found, cellulose microfibrils occur intertwined with hemicelluloses and pectins. The rigidity of this polysaccharide matrix provides plant cell walls with structural support, but this rigidity also restricts cellular growth and development. Irreversible, non-enzymatic loosening of structural carbohydrates by expansin proteins is key to successful cell wall growth in plants and green algae. Here, we find that expansin genes are distributed far more broadly throughout diverse bacterial and fungal lineages lacking cellulosic cell walls than previously known. Multiple horizontal gene transfer events are in part responsible for their unusually wide phylogenetic distribution. Together, these results suggest that in addition to being the key evolutionary innovation by which eukaryotes remodel structural cellulose in their cell walls, expansins likely have remarkably broad and under-recognized utility for microbial species that interact with plant and algal structural cellulose in diverse ecological contexts.
Practical considerations for improved reliability and precision during compound specific analysis of δ15N in amino acids using a single combined oxidation-reduction reactor
Authors: Riekenberg Philip M. , van der Meer Marcel , Schouten Stefan
Published: May 2019

RATIONALE

There has been increased interest in the analysis for δ15N in amino acids to gain simultaneous insight into both trophic relationships and source producers within ecosystems. New developments in gas chromatography combustion isotope ratio mass spectrometry equipment has led to variable outcomes in performance due to limited information about best practices for new systems.

METHODS

Precision for δ15N in amino acids using the single combined oxidation-reduction reactor is improved across a sequence of analyses if the reactor is oxidized for a substantial period (2 h), immediately followed with a conditioning run of alkanes prior to analysis for N, and the liquid N2 CO2 trap is left immersed throughout. A five point calibration curve using amino acids with a range of δ15N values from −2.4‰ to +61.5‰ was used in combination with a 13 amino acid mixture to correct for offsets during derivatization.

RESULTS

Combining the improved setup with normalization techniques using both internal and external standards allows for a reliable throughput of ~25 samples per week. It allowed for a reproducible level of error of <±0.5‰ within standards repeated 10 times across each sequence and a sample error of (±0.18‰), which is lower than analytical error typically associated with δ15N-amino acid analysis (±1‰).

CONCLUSIONS

A few practical considerations regarding oxidation and conditioning of the combustion reactor allow for increased sequence capacity with the single combined oxidation-reduction reactor. These considerations combined with normalization techniques result in a higher throughput and reduced analytical error during analysis of δ15N in amino acids.