Glucose control in the ICU

Purpose of review Critically ill patients usually develop hyperglycemia, which is associated with adverse outcome. Controversy exists whether the relationship is causal or not. This review summarizes recent evidence regarding glucose control in the ICU. Recent findings Despite promising effects of tight glucose control in pioneer randomized controlled trials, the benefit has not been confirmed in subsequent multicenter studies and one trial found potential harm. This discrepancy could be explained by methodological differences between the trials rather than by a different case mix. Strategies to improve the efficacy and safety of tight glucose control have been developed, including the use of computerized treatment algorithms. Summary The ideal blood glucose target remains unclear and may depend on the context. As compared with tolerating severe hyperglycemia, tight glucose control is well tolerated and effective in patients receiving early parenteral nutrition when provided with a protocol that includes frequent, accurate glucose measurements and avoids large glucose fluctuations. All patient subgroups potentially benefit, with the possible exception of patients with poorly controlled diabetes, who may need less aggressive glucose control. It remains unclear whether tight glucose control is beneficial or not in the absence of early parenteral nutrition. Correspondence to Greet Van den Berghe, MD, PhD, Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, B-3000, Leuven, Belgium. Tel: +32 16 344021; fax +32 16 344015; e-mail: greet.vandenberghe@kuleuven.be Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Thoracic trauma in military settings: a review of current practices and recommendations

Purpose of review To examine current literature on thoracic trauma related to military combat and to explore its relevance to the civilian population. Recent findings Damage control resuscitation (DCR) has improved the management of hemorrhaging trauma patients. Permissive hypotension below 110 mmHg and antifibrinolytic use during DCR is widely accepted, whereas the use of freeze-dried plasma and whole blood is gaining popularity. The Modified Physiologic Triaging Tool can be used for primary triage and it may have applications in civilian trauma systems. Although Tactical Combat Casualty Care protocol recommends the Cric-Key device for surgical cricothyroidotomies, other devices may offer comparable performance. Recommendations for regional anesthesia after blunt trauma are not well defined. Increasing amounts of evidence favor the use of extracorporeal membrane oxygenation for refractory hypoxemia and resuscitative endovascular balloon occlusion of the aorta (REBOA) for severe hemorrhage. REBOA outcomes are potentially improved by partial occlusion and small 7 Fr catheters. Summary The Global War on Terror has provided opportunities to better understand and treat thoracic trauma in military settings. Trauma registries and other data sources have contributed to significant advancements in the management of thoracic trauma in military and civilian populations. Correspondence to Robert Mansky, 545 First Ave, Apt 8I, New York, NY 10016, USA. Tel: +1 516 672 5589; e-mail: rmansky@gmail.com Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Noninvasive ventilation versus oxygen therapy in patients with acute respiratory failure

Purpose of review High-flow nasal cannula oxygen therapy (HFOT) is becoming an alternative to noninvasive ventilation (NIV) and standard oxygen in management of patients with acute respiratory failure. Recent findings Patients with de novo acute respiratory failure should be managed with HFOT rather than NIV. Indeed, the vast majority of patients with de novo respiratory failure meet the criteria for ARDS, and NIV does not seem protective, as patients generate overly high tidal volume that may worsen underlying lung injury. However, NIV remains the first-line oxygenation strategy in postoperative patients and those with acute hypercapnic respiratory failure when pH is equal to or below 7.35. During preoxygenation, NIV also seems to be more efficient than standard oxygen using valve-bag mask to prevent profound oxygen desaturation. In postoperative cardiothoracic patients, HFOT could be an alternative to NIV in the management of acute respiratory failure. Summary Recent recommendations for managing patients with acute respiratory failure have been established on the basis of studies comparing NIV with standard oxygen. Growing use of HFOT will lead to new studies comparing NIV versus HFOT in view of more precisely defining the appropriate indications for each treatment. Correspondence to Jean-Pierre Frat, Médecine Intensive Réanimation, CHU de Poitiers, 2 rue la Milétrie, 86021 Poitiers Cedex, France. Tel: +33 5 49 44 40 07; e-mail: jean-pierre.frat@chu-poitiers.fr Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The effectiveness of noise interventions in the ICU

Purpose of review Excessive noise has direct adverse physiological and psychological effects, and may also have indirect negative health consequences by reducing sleep quality and quantity. This review presents a synthesis of the epidemiology of noise in the ICU, and the potential interventions designed to attenuate noise and protect patients. Recent findings Noise increases cortisol release, oxygen consumption, and vasoconstriction. ICU noise levels are excessive throughout the 24-h cycle, irrespective of level of intervention or whether the patient is in a side room or open ward. Direct measurement suggests that noise is a substantial contributor to poor sleep quantity and quality in the ICU and is frequently recalled by survivors of critical illness as a negative experience of ICU admission. Noise abatement, environmental masking and pharmacological interventions may all reduce the impact of noise on patients. However, the sustainability of behavioural interventions remains uncertain and high-quality evidence demonstrating the benefit of any intervention on patient-centered outcomes is lacking. Summary Noise levels in the ICU are consistently reported to reach levels likely to have both direct and indirect adverse health consequences for both patients and staff. Noise reduction, abating the transmission of noise and pharmacological modulation of the adverse neural effects of noise are all potentially beneficial strategies, although definitive evidence of improved patient-centered outcomes is lacking. Correspondence to Lori Delaney, MIHM, MN, PGD Crit Care, PGC Ed, Faculty of Nursing, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia. E-mail: Lori.delaney@qut.edu.au Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Telemedicine in the ICU: clinical outcomes, economic aspects, and trainee education

Purpose of review The evidence base for telemedicine in the ICU (tele-ICU) is rapidly expanding. The last 2 years have seen important additions to our understanding of when, where, and how telemedicine in the ICU adds value. Recent findings Recent publications and a recent meta-analysis confirm that tele-ICU improves core clinical outcomes for ICU patients. Recent evidence further demonstrates that comprehensive tele-ICU programs have the potential to quickly recuperate their implementation and operational costs and significantly increase case volumes and direct contribution margins particularly if additional logistics and care standardization functions are embedded to optimize ICU bed utilization and reduce complications. Even though the adoption of tele-ICU is increasing and the vast majority of today's medical graduates will regularly use some form of telemedicine and/or tele-ICU, telemedicine modules have not consistently found their way into educational curricula yet. Tele-ICU can be used very effectively to standardize supervision of medical trainees in bedside procedures or point-of-care ultrasound exams, especially during off-hours. Lastly, tele-ICUs routinely generate rich operational data, as well as risk-adjusted acuity and outcome data across the spectrum of critically ill patients, which can be utilized to support important clinical research and quality improvement projects. Summary The value of tele-ICU to improve patient outcomes, optimize ICU bed utilization, increase financial performance and enhance educational opportunities for the next generation of providers has become more evident and differentiated in the last 2 years. Correspondence to Christian D. Becker, MD, PhD, Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. Tel: +1 914 493 1040; fax: +1 914 493 8373; e-mail: christian.becker@wmchealth.org Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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In Vitro Activity of Tedizolid in Comparison with Other Oral and Intravenous Agents Against a Collection of Community-Acquired Methicillin-Resistant Staphylococcus aureus (2014–2015) in the United States

Microbial Drug Resistance, Ahead of Print.


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Prevalence and Genetic Characteristics of Methicillin-Resistant Staphylococcus aureus and Coagulase-Negative Staphylococci Isolated from Oral Cavity of Healthy Children in Japan

Microbial Drug Resistance, Ahead of Print.


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TP901-1 Phage Recombinase Facilitates Genome Engineering in Drosophila melanogaster

Molecular biology techniques have a large impact on biomedical research and the availability of diverse tools to perform genome manipulations advances the ease of executing complicated genetic research. Here, we introduce in the fruit fly another such tool by harnessing the phage recombinase TP901-1 to perform site-directed recombination that leads to recombinase-mediated cassette exchange (RMCE). The TP901-1 system complements already existing recombination systems and enhances genome engineering in the fruit fly and other organisms.

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Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed

Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (Canis lupus familiaris), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and has subsequently been found in this breed in Europe and the USA. The objective of the present study was to determine the genetic basis of goniodysgenesis in Border Collies. Clinical diagnosis was based on results of examinations by veterinary ophthalmologists of affected and unaffected dogs from eleven different countries. Genotyping using the Illumina high density canine single nucleotide variant genotyping chip was used to identify a candidate genetic region. There was a highly significant peak of association over chromosome 17, with a p-value of 2 x 10^–13. Expression profiles and evolutionary conservation of candidate genes were assessed using public databases. Whole genome sequences of three dogs with glaucoma, three severely affected by goniodysgenesis and three unaffected dogs identified a missense variant in the olfactomedin like 3 (OLFML3) gene in all six affected animals. This was homozygous for the risk allele in all nine cases with glaucoma and 12 of 14 other severely affected animals. Of 67 reportedly unaffected animals, only one was homozygous for this variant (offspring of parents both with goniodysgenesis who were also homozygous for the variant). Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed. The identification of a candidate genetic region and putative causative variant will aid breeders to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population.

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Cross-cultural Adaptation of the Neck Pain and Disability Scale: A Methodological Systematic Review

Neck pain is a common and uncomfortable symptom, adversely affecting the work and life of those affected. The Neck Pain and Disability Scale (NPDS) is widely used in neck pain assessment. It has been cross-culturally adapted into several languages to extend its reach to non-English-speaking countries. The aim of this study was to comprehensively evaluate the translation procedures and measurement properties of cross-cultural adaptations of the NPDS.

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Comparison of the history and physical examination for hip osteoarthritis and lumbar spinal stenosis

Leg pain associated with walking is sometimes incorrectly attributed to hip osteoarthritis (OA) or lumbar spinal stenosis (LSS).

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Gypsy moth genome provides insights into flight capability and virus-host interactions [Genetics]

Since its accidental introduction to Massachusetts in the late 1800s, the European gypsy moth (EGM; Lymantria dispar dispar) has become a major defoliator in North American forests. However, in part because females are flightless, the spread of the EGM across the United States and Canada has been relatively slow over...

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Whole-chromosome paints in maize reveal rearrangements, nuclear domains, and chromosomal relationships [Genetics]

Whole-chromosome painting probes were developed for each of the 10 chromosomes of maize by producing amplifiable libraries of unique sequences of oligonucleotides that can generate labeled probes through transcription reactions. These paints allow identification of individual homologous chromosomes for many applications as demonstrated in somatic root tip metaphase cells, in...

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Paternal comeback in mitochondrial DNA inheritance [Genetics]

Since the discovery of mtDNA in 1963 (1), it has been a common notion that inheritance of this small, but very essential, piece of DNA occurs in a strict maternal manner. One reason for this is that the paternal contribution of sperm mitochondria to the fertilized egg is about 1,000-fold...

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Opinion: To curate the molecular past, museums need a carefully considered set of best practices [Anthropology]

Biomolecular research has sparked a methodological revolution in the field of anthropology, and museums are now faced with the curatorial challenge of conserving and evaluating materials for these new methods. Since 2010, hundreds of genome-wide datasets from ancient human samples have been published, and thousands more have been generated; doubling...

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A Qualitative Exploration of Mothers’ Experiences Receiving Mental Health Services in a Supermarket Setting

Abstract

Objectives Innovative mental health care delivery models have been proposed as a method to address disparities in access and utilization. The aim of this study is to characterize patients' perspectives and experiences of participating in one such innovative delivery model, group cognitive behavioral therapy within a supermarket setting. Methods In this qualitative study, 16 mothers were interviewed to explore their experiences and perspectives of receiving group-based cognitive behavioral therapy in a supermarket setting, as part of their participation in an academic-community research collaborative whose mission is to address mental health needs within low-resourced communities. Data from semi-structured interviews were analyzed using inductive coding. Results Five themes related to receiving mental health services in a supermarket setting emerged from the data: (1) Participants reported a convergence of life stressors and their introduction to supermarket-based services; (2) Participants perceived the supermarket setting as convenient; (3) Participants perceived the supermarket setting as less stigmatizing; (4) Participants perceived services in the supermarket as an acceptable form of mental health treatment; and (5) Participants described the program staff as an influential component of their treatment experience. Conclusions Understanding patient experiences of various service delivery models is critical to improving access to treatment and addressing disparities in mental health service utilization and outcomes. This study supports the use of innovative delivery models to increase access to mental health services in low-resourced communities.

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Rat mesenteric small artery neurogenic dilation is predominantly mediated by β1‐adrenoceptors in vivo

Key points

The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilation caused by CGRP (and possibly substance P) released from sensory‐motor nerves and vasoconstriction caused by noradrenaline, ATP and NPY release from sympathetic nerves. Most studies on perivascular nerve mediated vasodilation are made in vitro. We here provide evidence that in vivo electrical perivascular nerve stimulation in rat mesenteric small arteries causes a large β1‐adrenoceptor mediated vasodilation, which contrasts with a smaller vasodilation caused by endogenous CGRP, which is only visible after inhibition of Y1 NPY receptors. Mesenteric arteries are densely innervated and the nerves are important regulators of vascular tone and hence blood pressure and blood flow . Perivascular sensory‐motor nerves have been shown to cause vasodilation in vitro. However, less is known about their function in vivo. Male Wistar rats (10‐12 weeks old; n = 72) were anaesthetized with ketamine (3 mg kg⁻¹) and xylazine (0.75 mg kg⁻¹) or pentobarbital (60 mg kg⁻¹). After a laparotomy, a section of 2^nd order mesenteric artery was visualized in an organ bath after minimal removal of perivascular adipose tissue. The effects of electrical field stimulation (EFS) and drugs on artery diameter and blood flow were recorded with intravital microscopy and laser speckle imaging. EFS caused vasodilation in arteries constricted with 1 μm U46619 in the presence of 140 μm suramin and 1 μm prazosin. The vasodilation was inhibited by 1 μm tetrodotoxin and 5 μm guanethidine but not by the 1 μm of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 μm of the Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilation. One μm atenolol inhibited the vasodilation while 0.1 μm of the β₂‐adrenoceptor selective antagonist ICI‐118,551 had no effect. Increasing the extracellular [K⁺] to 20 mm caused vasodilation but vasoconstriction in the presence of 1 μm BIBN4096bs, and constriction to 30 mm potassium was potentiated by BIBN4096bs. Atenolol but not BIBN4096bs increased contraction to EFS in the absence of suramin and prazosin. In mesenteric small arteries of anaesthetized rats, EFS failed to stimulate major dilation via sensory‐motor nerves but induced sympathetic β₁‐adrenoceptor mediated dilation.

This article is protected by copyright. All rights reserved

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Integrative single-cell analysis

Integrative single-cell analysis

Integrative single-cell analysis, Published online: 29 January 2019; doi:10.1038/s41576-019-0093-7

The functional interpretation of single-cell RNA sequencing (scRNA-seq) data can be enhanced by integrating additional data types beyond RNA-based gene expression. In this Review, Stuart and Satija discuss diverse approaches for integrative single-cell analysis, including experimental methods for profiling multiple omics types from the same cells, analytical approaches for extracting additional layers of information directly from scRNA-seq data and computational integration of omics data collected across different cell samples.

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A postural unloading task to assess fast corrective responses in the upper limb following stroke

Robotic technologies to measure human behavior are emerging as a new approach to assess brain function. Recently, we developed a robot-based postural Load Task to assess corrective responses to mechanical dist...

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Evaluation of biomechanical gait parameters of patients with Cerebral Palsy at three different levels of gait assistance using the CPWalker

Cerebral Palsy (CP) is the most common cause of permanent serious physical disability in childhood. Although many platforms have been developed, so far there are still not precise guidelines for the rehabilita...

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Integrative single-cell analysis

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Characterization of Toxoplasma gondii Spt5 like transcription elongation factor

Publication date: Available online 29 January 2019

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Pallabi Mitra, Abhijit S. Deshmukh, Rajkumar Gurupwar, Poonam Kashyap

Abstract

Elongation has emerged as a highly regulated step in the multistage process of transcription. Control of gene expression mediated through transcription elongation remains an unexplored area of study in Toxoplasma gondii where the demands of complex lifecycle necessitate a regulated transcription program. Here, we elucidate the central role of Spt5 homolog in T. gondii mRNA transcription. We demonstrate that TgSpt5 functions in conjunction with a small zinc finger protein TgSpt4. TgSpt5 interacts with TgRpb1, the largest subunit of RNA polymerase II and associates with actively transcribed genes. Enrichment of TgSpt5 towards the 3′ end of genes coinciding with P-Ser2 form of RNAPII, a marker of active elongation further underscores its pivotal role in transcription. TgSpt5 undergoes phosphorylation mediated through Toxoplasma Cdk9 homolog, TgCrk9, which appears crucial for its function. Inhibition of TgCrk9, which also regulates RNAPII by differential phosphorylation of its C terminal domain, results in loss of TgSpt5 enrichment at 3′ sites of the genes and an overall repressive effect on parasite progression. TgSpt5 along with TgSpt4 could successfully complement the loss of function mutations in yeast counterparts emphasizing its functional significance. Together, the results highlight the possible role of TgSpt5 in transcript elongation regulated through phosphorylation by TgCrk9.

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Generation of marker-free transgenic rice using CRISPR/Cas9 system controlled by floral specific promoters

Publication date: Available online 28 January 2019

Source: Journal of Genetics and Genomics

Author(s): Junjie Wang, Chun Wang, Kejian Wang

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Femur associated with the Deep Skull from the West Mouth of the Niah Caves (Sarawak, Malaysia)

Publication date: February 2019

Source: Journal of Human Evolution, Volume 127

Author(s): Darren Curnoe, Ipoi Datan, Hsiao Mei Goh, Mohammed S. Sauffi

Abstract

The skeletal remains of Pleistocene anatomically modern humans are rare in island Southeast Asia. Moreover, continuing doubts over the dating of most of these finds has left the arrival time for the region's earliest inhabitants an open question. The unique biogeography of island Southeast Asia also raises questions about the physical and cultural adaptations of early anatomically modern humans, especially within the setting of rainforest inhabitation. Within this context the Deep Skull from the West Mouth of the Niah Caves continues to figure prominently owing to its relative completeness and the greater certainty surrounding its geological age. Recovered along with this partial cranium in 1958 were several postcranial bones including a partial femur which until now has received little attention. Here we provide a description and undertake a comparison of the Deep Skull femur finding it to be very small in all of its cross-sectional dimensions. We note a number of size and shape similarities to the femora of Indigenous Southeast Asians, especially Aeta people from the Philippines. We estimate its stature to have been roughly 145–146 cm and body mass around 35 kg, confirming similarities to Aeta females. Its extreme gracility indicated by low values for a range of biomechanical parameters taken midshaft meets expectations for a very small (female) Paleolithic East Asian. Interestingly, the second moment of area about the mediolateral axis is enlarged relative to the second moment of area about the anteroposterior axis, which could potentially signal a difference in activity levels or lifestyle compared with other Paleolithic femora. However, it might also be the result of sexual dimorphism in these parameters as well as possibly reflecting changes associated with aging.

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Effectiveness of Physical Therapy Combined with Epidural Steroid Injection for Patients with Lumbar Spinal Stenosis: A Randomized Parallel-Group Trial

Publication date: Available online 29 January 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Amy Hammerich, Julie Whitman, Paul Mintkin, Thomas Denninger, Venu Akuthota, Eric E. Sawyer, Melissa Hofmann, John D. Childs, Joshua Cleland

Abstract

Objective

To examine the effectiveness of epidural steroid injection (ESI) and back education with and without physical therapy (PT) in patients with lumbar spinal stenosis (LSS).

Design

Randomized clinical trial.

Setting

Orthopaedic spine clinics.

Participants

390 patients were screened with 60 eligible and randomly selected to receive ESI and education with or without PT.

Interventions

54 patients received 1-3 injections and education in a 10 week intervention period with 31 receiving injections and education only (ESI) and 23 additionally receiving 8-10 sessions of multi-modal PT (ESI+PT).

Main Outcome Measures

Disability, pain, quality of life, and global rating of change were collected at 10 weeks, 6 months, and 1 year and analyzed using linear mixed model analysis.

Results

No significant difference was found between ESI and ESI+PT in the Oswestry Disability Index at any time point although the sample had significant improvements at 10 weeks (p < .001; 95% CI: -18.01, -5.51) and 1 year (p = .01; 95% CI: -14.57, -2.03) above MCID. Significant differences in SF36 were found for ESI+PT at 10 weeks with higher emotional role function (p = .03; 95% CI: -49.05, -8.01), emotional well-being (p = .02; 95% CI:-19.52, 2.99), and general health perception (p = .05; 95% CI: -17.20, -.78).

Conclusions

ESI plus PT was not superior to ESI alone for reducing disability in people with LSS. Significant benefit was found for the addition of PT related to quality of life factors of emotional function, emotional well-being, and perception of general health.

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Sensor measures of symmetry quantify upper limb movement in the natural environment across the lifespan

Publication date: Available online 29 January 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Beth A. Smith, Catherine E. Lang

Abstract

Knowledge of upper limb activity in the natural environment is critical for evaluating the effectiveness of rehabilitation services. Wearable sensors allow efficient collection of these data, and have the potential to be less burdensome than self-report measures of activity. Sensors can capture many different variables of activity and daily performance, many of which could be useful in identifying deviation from typical movement behavior and/or measuring outcomes from rehabilitation interventions. While it has potential, sensor measurement is just emerging and there is a lack of consensus on which variables of daily performance are valid, sensitive, specific, and useful. We propose that symmetry of full-day upper limb movement is a key variable. We describe here that symmetry is valid, robustly observed within a narrow range across the lifespan in typical development, and shows evidence of being different in populations with neuromotor impairment. Key next steps include the determination of sensitivity, specificity, minimal detectable change, and minimal clinically important change/difference. This information is needed to determine whether an individual belongs to the typical or atypical group, whether or not change has occurred, and whether or not that change is beneficial.

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Altered auditory feedback perception following an 8-week mindfulness meditation practice

Publication date: Available online 29 January 2019

Source: International Journal of Psychophysiology

Author(s): Daiki Miyashiro, Akira Toyomura, Tomosumi Haitani, Hiroaki Kumano

Abstract

Our own ongoing motor actions are perceived through sensory feedback pathways, and are integrated with neural processes to modulate further actions. This sensory feedback mechanism is known to contribute to the rehabilitation of impaired motor functions. Recent evidence also suggests that mindfulness meditation improves our awareness to sensation; therefore, enhancement of awareness to sensory feedback through mindfulness meditation training may have potential clinical applications. This study investigated an effect of eight-week practice of mindfulness meditation on speech perception/production processes. Among the thirty participants, half of them engaged in regular meditation practice of 10 min per day for eight weeks, and the other half were not given any instructions for their daily life. The change of speech performance in sentence reading under 200 ms delayed auditory feedback (DAF) condition were assessed compared to without delay condition. Also, event-related potential response to the short sound of /a/, were measured. The result showed that, after the eight-week practice, the meditation group showed significantly improved speech fluency in the DAF condition, when 16-min meditation was introduced before the experiments. Furthermore, significantly increased auditory evoked potentials were observed in the central-parietal region when the participants listened to the delayed auditory feedback sound of their own voice. These findings provide the first glimpses into the possible relationship between mindfulness meditation and auditory feedback. Different instructions for daily activity between the meditation and control groups should be considered in further studies.

Graphical abstract

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Pro‐contractile role of chloride in arterial smooth muscle: Postnatal decline potentially governed by sympathetic nerves

New Findings

What is the topic of this review?

This symposium report discusses previously unrecognized pro‐contractile role of chloride ions in rat arteries at early stages of postnatal development.

What advances does it highlight?

It highlights the postnatal decline in the contribution of chloride ions to regulation of arterial contractile responses and potential trophic role of sympathetic nerves in such developmental alterations.

Abstract

Chloride ions (Cl⁻) are important for smooth muscle contraction in adult vasculature. Arterial smooth muscle undergoes structural and functional remodeling during early postnatal development including changes in K⁺ currents, Ca²⁺‐handling and sensitivity. However, developmental change in the contribution of Cl⁻ to regulation of arterial contraction has not been explored yet. We provide here the first evidence that the role of Cl⁻ for α₁‐adrenergic arterial contraction prominently decreases during early postnatal ontogenesis. The trophic influence of sympathetic nerves is a potential mechanism for postnatal decline of Cl⁻ contribution to the vascular contraction.

This article is protected by copyright. All rights reserved

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Elbow angle modulates corticospinal excitability to the resting biceps brachii at both spinal and supraspinal levels

New Findings

What is the central question of this study?

Corticospinal excitability to biceps brachii is known to modulate according to upper‐limb posture. Here, cervicomedullary stimulation was used to investigate potential spinal contributions to elbow angle dependent changes in corticospinal excitability at rest.

What is the main finding and its importance?

At more extended elbow angles, biceps responses to cervicomedullary stimulation were decreased, whereas cortically‐evoked responses (normalised to cervicomedullary‐evoked responses) were increased. Results suggest decreased spinal excitability but increased cortical excitability as the elbow is placed in a more extended position, an effect that is unlikely due to cutaneous stretch receptor activation.

Abstract

Corticospinal excitability to biceps brachii is known to modulate according to upper‐limb posture. In Study 1, our aim was to investigate potential spinal contributions to this modulation and the independent effect of elbow angle. Biceps responses to transcranial magnetic stimulation (motor evoked potentials; MEPs) and electrical cervicomedullary stimulation (cervicomedullary motor evoked potentials; CMEPs) were measured at five elbow angles ranging from full extension to 130° of flexion. In Study 2, possible contributions of cutaneous stretch receptors to elbow angle dependent excitability changes were investigated by eliciting MEPs and CMEPs under three conditions of skin stretch about the elbow (stretch to mimic full extension, no stretch, stretch to mimic flexion). Each study had 12 participants. Evoked potentials were acquired at rest with participants seated, the shoulder flexed 90° and forearm supinated. MEPs and CMEPs were normalised to maximal compound muscle action potentials (Mmax). In Study 1, as the elbow was moved to more extended positions, there were no changes in MEPs (p = 0.963), progressive decreases in CMEPs (p < 0.0001; CMEPs at 130° flexion ∼220% of full extension) and increases in MEP/CMEP ratio (p = 0.019; MEP/CMEP at 130° flexion ∼20% of full extension). In Study 2, there were no changes in MEPs (p = 0.830) or CMEPs (p = 0.209) between skin stretch conditions. Therefore, while results suggest a decrease in spinal and an increase in supraspinal excitability at more extended angles, the mechanism for these changes in corticospinal excitability to biceps is not cutaneous stretch receptor feedback.

This article is protected by copyright. All rights reserved

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Growth failure in focal dermal hypoplasia

Focal dermal hypoplasia (FDH) is a rare genetic disorder caused by mutations in the PORCN gene located on the X chromosome. Short stature was previously noted to be a common finding in FDH, however the etiology of this is unclear. The present study sought to elucidate specific causes for short stature by assessing growth charts, determining bone ages and auxologic measurements, examining laboratory data for the common causes of growth failure, assessing dietary intake, and performing a growth hormone stimulation test. Sixteen patients with FDH between the ages of 3 and 18 years of age consented to the study. While 11 out of 16 patients had short stature based on height less than 2 standard deviations below mid‐parental target height percentile and bone age not suggestive of likely catch‐up growth, only four had a BMI less than the 5th percentile for age. Laboratory studies did not support a gastrointestinal, allergy or autoimmune cause of growth failure. Three patients had results suggestive of possible growth hormone deficiency. Although short stature is a common feature in FDH, our data suggests that severe undernutrition is not common in this group and that there may be underlying treatable causes for this short stature in some patients.

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Repeated anodal trans‐spinal direct current stimulation results in long‐term reduction of spasticity in mice with spinal cord injury

Key points

Spasticity is a disorder of muscle tone that is associated with lesions of the motor system. This condition involves an overactive spinal reflex loop that resists passive lengthening of muscles. Previously, we established that application of anodal trans‐spinal direct current stimulation (tsDCS) for short periods of time to anaesthetized mice sustaining a spinal cord injury leads to an instantaneous reduction of spasticity. However, the long‐term effects of repeated a‐tsDCS and its mechanism of action remained unknown. Here, a‐tsDCS was performed for 7 days and this was found to cause long‐term reduction in spasticity, increase rate‐dependent depression in spinal reflexes, and improve ground and skill locomotion. Pharmacological, molecular, and cellular evidence further suggest that a novel mechanism involving Na‐K‐Cl cotransporter isoform 1 (NKCC1) mediates the observed long‐term effects of repeated a‐tsDCS.

Abstract

Spasticity can cause pain and fatigue, sleep disturbances, it can restrict daily activities such as walking, sitting, and bathing, and it can complicate rehabilitation efforts. Thus, spasticity negatively influences an individual's quality of life and novel therapeutic interventions are needed. We previously demonstrated in anaesthetized mice that a short period of trans‐spinal subthreshold direct current stimulation (tsDCS) reduces spasticity. In the present study, the long‐term effects of repeated tsDCS to attenuate abnormal muscle tone in awake female mice with spinal cord injuries were investigated. A motorized system was used to test velocity‐dependent ankle resistance and associated electromyographical activity. Analysis of ground and skill locomotion was also performed, while electrophysiological, molecular, and cellular studies were conducted to reveal a potential underlying mechanism of action. A four‐week reduction in spasticity was associated with an increase in rate‐dependent depression of spinal reflexes and ground and skill locomotion were improved following 7 d of a‐tsDCS. Secondary molecular, cellular, and pharmacological experiments further demonstrated that the expression of K‐Cl co‐transporter isoform 2 (KCC2) was not changed in animals with spasticity. However, Na‐K‐Cl cotransporter isoform 1 (NKCC1) was significantly up‐regulated in mice that exhibited spasticity. When mice were treated with a‐tsDCS, down regulation of NKCC1 was detected, and this level did not significantly differ from that in the non‐injured control mice. Thus, long lasting reduction of spasticity by a‐tsDCS via down‐regulation NKCC1 may constitute a novel therapy for spasticity following spinal cord injury.

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Vasodilatory function in human skeletal muscle feed arteries with advancing age: the role of adropin

Key points

This study sought to determine the impact of aging on endogenous adropin levels in human skeletal muscle feed arteries (SMFAs) and the role of adropin in age‐related vascular dysfunction. Adropin protein expression falls progressively with advancing age in the human peripheral vasculature and endothelial‐dependent vasodilation, typically attenuated with age, was strongly correlated with SMFA adropin protein levels. Adropin incubation restored age‐related endothelial‐dependent vasodilatory dysfunction and increased p‐eNOS/eNOS ratio in an age‐dependent manner in the SMFAs. The role of NO bioavailability was additionally evidenced by NOS blockade ablating both the positive vascular effects of adropin incubation and the relationship between endothelial function and adropin protein expression. Additional evidence of a mechanistic link between declining adropin and age‐related endothelial dysfunction was documented by a progressively increasing magnitude of effect of adropin‐induced eNOS‐mediated vasodilation with aging. Adropin, appears to be a novel therapeutic target to facilitate the restoration of endothelial function with aging.

Abstract

This study sought to determine the impact of advancing age on endogenous adropin levels in human skeletal muscle feed arteries (SMFAs) and the role of adropin in age‐related vascular dysfunction. Adropin protein expression and vasodilatory capacity was assesed in SMFAs from Young (Y, 27 ± 2 yrs, n = 10), Middle aged (MA, 54 ± 2 yrs, n = 10), and Old (O, 75 ± 2 yrs, n = 16) subjects. Endothelial‐dependent vasodilation, with and without adropin incubation, was assessed in response to flow‐induced shear stress and acetylcholine (ACh). Both SMFA adropin protein expression and endothelial‐dependent vasodilatory function exhibited a progressive, age‐related, reduction (Flow: Y: 65 ± 3; MA: 36 ± 3; O: 15 ± 2%; ACh: Y: 63 ± 2, MA: 34 ± 3 %; O: 23 ± 3 %, P<0.05). There was a strong positive correlation between SMFA adropin protein expression and both flow‐ (r = 0.81, P<0.05) and ACh‐ (r = 0.78, P<0.05). Adropin incubation in the MA and O SMFAs restored the vasodilatory response to flow (MA+Adropin: 59 ± 3; O+Adropin: 47 ± 3 %, P<0.05) and ACh (MA+Adropin: 59 ± 3 %; O+Adropin: 49 ± 2 %, P<0.05). A mechanistic link between adropin and NO biovavailabilty was supported by 1) an increased phosphorylated eNOS/eNOS protein expression with adropin incubation only in the MA and O SMFAs, 2) eNOS blockade ablating both the positive vascular effects of adropin incubation and the relationship between endothelial function and adropin protein expression and, finally, 3) a progressive increase in the magnitude of effect of adropin‐induced eNOS‐mediated vasodilation with advancing age. Adropin could be a novel therapeutic target to facilitate the restoration of endothelial function, through increased NO bioavailability, with advancing age.

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Associations between TMEM196 polymorphisms and NSAID-exacerbated respiratory disease in asthma

Background We previously found differences in the minor allele frequency (MAF) of single-nucleotide polymorphisms (SNPs) in transmembrane protein 196 (TMEM196) between 995 patients with aspirin-tolerant asthma (ATA) and 141 asthmatic patients with NSAID-exacerbated respiratory disease (NERD). In this study, we statistically analyzed the distributions of the genotypes and haplotypes of these SNPs to determine the exact association between TMEM196 genetic variants and the risk for NERD. Materials and methods Lewontin's D′ and r2 values were used to measure linkage disequilibrium between the biallelic loci having MAFs more than 0.05, and haplotypes were inferred using the PHASE algorithm (version 2.0). The genotype distribution was analyzed by logistic regression models using age of onset, smoking status (nonsmoker=0, ex-smoker=1, smoker=2), and BMI as covariates. Regression analysis of the association between SNPs and the risk of NERD was analyzed using SPSS version 12.0 and PLINK version 1.9. Results The MAF of rs9886152 C>T was significantly lower in NERD than in ATA [24.8 vs. 34.0%, odds ratio=0.64 (0.48–0.85), P=2.07×10−3, Pcorr=0.048]. The rate of the rs9886152 C>T minor allele was significantly lower in NERD than in ATA [44.0 vs. 56.4% in the codominant model, P=0.002, Pcorr=0.049, odds ratio=0.64 (0.48–0.85)]. An additional three SNPs (rs9639334 A>G, rs9638765 A>G, and rs2097811 G>A) showed similar associations with the risk of NERD. NERD patients had lower frequencies of the rs9639334 A>G minor allele (51.1 vs. 64.4%, P=0.002, Pcorr=0.043), rs9638765 A>G (49.7 vs. 64.2%, P=0.001, Pcorr=0.017), and rs2097811 G>A (51.1 vs. 64.5%, P=0.002, Pcorr=0.04) compared with ATA patients. Patients homozygous for the minor alleles of the four SNPs showed significantly less of an aspirin-induced decrease in forced expiratory volume in one second compared with those homozygous for the common alleles (P=0.003–0.012). Conclusion The minor alleles of the four SNPs in TMEM196 may exert a protective effect against the development of NERD and may be useful genetic markers to predict the risk of NERD. * Jong-Uk Lee and Hun Soo Chang contributed equally to the writing of this article. Correspondence to Jong-Sook Park, MD, PhD, Department of Internal Medicine, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do 420-021, Republic of Korea Tel: +82 326 215 105; fax: +82 326 215 023; e-mail: newstart1221@naver.com Received May 1, 2018 Accepted December 4, 2018 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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