Point-of-Care Ultrasonography Findings and Care Use Among Patients Undergoing Ultrasound-Guided Shoulder Injections.

Objective: The aims of the study were to assess the overall reduction of pain in patients undergoing ultrasound-guided shoulder injections and to characterize the preinjection point-of-care ultrasound findings and use of clinical services postinjection including the use of magnetic resonance imaging and surgeries. Design: Data of 172 patients who underwent ultrasound-guided subacromial subdeltoid injection or glenohumeral joint injection were reviewed for preinjection point-of-care ultrasound findings, change in pain intensity at 2 mos from baseline, and use of care at 6 mos' postinjection. Pain intensity was measured by the numeric rating scale and a dichotomous report of global impression of significant improvement in pain. Responders were defined as those with 50% or more reduction in numeric rating scale or those with global impression of 50% or more improvement. Results: There were 141 responders among the 172 patients analyzed. Full-thickness rotator cuff tears were higher in the ultrasound-guided subacromial subdeltoid injection group when compared with the glenohumeral joint injection group (P = 0.038) and abnormal bicipital tendon findings higher in the glenohumeral joint injection group (P = 0.016). There were no significant differences in specific abnormal U findings between responders versus nonresponders. Twelve patients had a shoulder magnetic resonance imaging and four patients underwent operative interventions after the injection. Conclusions: Overall pain reduction after ultrasound-guided shoulder injections was favorable in the short term. There was no specific preinjection point-of-care ultrasound findings associated with clinical pain reduction after injection. Additional imaging and operative intervention after ultrasound-guided shoulder injections seemed to be relatively low. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Could Activity Modifications Indicate Physical Decline Among Adults With Symptomatic Knee Osteoarthritis?.

Objectives: Mobility activity modifications indicate early functional losses that act as precursors to future declines among community-dwelling older adults. However, there is scarce evidence on whether activity modifications indicate poorer physical health among adults with symptomatic osteoarthritis, a major cause of disability. Our purpose was to investigate whether patient-reported mobility activity modifications indicated poorer physical health among adults with symptomatic knee osteoarthritis. Design: Secondary cross-sectional analysis of randomized trial data was performed. Preclinical Disability Questionnaire was used to group participants into the following three categories: difficulty, modified, and no difficulty walking/stair climbing. Kruskal Wallis and [chi]2 tests were used to compare clinical factors across groups. Results: Among 121 participants (median age = 60 yrs; 73% female; 60% white), less than 10% had modified walking/stair climbing. Compared with those with no walking difficulty, participants with modified walking had significantly less balance (P = 0.01) and global health (P = 0.01) as well as greater knee pain (P = 0.05) and physical disability (P = 0.04). Those with modified stair climbing had significantly smaller walking distances (P = 0.03) compared with those with no difficulty stair climbing. Conclusions: Activity modifications may signal early impairments in physical health among people with symptomatic knee osteoarthritis. If confirmed, patient-reported activity modifications may enhance symptom evaluation in osteoarthritis and enable a better understanding of the disablement process. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Mouse retinal ganglion cell signalling is dynamically modulated through parallel anterograde activation of cannabinoid and vanilloid pathways

Abstract

How retinal ganglion cells (RGCs) process and integrate synaptic, mechanical, swelling stimuli with light inputs is an area of intense debate. The nociceptive cation channel TRPV1 (transient receptor potential vanilloid type 1) modulates RGC Ca²⁺ signals and excitability yet the proportion of RGCs that express it remains unclear. Further, TRPV1's response to endocannabinoids (eCBs), the putative endogenous retinal activators unknown, as is the potential modulation by cannabinoid receptors (CBRs). The expression of TRPV1 in RGCs from the Ai9:Trpv1 reporter mouse was nonuniform with peak density in the early- and mid-peripheral retina. TRPV1 agonists including capsaicin (CAP) and the endocannabinoids (eCBs) anandamide and N-arachidonoyl-dopamine, elevated [Ca²⁺]_i in 30–40% of wild type RGCs, with effects suppressed by TRPV1 antagonists capsazepine (CPZ) and BCTC, and lacking in Trpv1^−/− cells. The cannabinoid receptor type 1 (CBR1) colocalized with TRPV1:tdTomato expression. Its agonists 2-arachidonoylglycerol (2-AG) and WIN55,122 inhibited CAP-induced [Ca²⁺]_i signals in adult, but not early postnatal, RGCs. The suppressive effect of 2-AG on TRPV1 activation was emulated by positive modulators of the protein kinase A pathway, inhibited by the CB1R antagonist rimonabant and G_i uncoupler pertussis toxin (PTX), and absent in Cnr1^−/− RGCs. We conclude that TRPV1 is a modulator of Ca²⁺ homeostasis in a subset of mouse RGCs that show peak expression in the mid-peripheral retina. Nonretrograde eCB-mediated modulation of RGC signalling involves a dynamic push-pull between direct TRPV1 activation and PKA-dependent regulation of channel inactivation, with potential functions in setting the bandwidth of postsynaptic responses, sensitivity to mechanical/excitotoxic stress and neuroprotection.

This article is protected by copyright. All rights reserved

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Hypertonic-NaCl versus osmotic stimuli: distinct OVLT neurones can sense the difference to control sympathetic outflow and blood pressure

Abstract

Despite large fluctuations in salt and water intake, mammals are able to maintain electrolyte concentrations, particularly sodium (Na⁺) as the major determinant of osmolality of the extracellular fluid (ECF), within narrow physiological limits (∼300 mOsm kg⁻¹).

This article is protected by copyright. All rights reserved

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Use of stylet in armored tube for nasotracheal intubation: Why not??

Related Articles

Use of stylet in armored tube for nasotracheal intubation: Why not??

Saudi J Anaesth. 2017 Jul-Sep;11(3):367-368

Authors: Bihani P, Bhatia PK, Mohhammad S, Sethi P

PMID: 28757852 [PubMed]

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Low prevalence of hepatitis B and hepatitis C virus serum markers in a cohort of pregnant women from Southern Italy

Mother-to-child transmission is still considered a major factor in the spread of hepatitis viruses. Nevertheless, epidemiological data on hepatitis B virus (HBV) and hepatitis C virus (HCV) in reproductive-age women are limited even in areas like the South of Italy where both viruses had been widespread.

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A Consumer’s Guide for Probiotics: 10 Golden Rules for a Correct Use

Probiotics are used all over the world as their beneficial effects on the human organism have been widely demonstrated. Certain probiotics can down-regulate production of pro-inflammatory cytokines and promote intestinal epithelial barrier functions, increasing an anti-inflammatory response and contributing to the host's overall health. The main mechanisms by which probiotic microorganisms can interact with the host are by modulating the immune system and the epithelial cell functions and interacting with intestinal gut microbiota.

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Indicators of suboptimal tumor necrosis factor antagonist therapy in inflammatory bowel disease

Inflammatory bowel disease (IBD) is refractory to treatment in one-half of patients.

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Low prevalence of hepatitis B and hepatitis C virus serum markers in a cohort of pregnant women from Southern Italy

Mother-to-child transmission is still considered a major factor in the spread of hepatitis viruses. Nevertheless, epidemiological data on hepatitis B virus (HBV) and hepatitis C virus (HCV) in reproductive-age women are limited even in areas like the South of Italy where both viruses had been widespread.

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A Consumer’s Guide for Probiotics: 10 Golden Rules for a Correct Use

Probiotics are used all over the world as their beneficial effects on the human organism have been widely demonstrated. Certain probiotics can down-regulate production of pro-inflammatory cytokines and promote intestinal epithelial barrier functions, increasing an anti-inflammatory response and contributing to the host's overall health. The main mechanisms by which probiotic microorganisms can interact with the host are by modulating the immune system and the epithelial cell functions and interacting with intestinal gut microbiota.

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Indicators of suboptimal tumor necrosis factor antagonist therapy in inflammatory bowel disease

Inflammatory bowel disease (IBD) is refractory to treatment in one-half of patients.

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Impedance cardiography in healthy children and children with congenital heart disease: Improving stroke volume assessment

Publication date: Available online 1 August 2017
Source:International Journal of Psychophysiology
Author(s): Ineke Nederend, Arend D.J. ten Harkel, Nico A. Blom, Gary G. Berntson, Eco J.C. de Geus
IntroductionStroke volume (SV) and cardiac output are important measures in the clinical evaluation of cardiac patients and are also frequently used in research applications. This study was aimed to improve SV scoring derived from spot-electrode based impedance cardiography (ICG) in a pediatric population of healthy volunteers and patients with a corrected congenital heart defect.Methods128 healthy volunteers and 66 patients participated. First, scoring methods for ambiguous ICG signals were optimized to improve agreement of B- and X-points with aortic valve opening/closure in simultaneously recorded transthoracic echocardiography (TTE). Building on the improved scoring of B- and X-points, the Kubicek equation for SV estimation was optimized by testing the agreement with the simultaneously recorded SV by TTE. Both steps were initially done in a subset of the sample of healthy children and then validated in the remaining subset of healthy children and in a sample of patients.ResultsSV assessment by ICG in healthy children strongly improved (intra class correlation increased from 0.26 to 0.72) after replacing baseline thorax impedance (Z0) in the Kubicek equation by an equation (7.337–6.208∗dZ/dtmax), where dZ/dtmax is the amplitude of the ICG signal at the C-point. Reliable SV assessment remained more difficult in patients compared to healthy controls.ConclusionsAfter proper adjustment of the Kubicek equation, SV assessed by the use of spot-electrode based ICG is comparable to that obtained from TTE. This approach is highly feasible in a pediatric population and can be used in an ambulatory setting.



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One gene member of the ADP-ribosylation factor family is heat-inducible and enhances seed germination in Nicotiana tabacum

Abstract

ADP ribosylation factors (ARFs), one group within the Ras superfamily of GTP-binding proteins, are ubiquitous within the eukaryotic kingdom. The functions of ARFs are extensive, and include regulatory roles in vesicular transportation, lipid metabolism, and microtubule dynamics, and the cellular processes related to these roles. Most ARFs have been identified from mammalian species and yeast; although little is known about the functional importance of ARFs in plants, it seems to be equally diverse and significant. We have been working on plant responses under heat stress, and showed that heat-shock can induce seed germination (Koo et al. in Plant Physiol 167:1030–1038, 2015). In the present study, we report nine ARF gene family members from tobacco (Nicotiana tabacum), all belonging to the same group (Class 1) in the phylogenetic analysis. One family member, NtARF1, was induced under high-temperature stress. To elucidate the biological function of NtARF1, we generated transgenic tobacco plants overexpressing NtARF1 and the seeds of these transgenic tobacco plants germinated earlier than the seeds of non-transgenic tobacco plants. We also classified ARF family genes in plant species through systematic genomic DNA sequence data-mining, focusing on the fully sequenced and extensively annotated genomes of Arabidopsis thaliana, Brachypodium distachyon, Medicago truncatula, Mimulus guttatus, Nicotiana benthamiana, Setaria italica, Solanum lycopercisum, and Solanum tuberosum, and of some major crops including rice, soybean, corn, and tobacco. The Class 1 of our phylogenetics analysis comprised the highest number of ARFs among the four groups obtained for all plant species analyzed, especially for crop plant species.

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Wis. firefighter-paramedic invited to meet with Trump after inventing special compass

Jeff Dykes' compass would direct firefighters through burning buildings; he will participate in a business roundtable with President Trump

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Toll ligand Spatzle3 controls melanization in the stripe pattern formation in caterpillars [Genetics]

A stripe pattern is an aposematic or camouflage coloration often observed among various caterpillars. However, how this ecologically important pattern is formed is largely unknown. The silkworm dominant mutant Zebra (Ze) has a black stripe in the anterior margin of each dorsal segment. Here, fine linkage mapping of 3,135 larvae...

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Severe viral respiratory infections in children with IFIH1 loss-of-function mutations [Genetics]

Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome...

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Date set for nation's first EMS Compact meeting

REPLICA FALLS CHURCH, Va. — The Recognition of EMS Personnel Licensure Compact (REPLICA) participating states announce that the first full meeting will be held on Oct. 7-8, 2017, in Oklahoma City,Oklahoma. Member state representatives will be officially seated on the Interstate Commission for EMS Personnel Practice (Interstate Commission). In addition, the public is invited to participate in a ...

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Free EMT certification courses offered to military veterans

By EMS1 Staff CLIFTON PARK, N.Y. — A free EMT certification class will be offered to military veterans by the Saratoga County Emergency Council this fall. The Saratogian reported that the aim of the class is to prepare students for a career in EMS while fostering personal growth. The free program will also include counseling and support referrals, local veteran resource access and career consulting ...

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Risk of Depressive Symptoms Associated with Morbidity in Postpartum Women in Rural Bangladesh

Abstract

Objectives Depression following pregnancy is common, but its extent and association with maternal morbidity in the first 6 months postpartum have not been well described in low resource settings such as rural Bangladesh. Methods We used data from a population-based, community trial of approximately 39,000 married rural Bangladeshi women aged 13–44 between 2001 and 2007 to examine the relation between women's reported morbidity symptoms from childbirth to 3 months postpartum, and subsequent depressive symptoms assessed at 6 months postpartum. We calculated crude and adjusted risk ratios for depressive symptoms following women's reports of reproductive, urinary, neurologic, nutrition and other illness measures constructed based on symptomatic reporting. Results In models adjusted for sociodemographic factors and co-morbidities, all postpartum illnesses were associated with an increased relative risk [RR, with 95% confidence intervals (CI) excluding 1] of depressive symptoms by 6 months postpartum. These morbidities included uterine prolapse (RR 1.20, 95% CI 1.04–1.39), urinary tract infection (RR 1.24, 95% CI 1.11–1.38), stress related incontinence (SRI) (RR 1.49, 95% 1.33–1.67), simultaneous SRI and continuously dripping urine (RR 1.60–2.96), headache [RR 1.20 (95% CI 1.12–1.28)], convulsions (RR 1.67, 95%CI 1.36–2.06), night blindness (RR 1.33, 95% CI 1.19–1.49), anemia (RR 1.38, 95% CI 1.31–1.46), pneumonia (RR 1.24, 95% CI 1.12–1.37), gastroenteritis (RR 1.24, 95% CI 1.17–1.31) and hepatobiliary disease (RR 2.10, 96% CI 1.69–2.60). Conclusions for Practice Illnesses during the first three postpartum months were risk factors for depressive symptoms, with the strongest associations noted for convulsions and hepatobiliary disease. Symptoms of depression may be of particular concern among women suffering from physical illnesses.

Clinical trial registration: ClinicalTrials.gov NCT0019882.

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UK EMS crews line road with ambulances for colleague who died of cancer

Lance Cox, 42, lost his battle with stomach cancer last month

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Distribution of 137Cs on components in urban area four years after the Fukushima Dai-ichi Nuclear Power Plant accident

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): K. Yoshimura, K. Saito, K. Fujiwara
Distribution of ¹³⁷Cs on components in urban areas such as roofs and roads is crucial for evaluating the behavior of radiocesium and ambient dose rates in the area. This study evaluated relative ¹³⁷Cs inventories, which are defined as the relative values of ¹³⁷Cs inventory on each component to that on a nearby permeable plane field, for 11 buildings in the evacuation zone about four years after the Fukushima Dai-ichi Nuclear Power Plant accident. The average relative inventory of paved ground accounted for 0.18 of that on permeable plane fields. Other components showed small average values of less than 0.1, indicating rapid removal of radiocesium from urban areas even without decontamination. The differences in the relative inventories on roads and roofs with those in the case of Europe suggest that human activity and component materials largely affect the reduction of radiocesium in urban area.



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Prognostic factors in critically ill patients with hematological malignancy admitted to the general intensive care unit: a single-center experience in Japan

Abstract

Purpose

This study aims to identify prognostic factors related to short-term and long-term outcomes of patients with hematological malignancy (HM) admitted to the intensive care unit (ICU) in Japan during ICU stay and after discharge from ICU.

Methods

We conducted a retrospective, observational study of 169 patients with HM admitted to the general ICU from January 2009 to December 2016. We examined prognostic factors affecting outcome during ICU stay and at 180 days after ICU discharge using logistic regression analysis.

Results

During ICU stay, 57 patients (33.7%) died. Invasive mechanical ventilation (OR 8.96, 95% CI 3.67–21.9; P < 0.001, the same hereinafter), the Sequential Organ Failure Assessment (SOFA) score within the first 24 h of ICU admission (1.25, 1.11–1.40; P < 0.001), and malignant lymphoma (0.30, 0.11–0.78; P = 0.014) were detected as factors associated with ICU outcome. Of 112 ICU survivors, 46 (41.1%) died within 180 days after ICU discharge. Duration of ICU stay (1.07, 1.01–1.13; P = 0.027) and the SOFA score at ICU discharge (1.24, 1.04–1.48; P = 0.016) were related to poor outcome at 180 days after ICU discharge.

Conclusions

In critically ill patients with HM, the use of invasive mechanical ventilation, a high SOFA score within the first 24 h of ICU admission, and malignant lymphoma as primary HM affected short-term ICU outcome. Increased duration of ICU stay and SOFA score at ICU discharge influenced long-term outcome at 180 days after ICU discharge.

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UK EMS crews line road with ambulances for colleague who died of cancer

Lance Cox, 42, lost his battle with stomach cancer last month

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Maximizing Opportunities: Family Planning and Maternal, Infant, and Young Child Nutrition Integration in Bondo Sub-County, Kenya

Abstract

Purpose This article shares learning from an innovative demonstration program integrating maternal, infant, and young child nutrition (MIYCN) and family planning (FP) services in western Kenya, providing recommendations for future work to expand MIYCN and FP integration. Description Six health facilities reorganized to integrate MIYCN and FP services and community health volunteers (CHVs) promoted MIYCN and FP in adjacent communities in Bondo Sub-County over a 1-year period. At the facility level, each provider was directed to provide both sets of services in a single room during FP, antenatal care, postnatal care, or child consultation visits (a "one stop shop" approach). At community level, CHVs were to conduct household visits equipped with new integrated materials and incorporate MIYCN and FP within community activities. Assessment Although the "one stop shop" approach, where one provider offers all integrated services in one room, was initially proposed for all facilities, this worked most effectively in the dispensary and health centers. The sub-county hospital adapted the approach such that integrated services were offered by more than one provider during a visit, with clients linked from one provider to another through same-day intra-facility referrals. CHVs were generally able to incorporate MIYCN and FP content within household visits and community activities; however some knowledge gaps were noted after initial training, necessitating additional refresher training. Conclusion This demonstration experience revealed that future replication efforts should enable sub-county team leadership, assess facility readiness, streamline data collection, build local buy-in, and prioritize dispensaries and health centers with high client loads.

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What Do Pediatricians Tell Parents About Bed-Sharing?

Abstract

Background and objectives Despite the risks of bed-sharing, little is known about what pediatricians tell parents about bed-sharing with infants and whether pediatricians provide specific recommendations outlined by the American Academy of Pediatrics (AAP). This study aimed to understand pediatricians' opinions about bed-sharing and the advice pediatricians provide to parents about bed sharing. Methods The study employed a qualitative study design and the conceptual framework of the Theory of Planned Behavior. 24 primary care pediatricians from a variety of practice settings were interviewed about the anticipatory guidance they provide to families whose infants are in the at-risk age group for SIDS. Results Pediatricians' opinions about bed-sharing differed widely both with respect to identifying bed-sharing as a topic they routinely address in anticipatory guidance as well as in what they tell parents about bed sharing. Some strongly and routinely advise against bed-sharing and identify bed-sharing as a clear risk to infants. Others believe bed-sharing to be both safe and useful. A third group allow the content of anticipatory guidance to be driven by parental concerns. Most pediatricians are clearer in their recommendation to place infants supine to sleep than in their recommendation to avoid bed-sharing. Conclusions Overall, there is considerable variation among pediatricians in the advice they provide about bed-sharing, and most advice is not congruent with the AAP recommendations. Additional efforts to educate pediatricians may be necessary to change attitudes and behaviors with respect to anticipatory guidance about safe sleep.

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Breastfeeding and Exposure to Past, Current, and Neighborhood Violence

Abstract

Objectives Breastfeeding has short- and long-term health benefits for children and mothers, but US breastfeeding rates are suboptimal. Exposure to violence may contribute to these low rates, which vary by race/ethnicity. We studied: (1) whether patterns of violence exposure differ by race/ethnicity and (2) whether these patterns are associated with breastfeeding outcomes. Methods We conducted a secondary analysis of data drawn from self-report surveys completed by a convenience sample of low-income postpartum women (n = 760) in upstate New York. Latent class analysis was used to identify groups of women with similar responses to seven violence measures, including childhood physical and/or sexual violence, experience of partner violence during or just after pregnancy (physical, emotional, verbal), and neighborhood violence (perceived or by ZIP code). Logistic regression and survival analysis were utilized to determine if classes were associated with breastfeeding initiation, duration, and exclusivity, controlling for demographics. Results Exposure to at least one form of violence was high in this sample (87%). We identified 4 classes defined by violence exposure (combining current and historical exposures). Violence exposure patterns differed between racial/ethnic groups, but patterns were inconsistently associated with breastfeeding plans or outcomes. For White women, history of violence exposure increased the likelihood of earlier breastfeeding cessation. By contrast, among Black women, history of violence exposure increased the likelihood of having a breastfeeding plan and initiating breastfeeding. Conclusions for Practice Some differences between violence exposure classes are likely due to the correlation between race/ethnicity and socioeconomic status in the community studied. Additional studies are warranted to better understand how exposure to violence is related to breastfeeding and how best to support women making decisions about intention, initiation, and duration of breastfeeding.

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Facilitators and Barriers to Disclosure of Postpartum Mood Disorder Symptoms to a Healthcare Provider

Abstract

Objectives This study explored perceived barriers and facilitators to disclosure of postpartum mood disorder (PPMD) symptoms to healthcare professionals among a community-based sample. Methods A sample of predominantly white, middle class, partnered, adult women from an urban area in the southeast United States (n = 211) within 3 years postpartum participated in an online survey including the Perceived Barriers to Treatment Scale, the Maternity Social Support Scale, the Depression, Anxiety and Stress Scales-21, and items querying PPMD disclosure. Perceived barriers were operationalized as factors, from the patient's perspective, that impede or reduce the likelihood of discussing her postpartum mood symptoms with a healthcare provider. Analyses examined: (1) characteristics associated with perceived barriers; (2) characteristics associated with perceived social support; and (3) characteristics, perceived barriers, and perceived social support as predictors of disclosure. Results Over half of the sample reported PPMD symptoms, but one in five did not disclose to a healthcare provider. Approximately half of women reported at least one barrier that made help-seeking "extremely difficult" or "impossible." Over one-third indicated they had less than adequate social support. Social support and stress, but not barriers, were associated with disclosure in multivariable models. Conclusions for Practice Many women experiencing clinically-significant levels of distress did not disclose their symptoms of PPMD. Beyond universal screening, efforts to promote PPMD disclosure and help-seeking should target mothers' social support networks.

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UK EMS crews line road with ambulances for colleague who died of cancer

Lance Cox, 42, lost his battle with stomach cancer last month

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UK EMS crews line road with ambulances for colleague who died of cancer

Lance Cox, 42, lost his battle with stomach cancer last month

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Monoallelic FGFR3 and Biallelic ALPL mutations in a Thai girl with hypochondroplasia and hypophosphatasia

Skeletal dysplasias are a complex group of more than 350 disorders with phenotypic and genotypic heterogeneity affecting bone and cartilage growth. We studied a 2-year-old girl and her 21-year-old mother with disproportionate short stature. In addition to typical features of hypochondroplasia found in both patients, the child had deformities of the extremity bones, metaphyseal flares, and bilateral transverse (Bowdler) fibular spurs with overlying skin dimples detected at birth. Intravenous pamidronate was started in the child since the age of 17 days, and then every two months. Exome sequencing revealed that the girl was heterozygous for a missense mutation (c.1651A>G, p.Ile538Val) in exon 13 of FGFR3, a known mutation for hypochondroplasia, inherited from her mother. Interestingly, the child also harbored compound heterozygous missense mutations in exon 12 of ALPL, c.1460C>T (p.Ala487Val) inherited from her mother and c.1479C>A (p.Asn493Lys) inherited from her healthy father. The former mutation was previously reported in perinatal hypophosphatasia while the latter was novel. Constantly reduced serum alkaline phosphatase levels including the one before the pamidronate administration and a substantially elevated level of plasma pyridoxal 5′-phosphate detected at age 28 months supported the diagnosis of hypophosphatasia. After a definite diagnosis was achieved, pamidronate was withdrawn at the age of 28 months. No adverse events were observed during pamidronate therapy. In conclusion, we describe a unique case with monoallelic FGFR3 and biallelic ALPL mutations leading to features of both hypochondroplasia and hypophosphatasia.

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Best practices in peri-operative management of patients with skeletal dysplasias

Patients with skeletal dysplasia frequently require surgery. This patient population has an increased risk for peri-operative complications related to the anatomy of their upper airway, abnormalities of tracheal-bronchial morphology and function; deformity of their chest wall; abnormal mobility of their upper cervical spine; and associated issues with general health and body habitus. Utilizing evidence analysis and expert opinion, this study aims to describe best practices regarding the peri-operative management of patients with skeletal dysplasia. A panel of 13 multidisciplinary international experts participated in a Delphi process that included a thorough literature review; a list of 22 possible care recommendations; two rounds of anonymous voting; and a face to face meeting. Those recommendations with more than 80% agreement were considered as consensual. Consensus was reached to support 19 recommendations for best pre-operative management of patients with skeletal dysplasia. These recommendations include pre-operative pulmonary, polysomnography; cardiac, and neurological evaluations; imaging of the cervical spine; and anesthetic management of patients with a difficult airway for intubation and extubation. The goals of this consensus based best practice guideline are to provide a minimum of standardized care, reduce perioperative complications, and improve clinical outcomes for patients with skeletal dysplasia.

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Three cases of multi-generational Pompe disease: Are current practices missing diagnostic and treatment opportunities?

Pompe disease (Glycogen storage disease type II, GSDII, or acid maltase deficiency) is an autosomal recessive metabolic myopathy with a broad clinical spectrum, ranging from infantile to late-onset presentations. In 2015, Pompe disease was added as a core condition to the Recommended Uniform Screening Panel for state newborn screening (NBS). The clinical importance of Pompe disease is evolving with the use of NBS, increasing awareness of the disease, and higher than previously reported disease prevalence; however, current practices miss additional diagnostic and potential treatment opportunities in close relatives of the family proband. In this report, we describe three families with multiple individuals in multiple generations affected by both infantile and late-onset clinical presentations of Pompe disease. The presence of multi-generational disease within these families highlights the importance of subsequent risk assessment through medical history and physical examination, with a low threshold for the screening of a proband's family members. We recommend enzymology (GAA activity assay) as the first screening method, as opposed to targeted mutation analysis, for at-risk family members. Given that the initial symptoms of the slowly progressive late-onset presentation of Pompe disease may be mild or non-specific, enzymatic testing of all parents of affected infants should be considered.

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UK EMS crews line road with procession for colleague who died of cancer

Lance Cox, 42, lost his battle with stomach cancer last month

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Transarterial chemoembolization with miriplatin vs. epirubicin for unresectable hepatocellular carcinoma: a phase III randomized trial

Abstract

Background

This prospective study investigated the superiority of transarterial chemoembolization (TACE) with miriplatin over TACE with epirubicin regarding overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC).

Methods

Patients with unresectable HCC were randomized 1:1 to receive TACE with miriplatin or epirubicin in lipiodol. The primary endpoint was OS; secondary endpoints were percentages of patients who achieved treatment effect (TE) 4 (100% necrotizing effect or tumor reduction), duration of time to TACE failure, and adverse events (AEs). OS was compared using a stratified log-rank test adjusted for clinical stage, Child–Pugh class, and institution.

Results

Of 257 patients enrolled from August 2008 to August 2010, 247 were analyzed for efficacy and toxicity (miriplatin, n = 124; epirubicin, n = 123). Baseline characteristics were well balanced between the two groups. Median OS times were 1111 days for miriplatin and 1127 days for epirubicin (adjusted hazard ratio 1.01, 95% confidence interval 0.73–1.40, P = 0.946). TE4 rates were 44.4% for miriplatin and 37.4% for epirubicin. Median times to TACE failure were 365.5 days for miriplatin and 414.0 days for epirubicin. AEs of grade 3 or higher, including elevated aspartate aminotransferase (miriplatin, 39.5%; epirubicin, 57.7%) and elevated alanine aminotransferase (miriplatin, 31.5%; epirubicin, 53.7%), were less frequent in the miriplatin than the epirubicin group.

Conclusions

OS after TACE with miriplatin was not superior to that after TACE with epirubicin; however, hepatic AEs were less frequent with miriplatin.

Clinical Trial Registration: JapicCTI-080632.

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Reply to “Prolongation of Terminal Latency of the Phrenic Nerve in Amyotrophic Lateral Sclerosis – Is it Clinically Useful, and what are the Mechanisms?”

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Jin-Sung Park, Donghwi Park




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EEG-arousal regulation as predictor of treatment response in patients suffering from obsessive compulsive disorder

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Anna-Lena Dohrmann, Katarina Stengler, Ina Jahn, Sebastian Olbrich
ObjectivesAim of this study was to analyze whether electroencephalogram (EEG)-based CNS-arousal markers differ for patients suffering from obsessive compulsive disorder (OCD) that either respond or do not respond to cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs) or their combination. Further the study aimed to identify specific response-predictors for the different therapy approaches.MethodsCNS-arousal from 51 unmedicated patients during fifteen-minute resting state was assessed using VIGALL (Vigilance Algorithm Leipzig). Clinical Global Impression (CGI) scores were used to assess response or non-response after three to six months following therapy (CBT, n=18; SSRI, n=11 or combination, n=22). Differences between Responders (R) and Non-Responders (NR) were identified using multivariate analysis of covariance (MANCOVA) models.ResultsMANCOVA revealed that Responders spent significant less time at the highest CNS-arousal stage 0. Further, low amounts of the highest CNS-arousal stages were specifically predictive for a response to a combined treatment approach.ConclusionsThe fact that CNS-arousal markers allowed discrimination between Responders and Non-Responders and also between Responders of different treatment arms underlines a possible clinical value of EEG-based markers.SignificanceThese results encourage further research on EEG-arousal regulation for determining pathophysiological subgroups for treatment response.



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Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub




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A double determination of central motor conduction time in the assessment of Hirayama disease

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Chaojun Zheng, Dongqing Zhu, Feizhou Lu, Yu Zhu, Xiaosheng Ma, Xinlei Xia M.D, Jianyuan Jiang
ObjectiveTo investigate central motor conduction time (CMCT) in patients with Hirayama disease (HD) and to analyse the role of motor nerve root lesions in the pathogenesis of HD.MethodsCMCT measured by F-wave (CMCT-F) and by paravertebral magnetic stimulation (CMCT-M) was performed on both abductor pollicis brevis (APB) and abductor digiti minimi (ADM) in 41 HD patients and 22 controls. All patients underwent neck-flexion magnetic resonance imaging evaluation.ResultsProlonged CMCT (CMCT-F and/or CMCT-M) was recorded in at least one tested muscle from 7/41 (17.1%) HD patients, and 4 cases presented significant prolonged CMCT-M with normal CMCT-F on the side with significant cervical cord forward-shifting. This asymmetric forward-shifting was identified in 13 HD patients, and forward-shifting on the symptomatic side was more obvious. Compared to the controls (ADM: 0.9±0.3 ms; APB: 0.8±0.3 ms) and the other 28 HD patients (symptomatic side: ADM: 0.8±0.2 ms, APB: 0.8±0.3 ms), increased nerve root conduction times were demonstrated in these symptomatic sides (ADM: 1.5±0.7 ms; APB: 1.2±0.6 ms) (P<0.05).ConclusionsMotor nerve root may be main lesion site in some HD patients, especially on the symptomatic side of patients with asymmetric neck-flexion cervical cord forward-shifting.SignificanceCompared to spinal motor neuron lesions, damage to motor nerve root (intra- and/or extra-medullary motor roots) may play an equally important role in the pathogenesis of HD. Abnormally increased forward traction in shorter nerve roots may be the cause for the main damage in motor nerve root.



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Prolongation of Terminal Latency of the Phrenic Nerve in Amyotrophic Lateral Sclerosis – Is it Clinically Useful, and what are the Mechanisms?

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Mamede de Carvalho




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Reply to “Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia”

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Antoine Guéguen, Claude Jardel, Marc Polivka, S. Veronica Tan, Françoise Gray, Catherine Vignal, Anne Lombès, Olivier Gout, Hugh Bostock




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Fine motor skills predict performance in the Jebsen Taylor Hand Function Test after stroke

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Kathrin Allgöwer, Joachim Hermsdörfer
ObjectiveTo determine factors characterizing the differences in fine motor performance between stroke patients and controls. To confirm the relevance of the factors by analyzing their predictive power with regard to the Jebsen Taylor Hand Function Test (JTHFT), a common clinical test of fine motor control.MethodsTwenty-two people with slight paresis in an early chronic phase following stroke and twenty-two healthy controls were examined.. Performance on the JTHFT, Nine-Hole Peg Test and 2-point discrimination was evaluated. To analyze object manipulation skills, grip forces and temporal measures were examined during 1) lifting actions with variations of weight and surface 2) cyclic movements 3) predictive/reactive catching tasks. Three other aspects of force control included 4) visuomotor tracking 5) fast force changes and 6) grip strength.ResultsBased on 9 parameters which significantly distinguished fine motor performance in the two groups, we identified three principal components (factors): grip force scaling, motor coordination and speed of movement. The three factors are shown to predict JTHFT scores via linear regression (R²=.687, p<.001).ConclusionsWe revealed a factor structure behind fine motor impairments following stroke and showed that it explains JTHFT results to a large extend.Significance: This result can serve as a basis for improving diagnostics and enabling more targeted therapy.



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Applying a pelvic corrective force induces forced use of the paretic leg and improves paretic leg EMG activities of individuals post-stroke during treadmill walking

Publication date: Available online 31 July 2017
Source:Clinical Neurophysiology
Author(s): Chao-Jung Hsu, Janis Kim, Rongnian Tang, Elliot J. Roth, William Z. Rymer, Ming Wu
ObjectiveTo determine whether applying a mediolateral corrective force to the pelvis during treadmill walking would enhance muscle activity of the paretic leg and improve gait symmetry in individuals with post-stroke hemiparesisMethodsFifteen subjects with post-stroke hemiparesis participated in this study.A customized cable-driven robotic system based over a treadmill generated a mediolateral corrective force to the pelvis toward the paretic side during early stance phase. Three different amounts of corrective force were applied. Electromyographic (EMG) activity of the paretic leg, spatiotemporal gait parameters and pelvis lateral displacement were collected.ResultsSignificant increases in integrated EMG of hip abductor, medial hamstrings, soleus, rectus femoris, vastus medialis and tibialis anterior were observed when pelvic corrective force was applied, with pelvic corrective force at 9% of body weight inducing greater muscle activity than 3% or 6% of body weight. Pelvis lateral displacement was more symmetric with pelvic corrective force at 9% of body weight.ConclusionsApplying a mediolateral pelvic corrective force toward the paretic side may enhance muscle activity of the paretic leg and improve pelvis displacement symmetry in individuals post-stroke.SignificanceForceful weight shift to the paretic side could potentially force additional use of the paretic leg and improve the walking pattern.



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The performing animal: causes and consequences of body remodeling and metabolic adjustments in red knots facing contrasting thermal environments

Using red knots (Calidris canutus) as a model, we determined how changes in mass and metabolic activity of organs relate to temperature-induced variation in metabolic performance. In cold-acclimated birds, we expected large muscles and heart as well as improved oxidative capacity and lipid transport, and we predicted that this would explain variation in maximal thermogenic capacity (M_sum). We also expected larger digestive and excretory organs in these same birds and predicted that this would explain most of the variation in basal metabolic rate (BMR). Knots kept at 5°C were 20% heavier and maintained 1.5 times more body fat than individuals kept in thermoneutral conditions (25°C). The birds in the cold also had a BMR up to 32% higher and a M_sum 16% higher than birds at 25°C. Organs were larger in the cold, with muscles and heart being 9–20% heavier and digestive and excretory organs being 21–36% larger than at thermoneutrality. Rather than the predicted digestive and excretory organs, the cold-induced increase in BMR correlated with changes in mass of the heart, pectoralis, and carcass. M_sum varied positively with the mass of the pectoralis, supracoracoideus, and heart, highlighting the importance of muscles and cardiac function in cold endurance. Cold-acclimated knots also expressed upregulated capacity for lipid transport across mitochondrial membranes [carnitine palmitoyl transferase (CPT)] in their pectoralis and leg muscles, higher lipid catabolism capacity in their pectoralis muscles [β-hydroxyacyl CoA-dehydrogenase (HOAD)], and elevated oxidative capacity in their liver and kidney (citrate synthase). These adjustments may have contributed to BMR through changes in metabolic intensity. Positive relationships among M_sum, CPT, and HOAD in the heart also suggest indirect constraints on thermogenic capacity through limited cardiac capacity.

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Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction

Intrauterine growth restriction (IUGR) is associated with persistent metabolic complications, but information is limited for IUGR infants. We determined glucose-stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR (n = 7) were compared with control lambs (n = 8). GSIS was measured at 8 ± 1 days of age, and at 15 ± 1 days, body weight-specific glucose utilization rates were measured with radiolabeled d-glucose during a hyperinsulinemic-euglycemic clamp (HEC). IUGR lambs weighed 23% less (P < 0.05) than controls at birth. Fasting plasma glucose and insulin concentrations were not different between IUGR and controls for either study. First-phase insulin secretion was enhanced 2.3-fold in IUGR lambs compared with controls. However, second-phase insulin concentrations, glucose-potentiated arginine-stimulated insulin secretion, and β-cell mass were not different, indicating that IUGR β-cells have an intrinsic enhancement in acute GSIS. Compared with controls, IUGR lambs had higher body weight-specific glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold) and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose utilization was not due to differences in skeletal muscle insulin receptor and glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during HEC were elevated in IUGR lambs compared with controls, but no differences were found for glycogen content or citrate synthase activity in liver and muscle. Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in young lambs are predicted from fetal studies but may promote conditions that exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants.

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Xanthine oxidase inhibition protects against Western diet-induced aortic stiffness and impaired vasorelaxation in female mice

Consumption of a high-fat, high-fructose diet [Western diet (WD)] promotes vascular stiffness, a critical factor in the development of cardiovascular disease (CVD). Obese and diabetic women exhibit greater arterial stiffness than men, which contributes to the increased incidence of CVD in these women. Furthermore, high-fructose diets result in elevated plasma concentrations of uric acid via xanthine oxidase (XO) activation, and uric acid elevation is also associated with increased vascular stiffness. However, the mechanisms by which increased xanthine oxidase activity and uric acid contribute to vascular stiffness in obese females remain to be fully uncovered. Accordingly, we examined the impact of XO inhibition on endothelial function and vascular stiffness in female C57BL/6J mice fed a WD or regular chow for 16 wk. WD feeding resulted in increased arterial stiffness, measured by atomic force microscopy in aortic explants (16.19 ± 1.72 vs. 5.21 ± 0.54 kPa, P < 0.05), as well as abnormal aortic endothelium-dependent and -independent vasorelaxation. XO inhibition with allopurinol (widely utilized in the clinical setting) substantially improved vascular relaxation and attenuated stiffness (16.9 ± 0.50 vs. 3.44 ± 0.50 kPa, P < 0.05) while simultaneously lowering serum uric acid levels (0.55 ± 0.98 vs. 0.21 ± 0.04 mg/dL, P < 0.05). In addition, allopurinol improved WD-induced markers of fibrosis and oxidative stress in aortic tissue, as analyzed by immunohistochemistry and transmission electronic microscopy. Collectively, these results demonstrate that XO inhibition protects against WD-induced vascular oxidative stress, fibrosis, impaired vasorelaxation, and aortic stiffness in females. Furthermore, excessive oxidative stress resulting from XO activation appears to play a key role in mediating vascular dysfunction induced by chronic exposure to WD consumption in females.

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Heads you gain, tails you lose

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Flexible ammonia handling strategies using both cutaneous and branchial epithelia in the highly ammonia-tolerant Pacific hagfish

Hagfish consume carrion, potentially exposing them to hypoxia, hypercapnia, and high environmental ammonia (HEA). We investigated branchial and cutaneous ammonia handling strategies by which Pacific hagfish (Eptatretus stoutii) tolerate and recover from high ammonia loading. Hagfish were exposed to HEA (20 mmol/l) for 48 h to elevate plasma total ammonia (T_Amm) levels before placement into divided chambers for a 4-h recovery period in ammonia-free seawater where ammonia excretion (J_Amm) was measured independently in the anterior and posterior compartments. Localized HEA exposures were also conducted by subjecting hagfish to HEA in either the anterior or posterior compartments. During recovery, HEA-exposed animals increased J_Amm in both compartments, with the posterior compartment comprising ~20% of the total J_Amm compared with ~11% in non-HEA-exposed fish. Plasma T_Amm increased substantially when whole hagfish and the posterior regions were exposed to HEA. Alternatively, plasma T_Amm did not elevate after anterior localized HEA exposure. J_Amm was concentration dependent (0.05–5 mmol/l) across excised skin patches at up to eightfold greater rates than in skin sections that were excised from HEA-exposed hagfish. Skin excised from more posterior regions displayed greater J_Amm than those from more anterior regions. Immunohistochemistry with hagfish-specific anti-rhesus glycoprotein type c (α-hRhcg; ammonia transporter) antibody was characterized by staining on the basal aspect of hagfish epidermis while Western blotting demonstrated greater expression of Rhcg in more posterior skin sections. We conclude that cutaneous Rhcg proteins are involved in cutaneous ammonia excretion by Pacific hagfish and that this mechanism could be particularly important during feeding.

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Effect of resistance exercise under conditions of reduced blood insulin on AMPK{alpha} Ser485/491 inhibitory phosphorylation and AMPK pathway activation

Insulin stimulates skeletal muscle glucose uptake via activation of the protein kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP-activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the AMPK α-subunit. Thus lower blood insulin concentrations may induce AMPK signal activation. Acute exercise is one method to stimulate AMPK activation; however, no study has examined the relationship between blood insulin levels and acute resistance exercise-induced AMPK pathway activation. Based on previous findings, we hypothesized that the acute resistance exercise-induced AMPK pathway activation would be augmented by disruptions in insulin secretion through a decrease in AMPKα Ser485/491 inhibitory phosphorylation. To test the hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting β-cells. Three days postinjection, the right gastrocnemius muscle from STZ and control rats was subjected to resistance exercise by percutaneous electrical stimulation. Animals were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream pathways in the muscle tissue was analyzed by Western blotting and real-time PCR. Notably, STZ rats showed a significant decrease in basal Akt and AMPKα Ser485/491 phosphorylation, but substantial exercise-induced increases in both AMPKα Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were observed. Although no significant impact on resistance exercise-induced Akt pathway activation or glucose uptake was found, resistance exercise-induced peroxisome proliferator-activated receptor (PPAR)- coactivator-1 α (PGC-1α) gene expression was augmented by STZ treatment. Collectively, these data suggest that circulating insulin levels may regulate acute resistance exercise-induced AMPK pathway activation and AMPK-dependent gene expression relating to basal AMPKα Ser485/491 phosphorylation.

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CRF and urocortin 3 protect the heart from hypoxia/reoxygenation-induced apoptosis in zebrafish

Fish routinely experience environmental hypoxia and have evolved various strategies to tolerate this challenge. Given the key role of the CRF system in coordinating the response to stressors and its cardioprotective actions against ischemia in mammals, we sought to characterize the cardiac CRF system in zebrafish and its role in hypoxia tolerance. We established that all genes of the CRF system, the ligands CRFa, CRFb, urotensin 1 (UTS1), and urocortin 3 (UCN3); the two receptor subtypes (CRFR1 and CRFR2); and the binding protein (CRFBP) are expressed in the heart of zebrafish: crfr1 > crfr2 = crfbp > crfa > ucn3 > crfb > uts1. In vivo, exposure to 5% O₂ saturation for 15 min and 90 min of recovery resulted in four- to five-fold increases in whole heart crfb and ucn3 mRNA levels but did not affect the gene expression of other CRF system components. In vitro, as assessed by monitoring caspase 3 activity and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells, pretreatment of excised whole hearts with CRF or UCN3 for 30 min prevented the increase in apoptosis associated with exposure to 1% O₂ saturation for 30 min with a 24-h recovery. Lastly, the addition of the nonselective CRF receptor antagonist αh-CRF_(9–41) prevented the cytoprotective effects of CRF. We show that the CRF system is expressed in fish heart, is upregulated by hypoxia, and is cytoprotective. These findings identify a novel role for the CRF system in fish and a new strategy to tolerate hypoxia.

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Cerebral oxygenation and regional cerebral perfusion responses with resistance breathing during central hypovolemia

Resistance breathing improves tolerance to central hypovolemia induced by lower body negative pressure (LBNP), but this is not related to protection of anterior cerebral blood flow [indexed by mean middle cerebral artery velocity (MCAv)]. We hypothesized that inspiratory resistance breathing improves tolerance to central hypovolemia by maintaining cerebral oxygenation (ScO₂), and protecting cerebral blood flow in the posterior cerebral circulation [indexed by posterior cerebral artery velocity (PCAv)]. Eight subjects (4 male/4 female) completed two experimental sessions of a presyncopal-limited LBNP protocol (3 mmHg/min onset rate) with and without (Control) resistance breathing via an impedance threshold device (ITD). ScO₂ (via near-infrared spectroscopy), MCAv and PCAv (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Hemodynamic responses were analyzed between the Control and ITD condition at baseline (T1) and the time representing 10 s before presyncope in the Control condition (T2). While breathing on the ITD increased LBNP tolerance from 1,506 ± 75 s to 1,704 ± 88 s (P = 0.003), both mean MCAv and mean PCAv were similar between conditions at T2 (P ≥ 0.46), and decreased by the same magnitude with and without ITD breathing (P ≥ 0.53). ScO₂ also decreased by ~9% with or without ITD breathing at T2 (P = 0.97), and there were also no differences in deoxygenated (dHb) or oxygenated hemoglobin (HbO₂) between conditions at T2 (P ≥ 0.43). There was no evidence that protection of regional cerebral blood velocity (i.e., anterior or posterior cerebral circulation) nor cerebral oxygen extraction played a key role in the determination of tolerance to central hypovolemia with resistance breathing.

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Inflammatory responses to acute elevations of carbon dioxide in mice

Health risks are described from elevated indoor air carbon dioxide (CO₂), which often ranges from 1,000 to 4,000 ppm, but the mechanisms are unknown. Here, we demonstrate that mice exposed for 2 h to 2,000 or 4,000 ppm CO₂ exhibit, respectively, 3.4 ± 0.9-fold (SE, n = 6) and 4.1 ± 0.7-fold (n = 10) elevations in circulating microparticles (MPs); neutrophil and platelet activation, and vascular leak in brain, muscle, and distal colon. Interleukin (IL)-1β content of MPs also increases after 2,000 ppm by 3.8 ± 0.6-fold (n = 6) and after 4,000 ppm CO₂ by 9.3 ± 1.1-fold (n = 10) greater than control. CO₂–induced vascular damage is abrogated by treating mice with an antibody to IL-1β or an IL-1β receptor inhibitor. Injecting naïve mice with CO₂-induced MPs expressing a protein found on mature neutrophils recapitulates vascular damage as seen with elevated CO₂, and destruction of MPs in CO₂-exposed mice abrogates vascular injuries without altering neutrophil or platelet activation. We conclude that environmentally relevant elevations of CO₂ trigger neutrophils to generate MPs containing high concentrations of IL-1β that cause diffuse inflammatory vascular injury.

NEW & NOTEWORTHY Elevated levels of CO₂ are often found in indoor air and cause adverse health effects, but the mechanisms have not been identified. In a murine model, environmentally relevant levels of CO₂ were found to cause diffuse vascular damage because neutrophils are stimulated to produce microparticles that contain high concentrations of interleukin-1β.

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Effect of exercise timing on elevated postprandial glucose levels

There is no consensus regarding optimal exercise timing for reducing postprandial glucose (PPG). The purpose of the present study was to determine the most effective exercise timing. Eleven participants completed four different exercise patterns 1) no exercise; 2) preprandial exercise (jogging); 3) postprandial exercise; and 4) brief periodic exercise intervention (three sets of 1-min jogging + 30 s of rest, every 30 min, 20 times total) in a random order separated by a minimum of 5 days. Preprandial and postprandial exercise consisted of 20 sets of intermittent exercise (1 min of jogging + 30 s rest per set) repeated 3 times per day. Total daily exercise volume was identical for all three exercise patterns. Exercise intensities were 62.4 ± 12.9% Vo_2peak. Blood glucose concentrations were measured continuously throughout each trial for 24 h. After breakfast, peak blood glucose concentrations were lower with brief periodic exercise (99 ± 6 mg/dl) than those with preprandial and postprandial exercise (109 ± 10 and 115 ± 14 mg/dl, respectively, P < 0.05, effect size = 0.517). After lunch, peak glucose concentrations were lower with brief periodic exercise than those with postprandial exercise (97 ± 5 and 108 ± 8 mg/dl, P < 0.05, effect size = 0.484). After dinner, peak glucose concentrations did not significantly differ among exercise patterns. Areas under the curve over 24 h and 2 h postprandially did not differ among exercise patterns. These findings suggest that brief periodic exercise may be more effective than preprandial and postprandial exercise at attenuating PPG in young active individuals.

NEW & NOTEWORTHY This was the first study to investigate the effect of different exercise timing (brief periodic vs. preprandial vs. postprandial exercise) on postprandial glucose (PPG) attenuation in active healthy men. We demonstrated that brief periodic exercise attenuated peak PPG levels more than preprandial and postprandial exercise, particularly in the morning. Additionally, PPG rebounded soon after discontinuing postprandial exercise. Thus, brief periodic exercise may be better than preprandial and postprandial exercise at attenuating PPG levels.

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Edmund Goodwyn and the first description of diving bradycardia

Diving bradycardia is a primordial oxygen-conserving reflex by which the heart rate of air-breathing vertebrates, including humans, slows down in response to water immersion. Its discovery is attributed to Paul Bert, whose seminal observation was published in 1870 as part of a series of experiments that examined physiological adaptations to asphyxia in ducks and other animals. However, Edmund Goodwyn, a British physician who studied medicine at the University of Edinburgh, had already described this reflex in his doctoral thesis, which was originally published in Latin in 1786 and again in English in 1788. Ironically, even though Goodwyn's work has yet to be recognized in the diving physiology literature, it was referenced in the very publication that contains Bert's original observation. Thus this article brings Goodwyn's work and its historical context to light and argues that he should be credited with the first description of diving bradycardia.

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Ventricular action potential adaptation to regular exercise: role of {beta}-adrenergic and KATP channel function

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K⁺ (K_ATP) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6–8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca²⁺ transient durations reflected the changes in APD, while Ca²⁺ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β₁-AR blocker atenolol, but not the β₂-AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β₁-AR. At 10 Hz, the K_ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β₁-AR responsiveness and K_ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca²⁺ influx; during exercise, an increase in K_ATP channel activity would shorten APD and, thus, protect the heart against Ca²⁺ overload or inadequate filling.

NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca²⁺ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the β-adrenergic receptor agonist dose-response curve rightward compared with controls by reducing β₁-adrenergic receptor responsiveness and that, at the high activation rate, myocytes from trained animals showed higher K_ATP channel function.

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Aortic arch compliance and idiopathic unilateral vocal fold paralysis

Unilateral vocal fold paralysis (UVP) occurs related to recurrent laryngeal nerve (RLN) impairment associated with impaired swallowing, voice production, and breathing functions. The majority of UVP cases occur subsequent to surgical intervention with approximately 12–42% having no known cause for the disease (i.e., idiopathic). Approximately two-thirds of those with UVP exhibit left-sided injury with the average onset at ≥50 yr of age in those diagnosed as idiopathic. Given the association between the RLN and the subclavian and aortic arch vessels, we hypothesized that changes in vascular tissues would result in increased aortic compliance in patients with idiopathic left-sided UVP compared with those without UVP. Gated MRI data enabled aortic arch diameter measures normalized to blood pressure across the cardiac cycles to derive aortic arch compliance. Compliance was compared between individuals with left-sided idiopathic UVP and age- and sex-matched normal controls. Three-way factorial ANOVA test showed that aortic arch compliance (P = 0.02) and aortic arch diameter change in one cardiac cycle (P = 0.04) are significantly higher in patients with idiopathic left-sided UVP compared with the controls. As previously demonstrated by other literature, our finding confirmed that compliance decreases with age (P < 0.0001) in both healthy individuals and patients with idiopathic UVP. Future studies will investigate parameters of aortic compliance change as a potential contributor to the onset of left-sided UVP.

NEW & NOTEWORTHY Unilateral vocal fold paralysis results from impaired function of the recurrent laryngeal nerve (RLN) impacting breathing, swallowing, and voice production. A large proportion of adults suffering from this disorder have an idiopathic etiology (i.e., unknown cause). The current study determined that individuals diagnosed with left-sided idiopathic vocal fold paralysis exhibited significantly greater compliance than age- and sex-matched controls. These seminal findings suggest a link between aortic arch compliance levels and RLN function.

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Strategies for obstacle avoidance during walking in the cat

Avoiding obstacles is essential for successful navigation through complex environments. This study aimed to clarify what strategies are used by a typical quadruped, the cat, to avoid obstacles during walking. Four cats walked along a corridor 2.5 m long and 25 or 15 cm wide. Obstacles, small round objects 2.5 cm in diameter and 1 cm in height, were placed on the floor in various locations. Movements of the paw were recorded with a motion capture and analysis system (Visualeyez, PTI). During walking in the wide corridor, cats' preferred strategy for avoiding a single obstacle was circumvention, during which the stride direction changed while stride duration and swing-to-stride duration ratio were preserved. Another strategy, stepping over the obstacle, was used during walking in the narrow corridor, when lateral deviations of walking trajectory were restricted. Stepping over the obstacle involved changes in two consecutive strides. The stride preceding the obstacle was shortened, and swing-to-stride ratio was reduced. The obstacle was negotiated in the next stride of increased height and normal duration and swing-to-stride ratio. During walking on a surface with multiple obstacles, both strategies were used. To avoid contact with the obstacle, cats placed the paw away from the object at a distance roughly equal to the diameter of the paw. During obstacle avoidance cats prefer to alter muscle activities without altering the locomotor rhythm. We hypothesize that a choice of the strategy for obstacle avoidance is determined by minimizing the complexity of neuro-motor processes required to achieve the behavioral goal.

NEW & NOTEWORTHY In a study of feline locomotor behavior we found that the preferred strategy to avoid a small obstacle is circumvention. During circumvention, stride direction changes but length and temporal structure are preserved. Another strategy, stepping over the obstacle, is used in narrow walkways. During overstepping, two strides adjust. A stride preceding the obstacle decreases in length and duration. The following stride negotiating the obstacle increases in height while retaining normal temporal structure and nearly normal length.

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Optimal motor synergy extraction for novel actions and virtual environments

Dimensionality reduction techniques such as factor analysis can be used to identify the smallest number of components (motor synergies) that explain motion. Lambert-Shirzad and Van der Loos (J Neurophysiol 117: 290–302, 2017) compared dimensionality reduction techniques in bimanual hand movements, concluding that nonnegative matrix factorization was the optimal technique for extracting meaningful synergies. Their results provide a useful measure for examining how the motor system deals with novel motor tasks that allow the actor to engage with a virtual environment.

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Learning temporal context shapes prestimulus alpha oscillations and improves visual discrimination performance

Time is an inseparable component of every physical event that we perceive, yet it is not clear how the brain processes time or how the neuronal representation of time affects our perception of events. Here we asked subjects to perform a visual discrimination task while we changed the temporal context in which the stimuli were presented. We collected electroencephalography (EEG) signals in two temporal contexts. In predictable blocks stimuli were presented after a constant delay relative to a visual cue, and in unpredictable blocks stimuli were presented after variable delays relative to the visual cue. Four subsecond delays of 83, 150, 400, and 800 ms were used in the predictable and unpredictable blocks. We observed that predictability modulated the power of prestimulus alpha oscillations in the parieto-occipital sites: alpha power increased in the 300-ms window before stimulus onset in the predictable blocks compared with the unpredictable blocks. This modulation only occurred in the longest delay period, 800 ms, in which predictability also improved the behavioral performance of the subjects. Moreover, learning the temporal context shaped the prestimulus alpha power: modulation of prestimulus alpha power grew during the predictable block and correlated with performance enhancement. These results suggest that the brain is able to learn the subsecond temporal context of stimuli and use this to enhance sensory processing. Furthermore, the neural correlate of this temporal prediction is reflected in the alpha oscillations.

NEW & NOTEWORTHY It is not well understood how the uncertainty in the timing of an external event affects its processing, particularly at subsecond scales. Here we demonstrate how a predictable timing scheme improves visual processing. We found that learning the predictable scheme gradually shaped the prestimulus alpha power. These findings indicate that the human brain is able to extract implicit subsecond patterns in the temporal context of events.

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No consistent effect of cerebellar transcranial direct current stimulation on visuomotor adaptation

Cerebellar transcranial direct current stimulation (ctDCS) is known to enhance adaptation to a novel visual rotation (visuomotor adaptation), and it is suggested to hold promise as a therapeutic intervention. However, it is unknown whether this effect is robust across varying task parameters. This question is crucial if ctDCS is to be used clinically, because it must have a consistent and robust effect across a relatively wide range of behaviors. The aim of this study was to examine the effect of ctDCS on visuomotor adaptation across a wide range of task parameters that were systematically varied. Therefore, 192 young healthy individuals participated in 1 of 7 visuomotor adaptation experiments in either an anodal or sham ctDCS group. Each experiment examined whether ctDCS had a positive effect on adaptation when a unique feature of the task was altered: position of the monitor, offline tDCS, use of a tool, and perturbation schedule. Although we initially replicated the previously reported positive effect of ctDCS on visuomotor adaptation, this was not maintained during a second replication study or across a large range of varying task parameters. At the very least, this may call into question the validity of using ctDCS within a clinical context where a robust and consistent effect across behavior would be required.

NEW & NOTEWORTHY Cerebellar transcranial direct current stimulation (ctDCS) is known to enhance motor adaptation and thus holds promise as a therapeutic intervention. However, understanding the reliability of ctDCS across varying task parameters is crucial. To examine this, we investigated whether ctDCS enhanced visuomotor adaptation across a range of varying task parameters. We found ctDCS to have no consistent effect on visuomotor adaptation, questioning the validity of using ctDCS within a clinical context.

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Cortical amplification models of experience-dependent development of selective columns and response sparsification

The development of direction-selective cortical columns requires visual experience, but the neural circuits and plasticity mechanisms that are responsible for this developmental transition are unknown. To gain insight into the mechanisms that could underlie experience-dependent increases in selectivity, we explored families of cortical amplifier models that enhance weakly biased feedforward signals. Here we focused exclusively on possible contributions of cortico-cortical connections and took feedforward input to be constant. We modeled pairs of interconnected columns that received equal and oppositely biased inputs. In a single-element model of cortical columns, we found two ways that cortical columns could receive biased feedforward input and exhibit strong but unselective responses to stimuli: 1) within-column recurrent excitatory connections could be strong enough to amplify both strong and weak feedforward input, or 2) columns that received differently biased inputs could have strong excitatory cross-connections that destroy selectivity. A Hebbian plasticity rule combined with simulated experience with stimuli weakened these strong cross-connections across cortical columns, allowing the individual columns to respond selectively to their biased inputs. In a model that included both excitatory and inhibitory neurons in each column, an additional means of obtaining selectivity through the cortical circuit was uncovered: cross-column suppression of inhibition-stabilized networks. When each column operated as an inhibition-stabilized network, cross-column excitation onto inhibitory neurons forced competition between the columns but in a manner that did not involve strong null-direction inhibition, consistent with experimental measurements of direction selectivity in visual cortex. Experimental predictions of these possible contributions of cortical circuits are discussed.

NEW & NOTEWORTHY Sensory circuits are initially constructed via mechanisms that are independent of sensory experience, but later refinement requires experience. We constructed models of how circuits that receive biased feedforward inputs can be initially unselective and then be modified by experience and plasticity so that the resulting circuit exhibits increased selectivity. We propose that neighboring cortical columns may initially exhibit coupling that is too strong for selectivity. Experience-dependent mechanisms decrease this coupling so individual columns can exhibit selectivity.

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Estimating the implicit component of visuomotor rotation learning by constraining movement preparation time

When sensory feedback is perturbed, accurate movement is restored by a combination of implicit processes and deliberate reaiming to strategically compensate for errors. Here, we directly compare two methods used previously to dissociate implicit from explicit learning on a trial-by-trial basis: 1) asking participants to report the direction that they aim their movements, and contrasting this with the directions of the target and the movement that they actually produce, and 2) manipulating movement preparation time. By instructing participants to reaim without a sensory perturbation, we show that reaiming is possible even with the shortest possible preparation times, particularly when targets are narrowly distributed. Nonetheless, reaiming is effortful and comes at the cost of increased variability, so we tested whether constraining preparation time is sufficient to suppress strategic reaiming during adaptation to visuomotor rotation with a broad target distribution. The rate and extent of error reduction under preparation time constraints were similar to estimates of implicit learning obtained from self-report without time pressure, suggesting that participants chose not to apply a reaiming strategy to correct visual errors under time pressure. Surprisingly, participants who reported aiming directions showed less implicit learning according to an alternative measure, obtained during trials performed without visual feedback. This suggests that the process of reporting can affect the extent or persistence of implicit learning. The data extend existing evidence that restricting preparation time can suppress explicit reaiming and provide an estimate of implicit visuomotor rotation learning that does not require participants to report their aiming directions.

NEW & NOTEWORTHY During sensorimotor adaptation, implicit error-driven learning can be isolated from explicit strategy-driven reaiming by subtracting self-reported aiming directions from movement directions, or by restricting movement preparation time. Here, we compared the two methods. Restricting preparation times did not eliminate reaiming but was sufficient to suppress reaiming during adaptation with widely distributed targets. The self-report method produced a discrepancy in implicit learning estimated by subtracting aiming directions and implicit learning measured in no-feedback trials.

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The sensorimotor system minimizes prediction error for object lifting when the objects weight is uncertain

A reliable mechanism to predict the heaviness of an object is important for manipulating an object under environmental uncertainty. Recently, Cashaback et al. (Cashaback JGA, McGregor HR, Pun HCH, Buckingham G, Gribble PL. J Neurophysiol 117: 260–274, 2017) showed that for object lifting the sensorimotor system uses a strategy that minimizes prediction error when the object's weight is uncertain. Previous research demonstrates that visually guided reaching is similarly optimized. Although this suggests a unified strategy of the sensorimotor system for object manipulation, the selected strategy appears to be task dependent and subject to change in response to the degree of environmental uncertainty.

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A distributed neural network model for the distinct roles of medial and lateral HVC in zebra finch song production

Male zebra finches produce a song consisting of a canonical sequence of syllables, learned from a tutor and repeated throughout its adult life. Much of the neural circuitry responsible for this behavior is located in the cortical premotor region HVC (acronym is name). In a recent study from our laboratory, we found that partial bilateral ablation of the medial portion of HVC has effects on the song that are qualitatively different from those of bilateral ablation of the lateral portion. In this report we describe a neural network organization that can explain these data, and in so doing suggests key roles for other brain nuclei in the production of song. We also suggest that syllables and the gaps between them are each coded separately by neural chains within HVC, and that the timing mechanisms for syllables and gaps are distinct. The design principles underlying this model assign distinct roles for medial and lateral HVC circuitry that explain the data on medial and lateral ablations. In addition, despite the fact that the neural coding of song sequence is distributed among several brain nuclei in our model, it accounts for data showing that cooling of HVC stretches syllables uniformly and to a greater extent than gaps. Finally, the model made unanticipated predictions about details of the effects of medial and lateral HVC ablations that were then confirmed by reanalysis of these previously acquired behavioral data.

NEW & NOTEWORTHY Zebra finch song consists of a string of syllables repeated in a nearly invariant sequence. We propose a neural network organization that can explain recent data indicating that the medial and lateral portions of the premotor cortical nucleus HVC have different roles in zebra finch song production. Our model explains these data, as well as data on the effects on song of cooling HVC, and makes predictions that we test in the singing bird.

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A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or rod depolarizing bipolar cell function

GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and underlie the human condition autosomal recessive complete congenital stationary night blindness. Mouse mutants for Grm6 are important models for this condition. Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen of mice maintained at The Jackson Laboratory. The Grm6^nob8 mouse has a reduced-amplitude b-wave component of the ERG, which reflects light-evoked DBC activity. Sequencing identified a missense mutation that converts a highly conserved methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent with prior studies of Grm6 mutant mice, the laminar size and structure in the Grm6^nob8 retina were comparable to control. The Grm6^nob8 phenotype is distinguished from other Grm6 mutants that carry a null allele by a reduced but not absent ERG b-wave, decreased but present expression of mGluR6 at DBC dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a reduced but not absent b-wave, there were a subset of retinal ganglion cells whose responses to light onset have times to peak within the range of those in control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is trafficked less than control. However, the mGluR6 that is localized to the DBC dendritic tips is able to initiate DBC signal transduction. The Grm6^nob8 mouse extends the Grm6 allelic series and will be useful for elucidating the role of mGluR6 in DBC signal transduction and in human disease.

NEW & NOTEWORTHY This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and bipolar cell function, a distinct phenotype from that seen in other Grm6 mouse models.

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The cerebellum contributes to proprioception during motion

Proprioception, the sense of limb position and motion, is essential for generating accurate movements. Limb position sense has typically been studied under static conditions (i.e., the fixed position of a limb in space), with less known about dynamic position sense (i.e., limb position during movement). Here we investigated how a person's estimate of hand position varies when using spatial or temporal information to judge the unseen hand's location during reaching. We assessed the acuity of dynamic position sense in two directions, orthogonal to hand movement, which only requires spatial information, and in line with hand movement, which has both spatial and temporal components. Our results showed that people have better proprioceptive acuity in the orthogonal condition where only spatial information is used. We then assessed whether cerebellar damage impairs proprioceptive acuity in both tasks during passive and active movement. Cerebellar patients showed reduced acuity in both tasks and in both movement conditions relative to age-matched controls. However, patients' deficits were most apparent when judgments of active movement relied on temporal information. Furthermore, both cerebellar patient and control performance correlated with the trial-to-trial variability of their active movements: subjects are worse at the proprioceptive tasks when movements are variable. Our results suggest that, during active movements, proprioceptive acuity may be reliant on the motor system's ability to predict motor output. Therefore, the resultant proprioceptive deficits occurring after cerebellar damage may be related to a more general impairment in movement prediction.

NEW & NOTEWORTHY We assessed limb position sense during movement in patients with cerebellar damage and found deficits in proprioceptive acuity during both passive and active movement. The effect of cerebellar damage was most apparent when individuals relied on both timing and spatial information during active movement. Thus proprioceptive acuity during active movements may be reliant on the motor system's ability to predict motor output.

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Transcribing the connectome: roles for transcription factors and chromatin regulators in activity-dependent synapse development

The wiring of synaptic connections in the developing mammalian brain is shaped by both intrinsic and extrinsic signals. One point where these regulatory pathways converge is via the sensory experience-dependent regulation of new gene transcription. Recent studies have elucidated a number of molecular mechanisms that allow nuclear transcription factors and chromatin regulatory proteins to encode aspects of specificity in experience-dependent synapse development. Here we review the evidence for the transcriptional mechanisms that sculpt activity-dependent aspects of synaptic connectivity during postnatal development and discuss how disruption of these processes is associated with aberrant brain development in autism and intellectual disability.

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Multisensory coding in the multiple-demand regions: vibrotactile task information is coded in frontoparietal cortex

At any given moment, our brains receive input from multiple senses. Successful behavior depends on our ability to prioritize the most important information and ignore the rest. A multiple-demand (MD) network of frontal and parietal regions is thought to support this process by adjusting to code information that is currently relevant (Duncan 2010). Accordingly, the network is proposed to encode a range of different types of information, including perceptual stimuli, task rules, and responses, as needed for the current cognitive operation. However, most MD research has used visual tasks, leaving limited information about whether these regions encode other sensory domains. We used multivoxel pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) data to test whether the MD regions code the details of somatosensory stimuli, in addition to tactile-motor response transformation rules and button-press responses. Participants performed a stimulus-response task in which they discriminated between two possible vibrotactile frequencies and applied a stimulus-response transformation rule to generate a button-press response. For MD regions, we found significant coding of tactile stimulus, rule, and response. Primary and secondary somatosensory regions encoded the tactile stimuli and the button-press responses but did not represent task rules. Our findings provide evidence that MD regions can code nonvisual somatosensory task information, commensurate with a domain-general role in cognitive control.

NEW & NOTEWORTHY How does the brain encode the breadth of information from our senses and use this to produce goal-directed behavior? A network of frontoparietal multiple-demand (MD) regions is implicated but has been studied almost exclusively in the context of visual tasks. We used multivariate pattern analysis of fMRI data to show that these regions encode tactile stimulus information, rules, and responses. This provides evidence for a domain-general role of the MD network in cognitive control.

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Motor recovery beginning 23 years after ischemic stroke

It is widely believed that most stroke recovery occurs within 6 mo, with little benefit of physiotherapy or other modalities beyond 1 yr. We report a remarkable case of stroke recovery beginning 23 yr after a severe stroke due to embolization from the innominate artery and subclavian artery, resulting from compression of the right subclavian artery by a cervical rib. The patient had a large right frontoparietal infarction with severe left hemiparesis and a totally nonfunctional spastic left hand. He experienced some recovery of hand function that began 23 yr after the stroke, 1 yr after he took up regular swimming. As a result, intensive physiotherapy was initiated, with repetitive large muscle movement and a spring-loaded mechanical orthosis that provides resistance to finger flexors and supports finger extensors. Within 2 yr, he could pick up coins with the previously useless left hand. Functional MRI studies document widespread distribution of the recovery in both hemispheres. This case provides impetus not only to more intensive and prolonged physiotherapy, but also to treatment with emerging modalities such as stem cell therapy and exosome and microRNA therapies.

NEW & NOTEWORTHY Widespread bilateral activation of both sides of the cerebrum and cerebellum are demonstrated on functional MRI after motor recovery of a completely nonfunctional left hand that began 23 yr after a severe stroke. This suggests that the generally accepted window of recovery beyond which further therapy is not indicated should be entirely reconsidered. Physiotherapy and new modalities in development might be indicated long after a stroke.

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Hierarchical differences in population coding within auditory cortex

Most models of auditory cortical (AC) population coding have focused on primary auditory cortex (A1). Thus our understanding of how neural coding for sounds progresses along the cortical hierarchy remains obscure. To illuminate this, we recorded from two AC fields: A1 and middle lateral belt (ML) of rhesus macaques. We presented amplitude-modulated (AM) noise during both passive listening and while the animals performed an AM detection task ("active" condition). In both fields, neurons exhibit monotonic AM-depth tuning, with A1 neurons mostly exhibiting increasing rate-depth functions and ML neurons approximately evenly distributed between increasing and decreasing functions. We measured noise correlation (r_noise) between simultaneously recorded neurons and found that whereas engagement decreased average r_noise in A1, engagement increased average r_noise in ML. This finding surprised us, because attentive states are commonly reported to decrease average r_noise. We analyzed the effect of r_noise on AM coding in both A1 and ML and found that whereas engagement-related shifts in r_noise in A1 enhance AM coding, r_noise shifts in ML have little effect. These results imply that the effect of r_noise differs between sensory areas, based on the distribution of tuning properties among the neurons within each population. A possible explanation of this is that higher areas need to encode nonsensory variables (e.g., attention, choice, and motor preparation), which impart common noise, thus increasing r_noise. Therefore, the hierarchical emergence of r_noise-robust population coding (e.g., as we observed in ML) enhances the ability of sensory cortex to integrate cognitive and sensory information without a loss of sensory fidelity.

NEW & NOTEWORTHY Prevailing models of population coding of sensory information are based on a limited subset of neural structures. An important and under-explored question in neuroscience is how distinct areas of sensory cortex differ in their population coding strategies. In this study, we compared population coding between primary and secondary auditory cortex. Our findings demonstrate striking differences between the two areas and highlight the importance of considering the diversity of neural structures as we develop models of population coding.

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Advantages of comparative studies in songbirds to understand the neural basis of sensorimotor integration

Sensorimotor integration is the process through which the nervous system creates a link between motor commands and associated sensory feedback. This process allows for the acquisition and refinement of many behaviors, including learned communication behaviors such as speech and birdsong. Consequently, it is important to understand fundamental mechanisms of sensorimotor integration, and comparative analyses of this process can provide vital insight. Songbirds offer a powerful comparative model system to study how the nervous system links motor and sensory information for learning and control. This is because the acquisition, maintenance, and control of birdsong critically depend on sensory feedback. Furthermore, there is an incredible diversity of song organizations across songbird species, ranging from songs with simple, stereotyped sequences to songs with complex sequencing of vocal gestures, as well as a wide diversity of song repertoire sizes. Despite this diversity, the neural circuitry for song learning, control, and maintenance remains highly similar across species. Here, we highlight the utility of songbirds for the analysis of sensorimotor integration and the insights about mechanisms of sensorimotor integration gained by comparing different songbird species. Key conclusions from this comparative analysis are that variation in song sequence complexity seems to covary with the strength of feedback signals in sensorimotor circuits and that sensorimotor circuits contain distinct representations of elements in the vocal repertoire, possibly enabling evolutionary variation in repertoire sizes. We conclude our review by highlighting important areas of research that could benefit from increased comparative focus, with particular emphasis on the integration of new technologies.

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