Structure and function of Achilles and patellar tendons following moderate slow resistance training in young and old men.

The aim of this study was to investigate the effect of aging and resistance training with a moderate load on the size and mechanical properties of the patellar (PT) and Achilles tendon (AT) and their associated aponeuroses; medial gastrocnemius (MG) and vastus lateralis (VL). Young (Y55; 24.8 ± 3.8 yrs, n = 11) and old men (O55; 70.0 ± 4.6 yrs, n = 13) were assigned to undergo a training program (12 weeks; 3 times/week) of moderate slow resistance training [55% of one repetition maximum (RM)] of the triceps surae and quadriceps muscles. Tendon dimensions were assessed using 1.5 T magnetic resonance imaging before and after 12 weeks. AT and PT cross sectional area (CSA) were determined every 10% of tendon length. Mechanical properties of the free AT, MG aponeurosis, PT, and VL aponeurosis were assessed using ultrasonography (deformation) and tendon force measurements. CSA of the AT but not PT was greater in O55 compared with Y55. At baseline, mechanical properties were generally lower in O55 than Y55 for AT, MG aponeurosis and VL aponeurosis (Young's modulus) but not for PT. CSA of the AT and PT increased equally in both groups following training. Further, for a given force, stiffness and Young's modulus also increased equally for VL aponeurosis and AT, for boths groups. The present study highlights that except for the PT, older men have lower tendon (AT, MG aponeurosis, and VL aponeurosis) mechanical properties than young men and 12-weeks of moderate slow resistance training appears sufficient to improve tendon size and mechanical adaptations in both young and older men. New and Noteworthy: These novel findings suggest that short-term moderate slow resistance training induces equal improvements in tendon size and mechanics regardless of age.

High-Fat Diet Modulates the Excitability of Neurons within the Brain-Liver Pathway.

Stimulation of hepatic sympathetic nerves increases glucose production and glycogenolysis. Activity of pre-sympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral and ventromedial medulla (VLM/VMM) largely influence the sympathetic output. Increased activity of the sympathetic nervous system (SNS) plays a role in the development and progression of metabolic diseases; however, despite the importance of the central circuits, the excitability of pre-sympathetic liver-related neurons remains to be determined. Here, we tested the hypothesis that the activity of liver-related neurons in the PVN and VLM/VMM is altered in diet-induced obese mice, as well as their response to insulin. Patch-clamp recordings were conducted from liver-related PVN neurons, VLM-projecting PVN neurons, and pre-sympathetic liver-related neurons in the ventral brainstem. Our data demonstrate that the excitability of liver-related PVN neurons increased in high-fat diet (HFD)-fed mice compared to mice fed with control diet. Insulin receptor expression was detected in a population of liver-related neurons, and insulin suppressed the firing activity of liver-related PVN and pre-sympathetic VLM/VMM neurons in HFD mice; however, it did not affect VLM-projecting liver-related PVN neurons. These findings further suggest that HFD alters the excitability of pre-autonomic neurons as well as their response to insulin.

In situ visualization of aortic dissection propagation in notched rabbit aorta using synchrotron X-ray tomography.

Aortic dissection is a complex, intramural, and dynamic condition involving multiple mechanisms, hence, difficult to observe. In the present study, a controlled in vitro aortic dissection was performed using tension-inflation tests on notched rabbit aortic segments. The mechanical test was combined with conventional (cCT) and synchrotron (sCT) computed tomography for in situ imaging of the macro- and micro-structural morphological changes of the aortic wall during dissection. We demonstrate that the morphology of the notch and the aorta can be quantified in situ at different steps of the aortic dissection, and that the notch geometry correlates with the critical pressure. The phenomena prior to propagation of the notch are also described, for instance the presence of a bulge at the tip of the notch is identified, deforming the remaining wall. Finally, our method allows us to visualize for the first time the propagation of an aortic dissection in real-time with a resolution that has never previously been reached. STATEMENT OF SIGNIFICANCE: With the present study, we investigated the factors leading to the propagation of aortic dissection by reproducing this mechanical process in notched rabbit aortas. Synchrotron CT provided the first visualisation in real-time of an aortic dissection propagation with a resolution that has never previously been reached. The morphology of the intimal tear and aorta was quantified at different steps of the aortic dissection, demonstrating that the early notch geometry correlates with the critical pressure. This quantification is crucial for the development of better criteria identifying patients at risk. Phenomena prior to tear propagation were also described, such as the presence of a bulge at the tip of the notch, deforming the remaining wall.

An atypical case of calf pain: Plantaris tendon axial instability.

Plantaris tendon (PT) might induce calf or Achilles pain. In this case report, a 59-year-old woman presented with axial instability of plantaris tendon; post Achilles tendon lengthening. She beneficiated from a needle tenotomy of the PT and had a prompt symptom alleviation. The patient was fully satisfied and had a SANE score of 95% at 12 months follow up and was able to return to moderate sports activities without limitations (hiking, Nordic walking). The instability of the PT might be considered for the differential diagnosis of medial calf pain for which needle tenotomy may be considered a valuable option.

Mineralocorticoid receptor antagonist treatment of established pulmonary arterial hypertension improves interventricular dependence in the SU5416-hypoxia rat model.

Treatment with mineralocorticoid receptor (MR) antagonists beginning at the outset of disease, or early thereafter, prevents pulmonary vascular remodeling in preclinical models of pulmonary arterial hypertension (PAH). However, the efficacy of MR blockade in established disease, a more clinically relevant condition, remains unknown. Therefore, we investigated the effectiveness of two MR antagonists, eplerenone (EPL) and spironolactone (SPL), after the development of severe right ventricular (RV) dysfunction in the rat SU5416-hypoxia (SuHx) PAH model. Cardiac magnetic resonance imaging (MRI) in SuHx rats at the end of week 5, before study treatment, confirmed features of established disease including reduced RV ejection fraction and RV hypertrophy, pronounced septal flattening with impaired left ventricular filling and reduced cardiac index. Five weeks of treatment with either EPL or SPL improved left ventricular filling and prevented the further decline in cardiac index compared with placebo. Interventricular septal displacement was reduced by EPL whereas SPL effects were similar, but not significant. Although MR antagonists did not significantly reduce pulmonary artery pressure or vessel remodeling in SuHx rats with established disease, animals with higher drug levels had lower pulmonary pressures. Consistent with effects on cardiac function, EPL treatment tended to suppress MR and proinflammatory gene induction in the RV. In conclusion, MR antagonist treatment led to modest, but consistent beneficial effects on interventricular dependence after the onset of significant RV dysfunction in the SuHx PAH model. These results suggest that measures of RV structure and/or function may be useful endpoints in clinical trials of MR antagonists in patients with PAH.

Sympathetic innervation of the mouse kidney and liver arising from prevertebral ganglia.

The sympathetic nervous system (SNS) plays a crucial role in the regulation of renal and hepatic functions. Although sympathetic nerves to the kidney and liver have been identified in many species, specific details are lacking in the mouse. In the absence of detailed information of sympathetic prevertebral innervation of specific organs, selective manipulation of a specific function will remain challenging. Despite providing major postganglionic inputs to abdominal organs, limited data are available about the mouse celiac-superior mesenteric complex. We used tyrosine hydroxylase (TH) and dopamine ß-hydroxylase (DbH) reporter mice to visualize abdominal prevertebral ganglia. We found that both the TH and DbH reporter mice are useful models for identification of ganglia and nerve bundles. We further tested if the celiac-superior mesenteric complex provides differential inputs to the mouse kidney and liver. The retrograde viral tracer, pseudorabies virus (PRV)-152 was injected into the cortex of the left kidney or the main lobe of the liver to identify kidney-projecting and liver-projecting neurons in the celiac-superior mesenteric complex. iDISCO immunostaining and tissue clearing were used to visualize unprecedented anatomical detail of kidney-related and liver-related postganglionic neurons in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia compared with TH-positive neurons. Kidney-projecting neurons were restricted to the suprarenal and aorticorenal ganglia, whereas only sparse labeling was observed in the celiac-superior mesenteric complex. In contrast, liver-projecting postganglionic neurons were observed in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia, suggesting spatial separation between the sympathetic innervation of the mouse kidney and liver.

Muscles adaptation to aging and training: architectural changes - a randomised trial.

BACKGROUND: To investigate how anatomical cross-sectional area and volume of quadriceps and triceps surae muscles were affected by ageing, and by resistance training in older and younger men, in vivo. METHODS: The old participants were randomly assigned to moderate (O55, n = 13) or high-load (O80, n = 14) resistance training intervention (12 weeks; 3 times/week) corresponding to 55% or 80% of one repetition maximum, respectively. Young men (Y55, n = 11) were assigned to the moderate-intensity strengthening exercise program. Each group received the exact same training volume on triceps surae and quadriceps group (Reps x Sets x Intensity). The fitting polynomial regression equations for each of anatomical cross-sectional area-muscle length curves were used to calculate muscle volume (contractile content) before and after 12 weeks using magnetic resonance imaging scans. RESULTS: Only Rectus femoris and medial gastrocnemius muscle showed a higher relative anatomical cross-sectional area in the young than the elderly on the proximal end. The old group displayed a higher absolute volume of non-contractile material than young men in triceps surae (+ 96%). After training, Y55, O55 and O80 showed an increase in total quadriceps (+ 4.3%; + 6.7%; 4.2% respectively) and triceps surae (+ 2.8%; + 7.5%; 4.3% respectively) volume. O55 demonstrated a greater increase on average gains compared to Y55, while no difference between O55 and O80 was observed. CONCLUSIONS: Muscle loss with aging is region-specific for some muscles and uniform for others. Equivalent strength training volume at moderate or high intensities increased muscle volume with no differences in muscle volume gains for old men. These data suggest that physical exercise at moderate intensity (55 to 60% of one repetition maximum) can reverse the aging related loss of muscle mass. TRIAL REGISTRATION: NCT03079180 in ClinicalTrials.gov . Registration date: March 14, 2017.

Meta-analysis of blood genome-wide expression profiling studies in pulmonary arterial hypertension.

Inflammatory cell infiltrates are a prominent feature of aberrant vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that immune effector cells contribute to disease progression. Genome-wide blood expression profiling studies have attempted to better define this inflammatory component of PAH pathobiology but have been hampered by small sample sizes, methodological differences, and very little gene-level reproducibility. The current meta-analysis (seven studies; 156 PAH patients/110 healthy controls) was performed to assess the comparability of data across studies and to possibly derive a generalizable transcriptomic signature. Idiopathic (IPAH) compared with disease-associated PAH (APAH) displayed highly similar expression profiles with no differentially expressed genes, even after substantially relaxing selection stringency. In contrast, using a false discovery rate of ≤1% and I2 < 40% (low-to-moderate heterogeneity across studies) both IPAH and APAH differed markedly from healthy controls with the combined PAH cohort yielding 1,269 differentially expressed, unique gene transcripts. Bioinformatic analyses, including gene-set enrichment, which uses all available data independent of gene selection thresholds, identified interferon, mammalian target of rapamycin/p70S6K, stress kinase, and Toll-like receptor signaling as enriched mechanisms within the PAH gene signature. Enriched biological functions and diseases included tumorigenesis, autoimmunity, antiviral response, and cell death consistent with prevailing theories of PAH pathogenesis. Although otherwise indistinguishable, APAH (predominantly PAH due to systemic sclerosis) had a somewhat stronger interferon profile than IPAH. Meta-analysis defined a robust and generalizable transcriptomic signature in the blood of PAH patients that can help inform the identification of biomarkers and therapeutic targets.

Efficacy of Platelet-Rich Plasma for the Treatment of Interstitial Supraspinatus Tears: A Double-Blinded, Randomized Controlled Trial.

BACKGROUND: The benefits of platelet-rich plasma (PRP) for the treatment of rotator cuff tears remain inconclusive, as it is administered either as an adjuvant to surgical repair or as a primary infiltration without targeting the index lesion, which could dilute its effect. PURPOSE: To determine whether PRP infiltrations are superior to saline solution infiltrations (placebo) at improving healing, pain, and function when injected under ultrasound guidance within isolated interstitial supraspinatus tears. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In this single-center, double-blinded, randomized controlled trial, 80 adults with symptomatic isolated interstitial tears of the supraspinatus, confirmed by magnetic resonance arthrography, were randomized to PRP or saline injections. Each patient received 2 injections with a 1-month interval. The primary outcome was the change in lesion volume, calculated on magnetic resonance arthrography, at 7 months. The secondary outcomes were improvements in shoulder pain and the Single Assessment Numerical Evaluation (SANE) score at >12 months. RESULTS: Preoperative patient characteristics did not differ between the 2 groups. At 7 months, there were no significant differences between the PRP and control groups in terms of a decrease in lesion size (-0.3 ± 23.6 mm3 vs -8.1 ± 84.7 mm3, respectively; P = .175); reduction of pain on a visual analog scale (VAS) (-2.3 ± 3.0 vs -2.0 ± 3.0, respectively; P = .586); and improvement in SANE (16.7 ± 20.0 vs 14.9 ± 29.0, respectively; P = .650), Constant (8.6 ± 13.0 vs 10.7 ± 19.0, respectively; P = .596), and American Shoulder and Elbow Surgeons (19.5 ± 20.0 vs 21.9 ± 28.0, respectively; P = .665) scores. At >12 months, there were no significant differences between the PRP and control groups in terms of a reduction of pain on a VAS (-3.3 ± 2.6 vs -2.3 ± 3.2, respectively; P = .087) or improvement in the SANE score (24.4 ± 27.5 vs 23.4 ± 24.9, respectively; P = .846). At 19.5 ± 5.3 months, the incidence of adverse effects (pain >48 hours, frozen shoulder, extension of lesion) was significantly higher in the PRP group than the control group (54% vs 26%, respectively; P = .020). CONCLUSION: PRP injections within interstitial supraspinatus tears did not improve tendon healing or clinical scores compared with saline injections and were associated with more adverse events. REGISTRATION: NCT02672085 (ClinicalTrials.gov identifier).

A combined experimental-numerical lamellar-scale approach of tensile rupture in arterial medial tissue using X-ray tomography.

Aortic dissection represents a serious cardio-vascular disease and life-threatening event. Dissection is a sudden delamination event of the wall, possibly leading to rupture within a few hours. Current knowledge and practical criteria to understand and predict this phenomenon lack reliable models and experimental observations of rupture at the lamellar scale. In an attempt to quantify rupture-related parameters, the present study proposes an analytical model that reproduces a uniaxial test on medial arterial samples observed under X-ray tomography. This model is composed of several layers that represent the media of the aortic wall, each having proper elastic and damage properties. Finite element models were created to validate the analytical model using user-defined parameters. Once the model was validated, an inverse analysis was used to fit the model parameters to experimental curves of uniaxial tests from a published study. Because this analytical model did not consider delamination strength between layers, a finite element model that included this phenomenon was also developed to investigate the influence of the delamination on the stress-strain curve through a sensitivity analysis. It was shown that shear delamination strength between layers, i.e. mode II separation, is essential in the rupture process observed experimentally.

Activation of ADAM17 (A Disintegrin and Metalloprotease 17) on Glutamatergic Neurons Selectively Promotes Sympathoexcitation.

Chronic activation of the brain renin-angiotensin system contributes to the development of hypertension by altering autonomic balance. Beyond the essential role of Ang II (angiotensin II) type 1 receptors, ADAM17 (A disintegrin and metalloprotease 17) is also found to promote brain renin-angiotensin system overactivation. ADAM17 is robustly expressed in various cell types within the central nervous system. The aim of this study was to determine whether ADAM17 modulates presympathetic neuronal activity to promote autonomic dysregulation in salt-sensitive hypertension. To test our hypothesis, ADAM17 was selectively knocked down in glutamatergic neurons using Cre-loxP technology. In mice lacking ADAM17 in glutamatergic neurons, the blood pressure increase induced by deoxycorticosterone acetate-salt treatment was blunted. Deoxycorticosterone acetate-salt significantly elevated cardiac and vascular sympathetic drive in control mice, while such effects were reduced in mice with ADAM17 knockdown. This blunted sympathoexcitation was extended to the spleen, with a lesser activation of the peripheral immune system, translating into a sequestration of circulating T cells within this organ, compared with controls. Within the paraventricular nucleus, Ang II-induced activation of kidney-related presympathetic glutamatergic neurons was reduced in ADAM17 knockdown mice, with the majority of cells no longer responding to Ang II stimulation, confirming the supportive role of ADAM17 in increasing presympathetic neuronal activity. Overall, our data highlight the pivotal role of neuronal ADAM17 in regulating sympathetic activity and demonstrate that activation of ADAM17 in glutamatergic neurons leads to a selective increase of sympathetic output, but not vagal tone, to specific organs, ultimately contributing to dysautonomia and salt-sensitive hypertension.

Postoperative Mobilization After Superior Rotator Cuff Repair: Sling Versus No Sling: A Randomized Prospective Study.

BACKGROUND: Patients are commonly advised to wear a sling for 4 to 6 weeks after rotator cuff repair despite negative effects of early immobilization and benefits of motion rehabilitation. The aim of this study was to compare clinical and radiographic outcomes up to 6 months following rotator cuff repair with and without postoperative sling immobilization. METHODS: We randomized 80 patients scheduled for arthroscopic repair of a small or medium superior rotator cuff tear into sling and no-sling groups (40 patients each). Passive mobilization was performed in both groups during the first 4 postoperative weeks, and this was followed by progressive active mobilization. Patients were evaluated clinically at 10 days and 1.5, 3, and 6 months and using ultrasound at 6 months. Univariable and multivariable analyses were performed to determine if postoperative scores were associated with sex, age at surgery, immobilization, arm dominance, a biceps procedure, resection of the distal part of the clavicle, or preoperative scores. RESULTS: The sling and no-sling groups had similar preoperative patient characteristics, function, and adjuvant procedures. At 10 days, there was no difference in pain between the 2 groups (mean pain score [and standard deviation], 5.2 ± 2.3 versus 5.2 ± 1.9, p = 0.996). In comparison with the sling group, the no-sling group showed greater mean external rotation (23.5° ± 15.6° versus 15.3° ± 14.6°, p = 0.017) and active elevation (110.9° ± 31.9° versus 97.0° ± 25.0°, p = 0.038) at 1.5 months as well as better mean active elevation (139.0° ± 24.7° versus 125.8° ± 24.4°, p = 0.015) and internal rotation (T12 or above in 50% versus 28%, p = 0.011) at 3 months. Ultrasound evaluation revealed no significant differences at 6 months in tendon thickness anteriorly (p = 0.472) or posteriorly (p = 0.639), bursitis (p = 1.000), echogenicity (p = 0.422), or repair integrity (p = 0.902). Multivariable analyses confirmed that the mean American Shoulder and Elbow Surgeons (ASES) score increased with patient age (beta, 0.60; p = 0.009), the Single Assessment Numeric Evaluation (SANE) decreased with sling immobilization (beta, -6.33; p = 0.014), and pain increased with sling immobilization (beta, 0.77; p = 0.022). CONCLUSIONS: No immobilization after rotator cuff repair is associated with better early mobility and functional scores in comparison with sling immobilization. Postoperative immobilization with a sling may therefore not be required for patients treated for a small or medium tendon tear. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Interaction between TRPV1-expressing neurons in the hypothalamus.

Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel expressed in the peripheral and central nervous systems. TRPV1-dependent mechanisms take part in a wide range of physiological and pathophysiological pathways including the regulation of homeostatic functions. TRPV1 expression in the hypothalamus has been described as well as evidence that TRPV1-dependent excitatory inputs to hypothalamic preautonomic neurons are diminished in diabetic conditions. Here we aimed to determine the functional expression of TRPV1 in two hypothalamic nuclei known to be involved in the central control of metabolism and to test the hypothesis that TRPV1-expressing neurons receive TRPV1-expressing inputs. A mouse model (TRPV1Cre/tdTom) was generated to identify TRPV1-expressing cells and determine the cellular properties of TRPV1-expressing neurons in adult mice. Our study demonstrated the functional expression of TRPV1 in the dorsomedial hypothalamic nucleus and paraventricular nucleus in adult mice. Our findings revealed that a subset of TRPV1Cre/tdTom neurons receive TRPV1-expressing excitatory inputs, indicating direct interaction between TRPV1-expressing neurons. In addition, astrocytes likely play a role in the modulation of TRPV1-expressing neurons. In summary, this study identified specific hypothalamic regions where TRPV1 is expressed and functional in adult mice and the existence of direct connections between TRPV1Cre/tdTom neurons. NEW & NOTEWORTHY Transient receptor potential vanilloid type 1 (TRPV1) is expressed in the hypothalamus, and TRPV1-dependent regulation of preautonomic neurons is decreased in hyperglycemic conditions. Our study demonstrated functional expression of TRPV1 in two hypothalamic nuclei involved in the control of energy homeostasis. Our results also revealed that a subset of TRPV1-expressing neurons receive TRPV1-expressing excitatory inputs. These findings suggest direct interaction between TRPV1-expressing neurons.

Determinant Role of Electrogenerated Reactive Nucleophilic Species on Selectivity during Reduction of CO2 Catalyzed by Metalloporphyrins.

This work provides insights to understand the selectivity during the reduction of CO2 with metalloporphyrin (MP) catalysts. The attack of a nucleophile on the carbon of the CO2 appears as an important event that triggers the catalytic reaction, and the nature of this nucleophile determines the selectivity between CO (or further reduced species) and HCOOH/HCOO-. For MP, the possible electrogenerated nucleophiles are the reduced metal-center and the hydride donor species, metal-hydride and phlorin-hydride ligand. The reduced metal-center activates the CO2 with the formation of the metal-carbon bond, which then gives rise to the formation of CO. The hydride donor species trigger the CO2 reduction by the attack of the hydride on the carbon of the CO2 (formation of a C-H bond), which results in the formation of HCOOH/HCOO- (formation of the metal-bonded formate intermediate is not involved). The MP with the metals Ni, Cu, Zn, Pd, Ag, Cd, Ga, In, and Sn are predicted to only form the phlorin-hydride intermediate and are thus suitable to produce HCOOH/HCOO-. This agrees well with the available experimental results. The MP with the metals Fe, Co, and Rh can form both the reduced-metal center and the hydride donor species (metal-hydride and phlorin-hydride), and thus are able to form both CO and HCOOH/HCOO-. The production of CO for Fe and Co is indeed observed experimentally, but not for Rh, probably due to the presence of axial ligands that may hinder the formation of the metal-bonded intermediates and thus drive the CO2RR to HCOOH/HCOO- via the phlorin intermediate.

Use of sacubitril/valsartan in acute decompensated heart failure: a case report.

Refractory heart failure typically requires costly long-term, continuous intravenous inodilator infusions while patients await mechanical circulatory support or cardiac transplantation. The combined angiotensin receptor blocker-neprilysin inhibitor, sacubitril/valsartan, is a novel therapy that can increase levels of endogenous vasoactive peptides. This therapy has been recommended as an alternative agent in patients with chronic heart failure with reduced ejection fraction and New York Heart Association class II-III symptoms. Here, we report a case of a patient with refractory stage D heart failure with reduced ejection fraction who was successfully weaned off continuous intravenous inodilator support using sacubitril/valsartan after prior failed attempts using standard therapies.

Spirometry and provocation tests for vocal fold dysfunction diagnosis: a retrospective case series.

AIMS: Vocal cord dysfunction (VCD) is characterised by paradoxical inspiratory laryngeal motion and is often misdiagnosed as asthma. Definitive diagnosis of VCD is difficult, because laryngoscopy is positive only during symptomatic episodes or upon provocation with exercise or inhaled irritants. The aims of the study were to better characterise the symptomatology of patients with VCD and to evaluate the potential usefulness of less-invasive diagnostic tools, namely provocation tests and spirometry. METHODS: Retrospective case series of 84 patients with a typical clinical history of VCD, in whom at least one of the three following diagnostic tests were performed: laryngoscopy, provocation testing, or spirometry. RESULTS: The mean age of the patients was 51 years and 74% were women. The principal comorbidities were rhinosinusitis (60%), gastro-oesophageal reflux disease (56%) and atopy (54%). Diagnosis of VCD was confirmed in 73/84 cases (87%), by laryngoscopy (8%), spirometry (84%) and/or provocation tests (68%). CONCLUSIONS: VCD remains an underdiagnosed condition. A negative finding on laryngoscopy can lead to false negative diagnosis if it is done when the patient is asymptomatic. Here we show that a clinical suspicion of VCD, evoked by medical history, can be confirmed in many cases by less invasive diagnostic tools such as spirometry and provocation tests. Future well-conducted prospective case-control studies are needed to draw firmer conclusions and to improve the diagnostic accuracy of this condition.  .

Overactivity of Liver-Related Neurons in the Paraventricular Nucleus of the Hypothalamus: Electrophysiological Findings in db/db Mice.

Preautonomic neurons in the paraventricular nucleus (PVN) of the hypothalamus play a large role in the regulation of hepatic functions via the autonomic nervous system. Activation of hepatic sympathetic nerves increases glucose and lipid metabolism and contributes to the elevated hepatic glucose production observed in the type 2 diabetic condition. This augmented sympathetic output could originate from altered activity of liver-related PVN neurons. Remarkably, despite the importance of the brain-liver pathway, the cellular properties of liver-related neurons are not known. In this study, we provide the first evidence of overall activity of liver-related PVN neurons. Liver-related PVN neurons were identified with a retrograde, trans-synaptic, viral tracer in male lean and db/db mice and whole-cell patch-clamp recordings were conducted. In db/db mice, the majority of liver-related PVN neurons fired spontaneously; whereas, in lean mice the majority of liver-related PVN neurons were silent, indicating that liver-related PVN neurons are more active in db/db mice. Persistent, tonic inhibition was identified in liver-related PVN neurons; although, the magnitude of tonic inhibitory control was not different between lean and db/db mice. In addition, our study revealed that the transient receptor potential vanilloid type 1-dependent increase of excitatory neurotransmission was reduced in liver-related PVN neurons of db/db mice. These findings demonstrate plasticity of liver-related PVN neurons and a shift toward excitation in a diabetic mouse model. Our study suggests altered autonomic circuits at the level of the PVN, which can contribute to autonomic dysfunction and dysregulation of neural control of hepatic functions including glucose metabolism.SIGNIFICANCE STATEMENT A growing body of evidence suggests the importance of the autonomic control in the regulation of hepatic metabolism, which plays a major role in the development and progression of type 2 diabetes mellitus. Despite the importance of the brain-liver pathway, the overall activity of liver-related neurons in control and diabetic conditions is not known. This is a significant gap in knowledge, which prevents developing strategies to improve glucose homeostasis via altering the brain-liver pathway. One of the key findings of our study is the overall shift toward excitation in liver-related hypothalamic neurons in the diabetic condition. This overactivity may be one of the underlying mechanisms of elevated sympathetic activity known in metabolically compromised patients and animal models.

Investigation of the HD-sEMG probability density function shapes with varying muscle force using data fusion and shape descriptors.

This work presents an evaluation of the High Density surface Electromyogram (HD-sEMG) Probability Density Function (PDF) shape variation according to contraction level. On that account, using PDF shape descriptors: High Order Statistics (HOS) and Shape Distances (SD), we try to address the absence of a consensus for the sEMG non-Gaussianity evolution with force variation. This is motivated by the fact that PDF shape information are relevant in physiological assessment of the muscle architecture and function, such as contraction level classification, in complement to classical amplitude parameters. Accordingly, both experimental and simulation studies are presented in this work. For data fusion, the watershed image processing technique was used. This technique allowed us to find the dominant PDF shape variation profiles from the 64 signals. The experimental protocol consisted of three isometric isotonic contractions of 30, 50 and 70% of the Maximum Voluntary Contraction (MVC). This protocol was performed by six subjects and recorded using an 8 × 8 HD-sEMG grid. For the simulation study, the muscle modeling was done using a fast computing cylindrical HD-sEMG generation model. This model was personalized by morphological parameters obtained by sonography. Moreover, a set of the model parameter configurations were compared as a focused sensitivity analysis of the PDF shape variation. Further, monopolar, bipolar and Laplacian electrode configurations were investigated in both experimental and simulation studies. Results indicated that sEMG PDF shape variations according to force increase are mainly dependent on the Motor Unit (MU) spatial recruitment strategy, the MU type distribution within the muscle, and the used electrode arrangement. Consequently, these statistics can give us an insight into non measurable parameters and specifications of the studied muscle primarily the MU type distribution.