Effects of gender and age on median and ulnar nerve sensory responses over ring finger

ObjectiveTo analyze the effect of gender on median nerve (MN) and ulnar nerve (UN) sensorial responses over ring finger (RF).Materials and methodsResults of individuals admitted to our ENMG laboratory between June 2011 and March 2012 for nerve conduction studies (NCSs) were retrospectively analyzed. Sensory NCSs were performed by standard antidromic technique.ResultsTotally, 112 normal recordings belong to 100 patients were included. Mean antidromic sensory conduction velocity of MNs (wrist-to-second finger) or UNs (wrist-to-fifth finger) was not different between two genders. Mean sensory nerve action potential (SNAP) amplitude of MN from second finger was also not different between two genders. However, mean SNAP amplitude of UN from fifth finger was higher in females. In RF’s sensorial response studies; mean peak latency of MN was similar between females and males (3.05 ± 0.25 ms vs. 3.14 ± 0.29 ms, p = 0.111), whereas one of UN was shorter in females (2.86 ± 0.22 ms vs. 3.04 ± 0.31 ms, p = 0.001). MN to UN latency difference to RF was greater in females than males (0.19 ± 0.15 ms vs. 0.10 ± 0.16 ms, p = 0.007). Mean SNAP amplitude of MN and UN were both higher in females than males (17.9 ± 7.1 μV vs. 14.1 ± 5.5 μV, p = 0.011 and 18.5 ± 8.0 μV vs. 12.9 ± 6.1 μV, p = 0.0009, respectively). All data of NCSs were re-analyzed after adjustment for age, and obtained findings regarding effect of aging are also included.ConclusionGender has a prominent effect on RF’s sensorial responses. Normative values regarding them should be prepared with adjustment for gender.     

Rotator cuff tendinopathy alters the muscle activity onset and kinematics of scapula

Athletes with rotator cuff (RC) tendinopathy demonstrate an aberrant pattern of scapular motion which might relate to deficits in the scapular muscles. This study aimed to determine whether alteration in scapular kinematics is associated with deficits in the activity onset of scapular muscles. Forty-three male volleyball players (17 asymptomatic and 26 with RC tendinopathy) joined the study. Three-dimensional scapular kinematics was quantified using an acromial marker cluster method. The activity onset of the upper (UT), middle (MT), and lower trapezius (LT), and serratus anterior (SA) during arm abduction was assessed with electromyography. Athletes with RC tendinopathy demonstrated less scapular upward rotation (6.6 ± 2.3 vs. 8.2 ± 1.1°, p = 0.021) in the early phase of shoulder abduction from 0° to 30° when compared to asymptomatic athletes. The tendinopathy group had delayed activity onset of LT (14.1 ± 31.4 ms vs. 74.4 ± 45.1 ms, p < 0.001) and SA (−44.9 ± 26.0 ms vs. 23.0 ± 25.2 ms, p < 0.001) relative to UT when compared to the asymptomatic group. In asymptomatic athletes, earlier activity onset of MT and LT relative to UT was associated with more scapular upward rotation during 0–30° of abduction (r = 0.665, p = 0.021) and 30–60° of abduction (r = 0.680, p = 0.015), respectively. Our findings showed the control of the scapular upward rotation is related to the activity onset of the scapular muscles in athletes.     

Intérêt potentiel des images paramétriques des temps d’éjection et de relaxation en tomoscintigraphie des cavités cardiaques dans l’évaluation des cardiopathies asynchrones

Intraleft dyssynchrony is strongly correlated to contractile dysfunction associated to severe heart failure. Dyssynchrony is also a predictive marker for cardiac resynchronization therapy response. We measured dyssynchrony values for both ventricles from gated blood pool SPECT images.Material and methodsThree groups of patients were sampled from normal patients (n = 7), mild heart failure patients (n = 24) and severe heart failure patients (n = 9). Time-derivative parametric images were obtained from 24-time bins gated blood pool SPECT data. We measured intraleft and interventricular contractile and relaxing dyssynchrony values from these images.ResultsIntraleft dispersions values linked to ventricular peak emptying rate were 107 ± 21 ms, 141 ± 58 ms and 515 ± 104 ms for each of the three groups. The values linked to left ventricular peak filling rate were 122 ± 62 ms, 219 ± 117 ms and 603 ± 164 ms respectively. Statistical significant differences (p < 0.01) were observed both for contractile and relaxing phases for severe heart failure patients. Mild heart failure patients had isolated statistical significant (p < 0.01) alterations of the ventricular relaxing phase. Correlation between isotopic dyssynchrony values and left ejection fraction led to a R square coefficient of 0.71 and 0.64 for time to peak emptying and to peak filling respectively. Correlation to QRS width values led to a R square coefficient of 0.76 and 0.62 respectively.ConclusionVentricular dyssynchrony correlated to the importance of the ventricular mechanical dysfunctions is a robust predictor of heart failure. Separate analysis of contractile and relaxing dyssynchrony may lead to a better understanding and characterization of the mechanical dysfunctions involved in heart failure.     

Algorithmic detection of the beginning and end of bipolar electrograms: Implications for novel methods to assess local activation time during atrial tachycardia

Activation mapping is required to effectively ablate atrial tachycardia (AT). Conventional tools to assess local activation time (LAT) are based upon the peak of the bipolar electrogram (B-EGM, LAT_Peak) and the maximal negative slope of the unipolar electrogram (U-EGM, LAT_Slope). Bipolar electrograms are influenced by wavefront direction, bipole orientation, and inter-electrode spacing causing ambiguity in peak detection, whereas unipolar electrograms are disturbed by the presence of far-field signals. We developed a new algorithm to detect the beginning and end of bipolar electrograms (t_begin and t_end). Then, we introduced new LAT methods related to the onset of B-EGMs (LAT_Onset), the center of mass of B-EGMs (LAT_CoM), and the slope of U-EGMs within a pre-defined window (LAT_Slope-hybrid).In total 3752 recordings from 31 AT patients were retrospectively analyzed. The signal-to-noise ratio (SNR) for B-EGMs was calculated to differentiate algorithmically high from low quality electrograms (HQ and LQ). In a subset of 328 B-EGMs, five experts validated the t_begin as determined by the algorithm by visual rating. The newly developed LAT methods were compared to the conventional LAT methods and to one another (Bland–Altman plots) in both HQ (n = 3003) and LQ EGMs (n = 749).The t_begin algorithm was accurate (deviation < ±10 ms) in 96 ± 4% of HQ and 91 ± 8% of LQ B-EGMs. BA plots revealed the following difference (bias) and variation in HQ and LQ EGMs respectively: (1) LAT_Onset vs. LAT_Peak: 27 ± 30 ms and 24 ± 62 ms; (2) LAT_CoM vs. LAT_Peak: 0 ± 16 ms and 2 ± 38 ms; (3) LAT_Slope-hybrid vs. LAT_Slope: 1 ± 32 ms and 15 ± 110 ms; (4) LAT_Onset vs. LAT_CoM: 22 ± 24 ms and 18 ± 22 ms; (5) LAT_Onset vs. LAT_Slope-hybrid: 16 ± 18 ms and 13 ± 22 ms; and (6) LAT_CoM vs. LAT_Slope-hybrid: 5 ± 20 ms and 4 ± 18 ms.In the present study, we introduced three new methods to assess local activation time in AT, based upon an algorithm detecting accurately the beginning and end of the B-EGM complex. BA analysis of the new methods showed similar variation in high and low quality EGMs, suggesting that they introduce less ambiguity than the conventional peak method. LAT_Onset consistently yielded an earlier activation moment. LAT_Slope-hybrid – by blanking far-field potentials – seems to be the optimal method for detection of the maximal negative slope in U-EGMs. Interestingly, LAT_CoM in B-EGMs coincided with the maximal negative slope in U-EGMs, suggesting its physiological sense and future use. The new LAT methods can be implemented in real-time mapping applications.     

Effect Of Levothyroxine Treatment On Qt Dispersion In Patients With Subclinical Hypothyroidism

ObjectiveTo examine the effect of levothyroxine treatment in patients with subclinical hypothyroidism on electrocardiographic variables, especially on ventricular repolarization-related factors.Methods:Sixteen women (mean age, 48.2 years) with subclinical hypothyroidism were treated with levothyroxine for 16 weeks. All standard 12-lead electrocardiograph-ic recordings were scanned and transferred to a computer, and the QT intervals were measured on 300 times magnified recordings. QT dispersion, which reflects the heterogeneity of the ventricular repolarization, was calculated by the difference between the QT maximum and the QT minimum.ResultsWe found that, after 16 weeks of levothyroxine treatment, the QT interval decreased from 387.2 ± 10.8 ms to 345.6 ± 13.0 ms (P < 40.0001). The study patients exhibited a significant reduction of QT dispersion from 46.5 ± 5.3 ms to 30.7 ± 5.8 ms (P < 0.0001). On linear regression analysis, a positive relationship was found between QT dispersion and logarithmic serum TSH levels (r = 0.492; P < 0.0001).ConclusionWe conclude that serum TSH concentration has a role in ventricular inhomogeneity and, therefore, that subclinical hypothyroidism may predispose to ventricular arrhythmias. A large-scale, multicenter, randomized trial should be undertaken to address the benefit-to-risk ratio of levothyroxine treatment on cardiac inhomogeneity in patients with subclinical hypothyroidism. (Endocr Pract. 2007;13:711-715)     

Does interhemispheric communication relate to the bilateral function of muscles? A study of scapulothoracic muscles using transcranial magnetic stimulation

Interhemispheric connections have been demonstrated between the motor cortex controlling muscle pairs. However, these investigations have tended to concentrate upon hand muscles. We have extended these investigations to proximal muscles that control the scapula upon the trunk and help to move and stabilise the shoulder. Using a paired pulse transcranial magnetic stimulation protocol, the interhemispheric interactions between different shoulder girdle muscle pairs, serratus anterior, upper trapezius and lower trapezius were investigated. Test motor evoked potentials were conditioned using conditioning pulse intensities of 80% and 120% of active motor threshold at three different condition-test intervals, during three different tasks. Interhemispheric inhibition was observed in upper trapezius using a conditioning intensity of 120% and condition-test interval of 8 ms (17 ± 18%, p < 0.007). A trend towards inhibition was observed in lower trapezius and serratus anterior using a conditioning intensity of 120% and a condition-test interval of 8 ms (13 ± 22%; p < 0.07 and 10 ± 19% respectively; p < 0.07). No interhemispheric facilitation was evoked. The study demonstrates that a low level of interhemispheric inhibition rather than interhemispheric facilitation could be evoked between these muscle pairs.     

Heart rate and arterial pressure variability and baroreflex sensitivity in ovariectomized spontaneously hypertensive rats

AimsThe present study evaluated the effects of ovariectomy on heart rate and arterial pressure variability and cardiac baroreflex sensitivity (BRS) in female spontaneously hypertensive (SHR) and Wistar–Kyoto rats (WKY).Main methodsSham-surgery animals were used as control. Sixteen weeks after ovariectomy or sham-surgery, animals were recorded. Time series of pulse interval (PI) and systolic AP (SAP) were analyzed by means of autoregressive spectral analysis, which quantifies the power of very low (VLF = 0.01–0.25 Hz), low (LF = 0.25–0.75 Hz) and high frequency (HF = 0.75–2.5 Hz) bands. BRS was assessed by means of linear regression between changes of PI and SAP induced by vasoactive drugs or calculation of α-index, a spontaneous BRS index.Key findingsThere was no difference in baseline PI or SAP between ovariectomized and sham SHR. Spectral analysis of heart rate variability suggested a shift of sympatho-vagal balance toward sympathetic predominance in ovariectomized SHR (LF/HF = 1.8 ± 0.2 versus 0.7 ± 0.2 in sham SHR, p < 0.05). Ovariectomy increased total variance and VLF power of SAP in SHR (29.1 ± 9.6 mmHg² and 18.6 ± 6.3 mmHg² versus 9.1 ± 2.1 mmHg² and 4.3 ± 1.4 mmHg², respectively, in sham SHR, p < 0.05). In addition, ovariectomy reduced reflex bradycardia in SHR (0.18 ± 0.03 ms/mmHg versus 0.34 ± 0.06 ms/mmHg in sham SHR, p < 0.05). Ovariectomy did not affect heart rate and SAP variability or BRS in WKY.SignificanceThese data showed that ovarian hormones deprivation induced marked changes on cardiovascular control, increasing SAP variability and cardiac sympatho-vagal balance and blunting BRS in female hypertensive animals, which reinforce the possible protective role of ovarian hormones on the cardiovascular system.     

Limited versus total epithelial debridement ocular surface injury: Live fluorescence imaging of hemangiogenesis and lymphangiogenesis in Prox1-GFP/Flk1::Myr-mCherry mice

BackgroundImmunohistochemical staining experiments have shown that both hemangiogenesis and lymphangiogenesis occur following severe corneal and conjunctival injury and that the neovascularization of the cornea often has severe visual consequences. To better understand how hemangiogenesis and lymphangiogenesis are induced by different degrees of ocular injury, we investigated patterns of injury-induced corneal neovascularization in live Prox1-GFP/Flk1::myr-mCherry mice, in which blood and lymphatic vessels can be imaged simultaneously in vivo.MethodsThe eyes of Prox1-GFP/Flk1::myr-mCherry mice were injured according to four models based on epithelial debridement of the: A) central cornea (a 1.5-mm-diameter circle of tissue over the corneal apex), B) total cornea, C) bulbar conjunctiva, and D) cornea + bulbar conjunctiva. Corneal blood and lymphatic vessels were imaged on days 0, 3, 7, and 10 post-injury, and the percentages of the cornea containing blood and lymphatic vessels were calculated.ResultsNeither central corneal nor bulbar conjunctival debridement resulted in significant vessel growth in the mouse cornea, whereas total corneal and corneal + bulbar conjunctival debridement did. On day 10 in the central cornea, total cornea, bulbar conjunctiva, and corneal + bulbar conjunctival epithelial debridement models, the percentage of the corneal surface that was occupied by blood vessels (hemangiogenesis) was 1.9 ± 0.8%, 7.14 ± 2.4%, 2.29 ± 1%, and 15.05 ± 2.14%, respectively, and the percentage of the corneal surface that was occupied by lymphatic vessels (lymphangiogenesis) was 2.45 ± 1.51%, 4.85 ± 0.95%, 2.95 ± 1.27%, and 4.15 ± 3.85%, respectively.ConclusionsSubstantial corneal debridement was required to induce corneal neovascularization in the mouse cornea, and the corneal epithelium may therefore be partially responsible for maintaining corneal avascularity.General significanceOur study demonstrates that GFP/Flk1::myr-mCherry mice are a useful model for studying coordinated hemangiogenic and lymphangiogenic responses.     

Effect of preischemic β-adrenoceptor stimulation on postischemic contractile dysfunction

AimsShort periods of preischemic β-adrenoceptor stimulation protect hearts against postischemic left ventricular dysfunction. It was the aim of this study to decide whether this procedure mimics ischemic preconditioning by the generation of preischemic hemodynamic and energetic stress or whether it represents an endogenous phenomenon and to investigate the influence of age and hypertension.Main methodsIsolated rat hearts were investigated ex vivo by Langendorff perfusion and exposed to an established ischemia/reperfusion protocol (45 min no-flow ischemia and 90 min reperfusion). Left ventricular developed pressure (LVDP), rate pressure product, and ± dP/dt were analyzed.Key findingsIsoprenaline concentration dependently increased LVDP up to 40 ± 15 mm Hg (approximately EC₅₀ of 9.9 ± 0.5 nM). Isoprenaline given prior to ischemia attenuated the subsequent postischemic ventricular dysfunction (approximately EC₅₀ of 1.4 ± 0.2 pM). However, concentrations high enough to improve LVDP in normoxic hearts did not improve postischemic recovery albeit a significant reduction of hypercontraction-induced cell damage. The effect on functional recovery was attenuated by atenolol, H89, and wortmannin suggesting that β-adrenoceptor stimulation, protein kinase A, and PI 3-kinase activation are involved. The effect was conserved in hearts from 13 month old rats but lost in age-matched spontaneously hypertensive rats.SignificanceThe study identifies preischemic β-adrenoceptor stimulation as a pharmacological preconditioning protocol that does not simply mimic classical ischemic preconditioning by induction of hemodynamic or energetic stress prior to a prolonged ischemic period. The observed loss of effectiveness in hypertensives may contribute to the reduced ischemic tolerance of hypertensives.     

Efecto positivo de la terapia de luz brillante sobre el estado de ánimo y la calidad del sueño en las personas mayores institucionalizadas

IntroductionBright light exposure during the day has a positive effect on health and its deficit can cause multiple physiological and cognitive disorders, including depression. The aim of this study was to evaluate the effect of bright light therapy (BLT) on the quality of sleep and mood emotional state; cognitive status, global deterioration and quality of life in institutionalized elderly.Material and methodsThis is a study with repeated measures design. Thirty-seven older people admitted to a nursing home. The study lasted 3 weeks. The first week, the reference values were established with the Oviedo Sleep Questionnaire, Yesavage Depression Scale, Mini-Mental, Global Scale of Impairment and European Quality of Life Questionnaire. During the second week, they were exposed to BLT (7,000-10,000 lx at eye level) between 9:30 a.m. and 11:00 a.m. During the third week, all the data were re-evaluated.ResultsAll variables improved significantly after the application of light therapy. Sleep (COS) pre-test 4.1 ± 1.49, post-test 4.9 ± 1.46, p: 0.01), mood (pre-test 3.65 ± 2.78, post-test 2.65 ± 2.9, p: 0.01), cognitive state (pre-test 22.72 ± 6.53, post-test 24 ± 5.92, p: 0.001), state of global deterioration (pre-test 3.10 ± 1.26, post-test 2.72 ± 5.92, p: 0.001) and health-related quality of life (pre-test 6.93 ± 1.86, post-test 7.82 ± 1.62, p: 0.001).ConclusionsSleep quality, mood, cognitive status, global deterioration status and quality of life significantly improved after the application of light bright therapy.     

The influence of pre-operative risk on the number of circulating endothelial progenitor cells during cardiopulmonary bypass

Background aimsThe number of circulating endothelial progenitor cells (EPC) depends on cytokine release and is also associated with cardiovascular risk factors. During cardiopulmonary bypass (CPB) the endothelium is the first organ to be affected by mechanical and immunologic stimuli. We hypothesized that the magnitude of EPC mobilization by CPB correlates with the pre-operative cardiovascular morbidity profile.MethodsEPC were quantified in blood samples from 30 patients who underwent cardiac surgery by magnetic bead isolation and fluorescence-activated cell sorting (FACS) analysis, based on concomitant expression of CD34, CD133 and CD309. Patients were divided into two groups based on the European System for Cardiac Operative Risk Evaluation (EuroSCORE): low risk (LR) and high risk (HR). Ten healthy volunteers served as controls. Samples were obtained before the start of CPB and at 1 and 24 h post-operatively. Plasma samples were collected for determination of release levels of cytokines and growth factors.ResultsAll CPB patients showed a significantly reduced basal number of EPC compared with healthy individuals (LR 5.60 ± 0.39/mL, HR 3.89 ± 0.34/ mL, versus control 0.807 ± 0.82/mL, P = 0.012 versus LR, P < 0.001 versus HR). CPB induced EPC release that peaked 1 h after surgery (pre-operative 4.79 ± 0.32/mL, 1 h 57.49 ± 5.31/mL, 24 h 6.67 ± 1.05/mL, P < 0.001 pre-operative versus 1 h, P < 0.001 pre-operative versus 24 h) and was associated with the duration of CPB. However, EPC release was significantly attenuated in HR patients (33.09 ± 3.58/mL versus 81.89 ± 4.36/mL at 1 h after CPB, P < 0.0001) and inversely correlated with the pre-operative EuroSCORE. Serum granulocyte–colony-stimulating factor (G-CSF), stem cell factor (SCF) and vascular endothelial growth factor (VEGF) levels increased throughout the observation period and were also correlated with the EPC count.ConclusionsCardiovascular risk factors influence the mobilization of EPC from the bone marrow after stimulation by CPB. This could be secondary to impaired mobilization or the result of increased EPC turnover, and may have implications for future cell therapy strategies in cardiac surgical patients.     

Torque-onset determination: Unintended consequences of the threshold method

Background: Compared with visual torque-onset-detection (TOD), threshold-based TOD produces onset bias, which increases with lower torques or rates of torque development (RTD). Purpose: To compare the effects of differential TOD-bias on common contractile parameters in two torque-disparate groups. Methods: Fifteen boys and 12 men performed maximal, explosive, isometric knee-extensions. Torque and EMG were recorded for each contraction. Best contractions were selected by peak torque (MVC) and peak RTD. Visual-TOD-based torque-time traces, electromechanical delays (EMD), and times to peak RTD (tRTD) were compared with corresponding data derived from fixed 4-N m- and relative 5%MVC-thresholds. Results: The 5%MVC TOD-biases were similar for boys and men, but the corresponding 4-N m-based biases were markedly different (40.3 ± 14.1 vs. 18.4 ± 7.1 ms, respectively; p < 0.001). Boys–men EMD differences were most affected, increasing from 5.0 ms (visual) to 26.9 ms (4 N m; p < 0.01). Men’s visually-based torque kinetics tended to be faster than the boys’ (NS), but the 4-N m-based kinetics erroneously depicted the boys as being much faster to any given %MVC (p < 0.001). Conclusions: When comparing contractile properties of dissimilar groups, e.g., children vs. adults, threshold-based TOD methods can misrepresent reality and lead to erroneous conclusions. Relative-thresholds (e.g., 5% MVC) still introduce error, but group-comparisons are not confounded.     

Anosmia does not impair the anxiolytic-like effect of lavender essential oil inhalation in mice

AimThe inhalation of Lavandula angustifolia (lavender) essential oil has anxiolytic-like effects in animal models and humans, but its mechanism of action is still not fully understood. The inhalation of essential oils can induce anxiolytic effects through the central nervous system (e.g., lung absorption and bloodstream transport) or stimulation of the olfactory system and secondary activation of brain regions. Thus, the main objective of the present study was to evaluate whether the perception of lavender essential oil aroma, when inhaled, is necessary to obtain its anxiolytic-like effects in mice tested in the marble-burying test.Main methodsAnosmia was induced by irrigating the nasal cavity with zinc gluconate + zinc acetate so that the mice could not detect odors in the olfactory discrimination test. The marble-burying test was used to evaluate the anxiolytic-like effects of inhaled lavender essential oil.Key findingsAnosmia did not interfere with the anxiolytic-like effect of lavender essential oil inhalation in the marble-burying test at concentrations of 2.5% (number of marbles buried: vehicle, 4.7 ± 1.0; zinc, 6.2 ± 2.2; p > 0.10) and 5% (number of marbles buried: vehicle, 3.4 ± 0.8; zinc, 4.3 ± 0.9; p > 0.10). Lavender essential oil at a concentration of 0.5% was ineffective.SignificanceThese results suggest that olfactory system activation is unlikely to participate in the anxiolytic-like effect of lavender essential oil inhalation.     

Conduction velocity of the human phrenic nerve in the neck

PurposeTo measure phrenic nerve conduction velocity in the neck in humans.ScopeWe studied 15 healthy subjects (9 men, 32.4 ± 6.7). We performed bipolar electrical phrenic stimulation in the neck, from a distal and a proximal stimulation site, and recorded diaphragm electromyographic responses on the surface of the chest. The ratio of the between-site distance to the latency difference provided phrenic velocities. Ulnar motor velocity was assessed similarly. In addition, five homogeneous patients with Charcot-Marie-Tooth disease type 1A (CMT1A) were studied for validation purposes. We obtained diaphragmatic responses from the two stimulation sites in all cases. The distal latencies (anterior axillary line recording) were 6.51 ± 0.63 ms (right) and 6.13 ± 0.64 ms (left). The minimal between site distance was 39 mm. Phrenic motor velocity was 55.2 ± 6.3 m s^?1 (right) and 56.3 ± 7.2 m s^?1 (left). In CMT1A, phrenic velocities were 17.1 ± 8.1 m s^?1 (from 7 to 32 m s^?1) and were similar to ulnar and median velocities.ConclusionsPhrenic nerve velocities can be estimated in humans and compare with upper limb motor conduction velocities. This should refine the investigation of phrenic function in peripheral neuropathies.     

Synthesis,radiosynthesis and first in vitro evaluation of novel PET-tracers for the dopamine transporter: [11C]IPCIT and [18F]FE@IPCIT

IntroductionPresent data indicate that merging beneficial structural elements from previously published DAT-ligands highest DAT affinity, selectivity and a suitable metabolic profile should be achieved. This combination led to the development of IPCIT and FE@IPCIT.MethodsPrecursor synthesis was done starting from cocaine in a six step reaction. O-[¹¹C]-methylation was established using [¹¹C]methyl iodide, optimized and subsequently automated. Small scale ¹⁸F-fluroroethylation as well as optimization of reaction parameters and automation were performed. Affinity and selectivity of the candidate substances were tested in standard binding experiments on human membranes. Metabolic stability and blood–brain-barrier (BBB) penetration were determined.ResultsPrecursor compound, IPCITacid, and reference compounds, IPCIT and FE@IPCIT, were obtained in 4.9%, 12.7% and 4.1% yield, respectively. Automated radiosynthesis of [¹¹C]IPCIT yielded 1.9 ± 0.7 GBq (12.5 ± 4%, corrected for decay). Optimum parameters for ¹⁸F-fluoroethylation were 110 °C for 15 min under TBAH catalysis, yielding 67 ± 16% radiochemical incorporation. Affinity was determined as 1.7 ± 0.6 nM for IPCIT, 1.3 ± 0.2 nM for FE@IPCIT and 37 ± 13 nM for the precursor molecule, IPCIT-acid. Results from in vitro and in silico evaluations revealed high stability but also high lipophilicity.ConclusionPresent data indicate high affinity and stability of both IPCIT and FE@IPCIT. Radiolabelling, optimization of reaction parameters and automation succeeded. On the other hand, data concerning BBB-penetration are not promising.     

Metabolic control and chronic complications during a 3-year follow-up period in a cohort of type 2 diabetic patients attended in primary care in the Community of Madrid (Spain)

BackgroundOur aim was to analyze both metabolic control and chronic complications of type 2 diabetes mellitus (T2D) patients regularly attended in primary care during a 3 years of follow-up in the Community of Madrid (Spain).MethodsFrom 2007 to 2010 we prospectively included 3268 patients with T2D attended by 153 primary care physicians from 51 family health centers. An prospective cohort study with annual evaluation over 3 years to the same population was performed. We measured the goals of control in diabetic patients and the incidence of chronic complications of diabetes during the study period.ResultsA significant decrease in serum glucose levels (143 ± 42 mg/dl vs 137 ± 43 mg/dl, p < 0.00), HbA1c (7.09 ± 1.2% vs 7.02 ± 1.2%, p < 0.00), total cholesterol (191.4 ± 38 mg/dl vs 181.5 ± 36 mg/dl, p < 0.00), LDL cholesterol (114.7 ± 31 mg/dl vs 105.5 ± 30 mg/dl, p < 0.00) and triglyceride levels (144.5 ± 93 mg/dl vs 138 ± 84 mg/dl, p < 0.00) during study period was documented. On the contrary, a significant elevation in HDL cholesterol levels was observed (49.2 ± 14 mg/dl vs 49.9 ± 16 mg/dl, p < 0.00). The incidence of diabetic complications throughout the study period was low, with a incidence of coronary heart disease of 6.2%, peripheral arterial disease 3%, ischemic stroke 2.8%, diabetic foot 11.2%, nephropathy 5.9%, retinopathy 4.5%, and neuropathy 3%.ConclusionMetabolic control in T2D patients attended in primary care in the Community of Madrid throughout 3 years is adequate and is accompanied by low percent of chronic diabetic complications during this period of follow-up.     

Ultrasonographic quantification of architectural response in tibialis anterior to neuromuscular electrical stimulation

While muscle contraction in voluntary efforts has been widely investigated, little is known about contraction during neuromuscular electrical stimulation (NMES). The aim of this study was to quantify in vivo muscle architecture of agonist and antagonist muscles at the ankle joint during NMES. Muscle fascicle lengths and pennation angles of the tibialis anterior (TA) and lateral gastrocnemius muscles were assessed via ultrasonography in 8 healthy young males. Measures were obtained during maximal NMES and torque-matched voluntary dorsiflexion contractions. In the TA, NMES induced a shorter fascicle length (67.2 ± 8.1 mm vs 74.6 ± 11.4 mm; p = 0.04) and a greater pennation angle (11.0 ± 2.4° vs 9.3 ± 2.5°; p = 0.03) compared with voluntary torque-matched dorsiflexion contractions. Architectural responses in the antagonist lateral gastrocnemius muscle did not significantly differ from rest or between voluntary and electrically induced contractions (p > 0.05). Contraction of the antagonist muscle was not a contributing factor to a greater fascicle shortening and increased pennation angle in the TA during NMES. TA architectural response during NMES likely arose from the contribution of muscle synergists during voluntary contractions coupled with a potentially localized contractile activity under the stimulation electrodes during NMES induced contractions.     

Radiological properties of 3D printed materials in kilovoltage and megavoltage photon beams

PurposeThis study evaluates the radiological properties of different 3D printing materials for a range of photon energies, including kV and MV CT imaging and MV radiotherapy beams.MethodsThe CT values of a number of materials were measured on an Aquilion One CT scanner at 80 kVp, 120 kVp and a Tomotherapy Hi Art MVCT imaging beam. Attenuation of the materials in a 6 MV radiotherapy beam was investigated.ResultsPlastic filaments printed with various infill densities have CT values of −743 ± 4, −580 ± 1 and −113 ± 3 in 120 kVp CT images which approximate the CT values of low-density lung, high-density lung and soft tissue respectively. Metal-infused plastic filaments printed with a 90% infill density have CT values of 658 ± 1 and 739 ± 6 in MVCT images which approximate the attenuation of cortical bone. The effective relative electron density RED_eff is used to describe the attenuation of a megavoltage treatment beam, taking into account effects relating to the atomic number and mass density of the material. Plastic filaments printed with a 90% infill density have RED_eff values of 1.02 ± 0.03 and 0.94 ± 0.02 which approximate the relative electron density RED of soft tissue. Printed resins have RED_eff values of 1.11 ± 0.03 and 1.09 ± 0.03 which approximate the RED of bone mineral.Conclusions3D printers can model a variety of body tissues which can be used to create phantoms useful for both imaging and dosimetric studies.     

Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)     

Profil évolutif de la dénervation cardiaque sympathique dans l’amylose héréditaire à transthyrétine

IntroductionCardiac amyloidosis is a rare disease with poor prognosis, requiring an early diagnosis. I123-MIBG plays an important role in early evaluation of sympathetic cardiac innervation, which is decreased due to amyloid infiltration. The aim of this study was to assess the temporal evolution of cardiac denervation in patients with hereditary amyloidosis, particularly the rate of progression and regional abnormalities; and to identify progression markers.MethodsForty-six patients were included. All of them were carriers of a TTR mutation or received domino liver transplantation, and underwent at least two evaluations of cardiac innervation with MIBG, between February 2011 and February 2018. Progression of cardiac denervation was determined by comparing the H/M ratio at first and final assessment. Regional abnormalities were evaluated using the perfusion/innervation mismatch on a 17 segments model. Logistic regression analysis was used to identify predictors of progression.ResultsTwenty-two patients were stable and 24 were progressive. The mean delay between two MIBG scans was 3.2 ± 1.3 years. Late H/M decreased by 3.9%/year in progressive group, and tended to accelerate after symptoms onset (− 1.4 ± 5.4 vs − 0.49 ± 2.9, P = 0.03). Regional abnormalities were initally located in the infero-latéral segments and extended to the inferior and lateral walls at final assessment. LVEF (OR: 0.90, P = 0.003) and initiation of amyloidosis targeted treatment (OR = 5,35, P = 0.003) were independent predictors of sympathetic denervation progression.ConclusionProgression of myocardial sympathetic denervation in hereditary amyloidosis is slow, but accelerates after symptoms onset. LVEF and treatment are potential progression markers. Regional abnormalities are mainly located in the inferolateral segments and tend to extend at the borders of the denervated area.