The Prevalence of Allergic Rhinitis toAmbrosia Elatior in OlteniaArea and the Association with Allergic Conjunctivitis or Asthma.

Introduction-Ambrosia elatior pollen sensitivity can lead to respiratory diseases such as rhinitis, asthma and allergic conjunctivitis. Ambrosia is quite an important source of pollen and it is thought to be an invasive plant. Sensitivity prevalence to Ambrosia pollen varies from one country to another. The aim of the present study was to assess the prevalence of pollen allergic rhinitis caused by Ambrosia elatior in the Oltenia area located in the south west part of Romania. Material and method - The study was carried on 1004 patients with allergic rhinitis. All the patients experienced symptoms of allergic rhinitis, associated with /without conjunctivitis or asthma, and positive skin tests to aeroallergens. Results - In the group under study, 48,80% of the cases are sensitized to Ambrosia elatior pollen. The number of patients with allergic rhinitis and pollen sensitivity to Ambrosia is higher in 2014-2015 compared to 2012, i.e. 282 cases and the symptoms are moderate-severe. Conclusions - Ambrosia elatior pollen has become a major source of aeroallergen in Oltenia area.

Combination of Olanzapine Pamoate with Melatonin and Metformin: Quantitative Changes in Rat Adipose Tissue.

Olanzapine is one of the atypical antipsychotics widely used in the treatment of schizophrenia and has been associated with metabolic changes as adverse effects, including hyperglycemia, dyslipidemia, and weight gain. In a batch of adult female Wistar rats, we studied the prolonged-release intramuscular olanzapine pamoate induced quantitative changes of visceral and subcutaneous adipose tissue. We also assessed the effects of the combinations of olanzapine pamoate with melatonin, metformin, and melatonin plus metformin, administered by gastric gavage. A higher mean weight of the visceral and subcutaneous adipose tissue per animal was noted in the olanzapine pamoate exposed group compared to controls. The association with melatonin, metformin, or the combination of melatonin with metformin attenuated the olanzapine-induced adipose deposit tissue growth. The effect was more pronounced for the combination of olanzapine with melatonin and metformin. Because most of the results were not statistically significant we can deduce that in the chronic experiment, adaptive type modifications of the receptors on which both olanzapine and melatonin act can occur.

Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients.

STUDY QUESTION: Will the addition of 24-chromosome microarray analysis on miscarriage tissue combined with the standard American Society for Reproductive Medicine (ASRM) evaluation for recurrent miscarriage explain most losses? SUMMARY ANSWER: Over 90% of patients with recurrent pregnancy loss (RPL) will have a probable or definitive cause identified when combining genetic testing on miscarriage tissue with the standard ASRM evaluation for recurrent miscarriage. WHAT IS KNOWN ALREADY: RPL is estimated to occur in 2-4% of reproductive age couples. A probable cause can be identified in approximately 50% of patients after an ASRM recommended workup including an evaluation for parental chromosomal abnormalities, congenital and acquired uterine anomalies, endocrine imbalances and autoimmune factors including antiphospholipid syndrome. STUDY DESIGN, SIZE, DURATION: Single-center, prospective cohort study that included 100 patients seen in a private RPL clinic from 2014 to 2017. All 100 women had two or more pregnancy losses, a complete evaluation for RPL as defined by the ASRM, and miscarriage tissue evaluated by 24-chromosome microarray analysis after their second or subsequent miscarriage. PARTICIPANTS/MATERIALS, SETTING, METHODS: Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities, and 24-chromosome microarray evaluation for products of conception (POC); pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; and blood tests for thyroid stimulating hormone (TSH), prolactin and hemoglobin A1c) were evaluated. We excluded cases where there was maternal cell contamination of the miscarriage tissue or if the ASRM evaluation was incomplete. A cost analysis for the evaluation of RPL was conducted to determine whether a proposed procedure of 24-chromome microarray evaluation followed by an ASRM RPL workup (for those RPL patients who had a normal 24-chromosome microarray evaluation) was more cost-efficient than conducting ASRM RPL workups on RPL patients followed by 24-chromosome microarray analysis (for those RPL patients who had a normal RPL workup). MAIN RESULTS AND THE ROLE OF CHANCE: A definite or probable cause of pregnancy loss was identified in the vast majority (95/100; 95%) of RPL patients when a 24-chromosome pair microarray evaluation of POC testing is combined with the standard ASRM RPL workup evaluation at the time of the second or subsequent loss. The ASRM RPL workup identified an abnormality and a probable explanation for pregnancy loss in only 45/100 or 45% of all patients. A definite abnormality was identified in 67/100 patients or 67% when initial testing was performed using 24-chromosome microarray analyses on the miscarriage tissue. Only 5/100 (5%) patients, who had a euploid loss and a normal ASRM RPL workup, had a pregnancy loss without a probable or definitive cause identified. All other losses were explained by an abnormal 24-chromosome microarray analysis of the miscarriage tissue, an abnormal finding of the RPL workup, or a combination of both. Results from the cost analysis indicated that an initial approach of using a 24-chromosome microarray analysis on miscarriage tissue resulted in a 50% savings in cost to the health care system and to the patient. LIMITATIONS, REASONS FOR CAUTION: This is a single-center study on a small group of well-characterized women with RPL. There was an incomplete follow-up on subsequent pregnancy outcomes after evaluation, however this should not affect our principal results. The maternal age of patients varied from 26 to 45 years old. More aneuploid pregnancy losses would be expected in older women, particularly over the age of 35 years old. WIDER IMPLICATIONS OF THE FINDINGS: Evaluation of POC using 24-chromosome microarray analysis adds significantly to the ASRM recommended evaluation of RPL. Genetic evaluation on miscarriage tissue obtained at the time of the second and subsequent pregnancy losses should be offered to all couples with two or more consecutive pregnancy losses. The combination of a genetic evaluation on miscarriage tissue with an evidence-based evaluation for RPL will identify a probable or definitive cause in over 90% of miscarriages. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study and there are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Algorithm for Calculating the Protein Intake in Enteral and Parenteral Nutrition in Premature Infants.

INTRODUCTION: Calculating the exact nutritional balance especially for the premature infant has always been a challenge for the daily practice of the clinician. PURPOSE: we intend to establish a simplified formula and mathematical algorithms to calculate the necessary amino acids and proteins for the nutrition of the premature newborn, covering most of the international recommendations and also to give to the neonatal intensive care physician the opportunity of their rapid customization for each case. METHODS: following an extensive literature revision we have established the protein intake recommendations, indications and contraindications for enteral and parenteral nutrition in premature infants, by age of gestation, birth weight and postnatal age. Then, these recommendations were translated into simplified mathematical equations and we have proceeded to develop logical algorithms to enable the rapid choice of the best equation that fits each individual case with all its peculiarities, at a defined time. RESULTS: for all three premature categories, we have identified intervals for enteral and parenteral nutrition, which were translated into mathematical formulas and management regulations and then transposed into logic algorithms. CONCLUSIONS: although mathematically one can use a simplified calculation, for a rapid appreciation, the clinician is still required to go through these algorithms daily and sometimes several times a day. Moreover, to optimize protein intake, we have to calculate the protein / energy ratio and the non-protein calories / gram of protein ratio. This involves extending the calculation for the carbohydrates, fats and calories-practically the entire nutrition.

A Simple Method of Calculation in Excel for the Protein Requirements in Preterm New Borns.

INTRODUCTION: The nutritional balance between the nutritional requirements of the organism and the intake is a very delicate thing to adjust especially when it comes to the premature new-born in whom often the oral feeding is very challenging and the need for parenteral feeding is very pressing. PURPOSE: The goal of this article is to present a simple method of calculation for the amino acid parenteral intake in preterm infants using the Excel spreadsheet platform as a platform. MATERIAL AND METHOD: Using Excel commands, we translate the algorithms for the protein requirements calculation into an electronic format. This will allow the creation of a template that quickly identifies the need for proteins according to the clinical and evolutional features of the premature new-born, significantly reducing the duration of the calculation. RESULTS: This method is easy to perform, simple and efficient. The calculation template has significantly reduced the errors and the actual working time with the algorithms. These effects are very obvious in intensive care units that take care of a large number of premature babies. CONCLUSIONS: Computerized calculation allows a decrease in calculation errors and also reduces the time actually allocated for the calculation, especially for the very complicated algorithms. Following this template in Excel, we can create separate modules for the algorithms necessary to calculate the needs for the intake of liquids, calories, lipids, and minerals.

Urinary tract infection with Klebsiella pneumoniae in Patients with Chronic Kidney Disease.

Study Motivation: After assessing electronic databases of medical scientific literature, we have observed that the interrelation between urinary tract infections (UTIs) and chronic kidney disease (CKD) is poorly studied, especially when UTIs are caused by Klebsiella pneumoniae (K. pneumoniae). MATERIALS AND METHODS: K. pneumoniae was isolated in 14 urine samples from patients with CKD addmited in the Nephrology Department of the County Emergency Clinical Hospital Craiova. The isolated strains were statistically analyzed in the correlation with the different clinical and functional parameters (age, gender, CKD stage, comorbidities, biochemical parameters-serum urea, creatinine, uric acid and blood electrolytes). The degree of K. pneumoniae susceptibility to antibiotics from different pharmacodynamic classes was assessed. RESULTS: UTIs with K. pneumoniae in patients with CKD in the investigated period represented 0.51% from the total admissions in the clinic and 32.60% from cases of UTI. Eleven patients with this type of infection (78.56%) were in stage 4 and 5 CKD, and from them 4 also had diabetes mellitus type 2 (28.57%). We observed an increased level for serum creatinine (100%), blood urea (85.71%), and serum uric acid (45.45%). Two patients died after installation of cardiovascular changes in CKD, at advanced ages and in the presence of urinary infection. Multiple drug resistance occurred in 6 strains of K. pneumoniae correlated with the degree of kidney failure, advanced age, male gender, and diabetes mellitus. CONCLUSIONS: UTI with K. pneumoniae in patients with CKD is the second cause of urinary infection which raises problems of unfavorable evolution of CKD and also the recurrence of UTI with multiple drug resistance in CKD, which may lead to pharmacotherapeutical problems.

European symposium on the awareness of allergy: report of the promotional campaign in the European Parliament (26-28 April 2016).

From 26 to 28 of April 2016, an allergy awareness campaign was organized by the European Academy of Allergy and Clinical Immunology and the European Federation of Allergy and Airway Diseases Patients Associations in the European Parliament in Brussels, with support of the European Parliament's Interest group on Allergy and Asthma and was co-hosted by the Members of the European Parliament David Borrelli, Sirpa Pietikainen and Nessa Childers. Skin prick tests (SPTs) were performed to gain attention for the increasing prevalence of allergic airway diseases in Europe. Since more than 30% of the total European population suffers from airway allergies and asthma, reaching a higher level of awareness and elaboration of an active prevention plan is mandatory. Of the 406 individuals undergoing SPT in the European Parliament, 211 participants (52%) reported to have suffered from an allergy in the past, with allergic symptoms being present in the nose and eyes (40% and 36%, respectively), the skin (27%), lower airways (14%) and the gut (8%). Of the 381 SPT with reliable results, cutaneous hypersensitivity was found in 201 (53%) participants. Of those with positive SPT (n = 201), 70 participants (35%) were monosensitized while 131 participants (65%) were polysensitized. The positive skin reactions were found mostly for grass pollen (n = 108), followed by Dermatophagoides pteronyssinus (n = 105), Dermatophagoides farina (n = 96) and birch pollen (n = 85). Of note, 54 individuals (14% of the total tested population) without reported allergy or allergic symptoms showed a positive SPT without clinical relevance. This report summarizes the main idea and goals of the symposium: chronic airway diseases are a major and growing health problem in Europe. Therefore, a joint preventive action plan needs to be developed for a better health status of European citizens.

Reduced graphene oxide growth on 316L stainless steel for medical applications.

We report a new method for the growth of reduced graphene oxide (rGO) on the 316L alloy of stainless steel (SS) and its relevance for biomedical applications. We demonstrate that electrochemical etching increases the concentration of metallic species on the surface and enables the growth of rGO. This result is supported through a combination of Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), scanning electron microscopy (SEM), density functional theory (DFT) calculations and static water contact angle measurements. Raman spectroscopy identifies the G and D bands for oxidized species of graphene at 1595 cm(-1) and 1350 cm(-1), respectively, and gives an ID/IG ratio of 1.2, indicating a moderate degree of oxidation. XPS shows -OH and -COOH groups in the rGO stoichiometry and static contact angle measurements confirm the wettability of rGO. SEM and AFM measurements were performed on different substrates before and after coronene treatment to confirm rGO growth. Cell viability studies reveal that these rGO coatings do not have toxic effects on mammalian cells, making this material suitable for biomedical and biotechnological applications.

Undergraduate teaching of occupational medicine in European schools of medicine.

PURPOSE: General practitioners play or should play a role in occupational medicine (OM), either in diagnosing occupational diseases or in counseling on return to work. Nevertheless, their training has been reported to be insufficient in most single country studies. AIMS: The objectives of this study were to analyze the content and extent of undergraduate teaching of OM in European medical schools. METHODS: An e-mail questionnaire survey of the teaching of OM to undergraduates was undertaken from December 2010 to April 2011 in all medical schools and medical faculties listed in 27 European countries (n = 305). RESULTS: Among the 305 universities identified, 135 answered to the questionnaire, giving a response rate of 44%. The mean number of hours given to formal instruction in occupational medicine to medical undergraduates was 25.5 h. Nevertheless, this number of hours varied widely between countries, but also within countries. Overall, 27% of medical schools gave their students 10 h of teaching or less, 52% 20 h or less and 69% 30 h or less. Whereas occupational diseases and principles of prevention were covered in most schools, disability and return to work were very poorly represented among the topics that were taught to students. CONCLUSION: Dedicated undergraduate teaching on occupational health or OM in European medical schools is present in most medical schools, usually at a low level, but is very variable between and within countries. Medical schools across Europe are very unequal to provide qualifying doctors education on the topics they will frequently come across in their working lives.

On the feasibility of using motor imagery EEG-based brain-computer interface in chronic tetraplegics for assistive robotic arm control: a clinical test and long-term post-trial follow-up.

STUDY DESIGN: Survey and long-term clinical post-trial follow-up (interviews/correspondence) on nine chronic, post spinal cord injury (SCI) tetraplegics. OBJECTIVE: To assess feasibility of the use of Electroencephalography-based Brain-Computer Interface (EEG-BCI) for reaching/grasping assistance in tetraplegics, through a robotic arm. SETTINGS: Physical and (neuromuscular) Rehabilitation Medicine, Cardiology, Neurosurgery Clinic Divisions of TEHBA and UMPCD, in collaboration with 'Brain2Robot' (composed of the European Commission-funded Marie Curie Excellence Team by the same name, hosted by Fraunhofer Institute-FIRST), in the second part of 2008. METHODS: Enrolled patients underwent EEG-BCI preliminary training and robot control sessions. Statistics entailed multiple linear regressions and cluster analysis. A follow-up-custom questionnaire based-including patients' perception of their EEG-BCI control capacity was continued up to 14 months after initial experiments. RESULTS: EEG-BCI performance/calibration-phase classification accuracy averaged 81.0%; feedback training sessions averaged 70.5% accuracy for 7 subjects who completed at least one feedback training session; 7 (77.7%) of 9 subjects reported having felt control of the cursor; and 3 (33.3%) subjects felt that they were also controlling the robot through their movement imagination. No significant side effects occurred. BCI performance was positively correlated with beta (13-30 Hz) EEG spectral power density (coefficient 0.432, standardized coefficient 0.745, P-value=0.025); another possible influence was sensory AIS score (range: 0 min to 224 max, coefficient -0.177, standardized coefficient -0.512, P=0.089). CONCLUSION: Limited but real potential for self-assistance in chronic tetraplegics by EEG-BCI-actuated mechatronic devices was found, which was mainly related to spectral density in the beta range positively (increasing therewith) and to AIS sensory score negatively.

Susceptibility of primary human endothelial cells to C. perfringens beta-toxin suggesting similar pathogenesis in human and porcine necrotizing enteritis.

Clostridium perfringens type C causes fatal necrotizing enteritis in different mammalian hosts, most commonly in newborn piglets. Human cases are rare, but the disease, also called pigbel, was endemic in the Highlands of Papua New Guinea. Lesions in piglets and humans are very similar and characterized by segmental necro-hemorrhagic enteritis in acute cases and fibrino-necrotizing enteritis in subacute cases. Histologically, deep mucosal necrosis accompanied by vascular thrombosis and necrosis was consistently reported in naturally affected pigs and humans. This suggests common pathogenetic mechanisms. Previous in vitro studies using primary porcine aortic endothelial cells suggested that beta-toxin (CPB) induced endothelial damage contributes to the pathogenesis of C. perfringens type C enteritis in pigs. In the present study we investigated toxic effects of CPB on cultured primary human macro- and microvascular endothelial cells. In vitro, these cells were highly sensitive to CPB and reacted with similar cytopathic and cytotoxic effects as porcine endothelial cells. Our results indicate that porcine and human cell culture based in vitro models represent valuable tools to investigate the pathogenesis of this bacterial disease in animals and humans.

Effects of season and reproductive state on lipid intake and fatty acid composition of gastrointestinal tract contents in the European hare.

We investigated lipid content and fatty acid (FA) composition of gastrointestinal tract contents in free-living, herbivorous European hares (Lepus europaeus). Mean crude fat content in hare stomachs and total gastrointestinal (GI) tracts was higher than expected for typical herbivore forages and peaked in late fall when hares massively deposited body fat reserves. Changes of FA proportions in different parts of the GI-tract indicated a highly preferential absorption of polyunsaturated fatty acids (PUFA). A further reduction of PUFA content in the caecum, along with the appearance of odd-chained FAs in caecum, caecotrophes, and colon content, pointed to a biohydrogenation of PUFA in the hare's hindgut. GI-tract contents showed significant seasonal changes in their FA composition. Among PUFA, α-linolenic acid peaked in spring while linoleic acid was predominant in late summer and fall, which probably reflected changes in the plant composition of forage. However, independent of seasonal changes, GI-tracts of lactating females showed a significantly (+33%) higher content of linoleic acid, a FA that is known to increase reproductive performance in European hares. This finding suggests that lactating females actively selected dietary plants rich in linoleic acid, a PUFA that may represent a limited resource for European hares.

Study of the ground multiplet of Kramers rare earth ions in solid matrices by multifrequency electron paramagnetic resonance spectroscopy: Nd3+ in PbWO4 single-crystals.

A multifrequency electron paramagnetic resonance (EPR) investigation of Nd(3+) impurities in PbWO(4) single-crystals at the conventional microwave frequency (MF) 9.43 GHz, and at the 95, 190, and 285 GHz high frequencies was carried out. The resulting spectra are well described at all frequencies by an axial spin-Hamiltonian corresponding to an effective electron spin of one-half and to a tetragonal symmetry. For the magnetic field along the tetragonal axis, the g(parallel)-factor and the hyperfine constant A(parallel) of the lowest doublet of the ground multiplet decreases with frequency increase. For the magnetic field perpendicular to the tetragonal axis, the g(perpendicular)-factor exhibits a small azimuthal angular dependence that increases with increasing the frequency due to the S(4) site symmetry. The azimuthal angular dependence allows to clearly distinguish between different local axial symmetries. These properties are interpreted as high field/frequency (HF) effects associated with the mixing by the large Zeeman interaction of some of the upper-lying doublets of the ground multiplet into the lowest-lying doublet states. We show that from the combined analysis of the multifrequency MF- and HF-EPR spectra and of the optical data, an accurate description of the ground multiplet of the Kramers rare earth ions in solid matrices can be derived.

[Visual evoked potentials in the in evaluation of the safety profile of levocetirizine]. / Potentiale evocate vizual în evaluarea profilului de siguranta al levocetirizinei.

UNLABELLED: Because human histamine H1 receptors were visualized at different brain levels, we evaluated the effects of levocetirizine (LCZ) on the visual evoked potentials (VEP). MATERIAL AND METHOD: Eighteen volunteer subjects were included in a placebo-controlled study, VEP recordings (pattern-reversal technique) were performed at baseline and 240 min. post-medication, and the N75-P100-N135 complex parameters (latency, duration, amplitude and surface of the components) were measured in the leads FzOL5, FzOz and FzOR5. RESULTS: LCZ 5 mg p.o. induced no statistically significant changes, neither in the mean values of all P100 parameters, nor in the mean latency of N75 and N135 components. No unilateral or bilateral alterations of VEP parameters were detected, suggesting that LCZ has no influence on the functional integrity of visual sensorial pathway. CONCLUSION: Our study may initiate a novel approach in the neurological safety profile evaluation of new H, antihistamines using VEP, with the advantage of no radiological exposure.

Evaluation of achievable registration accuracy of the femur during minimally invasive total hip replacement.

The aim of the paper was to investigate whether accurate, point-based registration of the intra-operative femur will be achieved within the context of minimally invasive surgery for total hip replacement. Computer tomography images, collected for pre-operative planning purposes, were used to simulate the intra-operative registration procedure using algorithms for various levels of measurement noise, different small areas of the femur available to the surgeon, and a limited number of collected data points (20-60). This helped with the choice of design variables to perform in vitro registration on a plastic bone model to validate the procedure, which included a multistart algorithm developed for intra-operative registration. The algorithm minimised the distance between the measured and image-derived surfaces and was able to cope with the presence of multiple local minima given sufficient computational effort, even with realistically large measurement noise. It was found that, if a small patch of the femur was used, accessible by a needle that could at times penetrate thin layers of soft tissue, errors in the order of 1.0 mm in translation and 0.5 degrees in rotation were achievable.

Delocalization of spin projection in weak exchange linear chains, evidenced by multi-frequency HF-EPR spectroscopy.

High-field electron paramagnetic resonance (HF-EPR) spectroscopy was used to investigate the unusual temperature and frequency dependence of the powder spectrum of the Gd(HBPz3)2 tropolonate complex (GdTrp). A new type of H/T effect is evidenced. This effect is interpreted in terms of the formation of spin projection states delocalized and quasidelocalized along linear chains of Gd3+ ions in high magnetic fields due to the competition between the weak dipole and exchange spin-spin interaction and the particular structure of the molecular complex. The number of ions in the chain depends strongly on the orientation of the magnetic field and on the relaxation processes.

Ambient ozone in forests of the Central and Eastern European mountains.

Ambient ozone (O(3)) concentrations in the forested areas of the Central and Eastern European (CEE) mountains measured on passive sampler networks and in several locations equipped with active monitors are reviewed. Some areas of the Carpathian Mountains, especially in Romania and parts of Poland, as well as the Sumava and Brdy Mountains in the Czech Republic are characterized by low European background concentrations of the pollutant (summer season means approximately 30 ppb). Other parts of the Carpathians, especially the western part of the range (Slovakia, the Czech Republic and Poland), some of the Eastern (Ukraine) and Southern (Romania) Carpathians and the Jizerske Mountains have high O(3) levels with peak values >100 ppb and seasonal means approximately 50 ppb. Large portions of the CEE mountain forests experience O(3) exposures that are above levels recommended for protection of forest and natural vegetation. Continuation of monitoring efforts with a combination of active monitors and passive samplers is needed for developing risk assessment scenarios for forests and other natural areas of the CEE Region.

New asthma drugs acting on gene expression.

New asthma drugs acting on transcription are transcription factor agonists (dissociated steroids, peroxisome proliferator-activated receptor gamma agonists), transcription factor inhibitors (NF-kappaB / AP-1 inhibitors, STAT6 inhibitors), inhibitors of protein kinases acting on transcription factors (p38 MAP kinase inhibitors), and chromatin modifying agents. Pharmacological approach of translation in asthma includes therapeutic ribozymes and antisense oligonucleotides targeting receptors (adenosine A1 receptor, alpha chain of IL-5 receptor, common beta chain of IL-3/IL-5/GM-CSF receptor), cytokines (IL-4, IL-5, SCF), signal transduction molecules (Syk, Lyn), transcription factors (STAT-6, GATA-3). Some of these drugs acting on gene expression have the potential to improve therapeutic benefits compared with traditional drugs.

End points of planar reaching movements are disrupted by small force pulses: an evaluation of the hypothesis of equifinality.

A single force pulse was applied unexpectedly to the arms of five normal human subjects during nonvisually guided planar reaching movements of 10-cm amplitude. The pulse was applied by a powered manipulandum in a direction perpendicular to the motion of the hand, which gripped the manipulandum via a handle at the beginning, at the middle, or toward the end the movement. It was small and brief (10 N, 10 ms), so that it was barely perceptible. We found that the end points of the perturbed motions were systematically different from those of the unperturbed movements. This difference, dubbed "terminal error," averaged 14.4 +/- 9.8% (mean +/- SD) of the movement distance. The terminal error was not necessarily in the direction of the perturbation, although it was affected by it, and it did not decrease significantly with practice. For example, while perturbations involving elbow extension resulted in a statistically significant shift in mean end-point and target-acquisition frequency, the flexion perturbations were not clearly affected. We argue that this error distribution is inconsistent with the "equilibrium point hypothesis" (EPH), which predicts minimal terminal error is determined primarily by the variance in the command signal itself, a property referred to as "equifinality." This property reputedly derives from the "spring-like" properties of muscle and is enhanced by reflexes. To ensure that terminal errors were not due to mid-course voluntary corrections, we only accepted trials in which the final position was already established before such a voluntary response to the perturbation could have begun, that is, in a time interval shorter than the minimum reaction time (RT) for that subject. This RT was estimated for each subject in supplementary experiments in which the subject was instructed to move to a new target if perturbed and to the old target if no perturbation was detected. These RT movements were found to either stop or slow greatly at the original target, then re-accelerate to the new one. The average latency of this second motion was used to estimate the voluntary RT for each subject (316 ms mean). Additionally, we found that the hand neither exerted target-oriented force against the handle nor drifted toward the desired end point just before coming to rest, making it unlikely that the mechanical properties of the manipulandum prevented the hand from reaching its intended target.

Isolated myocyte contractile function is normal in postinfarct remodeled rat heart with systolic dysfunction.

BACKGROUND: Postinfarction ventricular remodeling is associated with lengthening and contractile dysfunction of the remote noninfarcted myocardium. Mechanisms underlying this phenomenon remain unclear. METHODS AND RESULTS: We studied serial changes in global left ventricular (LV) structure and function in infarcted (1, 2, 4, and 6 weeks after myocardial infarction) and sham-operated rat hearts and correlated them with structural and functional changes in myocytes isolated from the remote LV myocardium in the same hearts. Rats with myocardial infarction developed significant remodeling. The heart weight-to-body weight ratios were increased. LV volumes at filling pressure of 10 mm Hg were higher (305+/-28 versus 215+/-12 microL, P<.01). This was accompanied by global LV dysfunction (in vivo LV end-diastolic pressure, 4+/-1 versus 23+/-1.6 mm Hg; Langendorff LV developed pressure, 105+/-4 versus 62+/-9 mm Hg, P<.001 for both). Myocytes isolated from these hearts showed significant structural remodeling (LV myocytes, 24% longer and 15% wider; right ventricular myocytes, 38% longer and 31% wider, all P<.05). LV myocyte length correlated with changes in LV volume (r=.79) and function (LV developed pressure, r=-.81). However, LV myocytes from the same hearts showed normal contractile function and intracellular Ca2+ transients at baseline and during inotropic stimulation with increasing extracellular Ca2+ (1 to 6 mmol/L). The shortening-frequency relationship was also similar in myocytes from sham and myocardial infarction rats. CONCLUSIONS: Postinfarct LV remodeling occurs predominantly by myocyte lengthening rather than by myocyte slippage. However, contractile function of the unloaded myocytes from the remote noninfarcted LV myocardium of the remodeled heart is normal. Therefore, myocyte contractile abnormalities may not contribute to global dysfunction of the remodeled heart. Reduced myocyte mass and nonmyocyte factors like increased wall stress, altered LV geometry, and changes in the myocardial interstitium may be more important in the genesis of postinfarct LV dysfunction in this model.