Methods for estimating neural firing rates,and their application to brain–machine interfaces

Neural spike trains present analytical challenges due to their noisy, spiking nature. Many studies of neuroscientific and neural prosthetic importance rely on a smoothed, denoised estimate of a spike train’s underlying firing rate. Numerous methods for estimating neural firing rates have been developed in recent years, but to date no systematic comparison has been made between them. In this study, we review both classic and current firing rate estimation techniques. We compare the advantages and drawbacks of these methods. Then, in an effort to understand their relevance to the field of neural prostheses, we also apply these estimators to experimentally gathered neural data from a prosthetic arm-reaching paradigm. Using these estimates of firing rate, we apply standard prosthetic decoding algorithms to compare the performance of the different firing rate estimators, and, perhaps surprisingly, we find minimal differences. This study serves as a review of available spike train smoothers and a first quantitative comparison of their performance for brain–machine interfaces.     

Ultrasound-directed drug delivery

It has been proven, that the cellular uptake of drugs and genes is increased, when the region of interest is under ultrasound insonification, and even more when a contrast agent is present. This increased uptake has been attributed to the formation of transient porosities in the cell membrane, which are big enough for the transport of drugs into the cell (sonoporation). Owing to this technique, new ultrasound contrast agents that incorporate a therapeutic compound have become of interest. Combining ultrasound contrast agents with therapeutic substances, such a chemotherapeutics and virus vectors, may lead to a simple and economic method to instantly cure upon diagnosis, using conventional ultrasound scanners. There are two hypotheses for explaining the sonoporation phenomenon, the first being microbubble oscillations near a cell membrane, the second being microbubble jetting through the cell membrane. Based on modeling, high-speed photography, and recent cellular uptake measurements, it is concluded that microbubble jetting behavior is less likely to be the dominant sonoporation mechanism. Ultrasound-directed drug delivery using microbubbles is a promising method that has great potential in the treatment of malignant disorders.     

Three-dimensional surface model analysis in the gastrointestinal tract

The biomechanical changes during functional loading and unloading of the human gastrointestinal (GI) tract are not fully understood. GI function is usually studied by introducing probes in the GI lumen. Computer modeling offers a promising alternative approach in this regard, with the additional ability to predict regional stresses and strains in inaccessible locations. The tension and stress distributions in the GI tract are related to distensibility (tension-strain relationship) and smooth muscle tone. More knowledge on the tension and stress on the GI tract are needed to improve diagnosis of patients with gastrointestinal disorders. A modeling framework that can be used to integrate the physiological, anatomical and medical knowledge of the GI system has recently been developed. The 3-D anatomical model was constructed from digital images using ultrasonography, computer tomography (CT) or magnetic resonance imaging (MRI). Different mathematical algorithms were developed for surface analysis based on thin-walled structure and the finite element method was applied for the mucosa-folded three layered esophageal model analysis. The tools may be useful for studying the geometry and biomechanical properties of these organs in health and disease. These studies will serve to test the structurefunction hypothesis of geometrically complex organs.     

Morphology and motor function of the gastrointestinal tract examined with endosonography

Endosonography is a useful tool for studying the morphology and motor function of the gastrointestinal tract. Intraluminal ultrasonography is the common denomination of ultrasound examinations using intracorporal transducers which are inserted into the GI tract. Thus, the visceral wall and adjacent structures can be imaged in detail. This review describes the usefulness of endosonography in gastroenterology, in particular with respect to studies of the biomechanical and motor function of the gastrointestinal tract. New techniques such as 3-D EUS, elastography and strain rate imaging are discussed.     

Impaired accommodation of the proximal stomach in children with recurrent abdominal pain

BACKGROUND: A new ultrasonographic method was applied in children with recurrent abdominal pain, to study accommodation of the proximal stomach to a meal. METHODS: After an overnight fast, 20 patients with recurrent abdominal pain (age, 7-14 years) and 23 healthy control subjects (age, 7-13 years), were scanned by a 5-MHz transducer positioned in the epigastrium, to monitor the size of the proximal stomach before and after a test meal of meat soup. RESULTS: Children with recurrent abdominal pain had a significantly smaller sagittal area of the proximal stomach at 10 and 20 minutes after the meal than in healthy control subjects (P = 0.01 for both) and significantly higher emptying fraction of the proximal stomach at 10 minutes after the meal than in healthy control subjects (P = 0.02). There was no significant difference in emptying of the distal stomach between the patients and healthy control subjects. Children with recurrent abdominal pain experienced more symptoms (pain, bloating) in response to the test meal than did healthy control subjects. CONCLUSION: The results support the view that recurrent abdominal pain in children may be a motility disorder that can be detected in the proximal stomach as an impairment of adaptive relaxation in response to a meal. This new ultrasonographic method may become a valuable diagnostic tool in patients with recurrent abdominal pain.     

Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy

AIMS: To examine if increased concentrations of matrix metalloproteinase-8 (MMP-8) in amniotic fluid are associated with the development of cerebral palsy at the age of three years. METHODS: The relationship between amniotic fluid concentrations of MMP-8 and the development of cerebral palsy was examined in 116 preterm singleton newborns (gestational age at birth < 35 weeks) born to mothers who underwent amniocentesis and were followed for at least 3 years. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. MMP-8 concentrations were measured by specific immunoassays. Cerebral palsy was diagnosed by neuro developmental assessment at the age of three years. RESULTS: Median amniotic fluid concentration of MMP-8 was significantly higher in mothers whose newborns developed cerebral palsy than in mothers whose newborns did not develop cerebral palsy (median 153.9 [range < 0.3-1535.9] ng/ml vs median 6.4 [range < 0.3-3836.8] ng/ml; p < 0.01). Neonates who developed cerebral palsy were delivered at earlier gestational age than those without cerebral palsy. After adjustment for the gestational age at birth and the results of amniotic fluid culture, elevated concentrations of amniotic fluid MMP-8 significantly increased the odds of development of cerebral palsy (odds ratio, 6.0; 95% confidence interval, 1.1-33.0; p < 0.05). CONCLUSION: Increased concentrations of amniotic fluid MMP-8 are associated with the subsequent development of cerebral palsy at the age of 3 years.     

Biovar diversity of Ureaplasma urealyticum in amniotic fluid: distribution,intrauterine inflammatory response and pregnancy outcomes

OBJECTIVE: The objective of this study was to determine the distribution of two biovars of Ureaplasma urealyticum (parvo and T960) in human amniotic fluid and to examine whether the magnitude of the intrauterine inflammatory response and pregnancy outcomes are different between patients with microbial invasion of the amniotic cavity with "parvo biovar" and those with "T960 biovar". STUDY DESIGN: This cohort included 77 preterm singleton pregnancies (gestational age < 37 weeks) in whom U. urealyticum was detected from amniotic fluid using the polymerase chain reaction (PCR). Amniotic fluid was obtained by transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. U. urealyticum was biotyped by PCR methods. Amniotic fluid inflammatory response was determined by amniotic fluid white blood cell count and interleukin-6 concentration. RESULTS: 1) The "parvo biovar" was detected in 82% (63/77) and "T960 biovar" was in 18% (14/77) of cases; 2) U. urealyticum was isolated by conventional culture method from amniotic fluid in 56% (35/63) of cases with positive for "parvo biovar" and in 50% (7/14) of cases with positive for "T960 biovar"; 3) There were no significant differences in the median gestational age at amniocentesis, gestational age at delivery, birth weight, amniotic fluid white blood cell count, amniotic fluid interleukin-6 concentration and the rates of clinical chorioamnionitis, histologic chorioamnionitis, funisitis and neonatal morbidity between patients in the two biovar groups. CONCLUSIONS: 1) The "parvo biovar" is more frequently isolated from amniotic fluid of preterm gestations than the "T960 biovar"; 2) Biovar diversity of U. urealyticum in amniotic fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.     

Conservative treatment of female stress incontinence with imipramine

The results of a clinical study of conservative treatment of women with stress incontinence are presented. A daily dose of 75 mg. imipramine hydrochloride was given for 4 weeks. Special attention was paid to the effects of imipramine on the functional urethral length and maximum urethral closure pressure. A total of 21 women (71 per cent) stated that they were continent after treatment with imipramine, while 9 (29 per cent) did not improve and treatment was stopped. According to our results, imipramine extended the functional urethral length and made it independent of stress factors in women who were continent after treatment with imipramine. In patients with persistent incontinence the functional urethral length was extended significantly but was shortened with stress despite imipramine therapy. We believe that imipramine could be an alternative treatment in selected cases with stress incontinence.     

Secretion of polyalbumin receptors in vitro

The nature of hepatitis B surface antigen (HBsAg)-associated receptors for polymerized human serum albumin (pHSA-R) and their relationship to hepatitis B e antigen (HBeAg) and human serum proteins have not been defined. We studied by radioimmunoassay and by electron microscopy HBsAg-associated pHSA-R secreted in vitro by a human hepatocellular carcinoma cell line (PLC/PRF/5) and by mouse 3T3 fibroblasts after transfection with cloned hepatitis B virus (HBV) DNA (4.10 cells). PLC/PRF/5 cells expressed only HBsAg, whereas 4.10 cells secreted also HBeAg. There was no significant difference in the production of HBsAg, HBeAg, and pHSA-R when the cells were cultured in the presence or absence of fetal calf serum. Secretion of pHSA-R by the two cell lines for a given amount of HBsAg was equal irrespective of the presence or absence of HBeAg. Supernatants from both cell lines grown in serum-free medium did not contain any Clq or albumin when tested by immunodiffusion. The ability of a transfected mouse cell line to produce HBsAg with pHSA-R activity strongly suggests that pHSA-R is coded by the HBV genome and does not depend on the presence of human serum proteins. In addition, our findings fail to demonstrate any correlation between HBeAg production and pHSA-R.     

Tansvaginal needle suspension operation: the way we do it. Clinical and urodynamic study: long-term results

OBJECTIVES: To evaluate the long-term results of the transvaginal needle suspension operation for urinary stress incontinence. MATERIALS AND METHODS: A total of 88 women with proved genuine stress incontinence were treated with transvaginal needle suspension with fixation of suspension sutures to the rectus fascia using the technique of crossing suspension sutures. By using this method the proximal end of suspension suture from one side is tied with the distal end of suspension suture from the other side. The suspension sutures fixed in this way ensure 3-4 cm of rectus fascia which is used as a carrier of the suspension sutures. The same urologist peformed 88 consecutive operations. Clinical and urodynamic evaluations were performed at 6 months, 1 year and 5 years after surgery with the same technique and the same equipment. RESULTS: Analysis of the questionnaire showed that 81 patients (92.0%) were continent after 6 months while 78 (88.6%) patients were still continent after 1 year. After 5 years (n = 71) there were only continent 54 (76.0%) and incontinent patients (n = 17, 23.9%). Urodynamic analysis showed that 49 (69.0%) patients were continent after 5 years (n= 71). The increase in the number of incontinent patients is achieved at the cost of the previously continent patients. Of the 22 incontinent patients (after 5 years), 16 were still stress incontinent, while 6 (8.3%) patients had urge incontinence due to de novo detrusor instability. Three patients (n = 88, 3.4%) had undergone unilateral suture removal due to infection without influence on their continence status. In 2 patients (n = 88, 2.2%) the clinical pictures were highly suggestive of ilioinguinal nerve entrapment. CONCLUSIONS: Our results suggest that the transvaginal needle suspension operation is satisfactory for the management of genuine stress incontinence in women. However, we believe that the success of any suspension operation lies in adequate mobilization of the bladder neck and urethra (anterior vaginal wall) as well as in a surgeon's familiarity with the procedure.