Mathematical Modeling and Evaluation of Human Motions in Physical Therapy Using Mixture Density Neural Networks.

OBJECTIVE: The objective of the proposed research is to develop a methodology for modeling and evaluation of human motions, which will potentially benefit patients undertaking a physical rehabilitation therapy (e.g., following a stroke or due to other medical conditions). The ultimate aim is to allow patients to perform home-based rehabilitation exercises using a sensory system for capturing the motions, where an algorithm will retrieve the trajectories of a patient's exercises, will perform data analysis by comparing the performed motions to a reference model of prescribed motions, and will send the analysis results to the patient's physician with recommendations for improvement. METHODS: The modeling approach employs an artificial neural network, consisting of layers of recurrent neuron units and layers of neuron units for estimating a mixture density function over the spatio-temporal dependencies within the human motion sequences. Input data are sequences of motions related to a prescribed exercise by a physiotherapist to a patient, and recorded with a motion capture system. An autoencoder subnet is employed for reducing the dimensionality of captured sequences of human motions, complemented with a mixture density subnet for probabilistic modeling of the motion data using a mixture of Gaussian distributions. RESULTS: The proposed neural network architecture produced a model for sets of human motions represented with a mixture of Gaussian density functions. The mean log-likelihood of observed sequences was employed as a performance metric in evaluating the consistency of a subject's performance relative to the reference dataset of motions. A publically available dataset of human motions captured with Microsoft Kinect was used for validation of the proposed method. CONCLUSION: The article presents a novel approach for modeling and evaluation of human motions with a potential application in home-based physical therapy and rehabilitation. The described approach employs the recent progress in the field of machine learning and neural networks in developing a parametric model of human motions, by exploiting the representational power of these algorithms to encode nonlinear input-output dependencies over long temporal horizons.

Anatomical patterns of colonization of pets with staphylococcal species in homes of people with methicillin-resistant Staphylococcus aureus (MRSA) skin or soft tissue infection (SSTI).

Methicillin-resistant strains of Staphylococcus aureus (MRSA), Staphylococcus pseudintermedius (MRSP), and other pathogenic staphylococci can cause infections in companion animals and humans. Identification of colonized animals is fundamental to research and practice needs, but harmonized methods have not yet been established. To establish the optimal anatomic site for the recovery of methicillin-resistant coagulase positive staphylococci (CPS), survey data and swabs were collected from 196 pets (dogs, cats, reptiles, birds, fish and pocket pets) that lived in households with an MRSA-infected person. Using broth-enrichment culture and PCR for speciation, S. aureus was identified in 27 of 179 (15%) pets sampled at baseline and 19 of 125 (15%) pets sampled at a three-month follow-up home visit. S. pseudintermedius was isolated from 33 of 179 (18%) pets sampled at baseline and 21 of 125 (17%) of pets sampled at follow-up. The baseline MRSA and MRSP prevalence was 8% and 1% respectively from 145 mammalian pets. The follow-up MRSA and MRSP prevalence was 7% and <1% respectively from 95 mammalian pets. The mouth was the most sensitive single site sampled for isolation of S. aureus and S. pseudintermedius in mammals. In a subset of pets, from which all available isolates were identified, dual carriage of S. aureus and S. pseudintermedius was 22% at baseline and 11% at follow-up. These results identify the mouth as the most sensitive site to screen for pathogenic staphylococci and suggest that it should be included in sampling protocols.

Modeling pathogenesis of Huntington's disease with inducible neuroprogenitor cells.

Huntington's disease (HD) is caused by an abnormal expansion of CAG trinucleotide repeats encoding polyglutamine (polyQ) in the first exon of the huntingtin (htt) gene. Despite considerable efforts, the pathogenesis of HD remains largely unclear due to a paucity of models that can reliably reproduce the pathological characteristics of HD. Here, we report a neuronal cell model of HD using the previously established tetracycline regulated rat neuroprogenitor cell line, HC2S2. Stable expression of enhanced green fluorescence protein tagged htt exon 1 (referred to as 28Q and 74Q, respectively) in the HC2S2 cells did not affect rapid neuronal differentiation. However, compared to the cells expressing wild type htt, the cell line expressing mutant htt showed an increase in time-dependent cell death and neuritic degeneration, and displayed increased vulnerability to oxidative stress. Increased protein aggregation during the process of neuronal aging or when the cells were exposed to oxidative stress reagents was detected in the cell line expressing 74Q but not in its counterpart. These results suggest that the neuroprogenitor cell lines mimic the major neuropathological characteristics of HD and may provide a useful tool for studying the neuropathogenesis of HD and for high throughput screening of therapeutic compounds.

Hepatic epithelioid haemangioendothelioma: challenges in diagnosis and management.

BACKGROUND: Hepatic epithelioid haemangioendothelioma (HEH) is a rare, low grade malignant neoplasm of endothelial origin which is difficult to diagnose and has a variable outcome. We review five HEH cases from our centre with the aim of identifying clinical predictors of outcome and various therapeutic options. METHODS: A search was made on the WA Liver Transplant registry for cases with histologically confirmed HEH. Their medical records were reviewed. A literature search was conducted through Medline using terms to compare the results from this series with those of other series. RESULTS: Five patients were identified to have HEH. The mean age was 44.2years (range 34-53years). Four of five patients presented with dyspepsia and two patients had clinical evidence of portal hypertension with ascites. Two patients had radiologically diffuse disease and three patients had discrete nodular liver involvement. The mean duration from presentation of symptoms to diagnosis of HEH was 26.8months. Liver transplantation was performed in one patient with diffuse HEH who is alive with no disease recurrence at 3years. Three patients with radiologically stable disease followed with 6monthly surveillance imaging are currently alive and well. The median survival of all five patients was 5years (range 1.5-16years) at the time of follow up. CONCLUSIONS: These results support the role of surveillance alone for patients with focal and radiologically stable disease. Patients with diffuse HEH with hepatic decompensation should be considered for transplantation. However, numbers are small and an international registry is required to make firm comparisons.

Effects of reboxetine on Hamilton Depression Rating Scale factors from randomized, placebo-controlled trials in major depression.

Reboxetine is the first selective norepinephrine reuptake inhibitor (NRI) approved for the treatment of major depressive disorder (MDD). Although reboxetine has demonstrated efficacy for the treatment of depression, its effects on specific depressive symptoms have not been reported. We evaluated the effects of reboxetine on four Hamilton Depression Rating Scale (HAM-D) factors: psychomotor retardation, anxiety, cognitive disturbance and insomnia. Data were obtained from four short-term (4-8-week), randomized, placebo-controlled trials of reboxetine for the treatment of MDD. For each study, mean changes in HAM-D symptom factor scores from randomization to the study endpoint were compared between reboxetine and placebo. In addition, data from all four studies were pooled to determine the proportions of patients who either improved or worsened with treatment were compared between placebo (n = 353) and reboxetine (n = 350) treatment groups. Compared to placebo, reboxetine significantly improved psychomotor retardation in all four trials. Cognitive disturbance and anxiety were improved in three of four trials, and insomnia was improved in one trial with a positive trend in the second trial. Reboxetine, a selective NRI, improves symptoms of psychomotor retardation, anxiety and cognitive disturbance during treatment of MDD.

Influence of the severity of cognitive impairment on the effect of the Gnkgo biloba extract EGb 761 in Alzheimer's disease.

OBJECTIVE: To explore the treatment effect of EGb 761((R)) (EGb) in Alzheimer's disease depending on baseline severity. METHODS: We applied stratification to the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with 120 mg of EGb, using cutoff points of 23 and 14 for the Mini-Mental State Examination (MMSE) score. Outcome measures used were the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) and the Geriatric Evaluation by Relative's Rating Instrument (GERRI). RESULTS: In the severity stratum 1 (MMSE >23), the placebo group did not show significant changes, while the EGb group improved significantly by 1.7 points on the ADAS-Cog and by 0.09 points on the GERRI. In the severity stratum 2 (MMSE <24), the placebo group worsened by 4.1 points on the ADAS-Cog and 0.18 points on the GERRI, whereas the EGb group showed 60% less decline on the ADAS-Cog (treatment difference of 2.5 points) and no change on the GERRI (treatment difference of 0.25 points). The most severely impaired subgroup (MMSE <15) showed slightly more pronounced worsening for both treatment groups. However, in comparison to placebo, EGb induced virtually the same magnitude of effect as was observed in the entire stratum 2. CONCLUSIONS: The results of this retrospective analysis indicated that a treatment effect favorable to EGb could be observed with respect to cognitive performance (p = 0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. However, the relative changes from baseline measured at endpoint depended heavily on the severity at baseline. Improvement was observed in the group of patients with very mild to mild cognitive impairment, while in more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo.

Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline.

BACKGROUND: Several different classes of antidepressants have been associated with sexual adverse effects. This double-blind, randomized trial compared the effects of nefazodone and sertraline on reemergence of sexual dysfunction in depressed patients who had experienced sexual dysfunction as a result of sertraline treatment. Depressive symptoms were also monitored. METHOD: One hundred five patients with DSM-III-R major depressive episode who were experiencing sexual dysfunction attributable to sertraline (100 mg/day) were screened for entry. Eligible patients entered a 1-week washout period that was followed by a 7- to 10-day single-blind placebo phase. Patients without symptoms of sexual dysfunction at the end of the single-blind placebo phase were randomly assigned to receive double-blind treatment with either nefazodone (400 mg/day) or sertraline (100 mg/day) for 8 weeks. RESULTS: Nearly 3 times more sertraline-treated patients (76%; 25/33) experienced reemergence of sexual dysfunction (ejaculatory and/or orgasmic difficulty) than did nefazodone-treated patients (26%; 10/39) (p < .001). In addition, patients treated with nefazodone were more satisfied with their sexual functioning than were patients treated with sertraline. Both treatment groups demonstrated a similar and sustained improvement in depressive symptoms. Both drugs were well tolerated, and the overall incidence of adverse reactions was similar for both treatment groups; however, 9 sertraline-treated patients (26%) discontinued because of adverse events compared with 5 nefazodone-treated patients (12%). Of the patients discontinuing therapy for adverse events, 5 of the sertraline-treated patients did so because of sexual dysfunction reported as an adverse event, whereas only 1 of the nefazodone-treated patients discontinued therapy secondary to sexual dysfunction. CONCLUSION: In this sample of patients with major depression who had recovered from sexual dysfunction induced by treatment with sertraline, nefazodone treatment resulted in significantly less reemergence of sexual dysfunction than did renewed treatment with sertraline and provided continued antidepressant activity.

The effects of antidepressants on sexual functioning in depressed patients: a review.

Sexual dysfunction has long been noted as both a symptom of depressive illness and as a side effect of many of the medications used to treat depression. Although most people suffering from a major depressive illness would like to be sexually active, half experience a decrease in desire or sexual performance. Antidepressant medications often interfere with several parts of the sexual response. This review compares data from different types of research into the effect of antidepressant medications on the sexual response: case reports, chart reviews, and single- and double-blind studies with and without active control medications. From this review, it is clear that antidepressants of most classes interfere with human sexual functioning, with the notable exceptions of bupropion and nefazodone.

A 24-week randomized trial of controlled-release physostigmine in patients with Alzheimer's disease.

OBJECTIVE: To evaluate the safety and efficacy of controlled-release physostigmine, an acetylcholinesterase inhibitor, in patients with probable AD of mild to moderate severity. METHODS: A prospective, 24-week, randomized, multicenter, double-blind, parallel group study of patients was conducted. The study enrolled 475 patients at 24 sites. Patients met criteria for probable AD and were randomized to one of three arms: placebo, controlled-release (CR) physostigmine 30 mg daily, or CR physostigmine 36 mg daily. Dosage was escalated by a forced upward titration during the first 6 to 9 weeks of the trial, then maintained at a constant dose to 24 weeks. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change-Plus with caregiver input (CIBIC+). Secondary outcome measures included the Clinical Global Impression of Change (CGIC), the Geriatric Evaluation by Relatives Rating Instrument, and an Instrumental Activities of Daily Living Scale. RESULTS: In an intent-to-treat population, the last observation carried forward analysis revealed a 2.9-point ADAS-Cog (p = 0.002) difference between physostigmine and placebo-treated patients for both dosages, and a 0.26 to 0.31-point difference on the CIBIC+ (p = 0.048). There were no significant differences on the secondary outcome measures except for a difference on the CGIC when analyzed by use of the Cochran-Mantel-Haenszel statistic (p = 0.014). There were significant increases in gastrointestinal side effects including nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain for patients on either dose of physostigmine, resulting in a high dropout rate. Agitation was decreased significantly. There was no evidence of cardiac rhythm disturbance or liver function abnormalities. CONCLUSION: CR physostigmine enhanced cognitive and global function. It is relatively safe for the treatment of cognitive dysfunction secondary to AD. However, in light of the gastrointestinal side effects, a lower starting dose and a flexible titration schedule might lead to a more favorable adverse event profile in the clinical arena.

Acute pulmonary embolism: diagnosis with MR angiography.

PURPOSE: To prospectively evaluate pulmonary magnetic (MR) angiography as a diagnostic examination for acute pulmonary embolism (PE). MATERIALS AND METHODS: Thirty-six consecutive patients (19 women, 17 men; age range, 28-84 years) underwent pulmonary digital subtraction angiography (DSA) and pulmonary MR angiography. MR angiograms were obtained during suspended respiration and the pulmonary arterial phase of gadolinium-based contrast medium injection. A steady-state gradient-recalled-echo sequence with free induction decay sampling was used. DSA studies were interpreted for the presence of acute PE by two independent radiologists; an adjudicator made the final decision on discordant interpretations. RESULTS: By using DSA, a total of 19 acute pulmonary emboli were depicted in 13 patients. Prospectively, 13 of these emboli were depicted by using MR angiography. MR angiography missed six emboli: Four required the DSA adjudicator to make the decision, and one was in a patient whose MR angiogram was acquired during breathing. Four of these six emboli were small subsegmental emboli, and two were segmental. CONCLUSION: Performed without pulmonary arterial catheterization, iodinated contrast media, or ionizing radiation, pulmonary MR angiography had a high accuracy for depicting lobar and segmental emboli, but was unable to depict four of five subsegmental emboli.

Sibutramine produces dose-related weight loss.

OBJECTIVE: Sibutramine is a weight control drug that inhibits the reuptake of both serotonin and norepinephrine. In animals, it reduces food intake and increases thermogenesis and preliminary data in human beings showed weight loss. This paper reports a 24-week dose-ranging study to determine the effect of sibutramine on body weight of patients with obesity. RESEARCH METHODS AND PROCEDURES: Seven clinical centers screened 1463 patients with obesity and randomized 1047 to 24 weeks of treatment with 1 of 6 doses of sibutramine (1, 5, 10, 15, 20, or 30 mg) or placebo once daily. Six hundred eighty-three patients completed the study. A two-week placebo run-in period was used to initiate a standardized program of diet, physical activity, and lifestyle changes. RESULTS: Weight loss was dose-related and statistically significant vs. placebo (p<0.05) across all time-points for a 5 mg/day to 30 mg/day dosage of sibutramine. At week 24, percent weight loss from baseline for completers was: placebo, 1.2%; 1 mg, 2.7%; 5 mg, 3.9%; 10 mg, 6.1%; 15 mg, 7.4%; 20 mg, 8.8%; and 30 mg, 9.4%. Weight loss achieved at week 4 was predictive of weight loss achieved at week 24. Patients losing weight demonstrated an increase in serum high density lipoprotein cholesterol and reductions in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, and uric acid. Small mean increases in blood pressure and pulse rate (with considerable individual variability) were observed in patients treated with sibutramine. The most frequent adverse events were dry mouth, anorexia, and insomnia. DISCUSSION: Sibutramine administered once daily for 24 weeks in the weight loss phase of treatment for uncomplicated obesity produced dose-related weight loss and was well tolerated. Improvements in serum lipids and uric acid accompany sibutramine-induced weight loss. Most of the adverse events observed on sibutramine are related to its pharmacology, including small mean increases in blood pressure and heart rate.

The crystal structure of citrate synthase from the hyperthermophilic archaeon pyrococcus furiosus at 1.9 A resolution,.

The crystal structure of the closed form of citrate synthase, with citrate and CoA bound, from the hyperthermophilic Archaeon Pyrococcus furiosus has been determined to 1.9 A. This has allowed direct structural comparisons between the same enzyme from organisms growing optimally at 37 degrees C (pig), 55 degrees C (Thermoplasma acidophilum) and now 100 degrees C (Pyrococcus furiosus). The three enzymes are homodimers and share a similar overall fold, with the dimer interface comprising primarily an eight alpha-helical sandwich of four antiparallel pairs of helices. The active sites show similar modes of substrate binding; moreover, the structural equivalence of the amino acid residues implicated in catalysis implies that the mechanism proceeds via the same acid-base catalytic process. Given the overall structural and mechanistic similarities, it has been possible to make detailed structural comparisons between the three citrate synthases, and a number of differences can be identified in passing from the mesophilic to thermophilic to hyperthermophilic citrate synthases. The most significant of these are an increased compactness of the enzyme, a more intimate association of the subunits, an increase in intersubunit ion pairs, and a reduction in thermolabile residues. Compactness is achieved by the shortening of a number of loops, an increase in the number of atoms buried from solvent, an optimized packing of side chains in the interior, and an absence of cavities. The intimate subunit association in the dimeric P. furiosus enzyme is achieved by greater complementarity of the monomers and by the C-terminal region of each monomer folding over the surface of the other monomer, in contrast to the pig enzyme where the C-terminus has a very different fold. The increased number of intersubunit ion pairs is accompanied by an increase in the number involved in networks. Interestingly, all loop regions in the P. furiosus enzyme either are shorter or contain additional ion pairs compared with the pig enzyme. The possible relevance of these structural features to enzyme hyperthermostability is discussed.

The effect of added-purpose and meaningful occupation on motor learning.

OBJECTIVE: Numerous studies in the occupational therapy literature have investigated the effects of added-purpose (multidimensional, goal-oriented) occupation on performance. Motor learning research has demonstrated that factors that enhance performance measures do not necessarily enhance motor learning. This study examined the effects of both added-purpose and meaningful occupation on motor learning. METHOD: Twenty subjects (university students) were randomly assigned to either an added-purpose or rote exercise condition. After a skill acquisition phase, retention and transfer scores were obtained, and subjects were asked to rate the meaningfulness of the occupation on a visual analog scale. RESULTS: A two-way analysis of variance indicated that only the added-purpose occupation resulted in significantly greater motor learning. Additionally, the added-purpose scores were not influenced by the level of meaning assigned to the occupation. CONCLUSION: This study is the first to demonstrate how added-purpose can enhance a more permanent aspect of performance: motor learning. Further research is necessary to determine whether occupations that both are meaningful and have added-purpose are the most effective in enhancing motor learning.

Complete pre-operative imaging assessment of abdominal aortic aneurysm with spiral CT angiography.

PURPOSE: A prospective evaluation of spiral CT angiography (SCTA) as the sole pre-operative imaging modality for abdominal aortic aneurysm repair. MATERIALS AND METHODS: Spiral CT angiography was compared with conventional transfemoral angiography in 30 patients and results correlated with surgical findings in 22 patients. The following features were assessed: renal artery number and disease; upper and lower aneurysm extent; aneurysm size; perianeurysmal inflammation; iliac artery disease; radiation dose; and contrast usage. RESULTS: Spiral CT angiography agreed with conventional angiography in all cases of severe stenosis or occlusion of renal arteries and had 90% agreement overall for renal artery disease. Two of nine accessory renal arteries seen at conventional angiography were missed. For showing aneurysm extent SCTA was 100% sensitive, and performed better than conventional angiography. Aneurysm size was better shown with SCTA. In iliac disease SCTA, as performed in this study, was poor for mild-moderate disease, but detected four of six severely stenosed/occluded iliac arteries seen at conventional angiography. Prospective sensitivity for perianeurysmal inflammation was 33%. Radiation dose for SCTA was approximately twice and contrast dose approximately three times that for conventional angiography. CONCLUSION: Spiral CT angiography can provide all the necessary imaging information to plan aneurysm repair in the non-claudicant.

Transhepatic venous angioplasty and stenting: a treatment option in bleeding from gastric varices secondary to pancreatic carcinoma.

We present a case of recurrent variceal bleeding due to subtotal occlusion of the splenoportal junction by a pancreatic carcinoma. This was effectively treated by transhepatic venous angioplasty and stenting.

Endovascular surgery.

The procedures used in the treatment of peripheral arterial disease are evolving constantly. The most rapid changes have been in the use of endovascular techniques in which the interventions are occurring from within the blood vessel either in the radiology suite percutaneously or in the operating theatre by open access. The following article attempts to bring together these two disciplines and to address them with a unified approach.

A double-blind trial of low- and high-dose ranges of gepirone-ER compared with placebo in the treatment of depressed outpatients.

We report the results of a double-blind study comparing the efficacy and safety of low-dose (10-50 mg) and high-dose (20-100 mg) ranges of gepirone-extended release (ER) and placebo in 145 outpatients with major depressive disorder. At multiple time points and endpoint (Week 6), statistically significant reductions in Hamilton Rating Scale for Depression (HAM-D) scores were recorded for high-dose gepirone-ER compared to placebo. Analysis of the 17-item HAM-D and 28-item HAM-D scores indicated a relatively early onset of antidepressant efficacy with statistically significant results at treatment Weeks 1, 2, 4, and 6. A rapid response was evident in the high-dose group, beginning at Week 1 (p < .05). The most frequently reported adverse experiences were headache, nausea, dizziness, and insomnia. The results indicate that gepirone-ER is clearly superior to placebo in terms of antidepressant efficacy. When used at higher doses, gepirone-ER appears to be efficacious, safe, and well-tolerated in depressed out-patients.

Percutaneous varicocele embolization in the treatment of infertility.

Clinical and sub-clinical varicoceles are associated with infertility and abnormal sperm parameters. Percutaneous embolization is a minimally invasive, safe, outpatient method of treatment which is cost effective in comparison to surgery. This study is a retrospective review of embolization of the spermatic vein using stainless steel occluding spring coils, performed in 116 males from two infertility clinics. Follow-up results were complete in 87 patients of which 79 (91%) were successful both technically and clinically and all had sperm analysis performed both before and within 2 years after embolization. There was a highly significant increase in motility (mean 35% before, mean 46% after, p < 0.001). Sperm density showed a trend towards improvement, but only p < 0.10, and there was no significant change in semen volume or morphology. The partners of 29 men (33%) became pregnant in a total of 241 years of follow-up.