Target Organ Toxicity in Rats After Subchronic Oral Exposure to Soil Extracts Containing a Complex Mixture of Contaminants.

Complex mixtures of unknown contaminants present a challenge to identify toxicological risks without using large numbers of animals and labor-intensive screens of all organs. This study examined soil extracts from a legacy-contaminated pesticide packaging and blending site. HepG2 cytotoxicity was used as an initial screen of 18 soil samples; then, three extracts (A, B and C) from different locations at the study site were used for testing in animals. The first two extracts were identified as the most toxic in vitro, and the latter extract obtained from a location further from these two toxic sampling sites. Then, target organ toxicities were identified following biweekly oral gavage for one month of three soil extracts (0.1% in polyethylene glycol or PEG) compared to vehicle control in male Sprague-Dawley rats (n = 9-10/group). Exposure to extract A significantly increased neutrophils and lymphocytes compared to control. In contrast, all extracts increased plasma α-2 macroglobulin and caused mild-to-moderate lymphocytic proliferation within the spleen white pulp, all indicative of inflammation. Rats exposed to all soil extracts exhibited acute tubular necrosis. Cholinesterase activity was significantly reduced in plasma, but not brain, after exposure to extract A compared to control. Increased hepatic ethoxyresorufin-o-deethylase activity compared to control was observed following exposure to extracts A and B. Exposure to soil extract C in rats showed a prolonged QTc interval in electrocardiography as well as increased brain lipid peroxidation. Candidate contaminants are organochlorine, organophosphate/carbamate pesticides or metabolites. Overall, HepG2 cytotoxicity did not successfully predict the neurotoxicity and cardiotoxicity observed with extract C but was more successful with suspected hydrocarbon toxicities in extracts A and B. Caution should be taken when extrapolating the observation of no effects from in vitro cell culture to in vivo toxicity, and better cell culture lines or assays should be explored.

Feed preference and feeding behaviours in grower broilers fed diets containing wheat naturally contaminated with fusarium mycotoxins.

1. Two trials were conducted to determine the effect of feeding diets contaminated with fusarium mycotoxins (primarily deoxynivalenol (DON)) on broiler chicken feed preference, feeding behaviour and growth performance. 2. A total of 120 male Ross 308 chicks (4 birds/cage, 30 cages) were fed a common corn-based starter diet from 1 to 20 d of age. At 21 d, 15 cages were randomly assigned to the feed preference trial or a feeding behaviour trial. Three wheat-based experimental diets (0.14, 2.27 and 5.84 mg/kg DON) were prepared with a clean wheat and a naturally contaminated wheat. Broilers were ad libitum fed the experimental diets during 21-27 d. 3. In the preference trial, each cage's feeder was split into two equal-sized compartments so birds were provided a choice of two diets (control vs. low, control vs. high and low vs. high DON). In the feeding behaviour trial, diets were randomly assigned to 15 cages (5 cages/diet). Feeding and drinking behaviour was recorded for 1 h before and after the dark period and 1-h period at 9 h after the light was turned on (middle of day). Growth performance was assessed at 27 d. 4. In the preference trial, broilers preferred the control diet over low (93.0 vs. 66.1 g/d, P < 0.01) and high (104.4 vs. 50.4 g/d, P < 0.01) DON diets. At all three timepoints, where behaviour was recorded, birds offered the DON diets spent more time at the feeder compared to birds provided control diets (P < 0.05). Control birds had lower feed to gain ratio (1.65) than birds fed low (1.82) and high (1.94) DON diets (P < 0.01). 5. It is clear that broilers are sensitive to the presence of fusarium mycotoxins and that moderate levels of DON negatively affect feed preference and growth performance when fed during the grower period.

Retroileal colorectal anastomosis: an old technique, still relevant.

Retroileal colorectal anastomosis is an infrequently used technique providing tension-free anastomosis after extended left-sided colonic resection, which was first described by Turnbull in 1972. The authors describe the use of a retroileal colorectal anastomosis in a patient with chronic Candida albicans and Enterococcal retroperitoneal abscess. The patient's condition was most likely secondary to an anastomotic leak and colonic fistula post en bloc resection for recurrence of a left renal cell carcinoma. After failure of antimicrobial therapy and percutaneous drainage, surgical intervention was required. This involved resection of the existing colocolonic anastomosis and drainage of the retroperitoneal abscess. A retroileal colorectal anastomosis was then necessary to ensure a tension-free anastomosis. To the best of our knowledge, this is the first reported case of retroileal anastomosis used for this purpose. It highlights the importance of this technique in the surgeon's armamentarium.

Unscheduled undergraduate teaching in surgery: a multi-institutional analysis.

A significant amount of valuable undergraduate medical teaching may be informal, unscheduled and delivered by non-consultant hospital doctors (NCHDs). 800 Questionnaires were distributed to consultants, NCHDs and medical students in Irish teaching hospitals. The aim was to quantify the level of unscheduled teaching carried out in these hospitals and the manner in which it was performed. The response rate was 46% (364/800). 71% of doctors who replied are independently teaching undergraduate medical students (77/109), including 71% of interns and senior house officers (48/68). Students tend to prefer small group teaching. Fifty-six percent of students suggest they would benefit from more surgical teaching time (144/255). No interns surveyed were scheduled to teach as part of a formal curriculum. A significant amount of unscheduled teaching by interns and senior house officers takes place in Irish hospitals. It may prove beneficial to incorporate interns into scheduled surgical teaching curricula.

Linking pesticide exposure to neurodegenerative diseases: An in vitro investigation with human neuroblastoma cells.

Although many organochlorine pesticides (OCPs) have been banned or restricted because of their persistence and linkage to neurodegenerative diseases, there is evidence of continued human exposure. In contrast, registered herbicides are reported to have a moderate to low level of toxicity; however, there is little information regarding their toxicity to humans or their combined effects with OCPs. This study aimed to characterize the mechanism of toxicity of banned OCP insecticides (aldrin, dieldrin, heptachlor, and lindane) and registered herbicides (trifluralin, triallate, and clopyralid) detected at a legacy contaminated pesticide manufacturing and packing site using SH-SY5Y cells. Cell viability, LDH release, production of reactive oxygen species (ROS), and caspase 3/7 activity were evaluated following 24 h of exposure to the biocides. In addition, RNASeq was conducted at sublethal concentrations to investigate potential mechanisms involved in cellular toxicity. Our findings suggested that aldrin and heptachlor were the most toxic, while dieldrin, lindane, trifluralin, and triallate exhibited moderate toxicity, and clopyralid was not toxic to SH-SY5Y cells. While aldrin and heptachlor induced their toxicity through damage to the cell membrane, the toxicity of dieldrin was partially attributed to necrosis and apoptosis. Moreover, toxic effects of lindane, trifluralin, and triallate, at least partially, were associated with ROS generation. Gene expression profiles suggested that decreased cell viability induced by most of the tested biocides was related to inhibited cell proliferation. The dysregulation of genes encoding for proteins with anti-apoptotic properties also supported the absence of caspase activation. Identified enriched terms showed that OCP toxicity in SH-SY5Y cells was mediated through pathways associated with the pathogenesis of neurodegenerative diseases. In conclusion, this study provides a basis for elucidating the molecular mechanisms of pesticide-induced neurotoxicity. Moreover, it introduced SH-SY5Y cells as a relevant in vitro model for investigating the neurotoxicity of pesticides in humans.

Herbicides and pesticides synergistically interact at low concentrations in complex mixtures.

Assessing a complex mixture of pesticides at the impacted sites has been challenging for risk assessors for 50 years. The default assumption is that at low concentrations, pesticides interact additively with one another; thus, the risk posed by each component of a complex mixture could be simply added up. The EPA interaction-based hazard index (HIInteraction) modifies this assumption using a binary weight-of-evidence (BINWOE). However, data gaps often preclude HIInteraction use at most sites. This study evaluated these assumptions using the BINWOE to estimate the hazard index (HI) of select pesticide mixtures. The lack of in vivo binary interaction data led us to use a cell line, SH-SY5Y, to obtain the data necessary for the BINWOE approach. In the risk assessment, we considered the most active exposure scenario inhaling a mixture of volatile pesticides from contaminated soil and groundwater. The potential interactions between pesticides in 15 binary mixtures were investigated using the MTT assay in SH-SY5Y cells. Our findings showed that 60% of the binary mixtures elicited synergism (in at least one concentration), 27% displayed antagonism, and 13% showed additive effects in SH-SY5Y cells. Combining human safety data with in vitro interaction data indicated that adults and toddlers were at the highest risk when considering industrial and commercial land use, respectively, compared to other subpopulations. Incorporating interaction data into the risk assessment either increased the risk by up to 20% or decreased the risk by 2%, depending on the mixture. Our results demonstrate the predominant synergistic interactions, even at low concentrations, altered risk characterization at the complex operating site. Most concerning, organochlorine pesticides with the same mechanism of action did not follow dose additivity when evaluated by SH-SY5Y cell lines. Based on our observations, we caution that current HI methods based on additivity assumptions may underestimate the risk of organochlorine mixtures.

Impaired memory in Sprague-Dawley rats exposed to complex groundwater mixtures of contaminants is associated with reduced cranial blood flow and hippocampal neurotoxicity.

Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10 % v/v low impact groundwater, and (iii) 0.01 %, 0.1 %, 1 %, and 10 % high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.

Exercise in the community for people with minimal gait impairment due to MS: an assessor-blind randomized controlled trial.

BACKGROUND: While there is an increasing body of evidence supporting the efficacy of exercise in people with multiple sclerosis (MS), additional information on the effectiveness of combining aerobic and resistance training, and yoga is required. OBJECTIVES: This study evaluated the effectiveness of community exercise interventions for people with MS having minimal gait impairment. METHODS: A multi-centred, block-randomised, assessor-blinded, controlled trial was conducted. Participants were randomised in groups of eight to physiotherapist (PT)-led exercise (n = 80), yoga (n = 77), fitness instructor (FI)-led exercise (n = 86) and they took part in weekly community-based group exercise sessions. Those in the control group were asked not to change of their exercise habits (n = 71). The primary outcome was the Multiple Sclerosis Impact Scale (MSIS) 29v2 physical component, measured before and after the 10-week intervention. Secondary outcomes were the MSIS 29v2 psychological component, the Modified Fatigue Impact Scale (MFIS) and the 6-Minute Walk Test (6MWT). RESULTS: The group x time interaction approached significance for the MSIS-29v2 physical component (f = 2.48, p = 0.061) and MFIS total (f = 2.50, p = 0.06), and it was significant for the MFIS physical subscale (f = 4.23, p = 0.006). All three exercise interventions led to a statistically significant improvement on the MSIS-29 psychological component and both the MFIS total and physical subscales, which were greater than the control (p < 0.05). Only the PT-led and FI-led interventions significantly improved the MSIS-29 physical and 6MWT to levels greater than the control (p < 0.05). CONCLUSIONS: This study provides evidence for the positive effect of exercise on the physical impact of MS and fatigue. The group nature of the classes may have contributed to the positive effects seen on the psychological impact of MS.

Phylogenetic analysis and molecular methods for the detection of lymphocystis disease virus from yellow perch, Perca flavescens (Mitchell).

Lymphocystis disease is a prevalent, non-fatal disease that affects many teleost fish and is caused by the DNA virus lymphocystis disease virus (LCDV). Lymphocystis-like lesions have been observed in yellow perch, Perca flavescens (Mitchell), in lakes in northern Alberta, Canada. In an effort to confirm the identity of the virus causing these lesions, DNA was extracted from these lesions and PCR with genotype generic LCDV primers specific to the major capsid protein (MCP) gene was performed. A 1357-base pair nucleotide sequence corresponding to a peptide length of 452 amino acids of the MCP gene was sequenced, confirming the lesions as being lymphocystis disease lesions. Phylogenetic analysis of the generated amino acid sequence revealed the perch LCDV isolate to be a distinct and novel genotype. From the obtained sequence, a real-time PCR identification method was developed using fluorgenic LUX primers. The identification method was used to detect the presence/absence of LCDV in yellow perch from two lakes, one where lymphocystis disease was observed to occur and the other where the disease had not been observed. All samples of fin, spleen and liver tested negative for LCDV in the lake where lymphocystis disease had not been observed. The second lake had a 2.6% incidence of LCD, and virus was detected in tissue samples from all individuals tested regardless of whether they were expressing the disease or not. However, estimated viral copy number in spleen and liver of symptomatic perch was four orders of magnitude higher than that in asymptomatic perch.

Health status of fathead minnow (Pimephales promelas) populations in a municipal wastewater effluent-dominated stream in the Canadian prairies, Wascana Creek, Saskatchewan.

Their unique hydrological and climatic conditions render surface water systems in the southern Canadian Prairies at an elevated risk from exposure to contaminants released from municipal wastewater effluents (MWWEs). The aim of this study was to characterize the potential health effects and their underlying molecular mechanisms in populations of fathead minnow (Pimephales promelas; FHM) in Wascana Creek, an effluent dominated stream in Southern Saskatchewan, Canada. Studies were conducted during the spawning season in 2014 and 2015 to assess responses in terms of overall health, reproductive functions, plasma sex steroid hormone levels, and expression of selected genes along the hypothalamus-pituitary-gonadal axis. FHM downstream of the effluent fallout had lower gonadosomatic indices and significantly greater hepatosomatic indices compared to upstream populations. In both male and female FHMs, significantly greater occurrence and severity of gonadal degradation and delayed maturation were observed in downstream fish compared to upstream fish. Downstream males also displayed lower scores of secondary sexual characteristics and a decreasing trend in plasma 11-ketotestosterone levels. Interestingly, no indications of exposure to estrogenic compounds, such as occurrence of testicular oocytes were observed, which was in accordance with the lack of presence of key biomarkers of estrogenic exposure, such as induction of vitellogenin. In general, expression of the majority of transcripts measured in FHMs downstream of the effluent fallout was significantly downregulated, which supports observations of the general deterioration of the health and reproductive status of these fish. Chemical analysis indicated that 10 pharmaceuticals and personal care products (PPCPs) were present at the downstream site, some at sufficiently great concentrations that may present a risk to aquatic organisms. With continuous exposure to a diverse number of stressors including high nutrient and ammonia levels, the presence of a variety of PPCPs and other contaminants, Wascana Creek should be considered as an ecosystem at risk.

Non-monotonicity on a spatio-temporally defined cyclic task: evidence of two movement types?

We tested 23 healthy participants who performed rhythmic horizontal movements of the elbow. The required amplitude and frequency ranges of the movements were specified to the participants using a closed shape on a phase-plane display, showing angular velocity versus angular position, such that participants had to continuously control both the speed and the displacement of their forearm. We found that the combined accuracy in velocity and position throughout the movement was not a monotonic function of movement speed. Our findings suggest that specific combinations of required movement frequency and amplitude give rise to two distinct types of movements: one of a more rhythmic nature, and the other of a more discrete nature.

Prevalence of Batrachochytrium dendrobatidis in three species of wild frogs on Prince Edward Island, Canada.

Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has resulted in the decline or extinction of approximately 200 frog species worldwide. It has been reported throughout much of North America, but its presence on Prince Edward Island (PEI), on the eastern coast of Canada, was unknown. To determine the presence and prevalence of Bd on PEI, skin swabs were collected from 115 frogs from 18 separate sites across the province during the summer of 2009. The swabs were tested through single round end-point PCR for the presence of Bd DNA. Thirty-one frogs were positive, including 25/93 (27%) green frogs Lithobates (Rana) clamitans, 5/20 (25%) northern leopard frogs L. (R.) pipiens, and 1/2 (50%) wood frogs L. sylvaticus (formerly R. sylvatica); 12 of the 18 (67%) sites had at least 1 positive frog. The overall prevalence of Bd infection was estimated at 26.9% (7.2-46.7%, 95% CI). Prevalence amongst green frogs and leopard frogs was similar, but green frogs had a stronger PCR signal when compared to leopard frogs, regardless of age (p < 0.001) and body length (p = 0.476). Amongst green frogs, juveniles were more frequently positive than adults (p = 0.001). Green frogs may be the most reliable species to sample when looking for Bd in eastern North America. The 1 wood frog positive for Bd was found dead from chytridiomycosis; none of the other frogs that were positive for Bd by PCR showed any obvious signs of illness. Further monitoring will be required to determine what effect Bd infection has on amphibian population health on PEI.

The nucleus-limited Hsr-omega-n transcript is a polyadenylated RNA with a regulated intranuclear turnover.

The Drosophila Hsr-omega puff, one of the largest heat shock puffs, reveals a very unusual gene, identified by heat shock but constitutively active in nearly all cell types. Surprisingly, Hsr-omega yields two transcription end-products with very different roles. The larger, omega-n, is a nuclear RNA with characteristics suggesting a new class of nuclear RNAs. Although it neither leaves the nucleus nor undergoes processing, omega-n RNA is polyadenylated, showing that polyadenylation is not limited to cytoplasmic RNA, but possibly has a function in the nucleus. The amount of omega-n within the nucleus is specifically regulated by both transcription and turnover. Heat shock and several other agents cause rapid increases in omega-n. A rapid return to constitutive levels follows withdrawal of the agents. Degradation of omega-n is inhibited by actinomycin D, suggesting a novel intranuclear mechanism for RNA turnover. Within the nucleus, some omega-n RNA is concentrated at the transcription site; however, most is evenly distributed over the nucleus, showing no evidence of a concentration gradient which might be produced by simple diffusion from the site of transcription. Previous studies suggested that omega-n has a novel regulatory role in the nucleus. The actinomycin D-sensitive degradation system makes possible rapid changes in the amount of omega-n, allowing the putative regulatory activities to reflect cellular conditions at a given time. Omega-n differs from the best studied nuclear RNAs, snRNAs, in many ways. Omega-n demonstrates the existence of intranuclear mechanisms for RNA turnover and localization that may be used by a new class of nuclear RNAs.

An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy.

BACKGROUND: A phase 3 study demonstrated that panitumumab, a human monoclonal anti-epidermal growth factor receptor antibody, significantly prolonged progression-free survival versus best supportive care (BSC) in patients with chemorefractory metastatic colorectal cancer. PATIENTS AND METHODS: This open-label extension study evaluated panitumumab monotherapy in BSC patients with radiographically documented disease progression in the phase 3 study. Patients received panitumumab 6 mg/kg every 2 weeks. The primary end point was safety; efficacy was also evaluated. RESULTS: One hundred and seventy-six patients were randomly assigned to the BSC arm of the phase 3 study received >/=1 panitumumab dose in this extension study. Panitumumab was well tolerated. The most frequent treatment-related adverse events were skin toxic effects. Three (2%) patients had a grade 4 treatment-related adverse event. There were no infusion reactions. One (0.6%) patient had a complete response; 19 (11%) patients had a partial response; and 58 (33%) patients had stable disease. Median progression-free survival time was 9.4 [95% confidence interval (CI): 8.0-13.4) weeks. Median overall survival time was 6.3 (95% CI: 5.1-6.8) months. Anti-panitumumab antibodies were detected in 3 (4.2%) of 71 patients with a post-baseline sample. CONCLUSIONS: These findings are comparable to those from the phase 3 study and support panitumumab monotherapy for chemorefractory colorectal cancer.

Melena as an unusual presentation of gastrointestinal stromal tumour, a case report.

INTRODUCTION: Gastrointestinal Stromal Tumors (GISTs) are a rare slow growing malignancy, accounting for less than 1% of all gastrointestinal (GI) tract tumors. These tumors are usually discovered incidentally by endoscopy, surgery or radiology. However on occasions they may present with significant symptoms including GI blood loss. This case report discusses an atypical presentation of a GIST in a 57-year-old female. CASE PRESENTATION: A 57-year-old woman presented to the emergency department following one episode of melena. This occurred on a background of two previous presentations with melena over a 10-year period. She had a preceding surgery for a Meckel's Diverticulum. She was admitted for monitoring and investigation. An emergency upper endoscopy showed no upper gastrointestinal pathology to account for the bleeding. Her condition deteriorated with development of hypovolemic shock, requiring blood transfusion. An urgent CT angiogram identified a large mass in the distal ileum. The patient underwent an emergency laparotomy, where a 9.1 cm tumor located on the distal one-third of the ileum was resected. Histopathology confirmed the mass was a GIST. The patient had a successful post-operative period and subsequent treatment with Imatinib. DISCUSSION: The majority of GISTs are found incidentally. This case report describes an unusual presentation of a GIST in which the tumor bled into the intestinal lumen causing significant melena and life threatening hemorrhage. CONCLUSION: We conclude that GIST should be considered as a possible differential in rare cases of GI bleeding where more common causes have been ruled out.

Hyperactivity of neutrophil leukotactic responses during active bacterial infection.

To determine if changes in neutrophil leukocyte function occur during active bacterial infection, the neutrophils of 25 patients with active bacterial infection and 25 age-matched controls were compared for leukotactic activity, random mobility, and nitroblue tetrazolium reduction. The neutrophil leukocytes of patients with bacterial infection were hyperactive in unidirectional movement toward a chemotactic stimulus as measured in the leukotactic assay and usually had increased nitroblue tetrazolium reduction. The mean leukotactic index was 165+/-56 in patients with bacterial infection and 70+/-11 in controls (P < 0.001). After 7-10 days of appropriate therapy with clinical and bacteriological response, leukotactic activity returned to normal values. A hyperactive leukotactic response continued, however, in patients with persisting bacterial infection. The hyperactive leukotactic response of circulating neutrophils appears to be an early and sensitive event in the inflammatory cycle stimulated by bacterial infection and may aid in the localization of invading bacteria.

The two Drosophila telomeric transposable elements have very different patterns of transcription.

The transposable elements HeT-A and TART constitute the telomeres of Drosophila chromosomes. Both are non-long terminal repeat (LTR) retrotransposons, sharing the remarkable property of transposing only to chromosome ends. In addition, strong sequence similarity of their gag proteins indicates that these coding regions share a common ancestor. These findings led to the assumption that HeT-A and TART are closely related. However, we now find that these elements produce quite different sets of transcripts. HeT-A produces only sense-strand transcripts of the full-length element, whereas TART produces both sense and antisense full-length RNAs, with antisense transcripts in more than 10-fold excess over sense RNA. In addition, features of TART sequence organization resemble those of a subclass of non-LTR elements characterized by unequal terminal repeats. Thus, the ancestral gag sequence appears to have become incorporated in two different types of elements, possibly with different functions in the telomere. HeT-A transcripts are found in both nuclear and cytoplasmic cell fractions, consistent with roles as both mRNA and transposition template. In contrast, both sense and antisense TART transcripts are almost entirely concentrated in nuclear fractions. Also, TART open reading frame 2 probes detect a cytoplasmic mRNA for reverse transcriptase (RT), with no similarity to TART sequence 5' or 3' of the RT coding region. This RNA could be a processed TART transcript or the product of a "free-standing" RT gene. Either origin would be novel. The distinctive transcription patterns of both HeT-A and TART are conserved in Drosophila yakuba, despite significant sequence divergence. The conservation argues that these sets of transcripts are important to the function(s) of HeT-A and TART.

Osteochondritis dissecans of the knee; long-term clinical outcome following arthroscopic debridement.

We reviewed 32 knees in 26 patients who had previously undergone arthroscopic debridement for symptomatic osteochondritis dissecans (OCD) of the knee. The patients were followed up at a minimum of 11 years following surgery and were evaluated clinically using the American Knee Society Clinical Rating Score. Additional evaluation was performed using the Hughston Scale to include radiographic assessment. The mean American Knee Society Score was 179 (out of 200), indicating good clinical function. Radiographically, however, only 29% scored excellent or good on the Hughston Scale. Younger patients with a small, stable (and therefore preserved), medial femoral condyle lesion had the best prognosis. Whilst more novel and complex options such as chondrocyte implantation are being assessed for the treatment of OCD, it is clear that within this study group careful debridement with removal of loose tissue can achieve good clinical results in the long term. There was however radiographic evidence of early degenerative joint disease in 17/24 (71%) of patients reviewed. Patients undergoing excision of OCD fragments did worse than those in whom the fragment was preserved, however the risk of further surgery is raised if a fragment is left in situ at initial surgery.

Design and Characterization of Hand Module for Whole-Arm Rehabilitation Following Stroke.

In 1991, a novel robot named MIT-MANUS was introduced as a test bed to study the potential of using robots to assist in and quantify the neurorehabilitation of motor function. It introduced a new modality of therapy, offering a highly backdrivable experience with a soft and stable feel for the user. MIT-MANUS proved an excellent fit for shoulder and elbow rehabilitation in stroke patients, showing a reduction of impairment in clinical trials with well over 300 stroke patients. The greatest impairment reduction was observed in the group of muscles exercised. This suggests a need for additional robots to rehabilitate other target areas of the body. Previous work has expanded the planar MIT-MANUS to include an antigravity robot for shoulder and elbow, and a wrist robot. In this paper we present the "missing link": a hand robot. It consists of a single-degree-of-freedom (DOF) mechanism in a novel statorless configuration, which enables rehabilitation of grasping. The system uses the kinematic configuration of a double crank and slider where the members are linked to stator and rotor; a free base motor, i.e., a motor having two rotors that are free to rotate instead of a fixed stator and a single rotatable rotor (dual-rotor statorless motor). A cylindrical structure, made of six panels and driven by the relative rotation of the rotors, is able to increase its radius linearly, moving or guiding the hand of the patients during grasping. This module completes our development of robots for the upper extremity, yielding for the first time a whole-arm rehabilitation experience. In this paper, we will discuss in detail the design and characterization of the device.

Needle-free small-volume liquid injection system powered by a rotary actuator.

Controllable jet injection could provide a fast, repeatable method for delivery of small volume, high viscosity drugs to the dermis. We have developed a compact, lightweight jet injector that uses a small commercial rotary motor and differential screw to create a jet of fluid with sufficient force to deliver drug into tissue. Clear tissue analogue and ex vivo tissue were used to demonstrate repeatable delivery of <;10 µL of fluid using the device. The fluid when forced through a narrow orifice (108 µm) reaches a velocity of >250 m/s with an injection time of <;3 ms.