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Being able to adapt our movements to changing circumstances allows people to maintain performance across a wide range of tasks throughout life, but it is unclear whether visuomotor learning abilities are fully developed in young children and, if so, whether they remain stable in the elderly. There is limited evidence of changes in motor adaptation ability throughout life, and the findings are inconsistent. Therefore, our goal was to compare visuomotor learning abilities throughout the lifespan. We used a shorter, gamified experimental task and collected data from participants in 5 age groups. Young children (M = 7 years), older children (M = 11 years), young adults (M = 20 years), adults (M = 40 years) and older adults (M = 67 years) adapted to a 45° visuomotor rotation in a centre-out reaching task. Across measures of rate of adaptation, extent of learning, rate of unlearning, generalization, and savings, we found that all groups performed similarly. That is, at least for short bouts of gamified learning, children and older adults perform just as well as young adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Clayton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To explore the effect of joint hypermobility on acuity, and precision, of hand proprioception., Materials and Methods: We compared proprioceptive acuity, and precision, between EDS patients and controls. We then measured any changes in their estimates of hand position after participants adapted their reaches in response to altered visual feedback of their hand. The Beighton Scale was used to quantify the magnitude of joint hypermobility., Results: There were no differences between the groups in the accuracy of estimates of hand location, nor in the visually induced changes in hand location. However, EDS patients' estimates were less precise when based purely on proprioception and could be partially predicted by Beighton score., Conclusions: EDS patients are less precise at estimating their hand's location when only afferent information is available, but the presence of efferent signalling may reduce this imprecision. Those who are more hypermobile are more likely to be imprecise.

It has been suggested that people with Ehlers-Danlos syndrome (EDS), or other similar connective tissue disorders, may have proprioceptive impairments, the reason for which is still unknown. We recently found that EDS patients were less precise than healthy controls when estimating their felt hand's position relative to visible peripheral reference locations, and that this deficit was positively correlated with the severity of joint hypermobility. We further explore proprioceptive abilities in EDS by having patients localize their non-dominant left hand at a greater number of workspace locations than in our previous study. Additionally, we explore the relationship between chronic pain and proprioceptive sensitivity. We found that, although patients were just as accurate as controls, they were not as precise. Patients showed twice as much scatter than controls at all locations, but the degree of scatter did not positively correlate with chronic pain scores. This further supports the idea that a proprioceptive impairment pertaining to precision is present in EDS, but may not relate to the magnitude of chronic pain.

Reaching movements are rapidly adapted following training with rotated visual feedback of the hand (motor recalibration). Our laboratory has also found that visuomotor adaptation results in changes in estimates of felt hand position (proprioceptive recalibration) in the direction of the visuomotor distortion (Cressman and Henriques 2009, 2010; Cressman et al. 2010). In the present study, we included an additional method for measuring hand proprioception [specifically, proprioceptive-guided reaches of the unadapted (left) hand to the robot-guided adapted (right) hand-target] and compared this with our original perceptual task (estimating the felt hand position of the adapted hand relative to visual reference markers/the body midline), as well as to no-cursor reaches with the adapted hand (reaching to visual and midline-targets), to better identify whether changes in reaching following adaptation to a 50° rightward-rotated cursor reflect sensory or motor processes. Results for the proprioceptive estimation task were consistent with previous findings; subjects felt their hand to be aligned with a reference marker when it was shifted approximately 4° more in the direction of the visuomotor distortion following adaptation compared with baseline conditions. Moreover, we found similar changes in the proprioceptive-guided reaching task such that subjects misreached 5° in the direction of the cursor rotation. However, these results were true only for proprioceptive-guided reaches to the adapted hand, as reaches to the body midline were not affected by adaptation. This suggests that proprioceptive recalibration is restricted to the adapted hand and does not generalize to the rest of the body; this truly reflects a change in the sensory representation of the hand rather than changes in the motor program. This is in contrast to no-cursor reaches made with the adapted hand, which show reach after-effects for both visual targets and the midline, suggesting that reaches with the adapted hand reflect more of a change in the motor system. Our results also shed light on previous studies that may have misattributed these sensory and motor changes.

Reaching movements are rapidly adapted following training with rotated visual feedback of the hand. Our laboratory has also found that this visuomotor adaptation results in changes in estimates of felt hand position (proprioceptive recalibration) in the direction of the visuomotor distortion (Cressman and Henriques in J Neurophysiol 102:3505-3518, 2009; Cressman et al. in Exp Brain Res 205:533-544, 2010). In the current study, we investigated proprioceptive acuity and proprioceptive recalibration in a group of individuals with Ehlers-Danlos syndrome (EDS), a degenerative condition associated with collagen malformation. Some studies have suggested that these patients may have proprioceptive impairments, but the exact nature of the impairment is unclear (Rombaut et al. in Clin Rheumatol 29:289-295, 2010a). In this study, we measured the ability of EDS patients to estimate their felt hand position and tested whether these estimates changed following visuomotor adaptation. We found EDS patients were less precise in estimating their felt hand position in the peripheral workspace compared to healthy controls. Despite this poorer sensitivity, they recalibrated hand proprioception to the same extent as healthy controls. This is consistent with other populations who experience proprioceptive deficits (e.g. the elderly, Parkinson's disease patients), suggesting that sensory noise does not influence the extent of either motor or sensory plasticity.

In the United States, the proportion of foodborne illness outbreaks associated with consumption of contaminated domestic and imported fresh fruits and vegetables (produce) has increased over the past several decades. To address this public health concern, the goal of this work was to identify and quantify factors associated with microbial contamination of produce in pre- and postharvest phases of the farm-to-fork continuum. From 2000 to 2003, we collected 923 samples of 14 types of produce (grown in the southern United States or in the northern border states of Mexico) from 15 farms and eight packing sheds located in the southern United States. To assess microbial quality, samples were enumerated for Escherichia coli, total aerobic bacteria, total coliforms, and total Enterococcus. Most produce types had significantly higher microbial concentrations when sampled at the packing shed than when sampled at the farm. In addition, we observed seasonal differences in the microbial concentrations on samples grown in the United States, with higher mean indicator concentrations detected in the fall (September, October, and November). We developed a predictive, multivariate logistic regression model to identify and quantify factors that were associated with detectable concentrations of E. coli contamination on produce. These factors included produce type (specifically, cabbage or cantaloupe), season of collection (harvested in the fall), and packing step (bin, box, conveyor belt, or turntable). These results can be used to identify specific mechanisms of produce contamination and propose interventions that may decrease the likelihood of produce-associated illness.

Background: Surgical resection of the pancreas is considered a final resort in the treatment of chronic pancreatitis. However, the opportunity to perform an islet autotransplant at the same time provides the potential to prevent the onset of diabetes., Methods: Pancreatectomy together with islet autotransplantation has been offered in our center since 1994. A total of 40 patients have now undergone this procedure. The follow-up times range from 6 months to 7 years. The data presented here include the annual postoperative oral glucose tolerance test and glycosylated hemoglobin (HbA(1c)) results, together with insulin and opiate requirements., Results: Nineteen male and 21 female patients (median age 44, range 21-65) have been transplanted. Pancreatitis was related to alcohol in 45% and was idiopathic in 40%. A median of 130108 (24332-1, 165538) islet equivalent (IEQ) were transplanted, which related to 2020 (320-23311) IEQ per kilogram of body weight. At 2 years posttransplant, 18 patients had a median HbA(1c) of 6.6% (5.2-19.3%), fasting C-peptide of 0.66 ng/mL (0.26-2.65 ng/mL), and required a median of 12 (0-45) units of insulin per day. At 6 years, these figures were 8% (6.1-11.1%), 1.68 ng/mL (0.9-2.78 ng/ml) and 43 U/day (6-86 U/day), respectively. The majority of patients no longer require opiate analgesia, 68% have been able to return to work, and one patient has had a baby., Conclusions: Islet autotransplantation offers a valuable addition to surgical resection of the pancreas, as a treatment for chronic pancreatitis; and even in cases in which insulin independence is not achieved, the potential beneficial effects of C-peptide make the procedure worthwhile.

Objective: To assess the safety and efficacy of islet autotransplantation (IAT) combined with total pancreatectomy (TP) to prevent diabetes., Summary Background Data: There have been recent concerns regarding the safety of TP and IAT. This is thought to be related to the infusion of large volumes of unpurified pancreatic digest into the portal vein. Minimizing the volume of islet tissue by purifying the pancreatic digest has not been previously evaluated in terms of the postoperative rate of death and complications, pain relief, and insulin independence., Method: During a 54-month period, 24 patients underwent pancreas resection with IAT. Islets were isolated using collagenase and a semiautomated method of pancreas digestion. Where possible, islets were purified on a density gradient and COBE processor. Islets were embolized into the portal vein, within the spleen and portal vein, or within the spleen alone. The total median volume of digest was 9.9 mL., Results: The median number of islets transplanted was 140,419 international islet equivalents per kilogram. The median increase in portal pressure was 8 mmHg. Early complications included duodenal ischemia, a wedge splenic infarct, partial portal vein thrombosis, and splenic vein thrombosis. Intraabdominal adhesions were the main source of long-term problems. Eight patients developed transient insulin independence. Three patients were insulin-independent as of this writing. Patients had significantly decreased insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. Of the patients alive and well as of this writing, four had failed to gain relief of their abdominal pain and were still opiate-dependent., Conclusion: Combined TP and IAT can be a safe surgical procedure. Unfortunately, almost all patients were still insulin-dependent, but they had decreased daily insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. A prospective randomized study is therefore needed to assess the long-term benefit of TP and IAT on diabetic complications.

Clinical and experimental studies of intrahepatic islet transplantation have allowed histological and systemic observations to be made, but the location of the transplanted islets makes it difficult to assess direct effects on the cells of the liver. An in vitro coculture model of Kupffer cells with islets or pancreatic acinar tissue is described, using porcine tissue and measuring the secretion of thromboxane B 2 , prostaglandin E 2 , 6-keto-prostaglandin F 1α , and prostaglandin F 2α as an indicator of Kupffer cell stimulation. The results have demonstrated activation of Kupffer cells in the presence of acinar or islet tissue, both when the cells were in direct contact and when separated by a membrane. This indicated that the stimulation was due to a soluble factor or factors, and was confirmed by the culture of Kupffer cells with acinar conditioned medium. The degree of stimulation was much greater with acinar tissue than with islets. In subsequent experiments, aprotinin, an enzyme activation inhibitor, was added to the cocultures in an attempt to reduce Kupffer cell activation. This had no effect, possibly due to the fact that the endogenous pancreatic enzymes may already be activated during digestion of the pancreas. Aprotinin alone caused an increase in secretion of eicosanoids from Kupffer cells. The high response to acinar tissue is of particular relevance to islet autotransplantation in which unpurified pancreatic digest is often transplanted. The clinical effectiveness of aprotinin in the light of these results is discussed. In conclusion, although unable to mimic the complex situation following intrahepatic islet transplantation, the coculture model described here allows the opportunity to assess the events relating to specific cell types, and will provide the scope to undertake more detailed studies on the mechanisms involved. The same model could be applied to the coculture of pancreatic tissue with hepatocytes to determine any effects on the normal function of hepatocytes.

Background: The shortage of organ donors relative to the number of patients on transplant waiting lists has led to a renewed interest in the use of non-heart-beating (NHB) organ donors in many centers. The lack of donors is also a problem for islet transplantation. The disparity between donor organs and potential recipients is further exacerbated by the requirement to transplant a large number of islets to increase the chance of success and the high level of variability in islet isolation yield. Non-heart-beating (NHB) donors have not previously been assessed as a source of islets for transplantation, and it is unknown what affects the additional factor of warm ischemic injury associated with NHB organs may have on the success of islet isolation., Methods: This study assesses the yield and function of islets from NHB donors and compares the results with islets obtained from heart-beating brain-dead (HB) donors., Results: There were no differences in the yield of islets per gram of pancreas, 1788 (0-4620) NHB vs. 1580 (26-2544) HB (median, range). The secretory function was also similar in both groups, with stimulation indices of 0.71-3.49 for NHB vs. 0.30-3.57 for HB (overall range). There was no correlation between islet yield and warm ischemia time in the NHB donor group., Conclusions: In conclusion, the study has demonstrated that it is possible to isolate large numbers of islets from NHB donor pancreata and that, where NHB donor programs exist, these could provide a significant addition to the number of potentially transplantable islets.

Nitric oxide synthase, induced by cytokines in insulin-containing cells, produces nitric oxide which inhibits function and may promote cell killing. Since glucagon was shown to prevent inducible nitric oxide synthase (iNOS) expression in rat hepatocytes it was of interest to examine the action of glucagon (and cyclic AMP) on iNOS induction in insulin-producing cells. Cultured RIN5F cells and primary rat and human islets of Langerhans were treated with interleukin 1beta (IL-1beta) or a combination of cytokines, and were co-treated or pre-treated with glucagon. In RIN5F cells, the activity of iNOS induced by IL-1beta (10 pM, 24 h), was significantly reduced by glucagon (1000 nM), which raises cyclic AMP, and by forskolin (1-10 microM), a non specific activator of adenylate cyclase. Glucagon and forskolin also decreased iNOS expression in RIN5F cells, and rat and human islets, as shown by Western blotting. The inhibitory action of IL-1beta (100 pM, 24 h) on rat islet insulin secretion was partially reversed by 1-h pre-treatment with glucagon (10-1000 nM), while the contrasting stimulatory effect of 48-h treatment with cytokines on insulin secretion from human islets was similarly prevented by glucagon (1000 nM) pre-treatment. These results suggest that glucagon inhibits iNOS expression in insulin-containing cells and imply that glucagon could modulate the inhibitory effects of cytokines., (Copyright 1999 Academic Press.)

Clinical islet transplantation is potentially the treatment of choice for people with type I diabetes. Rates of insulin independence in islet transplant recipients are disappointingly low, and the relative contribution of the rejection response compared with the loss of islet function is still unclear. We have compared the mixed lymphocyte islet coculture (MLIC) with the mixed lymphocyte acinar cell coculture (MLAC) and the mixed lymphocyte response (MLR) as in vitro models of allograft rejection to MHC and tissue-specific antigens expressed by human islets and acinar cells. The reduced number of MHC class II antigen-positive cells in islets and acinar tissue compared to those in the stimulator lymphocyte population of the MLR, correlated with a reduced proliferative response in the MLIC and MLAC. Enhancement of MHC class II antigen expression by islets using TNFalpha and IFNgamma did not increase their stimulatory capacity in the islet cocultures, which may have been due to a corresponding absence of B7 expression. The lack of T cell proliferation to acinar cells despite cytokine-induced enhancement of MHC class II expression and detectable B7 expression appeared to be due to the inhibitory effect of exocrine enzymes on lymphocyte proliferation. In conclusion, we suggest that a rejection response to islets and acinar tissue is possible due to the accompanying MHC class II-positive cells and that, in this model, islet and acinar-specific antigens do not significantly contribute to that response. Acinar cells may have the potential to stimulate lymphocytes directly, but this was not evident by proliferation in the MLAC. Rejection appears to contribute to the low survival rate of human islet allografts, but it is unlikely that this is the sole explanation, and other factors should be considered.

The collagenase digestion phase of islet isolation is variable and unpredictable. This results partly from the vagaries of collagenase itself but also from the complex effects of organ retrieval and storage on collagenase digestion. Improvements in the purification of islets by density gradient centrifugation will not result from the production of new density gradient media, but rather from the continued modification of the biochemical composition of the solvents in which established gradient media are dissolved. The challenge is to produce solutions that will minimise acinar tissue swelling without compromising islet yield and viability. It is sobering to note the low recovery of islets after 48-h tissue culture (56%), and it has to be concluded that present tissue culture techniques for human and porcine islets are inadequate. Part of the problem is that the media and techniques used for islet tissue culture were designed for single cell culture and were not formulated specifically for the culture of insulin-producing mini-organs with a high metabolic rate. Cell viability is notoriously difficult to quantify, and this is no less true for isolated islets than for other tissues. The main problem is that although it is possible to determine the viability of isolated islets by measuring specific cellular functions such as glucose-stimulated insulin release, it is impossible to compare this with the same function performed by islets within the native pancreas. For this reason, it is not possible in absolute terms to determine the effect of islet isolation on islet viability.

Cytokine-induced damage may contribute to destruction of insulin-secreting beta-cells in islets of Langerhans during autoimmune diabetes. There is considerable controversy (i) whether human and rat islets respond differently to cytokines, (ii) the extent to which cytokine damage is mediated by induction of nitric oxide formation, and (iii) whether the effects of nitric oxide on islets can be distinguished from those of reactive oxygen species or peroxynitrite. We have analyzed rat and human islet responses in parallel, 48 h after exposure to the nitric oxide donor S-nitrosoglutathione, the mixed donor 3-morpholinosydnonimine, hypoxanthine/xanthine oxidase, peroxynitrite, and combined cytokines (interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma). Insulin secretory response to glucose, insulin content, DNA strand breakage, and early-to-late stage apoptosis were recorded in each experiment. Rat islet insulin secretion was reduced by S-nitrosoglutathione or combined cytokines, but unexpectedly increased by peroxynitrite or hypoxanthine/xanthine oxidase. Effects on human islet insulin secretion were small; cytokines and S-nitrosoglutathione decreased insulin content. Both rat and human islets showed significant and similar levels of DNA damage following all treatments. Apoptosis in neonatal rat islets was increased by every treatment, but was at a low rate in adult rat or human islets and only achieved significance with cytokine treatment of human islets. All cytokine responses were blocked by an arginine analogue. We conclude: (i) Reactive oxygen species increased and nitric oxide decreased insulin secretory responsiveness in rat islets. (ii) Species differences lie mainly in responses to cytokines, applied at a lower dose and shorter time than in most studies of human islets. (iii) Cytokine effects were nitric oxide driven; neither reactive oxygen species nor peroxynitrite reproduced cytokine effects. (iv) Rat and human islets showed equal susceptibility to DNA damage. (v) Apoptosis was not the preferred death pathway in adult islets. (vi) We have found no evidence of human donor variation in the pattern of response to these treatments.

Staff educators and staff nurses developed an ostomy competency, with the guidance and expertise of the advanced practitioner and enterostomal nurse at a large teaching hospital. The competency improved the quality of care for surgical ostomy patients. Care was standardized and staff nurses' clinical knowledge was enhanced. Following the sessions, staff nurses verbalized increased confidence in working with patients with ostomies and demonstrated increased autonomy and problem-solving abilities. No variances in educational aspects of care were noted on clinical pathways.

Methods to minimize the effect of cold ischaemia on porcine islet isolation were investigated. Forty pancreata were randomized to intraductal collagenase delivery in University of Wisconsin solution (UW) or Hanks balanced salt solution (HBSS) (control) both before and after 65 min of cold pancreas storage. Collagenase was also administered in a specially designed cold storage solution (University of Leicester solution, ULEIC), before cold storage. Median islet yield was significantly greater if the pancreas was distended with collagenase in either UW (21524 islet equivalents (IEQ) per g) or ULEIC (19814 IEQ/g) before cold storage, compared with that after distension with HBSS (6924 IEQ/g) following cold storage (P < 0.05). Islet fragmentation, islet purification and glucose-stimulated insulin release were not significantly different after collagenase delivery in either UW or ULEIC compared with those after administration in HBSS. It is concluded that porcine islet yields can be improved significantly by intraductal collagenase administration in either UW or ULEIC immediately after excision of the pancreas.

Cell and tissue culture techniques have improved considerably since the first attempts to maintain explants of animal tissue in vitro. The two major developments that have allowed these improvements are the ability to produce continuous cell lines, thus allowing reproducible results to be obtained, and the definition of media for different cell types, thereby reducing the need for supplements of serum and other extraneous extracts. The requirements of islets in culture have been more difficult to define, largely because islets do not proliferate in culture and proliferation rate cannot therefore be used to measure the suitability of the medium. Further difficulties arise because islets are highly metabolically active "mini-organelles." Although many studies have been undertaken to try and optimize media for the culture islets of Langerhans, the media most commonly used are commercially available media developed for other cell types. There remains ample scope for further refinement of the composition of islet culture media, with the possibility of different media for islets from different species.