A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Paradoxical GH increase after oral glucose load in subjects with and without acromegaly.

OBJECTIVE: A paradoxical GH rise after the glucose load (GH-Par) is described in about one-third of acromegalic patients. Here, we evaluated the GH profile in subjects with and without acromegaly aiming to refine the definition of GH-Par. DESIGN: Observational case-control study. METHODS: Our cohort consisted of 60 acromegalic patients, and two groups of subjects presenting suppressed GH (< 0.4 µg/L) and high (non-acro↑IGF-1, n = 116) or normal IGF-1 levels (non-acro, n = 55). The distribution of GH peaks ≥ 120% from baseline, insulin, and glucose levels were evaluated over a 180-min time interval after glucose intake. RESULTS: A similar proportion of subjects in all three groups shows a GH ratio of ≥ 120% starting from 120 min. Re-considering the definition of paradoxical increase of GH within 90 min, we observed that the prevalence of GH peaks ≥ 120% was higher in acromegaly than in non-acro↑IGF-1 and non-acro (respectively 42%, 16%, and 7%, both p < 0.001). In patients without GH-Par, a late GH rebound was observed in the second part of the curve. Higher glucose peak (p = 0.038), slower decline after load, 20% higher glucose exposure (p = 0.015), and a higher prevalence of diabetes (p = 0.003) characterized acromegalic patients with GH-Par (with respect to those without). CONCLUSIONS: GH-Par response may be defined as a 20% increase in the first 90 min after glucose challenge. GH-Par, common in acromegaly and associated with an increased prevalence of glucose metabolism abnormalities, is found also in a subset of non-acromegalic subjects with high IGF-1 levels, suggesting its possible involvement in the early phase of the disease.

Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia.

PURPOSE: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. METHODS: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). RESULTS: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). CONCLUSIONS: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG.

Mouse Model of Spinal Cord Hypoperfusion with Immediate Paralysis Caused by Endovascular Repair of Thoracic Aortic Aneurysm.

BACKGROUND: A clinically relevant mouse model of thoracic endovascular aortic repair-induced ischemic spinal cord injury has been lacking since the procedure was first employed in 1991. The hypothesis was that ligation of mouse intercostal arteries would simulate thoracic endovascular aortic repair-induced ischemic spinal cord injury and behavioral deficit. The aim was to create a mouse model of thoracic endovascular aortic repair-induced spinal cord hypoperfusion by ligating five pairs of mouse intercostal vessels. METHODS: Mice were divided into sham (n = 53) and ligation (n = 60) groups. The procedures called for double ligation of three pairs and single ligation of two pairs of thoracic intercostal arteries in adult C57BL/6 mice. A laser Doppler probe was used in vivo on the spinal cords and intercostal arteries to document the extent of arterial ligation and spinal cord hypoperfusion. The Basso Mouse Scale for Locomotion, histological studies, and electron microscopy demonstrated postligation locomotive and histopathological changes. RESULTS: Ligation induced a significant and instantaneous drop in blood flow in the intercostal arteries (% change; mean = -63.81; 95% CI, -72.28 to -55.34) and the thoracic spinal cord (% change; mean = -68.55; 95% CI, -80.23 to -56.87). Paralysis onset was immediate and of varying degree, with behavioral deficit stratified into three groups: 9.4% exhibited severe paralysis, 37.5% moderate paralysis, and 53.1% mild paralysis at day 1 (n = 32; P < 0.001). Mild and moderate paralysis was transient, gradually improving over time. Severe paralysis showed no improvement and exhibited a higher mortality rate (83%; n = 15 of 18) compared to moderately (33%; n = 6 of 18) and mildly (24%; n = 6 of 25) paralyzed mice (P < 0.001). The overall ligation group survival rate (84%; n = 46 of 55) was significantly lower than the sham group (100%; n = 48 of 48) with P = 0.003. CONCLUSIONS: The mouse model generates reproducible spinal cord hypoperfusion and accompanying histopathological ischemic spinal cord damage. The resulting anatomical changes and variable behavioral deficits mimic the variability in radiological and clinical findings in human patients.

Evaluation of the aerobic biodegradability of process water produced by hydrothermal carbonization and inhibition effects on the heterotrophic biomass of an activated sludge system.

In this work, the aerobic biodegradability of the process water (PW) produced by hydrothermal carbonization (HTC) of dewatered anaerobic digested sludge and the toxicity assessment in regard to the heterotrophic activated biomass of a conventional activated sludge systems, are described. Such assessments are not yet reported in other scientific papers, so this paper seeks to contribute to the increase of knowledge regarding the valorization of the HTC process applied in a wastewater treatment plant (WWTP). For such purpose, two different respirometric techniques were applied - multi-OUR respirometry and manometric respirometry. PW resulted highly biodegradable: 83% of total COD was biodegradable, with a 58% of readily biodegradable (rbCOD) fraction. The BOD5/COD ratio was 0.42. Further, it was characterized by a high concentration of volatile fatty acids (VFAs) (i.e. 2031 mg/L), of which the major constituent was acetic acid (i.e. 80%), an easily degradable intermediate of many biological processes. Both the respirometric techniques showed that the assessed PW, after being diluted accordingly with the WWTP real operational conditions, did not imply short-term toxic effects on the activated sludge, neither using fresh biomass nor keeping the same one. According to these results, the recirculation of PW at the water line of WWTPs represents a promising approach not affected by specific toxicity issues, especially when the HTC process is integrated into a WWTP scheme.

Microglia Promote Increased Pain Behavior through Enhanced Inflammation in the Spinal Cord during Repeated Social Defeat Stress.

Clinical studies indicate that psychosocial stress contributes to adverse chronic pain outcomes in patients, but it is unclear how this is initiated or amplified by stress. Repeated social defeat (RSD) is a mouse model of psychosocial stress that activates microglia, increases neuroinflammatory signaling, and augments pain and anxiety-like behaviors. We hypothesized that activated microglia within the spinal cord facilitate increased pain sensitivity following RSD. Here we show that mechanical allodynia in male mice was increased with exposure to RSD. This stress-induced behavior corresponded with increased mRNA expression of several inflammatory genes, including IL-1ß, TNF-α, CCL2, and TLR4 in the lumbar spinal cord. While there were several adhesion and chemokine-related genes increased in the lumbar spinal cord after RSD, there was no accumulation of monocytes or neutrophils. Notably, there was evidence of microglial activation selectively within the nociceptive neurocircuitry of the dorsal horn of the lumbar cord. Elimination of microglia using the colony stimulating factor 1 receptor antagonist PLX5622 from the brain and spinal cord prevented the development of mechanical allodynia in RSD-exposed mice. Microglial elimination also attenuated RSD-induced IL-1ß, CCR2, and TLR4 mRNA expression in the lumbar spinal cord. Together, RSD-induced allodynia was associated with microglia-mediated inflammation within the dorsal horn of the lumbar spinal cord.SIGNIFICANCE STATEMENT Mounting evidence indicates that psychological stress contributes to the onset and progression of adverse nociceptive conditions. We show here that repeated social defeat stress causes increased pain sensitivity due to inflammatory signaling within the nociceptive circuits of the spinal cord. Studies here mechanistically tested the role of microglia in the development of pain by stress. Pharmacological ablation of microglia prevented stress-induced pain sensitivity. These findings demonstrate that microglia are critical mediators in the induction of pain conditions by stress. Moreover, these studies provide a proof of principle that microglia can be targeted as a therapeutic strategy to mitigate adverse pain conditions.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Longitudinal Recovery and Reduced Costs After 120 Sessions of Locomotor Training for Motor Incomplete Spinal Cord Injury.

OBJECTIVE: To determine the impact of long-term, body weight-supported locomotor training after chronic, incomplete spinal cord injury (SCI), and to estimate the health care costs related to lost recovery potential and preventable secondary complications that may have occurred because of visit limits imposed by insurers. DESIGN: Prospective observational cohort with longitudinal follow-up. SETTING: Eight outpatient rehabilitation centers that participate in the Christopher & Dana Reeve Foundation NeuroRecovery Network (NRN). PARTICIPANTS: Individuals with motor incomplete chronic SCI (American Spinal Injury Association Impairment Scale C or D; N=69; 0.1-45y after SCI) who completed at least 120 NRN physical therapy sessions. INTERVENTIONS: Manually assisted locomotor training (LT) in a body weight-supported treadmill environment, overground standing and stepping activities, and community integration tasks. MAIN OUTCOME MEASURES: International Standards for Neurological Classification of Spinal Cord Injury motor and sensory scores, orthostatic hypotension, bowel/bladder/sexual function, Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI), Berg Balance Scale, Modified Functional Reach, 10-m walk test, and 6-minute walk test. Longitudinal outcome measure collection occurred every 20 treatments and at 6- to 12-month follow-up after discharge from therapy. RESULTS: Significant improvement occurred for upper and lower motor strength, functional activities, psychological arousal, sensation of bowel movement, and SCI-FAI community ambulation. Extended training enabled minimal detectable changes at 60, 80, 100, and 120 sessions. After detectable change occurred, it was sustained through 120 sessions and continued 6 to 12 months after treatment. CONCLUSIONS: Delivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average 20-session insurance limit can reduce rehospitalizations and long-term health costs.

MiR-155 deletion reduces ischemia-induced paralysis in an aortic aneurysm repair mouse model: Utility of immunohistochemistry and histopathology in understanding etiology of spinal cord paralysis.

Spinal cord paralysis is relatively common after surgical repair of thoraco-abdominal aortic aneurysm (TAAA) and its etiology is unknown. The present study was designed to examine the histopathology of the disease and investigate whether miR-155 ablation would reduce spinal cord ischemic damage and delayed hindlimb paralysis induced by aortic cross-clamping (ACC) in our mouse model. The loss of locomotor function in ACC-paralyzed mice correlated with the presence of extensive gray matter damage and central cord edema, with minimal white matter histopathology. qRTPCR and Western blotting showed that the spinal cords of wild-type ACC mice that escaped paralysis showed lower miR-155 expression and higher levels of transcripts encoding Mfsd2a, which is implicated in the maintenance of blood-brain barrier integrity. In situ based testing demonstrated that increased miR-155 detection in neurons was highly correlated with the gray matter damage and the loss of one of its targets, Mfsd2a, could serve as a good biomarker of the endothelial cell damage. In vitro, we demonstrated that miR-155 targeted Mfsd2a in endothelial cells and motoneurons and increased endothelial cell permeability. Finally, miR-155 ablation slowed the progression of central cord edema, and reduced the incidence of paralysis by 40%. In sum, the surgical pathology findings clearly indicated that the epicenter of the ischemic-induced paralysis was the gray matter and that endothelial cell damage correlated to Mfsd2a loss is a good biomarker of the disease. MiR-155 targeting therefore offers new therapeutic opportunity for edema caused by traumatic spinal cord injury and diagnostic pathologists, by using immunohistochemistry, can clarify if this mechanism also is important in other ischemic diseases of the CNS, including stroke.

Consideration of Dose and Timing When Applying Interventions After Stroke and Spinal Cord Injury.

BACKGROUND AND PURPOSE: Nearly 4 decades of investigation into the plasticity of the nervous system suggest that both timing and dose could matter. This article provides a synopsis of our lectures at the IV STEP meeting, which presented a perspective of current data on the issues of timing and dose for adult stroke and spinal cord injury motor rehabilitation. SUMMARY OF KEY POINTS: For stroke, the prevailing evidence suggests that greater amounts of therapy do not result in better outcomes for upper extremity interventions, regardless of timing. Whether or not greater amounts of therapy result in better outcomes for lower extremity and mobility interventions needs to be explicitly tested. For spinal cord injury, there is a complex interaction of timing postinjury, task-specificity, and the microenvironment of the spinal cord. Inflammation appears to be a key determinant of whether or not an intervention will be beneficial or maladaptive, and specific retraining of eccentric control during gait may be necessary. RECOMMENDATIONS FOR CLINICAL PRACTICE: To move beyond the limitations of our current interventions and to effectively reach nonresponders, greater precision in task-specific interventions that are well-timed to the cellular environment may hold the key. Neurorehabilitation that ameliorates persistent deficits, attains greater recovery, and reclaims nonresponders will decrease institutionalization, improve quality of life, and prevent multiple secondary complications common after stroke and spinal cord injury.

Generalized annular granuloma associated with crowned dens syndrome, which resolved with colchicine treatment.

Granuloma annulare (GA) is a chronic, benign, and usually self-limiting cutaneous inflammatory disease, typically characterized by small, localized, skin-coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50-70% of localized GA cases are self-limiting and show spontaneous resolution after 1-2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low-dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA.

Test-retest reliability of the Neuromuscular Recovery Scale.

OBJECTIVE: To determine the test-retest reliability of the Neuromuscular Recovery Scale (NRS), a measure to classify lower extremity and trunk recovery of individuals with spinal cord injury (SCI) to typical preinjury performance of functional tasks without use of external and behavioral compensation. DESIGN: Multicenter observational study. SETTING: Five outpatient rehabilitation clinics. PARTICIPANTS: Physical therapists (N=13), trained and competent in conducting NRS, rated outpatients with SCI (N=69) using the NRS. Testing occurred on 2 days, separated by 24 to 48 hours, on the same patient by the same therapist. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Spearman rank correlation coefficients to compare NRS results. The NRS scores of motor performance were based on normal, preinjury function on 11 items: 4 treadmill-based items (standing and stepping), 7 overground/mat items (sitting, sit-up, reverse sit-up, trunk extension, sit to stand, standing, walking). RESULTS: Test-retest reliability was very strong for the NRS items. Ten of the 11 items exhibited Spearman correlation coefficients ≥.92, and lower bounds of the 95% confidence intervals (CIs) for these items met or exceeded .83. The exception was stand retraining (ρ=.84; 95% CI, .68-.96). The test-retest reliability of the measurement model-derived summary score was very strong (ρ=.99; 95% CI, .96-.99). CONCLUSIONS: The NRS had excellent test-retest reliability when conducted by trained therapists in adults with chronic SCI across all levels of injury severity. All raters had undergone standardized training in use of the NRS. The minimal requirement of training to achieve test-retest reliability has not been established.

Interrater reliability of the Neuromuscular Recovery Scale for spinal cord injury.

OBJECTIVE: To determine the interrater reliability of the Neuromuscular Recovery Scale (NRS), an outcome measure designed to classify people with complete or incomplete spinal cord injury (SCI) into 4 phase-of-injury groups by assessing motor performance based on normal preinjury function and disallowing use of compensation for 4 treadmill-based items and 6 overground/mat items. DESIGN: Masked comparison, multicenter observational study. SETTING: Outpatient rehabilitation. PARTICIPANTS: Raters (N=14) and a criterion standard expert assigned scores to 10 video NRS assessments of persons with SCI. The raters were volunteers from the NeuroRecovery Network. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Interrater reliability measured with the Kendall coefficient of concordance (W). RESULTS: Interrater reliability was generally strong (W=.91-.98; 95% confidence interval [CI], .65-.99), while lower reliability occurred for treadmill stand retraining (W=.87; 95% CI, .06-1) and seated trunk extension (W=.82; 95% CI, .28-.94). Less experienced raters assigned slightly lower scores than the expert for most items, but the difference was less than half a point and did not weaken concordance. CONCLUSIONS: NRS had strong interrater reliability, a necessary first step in establishing its utility as a clinical and research outcome measure.

Validity of the Neuromuscular Recovery Scale: a measurement model approach.

OBJECTIVE: To determine how well the Neuromuscular Recovery Scale (NRS) items fit the Rasch, 1-parameter, partial-credit measurement model. DESIGN: Confirmatory factor analysis (CFA) and principal components analysis (PCA) of residuals were used to determine dimensionality. The Rasch, 1-parameter, partial-credit rating scale model was used to determine rating scale structure, person/item fit, point-measure item correlations, item discrimination, and measurement precision. SETTING: Seven NeuroRecovery Network clinical sites. PARTICIPANTS: Outpatients (N=188) with spinal cord injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: NRS. RESULTS: While the NRS met 1 of 3 CFA criteria, the PCA revealed that the Rasch measurement dimension explained 76.9% of the variance. Ten of 11 items and 91% of the patients fit the Rasch model, with 9 of 11 items showing high discrimination. Sixty-nine percent of the ratings met criteria. The items showed a logical item-difficulty order, with Stand retraining as the easiest item and Walking as the most challenging item. The NRS showed no ceiling or floor effects and separated the sample into almost 5 statistically distinct strata; individuals with an American Spinal Injury Association Impairment Scale (AIS) D classification showed the most ability, and those with an AIS A classification showed the least ability. Items not meeting the rating scale criteria appear to be related to the low frequency counts. CONCLUSIONS: The NRS met many of the Rasch model criteria for construct validity.

Elevated MMP-9 in the lumbar cord early after thoracic spinal cord injury impedes motor relearning in mice.

Spinal cord injury results in distant pathology around putative locomotor networks that may jeopardize the recovery of locomotion. We previously showed that activated microglia and increased cytokine expression extend at least 10 segments below the injury to influence sensory function. Matrix metalloproteinase-9 (MMP-9) is a potent regulator of acute neuroinflammation. Whether MMP-9 is produced remote to the injury or influences locomotor plasticity remains unexamined. Therefore, we characterized the lumbar enlargement after a T9 spinal cord injury in C57BL/6 (wild-type [WT]) and MMP-9-null (knock-out [KO]) mice. Within 24 h, resident microglia displayed an activated phenotype alongside increased expression of progelatinase MMP-3 in WT mice. By 7 d, increases in active MMP-9 around lumbar vasculature and production of proinflammatory TNF-α were evident. Deletion of MMP-9 attenuated remote microglial activation and restored TNF-α expression to homeostatic levels. To determine whether MMP-9 impedes locomotor plasticity, we delivered lumbar-focused treadmill training in WT and KO mice during early (2-9 d) or late (35-42 d) phases of recovery. Robust behavioral improvements were observed by 7 d, when only trained KO mice stepped in the open field. Locomotor improvements were retained for 4 weeks as identified using state of the art mouse kinematics. Neither training nor MMP-9 depletion alone promoted recovery. The same intervention delivered late was ineffective, suggesting that lesion site sparing is insufficient to facilitate activity-based training and recovery. Our work suggests that by attenuating remote mechanisms of inflammation, acute treadmill training can harness endogenous spinal plasticity to promote robust recovery.

Low-temperature, low-pressure gas plasma application on Aspergillus brasiliensis, Escherichia coli and pistachios.

AIM: The aim of this study was to investigate the effect of plasma-enhanced chemical vapour deposition (PECVD) treatment on selected bacteria and spores and to contribute to the understanding of the synergistic effect of UV-directed plasma. METHODS AND RESULTS: The experiments were conducted on pure cultures of Aspergillus brasiliensis and Escherichia coli and on naturally contaminated pistachios that were exposed to pure oxygen-, pure argon- and to a mixture of oxygen-argon-generated plasma for different treatment times and at different micro-organism concentrations. Optical emission spectroscopy (OES) measurements were performed to observe the active species in the plasma. After exposure, the effectiveness of decontamination was assessed through microbiological techniques by calculating the growth reduction on a logarithmic scale. A treatment time of 30 min resulted in a 3·5 log reduction of A. brasiliensis using pure oxygen or argon, while treatment times of 5 min, 1 min and 15 s resulted in a 5·4 log reduction using a mixture of argon and oxygen (10 : 1 v/v). Treatment times of 1 min and 30 s resulted in a 4 log reduction of E. coli with oxygen and argon, respectively, which led to a complete elimination of the micro-organisms. Two-log reductions of fungi were achieved for pistachios after a treatment time of 1 min. CONCLUSIONS: These results suggest that this newly designed plasma reactor offers good potential applications for the reduction in micro-organisms on heat-sensitive materials, such as foods. The plasma that was generated with Ar/O2 was more effective than that which was generated with pure oxygen and pure argon. SIGNIFICANCE AND IMPACT OF THE STUDY: An improvement in the knowledge about PECVD mechanisms was acquired from the chemical and biological points of view, and the suitability of the method for treating dry food surfaces was demonstrated.

Hook-effect in MAGLUMI immunoassay for serum anti-GAD antibodies in neurological disorders: When "wrong" matrix is the right choice.

Antibodies against glutamic acid decarboxylase (anti-GAD) are a valuable diagnostic tool to detect severe autoimmune conditions as type 1 diabetes mellitus (T1DM) and anti-GAD related neurological disorders, having the latter more often anti-GAD concentrations in serum multiple times higher than in the former. Automated immunoassays, either with ELISA or chemiluminescent technology, are validated for diagnostic use in serum with analytical ranges suitable for T1DM diagnosis. In a patient presenting with a suspected autoimmune ataxia, anti-GAD testing on an automated chemiluminescent immunoassay (CLIA) resulted in slightly abnormal concentrations in serum (39.2 KIU/L) and very high concentrations in CSF (>280 KIU/L), thus prompting to proceed to serum dilutions to exclude a false negative result and a misdiagnosis. Different dilutions of serum resulted in nonlinear concentrations with endpoint result of 276,500 KIU/L at dilution 1:1000. CSF dilution was instead linear with endpoint result of 4050 KIU/L. In this case report we found that anti-GAD testing in CSF was essential to establish the clinical diagnosis and to suspect hook-effect in serum due to the excess of autoantibodies in this severe autoimmune condition.

Dual-task training for balance and mobility in a person with severe traumatic brain injury: a case study.

BACKGROUND AND PURPOSE: Attentional impairments following severe traumatic brain injury (TBI) are common and can lead to decreased functional mobility and balance, as well as deficits in previously automatic movements such as walking and stair climbing. The purpose of this case study was to determine the feasibility and potential value of incorporating a cognitive-motor dual-task training program into physical therapy for a patient with a severe TBI. CASE DESCRIPTION: The patient was a 26-year-old woman who sustained a severe TBI during a motor vehicle accident 46 days prior to physical therapy evaluation. On the 8-level Rancho Los Amigos Cognitive Function Scale, her functioning was classified as level IV. She had impairments in attention, functional mobility, and balance, all of which limited her ability to participate in activities of daily living. INTERVENTION: : Physical therapy was provided over 26 days within the inpatient rehabilitation setting. Interventions included mobility tasks such as walking, balancing, and stair climbing. Mobility training was paired with specific secondary cognitive and motor tasks. OUTCOMES: Dual-task training may have contributed to improvements on outcome measures designed to test divided attention including the Walking While Talking Test and Trail Making Test and a greater rate of improvement in walking speed and time to descend stairs when compared to the baseline phase. DISCUSSION: Addition of cognitive-motor dual-task training to standard physical therapy in the inpatient rehabilitation setting appears to be feasible and may have value for improving function in individuals with severe TBI. VIDEO ABSTRACT AVAILABLE: (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A41) for more insights from the authors.

Relationship between ASIA examination and functional outcomes in the NeuroRecovery Network Locomotor Training Program.

OBJECTIVE: To determine the effects of locomotor training on: (1) the International Standards for Neurological Classification of Spinal Cord Injury examination; (2) locomotion (gait speed, distance); (3) balance; and (4) functional gait speed stratifications after chronic incomplete spinal cord injury (SCI). DESIGN: Prospective observational cohort. SETTING: Outpatient rehabilitation centers in the NeuroRecovery Network (NRN). PARTICIPANTS: Individuals (n=225) with American Spinal Injury Association Impairment Scale (AIS) grade C or D chronic motor incomplete SCI having completed locomotor training in the NRN. INTERVENTION: The NRN Locomotor Training Program consists of manual-facilitated body weight-supported standing and stepping on a treadmill and overground. MAIN OUTCOME MEASURES: AIS classification, lower extremity pin prick, light touch and motor scores, ten-meter walk and six-minute walk tests, and the Berg Balance Scale. RESULTS: Significant gains occurred in lower extremity motor scores but not in sensory scores, and these were only weakly related to gait speed and distance. Final Berg Balance Scale scores and initial lower extremity motor scores were positively related. Although 70% of subjects showed significantly improved gait speed after locomotor training, only 8% showed AIS category conversion. CONCLUSIONS: Locomotor training improves gait speed to levels sufficient for independent in-home or community ambulation after chronic motor incomplete SCI. Changes in lower extremity motor and sensory scores do not capture the full extent of functional recovery, nor predict responsiveness to locomotor training. Functional classification based on gait speed may provide an effective measure of treatment efficacy or functional improvement after incomplete SCI.