Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (n = 12), Alzheimer's disease (n = 9), Parkinson's disease (n = 9), amyotrophic lateral sclerosis (n = 11), and controls (n = 5) using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson's disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer's disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a rare disorder endemic to Guam Island and the Kii Peninsula of Japan. It shows a unique combination of parkinsonism, amyotrophy, and dementia , and the123I-meta-iodobenzylguanidine uptake [Although Kii ALS/PDC shows several unique clinical features, including severe atrophy of the frontal and temporal lobes on magnetic resonance imaging (MRI), decreased cerebral blood flow in the frontal and temporal lobes on single-photon emission computed tomography (SPECT) , pigmente uptake , a postmβ) concentrations were measured with an enzyme-linked immunosorbent assay (ELISA) kit using a monoclonal antibody specific for t-tau, p-tau, and Aβ1–42 , and β-amyloid (1–42), Innogenetics, Ghent, Belgium). ELISA assays were carried out using several samples from each group on the same plate in a randomized manner and were repeated using randomized samples in the same manner in plural times. A factorial ANOVA was performed with CSF-t-tau, CSF-p-tau, and CSF-Aβ42, as dependent variables, with the diagnostic category  using JMP 9.0. All data were expressed as means ± SD. A P value less than 0.05 was considered statistically significant. The Ethics Committee of Mie University Graduate School of Medicine approved this study and the “Declaration of Helsinki” was followed. Informed consent was obtained from the patients or their families.We collected CSF samples from 12 patients with Kii ALS/PDC , nine patients with AD , 11 patients with ALS , nine patients with Parkinson's disease , and five disease control patients . All of the patients with Kii ALS/PDC were natives of Hohara village, which is an area of high ALS/PDC prevalence on the Kii Peninsula. We collected CSF samples over 10 years; therefore, the period between CSF collection and analysis was not standardized. The diagnosis of Kii ALS was made according to the Airlie House criteria, since the clinical symptoms of Kii ALS are essentially the same as those of classical ALS. The diagnosis of Kii PDC was made by a unique combination of levodopa-unresponsive parkinsonism and dementia, which are frequently accompanied by amyotrophy of the extremities and/or pyramidal tract signs. Mini-mental state examination (MMSE) was used for the evaluation of dementia and cut-off point was 23 (data not shown). The frontal lobes and/or temporal lobes of ALS/PDC patients showed atrophy on MRI and/or a decrease of cerebral blood flow on SPECT. CSF samples were immediately centrifuged at 1000 ×g for 15 min and stored at −80°C with polypropylene tube. The total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta  than in the other groups. However, the concentrations of CSF-t-tau and CSF-p-tau did not differ significantly between Kii ALS/PDC, ALS, C, and PD  compared to ALS and C and relatively reduced in Kii ALS/PDC  compared to ALS. Most of the ALS/PDC patients had CSF concentration values that fell below the cutoff based on C (β42 were significantly increased in AD (0.125 ± 0.02) compared with Kii ALS/PDC , ALS , PD , and C   in the Kii ALS/PDC patients. The number of C samples was small and the average age of control patients was low.CSF-A Figures . The consed on C . The rat< 0.014) . The conβ is not affected by age [Generally, CSF tau level gradually increase according to age and CSF Ad by age . CSF tauThus, the CSF values of C were not comparable to those of other groups. Nevertheless, the optimal cut-off values that discriminate C from AD were similar to those in previous reports , 7 in whβ42 concentration in the CSF was relatively decreased. The ratio of CSF-p-tau to CSF-Aβ42 segregates Kii ALS/PDC from AD. Because ALS/PDC is associated with tau pathology in the absence of amyloid plaques, the expectation was that ALS/PDC patients would not show the Alzheimer's disease (AD) profile of decreased Aβ42 but might show increased t-tau and/or p-tau in the CSF.The present study showed that CSF-t-tau and CSF-p-tau concentrations from patients with Kii ALS/PDC were not increased compared to those in the other disease groups, and Aβ42 indicates plaque pathology, and increased CSF-t-tau and CSF-p-tau indicate axonal degeneration and tangle pathology, respectively [β deposition is conspicuous in autopsied patients. Therefore, decreased CSF-Aβ42 may reflect Aβ pathology in the most recent patients. We analyzed the precise tau isoform of over 10 patients with autopsy-proven ALS/PDC recently and identified a 3R + 4R type, 4R > 3R type, and a 4R predominant type. The glial tau pathology is particularly related to the 4R isoform, and we consider Kii ALS/PDC to be a 4R-dominant tauopathy (unpublished data). Noguchi et al. examined the concentrations of CSF-t-tau, CSF-p-tau, and CSF-Aβ42 in patients with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD); the concentrations of CSF-t-tau and CSF-p-tau did not significantly differ between PSP, CBD, and controls, and the concentration of CSF-Aβ42 was significantly lower in PSP and CBD than in controls. The authors speculated that the absence of an increase of CSF-t-tau and CSF-p-tau concentrations might reflect 4R tau predominance and a reduction of CSF-Aβ42 might suggest deposition or mismetabolism of Aβ [In general, decreased CSF-Aectively . Recentlsm of Aβ . Taken tβ42 concentration was relatively decreased, suggest that CSF analysis may be useful to differentiate ALS/PDC from AD, ALS, and PD. Nevertheless there is a major limitation of the interpretation of the data. The size of each group is small, the age of the control group is much younger, and there were two populations in the AD group regarding the levels tau, p-tau, and Aβ/p-tau. Further study using groups with larger size of subjects is needed to confirm the proposed utility of the CSF biomarkers.Finally, the present findings, in which CSF-t-tau and CSF-p-tau concentrations were not increased and CSF-A


To the Editor: The central nervous system (CNS) manifestations of severe fever with thrombocytopenia syndrome (SFTS) include apathy, seizure, muscular tremor, and coma , glucose 74 mg/dL (reference 45–80 mg/dL), and CSF/blood glucose ratio 0.66 (reference 0.50–0.80). No bacteria or fungi were isolated from CSF. On HD 4, her headache worsened, and she displayed confused verbal responses and lacked orientation of time and place. No focal neurologic signs were observed. On HD 5, magnetic resonance imaging of the brain indicated no additional abnormalities of the parenchyma and extra-axial structures except for a focal parenchymal defect in the right midbrain that had been discovered as a sequelae of tuberculous meningitis 10 years earlier. On HD 7, follow-up CSF examination revealed no leukocytes, protein 57 mg/dL, glucose 209 mg/dL, and CSF/blood glucose ratio 0.62. SFTSV was detected by real-time reverse transcription PCR (2 to 6 × 101 copies/mL) during the first 7 hours (4–11 pm on HD 17); it then gradually decreased from 3 × 101 at 7 am on HD 18 to 6 × 100 copies/mL on HD 20, by which time the patient’s mental status had fully recovered , with a 5-day fever, myalgia, and headache. On hospital day (HD) 2, CSF examination revealed 1 leukocyte/mmtion PCR  in plasmtion PCR . On HD 8ecovered .This case is unique in that SFTS was detected in CSF in the absence of pleocytosis and with normal CSF protein and glucose levels, as in previous reports on influenza-associated acute encephalopathy (We are aware of 1 report of a favorable outcome of plasma exchange and ribavirin in 2 patients with SFTS and multiorgan failure in South Korea (We do not know whether the convalescent plasma therapy given to the patient described here actually had a positive effect because her IFA titer was already increasing around the time she received the plasma therapy. At the time of this writing, 2 patients with SFTS who were treated with intravenous immunoglobulin and corticosteroid had been reported (Performance of real-time reverse transcription PCR to detect severe fever with thrombocytopenia syndrome virus RNA.


Studies in animal models, in which internal hydrocephalus has been induced by obstructing the cerebrospinal fluid pathways, have documented an up-regulation of the concentrations of aquaporin-4 (AQP4) in the brain. In this study, the concentrations of aquaporin-1 (AQP1), AQP1, AQP4 and interleukin-6 (IL-6) were determined in the CSF of dogs with idiopathic communicating hydrocephalus before and after the reduction of intraventricular volume following ventriculo-peritoneal shunt (VP-shunt) treatment.The concentrations of AQP4 and IL-6 were increased in the cerebrospinal fluid of dogs with hydrocephalus compared to controls. Both parameters significantly decreased after surgical treatment, accompanied by decrease of ventricular size and the clinical recovery of the dogs. AQP1 was not detectable in CSF.Brain AQP4 up-regulation might be a compensatory response in dogs with hydrocephalus. Future determination of AQP4 at the mRNA and protein level in brain tissue is warranted to substantiate this hypothesis. Definitive treatment options for internal hydrocephalus in dogs and humans rely mostly on surgical implantation of CSF-draining shunt systems –4. MedicUnder certain pathological conditions changes in AQP4 expression have been found –14. StudA second water channel in the CNS, namely AQP1, is reported to be limited to choroid plexus epithelia within the CNS. Experimental depletion of the AQP1 gene in mice leads to a decrease in CSF production by the choroid plexus, demonstrating a role for AQP1 in CSF production . The proThe aim of the present study was to determine the concentration of AQP1and AQP4 in the CSF of dogs with idiopathic communicating hydrocephalus, and possible changes in these levels after reduction of intra-ventricular pressure following ventriculo-peritoneal shunting. Given the previously-reported relationship between IL-6 and white matter damage in neonatal children and the presence of white matter damage in internal hydrocephalus, we also investigated the relationship between IL-6 and the aquaporins. We hypothesised that increased ventricular volume is positively correlated to CSF levels of AQP4 and IL-6, and negatively correlated to AQP1 in dogs with idiopathic communicating hydrocephalus.Fourteen dogs with internal hydrocephalus, whose owners decided on surgical implantation of a ventriculo-peritoneal shunt (VP-shunt) system for permanent CSF drainage were prospectively selected between 2010 and 2014. The dogs had to meet the following criteria to be included in the study. (1) The hydrocephalus had to be diagnosed as idiopathic communicating, based on magnetic resonance imaging (MRI) of the brain without signs of parenchymal contrast enhancement or visual obstruction of CSF pathways. (2) Clinical re-evaluation, with CSF samples taken and immediately stored at −80 °C and both pre- and post-operative MRIs performed in our clinic to allow direct comparisons. (3) Medical pre-treatment using drugs to reduce CSF production  excluded dogs from the study. (4) In the follow up MRI, a decrease in ventricular volume had to be demonstrated as an indication for effective shunt treatment.CSF collection and MRI examination was also performed on a control group of 10 dogs that were donated to the clinic after euthanasia due to non-neurological diseases. CSF was taken within 2 min of death of the animals. Ventriculomegaly was an exclusion criterion for the dogs in this group.Collected data included the breed, age, gender, body-weight, type and duration of neurological deficits before and after surgery. Clinical data regarding the presenting signs and clinical improvement of the animals after shunting procedures were determined by a board certified neurologist. A standardised neurologic examination was performed prior to, and every day after surgery until discharge, and again 3 months after surgery.®) were acquired in all animals pre-operatively. The administration of a contrast agent was of course not feasible in the post-mortem scans in the control dogs but was useful to exclude other neurological diseases in the study group. T2-weighted transverse images of the head were chosen from the whole MR-dataset for image segmentation, using T2-Turbospin echo sequences . Slice thickness varied from 2–3 mm. The field of view measured 180 × 180 mm in small dogs and 210 × 210 mm in large dogs. The matrix was 288 × 288 in small dogs and 384 × 384 in large dogs leading to an in-plane pixel size between 0.625 × 0.625 and 0.54 × 0.54 mm.Diagnosis of idiopathic communicating hydrocephalus was made by MRI using a 1.0 Tesla scanner  and a solenoid surface coil (C3). For the MRI examination dogs were premedicated with diazepam (0.5 mg/kg IV) and l-methadone (0.5 mg/kg IV). Anesthesia was induced with propofol (4 mg/kg IV) and maintained after endotracheal intubation with isoflurane in oxygen. Sagittal, dorsal, and transverse T2-weighted, transverse FLAIR sequences, T1-weighted before and after intravenous administration of 0.2 mL/kg gadodiamide , which allowed manual image segmentation of the ventricular system and brain parenchyma on a slice-by-slice basis. The segmented partitions were calculated and graphically presented by the programme .Ventriculo-peritoneal shunting was performed as described elsewhere   to rule out inflammatory diseases of the brain. CSF was collected from the cisterna magna (1 mL per 5 kg body weight).The first CSF specimen for AQP and IL-6 analysis was collected from the pumping chamber during VP-shunt placement. After insertion of the ventricular catheter and connection of the pumping chamber, CSF was allowed to exit the ventricles via the shunt until pulsatile flow was observed in the transparent chamber. Depending on the ventricular volume and the size of the dog, 1–2 mL CSF was collected and stored in plastic tubes (Eppendorf tubes) at −80 °C for further analyses. The ventricular catheter was routinely tested for patency: 3 h after emptying the chamber via transcutaneous puncture, the chamber was checked for refilling by repeat puncture. The second CSF specimen was collected 3 months after shunt insertion from the subcutaneous pumping chamber.Approval by an ethics committee for the CSF collection was not required as all procedures are part of the therapeutic procedure or routine diagnostic workup of clinical patients [German Animal Experiment Act [“Tierschutzgesetz”], paragraph 9.2]. Verbal approval to examine the CSF for research purposes was obtained from the owners.Frozen CSF specimens were evaluated 4–26 months after sampling. A dog-specific ELISA Kit was used for analyses of AQP1 and AQP4 in CSF, according to the instructions provided by the manufacturer . The kit applied the competitive immunoassay technique using a monoclonal anti-AQP4-antibody and an AQP4 horseradish- peroxidase conjugate. Standards containing 0, 2.5, 5.0, 10, 25 and 50 ng/mL AQP4 were used to create a standard curve, which was used to calculate AQP4 concentrations in the biological samples. According to the manufacturer’s instructions no significant cross-reactivity or interference between AQP4 and its analogues was observed. The coefficient of variation within a given lot and between different lots was stated to be less than 10 %. Samples were determined in duplicate and the detection limit of the specific assay proved to be 0.1 ng/mL.IL-6 concentrations were determined by a bioassay based on the dose-dependent growth stimulation of IL-6 on the B9 hybridoma cell line , 28. ThiAll data was analysed using a statistical software package . AQP and IL-6 concentration before and after surgery were compared with controls. CSF volume before and after surgery may not only be dependent on ventricular distension, but also on the size of the dog .Correlation between AQP4 and IL-6 concentration in the preoperative CSF specimen was tested using Spearman`s correlation. Association of AQP4 and IL-6 with ventricular reduction was tested using the Chi square test. Breed, age, sex, clinical signs and duration of clinical signs are summarised in Table Results of CSF analyses are presented in Table P < 0.0127). Post hoc tests revealed a significant difference between the mean AQP4 concentrations before (11.32 ng/mL), and after surgery , and before surgery compared to controls . Postoperative AQP4 concentrations were not significantly different from controls (P > 0.05).Results of group comparisons are summarised in Fig. P < 0.0001). The mean total AQP4 quantity (325.8 ng) in dogs with internal hydrocephalus before surgery was significantly different from control dogs . After shunting, mean total AQP4 quantity was significantly different from pre-operative values , but not different from controls (P > 0.05). CSF volume was significantly reduced after surgery (P < 0.001). A reduction of ventricular volume was associated with AQP4 decrease (P < 0.001).Total AQP4 quantities were globally different between groups . The median IL-6 concentrations before surgery (62 IU/mL) was significantly higher than postoperative values  and higher when compared to controls . Postoperative values were not different to controls (P > 0.05). Total IL-6 quantities were significantly different between groups (P < 0.0001). Total IL-6 quantities were significantly higher in dogs with internal hydrocephalus than in control dogs before surgery  and significantly decreased after shunting , but were still significantly higher than in the control group (P < 0.01).IL-6 concentrations Fig.  were gloP = 0.449).Concentrations of AQP4 and IL-6 measured in the preoperative CSF specimens were not correlated , we considered it might be necessary to calculate AQP4 and IL-6 total quantities by multiplying by the ventricular volume. Although preoperative volumes in some dogs exceeded three times the volume of other hydrocephalic dogs, the differences in ventricular dimensions did not obscure differences in CSF AQP4 concentrations. In fact, the concentrations were comparable to those measured in children with hydrocephalus (13.3 in dogs vs. 11.32.ng/mL in children), as well as those in normal dogs to the values in unaffected children (9.5 in dogs vs. 8.61 ng/mL in children) .The main limitation of this study is therefore the heterogeneity of the examined dogs. Different dog breeds were examined without knowledge of the underlying cause of the CSF accumulation or of intraventricular pressure, with different degrees of ventricular dilatation and different durations of clinical signs. Dogs with hydrocephalus were younger than control dogs. Furthermore, CSF from the control group was taken after euthanasia and also not from the intraventricular site, which might also have a potential influence on measured AQP4 and IL-6 levels.While we were able to measure AQP4 in the CSF of normal and hydrocephalic dogs, AQP1 levels were below the detection limit in all samples. Interestingly, analysis of AQP1 expression after the induction of hydrocephalus in rodents has revealed conflicting results. In mice, it has been shown that AQP1 is down-regulated after induction of hydrocephalus, rather suggesting a compensatory response to hydrocephalus , howeverAn increase in ventricular dimension is accompanied by increases in AQP4 and IL-6 concentrations in the CSF of dogs with idiopathic communicating hydrocephalus. All were greatly reduced or normalised after shunt treatment. Therefore AQP4 and IL-6 in CSF can be indicators of ventriculomegaly, of cellular damage, and of improvement after the treatment of hydrocephalus. Based on the results of this study, a brain tissue-based determination of AQP4 at the mRNA and protein level might be rewarding to analyse the potential role of AQP4 in the compensation of extracellular fluid overload in dogs with communicating hydrocephalus.


Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART).We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal  or impaired . The NCI group included subjects with asymptomatic  or mild  HAND. CSF biomarkers were analyzed on two occasions.Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group  but not in the NCN group . Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06).Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies. With antiretroviral therapy (ART) the incidence of HIV-associated dementia (HAD), the most severe form of HIV-associated neurocognitive disorders (HAND), has been dramatically reduced , 2. HoweThe light subunit of the neurofilament protein (NFL) is a major structural element of myelinated axons, and NFL concentration in CSF is a sensitive marker of neuronal damage in several neurologic diseases–10. In HAlthough the clinical relevance of the milder forms of HAND, particularly ANI, has been questioned , 16, recWe identified subjects from longitudinal neuroAIDS studies at the HIV Neurobehavioral Research Program (HNRP), including the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study, an ongoing observational multicenter cohort study which has been described in detail previously . IndividSubjects included from the longitudinal studies underwent a venipuncture, lumbar puncture (LP), neurological assessment, comprehensive neurocognitive testing, detailed substance use history, a fully-structured psychiatric interview for lifetime and current (30-day) diagnoses of major depression and alcohol and other psychoactive substance use disorders, and a measure of mood symptoms in the previous fourteen days. Details of the assessments, including assessment of comorbidities, have been reported in detail previously , 17.Data collection for the study was approved by the UCSD Human Research Protection Program (# 110089), and all study participants provided written informed consent. De-identified data and biological samples were obtained with the permission of the CHARTER steering committee and HNRP Research Review Committee.Clinical laboratory assessments of CSF WBC and CD4+ T-lymphocyte count were performed at each participating site. Plasma and CSF HIV-1 RNA was quantified using RT-PCR  with a lower limit of quantification of 50 copies/ml.For CSF biomarker analysis, we used cell-free specimens of CSF stored at -80°C and not thawed until analysis. CSF NFL was measured using a sandwich ELISA method with a lower limit of quantification of 50 ng/l  at the Clinical Neurochemistry Laboratory at the University of Gothenburg according to the manufacturers description. CSF NFL concentrations have previously been shown to increase with normal ageing in healthy individuals . The upp10 transformed where appropriate for the tests used. For comparisons of continuous variables between independent groups, the Mann-Whitney test or T-test was used, as appropriate. Comparisons of categorical variables were analyzed using Fishers exact test or χ2-test. Correlations were explored using Pearson correlation. Analyses involving repeated measurements were performed with linear mixed effects models.Descriptive statistics were performed using Prism  or SPSS (IBM SPSS version 20) software. Continuous variables were logNinety-nine subjects  who fulfilled inclusion criteria were identified from the HNRP studies and included in the analysis. Twenty-nine subjects were classified as NCN and 70 as NCI (37 with ANI and 33 with MND). The median (IQR) interval between visits for the whole study population was 249 (182–366) days. Subject baseline characteristics of the two groups are shown in + T- cell count was high in both groups, although statistically significantly lower in the NCI subject group at baseline (+ T-cell count was 514 (349–776) cells/mm3 in the NCI group, and 640 (418–941) cells/mm3 in the NCN group (p = 0.12). Additionally, the NCN group had a longer history of viral suppression in plasma than the NCI group  also had a baseline HIV-1 RNA <50 copies/ml in CSF. ART regimens were similar in the two patient groups . By studbaseline , but notCI group . AlthougAt follow up, three patients had detectable HIV-1 RNA in plasma , two in CSF (59 and 925 copies/ml) and one patient had detectable HIV-1 RNA in both plasma and CSF , all in the NCI group. All subjects with detectable CSF HIV-1 RNA had CSF neopterin above the upper normal reference value at follow up (range 15.1–60 nmol/l). However, none of the subjects with viral RNA above detection level in either plasma or CSF had CSF NFL above the upper normal age-adjusted reference.An overview of the distribution of CSF biomarkers at baseline and follow up in the study groups is shown in 10 CSF neopterin, this difference corresponded to 25% higher geometric mean CSF neopterin levels in the NCI group (p = 0.04) (CSF neopterin levels were higher in the NCI group. Baseline median (IQR) neopterin was 7.2 (4.9–10.9) nmol/l in the NCI-group, and 4.8 (4.7–7.4) nmol/l in the NCN group. At follow up, neopterin in the NCI and NCN groups was 6.3 (4.8–10.2) and 4.9 (4.6–7.2) nmol/l, respectively. In linear mixed model analysis of log = 0.04) .Using the previously defined age-related laboratory cut-off levels for CSF NFL, 13/70 (19%) patients in the NCI group had NFL above the upper normal age-related reference in at least one sample, compared to only one  patient in the NCN group (p = 0.06). For CSF neopterin, 46/70 (66%) in the NCI group compared to 12/28 (43%) in the NCN group had neopterin above the upper normal reference of 5.8 nmol/l on at least one occasion (p = 0.04).+ T-cell count, time undetectable in plasma) did not remain significant predictors of either biomarker in multivariate analysis. Although the time between visits varied in the study population, no correlation was found between time between visits and change in CSF NFL or CSF neopterin.CSF NFL was significantly correlated to CSF neopterin in the NCI group , whereas no correlation between the biomarkers was seen in the NCN group . Additional weak correlations found between CSF NFL or neopterin and other factors  . Median Median (IQR) baseline CSF neopterin was 7.0 (4.9–9.4) nmol/l in NCI-stable and 7.7 (4.9–13.0) in NCI-decline subjects. Corresponding CSF neopterin at follow up was 6.1 (4.8–9.3) and 6.3 (4.9–13.6) nmol/l, respectively. Although geometric mean CSF neopterin was 21% higher in NCI-decline patients, this difference did not reach statistical significance (p = 0.1) . FurtherThe clinical and pathological importance of the milder HAND forms (particularly ANI) has been questioned in patients responding well to ART. In the present study of effectively treated, virally suppressed HIV-1 infected patients, we demonstrate that patients with milder forms of HAND (ANI and MND) had a higher degree of intrathecal immune activation than patients without neurocognitive impairment, suggesting that even the milder forms of HAND may represent a clinically significant pathologic process within the CNS. Moreover, the correlation between CSF NFL and neopterin found in the NCI patient group, but not in the NCN group, indicates a mechanistic association between CNS inflammation, neuronal damage and neurocognitive impairment during effective ART.In patients with HIV-associated dementia, the most severe form of HAND, HIV-1 infection in the CNS initiates a neuropathological inflammatory response known as HIV encephalitis (HIVE). HIVE is characterized by immune activation and neuronal damage that is measurable in the CSF of patients with HIV-associated dementia , 23, 24.+ T-cell counts [Previous studies have shown substantially increased levels of CSF NFL in patients with HAD, and mild elevations in some untreated neurologically asymptomatic patients, mainly with low CD4l counts , 12. Howl counts . In the l counts . In the The higher levels of CSF neopterin found in subjects with NCI in the current analysis suggest that even the milder forms of HAND may result from an ongoing pathological process within the CNS. However, we found no clear biomarker evidence of a link between neuroinflammation and neurocognitive decline. All of the NCN subjects in the study were stable in neurocognitive performance, including only NCI subjects in the evaluation of CSF biomarkers in relation to neurocognitive decline. Although neopterin tended to be higher in subjects with baseline impairment and NP-decline, this difference was non-significant (p = 0.1). Neopterin is a sensitive marker of macrophage and microglial activation, and almost all of the neopterin detected in CSF originates from inside the CNS . Althoug+ T-cell count prior to initiation of ART. Although the NCI group in the present study had increased immune activation as a reflection of an active immunologic process, we did not find a significant relationship between decline in neurocognitive performance and the CSF biomarkers measured in this study, indicating that effective ART may be sufficient in limiting CNS damage in most patients. However, recent data suggest an increased risk for progression to symptomatic HAND in individuals with ANI [The currently used diagnostic criteria of HAND have been criticized for overestimating the prevalence of impairment in patients on ART, thereby obscuring identification of the actual burden of HIV-related brain disease and that milder forms of HAND (mainly ANI) may have little clinical significance , 16. Thewith ANI . AlthougIn this study, all subjects were using effective, virally suppressive combination ART, and individuals with known significant comorbid conditions that could influence either NP-test result or CSF biomarkers were excluded. However, we cannot rule out the presence of background factors such as prior drug use, abdominal obesity or other components of the metabolic syndrome or otherThe findings in this study indicate that milder HAND forms may be a clinically significant reflection of an ongoing pathologic process within the CNS in some patients, where viral suppression alone is not sufficient to eliminate neuronal inflammation. The correlation found between CSF neopterin and NFL in subjects with neurocognitive impairment also indicates a mechanistic association between immune activation, neuronal damage and neurocognitive impairment during effective ART. Although standard ART is likely sufficient to prevent neurologic complications in most patients, effective control of viral replication through ART alone may not be sufficient in all cases. Methods of identifying individual patients at risk of developing, as well as progressing in HAND are needed, where the use of CSF biomarkers and neuropsychological testing will likely continue to be important tools.S1 Data(XLSX)Click here for additional data file.


With increasing morbidity and mortality attributable to non-communicable disease, primary healthcare providers are urged to increasingly support people in making healthy lifestyle choices. Many chronic physical diseases associated with lifestyle behaviours have been linked to neuromusculoskeletal disorders and pain. Chiropractors, as primary healthcare professionals, are in a position to provide preventative and promotional healthcare to patients, however, it is unknown to what extent such care is provided, particularly in the United Kingdom (UK).This study was a cross sectional online questionnaire distributed to four UK chiropractic associations. The responses were collected over a period of two months from March 26th 2012 to May 25th 2012. Descriptive analyses were performed to identify the trends in current practice of chiropractors in the UK. Additionally, subgroup analyses of all items were performed using Pearson Chi-Square tests to determine statistically significant differences between respondents based on gender, years in practice, educational institution and association membership.Of the 2,448 members in the four participating associations, 509 chiropractors (approximately 21%) completed the survey. The great majority of UK chiropractors surveyed report evaluating and monitoring patients in regards to posture (97.1%), inactivity/overactivity (90.8%) and movement patterns (88.6%). Slightly fewer provide this type of care for psychosocial stress (82.3%), nutrition (74.1%) and disturbed sleep (72.9%). Still fewer do so for smoking (60.7%) and over-consumption of alcohol (56.4%). Verbal advice given by the chiropractor was reported as the most successful resource to encourage positive lifestyle changes as reported by 68.8% of respondents. Goal-setting is utilised by 70.7% to 80.4% of respondents concerning physical fitness issues. For all other lifestyle issues, goal-setting is used by approximately two-fifths (41.7%) or less. For smoking and over-consumption of alcohol, a mere one-fifth (20.0% and 20.6% respectively) of the responding chiropractors set goals.UK chiropractors are participating in promoting positive lifestyle changes in areas common to preventative healthcare and health promotion areas; however, more can be done, particularly in the areas of smoking and over-consumption of alcohol. In addition, goal-setting to support patient-provider relationships should be more widespread, potentially increasing the utility of such valuable advice and resources. One of the greatest challenges facing global public health is the burden of non-communicable diseases (NCDs). NCDs are non-infectious and non-transmittable which include chronic, slow progressing diseases. Statistics show that in 2008, of the 57 million deaths globally, 36 million where due to NCDs of which 80% were preventable . Top on In 2006, the Council on Chiropractic Education (CCE) in the United States of America (USA) suggested a set of standards indicating specific health promotional efforts that every chiropractor should perform and health promotion and prevention methods that ideally should be part of the curriculum at accredited USA chiropractic colleges . AccordiAcknowledging the debate within the chiropractic profession as to whether chiropractors serve as primary care providers or spine specialists, Evans and Rupert  argue thAlthough some patients seek chiropractic care for pain relief and end treatment when they become asymptomatic, Evans and Rupert  suggest Preventative health care and health promotion are of emerging importance to the chiropractic profession. Previous work in this area has been done by Evans et al.  who focuThe survey questionnaire was generated from November, 2011 to March, 2012. The items were organised into categories, namely, nutrition, physical activity, psychosocial well-being, smoking and alcohol consumption. Additionally, every item on the questionnaire had a comment box where the participants could leave additional issues that did not appear on the item lists. The information submitted in these comment boxes were not included in the data analysis, but rather used for interpretation and to direct future research.To reach a large number of chiropractors throughout the UK, the survey was distributed electronically through four UK chiropractic associations. The four participating UK associations were the British Chiropractic Association (BCA) , the McTThis research was ethically approved by the Anglo-European College of Chiropractic undergraduate ethics panel in March 2012.Five hundred and nine participants returned fully completed surveys. The total number of members of the four participating associations, which was provided through email request by the associations’ secretaries, sums up to 2,448 member chiropractors. The 509 respondents represent approximately 21% of chiropractic membership in these four associations; however, as individual chiropractors can be members of multiple associations, the response rate is potentially higher than 21%. Furthermore, the associations’ secretaries where unable to determine the number of members on their mailing lists, so the exact number of bulletin recipients as well as the actual response rate is unknown. Of the total respondents, 63% were BCA members, with another 25% representing the UCA, 11% representing the MCA, 3% representing the SCA and 4% representing other associations. Table Just under half of all respondents (44.6%) were female. Most 52.1%) had practiced for 10 years or less and the majority (54.2%) were trained at the AECC. Table .1% had pOf all respondents, 89.0% consider themselves to be evidence informed practitioners. Depending on the issue, 61.7 to 97.1% of the respondents agreed that the items associated with lifestyle issues were their responsibility to discuss. These issues included decreasing alcohol consumption, decreasing psychosocial stress, regular exercise, improving eating habits, improving posture, improving movement patterns, normalising sleep patterns and smoking cessation. The specific values for each issue are shown in Table 2  =13.85, p = .008) reflecting an increasing female representation in the profession over the most recent decades. Additionally, in regards to years in practice and association membership, the UCA had a statistically significant over-representation of respondents with fewer years in practice, χ2  =17.18, p = .002), while the BCA was over-represented by respondents with greater years in practice, χ2  =16.66, p = .002). This was not seen in the MCA or SCA.In order to determine any differences between subgroups, analyses were carried out using Pearson Chi-Square tests. This revealed that there was a statistically significant greater proportion of males with >20 years in practice, χ2  =9.74, p = .002), and psychosocial stress, χ2  =6.99, p = .008), as being behaviours they evaluate and/or monitor. Conversely, males reported poor posture, χ2  =5.98, p = .014), with higher frequency than females. In regards to the lifestyle changes for which the respondents set and/or re-evaluate goals with their patients, respondents in practice for ≤20 years reported doing so more frequently in regards to poor posture, χ2  =12.97, p = .011). On the other hand, respondents in practice for >20 years reported with higher frequency goal setting/re-evaluation for smoking, χ2  =11.35, p = .023).In relation to patient behaviours, a significantly greater number of female respondents reported disturbed sleep, χThis study indicates that the surveyed UK chiropractors are participating in preventative healthcare and health promotion activities, encouraging patients to make positive lifestyle changes especially in regards to physical activity and fitness. Although less in comparison to physical activity, our findings indicate that a fair degree of nutritional and psychosocial care is provided. These are potentially important components not only to individual patients, but to public health initiatives as highlighted by O’Connor et al. . The autThe results also show that just over half of the chiropractors reported smoking and over-consumption of alcohol as their responsibility to discuss. However, less of these same clinicians evaluate and monitor their patients for these behaviours. This is surprising as over-consumption of alcohol and smoking are not only known to lead directly to the development of NCDs, but additionally have quite severe consequences on skeletal and nervous system health -21. NeveAs preventative care and health promotion focus on the daily choices an individual makes regarding their long-term health objectives, goal-setting should be a core component. In a study by Holliday et al. , neuroloA significant limitation of this study is the estimated 79% non-response rate from the UK chiropractors in this survey. Although the approximate 21% response rate allows us to draw conclusions regarding the practices of those who responded, the UK chiropractic profession is not represented in its entirety. This leads to less than robust confidence in the generalisability of these attitudes and practices to the wider profession.Additionally, the chiropractors were asked to report general tendencies, not specific patient encounters, and interpretation between chiropractors may differ. This is particularly important where clinicians were asked to report the number of patient visits where goal-setting and re-evaluation of goals took place. Additionally, false reports, conscious or subconscious, might have occurred; however, this is an unavoidable limitation of the study design.Lastly, some issues were not included in the survey, but may have an impact on decreasing NCDs as suggested by the respondents in the comment boxes. These included pregnancy and birth plans, regular weight checks, work-life balance, supplements, prescription drugs, vaccinations, ergonomics, exposing oneself to adequate sunlight and spiritual pursuits.This survey explored the degree with which UK chiropractors engage with patients concerning efforts to support the potential reduction in the burden of NCDs. While being only a snapshot of the current situation for the chiropractors who responded, this study could serve as a starting point for further work in this area in the UK. Future studies in this field will not only be of interest to patients and chiropractors, but potentially to other health care professionals as well as policy makers. Further exploration of the patients’ perspective and the reasons why chiropractors do or do not consider it their responsibility to incorporate such care into their practices as well as seeking insight into successful methods being utilised in chiropractic practices should be explored.Links have been shown between chronic disease, smoking, obesity and depression with pain, particularly spinal pain. With the WHO calling on primary healthcare professionals to assist patients in developing sustained lifestyle changes, the goal of this study was to explore the chiropractic professions’ engagement with preventative healthcare and health promotion. This survey of a subset of UK chiropractors shows that a good degree of preventative healthcare and health promotion is already provided, especially in regards to physical activity, nutrition and psychosocial stress. However, goal-setting and re-evaluation of goals could be incorporated more routinely by UK chiropractors into their practices. The chiropractic profession has a valuable role in preventative healthcare and health promotion and many of those surveyed are already participating in decreasing the burden of NCDs in various aspects of patient care. However, as in most things, there is considerable room for improvement if desired.


Biofeedback is a process in which biological information is measured and fed back to a patient and clinician for the purpose of gaining increased awareness and control over physiological domains. Surface electromyography (SEMG), a measure of muscle activity, allows both a patient and clinician to have direct and immediate access to muscle functioning that is not possible with manual palpation or visual observation. SEMG biofeedback can be used to help “down-train” elevated muscle activity or to “up-train” weak, inhibited, or paretic muscles. This article presents a historical and clinical overview of SEMG and its use in chronic low back pain assessment and biofeedback training. Biofeedback is a process in which biological information is measured and fed back to a patient and clinician. Though biofeedback technology can be used for diagnostic purposes, it is most often used for self-regulation skills training. The goal of biofeedback training is to teach increased awareness and control over biological process. Due to limitations in the available technology at the time, first generation biofeedback equipment provided only an analogue needle display or a simple sound. As the technology improved in the 1970s, digital numerical displays became available. Biofeedback became computerized in the 1980s with the first Apple computers. Today, biofeedback has become much more sophisticated, allowing computerized multimedia colorful interactive displays and sounds, and allowing detailed recordings and statistical analysis of biological information. Despite these advances, the accuracy and meaningfulness of a biofeedback signal is dependent on the grade of the equipment and the skill of the practitioner, in knowing proper skin preparation, sensor placement, measurement settings, display setup, and signal interpretation . A number of biofeedback modalities are used in chronic pain management and physical rehabilitation, including autonomic nervous system measures , central nervous system measures ), and biomechanical measures (force and pressure) . SurfaceTraditional biofeedback involves an operant conditioning process in which movement toward the desired goal is shaped over time, with minimal therapist instruction . This trIn contrast to traditional biofeedback, SEMG biofeedback for purposes of muscle re-education lends itself to a more direct coaching methodology . A numbeThere are generally two goals with SEMG biofeedback training: to increase awareness of the target muscle(s); and to increase control of the muscle(s). A primary concept regarding SEMG biofeedback training with chronic pain patients is that they tend to be very poor at knowing how tense they are when compared with pain-free controls . A seminvs. control subjects in various static postures, the results have been equivocal, with some studies reporting significant differences, and others not [et al. (1991) found that SEMG biofeedback of the lumbar muscles in subjects with “mild” chronic back pain was superior to cognitive behavioral counseling (including relaxation without biofeedback) and medical “treatment as usual” in outcome measures of pain, functional interference, and affective distress [et al. (1991) study, found clinical improvements in both the SEMG biofeedback and cognitive behavioral groups, with no significant differences between the two [Lumbar SEMG measures, in both static and dynamic postures and movements, have been found to be reliable in both normal and CLBP subjects, and both within and between sessions ,28,29,30hers not . Howeverhers not . Flor etdistress . A simil the two . In a se the two . Correct the two . Interes the two . Whetherd = −1.71) in distinguishing between CLBP patients and control subjects [SEMG as an assessment tool has a long history within low back pain research. Beginning in the early 1950s, researchers first began evaluating lumbar muscle activity in different postures and movements ,44,45,46subjects . FR defisubjects , pain [4subjects ,54, and subjects . When assubjects , perceivsubjects .More recently, attempts have been made to actively modify abnormal FR in CLBP patients with SEMG biofeedback training. A biofeedback training protocol of surface EMG-assisted stretching (SEMGAS) has been described, which teaches CLBP patients how to relax into standing maximum voluntary flexion and achieve FR ,58,59. TAs one can find with a “SEMG biofeedback for low back pain” literature search, the majority of clinical studies on this topic were performed in the 1980s and 1990s. Few clinical outcome studies that focus on SEMG biofeedback for CLBP have appeared in the scientific literature since that time. Perhaps these new studies on SEMGAS indicate a sign of renewed interest in SEMG biofeedback for CLBP. Some other new clinical research avenues may also show relevance for CLBP treatment. Recent studies on the use of real-time muscle monitoring of neck and shoulder muscles with a portable EMG device have been investigated with promising results. In three randomized control trials, portable EMG biofeedback was found to be effective for reducing muscular tension and associated pain and perceived disability in females with chronic neck/shoulder pain who were working in low-impact jobs (including computer work) ,65,66. TIn conclusion, one thing is certain. Chronic pain, including CLBP, is at epidemic proportions. A new report has determined that 100 million people in the United States alone  have some form of chronic pain, and the majority of those have CLBP . Thus, a


This suggests high diagnostic power of our GBCA-HDL particles in the detection of vulnerable atherosclerotic plaques. Further, in contrast to discoidal, spherical GBCA-HDL exhibit hepatic clearance, which could further diminish adverse renal effects of Gd. Finally, activated macrophages are reliable indicators of any inflamed tissues and are implicated in other areas of unmet clinical need such as rheumatoid arthritis, sepsis and cancer, suggesting the expanded diagnostic and prognostic use of this method.Cardiovascular disease is the leading cause of death in Western cultures. The vast majority of cardiovascular events, including stroke and myocardial infarction, result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. Current imaging modalities including magnetic resonance imaging (MRI) aim to characterize anatomic and structural features of plaques rather than their content. Previously, we reported that macrophage-targeted delivery of gadolinium (Gd)-based contrast agent (GBCA-HDL) using high density lipoproteins (HDL)-like particles significantly enhances the detection of plaques in an apolipoprotein (apo) E knockout (KO) mouse model, with an atherosclerotic wall/muscle normalized enhancement ratio (NER) of 120% achieved. These particles are comprised of lipids and synthetic peptide fragments of the major protein of HDL, apo A-I, that contain a naturally occurring modification which targets the particles to macrophages. Targeted delivery minimizes the Gd dose and thus reduces the adverse effects of Gd. The aims of the current study were to test whether varying the GBCA-HDL particle shape and composition can further enhance atherosclerotic plaque MRI and control organ clearance of these agents. We show that the optimized GBCA-HDL particles are efficiently delivered intracellularly to and uptaken by both J774 macrophages  The buildup of plaque in arterial walls, better known as atherosclerosis, remains the leading cause of death in the United States and other Western cultures . The larInflammation plays a key role in all stages of atherosclerosis with macrophages involved in plaque pathogenesis ,8. High Magnetic resonance imaging (MRI) is a powerful and noninvasive method for the imaging of atherosclerosis . The usein vitro  x 100% was calculated.Images were analyzed using ImageJ  to measure the intensities of the cell pellet after incubation with GBCA-HDL , which is a genetically engineered mouse model of atherosclerosis. Male wild type (WT) C57BL/6 J mice  were used as controls. Apo E KO mice (n = 9) and WT mice (n = 4) were kept on either a Western diet comprising of 21% fat and 0.15% cholesterol or a normal chow diet, respectively, for a period of at least 5 months. Sample size calculations were performed as previously described to determine the number of mice needed to detect a significant change /(Iw/Im)pre x 100%. Intensity values in regions of interest (IROI) in the kidney and liver were also measured. The mean signal-to-noise ratio (SNR) for the regions of interest in the kidney and the liver were calculated using this formula: SNR = IROI / Inoise. The formula to calculate the relative SNR increase is defined as: SNR increase = (SNRpost / SNRpre − 1) x 100%.Images were analyzed using ImageJ to measure intensity values in regions of interest containing tissue directly surrounding the vessel lumen in the aortic vessel wall  analysis of variance (ANOVA). The ANOVA assumptions were ensured using the Kolmogorov-Smirnov test, and, where necessary, multiple comparisons by Bonferroni were performed. Results were considered statistically significant at in vitro macrophage uptake, we tested our paramagnetic and fluorescent HDL-like nanoparticles of either discoidal (dHDL) or spherical (sHDL) shape using the established J774A.1 macrophage line. To detect for Rhodamine B-labeled lipid uptake, fluorescent intensities in J774 cell lysates were measured after 2 h incubation at 37°C with either the dHDL or the sHDL formulations. T1-weighted MR imaging was performed on J774A.1 cell pellets after 2 h incubation at 37°C with either the dHDL or sHDL formulations. in vitro.To study To determine that the paramagnetic and fluorescent dHDL and sHDL particles are specifically uptaken by J774A.1 macrophages and not a result of lipid exchange , we labein vivo, we utilized apo E KO mice, which are known to develop plaques when fed a high fat, high cholesterol Western diet. For controls, age-matched WT mice fed a normal chow diet were utilized. After 5 months on the Western diet or a normal chow diet, apo E KO mice (n = 9) and WT mice (n = 4), respectively, were injected intravenously with a single dose of the paramagnetic and fluorescent dHDL or sHDL formulations at a dose of 0.05 mmol Gd kg −1. Axial T1-weighted images of the abdominal aorta were taken before (pre-imaging) and 4h, 24h, 48h and 72h after contrast agent administration. in vivo. The data also indicate that the NER and CNR values increase with time and reach a maximum at 72 h, which increases the diagnostic power of the method. Importantly, WT mice showed no contrast enhancement (results not shown), consistent with results from our previous study [To evaluate if paramagnetic and fluorescent dHDL and sHDL particles target atherosclerotic plaques us study .To preliminarily evaluate how GBCA-HDL are excreted, the SNR values of the kidney and liver were measured before and after contrast administration as previously described . Fig 4A Discriminating vulnerable plaques from stable plaques is of paramount importance. One of the challenging aspects in distinguishing between the two is choosing a distinctive target that is mostly present in vulnerable plaques . In thisAnother important issue is related to Gd toxicity as GBCAs have been associated with the serious and sometimes fatal condition known as NSF ,18,37. I-1. This as well as targeted delivery of our GBCA-HDL to macrophages demonstrated both in vitro (Figs in vivo (To help reduce the risk of NSF and increase the diagnostic power of our method as compared to our previous study , we incrtro Figs  and in v in vivo . Additio in vivo , spheric in vivo . The obsThe results obtained using the proposed contrast-enhanced imaging technology for the detection of vulnerable atherosclerotic plaques strongly encourage further development of our method for diagnostic imaging of atherosclerosis. In addition, broader applications in other inflammation-based disorders where macrophages are known to play a key role, such as rheumatoid arthritis and cancer might be readily achieved and are currently under investigation.in vitro and in vivo. This is a novel methodology that could substantially improve early diagnosis and prognosis of atherosclerosis as well as treatment efficacy evaluation.Magnetic resonance imaging of macrophage-enriched vulnerable atherosclerotic plaques is achieved by employing lipopeptide nanoparticles that contain gadolinium-based contrast agents and modified synthetic apolipoprotein A-I peptides, which target the particles to macrophages


Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes. Invasive fungal infections (IFIs) cause significant morbidity among solid organ transplant (SOT) recipients, with mortality ranging from 27 to 41% . Clinican = 248) were reported due to Aspergillus (n = 109), Candida (n = 49), and other molds (n = 49) . S–9. S Spo Sporothrix [ Sporothrix cyanescens (a different organism than S. schenckii) in a heart transplant recipient has been reported. In this case, the acquisition of the fungal infection was thought to be zoonotic and was not of certain pathologic significance [The 7th case was reported in a study designed to describe the interactions between itraconazole and cyclosporine . This seorothrix , 3. Addiificance , 15.n = 284) compared to 2012 (n = 198) [ Candida was noted most frequently, with cases of cryptococcosis, histoplasmosis, coccidioidomycosis, and aspergillosis being noted; nine cases were classified as other fungal infections [The impact of donor-derived fungal infections on SOT has not been fully elucidated and is only now beginning to be systematically studied . Since 2n = 198) . Of the n = 198) . Among tfections . Lung trfections . Even thfections ), when d Sporothrix schenckii infection. This lung transplant recipient had stable pulmonary function and no known risk factors (aside from IPF) for pulmonary sporotrichosis prior to transplantation. He then received a bilateral single lung transplant from which Sporothrix schenckii was isolated on the second day after transplant. Cultures taken from the recipient's native lungs  at the time of transplant were negative. Given these factors, we believe that this was likely a donor-derived infection. Other cases of donor-derived IFIs due to environmental molds have occurred in the setting of traumatic events in the donor such as near drowning (Apophysomyces elegans [ Scedosporium apiospermum [Scopulariopsis) [ S. schenckii was a real pathogen in this case.To our knowledge this is the first case of likely donor-derived elegans , Scedospospermum ), being ospermum , or receriopsis) . In our riopsis) . The cli Sporothrix schenckii infection in a lung transplant recipient, which was successfully treated with amphotericin and itraconazole. The true incidence and impact of donor-derived infections are still being delineated. Use of appropriate microbiologic data is essential in diagnosing these infections, and screening with sputum/bronchial cultures in lung transplant donors and recipients remains instrumental. Physicians should keep in mind the potential for donor-derived fungal infections in the proper clinical setting including rare pulmonary pathogens such as Sporothrix schenckii.In conclusion, we report the first case of probable donor-derived


To investigate whether water influx into cerebrospinal fluid (CSF) space is reduced in Alzheimer’s patients as previously shown in the transgenic mouse model for Alzheimer’s disease.15O]H2O synthesized on-line.Ten normal young volunteers , ten normal senior volunteers , and ten Alzheimer’s disease (AD) patients  participated in this study. All AD patients were diagnosed by neurologists specializing in dementia based on DSM-IV criteria. CSF dynamics were analyzed using positron emission tomography (PET) following an intravenous injection of 1,000 MBq [Water influx into CSF space in AD patients, expressed as influx ratio, (0.755 ± 0.089) was significantly reduced compared to young controls  and also compared to normal senior controls . Influx ratio in normal senior controls was significantly reduced compared to young controls (p < 0.01).Water influx into the CSF is significantly reduced in AD patients. β-amyloid clearance has been shown to be dependent on interstitial flow and CSF production. The current study indicates that reduction in water influx into the CSF may disturb the clearance rate of β-amyloid, and therefore be linked to the pathogenesis of AD.UMIN000011939UMIN Clinical Trials Registry  The brain lacks conventional lymphatics for clearing interstitial fluid of solutes not absorbed across capillaries. The cerebrospinal flow (CSF) system has long been suggested to play a role equivalent to the systemic lymphatic system. Nevertheless, the role of CSF as the brain’s lymphatic system has not received much attention. Recently, however, the classic CSF circulation theory where CSF is almost exclusively produced by choroid plexus is found to be incomplete. It is now understood that influx from the peri-capillary (Virchow-Robin) space into the CSF system, classically referred to as interstitial flow, plays a major role in CSF production –3. FurthWater homeostasis of the Virchow-Robin space and, therefore, interstitial flow is regulated by aquaporin-4 (AQP-4) ,3,10, anhttp://www.umin.ac.jp/ctr/index.htm). Participants were provided with contact names and telephone numbers in the event of any adverse event related to the study. All participants were followed up within one month of the study to further confirm the absence or occurrence of adverse events related to the study, not otherwise self-reported by the study participant or proxy to the study coordinator. Alzheimer’s patients are additionally followed up annually at the Memory Clinic.Ten normal young volunteers , ten normal senior volunteers , and ten Alzheimer’s disease (AD) patients  participated in this study. Participant recruitment was completed between October 1, 2013, and April 4, 2014 . All volPET imaging was performed using a combined PET/CT scanner  with a 15 cm field of view (FOV) positioned in the region of the cerebrum. To correct for photon attenuation, low-dose CT imaging was acquired in helical mode. The subject’s head rested on a foam cushioned headrest. A head strap was applied to minimize head movement.15O]H2O, synthesized on-line ([15O]CO2 + 4H2 → 2[15O]H2O + CH4) was injected intravenously into an antecubital vein via an automatic water injection system . The system delivered a 10 ml bolus over 10 seconds at 1 ml/sec with both pre- and post- flush of an inert saline solution. Immediately after starting the administration, emission data were acquired over 20 minutes in three-dimensional list mode with a 25.6 cm axial FOV and sorted into 40 time frames (40 × 30 seconds).1000 MBq [All emission scans were normalized for detector inhomogeneity and corrected for random coincidences, dead time, scattered radiation, and photon attenuation. For optimization of image quality, the 40 frames of the dynamic emission scans were reconstructed using 3D-OSEM (Ordered-Subset Expectation Maximization) with 2 iterations and 28 subsets. The resultant image quality allowed manual identification of regions of interest (ROIs). For the reconstruction algorithms, the data were collected in a 128 × 128 × 47 matrix with a voxel size of 2.0 × 2.0 × 3.27mm.0 is the baseline SUV. Subsequently, the ratio between SUVs of ventricle and cortex was defined as the influx ratio. The numerical data were subjected to the Mann-Whitney-Wilcoxon rank sum test for group analysis using IBM SPSS version 19.5 .The CT and PET image data were transferred to a Xeleris 1.1 workstation  for PET data analysis. Manually defined ROIs on the attenuation corrected axial images and CT images  were used to obtain the time-activity data of the scans of each subject. The tissue activity concentration in each ROI was expressed as the standardized uptake value , corrected for the subject’s body weight and administrated dose of radioactivity. Each tissue time activity concentration was determined by fitting the data using the following equation:Results are shown in Fluid-filled canals surrounding perforating arteries and veins in the brain parenchyma were recognized in the early era of modern medicine. They became known as the Virchow Robin space, so named after the first two scientists who described the structure in detail, namely, Rudolph Virchow and Charles Philippe Robin ,15. It wThe unique anatomical features of the brain’s vascular system ensure a properly functioning blood brain barrier (BBB) and are a result of modification of the systemic circulation system. A critical property of the BBB is prevention of free water permeability across capillary walls (tight endothelium). This is in strong contrast to systemic capillaries which possess a leaky endothelium. The molecular basis of the tight endothelium is the formation of tight junctions. Various tight junction proteins such as claudin and occludin play the role of “gating control” of paracellular transport. Passive water movement across brain capillaries is strongly restricted by these tight junctions. In systemic capillaries, active water transport across endothelial cells is accomplished by the water channel aquaporin 1 (AQP-1). In brain capillaries, such water movement is totally abolished through the active suppression of AQP-1 . AccordiIn contrast to the above situations, the peri-capillary Virchow Robin space receives constant water influx through AQP-4, another isoform of the aquaporin family, abundantly expressed in the perivascular endfeet of astrocytes . VirchowAlthough it is difficult to determine whether the observed reduction in water influx into the CSF system in AD patients is the primary abnormality or merely related to β-amyloid deposits in the brain, the clear cut differences between young normal volunteers and AD patients unequivocally indicated that AD patients have significant reduction in interstitial flow. Furthermore, the theoretical possibility of contribution by choroid plexus or the leptomeningeal vasculature to the water detected in the CSF compartment cannot be totally excluded. Nevertheless, the observed large range of influx ratios in senior controls without cognitive dysfunction, strongly suggests that reduction of water influx into the CSF itself is not a sufficient factor for the pathogenesis of AD, a situation similar to senile plaque formation. There must be additional factors that eventually lead to neural death and cortical dysfunction.Drainage of β-amyloid by interstitial flow through the Virchow Robin space into CSF is essential for maintaining proper homeostasis between β-amyloid production and clearance. The balance between β-amyloid production and its clearance appears to be vital for maintaining proper neural function. Disruption in β-amyloid homeostasis may play a critical role in the pathogenesis of senile plaque formation, and, hence, the development of Alzheimer’s disease. Assessment of the dynamic indices of production and clearance of β-amyloid in various cohort groups, including mild cognitive impairment (MCI), is warranted.S1 TREND Checklist(PDF)Click here for additional data file.


Granulocyte-colony stimulating factor (G-CSF) and bone marrow derived mononuclear cells (BM-MNCs) have both been shown to improve functional outcome following experimental stroke. These effects are associated with increased angiogenesis and neurogenesis. In the present study, we aimed to determine synergistic effects of G-CSF and BM-NMC treatment on long-term structural and functional recovery after photothrombotic stroke. To model the etiology of stroke more closely, we used spontaneously hypertensive (SH) rats in our experiment. Bone marrow derived mononuclear cells transplantation was initiated 1 h after the onset of photothrombotic stroke. Repeated G-CSF treatment commenced immediately after BM-MNC treatment followed by daily injections for five consecutive days. The primary endpoint was functional outcome after ischemia. Secondary endpoints included analysis of neurogenesis and angiogenesis as well as determination of infarct size. Granulocyte-colony stimulating factor treated rats, either in combination with BM-MNC or alone showed improved somatosensory but not gross motor function following ischemia. No beneficial effect of BM-MNC monotherapy was found. Infarct volumes were comparable in all groups. In contrast to previous studies, which used healthy animals, post-stroke neurogenesis and angiogenesis were not enhanced by G-CSF. In conclusion, the combination of G-CSF and BM-MNC was not more effective than G-CSF alone. The reduced efficacy of G-CSF treatment and the absence of any beneficial effect of BM-MNC transplantation might be attributed to hypertension-related morbidity. Stroke is a lethal disease, yet it disables more than it kills. Better controls of risk factors in preventing stroke and improved treatment options for those who have had a stroke are essential for diminishing its devastating consequences. There are substantial research efforts being made to develop treatments that improve the outcome following stroke. Both, the stimulation of endogenous bone marrow cells by the granulocyte colony-stimulating growth factor (G-CSF) and the transplantation of bone marrow mononuclear cells (BM-MNCs) were shown to enhance regeneration in a large number of animal stroke studies  guidelines ; (2) G-CSF 50 µg/kg/day (n = 14); (3) 5 million BM-MNCs/rat (n = 14); or (4) 5 million BM-MNCs/rat and G-CSF 50 µg/kg/day (n = 14). One animal of the placebo group died during surgery. BM-MNC transplantation was initiated 1 h after the onset of the photothrombosis. Repeated G-CSF treatment started immediately after BM-MNC treatment followed by daily injections for five consecutive days.All animal procedures were approved by the responsible ethics committee of the University of Münster and the appropriate authorities of the Federal State of North Rhine-Westphalia. The investigations were carried out in accordance with national and international animal welfare regulations and are reported in accordance with the Animal Research: Reporting The cell numbers used in our experiments were based on previous studies that investigated different intravenous cell therapies in animal stroke models  cells were filtered by a 100 µm cell strainer, counted and prepared for immunomagnetic depletion of granulocytes: bone marrow cells were incubated with 10 ng/ml Phycoerythrin-conjugated anti-rat granulocyte antibody  for 15 min at 4°C. Subsequently, cells were washed with cold PBS plus 0.5% fetal calf serum (FCS) and incubated with 200 µl anti-Phycoerythrin MicroBeads  in 800 µl PBS plus 5% FCS for 15 min at 4°C. After incubation, non-adsorbed MicroBeads were removed by a further washing step. The cell suspension was then resuspended in 500 µl PBS plus 0.5% FCS and magnetically separated by a LD-column according to the manufacturer’s instructions (Miltenyi). This procedure results in higher BM-MNC purity compared to standard density gradient centrifugation , rat anti-BrdU , mouse anti-neuronal nuclei and rat anti-CD31 , anti-Iba1 . Detection of anti-NeuN antibodies was done with a goat anti-mouse fluorescent dye . Bromodeoxyuridine antibodies were detected using a biotin conjugated goat-anti-rat antibody ; CD31-antibodies detection was done using a biotin conjugated goat-anti-rat antibody . Detection of Iba1-antibodies was performed using a biotin conjugated donkey anti-goat antibody .For signal amplification of BrdU-, CD31- and Iba1-signal, sections were incubated with horseradish peroxidase/streptavidin  and biotinyl tyramide (1:100). Bromodeoxyuridine, CD31- and Iba1-positive cells were visualized by a streptavidin/fluorescent dye . Nuclei counterstain was done with a tissue preserving medium containing 4′,6-diamidino-2-phenylindole . Immunoflurescence was computed and visualized with a Nikon Eclipse 80i fluorescence microscope  equipped with proper filter sets for AlexaFluor594, AlexaFluor488 and DAPI.Quantification of Iba1-positive cells was performed by counting absolute cell amounts covering four random squares (200 × 200 µm) within the ipsilateral boundary zone of the infarct of four separate brain sections per animal.Quantification of neurogenesis was performed as described previously . Three areas (20× magnification) depicting the ischemic border zone from three sections per animal, respectively, were photographed and subsequently analyzed. Vessel cross-sectional surface area and perimeter were measured using Neurolucida (MicroBrightField). Two vessels featuring a minimum length of 300 µm for two sections were analyzed per animal.According to the ARRIVE guidelines primary and secondary objectives were defined . Behavioral measurements were analyzed by area under the curve analysis using analysis of variance (ANOVA) followed by the Fisher protected least significant difference test. Student t-test with Bonferroni correction was used to compare data between two groups. An α error rate of 0.05 was taken as the criterion for significance.Randomization was carried out by the computer software “Research Randomizer” . The values presented in this study are means ± SEM. Statistical analyses were calculated using the Statistical Package of Social Sciences . The normality distribution of the data was assessed by graphical examination of the histograms and verified by the Shapiro-Wilk test .All experiments were performed on a total number of 55 animals  treated animals compared to vehicle treated animals. In addition, G-CSF treated animals also displayed a significantly improved somatosensory recovery compared to animals treated with BM-MNC alone (P < 0.05).The area under the curve analysis of the adhesive removal test revealed a statistically significant decrease of the somatosensory deficit in G-CSF (P = 0.859; one-way ANOVA, Figure The area under the curve analysis of the cylinder test did not reveal any significant treatment effects on the recovery of motor functions (P = 0.877; ANOVA, Figure As expected after photothrombotic stroke, infarct volumes did not differ between the four groups (P = 0.976; one-way ANOVA, Figure To investigate treatment effects on postischemic inflammation in the chronic phase following ischemia we analyzed the extent of the inflammatory response 28 days after infarct induction. The number of Iba1-positive cells with retracted processes and round cell bodies, representing activated microglia, did not differ between the different groups (P < 0.05; BM-MNC group: P < 0.001; G-CSF group: P < 0.01; BM-MNC+G-CSF group: P < 0.01, Students t- test with Bonferroni correction, Figure P = 0.101, contralateral: P = 0.108; multivariate ANOVA, Figure P = 0.948, contralateral: P = 0.743; ANOVA, Figure P = 0.095; one-way ANOVA, Figure P = 0.830; BM-MNC group: P = 0.637; G-CSF group: P = 0.349; BM-MNC+G-CSF group: P = 0.907, Students t-test with Bonferroni correction, Figure The analysis of postischemic neurogenesis revealed no significant treatment effects on the generation of new neurons in any of the analyzed regions in postischemic brains of SH animals Figures . As expeP = 0.236, one-way ANOVA, Figure P = 0.949, one-way ANOVA, Figure P = 0.848, one-way ANOVA, Figure To investigate effects of the different treatment groups on angiogenesis Figures , blood vThe present study investigated the hypothesis that the combination of G-CSF and BM-MNCs is more effective than either treatment alone. Granulocyte-colony stimulating factor treated rats, either in combination with BM-MNCs or alone, showed a significantly improved functional recovery compared to placebo rats measured by the adhesive removal test. In contrast, early BM-MNC monotherapy did not improve somatosensory rehabilitation. Regeneration of gross motor function as tested by the cylinder test remained unaffected in animals of all treatment groups. The observed improvement of functional recovery in G-CSF-treated animals was not due to infarct volume reduction, thus suggesting a true recovery-enhancing effect of G-CSF rather than neuroprotective actions. Post-stroke neurogenesis and angiogenesis were not significantly enhanced after G-CSF treatment. Furthermore, the extent of the local inflammatory response to cerebral ischemia were comparable in all treatment groups.Initial reports indicated that treatment with BM-MNC might reduce neurological impairment in animal models of focal cerebral ischemia after application in acute and subacute phases (Iihoshi et al., In addition, timing of cell administration may have limited the therapeutic impact of BM-MNC transplantation as a therapeutic efficacy of BM-MNC application was previously shown for a time window between 3 h and 7 days only (Iihoshi et al., While the efficacy of BM-MNC treatment on post-stroke regeneration is diminished by the occurrence of co-morbidities, the rehabilitative effects of G-CSF are still ascertainable, albeit seemingly less pronounced. Zhao et al.  reportedGranulocyte-colony stimulating factor treatment as well as transplantation of BM-MNC both potentiate angiogenesis and neurogenesis (Lee et al., Transplanted BM-MNCs (Brenneman et al., Our study has strength and limitations. The experiments were conducted in concordance with recommendations for good preclinical stroke research (Sutherland et al., Our study confirms the beneficial effect of G-CSF treatment on long-term functional recovery following cortical stroke in hypertensive animals. Angiogenesis and neurogenesis, which are regarded as decisive mechanisms of G-CSF-mediated regeneration in normotensive animals, remained unaffected by G-CSF treatment in hypertensive animals. Contrary to our hypothesis, the combination of G-CSF and BM-MNC was not more effective than G-CSF alone and the monotherapy with BM-MNC was without any effect on functional recovery. The reduced efficacy of G-CSF treatment and the absence of any beneficial effect of BM-MNC transplantation might be attributed to hypertension-related morbidity. The findings of our study further corroborate the importance of evaluating the efficacy of treatments and determining the underlying neuroregenerative mechanisms in animal models more adequately reflecting the characteristic pathophysiological state of stroke patients.Wolf-Rüdiger Schäbitz is an inventor on a patent claiming the use of granulocyte colony-stimulating factor for the treatment of stroke. The other authors report no conflicts.


The present study was conducted to know the current scenario of classical swine fever (CSF) in Bengaluru Urban, Bengaluru Rural, Chikkaballapur, Madikeri, Mandya, Bagalkot, Gadag, Yadgir, Koppal, and Bidar districts of Karnataka with the using of both antigen and antibody ELISA.We collected 218 sera and 121 blood samples from pigs from 10 different districts of Karnataka. Screening of sera for CSF IgG antibody and whole blood for CSF virus antigen were carried out using the CSF virus (CSFV) antibody and antigen ELISA kits, respectively.The mean seroprevalence was 41% (89/218) and prevalence of CSFV antigen in blood samples was 32% (39/121) for the 10 districts of Karnataka. Seroprevalence of 61%, 29%, 20%, and 21%; and antigen prevalence of 40%, 50%, 13%, and 12% were recorded for Bangalore, Mysore, Belgaum, and Gulbarga divisions of Karnataka, respectively.The study revealed an alarmingly high prevalence of CSF, both for the antigen (32%) and antibody (41%) in Karnataka. Southern Karnataka has the highest seroprevalence , which confirms the endemicity of the disease in that region. This could be attributed to the intensive pig farming practices in the region as compared to Northern Karnataka , where the commercial pig farming is still in infantile stages. Pestivirus, which belongs to the family Flaviviridae. CSF is a World Organization for Animal Health (OIE) listed disease and outbreaks are reportable, with resultant trade sanctions against the affected countries [Classical swine fever (CSF) is a highly contagious disease of swine that has caused major economic losses in industrialized pig producing countries around the world . CSF virountries . CSF is ountries . The disountries . Howeverountries . CSF is ountries , and theountries  and Bhutountries . As withountries .et al. [et al. [The first documented report of CSF in India dates back to 1962, where an outbreak in a piggery unit in Morol, a suburb of Mumbai (formerly Bombay), and later in other parts of the city were described , Damodaret al.  and Sain [et al.  from the [et al. . The dis [et al. .Because of the sporadic nature of the disease and the lower preference for the pig farming (barring North-Eastern states) in India, CSF has not been studied systematically and therefore epidemiology of the disease is largely not fully understood . OccurreHowever, there are not much data available on the seroprevalence of CSFV infection in Karnataka. The present study was undertaken to obtain the baseline epidemiological information on the prevalence of CSF by analyzing both antigen and antibody in whole blood and serum, respectively.Institutional Animal Ethics Committee of Veterinary College, KVAFSU, Hebbal, Bangalore has accorded permission for the collection of blood from pigs for the study.Blood (n=121) and serum samples (n=218) were collected from pigs inappropriate vacutainer tubes from 10 different districts of Karnataka during September, 2013 to July, 2014 . ClottedUnivariate descriptive statistical analysis was used to calculate the percent positivity of antigen prevalence, seroprevalence and also to draw the significant inference.The study was conducted to determine the prevalence of CSF in Karnataka. The mean prevalence of CSFV antigen in blood samples was 32% 39/121) and seroprevalence was 41% (89/218) for the 10 districts of Karnataka. Prevalence by antigen ELISA was shown to be 40%, 50%, 13%, and 12% and seroprevalence was 61%, 29%, 20%, and 21% for Bangalore, Mysore, Belgaum, and Gulbarga divisions of Karnataka, respectively  when compared to samples from Belgaum and Gulbarga divisions. The incumbent changes were seen in samples from Bangalore and Mysore divisions both for antigen and seroprevalence.During 2014, a CSF study conducted in Karnataka showed an overall 33% (173/517) and 43%, 33%, 12%, and 6% of seroprevalences recorded for Bangalore, Mysore, Gulbarga, and Belgaum divisions, respectively .An alarmingly high prevalence of CSF antigen (32%) and antibodies (41%) in Karnataka, and notable prevalence of disease in the northern region where the piggery is still in primitive stages, was revealed. The regional distribution of antigen and seroprevalence reveals that Southern Karnataka  has the highest CSF prevalence, confirming the endemicity of the disease in that region. The Northern part of Karnataka showed a lower antigen and seroprevalence when compared to the South .The high prevalence of CSF in the southern region was attributed to a large number of pig farms when compared to the North, and regular procurement of piglets from pig breeding farms located in the adjoining border areas of Tamil Nadu and Kerala, where there were no CSF vaccination campaigns. The low prevalence of the disease in North Karnataka is probably because of the presence of less organized pig farms in the region, due to non-consumption of pork by the residents for social and cultural reasons.et al. [The study conducted at National Institute of Veterinary Epidemiology and Disease Informatics, Bangalore during 2012-2013 showed the seroprevalence of CSF in Kerala and Tamil Nadu to be approximately 77% (31/40) and 100% (10/10), respectively . This waet al.  reportedSero-surveillance, especially using techniques such as ELISA, is highly useful in disease eradication programs as it helps for mass screening and is effective in early diagnosis in nearby regions of an outbreak and becomes a good tool for surveillance of negative herds in countries where monitoring of the disease is being practiced. Prevalence based on the presence of viral antigen in the sample is generally used to estimate the incidence of the disease and when a non-vaccinated herd is positive for CSF-specific antibodies, it is can be considered as an indicative of a CSF disease outbreak. The present study confirms the prevalence of the disease in various regions of Karnataka as it allowed screening of samples representing all the areas of the state.The study revealed an alarmingly high prevalence of CSF, both for the antigen (32%) and antibody (41%) in Karnataka. Southern Karnataka has the highest seroprevalence , which confirms the endemicity of the disease in that region. This could be attributed to the intensive pig farming practices in the region as compared to Northern Karnataka , where the commercial pig farming is still in infantile stages.SSP and DR designed the experiment. PC carried out the study along with BMC and SG. RS and GBMR analyzed the data and prepared the manuscript. SI and HR reviewed the manuscript. All authors participated in scientific discussion. All authors read and approved the final manuscript.


Real-time shear-wave elastography (SWE) is a newly developed method which can obtain the stiffness of tissues and organs based on tracking of shear wave propagation through a structure. Several studies have demonstrated its potential in the differentiation between diseased and normal tissue in clinical practices, however the applicability to testicular disease has not been well elucidated. We investigated the feasibility and reproducibility of SWE in the detection of testicular torsion. This prospective study comprised 15 patients with complete testicular torsion. Results obtained from SWE along with conventional gray-scale and color Doppler sonography and post-operative pathology were compared. The results revealed that (i) the size of injured testis was increased and the twisted testis parenchyma was heterogeneous. The blood flow signals in injured testis were barely visible or absent; (ii) The Young’s modulus, including Emean, Emax, Emin and SD values in the border area of torsional testis were higher than those of normal testis ; The Emax and SD values in the central area of the torsional testis were higher than the corresponding area of the normal testis  and Emin values was lower than those of normal testicles; (iii) The Young's modulus measurement between two physicians showed good agreement. The pathological findings were accordance with SWE measurement. SWE is a non-invasive, convenient and high reproducible method and may serve as an important alternative tool in the diagnosis and monitoring the progression of the acute scrotums, in additional to conventional Doppler sonography. Testicular torsion, mainly occurred during adolescence, is one of the common acute scrotums. Each year, testicular torsion affects one in 4,000 males younger than 25 years old and accounts for 25% to 35% of pediatric scrotal emergency and 50–60% of scrotal emergency in teenagers –2 had reConventional Doppler sonography is sensitive, frequently revealing testicular heterogeneity and swelling and absent flow. It can provide reliable evidence for testicular torsion –9. But tElastography is a widely applied method which reflects the stiffness of the lesion and improves diagnostic confidence . ConventShear Wave Elastography  is a new elastography modality, which is totally different to conventional elastography technology. Real-time SWE is more operator-independent, reproducible, and quantitative because it may acquire the absolute quantification value of tissue stiffness without compressions by the operator or other external force –24. SWE Previous studies have shown that SWE outlines lesion  vividly and is very helpful in disease differentiation , 29–31. Fifteen patients with testicular torsion, with age of 8.67±2.64years old, had undergone orchiectomy from June 2013 to September 2014 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The mean clinical courses were 5.6 days. Ten cases were involved in left side and five in right side. The main clinical manifestations and signs were acute testis pain and markedly swollen scrotum. Bilateral testicles and appendages of 15 patients were performed with conventional sonography and SWE examination.All images were obtained using the Aixplorer system  equipped with a 15–4 MHz linear array transducer. Fifteen patients were examined in the standard manner for scrotal assessment using the machine settings for testicular sonographic examination. The patients lay in supine position. Immobilization of the scrotal contents was achieved using tissues beneath the scrotum, and with the patient crossing his legs to prevent movement. The operator adjusted the pulse repetition frequency, focal zone; gain and wall filter as necessary to obtain optimal sonograms in each case. Bilateral transverse and longitudinal slices of the scrotum and inguinal region are performed to allow side-to-side comparison of their sizes, echo texture and blood flow signal. The scale of flow velocity was set at 1-4cm/s.Precompression is a substantial factor in obtaining accurate results with elastography so that the operator should place the transducer onto the skin surface with light contact using ample coupling gel and keeping the transducer stationary during acquisitions in order to reduce compression on the structures,33–34. SSPSS19.0 statistical software was used for data analysis. Subject characteristics are presented as means±SD. Independent two sample t-test was used for comparisons of continuous variables between normal and twisted testis groups. P<0.05 was considered significant.The normal shape and size, and good blood flow perfusion were seen in uninjured testis . The injThe Emean, Emax, Emin and SD values in the border area of torsional testis were higher than those of normal testis kPa; SD, 7.67±0.60 kPa vs 2.30±0.36 kPa), and the difference had a statistical significance (P<0.05) see Figs  and 3; TFor further detection of the repeatability of SWE, the central areas of torsional testis were selected and the Emean, Emax, Emin and SD values in all cases were measured by two senior physicians. The results showed that all measurements between two physicians had a good agreement (P>0.05) .The torsional testis pathological characteristics included hemorrhage and necrosis. The size of torsional testis increased and the testis infarction appeared dark red or jet black . In HE sPhysical examination findings are helpful in distinguishing among epididymitis, testicular torsion, and torsion appendix testis. Patients with testicular torsion were much more likely to have a tender testicle, an abnormal testicular lie, and/or an absent cremasteric reflex when compared with patients with epididymitis . The mosSo far, the most commonly used diagnostic modality is Doppler sonography, followed by radio-nuclide imaging.99mTC scan is considered as the “gold standard” for diagnosis of testicular torsion. Scintigraphy using technetium 99m pertechnetate to evaluate the painful testicle has nearly 100% sensitivity for testicular torsion by displaying the "cold nodules" in sick side of testicle[ testicle. But it  testicle. In addiColor Doppler sonography can provide real-time, high quality images about anatomy and blood perfusion of testis and is much easier, less expensive, safer, readily repeatable, and more convenient with equal accuracy. It has been widely used in preoperative diagnosis of acute scrotum diseases, with a sensitivity of 88.9% and specificity of 98.8%  and has Though color Doppler Imaging has good sensitivity and specificity for the diagnosis of testicular torsion, some study proposed that there is disadvantage of Color Doppler Imaging in the detection of low velocity blood flow in the testis . HemodynWhen testis is torsional, the edema, hemorrhage and necrosis may arise in the torsional testis. Single Young's modulus, for example, Emean reflects the mean tissue hardness of ROI; sometimes it might lead to underestimate the degree of inhomogeneity in target lesions. In our study, the Emean in the central area of normal and torsional testis had no significant differences , it didnGenerally, good repeatability is important for the widespread adoption of any imaging technique. Some research showed that elastography was feasible and reproducible in kidney, liver, and other organ diseases –45. For High-resolution US is excellent for detecting different organ disease but has suboptimal accuracy for differential diagnosis using grey scale and Doppler sonography. So many studies have focused on proving the efficacy and diagnostic accuracy of SWE in the detection of thyroid nodule, breast lesions, cirrhosis, chronic kidney disease, muscle tissues and prostate disease , 46–49.For testicle disease, benign lesions can mimic tumor at conventional US techniques . The difHowever, to the best of our knowledge, there are few studies to date regarding the clinical application of SWE for testicular torsion. Kantarci  introducOur study showed SWE is able to quantify torsional testis elasticity and yields additional diagnostic data for clinic to identify testicular torsion. SWE is a non-invasive, convenient and repeatable method and may serve as a complementary tool in the diagnosis and monitoring the progression of the acute scrotums, in additional to Doppler sonography.