The Feasibility of Virtual Fall Risk Screens and Evidence-Based Program Referrals Using an Algorithmic Approach.

AIMS: 1) Can virtual fall risk screens be performed safely? 2) Are older adults able to manage technology to participate in telehealth? 3) Does an algorithm aid in referral appropriate evidence-based (EBP) fall prevention programs? METHODS: An algorithm was piloted using the Zoom platform to screen for falls, to assign to intervention groups, and to guide referral to EBP. Statistical analysis of data included descriptive, parametric, and non-parametric tests. RESULTS: Forty-four participants, aged 55-94 years, were screened. A significant relationship between 30-second chair stand and referral between two programs was found (p<0.05). Spearman correlations revealed statistically significant negative correlation between 30-second chair stand and timed up-and-go (TUG) (r= -0.584; p=0.003). No safety incidents occurred. Ninety-five percent of screened participants managed technology requirements successfully. CONCLUSION: Virtual fall risk screens are feasible and offer clinicians an alternative means to screen and refer older adults for EBP.

Advancing Antiracism in Community-Based Research Practices in Early Childhood and Family Mental Health.

Structural racism-the ways that institutional policies, practices, and other norms operate to create and sustain race-based inequities1-has historically been foundational to the operations of academic medical centers and research institutions. Since its inception, academic medicine has depended on the exploitation of vulnerable communities to achieve medical, educational, and research goals.2 Research practices have long ignored or taken advantage of the individuals purportedly benefiting from the research, a dynamic most manifestly true for Black, Indigenous, and People of Color (BIPOC) communities in the United States. Reflecting current practices in racial justice work, we intentionally use the term "BIPOC" to highlight shared experiences within racially and ethnically minoritized communities, given the history of White supremacy in the United States. We acknowledge limitations of this term, which collapses myriad unique communities and histories into one construct. Specifically, child and adolescent psychiatry has historically been driven by Eurocentric approaches, paradigms, and methodology. These nonparticipatory dominant research practices have contributed to a lack of culturally responsive interventions for BIPOC communities, a paucity of evidence-based practices with demonstrated effectiveness within BIPOC communities, and disparities in access and quality of care.3 Mental health research involving BIPOC communities has been replete with exploitation and inequality.2.

Sequential removal of selenate, nitrate and sulfate and recovery of elemental selenium in a multi-stage bioreactor process with redox potential feedback control.

Bioreduction can facilitate oxyanions removal from wastewater. However, simultaneously removing selenate, nitrate and sulfate and recovering high-purity elemental selenium (Se0) from wastewater by a single system is difficult and may lead to carcinogenic selenium monosulfide (SeS) formation. To solve this issue, a two-stage biological fluidized bed (FBR) process with ethanol dosing based on oxidation-reduction potential (ORP) feedback control was developed in this study. FBR1 performance was first evaluated at various ORP setpoints (between -520 and -360 mV vs. Ag/AgCl) and elevated sulfate concentration. Subsequently, ethanol-fed FBR2 was used to reduce sulfate from FBR1 effluent, followed by an aerated sulfide oxidation reactor (SOR). At - 520 mV≤ ORPs≤ -480 mV, FBR1 removed 100 ±â€¯0.1% nitrate and 99.7 ±â€¯0.3% selenate without sulfate reduction. At ORPs ≥ -440 mV, selenate reduction was incomplete, whereas nitrate removal remained stable. Se0 recovery efficiency from FBR1 effluent was 37.5% with 71% Se purity. FBR2 converted 86% of the remaining sulfate in FBR1 effluent to hydrogen sulfide, but the over-oxidation of dissolved sulfide in SOR decreased the overall sulfate removal efficiency to ~46.3%. Overall, the two-stage FBR process with ORP feedback dosing of ethanol was effective for sequentially removing selenate, nitrate and sulfate and recovering Se0 from wastewater.

Potential of Acidithiobacillus ferrooxidans to Grow on and Bioleach Metals from Mars and Lunar Regolith Simulants under Simulated Microgravity Conditions.

The biomining microbes which extract metals from ores that have been applied in mining processes worldwide hold potential for harnessing space resources. Their cell growth and ability to extract metals from extraterrestrial minerals under microgravity environments, however, remains largely unknown. The present study used the model biomining bacterium Acidithiobacillus ferrooxidans to extract metals from lunar and Martian regolith simulants cultivated in a rotating clinostat with matched controls grown under the influence of terrestrial gravity. Analyses included assessments of final cell count, size, morphology, and soluble metal concentrations. Under Earth gravity, with the addition of Fe3+ and H2/CO2, A. ferrooxidans grew in the presence of regolith simulants to a final cell density comparable to controls without regoliths. The simulated microgravity appeared to enable cells to grow to a higher cell density in the presence of lunar regolith simulants. Clinostat cultures of A. ferrooxidans solubilised higher amounts of Si, Mn and Mg from lunar and Martian regolith simulants than abiotic controls. Electron microscopy observations revealed that microgravity stimulated the biosynthesis of intracellular nanoparticles (most likely magnetite) in anaerobically grown A. ferrooxidans cells. These results suggested that A. ferrooxidans has the potential for metal bioleaching and the production of useful nanoparticles in space.

Effect of ferrous iron loading on dewaterability, heavy metal removal and bacterial community of digested sludge by Acidithiobacillus ferrooxidans.

Acidithiobacillus ferrooxidans ILS-2 was adapted in digested sludge and used to treat sludge for dewaterability improvement. Results showed that increasing ferrous iron loading increased sludge dewaterability, but the inoculation of the bioleaching strain had little effect on sludge dewaterability compared to controls without the strain. The total extracellular polymeric substances (EPS) contents of sludges with and without bioleaching treatment were similar except for bioleaching treatment at 10% ferrous iron loading (on sludge total solids) where total EPS was higher with bioleaching treatment. However, bioleaching treatment for 48 h had a notable effect on removal of heavy metals, such as Mn, Ni and Zn, especially at the high loadings of ferrous iron. In the presence of A. ferrooxidans, the removal of Ni, Mn and Zn reached 93%, 88% and 80%, respectively, at a ferrous iron loading of 21%. The sequencing of 16S rRNA genes indicated that increasing ferrous iron loadings to 15% and 21% increased the relative abundance of Acidithiobacillus, Acidocella (with A. ferrooxidans) and Carboxylicivirga (without A. ferrooxidans) but decreased the abundance of Pseudomonas and Acinetobacter after 48 h treatment. This study enhanced the understanding of the correlations between bioleaching treatment of digested sludge, sludge dewaterability, heavy metal removal and bacterial communities.

Deliberate practice and self-recorded demonstration of skill proficiency: One baccalaureate nursing school's response to the COVID-19 pandemic.

AIM: The purpose of this study was to determine whether using self-video recording of the skill competency assessment would promote deliberate practice of nursing skills, clinical skill proficiency, limit virtual high stakes testing anxiety and facilitate progression of first semester baccalaureate nursing students during the global COVID-19 pandemic. DESIGN: A cross-sectional study was conducted during the Spring 2020 semester using self-reported student data from an end of course survey. METHODS: A 16 item instructor-designed survey of student's perceptions of critical thinking, preparation, availability of materials, practice, video recording skill demonstrations, self-reported levels of anxiety related to the virtual testing environment and type of skill assessment exam was provided to all first semester baccalaureate nursing students enrolled in the basic nursing skills course. RESULTS: Approximately half of the cohort (N = 33) voluntarily responded to the instructor designed survey. The greatest relationship was observed between 'adequate information for each version' of the test and 'adequate time to prepare' (rho (32) = 0.729 p = 0.000). Although 54.6% (n = 18) of the respondents believed performing the demonstration in the home environment caused them to 'think harder' about the tasks, 78.8% (n = 26) reported feeling less anxiety than while performing previous demonstrations in the lab. A Wilcoxon test examined the results of the anxiety for demonstration on campus and anxiety for demonstration at home and a significant difference was found (p = 0.000, 95% CI) indicating anxiety levels were significantly less when demonstrating in the home environment. A moderate positive correlation was identified between opportunity to repeat with less stress at home (rho (32) = 0.61, p = 0.000), while moderate negative correlations were found between opportunity to repeat and anxiety levels related to recording (rho (32) = -0.60, p = 0.000), opportunity to repeat and anxiety related to demonstration at home (rho (32) = -0.53, p = 0.002) and concern about recording and opportunity to repeat (rho (32) = -0.49, p = 0.004). CONCLUSIONS: Student success using remote assessment strategies during the Spring 2020 semester was similar to the success rate using traditional skill assessment methods in Fall 2019. Although the need for prompt feedback was identified as an area of improvement to promote deliberate practice, student video recording of skill proficiency was a viable solution for comprehensive remote assessment during the COVID-19 pandemic and campus closure. Although further study is recommended, findings have international implications for virtual teaching and learning in nursing education.

Bioleaching of Gold from Sulfidic Gold Ore Concentrate and Electronic Waste by Roseovarius tolerans and Roseovarius mucosus.

Gold bioleaching mediated by iodide oxidizing bacteria (IOB) has been proposed as a sustainable alternative to conventional technologies such as cyanidation. This study evaluated the ability of two IOB sourced from a commercial culture collection, Roseovarius (R.) tolerans DSM 11457T and R. mucosus DSM 17069T, to bioleach gold from electronic waste (e-waste) (1030 ppm gold) and sulfidic gold ore concentrate (45 ppm gold) using one-step, two-step and spent medium leaching at 1% pulp density over 10 days. Two-step bioleaching of ore concentrate resulted in the highest gold leaching yields (approximately ~100% and 34% for R. tolerans and R. mucosus, respectively), followed by spent medium leaching and one-step leaching. The yields remained low for e-waste with both strains (maximum 0.93% and 1.6% for R. tolerans and R. mucosus, respectively) and decreased over time, likely due to the instability of the solubilized gold at relatively low redox potentials (<300 mV vs. Ag/AgCl). Another limiting factor may be the partial inhibition of bacterial growth in the presence of the ore concentrate and e-waste. Therefore, future studies should evaluate the pre-treatment of the ore concentrate and e-waste to remove inhibitory and oxidant consuming compounds before bioleaching with IOB to optimize leaching yields.

Sequential hydrotalcite precipitation and biological sulfate reduction for acid mine drainage treatment.

Hydrotalcite precipitation is a promising technology for the on-site treatment of acid mine drainage (AMD). This technology is underpinned by the synthesis of hydrotalcite that can effectively remove various contaminants. However, hydrotalcite precipitation has only limited capacity to facilitate sulfate removal from AMD. Therefore, the feasibility of coupling biological sulfate reduction with the hydrotalcite precipitation to maximize sulfate removal was evaluated in this study. AMD emanating from a gold mine (pH 4.3, sulfate 2000 mg L-1, with various metals including Al, Cd, Co, Cu, Fe, Mn, Ni, Zn) was first treated using the hydrotalcite precipitation. Subsequently, biological treatment of the post-hydrotalcite precipitation effluent was conducted in an ethanol-fed fluidized bed reactor (FBR) at a hydraulic retention time (HRT) of 0.8-1.6 day. The hydrotalcite precipitation readily neutralized the acidity of AMD and removed 10% of sulfate and over 99% of Al, Cd, Co, Cu, Fe, Mn, Ni, Zn. The overall sulfate removal increased to 73% with subsequent FBR treatment. Based on 454 pyrosequencing of 16S rRNA genes, the identified genera of sulfate-reducing bacteria (SRB) included Desulfovibrio, Desulfomicrobium and Desulfococcus. This study showed that sulfate-rich AMD can be effectively treated by integrating hydrotalcite precipitation and a biological sulfate reducing FBR.

A Single Synonymous Variant (c.354G>A [p.P118P]) in ADAMTS13 Confers Enhanced Specific Activity.

Synonymous variants within coding regions may influence protein expression and function. We have previously reported increased protein expression levels ex vivo (~120% in comparison to wild-type) from a synonymous polymorphism variant, c.354G>A [p.P118P], of the ADAMTS13 gene, encoding a plasma protease responsible for von Willebrand Factor (VWF) degradation. In the current study, we investigated the potential mechanism(s) behind the increased protein expression levels from this variant and its effect on ADAMTS13 physico-chemical properties. Cell-free assays showed enhanced translation of the c.354G>A variant and the analysis of codon usage characteristics suggested that introduction of the frequently used codon/codon pair(s) may have been potentially responsible for this effect. Limited proteolysis, however, showed no substantial influence of altered translation on protein conformation. Analysis of post-translational modifications also showed no notable differences but identified three previously unreported glycosylation markers. Despite these similarities, p.P118P variant unexpectedly showed higher specific activity. Structural analysis using modeled interactions indicated that subtle conformational changes arising from altered translation kinetics could affect interactions between an exosite of ADAMTS13 and VWF resulting in altered specific activity. This report highlights how a single synonymous nucleotide variation can impact cellular expression and specific activity in the absence of measurable impact on protein structure.

Effect of Quorum Sensing on the Ability of Desulfovibrio vulgaris To Form Biofilms and To Biocorrode Carbon Steel in Saline Conditions.

Sulfate-reducing bacteria (SRB) are key contributors to microbe-induced corrosion (MIC), which can lead to serious economic and environmental impact. The presence of a biofilm significantly increases the MIC rate. Inhibition of the quorum-sensing (QS) system is a promising alternative approach to prevent biofilm formation in various industrial settings, especially considering the significant ecological impact of conventional chemical-based mitigation strategies. In this study, the effect of the QS stimulation and inhibition on Desulfovibrio vulgaris is described in terms of anaerobic respiration, cell activity, biofilm formation, and biocorrosion of carbon steel. All these traits were repressed when bacteria were in contact with QS inhibitors but enhanced upon exposure to QS signal molecules compared to the control. The difference in the treatments was confirmed by transcriptomic analysis performed at different time points after treatment application. Genes related to lactate and pyruvate metabolism, sulfate reduction, electron transfer, and biofilm formation were downregulated upon QS inhibition. In contrast, QS stimulation led to an upregulation of the above-mentioned genes compared to the control. In summary, these results reveal the impact of QS on the activity of D. vulgaris, paving the way toward the prevention of corrosive SRB biofilm formation via QS inhibition.IMPORTANCE Sulfate-reducing bacteria (SRB) are considered key contributors to biocorrosion, particularly in saline environments. Biocorrosion imposes tremendous economic costs, and common approaches to mitigate this problem involve the use of toxic and hazardous chemicals (e.g., chlorine), which raise health and environmental safety concerns. Quorum-sensing inhibitors (QSIs) can be used as an alternative approach to inhibit biofilm formation and biocorrosion. However, this approach would only be effective if SRB rely on QS for the pathways associated with biocorrosion. These pathways would include biofilm formation, electron transfer, and metabolism. This study demonstrates the role of QS in Desulfovibrio vulgaris on the above-mentioned pathways through both phenotypic measurements and transcriptomic approach. The results of this study suggest that QSIs can be used to mitigate SRB-induced corrosion problems in ecologically sensitive areas.

Activator of G protein signaling 3 forms a complex with resistance to inhibitors of cholinesterase-8A without promoting nucleotide exchange on Gα(i3).

Activator of G protein signaling 3 (AGS3) is a guanine nucleotide dissociation inhibitor (GDI) which stabilizes the Gα(i/o) subunits as an AGS3/Gα(i/o)-GDP complex. It has recently been demonstrated in reconstitution experiments that the AGS3/Gα(i/o)-GDP complex may act as a substrate of resistance to inhibitors of cholinesterase 8A (Ric-8A), a guanine exchange factor (GEF) for heterotrimeric Gα proteins. Since the ability of Ric-8A to activate Gα(i/o) subunits that are bound to AGS3 in a cellular environment has not been confirmed, we thus examined the effect of Ric-8A on cAMP accumulation in HEK293 cells expressing different forms of AGS3 and Gα(i3). Co-immunoprecipitation assays indicate that full-length AGS3 and its N- and C-terminal truncated mutants can interact with Ric-8A in HEK293 cells. Yeast two-hybrid assay further confirmed that Ric-8A can directly bind to AGS3S, a short form of AGS3 which is endogenously expressed in heart. However, Ric-8A failed to facilitate Gα(i)-induced suppression of adenylyl cyclase, suggesting that it may not serve as a GEF for AGS3/Gα(i/o)-GDP complex in a cellular environment.

Bacterial community and groundwater quality changes in an anaerobic aquifer during groundwater recharge with aerobic recycled water.

Managed aquifer recharge offers the opportunity to manage groundwater resources by storing water in aquifers when in surplus and thus increase the amount of groundwater available for abstraction during high demand. The Water Corporation of Western Australia (WA) is undertaking a Groundwater Replenishment Trial to evaluate the effects of recharging aerobic recycled water (secondary treated wastewater subjected to ultrafiltration, reverse osmosis, and ultraviolet disinfection) into the anaerobic Leederville aquifer in Perth, WA. Using culture-independent methods, this study showed the presence of Actinobacteria, Alphaproteobacteria, Bacilli, Betaproteobacteria, Cytophaga, Flavobacteria, Gammaproteobacteria, and Sphingobacteria, and a decrease in microbial diversity with an increase in depth of aquifer. Assessment of physico-chemical and microbiological properties of groundwater before and after recharge revealed that recharging the aquifer with aerobic recycled water resulted in elevated redox potentials in the aquifer and increased bacterial numbers, but reduced microbial diversity. The increase in bacterial numbers and reduced microbial diversity in groundwater could be a reflection of an increased denitrifier and sulfur-oxidizing populations in the aquifer, as a result of the increased availability of nitrate, oxygen, and residual organic matter. This is consistent with the geochemical data that showed pyrite oxidation and denitrification within the aquifer after recycled water recharge commenced.

A robust microfluidic in vitro cell perifusion system.

We present here a robust microfluidic cell perifusion device for in vitro primary tissue cell secretion studies. This system increases the sample concentration to perifusion volume ratio by an order of magnitude compared with standard multi-well plate static incubation assays. Further, this device achieves physiologically relevant flow rates, pressures, and temperature. It has been manufactured with typical machining facilities, principally drilling and milling. No specialist clean room equipment is required to replicate it. We show its capability here with hormone perifusion experiments on primary pancreatic tissue from mice. This device can increase cell secretion concentrations by up to a factor of 20, allowing for the first time the direct measurement of islet glucagon using mass spectrometry.

Glutamatergic modulatory therapy for Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the presence of chronic, fluctuating motor and vocal (phonic) tics. The disorder is commonly associated with a variety of comorbidities including obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), school problems, anxiety, and depression. Therapeutically, if tics are causing psychosocial or physical problems, symptomatic medications are often prescribed, typically alpha-adrenergic agonists or dopamine antagonists. Recognizing that therapy is often ineffective and frequently associated with unacceptable side-effects, there is an ongoing effort to identify new tic-suppressing therapies. Several lines of evidence are presented that support the use of glutamate modulators in TS including glutamate's major role in cortico-striatal-thalamo-cortical circuits (CSTC), the recognized extensive interaction between glutamate and dopamine systems, results of familial genetic studies, and data from neurochemical analyses of postmortem brain samples. Since insufficient data is available to determine whether TS is definitively associated with a hyper- or hypo-glutamatergic state, potential treatment options using either glutamate antagonists or agonists are reviewed. Data from studies using these agents in the treatment of OCD are presented. If validated, modulation of the glutamate system could provide a valuable new pharmacological approach in the treatment of tics associated with Tourette syndrome.

Childhood serum anti-fetal brain antibodies do not predict autism.

Autoimmune hypotheses for autism include in utero transplacental exposure to maternal antibodies and acquired postnatal insults. Previous work demonstrated that some mothers of children with autistic disorder have specific antibodies against human fetal brain that differentiate them from mothers with typical children. In the present study, Western immunoblotting was used to determine whether children with autistic spectrum disorders (n = 29) have serum reactivity against human fetal brain that differs from that of controls (n = 14). There was no significant difference in reactivity, corrected for serum immunoglobulin G content and brain actin content and with special attention to reactive bands at 36, 39, 61, and 73 kDa, between autistic children and normal control subjects. Thus, in contrast to mothers, antibody reactivity against human fetal brain as measured in children ages 3-12 years does not appear to be a useful biomarker for autism.

Antineuronal antibodies in OCD: comparisons in children with OCD-only, OCD+chronic tics and OCD+PANDAS.

Autoimmunity associated with a streptococcal infection has been proposed as a pathogenic mechanism for obsessive-compulsive disorder (OCD) in children. Antibrain antibody profiles were compared in children with OCD-only (n = 13; 14.1 +/- 3.1 years), OCD+PANDAS (n = 20; 11.3 +/- 1.5 years), OCD+Chronic Tic Disorder (n = 23; 13.4 +/- 3.5 years), and controls (n = 29; 12.4 +/- 2.4 years) using ELISA (orbitofrontal (OFC) and dorsolateral prefrontal cortex (DLPFC), caudate (CD), cingulate gyrus (CG)), immunoblotting (four regions plus putative antigens), and immunohistochemistry. ELISA and immunohistochemistry showed no differences among groups. Immunoblot showed that a greater percentage of individuals in the OCD+PANDAS cohort had reactive bands at 27 kDa (CD, CG, DLPFC), 36 kDa (CD), and 100 kDa (CD, OFC) and increased peak height at 67 kDa (all regions). Immunoblotting studies using the putative antigens (pyruvate kinase M1, aldolase C, alpha- and gamma-enolase) did not differ among groups. ASO titers were similar in all groups and did not correlate with immunoassays. It remains controversial whether childhood OCD is associated with autoimmune mechanisms.

Double-blind, crossover study of clonidine and levetiracetam in Tourette syndrome.

We compared the efficacy of clonidine and levetiracetam for treating tics in Tourette syndrome. Twelve subjects were enrolled; 10 (ages 8-27 years) with moderate to moderately severe tics completed a 15-week randomized, double-blind, flexible-dose crossover protocol. Initial medication doses were clonidine (0.05 mg, twice daily) or levetiracetam (10 mg/kg/day, divided twice daily). Doses were adjusted weekly, based on telephone assessment. The primary outcome measure was baseline-to-posttreatment (6-week) change in Total Tic Score of the Yale Global Tic Severity Scale. Secondary outcome measures included total Yale Global Tic Severity Scale and Clinical Global Impression scores and behavioral measures. The mean Total Tic Score improved significantly from baseline to posttreatment with clonidine (25.2 versus 21.8) compared with levetiracetam (22.7 versus 23.6) (P = 0.013). The mean total Yale Global Tic Severity Scale and Clinical Global Impression score did not change. For levetiracetam, no changes occurred in any scales. No significant change occurred in any secondary behavioral outcome measures for either group. The most commonly reported side effects were, for clonidine, sedation (n = 5), and for levetiracetam, irritability (n = 4). Treatment with clonidine, but not levetiracetam, resulted in a small reduction in Total Tic Score, with an effect size of 0.57.

Prenatal exposure to antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model.

A pregnant mouse model was used to compare the effect of IgG, administered E13-E18, from mothers of children with autistic disorder (MCAD), to controls (simple- and IgG-) on behavioral testing in offspring. Mice, exposed in-utero to MCAD-IgG, as adolescents, were more active during the first ten minutes of central field novelty testing and, as adults, displayed anxiety-like behavior on a component of the elevated plus maze and had a greater magnitude of startle following acoustic stimulation. On a social interaction paradigm, adult mice had alterations of sociability. Pilot studies of immune markers in MCAD IgG-exposed embryonic brains suggest evidence of cytokine and glial activation. These studies demonstrate that the transplacental passage of IgG from MCAD is capable of inducing long-term behavioral consequences.

Multiple Gi proteins participate in nerve growth factor-induced activation of c-Jun N-terminal kinases in PC12 cells.

Nerve growth factor (NGF)-mediated activation of mitogen-activated protein kinases (MAPK) is critical for differentiation and apoptosis of PC12 cells. Since NGF employs stress-activated c-Jun N-terminal kinase (JNK) to regulate both programmed cell death and neurite outgrowth of PC12 cells, we examined NGF-regulated JNK activity and the role of G(i/o) proteins. Induction of JNK phosphorylation by NGF occurred in a time- and dose-dependent manner and was partially inhibited by pertussis toxin (PTX). To discern the participation of various signaling intermediates, PC12 cells were treated with specific inhibitors prior to NGF challenge. NGF-elevated JNK activity was abolished by inhibitors of JNK, p38 MAPK, Src, JAK3 and MEK1/2. NGF-dependent JNK phosphorylation became insensitive to PTX treatment upon transient expressions of Galpha(z) or the PTX-resistant mutants of Galpha(i1-3) and Galpha(oA). Collectively, these studies indicate that NGF-dependent JNK activity may be mediated via G(i1-3) proteins, JAK3, Src, p38 MAPK and the MEK/ERK cascade.

Serum autoantibodies measured by immunofluorescence confirm a failure to differentiate PANDAS and Tourette syndrome from controls.

PANDAS and some cases of Tourette syndrome (TS) have been proposed to be post-streptococcal movement disorders in which antibodies produced against group A beta-hemolytic streptococcus cross react against brain epitopes. Attempts to identify disease specific anti-striatal antibodies in the serum of affected patients have focused on the use of Western immunoblotting and ELISA methodologies. In this study, immunohistochemical techniques were used to identify serum anti-striatal antibody reactivity. In positive samples, double staining with anti-GFAP (glial) and anti-MAP2 (neuronal) was used to establish localization of the immunofluorescence. No significant differences in immunofluorescence or localization were identified in patients with PANDAS (n=30) and TS (n=30) as compared to controls (n=30). IF reactivity did not correlate with tic severity or elevated titers of antistreptococcal antibodies. Further comparisons showed no correlation between autoreactivity determined by immunofluorescence and the presence of previously measured immunoblot reactivity against human caudate or putative antigens (pyruvate kinase M1 and aldolase C). These results confirm an inability to distinguish patient populations by antibody measurements and raise further concerns about the presence of an autoimmune mechanism in PANDAS and TS.