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Abstract The development of a basin‐specific comprehensive flood record using publicly available data for the James River Basin, Virginia. Using mixed surface analysis maps (NOAA, NWS), historical hurricane records (IBTrACS, HURDAT2), and flood and river gauge records (NWS, USGS), a database is created for analysis. Related to creating this database, a novel classification of six unique weather systems (non‐tropical and tropical) responsible for flooding is presented. The analysis includes Two‐Way tables with observed marginal and joint probabilities in various potential flood, storm, and regional combinations. Results show 233 tropical systems passed within the 500‐km study area, with 12.4%, or 29 systems of those systems causing flooding within the basin. An additional 713 events were non‐tropical, composing the majority of flood sources in the basin. Non‐tropical systems are responsible for 84% of the worst floods recorded, leading to an increased frequency of 6% yearly since 1941 and nearly 770% between 2014 and 2018. The findings of this study will be the basis for assessing land use and population patterns in the area, along with a future compound flooding model for the lower James River Basin.

It is believed that DNA double-strand breaks induced by Zika virus (ZIKV) infection in pregnant women is a main reason of brain damage (e.g. microcephaly, severe brain malformation, and neuropathy) in newborn babies [1,2], but its underlying mechanism is poorly understood. In this study, we report that the depletion of ERp57, a member of the protein disulphide isomerase (PDI) family, leads to the limited production of ZIKV in nerve cells. ERp57 knockout not only suppresses viral induced reactive oxygen species (ROS) mediated host DNA damage, but also decreases apoptosis. Strikingly, DNA damage depends on ERp57-bridged complex formation of viral protein NS2B/NS3. LOC14, an ERp57 inhibitor, restricts ZIKV infection and virus-induced DNA damage. Our work reveals an important role of ERp57 in both ZIKV propagation and virus-induced DNA damage, suggesting a potential target against ZIKV infection.

Purpose: This study aims to examine predisposing anatomic factors and subsequent post-decompression functional outcomes among high-intensity athletes with thoracic outlet syndrome (TOS). Materials and Methods : A single-institution retrospective review was performed on a prospective database of patients with TOS from 2018 to 2023 who had undergone operative decompression for TOS. Demographics, TOS characteristics, predisposing anatomy, operative details, and postoperative outcomes were examined. The primary outcome was postoperative return to sport. Secondary outcomes included vascular patency. Results : A total of 13 patients who were engaged in high-demand athletic activity at the time of their diagnosis were included. Diagnoses included 8 (62%) patients with venous TOS, 4 (31%) patients with neurogenic TOS, and 1 (8%) patient with arterial TOS. Mixed vascular and neurogenic TOS was observed in 3 (23%) patients. The mean age of the cohort was 30 years. Abnormal scalene structure was observed in 12 (92%) patients, and abnormal bone structures were noted in 4 (27%) patients; 2 (15%) with cervical ribs and 3 (23%) patients with clavicular abnormalities. Prior ipsilateral upper extremity trauma was reported in 4 (27%) patients. Significant joint hypermobility was observed in 8 (62%) patients with a median Beighton score of 6. Supraclavicular cervical and/or first rib resection with scalenectomy was performed in all patients. One case of postoperative pneumothorax was treated non-operatively. Ten (77%) patients returned to sport. Duplex ultrasonography showed subclavian vein patency in all 8 patients with venous TOS and wide patency with no drop in perfusion indices in the patient with arterial TOS. Conclusion : Athletes with TOS who required operative intervention had a high incidence of musculoskeletal aberrations and joint hypermobility. Supraclavicular decompression was associated with a high success rate, with overall good functional outcomes and good likelihood of patients returning to preoperative high-intensity athletics.

We describe the case of a 62-year-old man presenting 2 months after a reversed great saphenous vein femoropopliteal bypass performed for critical limb ischemia. He was found to have early, high-grade bypass graft stenosis on duplex ultrasound. Subsequent angiography demonstrated flow limitations secondary to two areas of retained venous valves in the proximal and mid-portions of the vein graft. The culprit valve lesions were successfully lysed endovascularly with a HawkOne (Medtronic) directional atherectomy device. This case demonstrates a safe, novel use of a directional atherectomy device for treatment of remnant valves causing hemodynamically significant flow problems in peripheral vein grafts.

Purpose: To identify demographic trends of foreign object genital injuries presenting to emergency departments from 2011 to 2020. Materials and Methods: The National Electronic Injury Surveillance System database reports consumer product-related injuries in United States ED visits. The database was queried to identify 375 cases of genital injuries from 2011 to 2020. Inclusion criteria consisted of cases reporting injuries involving the urethra, penis, or scrotum. Data was reported and analyzed using linear regression. Results: Based on 375 cases, an estimated 13,170 (95% confidence interval, 10,817–15,522) patients in the US suffered genital injuries due to foreign bodies between 2011 and 2020. These injuries involved the penis (65.9%), urethra (30.7%) and scrotum (3.5%). Of all patients, 11.8% required hospital admission after treatment of which injuries to the urethra were most common (44.0%). Most of these patients were ages 19 to 64 (66.1%). Consumer products most implicated included rings (50.7%), zippers (17.1%), and pens and pencils (10.3%). Injuries due to zippers and swimming apparel occurred significantly more frequently in patients ages 0–18 (p

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

Abstract Background Treatment of chronic illness accounts for over 90% of Medicare spending. Chronic lymphedema places 3–10 million Americans at risk for recurrent cellulitis. Without convincing predictions of the costs and benefits of lymphedema treatment, insurers are reluctant to fully cover treatment of this common condition. Earlier papers discussed the costs and benefits of the first 5, 7, and 10 years of a lymphedema treatment mandate in Virginia. This paper updates these costs and benefits to 16 years of experience, and includes the impacts of the Patient Protection and Affordable Care Act of 2010 and the transition to ICD-10-CM diagnostic codes in 2015. It provides added confidence that costs of a lymphedema treatment mandate are reasonable, and can result in health insurance contract savings for reduced medical visits and hospitalizations for lymphedema patients. Methods Virginia requires annual reporting of the segregated costs of each of its 30 medical mandates. Data on Virginia’s lymphedema treatment mandate for the years 2004 to 2019 have been collected from the series of annual reports. These data include actual lymphedema treatment claims data, utilization data, and claims-based estimates of the premium impact. Results The average actual lymphedema claim cost was $2.03 per individual contract and $3.54 per group contract for the years reported, representing 0.05 and 0.08% of average total claims. The estimated premium impact was 0.16–0.32% of total average premium for all mandated coverage contracts. While lymphedema claim costs increased 3–6% per year over the study period, generally following the rise of health care costs, claim costs as a percent of average contract claims fell at a rate of 1.26–1.52% per year over that period. Medical office visits for lymphedema-related services fell from 0.10 to 0.02 visits per year per contract from the beginning to the end of the study period, and hospitalizations for lymphedema or lymphedema-related cellulitis fell to almost zero. Conclusions The Virginia data confirmed previous conclusions that the costs of treatment of lymphedema are a small part of a typical health insurance contract, and that treatment of lymphedema by managing swelling results in lower overall medical costs and fewer hospitalizations. This is a potent model for reduction in healthcare costs while improving the quality of care for cancer survivors and others suffering with this chronic progressive condition.

A 37-year-old male with a history of chronic nephrolithiasis presented to the ED with gross hematuria, clot retention, and right flank pain. The patient had radiological findings of perinephric stranding, marked hydronephrosis, and marked thinning of the right renal parenchyma on computed tomography (CT), all suggestive of xanthogranulomatous pyelonephritis (XGP). The specimen following radical nephrectomy revealed urothelial carcinoma (UC) in a background of XGP but with no evidence of spread to regional lymph nodes. Follow-up imaging revealed hypodense lesions in the liver which demonstrated UC on biopsy. This is the first reported case of a young patient presenting with such an advanced stage of UC in the setting of XGP. It illustrates the link between inflammatory processes of the kidney and malignancy of the upper urinary tract.

Rising sea level in the next century exposes the Ports of Los Angeles and Long Beach to higher hazards from Alaskan tsunamis. By 2100, waves generated by an M8 Alaskan earthquake cause similar impacts in California to waves from an Alaskan M9 today.

Adult (3 month) mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TGAC8) adapt to an increased cAMP-induced cardiac workload (~30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here, we show classical cardiac hypertrophy markers were absent in TGAC8, and that total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TGAC8 was encased by thicker LV walls harboring an increased number of small cardiac myocytes, and a network of small interstitial proliferative non-cardiac myocytes compared to wild type (WT) littermates; Protein synthesis, proteosome activity, and autophagy were enhanced in TGAC8 vs WT, and Nrf-2, Hsp90α, and ACC2 protein levels were increased. Despite increased energy demands in vivo LV ATP and phosphocreatine levels in TGAC8 did not differ from WT. Unbiased omics analyses identified more than 2,000 transcripts and proteins, comprising a broad array of biological processes across multiple cellular compartments, which differed by genotype; compared to WT, in TGAC8 there was a shift from fatty acid oxidation to aerobic glycolysis in the context of increased utilization of the pentose phosphate shunt and nucleotide synthesis. Thus, marked overexpression of AC8 engages complex, coordinate adaptation "circuity" that has evolved in mammalian cells to defend against stress that threatens health or life (elements of which have already been shown to be central to cardiac ischemic pre-conditioning and exercise endurance cardiac conditioning) that may be of biological significance to allow for proper healing in disease states such as infarction or failure of the heart.

Low availability of sustainable biomass prevents transition of district heating in Europe away from fossil fuels. The need for sustainable fuels stems from current energy generation structure, which mainly relies on centralised combined heat and power operated as baseload units. Our study shows that districts with generation of renewable power, heat and synthetic natural gas can reach complete energy system decarbonisation even without biomass, only using wind and solar power as primary energy. It requires rethinking of interactions between electricity, gas and heating networks and a polygeneration solution with power-to-heat and power-to-gas technologies to fully utilise local solar and wind power and cover peak demands. Power-to-heat as baseload units supported with power-to-gas for seasonal and back-up energy storage are proposed as novel district heating approach. The operation of such polygeneration is tested successfully using a model of a Finnish district. Carbon dioxide circulation is analysed together with capacity requirements to synthetic natural gas and needed wind power installation. Resulting complete decarbonisation requires coordination and flexible operation of power-to-heat and power-to-gas capacity together with gas-fired combined heat and power plants and heat-only boilers, which ensures that renewable power production, heating and power needs, security of supply and grid limitations are met.

The hazard from earthquake-generated tsunami waves is not only determined by the earthquake’s magnitude and mechanisms, and distance to the earthquake area, but also by the geomorphology of the nearshore and onshore areas, which can change over time. In coastal hazard assessments, a changing coastal environment is commonly taken into account by increasing the sea-level to projected values (static). However, sea-level changes and other climate-change impacts influence the entire coastal system causing morphological changes near- and onshore (dynamic). We compare the run-up of the same suite of earthquake-generated tsunamis to a barrier island-marsh-lagoon-marsh system for statically adjusted and dynamically adjusted sea level and bathymetry. Sea-level projections from 2000 to 2100 are considered. The dynamical adjustment is based on a morphokinetic model that incorporates sea-level along with other climate-change impacts. We employ Representative Concentration Pathways 2.6 and 8.5 without and with treatment of Antarctic Ice-sheet processes (known as K14 and K17) as different sea-level projections. It is important to note that we do not account for the occurrence probability of the earthquakes. Our results indicate that the tsunami run-up hazard for the dynamic case is approximately three times larger than for the static case. Furthermore, we show that nonlinear and complex responses of the barrier island-marsh-lagoon-marsh system to climate change profoundly impacts the tsunami hazard, and we caution that the tsunami run-up is sensitive to climate-change impacts that are less well-studied than sea-level rise.

Abstract Boulders are excellent candidate deposits to study coastal inundation events by storms and tsunamis due to their significant preservation potential. However, it is difficult to infer how and what forcing dislodged the boulder. We present a new model that enables ensemble and Monte‐Carlo‐type simulations to study the sensitivity of boulder, the fluid flow, and environmental parameters. Our examples show that boulder transport is complex and nonlinear, and to acknowledge the uncertainties of the boulder's preexisting transport conditions, a range of velocities and environmental parameters should be used to quantify the flow that caused boulder dislodgement.

Introduction Opioid agonist treatment is effective for opioid dependence and newer extended-release buprenorphine (BUP-XR) injections represent a significant development. The Community Long-Acting Buprenorphine (CoLAB) study aims to evaluate client outcomes among people with opioid dependence receiving 48 weeks of BUP-XR treatment, and examines the implementation of BUP-XR in diverse community healthcare settings in Australia.Methods and analysis The CoLAB study is a prospective single-arm, multicentre, open-label trial of monthly BUP-XR injections in people with opioid dependence. Participants are being recruited from a network of general practitioner and specialist drug treatment services located in the states of New South Wales, Victoria and South Australia in Australia. Following a minimum 7 days on 8–32 mg of sublingual buprenorphine (±naloxone), participants will receive monthly subcutaneous BUP-XR injections administered by a healthcare practitioner at intervals of 28 days (−2/+14 days). The primary endpoint is participant retention in treatment at 48 weeks after treatment initiation. Secondary endpoints will evaluate dosing schedule variations, craving, withdrawal, substance use, health and well-being, and client-reported treatment experience. Qualitative and costing substudies will examine implementation barriers and facilitators at the client and provider level.Ethics and dissemination The study has received ethics approval from the St Vincent’s Hospital Sydney Human Research Ethics Committee (Ref. HREC/18/SVH/221). The findings will be disseminated via publication in peer-reviewed journals, presentations at national and international scientific conferences, and in relevant community organisation publications and forums.Trial registration number NCT03809143Protocol identifier CoLAB1801, V.4.0 dated 01 August 2019

Coastal boulder deposits (CBD), transported by waves at elevations above sea level and substantial distances inland, are markers for marine incursions. Whether they are tsunami or storm deposits can be difficult to determine, but this is of critical importance because of the role that CBD play in coastal hazard analysis. Equations from seminal work by Nott (1997), here referred to as the Nott Approach, are commonly employed to calculate nominal wave heights from boulder masses as a means to discriminate between emplacement mechanisms. Systematic review shows that this approach is based on assumptions that are not securely founded and that direct relationships cannot be established between boulder measurements and wave heights. A test using an unprecedented dataset of boulders moved by storm waves (with associated sea-state data) shows a lack of agreement between calculations and actual wave heights. The equations return unrealistically large heights, many of which greatly exceed sea states occurring during the boulder-moving storms. This underscores the finding that Nott-Approach wave-height calculations are unreliable. The result is general, because although the field data come from one region (the Aran Islands, Ireland), they represent a wide range of boulder masses and topographic settings and present a valid test of hydrodynamic equations. This analysis demonstrates that Nott Approach equations are incapable of distinguishing storm waves from tsunami transport and that wave heights hindcast from boulder masses are not meaningful. Current hydrodynamic understanding does not permit reliable computation of wave height from boulder measurements. A combination of field, numerical, and experimental approaches is required to quantify relationships between wave power and mass transport onshore. Many CBD interpreted as tsunami deposits based on Nott-Approach analysis may in fact have been emplaced during storms and should therefore be re-evaluated. This is especially important for CBD that have been incorporated into long-term coastal risk assessments, which are compromised if the CBD are misinterpreted. CBD dynamics can be better determined from a combination of detailed field measurements, modeling, and experiments. A clearer understanding of emplacement mechanisms will result in more reliable hazard analysis.

Consistent calibration and monitoring is a basic prerequisite for providing a reliable time series of global and regional sea-level variations from altimetry. The precisions of sea-level measurements and regional biases for six altimeter missions (Jason-1/2/3, Envisat, Saral, Sentinel-3A) are assessed in this study at 11 GNSS-controlled tide gauge stations in the German Bight (SE North Sea) for the period 2002 to 2019. The gauges are partly located at the open water, and partly at the coast close to mudflats. The altimetry is extracted at virtual stations with distances from 2 to 24 km from the gauges. The processing is optimized for the region and adjusted for the comparison with instantaneous tide gauge readings. An empirical correction is developed to account for mean height gradients and slight differences of the tidal dynamics between the gauge and altimetry, which improves the agreement between the two data sets by 15–75%. The precision of the altimeters depends on the location and mission and ranges from 1.8 to 3.7 cm if the precision of the gauges is 2 cm. The accuracy of the regional mission biases is strongly dependent on the mean sea surface heights near the stations. The most consistent biases are obtained based on the CLS2011 model with mission-dependent accuracies from 1.3 to 3.4 cm. Hence, the GNSS-controlled tide gauges operated operationally by the German Waterway and Shipping Administration (WSV) might complement the calibration and monitoring activities at dedicated CalVal stations.

Low elevation coastal zones (LECZ) are extensive throughout the southeastern United States. LECZ communities are threatened by inundation from sea level rise, storm surge, wetland degradation, land subsidence, and hydrological flooding. Communication among scientists, stakeholders, policy makers and minority and poor residents must improve. We must predict processes spanning the ecological, physical, social, and health sciences. Communities need to address linkages of (1) human and socioeconomic vulnerabilities; (2) public health and safety; (3) economic concerns; (4) land loss; (5) wetland threats; and (6) coastal inundation. Essential capabilities must include a network to assemble and distribute data and model code to assess risk and its causes, support adaptive management, and improve the resiliency of communities. Better communication of information and understanding among residents and officials is essential. Here we review recent background literature on these matters and offer recommendations for integrating natural and social sciences. We advocate for a cyber-network of scientists, modelers, engineers, educators, and stakeholders from academia, federal state and local agencies, non-governmental organizations, residents, and the private sector. Our vision is to enhance future resilience of LECZ communities by offering approaches to mitigate hazards to human health, safety and welfare and reduce impacts to coastal residents and industries.

A new method for the optimization of seasonal energy storage is presented and applied in a case study. The optimization method uses an interval halving approach to solve computationally demanding mixed integer linear programming (MILP) problems with both integer and non-integer operation variables (variables that vary from time step to time step in during energy storage system operation). The seasonal energy storage in the case study uses a reversible solid oxide cell (RSOC) to convert electricity generated by solar photovoltaic (PV) panels into hydrogen gas and to convert hydrogen gas back to electricity while also generating some heat. Both the case study results and the optimization method accuracy are examined and discussed in the paper. In the case study, the operation of the RSOC and hydrogen storage system is compared with the operation of a reference system without energy storage. The results of the study show that installing an RSOC and hydrogen storage system could increase the utilization of onsite renewable energy generation significantly. Overall, the optimization method presents a relatively accurate solution to the case study optimization problem and a sensibility analysis shows a clear and logical pattern.

Cone Beam Computed Tomography (CBCT) is a valuable imaging technique in oral and maxillofacial surgery (OMS) that can help direct a surgeon’s approach to a variety of conditions. A 3-dimensional analysis of head and neck anatomy allows practitioners to plan appropriately, operate with confidence, and assess results post-operatively. CBCT imaging has clear indications and limitations. CBCT offers the clinician 3-dimensional and multi-planar views for a more accurate diagnosis and treatment without the financial burden and radiation exposure of conventional computed tomography (CT) scans. Furthermore, CBCT overcomes certain limitations of 2-dimensional imaging, such as distortion, magnification, and superimposition. However, CBCT lacks the detailed depiction of soft tissue conditions for evaluation of pathologic conditions, head and neck infections, and temporomandibular joint (TMJ) disc evaluation. This review evaluates the evidence-based research supporting the application of CBCT in the various fields of oral and maxillofacial surgery, including dentoalveolar surgery, dental implants, TMJ, orthognathic surgery, trauma, and pathology, and will assess the value of CBCT in pre-operative assessment, surgical planning, and post-operative analysis when applicable. Additionally, the significant limitations of CBCT and potential areas for future research will be discussed.

BackgroundWe evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and ResultsPlasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. ConclusionsAlthough high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.

Evidence of the involvement of tryptophan and its metabolite, kynurenine, in various biological processes including cancer is constantly expanding. Analysis of cell extracts and culture media can allow for quick snapshots of the metabolic fluctuations occurring in vitro. Here, we describe a method for metabolite extraction from mammalian cells and analysis of extracted metabolites and cell culture media by HPLC with detection using an ultra-sensitive diode array detector.

Robert WeissAndroscoggin Cardiology Associates, Auburn, ME, USAAbstract: Nebivolol is a novel beta1-blocker with a greater degree of selectivity for beta1- adrenergic receptors than other agents in this class and a nitric oxide (NO)-potentiating, vasodilatory effect that is unique among beta-blockers currently available to clinicians (nebivolol is approved in Europe and is currently under review in the US). A NO-potentiating agent such as nebivolol may have an important role in hypertensive populations with reduced endothelial function such as diabetics, African-Americans and those with vascular disease. Nebivolol is a racemic mixture with beta-blocker activity residing in the d-isomer; in contrast, l-nebivolol is far more potent in facilitating NO release. Nebivolol is unique among betablockers in that, at doses

Abstract Background The development of permanent disability in multiple sclerosis (MS) is highly variable among patients, and the exact mechanisms that contribute to this disability remain unknown. Methods Following the idea that the brain has intrinsic network organization, we investigated changes of functional networks in MS patients to identify possible links between network reorganization and remission from clinical episodes in MS. Eighteen relapsing–remitting MS patients (RRMS) in their first clinical manifestation underwent resting-state functional MRI and again during remission. We used ten template networks, identified from independent component analysis, to compare changes in network coherence for each patient compared to those of 44 healthy controls from the Human Connectome Project test–retest dataset (two-sample t- test of pre-post differences). Combining a binomial test with Monte Carlo procedures, we tested four models of how functional coherence might change between the first clinical episode and remission: a network can change its coherence (a) with itself (“one-with-self”), (b) with another network (“one-with-other”), or (c) with a set of other networks (“one-with-many”), or (d) multiple networks can change their coherence with respect to one common network (“many-with-one”). Results We found evidence supporting two of these hypotheses: coherence decreased between the Executive Control Network and several other networks (“one-with-many” hypothesis), and a set of networks altered their coherence with the Cerebellar Network (“many-with-one” hypothesis). Conclusion Given the unexpected commonality of the Cerebellar Network’s altered coherence with other networks (a finding present in more than 70% of the patients, despite their clinical heterogeneity), we conclude that remission in MS may result from learning processes mediated by the Cerebellar Network.

Background: Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed with acute ischemic stroke (AIS), which is in turn linked to less favourable clinical prognoses. Nevertheless, the exact prevalence of CMBs and their influence on post-reperfusion therapy outcomes remain inadequately elucidated. Materials and Methods: Through systematic searches of PubMed, Embase and Cochrane databases, studies were identified adhering to specific inclusion criteria: (a) AIS patients, (b) age ≥ 18 years, (c) CMBs at baseline, (d) availability of comparative data between CMB-positive and CMB-negative groups, along with relevant post-reperfusion therapy outcomes. The data extracted were analysed using forest plots of odds ratios, and random-effects modelling was applied to investigate the association between CMBs and symptomatic intracerebral haemorrhage (sICH), haemorrhagic transformation (HT), 90-day functional outcomes, and 90-day mortality post-reperfusion therapy. Results: In a total cohort of 9776 AIS patients who underwent reperfusion therapy, 1709 had CMBs, with a pooled prevalence of 19% (ES 0.19; 95% CI: 0.16, 0.23, p < 0.001). CMBs significantly increased the odds of sICH (OR 2.57; 95% CI: 1.72; 3.83; p < 0.0001), HT (OR 1.53; 95% CI: 1.25; 1.88; p < 0.0001), as well as poor functional outcomes at 90 days (OR 1.59; 95% CI: 1.34; 1.89; p < 0.0001) and 90-day mortality (OR 1.65; 95% CI: 1.27; 2.16; p < 0.0001), relative to those without CMBs, in AIS patients undergoing reperfusion therapy (encompassing intravenous thrombolysis [IVT], endovascular thrombectomy [EVT], either IVT or EVT, and bridging therapy). Variations in the level of association can be observed among different subgroups of reperfusion therapy. Conclusions: This meta-analysis underscores a significant association between CMBs and adverse postprocedural safety outcomes encompassing sICH, HT, poor functional outcome, and increased mortality in AIS patients undergoing reperfusion therapy. The notable prevalence of CMBs in both the overall AIS population and those undergoing reperfusion therapy emphasizes their importance in post-stroke prognostication.

Alemtuzumab (anti-CD52 mAb) leads to a long-lasting disease activity suppression in patients with relapsing forms of multiple sclerosis (MS). In this study, we examined the change of the immune cell repertoire and the cellular reactivity after treatment with alemtuzumab. We analyzed the number of IFN-γ–secreting cells in presence of several peptides which had been eluted from the central nervous system (CNS) of MS patients and are possible targets of autoreactive T cells in MS. The patients showed a stabilized disease activity measured in clinical parameters and lesion formation after the treatment. We detected a reduction of the number of IFN-γ–secreting cells in the presence of every tested self-antigen. The number of IFN-γ–secreting cells was also reduced in the presence of non-self-antigens. We also found a clear change in the immune cell repertoire. After an almost complete depletion of all lymphocytes, the cell specificities showed different reconstitution patterns, resulting in different cell fractions. The percentage of CD4+ T cells was clearly reduced after therapy, whereas the fractions of B and NK cells were elevated. When we evaluated the number of IFN-γ–secreting cells in relation to the number of present CD4+ T cells, we still found a significant reduction. We conclude that the reduction of IFN-γ–secreting cells by alemtuzumab is not only due to a reduction of the CD4+ T cell fraction within the peripheral blood mononuclear cell (PBMC) compartment but might also be caused by functional changes or a shift in the distribution of different subtypes in the CD4+ T cell pool.

Introduction: Brain network modularity is a principle that quantifies the degree to which functional brain networks are divided into subnetworks. Higher modularity reflects a greater number of within-module connections and fewer connections between modules, and a highly modular brain is often interpreted as a brain that contains highly specialized brain networks with less integration between networks. Recent work in younger and older adults has demonstrated that individual differences in brain network modularity at baseline can predict improvements in performance after cognitive and physical interventions. The use of brain network modularity as a predictor of training outcomes has not yet been examined in children.Method: In the present study, we examined the relationship between baseline brain network modularity and changes (post-intervention performance minus pre-intervention performance) in cognitive and academic performance in 8- to 9-year-old children who participated in an after-school physical activity intervention for 9 months (N = 78) as well as in children in a wait-list control group (N = 72).Results: In children involved in the after-school physical activity intervention, higher modularity of brain networks at baseline predicted greater improvements in cognitive performance for tasks of executive function, cognitive efficiency, and mathematics achievement. There were no associations between baseline brain network modularity and performance changes in the wait-list control group.Discussion: Our study has implications for biomarkers of cognitive plasticity in children. Understanding predictors of cognitive performance and academic progress during child development may facilitate the effectiveness of interventions aimed to improve cognitive and brain health.

Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.

The effect of humidity on sheep wool during irradiation by an accelerated electron beam was examined. Each of the samples with 10%, 53%, and 97% relative humidity (RH) absorbed a dose of 0, 109, and 257 kGy, respectively. After being freely kept in common laboratory conditions, the samples were subjected to batch Co(II) sorption experiments monitored with VIS spectrometry for different lapses from electron beam exposure. Along with the sorption, FTIR spectral analysis of the wool samples was conducted for cysteic acid and cystine monoxide, and later, the examination was completed, with pH measuring 0.05 molar KCl extract from the wool samples. Besides a relationship to the absorbed dose and lapse, the sorptivity results showed considerable dependence on wool humidity under exposure. When humidity was deficient (10% RH), the sorptivity was lower due to limited transformation of cystine monoxide to cysteic acid. The wool pre-conditioned at 53% RH, which is the humidity close to common environmental conditions, demonstrated the best Co(II) sorptivity in any case. This finding enables the elimination of pre-exposure wool conditioning in practice. Under excessive humidity of 97% RH and enough high dose of 257 kGy, radiolysis of water occurred, deteriorating the sorptivity. Each wool humidity, dose, and lapse showed a particular scenario. The time and humidity variations in the sorptivity for the non-irradiated sample were a little surprising; despite the absence of electron irradiation, relevant results indicated a strong sensitivity to pre-condition humidity and lapse from the start of the monitoring.

Background: So far, many studies have shown that the risk of developing seizures and epilepsy is higher among patients with multiple sclerosis (MS) than in the general population. However, the causal link between these two diseases is still unclear. In addition, it is not clearly understood whether and to what extent the manifestation of seizures and epilepsy in patients with MS affects the clinical course and the long-term prognosis of the disease. We aimed to retrospectively identify and describe patients with MS and with seizures and epilepsy which were seen at the Department of Neurology of the University of Regensburg in Germany between the years 2003–2015.Methods: With the help of the electronic documentation system of hospital admitted patients followed by scrutinizing medical records of patients with MS for evidence of seizures and epilepsy, we identified patients with MS and seizures or epilepsy.Results: We identified 22 individuals (1.74%) out of 1,267 patients with MS with seizures or epilepsy. 18 of these 22 individuals met criteria for epilepsy (1.42%). Nine MS patients (40.9%) suffered from relapsing-remitting MS (RRMS) whereas 11 MS patients (50.0%) showed a secondary progressive disease course (SPMS). Five of those (45.5%) converted from RRMS to SPMS before they acquired epilepsy. None of the identified patients with MS and seizures or epilepsy suffered from primary progressive MS (PPMS). Moreover, two MS patients (9.1%) had a history of seizures before MS onset. Seizures were of focal onset in 17 patients with MS (77.3%). Fourteen out of these 17 MS patients presented with focal to bilateral tonic-clonic seizures (82.4%). Five MS patients (22.7%) showed tonic clonic seizures of unknown onset. Status epilepticus was reported in three patients with MS (13%), for one patient the data was inconclusive.Conclusion: The occurrence of seizures and epilepsy was higher than in the general population, suggesting a causal relationship between both diseases. In most cases, seizures occurred after the first manifestation of MS. The high frequency of focal seizures supports the concept of cerebral lesions in patients with MS playing an important role in precipitation of seizures and epilepsy.

Background: The literature concerning the effect of coffee and caffeine on Multiple Sclerosis (MS) with focus on fatigue is investigated in this review. Potentially clinically relevant effects were also assessed in studies concerning comparable neurodegenerative diseases, such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Since the existing studies obtained very inconclusive results, we systematically reviewed these studies to summarize the evidence on the possible effects of coffee and caffeine on those disease entities. Previous studies suggested that coffee and caffeine intake is associated with a reduced risk of developing MS and other neurological diseases.Methods: The PubMed database was searched using the keywords “coffee” OR “caffeine” in combination with keywords for each of the different diseases. Besides the keyword search, we included studies by reference list search. Studies on the effects of coffee and caffeine on the single neurological diseases were included for this review. A total of 51 articles met our inclusion criteria. The reviewed articles assessed the impact of coffee and caffeine on the susceptibility for neurological diseases, as well as the effect of coffee and caffeine on disease progression and possible symptomatic effects like on performance enhancement.Results: Higher intake of coffee and caffeine was associated with a lower risk of developing PD. In some of the MS studies there, is evidence for a similar effect and experimental studies confirmed the positive impact. Interestingly in MS coffee and caffeine may have a stronger impact on disease course compared to effects on disease susceptibility. In ALS no such beneficial effect could be observed in the clinical and experimental studies.Conclusion: This literature assessment revealed that coffee and especially caffeine could have a preventative role in the development of several neurodegenerative diseases if provided in comparatively high doses. The systematic assessment indicates that coffee and caffeine intake must not be considered as a health risk. Additional clinical studies are needed to fully understand how far coffee and caffeine intake should be considered as a potential therapeutic approach for certain disease entities and conditions.

Children are becoming increasingly inactive, unfit, and overweight, yet there is relatively little causal evidence regarding the effects of physical activity on brain health during childhood. The present study examined the effects of an after-school physical activity program (FITKids2) on the microstructure of white matter tracts in 7- to 9-year-old children. We measured the microstructural properties of white matter via diffusion tensor imaging in 143 children before and after random assignment to either a 9-month after-school physical activity program (N = 76, mean age = 8.7 years) or a wait list control group (N = 67, mean age = 8.7 years). Our results demonstrate that children who participated in the physical activity program showed increased white matter microstructure in the genu of the corpus callosum, with no changes in white matter microstructure in the wait list control group which reflects typical development. Specifically, children in the physical activity program showed increases in fractional anisotropy (FA) and decreases in radial diffusivity (RD) in the genu from pre- to post-test, thereby suggesting more tightly bundled and structurally compact fibers (FA) and increased myelination (RD), with no changes in estimates of axonal fiber diameter (axial diffusivity, AD). The corpus callosum integrates cognitive, motor, and sensory information between the left and right hemispheres of the brain, and the white matter tract plays a role in cognition and behavior. Our findings reinforce the importance of physical activity for brain health during child development.

In this study, a novel sizing methodology was developed for centralized and interconnected operating strategies of transactive microgrids and several variables were investigated including starting month, initial charge of battery, load variability, unit cost of solar panels and energy storage, number of systems, climate, and required reliability to determine their effect on total cost. The centralized strategy improved cost by seven to ten percent compared to the isolated strategy in every case. The interconnected strategy saved an incremental amount of money consistently compared to the isolated standard. The number of connected systems was not a strong effect. It was thought that increasing the number of systems would increase the benefit of energy sharing. Climate zones studied (“Cold”; “Hot-Dry/Mixed Dry”; “Mixed Humid”; and “Cold but with lower solar irradiation”) showed a large variation on cost with the Hot-Dry/Mixed Dry being the least expensive and Cold, with lower solar irradiation being the most expensive. Cost sensitivity analysis was performed showing that the unit cost of solar has a greater effect on the total cost. Required reliability of power, measured in outage hours, exhibited an inverse relation with cost.

Musical practice, including musical training and musical performance, has been found to benefit cognitive function in older adults. Less is known about the role of musical experiences on brain structure in older adults. The present study examined the role of different types of musical behaviors on brain structure in older adults. We administered the Goldsmiths Musical Sophistication Index, a questionnaire that includes questions about a variety of musical behaviors, including performance on an instrument, musical practice, allocation of time to music, musical listening expertise, and emotional responses to music. We demonstrated that musical training, defined as the extent of musical training, musical practice, and musicianship, was positively and significantly associated with the volume of the inferior frontal cortex and parahippocampus. In addition, musical training was positively associated with volume of the posterior cingulate cortex, insula, and medial orbitofrontal cortex. Together, the present study suggests that musical behaviors relate to a circuit of brain regions involved in executive function, memory, language, and emotion. As gray matter often declines with age, our study has promising implications for the positive role of musical practice on aging brain health.

After encounter with a central nervous system (CNS)-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1) rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J) mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

Early motor symptoms of neurodegenerative diseases often appear in combination with psychiatric symptoms, such as depression or personality changes, and are in danger of being misdiagnosed as psychogenic in young patients. We present the case of a 32-year-old woman who presented with rapid-onset depression, followed by a hypokinetic movement disorder and cognitive decline during pregnancy. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor gene, which led to the diagnosis of hereditary diffuse leukoencephalopathy with spheroids. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is probably an under-recognized disease. HDLS should be considered in patients with rapidly progressing parkinsonian symptoms and dementia accompanied by white matter lesions.

Background: Coffee and caffeine are considered to have beneficial effects in patients with multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS) that can lead to disability and chronic fatigue. Methods: In the present study the preference in terms of coffee and caffeine consumption in patients with MS was assessed. In total the opinions of 124 MS patients were explored with a questionnaire, which was developed to investigate the consumption behavior and associated beneficial and harmful effects of coffee and caffeine concerning symptoms of fatigue. Results: Our study showed that 37.1% of the included patients experience severe symptoms of fatigue. In our cohort, fatigue was not related to age, type of diagnosis or duration of the disease. The effects of coffee did not differ between MS patients with and without fatigue. Very few side effects linked to coffee consumption were reported, and we could demonstrate that coffee consumption had no negative impact on quality of sleep. A positive effect on everyday life was observed particularly among patients with a mid-level expanded disability status scale (EDSS). The strongest effects of coffee consumption were observed regarding a better ability to concentrate while fulfilling tasks, an expanded attention span and a better structured daily routine. Conclusions: Since coffee showed no severe side effects and in the absence of an effective fatigue therapy, coffee consumption might be a therapeutic approach for selected patients with MS-related fatigue.

Multiple sclerosis is a debilitating disorder resulting from scattered lesions in the central nervous system. Because of the high variability of the lesion patterns between patients, it is difficult to relate existing biomarkers to symptoms and their progression. The scattered nature of lesions in multiple sclerosis offers itself to be studied through the lens of network analyses. Recent research into multiple sclerosis has taken such a network approach by making use of functional connectivity. In this review, we briefly introduce measures of functional connectivity and how to compute them. We then identify several common observations resulting from this approach: (a) high likelihood of altered connectivity in deep-gray matter regions, (b) decrease of brain modularity, (c) hemispheric asymmetries in connectivity alterations, and (d) correspondence of behavioral symptoms with task-related and task-unrelated networks. We propose incorporating such connectivity analyses into longitudinal studies in order to improve our understanding of the underlying mechanisms affected by multiple sclerosis, which can consequently offer a promising route to individualizing imaging-related biomarkers for multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS) with different types of disease courses (relapsing-remitting, secondary-progressive, primary progressive) that leads to physical as well as mental disability. The symptoms comprise paresis or/and paralysis, ataxia, bladder dysfunction, visual problems as well as effects on cognition. There is limited data regarding the possible effects of sport climbing respectively therapeutic climbing on patients with MS. Sport climbing offers many potentially beneficial effects for patients with MS since there are effects on coordination, muscular strength, and cognition to name the most relevant ones. Also, disease models in rodents point toward such positive outcomes of climbing. Therefore, we assessed the currently available research literature on general effects of physical exercise, impact of climbing on body and mind and therapeutic climbing for prevention or therapy for the treatment of MS. The sparse published controlled trials that investigated this sport activity on different groups of patients with neurological or geriatric diseases grossly differ in study design and outcome parameters. Nevertheless, it appears that climbing offers the opportunity to improve some of the symptoms of patients with MS and can contribute to an enhanced quality of life.

We describe an 18-year-old patient who developed back pain, rapidly ascending sensomotory deficits, bladder dysfunction, Lhermitte’s sign, absent abdominal reflexes of all three levels, brisk tendon reflexes, and positive Babinski’s sign. Magnetic resonance imaging of the spinal cord showed a long segment of cervical and thoracic intramedullary signal hyperintensity suggesting a longitudinally extensive transverse myelitis possibly within the course of a fast progressing ascending immune-mediated hemorrhagic myelopathy. Throughout his illness, the patient deteriorated with tetraplegia, cardiac arrest, and respiratory failure although he received, after exclusion of infective causes, therapy with steroids, immunoglobulins, plasmapheresis, and cyclophosphamide. Interestingly, treatment with the C5-inhibitor eculizumab to prevent complement-mediated spinal cord injury achieved an arrest of clinical deterioration. We propose eculizumab as treatment in fast progressive and potentially fatal immune-mediated spinal cord injury. Furthermore, this case raises awareness for the process of clinical decision-making in severe myelopathies.

Tuberculous meningitis and meningoencephalitis are rare and dangerous complications of infections with mycobacteria-complex. Usually these are complications of systemic florid infection with Mycobacterium (M.) tuberculosis. They are most often seen in immune compromised patients. The confirmation of diagnosis can be elaborate and delayed due to long-term culture requirements for M. tuberculosis. We present a female patient, without history of immunosuppression, who was diagnosed with tuberculous meningoencephalitis using ELISpot to detect immune reactivity against mycobacterial antigens with lymphocytes from cerebrospinal fluid (CSF). ELISpot with CSF derived lymphocytes seems to be an appropriate method to diagnose tuberculous meningitis and meningoencephalitis and to make therapeutic decisions easier and earlier in atypical cases of infection with M. tuberculosis.

Here we report a stop-mutation in the BOD1 (Biorientation Defective 1) gene, which co-segregates with intellectual disability in a large consanguineous family, where individuals that are homozygous for the mutation have no detectable BOD1 mRNA or protein. The BOD1 protein is required for proper chromosome segregation, regulating phosphorylation of PLK1 substrates by modulating Protein Phosphatase 2A (PP2A) activity during mitosis. We report that fibroblast cell lines derived from homozygous BOD1 mutation carriers show aberrant localisation of the cell cycle kinase PLK1 and its phosphatase PP2A at mitotic kinetochores. However, in contrast to the mitotic arrest observed in BOD1-siRNA treated HeLa cells, patient-derived cells progressed through mitosis with no apparent segregation defects but at an accelerated rate compared to controls. The relatively normal cell cycle progression observed in cultured cells is in line with the absence of gross structural brain abnormalities in the affected individuals. Moreover, we found that in normal adult brain tissues BOD1 expression is maintained at considerable levels, in contrast to PLK1 expression, and provide evidence for synaptic localization of Bod1 in murine neurons. These observations suggest that BOD1 plays a cell cycle-independent role in the nervous system. To address this possibility, we established two Drosophila models, where neuron-specific knockdown of BOD1 caused pronounced learning deficits and significant abnormalities in synapse morphology. Together our results reveal novel postmitotic functions of BOD1 as well as pathogenic mechanisms that strongly support a causative role of BOD1 deficiency in the aetiology of intellectual disability. Moreover, by demonstrating its requirement for cognitive function in humans and Drosophila we provide evidence for a conserved role of BOD1 in the development and maintenance of cognitive features.

Normal and painful stimuli are detected by specialized subgroups of peripheral sensory neurons. The understanding of the functional differences of each neuronal subgroup would be strongly enhanced by knowledge of the respective subgroup transcriptome. The separation of the subgroup of interest, however, has proven challenging as they can hardly be enriched. Instead of enriching, we now rapidly eliminated the subgroup of neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia. Elimination was accomplished by brief treatment with TRPV1 agonists followed by the removal of compromised TRPV1(+) neurons using density centrifugation. By differential microarray and sequencing (RNA-Seq) based expression profiling we compared the transcriptome of all cells within sensory ganglia versus the same cells lacking TRPV1 expressing neurons, which revealed 240 differentially expressed genes (adj. p1.5). Corroborating the specificity of the approach, many of these genes have been reported to be involved in noxious heat or pain sensitization. Beyond the expected enrichment of ion channels, we found the TRPV1 transcriptome to be enriched for GPCRs and other signaling proteins involved in adenosine, calcium, and phosphatidylinositol signaling. Quantitative population analysis using a recent High Content Screening (HCS) microscopy approach identified substantial heterogeneity of expressed target proteins even within TRPV1-positive neurons. Signaling components defined distinct further subgroups within the population of TRPV1-positive neurons. Analysis of one such signaling system showed that the pain sensitizing prostaglandin PGD2 activates DP1 receptors expressed predominantly on TRPV1(+) neurons. In contrast, we found the PGD2 producing prostaglandin D synthase to be expressed exclusively in myelinated large-diameter neurons lacking TRPV1, which suggests a novel paracrine neuron-neuron communication. Thus, subgroup analysis based on the elimination rather than enrichment of the subgroup of interest revealed proteins that define subclasses of TRPV1-positive neurons and suggests a novel paracrine circuit.

Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease.

The beginning of advanced courses often requires a review of fundamental concepts. Such review is often tedious and boring for both student and instructor. Instead, an active learning exercise such as a modified Bingo exercise can serve to review and re-educate at the same time. Ninety-two university students rated their understanding of developmental psychology theories before and after participating in a modified Bingo exercise designed to review the fundamentals of the theories and concepts. Students reported an improvement of their perceived knowledge of developmental theories and for each of the theories reviewed. They rated the exercise as academically challenging, helpful to learn concepts, and not a waste of time. Students who reported being able to explain the theories to others at the conclusion of the exercise had higher test scores.