Search

We report on a patient with ciltacabtagene autoleucel-induced movement and neurocognitive toxicity, which was refractory to immunosuppression but responsive to combination dopaminergic therapy (carbidopa/levodopa, ropinirole, amantadine). Response was seen upon both initial treatment and rechallenge after unintended withdrawal. This is the first report of a successful symptomatic treatment of this well-described neurotoxic syndrome.

IntroductionThe SARS-CoV-2 pandemic represented a formidable scientific and technological challenge to public health due to its rapid spread and evolution. To meet these challenges and to characterize the virus over time, the State of California established the California SARS-CoV-2 Whole Genome Sequencing (WGS) Initiative, or “California COVIDNet”. This initiative constituted an unprecedented multi-sector collaborative effort to achieve large-scale genomic surveillance of SARS-CoV-2 across California to monitor the spread of variants within the state, to detect new and emerging variants, and to characterize outbreaks in congregate, workplace, and other settings.MethodsCalifornia COVIDNet consists of 50 laboratory partners that include public health laboratories, private clinical diagnostic laboratories, and academic sequencing facilities as well as expert advisors, scientists, consultants, and contractors. Data management, sample sourcing and processing, and computational infrastructure were major challenges that had to be resolved in the midst of the pandemic chaos in order to conduct SARS-CoV-2 genomic surveillance. Data management, storage, and analytics needs were addressed with both conventional database applications and newer cloud-based data solutions, which also fulfilled computational requirements.ResultsRepresentative and randomly selected samples were sourced from state-sponsored community testing sites. Since March of 2021, California COVIDNet partners have contributed more than 450,000 SARS-CoV-2 genomes sequenced from remnant samples from both molecular and antigen tests. Combined with genomes from CDC-contracted WGS labs, there are currently nearly 800,000 genomes from all 61 local health jurisdictions (LHJs) in California in the COVIDNet sequence database. More than 5% of all reported positive tests in the state have been sequenced, with similar rates of sequencing across 5 major geographic regions in the state.DiscussionImplementation of California COVIDNet revealed challenges and limitations in the public health system. These were overcome by engaging in novel partnerships that established a successful genomic surveillance program which provided valuable data to inform the COVID-19 public health response in California. Significantly, California COVIDNet has provided a foundational data framework and computational infrastructure needed to respond to future public health crises.

Electrocatalytic water splitting is a possible route to the expanded generation of green hydrogen; however, a long-term challenge is the requirement of fresh water as an electrolyzer feed. The use of seawater as a direct feed for electrolytic hydrogen production would alleviate fresh water needs and potentially open an avenue for locally generated hydrogen from marine hydrokinetic or off-shore power sources. One environmental limitation to seawater electrolysis is the generation of chlorine as a competitive anodic reaction. This work evaluates transition metal (W, Co, Fe, Sn, and Ru) doping of Mn-Mo-based catalysts as a strategy to suppress chlorine evolution while sustaining catalytic efficiency. Electrochemical evaluations in neutral chloride solution and raw seawater showed the promise of a novel Mn-Mo-Ru electrode system for oxygen evolution efficiency and enhanced catalytic activity. Subsequent stability testing in a flowing raw seawater flume highlighted the need for improved catalyst stability for long-term applications of Mn-Mo-Ru catalysts. This work highlights that elements known to be selective toward chlorine evolution in simple oxide form (e.g., RuO2) may display different trends in selectivity when used as isolated dopants, where Ru suppressed chlorine evolution in Mn-based catalysts.

Abstract. Background:. Epidemiological studies in patients with neuropathic pain demonstrate a strong association with psychiatric conditions such as anxiety; however, the precipitating pathology between these symptoms remains unclear. To investigate this, we studied the effects of lifelong stress on levels of neuropathic pain–like behavior and conversely, the effects of chronic neuropathic injury on anxiety-like status in male and female mice. In addition, we assayed this link in painful and painless diabetic peripheral neuropathy patients. Methods:. Male and female mice were subject to ongoing life-stress or control living conditions. Baseline sensitivity and anxiety tests were measured followed by spared nerve injury (SNI) to the sciatic nerve. Subsequent sensory testing occurred until 3 weeks after SNI followed by anxiety tests between 4 and 6 weeks after SNI. Results:. Levels of tactile or cold allodynia did not differ between adult mice subject to lifelong chronic stress, relative to nonstressed controls, for at least 3 weeks after SNI. By contrast, longer-term neuropathic mice of both sexes displayed pronounced anxiety-like behavior, regardless of exposure to stress. If sex differences were present, females usually exhibited more pronounced anxiety-like behavior. These ongoing anxiety behaviors were corroborated with plasma corticosterone levels in distinct animal groups. In addition, data from patients with painful and nonpainful diabetic neuropathy showed a clear relationship between ongoing pain and anxiety, with females generally more affected than males. Discussion:. Taken together, these data demonstrate a strong link between chronic neuropathic pain and chronic anxiety, with the driver of this comorbidity being neuropathic pain as opposed to on-going stress.

In order to motivate indigenous learners to learn science and instil their positive attitude towards the subject, conducive and simulative learning environment need to be specifically designed for them. This research is aimed to determine the effect of Kayeu Learning Outside the Classroom (LOC) primary science module on intrinsic motivation of indigenous learners. The treatment group (n=38) used the Kayeu LOC primary science module while the control group (n=35) used the conventional module, which are materials mandated by Ministry of Education (MOE). Three-point Likert scale intrinsic motivation questionnaire consisting of general and science constructs was administered before and after T&L to both groups. Analysis of MANOVA repeated measures showed there were no significant effects of the groups and time on the intrinsic motivation, and there was no significant interaction effect between time and the groups on intrinsic motivation. However, follow-up simple interaction analysis found that there is a significant main effect of the time and significant effect of interactions between time and the groups on the general construct.

Objectives Activated granulocytes and monocytes may contribute to the pathogenesis of Crohn's disease (CD). In small, uncontrolled studies, granulocyte/monocyte apheresis (GMA) has shown promise in treating CD. We conducted a randomised, double-blind study to compare GMA with a sham procedure in patients with moderate to severe CD. Design Patients with active CD as defined by a Crohn's Disease Activity Index (CDAI) of 220-450 were randomly allocated in a 2:1 ratio to treatment with GMA using the Adacolumn Apheresis System ( JIMRO, Takasaki, Japan) or sham apheresis. Ten apheresis sessions were scheduled over a 9-week period, and efficacy was evaluated at week 12. The primary end point was the proportion of patients achieving clinical remission (CDAI score ≼150 without use of prohibited drugs). Results Clinical remission was achieved by 17.8% of patients in the GMA group (n=157) compared with 19.2% of those in the sham control group (n=78) (absolute difference -1.4% (95% CI-12.8% to 8.5%), p=0.858). Clinical response (defined as a ≽100-point decrease in CDAI) was achieved by 28.0% and 26.9% of patients in the GMA and sham groups, respectively (p=1.000). The two treatments produced similar changes from baseline in CDAI and quality of life, as well as in disease severity assessed endoscopically. The incidence and types of adverse events did not differ between groups. Conclusions GMA was well tolerated, but this study did not demonstrate its effectiveness over a sham procedure in inducing clinical remission or response in patients with moderate to severe CD. Clinical trial registration number Clinical Trials.gov identifier NCT00162942. [ABSTRACT FROM AUTHOR]

Passive air samplers (PAS) are simple and cost-effective tools to monitor semivolatile organic compounds in air. Chemical uptake occurs by molecular diffusion from ambient air to a passive sampling medium (PSM). Previous calibration studies indicate that even for the same type of PAS, passive air sampling rates (R, m³air/d) can be highly variable due to the influence of a number of factors. Earlier studies mainly focused on factors (e.g., wind speed and temperature) influencing R via the kinetic resistance posed by the air boundary layer surrounding the PSM because that layer was deemed to be the main factor determining the uptake kinetics. Whereas recent calibration studies suggest that the PAS configuration can influence R, so far few studies have specifically focused on this factor. In this study, with the objective to understand the effect of PAS configurations on R, we applied a gravimetrical approach to study the kinetics of water vapor uptake from indoor air by silica gel placed inside cylindrical PAS of various configurations. We also conducted an indoor calibration for polychlorinated biphenyls on the same type of PAS using XAD-resin as the PSM. R was found to be proportional to the interfacial transfer area of the PSM but not the amount of the PSM because chemicals mainly accumulated in the outer layer of the PSM during the deployment time of the PAS. The sampler housing and the PSM can introduce kinetic resistance to chemical uptake as indicated by changes in R caused by positioning the PSM at different distances from the opening of the sampler housing and by using PSM of different diameters. Information gained from this study is useful for optimizing the PAS design with the objective to reduce the material and shipping costs without sacrificing sampling efficiency. [ABSTRACT FROM AUTHOR]

Human norovirus (NoV) research greatly relies on cell culture-propagable surrogate caliciviruses, including murine NoVs and the prototype 'recovirus' (ReCV), Tulane virus. However, the extreme biological diversity of human NoVs cannot be modelled by a uniform group of viruses or single isolate. Based on a diverse group of recently described ReCVs, a more advanced model reflecting human NoV biological diversity is currently under development. Here, we have reported the genotypic and serotypic relationships among 10 G1 ReCV isolates, including Tulane virus and nine other recent cell culture-adapted strains. Based on the amino acid sequences of virus capsid protein, VP1, and classification constraints established for NoVs, G1 ReCVs were separated into three genotypes, with variable organization of the three open reading frames. Interestingly, cross-neutralization plaque assays revealed the existence of four distinct serotypes, two of which were detected among the G1.2 strains. The amino acid (aa) difference between the two G1.2 ReCV serotypes (12%) was less than the minimum 13% difference established between NoV genotypes. Interestingly, one of the G1.3 ReCVs was equally neutralized by antisera raised against the G1.3 (6% aa difference) and G1.1 (25% aa difference) representative strains. These results imply the existence of a large number of human NoV serotypes, but also shared cross-neutralization epitopes between some strains of different genotypes. In conclusion, the newly developed ReCV surrogate model can be applied to address biologically relevant questions pertaining to enteric CV diversity., (© 2014 The Authors.)