Case Series of Guillain-Barré Syndrome After the ChAdOx1 nCoV-19 (Oxford–AstraZeneca) Vaccine

Purposeof Review: Vaccination has been associated with Guillain-Barre Syndrome (GBS). Amidst a global vaccination campaign to stop the spread of COVID-19, fears of GBS can contribute to vaccine-hesitancy. We describe three cases of GBS in Calgary, Canada presenting within 2 weeks of receiving the ChAdOx1 nCoV-19 (COVISHIELD) Oxford-AstraZeneca vaccination and review the available literature.Recent Findings:All three patients presented to hospital in Calgary, Alberta, Canada within a one-month time frame with GBS. Their clinical courses ranged from mild to severe impairment, all requiring immunomodulatory treatment.Summary:There is currently little evidence to support a causal relationship between vaccination and GBS. Furthermore, there is limited evidence to support recurrent GBS in patients with GBS temporally associated with vaccination. Neurologists should approach discussions with patients regarding GBS after vaccination carefully, so as not to misrepresent this relationship, and to educate patients that the risk of COVID-19 infection outweighs the small individual risk of a vaccine-associated adverse event.

Domestication reshaped the genetic basis of inbreeding depression in a maize landrace compared to its wild relative, teosinte

Inbreeding depression is the reduction in fitness and vigor resulting from mating of close relatives observed in many plant and animal species. The extent to which the genetic load of mutations contributing to inbreeding depression is due to large-effect mutations versus variants with very small individual effects is unknown and may be affected by population history. We compared the effects of outcrossing and self-fertilization on 18 traits in a landrace population of maize, which underwent a population bottleneck during domestication, and a neighboring population of its wild relative teosinte. Inbreeding depression was greater in maize than teosinte for 15 of 18 traits, congruent with the greater segregating genetic load in the maize population that we predicted from sequence data. Parental breeding values were highly consistent between outcross and selfed offspring, indicating that additive effects determine most of the genetic value even in the presence of strong inbreeding depression. We developed a novel linkage scan to identify quantitative trait loci (QTL) representing large-effect rare variants carried by only a single parent, which were more important in teosinte than maize. Teosinte also carried more putative juvenile-acting lethal variants identified by segregation distortion. These results suggest a mixture of mostly polygenic, small-effect partially recessive effects in linkage disequilibrium underlying inbreeding depression, with an additional contribution from rare larger-effect variants that was more important in teosinte but depleted in maize following the domestication bottleneck. Purging associated with the maize domestication bottleneck may have selected against some large effect variants, but polygenic load is harder to purge and overall segregating mutational burden increased in maize compared to teosinte.

Quantitative analysis of hillshed geomorphology and critical zone function: Raising the hillshed to watershed status

Landscapes are frequently delineated by nested watersheds and river networks ranked via stream orders. Landscapes have only recently been delineated by their interfluves and ridge networks, and ordered based on their ridge connectivity. There are, however, few studies that have quantitatively investigated the connections between interfluve networks and landscape morphology and environmental processes. Here, we ordered hillsheds using methods complementary to traditional watersheds, via a hierarchical ordering of interfluves, and we defined hillsheds to be landscape surfaces from which soil is shed by soil creep or any type of hillslope transport. With this approach, we demonstrated that hillsheds are most useful for analyses of landscape structure and processes. We ordered interfluve networks at the Calhoun Critical Zone Observatory (CZO), a North American Piedmont landscape, and demonstrated how interfluve networks and associated hillsheds are related to landscape geomorphology and processes of land management and land-use history, accelerated agricultural gully erosion, and bedrock weathering depth (i.e., regolith depth). Interfluve networks were ordered with an approach directly analogous to that first proposed for ordering streams and rivers by Robert Horton in the GSA Bulletin in 1945. At the Calhoun CZO, low-order hillsheds are numerous and dominate most of the observatory’s ∼190 km2 area. Low-order hillsheds are relatively narrow with small individual areas, they have relatively steep slopes with high curvature, and they are relatively low in elevation. In contrast, high-order hillsheds are few, large in individual area, and relatively level at high elevation. Cultivation was historically abandoned by farmers on severely eroding low-order hillsheds, and in fact agriculture continues today only on high-order hillsheds. Low-order hillsheds have an order of magnitude greater intensity of gullying across the Calhoun CZO landscape than high-order hillsheds. In addition, although modeled regolith depth appears to be similar across hillshed orders on average, both maximum modeled regolith depth and spatial depth variability decrease as hillshed order increases. Land management, geomorphology, pedology, and studies of land-use change can benefit from this new approach pairing landscape structure and analyses.

The Architecture of Cooperation Among Non-kin: Coalitions to Move Up in Nature’s Housing Market

The evolution of cooperation among non-kin poses a major theoretical puzzle: why should natural selection favor individuals who help unrelated conspecifics at a cost to themselves? The relevance of architecture to this question has rarely been considered. Here I report cooperation among non-kin in social hermit crabs (Coenobita compressus), where unrelated conspecifics work together to evict larger individuals from a housing market of architecturally remodeled shells. I present (1) the first detailed description of natural coalitions in the wild and (2) a theoretical framework, which examines the evolutionary benefits to each coalition member and predicts when forming a coalition will be successful. In the wild, important ecological and social constraints exist, which are built into the model. Based on these constraints, I show that coalitions can be a successful strategy if several key criteria hold: the coalition is necessary, effective, stable dyadically, and stable polyadically. Notably, the “splitting the spoils” problem—which often undermines non-kin cooperation—is eliminated via architecture: a small individual (C) who helps a medium individual (B) to evict a large individual (A) will ultimately benefit, since C will get B’s left behind shell after B moves into A’s shell. Coalitions, however, can break down due to added layers of social complexity involving third-party “free riders” and “cheaters,” which strategically butt in the architectural queue and thereby steal incentives from the smaller coalition member. Overall, therefore, substantial scope exists for both cooperation and conflict within nature’s housing market of architecture. Experiments are now needed to directly test the impact on coalitions of architecture, from the interior of homes up to whole housing markets.

Rapid Dynamic Naturalistic Monitoring of Bradykinesia in Parkinson’s Disease Using a Wrist-Worn Accelerometer

Motor fluctuations in Parkinson’s disease are characterized by unpredictability in the timing and duration of dopaminergic therapeutic benefits on symptoms, including bradykinesia and rigidity. These fluctuations significantly impair the quality of life of many Parkinson’s patients. However, current clinical evaluation tools are not designed for the continuous, naturalistic (real-world) symptom monitoring needed to optimize clinical therapy to treat fluctuations. Although commercially available wearable motor monitoring, used over multiple days, can augment neurological decision making, the feasibility of rapid and dynamic detection of motor fluctuations is unclear. So far, applied wearable monitoring algorithms are trained on group data. In this study, we investigated the influence of individual model training on short timescale classification of naturalistic bradykinesia fluctuations in Parkinson’s patients using a single-wrist accelerometer. As part of the Parkinson@Home study protocol, 20 Parkinson patients were recorded with bilateral wrist accelerometers for a one hour OFF medication session and a one hour ON medication session during unconstrained activities in their own homes. Kinematic metrics were extracted from the accelerometer data from the bodyside with the largest unilateral bradykinesia fluctuations across medication states. The kinematic accelerometer features were compared over the 1 h duration of recording, and medication-state classification analyses were performed on 1 min segments of data. Then, we analyzed the influence of individual versus group model training, data window length, and total number of training patients included in group model training, on classification. Statistically significant areas under the curves (AUCs) for medication induced bradykinesia fluctuation classification were seen in 85% of the Parkinson patients at the single minute timescale using the group models. Individually trained models performed at the same level as the group trained models (mean AUC both 0.70, standard deviation respectively 0.18 and 0.10) despite the small individual training dataset. AUCs of the group models improved as the length of the feature windows was increased to 300 s, and with additional training patient datasets. We were able to show that medication-induced fluctuations in bradykinesia can be classified using wrist-worn accelerometry at the time scale of a single minute. Rapid, naturalistic Parkinson motor monitoring has the clinical potential to evaluate dynamic symptomatic and therapeutic fluctuations and help tailor treatments on a fast timescale.

Rare Pathogenic Variants in Genes Implicated in Glutamatergic Neurotransmission Pathway Segregate with Schizophrenia in Pakistani Families

Schizophrenia is a disabling neuropsychiatric disorder of adulthood onset with high heritability. Worldwide collaborations have identified an association of ~270 common loci, with small individual effects and hence weak clinical implications. The recent technological feasibility of exome sequencing enables the identification of rare variants of high penetrance that refine previous findings and improve risk assessment and prognosis. We recruited two multiplex Pakistani families, having 11 patients and 19 unaffected individuals in three generations. We performed genome-wide SNP genotyping, next-generation mate pairing and whole-exome sequencing of selected members to unveil genetic components. Candidate variants were screened in unrelated cohorts of 508 cases, 300 controls and fifteen families (with 51 affected and 47 unaffected individuals) of Pakistani origin. The structural impact of substituted residues was assessed through in silico modeling using iTASSER. In one family, we identified a rare novel microduplication (5q14.1_q14.2) encompassing critical genes involved in glutamate signaling, such as CMYA5, HOMER and RasGRF2. The second family segregates two ultra-rare, predicted pathogenic variants in the GRIN2A (NM_001134407.3: c.3505C>T, (p.R1169W) and in the NRG3 NM_001010848.4: c.1951G>A, (p.E651K). These genes encode for parts of AMPA and NMDA receptors of glutamatergic neurotransmission, respectively, and the variants are predicted to compromise protein function by destabilizing their structures. The variants were absent in the aforementioned cohorts. Our findings suggest that rare, highly penetrant variants of genes involved in glutamatergic neurotransmission are contributing to the etiology of schizophrenia in these families. It also highlights that genetic investigations of multiplex, multigenerational families could be a powerful approach to identify rare genetic variants involved in complex disorders.

AT 200 YEARS OLD, DOSTOEVSKIJ HAS ARRIVED IN THE 21st CENTURY

Let's look into our time. Dostoevsky’s works, which have to be rediscovered by every generation, appear not only in a new way through colorful front pages (this is now part of the visual presentation), but also through new translations. For the past 30 years, Swetlana Geier has been responsible for the translation of the Russian poet's novels and stories into German. Now, in small individual publications, the names of new translators appear in all European languages.

ESTIMATION OF PHTHALATES IN BOTTLED DRINKING WATER, MANUFACTURED IN INDIA, USING LIQUID CHROMATOGRAPHY MASS SPECTROMETRY (LC-MS/MS)

Phthalate easters are known endocrine disrupter and possible carcinogen. Studies have carried out in different countries to investigate possible migration of phthalate easters into packaged drinking water and beverages and resultant toxic effect on human health. This study aimed to determine the level of phthalate migration into bottled drinking water, manufactured commercially in India and to identify a possible relationship between the amount and type of phthalate migration. Eight phthalate easters were investigated. The analysis included 375 samples (75 sets of 5 bottles each from 5 manufacturers, having same batch numbers and manufacturing dates) of drinking water packed in 1-Litre bottles made from polyethylene terephthalate (PET). The samples were incubated and analyzed at the Centre of Mass Spectrometry (Analytics Department) of the CSIR-Indian Institute of Chemical Technology, Hyderabad on Agilent 6420 QQQ MS/MS system coupled to Agilent 1290 UPLC pump and 0 Thermo TSQ Altis coupled to Thermo RSLC 3000 system at room temperature (27 C) and two temperatures of extreme conditions representing 0 0 refrigeration temperature (4 C) and summer outdoor temperature (45 C) at the interval of 0, 30, 60, 120 and 180 days, 180 days (6 months) being the projected self-life for bottled drinking water in India. Of eight investigated phthalate esters, Di-butyl Phthalate (DBP) was detected in 94% and Di-isobutyl phthalate (DiBP) in 80% of samples analyzed. The highest migration of 0.0027 mg/l was recorded from PET bottles to drinking water for DBP, followed by 0.0024 mg/l for DiBP. DEHP (Bis(2-ethylhexyl) phthalate) was detected in 40% of sample sets with maximum concentration of 0.0006 mg/l. DPP (Di-pentyl phthalate) was detected in the least number of samples (21.3%) and its maximum concentration observed was 0.0004 mg/l. Migration of all eight investigated esters were detected in drinking water samples stored for 180 days at the three temperature conditions. In other temperature and storage conditions, frequency of detection varied between 0-66%. This study did not account for the factors like source of raw water, manufacturing process, PET types (virgin or recycled), and composition, etcetera. This is probably reected in widely varied standard deviation. The phthalate levels measured in these samples pose no risk for human health considering reference dose determined by USEPA, EU and FSSAI, for daily oral exposure to the human population. Nevertheless, the accumulation of small individual quantity taken with time may increase the lifelong phthalate exposure and eventually threaten the exposed person's life. Further studies with larger sample size and variants may be desirable. Also, drinking water quality standards needs to be revisited to include all signicant phthalate esters.

Rapid dynamic naturalistic monitoring of bradykinesia in Parkinson’s disease using a wrist-worn accelerometer

IntroductionMotor fluctuations in Parkinson’s disease are characterized by unpredictability in the timing and duration of dopaminergic therapeutic benefit on symptoms including bradykinesia and rigidity. These fluctuations significantly impair the quality of life of many Parkinson’s patients. However, current clinical evaluation tools are not designed for the continuous, naturalistic (real-world) symptom monitoring needed to optimize clinical therapy to treat fluctuations. Although commercially available wearable motor monitoring, used over multiple days, can augment neurological decision making, the feasibility of rapid and dynamic detection of motor fluctuations is unclear. So far, applied wearable monitoring algorithms are trained on group data. Here, we investigate the influence of individual model training on short timescale classification of naturalistic bradykinesia fluctuations in Parkinson’s patients using a single wrist-accelerometer.MethodsAs part of the Parkinson@Home study protocol, 20 Parkinson patients were recorded with bilateral wrist-accelerometers for a one hour OFF medication session and a one hour ON medication session during unconstrained activities in their own homes. Kinematic metrics were extracted from the accelerometer data from the bodyside with the largest unilateral bradykinesia fluctuations across medication states. The kinematic accelerometer features were compared over the whole one-hour recordings, and medication-state classification analyses were performed on one-minute segments of data. The influence of individual versus group model training, data window length, and total amount of training patients included in group model training on classification was analyzed.ResultsStatistically significant areas under the curves (AUCs) for medication induced bradykinesia fluctuation classification were seen in 85% of the Parkinson patients at the single minute timescale using the group models. Individually trained models performed at the same level as the group trained models (mean AUC both 0.70, +/− respectively 0.18 and 0.10) despite the small individual training dataset. AUCs of the group models improved as the length of the feature windows was increased to 300 seconds, and with additional training patient datasets.ConclusionMedication induced fluctuations in bradykinesia can be classified using wrist worn accelerometery at the time scale of a single minute. Rapid, naturalistic Parkinson motor monitoring has important clinical potential to evaluate dynamic symptomatic and therapeutic fluctuations and help tailor treatments on a fast timescale.

Abstract P434: A Mouse Model To Control Vessel Diameter With Light

In diseases such as stroke, hypertension, vascular cognitive impairment, and Alzheimer’s disease, defects in the cerebrovascular system lead to reduced blood flow and vasoreactivity to stimuli. Recently, there has been increased appreciation for the role of small vessels in these vascular pathologies. For example, small vessel dysfunction can cause widespread microinfarcts and capillary stalling, which may underlie cognitive impairment in cases where large scale vascular abnormalities are not readily detected. However, vascular function is difficult to dissociate from concurrent neuronal deficits cause by damage to neuronal circuitry in brain pathology. Thus the ability to directly probe smooth muscle contraction of small, individual vessels in the intact brain would be a valuable tool for increasing our understanding of vascular contributions to cognitive impairment. We developed an experimental paradigm to optically probe the contractile function of arterioles in vivo with high spatiotemporal precision. This was done by expressing the excitatory opsin ReaChR in vascular smooth muscle cells and pericytes. Using a 594 nm light-emitting diode we were able to evoke widespread vasoconstriction across the cranial window. With a 1040 nm focused, pulsed laser for two-photon stimulation, we were able to evoke highly localized constrictions targeted to individual pial artery branches or penetrating arterioles. Our dual light-path imaging system allowed the optogenetic stimulation to be performed with simultaneous two-photon imaging to monitor vessel activity. Using a spatial light modulator, we were also able to constrict vessels both above and below the imaging plane. This is a powerful tool to assay vasoconstrictive function of single arterioles across 3-dimensional vascular networks in vivo. It also presents novel opportunities to study conductance of vascular signals and to modulate dynamics of functional hyperemia.