A Guide for Aspiring Neurology Educators.

Deans of medical schools have diverse roles and responsibilities. In this article, we use the career development trajectories of neurologists who have become education deans in student affairs and curriculum to offer advice to aspiring clinician educators of all levels and backgrounds. Although their roles differ, the advice they share is universal and essential for the career development of future clinician educators. ANN NEUROL 2024.

Small-bodied males invest in larger testes when highly ornamented.

Sperm competition and male mating rate are two non-mutually exclusive key evolutionary pressures selecting for larger testes within and across animal taxa. A few studies have tried to test the role of mating rate in the absence of sperm competition. Under the mating rate hypothesis, particular phenotypes of a given population that are expected to gain more mates (e.g., more ornamented males) are expected to make higher investments in testes size (a proxy for sperm production). We test this prediction in Polistes simillimus, a neotropical paper wasp in which females are single mated (no sperm competition) and males can mate with multiple partners. Testes size was predicted by body size (positive association), sexual ornamentation (negative association), and their interaction (among small males, testes size was positively related to ornamentation, but the opposite pattern was observed among large males). We propose that small-bodied well-ornamented males may face the highest risk of sperm depletion. Small-bodied males make relatively higher investment in testes size when highly ornamented. This strategy might be less profitable to large males, as they have overall larger testes. Our results provide strong evidence for the mating rate hypothesis.

Influence of Host Plants and Tending Ants on the Cuticular Hydrocarbon Profile of a Generalist Myrmecophilous Caterpillar.

In myrmecophilous organisms, which live in symbiosis with ants, cuticular hydrocarbons (CHCs) play a pivotal role in interspecific communication and defense against chemical-oriented predators. Although these interactions form complex information webs, little is known about the influence of biotic environmental factors on the CHC profiles of myrmecophiles. Here, we analyzed the effect of different host plants and tending ants on the larval CHC profile of Synargis calyce (Lepidoptera: Riodinidae), a polyphagous species with facultative myrmecophily. Groups of caterpillars were fed individually with three host plant species (without tending ants), and with two tending ant species. Through gas chromatography analysis, we compared the cuticular profiles of treatments and found a high similarity between plants and caterpillars (65-82%), but a low similarity between caterpillars and their tending ants (30 - 25%). Cluster analysis showed that caterpillars, ants, and plants form distinct groups, indicating that S. calyce caterpillars have their own chemical profile. These results are similar to those observed for Lycaenidae caterpillars indicating that there is functional convergence in the chemical strategies used by myrmecophilous caterpillar species with similar ecology. Also, the results suggest that the cuticular compounds of S. calyce are primarily influenced by their host plants rather than their tending ants. Thus, we propose that these caterpillars present a trade-off between camouflage and directly informing their presence to ants, maintaining their unique chemical profile, though slightly affected by biotic environmental factors.

Chemical signatures of egg maternity and Dufour's gland in Vespine wasps.

Cuticular hydrocarbons (CHCs) are often used in the chemical communication among social insects. CHCs can be used in nestmate recognition and as queen pheromones, the latter allows the regulation of the reproductive division of labor. In the common wasp Vespula vulgaris, CHCs and egg-marking hydrocarbons are caste-specific, being hydrocarbon queen pheromones and egg maternity signals. Whether these compounds are conserved among other Vespinae wasps remains unknown. Queens, virgin queens, reproductive workers, and workers belonging to four different wasp species, Dolichovespula media, Dolichovespula saxonica, Vespa crabro, and Vespula germanica, were collected and studied. The cuticular hydrocarbons, egg surface, and Dufour's gland composition were characterized and it was found that chemical compounds are caste-specific in the four species. Quantitative and qualitative differences were detected in the cuticle, eggs, and Dufour's gland. Some specific hydrocarbons that were shown to be overproduced in the cuticle of queens were also present in higher quantities in queen-laid eggs and in their Dufour's gland. These hydrocarbons can be indicated as putative fertility signals that regulate the division of reproductive labor in these Vespine societies. Our results are in line with the literature for V. vulgaris and D. saxonica, in which hydrocarbons were shown to be conserved queen signals. This work presents correlative evidence that queen chemical compounds are found not only over the body surface of females but also in other sources, such as the Dufour's gland and eggs.

Pitfalls in scalp EEG: Current obstacles and future directions.

Although electroencephalography (EEG) serves a critical role in the evaluation and management of seizure disorders, it is commonly misinterpreted, resulting in avoidable medical, social, and financial burdens to patients and health care systems. Overinterpretation of sharply contoured transient waveforms as being representative of interictal epileptiform abnormalities lies at the core of this problem. However, the magnitude of these errors is amplified by the high prevalence of paroxysmal events exhibited in clinical practice that compel investigation with EEG. Neurology training programs, which vary considerably both in the degree of exposure to EEG and the composition of EEG didactics, have not effectively addressed this widespread issue. Implementation of competency-based curricula in lieu of traditional educational approaches may enhance proficiency in EEG interpretation amongst general neurologists in the absence of formal subspecialty training. Efforts in this regard have led to the development of a systematic, high-fidelity approach to the interpretation of epileptiform discharges that is readily employable across medical centers. Additionally, machine learning techniques hold promise for accelerating accurate and reliable EEG interpretation, particularly in settings where subspecialty interpretive EEG services are not readily available. This review highlights common diagnostic errors in EEG interpretation, limitations in current educational paradigms, and initiatives aimed at resolving these challenges.

Evaluating adult care in Dravet syndrome upon transferring from pediatrics in the U.S.: A caregiver-based survey study.

Patients with Dravet syndrome (DS) and their caregivers must navigate a complex process upon transitioning from pediatric to adult healthcare settings. Our study examines the state of care transfer of patients with DS in the U.S. A 34-question e-survey evaluating patient demographics, clinical features, and details of the transfer process was sent to caregivers of adults with DS (≥18 years old) residing in the U.S. through the Dravet Syndrome Foundation. Forty-six responses were included in the analysis. Twenty-nine patients (n = 29/46) did not undergo transfer of care - mostly because they were still followed by pediatric neurologists/epileptologists (71%), whereas 17 (n = 17/46) underwent transfer of care. Adult neurology/epilepsy teams providing care never/rarely included a multidisciplinary team (71%), addressed patients' self-advocacy capabilities (53%), or legal guardianship/end-of-life decision-making (59%). Adult neurology/epilepsy teams were considered very much attentive/available (63%), attentive and accommodating to patients with behavioral/cognitive issues (50%), and knowledgeable about caring for patients with intellectual disability/behavioral issues (63%), collaborating with caregivers (75%), and DS - especially in adults (50%). Most caregivers (62.5%) rated the transfer process as good, very good, or excellent. Patients with DS and their caregivers would benefit from more accessible transition programs, which would be ideally equipped to deliver care tailored to these patients' needs.

Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study.

BACKGROUND: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. METHODS: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. RESULTS: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. CONCLUSIONS: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Electroencephalographic changes in purified pharmaceutical cannabidiol therapy.

OBJECTIVE: Evaluate electroencephalographic changes in patients receiving purified pharmaceutical cannabidiol (CBD). METHODS: A total of 104 EEG studies from 52 patients with pediatric-onset refractory epilepsy, who were enrolled in the FDA-approved expanded access investigational new drug program, were retrospectively analyzed for electroencephalographic changes in the background, interictal epileptiform discharges (IEDs), ictal findings, and sleep architecture after CBD treatment. RESULTS: Patients were between 18 months and 52 years of age. After CBD treatment, 88.4% (46/52) of patients had EEG changes. Eighty-nine percent of these patients had changes in their background, 74% in IEDs, 46% in ictal findings, and 17% in sleep architecture. Seven out of 52 patients had modified hypsarrhythmia on their pre-treatment EEG. The pattern resolved in 2/7 patients (29%), diminished in prevalence in 4/7 (57%) subjects, and remained unchanged in 1/7 (14%) cases. Electrographic improvement was seen in 70% (32/46) of the patients, and worsening in 7% (3/46) of the cases. At the post-CBD EEG, 83% had a reduction in the frequency of the most predominant seizure type, and 25% reported subjective cognitive improvement. Of these patients, 88% (p = 0.09) and 92% (p = 0.45) had corresponding EEG changes, respectively. CONCLUSION: Our results revealed electrographic changes in association with the CBD treatment. Despite these changes, a substantial association between specific electrographic findings and clinical outcomes was not established.

Blood Pressure Goals and Clinical Outcomes after Successful Endovascular Therapy: A Multicenter Study.

OBJECTIVE: Elevated systolic blood pressure (SBP) after successful revascularization (SR) via endovascular therapy (EVT) is a known predictor of poor outcome. However, the optimal SBP goal following EVT is still unknown. Our objective was to compare functional and safety outcomes between different SBP goals after EVT with SR. METHODS: This international multicenter study included 8 comprehensive stroke centers and patients with anterior circulation large vessel occlusion who were treated with EVT and achieved SR. SR was defined as modified thrombolysis in cerebral ischemia 2b to 3. Patients were divided into 3 groups based on SBP goal in the first 24 hours after EVT. Inverse probability of treatment weighting (IPTW) propensity analysis was used to assess the effect of different SBP goals on clinical outcomes. RESULTS: A total of 1,019 patients were included. On IPTW analysis, the SBP goal of <140mmHg was associated with a higher likelihood of good functional outcome and lower odds of hemicraniectomy compared to SBP goal of <180mmHg. Similarly, SBP goal of <160mmHg was associated with lower odds of mortality compared to SBP goal of <180mmHg. In subgroup analysis including only patients with pre-EVT SBP of ≥140mmHg, an SBP of <140mmHg was associated with a higher likelihood of good functional outcome, lower odds of symptomatic intracranial hemorrhage, and lower odds of requirement for hemicraniectomy compared to SBP goal of <180mmHg. INTERPRETATION: SBP goals of <140 and < 160mmHg following SR with EVT appear to be associated with better clinical outcomes than SBP of <180mmHg. ANN NEUROL 2020;87:830-839.

Juvenile hormone affects age polyethism, ovarian status and cuticular hydrocarbon profile in workers of the wasp Polybia occidentalis.

Division of labor is one of the most striking features in the evolution of eusociality. Juvenile hormone (JH) mediates reproductive status and aggression among nestmates in primitively eusocial Hymenoptera (species without morphologically distinct castes). In highly social species it has apparently lost its gonadotropic role and primarily regulates the division of labor in the worker caste. Polybia occidentalis, a Neotropical swarm-founding wasp, is an ideal model to understand how JH levels mirror social context and reproductive opportunities because of the absence of a clear morphological caste dimorphism. In this study, we tested the hypothesis that JH influences division of labor, ovary activation and cuticular hydrocarbon profiles of workers. Our observations confirmed that a JH analog (methoprene) and an inhibitor of JH biosynthesis (precocene) affected the cuticular chemical profile associated with age polyethism. Also, methoprene and precocene-I treatment of females influenced ovarian activation differently (individuals treated with methoprene expressed more activated ovaries while precocene treatment did not have significant effect). These results suggest that different hormonal levels induce a differential expression of cuticular chemicals associated with workers' age polyethism, which may be essential for keeping the social cohesion among workers throughout their lives in the colony. Furthermore, JH is likely to play a gonadotropic role in P. occidentalis. JH has apparently undergone certain modifications in social Hymenoptera, presenting multifaceted functions in different species.

Close-range cues used by males of Polistes dominula in sex discrimination.

Sexual pheromones are chemical molecules responsible for mediating sex recognition and mating events. Long- and close-range sexual pheromones act differently. The first type is released to attract potential partners, whereas the second coordinates the interactions after potential mating partners encounter each other. Cuticular hydrocarbons (CHCs) have been suggested to be important cues in the mating systems of several Hymenoptera species, although empirical data are still lacking for many species. Here, we evaluated whether males of the model species Polistes dominula can differentiate the sex of individuals based on their CHC composition. In August 2019, several post-worker emergent nests (n = 19) were collected in the vicinity of Leuven (Belgium) and taken to the lab (KU Leuven), where newly emerged females and males were sampled, marked individually, and kept in plastic boxes for at least a week before being used in the mating trials. Focal males were paired with females and males from different nests and subjected to five different conditions: (I) alive, (II) dead, (III) CHCs washed, (IV) CHCs partially returned, and (V) CHCs from the opposite sex. We videotaped the interactions for 10 min and analysed the duration and different behavioural interactions of the focal male. Our results indicate that CHCs may be used by males as cues to recognise a potential mating partner in P. dominula, since the focal males displayed specific courtship behaviours exclusively toward females. Although we cannot exclude that visual cues could also be used in combination with the chemical ones, we empirically demonstrate that CHCs may be important to convey sexual information at close range in mating systems, allowing fast decisions toward potential sexual partners or rivals.

SUDEP education among U.S. and international neurology trainees.

We evaluated baseline sudden unexpected death in epilepsy (SUDEP) knowledge and counseling practices among national and international adult neurology trainees with a 12-question online survey. The survey was emailed to all 169 U.S. neurology residency program directors and select international neurology/epilepsy program leaders. Program leaders were asked to distribute the survey link to adult neurology trainees. There were 161 respondents in the U.S. and 171 respondents outside the U.S. The latter were from 25 Latin American, European, Asian, and African countries. More than 90% of all trainees reported familiarity with SUDEP definition. Familiarity with SUDEP risk factors and mitigation measures ranged from 56% to 67% across these groups, with international trainees slightly more familiar with risk factors (67% vs. 61% in U.S.) but less familiar with mitigation measures (56% vs. 63% in U.S.). Approximately half of national (49%) and international (54%) trainees rarely or never counseled patients on SUDEP. Less than half of national (44%) and international (41%) trainees were educated about SUDEP. Many U.S. and adult neurology trainees remain unfamiliar with SUDEP risk factors and mitigation measures. Sudden unexpected death in epilepsy counseling falls below recommended standards. We suggest that worldwide neurology training programs' leaderships consider improving SUDEP education targeted at adult neurology trainees.

Surface treatments on CAD/CAM glass-ceramics: Influence on roughness, topography, and bond strength.

OBJECTIVE: To evaluate the influence of surface treatment on roughness (SA), topography, and shear bond strength (SBS) of computer-aided designer and manufacture (CAD/CAM) zirconia-reinforced lithium silicate (ZLS) and feldspathic (FEL) glass-ceramics. MATERIALS AND METHODS: FEL and ZLS specimens were submitted to 5% or 10% hydrofluoric acid (HF) or self-etching ceramic primer (MEP) and different application times (20, 40, and 60 s), or to sandblasting (Control, 20 s). Resin cement cylinders were bonded to the specimens and tested in shear (n = 10) after 24 h and 16-months of water storage. SA and topography were evaluated by atomic force (AFM, n = 10) and scanning electron microscopy. Data were analyzed by ANOVA and Bonferroni test (α = 0.05). RESULTS: Sandblasting promoted the highest SA for ZLS, but 10% HF (40, 60 s) promoted higher SBS at 16 months. 10% HF produced the highest SA for FEL, but sandblasting and 5% HF (20 s) maintained SBS after 16 months, without differences from 10% HF (20 s) (p > 0.05). Overall, MEP produced lower SA and SBS among groups (p < 0.05). HF displayed greater morphological changes on FEL. CONCLUSION: 10% HF (40 s) provided better results for ZLS, while 5% or 10% HF (20 s) was suitable for FEL. CLINICAL SIGNIFICANCE: Surface treatments influenced SA, topography, and SBS of materials. HF etching is the surface treatment of choice for both CAD/CAM glass-ceramics.

Polymorphism of the beta-casein gene and adaptability of Sindhi cows to semiarid conditions.

This study aimed to investigate the effect of beta-casein genotypes (A1A2 and A2A2) in three different thermal comfort conditions on the adaptability of Sindhi cows and as a tool for selecting thermotolerant cattle. Twelve Sindhi cows were used in a completely randomized design in a 2 × 3 factorial arrangement, with six replicates, with two genotypes, and three thermal comfort conditions. The climatic variables were recorded, while black globe temperature, humidity index, and radiant heat load were calculated. We measured respiratory rate, surface temperature, and rectal temperature while the heat tolerance coefficient was calculated. Genotype had no significant effect (p > 0.05) on any of the parameters measured. However, there was a thermal comfort condition effect (p < 0.05) on rectal temperature, surface temperature, and thermal gradients. The respiratory rate and heat tolerance coefficient were not significantly affected (p > 0.05). Therefore, although the results indicate substantial adaptability of Sindhi cows under any thermal conditions, the tested genotypes should not be used as a tool for selecting thermotolerant Sindhi cows.

Upward Gaze Palsy: a Valuable Sign to Distinguish Spinocerebellar Ataxias.

Spinocerebellar ataxias (SCAs) represent a large group of heredodegenerative diseases, with great phenotypic and genotypic heterogeneity. However, in the clinical neurological practice, some symptoms and signs might help differentiate the SCAs. This study's aims were to evaluate the frequency of upward gaze palsy (UGP) and investigate its role in assisting in the clinical differentiation of SCAs. We included 419 patients with SCAs (248 with SCA3, 95 with SCA10, 38 with SCA2, 22 with SCA1, 12 with SCA7, and 4 with SCA6). This study compared UGP with other known markers of disease severity-age of onset, disease duration, SARA score, and size of CAG expansion, and also other semiologic features, as bulging eyes. This sign was significantly more prevalent in SCA3 (64.11%), compared with SCA10 (3.16%; p < 0.001) and other SCAs (SCA1, SCA2, SCA7-11.84%; p < 0.001). UGP showed very high sensibility ins SCA3 (92.9), although lacking of specificity (64.1%). The odds ratio (OR) of UGP were also very high, 23.52 (95% CI 12.38-44.69), and was significantly correlated with larger CAG expansions, age, and disease duration in SCA3 patients, but not with age of onset or severity of the ataxic syndrome. This study showed that UGP is highly suggestive of SCA3 and has high sensitivity for the differential diagnosis among SCAs, and it could be of great value for bedside semiologic tool.

Dominance Hierarchy, Ovarian Activity and Cuticular Hydrocarbons in the Primitively Eusocial Wasp Mischocyttarus cerberus (Vespidae, Polistinae, Mischocyttarini).

The dominance hierarchy in primitively eusocial insect societies has been shown to be mainly regulated through aggressive interactions. Females that are generally more dominant stand out and occupy the queen position, meaning that they monopolize reproduction while others perform other tasks. Chemical communication is important for maintaining social cohesion. Cuticular hydrocarbons are recognized as the main molecules responsible for mediating social interactions, especially nestmate recognition and queen signalling. Many highly eusocial groups have been studied in recent years, but primitively eusocial groups, which are key to understanding the evolution of social behavior, remain unexplored. In this study, we investigated the connection between cuticular hydrocarbons in females expressed in different social contexts in the primitively eusocial wasp Mischocyttarus cerberus. Colonies in two different ontogenetic phases, pre- and post-worker emergence, were used. We observed and categorized behavioral interactions between individual females and collected all individuals in a nest to obtain information on size, ovary activation and chemical composition. Furthermore, we conducted experiments in which the alpha (dominant) females were removed from nests to produce a new dominance hierarchy. We found that females in different hierarchical positions had small chemical difference corresponding with ovary activity. Our results support the hypothesis that cuticular hydrocarbons are associated with social context in this primitively eusocial species, with some compounds being associated with hierarchical position and ovarian activity.

Meliponamycins: Antimicrobials from Stingless Bee-Associated Streptomyces sp.

Social insects establish complex interactions with microorganisms, some of which play defensive roles in colony protection. The important role of pollinators such as the stingless bee Melipona scutellaris in nature encouraged us to pursue efforts to study its associated microbiota. Here we describe the discovery of two novel cyclic hexadepsipeptides, meliponamycin A (1) and meliponamycin B (2), from Streptomyces sp. ICBG1318 isolated from M. scutellaris nurse bees. Their structures were established by interpretation of NMR and MS data, and the absolute configuration of the constituent amino acids was determined by the advanced Marfey's method. Compounds 1 and 2 showed strong activity against the entomopathogen Paenibacillus larvae and human pathogens Staphylococcus aureus and Leishmania infantum.

Charcot and His Passion for Dogs: A Historical Note.

Jean-Martin Charcot, one of the most brilliant neurologists in history, was a man of few words and few gestures. He had an impenetrable and unmovable face and was described as being austere, reserved, and shy. In contrast, in his personal life, he was a softhearted man who loved animals - especially dogs. In this historical note, we sought to look into the past and learn more about Dr. Charcot's personal life - which was robustly impacted by his passion for dogs.

Blood Pressure and Outcome After Mechanical Thrombectomy With Successful Revascularization.

Background and Purpose- Successful reperfusion can be achieved in more than two-thirds of patients treated with mechanical thrombectomy. Therefore, it is important to understand the effect of blood pressure (BP) on clinical outcomes after successful reperfusion. In this study, we investigated the relationship between BP on admission and during the first 24 hours after successful reperfusion with clinical outcomes. Methods- This was a multicenter study from 10 comprehensive stroke centers. To ensure homogeneity of the studied cohort, we included only patients with anterior circulation who achieved successful recanalization at the end of procedure. Clinical outcomes included 90-day modified Rankin Scale, symptomatic intracerebral hemorrhage (sICH), mortality, and hemicraniectomy. Results- A total of 1245 patients were included in the study. Mean age was 69±14 years, and 51% of patients were female. Forty-nine percent of patients had good functional outcome at 90-days, and 4.7% suffered sICH. Admission systolic BP (SBP), mean SBP, maximum SBP, SBP SD, and SBP range were associated with higher risk of sICH. In addition, patients in the higher mean SBP groups had higher rates of sICH. Similar results were found for hemicraniectomy. With respect to functional outcome, mean SBP, maximum SBP, and SBP range were inversely associated with the good outcome (modified Rankin Scale score, 0-2). However, the difference in SBP parameters between the poor and good outcome groups was modest. Conclusions- Higher BP within the first 24 hours after successful mechanical thrombectomy was associated with a higher likelihood of sICH, mortality, and requiring hemicraniectomy.

Social wasps are effective biocontrol agents of key lepidopteran crop pests.

Biocontrol agents can help reduce pest populations as part of an integrated pest management scheme, with minimal environmental consequences. However, biocontrol agents are often non-native species and require significant infrastructure; overuse of single agents results in pest resistance. Native biocontrol agents are urgently required for more sustainable multi-faceted approaches to pest management. Social wasps are natural predators of lepidopteran pests, yet their viability as native biocontrol agents is largely unknown. Here, we provide evidence that the social paper wasp Polistes satan is a successful predator on the larvae of two economically important and resilient crop pests, the sugarcane borer Diatraea saccharalis (on sugarcane Saccharum spp.) and the fall armyworm Spodoptera frugiperda (on maize Zea mays); P. satan wasps significantly reduce crop pest damage. These results provide the much-needed baseline experimental evidence that social wasps have untapped potential as native biocontrol agents for sustainable crop production and food security.