What Is Brain Damage and Does Electroconvulsive Therapy Cause It?

ABSTRACT: Surveys show public misperceptions and confusion about brain damage and electroconvulsive therapy (ECT). Fictional movies have misrepresented ECT to suggest brain damage and to ridicule mental illness and psychiatric patients. "Brain damage" has become a colloquial expression without consistent meaning. In contrast, brain injury is the medical term for destruction of brain cells, such as from kinetic impact (concussion), hypoxia, or infection. Studies of both high-resolution magnetic resonance imaging (MRI) and enzyme assays find that causes of brain injury are accompanied by observable structural changes on MRI and elevated blood and cerebrospinal fluid levels of brain enzymes that leak from injured brain cells. Concussion is also followed by intracerebral bleeding, progressive brain atrophy, diffuse axonal injury, cranial nerve injury, and 2-4 fold increased risk for dementia. In contrast, there is no evidence that ECT produces any of these. Studies of ECT patients find no brain edema, structural change persisting 6 months, or elevated levels of leaked brain enzymes. Statistical comparisons between brain injury and ECT effects indicate no similarity ( P < 0.00000001). Moreover, the kinetic, thermal, and electrical effects of ECT are far below levels that could possibly cause harm. This robust evidence shows that there is no basis to claim that ECT causes brain injury.

Incidental discovery of metastatic renal cell carcinoma at the vaginal wall: A case report.

Metastasis of renal cell carcinoma (RCC) to the vaginal wall has rarely been reported in the literature. We present a case of a 48-year-old who was found to have a solitary RCC metastasis at the vaginal wall, five years following radical nephrectomy. This case is noteworthy because this late presentation is unique, with prior reports of synchronous metastasis or metastasis within two years of nephrectomy, highlighting the need to consider metastatic RCC to the vagina a possibility even many years after treatment.

Dog ecology and rabies knowledge, attitude and practice (KAP) in the Northern Communal Areas of Namibia.

In 2021, a comprehensive dog demographic questionnaire combined with a KAP survey were conducted in the northern communal areas (NCAs) of Namibia with the aim of gaining a better understanding of dog populations, owner behaviour, and knowledge, attitudes and practices (KAP) relating to rabies. The survey of 3,726 households across the eight regions of the NCAs provided insights that will inform interventions in order to improve human rabies prevention and Namibia's dog rabies control strategy. The results showed a relatively low average human/dog ratio (HDR) of 5.4:1 indicating a surprisingly high dog population of at least 272,000 dogs in the NCAs, 93% of which appear to be owned but are free-roaming. Data analysis revealed opportunities but also highlighted needs for improvements in rabies surveillance and mass dog vaccinations. Although knowledge, attitude, and practice scores towards epidemiologic and clinical aspects, human rabies prevention, and dog rabies vaccination were deemed to be acceptable, the survey nevertheless revealed deficiencies in certain aspects in some of the population. Interestingly, data seemed to indicate relatively high dog bite incidences per 100,000 people, ranging between 262 and 1,369 and a certain number of unreported human rabies cases. Despite the very high number of dogs, only 50% of dog-owning households reported having vaccinated their dogs. In order to address these issues, the planning, announcement, and implementation of mass dog vaccination campaigns needs to be adapted to achieve adequate vaccination coverage. Another focus needs to be on rabies awareness and education if Namibia is to be significantly contributing to the global goal of "Zero by 30".

Long-term immunity induced by SPBN GASGAS in orally vaccinated dogs is non-inferior to inactivated rabies vaccines.

In a long-term immunogenicity study (1100 days post vaccination) in local Thai dogs the immune response of the oral rabies vaccine SPBN GASGAS was compared to those elicited by a commercial inactivated vaccine using immunobridging. Based on the detection of rabies virus binding (rVBA) and rabies virus neutralizing antibodies (rVNA) as measured by ELISA and Rapid Fluorescent Focus Inhibition Test (RFFIT) the long-term immune response in dogs vaccinated orally with the SPBNA GASGAS strain of rabies vaccine in a bait was non-inferior to a conventional inactivated rabies vaccine. The outcome of this study supports extending the originally claimed duration of immunity (DOI) of SPBN GASGAS after oral vaccination for dogs from 6 to 30 months.

clifford B.4.1 , an allele of CG1603 , causes tissue overgrowth in the Drosophila melanogaster eye.

Mutant B.4.1 , generated via EMS mutagenesis in Drosophila melanogaster , was studied by undergraduate students participating in the Fly-CURE. After inducing genetically mosaic tissue in the adult eye, B.4.1 mutant tissue displays a robust increase in cell division and a rough appearance. Complementation mapping and sequence analysis identified a nonsense mutation in the gene CG1603 , which we named clifford ( cliff ) due to observed increases in red-pigmented mutant tissue compared to controls. cliff encodes a zinc finger-containing protein implicated in transcriptional control. RNAi knockdown of cliff similarly results in rough eyes, confirming a role for Cliff in eye development.

Incidence and clinical relevance of paraneoplastic syndromes in patients with renal cell carcinoma.

BACKGROUND: Paraneoplastic syndromes (PNS) are defined as the signs and symptoms attributed to cytokines or hormones released from a tumor or a patient's immune system. PNS have been reported with many cancers for decades and data supporting their relevance in renal cell carcinoma (RCC) are largely historical. The widespread use of electronic medical record (EMR) systems provides a more robust method to capture data. The objective of this study was to establish contemporary data regarding the incidence and relevance of PNS in patients undergoing nephrectomy for suspected RCC. METHODS: In this retrospective single-institution study, 851 patients undergoing nephrectomy for suspected RCC between 2011 and 2018 were assessed for the presence or absence of PNS as defined by laboratory abnormalities. Factors associated with PNS and with all-cause mortality were examined. RESULTS: The incidence of PNS was 33.1% among 851 patients prior to nephrectomy. The most prevalent PNS were anemia (22.4%), thrombocytosis (7.5%), and elevated C-reactive protein (CRP) (7.4%). PNS were more common in women (39.2% vs. 29.4%, p = 0.0032) and higher stage RCC (31.1% of stage I vs. 54.2% of stage IV, p = 0.0036). Factors associated with the presence of PNS in multivariable analysis included female gender, high comorbidity, and stage IV RCC. Prenephrectomy PNS were associated with poorer survival in multivariable analysis (HR: 2.12, p = 0.0002). Resolution of PNS occurred in 52.1% of patients after nephrectomy, including 55.2% with stage I to III and 38.5% with stage IV RCC (p = 0.10). CONCLUSIONS: Using EMR data, laboratory evidence of PNS was present in one-third of a contemporary cohort of patients undergoing nephrectomy, with >50% of PNS resolving after surgery. Consistent with prior reports, PNS are more common in higher-stage RCC and are associated with poorer survival in RCC patients.

Emergency response using oral rabies vaccination of dogs -field data from Namibia demonstrate high efficiency.

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging for various reasons. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. While oral rabies vaccination (ORV) of dogs is primarily considered a tool to increase herd immunity, particularly by targeting free-roaming and stray dogs, here, we are showcasing an ORV-only approach as an emergency response model. Using a third-generation vaccine and a standardized egg-flavored bait, we assessed the effectiveness and vaccination under field conditions in the Zambezi region of Namibia. During this trial, with four teams and within four working days, 3097 dogs were offered a bait, of which 88,0% were considered vaccinated. Teams managed to vaccinate, on average, over 20 dogs/h, despite using a door-to-door vaccination approach. The favorable results both in terms of bait acceptance and successful vaccination as well as field applicability and effectiveness further support the great potential of ORV in dog rabies control programmes.

Suid alphaherpesvirus 1 of wild boar origin as a recent source of Aujeszky's disease in carnivores in Germany.

BACKGROUND: The high susceptibility of carnivores to Suid Alphaherpesvirus 1 [SuAHV1, synonymous pseudorabies virus (PrV)], renders them inadvertent sentinels for the possible occurrence of Aujeszky's disease (AD) in domestic and wild swine populations. The aim of this study was to epidemiologically analyse the occurrence of PrV infections in domestic and wild animals in Germany during the last three decades and to genetically characterise the causative PrV isolates. METHODS: PrV in dogs was detected using standard virological techniques including conventional and real time PCR, virus isolation or by immunohistochemistry. Available PrV isolates were characterized by partial sequencing of the open gC reading frame and the genetic traits were compared with those of archived PrV isolates from carnivores and domestic pigs from Germany before the elimination of AD in the domestic pig population. RESULTS: During 1995 and 2022, a total of 38 cases of AD in carnivores, e.g. dogs and red foxes, were laboratory confirmed. Sequencing and subsequent phylogenetic analysis of PrV isolates established a strong connection between AD cases in carnivores and the occurrence of PrV infections in European wild boars in the end phase of and after elimination of AD from the domestic pig population. While PrV infections occur at low numbers but regularly in hunting dogs, interestingly, PrV was not observed in grey wolves in Germany. In none of 682 dead-found grey wolves and wolf-dog hybrids tested from Germany during 2006-2022 could PrV infection be detected by molecular means. CONCLUSIONS: Although PrV has been eliminated from domestic pigs, spillover infections in domestic and wild carnivores should always be expected given the endemic presence of PrV in wild pig populations. Since detection of PrV DNA and virus in carnivores is sporadic even in areas with high seroprevalence of PrV in wild pigs, it may not reflect the full diversity of PrV.

From Field Tests to Molecular Tools-Evaluating Diagnostic Tests to Improve Rabies Surveillance in Namibia.

Rabies is endemic in Namibia and is present both in wildlife carnivores and domestic free-roaming dogs. The disease thus represents a challenge for public human and veterinary disease control. Namibia has implemented a national strategic plan to control rabies and the country's activities are supported by international organizations. To this end, rabies diagnosis at the Central Veterinary Laboratory (CVL) was improved in the frame of a World Organization for Animal Health (WOAH) laboratory twinning program: from practical sampling techniques and the use of lateral flow devices to a novel universal and discriminatory quantitative real-time Reverse transcription polymerase chain reaction (RT-qPCR), which easily identify dog-associated rabies viruses. The procedures applied and the results can be used as a template to improve rabies laboratory diagnosis.

Genesis of a functional astrocyte syncytium in the developing mouse hippocampus.

Astrocytes are increasingly shown to operate as an isopotential syncytium in brain function. Protoplasmic astrocytes acquire this ability to functionally go beyond the single-cell level by evolving into a spongiform morphology, cytoplasmically connecting into a syncytium, and expressing a high density of K+ conductance. However, none of these cellular/functional features exist in neonatal newborn astrocytes, which imposes a basic question of when a functional syncytium evolves in the developing brain. Our results show that the spongiform morphology of individual astrocytes and their spatial organization all reach stationary levels by postnatal day (P) 15 in the hippocampal CA1 region. Functionally, astrocytes begin to uniformly express a mature level of passive K+ conductance by P11. We next used syncytial isopotentiality measurement to monitor the maturation of the astrocyte syncytium. In uncoupled P1 astrocytes, the substitution of endogenous K+ by a Na+ -electrode solution ([Na+ ]p ) resulted in the total elimination of the physiological membrane potential (VM ), and outward K+ conductance as predicted by the Goldman-Hodgkin-Katz (GHK) equation. As more astrocytes are coupled to each other through gap junctions during development, the [Na+ ]p -induced loss of physiological VM and the outward K+ conductance is progressively compensated by the neighboring astrocytes. By P15, a stably established syncytial isopotentiality (-73 mV), and a fully compensated outward K+ conductance appeared in all [Na+ ]p -recorded astrocytes. Thus, in view of the developmental timeframe wherein a singular syncytium is anatomically and functionally established for intra-syncytium K+ equilibration, an astrocyte syncytium becomes fully operational at P15 in the mouse hippocampus.

Rabies in kudu: Revisited.

Rabies infects all mammals; however, transmission cycles are only maintained in certain bat and carnivore species. The high incidence of rabies in Greater Kudu (Tragelaphus strepsiceros) observed in Namibia for over 40 years has led to postulation that independent virus transmission is occurring within this antelope population. We have analysed extensive experimental, epidemiological, phylogeographic and deep sequence data, which collectively refute maintenance of an independent rabies cycle in kudu. As rabies in kudu continues to have a negative impact on the Namibian agricultural sector, measures to protect kudu have been investigated, including the use of a third-generation oral rabies vaccine. Initial results show protection of kudu from rabies infection via the oral route, with an appropriate bait design, different application schedules and vaccination doses further enhancing the immune response. Rabies in kudu is a complex interplay at the wildlife-livestock interface and requires a concerted approach to successfully control.

ERPs reveal an iconic relation between sublexical phonology and affective meaning.

Classical linguistic theory assumes that formal aspects, like sound, are not internally related to the meaning of words. However, recent research suggests language might code affective meaning such as threat and alert sublexically. Positing affective phonological iconicity as a systematic organization principle of the German lexicon, we calculated sublexical affective values for sub-syllabic phonological word segments from a large-scale affective lexical German database by averaging valence and arousal ratings of all words any phonological segment appears in. We tested word stimuli with either consistent or inconsistent mappings between lexical affective meaning and sublexical affective values (negative-valence/high-arousal vs. neutral-valence/low-arousal) in an EEG visual-lexical-decision task. A mismatch between sublexical and lexical affective values elicited an increased N400 response. These results reveal that systematic affective phonological iconicity - extracted from the lexicon - impacts the extraction of lexical word meaning during reading.

Pelvic Lymph Node Dissection at Radical Prostatectomy for Intermediate Risk Prostate Cancer: Assessing Utility and Nodal Metastases Within a Statewide Quality Improvement Consortium.

OBJECTIVE: To assess which patients with intermediate-risk PCa would benefit from a pelvic lymph node dissection (PLND) across the Michigan Urological Surgery Improvement Collaborative, given the discrepancy in recommendations. AUA guidelines for localized prostate cancer (PCa) state that PLND is indicated for patients with unfavorable intermediate-risk and high-risk PCa and can be considered in favorable intermediate-risk patients. NCCN guidelines recommend PLND when risk for nodal disease is ≥2%. METHODS: Data regarding all robot-assisted radical prostatectomy (RARP) (March 2012-October 2020) were prospectively collected, including patient, and surgeon characteristics. Univariate and multivariate analyses of PLND rate and lymph node involvement (LN+) were performed. RESULTS: Among 8,591 men undergoing RARP for intermediate-risk PCa, 80.2% were performed with PLND (n = 6883), of which 2.9% were LN+ (n = 198). According to the current AUA risk stratification system, 1.2% of favorable intermediate-risk PCa and 4.7% of unfavorable intermediate-risk PCa demonstrated LN+. There were also differences in the LN+ rates among the subgroups of favorable (0.0%-1.3%), and unfavorable (3.5%-5.0%) categories. Additional factors associated with higher LN+ rates include ≥50% cores positive, ≥35% involvement at any core, and unfavorable genomic classifier result, none of which contribute to the favorable/unfavorable subgroups. CONCLUSION: These data support PLND at RARP for all patients with unfavorable intermediate-risk PCa. Our data also indicate patients with favorable intermediate-risk prostate cancer at greatest risk for LN+ are those with ≥50% cores positive, ≥35% involvement at any core, and/or unfavorable genomic classifier result.

Ultrastructural view of astrocyte arborization, astrocyte-astrocyte and astrocyte-synapse contacts, intracellular vesicle-like structures, and mitochondrial network.

The complexity of astrocyte morphology and syncytial coupling through gap junctions are crucial for astrocyte function in the brain. However, the ultrastructural details of astrocyte arborization and interactions between neighboring astrocytes remain unknown. While a prevailing view is that synapses selectively contact peripheral astrocyte processes, the precise spatial-location selectivity of synapses abutting astrocytes is unresolved. Additionally, knowing the location and quantity of vesicles and mitochondria are prerequisites to answer two emerging questions - whether astrocytes have a signaling role within the brain and whether astrocytes are highly metabolically active. Here, we provided structural context for these questions by tracing and 3D reconstructing three neighboring astrocytes using serial block-face scanning electron microscopy. Our reconstructions reveal a spongiform astrocytic morphology resulting from the abundance of reflexive and leaflet processes. At the interfaces, varying sizes of astrocyte-astrocyte contacts were identified. Inside an astrocyte domain, synapses contact the entire astrocyte, and synapse-astrocyte contacts increase from soma to terminal leaflets. In contrast to densely packed vesicles at synaptic boutons, vesicle-like structures were scant within astrocytes. Lastly, astrocytes contain dense mitochondrial networks with a mitochondrial volume ratio similar to that of neurites. Together, these ultrastructural details should expand our understanding of functional astrocyte-astrocyte and astrocyte-neuron interactions.

Computer Vision for Detection of Body Posture and Behavior of Red Foxes.

The behavior of animals is related to their health and welfare status. The latter plays a particular role in animal experiments, where continuous monitoring is essential for animal welfare. In this study, we focus on red foxes in an experimental setting and study their behavior. Although animal behavior is a complex concept, it can be described as a combination of body posture and activity. To measure body posture and activity, video monitoring can be used as a non-invasive and cost-efficient tool. While it is possible to analyze the video data resulting from the experiment manually, this method is time consuming and costly. We therefore use computer vision to detect and track the animals over several days. The detector is based on a neural network architecture. It is trained to detect red foxes and their body postures, i.e., 'lying', 'sitting', and 'standing'. The trained algorithm has a mean average precision of 99.91%. The combination of activity and posture results in nearly continuous monitoring of animal behavior. Furthermore, the detector is suitable for real-time evaluation. In conclusion, evaluating the behavior of foxes in an experimental setting using computer vision is a powerful tool for cost-efficient real-time monitoring.

Comparative pathogenesis of different phylogroup I bat lyssaviruses in a standardized mouse model.

A plethora of bat-associated lyssaviruses potentially capable of causing the fatal disease rabies are known today. Transmitted via infectious saliva, occasionally-reported spillover infections from bats to other mammals demonstrate the permeability of the species-barrier and highlight the zoonotic potential of bat-related lyssaviruses. However, it is still unknown whether and, if so, to what extent, viruses from different lyssavirus species vary in their pathogenic potential. In order to characterize and systematically compare a broader group of lyssavirus isolates for their viral replication kinetics, pathogenicity, and virus release through saliva-associated virus shedding, we used a mouse infection model comprising a low (102 TCID50) and a high (105 TCID50) inoculation dose as well as three different inoculation routes (intramuscular, intranasal, intracranial). Clinical signs, incubation periods, and survival were investigated. Based on the latter two parameters, a novel pathogenicity matrix was introduced to classify lyssavirus isolates. Using a total of 13 isolates from ten different virus species, this pathogenicity index varied within and between virus species. Interestingly, Irkut virus (IRKV) and Bokeloh bat lyssavirus (BBLV) obtained higher pathogenicity scores (1.14 for IRKV and 1.06 for BBLV) compared to rabies virus (RABV) isolates ranging between 0.19 and 0.85. Also, clinical signs differed significantly between RABV and other bat lyssaviruses. Altogether, our findings suggest a high diversity among lyssavirus isolates concerning survival, incubation period, and clinical signs. Virus shedding significantly differed between RABVs and other lyssaviruses. Our results demonstrated that active shedding of infectious virus was exclusively associated with two RABV isolates (92% for RABV-DogA and 67% for RABV-Insectbat), thus providing a potential explanation as to why sustained spillovers are solely attributed to RABVs. Interestingly, 3D imaging of a selected panel of brain samples from bat-associated lyssaviruses demonstrated a significantly increased percentage of infected astrocytes in mice inoculated with IRKV (10.03%; SD±7.39) compared to RABV-Vampbat (2.23%; SD±2.4), and BBLV (0.78%; SD±1.51), while only individual infected cells were identified in mice infected with Duvenhage virus (DUVV). These results corroborate previous studies on RABV that suggest a role of astrocyte infection in the pathogenicity of lyssaviruses.