Basal Location Research Articles

Mapping Plasmodium transitions and interactions in the Anopheles female.

The human malaria parasite, Plasmodium falciparum , relies on Anopheles mosquitoes for transmission. Once ingested during blood feeding, most parasites die in the mosquito midgut lumen or during epithelium traversal. How surviving ookinetes interact with midgut cells and form oocysts is unknown, yet these steps are essential to initiate a remarkable, similarly uncharacterized growth process culminating in the production of thousands of infectious sporozoites. Here, using single-cell RNA sequencing of both parasites and mosquito cells across four time points and two metabolic conditions, we unveil key processes shaping developmental transitions and mosquito-parasite interactions occurring in the midgut. In depth functional analyses reveal processes regulating oocyst growth and identify the transcription factor Pf SIP2 as essential for sporozoite infection of human hepatocytes. By combining the analysis of shared mosquito-parasite barcodes with confocal microscopy, we discover that parasites preferentially interact with midgut progenitor cells during epithelial crossing, potentially using their basal location as an exit landmark. Additionally, we unveil tight connections between extracellular late oocysts and surrounding muscle cells that may ensure parasites adhere to the midgut without damaging it. Ultimately, our study provides fundamental insight into the molecular events characterizing previously inaccessible biological transitions and mosquito-parasite interactions, and identifies candidates for transmission-blocking strategies.

The C-terminus of CFAP410 forms a tetrameric helical bundle that is essential for its localization to the basal body.

Cilia are antenna-like organelles protruding from the surface of many cell types in the human body. Defects in ciliary structure or function often lead to diseases that are collectively called ciliopathies. Cilia and flagella-associated protein 410 (CFAP410) localizes at the basal body of cilia/flagella and plays essential roles in ciliogenesis, neuronal development and DNA damage repair. It remains unknown how its specific basal body location is achieved. Multiple single amino acid mutations in CFAP410 have been identified in patients with various ciliopathies. One of the mutations, L224P, is located in the C-terminal domain (CTD) of human CFAP410 and causes severe spondylometaphyseal dysplasia, axial (SMDAX). However, the molecular mechanism for how the mutation causes the disorder remains unclear. Here, we report our structural studies on the CTD of CFAP410 from three distantly related organisms, Homo sapiens, Trypanosoma brucei and Chlamydomonas reinhardtii. The crystal structures reveal that the three proteins all adopt the same conformation as a tetrameric helical bundle. Our work further demonstrates that the tetrameric assembly of the CTD is essential for the correct localization of CFAP410 in T. brucei, as the L224P mutation that disassembles the tetramer disrupts its basal body localization. Taken together, our studies reveal that the basal body localization of CFAP410 is controlled by the CTD and provide a mechanistic explanation for how the mutation L224P in CFAP410 causes ciliopathies in humans.

Metabolic regulation of single synaptic vesicle exo- and endocytosis in hippocampal synapses

Glucose has long been considered a primary energy source for synaptic function. However, it remains unclear to what extent alternative fuels, such as lactate/pyruvate, contribute to powering synaptic transmission. By detecting individual release events in hippocampal synapses, we find that mitochondrial ATP production regulates basal vesicle release probability and release location within the active zone (AZ), evoked by single action potentials. Mitochondrial inhibition shifts vesicle release closer to the AZ center and alters the efficiency of vesicle retrieval by increasing the occurrence of ultrafast endocytosis. Furthermore, we uncover that terminals can use oxidative fuels to maintain the vesicle cycle during trains of activity. Mitochondria are sparsely distributed along hippocampal axons, and we find that terminals containing mitochondria display enhanced vesicle release and reuptake during high-frequency trains. Our findings suggest that mitochondria not only regulate several fundamental features of synaptic transmission but may also contribute to modulation of short-term synaptic plasticity.

The first detection of coccidia (Conoidasida: Eimeriidae) DNA in Godlewski’s sculpin Abyssocottus (Limnocottus) godlewskii (Dybowski, 1874)

For the first time, fragments of the cox1 gene of a representative of the family Eimeriidae were obtained by high-throughput sequencing in the digestive tract of Godlewski’s sculpin Abyssocottus (Limnocottus) godlewskii (Dybowski, 1874). The nucleotide sequences of the coccidia, which accounted for less than 0.01% of the total data set, belonged to a single genotype and were significantly different from all previously known. Phylogenetic reconstruction based on the translated amino acid sequences reliably revealed the basal location of branches belonging to representatives of the family Eimeriidae among fishes. The question of the genus of the detected organism remains unresolved due to the limited nucleotide data for representatives of the genera Eimeria, Calyptospora, and Goussia from fish.

Skin cancer occurrence: single-center experiences from period 2020-2022.

<b><br>Introduction:</b> Skin cancers constitute a group of medical disorders remaining a field of interest for surgeons and dermatologists. Currently, this group is typically divided into malignant melanoma (MM) and keratinocyte cancers (KC).</br> <b><br>Aim:</b> The aim of this study is to analyze the cases of skin cancers treated in the Department of Plastic, Reconstructive, and Aesthetic Surgery in Lodz (Poland) during the COVID-19 pandemic (from 2020 to 2022) and then compare the results with the ones from the pre-pandemic period (from 2017 to 2019).</br> <b><br>Material and methods:</b> An analysis of histopathological files from the period between 2020 and 2022 was performed. It was based on the following criteria: sex, age, type of skin cancer, subtype of basal cell carcinoma (BCC), location, and dimensions of the tumor. The study sample consisted of 225 patients presenting 241 cases of skin cancers. There were 74 men and 151 women, with the mean age being 71.7.</br> <b><br>Results:</b> The most common skin cancer was BCC (175 cases, 72.6%) followed by SCC (59 cases, 24.5%), melanoma (5 cases, 2.1%), and other (2 cases, 0.8% - angiosarcoma and sweat gland carcinoma).</br> <b><br>Conclusions:</b> A marked reduction in the number of skin cancers detected during the pandemic period was reported on. Delay in the surgical treatment of skin tumors does not seem to affect the size of the removed lesion. Some models predicting that tumors would be larger after the confinement period are not applicable in reality. However, further investigations with larger samples from multiple centers are needed to confirm these findings and to work out standards on how to deal with healthcare crises in the future.</br&gt.

Use of a Local Anaesthetic/Antiseptic Formulation for the Treatment of Lambs Experimentally Infected with Orf Virus.

Contagious ecthyma is a highly transmissible eruptive viral disease of the skin and mucosa of sheep and goats distributed worldwide. The treatment of orf lesions is usually based on the use of antiseptics and antibiotics for the management of presumptive secondary infections, increasing risks of antimicrobial resistance. The wound dressing formulation Tri-Solfen® (TS) containing two local anaesthetics (lignocaine and bupivacaine), adrenaline and an antiseptic (cetrimide) in a gel formulation has been demonstrated to reduce suffering and enhance recovery in cattle and buffalo with oral and skin lesions due to foot-and-mouth disease virus infection and reduced the orf viral load in lambs. In the present study, experimental infection with the orf virus was conducted in 50 newborn lambs and 25 animals were treated after the presence of the first lesions with TS and repeated three days later. Daily clinical examination, haematological, serological, biomolecular and post-mortem analyses were conducted during 34 days after treatment. Results indicated that treatment had no effect on weight gain and clinical progression of the lesions. It was determined that seroconversion after experimental infection occurs 34 days after infection and suggested that the deep basal epithelial location of the orf lesions may have prevented the therapy from having altered the clinical course.

Repositioning and optimization of left ventricular lead position in nonresponders to cardiac resynchronization therapy is associated with improved ejection fraction, lower NT-proBNP values, and fewer heart failure symptoms.

Observational data suggest that an anterior or apical left ventricular (LV) position in cardiac resynchronization therapy (CRT) is associated with worse outcome and higher likelihood of "nonresponse." It is not known whether the benefits of optimizing LV lead position in a second procedure outweighs the procedural risks. To evaluate the clinical effects of LV lead repositioning. During the period 2015-2020, we identified all patients in whom the indication for the procedure was LV lead repositioning owing to "nonresponse" in combination with suboptimal LV lead position. All patients were followed with a structured visit 6 months post LV lead revision. Heart failure hospitalization and mortality data were gathered from the medical records and cross-checked with the population registry. A total of 25 patients were identified who fulfilled the inclusion criteria. All procedures were successful in establishing LV lead pacing in a lateral mid or basal location. Median follow-up was 2.5 years [1.1-3.7]. There were improvements in NYHA class (mean -0.5 ± 0.5 class, P < .001), LV ejection fraction (+5 [interquartile range 2-11] absolute %, P = .01), QRS duration (-36 [-44 to -8], P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (-615 [-2837 to +121] ng/L, P = .03). Clinical outcome was similar to a reference population with CRT (P = ns). In nonresponders to CRT with either an anterior or inferior LV lead position, it was feasible to perform LV lead repositioning in all cases, with a low complication rate. Changing the LV lead position was associated with improved LV ejection fraction, larger QRS reduction, and larger NT-proBNP reduction.

Unexpected record of the aquatic sloth Thalassocnus (Mammalia, Xenarthra, Folivora) in the upper Neogene of the Puna (Jujuy, Argentina)

ABSTRACT Xenarthra are, very probably, the most basally branching clade among Placentalia, and the result of the so-called “Splendid Isolation” of South America. Although this is the only endemic clade with living representatives, its current diversity is very poor compared with that achieved during most of the Cenozoic. One particular clade, Folivora (living and fossil sloths), includes one of the most enigmatic animals, Thalassocnus, the only genus of the subfamily Thalassocninae. It was originally interpreted as an aquatic sloth taking into account the previous records, which are limited to coastal areas of the latest Miocene and Pliocene of Peru and Chile. Here we present the first record of Thalassocnus from Argentina, which in turn represents the first finding of the genus in a continental sequence. The materials (JUY-P-0180, radius, ulna and part of the articulated left manus) were exhumed from the upper member of the Tafna Formation (Late Miocene–Pliocene) in the eastern Puna (Jujuy Province), Argentina. In agreement with our comparative study, the cladistic analysis corroborates its identification as belonging to the genus Thalassocnus, being placed in a relatively basal location. This finding is of paleobiogeographic and paleoenvironmental significance, due to its location, more than 1171 km away from the Peruvian locality (Sacaco) and more than 750 km from the nearest ones in Chile (Caldera). This extends the geographic range from 76°W to 65°53′W, and from typical littoral environments, to clearly more terrestrial ones. The evolutionary and paleobiogeographic history of Thalassocnus is more complex than previously interpreted.

ULTRASOUND CHARACTERISTIC OF EMBRYO, FETAL EGG AND CHORIONIC STRUCTURES IN PREGNANT WOMEN WITH MISCARRIAGE

The aim: The aim of the study was to assess the peculiarities of the formation and development of the fetoplacental system, to study the structures of the embryo, gestational sac, chorion in pregnant women with miscarriage. Materials and methods: A comprehensive ultrasound examination of 50 pregnant women was carried out in the period from 5 to 16 weeks of pregnancy, of which 25 - with a history of miscarriage (main group), and 25 - with an unremarkable medical history (control group). Results: We have identified the following echographic markers of adverse course and outcome of pregnancy in women with miscarriage in embryonic and early fetal periods:- lag of CRL of an embryo by 2 weeks and more at ultrasound examination in terms up to 9 weeks of gestation;- corporal or basal (near the stem of the embryo body) location of chorionic detachment with the formation of retrochorial hematoma with a volume of more than 25 ml;- pronounced progressive decrease in the volume of the gestational sac and amniotic cavity;- pronounced polyhydramnios with the presence of a coarse echopositive suspension in the amnioticcavity. The likelihood of spontaneous miscarriage and the formation of placental dysfunction is higher with the simultaneous detection of 2 or more echographic markers. Conclusions: Ultrasound examination is necessary to assess the echographic parameters of the formation and development of the embryo and extraembryonic structures in the first trimester with a history of miscarriage in order to the subsequent choice of rational tactics of pregnancy management.

Single-Session Stereotactic Radiosurgery for Large Benign Meningiomas: Medium-to Long-Term Results

The use of stereotactic radiosurgery for the treatment of intracranial meningiomas has been established as an effective and safe treatment modality. Larger meningiomas typically are managed by surgery followed by radiosurgery. Treatment of large meningiomas (usually defined as >10 cc) by stereotactic radiosurgery has been investigated in some recent reports, either by single-session, volume-staged, or the hypofractionation technique. We sought to assess the long-term efficacy and safety of single-session stereotactic radiosurgery for large (10 cc or more) intracranial benign meningiomas. In this retrospective study, we included 273 patients with large benign meningiomas (≥10 cc) who were treated by single-session SRS and followed up for more than 2 years. Tumors were in a basal location in 228 patients (84%). There were 161 tumors (59%) in the perioptic location. The median tumor volume was 15.5 (10-57.3 cc [interquartile range {IQR} 12.3 cc]). The median prescription dose was 12 Gy (9-15 Gy [IQR 1 Gy]). The median follow-up period was 6.1 years (2-18 years [IQR 5.5 years]). The tumor control rate was 90%. The progression-free survival at 5 and 10 years was 96% and 81%, respectively, for the whole cohort. Among 161 patients with perioptic meningiomas, favorable (better/stable) visual outcome was reported in 155 patients (96%) and unfavorable (worse) outcome in 6 patients (4%). Temporary adverse radiation effects were observed in 41 patients (15%) but only 16 (6%) were symptomatic. Stereotactic radiosurgery provides an effective and safe treatment option for large meningiomas.

Effect of Chronological Age on Pulse Rate Discrimination in Adult Cochlear-Implant Users.

Cochlear-implant (CI) users rely heavily on temporal envelope cues to understand speech. Temporal processing abilities may decline with advancing age in adult CI users. This study investigated the effect of age on the ability to discriminate changes in pulse rate. Twenty CI users aged 23 to 80 years participated in a rate discrimination task. They attempted to discriminate a 35% rate increase from baseline rates of 100, 200, 300, 400, or 500 pulses per second. The stimuli were electrical pulse trains delivered to a single electrode via direct stimulation to an apical (Electrode 20), a middle (Electrode 12), or a basal location (Electrode 4). Electrically evoked compound action potential amplitude growth functions were recorded at each of those electrodes as an estimate of peripheral neural survival. Results showed that temporal pulse rate discrimination performance declined with advancing age at higher stimulation rates (e.g., 500 pulses per second) when compared with lower rates. The age-related changes in temporal pulse rate discrimination at higher stimulation rates persisted after statistical analysis to account for the estimated peripheral contributions from electrically evoked compound action potential amplitude growth functions. These results indicate the potential contributions of central factors to the limitations in temporal pulse rate discrimination ability associated with aging in CI users.

Regular Use of Depot Medroxyprogesterone Acetate Causes Thinning of the Superficial Lining and Apical Distribution of Human Immunodeficiency Virus Target Cells in the Human Ectocervix.

BackgroundThe hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with an increased risk of acquiring human immunodeficiency virus (HIV). We hypothesize that DMPA use influences the ectocervical tissue architecture and HIV target cell localization.MethodsQuantitative image analysis workflows were developed to assess ectocervical tissue samples collected from DMPA users and control subjects not using hormonal contraception.ResultsCompared to controls, the DMPA group exhibited a significantly thinner apical ectocervical epithelial layer and a higher proportion of CD4+CCR5+ cells with a more superficial location. This localization corresponded to an area with a nonintact E-cadherin net structure. CD4+Langerin+ cells were also more superficially located in the DMPA group, although fewer in number compared to the controls. Natural plasma progesterone levels did not correlate with any of these parameters, whereas estradiol levels were positively correlated with E-cadherin expression and a more basal location for HIV target cells of the control group.ConclusionsDMPA users have a less robust epithelial layer and a more apical distribution of HIV target cells in the human ectocervix, which could confer a higher risk of HIV infection. Our results highlight the importance of assessing intact genital tissue samples to gain insights into HIV susceptibility factors.

The Effect of Interphase Gap on Neural Response of the Electrically Stimulated Cochlear Nerve in Children With Cochlear Nerve Deficiency and Children With Normal-Sized Cochlear Nerves.

This study aimed to compare the effects of increasing the interphase gap (IPG) on the neural response of the electrically stimulated cochlear nerve (CN) between children with CN deficiency (CND) and children with normal-sized CNs. Study participants included 30 children with CND and 30 children with normal-sized CNs. All subjects were implanted with a Cochlear Nucleus device with the internal electrode array 24RE[CA] in the test ear. The stimulus was a charge-balanced, cathodic leading, biphasic pulse with a pulse-phase duration of 50 μsec. For each subject, the electrically evoked compound action potential (eCAP) input/output (I/O) function was measured for 6 IPGs (i.e., 7, 14, 21, 28, 35, and 42 μsec) at 3 electrode locations across the electrode array. For each subject and each testing electrode, the highest stimulation used to measure the eCAP I/O function was the maximum comfortable level measured with an IPG of 42 μsec. Dependent variables (DVs) were the maximum eCAP amplitude, the eCAP threshold, and the slope of the eCAP I/O function estimated using both linear and sigmoidal regression functions. For each DV, the size of the IPG effect was defined as the proportional change relative to the result measured for the 7 μsec IPG at the basal electrode location. Generalized linear mixed effect models with subject group, electrode location, and IPG duration as the fixed effects and subject as the random effect were used to compare these DVs and the size of the IPG effect on these DVs. Children with CND showed smaller maximum eCAP amplitudes, higher eCAP thresholds, and smaller slopes of eCAP I/O function estimated using either linear or sigmoidal regression function than children with normal-sized CNs. Increasing the IPG duration resulted in larger maximum eCAP amplitudes, lower eCAP thresholds and larger slopes of eCAP I/O function estimated using sigmoidal regression function at all three electrode locations in both study groups. Compared with children with normal-sized CNs, children with CND showed larger IPG effects on both the maximum eCAP amplitude and the slope of the eCAP I/O function estimated using either linear or sigmoidal regression function, and a smaller IPG effect on the eCAP threshold than those measured in children with normal-sized CNs. Increasing the IPG increases responsiveness of the electrically stimulated CN in both children with CND and children with normal-sized CNs. The maximum eCAP amplitude and the slope of the eCAP I/O function measured in human listeners with poorer CN survival are more sensitive to changes in the IPG. In contrast, the eCAP threshold in listeners with poorer CN survival is less sensitive to increases in the IPG. Further studies are warranted to identify the best parameters of eCAP results for predicting CN survival before this eCAP testing paradigm can be used as a clinical tool for evaluating neural health for individual cochlear implant patients.

Correlation between risk factors of cerebrovascular disease and calcified plaque characteristics in patients with atherosclerotic severe carotid stenosis

ABSTRACTObjectives: The aim of this study was to evaluate the relationship between the risk factors of cerebral vascular diseases (CVD) and the characteristics of calcified plaques in patients with severe carotid arteriosclerosis stenosis (SCAS).Methods: A total of 402 patients with SCAS who were treated in our hospital between January to December 2016 were included in this study. The patients were divided into calcified plaque group and non-calcified plaque group according to the ultrasonography and computerized tomography angiography (CTA) or digital subtraction angiography (DSA) imaging of SCAS-responsible plaque and the characteristics of calcified plaques evaluated by high-frequency ultrasound.Results: The patients with long-term diabetes mellitus or higher levels of fasting blood glucose were more likely to develop calcified plaques (P = 0.00 and P = 0.021, respectively). In addition, the patients with calcified plaques were mostly smokers (P = 0.016). Their smoking duration and accumulative smoking exposure were higher than those without calcified plaque (P = 0.006 and P = 0.007, respectively). The basal location of calcification (P = 0.004) and the type of patchy calcification (P = 0.00) were both easier to appear in smokers, while non-smokers were more likely to have small granular calcification (P = 0.002). Furthermore, the carotid plaque calcification with mixed-location were more frequently seen in patients with hypertension (P = 0.016). The risk factors independently associated with plaque calcification were significantly associated with smoking status, smoking age, and accumulative smoking exposure, as well as age and diabetes mellitus (all P < 0.05).Conclusion: Smoking, diabetes mellitus and age were independent risk factors for carotid plaque calcification. Smoking and hypertension were associated with specific locations and types of plaque calcification.

ORAL MELANOACANTHOMA ASSOCIATED WITH PSEUDOMELANOCYTIC NESTS: AN IMMUNOHISTOCHEMICAL STUDY

Oral melanoacanthoma is an uncommon pigmented lesion of the oral mucosa characterized by the presence of acanthosis and dendritic pigment-laden melanocytes located in the prickle cell layer of the epithelium. Pseudomelanocytic nests (PNs) represent cellular aggregates of keratinocytes, macrophages, and melanocytes, usually located in close relationship with lichenoid inflammation, which if not recognized can be misdiagnosed as melanoma. A 41-year-old white woman was referred presenting a pigmented gingival lesion located between the left maxillary central and lateral incisors with 1 year of evolution. After excisional biopsy, microscopy showed typical melanoacanthoma associated with PNs. PNs and dendritic melanocytes were evidenced by Fontana-Masson stain. Immunohistochemistry revealed positivity for AE1/AE3, CD68, and CD163 in PNs, while HMB-45 and Melan-A highlighted dendritic melanocytes. SOX-10 positivity was observed in few melanocytes in basal location. To our knowledge, this is the first report of oral melanoacanthoma associated with PNs. FAPESP (2016/11419-0 and 2017/02502-4).

Cardiac magnetic resonance imaging with late gadolinium enhancement in acute myocarditis: Towards differentiation between immune-mediated and viral-related aetiologies

Diagnosing immune-mediated myocarditis is challenging because of non-specific clinical signs and symptoms. Cardiac magnetic resonance imaging (CMR) provides subepicardial late gadolinium enhancement (LGE) in the setting of acute myocarditis, but the diagnostic value of LGE pattern for differentiating between immune-mediated and viral-related aetiologies remains unknown. To determine the value of LGE pattern for differentiating between immune-mediated and viral-related aetiologies in patients with acute myocarditis. One hundred and five patients with acute myocarditis who underwent CMR, including LGE variables, were included retrospectively. Viral-related aetiology was retained with a negative autoimmune and autoinflammatory assessment at diagnosis and 6-month follow-up. Aetiology was immune-mediated in 31 patients and viral-related in 74 patients. Patients with immune-mediated myocarditis were older (55±16 vs. 31±12years; P<0.001) and more likely to be female (52% vs. 14%; P<0.001) than those with viral-related myocarditis. There was no difference in left ventricular ejection fraction between the immune-mediated and viral-related myocarditis groups (53±15% vs. 57±8%; P=0.61). Regarding LGE, patients with viral-related myocarditis were more likely to have basal anteroseptal, mid anteroseptal, mid anterior and basal anterolateral location. Patients with immune-mediated myocarditis were more likely to have apical septal, apical inferior, apical lateral, mid anterolateral and basal inferior location. Segments with difference in prevalence of LGE between aetiologies were summed to build a score where positive significant association with immune-mediated myocarditis was quoted 1 and positive significant association with viral-related myocarditis was quoted -1. A score≥0 differentiated immune-mediated from viral-related myocarditis with 94% sensitivity and 77% specificity (area under the receiver operating characteristic curve 0.88; P<0.001). CMR provides arguments for differentiating immune-mediated from viral-related acute myocarditis by showing preferential LGE localization in apical septal, apical inferior, apical lateral and basal inferior segments.

Soil chemistry, and not short-term (1-2 year) deer exclusion, explains understory plant occupancy in forests affected by acid deposition.

The loss of species diversity and plant community structure throughout the temperate deciduous forests of North America have often been attributed to overbrowsing by white-tailed deer (Odocoileus virginanus). Slow species recovery following removal from browsing, or reduction in deer density, has been termed a legacy effect of past deer herbivory. However, vegetation legacy effects have also coincided with changes to soil chemistry throughout the north-eastern USA. In this paper, we assess the viability of soil chemistry (i.e. pH, extractable nutrients and extractable metals) and other factors (topography, light, overstory basal area and location) as alternative explanations for a lack of vegetation recovery. We compared the relative effects of soil chemistry, site conditions and short-term (1-2 year) deer exclusion on single-species occupancy probabilities of 10 plant taxa common to oak-hickory forests in central Pennsylvania. We found detection for all modelled species was constant and high ( > 0.65), and occupancy probability of most taxa was best explained by at least one soil chemistry parameter. Specifically, ericaceous competing vegetation was more likely to occupy acidic (pH < 3.5), base cation-poor (K < 0.20 cmolc kg-1) sites, while deer-preferred plants were less likely to occur when soil manganese exceeded 0.1 cmolc kg-1. Short-term deer exclusion did not explain occupancy of any plant taxon, and site conditions were of nominal importance. This study demonstrates the importance of soil chemistry in shaping plant community composition in the north-central Appalachians, and suggests soil as an alternative, or additional, explanation for deer vegetation legacy effects. We suggest that the reliance on phyto-indicators of deer browsing effects may overestimate the effects of browsing if those species are also limited by unfavourable soil conditions. Future research should consider study designs that address the complexity of deer forest interactions, especially in areas with complex site-vegetation histories.

Probing hair cell\u2019s mechano-transduction using two-tone suppression measurements

When two sound tones are delivered to the cochlea simultaneously, they interact with each other in a suppressive way, a phenomenon referred to as two-tone suppression (2TS). This nonlinear response is ascribed to the saturation of the outer hair cell’s mechano-transduction. Thus, 2TS can be used as a non-invasive probe to investigate the fundamental properties of cochlear mechano-transduction. We developed a nonlinear cochlear model in the time domain to interpret 2TS data. The multi-scale model incorporates cochlear fluid dynamics, organ of Corti (OoC) mechanics and outer hair cell electrophysiology. The model simulations of 2TS show that the threshold amplitudes and rates of low-side suppression are dependent on mechano-transduction properties. By comparing model responses to existing 2TS measurement data, we estimate intrinsic characteristics of mechano-transduction such as sensitivity and adaptation. For mechano-transduction sensitivity at the basal location (characteristic frequency of 17 kHz) at 0.06 nm−1, the simulation results agree with 2TS measurements of basilar membrane responses. This estimate is an order of magnitude higher than the values observed in experiments on isolated outer hair cells. The model also demonstrates how the outer hair cell’s adaptation alters the temporal pattern of 2TS by modulating mechano-electrical gain and phase.

Abstract 77: Perihematomal Edema Expansion Rate is Associated With Poor Functional Outcomes in Basal Ganglia Intracerebral Hemorrhage

Background: Perihematomal edema (PHE) has been associated with poor outcomes in deep spontaneous intracerebral hemorrhage (ICH). However, it is unknown if specific deep location (thalamus versus basal ganglia) modifies the effect of PHE on functional outcome. Methods: We used data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial. We included patients who had deep ICH and available neuroimaging and 3-month functional outcome data. We calculated the 24-hour PHE expansion rate as the difference in PHE volume between baseline and 24-hour CT scan divided by hours between scans. We used logistic regression models to evaluate the relationship between PHE expansion rate (natural-log transformed) and poor outcome (3-month modified Rankin Scale [mRS] score 4-6), with subgroup analyses to determine the effect of thalamic vs basal ganglia location on this association. Results: Out of 1000 subjects enrolled in ATACH-2, 870 (87%) had supratentorial, deep ICH. Of these, 754 (87%) had complete neuroimaging and outcome data (thalamus n=324, basal ganglia n=430). Overall, PHE expansion rate was associated with poor outcome in univariable (OR 1.3, 1.2-1.5, p&lt;0.001) but not multivariable models (OR 1.1, 0.9-1.3, p=0.24). Median PHE expansion rate was faster in basal ganglia versus thalamic ICH (0.03 [0.09] mL/hr vs 0.01 [0.04] mL/hr, p&lt;0.001). In basal ganglia ICH, PHE expansion rate was associated with poor outcome (OR 1.4, 1.1-1.8, p=0.01) in a multivariable model including age, sex, race, admission GCS, ICH volume (natural log-transformed), presence of intraventricular hemorrhage (IVH), hematoma expansion, time to baseline scan, and treatment group. In thalamic ICH, PHE expansion rate was not associated with poor outcome in multivariable analysis (OR 0.9, 0.7-1.2, p=0.44). Conclusions: In the ATACH-2 trial population, 24-hour PHE expansion rate was associated with poor functional outcome among basal ganglia, but not thalamic, bleeds. These results provide further evidence that PHE is associated with functional outcomes and supports the existence of effect modification by the specific deep location involved.

Prevalence of Extracochlear Electrodes: Computerized Tomography Scans, Cochlear Implant Maps, and Operative Reports.

To quantify and compare the number of cochlear implant (CI) electrodes found to be extracochlear on postoperative computerized tomography (CT) scans, the number of basal electrodes deactivated during standard CI mapping (without knowledge of the postoperative CT scan), and the extent of electrode insertion noted by the surgeon. Retrospective. Academic Medical Center. Two hundred sixty-two patients underwent standard cochlear implantation and postoperative temporal bone CT scanning. Scans were analyzed to determine the number of extracochlear electrodes. Standard CI programming had been completed without knowledge of the extracochlear electrodes identified on the CT. These standard CI maps were reviewed to record the number of deactivated basal electrodes. Lastly, each operative report was reviewed to record the extent of reported electrode insertion. 13.4% (n = 35) of CIs were found to have at least one electrode outside of the cochlea on the CT scan. Review of CI mapping indicated that audiologists had deactivated extracochlear electrodes in 60% (21) of these cases. Review of operative reports revealed that surgeons correctly indicated the number of extracochlear electrodes in 6% (2) of these cases. Extracochlear electrodes were correctly identified audiologically in 60% of cases and in surgical reports in 6% of cases; however, it is possible that at least a portion of these cases involved postoperative electrode migration. Given these findings, postoperative CT scans can provide information regarding basal electrode location, which could help improve programming accuracy, associated frequency allocation, and audibility with appropriate deactivation of extracochlear electrodes.