Period Of Deprivation Research Articles

Revisiting Estrogen for the Treatment of Endocrine-Resistant Breast Cancer: Novel Therapeutic Approaches.

Estrogen receptor (ER)-positive breast cancer is the most common subtype, representing 70-75% of all breast cancers. Several ER-targeted drugs commonly used include the selective estrogen receptor modulator (SERM), tamoxifen (TAM), aromatase inhibitors (AIs) and selective estrogen receptor degraders (SERDs). Through different mechanisms of action, all three drug classes reduce estrogen receptor signaling. Inevitably, resistance occurs, resulting in disease progression. The counterintuitive action of estrogen to inhibit ER-positive breast cancer was first observed over 80 years ago. High-dose estrogen and diethylstilbestrol (DES) were used to treat metastatic breast cancer accompanied by harsh side effects until the approval of TAM in the 1970s. After the development of TAM, randomized trials comparing TAM to estrogen found similar or slightly inferior efficacy but much better tolerability. After decades of research, it was learned that estrogen induces tumor regression only after a period of long-term estrogen deprivation, and the mechanisms of tumor regression were described. Despite the long history of breast cancer treatment with estrogen, this therapeutic modality is now revitalized due to the development of novel estrogenic compounds with improved side effect profiles, newly discovered predictive biomarkers, the development of non-estrogen small molecules and new combination therapeutic approaches.

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency.

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/-) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/- rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/- rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/- males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).

Dexmedetomidine attenuates sleep deprivation-induced inhibition of hippocampal neurogenesis via VEGF-VEGFR2 signaling and inhibits neuroinflammation

Long periods of sleep deprivation (SD) have serious effects on health. While the α2 adrenoceptor agonist dexmedetomidine (DEX) can improve sleep quality for patients who have insomnia, the effect of DEX on cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h SD daily for seven days. DEX (100 μg/kg) was administered intravenously twice daily (at 1:00 p.m. and 3:00 p.m.) during seven days of SD. We found that systemic administration of DEX attenuated cognitive deficits by performing the Y maze and novel object recognition tests and increased DCX+, SOX2+, Ki67+, and BrdU+NeuN+/NeuN+ cell numbers in the dentate gyrus (DG) region of SD mice by using immunofluorescence, western blotting, and BrdU staining. DEX did not reverse the decrease in DCX+, SOX2+, or Ki67+ cell numbers in SD mice after administration of the α2A-adrenoceptor antagonist BRL-44408. Furthermore, the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) expression was upregulated in SD+DEX mice compared with SD mice. Luminex analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of neuroinflammation, including IL-1α, IL-2, CCL5, and CXCL1. Our results suggested that DEX alleviated the impaired learning and memory of SD mice potentially by inducing hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway and by suppressing neuroinflammation, and α2A adrenoceptors are required for the neurogenic effects of DEX after SD. This novel mechanism may add to our knowledge of DEX in the clinical treatment of impaired memory caused by SD.

Duration of deprivation of the right to hold certain positions or engage in certain activities: theory and practice problems

Purpose. The objective of the study is to clarify the criminal law issues related to the determination of the terms of deprivation of the right to hold certain positions or engage in certain activities as a special type of punishment. To achieve this objective, an appropriate methodology was applied, in particular, philosophical, general scientific and special scientific methods were used. For example, the dialectical method was used to identify the essential features of deprivation of the right to hold certain positions or engage in certain activities; the historical and legal ones - when studying the problem of determining the optimal terms of deprivation of the right to hold certain positions or engage in certain activities in the national criminal law doctrine; the comparative legal method - to clarify the specifics of the relationship between deprivation of a right and restriction of a right; typological one - to reveal the peculiarities of criminal law differentiation of terms of deprivation of the right to hold certain positions or engage in certain activities; systemic and structural methods were used to study the deprivation of the right to hold certain positions or engage in certain activities in the system of criminal punishment; formal and dogmatic ones - when analyzing the provisions of current criminal legislation of Ukraine establishing deprivation of the right to hold certain positions or engage in certain activities as a type of punishment. Results. Establishing the periods of deprivation of the right to hold certain positions or engage in certain activities in absolutely certain amounts contradicts the general principles of sentencing, eliminates the court's authority to impose an optimal punishment, and also negatively affects the mechanism of criminal law regulation. Scientific novelty. Deprivation of the right to hold certain positions or engage in certain activities is an effective form of preventing and combating crime, as it provides for the harmonization of the relevant punitive properties with the personal characteristics of the perpetrator. Practical importance. In order to enhance the criminal legal impact of deprivation of the right to hold certain positions or engage in certain activities, the duration should be set in relatively defined amounts with the mandatory definition of both the maximum and minimum limits.

0210 Conservation of Prior Slow Wave Sleep Does Not Provide Resilience to Neurobehavioral Impairment during Total Sleep Deprivation

Abstract Introduction Slow wave sleep (SWS) is thought to play a critical, if not unique, role in resilience and recovery of waking function. It has been posited that if SWS is preserved, the impact of sleep restriction on subsequent neurobehavioral functioning should be minimal. In this context, we investigated the effects of a delayed and restricted sleep opportunity on SWS and on neurobehavioral impairment during a subsequent period of total sleep deprivation (TSD). Methods N=21 healthy adults (21–38y, 9f) underwent three separate periods of 36h TSD, each preceded by one week of prior sleep extension to 12h time in bed (TIB) per night (PSE condition, twice), or prior sleep restriction to 6h TIB per night (PSR condition, once). The last night of each condition was spent inside the laboratory. TIB for the pre-TSD night was 22:00–10:00 (PSE) or 04:00–10:00 (PSR). During each 36h TSD period, subjects completed a neurobehavioral task battery every 2h including a digit-symbol substitution test (DSST) measuring cognitive throughput and the Karolinska Sleepiness Scale (KSS) measuring subjective sleepiness. Following TSD, subjects had a 12h sleep opportunity (22:00–10:00). Sleep was recorded polysomnographically during both pre- and post-TSD nights. Results The pre-TSD night in the PSR condition had less total sleep time, with significant reductions (p< 0.001) in N1, N2, and REM durations compared to the PSE condition. There were no significant differences between the PSE and PSR conditions in SWS duration (p=0.40). Moreover, in the post-TSD night, there were no significant differences (p>0.1) between the PSE and PSR conditions in any of the sleep stages, including SWS. Neurobehavioral functioning during TSD exhibited significant effects (p< 0.02) of prior sleep condition on DSST throughput and KSS sleepiness, with reduced throughput and increased sleepiness in the PSR condition relative to the PSE condition. Conclusion SWS was remarkably conserved in delayed, restricted sleep compared to extended sleep. However, this conservation of SWS did not prevent exacerbation of DSST throughput deficits or KSS sleepiness from prior sleep restriction during subsequent TSD. As such, other aspects of sleep besides SWS are also important in mediating sleep-induced resilience and recovery. Support (if any) NASA NAG9-1161, CDMRP W81XWH-20-1-0442, ARO W911NF2210223.

A correlation between seasonally changing photoperiod, whole body lipid, and condition factor in juvenile spring Chinook salmon (Oncorhynchus tshawytscha).

The regulation of lipid stores is a central process for the physiology and ecology of fishes. Seasonal variation in lipid stores has been directly linked to survival of fishes across periods of food deprivation. We assessed whether a seasonally changing photoperiod was correlated to seasonal changes in energetic status to help better understand these important processes. Groups of first feeding Chinook salmon fry were introduced to a seasonal photoperiod cycle, but the point of entrance into the seasonal cycle varied from near the winter solstice (December), to either side of the spring equinox (February & May). Temperature and feeding rate were similar for all treatments. Subsequently, condition factor and whole body lipid content were assessed through a seasonal progression. Throughout most of the experiment, length and weight did not differ between the different photoperiod treatments, however whole body lipid and Fulton's condition factor did. Furthermore, changes in both whole body lipid and Fulton's condition factor in all treatment groups followed a similar seasonal pattern that was inversely related to day length (highest K and lipid levels found during days with the least light). These results suggest that regardless of age or size, there is a correlation between seasonal changes in photoperiod and changes in body composition in juvenile Chinook salmonids.

Tfap2b acts in GABAergic neurons to control sleep in mice

Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, reduces sleep in mice. The cell types and mechanisms through which Tfap2b controls sleep in mammals are, however, not known. In mice, Tfap2b acts during early embryonic stages. In this study, we used RNA-seq to measure the gene expression changes in brains of Tfap2b−/− embryos. Our results indicated that genes related to brain development and patterning were differentially regulated. As many sleep-promoting neurons are known to be GABAergic, we measured the expression of GAD1, GAD2 and Vgat genes in different brain areas of adult Tfap2b+/− mice using qPCR. These experiments suggested that GABAergic genes are downregulated in the cortex, brainstem and cerebellum areas, but upregulated in the striatum. To investigate whether Tfap2b controls sleep through GABAergic neurons, we specifically deleted Tfap2b in GABAergic neurons. We recorded the EEG and EMG before and after a 6-h period of sleep deprivation and extracted the time spent in NREM and in REM sleep as well as delta and theta power to assess NREM and REM sleep, respectively. During baseline conditions, Vgat-tfap2b−/− mice exhibited both shortened NREM and REM sleep time and reduced delta and theta power. Consistently, weaker delta and theta power were observed during rebound sleep in the Vgat-tfap2b−/− mice after sleep deprivation. Taken together, the results indicate that Tfap2b in GABAergic neurons is required for normal sleep.

No food for thought: An intermediate level of food deprivation enhances memory in Lymnaea.

Nutritional status plays an important role in cognitive functioning but there is disagreement on the role that food deprivation plays in learning and memory. In this study, we investigated the behavioral and transcriptional effects induced by different lengths of food deprivation: 1 day, which is a short-time period of food deprivation, and 3 days, which is an 'intermediate' level of food deprivation. Snails were subjected to different feeding regimens and then trained for operant conditioning of aerial respiration where they received a single 0.5h training session followed by a long-term memory (LTM) test 24h later. Immediately after the memory test, snails were sacrificed and the expression levels of key genes for neuroplasticity, energy balance, and stress response were measured in the central ring ganglia. We found that 1 day of food deprivation was not sufficient to enhance snails' LTM formation and subsequently did not result in any significant transcriptional effects. However, 3 days of food deprivation resulted in enhanced LTM formation and caused the upregulation of neuroplasticity and stress-related genes and the downregulation of serotonin-related genes. These data provide further insight into how nutritional status and related molecular mechanisms impact cognitive function.

SAG treatment ameliorates memory impairment related to sleep loss by upregulating synaptic plasticity in adolescent mice

Adequate sleep during the developmental stage can promote learning and memory functions because synaptic protein synthesis at primed synapses during sleep profoundly affects neurological function. The Sonic hedgehog (Shh) signaling pathway affects neuroplasticity in the hippocampus during the development of the central nervous system. In this study, the changes in synaptic morphology and function induced by sleep deprivation and the potential therapeutic effect of a Shh agonist (SAG) on these changes were investigated in adolescent mice. Adolescent mice were subjected to sleep deprivation for 20 hrs (2 pm to 10 am the next day) and were free to sleep for the remaining 4 hrs per day for 10 consecutive days. Sleep-deprived mice were injected with SAG (10 mg/kg body weight, i.p.) or saline (i.p.) every day 5 min before the onset of the 20 h sleep deprivation period. Chronic sleep deprivation impaired recognition and spatial memory, decreased the number of dendritic spines and mEPSCs of hippocampal CA1 pyramidal neurons, decreased the postsynaptic density, and reduced Shh and glioma-associated oncogene homolog 1 (Gli1) expression. SAG significantly protected against sleep deprivation-induced memory dysfunction, increased the CA1 pyramidal neuronal dendritic spine number and mEPSC frequency, and increased Gli1 expression. In conclusion, sleep deprivation induces memory impairment in adolescent mice, and SAG treatment prevents this impairment, probably by enhancing synaptic function in the hippocampal CA1 region.

Crossmodal plasticity following short-term monocular deprivation

A brief period of monocular deprivation (MD) induces short-term plasticity of the adult visual system. Whether MD elicits neural changes beyond visual processing is yet unclear. Here, we assessed the specific impact of MD on neural correlates of multisensory processes. Neural oscillations associated with visual and audio-visual processing were measured for both the deprived and the non-deprived eye. Results revealed that MD changed neural activities associated with visual and multisensory processes in an eye-specific manner. Selectively for the deprived eye, alpha synchronization was reduced within the first 150 ms of visual processing. Conversely, gamma activity was enhanced in response to audio-visual events only for the non-deprived eye within 100–300 ms after stimulus onset. The analysis of gamma responses to unisensory auditory events revealed that MD elicited a crossmodal upweight for the non-deprived eye. Distributed source modeling suggested that the right parietal cortex played a major role in neural effects induced by MD. Finally, visual and audio-visual processing alterations emerged for the induced component of the neural oscillations, indicating a prominent role of feedback connectivity. Results reveal the causal impact of MD on both unisensory (visual and auditory) and multisensory (audio-visual) processes and, their frequency-specific profiles. These findings support a model in which MD increases excitability to visual events for the deprived eye and audio-visual and auditory input for the non-deprived eye.

Nutritional and reproductive status affect amino acid appetite in house crickets (Acheta domesticus).

We examined amino acid appetite in the omnivorous house cricket (Acheta domesticus), a common model organism for both research and teaching. Our first experiment addressed the hypothesis that house crickets can discriminate between sucrose and essential amino acids (EAA), and that preference for the latter would be affected by prior feeding experience. To test this hypothesis, we compared feeding responses of juvenile and adult crickets following pre-feeding with sucrose or an essential amino acid mixture, predicting that sucrose-only pre-feeding would enhance subsequent intake of amino acids in a two-choice preference test. Based on previous studies, we also predicted that amino acid consumption would be enhanced in females compared to males, and in mated compared to virgin females. Hence we compared responses in male and female last instar nymphs, adult males, virgin females, mated females, and mated females allowed to lay eggs. The second experiment examined how extended periods of essential amino acid deprivation (48 h to 6 days) affected appetite for these nutrients in adult male and female insects. Finally, we examined growth and survival of juvenile and adult crickets fed a holidic diet lacking all amino acids and protein. Our results demonstrated that house crickets can distinguish EAA from sucrose and that consumption of the former is enhanced following sucrose-only pre-feeding. We also found sex and developmental differences, with juvenile and virgin females showing a greater preference for EAA than juvenile or adult males. Contrary to expectation, mated females preferred sucrose over EAA both prior to and after egg laying. We also found that the crickets of both sexes increased their intake of EAA when exposed to longer periods of deprivation, indicating that they engage in compensatory feeding on these nutrients. Finally, as expected we found that growth was severely limited in juveniles fed a diet lacking all amino acids, but adults and many juveniles survived for 30 days on this diet.

Disordered eating during pregnancy among individuals participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)

BackgroundFood insecurity is associated with adverse psychosocial and health consequences in pregnancy. In non-pregnant populations, evidence suggests that food insecurity is linked to eating pathology, independent of depression or anxiety. Food assistance programs intended to reduce food insecurity, such as the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), may unintentionally contribute to eating pathology through a “feast-or-famine” cycle (i.e., cyclical periods of food deprivation and food access over the benefit month). Thus, the present study examined associations between WIC participation and disordered eating in pregnancy, covarying for depressive symptoms. MethodsThe present study is a secondary analysis of the Pittsburgh Girls Study (PGS), a 21-year prospective longitudinal study that over-sampled households in low resourced neighborhoods. The present analysis included a subset of pregnant PGS participants (N = 210; 13–25 years of age) who reported on WIC participation, and disordered eating and depressive symptoms on validated measures. ResultsNegative binomial regression models covarying for participant's age at conception and gestational age at assessment found that WIC participation was associated with higher scores on overall eating pathology as well as dieting and oral control subscales, but not bulimic or food preoccupation subscales, or a binge-eating item. Patterns of findings did not change when depressive symptom severity was included in models. DiscussionWIC participation was associated with eating pathology during pregnancy. Future research should clarify directional relationships among food insecurity, food assistance, and eating behavior in pregnancy to promote health equity.

Differential effects of continuous and intermittent daytime food deprivation periods on metabolism and reproductive performance in diurnal zebra finches

We investigated whether food availability effects on metabolism and reproduction are the result of the sum effect of daily feeding (food availability) and starvation (food deprivation) periods. Adult zebra finches were paired and subjected to a time-restricted feeding (TRF) regimen consisting of continuous and intermittent daytime food deprivation periods. Birds were given food during the 12-h day for a total of 4-h in the evening (1 *4-h, hour 8–12), or in 2 splits of 2 h each (2 * 2-h) or 4 splits 1 h each (4 * 1-h), with controls on food ad libitum, until they had the first egg clutch. TRF caused significant changes in hepatic expression of metabolism-associated sirt1, egr1, pparα and foxo1 genes despite no difference in the food intake, body mass and blood glucose levels. Importantly, TRF resulted in a significant reduction in plasma testosterone and estradiol levels, delayed nest-building and egg laying, and reduced clutch size. Concurrently, under TRF regimes, we found a significantly lower expression of th and mtr genes linked with motivation and affiliation (but not of dio2, dio3, gnrh1 and gnih genes linked with gonadal maturation) in the hypothalamus, and of star and hook 1 genes in the testes and star, cyp19 and erα genes in the ovary. These results demonstrate the importance of daily food deprivation times on the metabolism and reproduction, and suggest a possible provisioning of energy available from daily feeding for the maintenance of body condition at the expense of reproduction performance in diurnal animals.

Use of copeptin in interpretation of the water deprivation test.

Currently, the water deprivation test remains the standard method for distinguishing primary polydipsia (PP) from cranial diabetes insipidus (cDI) and nephrogenic diabetes insipidus (nDI). There is increasing interest in a direct estimate of antidiuretic hormone using plasma copeptin as a stable and reliable surrogate marker. We present our experience of measuring copeptin during the water deprivation test. Forty-seven people (17 men) underwent a standard water deprivation test between 2013 and 2021. Plasma copeptin was measured at the start of the test and at the end of the period of water deprivation (maximum osmotic stimulation). Results were classified using prespecified diagnostic criteria. As it is known that a significant proportion of tests will reveal indeterminate results, a final diagnosis was obtained by including relevant pre- and post-test clinical criteria. This diagnosis was then used to plan individual treatment. Basal and stimulated copeptin were significantly higher in the nephrogenic DI group than other categories (p< .001). There was no significant difference in basal or stimulated copeptin between PP, cDI or partial DI. Nine results were indeterminate where the serum and urine osmolality did not give a unified diagnosis. Stimulated copeptin was helpful in reclassifying these patients into the final diagnostic groups. Plasma copeptin has additional clinical utility in interpretation of the water deprivation test and may continue to have a place alongside newer stimulation tests.

Protective Potential of β-Hydroxybutyrate against Glucose-Deprivation-Induced Neurotoxicity Involving the Modulation of Autophagic Flux and the Monomeric Aβ Level in Neuro-2a Cells

Hypoglycemia has been known as a potential contributory factor to neurodegenerative diseases, such as Alzheimer's disease. There may be shared pathogenic mechanisms underlying both conditions, and the ketone body, β-hydroxybutyrate (BHB), as an alternative substrate for glucose may exert neuroprotection against hypoglycemia-induced injury. To investigate this, Neuro-2a cells were subjected to a 24 h period of glucose deprivation with or without the presence of BHB. Cell viability, reactive oxygen species (ROS) production, apoptosis, autophagy, and adenosine triphosphate (ATP) and beta-amyloid peptide (Aβ) levels were evaluated. The results show that Neuro-2a cells deprived of glucose displayed a significant loss of cell survival with a corresponding decrease in ATP levels, suggesting that glucose deprivation was neurotoxic. This effect was likely attributed to the diverse mechanisms including raised ROS, defective autophagic flux and reduced basal Aβ levels (particularly monomeric Aβ). The presence of BHB could partially protect against the loss of cell survival induced by glucose deprivation. The mechanisms underlying the neuroprotective actions of BHB might be mediated, at least in part, through restoring ATP, and modulating ROS production, autophagy flux efficacy and the monomeric Aβ level. Results imply that a possible link between the basal monomeric Aβ and glucose deprivation neurotoxicity, and treatments designed for the prevention of energy impairment, such as BHB, may be beneficial for rescuing surviving cells in relation to neurodegeneration.

Differential response of luminal and basal breast cancer cells to acute and chronic hypoxia

Hypoxia is linked to disease progression and poor prognosis in several cancers, including breast cancer. Cancer cells can encounter acute, chronic, and/or intermittent periods of oxygen deprivation and it is poorly understood how the different breast cancer subtypes respond to such hypoxia regimes. Here, we assessed the response of representative cell lines for the luminal and basal A subtype to acute (24 h) and chronic hypoxia (5 days). High throughput targeted transcriptomics analysis showed that HIF-related pathways are significantly activated in both subtypes. Indeed, HIF1⍺ nuclear accumulation and activation of the HIF1⍺ target gene CA9 were comparable. Based on the number of differentially expressed genes: (i) 5 days of exposure to hypoxia induced a more profound transcriptional reprogramming than 24 h, and (ii) basal A cells were less affected by acute and chronic hypoxia as compared to luminal cells. Hypoxia-regulated gene networks were identified of which hub genes were associated with worse survival in breast cancer patients. Notably, while chronic hypoxia altered the regulation of the cell cycle in both cell lines, it induced two distinct adaptation programs in these subtypes. Mainly genes controlling central carbon metabolism were affected in the luminal cells whereas genes controlling the cytoskeleton were affected in the basal A cells. In agreement, in response to chronic hypoxia, lactate secretion was more prominently increased in the luminal cell lines which were associated with the upregulation of the GAPDH glycolytic enzyme. This was not observed in the basal A cell lines. In contrast, basal A cells displayed enhanced cell migration associated with more F-actin stress fibers whereas luminal cells did not. Altogether, these data show distinct responses to acute and chronic hypoxia that differ considerably between luminal and basal A cells. This differential adaptation is expected to play a role in the progression of these different breast cancer subtypes.

Iron limitation effect on H2/CO2 biomethanation: Experimental and model analysis

Trace metals are indispensable for the metalloenzymes involved for efficient H2/CO2 biomethanation. In-depth understanding of trace metals requirements of methanogens cannot only lead to robust and stable operation, but also can enhance CH4 productivity. In this study, the effect of Fe, Mn, Co, Ni, Cu, Zn, Se, Mo and W on the H2/CO2 biomethanation was examined. In a period of nutrient deprivation, suppression of hydrogenotrophic archaea was revealed at higher feed gas rates, leading to a significant drop in CH4 content and a concomitant rise in acetic acid concentration. After nutrient supplementation, the increase in Co, Ni and Fe concentrations were pivotal factors for enhanced methanogenic activity, leading to a CH4 content of more than 98% in the outlet biogas and a sharp drop in acetic acid concentration. Moreover, mathematical modeling was employed to simulate the influence of the most prominent element, iron, on the biomethanation process. The amended BioModel demonstrated that Fe limitation suppresses hydrogenotrophic archaea which consequently leads to H2 accumulation and growth of homoacetogenic bacteria.

Clinical and Social Outcomes of Cochlear Implantation in Older Prelinguals.

Cochlear implantation in late implanted prelinguals necessitates a complex decision-making process for clinicians and patients due to the uncertainty of achieving adequate benefit in auditory and speech perception. This study longitudinally evaluated clinical and social outcomes of prelingually deaf children with implantation in their late childhood. Subjects and. A total of 113 (49 females and 64 males) participants, with an age range of 5-15 years, were assessed for the pre-implant parameters such as hearing loss etiology, aided responses, anatomical aspects, and psychological evaluation. The Category of Auditory Performance, Speech Awareness Threshold, Speech Reception Threshold, and Speech Discrimination Score were administered to assess the patient's auditory skills. Further, the Speech Intelligibility Rating scale was administered to evaluate the patient's speech intelligibility at 3, 6, 9, 12, 18, and 24 months post-surgery. Subjectively perceived benefits were evaluated using the satisfaction rating scale and a questionnaire. The statistical results showed a significant impact of cochlear implantation in all domains. Positive impact and improvement post-implantation were noted in all the spheres, including auditory, linguistic, social, and educational. The study highlighted that the outcomes of a cochlear implant at a later age might not parallel with the implantation at a younger age. However, this still provides measurable benefits even after a longer period of auditory deprivation.

Evaluation of mouse behavioral responses to nutritive versus nonnutritive sugar using a deep learning-based 3D real-time pose estimation system

Animals are able to detect the nutritional content of sugar independently of taste. When given a choice between nutritive sugar and nonnutritive sugar, animals develop a preference for nutritive sugar over nonnutritive sugar during a period of food deprivation (Buchanan et al., 2022; Dus et al., 2011; 2015; Tan et al., 2020; Tellez et al., 2016). To quantify behavioral features during an episode of licking nutritive versus nonnutritive sugar, we implemented a multi-vision, deep learning-based 3D pose estimation system, termed the AI Vision Analysis for Three-dimensional Action in Real-Time (AVATAR)(Kim et al., 2022). Using this method, we found that mice exhibit significantly different approach behavioral responses toward nutritive sugar versus nonnutritive sugar even before licking a sugar solution. Notably, the behavioral sequences during the approach toward nutritive versus nonnutritive sugar became significantly different over time. These results suggest that the nutritional value of sugar not only promotes its consumption but also elicits distinct repertoires of feeding behavior in deprived mice.

Effects of Positive Fighting Experience and Its Subsequent Deprivation on the Expression Profile of Mouse Hippocampal Genes Associated with Neurogenesis.

The hippocampus is known as the brain region implicated in visuospatial processes and processes associated with learning and short- and long-term memory. An important functional characteristic of the hippocampus is lifelong neurogenesis. A decrease or increase in adult hippocampal neurogenesis is associated with a wide range of neurological diseases. We have previously shown that in adult male mice with a chronic positive fighting experience in daily agonistic interactions, there is an increase in the proliferation of progenitor neurons and the production of young neurons in the dentate gyrus (in hippocampus), and these neurogenesis parameters remain modified during 2 weeks of deprivation of further fights. The aim of the present work was to identify hippocampal genes associated with neurogenesis and involved in the formation of behavioral features in mice with the chronic experience of wins in aggressive confrontations, as well as during the subsequent 2-week deprivation of agonistic interactions. Hippocampal gene expression profiles were compared among three groups of adult male mice: chronically winning for 20 days in the agonistic interactions, chronically victorious for 20 days followed by the 2-week deprivation of fights, and intact (control) mice. Neurogenesis-associated genes were identified whose transcription levels changed during the social confrontations and in the subsequent period of deprivation of fights. In the experimental males, some of these genes are associated with behavioral traits, including abnormal aggression-related behavior, an abnormal anxiety-related response, and others. Two genes encoding transcription factors (Nr1d1 and Fmr1) were likely to contribute the most to the between-group differences. It can be concluded that the chronic experience of wins in agonistic interactions alters hippocampal levels of transcription of multiple genes in adult male mice. The transcriptome changes get reversed only partially after the 2-week period of deprivation of fights. The identified differentially expressed genes associated with neurogenesis and involved in the control of a behavior/neurological phenotype can be used in further studies to identify targets for therapeutic correction of the neurological disturbances that develop in winners under the conditions of chronic social confrontations.