µ-opioid receptor modulation of the glutamatergic/GABAergic midbrain inputs to the mouse dorsal hippocampus.

We used virus-mediated anterograde and retrograde tracing, optogenetic modulation, immuno-staining, in-situ hybridization, and patch clamp recordings in acute brain slices to study the release mechanism and µ-opioid modulation of the dual glutamatergic/GABAergic inputs from the VTA and supramammillary nucleus to the granule cells of dorsal hippocampus of male and female mice. In keeping with previous reports showing that the two transmitters are released by separate active zones within the same terminals, we found that the short-term plasticity and pharmacological modulation of the glutamatergic and GABAergic currents are indistinguishable. We further found that glutamate and GABA release at these synapses are both virtually completely mediated by N- and P/Q-type calcium channels. We then investigated µ-opioid modulation of these synapses and found that activation of µ-opioid receptors strongly inhibits the glutamate and GABA release, mostly through inhibition of presynaptic N-type channels. However, the modulation by µ-opioid receptors of these dual synapses is complex, as it likely includes also a disinhibition due to down-modulation of local GABAergic interneurons which make direct axo-axonic contacts with the dual glutamatergic/GABAergic terminals. We discuss how this opioid modulation may enhance LTP at the perforant path inputs, potentially contributing to reinforce memories of drug-associated contexts.Significance Statement Corelease of an excitatory (glutamate) and an inhibitory (GABA) neurotransmitter from the same synapse is a rare finding in the nervous system and the detailed mechanisms of this transmission are still incompletely described. Here we show that in dual glutamatergic/GABAergic synapses from the midbrain to the dentate gyrus of the dorsal hippocampus similar calcium microdomains control the release of both transmitters. Additionally, we show that activation of µ-opioid receptors limits release by strong inhibition of presynaptic N-type calcium channels in the mixed glutamatergic/GABAergic terminals, while likely potentiating release by inhibition of axo-axonic synapses from local inhibitory interneurons. Modulation of these synapses by µ-opioid receptors might help reinforce memories of drug-associated contexts.

Innovative 3D printing and molding process for secondary-skin-collimator fabrication.

Purpose. Secondary skin collimation (SSC) is essential for shielding normal tissues near tumors during electron and orthovoltage radiation treatments. Traditional SSC fabrication methods, such as crafting in-house lead sheets, are labor-intensive and produce SSCs with low geometric accuracy. This study introduces a workflow that integrated 3D scanning and 3D printing technologies with an in-house mold process, enabling the production of patient-specific SSCs within six hours.Methods. An anthropomorphic head phantom was scanned with a handheld 3D scanner. The resulting scan data was imported into 3D modeling software for design. The completed model was exported to a 3D printer as a printable file. Subsequently, molten Cerrobend was poured into the mold and allowed to set, completing the SSC production. Geometric accuracy was assessed using CT images, and the shielding effectiveness was evaluated through film dosimetry.Results. The 3D printed mold achieved submillimeter accuracy (0.5 mm) and exhibited high conformity to the phantom surface. It successfully endured the weight and heat of the Cerrobend during pouring and curing. Dosimetric analysis conducted with radiochromic film demonstrated good agreement between the measured and expected attenuation values of the SSC slab, within ±3%.Conclusions. This study presents a proof of concept for novel mold room workflows that produce patient-specific SSCs within six hours, a significant improvement over the traditional SSC fabrication process, which takes 2-3 days. The submillimeter accuracy and versatility of 3D scanning and printing technologies afford greater design freedom and enhanced delivery accuracy for cases involving irregular geometries.

Lactic acid bacteria in Asian fermented foods and their beneficial roles in human health.

Fermented foods have been a staple in human diets for thousands of years, garnering attention for their health and medicinal benefits. Rich in lactic acid bacteria (LAB) with probiotic properties, these foods play a crucial role in positively impacting the host's gut microbiome composition and overall health. With a long history of safe consumption, fermented foods effectively deliver LAB to humans. Intake of LAB from fermented foods offers three main benefits: (1) enhancing digestive function and managing chronic gastrointestinal conditions, (2) modulating the immune system and offering anti-inflammatory effects to prevent immune-related diseases, and (3) synthesizing vitamins and various bioactive compounds to improve human health. In this review, we highlighted the diverse LAB present in Asian fermented foods and emphasized LAB-rich fermented foods as a natural and effective solution for health enhancement and disease prevention.

Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia.

We performed a comprehensive study of the morphological, functional, and genetic features of moonwalker (MWK) mice, a mouse model of spinocerebellar ataxia caused by a gain of function of the TRPC3 channel. These mice show numerous behavioral symptoms including tremor, altered gait, circling behavior, impaired motor coordination, impaired motor learning and decreased limb strength. Cerebellar pathology is characterized by early and almost complete loss of unipolar brush cells as well as slowly progressive, moderate loss of Purkinje cell (PCs). Structural damage also includes loss of synaptic contacts from parallel fibers, swollen ER structures, and degenerating axons. Interestingly, no obvious correlation was observed between PC loss and severity of the symptoms, as the phenotype stabilizes around 2 months of age, while the cerebellar pathology is progressive. This is probably due to the fact that PC function is severely impaired much earlier than the appearance of PC loss. Indeed, PC firing is already impaired in 3 weeks old mice. An interesting feature of the MWK pathology that still remains to be explained consists in a strong lobule selectivity of the PC loss, which is puzzling considering that TRPC is expressed in every PC. Intriguingly, genetic analysis of MWK cerebella shows, among other alterations, changes in the expression of both apoptosis inducing and resistance factors possibly suggesting that damaged PCs initiate specific cellular pathways that protect them from overt cell loss.

Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine.

Peptide and protein nanostructures with tunable structural features, multifunctionality, biocompatibility and biomolecular recognition capacity enable development of efficient targeted drug delivery tools for precision medicine applications. In this review article, we present various techniques employed for the synthesis and self-assembly of peptides and proteins into nanostructures. We discuss design strategies utilized to enhance their stability, drug-loading capacity, and controlled release properties, in addition to the mechanisms by which peptide nanostructures interact with target cells, including receptor-mediated endocytosis and cell-penetrating capabilities. We also explore the potential of peptide and protein nanostructures for precision medicine, focusing on applications in personalized therapies and disease-specific targeting for diagnostics and therapeutics in diseases such as cancer.

Bidirectional Regulation of GABAA Reversal Potential in the Adult Brain: Physiological and Pathological Implications.

In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABAA channels are permeable to anions, the reversal potential of GABAA is very close to that of Cl-, which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl-, respectively. Due to the closeness between GABAA reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABAA a uniquely flexible signaling system. In most neurons of the adult brain, the GABAA reversal potential is slightly more negative than the resting membrane potential, which makes GABAA hyperpolarizing. Alterations in GABAA reversal potential are a common feature in numerous conditions as they are the consequence of an imbalance in the NKCC1-KCC2 activity ratio. In most conditions (including Alzheimer's disease, schizophrenia, and Down's syndrome), GABAA becomes depolarizing, which causes network desynchronization and behavioral impairment. In other conditions (neonatal inflammation and neuropathic pain), however, GABAA reversal potential becomes hypernegative, which affects behavior through a potent circuit deactivation.

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration.

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations. In parallel, we describe a large population of stem-like alveolar tuft cells that express the endodermal stem cell markers Sox9 and Lgr5 and a receptor profile making them uniquely sensitive to cues produced by pleural Mesothelium. We hypothesized that crosstalk from mesothelial cells to alveolar tuft cells might be central to the regulation of post-penumonectomy lung regeneration. Following pneumonectomy, we find that mesothelial cells display radically altered phenotype and ligand expression, in a pattern that closely tracks with parenchymal epithelial proliferation and alveolar tissue growth. During an initial pro-inflammatory stage of tissue regeneration, Mesothelium promotes epithelial proliferation via WNT ligand secretion, orchestrates an increase in microvascular permeability, and encourages immune extravasation via chemokine secretion. This stage is followed first by a tissue remodeling period, characterized by angiogenesis and BMP pathway sensitization, and then a stable return to homeostasis. Coupled with key changes in parenchymal structure and matrix production, the cumulative effect is a now larger organ including newly-grown, fully-functional tissue parenchyma. This study paints Mesothelial cells as a key orchestrating cell type that defines the boundary of the lung and exerts critical influence over the tissue-level signaling state regulating resident stem cell populations. The cellular circuits unearthed here suggest that human lung regeneration might be inducible through well-engineered approaches targeting the induction of tissue regeneration and safe return to homeostasis.

Hypernegative GABAA Reversal Potential in Pyramidal Cells Contributes to Medial Prefrontal Cortex Deactivation in a Mouse Model of Neuropathic Pain.

Deactivation of the medial prefrontal cortex (mPFC) has been broadly reported in both neuropathic pain models and human chronic pain patients. Several cellular mechanisms may contribute to the inhibition of mPFC activity, including enhanced GABAergic inhibition. The functional effect of GABAA(γ-aminobutyric acid type A)-receptor activation depends on the concentration of intracellular chloride in the postsynaptic neuron, which is mainly regulated by the activity of Na-K-2Cl cotransporter isoform 1 (NKCC1) and K-Cl cotransporter isoform 2 (KCC2), 2 potassium-chloride cotransporters that import and extrude chloride, respectively. Recent work has shown that the NKCC1-KCC2 ratio is affected in numerous pathological conditions, and we hypothesized that it may contribute to the alteration of mPFC function in neuropathic pain. We used quantitative in situ hybridization to assess the level of expression of NKCC1 and KCC2 in the mPFC of a mouse model of neuropathic pain (spared nerve injury), and we found that KCC2 transcript is increased in the mPFC of spared nerve injury mice while NKCC1 is not affected. Perforated patch recordings further showed that this results in the hypernegative reversal potential of the GABAA current in pyramidal neurons of the mPFC. Computational simulations suggested that this change in GABAA reversal potential is sufficient to significantly reduce the overall activity of the cortical network. Thus, our results identify a novel pathological modulation of GABAA function and a new mechanism by which mPFC function is inhibited in neuropathic pain. Our data also help explain previous findings showing that activation of mPFC interneurons has proalgesic effect in neuropathic, but not in control conditions. PERSPECTIVE: Chronic pain is associated with the presence of depolarizing GABAA current in the spinal cord, suggesting that pharmacological NKCC1 antagonism has analgesic effects. However, our results show that in neuropathic pain, GABAA current is actually hyperinhibitory in the mPFC, where it contributes to the mPFC functional deactivation. This suggests caution in the use of NKCC1 antagonism to treat pain.

Mono-(2-ethylhexyl)-phthalate potentiates methylglyoxal-induced blood-brain barrier damage via mitochondria-derived oxidative stress and bioenergetic perturbation.

Phthalates in contaminated foods and personal care products are one of the most frequently exposed chemicals with a public health concern. Phthalate exposure is related to cardiovascular diseases, including diabetic vascular complications and cerebrovascular diseases, yet the mechanism is still unclear. The blood-brain barrier (BBB) integrity disruption is strongly associated with cardiovascular and neurological disease exacerbation. We investigated BBB damage by di-(2-ethylhexyl) phthalate (DEHP) or its metabolite mono-(2-ethylhexyl) phthalate (MEHP) using brain endothelial cells and rat models. BBB damage by the subthreshold level of MEHP, but not a DEHP, significantly increased by the presence of methylglyoxal (MG), a reactive dicarbonyl compound whose levels increase in the blood in hyperglycemic conditions in diabetic patients. Significant potentiation in apoptosis and autophagy activation, mitochondria-derived reactive oxygen species (ROS) production, and mitochondrial metabolic disturbance were observed in brain ECs by co-exposure to MG and MEHP. N-acetyl cysteine (NAC) restored autophagy activation as well as tight junction protein impairment induced by co-exposure to MG and MEHP. Intraperitoneal administration of MG and MEHP significantly altered mitochondrial membrane potential and tight junction integrity in rat brain endothelium. This study may provide novel insights into enhancing phthalate toxicity in susceptible populations, such as diabetic patients.

The CERV protein of Cer1, a C. elegans LTR retrotransposon, is required for nuclear export of viral genomic RNA and can form giant nuclear rods.

Retroviruses and closely related LTR retrotransposons export full-length, unspliced genomic RNA (gRNA) for packaging into virions and to serve as the mRNA encoding GAG and POL polyproteins. Because gRNA often includes splice acceptor and donor sequences used to splice viral mRNAs, retroelements must overcome host mechanisms that retain intron-containing RNAs in the nucleus. Here we examine gRNA expression in Cer1, an LTR retrotransposon in C. elegans which somehow avoids silencing and is highly expressed in germ cells. Newly exported Cer1 gRNA associates rapidly with the Cer1 GAG protein, which has structural similarity with retroviral GAG proteins. gRNA export requires CERV (C. elegans regulator of viral expression), a novel protein encoded by a spliced Cer1 mRNA. CERV phosphorylation at S214 is essential for gRNA export, and phosphorylated CERV colocalizes with nuclear gRNA at presumptive sites of transcription. By electron microscopy, tagged CERV proteins surround clusters of distinct, linear fibrils that likely represent gRNA molecules. Single fibrils, or groups of aligned fibrils, also localize near nuclear pores. During the C. elegans self-fertile period, when hermaphrodites fertilize oocytes with their own sperm, CERV concentrates in two nuclear foci that are coincident with gRNA. However, as hermaphrodites cease self-fertilization, and can only produce cross-progeny, CERV undergoes a remarkable transition to form giant nuclear rods or cylinders that can be up to 5 microns in length. We propose a novel mechanism of rod formation, in which stage-specific changes in the nucleolus induce CERV to localize to the nucleolar periphery in flattened streaks of protein and gRNA; these streaks then roll up into cylinders. The rods are a widespread feature of Cer1 in wild strains of C. elegans, but their function is not known and might be limited to cross-progeny. We speculate that the adaptive strategy Cer1 uses for the identical self-progeny of a host hermaphrodite might differ for heterozygous cross-progeny sired by males. For example, mating introduces male chromosomes which can have different, or no, Cer1 elements.

Intraoperative challenges and complications of cataract surgery between cataract surgery alone and phacovitrectomy in eyes with diabetic retinopathy: efficacy of illuminated chopper-assisted cataract surgery.

BACKGROUND: To compare the intraoperative challenges, complications, and operation time of illuminated chopper-assisted cataract surgery between cataract surgery only and phacovitrectomy in eyes with diabetic retinopathy. METHODS: One university hospital, retrospective case series. Two hundred ninety-five eyes of 295 consecutive patients with diabetic retinopathy who underwent cataract surgery only or phacovitrectomy were retrospectively reviewed. Intraoperative challenges and complications of cataract surgery were thoroughly analyzed by 3D viewing of digitally recorded videos. The pupil diameter, operation time, and improved efficacy (100/operation time × pupil diameter) were compared between the cataract surgery only and phacovitrectomy groups. RESULTS: Of the 295 eyes, 211 underwent cataract surgery only, and 84 underwent phacovitrectomy. Intraoperative challenges such as small pupil, miosis, or poor red reflex occurred more frequently (46 [21.8%] vs. 28 [33.3%], p = 0.029); pupil diameter was smaller (7.34 ± 0.94 vs. 6.89 ± 0.88 mm, p < 0.001) in the phacovitrectomy group than in the cataract surgery only group; however, rates of posterior capsule rupture and operation time were not different between the two groups (0 [0%] vs. 1 [1.2%], p = 0.285; 16.54 ± 2.65 vs. 16.31 ± 4.30 min, p = 0.434). Improved efficacy was higher in the phacovitrectomy group (0.85 ± 0.18 vs. 0.97 ± 0.28, p = 0.002). CONCLUSIONS: The use of an illuminated chopper is a potential solution for diabetic cataract surgery, particularly in phacovitrectomy, by decreasing the use of supplemental devices, operation time, and posterior capsule rupture. TRIAL REGISTRATION: Retrospectively registered.

Improved visibility of illuminated chopper-assisted cataract surgery involving iris challenges.

Purpose: The aim of this study was to evaluate the efficacy of the illuminated chopper-assisted cataract surgery in terms of shortening the surgical time and reducing the use of pupil expansion devices in eyes with iris challenges. Methods: This was a retrospective case series of a university hospital. Four hundred forty-three eyes of 433 consecutive patients who underwent illuminated chopper-assisted cataract surgery were included in this study. Cases with preoperative or intraoperative miosis, iris prolapse, and intraoperative floppy iris syndrome were included in the iris challenge group. Use of tamsulosin, iris hooks, pupil size, surgical time, and improved visibility (100/surgical time × pupil size) were compared between eyes with and without iris challenges. Mann-Whitney U test, Pearson's Chi-square test, and Fisher's exact test were used for statistical analysis. Results: Of 443 eyes, 66 were included in the iris challenge group (14.9%). Tamsulosin use was more common in patients with iris challenges and iris hooks were used more frequently (9.1% vs. 0%, P < 0.001) in patients with iris challenges than in those without iris challenges. Pupil size was smaller in patients with iris challenges (6.01 vs. 7.64 mm, P < 0.001). However, surgical time was not different (16.9 vs. 16.5 min, P = 0.064) between the two groups. As a result, improved visibility was calculated to be higher in patients with iris challenges (1.05 vs. 0.81, P < 0.001). Conclusion: In terms of surgical time and improved visibility, using the illuminated chopper simplified cataract surgery involving iris challenges. The use of an illuminated chopper is expected to be a good solution for challenging cataract surgeries.

Impaired muscarinic modulation of the rat prelimbic cortex in neuropathic pain is sexually dimorphic and associated with cold allodynia.

Cholinergic modulation of the brain cortex is critical for cognitive processes, and altered cholinergic modulation of the prefrontal cortex is emerging as an important mechanism of neuropathic pain. Sex differences in pain prevalence and perception are well known, yet the precise nature of the mechanisms responsible for sexual dimorphism in chronic neuropathic pain are poorly understood. Here we investigated potential sex differences in cholinergic modulation of layer five commissural pyramidal neurons of the rat prelimbic cortex in control conditions and in the SNI model of neuropathic pain. We discovered that cholinergic modulation is stronger in cells from male compared with female rats, and that in neuropathic pain rats, cholinergic excitation of pyramidal neurons was more severely impaired in males than in females. Finally, we found that selective pharmacological blockade of the muscarinic M1 subunit in the prefrontal cortex induces cold sensitivity (but not mechanical allodynia) in naïve animals of both sexes.

A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply.

Introduction: Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. Methods: The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Results: Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 µm vasculature spacing and 18.9 µM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. Conclusion: We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments.

The Effects of Horticultural Activity Program on Vegetable Preference of Elementary School Students.

This study was conducted to investigate effects of a horticultural activity program based on a mediating variable model for improving vegetable preference among elementary students. A quasi-experimental design was employed with 136 students and 136 primary carers in Seoul, South Korea. Based on the mediation model for improving children's vegetable preference, 12 sessions were conducted, including gardening, nutrition education, and cooking activities using harvests. The program was conducted weekly for 12 weeks from March to July 2019. To investigate the effect of this program, mediating factors of the children were evaluated before and after the program. Pearson correlation analysis was used to identify the mediating factors. The nutrition index, attitude, knowledge, and eating habits of the primary carers were evaluated. Results showed children's nutrition and gardening knowledge, dietary self-efficacy, outcome expectancies, and vegetable preference were significantly improved (p < 0.001). Primary carers showed significant improvement in the nutrition index, knowledge, and attitude (p < 0.05). The correlation analysis confirmed that most of the mediating factors had significant correlations (p < 0.05). Therefore, administering a structured program involving horticultural activities and nutrition education as mediating factors for 12 sessions was effective in improving eating behavior for vegetables elementary school students and primary carers.

Activation of the dorsal, but not the ventral, hippocampus relieves neuropathic pain in rodents.

ABSTRACT: Accumulating evidence suggests hippocampal impairment under the chronic pain phenotype. However, it is unknown whether neuropathic behaviors are related to dysfunction of the hippocampal circuitry. Here, we enhanced hippocampal activity by pharmacological, optogenetic, and chemogenetic techniques to determine hippocampal influence on neuropathic pain behaviors. We found that excitation of the dorsal (DH), but not the ventral (VH) hippocampus induces analgesia in 2 rodent models of neuropathic pain (SNI and SNL) and in rats and mice. Optogenetic and pharmacological manipulations of DH neurons demonstrated that DH-induced analgesia was mediated by N-Methyl-D-aspartate and µ-opioid receptors. In addition to analgesia, optogenetic stimulation of the DH in SNI mice also resulted in enhanced real-time conditioned place preference for the chamber where the DH was activated, a finding consistent with pain relief. Similar manipulations in the VH were ineffective. Using chemo-functional magnetic resonance imaging (fMRI), where awake resting-state fMRI was combined with viral vector-mediated chemogenetic activation (PSAM/PSEM89s) of DH neurons, we demonstrated changes of functional connectivity between the DH and thalamus and somatosensory regions that tracked the extent of relief from tactile allodynia. Moreover, we examined hippocampal functional connectivity in humans and observe differential reorganization of its anterior and posterior subdivisions between subacute and chronic back pain. Altogether, these results imply that downregulation of the DH circuitry during chronic neuropathic pain aggravates pain-related behaviors. Conversely, activation of the DH reverses pain-related behaviors through local excitatory and opioidergic mechanisms affecting DH functional connectivity. Thus, this study exhibits a novel causal role for the DH but not the VH in controlling neuropathic pain-related behaviors.

Depolarizing GABAA current in the prefrontal cortex is linked with cognitive impairment in a mouse model relevant for schizophrenia.

Cognitive impairment in schizophrenia (CIAS) is the most critical predictor of functional outcome. Limited understanding of the cellular mechanisms of CIAS hampers development of more effective treatments. We found that in subchronic phencyclidine (scPCP)-treated mice, an animal model that mimics CIAS, the reversal potential of GABAA currents in pyramidal neurons of the infralimbic prefrontal cortex (ILC) shifts from hyperpolarizing to depolarizing, the result of increased expression of the chloride transporter NKCC1. Further, we found that in scPCP mice, the NKCC1 antagonist bumetanide normalizes GABAA current polarity ex vivo and improves performance in multiple cognitive tasks in vivo. This behavioral effect was mimicked by selective, bilateral, NKCC1 knockdown in the ILC. Thus, we show that depolarizing GABAA currents in the ILC contributes to cognitive impairments in scPCP mice and suggest that bumetanide, an FDA-approved drug, has potential to treat or prevent CIAS and other components of the schizophrenia syndrome.

Profiles of decent work: General trends and group differences.

Recent trends in the labor market-marked by instability and insecurity-have further ignited a discourse on the significance of decent work in people's lives. Scholars have mostly studied the multidimensional decent work construct using the composite scores of the Decent Work Scale (DWS; Duffy et al., 2017). However, there may be different combinations of decent work beyond the simple continuum of composite scores. Thus, we employed latent profile analysis to identify profiles of decent work using the 5 subscales of the DWS as indicators. As a result, 5 different groups with distinct profiles emerged: (a) average, (b) low health care, (c) indecent work, (d) only health care, and (e) decent work. Subsequent analyses comparing each group on demographics (gender, employment, education), theoretical predictors (economic constraints, marginalization, work volition), and theoretical outcomes (job satisfaction, life satisfaction) revealed notable differences across the 5 groups. Implications, limitations, and future directions of the results are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Excitatory VTA to DH projections provide a valence signal to memory circuits.

The positive or negative value (valence) of past experiences is normally integrated into neuronal circuits that encode episodic memories and plays an important role in guiding behavior. Here, we show, using mouse behavioral models, that glutamatergic afferents from the ventral tegmental area to the dorsal hippocampus (VTA→DH) signal negative valence to memory circuits, leading to the formation of fear-inducing context memories and to context-specific reinstatement of fear. To a lesser extent, these projections also contributed to opioid-induced place preference, suggesting a role in signaling positive valence as well, and thus a lack of dedicated polarity. Manipulations of VTA terminal activity were more effective in females and paralleled by sex differences in glutamatergic signaling. By prioritizing retrieval of negative and positive over neutral memories, the VTA→DH circuit can facilitate the selection of adaptive behaviors when current and past experiences are valence congruent.

Women attaining decent work: The important role of workplace climate in Psychology of Working Theory.

Grounded in Psychology of Working Theory (PWT), the current study investigated predictors of decent work among a sample of employed women (N = 528). A structural equation model was examined finding that women's experiences of marginalization, work volition, and career adaptability all directly predicted the attainment of decent work, and economic constraints and marginalization experiences indirectly predicted decent work via work volition. Additionally, workplace climate for women employees was examined as both a predictor and moderator variable to explore best positioning of this additive construct. Workplace climate did not significantly moderate any model paths; however, it was a unique predictor of work volition and decent work, suggesting that this construct may be better positioned as a predictor variable in understanding the work experiences of women. These results highlight the importance of further investigating the role of workplace climate in PWT as well as the need for refining our understanding of how marginalized employees achieve decent work. Implications of the present study's results are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).