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BioRxiv : the Preprint Server For... Jun 2024Traumatic social experiences redefine socially motivated behaviors to enhance safety and survival. Although many brain regions have been implicated in signaling a social...
Traumatic social experiences redefine socially motivated behaviors to enhance safety and survival. Although many brain regions have been implicated in signaling a social threat, the mechanisms by which global neural networks regulate such motivated behaviors remain unclear. To address this issue, we first combined traditional and modern behavioral tracking techniques in mice to assess both approach and avoidance, as well as sub-second behavioral changes, during a social threat learning task. We were able to identify previously undescribed body and tail movements during social threat learning and recognition that demonstrate unique alterations into the behavioral structure of social motivation. We then utilized inter-regional correlation analysis of brain activity after a mouse recognizes a social threat to explore functional communication amongst brain regions implicated in social motivation. Broad brain activity changes were observed within the nucleus accumbens, the paraventricular thalamus, the ventromedial hypothalamus, and the nucleus of reuniens. Inter-regional correlation analysis revealed a reshaping of the functional connectivity across the brain when mice recognize a social threat. Altogether, these findings suggest that reshaping of functional brain connectivity may be necessary to alter the behavioral structure of social motivation when a social threat is encountered.
PubMed: 38948883
DOI: 10.1101/2024.06.17.599379 -
BioRxiv : the Preprint Server For... Jun 2024Duchenne muscular dystrophy (DMD) is marked by the genetic deficiency of the dystrophin protein in striated muscle whose consequence is a cascade of cellular changes...
Duchenne muscular dystrophy (DMD) is marked by the genetic deficiency of the dystrophin protein in striated muscle whose consequence is a cascade of cellular changes that predispose the susceptibility to contraction injury central to DMD pathology. Recent evidence identified the proliferation of microtubules enriched in post-translationally modified tubulin as a consequence of dystrophins absence that increases the passive mechanics of the muscle fiber and the excess mechanotransduction elicited reactive oxygen species and calcium signals that promote contraction injury. Motivated by evidence that acutely normalizing the disease microtubule alterations reduced contraction injury in murine DMD muscle ( ), here we sought the direct impact of these microtubule alterations independent of dystrophins absence and the multitude of other changes consequent to dystrophic disease. To this end we used acute pharmacologic (epithiolone-D, EpoD; 4 hours) or genetic (vashohibin-2 and small vasohibin binding protein overexpression via AAV9; 2 weeks) strategies to effectively model the proliferation of detyrosination enriched microtubules in the muscle. Quantifying nerve evoked plantarflexor function we find no alteration in peak torque nor contraction kinetics in WT mice modeling these DMD relevant MT alterations. Quantifying the susceptibility to eccentric contraction injury we show EpoD treatment proffered a small but significant protection from contraction injury while VASH/SVBP had no discernable impact. We conclude that the disease dependent MT alterations act in concert with additional cellular changes to predispose contraction injury in DMD.
PubMed: 38948772
DOI: 10.1101/2024.06.19.599775 -
BioRxiv : the Preprint Server For... Jun 2024Chronic social defeat stress (CSDS), a widely used rodent model of stress, reliably leads to decreased social interaction in stress susceptible animals. Here, we...
Chronic social defeat stress (CSDS), a widely used rodent model of stress, reliably leads to decreased social interaction in stress susceptible animals. Here, we investigate a role for fear learning in this response using 129Sv/Ev mice, a strain that is more vulnerable to CSDS than the commonly used C57BL/6 strain. We first demonstrate that defeated 129Sv/Ev mice avoid a CD-1 mouse, but not a conspecific, indicating that motivation to socialize is intact in this strain. CD-1 avoidance is characterized by approach behavior that results in running in the opposite direction, activity that is consistent with a threat response. We next test whether CD-1 avoidance is subject to the same behavioral changes found in traditional models of Pavlovian fear conditioning. We find that associative learning occurs across 10 days CSDS, with defeated mice learning to associate the color of the CD-1 coat with threat. This leads to the gradual acquisition of avoidance behavior, a conditioned response that can be extinguished with 7 days of repeated social interaction testing (5 tests/day). Pairing a CD-1 with a tone leads to second-order conditioning, resulting in avoidance of an enclosure without a social target. Finally, we show that social interaction with a conspecific is a highly variable response in defeated mice that may reflect individual differences in generalization of fear to other social targets. Our data indicate that fear conditioning to a social target is a key component of CSDS, implicating the involvement of fear circuits in social avoidance.
PubMed: 38948731
DOI: 10.1101/2024.06.18.599597 -
BioRxiv : the Preprint Server For... Jun 2024Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for...
UNLABELLED
Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for both division and survival. The IM TolQ-TolR complex is the essential part of the Tol-Pal system, serving as a conduit for PMF energy transfer to the outer membrane. Here we present cryo-EM reconstructions of TolQ in apo and TolR- bound forms at atomic resolution. The apo TolQ configuration manifests as a symmetric pentameric pore, featuring a trans-membrane funnel leading towards a cytoplasmic chamber. In contrast, the TolQ-TolR complex assumes a proton non-permeable stance, characterized by the TolQ pentamer's flexure to accommodate the TolR dimer, where two protomers undergo a translation-based relationship. Our structure-guided analysis and simulations support the rotor-stator mechanism of action, wherein the rotation of the TolQ pentamer harmonizes with the TolR protomers' interplay. These findings broaden our mechanistic comprehension of molecular stator units empowering critical functions within the Gram-negative bacterial cell envelope.
TEASER
Apo TolQ and TolQ-TolR structures depict structural rearrangements required for cell envelope organization in bacterial cell division.
PubMed: 38948712
DOI: 10.1101/2024.06.19.599759 -
Journal of Family Medicine and Primary... May 2024It has been well reported that medical students do not follow healthy diets overall. Effectively guiding patients to change their health behavior is a crucial skill for...
INTRODUCTION
It has been well reported that medical students do not follow healthy diets overall. Effectively guiding patients to change their health behavior is a crucial skill for primary care providers and family physicians. Our objective was to investigate medical students' dietary decision-making, including the motivations and barriers that influence their dietary choices.
METHODS
A self-administered online questionnaire was conducted among preclinical students at one allopathic medical school in the United States. The survey was comprised of questions about students' dietary goals, habits, and the barriers they face in reaching their nutritional ideals. Trends in the percentage of students who selected each survey answer choice were interpreted.
RESULTS
Of the 363 preclinical students provided with the optional survey, 71 (19.6%) chose to participate. The participants' dietary decisions were predominately driven by convenience. Most students wanted to eat nutritiously to support their well-being but had been eating less healthily since starting medical school due to financial limitations and limited time. Approximately half (46.5%, 33/71) of the participants stated that they would buy the in-house food provided at the medical school campus more often if it better matched their dietary goals, but 36.6% (26/71) would only do so if the new foods were affordable compared to competitor's prices.
CONCLUSION
There is an opportunity to help medical students meet their dietary goals, which are negatively impacted by personal and structural academic barriers. Further research is needed on the obstacles that institutions face in offering healthy, affordable options to medical students.
PubMed: 38948602
DOI: 10.4103/jfmpc.jfmpc_1016_23 -
Journal of Family Medicine and Primary... May 2024In the United States, access to evidence-based behavioral health treatment remains limited, contributing to inadequate treatment for individuals with depression and...
CONTEXT AND AIMS
In the United States, access to evidence-based behavioral health treatment remains limited, contributing to inadequate treatment for individuals with depression and anxiety disorders. The Collaborative care model (CoCM), the integration of behavioral healthcare into primary care, has been shown to be effective in addressing this issue, particularly when delivered virtually through telehealth platforms. While collaborative care has been shown to be effective, little has been studied to understand the impact of patient treatment factors on patient improvement. This study aims to analyze factors associated with patient improvement, measured by PHQ-9 and GAD-7 score changes, in patients with depression and anxiety disorders from Concert Health, a national behavioral medical group offering collaborative care across 18 states.
METHODS AND MATERIAL
Stepwise logistic regression models were utilized to identify factors influencing patient improvement in standardized symptom screener scores (PHQ-9 and GAD-7). Relevant patient-level data, including demographics, clinical engagement, insurance type, clinical touchpoints, and other variables, were analyzed. Results are presented as odds ratios (ORs).
RESULTS AND CONCLUSIONS
We find that increased clinical touchpoints were associated with improved outcomes in both depression (PHQ-9) and anxiety (GAD-7) populations. Commercial insurance was linked to a greater likelihood of improvement relative to Medicaid, and the use of C-SSRS suicide screeners had varied effects on patient outcomes depending on the diagnosis. The duration of time spent in appointments showed a nuanced impact, suggesting an optimal length for touchpoints. Psychiatric consults also impact patient outcomes in both populations. This study sheds light on factors influencing patient outcomes in virtual collaborative care for depression and anxiety disorders, which may be used to inform and motivate further research and allow providers to better optimize and understand the impacts of treatment choices in collaborative care settings.
PubMed: 38948587
DOI: 10.4103/jfmpc.jfmpc_1493_23 -
Frontiers in Pharmacology 2024"Kratom" refers to an array of bioactive products derived from , a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and...
BACKGROUND
"Kratom" refers to an array of bioactive products derived from , a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences.
METHODS
We collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types.
RESULTS
Codes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information.
CONCLUSION
As in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making.
PubMed: 38948457
DOI: 10.3389/fphar.2024.1412397 -
Proceedings of the International... May 2024High performance RF coils are needed for better SNR so that higher resolution and spectral dispersion can be obtained in small animal MR imaging.
MOTIVATION
High performance RF coils are needed for better SNR so that higher resolution and spectral dispersion can be obtained in small animal MR imaging.
GOALS
To develop a surface coil with improved SNR over the conventional surface coil for small animal imaging at 7T.
APPROACH
A small animal surface coil is designed based on multimodal surface coil technique. The coil is investigated and compared with conventional surface coil using full-wave electromagnetic simulations.
RESULTS
The multimodal surface coil shows superior B1 field efficiency and lower E field over standard coils, indicating a potential to gain SNR and resolution.
IMPACT
The proposed multimodal surface coil can operate at high frequency and provides improved SNR over conventional surface coils at 7T, opening avenues for highly efficient coil design in small animal imaging, ultimately enabling the detection of previously indiscernible physiological details.
PubMed: 38948448
DOI: No ID Found -
Proceedings of the International... May 2024Low-field MRI has garnered significant attention in recent years due to its unique advantages in safety, cost-effectiveness and accessibility. However, lower field...
MOTIVATION
Low-field MRI has garnered significant attention in recent years due to its unique advantages in safety, cost-effectiveness and accessibility. However, lower field strength comes with an inherently lower SNR as its primary limitation.
GOALS
In this work, we introduce a novel volume RF coil design using coupled stack-up resonators to mitigate this challenge.
APPROACH
To demonstrate the proposed design, we take 0.5T as an example field strength and designed a prototype coupled stack-up volume coil operating in the 20MHz range.
RESULTS
Compared to the birdcage coil, the proposed design significantly improves RF field efficiency and homogeneity, ultimately enhancing the performance of low-field MRI.
IMPACT
The proposed stack-up volume coil outperforms the standard birdcage coil in B1 efficiency and field homogeneity at low fields, ultimately improving the performance of low-field MRI and advancing its applications.
PubMed: 38948446
DOI: No ID Found -
Journal of Multidisciplinary Healthcare 2024
PubMed: 38948394
DOI: 10.2147/JMDH.S481908