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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 2024About one-third of all human cancers encode abnormal RAS proteins locked in a constitutively activated state to drive malignant transformation and uncontrolled tumor...
About one-third of all human cancers encode abnormal RAS proteins locked in a constitutively activated state to drive malignant transformation and uncontrolled tumor growth. Despite progress in development of small molecules for treatment of mutant KRAS cancers, there is a need for a pan-RAS inhibitor that is effective against all RAS isoforms and variants and that avoids drug resistance. We have previously shown that the naturally occurring bacterial enzyme RAS/RAP1-specific endopeptidase (RRSP) is a potent RAS degrader that can be re-engineered as a biologic therapy to induce regression of colorectal, breast, and pancreatic tumors. Here, we have developed a strategy for in vivo expression of this RAS degrader via mRNA delivery using a synthetic nonviral gene delivery platform composed of the poly(ethylene glycol)--poly(propylene sulfide) (PEG--PPS) block copolymer conjugated to a dendritic cationic peptide (PPDP2). Using this strategy, PPDP2 is shown to deliver mRNA to both human and mouse pancreatic cells resulting in RRSP gene expression, activity, and loss of cell proliferation. Further, pancreatic tumors are reduced with residual tumors lacking detectable RAS and phosphorylated ERK. These data support that mRNA-loaded synthetic nanocarrier delivery of a RAS degrader can interrupt the RAS signaling system within pancreatic cancer cells while avoiding side effects during therapy.
PubMed: 38948803
DOI: 10.1101/2024.06.11.598439 -
BioRxiv : the Preprint Server For... Jun 2024Social touch is critical for communication and to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch, especially...
Social touch is critical for communication and to impart emotions and intentions. However, certain autistic individuals experience aversion to social touch, especially when it is unwanted. We used a novel social touch assay and Neuropixels probes to compare neural responses to social vs. non-social interactions in three relevant brain regions: vibrissal somatosensory cortex, tail of striatum, and basolateral amygdala. We find that wild type (WT) mice showed aversion to repeated presentations of an inanimate object but not of another mouse. Cortical neurons cared most about touch context (social vs. object) and showed a preference for social interactions, while striatal neurons changed their preference depending on whether mice could choose or not to interact. Amygdalar and striatal neurons were preferentially modulated by forced object touch, which was the most aversive. In contrast, the knockout (KO) model of autism found social and non-social interactions equally aversive and displayed more aversive facial expressions to social touch when it invaded their personal space. Importantly, when KO mice could choose to interact, neurons in all three regions did not discriminate social valence. Thus, a failure to differentially encode social from non-social stimuli at the circuit level may underlie social avoidance in autism.
PubMed: 38948773
DOI: 10.1101/2024.06.19.599778 -
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 -
Journal of Family Medicine and Primary... May 2024Telephobia is a kind of anxiety disorder in which the individual is afraid of either answering or making telephone calls. This study was conducted to determine the...
BACKGROUND
Telephobia is a kind of anxiety disorder in which the individual is afraid of either answering or making telephone calls. This study was conducted to determine the prevalence of telephobia among medical students and to determine the association of socio-demographic and other factors with this disorder.
METHODS
A total of 320 undergraduate medical students were enrolled at a tertiary medical college in Western India, of which 300 (93.75%) responded to the survey. A stratified sampling strategy with the proportional allocation method was used in which 40 males and 20 females were selected from each year of students, spanning 5 years. A specially designed semi-structured questionnaire was used for the study, consisting of demographic data, purpose of using the internet, gadget used, and a 10-item telephobia questionnaire modified from the Severity Measure for Agoraphobia-Adult (SMA-A) Questionnaire to measure student's avoidance of telephone calling and receiving.
RESULTS
The mean age of the study participants was 21.91 (±1.84) years, and most of the students were urban residents (184, 61.3%). The prevalence of mild, moderate, and severe telephobia was 33.0%, 7.67%, and 1.33%, respectively, giving an overall prevalence of 42%. Univariate analysis revealed that male gender (χ = 9.822, df = 3, = 0.0201), higher duration of internet usage (χ = 41.15, df = 9, value < 0.000), and viewing porn (χ = 15.94, df = 3, = 0.0011) had significant association with higher severity of telephobia. Viewing of porn sites was reported by 65 (21.7%) medical students, exclusively among males.
CONCLUSION
A prevalence of 9% moderate to severe telephobia among medical students is much alarming, which may aggravate further as the students move from academic to clinical settings. The phenomenon of telephobia needs further exploration, to find its determinants and predictors, especially among vulnerable populations.
PubMed: 38948634
DOI: 10.4103/jfmpc.jfmpc_1673_23 -
Journal of Family Medicine and Primary... May 2024(body constitution) is the essential fundamental of Ayurveda. In female physiology, it plays a crucial role in determining the age of menarche and menopause. Recent...
INTRODUCTION
(body constitution) is the essential fundamental of Ayurveda. In female physiology, it plays a crucial role in determining the age of menarche and menopause. Recent research has shown that early menopause occurs in tribal women. Vagbhata states that a female has a longer menstrual life [i.e., reproductive period] compared to the and females. This study was done to estimate in females who attain early and premature menopause in the tribal population to provide optimal care for tribal women through primary and whole health systems.
MATERIALS AND METHODS
This cross-sectional questionnaire survey study was carried out in four villages of Nagpur district territory of Eastern Maharashtra, the central zone of India after seeking permission from IEC. A multistage sampling technique was used to select the 80%, and above tribal people, 169 married women who attained early or premature menopause were included. Post-menopausal women were selected for the study, and females with hysterectomy, secondary amenorrhea, and other major illnesses were excluded from the study. Data were collected by survey method with the help of a pre-validated questionnaire.
OBSERVATION AND RESULT
Out of 169 females 57.98% of females were of , 24.85% of females were of , and 17.15% of females were of . The prevalence of early or premature menopause of females is 57.98.
DISCUSSION
characteristics such as , , , and in females lead to early or premature menopause. To avoid early or premature menopause in tribal females, ghee (ghrit) and milk can be included in dietary habits, lifestyle modification, and awareness counseling may prove beneficial.
CONCLUSION
Early or premature menopause is observed largely in females of Nagpur district, Eastern Maharashtra, tribal zone of Central Inda.
PubMed: 38948555
DOI: 10.4103/jfmpc.jfmpc_376_23 -
Journal of Family Medicine and Primary... May 2024Rabies has significant health and economic consequences for both humans and animals. Annually, India witnesses 17.4 million dog bites, yet only 3 million individuals...
INTRODUCTION
Rabies has significant health and economic consequences for both humans and animals. Annually, India witnesses 17.4 million dog bites, yet only 3 million individuals receive post-exposure prophylaxis (PEP). There is a shortage of anti-rabies vaccine in India as quoted in many news reports. In India, lack of documentation of previous vaccination against animal bites is there, hence resulting in the re-administration of the anti-rabies vaccine, leading to a significant biological loss (anti-rabies vaccine).
MATERIAL AND METHODS
A cross-sectional, retrospective study was conducted. Data was collected, and analyzed from June 2021 to June 2023 a period of 2 years.
RESULTS
Majority of the patients reported within the first 24 hours after being bitten while approximately one-third reported after 24 hours. Majority were Category 3 bites and unprovoked. Males, lower-middle class, and bites on lower extremities were common among 4291 patients attending the clinic. Out of 217 re-exposure cases, 185 did not have any documentation regarding their previous treatment of animal bites.
CONCLUSION
Among 4291 patients attending the clinic, majority were Category 3 bites on the lower extremities. 85.25% of re-exposure cases had to be administered a full course of treatment due to a lack of documentation leading to rabies as a biological wastage. This avoidable wastage can be a resource for treating more patients.
PubMed: 38948549
DOI: 10.4103/jfmpc.jfmpc_1612_23 -
Innovation in Aging 2024In most western countries, older adults depend on private cars for transportation and do not proactively plan for driving cessation. The objective of this review was to... (Review)
Review
BACKGROUND AND OBJECTIVES
In most western countries, older adults depend on private cars for transportation and do not proactively plan for driving cessation. The objective of this review was to examine current research studies outlining effective interventions and strategies to assist older adults during their transition from driver to driving retirement or cessation.
RESEARCH DESIGN AND METHODS
A search was completed across 9 databases using key words and MeSH terms for drivers, cessation of driving, and older adult drivers. Eligibility screening of 9,807 titles and abstracts, followed by a detailed screening of 206 papers, was completed using the Covidence platform. Twelve papers were selected for full-text screen and data extraction, comprising 3 papers with evidence-based intervention programs and 9 papers with evidence-informed strategies.
RESULTS
Three papers met the research criteria of a controlled study for programs that support and facilitate driving cessation for older adults. Nine additional studies were exploratory or descriptive, which outlined strategies that could support older drivers, their families, and/or healthcare professionals during this transition. Driving retirement programs/toolkits are also presented.
DISCUSSION AND IMPLICATIONS
The driver retirement programs had promising results, but there were methodological weaknesses within the studies. Strategies extracted contributed to 6 themes: of the topic, is important, is critical, away from assessment to proactive planning, is needed, and should be the end result. Meeting the transportation needs of older adults will be essential to support aging in place, out-of-home mobility, and participation, particularly in developed countries where there is such a high dependency on private motor vehicles.
PubMed: 38948542
DOI: 10.1093/geroni/igae054 -
Cancer Innovation Feb 2024Colorectal cancer is among the well-known forms of cancer and a prominent cause of cancer demises worldwide. In vitro experiments reinforced by animal studies, as well... (Review)
Review
Colorectal cancer is among the well-known forms of cancer and a prominent cause of cancer demises worldwide. In vitro experiments reinforced by animal studies, as well as epidemiological studies of human colorectal cancer propose that the growth of this disease can be moderated by eating aspects. Dietary intake including green vegetables and fruits may result in the reduction of colon cancer chances. The finding suggests that the combinations of dietary nutrients may deliver additive or synergistic effects and might be a powerful method to avoid or eradicate colon cancer beginning and/or development. Flavonols are one of the most widespread dietary nutrients of the polyphenols-flavonoids and major constituent of and Brassicaceae vegetables. Flavonols present in vegetables of and Brassicaceae family are kaempferol, myricetin, quercetin, and isorhamnetin. These flavonols are claimed to have antiproliferative activity in vivo and in vitro against colorectal cancer. The objective of this review is to summarize the role of flavonols obtained from dietary sources in the prevention and treatment of colorectal cancer.
PubMed: 38948535
DOI: 10.1002/cai2.99 -
F1000Research 2023Getting acceptable cosmetic results in the soft tissues of the face serves as the foundation for orthodontic treatment planning. Also, in order to achieve healthy static...
Comparative evaluation and co-relation in variation of curve of Spee and curve of Wilson in Class II div. 1, Class II div. 2, and Class III as against Class I malocclusion in central India population- an in vitro study.
INTRODUCTION
Getting acceptable cosmetic results in the soft tissues of the face serves as the foundation for orthodontic treatment planning. Also, in order to achieve healthy static and dynamic occlusal interactions, the teeth must be positioned within the basal bone at the correct position, angle, and inclination. To avoid periodontal issues, provide stability, and achieve a functional occlusion, it is essential to ascertain the individual's dental arch form before starting of treatment and thus to utilise the mechanics that follow throughout the treatment.
OBJECTIVES
To evaluate and compare variation in Curve of Spee and Curve of Wilson in Class II Div.-1, Class II-Div-2 and Class-III as against Class I malocclusion in central India population.
METHODOLOGY
Irreversible hydrocolloid impression will be taken with perforated metal stock trays and stone cast will be poured. This will be scanned using CAD CAM machine and curve of Spee and Wilson will be measured using reverse engineering.
EXPECTED RESULT
It will assist us in treatment planning for preventing periodontal issues, assuring stability, and achieving functional occlusion by evaluating and comparing the Spee and Wilson curves in Class II Divison-1, Class II Divison-2, and Class-III malocclusion with Class-I malocclusion.
CONCLUSION
Every single patient receiving orthodontic treatment has the COS, which is crucial to achieving a stable occlusion. Almost every patient who receives orthodontic treatment eventually experiences the Spee Curve. Since there aren't many studies examining the relationship between the Curves of Spee and Wilson, their impact on dentoskeletal morphology, and their role in occlusal stability.
PubMed: 38948508
DOI: 10.12688/f1000research.133330.2