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1.
Ann Hum Biol ; 51(1): 2359920, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38994897
3.
J Couns Psychol ; 71(2): 104-114, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38376930

ABSTRACT

Meditation apps are the most commonly used mental health apps. However, the optimal dosing of app-delivered meditation practice has not been established. We examined whether the distribution of meditation practices across a day impacted outcomes in a distressed population. We investigated the effects of meditation practice frequency in a 2-week compassion-based meditation intervention delivered via the Healthy Minds Program app. Undergraduates with clinically elevated depression and/or anxiety (N = 351) were randomized to a massed (one 20-min meditation per day) or distributed condition (two 10-min meditations per day). Psychological distress (primary outcome; composite of depression and anxiety), experiential avoidance, fear of missing out, loneliness, and self-compassion were assessed pre- and post-intervention. Psychological distress, loneliness, and informal meditation practice were also assessed daily. Practice time and frequency were assessed using app data. Results support feasibility of the study design, success of the manipulation, and acceptability of the intervention. Pooled across conditions, participants exhibited pre-post improvements on all outcomes (absolute value of ds = 0.12-0.63, p ≤ .010) and trajectories of improvement on daily distress and loneliness (p ≤ .010). No between-group differences were observed on changes in pre-post or daily measures (ps = .158-.729). When total amount of meditation practice per day is held constant, the distribution of practice may not influence outcomes for distressed beginners. Although only a first test of dose frequency effects, findings support flexibility in the distribution of meditation throughout the day, which may increase accessibility. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Meditation , Humans , Emotions , Anxiety/therapy , Anxiety Disorders , Databases, Factual
4.
Microsurgery ; 44(2): e31152, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38363113

ABSTRACT

INTRODUCTION: The main innervation of the trapezius muscle is provided by the spinal accessory nerve. Several studies describe the contributions of cervical plexus roots to the trapezius muscle innervation, either directly or through connections with the spinal accessory nerve. There is no adequate understanding of how the trapezius muscle is affected after using the spinal accessory nerve in nerve transfer procedures with the usual technique, preserving at least 1 branch for the upper trapezius. METHODS: We evaluated 20 patients with sequelae of traumatic brachial plexus injury who underwent surgical procedures for brachial plexus repair or free muscle transfer, which included the spinal accessory nerve transfer technique and were followed for a minimum of 1 year. The three portions trapezius muscle were evaluated by physical examination, magnetic resonance imaging (analysis of fatty degeneration) and electromyography. RESULTS: In all evaluation methods, the middle and lower portions of the trapezius muscle showed more significant morphological and/or functional impairment than the upper portion, in most cases. There was a statistically significant difference in all the complementary exams results, between the affected side (with sacrifice of the nerve) versus the normal side, in the middle and lower portions of the trapezius muscle. CONCLUSIONS: Physical examination alone is not sufficient to determine the residual functionality of the trapezius muscle. Magnetic resonance imaging and electromyography are useful tools to assess both morphological involvement of the trapezius muscle and nerve conduction impairment of the trapezius muscle, respectively. The results suggest that the middle and lower portions of the trapezius muscle are affected by previous SAN transfer and should be considered with caution for further muscle transfer procedures.


Subject(s)
Brachial Plexus , Nerve Transfer , Superficial Back Muscles , Humans , Accessory Nerve/surgery , Superficial Back Muscles/innervation , Brachial Plexus/surgery , Cervical Plexus/anatomy & histology , Cervical Plexus/physiology , Electromyography , Nerve Transfer/methods
5.
Chem Biol Interact ; 388: 110834, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38103879

ABSTRACT

The present study investigates the anti-neoplastic activity of a platinum (II) complex, Pt(II)5ClSS, and its platinum (IV) di-hydroxido analogue, Pt(IV)5ClSS, against mesenchymal cells (MCs), lung (A549), melanoma (A375) and breast (MDA-MB-231) cancer cells. Both complexes exhibited up to 14-fold improved cytotoxicity compared to cisplatin. NMR was used to determine that ∼25 % of Pt(IV)5ClSS was reduced to Pt(II)5ClSS in the presence of GSH (Glutathione) after 72 h. The complex 1H NMR spectra acquired for Pt(II)5ClSS with GSH shows evidence of degradation and environmental effects (∼30 %). The prominence of the 195Pt peak at âˆ¼ -2800 ppm suggests that a significant amount of Pt(II)5ClSS remained in the mixture. Pt(II)5ClSS and Pt(IV)5ClSS have shown exceptional selectivity to cancer cells in comparison to MCs (IC50 > 150 µM). Western blot analysis of Pt(II)5ClSS and Pt(IV)5ClSS on A549 cells revealed significant upregulation of cleaved PARP-1, BAX/Bcl2 ratio, cleaved caspase 3 and cytochrome thus suggesting apoptosis was induced through the intrinsic pathway. Flow cytometry also revealed significant cell death by apoptosis. Treatment with Pt(II)5ClSS and Pt(IV)5ClSS also showed significant amounts of free radical production while the COMET assay showed that both complexes cause minimal DNA damage. Cellular uptake results via ICP-MS suggest a time-dependent active mode of transport for both complexes with Pt(II)5ClSS being transported at a higher rate compared to Pt(IV)5ClSS. A Dose Escalation Study carried out on BALB/c mice showed that Pt(II)5ClSS and Pt(IV)5ClSS were approximately 8- folds and 12.5-folds, respectively, more tolerated than cisplatin. The present study provides evidence that both complexes may have the characteristics of an efficient and potentially safe anti-tumor drug that could support NSCLC treatment.


Subject(s)
Antineoplastic Agents , Lung Neoplasms , Prodrugs , Animals , Mice , Cisplatin/pharmacology , Cisplatin/chemistry , Platinum/chemistry , Prodrugs/chemistry , Lung Neoplasms/drug therapy , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis
6.
Brain Behav Immun ; 115: 480-493, 2024 01.
Article in English | MEDLINE | ID: mdl-37924961

ABSTRACT

BACKGROUND: The staggering morbidity associated with chronic inflammatory diseases can be reduced by psychological interventions, including Mindfulness-Based Stress Reduction (MBSR). Proposed mechanisms for MBSR's beneficial effects include changes in salience network function. Salience network perturbations are also associated with chronic inflammation, including airway inflammation in asthma, a chronic inflammatory disease affecting approximately 10% of the population. However, no studies have examined whether MBSR-related improvements in disease control are related to changes in salience network function. METHODS: Adults with asthma were randomized to 8 weeks of MBSR or a waitlist control group. Resting state functional connectivity was measured using fMRI before randomization, immediately post-intervention, and 4 months post-intervention. Using key salience network regions as seeds, we calculated group differences in change in functional connectivity over time and examined whether functional connectivity changes were associated with increased mindfulness, improved asthma control, and decreased inflammatory biomarkers. RESULTS: The MBSR group showed greater increases in functional connectivity between salience network regions relative to the waitlist group. Improvements in asthma control correlated with increased functional connectivity between the salience network and regions important for attention control and emotion regulation. Improvements in inflammatory biomarkers were related to decreased functional connectivity between the salience network and other networks. CONCLUSIONS: Increased resting salience network coherence and connectivity with networks that subserve attention and emotion regulation may contribute to the benefits of MBSR for patients with asthma. Understanding the neural underpinnings of MBSR-related benefits in patients is a critical step towards optimizing brain-targeted interventions for chronic inflammatory disease management.


Subject(s)
Asthma , Mindfulness , Adult , Humans , Chronic Disease , Asthma/therapy , Inflammation , Biomarkers , Magnetic Resonance Imaging
7.
Brain Stimul ; 16(6): 1753-1763, 2023.
Article in English | MEDLINE | ID: mdl-38043646

ABSTRACT

BACKGROUND: Synchronizing a TMS pulse with a person's underlying EEG rhythm can modify the brain's response. It is unclear if synchronizing rTMS trains might boost the antidepressant effect of TMS. In this first-in-human trial, we demonstrated that a single TMS pulse over the prefrontal cortex produces larger effects in the anterior cingulate depending on when it is fired relative to the individual's EEG alpha phase. OBJECTIVE/HYPOTHESES: We had three hypotheses. 1) It is feasible to synchronize repetitive TMS (rTMS) delivery to a person's preferred prefrontal alpha phase in each train of every session during a 30-visit TMS depression treatment course. 2) EEG-synchronized rTMS would produce progressive entrainment greater than unsynchronized (UNSYNC) rTMS. And 3) SYNC TMS would have better antidepressant effects than UNSYNC (remission, final Hamilton Depression Rating <10). METHODS: We enrolled (n = 34) and treated (n = 28) adults with treatment resistant depression (TRD) and randomized them to receive six weeks (30 treatments) of left prefrontal rTMS at their individual alpha frequency (IAF) (range 6-13 Hz). Prior to starting the clinical trial, all patients had an interleaved fMRI-EEG-TMS (fET) scan to determine which phase of their alpha rhythm would produce the largest BOLD response in their dorsal anterior cingulate. Our clinical EEG-rTMS system then delivered the first TMS pulse in each train time-locked to this patient-specific 'preferred phase' of each patient's left prefrontal alpha oscillation. We randomized patients (1:1) to SYNC or UNSYNC, and all were treated at their IAF. Only the SYNC patients had the first pulse of each train for all sessions synchronized to their individualized preferred alpha phase (75 trains/session ×30 sessions, 2250 synchronizations per patient over six weeks). The UNSYNC group used a random firing with respect to the alpha wave. All other TMS parameters were balanced between the two groups. The system interfaced with a MagStim Horizon air-cooled Fig. 8 TMS coil. All patients were treated at their IAF, coil in the F3 position, 120 % MT, frequency 6-13 Hz, 40 pulses per train, average 15-s inter-train interval, 3000 pulses per session. All patients, raters, and treaters were blinded. RESULTS: In the intent to treat (ITT) sample, both groups had significant clinical improvement from baseline with no significant between-group differences, with the USYNC group having mathematically more remitters but fewer responders. (ITT -15 SYNC; 13 UNSYNC, response 5 (33 %), 1 (7 %), remission 2 (13 %), 6 (46 %). The same was true with the completer sample - 12 SYNC; 12 UNSYNC, response 4, 4 (both 30 %), remission 2 (17 %), 3 (25 %)). The clinical EEG phase synchronization system performed well with no failures. The average treatment session was approximately 90 min, with 30 min for placing the EEG cap and the actual TMS treatment for 45 min (which included gathering 10 min of resting EEG). Four subjects (1 SYNC) withdrew before six weeks of treatment. All 24 completer patients were treated for six weeks despite the trial occurring during the COVID pandemic. SYNC patients exhibited increased post-stimulation EEG entrainment over the six weeks. A detailed secondary analysis of entrainment data in the SYNC group showed that responders and non-responders in this group could be cleanly separated based on the total number of sessions with entrainment and the session-to-session precision of the entrained phase. For the SYNC group only, depression improvement was greater when more sessions were entrained at similar phases. CONCLUSIONS: Synchronizing prefrontal TMS with a patient's prefrontal alpha frequency in a blinded clinical trial is possible and produces progressive EEG entrainment in synchronized patients only. There was no difference in overall clinical response in this small clinical trial. A secondary analysis showed that the consistency of the entrained phase across sessions was significantly associated with response outcome only in the SYNC group. These effects may not simply be due to how the stimulation is delivered but also whether the patient's brain can reliably entrain to a precise phase. EEG-synchronized clinical delivery of TMS is feasible and requires further study to determine the best method for determining the phase for synchronization.


Subject(s)
Depressive Disorder, Treatment-Resistant , Adult , Humans , Depressive Disorder, Treatment-Resistant/therapy , Transcranial Magnetic Stimulation/methods , Treatment Outcome , Antidepressive Agents/therapeutic use , Alpha Rhythm , Double-Blind Method , Prefrontal Cortex/physiology
8.
Res Sq ; 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38106062

ABSTRACT

Transcranial magnetic stimulation (TMS) is a non-invasive FDA-approved therapy for major depressive disorder (MDD), specifically for treatment-resistant depression (TRD). Though offering promise for those with TRD, its effectiveness is less than one in two patients (i.e., less than 50%). Limits on efficacy may be due to individual patient variability, but to date, there are no established biomarkers or measures of target engagement that can predict efficacy. Additionally, TMS efficacy is typically not assessed until a six-week treatment ends, precluding interim re-evaluations of the treatment. Here, we report results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient's individual electroencephalographic (EEG) prefrontal alpha oscillation indexed by functional magnetic resonance imaging (fMRI). Among responders, synchronized rTMS produces two systematic changes in brain dynamics: a reduction in global cortical excitability and enhanced phase entrainment of cortical dynamics. These effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly biomarker tracking enables efficacy prediction and dynamic adjustments through a treatment course, improving the overall response rates. This innovative approach advances the prospects of individualized medicine in MDD and holds potential for application in other neuropsychiatric disorders.

9.
Front Psychol ; 14: 1257390, 2023.
Article in English | MEDLINE | ID: mdl-38022957

ABSTRACT

Music is widely recognised as a human universal, yet there is no agreed explanation for its function, or why and when it evolved. I summarise experimental evidence that the primary function of musicking lies in social bonding, both at the dyadic and community levels, via the effect that performing any form of music has on the brain's endorphin system (the principal neurohormonal basis for social bonding in primates). The many other functions associated with music-making (mate choice, pleasure, coalition signalling, etc) are all better understood as derivative of this, either as secondary selection pressures or as windows of evolutionary opportunity (exaptations). If music's function is primarily as an adjunct of the social bonding mechanism (a feature it shares with laughter, feasting, storytelling and the rituals of religion), then reverse engineering the problem suggests that the capacity for music-making most likely evolved with the appearance of archaic humans. This agrees well with anatomical evidence for the capacity to sing.

10.
medRxiv ; 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37873424

ABSTRACT

Transcranial magnetic stimulation (TMS) is an FDA-approved therapy for major depressive disorder (MDD), specifically for patients who have treatment-resistant depression (TRD). However, TMS produces response or remission in about 50% of patients but is ineffective for the other 50%. Limits on efficacy may be due to individual patient variability, but to date, there are no good biomarkers or measures of target engagement. In addition, TMS efficacy is typically not assessed until a six-week treatment ends, precluding the evaluation of intermediate improvements during the treatment duration. Here, we report on results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient's individual electroencephalographic (EEG) prefrontal alpha oscillation informed by functional magnetic resonance imaging (fMRI). We find that, in responders, synchronized delivery of rTMS produces two systematic changes in brain dynamics. The first change is a decrease in global cortical excitability, and the second is an increase in the phase entrainment of cortical dynamics. These two effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly tracking of these biomarkers allows for efficacy prediction and potential of dynamic adjustments through a treatment course, improving the overall response rates.

11.
Sci Rep ; 13(1): 14575, 2023 09 04.
Article in English | MEDLINE | ID: mdl-37666889

ABSTRACT

The personal network of relationships is structured in circles of friendships, that go from the most intense relationships to the least intense ones. While this is a well established result, little is known about the stability of those circles and their evolution in time. To shed light on this issue, we study the temporal evolution of friendships among teenagers during two consecutive academic years by means of a survey administered on five occasions. We show that the first two circles, best friends and friends, can be clearly observed in the survey but also that being in one or the other leads to more or less stable relationships. We find that being in the same class is one of the key drivers of friendship evolution. We also observe an almost constant degree of reciprocity in the relationships, around 60%, a percentage influenced both by being in the same class and by gender homophily. Not only do our results confirm the mounting evidence supporting the circle structure of human social networks, but they also show that these structures persist in time despite the turnover of individual relationships-a fact that may prove particularly useful for understanding the social environment in middle schools.


Subject(s)
Friends , Lewis Blood Group Antigens , Adolescent , Humans , Longitudinal Studies , Schools , Students
12.
Sci Rep ; 13(1): 15953, 2023 09 24.
Article in English | MEDLINE | ID: mdl-37743388

ABSTRACT

Mind-body interventions such as mindfulness-based stress reduction (MBSR) may improve well-being by increasing awareness and regulation of physiological and cognitive states. However, it is unclear how practice may alter long-term, baseline physiological processes, and whether these changes reflect improved well-being. Using respiration rate (RR), which can be sensitive to effects of meditation, and 3 aspects of self-reported well-being (psychological well-being [PWB], distress, and medical symptoms), we tested pre-registered hypotheses that: (1) Lower baseline RR (in a resting, non-meditative state) would be a physiological marker associated with well-being, (2) MBSR would decrease RR, and (3) Training-related decreases in RR would be associated with improved well-being. We recruited 245 adults (age range = 18-65, M = 42.4): experienced meditators (n = 42), and meditation-naïve participants randomized to MBSR (n = 72), active control (n = 41), or waitlist control (n = 66). Data were collected at pre-randomization, post-intervention (or waiting), and long-term follow-up. Lower baseline RR was associated with lower psychological distress among long-term meditators (p* = 0.03, b = 0.02, 95% CI [0.01, 0.03]), though not in non-meditators prior to training. MBSR decreased RR compared to waitlist (p = 0.02, Cohen's d = - 0.41, 95% CI [- 0.78, - 0.06]), but not the active control. Decreased RR related to decreased medical symptoms, across all participants (p* = 0.02, b = 0.57, 95% CI [0.15, 0.98]). Post-training, lower RR was associated with higher PWB across training groups compared to waitlist (p* = 0.01, b = 0.06, 95% CI [0.02, 0.10]), though there were no significant differences in change in PWB between groups. This physiological marker may indicate higher physical and/or psychological well-being in those who engage in wellness practices.


Subject(s)
Meditation , Psychological Distress , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Self Report , Respiratory Rate , Physical Examination
13.
Brain Stimul ; 16(3): 830-839, 2023.
Article in English | MEDLINE | ID: mdl-37187457

ABSTRACT

BACKGROUND: The communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited. METHODS: Here, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Six runs (276 total trials) were acquired in each participant. Phase at each TMS pulse was determined post-hoc using single-trial sorting. Results were examined in two independent datasets: healthy volunteers (HV) (n = 11) and patients with major depressive disorder (MDD) (n = 17) collected as part of an ongoing clinical trial. RESULTS: In both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC fMRI-derived effective connectivity (EC) was modulated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS pulses during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group. DISCUSSION: Results demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest potential clinical applications whereby TMS is synchronized to the brain's internal rhythms in order to more efficiently engage deep therapeutic targets.


Subject(s)
Depressive Disorder, Major , Transcranial Magnetic Stimulation , Animals , Humans , Brain , Alpha Rhythm , Dorsolateral Prefrontal Cortex , Prefrontal Cortex , Electroencephalography , Magnetic Resonance Imaging
14.
Sci Rep ; 13(1): 6120, 2023 04 14.
Article in English | MEDLINE | ID: mdl-37059731

ABSTRACT

In contrast to long-term relationships, far less is known about the temporal evolution of transient relationships, although these constitute a substantial fraction of people's communication networks. Previous literature suggests that ratings of relationship emotional intensity decay gradually until the relationship ends. Using mobile phone data from three countries (US, UK, and Italy), we demonstrate that the volume of communication between ego and its transient alters does not display such a systematic decay, instead showing a lack of any dominant trends. This means that the communication volume of egos to groups of similar transient alters is stable. We show that alters with longer lifetimes in ego's network receive more calls, with the lifetime of the relationship being predictable from call volume within the first few weeks of first contact. This is observed across all three countries, which include samples of egos at different life stages. The relation between early call volume and lifetime is consistent with the suggestion that individuals initially engage with a new alter so as to evaluate their potential as a tie in terms of homophily.


Subject(s)
Cell Phone , Social Support , Humans , Emotions , Ego , Italy
15.
Sci Rep ; 13(1): 4072, 2023 03 11.
Article in English | MEDLINE | ID: mdl-36906682

ABSTRACT

Seminal studies suggest that being mimicked increases experienced social closeness and prosocial behavior to a mimicking confederate (i.e., interaction partner). Here we reexamine these results by considering the role of empathy-related traits, an indirect proxy for endorphin uptake, and their combined effects as an explanation for these results. 180 female participants were mimicked or anti-mimicked in an interaction with a confederate. The effects of being mimicked versus anti-mimicked in relation to empathy-related traits and endorphin release (assessed indirectly via pain tolerance) on experienced closeness and prosocial behavior were assessed using Bayesian analyses. Our results suggest that high individual empathy-related traits increase social closeness to the anti-mimicking and mimicking confederate and to one's romantic partner, as compared to mimicry alone. Results furthermore strongly suggest that high individual empathy-related traits increase prosocial behavior (donations and willingness to help) as compared to mimicry alone. These findings extend previous work by highlighting that empathy-related traits are more influential in creating positive effects on social closeness and prosocial behavior than a one-shot mimicking encounter.


Subject(s)
Altruism , Social Behavior , Humans , Female , Empathy , Bayes Theorem , Pain Threshold
16.
Biol Rev Camb Philos Soc ; 98(4): 1278-1309, 2023 08.
Article in English | MEDLINE | ID: mdl-37001905

ABSTRACT

Comparative analyses are the backbone of evolutionary analysis. However, their record in producing a consensus has not always been good. This is especially true of attempts to understand the factors responsible for the evolution of large brains, which have been embroiled in an increasingly polarised debate over the past three decades. We argue that most of these disputes arise from a number of conceptual errors and associated logical fallacies that are the result of a failure to adopt a biological systems-based approach to hypothesis-testing. We identify four principal classes of error: a failure to heed Tinbergen's Four Questions when testing biological hypotheses, misapplying Dobzhansky's Dictum when testing hypotheses of evolutionary adaptation, poorly chosen behavioural proxies for underlying hypotheses, and the use of inappropriate statistical methods. In the interests of progress, we urge a more careful and considered approach to comparative analyses, and the adoption of a broader, rather than a narrower, taxonomic perspective.


Subject(s)
Acclimatization , Biological Evolution , Brain
17.
J Med Chem ; 65(24): 16481-16493, 2022 12 22.
Article in English | MEDLINE | ID: mdl-36480933

ABSTRACT

A novel platinum(II) complex 47OMESS(II) and its platinum(IV) derivative 47OMESS(IV) were synthesized and characterized. Cytotoxicity studies against mesenchymal cells (MCs) and lung (A549), breast (MDA-MB-231), and melanoma (A375) cancer cells demonstrated 7-20-fold superior activity for both complexes relative to cisplatin. Remarkably, 47OMESS(IV) demonstrated 17-22-fold greater selectivity toward the cancerous cells compared to the non-cancerous MCs. Western blot analysis on A549 cells showed the involvement of the intrinsic apoptotic pathway. Cellular fractionation and uptake experiments in A549 cells using ICP-mass spectrometry (MS) indicated that 47OMESS(II) and 47OMESS(IV) cross the cellular membrane predominantly via active transport mechanisms. The significant improvement in selectivity that is exhibited by 47OMESS(IV) is reported for the first time for this class of complexes.


Subject(s)
Antineoplastic Agents , Platinum , Humans , Platinum/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cisplatin/pharmacology , Apoptosis , A549 Cells , Cell Line, Tumor
18.
Front Microbiol ; 13: 1032495, 2022.
Article in English | MEDLINE | ID: mdl-36439813

ABSTRACT

The relationship between social behaviour and the microbiome is known to be reciprocal. Research in wild animal populations, particularly in primate social groups, has revealed the role that social interactions play in microbial transmission, whilst studies in laboratory animals have demonstrated that the gut microbiome can affect multiple aspects of behaviour, including social behaviour. Here we explore behavioural variation in a non-captive animal population with respect to the abundance of specific bacterial genera. Social behaviour based on grooming interactions is assessed in a population of rhesus macaques (Macaca mulatta), and combined with gut microbiome data. We focus our analyses on microbiome genera previously linked to sociability and autistic behaviours in rodents and humans. We show in this macaque population that some of these genera are also related to an individual's propensity to engage in social interactions. Interestingly, we find that several of the genera positively related to sociability, such as Faecalibacterium, are well known for their beneficial effects on health and their anti-inflammatory properties. In contrast, the genus Streptococcus, which includes pathogenic species, is more abundant in less sociable macaques. Our results indicate that microorganisms whose abundance varies with individual social behaviour also have functional links to host immune status. Overall, these findings highlight the connections between social behaviour, microbiome composition, and health in an animal population.

19.
Nat Hum Behav ; 6(10): 1333-1343, 2022 10.
Article in English | MEDLINE | ID: mdl-36258130

ABSTRACT

Intense sociality has been a catalyst for human culture and civilization, and our social relationships at a personal level play a pivotal role in our health and well-being. These relationships are, however, sensitive to the time we invest in them. To understand how and why this should be, we first outline the evolutionary background in primate sociality from which our human social world has emerged. We then review defining features of that human sociality, putting forward a framework within which one can understand the consequences of mass social isolation during the COVID-19 pandemic, including mental health deterioration, stress, sleep disturbance and substance misuse. We outline recent research on the neural basis of prolonged social isolation, highlighting especially higher-order neural circuits such as the default mode network. Our survey of studies covers the negative effects of prolonged social deprivation and the multifaceted drivers of day-to-day pandemic experiences.


Subject(s)
COVID-19 , Pandemics , Humans , Animals , Pandemics/prevention & control , COVID-19/epidemiology , Social Isolation , Mental Health , Brain/diagnostic imaging
20.
Brain Behav Immun Health ; 25: 100509, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36177306

ABSTRACT

Background: Psychological distress and comorbid psychopathology contribute to exacerbation risk in patients with asthma. Thus, interventions designed to reduce stress and improve emotion regulation, such as Mindfulness-Based Stress Reduction (MBSR), may augment standard care. Few studies have addressed this question and a paucity of data exists to determine the ability of MBSR to impact clinical outcomes in asthma. Methods: This randomized controlled trial investigated effects of MBSR training on asthma control and airway inflammation, in relation to psychological symptoms, in adults with asthma. Participants were randomized to an 8-week MBSR training (n = 35) or wait-list control group (n = 34). Clinically relevant asthma assessments, including Asthma Control Questionnaire and inflammatory biomarkers, were collected at baseline and six approximately-monthly follow-ups. Self-reported mindfulness, distress, depression, and anxiety symptoms were assessed at baseline, post-intervention, and study completion. Chronic stress level was determined at baseline only. Results: Asthma control improved significantly in individuals randomized to MBSR, relative to wait-list controls (p = .01; effect size d = 0.76), which was maintained at 4mo post-intervention. 32% of MBSR participants achieved a clinically significant improvement, based on the ACQ6 Minimally Important Difference, relative to 12% of wait-list participants. Moreover, MBSR-related improvement in asthma control was associated with a reduction in distress (p = .043) and the intervention was most efficacious for those with the highest baseline depressive symptoms (p = .023). Importantly, MBSR also reduced levels of exhaled nitric oxide, a biomarker of airway inflammation, relative to wait-list controls (p < .05). Conclusion: Supporting and extending extant evidence of mind-body relationships in asthma and the benefits of stress reduction for these patients, this is, to the best of our knowledge, the first RCT to demonstrate that training in MBSR improves clinically relevant asthma outcomes. MBSR may thus be a valuable addition to optimal asthma management, particularly for those with comorbid psychopathology. Clinical trial registration: NCT02157766.

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