Abstract

Background
Depression results from interactions between biological, social, and psychological factors. Literature shows that depression is associated with abnormal brain structure, and that socioeconomic status (SES) is associated with depression and brain structure. However, limited research considers the interaction between each of these factors.
Methods
Multivariate regression analysis was conducted using UK Biobank data on 39,995 participants to examine the relationship between depression and brain volume in 23 cortical regions for the whole sample and then separated by sex. It then examined whether SES affected this relationship.
Results
Eight out of 23 brain areas had significant negative associations with depression in the whole population. However, these relationships were abolished in seven areas when SES was included in the analysis. For females, three regions had significant negative associations with depression when SES was not included, but only one when it was. For males, lower volume in six regions was significantly associated with higher depression without SES, but this relationship was abolished in four regions when SES was included. The precentral gyrus was robustly associated with depression across all analyses.
Limitations
Participants with conditions that could affect the brain were not excluded. UK Biobank is not representative of the general population which may limit generalisability. SES was made up of education and income which were not considered separately.
Conclusions
SES affects the relationship between depression and cortical brain volume. Health practitioners and researchers should consider this when working with imaging data in these populations.

Introduction

Mental health problems are significant public health issues within the UK and worldwide, with depression being one of the most prevalent. Research shows that there is a relationship between depression and brain structure (Tang et al., 2007; Kronmüller et al., 2009; Bos et al., 2018; Maggioni et al., 2019), and that social factors, including socioeconomic status (SES), are associated with both depression (Delgadillo et al., 2016; Marmot, 2010; Freeman et al., 2016) and changes in brain structure (Kweon et al., 2022; Colich et al., 2020; Jednoróg et al., 2012; Noble et al., 2015). However, these three factors are rarely all considered together. Given the impact of depression on both the individual and society, as discussed below, understanding the mechanisms of this disorder, to improve prevention and treatment options, is of critical importance.

Around 1 in 6 adults in England met the criteria for a common mental health disorder in the week prior to being surveyed (McManus et al., 2016). Mental health problems are one of the leading contributors to overall worldwide disease burden and are reported to account for 16 % of Disability Adjusted Life Years (DALYs, Arias et al., 2022). They confer substantial societal and economic implications with an estimated annual cost in England of £77 billion (Kirkwood et al., 2010). Depression is one of the most prevalent mental health problems, affecting approximately 5 % of adults (World Health Organization, WHO, 2023) and 280 million people globally (Institute of Health Metrics and Evaluation, 2023). Depression can be long-lasting with a single chronic episode, or recurrent, with many episodes over a long time, and has a substantial impact on an individual’s ability to function and cope with daily life. The risk of suicide is reported to be about 15 times higher in those with depression than the general population (Cipriani et al., 2005). This is however likely to be an underestimate as many who die by suicide have undiagnosed depressive symptoms.

Conclusion

This study is, to our knowledge, the first study to examine the relationship between depression, cortical volume, and SES in a middle-aged to older sample of this size. Given that SES appears to impact the relationship between depression and brain structure, we posit that SES should be a consideration for clinicians and scientists working with imaging data in these populations. Future research involving large-scale longitudinal data is needed to elucidate the causal relationships between the factors examined in this study.

Abstract

Excessive reassurance-seeking in OCD has been linked to the maintenance of OCD, functioning as a type of checking ritual. Current treatments recommend the imposition of the extinction of seeking and providing reassurance; however, this is not well tolerated. Although it has been suggested that the provision of support may provide a more helpful alternative, there is no empirical evidence for this. In the present study, 36 participants with OCD engaged with two personalised semi-idiographic scenarios in which they imagined seeking and receiving reassurance and seeking and receiving emotional support in counterbalanced order. The primary outcome measure was anticipated urge to seek reassurance, which was found to significantly decrease in the imagined support condition relative to the imagined reassurance condition regardless of order of presentation. Emotional support was perceived as significantly more acceptable when compared to imagining reassurance in terms of higher ratings of perceived helpfulness in managing emotions, feelings of calmness and closeness, and the sense that they were fighting OCD together. These findings provide preliminary evidence for the value of encouraging the seeking and giving of emotional support as an alternative to reassurance. Implications for clinical work and further research are discussed.

Introduction

Obsessive-compulsive disorder (OCD) is a common and pervasive mental health disorder characterised by the presence of severe and disabling obsessions and compulsions, (American Psychological Association, 2023). Thought to have a lifetime prevalence of around 2% (Cervin, 2023). OCD is associated with increased autoimmune disorders (de la Cruz et al., 2022), long-term socioeconomic difficulties (Pérez-Vigil et al., 2018), significantly impaired quality of life (Eisen et al., 2006; Macy et al., 2013), and significant strains on peer and family relationships (Grover & Dutt, 2011; Walseth et al., 2017).

Cognitive theories of OCD focus on the threat of harm to self and/or others, and an inflated sense of responsibility for such harm, as the precipitating factors and motivators of the responses that maintain OCD (Rachman, 2002; Salkovskis, 1985; Salkovskis & Warwick, 1985; Smith et al., 2022). Compulsive behaviours motivated by responsibility beliefs are considered key maintaining responses, functioning as safety-seeking behaviours (SSB) intended to achieve certainty that harm or responsibility for it is eliminated (Salkovskis, 1991). Like most SSBs, however, checking has the effect of preventing disconfirmation and maintaining pre-occupation (Osborne & Williams, 2013). For example, with each instance of checking the memory of previous checks is tarnished (Radomsky et al., 2006). As such, the level of certainty of safety tends to decrease, and checking is perpetuated (Rachman, 2002; Tolin et al., 2002). Recent work thus suggests that excessive reassurance-seeking (ERS) is a special type of checking. Defined as the “verbal and/or non-verbal interaction with someone who you perceive has access to potentially threat relieving information, with the intention of increasing your perceived sense of certainty from harm” (Halldorsson & Salkovskis, 2023), in practice, this often looks like requests or comments (verbal or non-verbal) that search for certainty that their feared outcome is untrue (e.g., “did I do that properly?“, “am I a bad person?” etc.) with responses provided that attempt to provide this certainty (e.g., “Yes you did”, “No you aren’t a bad person”. Unlike most other forms of checking, this interaction has the additional function of transferring responsibility onto others (Rachman, 2002; Salkovskis, 1999).

Conclusion

The present study highlights the anticipated advantages of seeking and receiving emotional support as opposed to reassurance. People with OCD imagined support as not only more effective in the long-term, but also as more acceptable when compared to reassurance. Future research may benefit from assessing these outcomes in caregivers of those with OCD also, in addition to in-vivo experiments that can investigate the effectiveness and acceptability of reassurance in practice.

Abstract

Osteoporosis is a systemic bone disease characterized by reduced bone mass and deterioration of the microstructure of bone tissue, leading to an increased risk of fragility fractures and affecting human health worldwide. Food-derived peptides are widely used in functional foods due to their low toxicity, ease of digestion and absorption, and potential to improve osteoporosis. This review summarized and discussed methods of diagnosing osteoporosis, treatment approaches, specific peptides as alternatives to conventional drugs, and the laboratory preparation and identification methods of peptides. It was found that peptides interacting with RGD (arginine-glycine-aspartic acid)-binding active sites in integrin could alleviate osteoporosis, analyzed the interaction sites between these osteogenic peptides and integrin, and further discussed their effects on improving osteoporosis. These may provide new insights for rapid screening of osteogenic peptides, and provide a theoretical basis for their application in bone materials and functional foods.

Osteoporosis

As the global population ages, the prevalence of diseases associated with aging, such as diabetes, arthritis, and dementia, also increases ( Li et al., 2021 , Lopes et al., 2022 ). Among these, the increasing incidence of chronic diseases such as osteoporosis have caused a significant societal burden ( Su et al., 2020 ). Osteoporosis affects more than 200 million people worldwide ( Shen et al., 2022 ). By 2030, the number of hip fractures among males are estimated to increase by 51.8% globally, and females are at even higher risk ( Gasparik et al., 2023 ). The increasing incidence of osteoporosis may contribute to a higher risk of fractures and reduced life expectancy, necessitating investigations on the prevention and treatment of this condition.

In the human body, normal bone metabolism involves persistent bone tissue remodeling through osteoblast-dependent bone formation and osteoclast-dependent bone resorption. Enhanced bone resorption leads to reduced bone density, a primary factor in the development of osteoporosis ( Malluche, Davenport, Lima, & Monier-Faugere, 2022 ). Osteoporosis is characterized by reduced bone density, deteriorating bone microstructure, and aggravated bone fragility, which increase the risk of fracture. These changes in bone structure are closely linked to the activities of osteoblasts and osteoclasts: osteoblasts secrete non-collagen proteins to regulate the mineralization of bone matrix, while osteoclasts are responsible for bone resorption ( Kittivanichkul, Watanabe, Nagaoka, & Malaivijitnond, 2016 ). Osteocytes, the most abundant cells in mature bone ( Fig. 1 ), interact with osteoblasts and osteoclasts to influence bone formation and resorption and are closely related to osteoporosis.

Perspectives

The value of food protein digests and bioactive peptides as functional foods in the future cannot be estimated. A healthy diet should contain osteogenic peptides that have been investigated through preclinical research and clinical trials. Prediction of osteogenic peptides directly from enzymatic hydrolysis products has significantly reduced the cost of osteogenic peptides compared to multi-step purification, isolation, screening and identification. Moreover, advanced and powerful technologies, such as mass spectrometry, protein purification, bioinformatics, crystallography, micro-computed tomography, and biofilm interference, are widely utilized to study molecular structure and provide a theoretical basis for understanding the relationship between structure and activity at the molecular level. In this review, the evaluation methods and treatment methods of osteoporosis are reviewed, and it is found that osteopoietic peptides from food sources are a potential source to replace drugs with side effects for osteoporosis treatment. Peptides can improve osteoporosis by interacting with RGD binding sites within integrins, which may be used in future computer simulations to rapidly predict and screen new methods of osteogenic peptides. Taken together, these not only improve the safety of osteoporosis treatment but also reduce the cost of screening osteogenic peptides. This review aims to encourage studies on the structure-activity relationships between osteogenic peptides and integrins that regulate cell adhesion, promoting osteoblast and inhibiting osteoclast proliferation and differentiation. Osteogenic peptides also have the potential for application in the development of bioadhesives for bone materials. Therefore, research ideas for predicting and screening bone-forming active peptides have been summarized, these ideas may lead to the development of bone materials, active drugs that promote bone formation and functional foods.

Abstract

• Delayed-onset seizures after deep brain stimulation (DBS) surgery were seldom reported in previous studies. We studied 341 PD patients who underwent STN-DBS surgery from 2006 to 2021 in our department retrospectively.

• Five patients experienced seizures after DBS surgery with an incidence of 1.47 %. All 5 seizures cases were characterized as delayed-onset with an average time of 12 days postoperatively, which was different from the previous studies. In the further risk factors analysis of seizures, we found that the average diameter of peri-electrode edema of patients with seizures was larger than the average diameter of patients without seizures, which indicated that peri-electrode edema was risk factor for delayed-onset seizures after DBS surgery.

• Further multivariate analysis confirmed the result. Our study is the first report focusing on clinical characteristics and risk factors of delayed-onset seizures after DBS surgery based on a case series.

• Although DBS related seizure is uncommon complication, patients who experienced seizures are still exposed in risks of trauma and damage to the implanted simulator. We believe that these findings were useful for prevention and management of seizures associated with DBS surgery.

Introduction

Deep brain stimulation (DBS) is a well-established surgical therapy for some movement and psychiatric disorders. Patients are exposed in risks of trauma and implanted simulator damage when seizures occur, though seizures are not common postoperative adverse event of deep brain stimulation surgery. Previous studies indicated that the risk factors for seizures related to DBS included hemorrhage, peri-electrode edema, and increased age [1, 2, 3]. Most of the seizures occurred during electrode implantation procedures or within 48 h after DBS surgery [1, 2, 3], and delayed-onset seizures were seldom reported. However, this seizures incidence time-point presents quite different from those reports when retrospectively screening those PD patients who underwent subthalamic nucleus (STN) DBS in our center. We found that the seizures after DBS surgery were mainly delayed-onset (1–2 weeks after surgery). Therefore, this study summarized the clinical characteristics of delayed-onset seizures after DBS surgery and analyzed related risk factors.

Conclusions

Delayed-onset seizure after STN-DBS treating PD patients was uncommon with an incidence of 1.47 %. The seizures were transient and self-limiting, not easily developing into chronic epilepsy. Peri-electrode edema was a risk factor for delayed-onset seizures after DBS surgery. Patients with an average peri-electrode edema diameter > 2.70 cm had a higher risk to develop seizures.

Abstract

Nowadays, it is an established concept that the capability to reach a specialised cell identity via differentiation, as in the case of multi- and pluripotent stem cells, is not only determined by biochemical factors, but that also physical aspects of the microenvironment play a key role; interpreted by the cell through a force-based signalling pathway called mechanotransduction. However, the intricate ties between the elements involved in mechanotransduction, such as the extracellular matrix, the glycocalyx, the cell membrane, Integrin adhesion complexes, Cadherin-mediated cell/cell adhesion, the cytoskeleton, and the nucleus, are still far from being understood in detail. Here we report what is currently known about these elements in general and their specific interplay in the context of multi- and pluripotent stem cells. We furthermore merge this overview to a more comprehensive picture, that aims to cover the whole mechanotransductive pathway from the cell/microenvironment interface to the regulation of the chromatin structure in the nucleus. Ultimately, with this review we outline the current picture of the interplay between mechanotransductive cues and epigenetic regulation and how these processes might contribute to stem cell dynamics and fate.

Introduction

One of the basic principles enabling multicellular life is the differentiation of stem cells (SCs), into specialised cells with a defined identity, shape, and function ( McBeath et al., 2004 ) ( Tewary et al., 2018 ). SCs are defined as cells that are clonogenic, which defines their capability of both, self-renewing and retaining multilineage differentiation potency. In vertebrates, the Zygote represents the earliest stem cell (totipotent) in ontogeny, from which originate the pluripotent stem cells (PSCs) of the inner cell mass of the blastocyst ( Dean et al., 2003 , Smith, 2017 ). Soon thereafter, PSCs continue to expand during embryo development becoming progressively committed in their cell fate and acquiring a more restricted potency ( Dean et al., 2003 , Osorno et al., 2012 , Smith, 2017 ). Even at the end of embryogenesis, when the organism is fully formed, and its organs are composed of functionally mature cells, some SCs are still present. These cells, which possess a more limited differentiating potential (multipotent), in turn, give rise to a progeny of precursor cells and, finally, to functionally mature cells. Some examples are represented by the hematopoietic SCs in the bone marrow, the intestinal SCs in the gut’s crypts, the epithelial SCs in the epidermis or the mesenchymal stem cells (MSCs) which play an important role in the maintenance and regeneration of bones and cartilage ( Barker, 2014 , Evans et al., 2013 , Guan et al., 2012 , Tewary et al., 2018 , Watt, 2002 , Weissman, 2000 ).

The inherent high level of plasticity characterising SCs is at the base of their capability to respond precisely to appropriate stimuli with differentiative behaviour. Understanding this essential principle of multicellular life; i.e., the regulation of cell identity and fate, is one of the most important fields of research in modern cell biology, primarily due to its impact on the development of new therapeutic approaches in regenerative medicine. Such knowledge can directly benefit stem cell bioengineering by leveraging the SC plasticity and control over SC behaviour for the application in tissue engineering, patient-specific disease modelling and cell therapies ( Tewary et al., 2018 ).

Conclusions

In recent years there has been a fascinating expansion of our knowledge about the interplay between mechanotransductive signalling and chromatin regulation, and how this impacts on multi- and pluripotent stem cell dynamics, which we try to highlight in this review.

However, what shapes the life of a cell and its identity, from the outside (biophysical and structural cues of the cellular microenvironment) and from the inside (nuclear and chromatin organisation) and how it is connected (mechanotransduction and epigenetics) are highly relevant biological issues that are yet far from being understood in detail. Starting from the stem cell/microenvironment interface, a much more detailed understanding of the nanoscale events in this interface is necessary to unravel 1) what the SC perceives of the biophysical nature and the 3D adhesion site configuration and 2) how the immanent nanoscale information is interpreted and converted, through force-based actions, into a remodelling at the level of the IACs, cell/cell adhesions, cytoskeleton and nucleus.

Abstract

Developmental prosopagnosia (DP) is a condition that indicates the inability to recognize individuals by their faces from birth, without any history of brain damage. The assessment of face recognition ability and diagnosis of DP involve the use of face tests such as the Cambridge Face Memory Test (CFMT) and the Cambridge Face Perception Test, along with self-reported measures like the 20-Item Prosopagnosia Index (PI20). Face recognition accuracy is affected by anxiety. However, previous studies on the relationship between face recognition ability and anxiety have not used the PI20 measure. This study aimed to investigate the relationship between self-reported measures of face recognition ability and anxiety tendencies among healthy young individuals for DP diagnosis and its implications. We used a face recognition test, involving the PI20, CFMT, Visual Perception Test for Agnosia–Famous Face Test (VPTA–FFT), and State-Trait Anxiety Inventory (STAI). We assessed the performance of 116 Japanese young adults (75 females, median age of 20.7 years, with a standard deviation of 1.2). Subsequently, we conducted a statistical analysis to examine the relationship between the outcomes of the face recognition tests and STAI scores using Pearson correlation analysis and single correlation coefficients. The results showed a positive correlation between state anxiety and PI20 (r = 0.308, p = 0.007), and a weak positive correlation was also observed between trait anxiety and PI20 (r = 0.268, p = 0.04). In contrast, there was no correlation between CFMT and VPTA–FFT with respect to STAI. The results of the hierarchical multiple regression analysis also suggested that the correlation between the performance on the PI20 (self-report) and objective measures of face recognition performance (the CFMT and the VPTA–FFT) are driven by differences in anxiety. This study is the first to explore the relationship between face recognition abilities and anxiety using the PI20 self-report measure. There are implications for future research on the diagnosis of DP and the relationship between anxiety and face recognition.

Introduction

Face recognition ability enables individuals to differentiate and identify faces, playing a crucial role in interpersonal recognition and everyday communication. Clinical and functional imaging studies have highlighted that brain lesions, particularly in regions such as the fusiform gyrus, can lead to face recognition impairment. In recent years, there has been a growing interest in the field of face recognition research regarding developmental prosopagnosia (DP). DP refers to a condition in which individuals experience lifelong impairments in face recognition despite possessing normal visual and intellectual capabilities since birth. Clinically, there is no indication of overt central nervous system disorders, and neuroimaging studies also reveal the absence of organic brain lesions (Bate & Tree, 2017; Behrmann & Avidan, 2005; Cook & Biotti, 2016; Duchaine & Nakayama, 2006a). Epidemiological studies in Europe and Asia have reported a prevalence rate of approximately 1.9 %–2.9 % of the population (Bowles et al., 2009; Kennerknecht et al., 2006; Kennerknecht et al., 2008). People with DP encounter challenges and psychosocial difficulties in their interpersonal interactions due to impaired face recognition (Yardley et al., 2008). Early diagnosis and support are crucial, especially before adulthood and entering the workforce.

Currently, diagnosing DP presents challenges due to the absence of established strict objective criteria or biological markers (Barton & Corrow, 2016; Susilo & Duchaine, 2013). Previous studies have revealed ambiguous criteria for diagnosing DP and differentiating it from conditions other than DP in face recognition tests (Bate & Tree, 2017; Dalrymple & Palermo, 2016). Dalrymple and Palermo (2016) provided guidelines that define DP as objectively poor performance on face memory tests and a subjective feeling of repeated face recognition failures in daily life. The authors emphasized the importance of using questionnaires and interviews to assess face recognition difficulties in daily life and highlighted the limitations of relying solely on questionnaires for DP diagnosis, as individuals with DP may lack accurate insight into their own face recognition abilities.

Conclusions

The present study is the first to investigate the relationship between self-reported face recognition abilities and anxiety in young, healthy Japanese individuals using the self-perception face recognition test PI20. The findings indicated that unlike the objective face recognition tests CFMT and VPTA–FFT that showed no association with anxiety, the self-perception test scores may be influenced by state anxiety. Self-reporting, at least in its current form, provides limited insights into predicting face recognition performance in young individuals and diagnosing DP. Therefore, self-reporting is insufficient to evaluate face recognition abilities in young individuals, and DP cannot be diagnosed solely based on self-perception tests. It is necessary to combine self-perceived indicators of face recognition impairment with other perception-based face recognition function tests and consider the presence and extent of anxiety tendencies. Our findings have significant psychological implications for understanding face recognition impairments, DP diagnosis, and clinical practices. In the future, expanding research to investigate the interaction between facial and expression recognition abilities and anxiety is expected to enhance the accurate diagnosis and support for young individuals with facial recognition impairments.

Abstract

Background. The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson’s disease, PD. Objective. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. Methods. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson’s Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck’s Depression Inventory (BDI). Results. In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤30%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients’ self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. Conclusions. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient’s subjective evaluation.

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease, causing severe disability with increasing prevalence. A diagnosis of PD is based on the motor manifestations: bradykinesia, rigidity, and tremor, and clinical symptoms related to the loss of dopamine. In PD, these symptoms of parkinsonism are related to a neurodegenerative pathological process involving misfolding and aggregation of α-synuclein and formation of inclusion bodies, Lewy bodies, primarily in dopaminergic neurons. A diagnosis of PD is clinicopathological and requires both this pathological hallmark as well as the clinical phenomenology. In 2015, the Movement Disorder Society (MDS) put forward updated clinical diagnostic criteria for PD to increase early diagnostic accuracy in patients with Lewy body pathology Parkinson’s disease [1]. Dopaminergic neuronal loss in addition to Lewy body formation is central in the pathology of PD. In the diagnostic criteria from 2015, the importance of this pathological hallmark is emphasized even more than in earlier diagnostic criteria [2], through suggestion of operational criteria including (i) support by objective measurement of effect on motor symptoms showing a >30% improvement with dopaminergic medication in the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), (ii) a clearly documented history of marked changes with medication from the patient or the caregiver, and also that (iii) lack of sufficient motor improvement should be an exclusion criterion [3].

While the diagnostic criteria of PD from MDS have been validated against expert clinical diagnosis and the United Kingdom Brain Bank criteria from 1988 [4], the clinical importance of having this definition of the effect of medication in a movement disorder clinic may still be more thoroughly evaluated.

Treatment with levodopa (L-dopa) is the most efficient dopaminergic therapy and the golden standard treatment for PD [1]. An evaluation of dopaminergic effect is therefore necessarily based on treatment with L-dopa. To evaluate the treatment effect in an objective manner, the standardized acute levodopa challenge test (LDCT) can be used to assess motor symptoms both OFF and ON medication to evaluate the L-dopa response. Besides using LDCT in a diagnostic approach, the acute LDCT protocol has been described and used in the measurement of disease progression [5]. In addition, it has been widely accepted as an evaluation of levodopa effect as a preoperative evaluation before deep brain stimulation of the subthalamic nucleus (STN-DBS) [6].

Conclusion

We have performed a clinically relevant evaluation of levodopa response in a group of patients with PD with both a self-reported good and poor L-dopa response. An acute LDCT was performed as an objective measure, but a surprisingly large discrepancy was found between the subjectively reported usual response and the acute effect. As patients all otherwise had a diagnosis of PD, a good effect should be found for both the subjective and objective evaluation in accordance with diagnostic criteria. Our study sheds light on the importance of questioning the reported effect when making a diagnosis. The mean LCDT was close to 30% in most cases, but our study indicates that an acute effect of less than 30% should sometimes be expected.

In conclusion, this study showed that the LCDT can be used as a diagnostic support and that it is a valuable tool in addition to the self-reported effect from the patient. But also, that conclusions based on an acute effect of less than 30% should be evaluated with caution, as this was the case in 56.8% of the patients with PD in our study.

Abstract

Background
Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities. The premise of this randomized clinical trial is that, in a population at risk, a 48-month program of dietary weight loss and exercise will result in less incident structural knee OA compared to control.

Methods/design
The Osteoarthritis Prevention Study (TOPS) is a Phase III, assessor-blinded, 48-month, parallel 2 arm, multicenter randomized clinical trial designed to reduce the incidence of structural knee OA. The study objective is to assess the effects of a dietary weight loss, exercise, and weight-loss maintenance program in preventing the development of structural knee OA in females at risk for the disease. TOPS will recruit 1230 ambulatory, community dwelling females with obesity (Body Mass Index (BMI) ​≥ ​30 ​kg/m2) and aged ≥50 years with no radiographic (Kellgren-Lawrence grade ≤1) and no magnetic resonance imaging (MRI) evidence of OA in the eligible knee, with no or infrequent knee pain. Incident structural knee OA (defined as tibiofemoral and/or patellofemoral OA on MRI) assessed at 48-months from intervention initiation using the MRI Osteoarthritis Knee Score (MOAKS) is the primary outcome. Secondary outcomes include knee pain, 6-min walk distance, health-related quality of life, knee joint loading during gait, inflammatory biomarkers, and self-efficacy. Cost effectiveness and budgetary impact analyses will determine the value and affordability of this intervention.

Discussion
This study will assess the efficacy and cost effectiveness of a dietary weight loss, exercise, and weight-loss maintenance program designed to reduce incident knee OA.

Backgrounds

Osteoarthritis (OA), the leading cause of disability among adults, has no cure and is associated with significant comorbidities [1]. Its increased prevalence and severity make it burdensome for people afflicted with the disease, and for health care organizations intended to administer care [2]. Obesity and OA were first linked in 1945 and this relationship has since been verified repeatedly [[3], [4], [5], [6]]. Obesity is a major risk factor associated with knee pain; people with obesity were 2.7 times more likely to have knee OA than adults without obesity [7].

Our mechanistic model, influenced by the seminal work of Griffin and Guilak [8], supports the premise that dietary weight loss and exercise may reduce knee joint loads, lower inflammation, and increase self-efficacy resulting in a lower incidence of structural knee OA (Fig. 1). Previous work showed that weight loss decreased knee joint loads such that every pound lost was associated with a 4-pound reduction in knee compressive forces while walking. The cumulative effect of this load reduction, over thousands of steps per day, reduces microdamage to the subchondral plate and calcified cartilage [9]. These areas are close to the overlying articular cartilage and likely protect articular cartilage integrity (Fig. 1).

Discussion

Implementing a randomized clinical trial designed to prevent incident knee OA presents numerous challenges. OA disease status and severity are defined structurally via x-ray [36] or MRI [19] and clinically using a combination of symptoms reported by the patient and derived from a physical exam [66]. The primary outcome measure for TOPS is structural knee OA using MRI, due to its superior sensitivity and granularity compared to radiographic assessments. In addition, the use of radiographic assessments as the primary outcome measure to determine the presence or absence of incident knee OA would have increased the sample size by 478 participants (39 ​%), requiring additional clinical centers and greater costs to test the hypothesis effectively.

Losing weight and preventing weight regain are difficult [67]. Biological changes fight attempts to maintain weight loss; the body acts in starvation mode increasing feelings of hunger, satiety is suppressed, metabolic rate slows, all in an attempt to defend higher body weights [68]. Psychosocial obstacles include decreased self-efficacy, increased chronic perceived psychosocial stress, and using food for comfort; environmental obstacles include large food portions and food availability [69]. Our previous work provides encouragement that most of the weight-loss attained by the TOPS diet and exercise group can be retained long-term with implementation of the weight-loss maintenance program. In a subsample of the IDEA cohort (N ​= ​94), the diet-only group retained 5.8 ​kg (65 ​%) of an 8.9 ​kg weight loss 3.5 years following completion of the 18-month diet intervention [70]. Maintenance of this clinically important weight-loss occurred without any post-intervention interaction with the study staff.

Abstract

To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF). Isoproterenol was injected into rats to create CHF models. The rats were then subsequently divided into saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Compared to the CHF group, the canagliflozin combined with the aerobic exercise group had superior ventricular remodeling and cardiac function. In rats treated with canagliflozin combined with aerobic exercise, the expression of cytochrome P450 (CYP) 4A3, CYP4A8, COL1A1, COL3A1, and FN1 was reduced, while the expression of CYP26B1, ALDH1A2, and CYP1A1 increased significantly. Additionally, canagliflozin combined with aerobic exercise decreased the phosphorylation of AKT and ERK1/2. Canagliflozin combined with aerobic exercise has a positive effect on the development of CHF via the regulation of retinol metabolism and the AKT/ERK signaling pathway.

Introduction

Chronic heart failure (CHF), the most prevalent form of cardiovascular illness, is a global health issue with a high death and morbidity rate.1 The disease affects about 2% of the adult population worldwide, and the 5-year mortality rate is estimated to be between 45 and 60%.2 CHF is a complex condition characterized by a cardiac muscle’s inability to maintain blood supply to peripheral tissues, resulting in decreased systemic energy metabolism.3 Multiple studies have demonstrated that regulating cardiac energy metabolism is critical for treatment.4,5 The β-oxidation of fatty acids in the mitochondria satisfies the heart’s high energy requirements. Oliveros et al. observed previously observed that a vitamin A deficit paired antioxidant defenses, promoted lipid peroxidation in the adult rat heart, and altered aortic lipid metabolism.6 The peroxisome proliferator-activated receptor (PPAR) is a ligand-activated nuclear transcription factor.7 PPAR modulates fatty acid oxidation (FAO) and mitochondrial bioenergetics, suppresses myocardial remodeling and fibrosis, and improves HF.8 Consequently, we must investigate new techniques for enhancing cardiac function by ameliorating abnormalities of cardiac energy metabolism, preventing cardiac remodeling and fibrosis, and thereby preventing or postponing the advancement of heart failure.

Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT-2), has been demonstrated to benefit HF with a lower ejection fraction.9 SGLT-2 inhibitors (canagliflozin, and so forth) for patients with CHF, improve the quality of life, and reduce mortality, morbidity, and readmission rates.10 In diabetic and nondiabetic subjects, canagliflozin treatment significantly reduced the risk of cardiovascular death, myocardial infarction, and hospitalization for hypertension.11 In addition, SGLT-2 inhibitors can improve fatty acid metabolism and utilize ketone bodies to create mitochondrial energy, so enhancing the aerobic metabolism of skeletal muscle, inhibiting anaerobic metabolism, and enhancing aerobic exercise capacity.12 Canagliflozin has been demonstrated to decrease myocardial glucose metabolism, enhance myocardial fatty acid metabolism, and increase the circulation of ketone bodies,13 thereby ameliorating heart failure via modifying myocardial energy metabolism and oxidative stress.14

Results

Canagliflozin combined with aerobic exercise improved isoproterenol-induced cardiac dysfunction
To investigate the effect of canagliflozin combined with aerobic exercise on CHF, cardiac function was assessed using echocardiography. After 10 days of ISO administration, the levels of LVEF (p < 0.001) and LVFS (p < 0.001) in the ISO group were significantly lower than in the control group, indicating that the CHF rat model was successfully established. LVEF and LVFS levels were significantly higher in the ISO+CA group (LVEF, p < 0.05; LVFS, p < 0.05), the ISO+AE group (LVEF, p < 0.05; LVFS, p < 0.05), and the ISO+AE+CA group (LVEF, p < 0.01; LVFS, p < 0.01). Moreover, compared to the ISO group, the levels of LVIDs (p < 0.05) and LVESV (p < 0.05) were significantly reduced in the ISO+AE+CA group but not in the ISO+CA group (LVIDs, p = 0.21; LVESV, p = 0.21). (Figures 1A and 1B, Table 1).

Abstract

The current paper aimed to analyze quantitatively the trends of four major schools of thought in scientific Psychology (neuroscience, cognitivism, behaviorism, psychoanalysis) and their intersections, covering the period from 1979 to 2020. We utilized a rigorous methodology across three distinct sources: Mainstream Psychology (MP), Highly Influential Journal (HIJ), and non-English papers (NEP). Our findings align with previous research in two aspects: psychoanalysis and behaviorism have significantly declined, cognitivism remains a prominent trend. However, we deviate from prior studies by recognizing that neuroscience may be considered the most influential trend and that trends exhibit less linearity than previously assumed. We also acknowledge the significance of NEP, which manifest an independent pattern as compared to the other sources and that may reveal what happens in the “periphery” of Psychology. It is noteworthy that NEP demonstrated a still lively contribution from psychoanalysis. Our study also highlights the insularity and lack of cross-fertilization among psychological subdisciplines, despite the widespread claims to the contrary. It eventually supports the inference that scientific Psychology is a non-paradigmatic or pre-paradigmatic discipline, pointing out the dominance of applied psychology and confuting the notion of overarching “grand theories”.

History of the empirical analyses of trends in psychology

The study conducted by Friman et al. (1993) was one of the pioneering empirical investigations into the trends of subdisciplines within the field of Psychology. The authors specifically focused on psychoanalysis, behaviorism, and cognitivism during the years 1979–1988, utilizing data obtained from the Social Science Journal of Citation Reports (SSJCR). In their research, the authors selected four influential journals that represented each subdiscipline, taking into consideration various criteria, including a relatively high Impact Factor (IF)1 (for further details see Friman et al., 1993, pp. 659-660). For instance, Cognitive Psychology, Cognition, Journal of Experimental Psychology: Learning, Memory, and Cognition, and Memory & Cognition, aligned with the cognitive approach.

In the study conducted by Friman et al. (1993), the four selected journals representing each sub-discipline were examined using four different indexes: IF, Immediacy Index (II),2 citation number (the number of times the journal has been cited during a given year), and source items (the number of citable items the journal has produced during a given year). These indexes were calculated for each journal on an annual basis, and then averaged across the four journals to obtain single indexes for each sub-discipline. The three indexes were eventually plotted against each other. The main finding of the study indicated a significant increase in prominence for the cognitive school of thought. However, it was observed that the citation numbers and source items for behaviorism and psychoanalysis, although lower than those of cognitivism, were not substantially inferior. Despite the rise of the cognitive school, the study did not provide evidence for a clear-cut Kuhnian paradigmatic shift. Additionally, when considering the broader context of the social sciences, all three sub-disciplines (cognitive, behaviorism, and psychoanalysis) performed relatively well in comparison to other indexed journals in the SSJCR.

Conclusion

Taking a more speculative and substantial perspective on the history of Psychology, it can be inferred from the current data that over the past 40 years, the major scientific discourses have predominantly centered around the brain. Many recent studies (Bittermann & Fischer, 2018; Tracy et al., 2004; Yeung, Goto, & Leung, 2017; Wieczorek et al., 2021) suggest an increasing importance in neuroscience within Psychology and more widely across all natural sciences, and Benjafield (2020) highlights how the vocabulary of Psychology is more dependent on Biology than vice versa. These observations suggest an imbalance favoring biologically-based theories over emergentist/spiritualistic ones, although it does not necessarily imply a complete endorsement of materialism by neuroscientists. Rather, it might signify only an informal inclination towards biologically-based explanations. It is noteworthy that psychological researchers rarely adopt a clear ontological standpoint on “mind” and “behavior” and generally avoid extensive engagement with philosophical and theoretical issues (Henriques, 2011; Zagaria et al., 2020).

All things considered, the enduring and relatively stable patterns observed over a 40-year period are indicative of the robustness and vitality of Psychology as a discipline. These patterns demonstrate that the theoretical assumptions regarding the mind have exhibited relative stability over an extended duration.

Abstract

Oral cavity stem cells (OCSCs) have been the focus of intense scientific efforts due to their accessibility and stem cell properties. The present work aims to compare the different characteristics of 6 types of dental stem cells derived from the oral cavity: dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), bone marrow mesenchymal stem cells (BMSC), and gingival mesenchymal stem cells (GMSC). Using immunofluorescence and real-time polymerase chain reaction techniques, we analysed the cells for stem cell, differentiation, adhesion, and extracellular matrix markers; the ability to proliferate in vitro; and multilineage differentiation potential. Markers such as vimentin, CD44, alkaline phosphatase, CD146, CD271, CD49f, Oct 3/4, Sox 9, FGF7, nestin, and BMP4 showed significant differences in expression levels, highlighting the heterogeneity and unique characteristics of each cell type. At the same time, we confirmed that all cell types successfully differentiated into osteogenic, chondrogenic, or adipose lineages, with different readiness. In conclusion, our study reveals the distinct properties and potential applications of various dental-derived stem cells. These findings contribute to a deeper understanding of OCSCs and their significance in future clinical applications.

Introduction

Bone marrow mesenchymal stem cells (BMSCs) exhibit high proliferation ability and multilineage differentiation potential. They were the first mesenchymal stem cells (MSCs) to be described, isolated from adults’ bone marrow aspirate.1 They have been extensively researched in human and animal model systems using in vivo and in vitro cell cultures. Further, they have bridged the divide and are integrated into various trials for clinical applications, with mixed success.2,3 BMSCs are not easily accessible, and an invasive procedure is required. Therefore, further research in the field, aiming at identifying alternative stem cell sources, has led to the discovery of oral cavity stem cells (OCSCs).

Currently, several different types of OCSCs are well known, including dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), dental follicle stem cells (DFSC), and gingival mesenchymal stem cells (GMSC).

Conclusions

This analysis of oral cavity–derived stem cells has exposed distinct and specific expression patterns of surface markers, ECM components, ECM remodelling enzymes, collagen genes, integrins, and differentiation potential. These findings may provide insights into the functional properties of these cell populations. Оur study aims to uncover the nuanced characteristics specific to each distinct cell type. Through experimentation and analysis, we anticipate to not only understand their individual functionalities but also gain deeper insights into their collective behaviour. Understanding both their shared characteristics and distinct attributes is an important step in using their regenerative potential in various tissue repair and regeneration contexts, thereby advancing the field of regenerative medicine and tissue engineering. By contributing meaningfully to the advancement of knowledge in regenerative medicine and tissue engineering, we aspire to pave the way for transformative breakthroughs in health care.

Objective
To investigate the influence of aerobic exercise on myocardial injury, NF-B expression, glucolipid metabolism and inflammatory factors in rats with Coronary Heart Disease (CHD) and explore the possible causative role.

Methods
45 Sprague Dawley® rats were randomized into model, control and experimental groups. A high-fat diet was adopted for generating a rat CHD model, and the experimental group was given a 4-week aerobic exercise intervention. ECG was utilized to evaluate the cardiac function of the rats; HE staining to evaluate the damage of myocardial tissue; TUNEL staining to evaluate cardiomyocyte apoptosis level; ELISA to assay the contents of inflammatory factors and glucolipid metabolism in cardiomyocytes; qPCR to assay IB- and NF-B mRNA expression; Western-blot to assay the apoptosis-related proteins and NF-B signaling pathway-related proteins expressions in myocardial tissue.

Results
In contrast to the model group, aerobic exercise strongly improved the rat’s cardiac function and glucolipid metabolism (p < 0.01), enhanced IL-10 content, Bcl-2/Bax level as well as IB- protein and mRNA expression (p < 0.01), and reduced myocardial injury and cardiomyocyte apoptosis, the contents of IL-6, IL-1 and TNF-, Caspase 3 level, NF-B mRNA and protein expression and p-p38 and p-STAT3 expressions (p < 0.01).

Conclusion
Aerobic exercise can not only effectively reduce myocardial injury, the release of inflammatory factors and NF-B expression in CHD rats, but also improve cardiac function and glucolipid metabolism. Its mechanism is likely to be related to the inhibition of the NF-B signaling pathway.

Introduction

Coronary Heart Disease (CHD) refers to coronary artery lumen stenosis or even blockage caused by atherosclerosis, which causes myocardial ischemia, hypoxia and even necrosis, and is also known as ischemic heart disease. 1 , 2 Physiological, genetic and environmental factors that cause aberrant glucolipid metabolism and inflammatory response disorders are the dominating incentives that induce atherosclerosis and the primary pathophysiological basis of CHD. 3 , 4 With the improvement in living standards, the incidence of CHD is increasing year by year, posing a huge economic burden on families and countries. Reducing the mortality and extending the survival time of CHD patients is a major challenge that cardiovascular disease researchers and clinicians urgently need to solve.

Considerable evidence shows that vascular endothelial injury will raise the adhesion and permeability of vascular endothelium, and then multiple inflammatory factors will gather and produce an inflammatory fiber proliferation reaction, which eventually gives rise to atherosclerosis. 7 , 8 , 9 Nuclear Factor Kappa B (NF-B) takes part in not only the occurrence but also the development of inflammatory response. NF-B inhibitor protein IB- can accelerate the dissociation of NF-B. The dissociated NF-B can be rapidly transferred to the nucleus, modulating the transcription and translation processes of diverse inflammatory factors and adhesion factors, and is an important cytokine that modulates the activation and cascade amplification of inflammatory factors. 10 , 11 Schiffmann et al. 12 have demonstrated that CHD patients will have apparent glucolipid metabolism disorder. Over-nutrition and sedentary behaviors will strikingly accelerate the accumulation of fat and glucose in the body, which in turn will aggravate the vascular endothelial damage of patients. Substantial evidence indicates that aerobic exercise can efficaciously regulate glucolipid metabolism in the body, reduce the activity of lipoprotein lipase, lower blood lipid and blood sugar levels, and reduce body weight. 13 , 14 Ornish et al. 15 demonstrated that long-term aerobic exercise can apparently reduce blood lipid levels and reduce vascular endothelial damage in patients with cardiovascular disease. At present, there are few studies on the impact of aerobic exercise on myocardial damage, glucolipid metabolism, and inflammation in CHD. This investigation aimed to build a rat CHD model to study the influence of aerobic exercise on myocardial damage, NF-B expression, glucolipid metabolism and inflammatory responses in CHD rats, as well as to further explore its possible causative role.

Abstract

Suicide is a major public health problem worldwide with far-reaching effects on families, communities, and societies. Influencing factors range from macro-level interventions like alcohol control policies and suicide prevention programs to individual contributors such as alcohol abuse and domestic violence. This study aimed to examine the relationship between Chile’s suicide rate changes from 2002 to 2015 and the Alcohol Act of 2004, a national suicide prevention program implemented in 2007, alcohol abuse, and domestic violence. Assembling a unique longitudinal dataset from Chilean public institutions, the study employed an instrumental variable time-series cross-regional design. Results indicated that the Alcohol Act was not associated with suicide rates, domestic violence exhibited a significant association with increased suicide rates, and the national suicide prevention program was linked to reductions in suicide rates, especially among males. These findings align with research from neighbouring countries, showcasing the efficacy of suicide prevention programs in decreasing suicide rates in Chile. Results highlight the importance of integrating protocols to early-detect domestic violence in suicide prevention programs, as well as the need to further improving alcohol control policies to complement suicide prevention programs.

Introduction

Suicide is a major public health problem worldwide with effects on families, communities, and society. Globally, there are 703,000 annual deaths by suicide (World Health Organization, 2021). The global age-standardized suicide rate in males (12.6 per 100,000) is more than double that in females (5.4 per 100,000) (World Health Organization, 2021). Suicide prevention is a priority for the WHO and is included as an indicator in the United Nations Sustainable Development Goals (World Health Organization, 2021).

Alcohol use is a substantive risk factor for both deaths by suicide and suicide attempts (Amiri and Behnezhad, 2020; Isaacs et al., 2022; Perez et al., 2022). Furthermore, acute high-dose alcohol use increases the risk of suicide (Borges et al., 2017; Conner and Bagge, 2019; Razvodovsky, 2009) and contributes to the adoption of more violent suicide means (Choi et al., 2018; Yeskendir et al., 2022). Studies have consistently found that alcohol abuse and intoxication are prevalent in suicidal behavior (Norström and Rossow, 2016). Hence, strategies to control alcohol abuse and intoxication could impact suicides attributable to alcohol use (Anderson et al., 2009; Babor et al., 2010; Ilhan and Yapar, 2020).

Conclusion

The reduction in suicide mortality following the implementation of Chile’s Suicide Prevention Program leads us to the conclusion that, despite using a crude operationalization, this policy incorporates changes that help anticipate triggers of suicidal behavior in targeted populations. Future research as well improvements in Chile’s Suicide Prevention Program should aim to better understand the mechanisms linking alcohol abuse, domestic violence, and suicide. From a research perspective, better relevant variables, including policy implementation and design, and other measurements of alcohol abuse and domestic violence should be explored further. From a suicide prevention policy perspective, it is advisable to consider a more explicit integration of at-risk groups, such as victims of domestic violence and/or individuals with alcohol related risks, into the early warning systems of Chile’s Suicide Prevention Program.