Clinical Implications Research Articles

SERPINH1 promoted the proliferation and metastasis of colorectal cancer by activating PI3K/Akt/mTOR signaling pathway

BACKGROUND Serpin peptidase inhibitor clade H member 1 (SERPINH1) was initially recognized as an oncogene implicated in various human malignancies. Nevertheless, the clinical relevance and functional implications of SERPINH1 in colorectal cancer (CRC) remain largely elusive. AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism. METHODS Quantitative real-time polymerase chain reaction, western blotting analysis, The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues. A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC. RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues, manifested at both mRNA and protein tiers. Elevated SERPINH1 levels correlated closely with advanced T stage, lymph node involvement, and distant metastasis, exhibiting a significant association with poorer overall survival among CRC patients. Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation, invasion, and migration in vitro , while conversely, SERPINH1 knockdown elicited the opposite effects. Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation. Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation, thereby facilitating CRC cell invasion and migration. CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC, potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.

Impact of tibial transverse transport in tissue regeneration and wound healing with perspective on diabetic foot ulcers

In this editorial, we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes . We focus on the clinical significance of tibial transverse transport (TTT) as an effective treatment for patients with diabetic foot ulcers (DFU). TTT has been associated with tissue regeneration, improved blood circulation, reduced amputation rates, and increased expression of early angiogenic factors. Mechanistically, TTT can influence macrophage polarization and growth factor upregulation. Despite this potential, the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development. These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation, and blood vessel and bone marrow improvement. Immunomodulation via systemic responses contributes to its therapeutic potential. Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT. This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease. Here, we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.

Methods and associations of suicidality in Kenyan high school students: clinical and public health implications.

Most evidence on suicidal thoughts, plans and attempts comes from Western countries; prevalence rates may differ in other parts of the world. This study determined the prevalence of suicidal thoughts, plans and attempts in high school students in three different regional settings in Kenya. This was a cross-sectional study of 2652 high school students. We asked structured questions to determine the prevalence of various types of suicidality, the methods planned or effected, and participants' gender, age and form (grade level). We provided descriptive statistics, testing significant differences by chi-squared and Fisher's exact tests, and used logistic regression to identify relationships among different variables and their associations with suicidality. The prevalence rates of suicidal thoughts, plans and attempts were 26.8, 14.9 and 15.7%, respectively. These rates are higher than those reported for Western countries. Some 6.7% of suicide attempts were not associated with plans. The most common method used in suicide attempts was drinking chemicals/poison (18.8%). Rates of suicidal thoughts and plans were higher for older students and students in urban rather than rural locations, and attempts were associated with female gender and higher grade level - especially the final year of high school, when exam performance affects future education and career prospects. Suicidal thoughts, plans and attempts are prevalent in Kenyan high school students. There is a need for future studies to determine the different starting points to suicidal attempts, particularly for the significant number whose attempts are not preceded by thoughts and plans.

Prevalence and Clinical Implications of Osteosarcopenia in Patients with Acute Stroke: A Cross-sectional Study.

To investigate the prevalence and risk factors of osteosarcopenia in patients with acute stroke. Overall, 224 patients within 2 weeks of having a stroke were enrolled. Demographic characteristics, National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), modified Barthel Index (MBI), Functional Ambulation Category (FAC), Berg Balance Scale (BBS), and handgrip strength were recorded. Body composition was evaluated using dual-energy X-ray absorptiometry. Patients who met the diagnostic criteria for osteoporosis and sarcopenia were defined as having osteosarcopenia. The overall prevalence of osteoporosis and sarcopenia was 46.9% and 50.9%, respectively. The prevalence of osteoporosis without sarcopenia, sarcopenia without osteoporosis, and osteosarcopenia was 18.3%, 22.3%, and 28.6%, respectively. The proportion of female sex (71.9%), median age, and NIHSS score were significantly higher, and mRS, BBS, MBI, FAC, and grip strength were significantly lower in patients with osteosarcopenia. Older age (≥65-years) (OR, 15.4), female sex (OR, 6.23), and lower BMI (<25 kg/m 2 ) (OR, 43.13) were independently associated with the likelihood of osteosarcopenia. Osteosarcopenia may occur in acute stroke survivors. Patients with osteosarcopenia have a significantly higher stroke severity and disability. A comprehensive diagnostic approach is imperative for osteosarcopenia, thereby facilitating implementation of optimal rehabilitative strategies.

Mini Endoscopic Septoplasty for High Localized Nasal Septum Deviation: Surgical Technique, Outcomes, and Comparison With Regular Septoplasty.

This prospective cohort study aimed to describe the technique of mini endoscopic septoplasty for patients with a high localized nasal septum deviation in front of the middle turbinate and chronic sinusitis or nasal sinus fungus ball. Our primary objective was to investigate the indications and outcomes of this procedure, and the secondary objective was to compare it with regular endoscopic septoplasty. Patients with chronic sinusitis or nasal sinus fungus ball and high localized nasal septum deviation underwent mini endoscopic septoplasty, while those with a broad deviation of the nasal septum underwent regular endoscopic septoplasty. The study evaluated the procedure duration, blood loss, and complications associated with both methods. All patients were followed up for 3 months. Thirty patients underwent mini endoscopic septoplasty; another 30 underwent regular endoscopic septoplasty. Mini endoscopic septoplasty demonstrated a significantly shorter procedure duration and lower blood loss than regular endoscopic septoplasty. Neither group experienced operative complications, such as nasal septum perforation or hematoma. Mini endoscopic septoplasty is a safe, time-efficient, and effective technique indicated for highly localized nasal septum deviations in patients with chronic sinusitis or nasal sinus fungus ball. This procedure offers advantages in terms of the surgical approach and postoperative debridement. Future research could explore the broader clinical implications of these findings.

Review: The Role of Dual-Energy Computed Tomography in Detecting Monosodium Urate Deposits in Vascular Tissues.

To highlight novel findings in the detection of monosodium urate deposits in vessels using dual energy computed tomography, and to discuss the potential clinical implications for gout and hyperuricemia patients. Gout is an independent risk factor for cardiovascular disease. However, classical risk calculators do not take into account these hazards, and parameters to identify patients at risk are lacking. Monosodium urate measured by dual energy computed tomography is a well-established technology for the detection and quantification of monosodium urate deposits in peripheral joints and tendons. Recent findings also suggest its applicability to identify vascular urate deposits. Dual energy computed tomography is a promising tool for detection of cardiovascular monosodium urate deposits in gout patients, to better delineate individuals at increased risk for cardiovascular disease.

Holding the hope? Therapist and client perspectives on long COVID recovery: A Q-methodology.

Long COVID is a global health concern which has debilitating effects on the individual experiencing it. In the United Kingdom, psychological therapies are being offered to people with long COVID, although the evidence for these therapies is yet to be demonstrated. This research aimed to understand how therapists and clients define and understand recovery from long COVID, and use hope theory to interpret the results. An online Q-methodology was employed, where participants sorted a range of statements pertaining to long COVID recovery based on their level of agreement with them. These arranged statements (Q-sorts) were collated and factor analysed to explore and compare underlying perspectives. Sixteen participants were recruited for the study, including eleven clients, four IAPT therapists and one therapist working in the broader long COVID pathway. A four-factor model is reported, including (1) Psychological Pathways to Recovery, (2) Social Context and Agency, (3) Physiological Goals of Recovery and (4) Personal Meaning Making. All IAPT therapists loaded onto the psychological pathways factor, whereas the remaining participants shared more diverse perspectives. The belief that long COVID recovery was possible, taken as an indicator of hopefulness, was rated highest for Factor 1, Psychological Pathways to Recovery, and Factor 3, Physiological Recovery Goals. This suggested that having a clear definition of recovery, or clear guidance on how to intervene, promoted hopefulness and, theoretically, well-being. However, clients reported experiences of being invalidated and disbelieved by health professionals, with psychological explanations sometimes being experienced as dismissive and invalidating. Clinical implications and future research directions are discussed.

The Effectiveness of Education with Picture Media to Increase Students’ Knowledge and Attitudes about Maintaining the Cleanliness of the External Genitalia at Al-Azhar26 Junior High School Yogyakarta

Background: Cleanliness of women’s genitals is related to the menstrual cycle. The education of menstruation with picture media increases women’s awareness to maintain the cleanliness of the external genital because picture media shows effects of risk behavior if do not maintain the cleanliness. Women with a better understanding of menstruation often have a safe and clean way to manage their menstrual bleeding. Poor knowledge, attitudes and actions towards external genitalia hygiene in adolescent girls have clinical implications, namely the occurrence of infections in the reproductive system and urinary tract infections. In developing countries, this problem needs more serious attention.Objective: This study aims to analyze the effectiveness of education with picture media to increase students’ knowledge and attitudes about maintaining the cleanliness of the external genitalia at Al-Azhar 26 Junior High School Yogyakarta.Methods: This research is a quantitative study with a quasi-experimental design and uses analytic research with a One Group Pretest- Postest Design. In this study there was no control group, data collection using a questionnaire. The population was made up of Grade VIII students of junior high schools who were actively studying at MTs Al- Azhar 26 Yogyakarta. Respondents came from junior high school students because junior high school students represented teenagers and their intellectual abilities were not much different. The research sample was taken by using a total sampling technique of 60 samples. The treatment procedure was after completing the pre-test, students were given education about external genital hygiene with picture media. After receiving education, students were asked to fill out a post test, after the data was collected, data analysis was carried out using the Wilcoxon test. Ethical permission for this research from FKIK UMY with number 106/EC-KEPK FKIK UMY/IV/2021.Results: Respondents are 60, aged 12 and 13 years. The mean value of knowledge before intervention is 7,02, the mean value of knowledge after intervention is 13,68. The mean value of the attitude before the intervention was 15.35, the mean value of the attitude after the intervention was 33.23. The results of the test on the level of knowledge of the respondents using the Wilcoxon test obtained a value of p = 0.001 (p &lt;0.05), this is a significant result in increasing the level of knowledge of respondents about external genitalia hygiene. The results of the test on respondents’ attitudes using the Wilcoxon test obtained p value = 0.001 (p &lt; 0.05), this is a significant result in increasing respondents’ attitudes about the external genitalia.Conclusion: counseling about genital hygiene is effective in increasing knowledge and attitudes about female genitalia in Yogyakarta. Efforts to improve external genital hygiene in adolescents need to be continuously improved with education that is carried out continuously and carried out using various methods.International Journal of Human and Health Sciences Vol. 08 No. 02 Apr’24 Page: 157-164

How do people with intellectual disabilities understand friendship? A systematic meta-synthesis.

Previous systematic reviews of the relationships of people with intellectual disabilities have included consideration of intimate relationships. In this paper, we report a systematic review of papers describing friendship only. A systematic qualitative meta-synthesis of the research exploring experiences of friendship as reported by people with intellectual disabilities. Seven papers met the inclusion criteria for analysis. Three superordinate themes were identified. (1) Reciprocity, 'Someone who helps me, and I help them'. (2) The building blocks of friendships, 'I can tell her some secrets'. (3) Managing friendship difficulties, 'In real life it's much harder'. People with intellectual disabilities value friendship and actively engage in reciprocal exchanges. We explore the strengths and limitations of current research, clinical implications, and directions for future research.

Wearable laser Doppler flowmetry for non-invasive assessment of diabetic foot microcirculation: methodological considerations and clinical implications.

Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Diabetic patients showed significantly reduced mean BF in the neurogenic () and heart () components at the M1 and M5 regions () compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic () and myogenic () components at the M1 region, as well as in the endothelial () component at the M5 region and in the myogenic component at the dorsal foot (), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region () and heel area (). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region () and heel area () in diabetic patients. This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

Schizencephaly: Etiopathogenesis, Classification, Therapeutic, and Rehabilitative Approach

AbstractSchizencephaly is an uncommon anomaly in neuronal migration characterized by complete clefts that extend from the pia mater to the ependymal surface of the ventricular system. These clefts are encompassed by displaced gray matter and filled with cerebrospinal fluid. Typically, they are found most often in the frontal lobe or the area around the lateral sulcus and can occur on one or both sides. The size, location, and type of these clefts carry significant clinical and prognostic implications. Moreover, they are frequently associated with other central nervous system malformations, including the absence of the septum pellucidum, septo-optic dysplasia, optic nerve hypoplasia, pachygyria, polymicrogyria, cortical dysplasia, heterotopia, and dysplasia of the corpus callosum. Occurrence of schizencephaly is almost always sporadic but its etiopathogenesis is yet to be fully understood. Most likely environmental factors, including exposure to teratogens, viral infections, and maternal factors, operate jointly with genetic defects. To date COL4A1, EMX2, SHH, and SIX3 are the genes identified as possible pathogenetic target. It is interesting to notice that schizencephaly is commonly seen in abandoned or adopted children, as proof of causative effect of intrautero insults. Clinical presentations widely vary and symptoms include a spectrum of cognitive impairment, limb paresis/tetraparesis, and epileptic seizures either with early or late onset; anyway, none of these symptoms is ever-present and patients with schizencephaly can also have normal neurocognitive and motor development. Diagnostic gold standard for schizencephaly is magnetic resonance imaging, which allows to identify and characterize typical clefts. Treatment of schizencephaly is symptomatic and supportive and depends on the severity of morbidity resulting from the malformation. Therapy includes antiepileptic drugs, psychomotor rehabilitation, and in selected cases surgical approach.

A Beginner's Guide to Artificial Intelligence for Ophthalmologists.

The integration of artificial intelligence (AI) in ophthalmology has promoted the development of the discipline, offering opportunities for enhancing diagnostic accuracy, patient care, and treatment outcomes. This paper aims to provide a foundational understanding of AI applications in ophthalmology, with a focus on interpreting studies related to AI-driven diagnostics. The core of our discussion is to explore various AI methods, including deep learning (DL) frameworks for detecting and quantifying ophthalmic features in imaging data, as well as using transfer learning for effective model training in limited datasets. The paper highlights the importance of high-quality, diverse datasets for training AI models and the need for transparent reporting of methodologies to ensure reproducibility and reliability in AI studies. Furthermore, we address the clinical implications of AI diagnostics, emphasizing the balance between minimizing false negatives to avoid missed diagnoses and reducing false positives to prevent unnecessary interventions. The paper also discusses the ethical considerations and potential biases in AI models, underscoring the importance of continuous monitoring and improvement of AI systems in clinical settings. In conclusion, this paper serves as a primer for ophthalmologists seeking to understand the basics of AI in their field, guiding them through the critical aspects of interpreting AI studies and the practical considerations for integrating AI into clinical practice.

Dataset of weekly intra-treatment diffusion weighted imaging in head and neck cancer patients treated with MR-Linac

Radiation therapy (RT) is a crucial treatment for head and neck squamous cell carcinoma (HNSCC); however, it can have adverse effects on patients’ long-term function and quality of life. Biomarkers that can predict tumor response to RT are being explored to personalize treatment and improve outcomes. While tissue and blood biomarkers have limitations, imaging biomarkers derived from magnetic resonance imaging (MRI) offer detailed information. The integration of MRI and a linear accelerator in the MR-Linac system allows for MR-guided radiation therapy (MRgRT), offering precise visualization and treatment delivery. This data descriptor offers a valuable repository for weekly intra-treatment diffusion-weighted imaging (DWI) data obtained from head and neck cancer patients. By analyzing the sequential DWI changes and their correlation with treatment response, as well as oncological and survival outcomes, the study provides valuable insights into the clinical implications of DWI in HNSCC.

Receptivity to the Weight and Heft of the Natural World in our Inner Selves.

Through the literary explorations and poetry of Alice Oswald, and through analysis of detailed clinical material from a Kleinian perspective, the authors expand the bounds of reverie as it is usually construed in psychoanalytic consulting rooms. The authors draw attention to the presence of a relationship to the more-than-human world as an integral aspect of our internal experience, and to the value of consideration of the quality and dynamic meaning of connections to the natural world in ordinary analytic work. The relationship to the primary object heavily influences the form taken by the relationship to the natural world, but once established, this connection has the possibility for a life of its own, that can provide a different kind of containment than the human variety, allow experimentation with new ways of being, and can strengthen the ego. The authors address the clinical implications of listening enhanced by an ear for affiliation to the natural world.

Comparing Fetal Ultrasound Biometric Measurements to Neonatal Anthropometry at the Extremes of Birthweight.

Error in birthweight prediction by sonographic estimated fetal weight (EFW) has clinical implications, such as avoidable cesarean or misclassification of fetal risk in labor. We aimed to evaluate optimal timing of ultrasound and which fetal measurements contribute to error in fetal ultrasound estimations of birth size at the extremes of birthweight. We compared differences in head circumference (HC), abdominal circumference (AC), femur length, and EFW between ultrasound and corresponding birth measurements within 14 (n = 1,290) and 7 (n = 617) days of birth for small- (SGA, <10th percentile), appropriate- (AGA, 10th-90th), and large-for-gestational age (LGA, >90th) newborns. Average differences between EFW and birthweight for SGA neonates were: -40.2 g (confidence interval [CI]: -82.1, 1.6) at 14 days versus 13.6 g (CI: -52.4, 79.7) at 7 days; for AGA, -122.4 g (-139.6, -105.1) at 14 days versus -27.2 g (-50.4, -4.0) at 7 days; and for LGA, -242.8 g (-306.5, -179.1) at 14 days versus -72.1 g (-152.0, 7.9) at 7 days. Differences between fetal and neonatal HC were larger at 14 versus 7 days, and similar to patterns for EFW and birthweight, differences were the largest for LGA at both intervals. In contrast, differences between fetal and neonatal AC were larger at 7 versus 14 days, suggesting larger error in AC estimation closer to birth. Using a standardized ultrasound protocol, SGA neonates had ultrasound measurements closer to actual birth measurements compared with AGA or LGA neonates. LGA neonates had the largest differences between fetal and neonatal size, with measurements 14 days from delivery showing 3- to 4-fold greater differences from birthweight. Differences in EFW and birthweight may not be explained by a single fetal measurement; whether estimation may be improved by incorporation of other knowable factors should be evaluated in future research. · Ultrasound measurements may be inadequate to predict neonatal size at birth.. · Birthweight estimation error is higher for neonates >90th percentile.. · There is higher error in AC closer to birth..

Dysregulation of BCL-2 family proteins in blood neoplasm: therapeutic relevance of antineoplastic agent venetoclax

During cellular stress, the master regulators of intrinsic self-death (apoptosis) are BCL-2 family proteins. The BCL-2 family proteins play a key role in apoptosis and are tightly regulated via other BCL-2 family proteins, non-BCL-2 protein suppressors, and epigenetic modifications. As the name implies, these proteins possess one or two of the four BCL-2 homology domains (BH1–BH4). According to their roles, they are classified as pro-apoptotic or pro-survival proteins. BH-3-only proteins possess a single BH3 domain and are specific/key effector proteins for intracellular death commitment, particularly in the context of cell survival and programmed cell death. This delicate interplay among the BCL-2 family members is essential for maintaining the primary hemostasis, or balance, of cell fate. The anti-apoptotic proteins, such as BCL-2 and BCL-XL, promote cell survival by inhibiting apoptosis. On the other hand, the pro-apoptotic proteins, such as BAX and BAK, drive apoptosis. It ensures that cells are able to respond appropriately to various internal and external signals, ultimately determining whether a cell survives or undergoes programmed cell death. Understanding and targeting this delicate balance is a promising avenue for developing therapeutic strategies to modulate cell fate and treat various diseases. The molecular pathogenesis of BCL-2 family proteins in blood disorders involves differential expression of these components resulting in the dysregulation of the pathway contributing to cell survival and resistance to apoptosis as observed in follicular lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, and acute myeloid leukemia. Such dysregulation is a major impediment to standard therapies and aids in chemo resistance. Studies show some promising clinical outcomes with antineoplastic agent venetoclax either as a monotherapy or in combination with other agents. This review discusses recent studies on the regulation of BCL-2 family proteins which might provide a molecular landscape for their clinical implications in blood disorders.

Long-term clinical and radiographic outcomes of arthroscopic acromioclavicular stabilization for acute acromioclavicular joint dislocation.

Standard open acromioclavicular (AC) stabilization is associated with increased postoperative complications including deltoid injury, infection, tunnel complications, loss of reduction, and wound/cosmetic concerns. Arthroscopy may offer superior visualization and advantages that limit these risks. The aim of this prospective non-randomized study is to evaluate advantages and long-term reliability of arthroscopic AC stabilization. Thirty-two patients with acute grade III, IV and V AC dislocations underwent arthroscopic AC reconstruction with long-term assessment by clinical AC examination, Simple Shoulder Test, American Shoulder and Elbow Surgeons scores, visual analog scale, Specific AC Score and Quick Disabilities of the Arm, Shoulder and Hand scores. Radiographs verified conservation of initial reduction and presence of coracoclavicular (CC) ossifications. Complications, revision rate and satisfaction were assessed and compared to the literature. Mean follow-up time was 67.6 months. All clinical outcome scores improved and differences were statistically significant (P<0.001). Initial postoperative radiographs consistently showed complete reduction. Two patients experienced relapse to grade II AC dislocation without clinical implications. In total, 71.8% showed CC ossifications without functional impairment, and in 31.3% concomitant injuries were observed. Reintervention rate was 9.4% and 96.7% of patients were satisfied with procedure outcomes. Arthroscopic stabilization for acute AC joint dislocations offers satisfactory clinical and radiographic outcomes, and our results show that the arthroscopic technique is reliable in the long run. We report better reduction in maintenance, fewer complications and similar reoperation rates compared to other techniques.

The role of platelets in central hubs of inflammation: A literature review.

Platelets are increasingly recognized for their multifaceted roles in inflammation beyond their traditional involvement in haemostasis. This review consolidates knowledge on platelets as critical players in inflammatory responses. This study did an extensive search of electronic databases and identified studies on platelets in inflammation, focusing on molecular mechanisms, cell interactions, and clinical implications, emphasizing recent publications. Platelets contribute to inflammation via surface receptors, release of mediators, and participation in neutrophil extracellular trap formation. They are implicated in diseases like atherosclerosis, rheumatoid arthritis, and sepsis, highlighting their interaction with immune cells as pivotal in the onset and resolution of inflammation. Platelets are central to regulating inflammation, offering new therapeutic targets for inflammatory diseases. Future research should explore specific molecular pathways of platelets in inflammation for therapeutic intervention.

Philosophy of psychiatry: theoretical advances and clinical implications.

Work at the intersection of philosophy and psychiatry has an extensive and influential history, and has received increased attention recently, with the emergence of professional associations and a growing literature. In this paper, we review key advances in work on philosophy and psychiatry, and their related clinical implications. First, in understanding and categorizing mental disorder, both naturalist and normativist considerations are now viewed as important - psychiatric constructs necessitate a consideration of both facts and values. At a conceptual level, this integrative view encourages moving away from strict scientism to soft naturalism, while in clinical practice this facilitates both evidence-based and values-based mental health care. Second, in considering the nature of psychiatric science, there is now increasing emphasis on a pluralist approach, including ontological, explanatory and value pluralism. Conceptually, a pluralist approach acknowledges the multi-level causal interactions that give rise to psychopathology, while clinically it emphasizes the importance of a broad range of "difference-makers", as well as a consideration of "lived experience" in both research and practice. Third, in considering a range of questions about the brain-mind, and how both somatic and psychic factors contribute to the development and maintenance of mental disorders, conceptual and empirical work on embodied cognition provides an increasingly valuable approach. Viewing the brain-mind as embodied, embedded and enactive offers a conceptual approach to the mind-body problem that facilitates the clinical integration of advances in both cognitive-affective neuroscience and phenomenological psychopathology.

The typical and atypical developing mind: a common model.

We present a theory of atypical development based on a developmental theory of the typical mind integrating developmental, cognitive, and psychometric theory and research. The paper comprises three parts. First, it outlines the theory of typical development. The theory postulates central cognitive mechanisms, such as relational integration, executive and inferential processes, and domain-specific processes underlying different environmental relations, such as visuospatial or quantitative relations. Cognitive development advances in cycles satisfying developmental priorities in mastering these systems, such as executive control from 2-6 years, inferential control from 7-11 years, and truth control from 12-18 years. Second, we discuss atypical development, showing how each neurodevelopmental disorder emerges from deficiencies in one or more of the processes comprising the architecture of the mind. Deficiencies in relational integration mechanisms, together with deficiencies in social understanding, yield autism spectrum disorder. Deficiencies in executive processes yield attention-deficit and hyperactivity disorder. Deficiencies in symbolic representation yield specialized learning difficulties, such as dyslexia and dyscalculia. Finally, we discuss clinical and educational implications, suggesting the importance of early diagnosis of malfunctioning in each of these dimensions and specific programs for their remediation.