Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems.

The classic output pathways of the basal ganglia are known as the direct-D1 and indirect-D2, or Go/No-Go, pathways. Balance of the activity in these canonical direct-indirect pathways is considered a core requirement for normal movement control, and their imbalance is a major etiologic factor in movement disorders including Parkinsons disease. We present evidence for a conceptually equivalent parallel system of direct-D1 and indirect-D2 pathways that arise from striatal projection neurons (SPNs) of the striosome compartment rather than from the matrix. These striosomal direct (S-D1) and indirect (S-D2) pathways, as a pair, target dopamine-containing neurons of the substantia nigra (SNpc) instead of the motor output nuclei of the basal ganglia. The novel anatomically and functionally distinct indirect-D2 striosomal pathway targets dopaminergic SNpc cells indirectly via a core region of the external pallidum (GPe). We demonstrate that these S-D1 and S-D2 pathways oppositely modulate striatal dopamine release in freely behaving mice under open-field conditions and oppositely modulate locomotor and other movements. These S-D1 and S-D2 pathways further exhibit different, time-dependent responses during performance of a probabilistic decision-making maze task and respond differently to rewarding and aversive stimuli. These contrasts depend on mediolateral and anteroposterior striatal locations of the SPNs as are the classic direct and indirect pathways. The effects of S-D1 and S-D2 stimulation on striatal dopamine release and voluntary locomotion are nearly opposite. The parallelism of the direct-indirect circuit design motifs of the striosomal S-D and S-D2 circuits and canonical matrix M-D1 and M-D2, and their contrasting behavioral effects, call for a major reformulation of the classic direct-indirect pathway model of basal ganglia function. Given that some striosomes receive limbic and association cortical inputs, the S-D1 and S-D2 circuits likely influence motivation for action and behavioral learning, complementing and possibly reorienting the motoric activities of the canonical matrix pathways. At a fundamental level, these findings suggest a unifying framework for aligning two sets of circuits that share the organizational motif of opponent D1 and D2 regulation, but that have different outputs and can even have opposite polarities in their targets and effects, albeit conditioned by striatal topography. Our findings further delineate a potentially therapeutically important set of pathways influencing dopamine, including a D2 receptor-linked S-D2 pathway likely unknowingly targeted by administration of many therapeutic drugs including those for Parkinsons disease. The novel parallel pathway model that we propose here could help to account for the normally integrated modulatory influence of the basal ganglia on motivation for actions as well as the actions themselves.

Deep learning-based long-term risk evaluation of incident type 2 diabetes using electrocardiogram in a non-diabetic population: a retrospective, multicentre study.

Background: Diabetes is a major public health concern. We aimed to evaluate the long-term risk of incident type 2 diabetes in a non-diabetic population using a deep learning model (DLM) detecting prevalent type 2 diabetes using electrocardiogram (ECG). Methods: In this retrospective study, participants who underwent health checkups at two tertiary hospitals in Seoul, South Korea, between Jan 1, 2001 and Dec 31, 2022 were included. Type 2 diabetes was defined as glucose ≥126 mg/dL or glycated haemoglobin (HbA1c) ≥ 6.5%. For survival analysis on incident type 2 diabetes, we introduced an additional variable, diabetic ECG, which is determined by the DLM trained on ECG and corresponding prevalent diabetes. It was assumed that non-diabetic individuals with diabetic ECG had a higher risk of incident type 2 diabetes than those with non-diabetic ECG. The one-dimensional ResNet-based model was adopted for the DLM, and the Guided Grad-CAM was used to localise important regions of ECG. We divided the non-diabetic group into the diabetic ECG group (false positive) and the non-diabetic ECG (true negative) group according to the DLM decision, and performed a Cox proportional hazard model, considering the occurrence of type 2 diabetes more than six months after the visit. Findings: 190,581 individuals were included in the study with a median follow-up period of 11.84 years. The areas under the receiver operating characteristic curve for prevalent type 2 diabetes detection were 0.816 (0.807-0.825) and 0.762 (0.754-0.770) for the internal and external validations, respectively. The model primarily focused on the QRS duration and, occasionally, P or T waves. The diabetic ECG group exhibited an increased risk of incident type 2 diabetes compared with the non-diabetic ECG group, with hazard ratios of 2.15 (1.82-2.53) and 1.92 (1.74-2.11) for internal and external validation, respectively. Interpretation: In the non-diabetic group, those whose ECG was classified as diabetes by the DLM were at a higher risk of incident type 2 diabetes than those whose ECG was not. Additional clinical research on the relationship between the phenotype of ECG and diabetes to support the results and further investigation with tracked data and various ECG recording systems are suggested for future works. Funding: National Research Foundation of Korea.

High-resolution knee plain radiography image synthesis using style generative adversarial network adaptive discriminator augmentation.

In this retrospective study, 10,000 anteroposterior (AP) radiography of the knee from a single institution was used to create medical data set that are more balanced and cheaper to create. Two types of convolutional networks were used, deep convolutional GAN (DCGAN) and Style GAN Adaptive Discriminator Augmentation (StyleGAN2-ADA). To verify the quality of generated images from StyleGAN2-ADA compared to real ones, the Visual Turing test was conducted by two computer vision experts, two orthopedic surgeons, and a musculoskeletal radiologist. For quantitative analysis, the Fréchet inception distance (FID), and principal component analysis (PCA) were used. Generated images reproduced the features of osteophytes, joint space narrowing, and sclerosis. Classification accuracy of the experts was 34%, 43%, 44%, 57%, and 50%. FID between the generated images and real ones was 2.96, which is significantly smaller than another medical data set (BreCaHAD = 15.1). PCA showed that no significant difference existed between the PCs of the real and generated images (p > 0.05). At least 2000 images were required to make reliable images optimally. By performing PCA in latent space, we were able to control the desired PC that show a progression of arthritis. Using a GAN, we were able to generate knee X-ray images that accurately reflected the characteristics of the arthritis progression stage, which neither human experts nor artificial intelligence could discern apart from the real images. In summary, our research opens up the potential to adopt a generative model to synthesize realistic anonymous images that can also solve data scarcity and class inequalities.

The sexual brain, genes, and cognition: A machine-predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children.

Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children (N = 9,658, ages 9-10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC-AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence (pfdr < .001, ηp2  = .011-.034; adjusted for covariates) and higher cognitive genome-wide polygenic scores (GPSs) (pfdr < .001, ηp2 < .005). Structural equation models revealed that the GPS-intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006-.009; p = .002-.022; sex-stratified analysis). The finding of the sex modulatory effect on the gene-brain-cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence.

Clinical Implication of the Regional Thickness of the Lower Facial Skin, Superficial Fat, and Superficial Musculoaponeurotic System on High-Intensity Focused Ultrasound Treatment.

BACKGROUND: Knowledge of the topographic thickness of the skin and soft tissues is necessary when performing a high-intensity focused ultrasound (HIFU) procedure. Thermal tissue injury to the superficial musculoaponeurotic system (SMAS) or deeper can injure the facial nerve and its branches. OBJECTIVE: To demonstrate the topographic thickness of the lower facial skin, superficial fat, and SMAS. MATERIALS AND METHODS: The ultrasound data of 200 healthy patients who underwent lower facial rejuvenation were retrospectively reviewed. RESULTS: The mean age was 41.1 ± 13.7 years (range, 19-76 years). The jowl had thinner skin, thicker superficial fat, and deeper superficial and deep margins of the SMAS than the preauricle or lower cheek. The thickness of the superficial fat decreased with age, especially on the preauricle, lower cheek, and jowl. Women had thicker superficial fat than men on the preauricle and lower cheek. The superficial and deep margins of the SMAS were located more superficially in old and male patients with a slim facial figure than in young and female patients with a chubby facial figure. CONCLUSION: The present findings provide anatomical information regarding the superficial fat and SMAS, which is useful in determining the focal penetration depth of HIFU treatment for lower face rejuvenation.

The efficacy and safety of microneedle monopolar radiofrequency for the treatment of periorbital wrinkles.

BACKGROUND: Treatment of periorbital wrinkles is a challenging task because of its anatomical significance and delicate nature. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a microneedle monopolar radiofrequency (RF) device for treating periorbital wrinkles. METHODS AND MATERIALS: This retrospective study involved 21 patients who were treated for periorbital wrinkles using a RF device. The type of microneedle used, clinical photography, VISIA wrinkle score, and adverse events were collected from the medical chart. Two independent dermatologists assessed the photographs. RESULTS: There were 18 female and 3 male patients with a mean age of 50.24 years. The severity of wrinkle was improved according to photographic assessment and VISIA wrinkle score at 6-month post-treatment. When 21 sites treated with a long microneedle (LMN, 1.5 mm) and the other 21 sites treated with a short microneedle (SMN, 0.8 mm) were compared, significant improvement in the VISIA wrinkle score was observed only in those treated with the LMN. No serious adverse events, including scarring and postinflammatory hyperpigmentation, occurred. CONCLUSIONS: We demonstrated the efficacy and safety of the microneedle monopolar RF device in treating periorbital wrinkles. The LMN was superior to the SMN in reducing VISIA wrinkle score.

Baumann Skin Type in the Korean Male Population.

BACKGROUND: Research into the Baumann skin type (BST) has recently expanded, with growing interest in the development of an efficient and effective skin type classification system for better understanding of this skin condition. OBJECTIVE: We aimed to identify male-specific skin type characteristics with investigation into the distribution of BST by age and region in the Korean male population and to determine the intrinsic and extrinsic factors related to skin type. METHODS: A questionnaire was administered to collect information about age, region, working behavior, drinking behavior, smoking behavior, usual habit of sun protection, medical history, and the BST which consisted of four parameters; oily (O) or dry (D), sensitive (S) or resistant (R), pigmented (P) or non-pigmented (N), and wrinkled (W) or tight (T). RESULTS: We surveyed 1,000 Korean males aged between 20 and 60 years who were divided equally by age and region. Of the total respondents, OSNW type accounted for the largest percentage and ORPW type the lowest. In terms of Baumann parameters, O type was 53.5%, S type was 56.1%, N type was 84.4% and W type was 57.5%. Several behavioral factors were found to have various relationships with the skin type. CONCLUSION: The predominant skin type in the Korean male respondents was OSNW type, and the distribution of skin types with regards to age and region was reported to be distinct. Therefore, skin care should be customized based on detailed skin types considering the various environmental factors.

Obstructive sleep apnea in postmenopausal women: a comparative study using drug induced sleep endoscopy / Apneia obstrutiva do sono em mulheres na pós-menopausa: estudo comparativo usando endoscopia do sono induzido por fármaco

Abstract Introduction: The key to successful treatment of OSAS is to individually tailor such treatment. Thus, it is very important to determine the severity of OSAS, its pattern, and the extent of collapse, by gender, age, and BMI. Objective: The objective of the study was to understand the characteristics of obstructive sleep apnea in postmenopausal women by comparing postmenopausal and premenopausal subjects, and men, using DISE. We hope that our work will help the medical community to consult on, diagnose, and treat OSAS more effectively. Methods: A total of 273 patients (195 males and 78 females) diagnosed with OSAS were enrolled. Female patients were divided into pre-menopausal (n = 41) and post-menopausal patients (n = 37). The group of post-menopausal female patients was matched with a group of male patients with similar age and body mass index (BMI). DISE findings were compared between pre-menopausal female patients and post-menopausal female patients, and also between post-menopausal female patients and male patients matched for age and BMI. Results: Upon PSG examination, post-menopausal patients (who had a significantly higher BMI than did pre-menopausal patients; 25.6 kg/m2 vs. 23.5 kg/m2; p = 0.019) tended to have a higher AHI and a lower lowest SaO2, but the differences did not attain statistical significance. With DISE analysis, post-menopausal female patients showed higher values in all obstruction sites, with significantly higher value in lateral diameter of retropalatal (1.49 vs. 0.90; p = 0.001) and retrolingual levels (1.14 vs. 0.61; p = 0.003) compared to pre-menopausal females patients. Post-menopausal female patients showed significantly more retrolingual collapse (antero-posterior, AP, p ≤ 0.0001, and lateral diameter, p = 0.042) in the lower BMI group (BMI < 25) and more concentric retropalatal collapse (lateral diameter, p = 0.017 and tonsillar obstruction, p = 0.003) in higher BMI group (BMI ≥ 25) than BMI and age matched male patients. Conclusion: Post-menopausal female patients showed a different pattern of airway obstruction compared to pre-menopausal female patients and male patients matched for age and BMI based on DISE findings.

Resumo Introdução: A chave para o sucesso do tratamento da síndrome da apneia obstrutiva do sono (SAOS) é adaptar individualmente esse tratamento. Assim, é muito importante determinar a gravidade da SAOS, seu padrão e a medida do colapso, por sexo, idade e IMC. Objetivo: O objetivo do estudo foi compreender as características da apneia obstrutiva do sono em mulheres na pós-menopausa, comparando estas características entre mulheres na pós-menopausa e pré-menopausa, e homens, utilizando endoscopia do sono induzido por fármacos (DISE). Esperamos que o nosso estudo ajude a comunidade médica a diagnosticar e tratar a SAOS de maneira mais eficaz. Método: Foram recrutados 273 pacientes (195 do sexo masculino e 78 do feminino) com diagnóstico de SAOS. As pacientes do sexo feminino foram divididas em pacientes na pré-menopausa (n = 41) e na pós-menopausa (n = 37). O grupo de pacientes do sexo feminino na pós-menopausa foi pareada com um grupo de pacientes do sexo masculino com idade e Índice de Massa Corporal (IMC) semelhantes. Os achados da DISE foram comparados entre as pacientes do sexo feminino na pré-menopausa e as pacientes do sexo feminino pós-menopausa e também entre pacientes do sexo feminino na pós-menopausa e pacientes do sexo masculino pareados por idade e IMC. Resultados: Ao exame de PSG, as pacientes na pós-menopausa (que tinham um IMC significativamente maior do que as pacientes na pré-menopausa; 25,6 vs. 23,5 kg/m2; p = 0,019) tenderam a ter um IAH superior e uma saturação arterial de oxigênio (SaO2) mínima menor, mas as diferenças não atingiram significância estatística. Na análise do DISE, pacientes do sexo feminino pós-menopausa apresentaram valores mais elevados em todos os locais de obstrução, com um valor significativamente maior de diâmetro lateral dos níveis retropalatal (1,49 vs. 0,90; p = 0,001) e retrolingual (1,14 vs. 0,61; p = 0,003) em comparação com pacientes do sexo feminino na pré-menopausa. As pacientes do sexo feminino na pós-menopausa apresentaram colapso significativamente mais retrolingual (anteroposterior, AP, p ≤ 0,0001 e diâmetro lateral, p = 0,042) no grupo de IMC menor (IMC < 25) e colapso retropalatal mais concêntrico (diâmetro lateral, p = 0,017 e obstrução tonsilar, p = 0,003) no grupo de maior IMC (IMC ≥ 25) do que pacientes do sexo masculino pareados por IMC e idade. Conclusão: Com base nos achados do DISE, as pacientes do sexo feminino na pós-menopausa apresentaram um padrão diferente de obstrução das vias respiratórias em comparação com pacientes do sexo feminino na pré-menopausa e com os pacientes do sexo masculino pareados por idade e IMC.

Targeting of sebaceous glands to treat acne by micro-insulated needles with radio frequency in a rabbit ear model.

BACKGROUND AND OBJECTIVES: Many studies have investigated the application of micro-insulated needles with radio frequency (RF) to treat acne in humans; however, the use of a micro-insulated needle RF applicator has not yet been studied in an animal model. The purpose of this study was to evaluate the effectiveness of a micro-insulated needle RF applicator in a rabbit ear acne (REA) model. STUDY DESIGN/MATERIALS AND METHODS: In this study, we investigated the effect of selectively destroying the sebaceous glands using a micro-insulated needle RF applicator on the formation of comedones induced by application of 50% oleic acid and intradermal injection of P. acnes in the orifices of the external auditory canals of rabbits. The effects of the micro-insulated needle RF applicator treatment were evaluated using regular digital photography in addition to 3D Primos imaging evaluation, Skin Visio Meter microscopic photography, and histologic analyses. RESULTS: Use of the micro-insulated needle RF applicator resulted in successful selective destruction of the sebaceous glands and attenuated TNF-alpha release in an REA model. The mechanisms by which micro-insulated needles with RF using 1 MHz exerts its effects may involve inhibition of comedone formation, triggering of the wound healing process, and destruction of the sebaceous glands and papules. CONCLUSION: The use of micro-insulated needles with RF applicators provides a safe and effective method for improving the appearance of symptoms in an REA model. The current in vivo study confirms that the micro-insulated needle RF applicator is selectively destroying the sebaceous glands. Lasers Surg. Med. 49:395-401, 2017. © 2016 Wiley Periodicals, Inc.

Obstructive sleep apnea in postmenopausal women: a comparative study using drug induced sleep endoscopy.

INTRODUCTION: The key to successful treatment of OSAS is to individually tailor such treatment. Thus, it is very important to determine the severity of OSAS, its pattern, and the extent of collapse, by gender, age, and BMI. OBJECTIVE: The objective of the study was to understand the characteristics of obstructive sleep apnea in postmenopausal women by comparing postmenopausal and premenopausal subjects, and men, using DISE. We hope that our work will help the medical community to consult on, diagnose, and treat OSAS more effectively. METHODS: A total of 273 patients (195 males and 78 females) diagnosed with OSAS were enrolled. Female patients were divided into pre-menopausal (n=41) and post-menopausal patients (n=37). The group of post-menopausal female patients was matched with a group of male patients with similar age and body mass index (BMI). DISE findings were compared between pre-menopausal female patients and post-menopausal female patients, and also between post-menopausal female patients and male patients matched for age and BMI. RESULTS: Upon PSG examination, post-menopausal patients (who had a significantly higher BMI than did pre-menopausal patients; 25.6kg/m2 vs. 23.5kg/m2; p=0.019) tended to have a higher AHI and a lower lowest SaO2, but the differences did not attain statistical significance. With DISE analysis, post-menopausal female patients showed higher values in all obstruction sites, with significantly higher value in lateral diameter of retropalatal (1.49 vs. 0.90; p=0.001) and retrolingual levels (1.14 vs. 0.61; p=0.003) compared to pre-menopausal females patients. Post-menopausal female patients showed significantly more retrolingual collapse (antero-posterior, AP, p≤0.0001, and lateral diameter, p=0.042) in the lower BMI group (BMI<25) and more concentric retropalatal collapse (lateral diameter, p=0.017 and tonsillar obstruction, p=0.003) in higher BMI group (BMI≥25) than BMI and age matched male patients. CONCLUSION: Post-menopausal female patients showed a different pattern of airway obstruction compared to pre-menopausal female patients and male patients matched for age and BMI based on DISE findings.

Self-powered cardiac pacemaker enabled by flexible single crystalline PMN-PT piezoelectric energy harvester.

A flexible single-crystalline PMN-PT piezoelectric energy harvester is demonstrated to achieve a self-powered artificial cardiac pacemaker. The energy-harvesting device generates a short-circuit current of 0.223 mA and an open-circuit voltage of 8.2 V, which are enough not only to meet the standard for charging commercial batteries but also for stimulating the heart without an external power source.

Selective sebaceous gland electrothermolysis as a treatment for acne: a prospective pilot study.

Although many therapeutic options exist for acne, relapse often occurs after treatment is stopped. Some preliminary evidence suggests that selective electrothermolysis of the sebaceous glands may represent a novel therapeutic intervention. This trial was conducted to evaluate the efficacy and tolerability of selective sebaceous gland electrothermolysis for the treatment of facial acne. Twelve patients with facial acne were enrolled, all of whom underwent three sessions of therapy. During each session, a 1.5-mm long needle with 0.45-mm of base insulation was inserted into pores of acne lesions. Upon insertion, a high-frequency electrical current was applied for 0.25-0.50 seconds, for a total output of 40 W. Each treatment session took approximately 30-60 minutes. Subject response to therapy was evaluated at one month and 12 months after the final treatment. All the enrolled subjects completed the study and all reported satisfaction with treatment results. In all cases, a reduction in inflammatory and noninflammatory lesion counts was observed after three sessions of selective electrothermolysis, although a few small papules and comedones persisted in several areas of untreated facial skin. Mean lesion reduction at one month after the final treatment was 98.14% for inflammatory lesions and 83.09% for noninflammatory lesions. Clinical success was achieved in the majority of patients (seven of 12 patients) at one month after the second treatment and in all patients at one month after the final treatment. All patients reported transient post-treatment erythema, which faded after a few days. Clinically evident relapse occurred in two of 12 patients (16.7%) one year after the final treatment session. Selective sebaceous gland electrothermolysis can be a safe and effective method of achieving consistent remission in acne.

Fractional photothermolysis for the treatment of acne scars: a report of 27 Korean patients.

OBJECTIVES: Atrophic post-acne scarring remains a therapeutically challenging condition despite various currently available technologies. Fractional photothermolysis (FP) is a novel concept of cutaneous resurfacing which induces non-contiguous microscopic thermal injury. The aim of this study is to evaluate the safety and efficacy of FP in the treatment of acne scars in Asian patients. METHODS: A total of 27 Korean patients (Fitzpatrick skin types IV or V) with moderate to severe facial acne scars received three to five sessions of FP treatment (Fraxel Laser; Reliant Technologies, CA, USA), each spaced 3-4 weeks apart. Standardized digital photographs were obtained before each treatment and 3 months after the final treatment. In addition, the patients' perceived degrees of improvement were assessed 3 months after the final treatment using a five-point grading scale. RESULTS: FP led to marked improvement in the appearance of acne scars at 3 months post-treatment. Patients' self-assessed degrees of improvement were as follows: excellent improvement in eight patients (30%), significant improvement in 16 patients (59%), and moderate improvement in three patients (11%). Adverse events were limited to transient pain, erythema and edema. CONCLUSIONS: The 1550-nm erbium-doped FP is associated with significant patient-reported improvement in the appearance of acne scars, with minimal downtime.