Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure.

Perfluorooctane sulfonate (PFOS), a class of synthetic chemicals detected in various environmental compartments, has been associated with dysfunctions of the human central nervous system (CNS). However, the underlying neurotoxicology of PFOS exposure is largely understudied due to the lack of relevant human models. Here, we report bioengineered human midbrain organoid microphysiological systems (hMO-MPSs) to recapitulate the response of a fetal human brain to multiple concurrent PFOS exposure conditions. Each hMO-MPS consists of an hMO on a fully 3D printed holder device with a perfusable organoid adhesion layer for enhancing air-liquid interface culturing. Leveraging the unique, simply-fabricated holder devices, hMO-MPSs are scalable, easy to use, and compatible with conventional well-plates, and allow easy transfer onto a multiple-electrode array (MEA) system for plug-and-play measurement of neural activity. Interestingly, the neural activity of hMO-MPSs initially increased and subsequently decreased by exposure to a concentration range of 0, 30, 100, to 300 µM of PFOS. Furthermore, PFOS exposure impaired neural development and promoted neuroinflammation in the engineered hMO-MPSs. Along with PFOS, our platform is broadly applicable for studies toxicology of various other environmental pollutants.

Diagnostic Value of Nutritional Risk Index and Other Indices for Predicting Sarcopenia in the Middle-Aged and Elderly Population of China Without Cancer: A ROC Curve Analysis.

Background: Emerging evidence suggests that systemic inflammatory and nutritional biomarkers, along with derived indices, could serve as predictors for sarcopenia in cancer population. This study aimed to compare these predictors, focusing on the nutritional risk index (NRI) and evaluate its diagnostic value, for sarcopenic patients without cancer. Methods: This cross-sectional retrospective study included 1674 participants. Sarcopenia is defined by skeletal muscle mass index (SMI). Laboratory data reflected the values of systemic inflammatory and nutritional biomarkers, from which the derived indices were calculated. Multiple logistic regression analysis, ROC curve analysis, and the Youden index were utilized to assess the association between these markers and sarcopenia and determine the cutoff value for predicting sarcopenia. Results: Among all participants (1110 men and 564 women, mean age 61.97 ± 9.83 years), 398 individuals were diagnosed with sarcopenia, indicating a prevalence of 23.78% in China's middle-aged and elderly population without cancer. Logistic regression analysis revealed significant associations between all biomarkers and derived indices with sarcopenia. Following adjustment for potential confounders, lower NRI values were significantly associated with a higher incidence of sarcopenia. For sarcopenia diagnosis, the area under the curve (AUC) for NRI was 0.769 ([95% CI, 0.742, 0.796], P < 0.001), with a cutoff value of 106.016, sensitivity of 75.6% and specificity of 66.1%. NRI demonstrated greater predictive advantage for sarcopenia incidence in men compared to women. Conclusion: A lower NRI value was associated with a higher prevalence of sarcopenia. NRI shows promise for early, rapid, and effective sarcopenia screening, particularly in China's middle-aged and elderly male population without cancer.

Exploiting Sound for Emerging Applications of Extracellular Vesicles.

Extracellular vesicles are nano- to microscale, membrane-bound particles released by cells into extracellular space, and act as carriers of biomarkers and therapeutics, holding promising potential in translational medicine. However, the challenges remain in handling and detecting extracellular vesicles for disease diagnosis as well as exploring their therapeutic capability for disease treatment. Here, we review the recent engineering and technology advances by leveraging the power of sound waves to address the challenges in diagnostic and therapeutic applications of extracellular vesicles and biomimetic nanovesicles. We first introduce the fundamental principles of sound waves for understanding different acoustic-assisted extracellular vesicle technologies. We discuss the acoustic-assisted diagnostic methods including the purification, manipulation, biosensing, and bioimaging of extracellular vesicles. Then, we summarize the recent advances in acoustically enhanced therapeutics using extracellular vesicles and biomimetic nanovesicles. Finally, we provide perspectives into current challenges and future clinical applications of the promising extracellular vesicles and biomimetic nanovesicles powered by sound.

Automatic Recognition of Concealed Fish Bones under Laryngoscopy: A Practical AI Model Based on YOLO-V5.

BACKGROUND: Fish bone impaction is one of the most common problems encountered in otolaryngology emergencies. Due to their small and transparent nature, as well as the complexity of pharyngeal anatomy, identifying fish bones efficiently under laryngoscopy requires substantial clinical experience. This study aims to create an AI model to assist clinicians in detecting pharyngeal fish bones more efficiently under laryngoscopy. METHODS: Totally 3133 laryngoscopic images related to fish bones were collected for model training and validation. The images in the training dataset were trained using the YOLO-V5 algorithm model. After training, the model was validated and its performance was evaluated using a test dataset. The model's predictions were compared to those of human experts. Seven laryngoscopic videos related to fish bone were used to validate real-time target detection by the model. RESULTS: The model trained in YOLO-V5 demonstrated good generalization and performance, with an average precision of 0.857 when the intersection over union (IOU) threshold was set to 0.5. The precision, recall rate, and F1 scores of the model are 0.909, 0.818, and 0.87, respectively. The overall accuracy of the model in the validation set was 0.821, comparable to that of ENT specialists. The model processed each image in 0.012 s, significantly faster than human processing (p < 0.001). Furthermore, the model exhibited outstanding performance in video recognition. CONCLUSION: Our AI model based on YOLO-V5 effectively identifies and localizes fish bone foreign bodies in static laryngoscopic images and dynamic videos. It shows great potential for clinical application. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2162-2169, 2024.

Association between osteoporosis and cardiovascular disease in elderly people: evidence from a retrospective study.

Objective: This study aimed to investigate the associations between osteoporosis, biochemical indexes, bone mineral density (BMD), and cardiovascular disease. Methods: A cross-sectional study design was used to examine the relationships between these parameters. Logistic regression and correlation analyses were conducted to assess the associations between elevated levels of triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), homocysteine, and the presence of osteoporosis. Additionally, correlations between BMD and biochemical indexes were analyzed. The incidence of cardiovascular disease and its correlation with BMD were evaluated. Receiver operating characteristic (ROC) analysis was performed to determine the utility of BMD in identifying cardiovascular disease. Results: The results revealed that elevated triglyceride, total cholesterol, and LDL levels were positively associated with osteoporosis, while higher HDL levels and homocysteine were negatively associated. Correlation analysis demonstrated negative correlations between triglyceride levels and BMD, and positive correlations between total cholesterol and HDL levels with BMD. LDL levels showed a weak negative correlation, and homocysteine levels exhibited a strong negative correlation with BMD. The osteoporosis group had lower BMD and a higher incidence of cardiovascular disease compared to the non-osteoporosis group. Logistic regression analysis confirmed the correlation between lower BMD and increased risk of cardiovascular disease. Conclusion: This study provides evidence supporting the associations between osteoporosis, biochemical indexes, BMD, and cardiovascular disease. Aberrations in lipid profiles and homocysteine levels may contribute to osteoporosis development. Lower BMD, particularly in individuals with osteoporosis, appears to increase the risk of cardiovascular disease. BMD shows promise as a diagnostic tool for identifying individuals at risk of cardiovascular disease. Further research is needed to elucidate the underlying mechanisms and establish the clinical implications of these relationships. Future longitudinal studies are necessary to determine causality and long-term prognostic implications.

Application Effect of Modified Through and Through Suture in Anterior Chondrectomy of Auricular Pseudocyst.

Objective: To introduce a novel method of modified through and through suture with collagen sutures in conjunction with anterior chondrectomy of auricular pseudocyst and assess its therapeutic efficacy. Subjects and Methods: The study comprised 87 patients with unilateral auricular pseudocyst, treated in our department from December 2019 to November 2021. Following anterior chondrectomy of the cyst, modified through and through suture was performed using collagen sutures. Evaluation of successful resolution of the problem, assessment of complications, recurrence, and ultimate ear cosmesis was undertaken with a minimum of 6 months follow-up. Results: There were 83 males and 4 females, ages ranged from 26-78 years old, with a median age of 41 years. The right and left ears were affected in, 52 and 35 patients, respectively. Local skin color deepening was found in 15 patients within 3 months, which returned to normal within 5 months. During the follow-up, such complications as anaphylaxis, hematocele in the surgical cavity, incision infection, and deformity were not observed in any patients. All patients were cured with a single operation without relapse. Conclusion: The modified through and through suture with collagen sutures in conjunction with anterior chondrectomy of an auricular pseudocyst is characterized by a straightforward, single-stage operation, with no relapses, few complications, restoration of normal ear cosmesis, and high patient acceptance.

Brain Organoid Computing for Artificial Intelligence.

Brain-inspired hardware emulates the structure and working principles of a biological brain and may address the hardware bottleneck for fast-growing artificial intelligence (AI). Current brain-inspired silicon chips are promising but still limit their power to fully mimic brain function for AI computing. Here, we develop Brainoware , living AI hardware that harnesses the computation power of 3D biological neural networks in a brain organoid. Brain-like 3D in vitro cultures compute by receiving and sending information via a multielectrode array. Applying spatiotemporal electrical stimulation, this approach not only exhibits nonlinear dynamics and fading memory properties but also learns from training data. Further experiments demonstrate real-world applications in solving non-linear equations. This approach may provide new insights into AI hardware.

Acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease.

Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard 'self-injectable epinephrine' strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine.

Engineering human spinal microphysiological systems to model opioid-induced tolerance.

pioids are commonly used for treating chronic pain. However, with continued use, they may induce tolerance and/or hyperalgesia, which limits therapeutic efficacy. The human mechanisms of opioid-induced tolerance and hyperalgesia are significantly understudied, in part, because current models cannot fully recapitulate human pathology. Here, we engineered novel human spinal microphysiological systems (MPSs) integrated with plug-and-play neural activity sensing for modeling human nociception and opioid-induced tolerance. Each spinal MPS consists of a flattened human spinal cord organoid derived from human stem cells and a 3D printed organoid holder device for plug-and-play neural activity measurement. We found that the flattened organoid design of MPSs not only reduces hypoxia and necrosis in the organoids, but also promotes their neuron maturation, neural activity, and functional development. We further demonstrated that prolonged opioid exposure resulted in neurochemical correlates of opioid tolerance and hyperalgesia, as measured by altered neural activity, and downregulation of µ-opioid receptor expression of human spinal MPSs. The MPSs are scalable, cost-effective, easy-to-use, and compatible with commonly-used well-plates, thus allowing plug-and-play measurements of neural activity. We believe the MPSs hold a promising translational potential for studying human pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.

Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform.

The aging of the immune system drives systemic aging and the pathogenesis of age-related diseases. However, a significant knowledge gap remains in understanding immune-driven aging, especially in brain aging, due to the limited current in vitro models of neuroimmune interaction. Here, the authors report the development of a human brain organoid microphysiological analysis platform (MAP) to discover the dynamic process of immune-driven brain aging. The organoid MAP is created by 3D printing that confines organoid growth and facilitates cell and nutrition perfusion, promoting organoid maturation and their committment to forebrain identity. Dynamic rocking flow is incorporated into the platform that allows to perfuse primary monocytes from young (20 to 30-year-old) and aged (>60-year-old) donors and culture human cortical organoids to model neuroimmune interaction. The authors find that the aged monocytes increase infiltration and promote the expression of aging-related markers (e.g., higher expression of p16) within the human cortical organoids, indicating that aged monocytes may drive brain aging. The authors believe that the organoid MAP may provide promising solutions for basic research and translational applications in aging, neural immunological diseases, autoimmune disorders, and cancer.

Human Spinal Organoid-on-a-Chip to Model Nociceptive Circuitry for Pain Therapeutics Discovery.

The discovery of new pain therapeutics targeting human nociceptive circuitry is an emerging, exciting, and rewarding field. However, current models for evaluating prospective new therapeutics [e.g., animals and two-dimensional (2D) in vitro cultures] fail to fully recapitulate the complexity of human nociceptive neuron and dorsal horn neuron biology, significantly limiting the development of novel pain therapeutics. Here, we report human spinal organoid-on-a-chip devices for modeling the biology and electrophysiology of human nociceptive neurons and dorsal horn interneurons in nociceptive circuitry. Our device can be simply made through the integration of a membrane with a three-dimensional (3D)-printed organoid holder. By combining air-liquid interface culture and spinal organoid protocols, our devices can differentiate human stem cells into human sensori-spinal-cord organoids with dorsal spinal cord interneurons and sensory neurons. By easily transferring from culture well plates to the multiple-electrode array (MEA) system, our device also allows the plug-and-play measurement of organoid activity for testing nociceptive modulators (e.g., mustard oil, capsaicin, velvet ant venom, etc.). Our organoid-on-a-chip devices are cost-efficient, scalable, easy to use, and compatible with conventional well plates, allowing the plug-and-play measurement of spinal organoid electrophysiology. By the integration of human sensory-spinal-cord organoids with our organoid-on-a-chip devices, our method may hold the promising potential to screen and validate novel therapeutics for human pain medicine discovery.

Severe bleeding after operation of preauricular fistula: A case report.

BACKGROUND: Severe eyelid edema and blood accumulation in the submandibular space after preauricular fistula surgery is rarely reported. CASE SUMMARY: We report a 4-year-old girl with eyelid edema and swelling of the submandibular region after preauricular fistula resection under general anesthesia. When drug treatment failed, neck computed tomography examination was performed, which confirmed severe bleeding in the submandibular space. Later, exploration and ligation of the superficial temporal artery were performed under general anesthesia to stop the bleeding. The child was successfully treated, and there were no abnormalities over 1 year of follow-up. CONCLUSION: When severe bleeding occurs after preauricular fistula surgery, superficial temporal artery rupture should be considered as a cause.

The Efficacy of Pyogenic Cavity Aerobic Therapy with Negative Pressure Drainage in the Treatment of Deep Neck Space Infections.

OBJECTIVE: To determine the effectiveness of pyogenic cavity aerobic therapy with negative pressure drainage in the treatment of deep neck space infections (DNSI). METHODS: The study was a prospective, observational analysis of 36 cases of DNSI at a tertiary care center. The patients were divided into two groups according to the treatment method. Group A was treated with pyogenic cavity aerobic therapy with negative pressure drainage and included 13 patients (6 males and 7 females), while group B was treated with traditional incision debridement drainage and included 23 patients (12 males and 11 females). The average hospitalization days and doctors' workload (ie, average days of postoperative dressing changes) were analyzed and compared between the two groups. RESULTS: The mean hospitalization days in the traditional dressing group were 26.74 ± 3.39 days, while the average days of postoperative dressing change were 25.91 ± 3.43 days. In contrast, the averages for hospitalization days and days of postoperative dressing changes in the pyogenic cavity aerobic therapy plus negative pressure drainage were 11.08 ± 2.11 and 3.69 ± 0.21 days, respectively. All 36 patients were cured. Compared with the group B, group A had a shorter hospital stays and lower doctor workloads (P < 0.001). CONCLUSION: Pyogenic cavity aerobic therapy is an effective and simple method for changing dressings after DNSI. This therapy, when combined with negative pressure drainage, shortens hospitalization days and days that require a dressing change. This has reduced the workload of clinical doctors and pain experienced by patients. This therapy also has a high degree of safety and a very satisfactory curative effect.

[ECMO assisted in the rescue of thyroid tumor pressing the cervical trachea and causing suffocation: a case report].

A 74-year-old woman suffered from asphyxia due to a huge thyroid mass compressing cervical trachea. The patient developed dyspnea, orthopnea, shortness of breath. SpO2 was about 90% under high flow oxygen inhalation. Protuberant mass was seen in the anterior midline of neck. The palpation was hard, the boundary was not clear, and the trachea couldn't be touched. Neck CT showed a huge mass in the thyroid and severe tracheal compression. And electronic laryngoscopy showed paralysis in bilateral vocal cord, which were fixed in the paramedian position. With the further development of the disease, the patient appeared asphyxia and was in critical condition. After multidisciplinary consultation, considering the high risk of direct intubation, ECMO was used to assist and performed "total thyroidectomy + tracheostomy" under general anesthesia. The patient got successful treatment finally.

Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women.

This study aims to explore the relationship between the iodine status and thyroid dysfunction (TD) in pregnant women and establish a model to guide them to prevent excessive iodine intake. A total of 515 pregnant women were enrolled in the study. Urinary iodine concentration (UIC), thyroid hormones, and thyroid autoantibodies were measured, and then a logistic regression model was established. The median UIC of pregnant women was 174 ± 120 µg/L. Multivariate logistic regression analysis indicated that multivitamin supplements containing iodine and frequent seafood consumption were risk factors for excessive iodine (UIC ≥500 µg/L). Besides, excessive iodine was a risk factor for TD. Iodine excess was associated with a high prevalence of TD in pregnant women, especially TPOAb-positive women (P < 0.05). A logistic regression model based on potential risk factors was established to predict the risk of excessive iodine intake among pregnant women and provide guidance to minimize the risk of excessive iodine intake, thus reducing the risk of TD.

[Pollution Levels and Risk Assessment of Heavy Metals from Atmospheric Deposition in Nanjing].

In order to evaluate the pollution levels of and risk from heavy metals in the atmospheric deposition of different functional urban districts, dust samples were collected from 20 sampling sites in typical industrial, traffic, residential, and educational districts of Nanjing. The concentrations of As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Ti, V, and Zn were analyzed. The potential ecological risk and health risk were evaluated using the potential ecological risk index and U.S. EPA's health risk assessment models. Enrichment factors, correlation analysis, and principal component analysis were used to analyze the sources of heavy metals. Results showed that the concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn were the highest in the industrial district and the concentrations of Ba, Ni, Ti, and V were the highest in the traffic district. The value of the potential ecological risk index was the highest in the industrial district and lowest in the educational district. Meanwhile, the ecological risk of Cr was the highest, achieving a moderate ecological hazard level. None of the studied heavy metals had noncarcinogenic risk or carcinogenic risk, according to the results of health risk assessment. Source analysis indicated that heavy metals in the atmospheric deposition from the study areas were mainly from traffic and industrial activities, coal combustion, natural process and life sources.

Magnetic Properties as a Proxy for Predicting Fine-Particle-Bound Heavy Metals in a Support Vector Machine Approach.

The development of a reasonable statistical method of predicting the concentrations of fine-particle-bound heavy metals remains challenging. In this study, daily PM2.5 samples were collected within four different seasons from a Chinese mega-city. The annual average PM2.5 concentrations determined in industrial, city center, and suburban areas were 90, 81, and 85 µg m-3, respectively. Environmental magnetic measurements, including magnetic susceptibility, anhysteretic remanent magnetization, isothermal remanent magnetization, hysteresis loops, and thermomagnetism, indicated that the main magnetic mineral of PM2.5 is low-coercivity pseudosingle domain (PSD) magnetite. Using a support vector machine (SVM), both the volume- and mass-related concentrations of heavy metals were predicted by the PM2.5 mass concentrations and meteorological factors, with or without magnetic properties as input variables. The inclusion of magnetic variables significantly improved the prediction results for most heavy metals. Predictions based on models that included the magnetic properties of the metals Al, Fe, Mn, Ni, and Ti were promising, with R values of >0.8 in both the training and the test stages as well as relatively low errors. Our results demonstrate that the inclusion of environmental magnetism in a SVM approach aids in the effective monitoring and assessment of airborne heavy-metal contamination in cities.

[Feasibility of focused transthoracic echocardiography in intensive care unit performed by intensivists].

OBJECTIVE: To assess the clinical applicability of focused transthoracic echocardiography (TTE) in intensive care unit (ICU) performed by intensivists and its impacts on clinical managements. METHODS: After 12-hour tutorials and initial cardiac clinical assessments, intensivists performed a focused TTE (2-4 views of 2D, without Doppler or M mode) examination in 88 patients to assess left ventricular function and left ventricular volume status, and rule out local ventricular wall motion abnormalities and significant pericardial effusions. Each investigation was immediately reviewed by an echocardiograph to determine the technical quality of the TTE and the accuracy of the intensivist's interpretation. RESULTS: Intensivists successfully performed a diagnostic focused TTE in 86 patients (97.7%) and interpreted correctly in 75 patients (85.2%). Management including fluid treatment, inotropic agent and vasoactive agent in 22.7% of patients were changed directly based on the focused TTE, 45.5% of patients were provided with valuable information, while 31.8% of them with non-valuable information. The mean focused TTE acquisition time of the intensivist was (11.2±5.2) minutes. CONCLUSIONS: After a brief standard training in using echocardiographic system, intensivists can successfully performed and correctly interpreted a focused TTE for critically ill patients. Our study demonstrates that new information can be provided by focused TTE, which can alter management in a significant number of patients. The present study supports incorporating bedside goal-directed, focused TTE into intensivists' training programs in China.

[The expression of Neuritin protein in the visual cortex of monocular form deprived adult rats].

OBJECTIVE: To investigate the expression of Neuritin protein in the visual cortex of normal (N90), monocular deprived (MD) and reverse suture (RS) adult Wistar rats, explore whether the visual cortex of adult rats remains the plasticity. METHODS: It was an experimental research. The 35 healthy rats were divided into 7 groups, 5 in every group. The time-point for normal control and MD groups is postnatal 90 days. The time-point for RS group is 6, 12, 24, 48 h and 1 week under the RS rats were exposed to light environment. MD and RS groups were sutured right eyelid at postnatal 14 days up to postnatal 90 days. That time the right eyes were opened and the same time tarsorrhaphy was performed on the left eyes in RS groups. The visual cortex of left cerebrum in the normal control group and MD group were obtained in P90 rats, and those of RS group were acquired in corresponding time points. Expression of the Neuritin protein in the visual cortex of rats was detected by immunohistochemistry stain methods. RESULTS: Expression of Neuritin protein A of the group of N90, MD, RS 6 h, RS 12 h, RS 24 h, RS 48 h, RS 1 week were 0.1097±0.0136, 0.0259±0.0057, 0.04751±0.0069, 0.05189±0.0057, 0.0649±0.0055, 0.0835±0.0097, 0.0845±0.0098 (F=105.57, P<0.05), the count in the visual cortex of rats were 163.90±5.82, 142.00±3.65, 150.00±5.46, 152.10±5.04, 156.40±5.25, 156.40±6.04, 155.80±6.54 (F=15.39, P<0.05). The expression of Neuritin protein in the visual cortex of rats in the MD group was considerably lower than that of the normal control group. The expression of Neuritin protein in the visual cortex of rats in the RS 6, 12, 24, 48 h and 1 week group was evidently higher than that in the MD group. CONCLUSIONS: The dynamic change of Neuritin protein expression in the visual cortex of the MD rats and RS rats indicates that the visual cortex of adult rats with MD beyond the sensitive period of visual development remain the plasticity to some extent. It provides an experimental basis for the amblyopic treatment in elder children and adults.