Quarter-Annulus Si-Photodetector with Equal Inner and Outer Radii of Curvature for Reflective Photoplethysmography Sensors.

Reflection-type photoplethysmography (PPG) pulse sensors used in wearable smart watches, true wireless stereo, etc., have been recently considered a key component for monitoring biological signals such as heart rate, SPO3, and blood pressure. Typically, the optical front end (OFE) of these PPG sensors is heterogeneously configured and packaged with light sources and receiver chips. In this paper, a novel quarter-annulus photodetector (NQAPD) with identical inner and outer radii of curvature has been developed using a plasma dicing process to realize a ring-type OFE receiver, which maximizes manufacturing efficiency and increases the detector collection area by 36.7% compared to the rectangular PD. The fabricated NQAPD exhibits a high quantum efficiency of over 90% in the wavelength of 500 nm to 740 nm and the highest quantum efficiency of 95% with a responsivity of 0.41 A/W at the wavelength of 530 nm. Also, the NQAPD is shown to increase the SNR of the PPG signal by 5 to 7.6 dB compared to the eight rectangular PDs. Thus, reflective PPG sensors constructed with NQAPD can be applied to various wearable devices requiring low power consumption, high performance, and cost-effectiveness.

Dual Growth Factor Delivery Using Photo-Cross-Linkable Gelatin Hydrogels for Effectively Reinforced Regeneration of the Rotator Cuff Tendon.

Rotator cuff tears are currently treated with drugs (steroids and nonsteroidal anti-inflammatory drugs) and surgery. However, the damaged rotator cuff requires a considerable amount of time to regenerate, and the regenerated tissue cannot restore the same level of function as that before the damage. Although growth factors can accelerate regeneration, they are difficult to be used alone because of the risk of degradation and the difficulties in ensuring their sustained release. Thus, hydrogels such as gelatin are used, together with growth factors. Gelatin is a biocompatible and biodegradable hydrogel derived from collagen; therefore, it closely resembles the components of native tissues and can retain water and release drugs continuously, while also showing easily tunable mechanical properties by simple modifications. Moreover, gelatin is a natural biopolymer that possesses the ability to form hydrogels of varying compositions, thereby facilitating effective cross-linking. Therefore, gelatin can be considered to be suitable for rotator-to-tendon healing. In this study, we designed photo-cross-linkable gelatin hydrogels to enhance spacing and adhesive effects for rotator cuff repair. We mixed a ruthenium complex (Ru(II)bpy32+) and sodium persulfate into gelatin-based hydrogels and exposed them to blue light to induce gelation. Basic fibroblast growth factor and bone morphogenetic protein-12 were encapsulated in the gelatin hydrogel for localized and sustained release into the wound, thereby enhancing the cell proliferation. The effects of these dual growth factor-loaded hydrogels on cell cytotoxicity and tendon regeneration in rotator cuff tear models were evaluated using mechanical and histological assessments. The findings confirmed that the gelatin hydrogel was biocompatible and that treatment with the dual growth factor-loaded hydrogels in in vivo rotator cuff tear models promoted regeneration and functional restoration in comparison with the findings in the nontreated group. Therefore, growth factor-loaded gelatin-based hydrogels may be suitable for the treatment of rotator cuff tears.

Structural control of self-assembled peptide nanostructures to develop peptide vesicles for photodynamic therapy of cancer.

Vesicles such as liposomes, polymersomes, and exosomes have been widely used as drug delivery carriers; however, peptide vesicles (peptidesomes) despite their potential utility are far less well developed. Peptidesomes are distinctive because peptides play dual roles as a self-assembly building block and a bioactive functional unit. In order for peptidesomes to become successful nanodrugs, the issues related to differences in nanostructural properties between in vitro and in vivo conditions should be addressed. Here, we delineate a multivariate approach to feedback control the structures of peptide building blocks, nanoparticle size, drug loading process, nanoparticle aggregation, cytotoxicity, cell targeting capability, endosome disruption function, protease resistance, and in vivo performance, which eventually enabled the successful development of a highly efficacious peptidesome for in vivo cancer therapy. This study lays the groundwork for the successful in vivo translation of peptide nanodrugs.

A comparative study of the traditional medicine systems of South Korea and Taiwan: Focus on administration, education and license.

BACKGROUND: Traditional medicine (TM) is widely used in South Korea and Taiwan, and both societies have similar systems for the management of TM. This study aimed to compare the TM systems in South Korea and Taiwan. METHODS: We searched for studies on the TM systems and collected statistical data from the websites of relevant government agencies in both countries. Interviews were conducted with experts on TM and officials from government agencies. The two TM systems were described and examined in terms of policies, resources, utilization, licensing, and educational systems. RESULTS: Both South Korea and Taiwan have a dual system that separates the administration, licensing and educational systems between TM and Western Medicine (WM), and the TM systems are well established and highly standardized. Comparing with South Korea, however, Taiwan has a more flexible dual medical system in which education courses for producing dual licensure are provided. Additionally, in the system in Taiwan, dual license holders can use both TM and WM methods without limitations and WM doctors can apply acupuncture under some circumstances. Because of the strict dual medical system in South Korea, TM and WM conflict with each other on most health issues. CONCLUSION: Both South Korea and Taiwan have the advantages of preserving TM, as TM and WM are systemically independent and together provide a more holistic approach. The institutionalization of TM in South Korea and Taiwan may be a good reference for countries considering modernization of their TM.

Cerebral Oxygenation and Autoregulation in Preterm Infants (Early NIRS Study).

OBJECTIVE: To determine if decreased cerebral oxygenation or altered cerebral autoregulation as measured by near-infrared spectroscopy (NIRS) in the first 96 postnatal hours is associated with an increased risk of death or severe neuroradiographic abnormalities in very preterm infants. STUDY DESIGN: The Early NIRS prospective, multicenter study enrolled very preterm infants with a birth weight of <1250 g from 6 tertiary neonatal intensive care units. Mean arterial blood pressure and cerebral oxygen saturation (Csat) were continuously monitored using a neonatal sensor until 96 hours of age. Moving window correlations between Csat and mean arterial blood pressure determined time periods with altered cerebral autoregulation, and percentiles of correlation were compared between infants with and without the adverse outcome of mortality or severe neuroradiographic abnormalities by early cranial ultrasound. RESULTS: Of 103 subjects with mean gestational age of 26 weeks, 21 (20%) died or had severe neuroradiographic abnormalities. Infants with adverse outcomes had a lower mean Csat (67 ± 9%) compared with those without adverse outcomes (72 ± 7%; P = .02). A Csat of <50% was identified as a cut-point for identifying infants with adverse outcome (area under the curve, 0.76). Infants with adverse outcomes were more likely to have significant positive or negative correlations between Csat and mean arterial blood pressure, indicating impaired cerebral autoregulation (P = .006). CONCLUSIONS: Early NIRS monitoring may detect periods of lower cerebral oxygenation and altered cerebral autoregulation, identifying preterm infants at risk for mortality or neuroradiographic injury. An improved understanding of the relationship between altered hemodynamics and cerebral oxygenation may inform future strategies to prevent brain injury.

Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects.

Blood glucose homeostasis is well maintained by coordinated control of various hormones including insulin and glucagon as well as cytokines under normal conditions. However, chronic exposure to diabetic environment with high fat/high sugar diets and physical/mental stress can cause hyperglycemia, one of main characteristics of insulin resistance, metabolic syndrome, and diabetes. Hyperglycemia impairs organogenesis and induces organ abnormalities such as cardiac defect in utero. It is a risk factor for the development of metabolic diseases in adults. Resulting glucotoxicity affects peripheral tissues and vessels, causing pathological complications including diabetic neuropathy, nephropathy, vessel damage, and cardiovascular diseases. Moreover, chronic exposure to hyperglycemia can deteriorate cognitive function and other aspects of mental health. Recent reports have demonstrated that hyperglycemia is closely related to the development of cognitive impairment and dementia, suggesting that there may be a cause-effect relationship between hyperglycemia and dementia. With increasing interests in aging-related diseases and mental health, diabetes-related cognitive impairment is attracting great attention. It has been speculated that glucotoxicity can result in structural damage and functional impairment of brain cells and nerves, hemorrhage of cerebral blood vessel, and increased accumulation of amyloid beta. These are potential mechanisms underlying diabetes-related dementia. Nutrients and natural food components have been investigated as preventive and/or intervention strategy. Among candidate components, resveratrol, curcumin, and their analogues might be beneficial for the prevention of diabetes-related cognitive impairment. The purposes of this review are to discuss recent experimental evidence regarding diabetes and cognitive impairment and to suggest potential nutritional intervention strategies for the prevention and/or treatment of diabetes-related dementia.

Alterations in Anatomical Covariance in the Prematurely Born.

Preterm (PT) birth results in long-term alterations in functional and structural connectivity, but the related changes in anatomical covariance are just beginning to be explored. To test the hypothesis that PT birth alters patterns of anatomical covariance, we investigated brain volumes of 25 PTs and 22 terms at young adulthood using magnetic resonance imaging. Using regional volumetrics, seed-based analyses, and whole brain graphs, we show that PT birth is associated with reduced volume in bilateral temporal and inferior frontal lobes, left caudate, left fusiform, and posterior cingulate for prematurely born subjects at young adulthood. Seed-based analyses demonstrate altered patterns of anatomical covariance for PTs compared with terms. PTs exhibit reduced covariance with R Brodmann area (BA) 47, Broca's area, and L BA 21, Wernicke's area, and white matter volume in the left prefrontal lobe, but increased covariance with R BA 47 and left cerebellum. Graph theory analyses demonstrate that measures of network complexity are significantly less robust in PTs compared with term controls. Volumes in regions showing group differences are significantly correlated with phonological awareness, the fundamental basis for reading acquisition, for the PTs. These data suggest both long-lasting and clinically significant alterations in the covariance in the PTs at young adulthood.

Fabrication of Multicomponent Multivesicular Peptidoliposomes and Their Directed Cytoplasmic Delivery.

A novel self-assembly strategy for the formation of multicomponent and multicompartment vesicles via the hierarchical assembly of the cyclic peptide and lipid building blocks is reported. The primary driving force underlying the formation of dual-component (i.e., peptide and lipid) heteromultivesicular vesicles (hMVVs) is the differential thermostability between the supramolecular building blocks. Furthermore, the combination of the differential thermostability and charge-based separation further enables the fabrication of the hMVVs that incorporate up to four different components (i.e., two different building blocks and two different encapsulated molecules). The quadruple-component hMVVs consist of cyclic peptides, lipids, negatively charged green fluorescent probes (GFPr), and positively charged red fluorescent probes (RFPr). Intracellular delivery study shows that cellular localization of hMVVs is directed by the function of hMVV envelopes, and the nuclear localization signal (NLS) of peptide vesicles appears to use different cellular pathways depending on the site of action (i.e., extracellular space or cytoplasm). This study provides the hierarchical peptide-based hMVVs with sophisticated architectures and cell delivery characteristics, thus making a step toward artificial cells or viruses.

Does prenatal stress alter the developing connectome?

Human neurodevelopment requires the organization of neural elements into complex structural and functional networks called the connectome. Emerging data suggest that prenatal exposure to maternal stress plays a role in the wiring, or miswiring, of the developing connectome. Stress-related symptoms are common in women during pregnancy and are risk factors for neurobehavioral disorders ranging from autism spectrum disorder, attention deficit hyperactivity disorder, and addiction, to major depression and schizophrenia. This review focuses on structural and functional connectivity imaging to assess the impact of changes in women's stress-based physiology on the dynamic development of the human connectome in the fetal brain.

Prenatal stress alters amygdala functional connectivity in preterm neonates.

Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

Association of Plasma Semaphorin 3A With Phenotypes of Diabetic Retinopathy and Nephropathy.

PURPOSE: To investigate whether diabetic retinopathy phenotypes and albuminuria are associated with the overexpression of plasma semaphorin 3A (Sema3A). METHODS: The study group with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR), the diabetes without diabetic retinopathy group, and the control group without diabetes consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naïve diabetic macular edema (DME) and senile cataract surgery, respectively. In all subjects, the plasma Sema3A levels before intravitreal bevacizumab injections or cataract surgery were measured by enzyme-linked immunosorbent assay. In the patients with DME, the capillary nonperfusion area (measured by fluorescein angiography), total macular volume (measured by spectral-domain optical coherence tomography), and the urine albumin-to-creatinine ratio were determined. RESULTS: Severe NPDR (57 eyes) and PDR groups (51 eyes) both had significantly higher Sema3A levels than the control (58 eyes) and diabetes without diabetic retinopathy groups (54 eyes) (P < 0.001). Moreover, the PDR group had higher Sema3A levels than the severe NPDR group (P < 0.001). Plasma Sema3A levels correlated positively with the retinal nonperfusion area size (r = 0.844, P = 0.004), total macular volume (r = 0.765, P = 0.005), and the urine albumin-to-creatinine ratio (r = 0.752, P < 0.001). When DME patients were divided into normo-, micro-, and macroalbuminuria groups, the macroalbuminuria group had significantly higher plasma Sema3A levels than the microalbuminuria group or the normoalbuminuria group (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: The plasma Sema3A levels correlated significantly with the phenotypes of diabetic retinopathy and albuminuria. This suggests that Sema3A may be a potential biomarker for diabetic retinopathy and nephropathy.

Functional magnetic resonance connectivity studies in infants born preterm: suggestions of proximate and long-lasting changes in language organization.

Sophisticated neuroimaging strategies demonstrate alterations in functional connectivity at school age, adolescence, and young adulthood in individuals born preterm. Recent data suggest these alterations are present in the postnatal period prior to term-equivalent age in neonates born preterm. Likewise, functional organization increases across development, but the influence of preterm birth on this fundamental infrastructure is immediate and unchanging. This article briefly reviews the current methods of measuring functional connectivity throughout development in those born preterm, and the association of functional connectivity with language disorders. Taken together, these data suggest that the effects of preterm birth on the functional organization of language in the developing brain are both proximate and long-lasting.

The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer.

We evaluated the prognostic value of F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters for limited-stage small-cell lung cancer (LS-SCLC).We retrospectively enrolled 59 LS-SCLC patients who underwent pretreatment FDG PET/CT. Various PET parameters were measured in all malignant lesions, and we recorded the highest maximum standardized uptake value (SUVmax), and sum of metabolic tumor volume (MTVsum) and total lesion glycolysis (TLGsum). The relationship between the highest SUVmax and volumetric PET parameters was evaluated. The prognostic significances of PET parameters and clinical variables were assessed using Cox's proportional hazard regression analysis. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method.The SUVmax of the highest metabolic lesion had a significant positive correlation with MTVsum and TLGsum (P < 0.001). Upon multivariate analysis, the highest SUVmax was an independent predictor of OS (1 unit increase, hazard ratio [HR]: 1.133, P = 0.003) and MTVsum was a significant prognostic factor of PFS (10-cm increase, HR: 1.027, P = 0.034) after adjusting for age, sex, performance status, tumor stage, and treatment modality. The highest SUVmax was a prognostic factor for PFS with marginal significance (1 unit increase, HR: 1.078, P = 0.053). Patients with higher SUVmax (≥11) were also characterized by a significantly shorter median OS (P < 0.001) and PFS (P = 0.002) compared with patients with lower SUVmax.The highest SUVmax is an independent prognostic factor for survival in LS-SCLC patients. Therefore, the highest SUVmax might be a possible imaging biomarker for risk stratification in LS-SCLC. A further study in a large cohort is needed to validate the prognostic significance of the parameter.