DOI- and TOF-capable PET array detector using double-ended light readout and stripline-based row and column electronic readout.

We investigate a highly multiplexing readout for depth-of-interaction (DOI) and time-of-flight PET detector consisting of an N×N crystals whose light outputs at the front and back ends are detected by using silicon photomultipliers (SiPM). The front N×N SiPM array is read by using a stripline (SL) configured to support discrimination of the row position of the signal-producing crystal. The back N×N SiPM array is similarly read by an SL for column discrimination. Hence, the detector has only four outputs. We built 4×4 and 8×8 detector modules (DM) by using 3.0×3.0×20 mm3 lutetium-yttrium oxyorthosilicates. The outputs were sampled and processed offline. For both DMs, crystal discrimination was successful. For the 4×4 DM, we obtained an average energy resolution (ER) of 14.1%, an average DOI resolution of 2.5 mm, a non DOI-corrected coincidence resolving time (CRT), measured in coincidence with a single-pixel reference detector, of about 495 ps. For the 8×8 DM, the average ER, average DOI resolution and average CRT were 16.4%, 2.9 mm, and 641 ps, respectively. We identified the intercrystal scattering as a probable cause for the CRT deterioration when the DM was increased from 4×4 to 8×8.

Abnormal prefrontal cortical activation during the GO/NOGO and verbal fluency tasks in adult patients with comorbid generalized anxiety disorder and attention-deficit/hyperactivity disorder: An fNIRS study.

Generalized anxiety disorder (GAD) and adult attention-deficit/hyperactivity disorder (ADHD) are commonly reported comorbidities. Adult GAD patients with comorbid ADHD are often underdiagnosed and undertreated. To explore the clinical value of functional near-infrared spectroscopy (fNIRS) data for assisting in the accurate diagnosis of ADHD in individuals with GAD, haemoglobin (HbO) concentration changes in the prefrontal cortex (PFC) were detected via fNIRS in 49 patients with both GAD and ADHD, 46 patients with GAD, and 34 healthy controls (HCs) during a verbal fluency task (VFT) and a GO/NOGO task. The correlations between PFC fNIRS data and the severity of inattention and hyperactivity symptoms assessed using the adult ADHD Self-Report Scale (ASRS) were analyzed. Our results showed that, during the GO/NOGO task, channels in the left dorsolateral PFC (channels 28 and 29) were hyperactivated, while channels in the medial PFC (channels 36, 37, and 47) were hypoactivated in participants with ADHD and GAD compared with those with GAD alone. During the VFT, compared with the HC group, both the ADHD + GAD group and the GAD group exhibited significantly decreased HbO activation in the medial PFC (channels 37, 38, and 48) and in the left ventrolateral PFC (channel 39); moreover, no difference was found between the ADHD + GAD group and the GAD group. Activation in the left dorsolateral PFC (channels 28 and 29) during the GO/NOGO task showed a significant positive correlation with ASRS-inattention scores. Our results indicated that fNIRS data collected during the GO/NOGO task may help to distinguish patients with comorbid GAD and ADHD from those with GAD alone.

Effect of extreme high temperature on cognitive function at different time scales: A national difference-in-differences analysis.

BACKGROUND: Mounting evidence has demonstrated that high temperature was associated with adverse health outcomes, especially morbidity and mortality. Nonetheless, the impact of extreme high temperature on cognitive performance, which is the fundamental capacity for interpreting one's surroundings, decision-making, and acquiring new abilities, has not been thoroughly investigated. METHODS: We aimed to assess associations between extreme high temperature at different time scales and poor cognitive function. We used longitudinal survey data from the three waves of data from China Family Panel Study, providing an 8-year follow-up of 53,008 participants from China. We assessed temperature and extreme high temperature exposure for each participant based on the residential area and date of cognitive test. We defined the proportion of days/hours above 32 °C as the metric of the exposure to extreme high temperature. Then we used generalized additive model and difference-in-differences approach to explore the associations between extreme high temperature and cognitive function. RESULTS: Our results demonstrated that either acute exposure or long-term exposure to extreme high temperature was associated with cognitive decline. At hourly level, 0-1 hour acute exposure to extreme high temperature would induce -0.93 % (95 % CI: -1.46 %, -0.39 %) cognitive change. At annual level, 10 percentage point increase in the hours proportion exceeding 32 °C in the past two years induced -9.87 % (95 % CI: -13.99 %, -5.75 %) cognitive change. Furthermore, subgroup analyses indicated adaptation effect: for the same 10 percentage increase in hours proportion exceeding 32 °C, people in warmer areas had cognitive change of -6.41 % (-11.22 %, -1.61 %), compared with -15.30 % (-21.07 %, -9.53 %) for people in cool areas. CONCLUSION: Our results demonstrated that extreme high temperature was associated with reduced cognitive function at hourly, daily and annual levels, warning that people should take better measures to protect the cognitive function in the context of climate change.

Safety and efficacy of the flow diverter device for treating middle cerebral artery aneurysms of the proximal (M1) segment related to the lenticulostriate arteries: A single-center experience.

BACKGROUND: Experience using flow diverter devices (FDDs) to treat proximal (M1) middle cerebral artery aneurysms associated with the lenticulostriate artery (M1A-LA) remains limited. This study aimed to examine the efficacy and safety of an FDD to manage M1A-LA. METHOD: Patients with M1A-LA who received FDD treatment at a single center were included in the analysis. Data on the baseline characteristics, postoperative conditions, and follow-up results of the participants were recorded and analyzed. The aneurysms were categorized into three subtypes based on morphology and location. Aneurysms confined to the M1 segment were categorized as subtype A. Those extending to the M2 segment were classified as subtype B. Aneurysms designated as subtype C were confined to the M1 segment but with another independent aneurysm in the distal artery and the presence of healthy vessels between the two. Subgroup analyses were conducted on these subtypes and aneurysm sizes. To assess the consistency of follow-up results, Cronbach's kappa/alpha was used to calculate inter-rater variability. Somers's D coefficient was used to assess the correlation between each subgroup and the imaging outcomes; Fisher's exact test was used to compare the variability among the subgroups. RESULT: The cohort comprised 11 patients. Their Modified Rankin Scale scores between the perioperative and follow-up periods did not differ. During the follow-up period, four patients had completely occluded aneurysms, and five patients had partial occlusions. The remaining patients did not present with changes in their aneurysms. The kappa coefficient was 0.864 (p < 0.001). M1A-LA was divided into subtypes A, B, and C. Subtype A (defined as an aneurysm completely located in the M1 segment) had a higher complete occlusion rate than that of subtypes B and C, Somers's D R/C correlation coefficient was 0.553, with a 95% confidence interval of 0.1229-0.9823 (p = 0.009). The radiographic follow-up findings were not significantly correlated with the size of the aneurysm (p = 0.121) or the use of coiling (p = 0.903). No significant differences in subtypes (p = 0.264), aneurysm size (p = 0.657), or coiling use (p > 0.999) were observed. CONCLUSION: FDDs were safe and possibly effective against M1A-LA. However, they were not as effective as for intracranial aneurysms in other locations. FDDs are a satisfactory treatment option for M1A-LA, particularly for subtype A aneurysms.

Magnesium promotes vascularization and osseointegration in diabetic states.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Enhanced the treatment of ischemic stroke through intranasal temperature-sensitive hydrogels of edaravone and borneol inclusion complex.

Since ischemic stroke occurs by a combination of multiple mechanisms, therapies that modulate multiple mechanisms are required for its treatment. The combination of edaravone (EDA) and borneol can significantly ameliorate the symptoms of neurological deficits in cerebral ischemia-reperfusion model in rats. In this study, the solubility of borneol and edaravone was improved by hydroxypropyl-ß-cyclodextrin and PEG400. Furthermore, a nasal temperature-sensitive hydrogel containing both edaravone and borneol inclusion complex (EDA-BP TSGS) was developed to overcome the obstacles of ischemic stroke treatment including the obstruction of the blood-brain barrier (BBB) and the unavailability and untimely of intravenous injection. The effectiveness of the thermosensitive hydrogel was investigated in transient middle cerebral artery occlusion/reperfusion model rats (MCAO/R). The results showed that EDA-BP TSGS could significantly alleviate the symptoms of neurological deficits and decrease the cerebral infarct area and the degree of brain damage. In summary, nasal EDA-BP TSGS is a secure and effective brain-targeting formulation that may provide a viable option for the clinical prophylaxis and treatment of ischemic stroke.

Evaluation of the accuracy of implant placement by using implant positional guide versus freehand: a prospective clinical study.

PURPOSE: The aim of this study is to examine and compare the accuracy of implant placement using implant positional guide and freehand. METHODS: 48 implants were placed in patients with single tooth loss with implant positional guide and freehand, respectively. The accuracy of implant placement was assessed by comparing the actual and planned position, including four parameters: coronal deviation, apical deviation, angular deviation, and vertical deviation. RESULTS: Comparing all the variables, it has been found that the implant positional guide is more accurate than the freehand. All parameters describing in the deviation were significantly lower in the implant positional guide group than the freehand. CONCLUSIONS: The implant positional guide can act as a practicable tool for dental implant surgery. It is a promising technology that guarantees low cost and high precision in implant surgery. However, based on the restricted evidence from clinical studies, longer follow-up periods, larger population studies, and standardized experimental studies are required. Trial registration CHICTR, ChiCTR2300071024. Registered 28 April 2023-CHICTR, ChiCTR2300071024. Registered 28 April 2023-Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=195424 .

Heat exposure intervention, anxiety level, and multi-omic profiles: A randomized crossover study.

BACKGROUND: Climate change has led to the frequent occurrence of high-temperature weather, which has various adverse effects on health, ranging from blood metabolism to systemic organ function. In particular, the sequelae of heat stress injury in most people are related to the nervous system. However, the mechanisms between heat stress and mental health conditions, especially heat stress and anxiety, remain unclear. OBJECTIVE: We attempted to elucidate the effect of heat exposure intervention on anxiety levels in the population and its mechanism. METHODS: We first carried out a randomized controlled trial in 20 college students in Beijing, China, to observe the results of the effects of heat exposure intervention on human anxiety. Then, we collected blood samples before and after heat exposure experiment and used metabolomic and transcriptomic approaches to quantify serum metabolites and ELISA measurements to explore the underlying mechanisms. RESULTS: We found that even 1.5-hour heat exposure intervention significantly increased anxiety levels. Heat stress-induced anxiety was mediated by the activation of the HPA axis, inflammation, oxidative stress, and subsequently unbalanced neurotransmitters. Metabolites such as BDNF, GABA, and glucocorticoids released by the adrenal glands are biomarkers of heat stress-induced anxiety. CONCLUSIONS: We have demonstrated a causal link between heat stress and anxiety, explored possible biological pathway between heat stress and anxiety. Heat stress can cause the activation of the HPA axis and lead to changes in the body's metabolism, resulting in a series of changes such as inflammation and oxidative stress, leading to anxiety. This study reveals hidden health cost of climate change that has been underexplored, and also reminds us the importance of immediate climate actions.

Smart Liposomal Nanocarrier Enhanced the Treatment of Ischemic Stroke through Neutrophil Extracellular Traps and Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase-Stimulator of Interferon Genes (cGAS-STING) Pathway Inhibition of Ischemic Penumbra.

Brain inflammation is regarded as one of the leading causes that aggravates secondary brain injury and hinders the prognosis of ischemic stroke. After ischemic stroke, high quantities of peripheral neutrophils are recruited to brain lesions and release neutrophil extracellular traps (NETs), leading to the aggravation of blood-brain barrier (BBB) damage, activation of microglia, and ultimate neuronal death. Herein, a smart multifunctional delivery system has been developed to regulate immune disorders in the ischemic brain. Briefly, Cl-amidine, an inhibitor of peptidylarginine deiminase 4 (PAD4), is encapsulated into self-assembled liposomal nanocarriers (C-Lipo/CA) that are modified by reactive oxygen species (ROS)-responsive polymers and fibrin-binding peptide to achieve targeting ischemic lesions and stimuli-responsive release of a drug. In the mouse model of cerebral artery occlusion/reperfusion (MCAO), C-Lipo/CA can suppress the NETs release process (NETosis) and further inhibit the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway in an ischemic brain. In addition, MCAO mice treated with C-Lipo/CA significantly mitigated ischemic and reperfusion injury, with a reduction in the area of cerebral infarction to 12.1%, compared with the saline group of about 46.7%. These results demonstrated that C-Lipo/CA, which integrated microglia regulation, BBB protection, and neuron survival, exerts a potential therapy strategy to maximize ameliorating the mortality of ischemic stroke.

Efficacy and safety of Danggui Niantong Decoction in patients with gout: a systematic review and meta-analysis.

Background: This study aims to evaluate the efficacy and safety of Danggui Niantong Decoction (DGNT) systematically on gout treating. Methods: This study was registered in PROSPERO, and the registration number was CRD42021271607. By the end of December, 2022, literature research was conducted among eight electronic databases. Main results of this study were blood uric acid (BUA) and Creactive protein (CRP). Secondary outcomes were erythrocyte sedimentation rate (ESR), serum creatinine (Scr), urinary protein quantified at 24 h (Upro), and interleukin-8 (IL-8). Study screening, data collection, as well as quality assessment were performed by two reviewers independently, and analysis was completed using Stata (SE15.0) and Review Manager (5.4). Results: A total number of 13 studies were included in our meta-analysis (n = 1,094 participants). Results showed DGNT combined with conventional western medicine (CWM) was more effective than WM alone in BUA (weighted mean differences (WMD) = -3.49, 95% confidence interval (CI) [-50.36, -32.59], p = 0.000), CRP (WMD = -41.48, 95% CI [-4.32, -2.66], p = 0.017), ESR (WMD = -6.23, 95% CI [-9.28, -3.17], p = 0.019), Scr (WMD = -18.64, 95% CI [-23.09, -14.19], p = 0.001), Upro (WMD = -0.72, 95% CI [-0.91, -0.53], p = 0.000), and IL-8 (WMD = -4.77, 95% CI [-11.48, 1.94], p = 0.000). None of the adverse effects noted were severe, and no life-threatening event was reported. Conclusion: This study shows that DGNT combined with CWM seems to have an effective clinical therapeutic potential. In addition, it also provides a scientific basis for better clinical application of DGNT in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271607; Identifier: PROSPERO, CRD42021271607.

Lepr-Expressing PDLSCs Contribute to Periodontal Homeostasis and Respond to Mechanical Force by Piezo1.

Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as a distinct periodontal ligament stem cell (PDLSC) population by single-cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs are located in the peri-vascular niche, possessing multilineage potential and contributing to tissue repair in response to injury. Ablation of Lepr+ PDLSCs disrupts periodontal homeostasis. Hyper-loading and unloading of occlusal forces modulate Lepr+ PDLSCs activation. Piezo1 is demonstrated that mediates the mechanosensing of Lepr+ PDLSCs by conditional Piezo1-deficient mice. Meanwhile, Yoda1, a selective activator of Piezo1, significantly accelerates periodontal tissue growth via the induction of Lepr+ cells. In summary, Lepr marks a unique multipotent PDLSC population in vivo, to contribute toward periodontal homeostasis via Piezo1-mediated mechanosensing.

SAD score of intracranial aneurysms for rupture risk assessment based on high-resolution vessel wall imaging.

OBJECTIVE: We aimed to develop a comprehensive model that integrates the radiological, morphological, and clinical factors to assess rupture risk for intracranial aneurysms. METHODS: We prospectively enrolled patients with intracranial saccular aneurysms who underwent high-resolution vessel wall imaging (HR-VWI) preoperatively. Clinical characteristics, aneurysm features and aneurysm wall enhancement scale (AWES) were recorded. AWES was categorized into three grades (no/faint/strong enhancement) by comparing AWE to enhancement of the pituitary infundibulum or choroid plexus on HR-VWI. Univariate and multivariate logistic regression analyses were performed to determine risk factors associated with aneurysmal rupture. RESULTS: A total of 25 ruptured and 116 unruptured aneurysms were included. Multivariate logistic regression analysis revealed that non-ICA site (OR 6.25, 95% CI 1.35-28.30, P = 0.019), AWES (OR 5.99, 95% CI 2.51-14.29, P < 0.001) and daughter sac or lobulated shape (OR 6.22, 95% CI 1.68-23.16, P = 0.006) were independent factors associated with ruptured aneurysms. The "SAD" model was generated and named after the first letters of each of these factors. SAD scores of 0-4 predicted 0, 2%, 12%, 42% and 100% ruptured aneurysms, respectively. The area under the receiver operating characteristic curve for the SAD model was 0.8822. CONCLUSION: The SAD model aids in distinguishing aneurysm rupture status and in managing unruptured aneurysms. Larger cohort studies are needed to confirm its applicability in predicting the rupture risk of unruptured aneurysms.

Stretchable and transparent alginate ionic gel film for multifunctional sensors and devices.

Flexible and stretchable substrates based on pure natural polymers have attracted widespread attention for next-generation "green" electronics. However, fabrication of stretchable and "green" electronic sensors with integrated high stretchability, optical transmittance and good conductivity still remains tremendous challenges. Herein, alginate ionic gel films (AIGFs) with integrated high stretchability (tensile strength of 4.13 MPa and 191.1 % fracture strain) and excellent transparent properties (transparency of ∼92 %) are achieved by the glycerol inducing physical crosslinking and CaCl2 initiating ionic crosslinking, a simple soaking and drying strategy. The obtained gel films not only exhibit good ionic conductivity, but also high reliability, wide-range sensing, and multiple sensitivity to external stimulus. More importantly, these ionic conductive gel films as green substrates are successfully utilized for construction of flexible and patterned optoelectronic devices. This promising strategy will open up new powerful routes to construct highly stretchable, transparent, and ionic conductive substrates for multifunctional sensors and devices.

Cascaded Multi-Modal Mixing Transformers for Alzheimer's Disease Classification with Incomplete Data.

Accurate medical classification requires a large number of multi-modal data, and in many cases, different feature types. Previous studies have shown promising results when using multi-modal data, outperforming single-modality models when classifying diseases such as Alzheimer's Disease (AD). However, those models are usually not flexible enough to handle missing modalities. Currently, the most common workaround is discarding samples with missing modalities which leads to considerable data under-utilisation. Adding to the fact that labelled medical images are already scarce, the performance of data-driven methods like deep learning can be severely hampered. Therefore, a multi-modal method that can handle missing data in various clinical settings is highly desirable. In this paper, we present Multi-Modal Mixing Transformer (3MT), a disease classification transformer that not only leverages multi-modal data but also handles missing data scenarios. In this work, we test 3MT for AD and Cognitively normal (CN) classification and mild cognitive impairment (MCI) conversion prediction to progressive MCI (pMCI) or stable MCI (sMCI) using clinical and neuroimaging data. The model uses a novel Cascaded Modality Transformers architecture with cross-attention to incorporate multi-modal information for more informed predictions. We propose a novel modality dropout mechanism to ensure an unprecedented level of modality independence and robustness to handle missing data scenarios. The result is a versatile network that enables the mixing of arbitrary numbers of modalities with different feature types and also ensures full data utilization in missing data scenarios. The model is trained and evaluated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with the state-of-the-art performance and further evaluated with The Australian Imaging Biomarker & Lifestyle Flagship Study of Ageing (AIBL) dataset with missing data.

Stretchable and sensitive sodium alginate ionic hydrogel fibers for flexible strain sensors.

Ionic conductive hydrogel fibers based on natural polymers provide an immense focus for a new generation of electronics due to their flexibility and knittability. The feasibility of utilizing pure natural polymer-based hydrogel fibers could be drastically improved if their mechanical and transparent performances satisfy the requirements of actual practice. Herein, we report a facile fabrication strategy for significantly stretchable and sensitive sodium alginate ionic hydrogel fibers (SAIFs), by glycerol initiating physical crosslinking and by CaCl2 inducing ionic crosslinking. The obtained ionic hydrogel fibers not only show significant stretchability (tensile strength of 1.55 MPa and fracture strain of ∼161 %), but also exhibit wide-range sensing, satisfactorily stable, rapidly responsive, and multiply sensitive abilities to external stimulus. In addition, the ionic hydrogel fibers have excellent transparency (over 90 % in a wide wavelength range), and good anti-evaporation and anti-freezing properties. Furthermore, the SAIFs have been easily knitted into a textile, and successfully applied as wearable sensors to recognize human motions, by observing the output electrical signals. Our methodology for fabrication intelligent SAIFs will shed light on artificial flexible electronics and other textile-based strain sensors.

Ticagrelor is related to nuisance bleeding after flow diversion of unruptured intracranial aneurysms.

Nuisance bleeding (NB) without urgent medical attention is rarely characterized despite its frequent occurrence in patients with cerebral aneurysms undergoing flow diversion (FD) who are maintained on dual antiplatelet therapy (DAPT). This study explored the risk factors for NB. Patients with unruptured cerebral aneurysms who underwent intervention using FD (July 2018 to May 2022) and had follow-up data were enrolled. Patient demographics, clinical characteristics, aneurysm features and follow-up data were analysed. Bleeding complications were classified as NB, internal bleeding and alarming bleeding. NB was characterized by easy bruising, bleeding from small cuts and nonfatal petechiae and ecchymosis. Univariate and multivariate logistic regression analyses were performed to determine risk factors for NB. This study assessed 121 patients. Of these, 52 (43.0%) patients had NB. Compared with the non-bleeding group, the NB group had more females (82.7% vs. 56.5%; p = 0.003), lower smoking rate (7.7% vs. 23.2%; p = 0.027) and smaller aneurysms (6.65 mm [4.60-9.60 mm] vs. 8.82 mm [5.65-15.65 mm]; p = 0.007) and had more patients maintained on ticagrelor-containing DAPT regimen (90.4% vs. 66.7%; p = 0.002). Multivariate logistic regression revealed that ticagrelor-containing DAPT regimen (odds ratio, 3.91; 95% confidence interval, 1.29-11.87; p = 0.016) was associated with NB. These results suggest that NB is a common bleeding complaint in patients on DAPT. In patients undergoing FD, DAPT with ticagrelor was the only independent risk factor for NB.

Potentially inappropriate medication and frailty in older adults: A systematic review and meta-analysis.

OBJECTIVES: The purpose of this study was to systematically assess existing studies to demonstrate the association between potentially inappropriate medication (PIM) and frailty. DESIGN: Systematic review and meta-analysis. METHODS: We searched major electronic databases (PubMed, Web of Science, the Cochrane Library, Embase, CINHAL, PsycInfo, China National Knowledge Infrastructure, China Biology Medicine disk, Weipu, and Wanfang) from their inception until February 25, 2023 (data updated on May 4, 2023), for observational studies investigating PIM and frailty. I2 was used to measure the heterogeneity between studies quantitatively. A random effect model calculated pooled effect size owing to high heterogeneity. Subgroup analysis was conducted to explore sources of heterogeneity. Additionally, the studies' quality was evaluated using the Newcastle Ottawa Scale (a modified Newcastle Ottawa Scale was used to evaluate cross-sectional studies). RESULTS: Twenty-four studies were included for systematic review, 14 of which were included in the meta-analysis. After pooling the effect size, the odds ratio with PIM as the dependent variable was 1.12 (95%CI: 1.01-1.25), and that with frailty as the dependent variable was 1.75 (95%CI: 1.25-2.43), indicating a bidirectional association between PIM and frailty. CONCLUSIONS: PIM and frailty interact with each other and have a bidirectional association, thus providing additional information for early clinical identification and prevention of frailty, and medication safety management.

Alpha-ketoglutarate promotes alveolar bone regeneration by modulating M2 macrophage polarization.

Objectives: Alpha-ketoglutarate (αKG) is an essential metabolite that plays a crucial role in skeletal homeostasis. Here we aim to investigate the effect of αKG on alveolar socket healing and reveal the underlying mechanism in the view of macrophage polarization. Methods: In a murine model pretreated with or without αKG, mandibular first molars were extracted. Mandibular tissues were harvested for microCT and histological analyses. Immunofluorescence was used to evaluate macrophage polarization during healing process. Macrophages with αKG/vehicle supplementation in vitro were proceeded to quantitative real-time PCR and flow cytometry to further elucidate the mechanism. Results: MicroCT and histological analyses showed accelerated healing and enhanced bone regeneration of extraction sockets in experimental group. αKG increased new bone volume in alveolar sockets and promoted the activity of both osteoblastogenesis and osteoclastogenesis. αKG administration reduced M1 pro-inflammatory macrophages in an early phase and promoted anti-inflammatory M2 macrophage polarization in a later phase. Consistently, the expressions of M2 marker genes were augmented in αKG group, while M1 marker genes were downregulated. Flow cytometry revealed the increased ratio of M2/M1 macrophages in cells treated with αKG. Conclusions: αKG accelerates the healing process of extraction sockets via orchestrating macrophage activation, with promising therapeutic potential in oral clinics.

Reconstruction of Thumb Defects Using the Second Dorsal Metacarpal Artery Flap with Two Pivot Points.

BACKGROUND: This study aimed to introduce reconstruction of thumb defects using the second dorsal metacarpal artery (DMA) flap with two pivot points. METHODS: A retrospective study was conducted with 43 patients (group A) who underwent thumb reconstruction using the second DMA flap with two pivot points from July of 2012 to May of 2019. For comparison, the authors reviewed another cohort of 34 patients (group B) undergoing thumb reconstruction using the first DMA flap. Flap sensation and donor-site morbidity were assessed. RESULTS: In group A, the mean two-point discrimination was 8.7 mm (range, 6 to 12 mm) and 9.7 mm (range, 7 to 12 mm) on the innervated and noninnervated flaps at the final follow-up, with a significant difference ( P = 0.012). In group B, the mean two-point discrimination of the flaps was 7.4 mm (range, 6 to 10 mm). By comparison, group B presented better discriminatory sensation than innervated flaps with double pivot points ( P = 0.002). Based on the visual analogue scale score, the mean score of scar pain and appearance of the donor site were 0.1 (range, 0 to 3) and 0.4 (range, 0 to 2) in group A, and 0.5 (range, 0 to 3) and 1.0 (range, 0 to 4) in group B. By comparison, group A presented lower incidence of scar pain ( P = 0.020) and better appearance of the donor site ( P = 0.019). CONCLUSIONS: The second DMA flap with two pivot points has a long vascular pedicle, which allows the flap to repair thumb defects. It is associated with low donor-site morbidity but suboptimal sensory recovery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Droplet Generation, Vitrification, and Warming for Cell Cryopreservation: A Review.

Cryopreservation is currently a key step in translational medicine that could provide new ideas for clinical applications in reproductive medicine, regenerative medicine, and cell therapy. With the advantages of a low concentration of cryoprotectant, fast cooling rate, and easy operation, droplet-based printing for vitrification has received wide attention in the field of cryopreservation. This review summarizes the droplet generation, vitrification, and warming method. Droplet generation techniques such as inkjet printing, microvalve printing, and acoustic printing have been applied in the field of cryopreservation. Droplet vitrification includes direct contact with liquid nitrogen vitrification and droplet solid surface vitrification. The limitations of droplet vitrification (liquid nitrogen contamination, droplet evaporation, gas film inhibition of heat transfer, frosting) and solutions are discussed. Furthermore, a comparison of the external physical field warming method with the conventional water bath method revealed that better applications can be achieved in automated rapid warming of microdroplets. The combination of droplet vitrification technology and external physical field warming technology is expected to enable high-throughput and automated cryopreservation, which has a promising future in biomedicine and regenerative medicine.