Glucose starvation induces a switch in the histone acetylome for activation of gluconeogenic and fat metabolism genes.

Acetyl-CoA is a key intermediate situated at the intersection of many metabolic pathways. The reliance of histone acetylation on acetyl-CoA enables the coordination of gene expression with metabolic state. Abundant acetyl-CoA has been linked to the activation of genes involved in cell growth or tumorigenesis through histone acetylation. However, the role of histone acetylation in transcription under low levels of acetyl-CoA remains poorly understood. Here, we use a yeast starvation model to observe the dramatic alteration in the global occupancy of histone acetylation following carbon starvation; the location of histone acetylation marks shifts from growth-promoting genes to gluconeogenic and fat metabolism genes. This reallocation is mediated by both the histone deacetylase Rpd3p and the acetyltransferase Gcn5p, a component of the SAGA transcriptional coactivator. Our findings reveal an unexpected switch in the specificity of histone acetylation to promote pathways that generate acetyl-CoA for oxidation when acetyl-CoA is limiting.

Spt4 is selectively required for transcription of extended trinucleotide repeats.

Lengthy trinucleotide repeats encoding polyglutamine (polyQ) stretches characterize the variant proteins of Huntington's disease and certain other inherited neurological disorders. Using a phenotypic screen to identify events that restore functionality to polyQ proteins in S. cerevisiae, we discovered that transcription elongation factor Spt4 is required to transcribe long trinucleotide repeats located either in ORFs or nonprotein-coding regions of DNA templates. Mutation of SPT4 selectively decreased synthesis of and restored enzymatic activity to expanded polyQ protein without affecting protein lacking long-polyQ stretches. RNA-seq analysis revealed limited effects of Spt4 on overall gene expression. Inhibition of Supt4h, the mammalian ortholog of Spt4, reduced mutant huntingtin protein in neuronal cells and decreased its aggregation and toxicity while not altering overall cellular mRNA synthesis. Our findings identify a cellular mechanism for transcription through repeated trinucleotides and a potential target for countermeasures against neurological disorders attributable to expanded trinucleotide regions.

Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study.

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

Detecting outliers beyond tolerance limits derived from statistical process control in patient-specific quality assurance.

BACKGROUND: Tolerance limit is defined on pre-treatment patient specific quality assurance results to identify "out of the norm" dose discrepancy in plan. An out-of-tolerance plan during measurement can often cause treatment delays especially if replanning is required. In this study, we aim to develop an outlier detection model to identify out-of-tolerance plan early during treatment planning phase to mitigate the above-mentioned risks. METHODS: Patient-specific quality assurance results with portal dosimetry for stereotactic body radiotherapy measured between January 2020 and December 2021 were used in this study. Data were divided into thorax and pelvis sites and gamma passing rates were recorded using 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria. Statistical process control method was used to determine six different site and criterion-specific tolerance and action limits. Using only the inliers identified with our determined tolerance limits, we trained three different outlier detection models using the plan complexity metrics extracted from each treatment field-robust covariance, isolation forest, and one class support vector machine. The hyperparameters were optimized using the F1-score calculated from both the inliers and validation outliers' data. RESULTS: 308 pelvis and 200 thorax fields were used in this study. The tolerance (action) limits for 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria in the pelvis site are 99.1% (98.1%), 95.8% (91.1%), and 91.7% (86.1%), respectively. The tolerance (action) limits in the thorax site are 99.0% (98.7%), 97.0% (96.2%), and 91.5% (87.2%). One class support vector machine performs the best among all the algorithms. The best performing model in the thorax (pelvis) site achieves a precision of 0.56 (0.54), recall of 1.0 (1.0), and F1-score of 0.72 (0.70) when using the 2%/2 mm (2%/1 mm) criterion. CONCLUSION: The model will help the planner to identify an out-of-tolerance plan early so that they can refine the plan further during the planning stage without risking late discovery during measurement.

The relationship between kidney disease and mitochondria: a bibliometric study.

BACKGROUND: Due to its highly reabsorptive function, the kidney is a mitochondria-dependent organ. Research on the association between mitochondria and kidney disease has always been a serious focus of researchers, with many publications. Bibliometrics is a secondary analysis of published literature that extracts relevant information to gain insights into hotspots and trends in the field. Through bibliometric analysis, we aimed to understand the development trends and hotspots in the field of research on the association between kidney disease and mitochondria. METHOD: Three bibliometric mapping tools (Biblimetrix R Package, VOS Viewer, CiteSpace) were used to provide an overview of the literature and analyze the co-occurrence of keywords and reference citations. RESULTS: A total of 2672 relevant research articles were included. The co-occurrence network identified three clusters related to the association between mitochondria and kidney disease, including experimental methods, research mechanisms, and disease phenotypes. We found that research in this field has shifted from disease-level studies to mechanism-based studies, with the most prominent disease being diabetic nephropathy and the most prominent pathogenic mechanism being related to mitochondrial ROS production. CONCLUSION: The bibliometric analysis provided a comprehensive understanding of the progress of research on the role of mitochondria in kidney disease, enriching the review literature in this field.

Handheld common-path swept-source optical coherence tomography angiography.

This study develops a handheld optical coherence tomography angiography (OCTA) system that uses a high-speed (200 kHz) swept laser with a dual-reference common-path configuration for stable and fast imaging. The common-path design automatically avoids polarization and dispersion mismatches by using one circulator as the primary system element, ensuring a cost-effective and compact design for handheld probe use. With its stable envelope (i.e., sub-µm shifts) and phase variation (corresponding to nm changes in axial displacement), the minimum detectable flow velocity is ∼ 0.08 mm/s in our experiment, which gives the common-path setup a high potential for application in a handheld OCTA system for clinical skin screening. In vivo skin structures and microvasculature networks on the dorsum of the hand and cheek of a healthy human are imaged successfully.

Baseline characteristics and treatment response predictive of nAMD outcomes with ranibizumab therapy in treatment-naive patients: the RACER subgroup analysis.

BACKGROUND: The Ranibizumab AMD Clinical Efficacy Study (RACER) conducted in treatment-naive adult Taiwanese patients with neovascular age-related macular degeneration (nAMD) suggested the importance of early and intensive dosing of ranibizumab for optimal treatment outcomes. This subgroup analysis aims to provide clinical information on treatment response that can potentially guide on maintaining the treatment or switching anti-VEGF agents in the real-world setting. METHODS: Visual acuity (VA) and central retinal thickness (CRT) were assessed in the RACER subgroup population. Subgroup analysis sets were categorised based on: (1) baseline best-corrected VA (BCVA; ≤ 48 and > 48 letters); (2) baseline CRT (≤ 325 or > 325 µm); and (3) treatment response after three monthly initial injections: < or ≥ 5-letter gain in BCVA and reduction of < or ≥ 50 µm in CRT. RESULTS: Patient age, sex, nAMD duration and number of ranibizumab injections did not differ significantly between the treatment subgroups. Poor baseline BCVA (≤ 48 letters) and baseline CRT severity (> 325 µm) were predictors of maximum BCVA gains (9.6 ± 12.9 letters [95%CI: 6.3 to 12.9] and 5.1 ± 18.3 letters [95%CI: - 0.5 to 10.8] at Months 3 and 12, respectively) and better CRT reductions (- 127.6 ± 104.2 µm and - 104.2 ± 107.4 µm at Months 3 and 12, respectively; both P < 0.001). For the subgroup showing favourable treatment improvement with BCVA gains ≥ 5 letters after three monthly initial injections, 75.6% of patients maintained follow-up at Month 12 with a mean of 6.5 ± 14.3 letter gains (95% CI: 1.2 to 11.7). The BCVA gains < 5-letter subgroup nevertheless had stable BCVA (0.4 ± 12.1 letter gains) and CRT (- 41.9 ± 61.2 µm) at Month 12, respectively. In the subgroup with ≥ 50 µm CRT reduction after three monthly initial injections, there are significantly higher BCVA improvements vs. the < 50 µm CRT reduction subgroup at Month 3 (5.0 ± 8.6 letter gains vs. 1.5 ± 11.6 letter gains, respectively; intergroup P = 0.005). CONCLUSION: Lower baseline BCVA and higher baseline CRT were associated with BCVA gains and CRT reductions throughout the 12-month study period. Early CRT improvements after three monthly initial injections were associated with BCVA gains as early as Month 3.

Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation.

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.

Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£è€ å’ŒåŒ»åŠ¡äººå‘˜çš„å¿ƒç†ç¤¾ä¼šå±æœºå¹²é¢„ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS: Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.

Optimal approaches and criteria to treat-and-extend regimen implementation for Neovascular age-related macular degeneration: experts consensus in Taiwan.

The management of neovascular age-related macular degeneration (nAMD) has taken a major stride forward with the advent of anti-VEGF agents. The treat-and-extend (T&E) approach is a refined management strategy, tailoring to the individual patient's disease course and treatment outcome. To provide guidance to implementing anti-VEGF T&E regimens for nAMD in resource-limited health care systems, an advisory board was held to discuss and generate expert consensus, based on local and international guidelines, current evidence, as well as local experience and reimbursement policies. In the experts' opinion, treatment of nAMD should aim to maximize and maintain visual acuity benefits while minimizing treatment burden. Based on current evidence, treatment could be initiated with 3 consecutive monthly injections. After the initial period, treatment interval may be extended by 2 or 4 weeks each time for the qualified patients (i.e. no BCVA loss ≥5 ETDRS letters and dry retina), and a maximum interval of 16 weeks is permitted. For patients meeting the shortening criteria (i.e. any increased fluid with BCVA loss ≥5 ETDRS letters, or presence of new macular hemorrhage or new neovascularization), the treatment interval should be reduced by 2 or 4 weeks each time, with a minimal interval of 4 weeks. Discontinuation of anti-VEGF may be considered for those who have received 2-3 consecutive injections spaced 16 weeks apart and present with stable disease. For these individuals, regular monitoring (e.g. 3-4 months) is recommended and monthly injections should be reinstated upon signs of disease recurrence.

Effects of a teaching mode combining SimBaby with standardized patients on medical students' attitudes toward communication skills.

OBJECTIVE: To evaluate the effect of a teaching mode combining SimBaby with standardized patients (SP) on medical students' attitudes toward communication skills (CS). METHODS: Forty 8-year medical program students majoring in clinical medicine were randomly divided into the SimBaby group (n = 20) and the SP + SimBaby group (n = 20). The Communication Skills Attitude Scale (CSAS) was used to evaluate medical students' attitudes toward CS learning. RESULTS: In the SimBaby and SP + SimBaby groups, there were no statistically significant differences in the Positive Attitude Subscale (PAS) and Negative Attitude Subscale (NAS) scores between males and females (p > 0.05). Compared to the SimBaby group, the SP + SimBaby group showed statistically significant differences in PAS, NAS, and the two dimensions of importance in medical context and learning (p < 0.05). There were no statistically significant differences between groups in the dimensions of excusing and overconfidence (p > 0.05). CONCLUSION: Compared with SimBaby alone, the SP + SimBaby teaching mode can improve medical students' attitude toward CS learning, suggesting that the organic integration of multiple simulation-based medical teaching methods plays an important role in the acquisition of CS.

A Confidential QR Code Approach with Higher Information Privacy.

In present times, barcode decoders on mobile phones can extract the data content of QR codes. However, this convenience raises concerns about security issues when using QR codes to transmit confidential information, such as e-tickets, coupons, and other private data. Moreover, current secret hiding techniques are unsuitable for QR code applications since QR codes are module-oriented, which is different from the pixel-oriented hiding manner. In this article, we propose an algorithm to conceal confidential information by changing the modules of the QR Code. This new scheme designs the triple module groups based on the concept of the error correction capability. Additionally, this manner can conceal two secret bits by changing only one module, and the amount of hidden confidential information can be twice the original amount. As a result, the ordinary data content (such as URL) can be extracted correctly from the generated QR code by any barcode decoders, which does not affect the readability of scanning. Furthermore, only authorized users with the secret key can further extract the concealed confidential information. This designed scheme can provide secure and reliable applications for the QR system.

Comparison of Choroidal Thickness, Foveal Avascular Zone, and Macular Capillary Density in Macular Edema Secondary to Branch Retinal Vein Occlusion Treated with Ranibizumab or Aflibercept-A Prospective Study.

This prospective comparative case series aims to compare best-corrected visual acuity (BCVA), retinal microvasculature, and retinal structural changes in patients treated with either ranibizumab or aflibercept for macular edema (ME) secondary to treatment-naïve branch retinal vein occlusion (BRVO) by optical coherence tomography angiography (OCTA). Ten patients were enrolled with macular capillary density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and foveal avascular zone (FAZ) measured in both eyes before and after treatment. Final central retinal thickness and BCVA improved significantly (p < 0.05), and densities of SCP and DCP of BRVO sectors were significantly lower at baseline than fellow eye counterparts and remained persistently lower during treatment, particularly in the aflibercept group (p < 0.05). SCP density, DCP density of both BRVO sectors (p = 0.0001, p < 0.0001), and non-BRVO sectors (p < 0.0001, p < 0.0001) were significantly correlated with final BCVA for diseased eyes. Using multivariate general linear model analysis, and including OCTA parameters only, but not all of the available clinical data, DCP density of BRVO sectors in both eyes was the most predictive factor for final visual outcome (probability p < 0.0001). OCTA offered further qualitative and quantitative evaluation of treatment-naïve BRVO. Judging by OCTA parameters, not only in the diseased eye but also in the fellow eye, DCP density of BRVO sectors was the most predictive factor of final visual outcome.

Optical coherence tomography measurements as potential imaging biomarkers for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Retinal pathological changes may precede or accompany the deterioration of brain tissue in Parkinson's disease (PD). The purpose of this meta-analysis was to assess the usefulness of optical coherence tomography (OCT) measurements as potential imaging biomarkers for PD. METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched for observational studies (published prior to 30 May 2020) comparing the OCT measurements between PD patients and healthy controls (HCs). Our main end-points were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex thickness, macular thickness and macular volume. Pooled data were assessed by use of a random-effects model. RESULTS: A total of 36 observational studies were identified that included 1712 patients with PD (2548 eyes) and 1778 HCs (2646 eyes). Compared with the HC group, the PD group showed a significant reduction in mean pRNFL thickness (weighted mean difference [WMD] -3.51 µm, 95% confidence interval [CI] -4.84, -2.18; p = 0.000), all quadrants at the pRNFL (WMD range -7.65 to -2.44 µm, all p < 0.05), macular fovea thickness (WMD -5.62 µm, 95% CI -7.37, -3.87; p = 0.000), all outer sector thicknesses at the macula (WMD range -4.68 to -4.10 µm, all p < 0.05), macular volume (WMD -0.21 mm3 , 95% CI -0.36, -0.06; p < 0.05) and macular ganglion cell complex thickness (WMD -4.18 µm, 95% CI -6.07, -2.29; p < 0.05). CONCLUSIONS: Our pooled data confirmed robust associations between retinal OCT measurements and PD, highlighting the usefulness of OCT measurements as potential imaging biomarkers for PD.

Fiber-Needle Swept-Source Optical Coherence Tomography for the Real-Time Visualization of the Transversus Abdominis Plane Block Procedure in a Swine Model.

BACKGROUND: Fascia blocks (eg, the transversus abdominis plane [TAP] block) target the intermuscular fascia layers. Ultrasound techniques have allowed peripheral blocks to be performed with accuracy and safety, however, with limitations. Optical coherence tomography (OCT) is based on low-coherence interferometry. In this study, we examined the ability of OCT to identify the TAP. METHODS: A swept-source OCT probe was placed in a 17-gauge needle to obtain imaging. The needle was inserted within 2 different angle ranges (0°-30° and 30°-60°) on a slice of pork belly to assess imaging characteristics. A series of real-time OCT imaging of the muscle, fascia, and interfascial space was obtained. The tissue location of the needle tip was identified using near-infrared (NIR) imaging. In vivo OCT imaging was further done on 3 female 6-month-old native Chinese Landrance Duroc pigs. Real-time images of tissue layers were obtained with needle insertion. Ultrasound imaging of the OCT needle probe was also performed at the same time for needle trajectory guidance. After imaging, the OCT probe was removed, and 5 mL of normal saline was injected via the needle to confirm correct fascia plane identification. RESULTS: In and ex vivo studies showed clear visual distinction of muscle, fascia, and interfascial layer with OCT, with limitations. Independent validation of OCT criteria for the muscle/fascia differentiation by 20 OCT readers for the in vivo data demonstrated the sensitivity = 0.91, specificity = 0.90, and accuracy = 0.89. Although the angle of needle entry affected the depth of OCT penetration in the muscle, the attenuation coefficient values of the fascia and muscle tissue were statistically different (P < .001) and with high area under the receiver operating characteristics (ROC) curve (AUC) (AUC = 0.93 in 0°-30° and AUC = 1 in 30°-60°) for fascia identification. CONCLUSIONS: This study introduced a novel needle imaging probe method to identify the transversus abdominis fascia plane in real-time. Quantitative calculation of the attenuation coefficients can further aid objective identification by providing direct confirmation of the tip position, increasing the first-pass success rate, and decreasing the need for needle repositioning. Combining OCT and ultrasound may improve the accuracy of anesthetics placement.

LAMC1 is related to the poor prognosis of patients with gastric cancer and facilitates cancer cell malignancies.

Gastric cancer is a common malignancy in the alimentary system. The laminin subunit gamma 1 (LAMC1) is an important oncogene in human cancers. However, how and whether LAMC1 takes part in gastric cancer progression is largely uncertain. This study analyzed the association between clinical factors of patients and LAMC1 expression and explored the influence of LAMC1 silencing on cell proliferation, migration, invasion, the Warburg effect, protein kinase B (AKT) pathway, and mitogen-activated protein kinase (MEK)/extracellular regulated protein kinase (ERK) pathway in gastric cancer cells. Our results showed LAMC1 abundance was enhanced in gastric cancer samples and cells. LAMC1 was related to the clinical stage, tumor depth, lymph node metastasis, and distant metastasis of patients. LAMC1 silencing inhibited cell proliferation, migration, and invasion. Moreover, LAMC1 knockdown suppressed the Warburg effect via decreasing lactate production, lactate dehydrogenase (LDH) activity, and glucose uptake. LAMC1 interference blocked the activation of the AKT and MEK/ERK signaling. Collectively, LAMC1 knockdown constrained cell proliferation, migration, invasion, and the Warburg effect in gastric cancer cells via inactivating the AKT and MEK/ERK pathway.

Altered Cortical Reorganization and Brain Functional Connectivity in Phantom Limb Pain: A Functional MRI Study.

OBJECTIVES: Functional neuroimaging studies have shown that amputees have altered cortical reorganization and functional connectivity (FC). This study aimed to investigate whether patients with phantom limb pain (PLP) and PLP-free lower limb amputees exhibit changes in corresponding primary cortical motor area/somatosensory cortex (M1/S1) cortical reorganization and supplementary motor area (SMA) network FC. The association between functional magnetic resonance imaging (fMRI) changes and clinical parameters is also explored. METHODS: A total of 10 PLP patients were matched with 10 PLP-free amputees and 10 healthy controls (HCs). Before undergoing fMRI, all participants completed questionnaires evaluating pain, anxiety, depression, and health-related quality of life. Task-related activation and regions of interest (ROI)-wise connectivity analysis were applied to differentiate the brain regions of amputees from those of HCs. Linear correlation analysis was used to evaluate the correlation between altered FC and clinical manifestations. RESULTS: As compared with HCs, PLP patients showed increased cortical activation in M1/S1 when moving the intact foot, imagining phantom big toe movement, or having the corresponding thumb stimulated. The increased FC in the SMA network included the SMA-caudate nucleus, SMA-bilateral insula, and SMA-anterior cingulate cortex. Furthermore, results of the linear correlation analysis demonstrated that this increased FC was positively correlated with VAS scores, negatively correlated with Medical Outcomes Study 36-item Short-Form (SF-36) scores, and not correlated with anxiety or depression scores. CONCLUSIONS: Phantom limb pain in lower limb amputees is associated with M1/S1 cortical reorganization and altered SMA network FC in different areas of the brain, which could help to support our understanding of the central mechanism of PLP.

[Epidemiological and clinical features of children with mild coronavirus disease 2019].

OBJECTIVE: To study the epidemiological and clinical features of children with mild coronavirus disease 2019 (COVID-19). METHODS: The children who were diagnosed with mild COVID-19 in the Wuchang Shelter Hospital in Wuhan from February 5 to March 10, 2020 were enrolled as subjects. The clinical, laboratory, and lung imaging data were collected during hospitalization and isolation. This was a retrospective single-center case series analysis. RESULTS: A total of 1 124 patients with mild COVID-19 were admitted from February 5 to March 10, 2020, including 13 children (1.16%). All the 13 children (7 boys and 6 girls) were residents of Wuhan in China, with a median age of 16 years (range: 10-18 years). Of all the 13 children, 9(69%) were from family clusters of COVID-19 and 4(31%) had unknown sources of infection. The mean time from exposure to onset was 6.8 days (range: 2-13 days) in 9 children with a definite history of exposure. There were 6 symptomatic children with the main manifestations of fever, cough, weakness, and myalgia, and the mean time from onset to hospitalization was 9.2 days. Of all the 13 children, 7(54%) were asymptomatic with positive nucleic acid test of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There were 4 children (31%) with abnormal lung CT findings, mainly patchy shadows or ground-glass opacities in the lung field, and 6 children (46%) had no symptoms with normal lung CT findings. All children had normal routine blood test results and C-reactive protein levels. Eight children underwent SARS-CoV-2 IgM and IgG tests at least once, among whom 6 had negative SARS-CoV-2 IgM but positive IgG, and 2 underwent SARS-CoV-2 IgM and IgG tests twice and had negative results. Of all the 13 children, 11(85%) had negative results of two SARS-CoV-2 nucleic acid tests during hospitalization and were discharged, and 2(15%) had positive results of four SARS-CoV-2 nucleic acid tests and were transferred to another hospital and lost to follow-up. Among the 11 children who were followed up, 1 had positive results of two SARS-CoV-2 nucleic acid tests at the isolation point, and 10 had negative results. The mean hospital stay was 10.9 days for the 13 children. Eleven children recovered during follow-up, with good living and learning conditions. CONCLUSIONS: Children with mild COVID-19 often have an uncertain history of exposure and may not have any clinical symptoms. Etiological diagnosis is more important than clinical diagnosis. The disappearance of clinical manifestations may not parallel with the result of SARS-CoV-2 nucleic acid test. SARS-CoV-2 has a long detoxification time, and there may be recurrent cases of SARS-CoV-2 positivity. Further studies are needed to investigate the production patterns of SARS-CoV-2 IgM and IgG and their effect on the body.

The impact of shared decision making with patient decision aids on the rotavirus vaccination rate in children: A randomized controlled trial.

Rotavirus vaccination reduces the incidence and severity of acute gastroenteritis due to rotavirus infection. However, because of a lack of understanding and private payment for the rotavirus vaccine, the rotavirus vaccination rate is still low in some countries. We intended to assess the impact of shared decision-making (SDM) with the assistance of patient decision aids (PDAs) on the rotavirus vaccination rate, and the knowledge, confidence, and congruence of value among baby's parents when decision-making. The study was a two-group, outcome assessor-blind, randomized, controlled trial. The families of 1-month-old infants for routine vaccination were enrolled; they were divided randomly into non-SDM and SDM groups. The influence of SDM on the acceptance of rotavirus vaccination was assessed when their infants were 2 months old. Outcome measures were decisional conflict, decision-making difficulties, and rotavirus vaccine knowledge, and the overall rotavirus vaccination rate. The study enrolled 180 participants. SDM, parents' education level, and rotavirus vaccination of a previous child were variables that influenced acceptance of rotavirus vaccination. The SDM group scored significantly higher for understanding the information on the oral rotavirus vaccine than the non-SDM group, which helped them to decide whether to vaccinate the baby against rotavirus. The rotavirus vaccination rate was 16.7% higher in the SDM group than the non-SDM group. SDM assisted with PDAs gives more information and helps infants' families understand what they need, reduces their decision conflict, and increases their baby's vaccination against rotavirus, which promotes public health. The clinical trial is registered at ClinicalTrials.gov (NCT03804489).

MANAGEMENT OF REFRACTORY LARGE MACULAR HOLE WITH AUTOLOGOUS NEUROSENSORY RETINAL FREE FLAP TRANSPLANTATION.

PURPOSE: To investigate the morphological and functional outcome of refractory large macular hole (MH) with autologous neurosensory retinal free flap transplantation. METHODS: This case series enrolled 10 patients suffering from refractory large MH at Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. All eyes underwent pars plana vitrectomy, a neurosensory retinal free flap with a 1.5 to 2-MH diameter was harvested. We used an adhesive agent such as whole blood or Viscoat to assist the stabilization of the retinal free flap and then use tamponade silicone oil to tamponade the vitreous cavity. Silicone oil was removed 6 months postoperatively. Main outcome measures including closure of MH and change in best-corrected visual acuity change were recorded. RESULTS: The mean age was 64.9 ± 11.5 years. Before presentation, all cases had received at least two vitreoretinal procedures including vitrectomy, internal limiting membrane peeling, and fluid-gas exchange. At last visit, closure of the MH was achieved in 9 of 10 (90%) cases. The mean preoperative best-corrected visual acuity and that after 12 months of surgery improved from 1.65 ± 0.43 logarithm of minimum angle of resolution to 0.88 ± 0.49 logarithm of minimum angle of resolution (P < 0.001). CONCLUSION: For eyes with refractory or large MH, autologous neurosensory retinal free flap under silicone oil tamponade may provide a new option to improve the anatomical and function outcome, especially in cases where insufficient internal limiting membrane is left.