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Abstract Background Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants. Based on the experimental results, we then applied regression-based methods to identify factors determining splicing decisions and their respective weights. Results Our statistical modeling is highly sensitive, accurately annotating the splicing defects of near-exon intronic variants, outperforming state-of-the-art predictive tools. We have incorporated the algorithm and branchpoint information into a web-based tool, SpliceAPP, to provide an interactive application. This user-friendly website allows users to upload any genetic variants with genome coordinates (e.g., chr15 74,687,208 A G), and the tool will output predictions for splicing error scores and evaluate the impact on nearby splice sites. Additionally, users can query branch site information within the region of interest. Conclusions In summary, SpliceAPP represents a pioneering approach to screening pathogenic intronic variants, contributing to the development of precision medicine. It also facilitates the annotation of splicing motifs. SpliceAPP is freely accessible using the link https://bc.imb.sinica.edu.tw/SpliceAPP . Source code can be downloaded at https://github.com/hsinnan75/SpliceAPP .

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.

Synthetic fibers are adopted to mix with conventional steel fibers (SF) for ultra-high performance concrete (UHPC) to improve chemical resistance and reduce self-weight. Polyoxymethylene fiber (POMF), as a type of lightweight, high-strength, corrosion-resistant synthetic fiber, is expected to replace SF generally used in UHPC. Due to the obvious difference of mechanical properties between POMF and SF, different POMF/SF hybrid ratios may affect the dynamic compression behavior of UHPC. To investigate the dynamic mechanical behavior of hybrid POMF/SF reinforced UHPC (HUHPC), axial compression and split Hopkinson pressure bar (SHPB) tests with strain rate from 40 to 170 s−1 of HUHPC were conducted. The fiber volume fraction was fixed at 3% and four different POMF/SF hybrid ratios (0:3, 1:2, 2:1, 3:0) were adopted. The effects of hybrid POMF/SF ratios on the dynamic compressive properties of HUHPC, including dynamic compressive strength, dynamic elastic modulus, dynamic increase factor (DIF), and impact toughness were discussed. The results show that HUHPC exhibits obvious strain rate sensitivity under impact loading. With the increase of strain rate, the dynamic compressive strength, dynamic elastic modulus, DIF and impact toughness of HUHPC increased. Based on the linear assumption of fiber volume fraction and dynamic compressive strength enhancement of UHPC, the calculated dynamic compressive strength of HUHPC is lower than the experimental values. As the strain rate increases, the propagation path of microcrack transforms from interface of fiber-matrix to penetrating the fiber, resulting in plastic deformation of SF and fracture of POMF, consuming a large amount of impact energy and improving the impact toughness resistance of HUHPC.

Abstract Background For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e., confounding by indication. Methods We conducted a retrospective cohort study of 9,090 IVF cycles collected by Lee Women’s Hospital in Taichung, Taiwan from 1998 to 2014. We utilized the method of propensity score matching to mimic a randomized controlled trial (RCT) where each patient with Day 5 transfer was matched by another patient with Day 3 transfer with respect to other clinical characteristics. Implantation rate, clinical pregnancy rate, and odds of live birth were compared for women underwent Day 5 transfer and Day 3 transfer to estimate the causal effects. We further investigated the causal effects in subgroups by stratifying age and anti-Mullerian hormone (AMH). Results Our analyses uncovered an evidence of a significant difference in implantation rate (p=0.04) favoring Day 5 transfer, and showed that Day 3 and Day 5 transfers made no difference in both odds of live birth (p=0.27) and clinical pregnancy rate (p=0.11). With the increase of gestational age, the trend toward non-significance of embryo transfer day in our result appeared to be consistent for subgroups stratified by age and AMH, while all analyses stratified by age and AMH were not statistically significant. Conclusions We conclude that for women without strong indications for Day 3 or Day 5 transfer, there is a small significant difference in implantation rate in favor of Day 5 transfer. However, the two protocols have indistinguishable outcomes on odds of live birth and clinical pregnancy rate.

Abstract Background Both follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) are widely used to assess the ovarian reserve in women for in vitro fertilization (IVF). However, studies also showed that both AMH and FSH are significantly associated with age: as age increases, AMH decreases and FSH increases. This study aims to investigate the mechanism of age effect on IVF live birth rate, particularly through mediation and interaction by AMH and FSH. Methods We conducted a retrospective cohort study of 13970 IVF cycles collected by eIVF from 2010 to 2016. A series of logistic mixed models were used to estimate the association of live birth and AMH (or FSH). The mediation effects and proportion mediated, were quantified by our previously proposed mediation analyses. We further investigated the FSH-modified mediation effects on live birth rate through AMH, accounting for the nonlinear age effect. Results Our analyses showed that age effect on live birth was mediated more by AMH than by FSH (18 vs. 6%). The mediation effect through AMH can be further modified by FSH level regardless of women’s age. Conclusions In summary, mediation model provides a new perspective elucidating the mechanism of IVF successful rate by age. The majority of the age effect on live birth rate remained unexplained by AMH and FSH, suggesting its importance and independent role in IVF.

Abstract Background The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein‐Barr virus (EBV) infection for NPC risk. Methods 1235 male NPC cases and 1262 hospital‐based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti‐EBV VCA IgA and anti‐EBV EA‐EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders. Results 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60‐fold (95% CI = 1.30‐1.97) and former smokers a borderline significant 1.27‐fold (95% CI = 1.00‐1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack‐years of cigarette smoking but not with age at smoking initiation. Among controls, anti‐EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19‐2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti‐EBV VCA IgA. Conclusion This study confirms the association between long‐term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti‐EBV VCA IgA antibodies.

Abstract Although acid‐sensing ion channels (ASICs) are proton‐gated ion channels responsible for sensing tissue acidosis, accumulating evidence has shown that ASICs are also involved in neurosensory mechanotransduction. However, in contrast to Piezo ion channels, evidence of ASICs as mechanically gated ion channels has not been found using conventional mechanoclamp approaches. Instead, ASICs are involved in the tether model of mechanotransduction, with the channels gated via tethering elements of extracellular matrix and intracellular cytoskeletons. Methods using substrate deformation‐driven neurite stretch and micropipette‐guided ultrasound were developed to reveal the roles of ASIC3 and ASIC1a, respectively. Here we summarize the evidence supporting the roles of ASICs in neurosensory mechanotransduction in knockout mouse models of ASIC subtypes and provide insight to further probe their roles in proprioception.

Background/purpose: To investigate nerve excitability changes in patients with fibromyalgia and the correlation with clinical severity. Methods: We enrolled 20 subjects with fibromyalgia and 22 sex and age-matched healthy subjects to receive nerve excitability test and nerve conduction study to evaluate the peripheral axonal function. Results: In the fibromyalgia cohort, the sensory axonal excitability test revealed increased superexcitability (%) (P = 0.029) compared to healthy control. Correlational study showed a negative correlation between increased subexcitability (%) (r = −0.534, P = 0.022) with fibromyalgia impact questionnaire (FIQ) score. Computer modeling confirmed that the sensory axon excitability pattern we observed in fibromyalgia cohort was best explained by increased Barrett–Barrett conductance, which was thought to be attributed to paranodal fast K+ channel dysfunction. Conclusion: The present study revealed that paranodal sensory K+ conductance was altered in patients with fibromyalgia. The altered conductance indicated dysfunction of paranodal fast K+ channels, which is known to be associated with the generation of pain.

AIM: To establish the necessity of silicone tube intubation in acute dacryocystitis (AD) patients undergoing endonasal endoscopic dacryocystorhinostomy (En-DCR). METHODS: Patients presenting with unilateral AD were randomly assigned to two treatment groups. En-DCR procedures were performed following lacrimal abscess formation, with the operation being performed with silicone intubation for patients in group B but not group A. Functional success was defined by an absence of additional AD episodes, no epiphora, and ostium patency as established via endoscopic evaluation or fluorescein irrigation. Operative success rates and demographic variables were compared between treatment groups. RESULTS: In total, 66 patients were analyzed in the present study (33 per group), with complete postoperative data having been successfully collected from 27 and 22 patients in group A and group B, respectively. All patients exhibited complete resolution of acute inflammation. Upon follow-up, granulation tissue was detected around the ostium at higher rates in group B (9/22, 40.9%) relative to group A (4/27, 14.8%). At the 12-month follow-up time point, patients in group A exhibited higher success rates (25/27, 92.6%) relative to patients in group B (20/22, 90.9%), but this difference was not significant. Cases of lacrimal passage reconstruction failure in both groups were attributed to excessive fibrous and/or granulation tissue formation proximal to the intranasal ostium. CONCLUSION: Given that these two operative approaches are associated with similar rates of operative success and in light of differences in granulation tissue formation, cost, and operative duration, these data do not support the routine silicone intubation of AD patients following En-DCR surgery.

Abstract Background The no-reflow phenomenon (NRP) is a serious complication of primary percutaneous coronary intervention (PPCI) and is an independent predictor of poor prognosis. We aimed to find a simple but effective risk stratification method for the prediction of NRP. Methods This retrospective single-center study included 454 consecutive patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI) and treated by PPCI, who were admitted to our emergency department between January 2017 and March 2019. The patients were divided according to the post-PPCI thrombolysis in the myocardial infarction flow rate: the NRP group and the control group. The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-HSF scores were calculated for all the patients in this study, and multivariable regression and receiver operating characteristic curve analyses were conducted to determine the independent predictors of NRP and the predictive value of the three scores. Results A total of 454 patients were analyzed in this study: 80 in the no-reflow group and 374 in the control group. The incidence of NRP was 17.6%. Creatine kinase-myocardial band, Killip class, stent length, and multivessel disease also independently predicted NRP. The CHA2DS2-VASc-HSF score had a higher predictive value than the other two scores, and a CHA2DS2-VASc-HSF score of ≥4 predicted NRP with a sensitivity of 72.5% and specificity of 66.5% (area under the curve: 0.755, 95% confidence interval [0.702–0.808]). Conclusion Although the CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-HSF scores can all be used as simple tools to predict NRP, our findings show that the CHA2DS2-VASc-HSF score had the highest predictive value. Thus, the CHA2DS2-VASc-HSF score may be an optimal tool for predicting high-risk patients.

Abstract Objective The present study investigates the peripheral neuropathy in Primary Sjögren's syndrome (pSS) using the nerve excitability test to further elucidate how peripheral nerves are affected by the autoantibodies. Methods Each patient received clinical evaluation, examination for anti‐SSA/Ro and anti‐SSB/La antibodies titer, paired motor and sensory nerve excitability test, thermal quantitative sensory test (QST), and nerve conduction study (NCS). Results A total of 40 pSS patients wasenrolled. Motor axonal study of the pSS with positive anti‐SSA/Ro or anti‐SSB/La antibodies (n = 28) was found to have increased stimulus for 50% compound muscle action potential (CMAP) (P

Abstract Aims/Introduction To elucidate whether axonal changes arise in the prediabetic state and to find a biomarker for early detection of neurophysiological changes. Materials and Methods We enrolled asymptomatic diabetes patients, as well as prediabetic and normoglycemic individuals to test sensory nerve excitability, and we analyzed those findings and their correlation with clinical profiles. Results In nerve excitability tests, superexcitability in the recovery cycle showed increasing changes in the normoglycemic, prediabetes and diabetes cohorts (−19.09 ± 4.56% in normoglycemia, −22.39 ± 3.16% in prediabetes and −23.71 ± 5.15% in diabetes, P = 0.002). Relatively prolonged distal sensory latency was observed in the median nerve (3.12 ± 0.29 ms in normoglycemia, 3.23 ± 0.38 ms in prediabetes and 3.45 ± 0.43 ms in diabetes, P = 0.019). Superexcitability was positively correlated with fasting plasma glucose (r = 0.291, P = 0.009) and glycated hemoglobin (r = 0.331, P = 0.003) in all participants. Conclusions Sensory superexcitability and latencies are the most sensitive parameters for detecting preclinical physiological dysfunction in prediabetes. In addition, changes in favor of superexcitability were positively correlated with glycated hemoglobin for all participants. These results suggest that early axonal changes start in the prediabetic stage, and that the monitoring strategy for polyneuropathy should start as early as prediabetes.

ObjectiveThis study investigated how peripheral axonal excitability changes in ischemic stroke patients with hemiparesis or hemiplegia, reflecting the plasticity of motor axons due to corticospinal tract alterations along the poststroke stage.MethodsEach subject received a clinical evaluation, nerve conduction study, and nerve excitability test. Nerve excitability tests were performed on motor median nerves in paretic and non-paretic limbs in the acute stage of stroke. Control nerve excitability test data were obtained from age-matched control subjects. Some patients underwent excitability examinations several times in subacute or chronic stages.ResultsA total of thirty patients with acute ischemic stroke were enrolled. Eight patients were excluded due to severe entrapment neuropathy in the median nerve. The threshold current for 50% compound muscle action potential (CMAP) was higher in paretic limbs than in control subjects. Furthermore, in the cohort with severe patients (muscle power ≤ 3/5 in affected hands), increased threshold current for 50% CMAP and reduced subexcitability were noted in affected limbs than in unaffected limbs. In addition, in the subsequent study of those severe patients, threshold electrotonus increased in the hyperpolarization direction: TEh (100-109 ms), and the minimum I/V slope decreased. The above findings suggest the less excitable and less accommodation in lower motor axons in the paretic limb caused by ischemic stroke.ConclusionUpper motor neuron injury after stroke can alter nerve excitability in lower motor neurons, and the changes are more obvious in severely paretic limbs. The accommodative changes of axons progress from the subacute to the chronic stage after stroke. Further investigation is necessary to explore the downstream effects of an upper motor neuron insult in the peripheral nerve system.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

Objectives: To conduct a meta-analysis to assess the efficacy of scalp acupuncture (SA) in patients with stroke and consequent hemiparesis regardless of brain infarction or intracerebral hemorrhage.Methods: A literature search of randomized controlled trials (RCTs) on SA for stroke was performed in five databases up to May 10, 2021. We investigated three types of outcome: motor function, sequelae of poststroke hemiparesis, and adverse effects. Methodological quality was assessed using the revised Cochrane risk of bias tool version 2.0.Results: Of 1,063 papers, 30 RCTs involving Fugl–Meyer Assessment were selected, among which 10 and four RCTs were selected for evaluation of courses lasting of 1 and 3 months, respectively. The meta-analysis of 1- and 3-month courses revealed significant differences in the motor function of the SA plus Western standard treatment group vs. Western standard treatment only (medication plus rehabilitation; P < 0.001). A 3-month course tended to result in better outcomes than a 1-month course.Conclusions: Our meta-analysis results reveal that SA improves motor function in patients with acute to chronic stroke, regardless of brain infarction or intracerebral hemorrhage. However, because of a lack of methodological quality, thoroughly planned clinical studies are still required.

The present study proposes a cognitive prosthesis device for face memory impairment as a proof-of-concept for the domain-specific cognitive prosthesis. Healthy subjects (n = 6) and a patient with poor face memory were enrolled. An acquaintance face recognition test with and without the use of cognitive prosthesis for face memory impairment, face recognition tests, quality of life, neuropsychological assessments, and machine learning performance of the cognitive prosthesis were followed-up throughout four weeks of real-world device use by the patient. The healthy subjects had an accuracy of 92.38 ± 4.41% and reaction time of 1.27 ± 0.12 s in the initial attempt of the acquaintance face recognition test, which changed to 80.48 ± 6.23% (p = 0.06) and 2.11 ± 0.20 s (p < 0.01) with prosthesis use. The patient had an accuracy of 74.29% and a reaction time of 6.65 s, which improved to 94.29% and 3.28 s with prosthesis use. After four weeks, the patient’s unassisted accuracy and reaction time improved to 100% and 1.23 s. Functional MRI study revealed activation of the left superior temporal lobe during face recognition task without prosthesis use and activation of the right precentral motor area with prosthesis use. The prosthesis could improve the patient’s performance by bypassing the brain area inefficient for facial recognition and employing the area more efficiently for the cognitive task.

The present article reviewed the pharmacologic therapies of traumatic brain injury (TBI), including current and potential treatments. Pharmacologic therapies are an essential part of TBI care, and several agents have well-established effects in TBI care. In the acute phase, tranexamic acid, antiepileptics, hyperosmolar agents, and anesthetics are the mainstay of pharmacotherapy, which have proven efficacies. In the post-acute phase, SSRIs, SNRIs, antipsychotics, zolpidem and amantadine, as well as other drugs, have been used to manage neuropsychological problems, while muscle relaxants and botulinum toxin have been used to manage spasticity. In addition, increasing numbers of pre-clinical and clinical studies of pharmaceutical agents, including potential neuroprotective nutrients and natural therapies, are being carried out. In the present article, we classify the treatments into established and potential agents based on the level of clinical evidence and standard of practice. It is expected that many of the potential medicines under investigation will eventually be accepted as standard practice in the care of TBI patients.

Abstract The “myodural bridge” was described in literatures as a dense fibrous tissue connecting the sub-occipital musculature with the spinal dura mater in human studies. Now the concept of “myodural bridge” was perceived as an exact anatomical structure presumably essential for critical physiological functions in human body, and might exist in other mammals as well. To determine the existence of the “myodural bridge” in other mammals and to lay a foundation for the functional study, we examined representatives in five different mammalian orders. Based on the anatomical dissections, P45 plastinated sections and histological sections, we found that a dense fibrous tissue connected the rectus capitisdorsalis minor and the spinal dura mater through the dorsal atlanto-occipital interspace with or without the medium of the posterior atlanto-occipital membrane. These observed connective tissues were very similar to the “myodural bridge” previously described in humans. We proposed that the “myodural bridge”, as an evolutionally conserved structure, presents in many other mammals. Moreover, we believed that the “myodural bridge” might be a homologous organ in mammals. Thus, this study could provide an insight for our understanding the physiological significance of the “myodural bridge”, especially in human.

Introduction: Abuse of nitrous oxide (N2O) has an unusually high lifetime prevalence in developed countries and represents a serious concern worldwide. Myeloneuropathy following the inhalant abuse is commonly attributed to the disturbance of vitamin B12 metabolism, with severe motor deficits are often noted. The present study aims to elucidate its underlying pathophysiology.Methods: Eighteen patients with N2O abuse or vitamin B12 deficiency were recruited. Comprehensive central and peripheral neuro-diagnostic tests were performed, including whole spine MRI, and thermal quantitative sensory testing (QST). Specifically, paired motor and sensory nerve excitability tests were performed in order to obtain a complete picture of the sensorimotor axonal damage.Results: The mean duration of N2O exposure for the N2O abuse patients was 17.13 ± 7.23 months. MRI revealed T2 hyperintensity in 87.5% of the N2O abuse patients and 50% of the vitamin B12 deficiency patients. In N2O abuse patients, the motor nerve excitability test showed decreased in peak response (7.08 ± 0.87 mV, P = 0.05), increased latency (7.09 ± 0.28 ms, P < 0.01), increased superexcitability (−32.95 ± 1.74%, P < 0.05), and decreased accommodation to depolarizing current [TEd (40–60 ms) 56.53 ± 0.70%, P < 0.05]; the sensory test showed only decreased peak response (30.54 ± 5.98 μV, P < 0.05). Meanwhile, motor test in vitamin B12 deficiency patients showed only decreased accommodation to depolarizing current [TEd (40–60 ms) 55.72 ± 1.60%, P < 0.01]; the sensory test showed decreased peak response (25.86 ± 3.44 μV, P < 0.05) increased superexcitability (−28.58 ± 3.71%, P < 0.001), increased subexcitability (8.31 ± 1.64%, P < 0.05), and decreased accommodation to depolarizing current [TEd (peak) 67.31 ± 3.35%, P < 0.001].Conclusion: Compared to vitamin B12 deficiency, N2O abuse patients showed prominent motor superexcitability changes and less prominent sensory superexcitability changes, hinting a unique pathological process different from that of vitamin B12 deficiency. N2O abuse might cause axonal dysfunction not only by blocking methionine metabolism but also by toxicity affecting the paranodal region.

Background Hyperglycemia is a known predictor of negative outcomes in stroke. Several glycemic measures, including admission random glucose, fasting glucose, and glycated hemoglobin (HbA1c), have been associated with bad neurological outcomes in acute ischemic stroke, particularly in nondiabetic patients. However, the predictive power of these glycemic measures is yet to be investigated. Methods This retrospective study enrolled 484 patients with acute ischemic stroke from January 2009 to March 2013, and complete records of initial stroke severity, neurological outcomes at three months, and glycemic measures were evaluated. We examined the predictive power of admission random glucose, fasting glucose, and HbA1c for neurological outcomes in acute ischemic stroke. Furthermore, subgroup analyses of nondiabetic patients and patients with diabetes were performed separately. Results Receiver operating characteristic (ROC) analysis revealed that admission random glucose and fasting glucose were significant predictors of poor neurological outcomes, whereas HbA1c was not (areas under the ROC curve (AUCs): admission random glucose = 0.564, p = 0.026; fasting glucose = 0.598, p = 0.001; HbA1c = 0.510, p = 0.742). Subgroup analyses of nondiabetic patients and those with diabetes revealed that only fasting glucose predicts neurological outcomes in patients with diabetes, and the AUCs of these three glycemic measures did not differ between the two groups. A multivariate logistic regression analysis of the study patients indicated that only age, initial stroke severity, and fasting glucose were independent predictors of poor neurological outcomes, whereas admission random glucose and HbA1c were not (adjusted odds ratio: admission random glucose = 1.002, p = 0.228; fasting glucose = 1.005, p = 0.039; HbA1c = 1.160, p = 0.076). Furthermore, subgroup multivariate logistic regression analyses of nondiabetic patients and those with diabetes indicated that none of the three glycemic measures were associated with poor neurological outcomes. Discussion Fasting glucose is an independent predictor of poor neurological outcomes in patients with acute ischemic stroke and had greater predictive power than that of admission random glucose and HbA1c. The predictive power of glycemic measures for poor neurological outcomes did not differ significantly between the nondiabetic patients and those with diabetes.

This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P

In the last two decades, many studies have focused on the muscles and dense connective tissues located in the suboccipital region. Our study investigated the existence of the second terminations originating from the suboccipital muscles, and the relationship between the variable types of the To Be Named Ligament (TBNL). Anatomical dissection was performed on 35 head-neck specimens. The existence of the second terminations of the suboccipital muscles was confirmed and various types of the TBNL were observed in this study. The second terminations originated from multiple suboccipital muscles including the rectus capitis posterior minor (RCPmi), rectus capitis posterior major (RCPma) and obliquus capitis inferior (OCI) muscles, merged and terminated at the TBNL. The overall incidence of the second terminations of the suboccipital muscles was 34.29% and it varied among the various suboccipital muscle origins. 28.57% of the second terminations originated from the RCPma; 11.43% was from the RCPmi and 8.57% was from the OCI. Furthermore, there was a significant relationship between the existence of second terminations and the particular type of the TBNL. 95% of the arcuate type of the TBNL was accompanied with the second terminations which attached to their turning part, whereas only 10% of all the radiate type of the TBNL was accompanied with the second terminations. This study for the first time described the second terminations originating from multiple suboccipital muscles and demonstrated the relationship with the various types of the TBNL. We speculated that the second terminations maintain the arcuate TBNL and transfer tensile forces to the Myodural Bridge (MDB), thereby modulating the physiological functions of the MDB.