Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke.

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).

Quality and safety of Telemedicine in acute ischemic stroke: Early experience in Taiwan.

BACKGROUND: Telemedicine helps to provide the safe management of stroke patients in the emergency department (ED) and has been used worldwide. However, we had limited experience of telestroke in Taiwan. We aimed to identify the quality of telestroke and compare it with the original face-to-face consultation model. METHODS: Among 178 consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (IVtPA) from January 1, 2018, to December 31, 2019, we compared two different consultation methods: face-to-face consultation and telestroke consultation. We collected data on demographics, the National Institutes of Health Stroke Scale (NIHSS) scores, Modified Rankin Scale (mRS) scores, time measurements (onset-to-arrival time, onset-to-telestroke activation time, and time of IVtPA administration (Door-to-Needle; DTN)). RESULTS: The mean age to receive a telestroke consultation was 66.6 years, 36% were female, and the median NIHSS score was 9. The median time from patient arrival to telestroke consult activation was 40 min, and the median DTN time was 11 min longer than for face-to-face consults (62 min versus 51 min, p = .01). Telestroke consultation, similar to a face-to-face consultation, resulted in safe IVtPA eligibility assessments and administration with post-thrombolysis ICH in 4% overall (4% telestroke, 3% face-to-face consultation; p = .851). The 90-day outcomes were not different for mRS score, dichotomized 0-2 (60% telestroke 59% face-to-face consultation; p = .961), or for mortality (16% telestroke, 9% face-to-face consultation; p = .292). CONCLUSION: In the ED, consultation via the telestroke program provides equal quality to the original face-to-face consultation model to manage ischemic stroke.

Intravenous Thrombolysis in Acute Ischemic Stroke After Idarucizumab Reversal of Dabigatran Effect: Analysis of the Cases From Taiwan.

BACKGROUND: Asians with atrial fibrillation carry a higher risk of ischemic stroke than non-Asians even under treatment of nonvitamin K antagonist oral anticoagulants. The purpose of the study was to observe the feasibility of intravenous thrombolytic therapy after administering a reversal agent, idarucizumab, in dabigatran-treated patients with acute ischemic stroke in Taiwan. METHODS: Dabigatran-treated patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) after idarucizumab reversal were enrolled in the retrospective nationwide study. The clinical data, treatment course, and outcomes were recorded. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. Any intracerebral hemorrhage (ICH) after rt-PA was detected by neuroimaging studies. RESULTS: Ten dabigatran-treated patients (6 men, mean age 71.10 ± 7.96 years) with acute ischemic stroke were included. Before stroke, the mean CHA2DS2-VASc score was 4.50 ± 1.57 and 8 patients (80%) received dabigatran 110 mg twice daily. All patients were treated with 5 g idarucizumab, following which the activated partial thromboplastin time normalized. Intravenous rt-PA (mean dose .78 mg/kg) was initiated a mean time of 11.11 minutes after idarucizumab infusion. The NIHSS score improved significantly after thrombolysis (16.0 ± 6.67 at admission to 9.38 ± 4.75 at discharge, P = .016). ICH developed in 3 patients (30%). Two of them were asymptomatic and 1 patient suffered from symptomatic ICH leading to mortality. CONCLUSION: Our data reconfirmed the feasibility of intravenous rt-PA for Asian stroke patients after reversal of dabigatran effect with idarucizumab.

A case control study on family history as a risk factor for herpes zoster and associated outcomes, Beijing, China.

BACKGROUND: Hospital-based case control studies have found family history of herpes zoster (HZ) was associated with risk of HZ, but the role of family history is not fully examined for other HZ-associated outcomes such as recurrent HZ, occurrence of postherpetic neuralgia (PHN), and HZ with different pain severities. METHODS: We conducted a population-based matched case control study. HZ cases that occurred during December 1, 2011 to November 30, 2012 were identified by face-to-face interview with all residents of eight selected communities/villages from three districts of Beijing, China. Medical records were reviewed for those who sought healthcare for HZ. For each case-patient, three, age-matched controls (±5 years) without HZ were enrolled from the same community/village of the matched case. Data on family history of HZ were collected by interview and only defined among first-degree relatives. RESULTS: A total of 227 case-patients and 678 matched controls were enrolled. Case-patients were more likely to report a family history of HZ [odds ratio (OR) =2.4, P = 0.002]. Compared with controls, association of family history decreased from HZ with PHN to HZ without PHN (OR = 6.0 and 2.3, respectively; P = 0.002 for trend), from recurrent HZ to primary HZ (OR = 9.4 and 2.2, respectively; P = 0.005 for trend), and from HZ with moderate or severe pain to HZ with mild or no pain (OR = 3.2 and 0.8, respectively; P < 0.001 for trend). CONCLUSIONS: Family history of HZ was associated with HZ occurrence and was more likely in HZ case-patients with PHN, recurrences, and painful HZ.

Safety of intravenous thrombolysis for ischaemic stroke in Asian octogenarians and nonagenarians.

BACKGROUND: symptomatic intracerebral haemorrhage (ICH) is a major concern of intravenous thrombolysis (IVT) for ischaemic stroke. Asians are considered more vulnerable to ICH than non-Asians. Reports on safety of IVT for Asian octogenarians and nonagenarians are limited. AIMS: the aims of our study were to compare the safety of IVT between octogenarians and nonagenarians and between Asian and Western patients. METHODS: patients receiving IVT for ischaemic stroke were prospectively registered from four hospitals in Taiwan. Octogenarians and nonagenarians were recruited for analysis. The primary safety outcome measure was symptomatic ICH. The secondary outcome measure was 3-month mortality. We searched the literature on IVT for ischaemic stroke for comparison. RESULTS: from January 2007 to December 2012, a total of 186 (18.3%) ischaemic stroke patients aged 80 and older, including 166 octogenarians and 20 nonagenarians, were recruited from 1,018 patients receiving IVT. Nine (4.8%) of recruited patients had symptomatic ICH, all in the octogenarian group (5.4%). Three-month mortality was 14.1% in recruited patients and without difference between the two age groups (P = 0.558). The results were comparable with reports on Western octogenarians and nonagenarians in the literature. CONCLUSION: octogenarians and nonagenarians receiving IVT have a similar safety outcome. Asian octogenarians and nonagenarians receiving IVT for ischaemic stroke are not at higher risk of symptomatic ICH and mortality than Western patients.

A clinical decision support tool to screen health records for contraindications to stroke thrombolysis-a pilot study.

BACKGROUND: The use of intravenous thrombolysis for stroke is limited by contraindications that may be difficult to identify promptly and accurately. Evidence supports the use of information technology-based clinical decision support (CDS) tools to achieve improvements in care delivery. The objective of this pilot study was to investigate the efficacy of a CDS tool to screen health records for contraindications to intravenous stroke thrombolysis. METHODS: A CDS tool was developed to rapidly screen health information in seven affiliated hospitals for contraindications to stroke thrombolysis. A fixed-sequence, 2-period crossover study was conducted to test the efficacy of the CDS tool. Four mock patient records derived from the stroke registry that contained a total of nine contraindication items in two or more of the hospitals were used for testing purposes. The test patients were preset and balanced between groups with and without the CDS tool appearing six times in each group before recruiting the participating physicians. Physicians who were responsible for thrombolytic therapy and willing to sign informed consent were recruited. The participating physicians were asked to check a list of contraindications for two of the patients by using a shared electronic medical record system among the seven hospitals with and without the CDS tool. The test time and missed contraindications were recorded and analyzed statistically. RESULTS: A total of 14 physicians who were responsible for stroke thrombolysis were approached, and 12 signed informed consent and took the test. By using the CDS tool, the test time was reduced significantly from 14.6 ± 7.4 to 7.3 ± 5.2 min (P = 0.010). In a total of 54 contraindications, the number of missed contraindications was reduced significantly from 23 (42.6 %) to seven (13.0 %) (P = 0.001). The difference of missed contraindication number between the two groups was statistically significant either per physician or per contraindication item. CONCLUSIONS: By screening health records for relevant contraindications, the use of a CDS tool may reduce the time needed to review medical records and reduce the number of missed contraindications for stroke thrombolysis.

Time cost of a nonclosing intravenous thrombolysis service for acute ischemic stroke.

BACKGROUND/PURPOSE: Intravenous thrombolysis for ischemic stroke saves societal costs. The aim of this study was to investigate the cost burden that hospitals may shoulder. METHODS: Stroke code activations between May 2009 and April 2011 were recorded and divided into groups based on work and duty time, as well as the period of the day or season. "Time cost of nonclosing service" (TCNS) per stroke code activation or intravenous thrombolysis treatment was calculated by dividing the time by the number of activations or thrombolysis treatments during that period. Comparisons were made among groups. RESULTS: There were a total of 634 stroke code activations in a period of 2 years, and intravenous thrombolysis was used in 132 (20.8%) of these cases. The rates of thrombolysis were not statistically different between the groups. Overall, the average TCNS for the stroke team was 27.6 hours per code activation and 132.7 hours per thrombolysis treatment. The TCNS during duty time was 1.38 times that during work time per stroke code activation and 1.46 times per thrombolysis treatment. In summer, the TCNS was 1.6 times that in winter per code activation and 2.2 times per thrombolysis treatment. During the late night hours, the TCNS was four times that of early night hours per code activation and 9.8 times per thrombolysis treatment. CONCLUSION: Our results demonstrate a large variation in the time cost of a nonclosing service for intravenous thrombolysis. Payment based on piece-rate compensation may not be appropriate and requires improvement.

Domino reaction of arylglyoxals with pyrazol-5-amines: selective access to pyrazolo-fused 1,7-naphthyridines, 1,3-diazocanes, and pyrroles.

New multicomponent domino reactions of arylglyoxals with pyrazol-5-amines have been established, providing selective access to unprecedented pyrazolo-fused 1,7-naphthyridines, 1,3-diazocanes, and pyrroles (up to 52 examples). The unreported dipyrazolo-fused 1,7-naphthyridines were regioselectively synthesized through a special double [3 + 2 + 1] heteroannulation accompanied by direct C-C formation between two electrophilic sites of arylglyoxals. The unusual [3 + 3 + 1 + 1] cyclization resulted in 20 examples of novel dipyrazolo-fused 1,3-diazocanes, whereas pyrrolo[2,3-c]pyrazoles were obtained in good yields by varying arylglyoxals 1 and pyrazol-5-amines 2 in the ratio 1:2. Mechanisms of formation of these three new types of heterocycles are also proposed.

The interpretable machine learning model associated with metal mixtures to identify hypertension via EMR mining method.

There are limited data available regarding the connection between hypertension and heavy metal exposure. The authors intend to establish an interpretable machine learning (ML) model with high efficiency and robustness that identifies hypertension based on heavy metal exposure. Our datasets were obtained from the US National Health and Nutrition Examination Survey (NHANES, 2013-2020.3). The authors developed 5 ML models for hypertension identification by heavy metal exposure, and tested them by 10 discrimination characteristics. Further, the authors chose the optimally performing model after parameter adjustment by Genetic Algorithm (GA) for identification. Finally, in order to visualize the model's ability to make decisions, the authors used SHapley Additive exPlanation (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) algorithm to illustrate the features. The study included 19 368 participants in total. A best-performing eXtreme Gradient Boosting (XGB) with GA for hypertension identification by 16 heavy metals was selected (AUC: 0.774; 95% CI: 0.772-0.776; accuracy: 87.7%). According to SHAP values, Barium (0.02), Cadmium (0.017), Lead (0.017), Antimony (0.008), Tin (0.007), Manganese (0.006), Thallium (0.004), Tungsten (0.004) in urine, and Lead (0.048), Mercury (0.035), Selenium (0.05), Manganese (0.007) in blood positively influenced the model, while Cadmium (-0.001) in urine negatively influenced the model. Study participants' hypertension associated with heavy metal exposure was identified by an efficient, robust, and interpretable GA-XGB model with SHAP and LIME. Barium, Cadmium, Lead, Antimony, Tin, Manganese, Thallium, Tungsten in urine, and Lead, Mercury, Selenium, Manganese in blood are positively correlated with hypertension, while Cadmium in blood is negatively correlated with hypertension.

Iron deficiency with or without anemia impairs prepulse inhibition of the startle reflex.

Iron deficiency (ID) during early life causes long-lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early-life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus-specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT-1). Our second model used a classic rat dietary-based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT-1 knockout model displayed reduced long-term potentiation (LTP) and elevated paired-pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia.

Synthesis of highly functionalized macrocycles by tandem multicomponent reactions and intramolecular Sonogashira cross-coupling.

An efficient chemoselective process for the synthesis of 14- and 15-membered triazole-containing macrocycle compounds has been developed through the combination of two multicomponent reactions and an intramolecular Sonogashira cross-coupling reaction.

Tetramethylpyrazine attenuates atherosclerosis development and protects endothelial cells from ox-LDL.

PURPOSE: We assessed whether tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii Franchat, attenuates atherosclerosis (AS) development in rabbits and protects endothelial cells injured by ox-LDL. METHODS: In vivo, rabbits subjected to atherosclerosis were treated with TMP (75 and 150 mg/kg) by oral gavage for 12 weeks. In vitro, rat aortic endothelial cells (RAECs) were stimulated by ox-LDL. RESULTS: TMP treatment with 75 and 150 mg/kg significantly reduced the relative atherosclerosis area ratio in the aorta (0.41 ± 0.042, 0.27 ± 0.047 vs. 0.66 ± 0.058 in AS), the ratio of intimal/medial thickness (0.54 ± 0.09, 0.39 ± 0.07 vs. 1.1 ± 0.3 in AS) and the number of monocytes in intimal (10.1 ± 2.8, 8.2 ± 2.0 vs. 14.1 ± 4.9 counts/mm(2) in AS). TMP also decreased levels of TC (15 ± 4.2 to 6.1 ± 1.2 mmol/L), TG (1.8 ± 0.3 to 1.08 ± 0.24 mmol/L), LDL-C (20.1 ± 4.3 to 10.2 ± 1.6 mmol/L) and increased HDL-C levels (0.40 ± 0.08 to 0.85 ± 0.17 mmol/L) in atherosclerosis rabbit plasma. TMP decreased the MCP-1 (187.3 ± 38.4 to 86.1 ± 17.2 pg/ml) and ICAM-1 (350.6 ± 43.7 to 260.6 ± 46.1 pg/ml) levels in plasma and inhibited LOX-1 expression in the rabbit aortas. Moreover, our in vitro study revealed that TMP suppressed monocyte adhesion to RAECs, inhibited RAEC migration, and down-regulated MCP-1 and ICAM-1 expression in ox-LDL-injured RAECs. Likewise, TMP inhibited LOX-1 and 5-LOX expression, and prevented nuclear accumulation of RelA/p65 and IκB degradation in ox-LDL-injured RAECs. Furthermore, TMP suppressed ox-LDL-induced activations of p-ERK, p-p38, and p-JNK MAPK. CONCLUSION: TMP produces a tangible protection in atherosclerosis and endothelial cells. TMP might be a potential protective agent for atherosclerosis.

Synthesis of novel isoquinolinone and 1,2-dihydroisoquinoline scaffolds via Ugi reaction and ring opening reaction of furans.

Combining the Ugi reaction with ring opening reaction of furans for the synthesis of novel isoquinolinone and 1,2-dihydroisoquinoline scaffolds has been developed. The isoquinolinone and 1,2-dihydroisoquinoline derivatives with unsaturated carbonyl moiety may open up many opportunities for further functionalizations.

In-hospital case management to increase anticoagulation therapy for stroke patients with atrial fibrillation: a hospital-based registry.

BACKGROUND/PURPOSE: Anticoagulation is underused for stroke patients with atrial fibrillation in Taiwan. An effective preventive measure is in great need of improvement. METHODS: In-hospital case management was implemented to monitor the diagnosis of atrial fibrillation and the use of warfarin. Timely feedback to treating physicians was made. Change in performance after the implementation was analyzed. RESULTS: A total of 2754 patients hospitalized for acute ischemic stroke or transient ischemic attack were included, 1216 before and 1538 after the intervention. The percentage of patients without electrocardiography examination decreased from 8.7% to 2.9% (p < 0.001). The diagnosis of atrial fibrillation increased from 11.5% (n = 140) to 15.9% (n = 244) (p = 0.001). The use of warfarin at discharge increased from 36.9% to 54.7% (p = 0.001). In-hospital case management was significantly related to the use of warfarin (odds ratio = 2.47, p < 0.001). The percentage of warfarin use was still significantly higher in the intervention group at 3 months of follow-up (45.9% vs. 27.8%, p = 0.002) and at 6 months of follow up (49.2% vs. 28.6%, p = 0.004). More patients' international normalized ratio was within the recommended range in the intervention group at 6 months' follow-up (30.5% vs. 9.1%, p = 0.039). CONCLUSION: Our study indicates that in-hospital case management may be an effective strategy to improve anticoagulation for eligible stroke patients.

[Analysis of measles immunity level in persistent populations in Beijing, 2012].

OBJECTIVE: To analyze the measles immunity level of persistent population in Beijing. METHODS: A total of 2125 objects from 10 age groups, who had been living in Beijing for over 6 months, were selected from urban and rural areas in Beijing in 2012. Demographic characteristics, history of measles and vaccine immunization were investigated by questionnaire. 5 ml blood sample of each subject was collected, and the Measles IgG antibody was measured by ELISA assay. RESULTS: Positive rate of measles antibody was 84.71% (1800/2125) and standardized positive rate was 88.07% . Median of antibody was 960.46 IU/L. Positive rate and median of measles antibody were significantly different between population from different age groups (χ(2) = 341.60, P < 0.01; H = 216.27, P < 0.01). Antibody positive rate and median were lowest in the <1 year age group, which were separately 43.06% (90/209) and 185.80 IU/L; and highest in the 1-4 (97.31% (181/186) and 2448.81 IU/L) and 5-9 years age group (96.46% (218/226) and 1910.72 IU/L). The range of antibody positive rate and median in adults of ≥ 15 years were 81.98%-90.14% and 744.38-1474.84 IU/L. Antibody positive rate and median in persistent population, which were separately 82.45% (883/1071) and 899.82 IU/L, were lower than those in migrant population, which were 87.00% (917/1054) and 166.19 IU/L, respectively (χ(2) = 8.51, P < 0.01;U = 538 704.00, P < 0.01). Antibody positive rate and median in population with vaccination history, which were separately 91.95% (891/969) and 1443.11 IU/L, were higher than those population without vaccination history and people whose history unknown (32.95% (57/173) , 127.33 IU/L; 86.67% (852/983) , 923.73 IU/L). The difference showed statistical significance (χ(2) = 399.92, P < 0.01; H = 202.11, P < 0.01). CONCLUSION: Among the persistent population in China, measles antibody level among the children aging 1-9 years old was high enough to prevent outbreak and epidemic of measles. However, we should try our best to strengthen the measles antibody level among the babies younger than 1 year old and the migrant population aging between 15 and 40 years old.

Cost supervision mining from EMR based on artificial intelligence technology.

BACKGROUND: To effectively monitor medical insurance funds in the era of big data, the study tries to construct an inpatient cost rationality judgement model by designing a virtuous cycle of inpatient cost supervision information system and exploring a complete set of inpatient cost supervision methods. OBJECTIVE: To lay the foundation for applying artificial intelligence (AI) technology in medical insurance cost control supervision and provide feasible paths and available tools for medical insurance cost control managers. METHODS: By way of collecting and cleaning electronic medical record (EMR) data from 2016 to 2018 of a city in East China, focusing on basic patient information and cost information, and using a combination of machine learning modeling and information system construction, the study tries to form a feasible inpatient cost supervision method and operation path. RESULTS: The set of the regulatory method, applied in nursing homes of a city in East China, is compelling. The accuracy rates of rationality judgement in different main diseases are stable up to 80%, the false positive rate is steady within 10%, and rehabilitation fee days of hospitalization, and the number of complications are important factors affecting the rationality of the inpatient cost. CONCLUSION: The model construction and optimization method combining machine learning and information system can make practical cost rationality judgement on medical institution's inpatient cost data, which can directly reflect the key influencing factors of relevant inpatient costs, and achieve the effect of guiding medical behavior and improving the efficiency of medical insurance fund use.

IDENTIFICATION OF SUBPHENOTYPES OF SEPSIS-ASSOCIATED LIVER DYSFUNCTION USING CLUSTER ANALYSIS.

ABSTRACT: Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, ß, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype ß (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.

Tf2O/DMSO-mediated dual activation of aryl phosphinate to access various aryl phosphonates.

A metal-free method for the dual activation of aryl phosphinate has been developed; the P-H and P-O bonds are sequentially activated by the Tf2O/DMSO system. Without the requirement of metals and unstable P-reagents, this one-pot procedure provides a convenient and practical access to a variety of aryl phosphonates. A mechanism involving twice generation of electrophilic P-species and two SN-processes is proposed on the basis of the control experiments.

TrkB as a potential synaptic and behavioral tag.

Late-phase long-term potentiation (L-LTP), a cellular model for long-term memory (LTM), requires de novo protein synthesis. An attractive hypothesis for synapse specificity of long-term memory is "synaptic tagging": synaptic activity generates a tag, which "captures" the PRPs (plasticity-related proteins) derived outside of synapses. Here we provide evidence that TrkB, the receptor of BDNF (brain-derived neurotrophic factor), may serve as a "synaptic tag." TrkB is transiently activated by weak theta-burst stimulation (TBS) that induces only early-phase LTP (E-LTP). This TrkB activation is independent of protein synthesis, and confined to stimulated synapses. Induction of L-LTP by strong stimulation in one synaptic pathway converts weak TBS-induced E-LTP to L-LTP in a second, independent pathway. Transient inhibition of TrkB around the time of weak TBS to the second pathway diminished L-LTP in that pathway without affecting the first one. Behaviorally, weak training, which induces short-term memory (STM) but not LTM, can be consolidated into LTM by exposing animals to novel but not familiar environment 1 h before training. Inhibition of TrkB during STM training blocked such consolidation. These results suggest TrkB as a potential tag for synapse-specific expression of L-LTP and LTM.

Covid-19 vaccine effectiveness during Omicron BA.2 pandemic in Shanghai: A cross-sectional study based on EMR.

Large-scale vaccination against the spread and mutation of COVID-19 is being implemented in many countries. We aimed to assess the effectiveness of certain vaccines (87.35% inactivated), mainly Sinovac - CoronaVac and Sinopharm (Beijing) - BBIBP-CorV, during the Omicron BA.2 pandemic by cross-sectional study. The study was conducted in a cabin hospital of Shanghai, China. A total of 1194 Covid-19 patients infected with Omicron BA.2 were enrolled and epidemiological survey information was collected from the subjects through electronic medical records and questionnaires, from March 23th to April 1st in 2022. Vaccine effectiveness was reflected by the occurrence of multi-dimensional symptoms while adjusting for confounding variables. In the unstandardized vaccinated group, the Covid-19 vaccine effectiveness of Omicron BA.2 in the male group was higher than in the female group (P = .0171). In the standardized vaccinated group, vaccine effectiveness in [20, 40) age group was higher than in other age groups (P = .0002). Adjusting for gender and age, Covid-19 vaccine effectiveness of Omicron BA.2 at the specific level was 87.42% (95% confidence interval [CI], 72.35-94.28, P < .0001), and 62.65% (95% CI, 1.47-85.84, P = .047) in the unstandardized vaccinated and the standardized vaccinated group, respectively. Covid-19 vaccine effectiveness of Omicron BA.2 was not apparent at the general level but remained effective for the specific symptom. Further development for the Covid-19 vaccine is necessary.