Neurochemical Predictors of Generalized Learning Induced by Brain Stimulation and Training.

Methods of cognitive enhancement for humans are most impactful when they generalize across tasks. However, the extent to which such "transfer" is possible via interventions is widely debated. In addition, the contribution of excitatory and inhibitory processes to such transfer is unknown. Here, in a large-scale neuroimaging individual differences study with humans (both sexes), we paired multitasking training and noninvasive brain stimulation (transcranial direct current stimulation, tDCS) over multiple days and assessed performance across a range of paradigms. In addition, we varied tDCS dosage (1.0 and 2.0 mA), electrode montage (left or right prefrontal regions), and training task (multitasking vs a control task) and assessed GABA and glutamate concentrations via ultrahigh field 7T magnetic resonance spectroscopy. Generalized benefits were observed in spatial attention, indexed by visual search performance, when multitasking training was combined with 1.0 mA stimulation targeting either the left or right prefrontal cortex (PFC). This transfer effect persisted for ∼30 d post intervention. Critically, the transferred benefits associated with right prefrontal tDCS were predicted by pretraining concentrations of glutamate in the PFC. Thus, the effects of this combined stimulation and training protocol appear to be linked predominantly to excitatory brain processes.

Stimulating prefrontal cortex facilitates training transfer by increasing representational overlap.

A recent hypothesis characterizes difficulties in multitasking as being the price humans pay for our ability to generalize learning across tasks. The mitigation of these costs through training has been associated with reduced overlap of constituent task representations within frontal, parietal, and subcortical regions. Transcranial direct current stimulation, which can modulate functional brain activity, has shown promise in generalizing performance gains when combined with multitasking training. However, the relationship between combined transcranial direct current stimulation and training protocols with task-associated representational overlap in the brain remains unexplored. Here, we paired prefrontal cortex transcranial direct current stimulation with multitasking training in 178 individuals and collected functional magnetic resonance imaging data pre- and post-training. We found that 1 mA transcranial direct current stimulation applied to the prefrontal cortex paired with multitasking training enhanced training transfer to spatial attention, as assessed via a visual search task. Using machine learning to assess the overlap of neural activity related to the training task in task-relevant brain regions, we found that visual search gains were predicted by changes in classification accuracy in frontal, parietal, and cerebellar regions for participants that received left prefrontal cortex stimulation. These findings demonstrate that prefrontal cortex transcranial direct current stimulation may interact with training-related changes to task representations, facilitating the generalization of learning.

Teaching practice and teachingof cell biology experiments for oversea medical students / 中华医学教育探索杂志

The teaching practiceof cell biology experiments for oversea medical students in School of Medicine of Tongji University was reported in the present article, and the teaching principles of careful plan, clear contents, concise textbook, flexible scheme, full preparation, earnest trial-lecture, orderly implementation and formative assessment were put forward.Based on the different teaching object, the paper mainly explained the differences and the basis of the experimental teaching process of the foreign students and the domestic medical students to provide experience for improving the teaching mode of this kind of course.

Optimum dose of oxycodone for anesthesia when combined with propofol in patients undergoing induced abortion / 中华麻醉学杂志

Objective To determine the optimum dose of oxycodone for anesthesia when combined with propofol in the patients undergoing induced abortion.Methods Three hundred patients, aged 18-40 yr, weighing 40-70 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , undergoing elective induced abortion, were randomly divided into 6 groups (n =50 each) using a random number table: fentanyl group (group F) and different doses of oxycodone groups (Q1-5 groups).In group F, fentanyl 1 μg/kg was intravenously injected.In Q1-5 groups, oxycodone hydrochloride 20, 40, 60, 100 and 150 μg/kg were intravenously injected, respectively.Propofol 2.5 mg/kg was intravenously injected 1 min later in all the patients, and the operation was started when the eyelash reflex disappeared.The occurrence of hypotension, bradycardia, body movement and respiratory depression during operation, and nausea and vomiting within 4 h after operation were recorded.The uterine contraction pain was assessed with numerical rating scale (NRS) at 30 min, 1 h and 4 h after operation.Patient's satisfaction was evaluated at 1 and 4 h after operation.Results With the prolongation of time, NRS score was gradually increased, and the degree of patient's satisfaction was gradually decreased in group F (P＜0.05).With the prolongation of time,NRS score was gradually decreased, and the degree of patient's satisfaction was gradually increased in Q1-2 groups (P＜0.05).There was no significant difference in NRS score and degree of patient's satisfaction between Q3-5 groups (P＞0.05).Compared with group F, NRS score was significantly decreased, and the degree of patient's satisfaction was increased at 4 h after operation in Q1-5 groups (P＜0.05).Compared with Q1-2 groups, NRS score was significantly decreased at 30 min and 4 h after operation, and the degree of patient's satisfaction was increased at 4 h after operation in Q3-5 groups (P＜0.05).Among the Q1-5 groups,the incidence of respiratory depression, body movement, and nausea and vomiting was the lowest in group Q4 (P＜0.05).Conclusion When combined with propofol, the optimum dose of oxycodone for anesthesia is 100 μg/kg in the patients undergoing induced abortion.

A Comparison of Job Satisfaction among Filipino Nurses Employed in the Philippines and Overseas

@#<p><strong>BACKGROUND AND OBJECTIVE:</strong> The shortage of nurses has led to increasing competition in the recruitment and retention of nurses globally. According to literature, retention of nurses is correlated with job satisfaction, making it an important topic for research. This study compared the level of general, intrinsic, and extrinsic job satisfaction of Filipino nurses employed locally and overseas. It identified the major motivators and problems that affect their job satisfaction.</p><p><strong>METHODS AND RESEARCH PARTICIPANTS:</strong> Eighty-four nurses were surveyed using the Minnesota Satisfaction Questionnaire. Fifty-five were locally-employed, while 29 were overseas Filipino nurses. The Mann-Whitney U Test was used to determine the significant difference in the level of satisfaction among the two groups. Answers on the open-ended questions were used to validate the quantitative data.</p><p><strong>RESULTS:</strong> The results showed that Filipino nurses employed both locally and overseas have an average level of general satisfaction. Both groups also showed a high degree of intrinsic satisfaction and an average degree of extrinsic satisfaction. There is no significant difference found in the level of general, intrinsic, and extrinsic job satisfaction of locally and overseas employed Filipino nurses.</p><p><strong>CONCLUSION:</strong> The study found that social service, an intrinsic factor, is the major motivating force of job satisfaction. Workload, an extrinsic factor, is the most common problem encountered for both groups of nurses. Salary serves as one of the factors that keeps Filipino nurses overseas satisfied, while it is one of the factors that causes dissatisfaction among locally-employed nurses.</p>

Nanometer detection of self-assembly morphology of sodium hyaluronate injection on mica / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the self-assembly morphology of sodium hyaluronate injection on mica using atomic force microscopy(AFM).</p><p><b>METHODS</b>Atomic force microscopy with nanometer resolution was used to observe the self-assembly morphology of different concentrations of sodium hyaluronate injection on mica at room temperature.</p><p><b>RESULTS</b>The self-assembly morphology of 0.001, 0.01, and 0.1 mg/ml sodium hyaluronate injection on mica featured piebald, reticular and dendritic structures, respectively. At 1 and 5 mg/ml, sodium hyaluronate injection displayed bacilliform and spherical structures on mica, respectively; the diameter and height of the particles of 5 mg/ml sodium hyaluronate was 197.97±78.48 nm and 30.79±18.67 nm, significantly greater than those of 0.1 mg/ml sodium hyaluronate injection (49.52±11.93 nm and 5.37±1.59 nm, respectively, P<0.05).</p><p><b>CONCLUSION</b>The self-assembly morphology of sodium hyaluronate injection on mica varies with its concentration. The piebald and reticular structure may facilitate the function of sodium hyaluronate, and the dendritic feature resembles the representative model of diffusion-limited aggregation (DLA).</p>

Evaluation of transcutaneous electroacupoint stimulation with the train-of-four mode for preventing nausea and vomiting after laparoscopic cholecystectomy / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of transcutaneous electroacupoint stimulation with a train-of-four (TOF) mode for the prevention of postoperative nausea and vomiting (PONV) in the patients undergoing laparoscopic cholecystectomy.</p><p><b>METHODS</b>Ninety-six ASA Grade I - II patients scheduled for laparoscopic cholecystectomy were randomized into Neiguan (P6) electroacupoint stimulation group (treated group) and a placebo control group (placement of electrodes without electroacupoint stimulation). The anesthetic regimen was standardized by needling at Neiguan on the left side and connecting the TOF peripheral nerve stimulator. The incidence of nausea, vomiting, severity, antiemetic dosage and the degree of pain were assessed at 0, 60, 120 min, and 24 h after surgery.</p><p><b>RESULTS</b>The incidence of nausea and vomiting, the dose of antiemetics and the occurrence of severe nausea were all significantly lower in the treated group compared with the control group and the score for pain was obviously reduced in patients of the treated group at 24 h post-operation (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Transcutaneous electroacupoint stimulation at P6 with the TOF mode could reduce the incidence and severity of nausea and vomiting with analgesic effects.</p>

Casirivimab and Imdevimab Treatment in Seropositive, Hospitalized COVID-19 Patients With Non-neutralizing or Borderline Neutralizing Antibodies

We conducted a post-hoc analysis in seropositive patients who were negative or borderline for functional neutralizing antibodies (nAbs) against SARS-CoV-2 at baseline from a phase 1/2/3 trial of casirivimab and imdevimab (CAS+IMD) treatment in hospitalized COVID-19 patients on low-flow or no supplemental oxygen prior to the emergence of Omicron-lineage variants. Patients were randomized to a single dose of 2.4 g CAS+IMD, 8.0 g CAS+IMD, or placebo. Patients seropositive for anti-SARS-CoV-2 antibodies at baseline were analyzed by their baseline nAb status. At baseline, 20.6% (178/864) of seropositive patients were negative/borderline for nAbs. CAS+IMD reduced viral load in patients who were negative/borderline for nAbs versus placebo, but not in patients who were positive for nAbs. We observed a trend in reduction of the proportion of patients who died or required mechanical ventilation (MV), as well as in all-cause mortality, by day 29 with CAS+IMD versus placebo in patients who were negative/borderline for nAbs. In those who were negative/borderline for nAbs, the proportions who died/needed MV from days 1-29 were 19.1% and 10.9%, and the proportions of patients who died from days 1-29 were 16.2% and 9.1%, in the placebo and CAS+IMD combined dose groups, respectively. No measurable harm or benefit in death/MV or all-cause mortality was observed in patients who were positive for nAbs. In hospitalized COVID-19 patients on low-flow or no supplemental oxygen, CAS+IMD reduced viral load, the risk of death or MV, and all-cause mortality in seropositive patients who were negative/borderline for nAbs. ImportanceThe clinical benefit of CAS+IMD in hospitalized seronegative patients with COVID-19 has previously been demonstrated, although these studies observed no clinical benefit in seropositive patients. As the prevalence of SARS-CoV-2 seropositive individuals rises due to both vaccination and previous infection, it is important to understand whether there is a subset of hospitalized patients with COVID-19, who have antibodies against SARS-CoV-2, who could benefit from anti-SARS-CoV-2 monoclonal antibody treatment. This post-hoc analysis demonstrates that there is a subset of hospitalized, seropositive patients with inadequate SARS-CoV-2 nAbs (ie, those who were negative or borderline for nAbs) who may still benefit from CAS+IMD treatment if infected with a susceptible variant. Therefore, utilizing seronegativity status alone to guide treatment decisions for patients with COVID-19 may fail to identify seropositive patients who could benefit from anti-SARS-CoV-2 monoclonal antibody therapies which retain activity against circulating strains, depending on how effectively their endogenous antibodies neutralize SARS-CoV-2.

Common genetic variants identify therapeutic targets for COVID-19 and individuals at high risk of severe disease

SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that a rare variant (MAF = 0.3%, odds ratio 0.60, P=4.5x10-13) that down-regulates ACE2 expression reduces risk of COVID-19 disease, providing human genetics support for the hypothesis that ACE2 levels influence COVID-19 risk. Further, we show that common genetic variants define a risk score that predicts severe disease among COVID-19 cases.

Genetic association analysis of SARS-CoV-2 infection in 455,838 UK Biobank participants

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, with results publicly browsable at https://rgc-covid19.regeneron.com.