Supporting and retaining competent primary care workforce in low-resource settings: lessons learned from a prospective cohort study.

OBJECTIVE: Assess whether local health facilities can adequately support the performance of general practitioners (GPs) trained by China's national compulsory services programme (CSP). DESIGN: Prospective cohort study. SETTING: Health facilities in middle and western rural areas in China, 2015-2022. PARTICIPANTS: Cohorts of CSP graduates from 2015 to 2019 in four major medical universities. MAIN OUTCOMES: Job performance measured by a 12-item Job Performance Scale; productivity measured by outpatient volume per day; turnover measured by ever changing jobs within the past year. RESULTS: 91.2%, 92.0% and 90.5% GPs working in township health centres reported inadequate medication, equipment and external assistance from higher level hospitals, while CSP graduates working in secondary or tertiary hospitals reported a lower rate of less than 60%. The top three tests reported as lacking were blood gases (67.7%), microbiology (61.6%) and cancer biomarkers (49.7%); the top three lacked procedures were CT scan (64.8%), MRI scan (58.1%) and ambulatory BP monitoring (55.8%); and the top three lacked drugs were drugs for cardiovascular diseases (23.3%), systematic hormonal preparations (17.7%) and traditional Chinese medicines (13.0%). Multivariable analysis showed that facility support was positively associated with job performance-adequate medication increased job performance by 2.2 points (95% CI 0.7 to 3.8), and adequate external assistance increased job performance by 3.3 points (95% CI 1.8 to 4.8). Facility support was also positively associated with productivity-adequate medication increased outpatients seen per day by 20% (95% CI 0.1 to 0.3), and adequate equipment increased outpatients seen per day by 12% (95% CI 0.0 to 0.2). Facility support did not have significant impact on turnover, but GPs who changed jobs in the past year were 1.9-2.3 times more likely to report adequate facility support. CONCLUSION: GPs in township health centres experienced a high prevalence of shortage in facility support. The identification of a positive association between facility support and performance and productivity has implications for future research and resources deployment in primary healthcare.

Cortical Contributions to Imagined Power Grip Task: An EEG-Triggered TMS Study.

Previous studies have demonstrated that motor imagery leads to desynchronization in the alpha rhythm within the contralateral primary motor cortex. However, the underlying electrophysiological mechanisms responsible for this desynchronization during motor imagery remain unclear. To examine this question, we conducted an investigation using EEG in combination with noninvasive transcranial magnetic stimulation (TMS) during index finger abduction (ABD) and power grip imaginations. The TMS was administered employing diverse coil orientations to selectively stimulate corticospinal axons, aiming to target both early and late synaptic inputs to corticospinal neurons. TMS was triggered based on the alpha power levels, categorized in 20th percentile bins, derived from the individual alpha power distribution during the imagined tasks of ABD and power grip. Our analysis revealed negative correlations between alpha power and motor evoked potential (MEP) amplitude, as well as positive correlations with MEP latency across all coil orientations for each imagined task. Furthermore, we conducted functional network analysis in the alpha band to explore network connectivity during imagined index finger abduction and power grip tasks. Our findings indicate that network connections were denser in the fronto-parietal area during imagined ABD compared to power grip conditions. Moreover, the functional network properties demonstrated potential for effectively classifying between these two imagined tasks. These results provide functional evidence supporting the hypothesis that alpha oscillations may play a role in suppressing MEP amplitude and latency during imagined power grip. We propose that imagined ABD and power grip tasks may activate different populations and densities of axons at the cortical level.

Palladium-Catalyzed Multicomponent Cascade Reaction of 3-Hydroxypropionitrile: Synthesis of Substituted Dihydrochalcones.

Direct access to substituted dihydrochalcones from the easily available starting materials 3-hydroxypropionitrile derivatives and arylboronic acids is described. The procedure involves a multicomponent aryl addition/hydroxyl elimination/reduction Heck approach in the presence of a Pd catalyst with excellent functional group tolerance and a wide range of substrates. In addition, mixed 1,3-diarylation of 3-hydroxypropanenitrile using two arylboronic acids with different electronic properties was also achieved.

A copper complex that combats triple negative breast cancer by restraining angiogenesis.

Angiogenesis and metastasis are major factors affecting the growth and invasion of triple negative breast cancer (TNBC). A phenanthroline copper(II) complex CPT8 modified with an alkyl chain-linked triphenylphosphonium group showed potent antiproliferative activity against a series of cancer cells including TNBC MDA-MB-231 cells. CPT8 induced mitophagy through activation of PINK1/Parkin and BNIP3 pathways in cancer cells due to damage to mitochondria. More importantly, CPT8 reduced the tube formation ability of human umbilical vein endothelial cells (HUVEC) through downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-angiogenic potential of CPT8 was confirmed by decreased vascular endothelial growth factor (VEGF) and CD34 expression in HUVEC. Moreover, CPT8 suppressed the expression of vascular endothelial cadherin and matrix metalloproteinases MMP2 and MMP9, leading to the inhibition of vasculogenic mimicry formation. CPT8 also weakened the metastatic potential of MDA-MB-231 cells. Downregulation of Ki67 and CD34 expression indicates that CPT8 suppressed tumor proliferation and vascularization in vivo, thus providing a unique metal drug candidate for the treatment of TNBC.

Transferable multi-modal fusion in knee angles and gait phases for their continuous prediction.

Objective.The gait phase and joint angle are two essential and complementary components of kinematics during normal walking, whose accurate prediction is critical for lower-limb rehabilitation, such as controlling the exoskeleton robots. Multi-modal signals have been used to promote the prediction performance of the gait phase or joint angle separately, but it is still few reports to examine how these signals can be used to predict both simultaneously.Approach.To address this problem, we propose a new method named transferable multi-modal fusion (TMMF) to perform a continuous prediction of knee angles and corresponding gait phases by fusing multi-modal signals. Specifically, TMMF consists of a multi-modal signal fusion block, a time series feature extractor, a regressor, and a classifier. The multi-modal signal fusion block leverages the maximum mean discrepancy to reduce the distribution discrepancy across different modals in the latent space, achieving the goal of transferable multi-modal fusion. Subsequently, by using the long short-term memory-based network, we obtain the feature representation from time series data to predict the knee angles and gait phases simultaneously. To validate our proposal, we design an experimental paradigm with random walking and resting to collect data containing multi-modal biomedical signals from electromyography, gyroscopes, and virtual reality.Main results.Comprehensive experiments on our constructed dataset demonstrate the effectiveness of the proposed method. TMMF achieves a root mean square error of0.090±0.022s in knee angle prediction and a precision of83.7±7.7% in gait phase prediction.Significance.We demonstrate the feasibility and validity of using TMMF to predict lower-limb kinematics continuously from multi-modal biomedical signals. This proposed method represents application potential in predicting the motor intent of patients with different pathologies.

Gating at cortical level contributes to auditory-motor synchronization during repetitive finger tapping.

Sensory integration contributes to temporal coordination of the movement with external rhythms. How the information flowing of sensory inputs is regulated with increasing tapping rates and its function remains unknown. Here, somatosensory evoked potentials to ulnar nerve stimulation were recorded during auditory-cued repetitive right-index finger tapping at 0.5, 1, 2, 3, and 4 Hz in 13 healthy subjects. We found that sensory inputs were suppressed at subcortical level (represented by P14) and primary somatosensory cortex (S1, represented by N20/P25) during repetitive tapping. This suppression was decreased in S1 but not in subcortical level during fast repetitive tapping (2, 3, and 4 Hz) compared with slow repetitive tapping (0.5 and 1 Hz). Furthermore, we assessed the ability to analyze temporal information in S1 by measuring the somatosensory temporal discrimination threshold (STDT). STDT increased during fast repetitive tapping compared with slow repetitive tapping, which was negatively correlated with the task performance of phase shift and positively correlated with the peak-to-peak amplitude (% of resting) in S1 but not in subcortical level. These novel findings indicate that the increased sensory input (lower sensory gating) in S1 may lead to greater temporal uncertainty for sensorimotor integration dereasing the performance of repetitive movement during increasing tapping rates.

Behavior-Dependent Corticocortical Contributions to Imagined Grasping: a BCI-triggered TMS study.

Previous studies have indicated that corticocortical neural mechanisms differ during various grasping behaviors. However, the literature rarely considers corticocortical contributions to various imagined grasping behaviors. To address this question, we examine their mechanisms by transcranial magnetic stimulation (TMS) triggered when detecting event-related desynchronization during right-hand grasping behavior imagination through a brain-computer interface (BCI) system. Based on the BCI system, we designed two experiments. In Experiment 1, we explored differences in motor evoked potentials (MEPs) between power grip and resting conditions. In Experiment 2, we used the three TMS coil orientations (lateral-medial (LM), posterior-anterior (PA), and anterior-posterior (AP) directions) over the primary motor cortex to elicit MEPs during imagined index finger abduction, precision grip, and power grip. We found that larger MEP amplitudes and shorter latencies were obtained in imagined power grip than in resting.We also detected lower MEP amplitudes during imagined power grip, while MEP amplitudes remained similar across imagined precision grip and index finger abduction in each TMS coil orientation. Differences in AP-LM latency were longer when subjects imagined a power grip compared with precision grip and index finger abduction. Based on our results, higher cortical excitability may be achieved when humans imagine precision grip and index finger abduction. Our results suggests that higher cortical excitability may be achieved when humans imagine precision grip and index finger abduction. We also propose that preferential recruitment of late synaptic inputs to corticospinal neurons may occur when humans imagine a power grip.

Shengmai (a traditional Chinese herbal medicine) for heart failure.

BACKGROUND: Heart failure is a major public health problem worldwide. Shengmai (a traditional Chinese herbal medicine) has long been used as a complementary treatment for heart failure in China. OBJECTIVES: To determine the effects (both benefits and harms) of Shengmai plus usual treatment versus usual treatment alone for heart failure. SEARCH STRATEGY: We searched CENTRAL and DARE on The Cochrane Library (Issue 3, 2008), MEDLINE (1966 to August 2008), EMBASE (1984 to August 2008), AMED (1985 to August 2008) and BIOSIS (1997 to August 2008) and CBM (1978 to August 2008). We added two new Chinese databases for the update; VIP (1989 to September 2008) and CNKI (1979 to September 2008). We also handsearched Chinese journals. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials (RCTs) of Shengmai plus usual treatment versus usual treatment alone or Shengmai versus placebo for heart failure, irrespective of blinding status, were included. More stringent inclusion criteria were applied in this update and only studies that have a clear description of randomisation methods are classed as true RCTs and hence included. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed methodological quality and extracted data. Dichotomous and continuous data were calculated as relative risk (RR), and mean differences (MD) or standardized mean difference (SMD). Random-effect model and fixed-effect model were used to perform meta-analysis for with and without heterogeneity respectively. MAIN RESULTS: Only six RCTs with a total of 440 patients were included in this updated review. Compared to usual treatment alone, Shengmai plus usual treatment in five trials indicated an improvement in NYHA classification (RR 0.37; 95% CI 0.25 to 0.54). Other benefits were observed, but were limited to low patient numbers and significant heterogeneity: ejection fraction, cardiac output, stroke volume, exercise test and ratio of peak early to late diastolic filling velocity. Only one RCT with 40 patients compared Shengmai to placebo, and improvements were seen in stroke volume, Heath and Cardic index and myocardial contractility. Two studies reported mild adverse effects, but no patients were withdrawn or needed medication due to these adverse effects. AUTHORS' CONCLUSIONS: Shengmai may be beneficial for heart failure compared to placebo or plus usual treatment compared to usual treatment alone. However, long-term and more high quality studies are needed to provide clear evidence for the future use of Shengmai.