Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the aftereffects observed. Here, we examined whether single sessions of a 15 Hz rTMS protocol, administered at suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Six right-handed men were included in this pilot study. HF-rTMS was delivered over the right M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105-120% of the individual resting motor threshold (RMT). To assess safety, electromyography (EMG) was monitored to control for signs of spread of excitation and brief EMG burst (BEB) after stimulation. Additionally, TMS side effects questionnaires and the numeric rating scale (NRS) were administered during each session. We assessed corticospinal excitability (CSE) and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and box and blocks test (BBT) scores, respectively. Overall, the sessions were tolerated and feasible without any pain development. However, EMG analysis during 15 Hz rTMS administration revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between 15 Hz rTMS SI and rMEP increase. No significant changes were highlighted for motor performance measures. Although feasible and tolerable by the AB individuals tested, the results demonstrate that when administered at suprathreshold intensities (≥ 105% RMT) the 15 Hz rTMS protocol reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such combinations of high-intensity and high-frequency stimulation protocols. The results also give insight into the nonlinear existent relationship between the SI and HF-rTMS effects on CSE.NEW & NOTEWORTHY The results of this pilot study show the effects of a therapeutically promising 15 Hz repetitive transcranial magnetic stimulation (rTMS) protocol, administered at different suprathreshold intensities in able-bodied individuals. Although tolerable and feasible with a neuromodulatory potential, 15 Hz rTMS might result in persistent excitability that needs to be closely monitored if administered at suprathreshold stimulation intensity. These results reaffirm the importance of feasibility studies, especially in translational animal-to-human research.

Aging-induced alterations in EEG spectral power associated with graded force motor tasks.

BACKGROUND: It has been demonstrated that in young and healthy individuals, there is a strong association between the amplitude of EEG-derived motor activity-related cortical potential or EEG spectral power (ESP) and voluntary muscle force. This association suggests that the motor-related ESP may serve as an index of central nervous system function in controlling voluntary muscle activation Therefore, it may potentially be used as an objective marker to track changes in functional neuroplasticity due to neurological disorders, aging, and following rehabilitation therapies. To this end, the relationship between the band-specific ESP-combined spectral power of EEG oscillatory and aperiodic (noise) components-and voluntary elbow flexion (EF) force has been analyzed in elder and young individuals. METHODS: 20 young (22.6 ± 0.87 year) and 28 elderly (74.79 ± 1.37 year) participants performed EF contractions at 20%, 50%, and 80% of maximum voluntary contraction (MVC) while high-density EEG signals were recorded. Both the absolute and relative ESPs were computed for the EEG frequency bands of interest. RESULTS: The MVC force generated by the elderly was foreseeably lower than that of the young participants. Compared to young, the elderly cohort's (1) total ESP was significantly lower for the high (80% MVC) force task; (2) relative ESP in beta band was significantly elevated for the low and moderate (20% MVC and 50% MVC) force tasks; (3) absolute ESP failed to have a positive trend with force for EEG frequency bands of interest; and (4) beta-band relative ESP did not exhibit a significant decrease with increasing force levels. CONCLUSIONS: As opposed to young subjects, the beta-band relative ESP in elderly did not significantly decrease with increasing EF force values. This observation suggests the use of beta-band relative ESP as a potential biomarker for age-related motor control degeneration.

[Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina].

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 µg·g~(-1)) was higher than that in GFA(0.03-10.41 µg·g~(-1)) and GS(0.04-13.66 µg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.

[Interpretation of the clinical guideline for point-of-care ultrasonography in the neonatal intensive care unit in the United States]. / ç¾Žå›½æ–°ç”Ÿå„¿é‡ç—‡ç›‘æŠ¤å®¤åºŠæ—å³æ—¶è¶ å£°æ£€æŸ¥çš„ä¸´åºŠæ–¹æ¡ˆè§£è¯».

In December 2022, the American Academy of Pediatrics released a clinical guideline for point-of-care ultrasonography (POCUS) in the neonatal intensive care unit (NICU). The guideline outlined the development and current status of POCUS in the NICU, and summarized the key elements and implementation guidelines for successful implementation of POCUS in the NICU. This article provides an overview of the key points of the clinical guideline and analyzes the current status of POCUS in China, providing a reference for the implementation of POCUS in neonatal care in China.

Cellular Calcium Signals in Cancer Chemoprevention and Chemotherapy by Phytochemicals.

Identifying novel agents for cancer treatment is critical because of obstacles with anticancer drug resistance and lack of drug effectiveness. Intracellular calcium ion (Ca2+), a common second messenger, regulates various cellular pathophysiological processes including cell proliferation, differentiation and apoptosis. Recent studies have shown that the remodeling of Ca2+ signals is associated with cancer occurrence, progression and metastasis. Ca2+ channels, transporter and pumps regulate calcium movement, and alteration of Ca2+ signal component expression/activity is associated with numerous cancer cell activities. Therefore, targeting Ca2+ signals is an attractive research focus in cancer treatment. Phytochemicals, secondary metabolites in plants, exhibit multifaceted effective anticancer activities in various cancers. Although the mechanisms of the anticancer effects of phytochemicals remain unclarified, studies have indicated that many phytochemicals inhibit cancer progression through modulating calcium signals. In this review, we summarize the phytochemicals with demonstrated anticancer effects through their influence on calcium signaling, which may provide new ideas and directions in cancer research.

Ultrasound-guided superficial serratus plane block for persistent post-mastectomy pain: four case reports.

BACKGROUND: Persistent post-mastectomy pain (PPMP) is common after surgery. Although multiple modalities have been used to treat this type of pain, including medications, physical therapy, exercise interventions, cognitive-behavioral psychology, psychosocial interventions, and interventional approaches, managing PPMP may be still a challenge for breast cancer survivors. Currently, serratus plane block (SPB) as a novel regional anesthetic technique shows promising results for controlling chronic pain. METHODS: We report four cases of patients with PPMP that were treated using superficial serratus plane block (SSPB) at our clinic. A retrospective review of effect of pain relief was collected through postprocedure interviews. RESULTS: We found that two of our patients were successfully treated with SSPB for pain after treatment for breast cancer. The third patient had an intercostobrachial nerve block that produced incomplete pain relief but had adequate pain relief with a SSPB. However, the fourth patient reported no pain relief after SSPB. CONCLUSION: These cases illustrate that the patients with PPMP could benefit from SSPB. Particularly, we find patients with a subjective sense of "tightness" relating to reconstructive surgeries may be a good candidate for SSPB. Further studies are warranted to evaluate this block for PPMP, as it is low risk and relatively simple to perform.

Lung ultrasound for the assessment of lung recruitment in neonates with massive pneumothorax during extracorporeal membrane oxygenation: a case report.

Bedside lung ultrasound may be an effective method for the assessment of lung recruitment in newborns with extracorporeal membrane oxygenation (ECMO). We report a case of a neonate who had severe hypoxemia with persistent pulmonary hypertension and massive pneumothorax due to meconium aspiration syndrome and was treated with ECMO. Positive pressure mechanical ventilation resulted in persistent massive air leakage from the disrupted pulmonary tissue. When ECMO was initiated, a "total lung rest" ventilation strategy was used to facilitate healing of the lung rupture and absorption of the pneumothorax. After complete absorption of the pneumothorax, lung recruitment was performed by progressively increasing the positive end-expiratory pressure under the guidance of lung ultrasound. Bedside lung ultrasound was successfully used to assess pneumothorax absorption and improvement of pulmonary inflammation and successfully guided the recruitment of collapsed alveoli and the withdrawal of ECMO.

Graph-theoretical analysis of EEG functional connectivity during balance perturbation in traumatic brain injury: A pilot study.

Traumatic brain injury (TBI) often results in balance impairment, increasing the risk of falls, and the chances of further injuries. However, the underlying neural mechanisms of postural control after TBI are not well understood. To this end, we conducted a pilot study to explore the neural mechanisms of unpredictable balance perturbations in 17 chronic TBI participants and 15 matched healthy controls (HC) using the EEG, MRI, and diffusion tensor imaging (DTI) data. As quantitative measures of the functional integration and segregation of the brain networks during the postural task, we computed the global graph-theoretic network measures (global efficiency and modularity) of brain functional connectivity derived from source-space EEG in different frequency bands. We observed that the TBI group showed a lower balance performance as measured by the center of pressure displacement during the task, and the Berg Balance Scale (BBS). They also showed reduced brain activation and connectivity during the balance task. Furthermore, the decrease in brain network segregation in alpha-band from baseline to task was smaller in TBI than HC. The DTI findings revealed widespread structural damage. In terms of the neural correlates, we observed a distinct role played by different frequency bands: theta-band modularity during the task was negatively correlated with the BBS in the TBI group; lower beta-band network connectivity was associated with the reduction in white matter structural integrity. Our future studies will focus on how postural training will modulate the functional brain networks in TBI.

Gene Manipulation Protocols in Autophagy.

Macroautophagy (referred to as autophagy hereafter) is a highly conserved catabolic process in eukaryotic cells. Autophagy is essential for cellular homeostasis through elimination and recycling of large cytoplasmic components, such as abnormal protein aggregates and damaged organelles, via lysosomal degradation. Since being originally identified by genetic screening in yeast, autophagy-related (ATG) genes have played a central role in autophagy research in different organisms, including plants, worms, flies, and mammals. Mouse models for monitoring autophagic activity or clarifying its biological functions have also been established. These mice are powerful tools to investigate roles of autophagy in vivo. Owing to the rapid technological advances in molecular biology, it is ever more efficient and simpler to manipulate autophagy-associated genes. Herein, we will introduce some commonly used approaches of gene silencing in mammalian cells, including CRIPSR/Cas9-mediated gene knockout and siRNA- and shRNA-mediated gene knockdown. We also summarized the common mouse models used for assessing autophagy. We hope to bring the researchers some useful information as they study autophagy.

[Comparative study on anti-depressant effect of Zhizichi Decoction and its solid fermentation product on CUMS rats].

Chronic unpredicted mild stress(CUMS) combined with isolated feeding was used to induce depressed rat model. The anti-depressant effects of Zhizichi Decoction(ZZCD) and its solid fermented product(ZZC) were analyzed by behavioral test and comparison of pathological tissues of hippocampus and liver, metabolic characteristics of intestinal flora, and relative abundance of species. The results showed that ZZC could increase sucrose preference, shorten the immobility time in the forced swim test and tail suspension test(P<0.05), and repair damaged hippocampus and liver tissues, and the effect was superior to that of ZZCD. The results of Biolog ECO plates showed that the average well color development(AWCD) of intestinal flora in the model group significantly decreased and the metabolic levels of sugar and amino acids were reduced, while the AWCD of the treatment groups increased. The metabolic levels of the two carbon sources were improved in the ZZC group, while only sugar metabolic level was elevated in the ZZCD group. Metagenomic analysis of intestinal flora showed that the ratio of Firmicutes/Bacteroidetes was 3.87 in the control group, 21.77 in the model group, 5.91 in the ZZC group, and 18.48 in the ZZCD group. Lactobacillus increased by 3.28 times, and Prevotella and Bacteroidetes decreased by 75.59% and 76.39%, respectively in the model group as compared with that in the control group. Lactobacillus decreased by 31.13%, and Prevotella and Bacteroidetes increased by more than three times in the ZZC group as compared with that in the model group, while the corresponding changes in the ZZCD group were not significant. ZZC could improve depression-like beha-viors by regulating the structure of intestinal flora and metabolic functions and repairing damaged hippocampus and liver tissues in depressed rats, showing an anti-depressant effect superior to that of ZZCD. This study is expected to provide a basis for the development of new anti-depressant food products.

Improved stability of long-duration sitting in spatial neglect after a single session of prism adaptation.

Spatial neglect after right brain stroke affects balance, and improvements in sitting balance after prism adaptation have been demonstrated using short-duration center of pressure (CoP) data. We present long-duration (5 min) CoP and trunk muscles electromyography recordings of a 61-year-old man with left-sided spatial neglect, before and after a single session of prism adaptation. His CoP-derived measures showed improved balance and postural stability in both the anterior-posterior and medial-lateral directions after prism adaptation. Concurrently, asymmetry in neuromuscular activations was reduced. The findings suggest that improved sitting balance may be associated with more symmetrical activation of trunk muscles after prism adaptation.

EEG Correlates of Central Origin of Cancer-Related Fatigue.

The neurophysiological mechanism of cancer-related fatigue (CRF) remains poorly understood. EEG was examined during a sustained submaximal contraction (SC) task to further understand our prior research findings of greater central contribution to early fatigue during SC in CRF. Advanced cancer patients and matched healthy controls performed an elbow flexor SC until task failure while undergoing neuromuscular testing and EEG recording. EEG power changes over left and right sensorimotor cortices were analyzed and correlated with brief fatigue inventory (BFI) score and evoked muscle force, a measure of central fatigue. Brain electrical activity changes during the SC differed in CRF from healthy subjects mainly in the theta (4-8 Hz) and beta (12-30 Hz) bands in the contralateral (to the fatigued limb) hemisphere; changes were correlated with the evoked force. Also, the gamma band (30-50 Hz) power decrease during the SC did not return to baseline after 2 min of rest in CRF, an effect correlated with BFI score. In conclusion, altered brain electrical activity during a fatigue task in patients is associated with central fatigue during SC or fatigue symptoms, suggesting its potential contribution to CRF during motor performance. This information should guide the development and use of rehabilitative interventions that target the central nervous system to maximize function recovery.

Portal venous gas by ultrasound in advance of impending necrotizing enterocolitis of a very low birth weight infant.

Necrotizing enterocolitis (NEC) is a serious complication of premature infants, portal venous gas (PVG) under X-ray, and ultrasound is a typical manifestation of this disease. We report a case of a very low birth weight (VLBW) infant with PVG unexpectedly detected by ultrasound before the onset of NEC. After positive ultrasound result, clinical manifestations, X-ray, and lab tests confirmed the diagnosis of NEC. This is the first report of a similar case, demonstrating the value of ultrasonography in prediction or early diagnosis of NEC, which may change our understanding of the disease and the timing of examination.

Functional Corticomuscular Signal Coupling Is Weakened during Voluntary Motor Action in Cancer-Related Fatigue.

Background and Purpose: Cancer-related fatigue (CRF) is widely recognized as one of the most common symptoms and side effects of cancer and/or its treatment. However, neuropathological mechanisms contributing to CRF are largely unknown, and the lack of knowledge makes CRF difficult to treat. Recent research has shown dissociation between changes in the brain and muscle signals during voluntary motor performance in cancer survivors with CRF, and this dissociation may be caused by an interruption in functional coupling (FC) of the two signals. The goal of this study was to assess the FC between EEG (cortical signal) and EMG (muscular signal) in individuals with CRF and compare the FC with that of healthy controls during a motor task that led to progressive muscle fatigue. Method: Eight cancer survivors with CRF and nine healthy participants sustained an isometric elbow flexion contraction (at 30% maximal level) until self-perceived exhaustion. The entire duration of the EEG and EMG recordings was divided into the first-half (less-fatigue stage) and second-half (more-fatigue stage) artifact-free epochs without overlapping. The EEG-EMG coupling (measured by coherence of the two signals) in each group and stage was computed. Coherence values at different frequencies were statistically analyzed using a repeated-measure general linear model. Results: The results demonstrated that compared to healthy controls, CRF participants sustained the contraction for a significantly shorter time and exhibited robust and significantly lower EEG-EMG coherence at the alpha (8~14 Hz) and beta (15~35 Hz) frequency bands. Both the CRF and healthy control groups exhibited significantly decreased EEG-EMG coherence from the less-fatigue to more-fatigue stages at the alpha and beta frequency bands, indicating fatigue-induced weakening of functional corticomuscular coupling. Conclusion: Impaired functional coupling between the brain and muscle signals could be a consequence of cancer and/or its treatment, and it may be one of the contributing factors to the abnormal feeling of fatigue that caused the early failure of sustaining a prolonged motor task.

High optical feedback tolerance of InAs/GaAs quantum dot lasers on germanium.

This work experimentally investigates the optical feedback sensitivity of InAs/GaAs quantum dot (Qdot) lasers epitaxially grown on Ge substrate. In comparison with a Qdot laser on GaAs substrate with identical epilayer and cavity structures, the Ge-based laser is found to exhibit lower sensitivity to the optical feedback, although it has a higher epitaxial defect density. Theoretical analysis proves that the high defect density strongly increases the damping factor while slightly reduces the linewidth broadening factor, which lead to high tolerance to the optical feedback. This work suggests the high potential of Qdot lasers on Ge for isolator-free operation in photonic integrated circuits.

[Clinical characteristics of five traditional Chinese medicine injections in treating heart failure based on Meta-analysis literature].

In this article, we analyze the clinical characteristics of five kinds of traditional Chinese medicine injections in treating heart failure based on Meta-analysis. A total of 24 Meta-analysis papers were included, which involved Shenfu Injection, Shenmai Injection, Shengmai Injection, Danhong Injection and Huangqi Injection. The numbers of literatures of Shenfu Injection, Shenmai Injection and Shengmai Injection are high than the other two injections. The efficiencies of these injections combined with Western medicine are higher than the Western medicine used alone. They can improve 6 minute walk test result, ejection fraction, the level of brain peptide sodium and so on. Shenfu Injection can also improve the living quality of patients' life, heart rate and other indicators. Shenfu Injection can be used for patients with Yin deficiency, while Shenmai Injection can be used for patients with Yin deficiency and Shengmai Injection can be used for patients with Qi and Yin deficiency. From this information, we can see that Western medicine combined with traditional Chinese medicine injections can significantly improve the clinical efficiency. These injections need to be used according to patients' symptom. In the present, as the quality of clinical research literature of traditional Chinese medicine injections is low, the efficiency and safety evaluation of Chinese medicine injections still requires higher level of clinical evidence.

The effect of motor overflow on bimanual asymmetric force coordination.

Motor overflow, typically described in the context of unimanual movements, refers to the natural tendency for a 'resting' limb to move during movement of the opposite limb and is thought to be influenced by inter-hemispheric interactions and intra-cortical networks within the 'resting' hemisphere. It is currently unknown, however, how motor overflow contributes to asymmetric force coordination task accuracy, referred to as bimanual interference, as there is need to generate unequal forces and corticospinal output for each limb. Here, we assessed motor overflow via motor evoked potentials (MEPs) and the regulation of motor overflow via inter-hemispheric inhibition (IHI) and short-intra-cortical inhibition (SICI) using transcranial magnetic stimulation in the presence of unimanual and bimanual isometric force production. All outcomes were measured in the left first dorsal interosseous (test hand) muscle, which maintained 30% maximal voluntary contraction (MVC), while the right hand (conditioning hand) was maintained at rest, 10, 30, or 70% of its MVC. We have found that as higher forces are generated with the conditioning hand, MEP amplitudes at the active test hand decreased and inter-hemispheric inhibition increased, suggesting reduced motor overflow in the presence of bimanual asymmetric forces. Furthermore, we found that subjects with less motor overflow (i.e., reduced MEP amplitudes in the test hemisphere) demonstrated poorer accuracy in maintaining 30% MVC across all conditions. These findings suggest that motor overflow may serve as an adaptive substrate to support bimanual asymmetric force coordination.

A homologue of vitamin K epoxide reductase in Solanum lycopersicum is involved in resistance to osmotic stress.

Vitamin K epoxide reductase (VKOR) exists widely in the chloroplasts of higher plants and plays important roles in redox regulation. However, investigations of plant VKOR function have primarily focused on VKOR from Arabidopsis, and knowledge concerning this function is therefore quite limited. In this study, Solanum lycopersicum was used to study the function of VKOR. Transcription level analysis revealed that SlVKOR (S. lycopersicum VKOR) expression was upregulated by salt or drought stress. To further investigate the function of SlVKOR in plants, we generated sense and antisense transgenic S. lycopersicum homozygotes at T2 generation plants. Compared with wild-type (WT) plants, the leaf disks of the SlVKOR overexpression plants retained a much higher percentage of chlorophyll after salt or drought treatment, whereas the antisense transgenic plants displayed an opposite response. The overexpressed plants displayed lower levels of H2O2 and superoxide anion radical (O2(·-)) than WT plants, whereas antisense plants accumulated considerably more H2O2 and O2(·-). The activities of reactive oxygen scavenger enzymes, including superoxide dismutase, peroxidase, ascorbate peroxidase and catalase, were consistent with the accumulation of reactive oxygen species. Based on these results, we suggest that SlVKOR is involved in resistance to salt or drought stress.

Strengthened Corticosubcortical Functional Connectivity during Muscle Fatigue.

The present study examined functional connectivity (FC) between functional MRI (fMRI) signals of the primary motor cortex (M1) and each of the three subcortical neural structures, cerebellum (CB), basal ganglia (BG), and thalamus (TL), during muscle fatigue using the quantile regression technique. Understanding activation relation between the subcortical structures and the M1 during prolonged motor performance should help delineate how central motor control network modulates acute perturbations at peripheral sensorimotor system such as muscle fatigue. Ten healthy subjects participated in the study and completed a 20-minute intermittent handgrip motor task at 50% of their maximal voluntary contraction (MVC) level. Quantile regression analyses were carried out to compare the FC between the contralateral (left) M1 and CB, BG, and TL in the minimal (beginning 100 s) versus significant (ending 100 s) fatigue stages. Widespread, statistically significant increases in FC were found in bilateral BG, CB, and TL with the left M1 during significant versus minimal fatigue stages. Our results imply that these subcortical nuclei are critical components in the motor control network and actively involved in modulating voluntary muscle fatigue, possibly, by working together with the M1 to strengthen the descending central command to prolong the motor performance.

Do stress fractures induce hypertrophy of the grafted fibula? A report of three cases received free vascularized fibular graft treatment for tibial defects.

The presence of large segmental defects of the diaphyseal bone is challenging for orthopedic surgeons. Free vascularized fibular grafting (FVFG) is considered to be a reliable reconstructive procedure. Stress fractures are a common complication following this surgery, and hypertrophy is the main physiological change of the grafted fibula. The exact mechanism of hypertrophy is not completely known. To the best of our knowledge, no studies have examined the possible relationship between stress fractures and hypertrophy. We herein report three cases of patients underwent FVFG. Two of them developed stress fractures and significant hypertrophy, while the remaining patient developed neither stress fractures nor significant hypertrophy. This phenomenon indicates that a relationship may exist between stress fractures and hypertrophy of the grafted fibula, specifically, that the presence of a stress fracture may initiate the process of hypertrophy.