Effects of rhythmic visual cues on cortical activation and functional connectivity features during stepping: an fNIRS study.

Introduction: Rhythmic visual cues (RVCs) may influence gait initiation by modulating cognition resources. However, it is unknown how RVCs modulate cognitive resources allocation during gait movements. This study focused on investigating the effects of RVCs on cortical hemodynamic response features during stepping to evaluate the changes of cognitive resources. Methods: We recorded cerebral hemoglobin concentration changes of 14 channels in 17 healthy subjects using functional near-infrared spectroscopy (fNIRS) during stepping tasks under exposure to RVCs and non-rhythmic visual cues (NRVCs). We reported mean oxygenated hemoglobin (HbO) concentration changes, ß-values, and functional connectivity (FC) between channels. Results: The results showed that, the RVC conditions revealed lower HbO responses compared to the NRVC conditions during the preparation and early stepping. Correspondingly, the ß-values reflected that RVCs elicited lower hemodynamic responses than NRVCs, and there was a decreasing trend in stimulus-evoked cortical activation as the task progressed. However, the FC between channels were stronger under RVCs than under NRVCs during the stepping progress, and there were more significant differences in FC during the early stepping. Discussion: In conclusion, there were lower cognitive demand and stronger FC under RVC conditions than NRVC conditions, which indicated higher efficiency of cognitive resources allocation during stepping tasks. This study may provide a new insight for further understanding the mechanism on how RVCs alleviate freezing of gait.

Influence of the ultra-fine fly ash dosages on the mechanical properties of the sulfoaluminate cement-based high water backfilling material.

To reduce the filling cost of high-water backfilling material (HWBM) in mining backfill and improve the recycling utilization of the industrial waste such as the coal fly ash. The ultra-fine fly ash (UFA) was added to the HWBM as a partial replacement in this work. Therefore, a series of experiments were performed to investigate the effect of UFA on the mechanical properties of the HWBM at the different curing conditions, then the hydration mechanism of the HWBM blended with UFA was analyzed by XRD and SEM method. The result indicates that the strength of the HWBM decreased with the increasing of UFA dosages, but the addition of UFA can improve the residual strength of the initial HWBM. Additionally, when the HWBM was cured at the laboratory air condition, its carbonation process was restrained obviously as the UFA dosages were less than 15% at the ages of 28 days, which indicates the UFA can improve the weathering resistance of the HWBM with the curing ages increasing effectively. The XRD and SEM results also shows that the degree of crystallinity of the HWBM increased when UFA dosages were less than 15% effectively, while there were few obvious changes on types of hydration products. It indicates that the main affects of UFA on the performance of HWBM is filler and dilution, which reduced the contact area between hydration products of HWBM and CO2 in the air, further improved the carbonation resistance of HWBM.

Meta-analysis assessing the effectiveness of SGLT2i+GLP1RA combination therapy versus monotherapy on cardiovascular and cerebrovascular outcomes in diabetic patients.

Relevant meta-analyses have confirmed the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) among patients with type 2 diabetes (T2D) and/or cardiorenal disease. However, it is not established whether the combination therapy of SGLT2i and GLP1RA will yield an additive benefit on cardiorenal endpoints. Lopez and colleagues recently did a cohort study (Lopez et al., Am. J. Cardiol., 2022, 181, 87-93) and aimed to address this issue. However, their findings are not consistent with those of previous studies. To confirm Lopez et al.'s findings (Lopez et al., Am. J. Cardiol., 2022, 181, 87-93) and address the aforementioned inconsistencies, we conducted a meta-analysis based on relevant studies. Our meta-analysis identified that SGLT2i + GLP1RA combination therapy was significantly associated with the reduced risks of cardiovascular/cerebrovascular atherosclerotic, heart failure-associated, and death outcomes compared with SGLT2i/GLP1RA monotherapy. These might support this combination therapy used for better reducing cardiovascular and death events in T2D patients, especially in those with high or very high cardiovascular risk. This is a commentary on a previous article (Lopez et al.'s study (Lopez et al., Am. J. Cardiol., 2022, 181, 87-93)) published outside of Frontiers. Therefore, we submitted this manuscript as an Opinion article, as suggested in the Author Guidelines.

Vibration Exposure Safety Guidelines for Surgeons Using Power-Assisted Liposuction (PAL).

BACKGROUND: As power-assisted liposuction (PAL) gains in popularity, plastic surgeons operating these devices experience occupational exposure to hand-transmitted vibration, which can result in hand-arm vibration syndrome, a debilitating neurovasculopathy. OBJECTIVES: The objective of the study was to determine vibration exposure from the utilization of a PAL device during surgery to generate recommendations for safe use. METHODS: Vibration emission of a commonly utilized PAL system (MicroAire-650, Surgical Instruments, Charlottesville, VA) was examined employing a vibration data logger under both controlled laboratory conditions and during 13 typical liposuction cases. Data were analyzed and compared with established safety limits of vibration exposure. RESULTS: The experiments demonstrated a mean vibration magnitude of typical liposuction surgeries to be 5.69 ±â€…0.77 m/s2 (range, 4.59-6.27 m/s2), which is significantly higher than the manufacturer declared value of 3.77 m/s2. Cannula size was shown to be the most significant contributor to vibration magnitude, with larger cannulas causing more vibration transmission. CONCLUSIONS: These results indicate that recommendations must be made to prevent undue occupational exposure to vibration from PAL. The MicroAire-650 can generally be safely utilized for less than 1.5 h/d. At exposure levels >1.5 h/d, there is increased risk of developing vibration-related injuries, and vibration-reducing strategies should be implemented. At exposure levels >6 h/d, the safety limit is exceeded and there is significantly increased risk of developing hand-arm vibration syndrome and vibration exposure should be halted.

[Predictive value of stroke-related early tracheotomy score for tracheotomy in neurocritical patients].

OBJECTIVE: To explore the predictive value of stroke-related early tracheotomy score (SET) for tracheotomy in neurocritical patients. METHODS: A retrospective analysis of the clinical data of neurocritical patients admitted to the department of intensive care unit (ICU) of the Xindu District People's Hospital of Chengdu from January 1st to December 31st, 2019. Patients were divided into tracheostomy group and non-tracheostomy group according to whether they underwent tracheotomy during hospitalization; according to SET score, patients were divided into groups with SET score < 10 points and SET score ≥ 10 points. The differences in gender, age, acute physiology and chronic health evaluation II (APACHE II), Glasgow coma score (GCS), SET score, the length of ICU stay and mechanical ventilation time were compared between the two groups. The receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of SET score for the length of ICU stay > 10 days, mechanical ventilation time > 5 days, and tracheotomy treatment, and the predictive value of APACHE II score for tracheotomy treatment. RESULTS: Among 66 patients, 35 cases underwent a tracheotomy, 31 cases did not; SET score < 10 points in 19 cases, while SET score ≥ 10 points in 47 cases. Compared with the non-tracheostomy group, there were more male patients in the tracheostomy group (cases: 27 vs. 13), the GCS score was lower (7.00±2.41 vs. 11.52±2.00), the APACHE II score and the SET score were higher (22.43±4.45 vs. 19.58±5.86, 16.11±3.67 vs. 8.61±4.27), and the length of ICU stay and mechanical ventilation time was longer [days: 27.54±18.82 vs. 7.45±5.30, 13 (9, 19) vs. 0 (0, 2)], and all differences were statistically significant (all P < 0.05). Compared with SET score < 10 points group, the proportion of traumatic brain injury and tracheotomy in the SET score ≥ 10 points group was higher (44.68% vs. 15.79%, 70.21% vs. 5.26%), the GCS score was lower (8.00±2.87 vs. 11.89±1.97), APACHE II score was higher (22.30±4.80 vs. 18.11±5.49), and the length of ICU stay and mechanical ventilation time was longer [days: 22.38±18.74 vs. 7.53±4.60, 9 (4, 16) vs. 0 (0, 2)], and the differences were statistically significant (all P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of SET score predicting the length of ICU stay > 10 days of neurocritical patients was 0.877, and the 95% confidence interval (95%CI) was 0.790-0.964 (P = 0.000), and its cut-off value was 13.50, the sensitivity was 80.0%, and the specificity was 87.1%. The SET score predicts the AUC for mechanical ventilation time > 5 days was 0.915, the 95%CI was 0.851-0.979 (P = 0.000), the cut-off value was 13.50, the sensitivity was 78.4%, and the specificity was 89.7%. SET score predicts the AUC of tracheotomy treatment was 0.919, 95%CI was 0.853-0.985 (P = 0.000), its cut-off value was 13.50, the sensitivity was 82.9%, and the specificity was 90.3%, which was significantly better than that of APACHE II score in predicting the value of tracheotomy (AUC was 0.647, 95%CI was 0.512-0.783, P = 0.040, its cut-off value was 17.50, the sensitivity was 91.4%, and the specificity was 41.9%). CONCLUSIONS: SET score has a good predictive value for the length of ICU stay, mechanical ventilation time and tracheotomy in neurocritical patients.

Riveting hammer vibration damages mechanosensory nerve endings.

Hand-arm vibration syndrome (HAVS) is an irreversible neurodegenerative, vasospastic, and musculoskeletal occupational disease of workers who use powered hand tools. The etiology is poorly understood. Neurological symptoms include numbness, tingling, and pain. This study examines impact hammer vibration-induced injury and recoverability of hair mechanosensory innervation. Rat tails were vibrated 12 min/d for 5 weeks followed by 5 week recovery with synchronous non-vibrated controls. Nerve fibers were PGP9.5 immunostained. Lanceolate complex innervation was compared quantitatively in vibrated vs sham. Vibration peak acceleration magnitudes were characterized by frequency power spectral analysis. Average magnitude (2515 m/s2 , root mean squared) in kHz frequencies was 109 times that (23 m/s2 ) in low Hz. Percentage of hairs innervated by lanceolate complexes was 69.1% in 5-week sham and 53.4% in 5-week vibration generating a denervation difference of 15.7% higher in vibration. Hair innervation was 76.9% in 5-weeks recovery sham and 62.0% in 5-week recovery vibration producing a denervation difference 14.9% higher in recovery vibration. Lanceolate number per complex (18.4 ± 0.2) after vibration remained near sham (19.3 ± 0.3), but 44.9% of lanceolate complexes were abnormal in 5 weeks vibrated compared to 18.8% in sham. The largest vibration energies are peak kHz accelerations (approximately 100 000 m/s2 ) from shock waves. The existing ISO 5349-1 standard excludes kHz vibrations, seriously underestimating vibration injury risk. The present study validates the rat tail, impact hammer vibration as a model for investigating irreversible nerve damage. Persistence of higher denervation difference after 5-week recovery suggests repeated vibration injury destroys the capability of lanceolate nerve endings to regenerate.

MiR-1256 inhibits cell proliferation and cell cycle progression in papillary thyroid cancer by targeting 5-hydroxy tryptamine receptor 3A.

Aberrant expression of miR-1256 has been reported to be closely associated with the development and progression of tumors, including colon cancer and lung cancer. However, study of its expression pattern and functional role in papillary thyroid cancer (PTC) is rare. Using quantitative real time PCR analysis, we found miR-1256 was significantly down-regulated in PTC tissues and cell lines. The correlation of miR-1256 expression with clinicopathological features was statistically analyzed. The results showed miR-1256 expression was significantly correlated with tumor size (p = 0.0124) and TNM stage (p = 0.0032). Restoring miR-1256 expression significantly inhibited proliferation and cell cycle progression of PTC cells demonstrated by CCK-8 and flow cytometry assays. Luciferase reporter assay and biotin-avidin pull-down assay showed miR-1256 can directly target 5-hydroxytryptamine receptor 3A (HTR3A) in PTC cells. The expression of miR-1256 was inversely correlated with HTR3A expression in PTC tissues. Knockdown of HTR3A imitated the suppressive effects of miR-1256 in PTC cells. Ectopic expression of HTR3A can antagonize the effects of miR-1256 on PTC cells. Furthermore, the suppressive effects of miR-1256 on the expression of PCNA, CDK4, Cyclin D1, and p21 were partially reversed by HTR3A overexpression in PTC cells. In summary, our data suggested that miR-1256 could suppress PTC cellular function by targeting HTR3A, which might be a potential therapeutic target for patients with PTC.

High serum nerve growth factor concentrations are associated with good functional outcome at 3 months following acute ischemic stroke.

BACKGROUND: Previous studies in animal model have demonstrated that neurotrophins were associated with functional outcome following stroke. However, the relationship between serum nerve growth factor (NGF) and functional outcome in stroke patients has not been explored. Our objective was to investigate the association between serum NGF concentrations at admission and functional outcome of patients at 3 month after stroke. METHODS: One-hundred eight-five patients with acute ischaemic stroke were recruited in our study. Serum NGF concentrations were measured by ELISA at admission. The stroke severity at admission was assessed by the National Institute of Health Stroke Scale (NIHSS). The modified Rankin Scale (mRS) was used to assess the functional outcome of patients at 3 month after stroke. In addition, 100 healthy controls were recruited. RESULTS: Serum NGF concentrations were higher in good functional outcome group (mRS score of 0-2) than that in poor functional outcome group (mRS score of 3-6) (9.51 ±â€¯2.33 vs. 8.12 ±â€¯1.61, P < 0.001). Meanwhile, the serum NGF concentrations in healthy group were lower than that in acute ischemic stroke patients (7.17 ±â€¯1.49 vs. 9.15 ±â€¯2.24, P < 0.001). Moreover, our results demonstrated that high serum NGF concentrations (>9.21 ng/l) were independently associated with the better functional prognosis at 3 months following the occurrence of stroke (OR 0.048, 95% CI 0.012-0.185, P < 0.001). CONCLUSIONS: High concentrations of serum NGF at admission may predict good functional outcome of patients at 3 months after acute cerebral ischemia stroke.

Brain-derived neurotrophic factor levels and depression during methamphetamine withdrawal.

BACKGROUND: Depression symptoms is highly comorbid with methamphetamine (METH) dependence. Except for the role in the pathophysiology of depression symptoms, brain-derived neurotrophic factor (BDNF) is also involved in the METH dependence. The present study aims to explore whether BDNF plays a role in the development of depression symptoms during METH withdrawal. METHODS: We recruited 179 patients with METH dependence who were followed up for two weeks. Ultimately, 131 (73.2%) patients finished the follow-up. Besides, 90 healthy controls were also recruited. Serum BDNF levels were measured by DuoSet ELISA Development System upon admission. The short form (13 items) of the Beck Depression Inventory (BDI) and Amphetamine Withdrawal Questionnaire (AWQ) were used to measure the depression and withdrawal symptoms. Patients with BDI score ≥ 8 were identified to have depression symptoms. RESULTS: Of the 131 patients, 64 (48.9%) were identified to have depression symptoms at the two-week endpoint. Patients with depression symptoms showed significantly lower BDNF levels than those with no depression symptoms. Serum BDNF levels (≤ 1251.0pg/ml) were independently associated with the development of depression symptoms during METH withdrawal (OR = 3.50, 95% CI, 1.14-10.73, p = 0.028). LIMITATIONS: BDNF levels were tested in serum but not in brain and the baseline BDI and AWQ scores between the depression and non-depression groups were not matched. Besides, the follow-up time was relatively short. CONCLUSIONS: Our study demonstrated that patients with serum BDNF levels ≤ 1251.0pg/ml had higher risk of depression symptoms during METH withdrawal.

Association Between Serum Levels of Vitamin D and the Risk of Post-Stroke Anxiety.

Low levels of serum vitamin D are common in patients with mood disorders and stroke. It has been shown that low levels of serum vitamin D indicate a risk of depression in post-stroke subjects. Our aim was to determine the relationship between vitamin D and post-stroke anxiety (PSA).A consecutive series of 226 first acute ischemic stroke patients were recruited and followed up for 1 month. Serum levels of vitamin D were measured within 24 hours of admission. Patients with significant clinical symptoms of anxiety and a Hamilton anxiety scale score >7 were diagnosed as having PSA. In addition, 100 healthy subjects were recruited as controls and underwent measurements of serum vitamin D.A total of 60 patients (26.55%) showed anxiety at 1 month. Both PSA patients and non-PSA patients had lower serum levels of vitamin D than healthy subjects. A significant relationship was found between PSA and serum levels of vitamin D. Low serum levels of vitamin D (≤38.48 nmol/L) were independently associated with the development of PSA (OR: 2.49, 95% CI: 1.21-5.13, P = 0.01).Serum vitamin D status is related to the occurrence of anxiety in post-stroke patients and may be an independent risk factor of PSA after 1 month.

The association between serum ferritin levels and post-stroke depression.

BACKGROUND: Post-stroke depression (PSD) is a common neuropsychiatric affective disorder occurring after stroke. Elevated serum ferritin levels have been reported to contribute to depression. Our aim was to determine whether there is a relationship between serum ferritin levels and PSD. METHODS: 196 ischemic stroke patients were consecutively recruited within the first 24h of stroke onset and were followed up for 2 months. Serum ferritin levels were assayed by electrochemiluminescence immunoassay at hospital admission. Clinical depression was diagnosed according to DSM-IV criteria and a HAMD -17 score of ≥ 7. Meanwhile, 100 normal control subjects were also recruited. RESULTS: We found that 56 stroke patients (28.6%) were diagnosed with PSD at two months. There was a significant intergroup difference in serum ferritin levels within 24h after admission (F=25.044, P<0.001). Serum ferritin levels were significantly higher at admission in PSD patients than in non-PSD patients and normal controls. There was a positive correlation between serum ferritin levels and hs-CRP at admission in PSD patients (r=0.129, P=0.042). In multivariate analyses, serum levels of ferritin ≥ 130.15 µg/L were independently associated with PSD at two months [odds ratio OR=5.388, 95%CI:1.725-16.829; P=0.004] after adjusting for all possible variables. LIMITATIONS: We excluded patients with severe aphasia and with serious conditions.In addition, the information for dietary intake was not recorded, which may influence body iron stores. CONCLUSION: Our findings show that elevated serum ferritin levels at admission are associated with PSD and may predict its development at 2 months post-stroke.

Targeted Expression of Channelrhodopsin-2 to the Axon Initial Segment Alters the Temporal Firing Properties of Retinal Ganglion Cells.

The axon initial segment (AIS) is essential for initiating action potentials and maintaining neuronal excitability in axon-bearing neurons in the CNS. There is increasing interest in the targeting of optogenetic tools to subcellular compartments, including the AIS, to gain precise control of neuronal activity for basic research and clinical applications. In particular, targeted expression of optogenetic tools in retinal ganglion cells (RGCs) has been explored as an approach for restoring vision after photoreceptor degeneration. Thus, understanding the effects of such targeting on spiking abilities and/or patterns is important. Here, we examined the effects of recombinant adeno-associated virus (rAAV)-mediated targeted expression of channelrhodopsin-2 (ChR2)-GFP with a NaV channel motif in mouse RGCs. We found that this targeted expression disrupted NaV channel clustering at the AIS and converted the spike firing patterns of RGCs from sustained to transient. Our results suggest that the clustering of membrane channels, including NaV channels, at the AIS is important for the ability of RGCs to generate sustained spike firing. Additionally, the targeting of optogenetic tools to the AIS with the NaV channel motif may offer a way to create transient light responses in RGCs for vision restoration.

Human acellular dermal matrix (AlloDerm®) dimensional changes and stretching in tissue expander/implant breast reconstruction.

BACKGROUND: Human acellular dermal matrix (HADM) is widely used for post-mastectomy tissue expander/implant breast reconstruction. Since HADM has been shown to stretch following placement in other surgical settings, we hypothesised that stretching would occur in breast reconstruction as well. The goal of the study was to quantify the in situ stretch properties of HADM over time in patients undergoing this procedure. METHODS: This was an open-label, prospective case series in adult women who underwent post-mastectomy tissue expander/implant breast reconstruction using HADM. HADM construct size was determined at postoperative day 1 and month 3 via ultrasound tracking of metallic 3-mm vessel clips embedded in the graft. Dimensional changes were further examined in four equally sized segments (medial, lateral and two central) of the matrix. Patient satisfaction was evaluated at month 3 (a modified version of the Breast Q™ patient questionnaire) and compared with satisfaction reported by a non-HADM reconstruction cohort. RESULTS: A total of 31 patients underwent breast reconstruction with HADM. Mean (standard deviation) perimeter increased from 38 (6) cm on postoperative day 1-42 (7) cm at month 3 (+11%; P=0.002). Surface area increased from 73 (22) to 88 (28) cm2 (+21%; range, 4-35%; P=0.002). The greatest expansion occurred in the HADM medial and lateral segments (range, 18-30% across the four segments). Patient satisfaction was comparable with that of non-HADM patients. Complications in the HADM group included late seroma, red breast syndrome and urinary tract infection. Complications in the non-HADM cohort included cellulitis, expander explantation, delayed wound healing and skin necrosis. CONCLUSIONS: During short-term follow-up, HADM exhibited a modest degree of stretching during tissue expander/implant breast reconstruction and was associated with few complications and a high level of patient satisfaction.

rAAV-mediated subcellular targeting of optogenetic tools in retinal ganglion cells in vivo.

Expression of optogenetic tools in surviving inner retinal neurons to impart retinal light sensitivity has been a new strategy for restoring vision after photoreceptor degeneration. One potential approach for restoring retinal light sensitivity after photoreceptor degeneration is to express optogenetic tools in retinal ganglion cells (RGCs). For this approach, restoration of ON and OFF center-surround receptive fields in RGCs, a key feature of visual information processing, may be important. A possible solution is to differentially express depolarizing and hyperpolarizing optogenetic tools, such as channelrhodopsin-2 and halorhodopsin, to the center and peripheral regions of the RGC dendritic field by using protein targeting motifs. Recombinant adeno-associated virus (rAAV) vectors have proven to be a powerful vehicle for in vitro and in vivo gene delivery, including in the retina. Therefore, the search for protein targeting motifs that can achieve rAAV-mediated subcellular targeted expression would be particularly valuable for developing therapeutic applications. In this study, we identified two protein motifs that are suitable for rAAV-mediated subcellular targeting for generating center-surround receptive fields while reducing the axonal expression in RGCs. Resulting morphological dendritic field and physiological response field by center-targeting were significantly smaller than those produced by surround-targeting. rAAV motif-mediated protein targeting could also be a valuable tool for studying physiological function and clinical applications in other areas of the central nervous system.

Action potential generation at an axon initial segment-like process in the axonless retinal AII amacrine cell.

In axon-bearing neurons, action potentials conventionally initiate at the axon initial segment (AIS) and are important for neuron excitability and cell-to-cell communication. However in axonless neurons, spike origin has remained unclear. Here we report in the axonless, spiking AII amacrine cell of the mouse retina a dendritic process sharing organizational and functional similarities with the AIS. This process was revealed through viral-mediated expression of channelrhodopsin-2-GFP with the AIS-targeting motif of sodium channels (Na(v)II-III). The AII processes showed clustering of voltage-gated Na+ channel 1.1 (Na(v)1.1) as well as AIS markers ankyrin-G and neurofascin. Furthermore, Na(v)II-III targeting disrupted Na(v)1.1 clustering in the AII process, which drastically decreased Na+ current and abolished the ability of the AII amacrine cell to generate spiking. Our findings indicate that, despite lacking an axon, spiking in the axonless neuron can originate at a specialized AIS-like process.