الملخص
Cancer chemotherapy often triggers peripheral neuropathy in patients, leading to neuropathic pain in the extremities. While previous research has explored various nerve stimulation to alleviate chemotherapy-induced peripheral neuropathy (CIPN), evidence on the effectiveness of noninvasive auricular vagus nerve stimulation (aVNS) remains uncertain. This study aimed to investigate the efficacy of non-invasive aVNS in relieving CIPN pain. To induce CIPN in experimental animals, oxaliplatin was intraperitoneally administered to rats (6 mg/kg). Mechanical and cold allodynia, the representative symptoms of neuropathic pain, were evaluated using the von Frey test and acetone test, respectively. The CIPN animals were randomly assigned to groups and treated with aVNS (5 V, square wave) at different frequencies (2, 20, or 100 Hz) for 20 minutes. Results revealed that 20 Hz aVNS exhibited the most pronounced analgesic effect, while 2 or 100 Hz aVNS exhibited weak effects. Immunohistochemistry analysis demonstrated increased c-Fos expression in the locus coeruleus (LC) in the brain of CIPN rats treated with aVNS compared to sham treatment. To elucidate the analgesic mechanisms involving the adrenergic descending pathway, α 1 -, α 2 -, or β-adrenergic receptor antagonists were administered to the spinal cord before 20 Hz aVNS. Only the β-adrenergic receptor antagonist, propranolol, blocked the analgesic effect of aVNS.These findings suggest that 20 Hz aVNS may effectively alleviate CIPN pain through β-adrenergic receptor activation.
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Purpose@#This study aims to systematically review the literature and conduct a meta-analysis to thoroughly analyze the outcomes of studies on simulation programs in psychiatric nursing. @*Methods@#We conducted an initial search from January 1, 2000, to September 30, 2023, using databases such as PubMed, EMBASE, CINAHL, the Cochrane Library, and Web of Science. A total of 2,571 articles were reviewed based on inclusion and exclusion criteria. We selected 35 articles for systematic literature review and subjected 20 of them to meta-analysis. Data analysis was conducted using descriptive statistics and the Comprehensive Meta-Analysis program. @*Results@#The number of psychiatric nursing simulation programs has increased since 2015. The most common programs used Standard Patients (SP), but studies using Virtual Reality (VR), audio, video, and other methods have recently been reported. The programs addressed various mental health issues, including depression, suicide, violence, alcohol problems, and mood disorders. Overall, considering all the studies, a significant effect was observed with a pooled Hedges’s g value of 0.56 (95% CI: 0.35~0.78; p<.001). @*Conclusion@#These findings highlight the importance of incorporating simulation-based education into nursing curricula to equip professionals with the skills to provide high-quality care to individuals with mental health problems. Further research is needed to explore the long-term benefits of these educational interventions on patient care.
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Preaxial polydactyly of the hand is one of the most common congenital hand anomalies. Several classification systems have been developed to classify these complex anomalies, of which the Wassel-Flat classification, based on the anatomical level of skeletal duplication, is the most widely used. Recently, a modified Wassel classification system was proposed to describe the type VII deformities and define the hypoplastic types more clearly. Surgical treatments for preaxial polydactyly of the hand are generally performed between 10 months and 2 years after birth. The purpose of operation is to construct a functional and cosmetically acceptable thumb. Since the clinical outcomes after remaining the radial side digit are poor, surgeons should try to remain the ulnar side digit as much as possible for the selection of the remaining digit. According to the type of preaxial polydactyly, various surgical procedures could be applied. This review presents the several classification systems for preaxial polydactyly of the hand and describes the applied surgical procedures according to the modified Wassel classification.
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Background@#This systematic literature review compared long-term outcomes between nonoperative treatment and vascularized bone graft (VBG) in patients with Kienböck disease. @*Methods@#We systematically reviewed studies on nonoperative treatment and VBG for Kienböck disease with a mean follow-up of ≥ 5 years. A systematic search was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase databases to select relevant articles. Data on patient demographics, treatment details, and outcomes were extracted. @*Results@#Twelve studies (6 for nonoperative treatment and 6 for VBG) were included. The proportion of wrists showing worsening Lichtman stages after treatment was 40.2% (95% confidence interval [CI], 25.7–56.6) and 17.0% (95% CI, 10.2%–26.9%) in the nonoperative treatment group and VBG group, respectively. No change in the stage was observed in 52.4% (95% CI, 25.5%–78.0%) and 77.8% (95% CI, 66.7%–86.0%) of the wrists in the nonoperative treatment group and VBG group, respectively. The proportion of wrists without pain at the final follow-up was 29.2% (95% CI, 16.6%–46.1%) and 35.9% (95% CI, 22.6%–52.0%) in the nonoperative treatment group and VBG group, respectively. The proportion of wrists with more than a moderate degree was 30.4% (95% CI, 22.7%–39.4%) and 12.9% (95% CI, 5.5%–27.4%) in the nonoperative treatment group and VBG group, respectively. The 95% CIs of the mean wrist range of motion and mean grip strength ratio of the affected side to the contralateral side substantially overlapped in the two groups. @*Conclusions@#The VBG group showed greater improvement in the radiographic stage and wrist pain than did the nonoperative treatment group after treatment, but meaningful differences in parameters were not observed. Further well-designed studies are needed to confirm the superiority of VBG to nonoperative treatment regarding radiographic and clinical outcomes.
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Cerebral ischemia can lead to a range of sequelae, including depression. The pathogenesis of depression involves neuronal change of the medial prefrontal cortex (mPFC). However, how cerebral ischemia-induced changes manifest across subregions and layers of the mPFC is not well understood. In this study, we induced cerebral ischemia in mice via transient bilateral common carotid artery occlusion (tBCCAO) and observed depressive-like behavior. Using whole-cell patch clamp recording, we identified changes in the excitability of pyramidal neurons in the prelimbic cortex (PL) and infralimbic cortex (IL), the subregions of mPFC. Compared to sham control mice, tBCCAO mice showed significantly reduced neuronal excitability in IL layer 2/3 but not layer 5 pyramidal neurons, accompanied by increased rheobase current and decreased input resistance. In contrast, no changes were observed in the excitability of PL layer 2/3 and layer 5 pyramidal neurons. Our results provide a new direction for studying the pathogenesis of depression following ischemic damage by showing that cerebral ischemia induces subregion- and layer-specific changes in the mPFC pyramidal neurons.
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Quantification of tyrosine hydroxylase (TH)-positive neurons is essential for the preclinical study of Parkinson’s disease (PD). However, manual analysis of immunohistochemical (IHC) images is labor-intensive and has less reproducibility due to the lack of objectivity. Therefore, several automated methods of IHC image analysis have been proposed, although they have limitations of low accuracy and difficulties in practical use. Here, we developed a convolutional neural network-based machine learning algorithm for TH+ cell counting. The developed analytical tool showed higher accuracy than the conventional methods and could be used under diverse experimental conditions of image staining intensity, brightness, and contrast. Our automated cell detection algorithm is available for free and has an intelligible graphical user interface for cell counting to assist practical applications. Overall, we expect that the proposed TH+ cell counting tool will promote preclinical PD research by saving time and enabling objective analysis of IHC images.
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Background@#The purpose of this study was to investigate the role of opioid-based intravenous patient-controlled analgesia (IV PCA) or continuous brachial plexus block (BPB) in controlling rebound pain after distal radius fracture (DRF) fixation under BPB as well as total opioid consumption. @*Methods@#A total of 66 patients undergoing surgical treatment for a displaced DRF with volar plate fixation were randomized to receive a single infraclavicular BPB (BPB only group) (n = 22), a single infraclavicular BPB with IV PCA (IV PCA group) (n = 22), or a single infraclavicular BPB with continuous infraclavicular BPB (continuous block group) (n = 22). The visual analog scale (VAS) for pain and the amount of pain medication were recorded at 4, 6, 9, 12, 24, and 48 h and two weeks postoperatively. @*Results@#At postoperative 9 h, the pain VAS score was significantly higher in the BPB only group (median: 2; Q1, Q3 [1, 3]) than in the IV PCA (0 [0, 1.8], P = 0.006) and continuous block groups (0 [0, 0.5], P = 0.009). At postoperative 12 h, the pain VAS score was significantly higher in the BPB only group (3 [3, 4]) than in the continuous block group (0.5 [0, 3], P = 0.004). The total opioid equivalent consumption (OEC) was significantly higher in the IV PCA group (350.3 [282.1, 461.3]) than in the BPB only group (37.5 [22.5, 75], P < 0.001) and continuous block group (30 [15, 75], P < 0.001); however, OEC was not significantly different between the BPB only group and the continuous block group (P = 0.595). @*Conclusions@#Although continuous infraclavicular BPB did not reduce total opioid consumption compared to BPB only, this method is effective for controlling rebound pain at postoperative 9 and 12 h following DRF fixation under BPB.
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Ca2+ transients can be observed in the distal dendrites of Purkinje cells (PCs) despite their lack of action potential backpropagation. These Ca2+events in distal dendrites require specific patterns of PC firing, such as complex spikes (CS) or simple spikes (SS) of burst mode. Unlike CS, which can act directly on voltage-gated calcium channels in the dendrites through climbing fiber inputs, the condition that can produce the Ca2+ events in distal dendrites with burst mode SS is poorly understood. Here, we propose the interspike interval threshold (ISIT) for Ca2+ transients in the distal dendrites of PC. We found that to induce the Ca2+ transients in distal dendrites the frequency of spike firing of PC should reach 250 Hz (3 ms ISI). Metabotropic glutamate receptor 1 (mGluR1) activation significantly relieved the ISIT and established cellular conditions in which spike firing with 50 Hz (19 ms ISI) could induce Ca 2+ transients in the distal dendrites. In contrast, blocking T-type Ca2+ channels or depleting the endoplasmic reticulum Ca2+ store resulted in a stricter condition in which spike firing with 333 Hz (2 ms ISI) was required. Our findings demonstrate that the PC has strict ISIT for dendritic Ca2+ transients, and this ISIT can be relieved by mGluR1 activation. This strict restriction of ISIT could contribute to the reduction of the signal-to-noise ratio in terms of collecting information by preventing excessive dendritic Ca2+ transients through the spontaneous activity of PC.
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Species in the genus Trametes (Basidiomycota, Polyporales) have been used in natural medicine for a long time. Many studies reported that mycelia or fruiting bodies of Trametes spp. exhibited effects of antioxidant, anti-inflammatory, anticancer, and antimicrobial activities.However, comparative analysis in this genus is scarce due to limitation of morphological identification and the sample number. In this study, the 19 strains of seven Trametes species were chosen to generate a five-gene-based phylogeny with the 31 global references. In addition, 39 culture extracts were prepared for 13 strains to test for anticancer and antibacterial activities. Strong anticancer activities were found in several extracts from T. hirsuta and T. suaveolens. Anticancer activities of T. suaveolens, T. cf. junipericola and T. trogii were first described here. The antibacterial ability of T. versicolor and T. hirsuta extracts has been confirmed. The antibacterial activities of T. suaveolens have been reported at the first time in this study. These results suggest an efficient application of the genus Trametes as the drug resources especially for anticancer agents.
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Background@#Suture ligation has been used widely for the treatment of rudimentary type extra digits, but several complications related to this treatment have been reported. The purpose of this study was to describe a new technique for excision of rudimentary preaxial polydactyly of the hand using electrocautery and assess its clinical outcomes. @*Methods@#The authors performed a retrospective study of 34 thumbs (32 patients) that had undergone excision of rudimentary preaxial polydactyly using electrocautery under local anesthesia. The mean follow-up period was 16.5 months. @*Results@#All children had full range of thumb motion without angular deformity at the most recent follow-up. There were no postoperative complications such as bleeding or infection. In 33 thumbs (97.1% of 34 thumbs), there were no signs of residual digit prominence. One thumb had a residual digit prominence at the extra digit removal site. In two thumbs, scar hypertrophy was evident at the operation site. All parents of the patients except two were very satisfied with this technique and the mean visual analog scale score for satisfaction was 9.5 ± 2.0 (range, 0–10). @*Conclusions@#Excision of rudimentary preaxial polydactyly of the hand with the use of electrocautery could remove an extra digit completely in 97.1% of the cases. This technique would be a useful alternative to suture ligation, surgical clip application, or surgical excision for the treatment of rudimentary preaxial polydactyly of the hand.
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Background@#The aim of this study was to analyze the inhibitory effects of copper, brass (78% copper, 22% tin), and stainless steel surfaces on multidrug-resistant Acinetobacter baumannii (MRAB), extended-spectrum beta-lactamase (ESBL) Escherichia coli , and carbapenem-resistant Klebsiella pneumoniae (CRKP). @*Methods@#MRAB, ESBL E. coli, and CRKP were isolated at Uijeongbu St. Mary's Hospital in 2020. A. baumannii ATCC BAA-747, E. coli ATCC 25922, and K. pneumoniae ATCC 700603 were used as reference strains. The initial bacterial cell count of each inoculum was adjusted to 8 log CFU/mL using phosphate buffered saline, Copper, brass, and stainless steel plates were inoculated with 9 mL of MRAB, ESBL E. coli, and CRKP inoculum solutions. The bacterial cell count was measured from the beginning to the 20th day in an incubator maintained at 35°C. @*Results@#MRAB, ESBL E. coli, and CRKP isolates were not detected on the copper and brass plates after 4, 5.5, and 6.5 hours, respectively. MRAB, ESBL E. coli, and CRKP isolates were not detected on the stainless steel plate after 15, 20, and 20 days, respectively. The bactericidal effects of copper and brass were much stronger than those of stainless steel. @*Conclusion@#The use of copper and copper alloys should be considered to prevent crossinfection in hospitals.
الملخص
Oxaliplatin, a third-generation platinum derivative, is the mainstay of current antineoplastic medications for advanced colorectal cancer therapy. However, peripheral neuropathic complications, especially cold allodynia, undermine the lifeprolonging outcome of this anti-cancer agent. Rosavin, a phenylpropanoid derived originally from Rhodiola rosea, exhibits a wide range of therapeutic properties. The present study explored whether and how rosavin alleviates oxaliplatin-induced cold hypersensitivity in mice. In the acetone drop test, cold allodynia behavior was observed from days 3 to 5 after a single injection of oxaliplatin (6 mg/kg, i.p.). Cold allodynia was significantly attenuated following rosavin treatment (10 mg/kg, i.p.). Specific endogenous 5-HT depletion by three consecutive pretreatments with parachlorophenylalanine (150 mg/kg/day, i.p.) abolished the analgesic action of rosavin; this effect was not observed following pretreatment with naloxone (opioid receptor antagonist, 10 mg/kg, i.p.). Furthermore, 5-HT1A receptor antagonist WAY-100635 (0.16 mg/kg, i.p.), but not 5-HT3 receptor antagonist MDL-72222 (1 mg/kg, i.p.), blocked rosavin-induced analgesia. These results suggest that rosavin may provide a novel approach to alleviate oxaliplatin-induced cold allodynia by recruiting the activity of 5-HT1A receptors.
الملخص
BACKGROUND@#Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCsladen acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury. @*METHODS@#The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining. @*RESULTS@#Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100b, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs.WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury. @*CONCLUSION@#WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.
الملخص
BACKGROUND@#Decellularized nerve allografting is one of promising treatment options for nerve defect. As an effort to develop more efficient nerve graft, recently we have developed a new decellularization method for nerve allograft. The aim of this study was to evaluate the effectiveness and biocompatibility of nerve graft decellularized by our newly developed method. @*METHODS@#Forty-eight inbred male Lewis rats were divided into two groups, Group I (autograft group, n = 25), Group II (decellularized isograft group, n = 23). Decellularized nerve grafts were prepared with our newly developed methods using amphoteric detergent and nuclease treatment. Serum cytokine level measurements at 0, 2, and 4 weeks and histologic evaluation for inflammatory cell infiltration at 6 and 16 weeks after nerve graft. @*RESULTS@#There was no significant difference in mean maximum isometric tetanic force and weight of tibialis anterior muscle or ankle angle at toe-off phase between two groups at 6 and 16 weeks survival time points (p > 0.05). There was no inflammatory cell infiltration in either group and histomorphometric assessments of 6- and 16-week specimens of the isograft group did not differ from those in the autograft group with regard to number of fascicle, cross sectional area, fascicle area ratio, and number of regenerated nerve cells. @*CONCLUSION@#Based on inflammatory reaction, axonal regeneration, and functional outcomes, our newly developed decellularized nerve grafts were fairly biocompatible and had comparable effectiveness to autografts for nerve regeneration, which suggested it would be suitable for nerve reconstruction as an alternative to autograft.
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Background@#The purpose of this study was to investigate the characteristics of women with subsequent distal radius fracture (DRF) and to compare bone fragility variables in women with initial and subsequent DRF. @*Methods@#We enrolled 227 women who experienced DRF (203 women with initial DRF and 24 women with subsequent DRF) between September 2016 and April 2019. We compared demographic characteristics and bone fragility variables, including bone mineral density, trabecular bone score, hip geometry, bicortical thickness of the distal radius, and fracture risk assessment tool (FRAX) scores between the 2 groups. To reduce bias, patients with subsequent DRF were propensity score-matched in a 1:2 manner with patients affected by initial DRF, and additional comparisons were performed. @*Results@#Patients in the subsequent DRF group were older than those in the initial DRF group, but this difference was not significant (P=0.091). The proportion of patients receiving treatment with osteoporosis medication was significantly higher in the subsequent DRF group (41.7% vs. 19.2%, P=0.011). Bone fragility variables did not differ significantly between the 2 groups. However, the ten-year probability of major osteoporotic fractures based on FRAX scores was significantly higher in patients with subsequent DRF (7.5% vs. 10.8%, P<0.001). Similar results were observed when comparing the propensity score-matched initial and subsequent DRF groups. @*Conclusions@#These findings suggest that the occurrence of subsequent DRF after initial DRF can be attributed to multiple factors rather than bone fragility alone. Systematic and multidisciplinary management would be helpful in preventing the occurrence of subsequent DRF after the initial DRF.
الملخص
Oxaliplatin, a third-generation platinum derivative, is the mainstay of current antineoplastic medications for advanced colorectal cancer therapy. However, peripheral neuropathic complications, especially cold allodynia, undermine the lifeprolonging outcome of this anti-cancer agent. Rosavin, a phenylpropanoid derived originally from Rhodiola rosea, exhibits a wide range of therapeutic properties. The present study explored whether and how rosavin alleviates oxaliplatin-induced cold hypersensitivity in mice. In the acetone drop test, cold allodynia behavior was observed from days 3 to 5 after a single injection of oxaliplatin (6 mg/kg, i.p.). Cold allodynia was significantly attenuated following rosavin treatment (10 mg/kg, i.p.). Specific endogenous 5-HT depletion by three consecutive pretreatments with parachlorophenylalanine (150 mg/kg/day, i.p.) abolished the analgesic action of rosavin; this effect was not observed following pretreatment with naloxone (opioid receptor antagonist, 10 mg/kg, i.p.). Furthermore, 5-HT1A receptor antagonist WAY-100635 (0.16 mg/kg, i.p.), but not 5-HT3 receptor antagonist MDL-72222 (1 mg/kg, i.p.), blocked rosavin-induced analgesia. These results suggest that rosavin may provide a novel approach to alleviate oxaliplatin-induced cold allodynia by recruiting the activity of 5-HT1A receptors.
الملخص
BACKGROUND@#Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCsladen acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury. @*METHODS@#The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining. @*RESULTS@#Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100b, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs.WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury. @*CONCLUSION@#WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.
الملخص
BACKGROUND@#Decellularized nerve allografting is one of promising treatment options for nerve defect. As an effort to develop more efficient nerve graft, recently we have developed a new decellularization method for nerve allograft. The aim of this study was to evaluate the effectiveness and biocompatibility of nerve graft decellularized by our newly developed method. @*METHODS@#Forty-eight inbred male Lewis rats were divided into two groups, Group I (autograft group, n = 25), Group II (decellularized isograft group, n = 23). Decellularized nerve grafts were prepared with our newly developed methods using amphoteric detergent and nuclease treatment. Serum cytokine level measurements at 0, 2, and 4 weeks and histologic evaluation for inflammatory cell infiltration at 6 and 16 weeks after nerve graft. @*RESULTS@#There was no significant difference in mean maximum isometric tetanic force and weight of tibialis anterior muscle or ankle angle at toe-off phase between two groups at 6 and 16 weeks survival time points (p > 0.05). There was no inflammatory cell infiltration in either group and histomorphometric assessments of 6- and 16-week specimens of the isograft group did not differ from those in the autograft group with regard to number of fascicle, cross sectional area, fascicle area ratio, and number of regenerated nerve cells. @*CONCLUSION@#Based on inflammatory reaction, axonal regeneration, and functional outcomes, our newly developed decellularized nerve grafts were fairly biocompatible and had comparable effectiveness to autografts for nerve regeneration, which suggested it would be suitable for nerve reconstruction as an alternative to autograft.
الملخص
Background@#The purpose of this study was to investigate the characteristics of women with subsequent distal radius fracture (DRF) and to compare bone fragility variables in women with initial and subsequent DRF. @*Methods@#We enrolled 227 women who experienced DRF (203 women with initial DRF and 24 women with subsequent DRF) between September 2016 and April 2019. We compared demographic characteristics and bone fragility variables, including bone mineral density, trabecular bone score, hip geometry, bicortical thickness of the distal radius, and fracture risk assessment tool (FRAX) scores between the 2 groups. To reduce bias, patients with subsequent DRF were propensity score-matched in a 1:2 manner with patients affected by initial DRF, and additional comparisons were performed. @*Results@#Patients in the subsequent DRF group were older than those in the initial DRF group, but this difference was not significant (P=0.091). The proportion of patients receiving treatment with osteoporosis medication was significantly higher in the subsequent DRF group (41.7% vs. 19.2%, P=0.011). Bone fragility variables did not differ significantly between the 2 groups. However, the ten-year probability of major osteoporotic fractures based on FRAX scores was significantly higher in patients with subsequent DRF (7.5% vs. 10.8%, P<0.001). Similar results were observed when comparing the propensity score-matched initial and subsequent DRF groups. @*Conclusions@#These findings suggest that the occurrence of subsequent DRF after initial DRF can be attributed to multiple factors rather than bone fragility alone. Systematic and multidisciplinary management would be helpful in preventing the occurrence of subsequent DRF after the initial DRF.
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The primary somatosensory (S1) cortex plays a key role in distinguishing different sensory stimuli. Vibrotactile touch information is conveyed from the periphery to the S1 cortex through three major classes of mechanoreceptors: slowly adapting type 1 (SA1), rapidly adapting (RA), and Pacinian (PC) afferents. It has been a long-standing question whether specific populations in the S1 cortex preserve the peripheral segregation by the afferent submodalities. Here, we investigated whether S1 neurons exhibit specific responses to two distinct vibrotactile stimuli, which excite different types of mechanoreceptors (e.g., SA1 and PC afferents). Using in vivo two-photon microscopy and genetically encoded calcium indicator, GCaMP6s, we recorded calcium activities of S1 L2/3 neurons. At the same time, static (<1 Hz) and dynamic (150 Hz) vibrotactile stimuli, which are known to excite SA1 and PC, respectively, were pseudorandomly applied to the right hind paw in lightly anesthetized mice. We found that most active S1 neurons responded to both static and dynamic stimuli, but more than half of them showed preferred responses to either type of stimulus. Only a small fraction of the active neurons exhibited specific responses to either static or dynamic stimuli. However, the S1 population activity patterns by the two stimuli were markedly distinguished. These results indicate that the vibrotactile inputs driven by excitation of distinct submodalities are converged on the single cells of the S1 cortex, but are well discriminated by population activity patterns composed of neurons that have a weighted preference for each type of stimulus.