Homogenizing out-of-plane cation composition in perovskite solar cells.

Perovskite solar cells with the formula FA1-xCsxPbI3, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice1,2, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells3,4. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.

Predicting adequate segmental lordosis correction in lumbar spinal stenosis patients undergoing oblique lumbar interbody fusion: a focus on the discontinuous segment.

PURPOSE: To identify the factors associated with a correction of the segmental angle (SA) with a total change greater than 10° in each level following minimally invasive oblique lumbar interbody fusion (MIS-OLIF). METHODS: Patients with lumbar spinal stenosis who underwent single- or two-level MIS-OLIF were reviewed. Segments with adequate correction of the SA >10° after MIS-OLIF in immediate postoperative radiograph were categorized as discontinuous segments (D segments), whereas those without such improvement were assigned as continuous segments (C segments). Clinical and radiological parameters were compared, and multivariate logistic regression analysis was performed to identify factors associated with SA correction >10° after MIS-OLIF. RESULTS: Of 211 segments included, 38 segments (18.0%) were classified as D segments. Compared with C segments, D segments demonstrated a significantly smaller preoperative SA (mean ± standard deviation [SD], - 1.1° ± 6.7° vs. 6.6° ± 6.3°, p < 0.001), larger change of SA (mean ± SD, 13.5° ± 3.4° vs. 3.1° ± 3.9°, p < 0.001), and a higher rate of presence of facet effusion (76.3% vs. 48.6%, p = 0.002). Logistic regression revealed preoperative SA (odds ratio (OR) [95% confidence interval (CI)]:0.733 [0.639-0.840], p < 0.001) and facet effusion (OR [95% CI]:14.054 [1.758-112.377], p = 0.027) as significant predictors for >10° SA correction after MIS-OLIF. CONCLUSION: Preoperative kyphotic SA and facet effusion can predict SA correction >10° following MIS-OLIF. For patients with lordotic SA and no preoperative facet effusion, supplemental procedures, such as anterior column release or posterior osteotomy, should be prepared for additional lumbar lordosis correction required for remnant global sagittal imbalance after MIS-OLIF.

Facet-Dependent Passivation for Efficient Perovskite Solar Cells.

Understanding the interplay between the surface structure and the passivation materials and their effects associated with surface structure modification is of fundamental importance; however, it remains an unsolved problem in the perovskite passivation field. Here, we report a surface passivation principle for efficient perovskite solar cells via a facet-dependent passivation phenomenon. The passivation process selectively occurs on facets, which is observed with various post-treatment materials with different functionality, and the atomic arrangements of the facets determine the alignments of the passivation layers. The profound understanding of facet-dependent passivation leads to the finding of 2-amidinopyridine hydroiodide as the material for a uniform and effective passivation on both (100) and (111) facets. Consequently, we achieved perovskite solar cells with an efficiency of 25.10% and enhanced stability. The concept of facet-dependent passivation can provide an important clue on unidentified passivation principles for perovskite materials and a novel means to enhance the performance and stability of perovskite-based devices.

Differential effects of two phosphodiesterase 4 inhibitors against lipopolysaccharide-induced neuroinflammation in mice.

BACKGROUND: Several phosphodiesterase 4 (PDE4) inhibitors have emerged as potential therapeutics for central nervous system (CNS) diseases. This study investigated the pharmacological effects of two selective PDE4 inhibitors, roflumilast and zatolmilast, against lipopolysaccharide-induced neuroinflammation. RESULTS: In BV-2 cells, the PDE4 inhibitor roflumilast reduced the production of nitric oxide and tumor necrosis factor-α (TNF-α) by inhibiting NF-κB phosphorylation. Moreover, mice administered roflumilast had significantly reduced TNF-α, interleukin-1ß (IL-1ß), and IL-6 levels in plasma and brain tissues. By contrast, zatolmilast, a PDE4D inhibitor, showed no anti-neuroinflammatory effects in vitro or in vivo. Next, in vitro and in vivo pharmacokinetic studies of these compounds in the brain were performed. The apparent permeability coefficients of 3 µM roflumilast and zatolmilast were high (> 23 × 10-6 cm/s) and moderate (3.72-7.18 × 10-6 cm/s), respectively, and increased in a concentration-dependent manner in the MDR1-MDCK monolayer. The efflux ratios were < 1.92, suggesting that these compounds are not P-glycoprotein substrates. Following oral administration, both roflumilast and zatolmilast were slowly absorbed and eliminated, with time-to-peak drug concentrations of 2-2.3 h and terminal half-lives of 7-20 h. Assessment of their brain dispositions revealed the unbound brain-to-plasma partition coefficients of roflumilast and zatolmilast to be 0.17 and 0.18, respectively. CONCLUSIONS: These findings suggest that roflumilast, but not zatolmilast, has the potential for use as a therapeutic agent against neuroinflammatory diseases.

Is endotracheal tube displacement during head and neck extension due to ascending movement or tracheal lengthening? An observational ultrasonographic study.

Complications of the endotracheal tube (ETT) displacement during head and neck positional changes are related to not only the tip position but also the cuff pressure against the larynx. Here, we evaluated movement of the ETT cuff relative to laryngeal structures as well as tip displacement from the carina.Sixty-two patients scheduled for thyroidectomy were recruited. The distance from the cricoid cartilage to the upper margin of the cuff (CC) and that from the ETT tip to the carina (TC) were measured using ultrasonography and fiberoptic bronchoscopy, respectively, during flexion and extension. The total tracheal length (TTL) was defined as the combination of CC, TC, and the distance from the upper margin of the cuff to the tip.During flexion, the CC and TC were 1.5 ± 0.6 and 2.9 ± 1.0 cm respectively. Seven patients (11.7%) exhibited excessively deep intubation. After adjusting the cuff position under ultrasonography (CC = 0), the tip position was corrected in 96.7%. While the TC increased by 2.1 ± 1.0 cm after the positional change in extension, the CC decreased by 0.6 ± 0.7 cm because the TTL lengthened (1.4 ± 1.1 cm). Four patients (6.7%) exhibited excessive cuff displacement beyond the cricoid cartilage, which could have been corrected under ultrasonography.In conclusion, the ETT cuff displaced toward the larynx in a less degree than the tip did from the carina due to the tracheal lengthening during head and neck extension. Nevertheless, we suggest that ultrasonographic assessment of cuff position may avoid ETT misplacement. Trial registration https://cris.nih.go.kr/ (approval no. KCT0005319); registered on May 14, 2019.

Probability for surgical treatment in patients with lumbar spinal stenosis according to the stenotic lesion severity: a 5-10-year follow-up study.

BACKGROUND: We aimed (1) to clarify difference in the natural history of lumbar spinal stenosis (LSS) with respect to surgical treatment according to severity of stenosis on magnetic resonance imaging (MRI) using qualitative grading system and (2) to estimate surgical probabilities depending on radiological severity. METHODS: With the design of retrospective observational study, a total of 1,248 patients diagnosed with LSS between 2011 and 2014 at our hospital were followed up for the mean duration of 7.7 years (5.17-9.8 years). We investigated severity of central and foraminal stenoses on initial MRI using qualitative grading system and whether surgical treatment was performed. Logistic regression models were used to identify risk factors for surgery. RESULTS: During the mean follow-up period of 7.7 years, grade 3 maximal central stenosis showed the highest percentage of surgical treatment (57.9%-62.3%) with no significant difference in surgical probabilities according to concomitant foraminal stenosis. Surgical probabilities in grade 2 and 3 maximal foraminal stenosis, were 22.2%-62.3% and 33.3%-57.9%, respectively, depending on concomitant central stenosis. Maximal central stenosis of grades 1, 2, and 3 (odds ratio [OR]: 1.79, 2.21, and 6.26, respectively), and maximal foraminal stenosis of grades 2 and 3 (OR: 2.22 and 2.12, respectively) were significant risk factors for surgical treatment. CONCLUSIONS: The high grades of maximal central and foraminal stenoses were risk factors for surgical treatment. Surgical probabilities were 57.9%-62.3% in grade 3 maximal central stenosis, 22.2%-62.3% and 33.3%-57.9%, respectively, in grade 2 and 3 maximal foraminal stenosis during the mean follow-up period of 7.7 years. These results indicate that the natural history of LSS differs according to grade of maximal central and foraminal stenoses.

Biaxially strained germanium crossbeam with a high-quality optical cavity for on-chip laser applications.

The creation of CMOS compatible light sources is an important step for the realization of electronic-photonic integrated circuits. An efficient CMOS-compatible light source is considered the final missing component towards achieving this goal. In this work, we present a novel crossbeam structure with an embedded optical cavity that allows both a relatively high and fairly uniform biaxial strain of ∼0.9% in addition to a high-quality factor of >4,000 simultaneously. The induced biaxial strain in the crossbeam structure can be conveniently tuned by varying geometrical factors that can be defined by conventional lithography. Comprehensive photoluminescence measurements and analyses confirmed that optical gain can be significantly improved via the combined effect of low temperature and high strain, which is supported by a three-fold reduction of the full width at half maximum of a cavity resonance at ∼1,940 nm. Our demonstration opens up the possibility of further improving the performance of germanium lasers by harnessing geometrically amplified biaxial strain.

Process of Obtaining Social Consensus and 3-Year Functional Outcomes of the First Hand Allotransplantation in Korea.

BACKGROUND: On February 2, 2017, the surgical team of ten board-certified hand specialists of W Hospital in Korea successfully performed the nation's first hand transplantation at Yeungnam University Medical Center (YUMC). This paper reports on the legal, financial, and cultural hurdles that were overcome to open the way for hand transplantation and its functional outcomes at 36 months after the operation. METHODS: W Hospital formed a memorandum of understanding with Daegu city and YUMC to comply with government regulations regarding hand transplantation. Campaigns were initiated in the media to increase public awareness and understanding. With the city's financial and legal support and the university's medical cooperation, a surgical team performed a left distal forearm hand transplantation from a brain-dead 48-year-old man to a 35-year-old left-handed man. RESULTS: With this successful allotransplantation, the Korean Act on Organ Transplantation has now been amended to include hand transplantation. Korean national health insurance has also begun covering hand transplantation. Functional outcome at 36 months after the operation showed satisfactory progress in both motor and sensory functions. The disabilities of the arm, shoulder, and hand score were 23. The final Hand Transplantation Score was 90 points. Functional brain magnetic resonance imaging shows significant cortical reorganization of the corticospinal tract, and reinnervation of intrinsic muscle is observed. CONCLUSIONS: Hand transplantation at the distal forearm shows very satisfactory outcomes in functional, aesthetical, and psychological aspects. Legal and financial barriers against hand transplantation have long been the most burdensome issues. Despite this momentous success, there have been no other clinical applications of vascularized composite allotransplantation due to the limited acceptance by Korean doctors and people. Further public education campaigns for vascularized composite allotransplantation are needed to increase awareness and acceptance.

High-fat diet-induced obesity exacerbates kainic acid-induced hippocampal cell death.

BACKGROUND: Obesity has deleterious effects on the brain, and metabolic dysfunction may exacerbate the outcomes of seizures and brain injuries. However, it is unclear whether obesity affects excitotoxicity-induced neuronal cell death. The purpose of this study was to investigate the effects of a high-fat diet (HFD) on neuroinflammation and oxidative stress in the hippocampus of kainic acid (KA)-treated mice. RESULTS: Mice were fed with a HFD or normal diet for 8 weeks and then received a systemic injection of KA. HFD-fed mice showed hypercholesterolemia, insulin resistance, and hepatic steatosis. HFD-fed mice showed greater susceptibility to KA-induced seizures, an increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, neuroinflammation, and oxidative stress. Furthermore, we found that KA treatment increased HFD-induced calpain1, nuclear factor E2-related factor 2, and heme oxygenase-1 expression in the hippocampus. CONCLUSIONS: These findings imply that complex mechanisms affected by obesity-induced systemic inflammation, neuroinflammation, ER stress, calcium overload, and oxidative stress may contribute to neuronal death after brain injury.

Open prospective study of ziprasidone in patients with schizophrenia with depressive symptoms: a multicenter study.

AIMS: The goal of this study was to examine the efficacy and safety of ziprasidone to treat depressive symptoms in Korean patients with schizophrenia who showed stable symptoms. METHODS: In this 8-week, open-label, prospective, non-randomized, multicenter study, 34 patients with schizophrenia who showed a stable response to previous medications, maintained a stable dose, and who had depressive symptoms, were recruited. Ziprasidone was the only antipsychotic agent allowed for 8 weeks after a 2-7-week washout period. RESULTS: Steady decreases were observed on the Montgomery-Asberg Depression Rating Scale, the Calgary Depression Scale for Schizophrenia, the Positive and Negative Syndrome Scale, and the Clinical Global Impression-Severity Scale scores. The Montgomery-Asberg Depression Rating Scale score was 20.26 ± 4.77 at baseline and 12.21 ± 7.94 at the end-point (P < 0.01). The Calgary Depression Scale for Schizophrenia score was 9.76 ± 4.11 at baseline and 5.00 ± 3.94 at the end-point (P < 0.01). The Positive and Negative Syndrome Scale total score was 75.24 ± 22.63 at baseline and 66.53 ± 24.28 at the end-point (P < 0.01). The Clinical Global Impression-Severity Scale score was 3.44 ± 0.66 at baseline and 3.15 ± 0.86 at the end-point (P < 0.05). No significant differences were observed for total scores on the Simpson and Angus Rating Scale, the Barnes Akathisia Rating Scale, or the Abnormal Involuntary Movement Scale between the baseline and end-point. CONCLUSIONS: Ziprasidone was effective for improving depressive symptom scores and was well tolerated. Switching to ziprasidone is a good strategy in patients with schizophrenia who are experiencing depressive symptoms.

Delayed and suspended replantation for complete amputation of digits and hands.

PURPOSE: To analyze the clinical outcome for delayed or suspended replantation of complete amputations of digits or hands, or both. METHODS: We analyzed 20 cases involving 28 digital and 4 hand amputations that underwent delayed or suspended replantation. In 15 cases of single-digit amputation, patients underwent delayed replantation the morning following amputation. With amputation of multiple digits, bilateral digits, or the hand, the important digits or dominant hand underwent immediate replantation, and we suspended the surgeries for the residual digits or non-dominant hand, or both, until the next morning. We then evaluated the mean warm and cold ischemic time for the operations, graft survival rates, and clinical outcomes. The mean follow-up period was 26 months. We evaluated the clinical results using the criteria of Chen. RESULTS: The mean warm and cold ischemic times in 15 cases of delayed replantation were 2 hours 4 minutes and 7 hours 21 minutes, respectively. In 8 cases of suspended replantation, the mean warm and cold ischemic times in the first operation were 5 hours 54 minutes and 2 hours 36 minutes, respectively. In the second operation, the cold ischemic time averaged 15 hours 48 minutes. In this series, 24 of 28 digits and all 4 hands survived. Total survival incidence in both delayed and suspended replantation was 88%, not statistically different from the overall survival incidence in 711 cases of immediate replantation during the same period (84%). In delayed replantation, we observed an excellent result with 6 digits and a good result with another 6 digits. In suspended cases, we observed a good result with one multiple-digit and one hand procedure and we obtained a fair result in 3 multiple-digit and 2 hand replantation procedures. CONCLUSIONS: Delayed and suspended replantations demonstrate results comparable to immediate replantation regarding graft survival and clinical outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Germanium p-i-n avalanche photodetector fabricated by point defect healing process.

In this Letter, we report Ge p-i-n avalanche photodetectors (APD) with low dark current (sub 1 µA below V(R)=5 V), low operating voltage (avalanche breakdown voltage=8-13 V), and high multiplication gain (440-680) by exploiting a point defect healing method (between 600°C and 650°C) and optimizing the doping concentration of the intrinsic region (p-type ~10¹7 cm⁻³). In addition, Raman spectroscopy and electrochemical capacitance voltage analyses were performed to investigate the junction interfaces in more detail. This successful demonstration of Ge p-i-n APD with low dark current, low operating voltage, and high gain is promising for low-power and high-sensitivity Ge PD applications.

Innovative Developments in Lumbar Interbody Cage Materials and Design: A Comprehensive Narrative Review.

This review comprehensively examines the evolution and current state of interbody cage technology for lumbar interbody fusion (LIF). This review highlights the biomechanical and clinical implications of the transition from traditional static cage designs to advanced expandable variants for spinal surgery. The review begins by exploring the early developments in cage materials, highlighting the roles of titanium and polyetheretherketone in the advancement of LIF techniques. This review also discusses the strengths and limitations of these materials, leading to innovations in surface modifications and the introduction of novel materials, such as tantalum, as alternative materials. Advancements in three-dimensional printing and surface modification technologies form a significant part of this review, emphasizing the role of these technologies in enhancing the biomechanical compatibility and osseointegration of interbody cages. In addition, this review explores the increase in biodegradable and composite materials such as polylactic acid and polycaprolactone, addressing their potential to mitigate long-term implant-related complications. A critical evaluation of static and expandable cages is presented, including their respective clinical and radiological outcomes. While static cages have been a mainstay of LIF, expandable cages are noted for their adaptability to the patient's anatomy, reducing complications such as cage subsidence. However, this review highlights the ongoing debate and the lack of conclusive evidence regarding the superiority of either cage type in terms of clinical outcomes. Finally, this review proposes future directions for cage technology, focusing on the integration of bioactive substances and multifunctional coatings and the development of patient-specific implants. These advancements aim to further enhance the efficacy, safety, and personalized approach of spinal fusion surgeries. Moreover, this review offers a nuanced understanding of the evolving landscape of cage technology in LIF and provides insights into current practices and future possibilities in spinal surgery.

Ideal Lumbar Lordosis Correction in Patients with Adult Spinal Deformity Without Adversely Impacting Pelvic Tilt and Pelvic Incidence Minus Lumbar Lordosis: A Study of 426 Cases.

STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the ideal pelvic incidence (PI) - lumbar lordosis (LL) range to prevent pelvic tilt (PT) undercorrection while avoiding PI-LL overcorrection following adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND: PI-LL and PT are the important sagittal parameters to be restored to an adequate range by surgery. Ideal PI-LL target without causing PI-LL overcorrection and PT undercorrection has not been documented. METHODS: We included patients with ASD undergoing ≥5-level fusion including the sacrum. Receiver operating characteristic (ROC) curve analysis was performed to calculate the lower limit of the ideal PI-LL without causing PI-LL overcorrection and the upper limit of ideal PI-LL without causing PT undercorrection. The calculated ideal PI-LL was validated in terms of proximal junctional kyphosis and failure (PJK and PJF) rates and clinical outcomes. Analyses were performed according to age subgroups (<70 and ≥70 y). RESULTS: In total, 426 patients were included in the study. Female patients were predominant (85.4%), with a mean age of 69.8 years. The lower limits of PI-LL were calculated as 4.9° for all patients, 2.3° for patients aged <70 years, and 7.9° for patients aged ≥70 years. Meanwhile, the upper limits of PI-LL were calculated as 12.7° for all patients, 12.5° for patients aged <70 years, and 13.3° for patients aged ≥70 years. There were no significant differences in the PJK and PJF rates among the new three PI-LL groups. Clinical outcomes were significantly better in patients with the ideal PI-LL group than those in patients with overcorrection or undercorrection groups for all age groups. CONCLUSION: The ideal PI-LL correction target without adversely impacting PT and PI-LL was calculated at 2.3°-12.5° for patients aged <70 years and 7.9°-13.3° for patients aged ≥70 years. These guideline parameters may help ensure optimal clinical outcomes without increasing the risk of PJK/F.

Are Surgical Outcomes Different According to Baseline Balance Status in Elderly Patients with Degenerative Sagittal Imbalance?

STUDY DESIGN: Retrospective study. OBJECTIVE: We sought to compare surgical outcomes according to baseline balance statuses in elderly patients with degenerative sagittal imbalance (DSI). SUMMARY OF BACKGROUND: Although optimal sagittal correction has been emphasized for good surgical outcomes, the effect of the state of preoperative balance on surgical outcome has been adequately described at present. METHODS: Patients aged ≥60 years with DSI who underwent ≥5-level fusion to the sacrum were included. Among them, only those who postoperatively achieved the optimal age-adjusted pelvic incidence (PI) - lumbar lordosis (LL) target were included in this study. Study participants were divided into two groups according to their preoperative sagittal vertical axis (SVA): compensatory balance (SVA <5 cm, group CB) and decompensation (SVA ≥5 cm, group D). Comparisons between the two groups were performed using the chi-squared test or Fisher's exact test for categorical variables and the independent t- test or Wilcoxon rank- sum test for continuous variables. RESULTS: A total of 156 patients whose postoperative sagittal alignment matched the age-adjusted PI-LL target constituted the study cohort. There were 59 patients in group CB and 97 patients in group D. Mean follow-up duration was 50.0 months after surgery. Immediate postoperatively, sacral slope and SVA were significantly greater in group D than in group CB. At last follow-up, the SVA was significantly greater in group D than in group CB (43.6 vs. 22.7 mm), while no significant differences were found in other sagittal parameters. The Oswestry disability index and Scoliosis Research Society -22 scores at the last follow-up were significantly worse in group D than in group CB. CONCLUSION: The SVA tended to experience less correction postoperatively, with evidence of further deterioration during follow-up in group D than in group CB. This suboptimal correction of SVA may contribute to the inferior clinical outcomes encountered in group D relative to group CB. Therefore, we recommend correction of PI-LL as close as possible to the lower limit of the suggested PI-LL target range in patients with evidence of preoperative decompensation.

Hook Fixation at Uppermost Instrumented Vertebra +1 Reduced Proximal Junctional Failure in Adult Patients With Spinal Deformity Having Achieved Optimal Deformity Correction by Sagittal Age-Adjusted Score.

BACKGROUND AND OBJECTIVES: Appropriate correction relative to the age-adjusted sagittal alignment target reduces the proximal junctional failure (PJF) risk. Nonetheless, a considerable number of patients suffer from PJF despite optimal correction. The aim of this study was to identify the risk factors of PJF that occurs despite optimal correction relative to the sagittal age-adjusted score (SAAS) in adult spinal deformity surgery. METHODS: Patients aged 60 years or older with adult spinal deformity who underwent ≥5-level fusion to the sacrum were initially screened. Among them, only patients who achieved optimal sagittal correction relative to the SAAS were included in the study. Optimal correction was defined as the SAAS point between -1 and +1. Various clinical and radiographic factors were compared between the PJF and no PJF groups and were further evaluated using multivariate analysis. RESULTS: The final study cohort comprised 127 patients. The mean age was 67 years, and there were 111 women (87.4%). A mean of total fusion length was 7.2. PJF occurred in 42 patients (33.1%), while 85 patients (66.9%) did not develop PJF. Multivariate analysis showed that a high body mass index (odds ratio [OR] = 1.153, 95% CI = 1.027-1.295, P = .016), a higher lordosis distribution index (LDI) (OR = 1.024, 95% CI = 1.003-1.045, P = .022), and no use of hook fixation (OR = 9.708, 95% CI = 1.121-76.923, P = .032) were significant risk factors of PJF development. In the receiver operating characteristic curve analysis, the cutoff value for the LDI was calculated as 61.0% (area under the curve = 0.790, P < .001). CONCLUSION: PJF developed in a considerable portion of patients despite optimal correction relative to the age-adjusted alignment. The risk factors of PJF in this patient group were high body mass index, high LDI exceeding 61%, and no use of hook fixation. PJF could be further decreased by properly managing these risk factors along with optimal sagittal correction.

Intrathecal gastrodin alleviates allodynia in a rat spinal nerve ligation model through NLRP3 inflammasome inhibition.

BACKGROUND: Gastrodin (GAS), a main bioactive component of the herbal plant, Gastrodia elata Blume, has shown to have beneficial effects on neuroinflammatory diseases such as Alzheimer's disease in animal studies and migraine in clinical studies. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. This study investigated the effects of GAS on the intensity of mechanical allodynia and associated changes in NLRP3 inflammasome expression at the spinal level using L5/6 spinal nerve ligation model (SNL) in rats. METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1ß (IL-1ß) and cellular expression were examined in the spinal cord and dorsal root ganglion. RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1ß were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS. CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1ß is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.

Antinociceptive effects of nefopam activating descending serotonergic modulation via 5-HT2 receptors in the nucleus raphe magnus.

BACKGROUND: Nefopam is a centrally acting antinociceptive drug; however, the underlying mechanisms are not fully understood. This study investigated the supraspinal mechanisms of nefopam. METHODS: The effects of intraperitoneally administered nefopam were assessed in rats using the formalin test, and the mechanisms were investigated by intrathecal or intra-nucleus raphe magnus (NRM) pre-treatment with the serotonin (5-HT) receptor antagonist or 5-HT2 receptor antagonist. The change in extracellular 5-HT levels was measured by spinal cord microdialysis. RESULTS: Intraperitoneally administered nefopam showed antinociceptive effects in the rat formalin test, which were reversed by intrathecal pre-treatment with 5-HT receptor antagonist dihydroergocristine. Microdialysis study revealed that systemic nefopam significantly increased 5-HT level in the spinal dorsal horn. Pretreatment of cinanserin, a 5-HT2 receptor antagonist, into the NRM blocked the antinociceptive effects of intraperitoneally delivered nefopam. Direct injection of nefopam into the NRM mimicked the effects of systemic nefopam, and this effect was reversed by intra-NRM cinanserin pre-treatment. The increase in spinal level of 5-HT by systemic nefopam was attenuated by intra-NRM cinanserin pre-treatment. CONCLUSION: The antinociceptive effects of systemically administered nefopam are mediated by 5-HT2 receptors in the NRM, which recruit the descending serotonergic fibres to increase the release of 5-HT into the spinal dorsal horn. SIGNIFICANCE: This study revealed supraspinal mechanisms of nefopam-produced analgesia mediated by 5-HT2 receptors in the NRM recruiting the descending serotonergic fibres to increase the release of 5-HT into the spinal dorsal horn. These observations support a potential role for nefopam in multimodal analgesia based on its distinct mechanisms of action that are not shared by the other analgesics.

Comparison of Surgical Burden, Radiographic and Clinical Outcomes According to the Severity of Baseline Sagittal Imbalance in Adult Spinal Deformity Patients.

OBJECTIVE: To determine the clinical impact of the baseline sagittal imbalance severity in patients with adult spinal deformity (ASD). METHODS: We retrospectively reviewed patients who underwent ≥ 5-level fusion including the pelvis, for ASD with a ≥ 2-year follow-up. Using the Scoliosis Research Society-Schwab classification system, patients were classified into 3 groups according to the severity of the preoperative sagittal imbalance: mild, moderate, and severe. Postoperative clinical and radiographic results were compared among the 3 groups. RESULTS: A total of 259 patients were finally included. There were 42, 62, and 155 patients in the mild, moderate, and severe groups, respectively. The perioperative surgical burden was greatest in the severe group. Postoperatively, this group also showed the largest pelvic incidence minus lumbar lordosis mismatch, suggesting a tendency towards undercorrection. No statistically significant differences were observed in proximal junctional kyphosis, proximal junctional failure, or rod fractures among the groups. Visual analogue scale for back pain and Scoliosis Research Society-22 scores were similar across groups. However, severe group's last follow-up Oswestry Disability Index (ODI) scores significantly lower than those of the severe group. CONCLUSION: Patients with severe sagittal imbalance were treated with more invasive surgical methods along with increased the perioperative surgical burden. All patients exhibited significant radiological and clinical improvements after surgery. However, regarding ODI, the severe group demonstrated slightly worse clinical outcomes than the other groups, probably due to relatively higher proportion of undercorrection. Therefore, more rigorous correction is necessary to achieve optimal sagittal alignment specifically in patients with severe baseline sagittal imbalance.

Unilateral Pediculectomy and Reduction with Short-Segment Pedicle Screw Fixation for Thoracolumbar Burst Fracture: A Case Series.

BACKGROUND: This study aimed to evaluate the efficacy of unilateral pediculectomy and reduction with short-segment pedicle screw fixation for thoracolumbar burst fracture. METHODS: We retrospectively reviewed patients who underwent a unilateral pediculectomy and reduction with short-segment fixation and interbody fusion for thoracolumbar burst fracture. The unilateral pediculectomy created sufficient space to approach the ventral side of the spinal cord for removing bone fragments and insertion of an interbody cage to correct kyphosis. Lumbar lordosis (LL), pelvic incidence (PI) minus LL, and segmental Cobb angle were measured at 3 time points: preoperatively, postoperatively, and final follow-up. Furthermore, sagittal vertical axis (SVA) was measured to assess global sagittal balance at the final follow-up. RESULTS: A total of 10 patients, with a mean age of 39.8 ± 21.0, underwent the surgical procedure. All patients had a thoracolumbar injury classification and severity score > 5. The mean follow-up period was 15.8 ± 13.9 months. The mean postoperative LL (46.0 ± 5.8) was significantly higher (P = 0.008) than the preoperative measurement (32.8 ± 8.2). The mean postoperative PI minus LL (2.2 ± 8.4) was not significantly lower (P = 0.051) than preoperative measurement (15.4 ± 12.6). The mean postoperative segmental Cobb angle (11.4 ± 8.4) was significantly higher (P < 0.001) than the preoperative measurement (-11.6 ± 10.9). At the final follow-up, the mean sagittal vertical axiswas 10.0 ± 28.8 mm. CONCLUSIONS: Unilateral pediculectomy and reduction with short-segment fixation and interbody fusion served as an efficient surgical method for thoracolumbar burst fracture.