Comparison of Functional and Cosmetic Outcomes According to Fracture Level in Gartland Type III Pediatric Supracondylar Humerus Fractures.

Background: Supracondylar humerus (SCH) fractures in children have been traditionally categorized according to the Wilkins-modified Gartland classification scheme, which is solely based on the degree of displacement. As this classification does not consider fracture patterns in the coronal or sagittal plane, the relationship between the fracture pattern and prognosis in SCH fractures remains unclear. Therefore, the purpose of this study was to evaluate the relationship between the fracture level and prognosis of pediatric SCH fractures. Methods: Medical records and radiographs of 786 patients with SCH fractures who underwent surgical treatment between March 2004 and December 2017 were reviewed. A total of 192 patients were included in this study. Anteroposterior elbow radiographs taken at the time of injury were evaluated to obtain the level of fracture. Functional outcomes were evaluated based on modified Flynn grading at the last follow-up. Results: Of 192 patients included in this study, 24 (12.1%), 148 (74.8%), and 20 (10.1%) had fractures in zone 1 (metaphyseal-diaphyseal area), zone 2 (between zones 1 and 3), and zone 3 (metaphyseal-epiphyseal area), respectively. There were significant differences in age at the time of injury (p = 0.011), direction of fracture displacement (p = 0.014), and loss of carrying angle (p < 0.001) between fractures in zone 3 and those in zone 1 or zone 2. Zone 3 fractures and classic zone 2 fractures also showed significant difference in outcomes, with zone 3 fractures having more unsatisfactory outcome than classic zone 2 fractures (p = 0.049). Conclusions: For SCH fractures, varus deformity of the elbow was more common in zone 3 (metaphyseal-epiphyseal area) than in the other zones. Thus, pediatric orthopedic surgeons should be mindful of the possibility of cubitus varus deformity when treating SCH fractures in zone 3. A thorough postoperative follow-up is required.

Comparison of Postoperative Nausea and Vomiting Incidence between Remimazolam and Sevoflurane in Tympanoplasty with Mastoidectomy: A Single-Center, Double-Blind, Randomized Controlled Trial.

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common adverse effect of general anesthesia, especially in middle ear surgery. Remimazolam is a newer benzodiazepine recently approved for use in general anesthesia. This study aimed to compare the incidence rate of PONV after tympanoplasty with mastoidectomy between using remimazolam and sevoflurane. Materials and Methods: This study included 80 patients undergoing elective tympanoplasty with mastoidectomy. The patients were randomly assigned to either the remimazolam or sevoflurane group. The primary outcome was the incidence rate of PONV 12 h after surgery. The secondary outcomes were the incidence rate of PONV 12-24 and 24-48 h after surgery, severity of PONV, incidence rate of vomiting, administration of rescue antiemetics, hemodynamic stability, and recovery profiles. Results: The incidence rate of PONV 0-12 h after tympanoplasty with mastoidectomy was significantly lower in the remimazolam group compared with that in the sevoflurane group (28.9 vs. 57.9%; p = 0.011). However, the incidence rate of delayed PONV did not differ between the two groups. PONV severity in the early periods after the surgery was significantly lower in the remimazolam group than in the sevoflurane group. The incidence rate of adverse hemodynamic events was lower in the remimazolam group than in the sevoflurane group, but there was no difference in the overall trends of hemodynamic data between the two groups. There was no difference in recovery profiles between the two groups. Conclusions: Remimazolam can significantly reduce the incidence rate of early PONV after tympanoplasty with mastoidectomy under general anesthesia.

Comparison of parameter types for the calibration of noninvasive continuous cardiac output monitoring of patients undergoing lumbar spinal surgery in the prone position.

BACKGROUND: Cardiac output (CO) decreases on reversing the patient's position to the prone position. Estimated continuous cardiac output (esCCO) systems can noninvasively and continuously monitor CO calibrated by patient information or transesophageal echocardiogram (TEE). OBJECTIVE: To compare the accuracy, precision, and trending ability of two calibration methods of CO estimation in patients in prone position. METHODS: The CO estimates calibrated by TEE (esT) and patient information (esP) of 26 participants were included. CO was collected at four time points. The accuracy and precision of agreement were evaluated using the Bland-Altman method. A four-quadrant plot was used for trending ability analysis. RESULTS: The bias between esP and TEE and between esT and TEE was 0.2594 L/min (95% limits of agreement (LoA): -1.8374 L/min to 2.3562 L/min) and 0.0337 L/min (95% LoA: -0.7381 L/min to 0.8055 L/min), respectively. A strong correlation was found between ΔesP and ΔTEE (p< 0.001, CCC = 0.700) and between ΔesT and ΔTEE (p< 0.001, CCC = 0.794). The concordance rates between ΔesP and ΔTEE and between ΔesT and ΔTEE were 91.9% and 97.1%, respectively. CONCLUSION: Despite limited accuracy and precision, esP showed acceptable trending ability. The trending ability of esCCO calibrated by the reference TEE value was comparable with that of TEE.

Quercetin and Isorhamnetin Reduce Benzo[a]pyrene-Induced Genotoxicity by Inducing RAD51 Expression through Downregulation of miR-34a.

Benzo[a]pyrene (B[a]P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated during B[a]P metabolism can cause DNA damage, such as BPDE-DNA adducts, 8-oxo-dG, and double-strand breaks (DSBs). In this study, we mechanistically investigated the effects of quercetin and its major metabolite isorhamnetin on the repair of B[a]P-induced DNA DSBs. Whole-transcriptome analysis showed that quercetin and isorhamnetin each modulate the expression levels of genes involved in DNA repair, especially those in homologous recombination. RAD51 was identified as a key gene whose expression level was decreased in B[a]P-treated cells and increased by quercetin or isorhamnetin treatment. Furthermore, the number of γH2AX foci induced by B[a]P was significantly decreased by quercetin or isorhamnetin, whereas RAD51 mRNA and protein levels were increased. Additionally, among the five microRNAs (miRs) known to downregulate RAD51, miR-34a level was significantly downregulated by quercetin or isorhamnetin. The protective effect of quercetin or isorhamnetin was lower in cells transfected with a miR-34a mimic than in non-transfected cells, and the B[a]P-induced DNA DSBs remained unrepaired. Our results show that quercetin and isorhamnetin each upregulates RAD51 by downregulating miR-34a and thereby suppresses B[a]P-induced DNA damage.

Immunomodulatory Effect and Bone Homeostasis Regulation in Osteoblasts Differentiated from hADMSCs via the PD-1/PD-L1 Axis.

Human mesenchymal stem cells (hMSCs) are promising candidates for stem cell therapy and are known to secrete programmed death-1 (PD-1) ligand 1 (PD-L1) regulating T cell-mediated immunosuppression. Given the limitations of current stem cell therapy approaches, improvements in immunomodulatory capacity and stem cell differentiation efficacy are needed. In this study, we propose novel strategies to overcome the challenges that remain in hMSC-mediated bone regeneration. We found that PD-1 is highly expressed in osteoblasts, and the PD-1/PD-L1 axis mediated the decreased proinflammatory cytokine expressions in differentiated osteoblasts cocultured with human adipose derived mesenchymal stem cells (hADMSCs). Moreover, the decrease was attenuated by PD-1/PD-L1 pathway inhibition. Osteogenic properties including osteogenic gene expression and calcium deposits were increased in osteoblasts cocultured with hADMSCs compared with those that were monocultured. Osteoblasts treated with PD-L1 and exosomes from hADMSCs also exhibited enhanced osteogenic properties, including calcium deposits and osteogenic gene expression. In our cocultured system that mimics the physiological conditions of the bone matrix, the PD-1/PD-L1 axis mediated the increased expression of osteogenic genes, thereby enhancing the osteogenic properties, while the calcium deposits of osteoblasts were maintained. Our results provide the therapeutic potentials and novel roles of the PD-1/PD-L1 axis in bone matrix for modulating the bone properties and immunosuppressive potentials that can aid in the prevention of bone diseases via maintaining bone homeostasis.

Anesthetic Management of Upper Tracheal Cancer Resection and Reconstruction: A Case Report.

Tracheal tumor resection and reconstruction is the primary treatment for tracheal tumors. The trachea is the surgical site as well as an important channel to ensure ventilation and maintain oxygenation during surgery. In this report, we describe the successful management of an upper tracheal tumor in a 50-year-old patient. The tumor was situated approximately 2-3 cm below the vocal cords, occluding the tracheal lumen by 80%. Conventional orotracheal intubation was expected to be impossible, and the patient was managed with an I-Gel supraglottic airway for mechanical ventilation with the assistance of venovenous extracorporeal membrane oxygenation (VV ECMO). After securing tracheal intubation via the tracheostomy site, VV ECMO was weaned off, and mechanical ventilation was changed to tracheal intubation. Eventually, tracheal tumor resection and reconstruction were successfully performed under general anesthesia. No specific events occurred during anesthetic management. Careful preoperative planning and good teamwork made the procedure possible without complications.

In-phase simultaneous spectral editing of lactate and alanine with suppression of J-coupled lipids by the modified selective multiple quantum coherence sequences.

1H magnetic resonance spectroscopy (MRS) with the multiple quantum coherence (MQC) technique allows for the detection of lactate, an end product of glycolysis, in the environment of lipids. The method can also be used to detect alanine, a byproduct of glutaminolysis. An issue is that when both lactate and alanine are detected together by the MQC technique, a phase mismatch arises between lactate and alanine signals due to off-resonance rotations and the difference in double quantum coherence frequencies between the two molecules. Such phase mismatch can cause errors in spectral fitting and metabolite quantification. In this study, we designed two pulse sequences that eliminate such phase differences of lactate and alanine while suppressing lipid signals by modifications of the Selective Multiple Quantum Coherence (Sel-MQC) sequence, a well-known MQC technique. Using the product operator formalism and the off-resonance rotation matrices, the phase evolutions of lactate and alanine during the spectrally selective pulses and the free precession times of the sequence at the single quantum, double quantum and zero quantum coherence states of these molecules were calculated. The multiple quantum (MQ) evolution time t1 that can remove the phase difference of lactate and alanine at the echo was calculated and fine-tuned with experiments. The lactate and alanine signal intensities and the editing efficiencies from the two modified Sel-MQC sequences were theoretically predicted by using the product operator evolutions and compared with the experimental data. The J-coupled lipid signals were successfully suppressed by both sequences. One of the two developed sequences was applied to a human body with a phantom of lactate and alanine, which resulted in successful in-phase editing of lactate and alanine and suppression of the lipid signals from the body. The study sets an important foundation for the noninvasive detection of lactate and alanine from tumors of cancer patients.

A Comparative Immunohistochemical Study of Wound Healing after Dental Diode Laser Treatment in the Rat Oral Mucosa.

This study aimed to examine the differences in healing patterns using two types of diode laser devices (laser A and laser B) and a steel scalpel for periodontal surgery through histological and immunohistochemical methods. Twenty 12-week-old male rats were assigned to three groups (3, 7, and 14 days). Square-shaped erosion wounds (2 × 2 mm2 diameter) were created on the hard palate of each rat. Two wounds were created using Laser A and a steel scalpel (Bard-Parker No. 15) on the right palate and using Laser B and a steel scalpel on the left side. Rats were sacrificed after 3, 7, and 14 days. Tissues were collected with a margin of 1 mm from the border of the erosional wound of the maxillary hard palate. Histological and immunohistochemical analyses were performed on the tissue samples after 3, 7, and 14 days. The tissue healing pattern and expression of inducible nitric oxide synthase (iNOS) and cluster of differentiation (CD) were observed under a light microscope. Statistical analysis was conducted using the Kruskal−Wallis H test for comparison among the groups (α = 0.05). In comparison to the wounds made with the scalpel, wounds treated with lasers A and B showed delayed healing patterns. There was no significant difference between the two laser treatment groups (p > 0.05). The expression of iNOS and CD68 was not significantly different among the three groups after 3 and 7 days (p > 0.05). On day 14, the groups treated with the dental diode lasers showed higher expression than the group treated with the steel scalpel, but no significant difference was observed (p > 0.05). Laser-induced wounds tended to heal slower than surgical wounds performed using a steel scalpel, but histological and immunohistochemical results showed no significant difference between the dental diode laser and scalpel groups.

Delayed anterolateral radial head dislocation secondary to radial shaft fracture malunion: A case report.

RATIONALE: Traumatic radial head dislocation (RHD) can occur due to hyperpronation injury with sequential disruption of the annular ligament, quadrate ligament, and the interosseous membrane. Although studies have shown that traumatic RHD is generally associated with Monteggia fracture-dislocation, traumatic RHD occurring with ipsilateral radial shaft fractures has rarely been reported. Delayed RHD secondary to the malunion of isolated radial shaft fractures is extremely rare. PATIENT CONCERNS: We report the case of a 12-year-old right-handed boy with progressive pain and limited range of motion in the right elbow. DIAGNOSIS: The patient was diagnosed with delayed RHD associated with radial shaft fracture malunion. INTERVENTIONS AND OUTCOMES: A corrective osteotomy was performed at the site of malunion with open reduction of the radial head using an extensile lateral approach. The annular ligament was disrupted. Forearm rotation causes radial head subluxation Therefore, the Bell Tawse procedure was additionally performed to reconstruct the annular ligament by turning down a strip of triceps tendon and anchoring it around the radial neck. LESSONS: Malunion of the radial shaft can cause delayed RHD with a limited elbow range of motion. Annular reconstruction using a strip of the triceps tendon and corrective osteotomy of the radial shaft with an extensile lateral approach may be useful for treating this rare entity or situation.

No Difference between Spinal Anesthesia with Hyperbaric Ropivacaine and Intravenous Dexmedetomidine Sedation with and without Intrathecal Fentanyl: A Randomized Noninferiority Trial.

To enhance the duration of single-shot spinal anesthesia, intrathecal fentanyl and intravenous dexmedetomidine are widely used as adjuvants to local anesthetics. This noninferiority trial evaluated whether hyperbaric ropivacaine alone can produce a noninferior duration of sensory block in comparison to hyperbaric ropivacaine with intrathecal fentanyl in patients under dexmedetomidine sedation. Methods. Fifty patients scheduled for elective lower limb surgery under spinal anesthesia were randomly assigned in a double-blind fashion to receive either hyperbaric ropivacaine 15 mg (Group R) or hyperbaric ropivacaine 15 mg with intrathecal fentanyl 20 µg (Group RF). Intravenous dexmedetomidine (1 µg/kg for 10 min, followed by 0.5 µg/kg/h) was administered in both groups. The primary outcome of this study was the time to two-dermatomal regression of sensory block. The noninferiority margin for the mean difference was -10 min. Characteristics of the block, intraoperative and postoperative side effects, postoperative pain score, and analgesic consumption were assessed as secondary outcomes. Results. There was no difference in the two-dermatomal regressions of sensory block between the two groups (Group R 70.4 ± 10.2 min, Group RF 71.2 ± 12.4 min, p = 0.804) with a mean difference of 0.8 min (-7.2 to 5.6, 95% confidence interval). Thus, the noninferiority of hyperbaric ropivacaine alone was established. There were no significant differences in the secondary outcomes between the two groups. Conclusions. Under intravenous dexmedetomidine sedation, the duration of spinal anesthesia with hyperbaric ropivacaine alone was noninferior to that of hyperbaric ropivacaine with intrathecal fentanyl. This suggests that addition of intrathecal fentanyl to hyperbaric ropivacaine may not be necessary in patients receiving intravenous dexmedetomidine.

CXCL16/CXCR6 Axis in Adipocytes Differentiated from Human Adipose Derived Mesenchymal Stem Cells Regulates Macrophage Polarization.

Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.

Curcumin Suppresses the Lipid Accumulation and Oxidative Stress Induced by Benzo[a]pyrene Toxicity in HepG2 Cells.

Benzo[a]pyrene (B[a]P) is a potentially hepatotoxic group-1 carcinogen taken up by the body through ingestion of daily foods. B[a]P is widely known to cause DNA and protein damages, which are closely related to cell transformation. Accordingly, studies on natural bioactive compounds that attenuate such chemical-induced toxicities have significant impacts on public health. This study aimed to uncover the mechanism of curcumin, the major curcuminoid in turmeric (Curcuma longa), in modulating the lipid accumulation and oxidative stress mediated by B[a]P cytotoxicity in HepG2 cells. Curcumin treatment reduced the B[a]P-induced lipid accumulation and reactive oxygen spicies (ROS) upregulation and recovered the cell viability. Cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) and Cytochrome P450 subfamily B polypeptide 1 (CYP1B1) downregulation resulting from decreased aryl hydrocarbon receptor (AhR) translocation into nuclei attenuated the effects of B[a]P-induced lipid accumulation and repressed cell viability, respectively. Moreover, the curcumin-induced reduction in ROS generation decreased the nuclear translocation of Nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of phase-II detoxifying enzymes. These results indicate that curcumin suppresses B[a]P-induced lipid accumulation and ROS generation which can potentially induce nonalcoholic fatty liver disease (NAFLD) and can shed a light on the detoxifying effect of curcumin.

A Low Dose of Naloxone Added to Ropivacaine Prolongs Femoral Nerve Blockade: A Randomized Clinical Trial.

Femoral nerve blocks (FNBs) are used as safe and useful procedures to control severe postoperative pain from total knee arthroplasty (TKA). Various adjuvants have been used to prolong the duration of the local anesthetic blockade. This study evaluated whether a low dose of naloxone administered with local anesthetics prolongs the duration of FNB. A prospective, randomized double-blind controlled study was conducted with 74 patients undergoing unilateral TKA. Through a single-bolus administration guided by ultrasound, the control group (group C) received 20 mL of 0.375% ropivacaine, while the naloxone group (group N) received 20 mL of 0.375% ropivacaine with 100 ng of naloxone. The time elapsed before the first analgesia request, the total amount of opioids consumed at 24 h postoperatively, the onset time of the sensory blockade, the visual analog pain scale (VAS) scores after arriving at the recovery room, after 6, 12, 18, and 24 h at rest and after 12, 18, and 24 h of activity, the quadricep strength before the FNB procedure and at 12 and 24 h postoperatively, the quality of sleep on the first night after surgery, the satisfaction score, and the incidence of postoperative complications were recorded. The time elapsed before the first analgesia request was significantly longer in group N (735.5 ± 187.2 min) than that in group C (602.6 ± 210.4 min) (P=0.003). The total dose of supplementary opioids consumed at 24 h postoperatively was significantly lower in group N (312.4 ± 141.7 µg) than that in group C (456.5 ± 279.5 µg) (P=0.007). Lower VAS scores were recorded in group N than that in group C at rest and during knee activity (rest, 12 h, P=0.001, 18 h, P=0.043; activity, 12 h, P=0.001). The addition of a low dose of naloxone to ropivacaine for FNB significantly delayed the first request for rescue analgesia and decreased the opioid consumption within 24 h, without significant complications.

Association between the high risk for obstructive sleep apnea and intracranial carotid artery calcification in patients with acute ischemic stroke.

PURPOSE: Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial carotid artery calcification (ICAC) is a marker for subclinical atherosclerosis and future cardiovascular events. We investigated the association between the high risk for OSA and ICAC in patients with acute ischemic stroke. METHODS: We retrospectively investigated 73 patients who were admitted to the hospital with acute ischemic stroke in the internal carotid artery (ICA) territory due to large-artery atherosclerosis. The risk for OSA was assessed using the Berlin Questionnaire, and patients were classified into low-risk (LR-OSA) and high-risk groups (HR-OSA). We compared the burden of ICAC between the two groups. Univariable and multivariable analyses were conducted to investigate the association of high risk for OSA with the presence of calcium in intracranial ICA. RESULTS: The HR-OSA group of 35 patients (48%) was significantly older and had a higher rate of hypertension and diabetes mellitus than the LR-OSA group. The HR-OSA group had more frequent ICAC (92% vs. 63%, p < 0.001), higher Agatston score (162.0 vs. 8.5, p < 0.001), and greater total volume of ICAC (261.2 mm3 vs. 20.1 mm3, p < 0.001) in the intracranial ICA. Presence of calcium in symptomatic intracranial ICA was positively correlated with age (odds ratio, OR, 1.432; 95% confidence interval, CI, 1.098-1.868) and HR-OSA (OR, 18.272; 95% CI, 0.500-668.401) in multivariable logistic regression analysis. CONCLUSIONS: This study showed that the presence of calcium in symptomatic intracranial ICA was related to high risk for OSA in patients with acute ischemic stroke.

Comparison between two different concentrations of a fixed dose of ropivacaine in interscalene brachial plexus block for pain management after arthroscopic shoulder surgery: a randomized clinical trial.

BACKGROUND: Only a few studies have evaluated the differences between varying concentrations of a fixed dose of local anesthetics. This study was conducted to compare the effects of two different concentrations of a fixed dose of ropivacaine used in ultrasound-guided interscalene brachial plexus block. METHODS: This prospective, randomized, double-blind study included 62 patients who underwent arthroscopic surgery under general anesthesia. The patients were randomly assigned to receive ultrasound-guided interscalene block with 75 mg of ropivacaine at one of two concentrations: 0.75% (10 ml; group C) or 0.375% (20 ml; group V). Time to onset of sensory blockade, degree of blockade, pulmonary function changes, analgesic duration of the interscalene block, postoperative opioid requirement within 24 h, postoperative pain scores, satisfaction, and incidence of complications were recorded. RESULTS: Although the time to onset of sensory blockade was shorter for group C (P = 0.015), successful blockade was achieved at 30 min after the interscalene block in both groups. The analgesic duration of the interscalene block was not significantly different between the groups. The amount of opioid used within 24 h after surgery was significantly reduced for group V compared with group C (P = 0.016). The rest of the parameters did not show any significant differences between the two groups. CONCLUSION: Compared with 10 ml of 0.75% ropivacaine, interscalene block with 20 ml of 0.375% ropivacaine could be effective for the reduction of postoperative opioid requirement within 24 h after surgery despite it might not prolong the analgesic duration.

Effect of subcritical water extraction conditions on the activity of alcohol metabolizing enzymes, ACE inhibition, and tyrosinase inhibition in Protaetia brevitarsis larvae.

In order to develop processing methods with high physiological activity for Protaetia brevitarsis larvae (PBL), subcritical water (SCW) extraction was applied. The dried powder (1 g) of PBL was extracted with 10 mL distilled water at 100, 200, and 300 °C for 30 min. The SCW treatment significantly (p < 0.05) increased some physiological activities of the PBL extracts. The SCW extract at 300 °C increased alcohol dehydrogenase, acetaldehyde dehydrogenase, and tyrosinase inhibitory activities from 192.3 ± 4.1% to 452.2 ± 0.5%, 125.4 ± 2.9% to 153.3 ± 0.4%, and - 7.0 ± 0.7% to 26.1 ± 1.4%, respectively, compared to the extract at 100 °C. Contrarily, the inhibition activity of angiotensin converting enzyme was the highest at 200 °C. These results suggest that SCW is a suitable method to extract and maintain the physiological activity of PBL.

Structural Evidence for Antihypertensive Effect of an Antioxidant Peptide Purified from the Edible Marine Animal Styela clava.

This study investigated the antihypertensive effects of an antioxidant peptide, Leu-Trp-His-Thr-His (LWHTH), purified from Styela clava peptic hydrolysate, to assess the bioactivity of the peptide and verify the value of S. clava as a health-promoting food. Also, the study presented structural evidence for the effects of LWHTH. The inhibitory effect of LWHTH on angiotensin I-converting enzyme (ACE) was assessed using enzyme reaction methods and the simulation methods in computational space. LWHTH inhibited ACE with an IC50 value of 16.42 ± 0.45 µM. The LWHTH structure was stable, and its ACE inhibitory effect was retained under simulated gastrointestinal conditions. In silico simulations revealed that LWHTH binds the active site of ACE, with residues LW making the ACE-LWHTH complex stable and residues HTH making the complex strong. Furthermore, LWHTH significantly reduced blood pressure in spontaneously hypertensive rats. These results demonstrate that LWHTH has the potential to be a healthy functional food with antihypertensive effects. Therefore, S. clava consumption may be beneficial for human health.

Impact of neutropenia on the clinical outcomes of Staphylococcus aureus bacteremia in patients with hematologic malignancies: a 10-year experience in a tertiary care hospital.

Staphylococcus aureus bacteremia is one of the most serious bacterial infections and may lead to worse clinical outcomes in patients with prolonged severe neutropenia. However, clinical data on S. aureus bacteremia in neutropenic patients with hematologic malignancies are limited. We conducted two case-control studies using a 10-year prospective cohort of patients with S. aureus bacteremia. Neutropenic and non-neutropenic hematologic malignancy patients were compared on clinical characteristics and treatment outcomes. An additional matched case-control study using solid tumor patients was conducted. Risk factors for 12-week mortality were analyzed. Of 1643 patients with S. aureus bacteremia, 64 (3.9%) neutropenic and 108 (6.6%) non-neutropenic patients with hematologic malignancies were included in the study. There were no significant differences in the incidence of metastatic infection between the two groups (17.2% vs. 17.6%, p = 0.95), in contrast with a previous study that observed no metastatic infection in neutropenic patients. Twelve-week mortality in neutropenic patients with hematologic malignancies tended to be lower than in non-neutropenic patients with hematologic malignancies (15.6% vs. 26.9%, p = 0.09) and was significantly lower than in neutropenic patients with solid tumors (15.6% vs. 45.8%, p = 0.003). Independent risk factors for mortality in hematologic malignancy patients with S. aureus bacteremia were high Charlson comorbidity score, high APACHE II score, and skin and soft tissue infection. Neutropenia was not independently associated with mortality. Our findings suggest that neutropenia in hematologic malignancies may not affect the incidence of metastatic infection or 12-week mortality of S. aureus bacteremia.

Dynamic Changes in Gene Mutational Landscape With Preservation of Core Mutations in Mantle Cell Lymphoma Cells.

While studies have identified a number of mutations in mantle cell lymphoma (MCL), the list may still be incomplete and contribution to the pathogenesis remains unclear. We analyzed the mutational landscape of four mantle cell lymphoma biopsies obtained during an 8-year period from the same patient with his normal cells serving as control; we also established a cell line from the final stage of the disease. Numerous mutations with high allelic burden have been identified in all four biopsies. While a large subset of mutations was seen only in individual biopsies, the core of 21 mutations persisted throughout the disease. This mutational core is also maintained in the cell line that also displays DNA-methylation and cytokine secretion profiles of the primary mantle cell lymphoma cells. This cell line is uniquely sensitive to clinically relevant inhibitors of Bruton's Tyrosine Kinase. The response to Bruton Tyrosine Kinase's inhibition is enhanced by inhibitors of CDK4/6 and mTOR. Among the mutations seen in the primary and cultured MCL cells, mutations of three genes are involved in the control of H3K4 methylation: demethylase KDM5C, present already in the early disease, and methyltransferase KMT2D and cofactor BCOR, both of which are seen late in the disease and are novel and predicted to be pathogenic. The presence of these mutations was associated with hypermethylation of H3K4. Restoration of KDM5C expression affected expression of numerous genes involved in cell proliferation, adherence/movement, and invasiveness.

Lack of choline elevation on proton magnetic resonance spectroscopy in grade I-III gliomas.

Elevated levels of choline are generally emphasized as marker of increased cellularity and cell membrane turnover in gliomas. In this study, we investigated the incidence rate of lack of choline/creatine and choline/water elevation in a population of grade I-III gliomas. A cohort of 41 patients with histopathologically confirmed gliomas underwent multi-voxel proton magnetic resonance spectroscopy on a 3 T magnetic resonance system prior to treatment. Peak areas for choline and myoinositol were measured from all voxels that exhibited hyperintensity on fluid-attenuated inversion recovery images and were normalized to creatine and unsuppressed water from each voxel. The average metabolite/creatine and metabolite/water ratios from these voxels were then computed. Similarly, average metabolite ratios were computed from normal brain parenchyma. Gliomas were considered for lack of choline elevation when choline/creatine and choline/water ratios from neoplastic regions were less than those from normal brain parenchyma regions. Six of 41 (14.6%) grade I-III gliomas showed lack of elevation for choline/creatine and choline/water ratios compared to normal brain parenchyma. Four of these six gliomas also demonstrated elevated levels of myoinositol/creatine ratio. All other gliomas (n = 35) had elevated choline levels from neoplastic regions relative to normal parenchyma. The sensitivity of choline/creatine or choline/water in determining a grade I-III glioma was 85.4%. These findings suggest that a lack of choline/creatine or choline/water elevation may be seen in some gliomas and low choline levels should not prevent us from considering the possibility of a grade I-III glioma.