Characterization and mechanism of simultaneous degradation of aflatoxin B1 and zearalenone by an edible fungus of Agrocybe cylindracea GC-Ac2.

Contamination with multiple mycotoxins is a major issue for global food safety and trade. This study focused on the degradation of aflatoxin B1 (AFB1) and zearalenone (ZEN) by 8 types of edible fungi belonging to 6 species, inclulding Agaricus bisporus, Agrocybe cylindracea, Cyclocybe cylindracea, Cyclocybe aegerita, Hypsizygus marmoreus and Lentinula edodes. Among these fungi, Agrocybe cylindracea strain GC-Ac2 was shown to be the most efficient in the degradation of AFB1 and ZEN. Under optimal degradation conditions (pH 6.0 and 37.4°C for 37.9 h), the degradation rate of both AFB1 and ZEN reached over 96%. Through the analysis of functional detoxification components, it was found that the removal of AFB1 and ZEN was primarily degraded by the culture supernatant of the fungus. The culture supernatant exhibited a maximum manganese peroxidase (MnP) activity of 2.37 U/mL. Interestingly, Agrocybe cylindracea strain GC-Ac2 also showed the capability to degrade other mycotoxins in laboratory-scale mushroom substrates, including 15A-deoxynivalenol, fumonisin B1, B2, B3, T-2 toxin, ochratoxin A, and sterigmatocystin. The mechanism of degradation of these mycotoxins was speculated to be catalyzed by a complex enzyme system, which include MnP and other ligninolytic enzymes. It is worth noting that Agrocybe cylindracea can degrade multiple mycotoxins and produce MnP, which is a novel and significant discovery. These results suggest that this candidate strain and its enzyme system are expected to become valuable biomaterials for the simultaneous degradation of multiple mycotoxins.

Topical hemostatic agents in spinal surgery.

Spinal surgery can be associated with significant intraoperative blood loss which may lead to various complications. As the number of patients undergoing spinal surgery increases over time, accurate and effective hemostasis becomes critically important. Despite various surgical hemostatic techniques, conventional interventions such as compression, suture, ligation, and heat-generating cautery, are not suitable for osseous and epidural venous plexus bleeding during spinal procedures. Therefore, a variety of hemostatic agents have been developed to promote hemostasis. As they differ in terms of mechanism, form, application and potential adverse reactions, it is important to understand the natural features of existing agents. Here we comprehensively review currently available topical hemostatic agents from different sources and summarize their mechanisms of action, applications, and current or potential utilization in spinal surgery. We found hemostatic agents from different sources exert hemostatic actions through different mechanisms. In addition, topical hemostatic agents play various roles in spinal surgery including as hemostatic agent, dura mater repair, drug-carrier, skin closure, and fibrosis prevention. Compressive neurological complications are the most common complications of these hemostatic agents. Therefore, optimal use in spinal environments should match their features, indications, and efficacy with clinical conditions.

Identification of two galectin-4 proteins (PcGal4-L and PcGal4-L-CRD) and their function in AMP expression in Procambarus clarkii.

Galectins, a family of lectins that bind to ß-galactoside, possess conserved carbohydrate recognition domains (CRDs) and play a crucial role in recognizing and eliminating pathogens in invertebrates. Two galectin-4 genes (PcGal4) isoforms, named PcGal4-L and PcGal4-L-CRD, were cloned from the cDNA library of Procambarus clarkia in our study. PcGal4-L contains an open reading frame (ORF, 1089 bp), which encodes a protein consisting of 362 amino acids including a single CRD and six low complexity regions. The full-length cDNA of PcGal4-L-CRD contains a 483 bp ORF that encodes a protein of 160 amino acids, with a single CRD and a low-complexity region. The difference between the two PcGal4 isoforms is that PcGal4-L has 202 additional amino acids after the CRD compared to the PcGal4-L-CRD. These two isoforms are grouped together with other galectins from crustaceans through phylogenetic analysis. Further study revealed that total PcGal4 (including PcGal4-L and PcGal4-L-CRD) was primarily expressed in the muscle, gills and intestine. The mRNA levels of total PcGal4 in gills and hemocytes were significantly induced after challenge with Aeromonas hydrophila. Both recombinant PcGal4-L and its spliced isoform, PcGal4-L-CRD, could directly bind to lipopolysaccharides, peptidoglycan and five tested microorganisms, inducing a wide spectrum of microbial agglutination. The spliced isoform PcGal4-L-CRD showed a stronger binding ability than PcGal4-L. In addition, when the PcGal4 was knockdown, transcriptions of seven antimicrobial peptides (AMPs) genes (ALF5, ALF6, ALF8, CRU1, CRU2, CRU3 and CRU4) in gills and seven AMPs genes (ALF5, ALF6, ALF8, ALF9, CRU1, CRU3 and CRU4) in hemocytes were significantly decreased. Meanwhile, the survival rate of P. clarkii decreased in the PcGal4-dsRNA group. In summary, these results indicate that PcGal4 can mediate the innate immunity in P. clarkii by bacterial recognition and agglutination, as well as regulating AMP expression, thus recognition and understanding of the functions of galectin in crustaceans in immune resistance.

Characterization and mechanism of aflatoxin degradation by a novel strain of Trichoderma reesei CGMCC3.5218.

Aflatoxins, which are produced mainly by Aspergillus flavus and A. parasiticus, are recognized as the most toxic mycotoxins, which are strongly carcinogenic and pose a serious threat to human and animal health. Therefore, strategies to degrade or eliminate aflatoxins in agro-products are urgently needed. We investigated 65 Trichoderma isolates belonging to 23 species for their aflatoxin B1 (AFB1)-degrading capabilities. Trichoderma reesei CGMCC3.5218 had the best performance, and degraded 100% of 50 ng/kg AFB1 within 3 days and 87.6% of 10 µg/kg AFB1 within 5 days in a liquid-medium system. CGMCC3.5218 degraded more than 85.0% of total aflatoxins (aflatoxin B1, B2, G1, and G2) at 108.2-2323.5 ng/kg in artificially and naturally contaminated peanut, maize, and feed within 7 days. Box-Behnken design and response surface methodology showed that the optimal degradation conditions for CGMCC3.5218 were pH 6.7 and 31.3°C for 5.1 days in liquid medium. Possible functional detoxification components were analyzed, indicating that the culture supernatant of CGMCC3.5218 could efficiently degrade AFB1 (500 ng/kg) with a ratio of 91.8%, compared with 19.5 and 8.9% by intracellular components and mycelial adsorption, respectively. The aflatoxin-degrading activity of the fermentation supernatant was sensitive to proteinase K and proteinase K plus sodium dodecyl sulfonate, but was stable at high temperatures, suggesting that thermostable enzymes or proteins in the fermentation supernatant played a major role in AFB1 degradation. Furthermore, toxicological experiments by a micronucleus assay in mouse bone marrow erythrocytes and by intraperitoneal injection and skin irritation tests in mice proved that the degradation products by CGMCC3.5218 were nontoxic. To the best of our knowledge, this is the first comprehensive study on Trichoderma aflatoxin detoxification, and the candidate strain T. reesei CGMCC3.5218 has high efficient and environment-friendly characteristics, and qualifies as a potential biological detoxifier for application in aflatoxin removal from contaminated feeds.

Extensive Spinal Epidural Abscess Resulting in Complete Paraplegia Treated by Selective Laminectomies and Irrigation.

BACKGROUND: Spinal epidural abscess (SEA) is an uncommon clinical entity that is often subject to delayed diagnosis and suboptimal treatment. Untreated disease leads to compression of the spinal cord, resulting in devastating complications. CASE PRESENTATION: A 56-year-old man visited our hospital for progressive lower back and lower extremity pain of several days' duration. Significant pyrexia (39.5°C) and elevated C-reactive protein (89.2 mg/L) were detected during admission, but no positive neurological examination findings were observed. Magnetic resonance imaging revealed pyogenic discitis at L3-4. Despite the administration of directed antibiotic therapy, the patient's condition rapidly deteriorated, culminating in complete paraplegia secondary to an extensive SEA from L4 to C7. Emergency spinal decompression surgery was canceled due to his poor clinical condition and refusal of informed consent. After further deterioration, he consented to two-level selective laminectomies and irrigation. CONCLUSIONS: In contrast with prior case reports, this case illustrates the natural history of an extensive SEA during conservative and late surgical treatment. Early diagnosis and timely surgical decompression are of great importance for extensive SEA.

Potential of Trichoderma spp. for Biocontrol of Aflatoxin-Producing Aspergillus flavus.

The inhibitory action of 20 antagonistic Trichoderma isolates against the aflatoxigenic isolate A. flavus ITEM 9 (Af-9) and their efficacy in reducing aflatoxin formation in vitro were examined. Production of metabolites with inhibitory effect by the Trichoderma isolates was also investigated. Antagonistic effect against Af-9 was assessed by inhibition of radial growth of the colonies and by fungal interactions in dual confrontation tests. A total of 8 out of 20 isolates resulted in a significant growth inhibition of 3-day-old cultures of Af-9, ranging from 13% to 65%. A total of 14 isolates reduced significantly the aflatoxin B1 (AfB1) content of 15-day-old Af-9 cultures; 4 were ineffective, and 2 increased AfB1. Reduction of AfB1 content was up to 84.9% and 71.1% in 7- and 15-day-old cultures, respectively. Since the inhibition of Af-9 growth by metabolites of Trichoderma was not necessarily associated with inhibition of AfB1 production and vice versa, we investigated the mechanism of reduction of AfB1 content at the molecular level by examining two strains: one (T60) that reduced both growth and mycotoxin content; and the other (T44) that reduced mycotoxin content but not Af-9 growth. The expression analyses for the two regulatory genes aflR and aflS, and the structural genes aflA, aflD, aflO and aflQ of the aflatoxin biosynthesis cluster indicated that neither strain was able to downregulate the aflatoxin synthesis, leading to the conclusion that the AfB1 content reduction by these Trichoderma strains was based on other mechanisms, such as enzyme degradation or complexation. Although further studies are envisaged to identify the metabolites involved in the biocontrol of A. flavus and prevention of aflatoxin accumulation, as well as for assessment of the efficacy under controlled and field conditions, Trichoderma spp. qualify as promising agents and possible alternative options to other biocontrol agents already in use.

Right ventricular diastolic dysfunction and failure: a review.

Right ventricular diastolic dysfunction and failure (RVDDF) has been increasingly identified in patients with cardiovascular diseases, including heart failure and other diseases with cardiac involvement. It is unknown whether RVDDF exists as a distinct clinical entity; however, its presence and degree have been shown to be a sensitive marker of end-organ dysfunction related to multiple disease processes including systemic hypertension, pulmonary hypertension, heart failure, and endocrine disease. In this manuscript, we review issues pertaining to RVDDF including anatomic features of the right ventricle, physiologic measurements, RVDDF diagnosis, underlying mechanisms, clinical impact, and clinical management. Several unique features of RVDDF are also discussed.

Multiplex PCR assay to detect Aspergillus, Penicillium and Fusarium species simultaneously.

A wide variety of mycotoxins is produced by mycotoxigenic fungi and naturally contaminates food and feed products worldwide. Synergistic effects of multi-toxins are potentially more harmful than exposure to a single compound and can induce acute and chronic toxicity to animals and humans. The aim of the present study is to timely and simultaneously identify the multiple mycotoxigenic fungi capable of causing synergistic toxicity to improve the safety level of food and feedstuff. Here, a multiplex polymerase chain reaction assay was developed for simultaneous detection of mycotoxigenic fungi belonging to the genera Aspergillus, Fusarium and Penicillium. Three pairs of genus-specific primers were designed based on internal transcribed spacer (ITS) sequences of Aspergillus and Penicillium, and Elongation factor 1 alpha (EF- 1α) of Fusarium. Amplicons of 170, 750 and 490 bp respectively for the corresponding primer pairs were detected; thus amplicon length is diagnostic for the individual fungal genus. The sensitivity of the developed method was tested with genomic DNA obtained from mould pure cultures and artificially contaminated maize grain powder. The sensitivity result showed that spore concentrations in the contaminated maize grain powder of 102 spores/mL were detected without prior incubation. This result suggests that the developed mPCR assay would allow a rapid, specific and simultaneous detection of various mycotoxigenic potential fungi based on the occurrence and size of the amplification products and thus to estimate the multi-mycotoxins contamination potential in food and feedstuff.

Surgical treatment of atlantoaxial subluxation by intraoperative skull traction and C1-C2 fixation.

BACKGROUND: Atlantoaxial subluxation (AAS) is a not rare abnormality between the atlas (C1) and axis (C2). For AAS patients with persistent neck pain and neurologic symptoms, surgical intervention is a good choice. Nevertheless, there were still few reports about the use of intraoperative skull traction and different fixation methods in treatment of AAS. METHODS: From January 2012 to December 2018, a total of 86 cases were admitted to our hospital and diagnosed as AAS. All the patients received atlantoaxial reduction with the help of intraoperative skull traction and C1-C2 fixation. Clinical and radiological parameters were collected through chart review. RESULTS: There were 86 cases included in this study. The mean operative time was 153.9 ± 73.9 min, and the mean amount of intraoperative blood loss was 219.1 ± 195.6 ml. 81 patients underwent posterior reduction, internal fixation and fusion. 5 patients underwent anterior release, followed by posterior internal fixation and fusion. 82 patients got satisfactory postoperative outcomes while complications occurred in 4 patients. Significant neurologic improvement was observed in these patients. Bone fusion was achieved on the midline sagittal reconstructed CT images at the latest follow-up in all these patients except 1 case. All the patients were followed up for 34.84 ± 15.86 months at average (range 12-60 months). The mean ADI value was 7.55 ± 1.67 mm at average preoperatively, and improved to 4.03 ± 1.21 mm postoperatively, and to 4.21 ± 0.99 mm at the latest follow-up. The mean A-A angle was 15.48 ± 9.82 degrees at average preoperatively, and improved to 21.61 ± 10.43 degrees postoperatively, and to 19.73 ± 8.13 degrees at the latest follow-up. The mean A-A height was 35.61 ± 7.66 mm at average preoperatively, and improved to 40.08 ± 8.5 mm postoperatively, and to 38.83 ± 6.97 mm at the latest follow-up. There were complications in 4 patients, including pedicle misplacement, pedicle screw fracture, infection and one death. CONCLUSION: Intraoperative skull traction can effectively facilitate the surgical procedures for ASS caused by different etiologies. Further research will be needed to investigate the safety and effectiveness of this method in the future.

Control of Aflatoxigenic Molds by Antagonistic Microorganisms: Inhibitory Behaviors, Bioactive Compounds, Related Mechanisms, and Influencing Factors.

Aflatoxin contamination has been causing great concern worldwide due to the major economic impact on crop production and their toxicological effects to human and animals. Contamination can occur in the field, during transportation, and also in storage. Post-harvest contamination usually derives from the pre-harvest infection of aflatoxigenic molds, especially aflatoxin-producing Aspergilli such as Aspergillusflavus and A. parasiticus. Many strategies preventing aflatoxigenic molds from entering food and feed chains have been reported, among which biological control is becoming one of the most praised strategies. The objective of this article is to review the biocontrol strategy for inhibiting the growth of and aflatoxin production by aflatoxigenic fungi. This review focuses on comparing inhibitory behaviors of different antagonistic microorganisms including various bacteria, fungi and yeasts. We also reviewed the bioactive compounds produced by microorganisms and the mechanisms leading to inhibition. The key factors influencing antifungal activities of antagonists are also discussed in this review.

Fropofol prevents disease progression in mice with hypertrophic cardiomyopathy.

AIMS: Increased myofilament contractility is recognized as a crucial factor in the pathogenesis of hypertrophic cardiomyopathy (HCM). Direct myofilament desensitization might be beneficial in preventing HCM disease progression. Here, we tested whether the small molecule fropofol prevents HCM phenotype expression and disease progression by directly depressing myofilament force development. METHODS AND RESULTS: Force, intracellular Ca2+, and steady-state activation were determined in isolated trabecular muscles from wild-type (WT) and transgenic HCM mice with heterozygous human α-myosin heavy chain R403Q mutation (αMHC 403/+). αMHC 403/+ HCM mice were treated continuously with fropofol by intraperitoneal infusion for 12 weeks. Heart tissue was analysed with histology and real-time PCR of prohypertrophic and profibrotic genes. Fropofol decreased force in a concentration-dependent manner without significantly altering [Ca2+]i in isolated muscles from both WT and αMHC 403/+ HCM mouse hearts. Fropofol also depressed maximal Ca2+-activated force and increased the [Ca2+]i required for 50% activation during steady-state activation. In whole-animal studies, chronic intra-abdominal administration of fropofol prevented hypertrophy development and diastolic dysfunction. Chronic fropofol treatment also led to attenuation of prohypertrophic and profibrotic gene expression, reductions in cell size, and decreases in tissue fibrosis. CONCLUSIONS: Direct inhibition of myofilament contraction by fropofol prevents HCM disease phenotypic expression and progression, suggesting that increased myofilament contractile force is the primary trigger for hypertrophy development and HCM disease progression.

Anesthetic Agents Isoflurane and Propofol Decrease Maximal Ca2+-Activated Force and Thus Contractility in the Failing Myocardium.

In the normal heart, frequently used anesthetics such as isoflurane and propofol can reduce inotropy. However, the impact of these agents on the failing myocardium is unclear. Here, we examined whether and how isoflurane and propofol influence cardiac contractility in intact cardiac muscles from rats treated with monocrotaline to induce heart failure. We measured force and intracellular Ca2+ ([Ca2 +]i) in trabeculae from the right ventricles of the rats in the absence or presence of propofol or isoflurane. At low to moderate concentrations, both propofol and isoflurane dose-dependently depressed cardiac force generation in failing trabeculae without altering [Ca2+]i At high doses, propofol (but not isoflurane) also decreased amplitude of [Ca2+]i transients. During steady-state activation, both propofol and isoflurane impaired maximal Ca2+-activated force (Fmax) while increasing the amount of [Ca2+]i required for 50% of maximal activation (Ca50). These events occurred without apparent change in the Hill coefficient, suggesting no impairment of cooperativity. Exposing these same muscles to the anesthetics after fiber skinning resulted in a similar decrement in Fmax and rise in Ca50 but no change in the myofibrillar ATPase-Ca2+ relationship. Thus, our study demonstrates that challenging the failing myocardium with commonly used anesthetic agents such as propofol and isoflurane leads to reduced force development as a result of lowered myofilament responsiveness to Ca2+ SIGNIFICANCE STATEMENT: Commonly used anesthetics such as isoflurane and propofol can impair myocardial contractility in subjects with heart failure by lowering myofilament responsiveness to Ca2+. High doses of propofol can also reduce the overall amplitude of the intracellular Ca2+ transient. These findings may have important implications for the safety and quality of intra- and perioperative care of patients with heart failure and other cardiac disorders.

Treatment of irreducible atlantoaxial dislocation using one-stage retropharyngeal release and posterior reduction.

INTRODUCTION: Irreducible atlantoaxial dislocation (IAAD) has been challenging for spine surgeons. Various methods have been used to treat IAAD, but no consensus has been reached. This study aimed to retrospectively analyze the efficacy of anterior submandibular retropharyngeal release and posterior reduction and fixation for IAAD. METHODS: From March 2007 to May 2015, 13 patients diagnosed with IAAD underwent anterior submandibular retropharyngeal release and sequential posterior reduction and fixation. The operation time, blood loss, postoperative complications, and Japanese Orthopaedic Association (JOA) scores were retrospectively recorded. RESULTS: The surgeries were accomplished successfully. The mean operative time was about 3.8 h. The mean estimated blood loss was about 130 mL. The patients experienced postoperative pharyngeal pain. Only one patient had a vague voice and increased oral discharge postoperatively. At the final follow-up, JOA scores had significantly increased (p < 0.05), and all the patients had solid bony fusion. CONCLUSION: The present study reinforces the efficacy and safety of anterior submandibular retropharyngeal release and posterior reduction and fixation for IAAD. It can achieve satisfactory clinical outcomes and is safe for experienced spine surgeons.

Anti-idiotypic nanobody-phage display-mediated real-time immuno-PCR for sensitive, simultaneous and quantitative detection of total aflatoxins and zearalenone in grains.

An anti-idiotypic nanobody-phage display-mediated immuno-polymerase chain reaction (PD-IPCR) method was developed for simultaneous quantitative detection of total aflatoxins and zearalenone in cereals. Two phages, displaying the variable domain of the heavy chain anti-idiotypic nanobody that binds aflatoxin- or zearalenone-specific monoclonal antibody (1C11 or 2D3), were used as competitors for corresponding analytes. Specific DNA sequences encoding anti-idiotypic nanobodies were used to design the primers for PCR amplification. The results indicated that detection limits for total aflatoxins and zearalenone in a sample were 0.03 and 0.09 ng mL-1, respectively. Recoveries of spiked aflatoxins and zearalenone were 80-118% and 76.7-111%, respectively. Validation results were in good agreement with the gold-standard high-performance liquid chromatography method. This report is the first to describe PD-IPCR for simultaneous quantitative detection of total aflatoxins and zearalenone in cereals.

Epidural adipose tissue-derived mesenchymal stem cell activation induced by lung cancer cells promotes malignancy and EMT of lung cancer.

BACKGROUND: Spinal metastasis is a major challenge in patients with advanced lung cancer, but the mechanisms in the organotropism of metastasis are still unclear. Adipose-derived mesenchymal stem cells (ADSCs) exhibit cancer-promoting properties that influence the tumour microenvironment; however, there is no research on ADSCs from epidural fat thus far. METHODS: In this study, we isolated and identified ADSCs from epidural adipose tissue for the first time. We examined the activation of epidural ADSCs treated with lung cancer cell-conditioned medium by immunohistochemistry, western blot and qRT-PCR assays. The expression of interleukin (IL)-6 family cytokines in the supernatants of ADSCs were evaluated by enzyme-linked immunosorbent assay. The effects of epidural ADSCs on the growth and invasion of lung cancer cells were evaluated with the CCK-8 and Transwell assays. The expression of signal transducer and activator of transcription 3 (STAT3), matrix metalloprotease and epithelial-mesenchymal transition markers were measured by western blot assays. RESULTS: Our results showed that ADSCs treated with lung cancer cell-conditioned medium expressed higher levels of the myofibroblast marker α-smooth muscle actin and fibroblast activation protein than ADSCs cultured alone. Then, we found that lung cancer cells induced ADSCs to secrete high levels of IL-6 family cytokines and activate the STAT3 signalling pathway. Moreover, activated epidural ADSCs exhibited the ability to promote lung cancer cell proliferation and invasion by elevating matrix metalloprotease expression and epithelial-mesenchymal transition in cancer cells. Furthermore, blocking IL-6 can counteract the differentiation and tumour-promoting effects of ADSCs. CONCLUSION: Our results suggest that ADSCs respond to lung cancer cells and are involved in the crosstalk between primary tumours and pre-metastatic niches in epidural fat.

Small Molecular Contaminant and Microorganism Can Be Simultaneously Detected Based on Nanobody-Phage: Using Carcinogen Aflatoxin and Its Main Fungal Aspergillus Section Flavi spp. in Stored Maize for Demonstration.

Simultaneous detection technology has become a hot topic in analytical chemistry; however, very few reports on how to simultaneously detect small molecular contaminants and microorganisms have been in place. Aflatoxins are a group of highly toxic and carcinogenic compounds, which are produced mainly by Aspergillus flavus and Aspergillus parasiticus from section Flavi responsible for aflatoxin accumulation in stored cereals. Both aflatoxins and Aspergillus section Flavi were used to demonstrate the duplex real-time RCR method of simultaneously detecting small molecular contaminants and microorganisms. The detection of aflatoxins and Aspergillus section Flavi was carried out depending on the anti-idiotypic nanobody-phage V2-5 and aflatoxin-synthesis related gene nor-1 (=aflD), respectively. The quantitative standard curves for simultaneous detection of aflatoxins and Aspergillus section Flavi were constructed, with detection limits of 0.02 ng/ml and 8 × 102 spores/g, respectively. Naturally contaminated maize samples (n = 25) were analyzed for a further validation. The results were in good agreement between the new developed method and the referential methods (high-performance liquid chromatography and the conventional plating counts).

Fropofol decreases force development in cardiac muscle.

Supranormal contractile properties are frequently associated with cardiac diseases. Anesthetic agents, including propofol, can depress myocardial contraction. We tested the hypothesis that fropofol, a propofol derivative, reduces force development in cardiac muscles via inhibition of cross-bridge cycling and may therefore have therapeutic potential. Force and intracellular Ca2+ concentration ([Ca2+]i) transients of rat trabecular muscles were determined. Myofilament ATPase, actin-activated myosin ATPase, and velocity of actin filaments propelled by myosin were also measured. Fropofol dose dependently decreased force without altering [Ca2+]i in normal and pressure-induced hypertrophied-hypercontractile muscles. Similarly, fropofol depressed maximum Ca2+-activated force ( Fmax) and increased the [Ca2+]i required for 50% of Fmax (Ca50) at steady state without affecting the Hill coefficient in both intact and skinned cardiac fibers. The drug also depressed cardiac myofibrillar and actin-activated myosin ATPase activity. In vitro actin sliding velocity was significantly reduced when fropofol was introduced during rigor binding of cross-bridges. The data suggest that the depressing effects of fropofol on cardiac contractility are likely to be related to direct targeting of actomyosin interactions. From a clinical standpoint, these findings are particularly significant, given that fropofol is a nonanesthetic small molecule that decreases myocardial contractility specifically and thus may be useful in the treatment of hypercontractile cardiac disorders.-Ren, X., Schmidt, W., Huang, Y., Lu, H., Liu, W., Bu, W., Eckenhoff, R., Cammarato, A., Gao, W. D. Fropofol decreases force development in cardiac muscle.

Unique Complications of Percutaneous Endoscopic Lumbar Discectomy and Percutaneous Endoscopic Interlaminar Discectomy.

BACKGROUND: Percutaneous endoscopic discectomy (PED) includes 2 main procedures: percutaneous endoscopic lumbar discectomy (PELD) and percutaneous endoscopic interlaminar discectomy (PEID), both of which are minimally invasive surgical procedures that effectively deal with lumbar degenerative disorders. Because of the challenging learning curve for the surgeon and the individual characteristics of each patient, preventing and avoiding complications is difficult. The most common complications, such as nucleus pulposus omission, nerve root injury, dural tear, visceral injury, nerve root induced hyperalgesia or burning-like nerve root pain, postoperative dysesthesia, posterior neck pain, and surgical site infection, are difficult to avoid; however, more focus on these issues perioperatively may be in order. Additionally, unique and unexpected complications can also occur, such as retroperitoneal hematoma (RPH), intraoperative seizures, and thrombophlebitis, among others. OBJECTIVE: We aim to delineate unique complications during PED and accumulate strategies to prevent significant morbidity and improve surgical techniques. STUDY DESIGN: A retrospective cohort study of patients undergoing PEID or PELD from October 2014 to January 2016. SETTING: Affiliated hospitals of Qingdao University. METHODS: Patients with lumbar disc herniation (LDH) who underwent PEID and PELD were retrospectively analyzed. Complications were recorded and analyzed pre and postoperatively. We assessed clinical outcomes using the visual analog scale (VAS) and Oswestry Disability Index (ODI) and classified the results into "excellent," "good," "fair," or "poor" based on the modified MacNab criteria. All of the patients were followed for more than one year to evaluate their recovery from complications. RESULTS: From October 2014 to January 2016, 426 patients with LDH underwent PEID (106 cases) or PELD (320 cases). Common complications and occurrence rates were as follows: the incomplete removal of herniated discs was 1.4% (6/426), recurrence 2.8% (12/426), nerve root injury 1.2% (5/426), dural tear 0.9% (4/426), and nerve root induced hyperalgesia or burning-like nerve root pain 2.3% (10/426); no posterior neck pain or surgical site infection occurred. Unique complications included: passage of the working channel through the spinal canal into the disc space (one case), super-elastic nerve hook caught by exiting nerve root (one case), epidural hematoma (one case), radicular artery injury and massive bleeding (one case) which was revised by micro-endoscopic discectomy, and intraoperative seizure (one case). No serious consequences occurred after active medical intervention, and most patients had good recovery by 3 months postoperatively with physical therapy. LIMITATIONS: The main limitations of this study are the retrospective study design, limited case number, and short follow-up period. CONCLUSIONS: PEDs are effective and minimally invasive methods for the surgical treatment of LDH, causing fewer complications due to the very minimal operational trauma for the muscle-ligament complex and stability of the spine. Nevertheless, because of the difficult learning curve for surgeons, lack of experience with the requisite surgical techniques, and enhanced clinical responsibility, a variety of problems may occur. Especially concerning are the unique complications mentioned here, which potentially lead to severe injury for the patient and require diligent preventive measures. KEY WORDS: Unique complications, epidural, hematoma, interlaminar, transforaminal, PEID, PELD.

The Genetic and Molecular Bases for Hypertrophic Cardiomyopathy: The Role for Calcium Sensitization.

Hypertrophic cardiomyopathy (HCM) affects millions of people around the world as one of the most common genetic heart disorders and leads to cardiac ischemia, heart failure, dysfunction of other organ systems, and increased risk for sudden unexpected cardiac deaths. HCM can be caused by single-point mutations, insertion or deletion mutations, or truncation of cardiac myofilament proteins. The molecular mechanism that leads to disease progression and presentation is still poorly understood, despite decades of investigations. However, recent research has made dramatic advances in the understanding of HCM disease development. Studies have shown that increased calcium sensitivity is a universal feature in HCM. At the molecular level, increased crossbridge force (or power) generation resulting in hypercontractility is the prominent feature. Thus, calcium sensitization/hypercontractility is emerging as the primary stimulus for HCM disease development and phenotypic expression. Cross-bridge inhibition has been shown to halt HCM presentation, and myofilament desensitization appears to reduce lethal arrhythmias in animal models of HCM. These advances in basic research will continue to deepen the knowledge of HCM pathogenesis and are beginning to revolutionize the management of HCM.