Antimicrobial peptides derived from the cartilage.-specific C-type Lectin Domain Family 3 Member A (CLEC3A) - potential in the prevention and treatment of septic arthritis.

OBJECTIVE: To investigate the antimicrobial activity of peptides derived from C-type Lectin Domain Family 3 Member A (CLEC3A), shed light on the mechanism of antimicrobial activity and assess their potential application in prevention and treatment of septic arthritis. DESIGN: We performed immunoblot to detect CLEC3A peptides in human cartilage extracts. To investigate their antimicrobial activity, we designed peptides and recombinantly expressed CLEC3A domains and used them to perform viable count assays using E.coli, P.aeruginosa and S.aureus. We investigated the mechanism of their antimicrobial activity by fluorescence and scanning electron microscopy, performed ELISA-style immunoassays and transmission electron microscopy to test for lipopolysaccharide binding and surface plasmon resonance to test for lipoteichoic acid (LTA) binding. We coated CLEC3A peptides on titanium, a commonly used prosthetic material, and performed fluorescence microscopy to quantify bacterial adhesion. Moreover, we assessed the peptides' cytotoxicity against primary human chondrocytes using MTT cell viability assays. RESULTS: CLEC3A fragments were detected in human cartilage extracts. Moreover, bacterial supernatants lead to fragmentation of recombinant and cartilage-derived CLEC3A. CLEC3A-derived peptides killed E.coli, P.aeruginosa and S.aureus, permeabilized bacterial membranes and bound lipopolysaccharide and LTA. Coating CLEC3A antimicrobial peptides (AMPs) on titanium lead to significantly reduced bacterial adhesion to the material. In addition, microbicidal concentrations of CLEC3A peptides in vitro displayed no direct cytotoxicity against primary human chondrocytes. CONCLUSIONS: We identify cartilage-specific AMPs originating from CLEC3A, resolve the mechanism of their antimicrobial activity and point to a novel approach in the prevention and treatment of septic arthritis using potent, non-toxic, AMPs.

Complications after mesial temporal lobe surgery via inferiortemporal gyrus approach.

OBJECT: The purpose of this study was to identify the complications associated with the inferior temporal gyrus approach to anterior mesial temporal lobe resection for temporal lobe epilepsy. METHODS: This retrospective study examined complications experienced by 483 patients during the 3 months after surgery. All surgeries were performed during 1998-2012 by the senior author (F.L.V.). RESULTS: A total of 13 complications (2.7%) were reported. Complications were 8 delayed subdural hematomas (1.6%), 2 superficial wound infections (0.4%), 1 delayed intracranial hemorrhage (0.2%), 1 small lacunar stroke (0.2%), and 1 transient frontalis nerve palsy (0.2%). Three patients with subdural hematoma (0.6%) required readmission and surgical intervention. One patient (0.2%) with delayed intracranial hemorrhage required readmission to the neuroscience intensive care unit for observation. No deaths or severe neurological impairments were reported. Among the 8 patients with subdural hematoma, 7 were older than 40 years (87.5%); however, this finding was not statistically significant (p = 0.198). CONCLUSIONS: The inferior temporal gyrus approach to mesial temporal lobe resection is a safe and effective method for treating temporal lobe epilepsy. Morbidity and mortality rates associated with this procedure are lower than those associated with other neurosurgical procedures. The finding that surgical complications seem to be more common among older patients emphasizes the need for early surgical referral of patients with medically refractory epilepsy.

A cadaveric model for measuring sinonasal continuous positive airway pressure-a proof-of-concept study.

BACKGROUND: Obstructive sleep apnea is a common respiratory disorder that can have negative effects on health and quality of life. Positive pressure therapy (CPAP) is the primary treatment. There is a lack of consensus on the risk of postoperative CPAP after endoscopic sinus or skull base surgery. We present a proof-of-concept cadaver model for measuring sinonasal pressure delivered by CPAP. METHODS: Three fresh cadaver heads were prepared by removing the calvaria and brain. Sphenoidotomies were made and sellar bone was removed. Pressure sensors were placed in the midnasal cavity, sphenoid sinus, and sella. CPAP was applied and the delivered pressure was recorded at increasing levels of positive pressure. Paired t tests and intraclass correlation coefficients were used to analyze results. RESULTS: Increases in positive pressure led to increased pressure recordings for all locations. Nasal cavity pressure was, on average, 81% of delivered CPAP. Pressure was highest in the sphenoid sinus. The effect of middle turbinate medialization on intrasphenoid pressure was not statistically significant in 2 heads. Intrasellar pressure was 80% of delivered CPAP with lateralized turbinates and 84% with medialized turbinates. Pressure recordings demonstrated excellent reliability for all locations. All heads developed non-sellar-based cranial base leaks at higher pressures. Cribriform region leaks were successfully sealed with DuraSeal®. CONCLUSION: Our proof-of-concept cadaver model represents a novel approach to measure pressures delivered to the nasal cavity and anterior skull base by CPAP. With further study, it may have broader clinical application to guide the safe postoperative use of CPAP in this population.

Evaluation of cranial base repair techniques utilizing a novel cadaveric CPAP model.

BACKGROUND: Although recent guidelines for obstructive sleep apnea recommend early postoperative use of continuous positive airway pressure (CPAP) after endonasal skull base surgery, the time of initiation of CPAP is unclear. In this study we used a novel, previously validated cadaveric model to analyze the pressures delivered to the cranial base and evaluate the effectiveness of various repair techniques to withstand positive pressure. METHODS: Skull base defects were surgically created in 3 fresh human cadaver heads and repaired using 3 commonly used repair techniques: (1) Surgicel™ onlay; (2) dural substitute underlay with dural sealant onlay; and (3) dural substitute underlay with nasoseptal flap onlay with dural sealant. Pressure microsensors were placed in the sphenoid sinus and sella, both proximal and distal to the repair, respectively. The effectiveness of each repair technique against various CPAP pressure settings (5-20 cm H2 O) was analyzed. RESULTS: Approximately 79%-95% of positive pressure administered reached the sphenoid sinus. Sellar pressure levels varied significantly across the 3 repair techniques and were lowest after the third technique. "Breach" points (CPAP settings at which sellar repair was violated) were lowest for the first group. All 3 specimens showed a breach after the first repair technique. For the second repair technique, only a single breach was created in 1 specimen at 20 cm H2 O. No breaches were created in the third group. CONCLUSION: Different skull base repair techniques have varying ability to withstand CPAP. Both second and third repair techniques performed in a nearly similar fashion with regard to their ability to withstand positive pressure ventilation.

The Role of Free Tissue Transfer in the Management of Chronic Frontal Sinus Osteomyelitis.

OBJECTIVES/HYPOTHESIS: Chronic frontal sinus infection is managed with a combination of medical and surgical interventions. Frontal bone osteomyelitis due to recurrent infection following trauma or prior open surgery may require more significant debridement. Free tissue transfer may allow for extensive debridement with replacement of tissue, and definitive eradication of osteomyelitis. STUDY DESIGN: Retrospective chart review. METHODS: Patients undergoing free flap obliteration of the frontal sinus for frontal bone osteomyelitis at a single institution were included in the study. Clinical, radiologic, and surgical data were collected. Surgeries before and after free flap obliteration were compared by Wilcoxon signed rank test. RESULTS: Fifteen patients were identified; however, one patient had less than 6 months of follow-up and was excluded from analysis. Of the remaining 14 patients, mean follow-up duration was 26 months (range, 6-120 months). Mean number of surgeries prior to free flap was 3.7 (range, 1-8 surgeries). Free flap obliteration resolved chronic frontal sinusitis in all patients. Two patients experienced postoperative infection, and the overall complication rate was 29%. Eight patients underwent cranioplasty (six immediate, two delayed) without complication. All patients received planned courses of postoperative antibiotics. A statistically significant decrease in the number of surgeries after free flap obliteration was observed P ≤ .01). CONCLUSIONS: Extensive debridement followed by free tissue transfer and antibiotics offers a definitive treatment for complicated, recurrent frontal osteomyelitis. Simultaneous cranioplasty provides immediate protective and aesthetic benefit without complication. Consideration should be given for free tissue transfer and cranioplasty earlier in the algorithm for treatment of refractory frontal sinus osteomyelitis. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1497-1504, 2019.

An inhibitor of DNA recombination blocks memory consolidation, but not reconsolidation, in context fear conditioning.

Genomic recombination requires cutting, processing, and rejoining of DNA by endonucleases, polymerases, and ligases, among other factors. We have proposed that DNA recombination mechanisms may contribute to long-term memory (LTM) formation in the brain. Our previous studies with the nucleoside analog 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP), a known inhibitor of DNA ligases and polymerases, showed that this agent blocked consolidation of conditioned taste aversion without interfering with short-term memory (STM). However, because polymerases and ligases are also essential for DNA replication, it remained unclear whether the effects of this drug on consolidation were attributable to interference with DNA recombination or neurogenesis. Here we show, using C57BL/6 mice, that ara-CTP specifically blocks consolidation but not STM of context fear conditioning, a task previously shown not to require neurogenesis. The effects of a single systemic dose of cytosine arabinoside (ara-C) on LTM were evident as early as 6 h after training. In addition, although ara-C impaired LTM, it did not impair general locomotor activity nor induce brain neurotoxicity. Importantly, hippocampal, but not insular cortex, infusions of ara-C also blocked consolidation of context fear conditioning. Separate studies revealed that context fear conditioning training significantly induced nonhomologous DNA end joining activity indicative of DNA ligase-dependent recombination in hippocampal, but not cortex, protein extracts. Finally, unlike inhibition of protein synthesis, systemic ara-C did not block reconsolidation of context fear conditioning. Our results support the idea that DNA recombination is a process specific to consolidation that is not involved in the postreactivation editing of memories.

Minimizing Septectomy for Endoscopic Transsphenoidal Approaches to the Sellar and Suprasellar Regions: A Cadaveric Morphometric Study.

The purpose of this study was to evaluate the effect of posterior septectomy size on surgical exposure and surgical freedom during the endoscopic transsphenoidal approach to the sella and parasellar region. Dissections were performed on 10 embalmed cadaver heads. Dissections started with wide bilateral sphenoidotomies, lateralization of middle turbinates, and a 5-mm posterior septectomy. The posterior septectomy was increased in 5-mm increments to a maximum of 35 mm, followed by bilateral middle turbinectomies. Surgical exposure was defined as the distance between the ipsilateral and contralateral limit of exposure as allowed by the posterior septum along a midsphenoid horizontal meridian. Surgical freedom was defined as the angle between the ipsilateral and contralateral limit. The mean baseline width of the posterior sphenoid sinus was 29.4 ± 3.7 mm. With a 5-mm septectomy, the mean width of surgical exposure was 21.1 ± 2.8 mm. The surgical exposure increased significantly with progressively larger posterior septectomy until a 20-mm posterior septectomy, after which no further increase in surgical exposure or freedom was obtained. Bilateral lateral opticocarotid recesses were accessible with a 15-mm posterior septectomy. The addition of bilateral middle turbinectomies did not significantly increase lateral exposure within the sphenoid sinus compared with middle turbinate lateralization.

Molecular ecological tools to decipher the role of our microbial mass in obesity.

After birth, our gastrointestinal (GI) tract is colonised by a highly complex assemblage of microbes, collectively termed the GI microbiota, that develops intimate interactions with our body. Recent evidence indicates that the GI microbiota and its products may contribute to the development of obesity and related diseases. This, coupled with the current worldwide epidemic of obesity, has moved microbiome research into the spotlight of attention. Although the main cause of obesity and its associated metabolic complications is excess caloric intake compared with expenditure, differences in GI tract microbial ecology between individuals might be an important biomarker, mediator or new therapeutic target. This can be investigated using a diverse set of complementary so called -omics technologies, such as 16S ribosomal RNA gene-targeted composition profiling, metabolomics, metagenomics, metatranscriptomics and metaproteomics. This review aims to describe the different molecular approaches and their contributions to our understanding of the role of the GI microbiota in host energy homeostasis. Correspondingly, we highlight their respective strengths, but also try to create awareness for their specific limitations. However, it is currently still unclear which bacterial groups play a role in the development of obesity in humans. This might partly be explained by the heterogeneity in genotype, lifestyle, diet and the complex ethology of obesity and its associated metabolic disorders (OAMD). Nevertheless, recent research on this matter has shown a conceptual shift by focusing on more homogenous subpopulations, through the use of both anthropometric (weight, total body fat) as well as biochemical variables (insulin resistance, hyperlipidaemia) to define categories. Combined with technological advances, recent data suggests that an OAMD associated microbiota can be characterised by a potential pro-inflammatory composition, with less potential for the production of short chain fatty acids and butyrate in particular.

Radiological diagnosis and therapy of pulmonary arteriovenous fistulae in a patient with an atypical clinical history: a case report.

Pulmonary arteriovenous fistulae were first managed nonsurgically by Porstmann in 1977 with homemade metallic coils (1). During the intervening twenty years better catheterization techniques have been developed and our understanding of the clinical outcomings of these lesions has improved. This report discusses the natural history of pulmonary arteriovenous fistulae, including the neurological and other complications, the importance of family screening in the detection of asymptomatic family members, the diagnostic strategy and the description of improved techniques for embolotherapy with stainless steel coils.

Cocaine sensitization increases I h current channel subunit 2 (HCN2) protein expression in structures of the mesocorticolimbic system.

Alteration of the biological activity among neuronal components of the mesocorticolimbic (MCL) system has been implicated in the pathophysiology of drug abuse. Changes in the electrophysiological properties of neurons involved in the reward circuit seem to be of utmost importance in addiction. The hyperpolarization-activated cyclic nucleotide current, I h, is a prominent mixed cation current present in neurons. The biophysical properties of the I h and its potential modulatory role in cell excitability depend on the expression profile of the hyperpolarization-activated cyclic nucleotide gated channel (HCN) subunits. We investigated whether cocaine-induced behavioral sensitization, an animal model of drug addiction, elicits region-specific changes in the expression of the HCN2 channel's subunit in the MCL system. Tissue samples from the ventral tegmental area, prefrontal cortex, nucleus accumbens, and hippocampus were analyzed using Western blot. Our findings demonstrate that cocaine treatment induced a significant increase in the expression profile of the HCN2 subunit in both its glycosylated and non-glycosylated protein isoforms in all areas tested. The increase in the glycosylated isoform was only observed in the ventral tegmental area. Together, these data suggest that the observed changes in MCL excitability during cocaine addiction might be associated with alterations in the subunit composition of their HCN channels.

[Paroxetine-induced neuroleptic malignant syndrome]. / Paroxetin-induziertes malignes neuroleptisches Syndrom.

We report on a 22-year-old schizophrenic patient who attempted suicide and suffered an epidural hemorrhage. 16 days after the neurosurgical operation. After several weeks of treatment with promethazine, 1 day after intake of paroxetin he partially lost consciousness and developed extrapyramidal symptoms and vegetative disorders. Hyper-Ck-aemia up to 680 U/l was observed. Malignant neuroleptic syndrome (MNS) was diagnosed, which led to withdrawal of paroxetin and promethazine. He was put on dantamacrine and amantadine until the symptoms resolved. To date there have been few reports on MNS under tricyclic antidepressants and selective serotonin inhibitors. The influence of the central serotonergic system on the pathophysiology of MNS is discussed.

CT of saber-sheath trachea. Correlation with clinical, chest radiographic and functional findings.

The diagnosis of saber-sheath trachea is easy at CT due to its cross-sectional imaging, but the significance of this CT sign has not been evaluated in the diagnosis of chronic obstructive pulmonary disease (COPD). Various signs of COPD were compared between a series of 20 patients with a saber-sheath trachea at CT (tracheal index < or = 66%) and a group of 20 pneumologic control patients without saber-sheath trachea (tracheal index > or = 70%). These signs included clinical and standard radiographic indices of COPD, sternum-spine distance and 3 functional tests of COPD: forced expiratory volume in one second, carbon monoxide diffusing lung capacity, and functional residual capacity (FRC). A significant difference was found between the 2 groups, concerning the values of FRC (p < 10(-4)) and of sternum-spine distance (p < 10(-2)). The tracheal index was significantly correlated with the FRC values (r = -0.611; p < 10(-5)) and with the sternum-spine distance (r = -0.322; p < 0.05). No other significant difference was observed. It is concluded that saber-sheath trachea is basically a sign of hyperinflation.

Off-axis multipass amplifier as a large aperture driver stage for fusion lasers.

A multipass amplifier configuration is described which has potential as a large aperture, high gain driver stage for fusion laser systems. We avoid the present limitations of large aperture switches by using an off-angle geometry that does not require an optical switch. The saturated gain characteristics of this multipass amplifier are optimized numerically. Three potential problems are investigated experimentally, self-lasing, output beam quality, and amplified spontaneous emission output. The results indicate comparable cost for comparable performance to a linear chain, with some operational advantage for the multipass driver stage.

Tratamento cirúrgico do megacolo chagásico pela técnica de Duhamel-Haddad: experiência no Hospital Geral de Goiânia; análise de 204 casos / Surgical treatment of chagasic megacolon by Duhamel-Haddad technic: experience in Hospital Geral de Goiânia, analysis of 204 cases

Os autores fazem uma análise retrospectiva de 204 pacientes operados de megacólon chagásico, com a técnica de Duhamel-Haddad; na Clínica de Colo-Proctologia do Hospital Geral de Goiânia - INAMPS, no período de janeiro de 1975 a dezembro de 1984. Cento e um pacientes eram do sexo masculino (49,5%) e cento e três do sexo feminino (50,5%). Analisam sua experiência no manuseio desta técnica, comparando a morbidade, a mortalidade e resultados funcionais com os obtidos por outros grupos. Levando em conta os resultados obtidos, consideram esta técnica relativamente fácil e que apresenta excelentes resultados

Sindrome de Peutz-Jeghers: apresentaçao de um caso / Peutz-Jeghers syndrome: a case report

Os autores apresentam um caso de Sindrome de Peutz-Jeghers atendido na Clinica de Colo-proctologia do Hospital Geral de Goiania - INAMPS, com quadro de choque hipovolemico devido a enterorragia. Apos tecerem comentarios a respeito das condutas propedeutica e terapeutica adotadas, discutem os principais aspectos clinicos da doença, levando em consideraçao a literatura existente sobre esta patologia.