Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases.

We and others have shown that [18F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [18F]-MK-6240 and [18F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [18F]-MK-6240 closely parallels that of [18F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing ß-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers.

Comparison of chemiluminiscence versus lateral flow assay for the detection of Helicobacter pylori antigen in human fecal samples.

Helicobacter pylori is a Gram-negative bacterium that causes chronic gastric inflammation, which can lead to gastric neoplasia. Therefore, early diagnosis of H. pylori infection is crucial for effective treatment and prevention of complications. The aim of this study was to compare the sensitivity and specificity of the STANDARD™ F H. pylori Ag FIA stool antigen test (SD Biosensor) with the LIAISON® Meridian H. pylori SA for the diagnosis of H. pylori infection. A total of 133 stool samples from patients with suspected H. pylori infection were compared using the STANDARD™ F H. pylori Ag FIA stool antigen test (SD Biosensor), based on lateral flow assay, with the LIAISON® Meridian H. pylori SA. Of the 45 positive samples with LIAISON, 44 were also positive while 1 was negative in the STANDARD™ antigen test. However, this discrepant sample showed a chemiluminescence index of 1.18, very close to the cut-off point of 1. On the other hand, of 88 negative samples obtained with LIAISON, 83 were negative and 5 were positive in the STANDARD™ antigen test. Moreover, STANDARD™ F H. pylori Ag FIA assay has shown a sensitivity of 97.8% (95% CI: 88.2-99.9), a specificity of 94.3% (95% CI: 87.2-98.1), a PPV of 83.9% (95% CI: 68.9-92.4) and a NPV of 99.3% ((95% CI: 95.3-99.9). In conclusion, the STANDARD™ F H. pylori Ag FIA (SD Biosensor) on the STANDARD™ F2400 analyser is a highly sensitive, specific and suitable assay for the detection of H. pylori in stool samples.

High expression of Toll-like receptors 2 and 9 and Th1/Th2 cytokines profile in obese asthmatic children.

Asthma is a common pulmonary disease with chronic inflammation of the airways, and obesity is a chronic state of low-grade inflammation. Toll-like receptors (TLRs) are involved in the innate immune response. This study was designed to analyze whether obesity has an effect on the immune response of patients with asthma. We included obese asthmatic, obese, asthmatic, and healthy children. Biochemical and anthropometric analyses were performed. Interleukin (IL)-2, interferon (IFN) gamma, IL-4, IL-10, IL-1beta, and tumor necrosis factor alpha were measured. Peripheral blood mononuclear cells were analyzed by immunostaining with anti-TLR2 and anti-TLR9 antibodies. The data were expressed as means ± SEM or medians and percentiles. Kruskal-Wallis test and Dunn's multiple comparison test were applied. Asthmatic patients, both obese and nonobese, exhibited a mild asthma phenotype; none had infectious process, exacerbation, or acute symptoms during the 30 days before the inclusion in the study. The IL-2 and IFN-gamma levels in the obese asthmatic group were lower than in the other three groups. IL-4 levels in the obese asthmatic group were almost equal to those of the asthmatic group and more than in the other two groups, without significant difference. There were higher levels of TLR2 and TLR9 in obese asthmatic patients than in the other three groups. There is a decrease in Th1 cytokines in obese asthmatic patients, and we only found a trend to an increased Th2 profile. Patients studied do not appear to fit into any of the endotypes described until now. This is the first study showing the high expression of TLR2 and TLR9 in obese asthmatic patients. It is necessary to study other cytokines in obese asthmatic patients to see if it is possible to fit them into any of the already described endotypes or if it is a distinct endotype.

Comparison of fidaxomicin, metronidazole and vancomycin for initial episode and recurrence of Clostridioides difficile infection - An observational cohort study.

Objectives: The main aim of this study was to compare the clinical outcomes of patients attended in our area with Clostridioides difficile infection (CDI) (sustained cure, recurrence or death) in relation to treatment to normal or hypervirulent C. difficile as a risk factor and to describe the resistance profile to metronidazole and vancomycin antibiotics in our hospital over a one-year period. Methods: A retrospective, cross-sectional and observational study was conducted between June 2022 and June 2023 to compare the clinical cure and/or recurrence of CDI in adult patients treated in a Spanish secondary Hospital depending on the prescribed antibiotic treatment. In addition, we performed an antimicrobial susceptibility study to vancomycin and metronidazole in all C. difficile isolated in bacterial culture. Results: Out of 194 selected patients the treatments were as follow: 43.81 % vancomycin, 21.65 % metronidazole, 8.25 % a combination of both, 6.70 % fidaxomicin and 19.59 % were untreated. Vancomycin and fidaxomicin patients had higher odds ratio of prolonged hospitalization (p = 0.041 and p = 0.040, respectively). Fidaxomicin had increased odds of suffering another episode of C. difficile (p = 0.009) and it was inferior to metronidazole for recurrent CDI (rCDI) (p = 0.035).Resistance profile for C. difficile was 4.07 % for vancomycin and 3.49 % for metronidazole. Hypervirulent C. difficile was identified in 17 (8.76 %) patients with 29.41 % of mortality (5/17; p > 0.05). Conclusion: Fidaxomicin treated patients had statistically increased odds of rCDI. Compared to other treatments, fidaxomicin was inferior to metronidazole for rCDI in our cohort;Hypervirulent C. difficile was not associated with death.Vancomycin resistance of C. difficile statistically decreased, whereas metronidazole resistance did not vary during the studied period.

Global Dynamics of Gastrointestinal Colonisations and Antimicrobial Resistance: Insights from International Travellers to Low- and Middle-Income Countries.

Gastrointestinal microorganism resistance and dissemination are increasing, partly due to international travel. This study investigated gastrointestinal colonisations and the acquisition of antimicrobial resistance (AMR) genes among international travellers moving between Spain and low- and middle-income countries (Peru and Ethiopia). We analysed 102 stool samples from 51 volunteers collected before and after travel, revealing significantly higher rates of colonisation by both bacteria and protists upon return. Diarrhoeagenic strains of E. coli were the most notable microorganism detected using RT-PCR with the Seegene Allplex™ Gastrointestinal Panel Assays. A striking prevalence of ß-lactamase resistance genes, particularly the TEM gene, was observed both before and after travel. No significant differences in AMR genes were found between the different locations. These findings highlight the need for rigorous surveillance and preventive strategies, as travel does not significantly impact AMR gene acquisition but does affect microbial colonisations. This study provides valuable insights into the intersection of gastrointestinal microorganism acquisition and AMR in international travellers, underscoring the need for targeted interventions and increased awareness.

Intragenomic diversity of the small subunit rDNA gene shows limited impact on the pathogenicity of Blastocystis infection in clinical patients.

The clinical significance of Blastocystis sp. remains to be fully elucidated. This study assesses whether Blastocystis subtype diversity can affect the outcome of the infection and the occurrence of clinical manifestations in infected individuals. Stool samples from 219 Blastocystis-positive patients by PCR targeting the ssu rDNA gene were fully genotyped by Sanger sequencing analyses. Co-infections by other parasitic, viral, and bacterial enteropathogens were identified by molecular and culture methods. Sequence analyses revealed the presence of six Blastocystis subtypes including ST1 (21.5 %), ST2 (17.8 %), ST3 (29.7 %), ST4 (22.8 %), ST6 (5.5 %), and ST7 (2.3 %), with a single sample harbouring a ST1+ST3 co-infection (0.5 %). Multivariate risk factor analyses using logistic regression models indicated that neither Blastocystis subtypes nor patient-associated variables including sex, country of origin, travelling history, and presence of nonspecific symptoms were positively associated with a higher likelihood of developing gastrointestinal symptoms (abdominal pain and diarrhoea). However, being of a young age (p-value: 0.003) and experiencing skin pruritus (p-value < 0.001) and eosinophilia (p-value: 0.016) were found to increase the odds of presenting gastrointestinal symptoms. Blastocystis subtypes based on variability within the ssu rDNA gene do not seem to be the main drivers of clinical manifestations in the surveyed clinical population.

A New Guanidine-Core Small-Molecule Compound as a Potential Antimicrobial Agent against Resistant Bacterial Strains.

The guanidine core has been one of the most studied functional groups in medicinal chemistry, and guanylation reactions are powerful tools for synthesizing this kind of compound. In this study, a series of five guanidine-core small molecules were obtained through guanylation reactions. These compounds were then evaluated against three different strains of Escherichia coli, one collection strain from the American Type Culture Collection (ATCC) of E. coli ATCC 35218, and two clinical extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (ESBL1 and ESBL2). Moreover, three different strains of Pseudomonas aeruginosa were studied, one collection strain of P. aeruginosa ATCC 27853, and two clinical multidrug-resistant isolates (PA24 and PA35). Among Gram-positive strains, three different strains of Staphylococcus aureus, one collection strain of S. aureus ATCC 29213, and two clinical methicillin-resistant S. aureus (MRSA1 and MRSA2) were evaluated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were reported, and the drop plate (DP) method was used to determine the number of viable suspended bacteria in a known beaker volume. The results from this assessment suggest that guanidine-core small molecules hold promise as therapeutic alternatives for treating infections caused by clinical Gram-negative and Gram-positive bacteria, highlighting the need for further studies to explore their potential. The results from this assessment suggest that the chemical structure of CAPP4 might serve as the basis for designing more active guanidine-based antimicrobial compounds, highlighting the need for further studies to explore their potential.

Study of the antimicrobial activity of cationic carbosilane dendrimers against clinical strains of multidrug-resistant bacteria and their biofilms.

Introduction: Antimicrobial Resistance is a serious public health problem, which is aggravated by the ability of the microorganisms to form biofilms. Therefore, new therapeutic strategies need to be found, one of them being the use of cationic dendritic systems (dendrimers and dendrons). Methods: The aim of this study is to analyze the in vitro antimicrobial efficacy of six cationic carbosilane (CBS) dendrimers and one dendron with peripheral ammonium groups against multidrug-resistant bacteria, some of them isolated hospital strains, and their biofilms. For this purpose, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC) and minimum eradication biofilm concentration (MBEC) studies were carried out. In addition, the cytotoxicity on Hela cells of those compounds that proved to be the most effective was analyzed. Results: All the tested compounds showed in vitro activity against the planktonic forms of methicillin-resistant Staphylococcus aureus and only the dendrimers BDSQ017, BDAC-001 and BDLS-001 and the dendron BDEF-130 against their biofilms. On the other hand, only the dendrimers BDAC 001, BDLS-001 and BDJS-049 and the dendron BDEF-130 were antibacterial in vitro against the planktonic forms of multidrug-resistant Pseudomonas aeruginosa, but they lacked activity against their preformed biofilms. In addition, the dendrimers BDAC-001, BDLS-001 and BDSQ-017 and the dendron BDEF-130 exhibited a good profile of cytotoxicity in vitro. Discussion: Our study demonstrates the possibility of using the four compounds mentioned above as possible topical antimicrobials against the clinical and reference strains of multidrug-resistant bacteria.

The Antimicrobial Resistance (AMR) Rates of Enterobacterales in a Rural Hospital from the Eastern Region, Ghana: A Retrospective Study, 2022.

Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance and often lack adequate surveillance due to a paucity of microbiological studies. In this 2022 study, our goal was to contribute to a more precise antimicrobial treatment by understanding the prevalence of resistance in a rural environment, promoting antibiotic stewardship, and raising awareness about antimicrobial resistance. We assessed the prevalence of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Enterobacterales in clinical samples from 2905 patients being treated at Saint Dominic's Hospital, Akwatia, in the countryside of the Eastern Region, Ghana, in the year 2022. To this purpose, the samples were cultured on agar plates prepared in the laboratory using purified Oxoid™ Thermo Scientific™ agar (Thermo Fisher Scientific; Waltham, MA, USA). Cystine Lactose Electrolyte-Deficient (CLED) agar was used for urine samples, while blood agar, chocolate agar, and MacConkey agar were used for the rest of the specimens tested (HVS, blood, BFA, sputum). Antimicrobial susceptibility was determined on site using the disc diffusion method (Kirby-Bauer test). MDR bacteria accounted for more than half (53.7%) of all microorganisms tested for three or more antibiotics and 37.3% of these were XDR. Multivariate regression analysis was performed to identify risk factors associated with acquiring MDR/XDR bacteria. The results showed an increased likelihood of MDR acquisition linked to being male (OR 2.39, p < 0.001 for MDR and OR 1.95, p = 0.027 for XDR), higher age (OR 1.01, p = 0.049 for MDR), non-sputum samples (OR 0.32, p = 0.009 for MDR), and urine samples (OR 7.46, p < 0.001 for XDR). These findings emphasize the urgency for surveillance and control of antimicrobial resistance; to this end, making accurate diagnostics, studying the microorganism in question, and conducting susceptibility testing is of the utmost importance.

Clinical Evolution and Risk Factors in Patients Infected during the First Wave of COVID-19: A Two-Year Longitudinal Study.

A limited number of longitudinal studies have examined the symptoms associated with long-COVID-19. We conducted an assessment of symptom onset, severity and patient recovery, and determined the percentage of patients who experienced reinfection up to 2 years after the initial onset of the disease. Our cohort comprises 377 patients (≥18 years) with laboratory-confirmed COVID-19 in a secondary hospital (Madrid, Spain), throughout March 3-16, 2020. Disease outcomes and clinical data were followed-up until August 12, 2022. We reviewed the evolution of the 253 patients who had survived as of April 2020 (67.1%). Nine died between April 2020 and August 2022. A multivariate regression analysis performed to detect the risk factors associated with long-COVID-19 revealed that the increased likelihood was associated with chronic obstructive lung disease (OR 14.35, 95% CI 1.89-109.09; p = 0.010), dyspnea (5.02, 1.02-24.75; p = 0.048), higher LDH (3.23, 1.34-7.52; p = 0.006), and lower D-dimer levels (0.164, 0.04-0.678; p = 0.012). Reinfected patients (n = 45) (47.8 years; 39.7-67.2) were younger than non-reinfected patients (64.1 years; 48.6-74.4)) (p < 0.001). Patients who received a combination of vaccines exhibited fewer symptoms (44.4%) compared to those who received a single type of vaccine (77.8%) (p = 0.048). Long-COVID-19 was detected in 27.05% (66/244) of patients. The early detection of risk factors helps predict the clinical course of patients with COVID-19. Middle-aged adults could be susceptible to reinfection, highlighting the importance of prevention and control measures regardless of vaccination status.

Trends in hospitalization and death rates among patients with head and neck cancer in Spain, 2009 to 2019.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, and prevalence is still substantially higher in men than in women. Causative factors include smoking and alcohol use, while human papillomavirus (HPV) infection is causally related to a subset of oropharyngeal cancers. In this retrospective study, we aimed to provide estimates on the clinical and economic burden of HNSCC in Spain. METHODS: We used the discharge reports from the Spanish Minimum Basic Data Set (MBDS), to retrospectively analyze hospital discharge data in individuals with a diagnosis of HNSCC in any diagnostic position, based on the ICD coding system (ICD-9-CM and ICD10 CM), from 2009 to 2019. RESULTS: A total of 175,340 admissions and 14,498 deaths due to laryngeal, pharyngeal and oral cavity cancer were recorded in Spain, of which 85% occurred in men. The most prevalent diagnoses were laryngeal cancer in men (50.9%) and oral cavity cancer in women (49.1%). In general, the hospitalization and death rates for all major head and neck cancer sites decreased in men and increased or remained stable in women during the study period. However, the corresponding rates for tonsil cancer, strongly associated with HPV infection, increased significantly in men. Overall, the economic burden of HNSCC during the study period was estimated at 100 million euros per year on average. CONCLUSION: HNSCC still places an important clinical and economic burden on the health system in Spain. Prevention strategies should be prioritized, and vaccination programs against HPV in both sexes should be reinforced.

The Nutraceutical Antihypertensive Action of C-Phycocyanin in Chronic Kidney Disease Is Related to the Prevention of Endothelial Dysfunction.

C-phycocyanin (CPC) is an antihypertensive that is not still wholly pharmacologically described. The aim of this study was to evaluate whether CPC counteracts endothelial dysfunction as an antihypertensive mechanism in rats with 5/6 nephrectomy (NFx) as a chronic kidney disease (CKD) model. Twenty-four male Wistar rats were divided into four groups: sham control, sham-treated with CPC (100 mg/Kg/d), NFx, and NFx treated with CPC. Blood pressure was measured each week, and renal function evaluated at the end of the treatment. Afterward, animals were euthanized, and their thoracic aortas were analyzed for endothelium functional test, oxidative stress, and NO production. 5/6 Nephrectomy caused hypertension increasing lipid peroxidation and ROS production, overexpression of inducible nitric oxide synthase (iNOS), reduction in the first-line antioxidant enzymes activities, and reduced-glutathione (GSH) with a down-expression of eNOS. The vasomotor response reduced endothelium-dependent vasodilation in aorta segments exposed to acetylcholine and sodium nitroprusside. However, the treatment with CPC prevented hypertension by reducing oxidative stress, NO system disturbance, and endothelial dysfunction. The CPC treatment did not prevent CKD-caused disturbance in the antioxidant enzymes activities. Therefore, CPC exhibited an antihypertensive activity while avoiding endothelial dysfunction.

Lidocaine affects the redox environment and the antioxidant enzymatic system causing oxidative stress in the hippocampus and amygdala of adult rats.

AIMS: Our objective was to investigate if oxidative stress is involved in the neural damage caused by lidocaine. MAIN METHODS: Male Wistar rats were used. The control group received 0.9% saline ip and the treated group received a single 60 mg/kg lidocaine dose ip. On days 1, 2, 5, and 10 after dosing, ten rats were sacrificed and their brains were quickly removed. The amygdala and hippocampus were dissected. Five samples were used to determine lipid peroxidation, reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG). Another five were used to measure antioxidant activities of glutathione peroxidase (GPX), catalase, Cu-Zn SOD (superoxide dismutase), Mn SOD, and total SOD. KEY FINDINGS: Ten days after injection of lidocaine, lipid peroxidation increases in the hippocampus because the ROS are enhanced from day 5, whereas in the amygdala lipid peroxidation and the ROS were enhanced only on the first day postinjection. Lidocaine causes an increased concentration of GSH and GSSG in the hippocampus from the first day. In the amygdala the GSH and GSSG content were increased at day 10. In the hippocampus the catalase activity was enhanced, whereas the total SOD and Cu-Zn SOD activities were decreased. In the amygdala the lidocaine enhances the activities of catalase and GPX, but no SOD isoenzymes were modified. SIGNIFICANCE: In this research we demonstrated that lidocaine affects the redox environment and promotes increases of the oxidative markers both in the hippocampus and amygdala but in a different pattern.

Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.

Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within the olfactory pathway. OEGs are thought to exclude OAs from contact with all other cells between the olfactory epithelium and the glomerulus of the olfactory bulb. These properties have lead to testing to determine whether OEGs support axonal growth following transplantation. The cellular interactions of transplanted OEGs will probably resemble those that occur within the normal pathway where interactions between OEGs and fibroblasts are prominent. No previous primate studies have focused on these interactions, knowledge of which is important if clinical application is envisioned. We describe the detailed intercellular interactions of OAs with supporting cells throughout the olfactory epithelium, the lamina propria, the fila olfactoria, and the olfactory nerve layer by using transmission electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment and variations of the endo- and perineurium formed by olfactory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. Perineurial cells contained intermediate filaments and were distinct from other fibroblasts and meningeal cells. OAs had direct contacts with astrocytes near the glia limitans. The properties of OEGs differed depending on whether astrocytic or fibroblastic processes were present. This indicates the importance of the cellular milieu in the structure and function of OEGs in primates.

Topiramate in the prophylactic treatment of migraine in children.

We present a prospective case series of 24 children diagnosed with migraine refractory to prophylactics and treated for 4 months with topiramate as the only prophylactic drug. At the final visit, the mean topiramate dose was 3.5 +/- 1.7 mg/kg/day. Nearly all patients (87.5%) reported a shorter duration of attacks, and the average pain intensity was rated as mild by 14 patients (58.3%). Eight (33.3%) patients had adverse events, none of which were serious. In our sample of pediatric patients, topiramate was effective for the prophylactic treatment of migraine in children. It was well tolerated at the doses used for titration and maintenance. Controlled trials are needed to verify the efficacy of topiramate for migraine in children.

Use of percutaneous endoscopy to place syringopleural or cystoperitoneal cerebrospinal fluid shunts: technical note.

The authors describe a technique for percutaneous endoscopic shunt placement to treat clinically symptomatic spinal cysts. Seven patients underwent the procedure--five with syringomyelia, one with a symptomatic perineurial cyst, and one with a large arachnoid cyst. In all patients the shunt was successfully placed, and clinical improvement occurred in six. In four patients the entire procedure was performed endoscopically, whereas in three conversion to an open surgical exposure was required for safe access of a syrinx cavity. Overall, however, the pleural or peritoneal catheter was successfully placed endoscopically in all seven patients. There were two cases of postoperative positional headaches of which one required valve revision. In one case the catheter migrated and required repositioning. Percutaneous endoscopic shunt placement appears feasible in appropriately selected patients.

Effects of epidural hypothermic saline infusion on locomotor outcome and tissue preservation after moderate thoracic spinal cord contusion in rats.

OBJECT: Regionally delivered hypothermia has advantages over systemic hypothermia for clinical application following spinal cord injury (SCI). The effects of local hypothermia on tissue sparing, neuronal preservation, and locomotor outcome were studied in a moderate thoracic spinal cord contusion model. METHODS: Rats were randomized to four treatment groups and data were collected and analyzed in a blinded fashion. Chilled saline was perfused into the epidural space 30 minutes postcontusion to achieve the following epidural temperatures: 24 +/- 2.3 degrees C (16 rats), 30 +/- 2.4 degrees C (13 rats), and 35 +/- 0.9 degrees C (13 rats). Hypothermia was continued for 3 hours when a 45-minute period of rewarming was instituted. In a fourth group a moderate contusion only was induced in 14 animals. Rectal (core) and T9-10 (epidural) temperatures were measured continuously. Locomotor testing, using the Basso-Beattie-Bresnahan (Ba-Be-Br) scale, was performed for 6 weeks, and rats were videotaped for subsequent analysis. The lesion/preserved tissue ratio was calculated throughout the entire lesion cavity and the total lesion, spinal cord, and spared tissue volumes were determined. The rostral and caudal extent of gray matter loss was also measured. At 6 weeks locomotor recovery was similar in all groups (mean Ba-Be-Br Scale scores 14.88 +/- 3.71, 14.83 +/- 2.81, 14.50 +/- 2.24, and 14.07 +/- 2.39 [p = 0.77] for all four groups, respectively). No significant differences in spared tissue volumes were found when control and treatment groups were compared, but gray matter preservation was reduced in the infusion-treated groups. CONCLUSIONS: Regional cooling applied 30 minutes after a moderate contusive SCI was not beneficial in terms of tissue sparing, neuronal preservation, or locomotor outcome. This method of cooling may reduce blood flow in the injured spinal cord and exacerbate secondary injury.

COMETARY SCIENCE. The landing(s) of Philae and inferences about comet surface mechanical properties.

The Philae lander, part of the Rosetta mission to investigate comet 67P/Churyumov-Gerasimenko, was delivered to the cometary surface in November 2014. Here we report the precise circumstances of the multiple landings of Philae, including the bouncing trajectory and rebound parameters, based on engineering data in conjunction with operational instrument data. These data also provide information on the mechanical properties (strength and layering) of the comet surface. The first touchdown site, Agilkia, appears to have a granular soft surface (with a compressive strength of 1 kilopascal) at least ~20 cm thick, possibly on top of a more rigid layer. The final landing site, Abydos, has a hard surface.

Percutaneous endoscopic cellular transplantation into the lower lumbar spinal cord.

OBJECTIVE: To explore the feasibility of performing percutaneous endoscopic cellular transplantation into the lumbar spinal cord of pigs to create intramedullary cellular trails. METHODS: The lumbar subarachnoid space was accessed using a 10-gauge needle inserted between L5 and L6. A 12.5-French flexible introducer sheath was fed over the needle into the subarachnoid space. A 3.2-mm-diameter flexible, steerable endoscope was then directed intradurally through the sheath. The thecal space was distended by saline infusion. A microcatheter with an attached needle then was advanced through the working channel into the dorsal surface of the lumbar spinal cord. Five microliters of Hoechst-labeled fibroblasts were injected while the catheter was withdrawn slowly to create a trail of cells within the spinal cord. The spinal canal then was perfused with fixative. The injected spinal cord segment was removed and studied histologically. Endoscopic video was analyzed offline. RESULTS: The endoscope could be navigated under visual guidance. The sacral and lumbar rootlets, the spinal cord, and associated vessels were visualized. In fixed sagittal sections, a linear trail of fluorescent fibroblasts could be seen within the lumbar spinal cord in each specimen. CONCLUSION: Percutaneous endoscopic cellular injection may be useful for cellular transplantation, may reduce surgical and anesthetic time, may be compatible with local anesthesia, may eliminate the need to disrupt spinal instrumentation and bone grafts, and may allow greater flexibility in the respective timing of spinal fixation and cellular transplantation after spinal cord injury. This is the first report of the use of endoscopic intraspinal cellular transplantation.