Ethanol and isopropanol inactivation of human coronavirus on hard surfaces.

BACKGROUND: The coronavirus disease 2019 pandemic has greatly increased the frequency of disinfecting surfaces in public places, causing a strain on the ability to obtain disinfectant solutions. An alternative is to use plain alcohols (EtOH and IPA) or sodium hypochlorite (SH). AIM: To determine the efficacy of various concentrations of EtOH, IPA and SH on a human coronavirus (HCoV) dried on to surfaces using short contact times. METHODS: High concentrations of infectious HCoV were dried on to porcelain and ceramic tiles, then treated with various concentrations of the alcohols for contact times of 15 s, 30 s and 1 min. Three concentrations of SH were also tested. Reductions in titres were measured using the tissue culture infectious dose 50 assay. FINDINGS: Concentrations of EtOH and IPA from 62% to 80% were very efficient at inactivating high concentrations of HCoV dried on to tile surfaces, even with a 15-s contact time. Concentrations of 95% dehydrated the virus, allowing infectious virus to survive. The dilutions of SH recommended by the Centers for Disease Control and Prevention (1/10 and 1/50) were efficient at inactivating high concentrations of HCoV dried on to tile surfaces, whereas a 1/100 dilution had substantially lower activity. CONCLUSIONS: Multiple concentrations of EtOH, IPA and SH efficiently inactivated infectious HCoV on hard surfaces, typical of those found in public places. Often no remaining infectious HCoV could be detected.

Alcohol-free hand sanitizer and other quaternary ammonium disinfectants quickly and effectively inactivate SARS-CoV-2.

BACKGROUND: SARS-CoV-2 is the virus responsible for the current global pandemic, COVID-19. Because this virus is novel, little is known about its sensitivity to disinfection. METHODS: We performed suspension tests against SARS-CoV-2 using three commercially available quaternary ammonium compound (Quat) disinfectants and one laboratory-made 0.2% benzalkonium chloride solution. FINDINGS: Three of the four formulations completely inactivated the virus within 15 s of contact, even in the presence of a soil load or when diluted in hard water. CONCLUSION: Quats rapidly inactivate SARS-CoV-2, making them potentially useful for controlling SARS-CoV-2 spread in hospitals and the community.

7X multiplexed, optofluidic detection of nucleic acids for antibiotic-resistance bacterial screening.

Rapid and accurate diagnosis of bacterial infections resistant to multiple antibiotics requires development of new bio-sensors for differentiated detection of multiple targets. This work demonstrates 7x multiplexed detection for antibiotic-resistance bacterial screening on an optofluidic platform. We utilize spectrally multiplexed multi-spot excitation for simultaneous detection of nucleic acid strands corresponding to bacterial targets and resistance genes. This is enabled by multi-mode interference (MMI) waveguides integrated in an optofluidic device. We employ a combinatorial three-color labeling scheme for the nucleic acid assays to scale up their multiplexing capability to seven different nucleic acids, representing three species and four resistance genes.

3× multiplexed detection of antibiotic resistant plasmids with single molecule sensitivity.

Bacterial pathogens resistant to antibiotics have become a serious health threat. Those species which have developed resistance against multiple drugs such as the carbapenems, are more lethal as these are last line therapy antibiotics. Current diagnostic tests for these resistance traits are based on singleplex target amplification techniques which can be time consuming and prone to errors. Here, we demonstrate a chip based optofluidic system with single molecule sensitivity for amplification-free, multiplexed detection of plasmids with genes corresponding to antibiotic resistance, within one hour. Rotating disks and microfluidic chips with functionalized polymer monoliths provided the upstream sample preparation steps to selectively extract these plasmids from blood spiked with E. coli DH5α cells. Waveguide-based spatial multiplexing using a multi-mode interference waveguide on an optofluidic chip was used for parallel detection of three different carbapenem resistance genes. These results point the way towards rapid, amplification-free, multiplex analysis of antibiotic-resistant pathogens.

Spiral T1 Spin-Echo for Routine Postcontrast Brain MRI Exams: A Multicenter Multireader Clinical Evaluation.

BACKGROUND AND PURPOSE: Spiral MR imaging has several advantages compared with Cartesian MR imaging that can be leveraged for added clinical value. A multicenter multireader study was designed to compare spiral with standard-of-care Cartesian postcontrast structural brain MR imaging on the basis of relative performance in 10 metrics of image quality, artifact prevalence, and diagnostic benefit. MATERIALS AND METHODS: Seven clinical sites acquired 88 total subjects. For each subject, sites acquired 2 postcontrast MR imaging scans: a spiral 2D T1 spin-echo, and 1 of 4 routine Cartesian 2D T1 spin-echo/TSE scans (fully sampled spin-echo at 3T, 1.5T, partial Fourier, TSE). The spiral acquisition matched the Cartesian scan for scan time, geometry, and contrast. Nine neuroradiologists independently reviewed each subject, with the matching pair of spiral and Cartesian scans compared side-by-side, and scored on 10 image-quality metrics (5-point Likert scale) focused on intracranial assessment. The Wilcoxon signed rank test evaluated relative performance of spiral versus Cartesian, while the Kruskal-Wallis test assessed interprotocol differences. RESULTS: Spiral was superior to Cartesian in 7 of 10 metrics (flow artifact mitigation, SNR, GM/WM contrast, image sharpness, lesion conspicuity, preference for diagnosing abnormal enhancement, and overall intracranial image quality), comparable in 1 of 10 metrics (motion artifacts), and inferior in 2 of 10 metrics (susceptibility artifacts, overall extracranial image quality) related to magnetic susceptibility (P < .05). Interprotocol comparison confirmed relatively higher SNR and GM/WM contrast for partial Fourier and TSE protocol groups, respectively (P < .05). CONCLUSIONS: Spiral 2D T1 spin-echo for routine structural brain MR imaging is feasible in the clinic with conventional scanners and was preferred by neuroradiologists for overall postcontrast intracranial evaluation.

Changing Trends in Brain Imaging Technique for Pediatric Patients with Ventriculoperitoneal Shunts.

BACKGROUND: Children with ventriculoperitoneal shunts (VPS) undergoing brain computed tomography (CT) for shunt malfunction evaluation are at risk for later malignancy due to radiation exposure. We aimed to determine if and how hospitals have adopted radiation-avoiding magnetic resonance imaging (MRI) techniques. METHODS: We performed a secondary analysis of the Pediatric Health Information System (PHIS) database. Children with VPS presenting to acute wards at 31 PHIS hospitals between January 1, 2007 and January 2, 2015 and receiving noncontrast neuroimaging on day of service 0/1 were included. Outcome measures were (1) incidence of MRI over time and (2) comparison of demographic characteristics between hospitals with MRI representing higher versus lower proportions (>15% or <15%) of total brain imaging. RESULTS: MRIs increased by 18.1% from 2007 to 2015. Hospitals were assigned to high-use (n = 12) or minimal-use (n = 19) MRI groups based on year 2014/2015 MRI percentages. The only identified difference was an older mean age in the high-use group (8.1 vs. 7.5 years; p = 0.03). CONCLUSIONS: MRI is increasingly used to evaluate patients with VPS. Hospitals with more MRI use had older patients and no increase in cost or length of stay. Initiating local quality improvement projects may help identify barriers to MRI uptake and increase use.

The Weekend Effect on Morbidity and Mortality Among Pediatric Epilepsy Admissions.

BACKGROUND: Pediatric epilepsy is one of the most common neurological disorders with low mortality and high morbidity, often requiring hospitalization. Weekend admissions have been shown to be associated with worse outcomes compared with their weekday counterparts. To date, no study has assessed the impact of weekend admission on clinical and quality outcomes in the pediatric epilepsy population. METHODS: Children with epilepsy were identified from the 2000, 2003, 2006, and 2009 Kids Inpatient Database. Quality outcomes were identified using the Centers of Medicare and Medicaid Services' hospital acquired conditions International Classification of Diseases, Ninth Edition; Clinical Modification (ICD-9CM) codes. Multivariable analyses were conducted to assess the association between weekend admission and inpatient mortality and hospital acquired condition occurrence. RESULTS: A total of 526,765 pediatric epilepsy discharges were identified, with 80% occurring on weekdays and 20% on weekends. Overall, the hospital acquired condition rate was 3.6% (3.2% vs 5.2% for weekday versus weekend) and inpatient mortality was 1.5% (1.2% vs 1.7%). Patients admitted on the weekend had 28% higher rates of hospital acquired conditions and 21% higher inpatient mortality rates compared with their weekday counterparts. Patients seen at nonpediatric centers had 10% to 28% lower rates of mortality, but 5% to 13% higher hospital acquired condition rates than those at pediatric centers. CONCLUSIONS: Weekend admission is significantly associated with worse clinical and quality outcomes compared with weekday admissions among pediatric epilepsy inpatients. Weekend admissions likely represent unplanned, at risk admissions, coupled with less staffing. Further study is needed to isolate clinical and systemic factors to decrease this disparity in this highly comorbid pediatric subgroup.

Pineal germ cell tumors: Two cases with review of histopathologies and biomarkers.

Pineal germ cell tumors (GCTs) are primarily seen in pediatric and Asian populations. These tumors are divided into germinomatous and non-germinomatous GCTs (NGGCTs). GCTs are thought to arise by misplacement of totipotent stem cells en route to gonads during embryogenesis. Intracranial GCTs display an affinity to develop along the pineal-suprasellar axis and have variable manifestations dependent upon the location of the tumor. Management and outcomes are driven by histopathologies. In this study, we highlight two cases of pineal GCTs and present a review of the literature with an emphasis on histopathologies and biomarkers.

Infra-Conus Single-Level Laminectomy for Selective Dorsal Rhizotomy: Technical Advance.

BACKGROUND/AIMS: Selective dorsal rhizotomy for spastic cerebral palsy is an effective and well-validated surgical approach. Multiple techniques have been described in the past including multiple laminectomies and a single-level laminectomy at the level of the conus. There is considerable technical challenge involved with a single-level laminectomy approach. METHODS: We report here a modification of the single-level laminectomy that selectively analyzes each individual nerve root with electromyography to separate dorsal and ventral nerve roots through comparison of stimulus responses. RESULTS: In 18 children with cerebral palsy who underwent this operation there was a mean improvement in the Modified Ashworth Scale of 2.0 with no reported incidence of muscle weakness, sensory loss, or neurogenic bladder. CONCLUSION: This approach allows for a modification of selective dorsal rhizotomy through a single-level laminectomy and tailors the selection of nerve root sectioning to the individual patient of interest while still maintaining its effectiveness.

PP2A inhibition with LB100 enhances cisplatin cytotoxicity and overcomes cisplatin resistance in medulloblastoma cells.

The protein phosphatase 2A (PP2A) inhibitor, LB100, has been shown in pre-clinical studies to be an effective chemo- and radio-sensitizer for treatment of various cancers. We investigated effects associated with LB100 treatment alone and in combination with cisplatin for medulloblastoma (MB) in vitro and in vivo in an intracranial xenograft model. We demonstrated that LB100 had a potent effect on MB cells. By itself, LB100 inhibited proliferation and induced significant apoptosis in a range of pediatric MB cell lines. It also attenuated MB cell migration, a pre-requirement for invasion. When used in combination, LB100 enhanced cisplatin-mediated cytotoxic effects. Cell viability in the presence of 1 uM cisplatin alone was 61% (DAOY), 100% (D341), and 58% (D283), but decreased with the addition of 2 µM of LB100 to 26% (DAOY), 67% (D341), and 27% (D283), (p < 0.005). LB100 suppressed phosphorylation of the STAT3 protein and several STAT3 downstream targets. Also, LB100 directly increased cisplatin uptake and overcame cisplatin-resistance in vitro. Finally, LB100 exhibited potent in vivo anti-neoplastic activity in combination with cisplatin in an intracranial xenograft model.

Discriminant ability of the Eating Assessment Tool-10 to detect aspiration in individuals with amyotrophic lateral sclerosis.

BACKGROUND: Oropharyngeal dysphagia is prevalent in individuals with amyotrophic lateral sclerosis (ALS) leading to malnutrition, aspiration pneumonia, and death. These factors necessitate early detection of at-risk patients to prolong maintenance of safe oral intake and pulmonary function. This study aimed to evaluate the discriminant ability of the Eating Assessment Tool (EAT-10) to identify ALS patients with unsafe airway protection during swallowing. METHODS: Seventy ALS patients completed the EAT-10 survey and underwent a standardized videofluoroscopic evaluation of swallowing. Two blinded raters determined airway safety using the Penetration Aspiration Scale (PAS). A between groups anova (safe vs penetrators vs aspirators) was conducted and sensitivity, specificity, area under the curve (AUC), and likelihood ratios calculated. KEY RESULTS: Mean EAT-10 scores for safe swallowers, penetrators, and aspirators (SEM) were: 4.28 (0.79) vs 7.10 (1.79) vs 20.50 (3.19), respectively, with significant differences noted for aspirators vs safe swallowers and aspirators vs penetrators (p < 0.001). The EAT-10 demonstrated good discriminant ability to accurately identify ALS penetrator/aspirators (PAS ≥3) with a cut off score of 3 (AUC: 0.77, sensitivity: 88%, specificity: 57%). The EAT-10 demonstrated excellent accuracy at identifying aspirators (PAS ≥6) utilizing a cut off score of 8 (AUC: 0.88, sensitivity: 86%, specificity: 72%, likelihood ratio: 3.1, negative predictive value: 95.5%). CONCLUSIONS & INFERENCES: The EAT-10 differentiated safe vs unsafe swallowing in ALS patients. This patient self-report scale could represent a quick and meaningful aide to dysphagia screening in busy ALS clinics for the identification and referral of dysphagic patients for further instrumental evaluation.

Surgery of the mind, mood, and conscious state: an idea in evolution.

Since the beginning of recorded history, humans have sought a physical means of altering disordered behavior and consciousness. This quest has spawned numerous innovations in neurosurgery and the neurosciences, from the earliest prehistoric attempts at trepanation to the electrocortical and anatomic localization of cerebral function that emerged in the 19th century. At the start of the 20th century, the overwhelming social impact of psychiatric illness intersected with the novel but imperfect understanding of frontal lobe function, establishing a decades-long venture into the modern origin of psychosurgery, the prefrontal lobotomy. The subsequent social and ethical ramifications of the widespread overuse of transorbital lobotomies drove psychosurgery to near extinction. However, as the pharmacologic treatment of psychiatric illness was established, numerous concomitant technical and neuroscientific innovations permitted the incremental development of a new paradigm of treating the disordered mind. In this article, we retrospectively examine these early origins of psychosurgery and then look to the recent past, present, and future for emerging trends in surgery of the psyche. Recent decades have seen a revolution in minimalism, noninvasive imaging, and functional manipulation of the human cerebrum that have created new opportunities and treatment modalities for disorders of the human mind and mood. Early contemporary efforts were directed at focal lesioning of abnormal pathways, but deep-brain stimulation now aims to reversibly alter and modulate those neurologic activities responsible for not only psychiatric disorders, but also to modulate and even to augment consciousness, memory, and other elements of cerebral function. As new tools become available, the social and medical impact of psychosurgery promises to revolutionize not only neurosurgery, but also humans' capability for positively impacting life and society.

Gas chromatography-mass spectrometry method for rapid identification and differentiation of Burkholderia pseudomallei and Burkholderia mallei from each other, Burkholderia thailandensis and several members of the Burkholderia cepacia complex.

AIMS: To develop a simple gas chromatography-mass spectrometry (GC-MS) method for the detection and differentiation of Burkholderia pseudomallei and Burkholderia mallei from each other, Burkholderia thailandensis and several members of the Burkholderia cepacia complex. METHODS AND RESULTS: Biomarkers were generated by one-step thermochemolysis (TCM) and analysed using a GC-MS system. Fragments of poly-3-hydroxybutyrate-co-hydroxyvalerate [poly(3HBA-co-3HVA)] produced by TCM were useful biomarkers. Several cellular fatty acid methyl esters were important in differentiating the various Burkholderia species. A statistical discrimination algorithm was constructed using a combination of biomarkers. The identities of four B. pseudomallei strains, four B. mallei strains and one strain of each near neighbour were confirmed in a statistically designed test using the algorithm. The detection limit for this method was found to be approximately 4000 cells. CONCLUSIONS: The method is fast, accurate and easy to use. The algorithm is robust against different growth conditions (medium and temperature). SIGNIFICANCE AND IMPACT OF THE STUDY: This assay may prove beneficial in a clinical diagnostic setting, where the rapid identification of B. pseudomallei is essential to effective treatment. This method could also be easily employed after a biological attack to confirm the presence of either B. pseudomallei or B. mallei.

Investigating the role of macrophages in tumor formation using a MaFIA mouse model.

Tumor-associated macrophages (TAMs) interact with tumors in their development, growth and metastatic activities. Using a transgenic mouse model that allows for the selective depletion of macrophages we were able to access the macrophage's potential to facilitate metastasis. In the MaFIA (Macrophage Fas-Induced Apoptosis) mouse, transgene-expressing cells of the myeloid lineage undergo death by apoptosis in the presence of the drug AP20187. Enhanced green fluorescent protein (EGFP) was fused to the suicide gene to allow identification of transgene-expressing cells. Tumor induction was accomplished by subdermal and intravenous injections of B16-F10 melanoma cells. Metastasis in mice with depleted macrophages was compared to metastasis in normal control mice. The lungs and kidneys were examined for metastatic cells. The macrophage-depleted groups showed significantly less metastasis (P>0.001) compared to the control groups. We theorize that macrophages may aid the metastatic process by fusing with melanoma cells. Using appropriate cell markers and fluorescence-activated cell sorting, we were able to detect a small population of double-positive cells. We confirmed cell fusion by microscopic analysis, visualizing the cell's morphology by both immunohistochemistry and immunofluorescence. The presence of double-positive cells suggests macrophage/cancer cell fusion could be a possible mechanism for metastasis.

Surgery of the mind, mood, and conscious state: an idea in evolution.

Since the beginning of recorded history, humans have sought a physical means of altering disordered behavior and consciousness. This quest has spawned numerous innovations in neurosurgery and the neurosciences, from the earliest prehistoric attempts at trepanation to the electrocortical and anatomic localization of cerebral function that emerged in the 19th century. At the start of the 20th century, the overwhelming social impact of psychiatric illness intersected with the novel but imperfect understanding of frontal lobe function, establishing a decades-long venture into the modern origin of psychosurgery, the prefrontal lobotomy. The subsequent social and ethical ramifications of the widespread overuse of transorbital lobotomies drove psychosurgery to near extinction. However, as the pharmacologic treatment of psychiatric illness was established, numerous concomitant technical and neuroscientific innovations permitted the incremental development of a new paradigm of treating the disordered mind. In this article, we retrospectively examine these early origins of psychosurgery and then look to the recent past, present, and future for emerging trends in surgery of the psyche. Recent decades have seen a revolution in minimalism, noninvasive imaging, and functional manipulation of the human cerebrum that have created new opportunities and treatment modalities for disorders of the human mind and mood. Early contemporary efforts were directed at focal lesioning of abnormal pathways, but deep-brain stimulation now aims to reversibly alter and modulate those neurologic activities responsible for not only psychiatric disorders, but also to modulate and even to augment consciousness, memory, and other elements of cerebral function. As new tools become available, the social and medical impact of psychosurgery promises to revolutionize not only neurosurgery, but also humans' capability for positively impacting life and society.

Man, mind, and machine: the past and future of virtual reality simulation in neurologic surgery.

OBJECTIVE: To review virtual reality in neurosurgery, including the history of simulation and virtual reality and some of the current implementations; to examine some of the technical challenges involved; and to propose a potential paradigm for the development of virtual reality in neurosurgery going forward. METHODS: A search was made on PubMed using key words surgical simulation, virtual reality, haptics, collision detection, and volumetric modeling to assess the current status of virtual reality in neurosurgery. Based on previous results, investigators extrapolated the possible integration of existing efforts and potential future directions. RESULTS: Simulation has a rich history in surgical training, and there are numerous currently existing applications and systems that involve virtual reality. All existing applications are limited to specific task-oriented functions and typically sacrifice visual realism for real-time interactivity or vice versa, owing to numerous technical challenges in rendering a virtual space in real time, including graphic and tissue modeling, collision detection, and direction of the haptic interface. CONCLUSIONS: With ongoing technical advancements in computer hardware and graphic and physical rendering, incremental or modular development of a fully immersive, multipurpose virtual reality neurosurgical simulator is feasible. The use of virtual reality in neurosurgery is predicted to change the nature of neurosurgical education, and to play an increased role in surgical rehearsal and the continuing education and credentialing of surgical practitioners.

Genome-wide linkage in Utah autism pedigrees.

Genetic studies of autism over the past decade suggest a complex landscape of multiple genes. In the face of this heterogeneity, studies that include large extended pedigrees may offer valuable insights, as the relatively few susceptibility genes within single large families may be more easily discerned. This genome-wide screen of 70 families includes 20 large extended pedigrees of 6-9 generations, 6 moderate-sized families of 4-5 generations and 44 smaller families of 2-3 generations. The Center for Inherited Disease Research (CIDR) provided genotyping using the Illumina Linkage Panel 12, a 6K single-nucleotide polymorphism (SNP) platform. Results from 192 subjects with an autism spectrum disorder (ASD) and 461 of their relatives revealed genome-wide significance on chromosome 15q, with three possibly distinct peaks: 15q13.1-q14 (heterogeneity LOD (HLOD)=4.09 at 29 459 872 bp); 15q14-q21.1 (HLOD=3.59 at 36 837 208 bp); and 15q21.1-q22.2 (HLOD=5.31 at 55 629 733 bp). Two of these peaks replicate earlier findings. There were additional suggestive results on chromosomes 2p25.3-p24.1 (HLOD=1.87), 7q31.31-q32.3 (HLOD=1.97) and 13q12.11-q12.3 (HLOD=1.93). Affected subjects in families supporting the linkage peaks found in this study did not reveal strong evidence for distinct phenotypic subgroups.

Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note.

Recent preclinical studies have demonstrated that convection-enhanced delivery (CED) can be used to perfuse the brain and brainstem with therapeutic agents while simultaneously tracking their distribution using coinfusion of a surrogate magnetic resonance (MR) imaging tracer. The authors describe a technique for the successful clinical application of this drug delivery and monitoring paradigm to the brainstem. Two patients with progressive intrinsic brainstem lesions (one with Type 2 Gaucher disease and one with a diffuse pontine glioma) were treated with CED of putative therapeutic agents mixed with Gd-diethylenetriamene pentaacetic acid (DTPA). Both patients underwent frameless stereotactic placement of MR imaging-compatible outer guide-inner infusion cannulae. Using intraoperative MR imaging, accurate cannula placement was confirmed and real-time imaging during infusion clearly demonstrated progressive filling of the targeted region with the drug and Gd-DTPA infusate. Neither patient had clinical or imaging evidence of short- or long-term infusate-related toxicity. Using this technique, CED can be used to safely perfuse targeted regions of diseased brainstem with therapeutic agents. Coinfused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of intrinsic brainstem and other central nervous system disorders may benefit from a similar treatment paradigm.