Implementation of an Enhanced Recovery After Surgery Protocol for Cranial Vault Remodeling Procedures.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been implemented across surgical disciplines, including cranial vault remodeling for craniosynostosis. The authors aim to describe the implementation of an ERAS protocol for cranial vault remodeling procedures performed for patients with craniosynostosis at a tertiary care hospital. DESCRIPTION: Institutional review board approval was received. All patients undergoing a cranial remodeling procedure for craniosynostosis at the authors' institution over a 10-year period were collected (n = 168). Patient and craniosynostosis demographics were collected as well as operative details. Primary outcome measures were intensive care unit length of stay (ICU LOS) and narcotic usage. Chi squared and independent t-tests were employed to determine significance. A significance value of 0.05 was utilized. RESULTS: During the time examined, there were 168 primary cranial vault remodeling procedures performed at the authors' institution - all of which were included in the analysis. Use of the ERAS protocol was associated with decreased initial 24-hour morphine equivalent usage (p < 0.01) and decreased total morphine equivalent usage (p < 0.01). Patients using the ERAS protocol experienced a shorter ICU LOS (p < 0.01), but the total hospital length of stay was unchanged. CONCLUSION: This study reiterates the benefit of developing and implementing an ERAS protocol for patients undergoing cranial vault remodeling procedures. The protocol resulted in an overall decreased ICU LOS and a decrease in narcotic use. This has implications for ways to maximize hospital reimbursement for these procedures, as well as potentially improve outcomes.

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant.

Ovine herpesvirus 2 (OvHV-2) and bovine herpesvirus 4 (BoHV-4) are gamma herpesviruses that belong to the genera Macavirus and Rhadinovirus, respectively. As with all herpesviruses, both OvHV-2 and BoHV-4 express glycoprotein B (gB), which plays an essential role in the infection of host cells. In that context, it has been demonstrated that a BoHV-4 gB-null mutant is unable to infect host cells. In this study, we used homologous recombination to insert OvHV-2 ORF 8, encoding gB, into the BoHV-4 gB-null mutant genome, creating a chimeric BoHV-4 virus carrying and expressing OvHV-2 gB (BoHV-4∆gB/OvHV-2-gB) that was infectious and able to replicate in vitro. We then evaluated BoHV-4∆gB/OvHV-2-gB as a potential vaccine candidate for sheep-associated malignant catarrhal fever (SA-MCF), a fatal disease of ungulates caused by OvHV-2. Using rabbits as a laboratory model for MCF, we assessed the safety, immunogenicity, and efficacy of BoHV-4∆gB/OvHV-2-gB in an immunization/challenge trial. The results showed that while BoHV-4∆gB/OvHV-2-gB was safe and induced OvHV-2 gB-specific humoral immune responses, immunization conferred only 28.5% protection upon challenge with OvHV-2. Therefore, future studies should focus on alternative strategies to express OvHV-2 proteins to develop an effective vaccine against SA-MCF.

Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Background: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care. Methods: We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to 581 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features. Results: We discovered that the serum white blood cell (WBC) count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of WBC count. By utilizing an objective PD-L1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PD-L1 expression in glioblastoma patients with high serum WBC counts. Conclusions: These findings suggest that in a subset of glioblastoma patients the incorporation of WBC count and PD-L1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, machine learning models allow the distillation of complex clinical data sets to uncover novel and meaningful clinical relationships.

Understanding baseline levels of physiological stress tolerance from excessive exercise in a holobenthic octopus species, Octopus pallidus.

Cephalopods receive a great deal of attention due to their socioeconomically important fisheries and aquaculture industries as well their unique biological features. However, basic information about their physiological responses under stress conditions is lacking. This study investigated the impact of a simple stressor, exercise to exhaustion, on the activity levels of antioxidant enzymes and the concentrations of molecules involved in oxidative stress response in the pale octopus (Octopus pallidus). Eight biochemical assays were measured in the humoral (plasma) and cellular (hemocyte) components of O. pallidus haemolymph, the invertebrate analogue to vertebrate blood. Overall, exercise resulted in an increase in activity of plasma catalase (CAT) and glutathione-S-transferase (GST) and the decrease in activity of plasms glutathione reductase (GR). In the hemocytes, the exercise elicited a different response, with a reduction in the activity of superoxide dismutase (SOD), GR, and glutathione peroxidase (GPX) and a reduction in nitric oxide (NO) concentration. Malondialdehyde (MDA) activity was similar in the plasma and haemocytes in control and exercised treatments, indicating that exercise did not induce lipid peroxidation. These results provide an important baseline for understanding oxidative stress in octopus, with exercise to exhaustion serving as a simple stressor which will ultimately inform our ability to detect and understand physiological responses to more complex stressors.

Case report: Side-firing intraoperative ultrasound guided endoscopic endonasal resection of a clival chordoma.

Clival chordomas are locally invasive midline skull base tumors arising from remnants of the primitive notochord. Intracranial vasculature and cranial nerve involvement of tumors in the paraclival region necessitates image guidance that provides accurate real-time feedback during resection. Several intraoperative image guidance modalities have been introduced as adjuncts to endoscopic endonasal surgery, including stereotactic neuronavigation, intraoperative ultrasound, intraoperative MRI, and intraoperative CT. Gross total resection of chordomas is associated with a lower recurrence rate; therefore, intraoperative imaging may improve long-term outcomes by enhancing the extent of resection. However, among these options, effectiveness and accessibility vary between institutions. We previously published the first use of an end-firing probe in the resection of a clival chordoma. End-firing probes provide a single field of view, primarily limited to depth estimation. In this case report, we discuss the benefits of employing a novel minimally invasive side-firing ultrasound probe as a cost-effective and time-efficient option to navigate the anatomy of the paraclival region and guide endoscopic endonasal resection of a large complex clival chordoma.

The utility of procalcitonin for diagnosing bacteremia and bacterial pneumonia in hospitalized oncology patients.

PURPOSE: Procalcitonin (PCT) is an inflammatory marker elevated in bacteremia and bacterial pneumonia. We aimed to assess the real-world diagnostic accuracy of PCT in hospitalized patients with malignancy. METHODS: A retrospective cohort of 715 patients with cancer who had PCT measured during 750 admissions was analyzed. Diagnosis of bacteremia was determined using blood culture data. Diagnosis of bacterial pneumonia was based on radiographic infiltrate and/or sputum culture. PCT's performance was assessed using receiver operating characteristic (ROC) curves, sensitivity, and specificity. RESULTS: Patients had bacteremia, bacterial pneumonia, or both during 210 admissions (28%). PCT elevation above 0.5 ng/mL was significantly associated with diagnosed infection in the overall population (p < 0.0001) and in subgroups with solid tumor malignancies (p < 0.0001) and hematologic malignancies (p = 0.008). PCT was associated with infectious status in patients with any metastases, but not those with primary lung cancer, lung metastases, neuroendocrine tumors, febrile neutropenia, or history of bone marrow transplant (BMT). The area under the ROC curve for PCT in the overall population was 0.655. An ideal cutoff of 0.21 ng/mL led to a sensitivity of 60% and specificity of 59%. At cutoffs of 0.5 ng/mL and 0.05 ng/mL, PCT's sensitivity was 39% and 94%, while specificity was 79% and 17%, respectively. CONCLUSION: In this large cohort of hospitalized oncology patients, PCT elevation was associated with diagnosed bacteremia and/or bacterial pneumonia. However, specificity was limited, and PCT elevation was not associated with diagnosed infection in some subpopulations. While PCT may have some diagnostic utility for hospitalized oncology patients, values must be interpreted cautiously and considering clinical context.

Side-firing intraoperative ultrasound applied to resection of pituitary macroadenomas and giant adenomas: A single-center retrospective case-control study.

Introduction: Multiple intraoperative navigation and imaging modalities are currently available as an adjunct to endoscopic transsphenoidal resection of pituitary adenomas, including intraoperative CT and MRI, fluorescence guidance, and neuronavigation. However, these imaging techniques have several limitations, including intraoperative tissue shift, lack of availability in some centers, and the increased cost and time associated with their use. The side-firing intraoperative ultrasound (IOUS) probe is a relatively new technology in endoscopic endonasal surgery that may help overcome these obstacles. Methods: A retrospective analysis was performed on patients admitted for resection of pituitary adenomas by a single surgeon at the University of Mississippi Medical Center. The control (non-ultrasound) group consisted of twelve (n=12) patients who received surgery without IOUS guidance, and the IOUS group was composed of fifteen (n=15) patients who underwent IOUS-guided surgery. Outcome measures used to assess the side-firing IOUS were the extent of tumor resection, postoperative complications, length of hospital stay (LOS) in days, operative time, and self-reported surgeon confidence in estimating the extent of resection intraoperatively. Results: Preoperative data analysis showed no significant differences in patient demographics or presenting symptoms between the two groups. Postoperative data revealed no significant difference in the rate of gross total resection between the groups (p = 0.716). Compared to the non-US group, surgeon confidence was significantly higher (p < 0.001), and operative time was significantly lower for the US group in univariate analysis (p = 0.011). Multivariate analysis accounting for tumor size, surgeon confidence, and operative time confirmed these findings. Interestingly, we noted a trend for a lower incidence of postoperative diabetes insipidus in the US group, although this did not quite reach our threshold for statistical significance. Conclusion: Incorporating IOUS as an aid for endonasal resection of pituitary adenomas provides real-time image guidance that increases surgeon confidence in intraoperative assessment of the extent of resection and decreases operative time without posing additional risk to the patient. Additionally, we identified a trend for reduced diabetes insipidus with IOUS.

A Vaccine Targeting Ovine Herpesvirus 2 Glycoprotein B Protects against Sheep-Associated Malignant Catarrhal Fever.

Malignant catarrhal fever (MCF) is a complex and often fatal disease of ungulates. Effective vaccines are needed to avoid MCF outbreaks and mitigate losses. This study aimed to evaluate a sheep-associated MCF (SA-MCF) vaccine candidate targeting ovine herpesvirus 2 (OvHV-2) glycoprotein B (gB). Rabbits were used as a laboratory animal model to test the safety, immunogenicity, and protective efficacy of a chimeric virus consisting of a recombinant, non-pathogenic strain of alcelaphine herpesvirus-1 encoding OvHV-2 ORF8 to express gB (AlHV-1∆ORF73/OvHV-2-ORF8). Viral-vectored immunizations were performed by using the AlHV-1∆ORF73/OvHV-2-ORF8 chimera alone or as a DNA prime (OvHV-2-ORF8)-virus boost regimen. The viral vector was inoculated by intravenous or intramuscular routes and the DNA was delivered by intradermal shots using a gene gun. The vaccine candidates were deemed safe as no clinical signs were observed following any of the immunizations. Anti-OvHV-2 gB antibodies with neutralizing activity were induced by all immunogens. At three weeks post-final immunization, all animals were challenged intranasally with a lethal dose of OvHV-2. MCF protection rates ranging from 66.7% to 71.4% were observed in vaccinated rabbits, while all mock-vaccinated animals developed the disease. The significant protective efficacy obtained with the vaccine platforms tested in this study encourages further trials in relevant livestock species, such as cattle and bison.

Risk Factors for Failure of Final Anatomic Surgical Reattachment in Retinal Detachments From Combat Ocular Trauma.

BACKGROUND AND OBJECTIVE: The goal of this study was to determine the anatomic outcome of traumatic retinal detachment (RD) from combat ocular trauma. MATERIALS AND METHODS: Retrospective study of patients sustaining a traumatic RD in Operation Iraqi Freedom and Operation Enduring Freedom who were evacuated to Walter Reed Army Medical Center from 2001 to 2011. The Fisher exact test, Wilcoxon rank sum test, and Agresti and Coull methods were used for analyses. RESULTS: There were 143 eyes of 134 patients in which a traumatic RD developed, of a total of 890 eyes of 652 patients in the Walter Reed Ocular Trauma Database. Based on our results, predictors for failure to reattach the retina include maculaoff status (P = .0002), open-globe injury (P = .03), proliferative vitreoretinopathy postoperatively (P = .002), and presence of hyphema (P = .02). Intraocular foreign body and time to initial retinal surgery did not increase risk for failure. Thirty-four percent (34%) of eyes failed to be reattached. CONCLUSIONS: Traumatic RD due to injury sustained in a combat zone resulted in poor prognosis, with 82.09% of eyes with RD having a best-corrected visual acuity worse than 20/200. The anatomic success of RD repair was shown to be 65.71%, likely owing to the severity of the injuries, concomitant systemic injuries, and delayed surgical intervention. [Ophthalmic Surg Lasers Imaging Retina 2022;53:493-501.].

Sequence-dependent mechanochemical coupling of helicase translocation and unwinding at single-nucleotide resolution.

We used single-molecule picometer-resolution nanopore tweezers (SPRNT) to resolve the millisecond single-nucleotide steps of superfamily 1 helicase PcrA as it translocates on, or unwinds, several kilobase-long DNA molecules. We recorded more than two million enzyme steps under various assisting and opposing forces in diverse adenosine tri- and diphosphate conditions to comprehensively explore the mechanochemistry of PcrA motion. Forces applied in SPRNT mimic forces and physical barriers PcrA experiences in vivo, such as when the helicase encounters bound proteins or duplex DNA. We show how PcrA's kinetics change with such stimuli. SPRNT allows for direct association of the underlying DNA sequence with observed enzyme kinetics. Our data reveal that the underlying DNA sequence passing through the helicase strongly influences the kinetics during translocation and unwinding. Surprisingly, unwinding kinetics are not solely dominated by the base pairs being unwound. Instead, the sequence of the single-stranded DNA on which the PcrA walks determines much of the kinetics of unwinding.

Physical activity advice in the UK bowel cancer screening setting: qualitative healthcare professional perspectives.

Providing physical activity advice in the bowel cancer screening setting could help to reduce the risk of cancer and cardiometabolic disease in older adults. This study investigated the views of healthcare professionals (HCPs) regarding the provision of physical activity advice as part of the UK Bowel Cancer Screening Programme. A purposive sample of HCPs (aged 22-63 years, with 1-26 years of experience) from four bowel cancer screening disciplines (four endoscopists, four colorectal surgeons, four staff nurses and four specialist screening practitioners) were recruited from a large National Health Service gastroenterology unit. Data collection used individual interviews and focus groups, with topics being guided by an a priori topic guide. All interviews and focus groups were audio-recorded and transcribed verbatim. Three key themes, which contextualize the views and perceptions of HCPs recruited to the study, emerged from the framework analysis: (i) appraisal of the concept; (ii) perceived barriers to implementation; (iii) steps to implementation. While the general concept was viewed positively, there were differences of opinion and a range of perceived barriers were revealed. Ideas for effective implementation were also presented, taking into consideration the need for time efficiencies and importance of optimizing effectiveness. This qualitative study provided important insights into the perceptions of HCPs regarding the provision of physical activity advice in the bowel cancer screening setting, and yielded novel ideas for effective implementation.

OvHV-2 Glycoprotein B Delivered by a Recombinant BoHV-4 Is Immunogenic and Induces Partial Protection against Sheep-Associated Malignant Catarrhal Fever in a Rabbit Model.

An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally modified to generate an attenuated vaccine strain. Alternative approaches for vaccine development are needed to deliver OvHV-2 antigens. Bovine herpesvirus 4 (BoHV-4) has been evaluated as a vaccine vector for several viral antigens with promising results. In this study, we genetically engineered BoHV-4 to express OvHV-2 glycoprotein B (gB) and evaluated its efficacy as an SA-MCF vaccine using a rabbit model. The construction of a viable recombinant virus (BoHV-4-AΔTK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. The immunization of rabbits with BoHV-4-AΔTK-OvHV-2-gB elicited strong humoral responses to OvHV-2 gB, including neutralizing antibodies. Following intra-nasal challenge with a lethal dose of OvHV-2, 42.9% of the OvHV-2 gB vaccinated rabbits were protected against SA-MCF, while all rabbits in the mock-vaccinated group succumbed to SA-MCF. Overall, OvHV-2 gB delivered by the recombinant BoHV-4 was immunogenic and partly protective against SA-MCF in rabbits. These are promising results towards an SA-MCF vaccine; however, improvements are needed to increase protection rates.

Proliferative Vitreoretinopathy After Combat Ocular Trauma in Operation Iraqi Freedom and Operation Enduring Freedom: 2001-2011.

BACKGROUND AND OBJECTIVE: To determine the risk factors associated with developing proliferative vitreoretinopathy (PVR) from combat ocular injuries in U.S. service members. PATIENTS AND METHODS: Retrospective review of associated risk factors and outcomes of PVR within the Walter Reed Ocular Trauma Database. Ocular injuries in U.S. service members wounded during Operation Enduring Freedom and Operation Iraqi Freedom from 2001 to 2011 were assessed, and of these all cases of PVR were studied. Principal outcome measures were the risk factors associated with PVR development and rate of final visual acuity (VA) less than 20/200. RESULTS: Eight hundred ninety eyes of 651 U.S. service members were evaluated. A total of 76 eyes (8.5%) of 66 patients developed PVR. Five patients had bilateral PVR. Nineteen patients had bilateral eye injuries. Sixty-one eyes (80.2%) had a final VA less than 20/200. PVR was found to be a significant risk factor for a poor final VA (P < .001). Retinal detachment (RD) was found in 52 eyes (68.4%) of patients. In patients with a RD, intraocular foreign bodies (IOFBs) (P < .001), unsuccessful repair (P = .002), and macular hemorrhage (P = .04) were significant risk factors for the development of PVR. Time to initial retina surgery was not found to be a risk factor for PVR development (P = .5). Time to initial retina surgery was available in 41 patients and the time to surgery on average was 22.56 days (range: 3 to 87 days). CONCLUSIONS: PVR occurs frequently in combat trauma and is a significant cause of poor final VA. In patients with PVR and RD, injuries caused by an IOFB, macular hemorrhage, or unsuccessful repair were significant risk factors for the development of PVR. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:556-563.].

Randomised clinical trial: combined impact and resistance training in adults with stable Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a predisposing factor for bone loss and muscle dysfunction, which could lead to osteoporotic fractures and physical disability, respectively. AIM: To assess the effect of 6 months of combined impact and resistance training on bone mineral density (BMD) and muscle function in adults with CD. METHODS: In this randomised controlled trial, 47 adults with stable CD were assigned to exercise (n = 23) or control (n = 24) groups and followed up for 6 months. The exercise group received usual care plus a 6-month combined impact and resistance training programme, involving three, 60-minute sessions per week and a gradual tapering of supervision to self-management. The control group received usual care alone. The primary outcomes were BMD (via dual energy X-ray absorptiometry) and muscle function (measures of upper and lower limb strength and endurance) at 6 months. RESULTS: At 6 months, BMD values were superior in the exercise group with statistical significance at lumbar spine (adjusted mean difference 0.036 g/cm2, 95% CI 0.024-0.048; P < 0.001), but not at femoral neck (0.018 g/cm2, 0.001-0.035; P = 0.059) or greater trochanter (0.013 g/cm2, -0.019 to 0.045; P = 0.415) after correcting for multiple outcomes. The exercise group also had superior values for all muscle function outcomes (P < 0.001; unadjusted mean differences ranging 22.6‒48.2%), and lower fatigue severity (P = 0.005). Three exercise-related adverse events were recorded: two instances of light-headedness and one of nausea. CONCLUSIONS: The intervention improved BMD and muscle function in adults with CD and appears as a suitable model of exercise for reducing future risk of osteoporotic fractures and disability. TRIAL REGISTRATION: ISRCTN11470370.

Determining the effects of DNA sequence on Hel308 helicase translocation along single-stranded DNA using nanopore tweezers.

Motor enzymes that process nucleic-acid substrates play vital roles in all aspects of genome replication, expression, and repair. The DNA and RNA nucleobases are known to affect the kinetics of these systems in biologically meaningful ways. Recently, it was shown that DNA bases control the translocation speed of helicases on single-stranded DNA, however the cause of these effects remains unclear. We use single-molecule picometer-resolution nanopore tweezers (SPRNT) to measure the kinetics of translocation along single-stranded DNA by the helicase Hel308 from Thermococcus gammatolerans. SPRNT can measure enzyme steps with subangstrom resolution on millisecond timescales while simultaneously measuring the absolute position of the enzyme along the DNA substrate. Previous experiments with SPRNT revealed the presence of two distinct substates within the Hel308 ATP hydrolysis cycle, one [ATP]-dependent and the other [ATP]-independent. Here, we analyze in-depth the apparent sequence dependent behavior of the [ATP]-independent step. We find that DNA bases at two sites within Hel308 control sequence-specific kinetics of the [ATP]-independent step. We suggest mechanisms for the observed sequence-specific translocation kinetics. Similar SPRNT measurements and methods can be applied to other nucleic-acid-processing motor enzymes.

Maternal bleeding complications following early versus delayed umbilical cord clamping in multiple pregnancies.

BACKGROUND: In 2015, the American Academy of Pediatrics recommended delayed umbilical cord clamping for at least 30-60 s for all infants. However, there is limited data regarding the maternal safety of delayed cord clamping in multiple pregnancies. We aimed to compare the maternal bleeding complications following early cord clamping (ECC) versus of delayed cord clamping (DCC) in multiple pregnancies. METHODS: A retrospective cohort study of pregnant women with multiples who delivered live-born infants at Sharp Healthcare Hospitals in San Diego, CA, USA during January 1st, 2016 - September 30th, 2017. Bleeding complications of 295 women who underwent ECC (less than 30 s) were compared with 154 women who underwent DCC (more than 30 s). ECC or DCC was performed according to individual obstetrician discretion. RESULTS: Four hundred forty-nine women with multiple pregnancies (N = 910 infants) were included in the study. 252 (85.4%) women underwent cesarean section in ECC group vs. 99 (64.3%) in DCC group. 58 (19.7%) women delivered monochorionic twins in ECC group vs. 32 (20.8%) women in DCC group. There was no increase in maternal estimate blood loss when DCC was performed comparing to ECC. There were no differences in operative time, post-delivery decrease in hematocrits, rates of postpartum hemorrhage, bleeding complications, maternal blood transfusions and therapeutic hysterectomy between the two groups. CONCLUSIONS: No differences in maternal bleeding complications were found with DCC in multiple pregnancies compared to ECC. Delayed cord clamping can be done safely in multiple pregnancies without any increased maternal risk.

Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease.

Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity.

Discovery of a gene conferring multiple-aminoglycoside resistance in Escherichia coli.

Bovine-origin Escherichia coli isolates were tested for resistance phenotypes using a disk diffusion assay and for resistance genotypes using a DNA microarray. An isolate with gentamicin and amikacin resistance but with no corresponding genes detected yielded a 1,056-bp DNA sequence with the closest homologues for its inferred protein sequence among a family of 16S rRNA methyltransferase enzymes. These enzymes confer high-level aminoglycoside resistance and have only recently been described in Gram-negative bacteria.