Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study.

It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting.

Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque.

OBJECTIVE: It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. APPROACH: An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. MAIN RESULTS: The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

Functional connectivity targeting for deep brain stimulation in essential tremor.

BACKGROUND AND PURPOSE: Deep brain stimulation of the thalamus has become a valuable treatment for medication-refractory essential tremor, but current targeting provides only a limited ability to account for individual anatomic variability. We examined whether functional connectivity measurements among the motor cortex, superior cerebellum, and thalamus would allow discrimination of precise targets useful for image guidance of neurostimulator placement. MATERIALS AND METHODS: Resting BOLD images (8 minutes) were obtained in 58 healthy adolescent and adult volunteers. Regions of interest were identified from an anatomic atlas and a finger movement task in each subject in the primary motor cortex and motor activation region of the bilateral superior cerebellum. Correlation was measured in the time series of each thalamic voxel with the 4 seeds. An analogous procedure was performed on a single subject imaged for 10 hours to constrain the time needed for single-subject optimization of thalamic targets. RESULTS: Mean connectivity images from 58 subjects showed precisely localized targets within the expected location of the ventral intermediate nucleus of the thalamus, within a single voxel of currently used deep brain stimulation anatomic targets. These targets could be mapped with single-voxel accuracy in a single subject with 3 hours of imaging time, though targets were reproduced in different locations for the individual than for the group averages. CONCLUSIONS: Interindividual variability likely exists in optimal placement for thalamic deep brain stimulation targeting of the cerebellar thalamus for essential tremor. Individualized thalamic targets can be precisely estimated for image guidance with sufficient imaging time.

Multiple factors may influence the performance of a visual prosthesis based on intracortical microstimulation: nonhuman primate behavioural experimentation.

We hypothesize that a visual prosthesis capable of evoking high-resolution visual perceptions can be produced using high-electrode-count arrays of penetrating microelectrodes implanted into the primary visual cortex of a blind human subject. To explore this hypothesis, and as a prelude to human psychophysical experiments, we have conducted a set of experiments in primary visual cortex (V1) of non-human primates using chronically implanted Utah Electrode Arrays (UEAs). The electrical and recording properties of implanted electrodes, the high-resolution visuotopic organization of V1, and the stimulation levels required to evoke behavioural responses were measured. The impedances of stimulated electrodes were found to drop significantly immediately following stimulation sessions, but these post-stimulation impedances returned to pre-stimulation values by the next experimental session. Two months of periodic microstimulation at currents of up to 96 µA did not impair the mapping of receptive fields from local field potentials or multi-unit activity, or impact behavioural visual thresholds of light stimuli that excited regions of V1 that were implanted with UEAs. These results demonstrate that microstimulation at the levels used did not cause functional impairment of the electrode array or the neural tissue. However, microstimulation with current levels ranging from 18 to 76 µA (46 ± 19 µA, mean ± std) was able to elicit behavioural responses on eight out of 82 systematically stimulated electrodes. We suggest that the ability of microstimulation to evoke phosphenes and elicit a subsequent behavioural response may depend on several factors: the location of the electrode tips within the cortical layers of V1, distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts.

A minimally invasive approach to long-term head fixation in behaving nonhuman primates.

We have designed a device for long-term head fixation for use in behaving nonhuman primates that is robust yet minimally invasive and simple to use. This device is a modified version of the halo system that is used in humans for cervical traction and stabilization after spinal column injuries. This device consists of an aluminum halo with four titanium skull pins offset from the halo by aluminum posts. The titanium pins insert onto small segments of cranially reinforcing titanium plate, which are attached to the skull with titanium cortex screws. The surgery involves four scalp incisions, placement of the reinforcing plates, insertion of the pins for attachment of the halo, and incision closure. After the halo is attached, the animal's head can be fixed to a primate chair using a custom-built attachment arm that provides three degrees of adjustability for proper positioning during behavioral tasks. We have installed this device on two Macaque monkeys weighing 7 and 10kg. The halos have been in place on these animals for up to 8 months without signs of discomfort or loss of fixation. Using this method of head fixation, we have been able to track the animals' eye positions with an accuracy of less than two visual degrees while they perform behavioral tasks.

The association between retinal vein ophthalmodynamometric force change and optic disc excavation.

AIM: Retinal vein ophthalmodynamometric force (ODF) is predictive of future optic disc excavation in glaucoma, but it is not known if variation in ODF affects prognosis. We aimed to assess whether a change in ODF provides additional prognostic information. METHODS: 135 eyes of 75 patients with glaucoma or being glaucoma suspects had intraocular pressure (IOP), visual fields, stereo optic disc photography and ODF measured on an initial visit and a subsequent visit at mean 82 (SD 7.3) months later. Corneal thickness and blood pressure were recorded on the latter visit. When venous pulsation was spontaneous, the ODF was recorded as 0 g. Change in ODF was calculated. Flicker stereochronoscopy was used to determine the occurrence of optic disc excavation, which was modelled against the measured variables using multiple mixed effects logistic regression. RESULTS: Change in ODF (p = 0.046) was associated with increased excavation. Average IOP (p = 0.66) and other variables were not associated. Odds ratio for increased optic disc excavation of 1.045 per gram ODF change (95% CI 1.001 to 1.090) was calculated. CONCLUSION: Change in retinal vein ODF may provide additional information to assist with glaucoma prognostication and implies a significant relationship between venous change and glaucoma patho-physiology.

Comment on "Age and evolution of the Grand Canyon revealed by U-Pb dating of water table-type speleothems".

Polyak et al. (Reports, 7 March 2008, p. 1377) reported that development of the western Grand Canyon began about 17 million years ago. However, their conclusion is based on an inappropriate conflation of Plio-Quaternary incision rates and longer-term rates derived from sites outside the Grand Canyon. Water-table declines at these sites were more likely related to local base-level changes and Miocene regional extensional tectonics.

EEG infraslow activity in absence and partial seizures.

It is currently assumed that for recording of infraslow activity (ISA) DC-coupled amplifiers are required. This report will demonstrate that this may not be the case and presents some data about its potential clinical usefulness. Archived EEGs of 29 seizures from 6 children with absence attacks, accompanied by 3 Hz classical spike-wave discharges (SW), were compared with 20 partial seizures from 10 adult patients. The data from the children were acquired on a Bio-logic system, those from the adults on a Grass-Telefactor instrument. In the children the original 30-minute routine EEG was used while in the adults stored videomonitored data were excerpted to provide 20-minute segments which included the preictal, ictal and postictal state. All data were analyzed with the BESA software package. The seizures were evaluated separately on conventional filter settings, full band of 0.01-to the upper limit of the instrument, and 0.01-0.1 Hz (infraslow activity, ISA). Filter settings of 0.01-0.1 Hz provided a better assessment of ISA than when the full band was evaluated. Absence seizures showed bilateral essentially synchronous ISA with a negative positive sequence in the frontal areas and opposite polarity in the posterior head regions. In partial seizures when seizure onset was clearly lateralizeable from conventional frequency settings ISA corresponded to that hemisphere, but the electrode position could be displaced to a neighboring one from the one which was maximally involved on conventional settings. Topographic analysis showed two types of ISA: one with focal spread only and the other where there was in addition an element of synchrony especially in the frontal areas. It is concluded that ISA can be recovered from conventional EEG recordings and may be helpful not only in determining the area(s) of seizure onset but can also differentiate truly focal seizures from those where an additional generalized seizure tendency is present. This is likely to be important when epilepsy surgery is performed in absence of a demonstrable structural lesion.

Prevalence and predictors of osteoporosis treatment in nursing home residents with known osteoporosis or recent fracture.

SUMMARY: We studied nursing home residents with osteoporosis or recent fracture to determine the frequency and predictors of osteoporosis treatment. There was wide variation in performance, and both clinical and systems variables predicted use. This study shows that improvement in osteoporosis care is possible and important for many nursing homes. INTRODUCTION: We determined the prevalence and predictors of osteoporosis evaluation and treatment in high-risk nursing home residents. METHODS: We identified 67 nursing facilities in North Carolina and Arizona with > 10 residents with osteoporosis or recent hip fracture. Medical records (n=895) were abstracted for osteoporosis evaluation [dual-energy X-ray absorptiometry (DXA), vitamin D level, serum calcium), treatment (calcium, vitamin D, osteoporosis medication, hip protectors), clinical, and systems covariates. Data were analyzed at the facility level using mixed models to account for the complex nesting of residents within providers and nursing facilities. RESULTS: Calcium and vitamin D was prescribed for 69% of residents, bisphosphonates for 19%, calcitonin for 14%, other pharmacologic therapies for 6%, and hip protectors for 2%. Overall, 36% received any bone protection (medication or hip protectors), with wide variation among facilities (0-85%). Factors significantly associated with any bone protection included female gender [odds ratio (OR) 2.4, (1.5-3.7)] and nonurban/suburban location [1.5, (1.1-2.2)]. Residents with esophagitis, peptic ulcer disease (PUD), or dysphagia [0.6, (0.4-0.9)] and alcohol abuse [0.2, (0.0-0.9)] were less likely to receive treatment. CONCLUSIONS: There is substantial variation in the quality of osteoporosis treatment across nursing homes. Interventions that improve osteoporosis quality of care are needed.

Potential double-flipping mechanism by E. coli MutY.

To understand the structural basis of the recognition and removal of specific mismatched bases in double-stranded DNAs by the DNA repair glycosylase MutY, a series of structural and functional analyses have been conducted. MutY is a 39-kDa enzyme from Escherichia coli, which to date has been refractory to structural determination in its native, intact conformation. However, following limited proteolytic digestion, it was revealed that the MutY protein is composed of two modules, a 26-kDa domain that retains essential catalytic function (designated p26MutY) and a 13-kDa domain that is implicated in substrate specificity and catalytic efficiency. Several structures of the 26-kDa domain have been solved by X-ray crystallographic methods to a resolution of up to 1.2 A. The structure of a catalytically incompetent mutant of p26MutY complexed with an adenine in the substrate-binding pocket allowed us to propose a catalytic mechanism for MutY. Since reporting the structure of p26MutY, significant progress has been made in solving the solution structure of the noncatalytic C-terminal 13-kDa domain of MutY by NMR spectroscopy. The topology and secondary structure of this domain are very similar to that of MutT, a pyrophosphohydrolase. Molecular modeling techniques employed to integrate the two domains of MutY with DNA suggest that MutY can wrap around the DNA and initiate catalysis by potentially flipping adenine and 8-oxoguanine out of the DNA helix.

Proliferation of lens epithelial cells on the Acrysof intraocular lens: clinical and histological features of a case.

Postoperative deposits on the surface of intraocular lenses (IOLs) have been demonstrated in vivo for many IOL material types. The Acrysof acrylic lens develops a granular material extending from the capsulorhexis margin onto the IOL's anterior surface during the first 4 weeks after surgery in a significant proportion of cases. Complete resolution of this membrane occurs by 3 months in almost all cases. The case is presented of an 81-year-old woman who had a persisting membrane coverng the IOL surface at 6 months. This membrane was removed surgically and pathology showed the constituent cells to be of lens epithelial cell origin.

Endocervical sampling: a comparison of endocervical brush, endocervical curette, and combined brush with curette techniques.

OBJECTIVE: This study was conducted to compare the collection of endocervical specimens by endocervical brush, curette, and a combined curette and brush technique. METHODS: Women underwent colposcopy with endocervical curettage using one of 3 collection methods. RESULTS: The endocervical brush produced equivalent amounts of tissue and endocervical cells compared to the curette alone or combined techniques. More squamous and glandular atypia and SIL/AIS were found when a brush was used, but a statistically significant difference was not noted. The brush alone produced a significantly greater percentage of samples that were insufficient for diagnosis and more specimens without stromal components. The brush with the curette as a combined technique provided no improvement in amounts of tissue, endocervical cells/clusters, or amount of stroma retrieved. CONCLUSION: Each technique has advantages and disadvantages in terms of what types of components are collected and what diagnosis may be determined from the sample taken.

The use of community surveys for health planning: the experience of 56 northwest rural communities.

A rural health services development program of the University of Washington School of Medicine has worked for 15 years with communities throughout the five-state region of Alaska, Idaho, Montana, Washington and Wyoming to strengthen their health systems. In the course of that work, 56 communities were surveyed about their utilization and opinions of local health systems. This database allows the following generalizations to be made about rural Northwest communities: (1) People think highly of their local hospitals, physicians and other key components of the acute medical care system and want their hospitals to remain open. Older respondents are more satisfied than younger respondents; (2) the typical hospital market share is 36 percent, the typical physician market share is 50 percent (3) satisfaction with discrete, well-funded services such as pharmacy, ambulance and dentistry is quite high, whereas satisfaction with mental health and substance abuse treatment is significantly lower; (4) the most commonly cited serious problems in surveyed communities were "too few physicians or- services" and "care is too expensive"; and (5) there is great variation between communities in both satisfaction and utilization.

Methods and limits of digital image compression of retinal images for telemedicine.

PURPOSE: To investigate image compression of digital retinal images and the effect of various levels of compression on the quality of the images. METHODS: JPEG (Joint Photographic Experts Group) and Wavelet image compression techniques were applied in five different levels to 11 eyes with subtle retinal abnormalities and to 4 normal eyes. Image quality was assessed by four different methods: calculation of the root mean square (RMS) error between the original and compressed image, determining the level of arteriole branching, identification of retinal abnormalities by experienced observers, and a subjective assessment of overall image quality. To verify the techniques used and findings, a second set of retinal images was assessed by calculation of RMS error and overall image quality. RESULTS: Plots and tabulations of the data as a function of the final image size showed that when the original image size of 1.5 MB was reduced to 29 KB using JPEG compression, there was no serious degradation in quality. The smallest Wavelet compressed images in this study (15 KB) were generally still of acceptable quality. CONCLUSIONS: For situations where digital image transmission time and costs should be minimized, Wavelet image compression to 15 KB is recommended, although there is a slight cost of computational time. Where computational time should be minimized, and to remain compatible with other imaging systems, the use of JPEG compression to 29 KB is an excellent alternative.

Structural similarities between MutT and the C-terminal domain of MutY.

One of the functions of MutY from Escherchia coli is removal of adenine mispaired with 7,8-dihydro-8-oxoguanine (8-oxoG), a common lesion in oxidatively damaged DNA. MutY is composed of two domains: the larger N-terminal domain (p26) contains the catalytic properties of the enzyme while the C-terminal domain (p13) affects substrate recognition and enzyme turnover. On the basis of sequence analyses, it has been recently suggested that the C-terminal domain is distantly related to MutT, a dNTPase which hydrolyzes 8-oxo-dGTP [Noll et al. (1999) Biochemistry 38, 6374-6379]. We have studied the solution structure of the C-terminal domain of MutY by NMR and find striking similarity with the reported solution structure of MutT. Despite low sequence identity between the two proteins, they have similar secondary structure and topology. The C-terminal domain of MutY is composed of two alpha-helices and five beta-strands. The NOESY data indicate that the protein has two beta-sheets. MutT is also a mixed alpha/beta protein with two helices and two beta-sheets composed of five strands. The secondary structure elements are similarly arranged in the two proteins.

Long-term topical timolol and blood lipids: the Blue Mountains Eye Study.

OBJECTIVES: To examine whether an association exists between long-term use of topical timolol and blood lipids, including high-density lipoprotein cholesterol (HDL-C), cholesterol, and triglycerides, among participants of the Blue Mountains Eye Study. METHODS: From 1992 through 1994, a detailed medical and eye examination was performed in 3,654 people aged 49 years or older, representing 82% of permanent residents in two postcode areas west of Sydney. Glaucoma and ocular hypertension were diagnosed, and an ophthalmic history was taken, including use of topical timolol. Fasting blood tests were performed in 89% of subjects. Lipid levels were compared in subjects using topical timolol for at least 1 year with those not using timolol, after excluding people using oral beta-blockers, topical beta1-selective agents, or oral lipid-lowering medications. RESULTS: Analyses compared blood lipids of 63 people who had used topical timolol for at least 1 year with 2,597 nonusers. No statistically significant differences were found in any blood lipid mean levels between treated and untreated people, after multivariate adjustment. However, subgroup analyses of men and women separately showed that male timolol users had a mean value of HDL-C 0.13 mmol/L (11%) lower then the mean value of male nonusers, while female timolol users had a mean value of HDL-C 0.09 mmol/L (5%) higher than the mean for female nonusers. There were no statistically significant associations between timolol treatment duration and HDL-C or other lipid levels. Previously reported adverse effects of oral beta-blockers on blood lipid levels were confirmed. CONCLUSIONS: These population-based data suggest that long-term administration of topical timolol for glaucoma or ocular hypertension can cause adverse effects on HDL-C in men, but not in women. The magnitude of the effect in men was similar to that previously described in a number of short-term studies.

Comparison of optic disc image assessment methods when examining serial photographs for glaucomatous progression.

AIM: To assess serial, simultaneous stereo optic disc images by four methods for glaucomatous progression. METHODS: Using varying techniques, two ophthalmologists assessed serial optic disc images of 52 eyes from 27 patients with a mean duration between images of 18 months. The neuroretinal rim width was qualitatively assessed by four assessment methods and compared with quantitative rim measurements made using PC based software. RESULTS: The highest sensitivity of 83% was achieved using computerised stereo chronoscopy. CONCLUSION: Stereo chronoscopy improved the detection of subtle optic disc changes when compared with simpler assessment techniques.

Postoperative deposits on the Acrysof intraocular lens.

PURPOSE: To report a commonly occurring change on the anterior surface of the Acrysof intraocular lens which is presumed to be due to the proliferation of lens epithelial cells from the capsulo-rhexis margin. METHOD: Forty-one consecutive cases (31 patients) of Acrysof intraocular lens implantation were followed prospectively. Clinical charts were reviewed for changes on or within the lens and visual acuity and refractive changes recorded. All cases were dilated at 3-5 weeks postoperatively to facilitate observation of changes. Representative slit lamp photos were taken. RESULTS: Deposits on the intraocular lens surface were noted on 18 of 41 lenses at 3-5 weeks post surgery. Deposits were not found on examinations conducted during the first postoperative week. All changes had fully resolved by 3 months. CONCLUSIONS: The changes recorded had no impact on visual acuity. The deposits noted do not represent clinically important pathology. They may be an unusual marker of biocompatibility with this lens. Surgeons using this lens should be aware of these changes.

Developing laser-induced glaucoma in rabbits.

PURPOSE: An animal mode of glaucoma is necessary for the study of its pathogenesis and treatment. The purpose of this study was to create open-angle glaucoma using a laser in rabbits. METHODS: The trabecular meshwork of anaesthetized, adult, pigmented and albino rabbits was ablated internally using a diode laser via a gonioscopy lens, or externally through the limbus. In albino rabbits we used Chinese ink to pigment the angle and methylcellulose to open the iridocorneal angle. The eyes were examined weekly and histological assessment was performed. RESULTS: The success rate of intra-ocular hypertension was low (15%) and a result of synechial angle closure. A narrow angle prevented access of the laser beam to the trabecular meshwork and promoted damage to the ciliary processes located on the posterior iris. CONCLUSIONS: Due to the unique anatomy of the rabbit eye, laser-induced glaucoma is difficult to achieve. To create a successful model it is necessary to widen the iridocorneal angle, selectively damage the trabecular meshwork and reduce inflammation.