Fluoroscopy-guided reduction and fibular nail fixation to manage unstable ankle fractures in patients with diabetes: a retrospective cohort study.

AIMS: Patients with diabetes are at increased risk of wound complications after open reduction and internal fixation of unstable ankle fractures. A fibular nail avoids large surgical incisions and allows anatomical reduction of the mortise. PATIENTS AND METHODS: We retrospectively reviewed the results of fluoroscopy-guided reduction and percutaneous fibular nail fixation for unstable Weber type B or C fractures in 24 adult patients with type 1 or type 2 diabetes. The re-operation rate for wound dehiscence or other indications such as amputation, mortality and functional outcomes was determined. RESULTS: Two patients developed lateral side wound infection, one of whom underwent wound debridement. Three other patients required re-operation for removal of symptomatic hardware. No patient required a below-knee amputation. Six patients died during the study period for unrelated reasons. At a median follow-up of 12 months (7 to 38) the mean Short Form-36 Mental Component Score and Physical Component Score were 53.2 (95% confidence intervals (CI) 48.1 to 58.4) and 39.3 (95% CI 32.1 to 46.4), respectively. The mean Visual Analogue Score for pain was 3.1 (95% 1.4 to 4.9). The mean Ankle Osteoarthritis Scale total score was 32.9 (95% CI 16.0 to 49.7). CONCLUSION: Fluoroscopy-guided reduction and fibular nail fixation of unstable ankle fractures in patients with diabetes was associated with a low incidence of wound and overall complications, while providing effective surgical fixation. Cite this article: Bone Joint J 2016;98-B:1197-1201.

Age-related changes in Egr1 transcription and DNA methylation within the hippocampus.

Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here, we show an age-related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging-related changes is an age-associated, CpG site-specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc.

A multicentre, prospective, randomised comparison of the sliding hip screw with the Medoff sliding screw and side plate for unstable intertrochanteric hip fractures.

OBJECTIVE: This study aimed to compare the dynamic hip screw (DHS) and Medoff sliding plate (MSP) for unstable intertrochanteric hip fractures. DESIGN: A randomised, prospective trial design was used. SETTING: The study was undertaken in two level-1 trauma centres and one community hospital. PATIENTS/PARTICIPANTS: A total of 163 patients with unstable intertrochanteric hip fractures (Orthopaedic Trauma Association (OTA) 31-A2) were randomised to DHS or MSP. Inclusion and exclusion criteria were designed to focus on isolated unstable intertrochanteric hip fractures in ambulatory patients. INTERVENTION: Randomisation was performed intra-operatively, after placement of a 135° guide wire. Follow-up assessments were performed at regular intervals for a minimum of 6 months. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was re-operation rate. The secondary outcome was patient function, evaluated using a validated outcome measure, the Hip Fracture Functional Recovery Score. Tertiary outcomes included: mortality, hospital stay, quality of reduction and malunion rate. RESULTS: A total of 86 patients were randomised to DHS and 77 to MSP. The groups had similar patient demographics, pre-fracture status and in-hospital course. The quality of reduction was the same for each group, but the operative time was longer in the MSP group (61.6 vs. 50.1min, P=0.01). The rate of re-operation was low (3/86 in DHS and 2/77 in MSP) with no statistically significant difference. The functional outcomes were the same for both groups, with functional recovery scores at 6 months of 51.0% in the DHS arm and 49.7% in the MSP arm. CONCLUSIONS: The two techniques produced similar results for the clinically important outcomes of the need for further surgery and functional status of the patients at 6 months' follow-up.

Fear conditioning is associated with synaptogenesis in the lateral amygdala.

Fear conditioning in the rat typically involves pairing a conditioned stimulus (tone) with an aversive unconditioned stimulus (foot shock) which elicits a freeze response. Although the circuitry that underlies this form of learning is well defined, potential synaptic changes associated with this form of learning have not been fully investigated. This experiment examined synaptic structural plasticity in the lateral amygdala which is critical for the acquisition of the conditioned fear response. Adult male rats were randomly allocated to either a paired, unpaired or tone only condition. One day after the initial fear conditioning session and 1 h after a probe trial confirmation of a conditioned fear response, the rats were perfused and the relevant tissue was embedded for electron microscopic analysis. Synaptic changes were quantified in the lateral amygdala using a stereological approach. The results showed a significant increase in the number of synapses in the conditioned animals compared to controls. This finding suggests that an increase in synaptic compliment in the amygdala may underlie the acquisition of the conditioned fear response.

Age-related changes in Arc transcription and DNA methylation within the hippocampus.

The transcription of genes that support memory processes are likely to be impacted by the normal aging process. Because Arc is necessary for memory consolidation and enduring synaptic plasticity, we examined Arc transcription within the aged hippocampus. Here, we report that Arc transcription is reduced within the aged hippocampus compared to the adult hippocampus during both "off line" periods of rest, and following spatial behavior. This reduction is observed within ensembles of CA1 "place cells", which make less mRNA per cell, and in the dentate gyrus (DG) where fewer granule cells are activated by behavior. In addition, we present data suggesting that aberrant changes in methylation of the Arc gene may be responsible for age-related decreases in Arc transcription within CA1 and the DG. Given that Arc is necessary for normal memory function, these subregion-specific epigenetic and transcriptional changes may result in less efficient memory storage and retrieval during aging.

Multidisciplinary forensic approach--investigation of a neonaticide and alleged concomitant rape.

In the case presented, a young woman claimed to have spontaneously aborted a 30-weeks old fetus conceived after being raped by her cousin. The police investigation was centred on a probable neonaticide, mitigated by a possible rape. In Israel, the crime of rape carries a heavy punishment similar to that of first degree murder. Thus the implementation of the most recent scientific forensic techniques is of paramount importance in charging or clearing a suspected rapist. The skeletonized fetal remains were found four months after the reputed abortion. The alleged neonaticide was supported by the results of the forensic clinical and anthropological examinations, while the rape accusation was dismissed by the results of the molecular biology identification of the skeletonized fetal remains. The aim of this report is to encourage the forensic community to apply a multi-disciplinary approach, thus maximizing the decision making competence of the courts of law.

Complexity of sensory environment drives the expression of candidate-plasticity gene, nerve growth factor induced-A.

Exposure of animals to an enriched environment triggers widespread modifications in brain circuitry and function. While this paradigm leads to marked plasticity in animals chronically or acutely exposed to the enriched environment, the molecular mechanisms that enable or regulate such modifications require further characterization. To this end, we have investigated the expression profiles of both mRNA and protein products of a candidate-plasticity gene, nerve growth factor induced-A (NGFI-A), in the brains of rats exposed to increased environmental complexity. We found that NGFI-A mRNA is markedly up-regulated throughout the brains of animals exposed to the enriched environment, but not in the brains of either handled-only or undisturbed control groups. The most pronounced effects were observed in the somatosensory and visual cortices, in layers III and V, while more modest increases were observed in all other cortical layers, with the exception of layer I. A striking NGFI-A mRNA up-regulation was also observed in the striatum and hippocampal formation, notably in the CA1 subfield, of animals exposed to the enriched environment paradigm. Immunocytochemistry was also used to investigate the distribution of NGFI-A protein in response to the environmental enrichment protocol. A marked increase in the number of NGFI-A positive nuclei was identified in the enriched environment condition, as compared to undisturbed and handled-only controls, throughout the rat brain. While the greatest number of NGFI-A immunolabeled neurons was found in cortical layers III and V, up-regulation of NGFI-A protein was also detectable in layers II, IV and VI, in both the somatosensory and visual cortices. NGFI-A immunopositive neurons were also more numerous in the CA1 subfield of the hippocampal formation of animals exposed to the enriched environment, but remained at basal levels in both control groups. Our results implicate NGFI-A as one of the possible early genetic signals that ultimately lead to plastic changes in the CNS.

Effects of chronic and acute methylphenidate hydrochloride (Ritalin) administration on locomotor activity, ultrasonic vocalizations, and neuromotor development in 3- to 11-day-old CD-1 mouse pups.

The present study examined the effects of chronic and acute treatment with methylphenidate hydrochloride (Ritalin) on isolation-induced ultrasonic vocalizations, spontaneous locomotor activity, and neuromotor coordination in 3- to 11-day-old CD-1 mouse pups. In Experiment 1, 3- to 11-day-old pups received daily injections of saline, 5 mg/kg or 20 mg/kg of methylphenidate hydrochloride, or no injection and were tested on postnatal Days 3, 5, 7, 9, and 11. Both doses of methylphenidate resulted in significant increases in locomotor activity at all ages, but had no significant effect on body weight, neuromotor development, or emission of ultrasonic vocalizations. In Experiment 2, pups were given a single dose of methylphenidate (5 or 20 mg/kg), saline, or no injection on one of postnatal Days 5, 7, 9, or 11. This acute methylphenidate treatment increased locomotor activity, but had no significant effects on ultrasonic vocalizations or neuromotor coordination. These results indicate that short-term, chronic methylphenidate treatment elevates locomotor responses, but has no immediate effects on anxietylike responses or on the development of neuromotor behavior of CD-1 mice in the first 11 days of life.

Upregulation of the immediate early gene arc in the brains of rats exposed to environmental enrichment: implications for molecular plasticity.

Exposure to an enriched environment, a procedure that induces plasticity in the cerebral cortex, is associated with pronounced morphological changes, including higher density of dendritic spines, enlargement of synaptic boutons, and other putative correlates of altered neurotransmission. Recently, it has been demonstrated that animals reared in an enriched environment setting for 3 weeks have less neuronal damage as a result of seizures and have decreased rates of spontaneous apoptosis. Even though clear morphological modifications are observed in the cerebral cortex of animals exposed to heightened environmental complexity, the molecular mechanisms that underlie such modifications are yet to be described. In the present work, we investigated the expression of the immediate early gene arc in the cortex of animals exposed to an enriched environment. Animals were exposed daily, for 1 h, to an enriched environment, for a total period of 3 weeks. Brains were processed for in-situ hybridization against arc mRNA. We found a marked upregulation of arc mRNA in the cerebral cortex of animals exposed to the enriched environment, when compared to undisturbed controls, an effect that was most pronounced in cortical layers III and V. Animals in an additional control group that were handled for 5 min daily, displayed intermediate levels of arc mRNA. Furthermore, arc expression was upregulated in the CA1, CA2 and CA3 hippocampal subfields and in the striatum, but to a lesser extent in the dentate gyrus of animals exposed to an enriched environment, as compared to the two control groups. Our results support the association between the upregulation of the immediate early gene arc and plasticity-associated anatomical changes in the cerebral cortex of the adult mammal.

Rapid kindling of the hippocampus protects against neural damage resulting from status epilepticus.

It has previously been reported that rats kindled via the standard kindling procedure do not exhibit the typical profile of neuropathology following status epilepticus. We wished to determine whether a 1-day rapid kindling procedure is also neuroprotective against cell damage resulting from prolonged seizure activity. We found that rats rapidly kindled from the dorsal hippocampus were more resistant to a kainic acid challenge 21-25 days after kindling than were unkindled control rats. Kindling prior to a kainic acid challenge also provided substantial protection against status epilepticus-induced damage in the CA3 region of the hippocampus and piriform cortex in most animals. Thus, despite the short kindling time period, rapid kindling is neuroprotective against status epilepticus-induced cell damage.

Reimbursement for complimentary/alternative medicine by California HMOs.

Beginning in the 1990s, researchers indicate a growing acceptance of complementary/alternative medicine in America. In this 1999 study, we surveyed California HMOs to determine the extent they reimburse for the following complementary/alternative therapies: nutrition counseling, chiropractic, acupuncture, massage and herbal medicine, as well as whether they require these providers to be licensed or otherwise credentialed. As hypothesized, California HMOs are more likely to reimburse for each of these therapies vs. an aggregate of 13 western U.S. states of which California is one. California's huge and competitive HMO market may be a factor.

Light-induced zif268 expression is dependent on noradrenergic input in rat visual cortex.

In the present paper we investigated the role of the noradrenergic projection from the locus coeruleus on the expression of the immediate early gene zif268 in the visual cortex of rats exposed to ambient light stimulation. Local administrations of 6-hydroxydopamine (6-OHDA), a specific toxin directed against the catecholaminergic system, were performed in the locus coeruleus prior to visual stimulation. Animals were stimulated for 2 h by ambient light, after a 2-week dark adaptation period. Sham-operated controls displayed a massive increase in the number of zif268 positive cells after light stimulation. To the contrary, lesioned animals demonstrated a dramatic reduction in the number of zif268 positive nuclei across all cortical layers. A few scattered immunopositive nuclei were identified in cortical layer IV, however, this region also underwent a significant reduction in the number of zif268 immunopositive nuclei. Our results indicate that the noradrenergic system plays an important role in the expression of zif268 in the visual cortex of rats exposed to ambient light after dark isolation.

Enzyme-catalyzed saccharification of model celluloses in the presence of lignacious residues.

Experiments were designed to determine the relevance of enzyme partitioning, between the cellulose and non-cellulose components of pretreated biomass, with respect to rates of cellulose saccharification in a typical biomass-to-ethanol process. The experimental system included three cellulose preparations (differing in physicochemical properties): a representative lignin-rich noncellulosic residue (prepared from dilute acid-pretreated switchgrass), an acid-extracted lignin preparation, and a complete Trichoderma reesei cellulase preparation. Enzyme-reactor conditions were typical of those commonly used in biomass-to-ethanol studies. The results were found to be dependent on both the lignin and cellulose preparations used. The noncellulosic lignacious residue, when supplemented at up to 40% (w/w) in cellulose-cellulase reaction mixtures, had little effect on rates and extents of cellulose saccharification. Overall, the results suggest that enzyme partitioning between cellulose and the noncellulosic component of a pretreated feedstock is not likely to have a major impact on cellulose saccharification in typical biomass-to-ethanol processes.

Administrative competencies for physician organizations with capitation.

In California, it is common for HMOs to capitate physician organizations (e.g., independent practice organizations and multispecialty medical groups) for all professional and outpatient ancillary services (and to share risk for inpatient care) under professional risk capitation contracts. This arrangement exports most of the financial risk from the HMO to the physician organization. When HMOs and physician organizations contract under these arrangements, HMOs delegate many of their administrative functions to physician organizations--giving the physician organization authority to make the decisions needed to manage capitated risk. As a result, administrators of physician organizations must be competent in such areas as provider network development, financial forecasting, utilization and quality management, contract negotiation, and establishing systems for claims, reporting, authorizations, and the like. In this study four HMO and 22 physician organization administrators were interviewed concerning key administrative competencies for managing capitation contracts. The competencies were assessed as key administrative work activities that required specific knowledge, skill, or ability to perform. Identifying these competencies is important for physician organizations preparing for capitated risk and will be essential for organizations preparing for HMO or Medicare capitation.

The in vitro elution characteristics of antibiotic-loaded CMW and Palacos-R bone cements.

An in vitro study was carried out comparing the elution characteristics of Palacos-R and CMW acrylic cements. Three groups of 6 antibiotic-loaded cement disks were prepared, incorporating 1.0 g vancomycin and 2.4 g tobramycin per 40 g packet of cement. Palacos-R bone cement was used for group 1, CMW 1 for group 2, and CMW 3 for group 3. The disks were placed in saline baths for 9 weeks. The baths were periodically sampled and elution rates calculated. CMW 1 released 24% less tobramycin and 36% less vancomycin than Palacos-R over the total study period (P < .05). CMW 3 released 34% less tobramycin and 38% less vancomycin than Palacos-R (P < .05). There was no significant difference in antibiotic release between CMW 1 and CMW 3. The in vitro elution characteristics of Palacos-R are superior to CMW.

A new method for the automated detection of spontaneous otoacoustic emissions embedded in noisy data.

There is, as yet, no universally agreed upon method for the detection of spontaneous otoacoustic emissions (SOAEs). In this paper, we augment extant techniques by presenting a new automated approach. The new procedure reliably labels the spectral peaks as SOAEs, rejects noisy data such as that due to body movements or breathing, provides a subject-specific measure of the probability that a particular peak is erroneously identified as a SOAE, and can be accomplished on-line. Comparison of results with this new approach and with methods undertaken previously in this laboratory and elsewhere are made. The estimated prevalence of SOAEs for the new method is as large as that for any method previously proposed.

Role and results of segmental allografts for acetabular segmental bone deficiency.

Acetabular reconstruction in both primary and revision hip arthroplasty often requires reconstruction of deficient acetabular bone stock. The exact role of allografts remains controversial. Published results of structural allografting are presented. Recent literature supports the use of segmental allografts for reconstruction of large segmental and combined defects.

Aryl thioglycoside-based affinity purification of exo-acting cellulases.

The influence of ligand-coupling chemistry and mobile-phase composition on the interaction of exo-acting cellulases with an immobilized complementary ligand was investigated. p-Aminophenyl 1-thio-beta-D-cellobioside (APTC) was used as a representative affinity ligand to which exo-acting cellulases (cellobiohydrolases, CBHs) preferentially bind. A "crude" cellulase preparation from the fungus Trichoderma reesei served as an enzyme source. The adsorption properties of the two principal exo-acting CBHs in this preparation, CBH I and CBH II, are shown to be distinctly different under several scenarios. Their relative affinities, based on column elution behavior and partition equilibrium experiments, are shown to be highly dependent on the functional groups employed for ligand coupling, the extent of functional group hydrolysis, the composition of the mobile phase, and the inherent nature of the enzymes. The dependency on the chemistry of the supporting matrix was illustrated using agarose supports containing cyanate ester, N-hydroxy-succinimide, and epoxy functional groups. When compared under apparent optimal conditions, the affinity of CBH II for immobilized APTC was approximately 10-fold that of CBH I. However, selective adsorption of CBH I or CBH II can be achieved by adjusting experimental parameters.