Concordance between epidemiological evaluation of probability of transmission and whole genome sequence relatedness among hospitalized patients acquiring Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae.

OBJECTIVES: We aimed to evaluate the concordance between epidemiologically determined transmission and genetic linkage of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp). METHODS: We included consecutive KPC-Kp carriers between December 2016 and April 2017 in a hospital endemic for KPC-Kp. We assessed epidemiological relatedness between patients by prospective investigations by the infection control team. The probability of epidemiological relatedness was classified into four groups: no suspected transmission, low, moderate and high probability of transmission. Whole-genome sequencing of isolates was performed. Genetic linkage between KPC-Kp isolates was expressed by distance between isolates in single nucleotide polymorphisms (SNPs). We established an SNP cut-off defining a different strain based on the reconstructed phylogenetic tree. We compared the epidemiological and genetic linkage of all isolates from all patients. RESULTS: The study included 25 KPC-Kp carriers with 49 isolates. SNP variance was available for 1129 crossed patient-isolate pairs. Genomic linkage, based on a cut-off of 80 SNPs to define related isolates, was found in 115/708 (16.2%) of isolates with no transmission suspected epidemiologically, 27/319 (8.5%) of low, 11/26 (42.3%) of moderate and 64/76 (84.2%) of high epidemiological transmission risk determination (p < 0.001 for trend). Similar results and significant trends were shown on sensitivity analyses using a lower SNP cut-off (six SNPs) and patient-isolate unique pairs, analysing the first isolate from each patient. CONCLUSIONS: While significant concordance between epidemiological and genomic transmission patterns was found, epidemiological investigations of transmission are limited by the possibility of unidentified transmissions or over-estimation of associations. Genetic linkage analysis is an important aid to epidemiological transmission assessment.

Systematic review of spica casting for the treatment of paediatric diaphyseal femur fractures.

PURPOSE: Paediatric femur fractures are commonly encountered and often successfully managed with spica casting. Despite spica casting's long history there is little formal guidance for optimal outcomes and no consolidation of existing literature. The purpose of this study is to review the available literature regarding the use of spica casting for the management of paediatric diaphyseal femur fractures. METHODS: The PubMed database was queried for all research articles including the phrase "spica". A total of 788 abstracts were reviewed for relevance to the current study. Data was extracted from all available research studies which specified tolerance for fracture angulation or shortening in the cast. Additionally, all articles describing alternative materials, methods for spica application, and complications of spica casting were reviewed. RESULTS: In all, 106 articles were found relevant to the management of diaphyseal femur fractures in the paediatric population. The aggregated, accepted fracture shortening decreased from 16 mm to 18 mm before age ten years to 12 mm to 14 mm after puberty. Aggregated, accepted angulation decreased from 14° to 16° varus/valgus and 18° to 22° pro/recurvatum before age two years, to 6° to 8° and 10° to 12° by puberty, respectively. The overall reported complication rate was 19.6%, with the most common complication being skin compromise in 8.2% of patients, followed by unacceptable angulation at the fracture site in 4.2% of patients and excessive limb shortening in 1.9% of patients. CONCLUSION: This article reviews the available spica casting literature and compiles the available data. Spica casting offers a safe, effective means for definitive management of paediatric diaphyseal femur fractures. Future research identifying the rate and pattern of remodelling as it relates to angulation and shortening at various patient ages, particularly beyond the aforementioned norms, would be valuable to identify true biological tolerances versus accepted expert opinion. LEVEL OF EVIDENCE LEVEL II: Review of level II evidence.

Tyrosine improves appetite, cognition, and exercise tolerance in activity anorexia.

PURPOSE: We have modified for mice the activity wheel model of Routtenberg to study the effects of tyrosine on exercise tolerance, behavior, and brain neurochemistry. METHODS: Mice were fed for 2 h.d(-1) over a 2-wk period. During the second week, each group was injected daily with either saline or tyrosine (100 mg.kg(-1).d(-1)) and exercised on a running wheel. Controls were in cages with inactivated wheels and received the same treatment and feeding protocols as the experimental groups. Food consumption and cognitive function (eight-arm maze) were evaluated for 1 wk. Brains were then assayed for adrenergic and serotonergic metabolites. RESULTS: Activity together with a restricted diet caused extreme weight loss (27%) (P < 0.001) together with decreased food consumption (22%) (P < 0.001). Tyrosine restored food consumption to that of the controls (P < 0.001) with no effect on weight, since there was a 22% increase in activity (P < 0.001). Saline injections caused an 18% decrease in activity (P < 0.001). Both activity and tyrosine improved maze performance (P < 0.05). In the hypothalamus, activity caused a significant increase in 5-hydroxytryptamine (5-HT) (P < 0.001), 5-hydroxyindoleacetic acid (5-HIAA) (P < 0.01), and dopamine (P < 0.05); tyrosine prevented the increase in 5-HT (P < 0.05) and increased 5-HIAA in the controls (P < 0.01). With regard to hippocampal 5-HT, there was a significant increase in 5-HIAA following activity (P < 0.05), whereas tyrosine caused significant increase in 5-HIAA in the controls (P < 0.01). Activity significantly decreased the level of hippocampal 3,4-dihydroxyphenylacetic acid (DOPAC), whereas tyrosine decreased its level only in the controls (both at P < 0.0001). The level of tyrosine hydroxylase increased with activity (P < 0.05), and tyrosine decreased it significantly (P < 0.05). CONCLUSION: Activity anorexia is associated with increased hypothalamic 5-HT concentrations. Tyrosine administration reverses this, and significantly improves food consumption, cognitive behavior, and activity performance. Such nutritional modulations may have implications for the treatment of eating disorders and, in normal circumstances, tyrosine may improve exercise tolerance and delay fatigue.

Recurrence methods in the analysis of learning processes.

The goal of most learning processes is to bring a machine into a set of "correct" states. In practice, however, it may be difficult to show that the process enters this target set. We present a condition that ensures that the process visits the target set infinitely often almost surely. This condition is easy to verify and is true for many well-known learning rules. To demonstrate the utility of this method, we apply it to four types of learning processes: the perceptron, learning rules governed by continuous energy functions, the Kohonen rule, and the committee machine.

Early versus late femoral fracture stabilization in multiply injured pediatric patients with closed head injury.

The purpose of this study was to analyze retrospectively pediatric femur fracture patients with concomitant head injury to determine whether time to fracture fixation affects central nervous system, orthopaedic, or additional complications. Twenty-five patients with a Head Abbreviated Injury Scale score of > or =3 and a femoral shaft fracture were reviewed. Patients were divided by time to treatment for their femur fracture. Average stay was 10.5 days for the early group and 18.5 days for the late group, the only statistically significant finding. Orthopaedic and central nervous system complications were similar between the two groups. Sixteen additional complications were found in the late group versus three for the early group. Femur fractures in the head-injured pediatric patient can be adequately addressed with early or late fixation with similar long-term outcomes. Early femur fracture fixation may decrease the length of hospital stay and the number of nonorthopaedic, nonneurologic complications.

A new on-line learning model.

We introduce a new supervised learning model that is a nonhomogeneous Markov process and investigate its properties. We are interested in conditions that ensure that the process converges to a "correct state," which means that the system agrees with the teacher on every "question." We prove a sufficient condition for almost sure convergence to a correct state and give several applications to the convergence theorem. In particular, we prove several convergence results for well-known learning rules in neural networks.

Diet restriction in mice causes a decrease in hippocampal choline uptake and muscarinic receptors that is restored by administration of tyrosine: interaction between cholinergic and adrenergic receptors influencing cognitive function.

We have studied the effects of diet restriction (DR) to 60% and 40% of daily requirements, and tyrosine administration on cognitive function in mice, to define the nutritional-neurochemical interactions on autonomic tone involved in behavior and energy regulation. Cognitive function in the Morris Water maze was significantly impaired after 40% DR compared to both control and 60% DR. It was restored after tyrosine in association with increased M1 cholinergic and beta-adrenergic receptor function, and decreased alpha-adrenergic function. DR to 40% significantly decreased choline uptake (p <.05) and M1 receptor number (Bmax) (p <.05), without changes in affinity (Kd), choline acetyl transferase (ChAT) or acetyl cholinesterase (AChE) activity. Tyrosine administration significantly increased choline uptake (Bmax) (p <.05) and M1 density in the 40% DR (p <.01) without changes in affinity. ChAT activity was decreased after tyrosine--significantly after 40% DR (p <.05) while AChE was not affected. Both M1 mRNA and protein were not influenced by DR or tyrosine administration. Tyrosine hydroxylase mRNA was decreased significantly by 40% DR (p <.01). The effect of DR and tyrosine appeared to be both pre- and post-synaptic, indicating modulation of cholinergic activity by adrenergic tone. Nutritional effect on behavior and autonomic tone may have implications for the treatment of mood changes associated with weight loss and semi-starvation.

Olanzapine-induced glucose dysregulation.

OBJECTIVE: To report a patient who developed severe exacerbation of type 2 diabetes mellitus after the initiation of olanzapine therapy. CASE SUMMARY: A 54-year-old African-American woman developed severe glucose dysregulation 12 days after the initiation of olanzapine. Prior to starting olanzapine therapy, the patient's diabetes was controlled by diet modification with a glycosylated hemoglobin of 6.5%. During olanzapine therapy, blood glucose concentrations could not be regulated despite use of antidiabetic agents, insulin, and dietary interventions. The patient also gained a total of 13 kg. Two weeks after discontinuation of all antipsychotic medications (olanzapine, quetiapine), the patient's blood glucose concentrations became better regulated and remained better controlled until discharge. DISCUSSION: All atypical antipsychotics are associated with weight gain. Obesity is a well-documented risk factor for developing type 2 diabetes mellitus. Currently there are only six published reports that implicate olanzapine as being associated with glucose dysregulation. The exact cause of glucose dysregulation with olanzapine is unclear, but weight gain does not seem to be the sole etiology. It has been hypothesized that serotonin (5-HT1A) antagonism may decrease the responsiveness of the pancreatic beta-cells. This would then result in inappropriately low insulin secretion and, therefore, hyperglycemia. Based on the Naranjo probability scale, the likelihood that olanzapine caused the glucose dysregulation in our patient was possible. CONCLUSIONS: Although olanzapine has shown greater clinical efficacy and is associated with fewer extrapyramidal side effects than typical antipsychotics, it may produce exacerbation or new emergence of diabetes mellitus. Further examination of the incidence and etiology of glucose dysregulation after the initiation of olanzapine therapy is necessary.

In-vivo strain measurements to evaluate the strengthening potential of exercises on the tibial bone.

Mechanical loading during physical activity produces strains within bones. It is thought that these forces provide the stimulus for the adaptation of bone. Tibial strains and rates of strain were measured in vivo in six subjects during running, stationary bicycling, leg presses and stepping and were compared with those of walking, an activity which has been found to have only a minimal effect on bone mass. Running had a statistically significant higher principal tension, compression and shear strain and strain rates than walking. Stationary bicycling had significantly lower tension and shear strains than walking. If bone strains and/or strain rates higher than walking are needed for tibial bone strengthening, then running is an effective strengthening exercise for tibial bone.

Do high impact exercises produce higher tibial strains than running?

BACKGROUND: Bone must have sufficient strength to withstand both instantaneous forces and lower repetitive forces. Repetitive loading, especially when bone strain and/or strain rates are high, can create microdamage and result in stress fracture AIM: To measure in vivo strains and strain rates in human tibia during high impact and moderate impact exercises. METHODS: Three strain gauged bone staples were mounted percutaneously in a rosette pattern in the mid diaphysis of the medial tibia in six normal subjects, and in vivo tibial strains were measured during running at 17 km/h and drop jumping from heights of 26, 39, and 52 cm. RESULTS: Complete data for all three drop jumps were obtained for four of the six subjects. No statistically significant differences were found in compression, tension, or shear strains with increasing drop jump height, but, at the 52 cm height, shear strain rate was reduced by one third (p = 0.03). No relation was found between peak compression strain and calculated drop jump energy, indicating that subjects were able to dissipate part of the potential energy of successively higher drop jumps by increasing the range of motion of their knee and ankle joints and not transmitting the energy to their tibia. No statistically significant differences were found between the principal strains during running and drop jumping from 52 cm, but compression (p = 0.01) and tension (p = 0.004) strain rates were significantly higher during running. CONCLUSIONS: High impact exercises, as represented by drop jumping in this experiment, do not cause higher tibial strains and strain rates than running and therefore are unlikely to place an athlete who is accustomed to fast running at higher risk for bone fatigue.

Effect of microwave oven induced mild hyperthermia on bone viability and strength.

Extracorporeal hyperthermia treatment of bone followed by reimplantation may be an option for treating bone tumors. However, intensive heat treatment, such as autoclaving, causes a decline of mechanical and biologic functions of bone tissue. In the current study, a microwave oven was used for minimal hyperthermic treatment, and it was found that complete eradication of all viable cells in rat bone could be achieved with minimal reduction in mechanical function. When the cells were evaluated histologically by special lactate dehydrogenase activity staining, complete bone cell death occurred after 60 seconds of heating in an empty Petri dish and after 30 seconds when heated in a Petri dish containing normal saline. Mechanical stiffness and strength of the bones, tested in three-point bending, showed no decrease after this heating. Microwave oven induced hyperthermia eradication of viable cells without significant damage to the mechanical properties may have clinical relevance in limb salvage tumor surgery.

The current status of the platelet 5-HT(2A) receptor in depression.

The author reviews the current status of the platelet serotonin (5-HT)(2A) receptor in depression. Considered are studies of receptor binding, and 5-HT-induced platelet activation and aggregation. 5-HT(2A) receptor density tends to increase in depression, although this more clearly relates to suicidality than depression per se. Indeed, data are consistent with the hypothesis that increased density of platelet 5-HT(2A) receptors may be a marker for increased risk of suicide. 5-HT-induced calcium mobilization is enhanced in unipolar depression; however, unlike in bipolar depression, baseline calcium levels are not. Despite inconsistencies, 5-HT-induced aggregation appears inhibited in depression. This may manifest as a relative inhibition, i.e. no change in aggregation response despite a higher density of 5-HT(2A) receptors. The inhibited aggregation response is state dependent, and acute phase proteins or components of the stress response may be factors. It is unclear if differences between depressed and normal subjects in disposition of 5-HT(2A) receptors are generally indicative of traits or states. Nonetheless, there is little evidence that the degree of departure from normal density or activity of platelet of 5-HT(2A) receptors reflects severity of depression.

Prevention of stress fractures using custom biomechanical shoe orthoses.

In a prospective study of stress fractures the hypothesis that training with custom made biomechanical shoe orthoses could lessen the incidence of stress fractures in infantry recruits was tested. Recruits were assigned randomly to groups and given soft biomechanical orthoses or semirigid biomechanical orthoses and compared with a control group that did not train in biomechanical orthoses. All recruits wore infantry boots with soles designed like those of basketball shoes. Recruits were examined biweekly during 14 weeks of basic training. The incidence of stress fractures was 15.7% for the recruits with the semirigid biomechanical orthoses, 10.7% for the recruits with the soft biomechanical orthoses, and 27% for the control group. The soft biomechanical orthoses were tolerated better by the recruits than were the semirigid devices. Among trainees at high risk for stress fractures, prophylactic use of custom made biomechanical orthoses may be warranted.

Effect of cane use on tibial strain and strain rates.

The effect of cane ambulation on hip biomechanics has been well studied, but its effect on tibial strains and strain rates is not known. To test the hypothesis that cane use may lower tibial strain and strain rates during walking, percutaneous axial extensometers were mounted on the right medial cortex of the midtibial diaphysis in seven male volunteers. In vivo peak-to-peak axial tibial strains and strain rates were measured for ipsilateral and contralateral cane usage and compared with a no cane control. Cane-assisted ambulation was not found to significantly lower strain magnitudes; however, tibial strain rates were significantly lowered by both ipsilateral and contralateral cane usage. We conclude that either ipsilateral or contralateral cane usage may be beneficial when lowering tibial strain rate is desired, such as in the treatment of tibia stress fracture or osteoarthrosis of the knee.

A role for the octamer-binding protein in preprotachykinin-A gene expression.

A rat Preprotachykinin-A promoter fragment has been previously identified which supports reporter gene activity in primary cultures of adult dorsal root ganglion neurons. That study demonstrated that two promoter domains which exhibit enhancer activity in these neurons are bound by the same classes of transcription factors. Further, the two domains exhibit similarities with respect to the relationship of bound transcription factors within each domain. This suggests that these domains may function in an identical manner or may act synergistically to regulate gene expression. These domains contain recognition motifs for at least three classes of transcription factors: octamer-binding proteins, Sp1-related proteins and an as yet unidentified but distinct factor. The definition of an octamer-binding protein site within these domains is of interest, as this class of factor has recently been suggested as mediating the effect of nerve growth factor in sensory neurons. Nerve growth factor is a well-characterized regulator of preprotachykinin-A gene expression. Definition of these sites within the promoter allows for the design of rational experiments to address the mechanism of transcriptional regulation of the rat preprotachykinin-A gene.

Effect of moderate bone hyperthermia on cell viability and mechanical function.

Extracorporeal hyperthermia treatment of bone followed by its reimplantation may be an optional treatment of bone tumors. In this study, the authors examined the minimal hyperthermic condition in which complete eradication of all viable cells in rat bone can be achieved and the mechanical effect of this treatment on the tested bone. When the results were evaluated histologically by special lactate dehydrogenase activity staining, it was found that complete bone cell death occurred after 30 minutes of heating at 60 degrees C. Cartilage cells, including those of the epiphysis, were more resistant to thermal damage. When the ability of the specimens to proliferate in cell cultures was tested, no growth was observed after heating at temperatures of 50 degrees C or greater. The mechanical stiffness tested in the Instron machine showed decreased bone stiffness at 70 degrees C but no change in the breaking load of the bones. Controlled hyperthermia's ability to eradicate viable cells without significant damage to the mechanical properties may have clinical relevance in limb salvage tumor surgery.

A comparison of the effect of shoes on human tibial axial strains recorded during dynamic loading.

Percutaneous axial extensometers were mounted on the medial cortex of the midtibial diaphysis in seven male volunteers and the effect of three different shoes on in vivo peak-to-peak axial compression-tension strains measured during dynamic loading. Zohar shoes had lower axial strains and strain rates during treadmill walking than Nike Air Max running shoes or Israeli infantry boots. During running on a running track, there was no statistically significant difference between the axial strains or strain rates between the shoes tested. Shoe gear can modify tibial strains and strain rates that contribute to the development of tibial stress fractures.