Chiari 1: Is decompression always necessary previous to scoliosis surgery?

The association between Chiari 1 malformation and scoliosis is well known in the literature. Prevalence has increased after the advent of magnetic resonance imaging. In children with this association, prophylactic suboccipital decompression prior to scoliosis correction is a common surgical procedure although the rationale for this surgical management and whether not performing it may lead to spinal cord injury has not been clearly elucidated. We conducted a systematic review of the literature with the aim to obtain strong data to support the hypothesis that it is safe to proceed with scoliosis correction without prior prophylactic suboccipital decompression for Chiari 1 in an asymptomatic population. Using the Prisma methodology, we analyzed 3250 studies published between 1972 and 2018. Only four studies met the inclusion criteria. None of the studies had a level of evidence high enough to recommend prophylactic decompression previous to correction of the spinal deformity.

Aneurysmal bone cyst and osteoblastoma: an extremely rare combination in the pediatric spine.

STUDY DESIGN: Case report. OBJECTIVE: To report the clinical and imaging findings of a patient with the extremely rare association of aneurysmal bone cyst and osteoblastoma in the cervical spine. To our knowledge, only three cases have been reported in the published literature in children under 16 years of age with this condition in the cervical spine. METHODS: The patient's history, physical examination, imaging findings, and management with a complete 4-year medical history, surgical intervention and radiological follow-up are reported. RESULTS: A 4-year 11-month-old boy was diagnosed with aneurysmal bone cyst in association of osteoblastoma and was treated with CT-guided intralesional injection calcitonin and methylprednisolone. During the course of intralesional therapy, a pathological fracture of C2 was produced. Subsequently, a widened intralesional excision and instrumented fusion from occiput to cervical spine (C0-C4) was performed. CONCLUSION: The association of aneurysmal bone cyst and osteoblastoma in spine is extremely rare. Although both are benign lesions, in the cervical location, complete removal of the tumors is challenging. Wide resection with reconstruction of the segments for stability associated with adjuvant treatment with calcitonin and corticosteroids provides a good option.

Analysis of the Structure and Function of FOX-4 Cephamycinase.

Class C ß-lactamases poorly hydrolyze cephamycins (e.g., cefoxitin, cefotetan, and moxalactam). In the past 2 decades, a new family of plasmid-based AmpC ß-lactamases conferring resistance to cefoxitin, the FOX family, has grown to include nine unique members descended from the Aeromonas caviae chromosomal AmpC. To understand the basis for the unique cephamycinase activity in the FOX family, we determined the first X-ray crystal structures of FOX-4, apo enzyme and the acyl-enzyme with its namesake compound, cefoxitin, using the Y150F deacylation-deficient variant. Notably, recombinant expression of N-terminally tagged FOX-4 also yielded an inactive adenylylated enzyme form not previously observed in ß-lactamases. The posttranslational modification (PTM), which occurs on the active site Ser64, would not seem to provide a selective advantage, yet might present an opportunity for the design of novel antibacterial drugs. Substantial ligand-induced changes in the enzyme are seen in the acyl-enzyme complex, particularly the R2 loop and helix H10 (P289 to N297), with movement of F293 by 10.3 Å. Taken together, this study provides the first picture of this highly proficient class C cephamycinase, uncovers a novel PTM, and suggests a possible cephamycin resistance mechanism involving repositioning of the substrate due to the presence of S153P, N289P, and N346I substitutions in the ligand binding pocket.

Selection against accumulating mutations in niche-preference genes can drive speciation.

Our current understanding of sympatric speciation is that it occurs primarily through disruptive selection on ecological genes driven by competition, followed by reproductive isolation through reinforcement-like selection against inferior intermediates/heterozygotes. Our evolutionary model of selection on resource recognition and preference traits suggests a new mechanism for sympatric speciation. We find speciation can occur in three phases. First a polymorphism of functionally different phenotypes is established through evolution of specialization. On the gene level, regulatory functions have evolved in which some alleles are conditionally switched off (i.e. are silent). These alleles accumulate harmful mutations that potentially may be expressed in offspring through recombination. Second mating associated with resource preference invades because harmful mutations in parents are not expressed in the offspring when mating assortatively, thereby dividing the population into two pre-zygotically isolated resource-specialist lineages. Third, silent alleles that evolved in phase one now accumulate deleterious mutations over the following generations in a Bateson-Dobzhansky-Muller fashion, establishing a post-zygotic barrier to hybridization.

Artificial neural networks in models of specialization, guild evolution and sympatric speciation.

Sympatric speciation can arise as a result of disruptive selection with assortative mating as a pleiotropic by-product. Studies on host choice, employing artificial neural networks as models for the host recognition system in exploiters, illustrate how disruptive selection on host choice coupled with assortative mating can arise as a consequence of selection for specialization. Our studies demonstrate that a generalist exploiter population can evolve into a guild of specialists with an 'ideal free' frequency distribution across hosts. The ideal free distribution arises from variability in host suitability and density-dependent exploiter fitness on different host species. Specialists are less subject to inter-phenotypic competition than generalists and to harmful mutations that are common in generalists exploiting multiple hosts. When host signals used as cues by exploiters coevolve with exploiter recognition systems, our studies show that evolutionary changes may be continuous and cyclic. Selection changes back and forth between specialization and generalization in the exploiters, and weak and strong mimicry in the hosts, where non-defended hosts use the host investing in defence as a model. Thus, host signals and exploiter responses are engaged in a red-queen mimicry process that is ultimately cyclic rather then directional. In one phase, evolving signals of exploitable hosts mimic those of hosts less suitable for exploitation (i.e. the model). Signals in the model hosts also evolve through selection to escape the mimic and its exploiters. Response saturation constraints in the model hosts lead to the mimic hosts finally perfecting its mimicry, after which specialization in the exploiter guild is lost. This loss of exploiter specialization provides an opportunity for the model hosts to escape their mimics. Therefore, this cycle then repeats. We suggest that a species can readily evolve sympatrically when disruptive selection for specialization on hosts is the first step. In a sexual reproduction setting, partial reproductive isolation may first evolve by mate choice being confined to individuals on the same host. Secondly, this disruptive selection will favour assortative mate choice on genotype, thereby leading to increased reproductive isolation.

Coevolution of exploiter specialization and victim mimicry can be cyclic and saltational.

Darwin's Principle of Divergence explains sympatric speciation as gradual and directional. Contradicting evidence suggests that species' traits evolve saltationally. Here, we model coevolution in exploiter-victim systems. Victims (resource population) have heritable, mutable cue phenotypes with different levels of defense. Exploiters have heritable, mutable perceptual phenotypes. Our simulations reveal coevolution of victim mimicry and exploiter specialization in a saltational and reversible cycle. Evolution is gradual and directional only in the specialization phase of the cycle thereby implying that specialization itself is saltational in such systems. Once linked to assortative mating, exploiter specialization provides conditions for speciation.

Does information sharing promote group foraging?

Individuals may join groups for several reasons, one of which is the possibility of sharing information about the quality of a foraging area. Sharing information in a patch-foraging scenario gives each group member an opportunity to make a more accurate estimate of the quality of the patch. In this paper we present a mathematical model in which we study the effect of group size on patch-leaving policy and per capita intake rate. In the model, group members share information equally in a random search for food. Food is distributed in patches according to a negative binomial distribution. A prediction from our model is that, the larger the group, the earlier each group member should leave the current patch. We also find that the benefit from enhanced exchange of information does not exceed the cost of sharing food with group members. The per capita intake rate decreases as the group size increases. Therefore, animals should only form groups when other factors outweigh the costs, which is easiest to achieve when the travelling time is short.

Statistical model of the interactions between Helicobacter pylori infection and gastric cancer development.

BACKGROUND: The bacterium Helicobacter pylori is associated with a number of gastrointestinal diseases, such as gastric ulcer, duodenal ulcer and gastric cancer. Several histological changes may be observed during the course of infection; some may influence the progression towards cancer. The aim of this study was to build a statistical model to discover direct interactions between H. pylori and different precancerous changes of the gastric mucosa, and in what order and to what degree those may influence the development of the intestinal type of gastric cancer. METHODS: To find direct and indirect interactions between H. pylori and different histological variables, log-linear analyses were used on a case-control study. To generate mathematically and biologically relevant statistical models, a designed algorithm and observed frequency tables were used. RESULTS: The results show that patients with H. pylori infection need to present with proliferation and intestinal metaplasia to develop gastric cancer of the intestinal type. Proliferation and intestinal metaplasia interacted with the variables atrophy and foveolar hyperplasia. Intestinal metaplasia was the only variable with direct interaction with gastric cancer. Gender had no effect on the variables examined. CONCLUSION: The direct interactions observed in the final statistical model between H. pylori, changes of the mucosa and gastric cancer strengthens and supports previous theories about the progression towards gastric cancer. The results suggest that gastric cancer of the intestinal type may develop from H. pylori infection, proliferation and intestinal metaplasia, while atrophy and foveolar hyperplasia interplay with the other histological variables in the disease process.

Front line workers in long-term care: the effect of educational interventions and stabilization of staffing ratios on turnover and absenteeism.

OBJECTIVE: Front line workers in long-term care play a crucial role in helping residents achieve their highest possible functional level. High turnover (rates in excess of 100% are common) and absenteeism threaten the ability of long-term care providers to meet this goal. The purpose of this study was to determine the effect of a formalized certified nursing assistant (CNA) education program and stabilization of staffing ratios on turnover and absenteeism. DESIGN AND SETTING: This study was a 12-month prospective, nonrandomized trial involving two long-term care facilities providing traditional intermediate and skilled care serving as study sites and a similar facility serving as a control. For historical comparisons, each facility served as its own control using data from the year before the interventions. INTERVENTIONS: An in-house educational program based on the State of North Carolina core curriculum for CNAs was instituted in each study site. During the study period, efforts were made to achieve stable staffing ratios of 1 CNA:8 residents for days, 1:10 for evenings, and 1:15 for nights. Traditional quality of care indicators and resident/surrogate satisfaction were tracked during the study period. RESULTS: Both study facilities showed a decline in turnover, with the decline reaching statistically significant levels at Facility B (134% to 41%, P = 0.0001). Absenteeism rates did not change significantly during the study period. Resident/surrogate satisfaction with nursing care was improved significantly at Facility B (P = 0.02). CONCLUSION: A formal education program in conjunction with stabilization of staffing ratios can result in lower turnover rates for CNA's and improved resident/surrogate satisfaction.

Isolation and expression of a mouse CB1 cannabinoid receptor gene. Comparison of binding properties with those of native CB1 receptors in mouse brain and N18TG2 neuroblastoma cells.

The predominant animal model in which the pharmacology of cannabinoids is studied is the mouse. Nonetheless, the structure and functional expression of the mouse cannabinoid receptor (CB1) gene have not been reported. We have cloned and expressed the gene for the mouse CB1 receptor and compared its properties with those of native mouse CB1 receptors in brain and N18TG2 neuroblastoma cells. The mouse CB1 gene was isolated from a mouse 129 strain genomic library. Sequence analysis of a 6-kb BamHI fragment of the mouse CB1 genomic clone indicates 95% nucleic acid identity between mouse and rat (99.5% amino acid identity) and 90% nucleic acid identity (97% amino acid identity) between mouse and human. Examination of the 5' untranslated sequence of the mouse CB1 genomic clone revealed a splice junction site approximately 60 bp upstream from the translation start site, indicating the possibility of splice variants of the CB1 receptors. The coding region of the mouse CB1 receptor was stably expressed in 293 cells, and binding by [3H]SR 141716A and [3H]CP-55,940 was determined. The Bmax and Kd values obtained with [3H]SR 141716A (921 +/- 58 fmol/mg and 0.73 +/- 0.13 nM, respectively) were similar to those of native mouse CB1 receptors in brain (Bmax of 1.81 +/- 0.44 pmol/mg, Kd of 0.16 +/- 0.01 nM) and N18TG2 cells (Bmax of 197 +/- 29 fmol/mg, Kd of 0.182 +/- 0.08 nM). The mouse CB1 receptor genomic clone will be a useful tool for studying the function and regulation of the CB1 receptor in mice.

Evaluation of a series of N-alkyl benzomorphans in cell lines expressing transfected delta- and mu-opioid receptors.

Transfection of individual opioid receptors in Chinese hamster ovary (CHO) cells provides a pure, homogeneous population of receptors for screening drug candidates, and an alternative to the use of selective ligands. To evaluate the potential of this system, we chose a series of (-)-5,9 alpha-dimethyl-2-hydroxy-N-substituted-6,7-benzomorphans, for which the receptor selectivity and in vivo activity had been characterized recently, and tested them in CHO cells stably transfected with either the rat delta-opioid receptor or the mouse mu-opioid receptor. [3H]Diprenorphine was used to measure opioid receptors in P2 membrane preparations. A Bmax of 7.58 +/- 0.8 pmol/mg protein and a Kd of 0.42 +/- 0.04 nM was obtained in the mu-opioid receptor expressing cell line used in these studies. In addition, [3H]naltrindole was used to confirm the delta-specificity of the cloned receptor. Both compounds gave a Bmax of 1.2 pmol/mg in the CHO cells expressing the rat delta-opioid receptor. Displacement assays were performed with eleven (-)-N-alkyl-benzomorphans in the absence and presence of 150 mM NaCl, as well as known delta- and mu-selective agonists. Sodium reduced agonist affinity in the transfected cell lines. The benzomorphan compounds displayed a range of affinities in the mu- and delta-opioid receptor expressing cell lines. Good correlations were found between their affinities at the cloned mu- and delta-opioid receptors and those in rat brain and monkey cortex (r2 from 0.73 to 0.89, P < 0.001). Comparative analysis of Ki values with in vivo potency in the mouse tail flick test indicated a high degree of correlation between antinociception and affinity in the mu-opioid receptor cell line (r2 = 0.83, p < 0.0001). Lesser correlations were found between antinociception in the mouse and affinity at the rat mu-opioid receptor (r2 = 0.6610) and at the monkey mu-opioid receptor (r2 = 0.695). In sum, these studies indicate that the cell lines expressing the cloned mu- and delta-opioid receptors are appropriate models for determining the binding affinities of this class of opioid compounds. The diminishing correlations found between species when comparing in vitro and in vivo activity suggest that caution should be taken when extrapolating binding data to pharmacological activity among species.

Molecular cloning and expression of a delta-opioid receptor from rat brain.

We have isolated and characterized a rat delta-opioid receptor. The deduced amino acid sequence (372 aa) closely resembles the murine delta-opioid receptor, DOR-1. In fact, 97% of the amino acid residues are conserved between the two species, while 93% of the nucleic acid residues are identical. A 6 kb mRNA was detected in rat cortex using rat DOR-1 as a probe. When expressed in COS cells, the clone shows high-affinity opioid binding with selectivity for delta-opioids. The rat delta-opioid receptor cDNA clone will be a useful tool for studying the function of delta-opioid receptor in rats.

Characteristics and outcomes of hospitalized older patients who develop hypocholesterolemia.

OBJECTIVES: This research project was undertaken to determine the clinical characteristics, lipoprotein abnormalities, and outcomes of older hospitalized patients who develop hypocholesterolemia. METHODS: The project had two parts: (1) a retrospective, case-control study of 50 hospitalized patients greater than or equal to 65 years old whose serum cholesterol was normal on admission (greater than or equal to 160 mg/dL) and fell to less than or equal to 120 mg/dL during hospitalization; (2) a laboratory study of lipoproteins in 17 hospitalized patients greater than or equal to 65 years old whose cholesterol was normal on admission but fell to less than or equal to 120 mg/dL during hospitalization. RESULTS: Case-control Study--Nine percent of patients greater than or equal to 65 years old developed hypocholesterolemia while in the hospital, and these patients were more likely than controls to have undergone surgery and to have nothing by mouth for 5 days or longer. Cases had a longer length of stay, more complications, and were slightly more likely to die in the hospital than controls. LABORATORY STUDY--Hypocholesterolemic patients had low concentrations of all lipoproteins (VLDL, LDL, HDL), and the LDL and HDL were enriched in triglyceride and depleted of cholesterol ester. CONCLUSION: Acquired hypocholesterolemia is a common finding in hospitalized older patients and is associated with poor outcomes. Patients who became hypocholesterolemic in the hospital had both a low concentration of lipoprotein particles and abnormalities in lipoprotein particle composition.

The effect of morphine upon CSF opioids in dogs.

Cerebrospinal fluid opioid activity was measured in dogs before and after morphine administration in order to investigate whether morphine results in an increase in CSF endogenous opioid levels. CSF was fractionated on a gel filtration column, and these fractions were assayed using a radioreceptor assay. Several peaks of opioid activity were seen in dog CSF both before and after morphine treatment. The predominant change in opioid peak patterns was the appearance after morphine treatment of a large peak in the elution position of morphine itself. Radiotracer studies verified that micromolar concentrations of morphine were present in CSF, which is enough morphine for potent binding activity. In addition to the increased activity in the elution position of morphine, several peaks of endogenous opioid activity showed increases after morphine treatment which were statistically significant.