Changes to the chemical composition of soot from heterogeneous oxidation reactions.
The atmospheric aging of soot particles, in which various atmospheric processes alter the particles' chemical and physical properties, is poorly understood and consequently is not well-represented in models. In this work, soot aging via heterogeneous oxidation by OH and ozone is investigated using an aerosol flow reactor coupled to a new high-resolution aerosol mass spectrometric technique that utilizes infrared vaporization and single-photon vacuum ultraviolet ionization. This analytical technique simultaneously measures the elemental and organic carbon components of soot, allowing for the composition of both fractions to be monitored. At oxidant exposures relevant to the particles' atmospheric lifetimes (the equivalent of several days of oxidation), the elemental carbon portion of the soot, which makes up the majority of the particle mass, undergoes no discernible changes in mass or composition. In contrast, the organic carbon (which in the case of methane flame soot is dominated by aliphatic species) is highly reactive, undergoing first the addition of oxygen-containing functional groups and ultimately the loss of organic carbon mass from fragmentation reactions that form volatile products. These changes occur on time scales comparable to those of other nonoxidative aging processes such as condensation, suggesting that further research into the combined effects of heterogeneous and condensational aging is needed to improve our ability to accurately predict the climate and health impacts of soot particles.


Dietary diversity and subsequent cause-specific mortality in the NHANES I epidemiologic follow-up study.
Human diets tend to be complex mixtures of foods and nutrients. Therefore, we examined the relation of a measure of overall diet quality (independent of intake of individual foods or nutrients) with mortality from cardiovascular disease (CVD), cancer, and non-CVD, non-cancer (other) causes. We used data from the NHANES I Epidemiologic follow-up study (n = 10,337; median follow-up time = 14 years; age 25-74 years at baseline), and included 988 CVD, 571 cancer, and 910 other cases. The 24-hour dietary recalls obtained at baseline were scored for quality using a dietary diversity score (DDS). The DDS (range 0-5) counts the number of major food groups--dairy, meat, grain, fruit, and vegetable consumed daily. Age-adjusted risk of mortality from all three causes (except cancer in women) was inversely related with DDS in both men and women. Adjustment for multiple covariates attenuated the relative risk estimates slightly for CVD and cancer mortality, but markedly for other mortality. The results are suggestive of an increased risk of CVD and cancer mortality associated with diets characterized by omission of several major food groups.


Task-specific robot base pose optimization for robot-assisted surgeries.
Preoperative planning and intra-operative system setup are crucial steps to successfully integrate robotically assisted surgical systems (RASS) into the operating room. Efficiency in terms of setup planning directly affects the overall procedural costs and increases acceptance of RASS by surgeons and clinical personnel. Due to the kinematic limitations of RASS, selecting an optimal robot base location and surgery access point for the patient is essential to avoid potentially critical complications due to reachability issues. To this end, this work proposes a novel versatile method for RASS setup and planning based on robot capability maps (CMAPs). CMAPs are a common tool to perform workspace analysis in robotics, as they are in general applicable to any robot kinematics. However, CMAPs have not been completely exploited so far for RASS setup and planning. By adapting global CMAPs to surgical procedure-specific tasks and constraints, a novel RASS capability map (RASSCMAP) is generated. Furthermore, RASSCMAPs can be derived to also comply with kinematic access constraints such as access points in laparoscopy. RASSCMAPs are versatile and applicable to any kind of surgical procedure; they can be used on the one hand for aiding in intra-operative experience-based system setup by visualizing online the robot's capability to perform a task. On the other hand, they can be used to find the optimal setup by applying a multi-objective optimization based on a genetic algorithm preoperatively, which is then transfered to the operating room during system setup. To illustrate these applications, the method is evaluated in two different use cases, namely, pedicle screw placement in vertebral fixation procedures and general laparoscopy. The proposed RASSCMAPs help in increasing the overall clinical value of RASS by reducing system setup time and guaranteeing proper robot reachability to successfully perform the intended surgeries.


Metabotropic and ionotropic transducers of glutamate signal inversely control cytoplasmic Ca2+ concentration and excitotoxicity in cultured cerebellar granule cells: pivotal role of protein kinase C.
We investigated the functional role of metabotropic glutamate receptors (mGluRs) in modulating glutamate-affected neuronal intracellular calcium concentration ([Ca2+]i) and cell viability in rat cerebellar granule cells. The mGluR agonist trans-1-amino-cyclopentane-1,3-dicarboxylic acid (tACPD) induced a transient increase in [Ca2+]i, which seemed to be developmentally regulated and maximal at 4 days in vitro. In addition, tACPD significantly prevented the [Ca2+]i rise produced by glutamate or by N-methyl-D-aspartate. The mGluR antagonists L-2-amino-3-phosphonopropionic and (+)-alpha-methyl-4-carboxyphenylglycine blocked the effects of tACPD but intrinsically, they magnified the glutamate-mediated [Ca2+]i elevation. The tACPD-mediated decrease in [Ca2+]i rise occurred under experimental conditions superimposable on those producing neuroprotection in glutamate-exposed cultures. tACPD affected neither [Ca2+]i elevation due to KCI nor that evoked by the calcium ionophore A 23187. The inhibitory effect of tACPD was also unaffected by K+ channel blockade produced by tetraethylammonium. The tACPD effects were fully mimicked by quisqualate and (RS)-3,5-dihydroxyphenylglycine, whereas they were only partially reproduced by (2S,1'S,2'S)-2-carboxycyclopropyl-glycine. L-2-Amino-4-phosphonobutyrate was inactive in preventing glutamate-mediated [Ca2+]i rise and neurotoxicity. The tACPD inhibitory responses seemed to be highly sensitive to protein kinase C blockade by bisindolylmaleimide or staurosporine, whereas they were weakly affected by the cAMP analogue dibutyryl cAMP. The protein kinase C activator 4beta-phorbol-12,13-dibutyrate reproduced mGluR-mediated inhibition of both glutamate-induced [Ca2+]i rise and neurotoxicity. In summary, these data suggest that activation of mGluR1-5 subtypes reduce glutamate-mediated (Ca2+]i rise through a mechanism involving protein kinase C activation. Such an effect results in neuroprotection.


Comparison of two abdominal training devices with an abdominal crunch using strength and EMG measurements.
The purpose of this study was to compare the training effects of the Ab-Flex (F), Ab-Roller (R) and standard crunch (C) on EMG production, isometric maximum voluntary contraction (MVC), and isokinetic average peak torque at 30 degrees/sec (ISO) of the abdominal muscles. It was hypothesized that the training devices would have similar value in a strength training program. this was a prospective study involving 18 training sessions of progressively increasing repetitions. Neuromuscular Research Laboratory, University of Pittsburgh. thirty-two subjects volunteered for this study, but only 26 completed the training. Each subject participated in recreational activity, but had not performed any abdominal training prior to starting this study. Each subject was randomly assigned to either the control group or one of the treatment groups. there were three interventions: two training devices (Ab-Flex and Ab-Roller) and the standard crunch, considered a control group. the pretest consisted of skin fold measurements (%), EMG activity (V) during the three interventions, and peak torque (Nm) plus EMG during the MVC and ISO tasks. The 18 training sessions over three weeks consisted of three sets of exercise with increasing repetitions from 10 to 20, by 2, every three sessions. The difference in pretest/posttest scores were compared using a One-way ANOVA on the mean differences (Mdiff) for each of: MVC, ISO (peak torque), and EMG for upper rectus (UR), lower rectus (LR), internal oblique (IO), and external oblique (EO). A T-Test was used to detect significance for the body fat measures. Mean differences (Mdiff) were normally distributed about zero for both MVC and ISO (MVC = -0.55, ISO = 4.57). The analysis by group showed no difference (p = 0.596) on the reported means (Nm) -3.16 (C), 5.84 (F) and -4.83 (R). The change associated to the treatment during MVC was only 4% (eta = 0.04). For the ISO the Mdiff (Nm) were 1.39 (C), 13.66 (F) and -2.06 (R) which were not significant (p = 0.127). The Ab-Flex was the only group to have a 95% confidence interval above zero, increasing by an average of 16.5%. There were no significant differences for the EMG activity for Mdiff or between group scores. No significant differences were found with this study. These results would suggest that using these devices does not add significantly to overall abdominal strength development, or reduction of body fat. A suggestion could be made that certain devices influence muscles differently.


Experimental and computational studies of the G[UUCG]C RNA tetraloop.
In prokaryotic ribosomal RNAs, most UUCG tetraloops are closed by a C-G base-pair. However, this preference is greatly reduced in eukaryotic rRNA species where many UUCG tetraloops are closed by G-C base-pairs. Here, biophysical properties of the C[UUCG]G and G[UUCG]C tetraloops are compared, using experimental and computational methods. Thermal denaturation experiments are used to derive thermodynamic parameters for the wild-type G[UUCG]C tetraloop and variants containing single deoxy substitutions in the loop. A comparison with analogous experiments on the C[UUCG]G motif shows that the two RNA species exhibit similar patterns in response to the substitutions, suggesting that their loop structures are similar. This conclusion is supported by NMR data that suggest that the essential UUCG loop structure is maintained in both tetraloops. However, NMR results show that the G[UUCG]C loop structure is disrupted prior to melting of the stem; this behavior is in contrast to the two-state behavior of the C[UUCG]G molecule. Stochastic dynamics simulations using the GB/SA continuum solvation model, run as a function of temperature, show rare conformational transitions in several G[UUCG]C simulations. These results lead to the conclusion that substitution of a G-C for a C-G closing base-pair increases the intrinsic flexibility of the UUCG loop.


Single agent chemotherapy for head and neck cancers. The murine subrenal capsule assay.
The murine subrenal capsule assay was used to determine chemotherapeutic sensitivities of metastatic, primary, or recurrent head and neck cancers. Tumor fragments (1 cu mm) were implanted under the renal capsule of 2- to 4-month-old normal female C57 BL/6 X DBA/2 F1 hybrid mice. Xenografts included 20 squamous cell carcinomas (SCCs), one mucoepidermoid carcinoma, one adenoid cystic carcinoma, and two melanomas. Groups of tumor-bearing mice were treated with chemotherapy daily for five days. Sensitivities of the tumor were assessed on day 6 by comparison of final implant size with initial implant size. Significant oncolytic activity was detected against 16 of 24 tumors (14 of 20 SCCs and both melanomas). Correlations between the in vivo assay and clinical studies are needed to determine its predictive value.


Probing the structural basis of RecQ helicase function.
RecQ helicases are a ubiquitous family of DNA unwinding enzymes required to preserve genome integrity, thus preventing premature aging and cancer formation. The five human representatives of this family play non-redundant roles in the suppression of genome instability using a combination of enzymatic activities that specifically characterize each member of the family. These enzymes are in fact not only able to catalyze the transient opening of DNA duplexes, as any other conventional helicase, but can also promote annealing of complementary strands, branch migration of Holliday junctions and, in some cases, excision of ssDNA tails. Remarkably, the balance between these different activities seems to be regulated by protein oligomerization. This review illustrates the recent progress made in the definition of the structural determinants that control the different enzymatic activities of RecQ helicases and speculates on the possible mechanisms that RecQ proteins might use to promote their multiple functions.


Synthesis, crystal structure, and cytotoxicity studies of titanacalix[4 and 8]arene complexes.
Reaction of 5,11,17,23-tetra-tert-butyl-dihydroxy-26,28-bis(2-pentoxy)calix[4]arene (L(OH)2(Opentyl)2) with [TiCl4] afforded the dichlorotitanoacalix[4]arene complex [TiCl2L(O)2(Opentyl)2] (1) in good yield. Hydrolysis of 1 led to the isolation of the complex {[TiL(O)3(Opentyl)]2(μ-OH)(μ-Cl)} (2). Reaction of 5,11,17,23,29,35,41,47-p-tert-butyl-49,50,51,52,53,54,55,56-octapropoxycalix[8]arene (L'(Opropyl)8) with [TiCl4] in refluxing toluene afforded, following work-up, a 35 : 65 mixture (3) of the complex [Ti(NCMe)Cl]2[TiCl(μ-O)]2L' and the silicone grease derived complex [Ti(NCMe)Cl]2[Ti(μ-O)]2[OSi(CH3)2OSi(CH3)2O]L' in which the grease replaces two chloride ligands. The molecular structures of 1·2MeCN, 2·7¼MeCN, and 3·10MeCN have been determined. The complexes were studied using in vitro cell assays and were found to have CC50 values in the range 111-186 μM, i.e. they have low toxicity.


Influencing Martensitic Transition in Epitaxial Ni-Mn-Ga-Co Films with Large Angle Grain Boundaries.
Magnetocaloric materials based on field-induced first order transformations such as Ni-Mn-Ga-Co are promising for more environmentally friendly cooling. Due to the underlying martensitic transformation, a large hysteresis can occur, which in turn reduces the efficiency of a cooling cycle. Here, we analyse the influence of the film microstructure on the thermal hysteresis and focus especially on large angle grain boundaries. We control the microstructure and grain boundary density by depositing films with local epitaxy on different substrates: Single crystalline MgO(0 0 1), MgO(1 1 0) and Al2O3(0 0 0 1). By combining local electron backscatter diffraction (EBSD) and global texture measurements with thermomagnetic measurements, we correlate a smaller hysteresis with the presence of grain boundaries. In films with grain boundaries, the hysteresis is decreased by about 30% compared to single crystalline films. Nevertheless, a large grain boundary density leads to a broadened transition. To explain this behaviour, we discuss the influence of grain boundaries on the martensitic transformation. While grain boundaries act as nucleation sites, they also lead to different strains in the material, which gives rise to various transition temperatures inside one film. We can show that a thoughtful design of the grain boundary microstructure is an important step to optimize the hysteresis.


A half-century of innovation in technology-preparing MRI for the 21st century.
MRI developed during the last half-century from a very basic concept to an indispensable non-ionising medical imaging technique that has found broad application in diagnostics, therapy control and far beyond. Due to its excellent soft-tissue contrast and the huge variety of accessible tissue- and physiological-parameters, MRI is often preferred to other existing modalities. In the course of its development, MRI underwent many substantial transformations. From the beginning, starting as a proof of concept, much effort was expended to develop the appropriate basic scanning technology and methodology, and to establish the many clinical contrasts (e.g., T1, T2, flow, diffusion, water/fat, etc.) that MRI is famous for today. Beyond that, additional prominent innovations to the field have been parallel imaging and compressed sensing, leading to significant scanning time reductions, and the move towards higher static magnetic field strengths, which led to increased sensitivity and improved image quality. Improvements in workflow and the use of artificial intelligence are among many current trends seen in this field, paving the way for a broad use of MRI. The 125th anniversary of the BJR is a good point to reflect on all these changes and developments and to offer some slightly speculative ideas as to what the future may bring.


Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT.
Natural killer (NK) cells can alter the outcome of hematopoietic cell transplantation (HCT) if donor alloreactivity targets the recipient. Since most NK cells express inhibitory killer-immunoglobulin receptors (KIRs), we hypothesized that the susceptibility of recipient cells to donor NK cell-mediated lysis is genetically predetermined by the absence of known KIR ligands. We analyzed data from 2062 patients undergoing unrelated donor HCT for acute myeloid leukemia (AML; n = 556), chronic myeloid leukemia (CML; n = 1224), and myelodysplastic syndrome (MDS; n = 282). Missing 1 or more KIR ligands versus the presence of all ligands protected against relapse in patients with early myeloid leukemia (relative risk [RR] = 0.54; n = 536, 95% confidence interval [CI] 0.30-0.95, P = .03). In the subset of CML patients that received a transplant beyond 1 year from diagnosis (n = 479), missing a KIR ligand independently predicted a greater risk of developing grade 3-4 acute graft-versus-host disease (GVHD; RR = 1.58, 95% CI 1.13-2.22; P = .008). These data support a genetically determined role for NK cells following unrelated HCT in myeloid leukemia.


In vitro evaluation of dentinal tubule penetration and biomineralization ability of a new root-end filling material.
Capasio is being developed as a new generation of endodontic material with potential use as a root-end filling material. The aim of this study was to compare the ability of Capasio and mineral trioxide aggregate (MTA) to penetrate human dentinal tubules and examine the interaction of Capasio and MTA with a synthetic tissue fluid (STF) and root canal walls in extracted human teeth. Root-end preparations were filled with Capasio or MTA, allowed to set for 4 weeks in STF, and then sectioned at 1, 2, and 3 mm from resected surface. Depth of penetration was evaluated by using scanning electron microscopy (SEM). Next, Capasio and MTA samples were prepared both in 1-g pellets and in root-end preparations. Samples were placed in STF, allowed to set, and then characterized by using SEM, energy dispersive x-ray analysis (EDXA), and x-ray diffraction (XRD) techniques. Penetration of Capasio into dentinal tubules was observed at all levels. No penetration of MTA into dentinal tubules was observed at any level. Both Capasio and MTA formed apatite crystals in the supernatant, on their exposed surfaces, and in the interfacial layers that were similar in structure and elemental composition when evaluated by using SEM and EDXA. XRD analysis of these crystals corresponds with those reported for hydroxyapatite. When used as a root-end filling material, Capasio is more likely to penetrate dentinal tubules. Both Capasio and MTA promote apatite deposition when exposed to STF.


Polymorphisms in the glucocorticoid receptor gene and in the glucocorticoid-induced transcript 1 gene are associated with disease activity and response to glucocorticoid bridging therapy in rheumatoid arthritis.
Glucocorticoids (GC) are widely used in rheumatoid arthritis (RA). Ongoing active disease due to GC resistance may unfavorably influence long-term disease outcome in RA. We studied the association between the presence of glucocorticoid receptor (GR) and glucocorticoid-induced transcript 1 (GLCCI1) gene polymorphisms, which modulate GC sensitivity, and baseline disease activity score (DAS) and efficacy of GC bridging therapy in RA. We prospectively studied in vivo GC sensitivity in 138 patients with recent-onset or longstanding RA. In vivo GC sensitivity was expressed as the relative decrease in DAS following 2 weeks of standardized GC therapy. All patients were genotyped for the GR polymorphisms BclI (rs41423247), N363S (rs6195), 9β (rs6198), ER22/23EK (rs6189 + rs6190), and the GLCCI1 variant rs37972 and subsequently divided in groups carrying a polymorphism associated with increased GC sensitivity (BclI-G allele, N363S-G allele, GLCCI1-C allele) or decreased GC sensitivity (9β-G allele, ER22/23EK-A/A allele, GLCCI1-T allele). Differences in baseline DAS and relative decrease in DAS in the different genotype groups were analyzed using analysis of covariance and linear regression. Baseline DAS was higher in patients who carried polymorphisms of the GR and GLCCI1 genes associated with decreased GC sensitivity. GLCCI1 genotype, but not GR genotypes, was associated with improvement in DAS in male patients with RA. The GLCCI1 gene minor allele (rs37972) may be associated with less efficient GC bridging therapy in male RA patients. Carriers of the BclI-G, N363S-G, or GLCCI1-C alleles had lower levels of baseline disease activity, suggesting a role for the GLCCI1 and GR gene in regulation of GC sensitivity to endogenously produced cortisol.


The intra-arterial injection of microglia protects hippocampal CA1 neurons against global ischemia-induced functional deficits in rats.
In the present study, we have attempted to elucidate the effects of the intra-arterial injection of microglia on the global ischemia-induced functional and morphological deficits of hippocampal CA1 neurons. When PKH26-labeled immortalized microglial cells, GMIR1, were injected into the subclavian artery, these exogenous microglia were found to accumulate in the hippocampus at 24 h after ischemia. In hippocampal slices prepared from medium-injected rats subjected to ischemia 48 h earlier, synaptic dysfunctions including a significant reduction of synaptic responses and a marked reduction of long-term potentiation (LTP) of the CA3-CA1 Schaffer collateral synapses were observed. At this stage, however, neither significant neuronal degeneration nor gliosis was observed in the hippocampus. At 96 h after ischemia, there was a total loss of the synaptic activity and a marked neuronal death in the CA1 subfield. In contrast, the basal synaptic transmission and LTP of the CA3-CA1 synapses were well preserved after ischemia in the slices prepared from the microglia-injected animals. We also found the microglial-conditioned medium (MCM) to significantly increase the frequency of the spontaneous postsynaptic currents of CA1 neurons without affecting the amplitude, thus indicating that MCM increased the provability of the neurotransmitter release. The protective effect of the intra-arterial injected microglia against the ischemia-induced neuronal degeneration in the hippocampus was substantiated by immunohistochemical and immunoblot analyses. Furthermore, the arterial-injected microglia prevented the ischemia-induced decline of the brain-derived neurotrophic factor (BDNF) levels in CA1 neurons. These observations strongly suggest that the arterial-injection of microglia protected CA1 neurons against the ischemia-induced neuronal degeneration. The restoration of the ischemia-induced synaptic deficits and the resultant reduction of the BDNF levels in CA1 neurons, possibly by the release of diffusible factor(s), might thus contribute to the protective effect of the arterial-injection of microglia against ischemia-induced neuronal degeneration.


Role of ancient lakes in genetic and phenotypic diversification of freshwater snails.
Endemic organisms of ancient lakes have been studied as models to understand processes of speciation and adaptive radiation. However, it remains unclear how ancient lakes play roles in genetic and phenotypic diversity of freshwater mollusks. In the present study, we focus on viviparid freshwater snails in the ancient lakes of East and Southeast Asia (Japan and China) to address this question. Using molecular phylogenetic analyses based on mitochondrial (COI, 16S) and nuclear genes (18S, 28S, H3), we show that patterns of species diversification in viviparid lineages. Colonization to ancient lakes occurred independently in China and Japan at least four times, with subsequent diversification into more than two species within each lake group. Morphological analyses of fossil related viviparids suggest parallel phenotypic evolution occurred in the different lakes and ages. Each lake contained a single lineage which was phenotypically diversified relative to those from other sites. Using genome-wide SNPs obtained by MIG-seq, we also examined the genetic structure of three Japanese viviparids, including two endemic species of ancient Lake Biwa. The results suggest that these two species diversified from the population of the third species living in wetlands surrounding the lake. These findings suggest that rapid diversification of lineages and phenotypic divergence can occur in ancient lakes compared to other habitats. Formation of large lakes probably promotes speciation and phenotypic divergence as a result of adaptation into different microhabitats. High numbers of ancient lakes could be a driver of species diversity in Asian viviparid snails.


Using Complexity and Network Concepts to Inform Healthcare Knowledge Translation.
Many representations of the movement of healthcare knowledge through society exist, and multiple models for the translation of evidence into policy and practice have been articulated. Most are linear or cyclical and very few come close to reflecting the dense and intricate relationships, systems and politics of organizations and the processes required to enact sustainable improvements. We illustrate how using complexity and network concepts can better inform knowledge translation (KT) and argue that changing the way we think and talk about KT could enhance the creation and movement of knowledge throughout those systems needing to develop and utilise it. From our theoretical refinement, we propose that KT is a complex network composed of five interdependent sub-networks, or clusters, of key processes (problem identification [PI], knowledge creation [KC], knowledge synthesis [KS], implementation [I], and evaluation [E]) that interact dynamically in different ways at different times across one or more sectors (community; health; government; education; research for example). We call this the KT Complexity Network, defined as a network that optimises the effective, appropriate and timely creation and movement of knowledge to those who need it in order to improve what they do. Activation within and throughout any one of these processes and systems depends upon the agents promoting the change, successfully working across and between multiple systems and clusters. The case is presented for moving to a way of thinking about KT using complexity and network concepts. This extends the thinking that is developing around integrated KT approaches. There are a number of policy and practice implications that need to be considered in light of this shift in thinking.


Lumbar canal stenosis: analyzing the role of stabilization and the futility of decompression as treatment.
OBJECTIVEThe authors report their current experience with their previously published novel form of treatment in 70 cases of lumbar canal stenosis. The treatment consisted of only fixation of the spinal segments by the transarticular screw fixation technique. No bone, ligament, osteophyte, or disc resection was done for spinal canal and neural foraminal decompression. The proposed treatment is based on the concept that vertical instability that results in telescoping of the facets on physical activity forms the nodal point of pathogenesis of lumbar canal stenosis.METHODSDuring the period June 2014 to May 2018, 70 patients presenting with the classically described symptoms of lumbar canal stenosis were treated surgically by only fixation of involved spinal segments. Apart from clinical and radiological guides, instability was diagnosed on the basis of physical observation of the status of articulation by direct manipulation of bones of the region. The operation involved transarticular insertion of 2 or 3 screws for each articulation. The Oswestry Disability Index and visual analog scale were used to assess the patients before and after surgery and at follow-up. Additionally, a personalized patient satisfaction score was used to assess the outcome of surgery.RESULTSClinical symptomatic recovery was observed in all patients in the immediate postoperative period. During the average follow-up period, 100% of patients had varying degrees of symptomatic relief. The patient satisfaction score suggested that all patients were very satisfied with the surgical procedure. The transarticular fixation technique provided strong spinal segment fixation and a reliable ground for bone arthrodesis. No patient needed any additional modality of treatment or reoperation for recurrence of symptoms.CONCLUSIONSSpinal instability is the nodal point of pathogenesis of spinal degeneration-related lumbar canal stenosis. Only fixation of the involved spinal segments is necessary-decompression by bone or soft-tissue resection is not necessary.


Emerging Insights for Translational Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Studies: Towards Prediction of Nose-to-Brain Transport in Humans.
To investigate the potential added value of intranasal drug administration, preclinical studies to date have typically used the area under the curve (AUC) in brain tissue or cerebrospinal fluid (CSF) compared to plasma following intranasal and intravenous administration to calculate measures of extent like drug targeting efficiencies (%DTE) and nose-to-brain transport percentages (%DTP). However, CSF does not necessarily provide direct information on the target site concentrations, while total brain concentrations are not specific to that end either as non-specific binding is not explicitly considered. Moreover, to predict nose-to-brain transport in humans, the use of descriptive analysis of preclinical data does not suffice. Therefore, nose-to-brain research should be performed translationally and focus on preclinical studies to obtain specific information on absorption from the nose, and distinguish between the different transport routes to the brain (absorption directly from the nose to the brain, absorption from the nose into the systemic circulation, and distribution between the systemic circulation and the brain), in terms of extent as well as rate. This can be accomplished by the use of unbound concentrations obtained from plasma and brain, with subsequent advanced mathematical modeling. To that end, brain extracellular fluid (ECF) is a preferred sampling site as it represents most closely the site of action for many targets. Furthermore, differences in nose characteristics between preclinical species and humans should be considered. Finally, pharmacodynamic measurements that can be obtained in both animals and humans should be included to further improve the prediction of the pharmacokinetic-pharmacodynamic relationship of intranasally administered CNS drugs in humans.


Prevalence of increased intraocular pressure in patients with Graves' ophthalmopathy and association with ophthalmic signs and symptoms in the north-west of Iran.
Graves' ophthalmopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease and is characterized by multiple ocular symptoms such as eyelid retraction, lid lag, proptosis, elevated intraocular pressure (IOP) and ultimately loss of vision. We aimed to investigate the prevalence of increased IOP in Graves' patients and association with ophthalmic signs and symptoms in north-west of Iran. This descriptive cross-sectional study recruited 93 patients with GO who were diagnosed based on clinical and laboratory examinations. A complete ocular examination and IOP measurements on forward gaze were performed using Goldman applanation tonometer. In this study, 93 patients with GO were evaluated from 2016 to 2017. Among these patients, 67 (72.05%) were female and 27 (27.95%) were male. The most common complaints of patients were lid retraction (62.36%), puffy eyelids (58.06%) and proptosis (46.23%), respectively. The duration of disease was 0-24 months in most patients. Most subjects were at grade 3 according to NOSPECS classification. Nine patients (9.6%) had an IOP greater than or equal to 21 mmHg. The mean IOP in subjects was 16.61±3.42 mmHg. The mean IOP in males and smokers was significantly higher than that of females and nonsmokers. The mean IOP increased significantly with a higher grade of disease, duration of disease, age and smoking. According to the results, females comprised the majority of the study population, while ocular complications were more prevalent among males. The highest IOP was seen in old cases of GO. The most prevalent ocular signs in patients were eyelid retraction and periorbital edema. The least prevalent sign was glaucomatous optic neuropathy. In this study, the prevalence of intra-ocular hypertension was higher than that of the general population, especially in males, old cases with a drug history of antithyroid medication and smokers.


Spatial resolution, contrast sensitivity, and sensitivity to defocus of chicken retinal ganglion cells in vitro.
The chicken has been extensively studied as an animal model for myopia because its eye growth is tightly controlled by visual experience. It has been found that the retina controls the axial eye growth rates depending on the amount and the sign of defocus imposed in the projected image. Glucagonergic amacrine cells were discovered that appear to encode for the sign of imposed defocus. It is not clear whether the downstream neurons, the retinal ganglion cells, still have access to this information-and whether it ultimately reaches the brain. We have analyzed the spike rates of chicken retinal ganglion cells in vitro using a microelectrode array. For this purpose, we initially defined spatial resolution and contrast sensitivity in vitro. Two classes of chicken retinal ganglions were found, depending on the linearity of their responses with increasing contrast. Responses generally declined with increasing defocus of the visual stimulus. These responses were well predicted by the modulation transfer function for a diffraction-limited defocused optical system, the first Bessel function. Thus, the studied retinal ganglion cells did not distinguish between a loss of contrast at a given spatial frequency due to reduced contrast of the stimulus pattern or because the pattern was presented out of focus. Furthermore, there was no indication that the retinal ganglion cells responded differently to defocus of either sign, at least for the cells that were recorded in this study.


Comparison of the Hatch of Newly Laid Lycorma delicatula (Hemiptera: Fulgoridae) Eggs From the United States After Exposure to Different Temperatures and Durations of Low Temperature.
Comparisons were made of the effects of temperature and duration of low temperature on hatch of newly laid egg masses of the invasive spotted lanternfly, Lycorma delicatula (White). Egg masses were collected in mid-October 2019 and estimated to be less than 14 d old. There was a significant positive nonlinear relationship between temperature and developmental rate (1/d) for eggs held at constant temperatures. The lower threshold for egg development was estimated as 7.39°C. Eggs held at constant 10, 15, and 20°C were estimated to require 635, 715, and 849 DD7.39, respectively, to develop. Egg hatch was variable, egg hatch rates were highest (58.4%) when held at a constant 15°C, though high rates (52.7%) were also obtained when eggs were held for 84 d at 10°C, then moved to 25°C. Almost all eggs enter diapause since very few eggs were able hatch when moved to 25°C after 7 d of chill at either 5 or 10°C. Chilling at 5 or 10°C increased percentage egg hatch as the duration in chill increased up to ~100 d and eggs held at 10°C were able to complete some or all the post-diapause development before being moved to 25°C. All egg masses were held at constant 16:8 (L:D) photoperiod and 65%RH. Our data suggest that temperature is the driving factor for diapause termination in spotted lanternfly, but other abiotic factors should be investigated. These identified developmental temperature threshold and degree day requirements for egg hatch will improve predictive distribution and phenological models.


Curated Collections for Educators: Five Key Papers on Evaluating Digital Scholarship.
Traditionally, scholarship that was recognized for promotion and tenure consisted of clinical research, bench research, and grant funding. Recent trends have allowed for differing approaches to scholarship, including digital publication. As increasing numbers of trainees and faculty turn to online educational resources, it is imperative to critically evaluate these resources. This article summarizes five key papers that address the appraisal of digital scholarship and describes their relevance to junior clinician educators and faculty developers. In May 2017, the Academic Life in Emergency Medicine Faculty Incubator program focused on the topic of digital scholarship, providing and discussing papers relevant to the topic. We augmented this list of papers with further suggestions by guest experts and by an open call via Twitter for other important papers. Through this process, we created a list of 38 papers in total on the topic of evaluating digital scholarship. In order to determine which of these papers best describe how to evaluate digital scholarship, the authorship group assessed the papers using a modified Delphi approach to build consensus. In this paper we present the five most highly rated papers from our process about evaluating digital scholarship. We summarize each paper and discuss its specific relevance to junior faculty members and to faculty developers. These papers provide a framework for assessing the quality of digital scholarship, so that junior faculty can recommend high-quality educational resources to their trainees. These papers help guide educators on how to produce high quality digital scholarship and maximize recognition and credit in respect to receiving promotion and tenure.


Anthocyanins profile of grape berries of Vitis amurensis, its hybrids and their wines.
Anthocyanins are responsible for the color of grapes and wine, an important attribute of their quality. Many authors have used anthocyanins profile to classify the grape cultivars and wine authenticity. The anthocyanin profiles of grape berries of Vitis amurensis, its hybrids and their wines were analyzed by HPLC-ESI-MS/MS. The results identified 17 anthocyanins in these grape cultivars, including 11 anthocyanin monoglucosides (five pyranoanthocyanin monoglucosides and one acylated pyranoanthocyanin monoglucoside) and six anthocyanin diglucosides. Likewise, 15 kinds of anthocyanins were detected in wines, including six diglucosides and nine monoglucosides of anthocyanidins, in which four pyranoanthocyanin monoglucosides (Petunidin-3-O-glucoside-4-acetaldehyde, Malvidin-3-O-glucoside-4-pyruvic acid, Malvidin-3-O-glucoside-acetaldehyde and Peonidin-3-O-glucoside-4-pyruvic acid) were detected. In addition, a total of 14 kinds of anthocyanins including six diglucosides and eight monoglucosides of anthocyanidins were identified in skins, in which two pyranoanthocyanin monoglucosides (Peonidin-3-O-glucoside-4-pyruvic acid, Malvidin-3-O-glucoside-4-vinylphenol) and one acylated pyranoanthocyanin monoglucoside (Malvidin-3-O-(6-O-acetyl)-glucoside-4-vinylphenol) were detected. The anthocyanins profile of grape skin of V. amurensis and its hybrids consist of the anthocyanin monoglucosides, diglucosides and pyranoanthocyanins. The wines produced resulted in a slightly different anthocyanin distribution. Pelargonidin-3,5-diglucosides was first found in the skins and wines, however, no acetyl was detected in wines. The principal component analysis results suggest that the anthocyanin profiles were helpful to classify these cultivars of V. amurensis.


The impact of taxing sugar-sweetened beverages on cola purchasing in Catalonia: an approach to causal inference with time series cross-sectional data.
Sugar-sweetened beverage (SSB) taxes related to the quantity of sugar have appeared as a popular regulatory tool around the world during the last decade showing important variations in their implementation and impact. We evaluated the impact of a new SSB tax implemented in Catalonia since May 1, 2017 on the purchased quantities and penetration rates of taxed and untaxed cola beverages. We use aggregate time series of cola beverages purchases in all 17 Spanish Autonomous Communities before and after the implementation of the SBB tax in Catalonia, from January 2013 to June 2019. A comparison between two different types of causal inference methods was conducted: a two-way fixed effects difference in differences model and a modified synthetic control model. Regular cola purchases decreased 12.1% and their penetration rate decreased by 1.27 points during the two post-intervention years using the preferred model. Diet cola purchases increased 17.0% and their penetration rate also increased by 1.65 points. Only regular cola results were robust to all placebo test checks. The SSB tax implemented in Catalonia in 2017 significantly reduced the volume and penetration rates of regular colas with no robust evidence for the substitution effect on diet colas.


High D-dimer levels increase the likelihood of pulmonary embolism.
Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.


[Need for rehabilitation services: theoretical considerations in "needs assessment"].
Several projects of the North German Association for Rehabilitation Research had focused on needs assessment in the field of medical rehabilitation to be provided by statutory pension funds. Their results prompted a more differentiated understanding of the concepts of rehabilitation-neediness, -ability and -prognosis and lead to the development of the "Lübecker algorithm". It is based on (a) assessing the present health disorder and its consequences in terms of activity limitations and participation restrictions, (b) defining rehabilitation goals, and (c) selecting a rehabilitative intervention. The three components form the corners of a triangle. Its connecting sides can be described in terms of norms and expectations (disorder-goals), theoretical considerations (disorder-intervention), and empirical evidence from systematic research (intervention-goals). Needs assessment can thus be--partly--objectified, and "need" can be safely distinguished from related concepts such as "burden of illness", "wish", "demand", "supply", and "provision".


Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: implication for breast cancer osteolytic bone metastases.
Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/beta-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/beta-catenin antagonist. In the present study, we demonstrated that activation of Wnt/beta-catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/beta-catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell-produced Dkk1 blocked Wnt3A-induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti-Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A-induced NF-kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A-induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer-produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases.


How healthcare organisations can act as institutional entrepreneurs in a context of change.
The aim of this paper is to illustrate and discuss how healthcare organisations can act as institutional entrepreneurs in a context of change. The authors conducted an in-depth longitudinal case study (2005-2008) of a healthcare organisation in the province of Quebec, Canada. Data collection consisted of real-time observations of senior managers (n = 87), interviews (n = 24) with decision-makers and secondary data analysis of documents. The paper reports on the extent to which entrepreneurial healthcare organisations can be a driving force in the creation of a new practice. The authors analyse the development of a diabetes reference centre by a healthcare organisation acting as an institutional entrepreneur that illustrates the conceptualisation of an innovation and the mobilisation of resources to implement it and to influence other actors in the field. The authors discuss the case in reference to three stages of change: emergence, implementation and diffusion. The results illustrate the different strategies used by managers to advance their proposed projects. This study helps to better understand the dynamics of mandated change in a mature field such as healthcare and the roles played by organisations in this process. By adopting a proactive strategy, a healthcare organisation can play an active role and strongly influence the evolution of its field. This paper is one of only a few to analyse strategies used by healthcare organisations in the context of mandated change.


Classical anticytokinins do not interact with cytokinin receptors but inhibit cyclin-dependent kinases.
Cytokinins are a class of plant hormones that regulate the cell cycle and diverse developmental and physiological processes. Several compounds have been identified that antagonize the effects of cytokinins. Based on structural similarities and competitive inhibition, it has been assumed that these anticytokinins act through a common cellular target, namely the cytokinin receptor. Here, we examined directly the possibility that various representative classical anticytokinins inhibit the Arabidopsis cytokinin receptors CRE1/AHK4 (cytokinin response 1/Arabidopsis histidine kinase 4) and AHK3 (Arabidopsis histidine kinase 3). We show that pyrrolo[2,3-d]pyrimidine and pyrazolo[4,3-d]pyrimidine anticytokinins do not act as competitors of cytokinins at the receptor level. Flow cytometry and microscopic analyses revealed that anticytokinins inhibit the cell cycle and cause disorganization of the microtubular cytoskeleton and apoptosis. This is consistent with the hypothesis that they inhibit regulatory cyclin-dependent kinase (CDK) enzymes. Biochemical studies demonstrated inhibition by selected anti-cytokinins of both Arabidopsis and human CDKs. X-ray determination of the crystal structure of a human CDK2-anticytokinin complex demonstrated that the antagonist occupies the ATP-binding site of CDK2. Finally, treatment of human cancer cell lines with anticytokinins demonstrated their ability to kill human cells with similar effectiveness as known CDK inhibitors.


Technology assessment and resource allocation for predictive genetic testing: a study of the perspectives of Canadian genetic health care providers.
With a growing number of genetic tests becoming available to the health and consumer markets, genetic health care providers in Canada are faced with the challenge of developing robust decision rules or guidelines to allocate a finite number of public resources. The objective of this study was to gain Canadian genetic health providers' perspectives on factors and criteria that influence and shape resource allocation decisions for publically funded predictive genetic testing in Canada. The authors conducted semi-structured interviews with 16 senior lab directors and clinicians at publically funded Canadian predictive genetic testing facilities. Participants were drawn from British Columbia, Alberta, Manitoba, Ontario, Quebec and Nova Scotia. Given the community sampled was identified as being relatively small and challenging to access, purposive sampling coupled with snowball sampling methodologies were utilized. Surveyed lab directors and clinicians indicated that predictive genetic tests were funded provincially by one of two predominant funding models, but they themselves played a significant role in how these funds were allocated for specific tests and services. They also rated and identified several factors that influenced allocation decisions and patients' decisions regarding testing. Lastly, participants provided recommendations regarding changes to existing allocation models and showed support for a national evaluation process for predictive testing. Our findings suggest that largely local and relatively ad hoc decision making processes are being made in relation to resource allocations for predictive genetic tests and that a more coordinated and, potentially, national approach to allocation decisions in this context may be appropriate.


Functionality of veterinary identification microchips following low- (0.5 tesla) and high-field (3 tesla) magnetic resonance imaging.
The ability to read patient identification microchips relies on the use of radiofrequency pulses. Since radiofrequency pulses also form an integral part of the magnetic resonance imaging (MRI) process, the possibility of loss of microchip function during MRI scanning is of concern. Previous clinical trials have shown microchip function to be unaffected by MR imaging using a field strength of 1 Tesla and 1.5. As veterinary MRI scanners range widely in field strength, this study was devised to determine whether exposure to lower or higher field strengths than 1 Tesla would affect the function of different types of microchip. In a phantom study, a total of 300 International Standards Organisation (ISO)-approved microchips (100 each of three different types: ISO FDX-B 1.4 × 9 mm, ISO FDX-B 2.12 × 12 mm, ISO HDX 3.8 × 23 mm) were tested in a low field (0.5) and a high field scanner (3.0 Tesla). A total of 50 microchips of each type were tested in each scanner. The phantom was composed of a fluid-filled freezer pack onto which a plastic pillow and a cardboard strip with affixed microchips were positioned. Following an MRI scan protocol simulating a head study, all of the microchips were accurately readable. Neither 0.5 nor 3 Tesla imaging affected microchip function in this study.


Propagation of Recombinant Genes through Complex Microbiomes with Synthetic Mini-RP4 Plasmid Vectors.
The promiscuous conjugation machinery of the Gram-negative plasmid RP4 has been reassembled in a minimized, highly transmissible vector for propagating genetically encoded traits through diverse types of naturally occurring microbial communities. To this end, the whole of the RP4-encoded transfer determinants (tra, mob genes, and origin of transfer oriT) was excised from their natural context, minimized, and recreated in the form of a streamlined DNA segment borne by an autoselective replicon. The resulting constructs (the pMATING series) could be self-transferred through a variety of prokaryotic and eukaryotic recipients employing such a rationally designed conjugal delivery device. Insertion of GFP reporter into pMATING exposed the value of this genetic tool for delivering heterologous genes to both specific mating partners and complex consortia (e.g., plant/soil rhizosphere). The results accredited the effective and functional transfer of the recombinant plasmids to a diversity of hosts. Yet the inspection of factors that limit interspecies DNA transfer in such scenarios uncovered type VI secretion systems as one of the factual barriers that check otherwise high conjugal frequencies of tested RP4 derivatives. We argue that the hereby presented programming of hyperpromiscuous gene transfer can become a phenomenal asset for the propagation of beneficial traits through various scales of the environmental microbiome.


Practice patterns of oral and maxillofacial surgeons in Australia: 1990 and 2000.
This study was undertaken to describe practice patterns of oral and maxillofacial surgeons in Australia and compare trends over time. All registered oral and maxillofacial surgeons in Australia were surveyed in 1990 and 2000 using mailed self-complete questionnaires. Data were available from 79 surgeons from 1990 (response rate = 73.8%) and 116 surgeons from 2000 (response rate = 65.1%). In both 1990 and 2000 the majority of surgeons worked 80+% of the time in the private sector (64.1 and 71.4%), had 80+% referrals from dental versus medical sources (74.0 and 74.7%), and had 80+% of patients from dentoalveolar rather than major maxillofacial surgery (70.7 and 69.7%). The percentage of dual qualified (dental plus medical degree) surgeons increased from 2.5% in 1990 to 17.1% in 2000 (P < 0.05; chi2). In 2000, surgeons who worked less than 80% in the private sector were more likely to report being overworked (57.9%) and that more surgeons were required in the public sector (65.0%) than those who worked 80% or more private (17.0 and 24.0%, respectively). Multivariate linear regressions of annual non-dentoalveolar surgical procedures per surgeon showed (P < 0.05) higher provision of implant (beta = 0.362), TMJ (beta = 0.267) and bone graft surgery (beta = 0.208) in 2000 compared to 1990, and higher provision of orthognathic (beta = 0.199), implant (beta = 0.194) and bone graft surgery (beta = 0.289) by dual qualified surgeons compared to those with only dental qualifications. Despite the mix of cases remaining predominantly dentoalveolar there was some change over time for selected non-dentoalveolar surgical procedures, with growth in the percentage of medically qualified surgeons and differences in surgery rates by qualification.


Metabolic syndrome and the role of dietary lifestyles in Alzheimer's disease.
Since Alzheimer's disease (AD) has no cure or preventive treatment, an urgent need exists to find a means of preventing, delaying the onset, or reversing the course of the disease. Clinical and epidemiological evidence suggests that lifestyle factors, especially nutrition, may be crucial in controlling AD. Unhealthy lifestyle choices lead to an increasing incidence of obesity, dyslipidemia and hypertension--components of the metabolic syndrome. These disorders can also be linked to AD. Recent research supports the hypothesis that calorie intake, among other non-genetic factors, can influence the risk of clinical dementia. In animal studies, high calorie intake in the form of saturated fat promoted AD-type amyloidosis, while calorie restriction via reduced carbohydrate intake prevented it. Pending further study, it is prudent to recommend to those at risk for AD--e.g. with a family history or features of metabolic syndrome, such as obesity, insulin insensitivity, etc.--to avoid foods and beverages with added sugars; to eat whole, unrefined foods with natural fats, especially fish, nuts and seeds, olives and olive oil; and to minimize foods that disrupt insulin and blood sugar balance.


Light emitting properties of Si+ self-ion implanted silicon-on-insulator from visible to infrared band.
The photoluminescence (PL) properties of silicon-on-insulator (SOI) samples, modified by the Si+ self-ion-implantation (SII) into Si thin film followed by annealing, have been well investigated. The well-known W-line can also be observed in SII SOI samples, its emitting behavior and structural evolution have been discussed in this article. The parallel PL pattern trend and the similar changes of temperature-dependent intensity suggest that luminescence center of I1 and I2 peaks located in the near-infrared band originates from the same interstitial-clusters (InCs). The PL peak at 1.762 eV can be ascribed to the quantum confinement (QC) from small-sized Si nanocrystals. Based on the electron spin resonance (ESR) experiments and the variation of normalized PL intensities at different annealing temperature (TA), the neutral oxygen vacancy (NOV) [O3≡Si-Si≡O3] is proposed to be responsible for the blue emission of P2 and P3 peaks, whose intensity can be restrained by the existence of the paramagnetic E1' defects [O3≡Si+]. The density of E1' defect is found to reduce with the increase of annealing temperature (TA). Our results provide a useful method to identify the origin of luminescence centers and pave a way for the application of new type optical defects on silicon based light emitting devices (LEDs).


A meta-analysis of the efficacy of ureteroscopic lithotripsy and extracorporeal shock wave lithotripsy on ureteral calculi.
To re-evaluated the clinic efficacy of ureteroscopic lithotripsy (URS) and extracorporeal shock wave lithotripsy (ESWL) on ureteral calculi with Cochrane systematic reviews in this paper. We searched clinical randomized controlled trials and prospective controlled trials in databases such as Cochrane library, Medline, Springer, Elsevier Science Direct, PubMed. Pooled estimate of risk ratios (RRs), standard mean difference (SMD) with 95% confidence intervals (CIs) were used as measure of effect sizes. Summary effect estimates were also stratified by sample size, study design and study region. The overall effect sizes were derived using a random-effects model or fixed-effects model when appreciated, and meta-analysis were conducted with software RewMan 5.0. The meta-analysis suggested that there were significant differences of post-treatment stone free rate, repeat treatment rate, patients' satisfaction, incidence of postoperative complications, operation time and hospital stays between ESWL treatment cases and URS treatment cases. But in the sample sizes analysis, there were no significant differences of the post-treatment stone free rate and repeat treatment rate when the sample sizes were less than 100. Compared to the ureteroscopic lithotripsy treatment, extracorporeal shock wave lithotripsy treatment provided a significantly lower post-treatment stone free rate, but it also obviously brought out less postoperative complications, shorter operation time and hospital stays.


Abuse of older adults before moving to old age homes in Pokhara Lekhnath Metropolitan City, Nepal: A cross-sectional study.
The number of older individuals relocating from their homes to old age homes is increasing in Nepal. This study was conducted to assess the reasons why older people chose to move to old age homes, the status and forms of abuse they experienced, and the risk factors associated with their abuse before moving to old age homes. This study was a cross sectional study conducted among older adults currently residing in all the old age homes of Pokhara Lekhnath Metropolitan City. Complete enumeration of the respondents was done and data was collected consecutively, using a semi-structured interview schedule, from all older adults aged 60 years and above who had been living in the homes for at least a month. The total sample size was 109. The collected data was analyzed using descriptive statistics and binary logistic regression was used as an inferential statistics to determine the predictors of abuse. A majority of the respondents (56.0%) came to old age homes on their own volition, 24.7% reported that they came to the homes because they were physically weak and they had no one to care for them at their residence, while 11% reported that they were forcefully sent by their caregivers. Out of total respondents, 60.6% reported that they experienced some form of abuse before they came to the old age home: most frequent was caregiver neglect (34.9%) and verbal abuse (34.9%), while few experienced financial abuse (2.8%). Women were at a higher risk of abuse than men (p<0.05, OR = 4.430, CI = 1.695-11.577) prior to their transfer to old age homes. A majority of the older adults who transferred to old age homes in Pokhara Lekhnath Metropolitan city had been earlier abused by their caregivers, mainly through neglect and verbal abuse, and women were at a higher risk for abuse than men.


Mutations in the charged residues of the amino terminus of rat liver fructose 6-phosphate,2-kinase:Fructose 2,6-bisphosphatase: effects on regulation.
Amino and carboxyl termini of the bifunctional enzyme Fru 6-P, 2-kinase:Fru 2,6-bisphosphatase regulate the relative activities of the kinase/phosphatase. The N-terminus of the rat liver bifunctional enzyme is highly basic, containing a protein kinase A phosphorylation site that regulates these enzyme activities in a reciprocal manner. To determine the role of charged residues in the N-terminal peptide, mutant enzymes were constructed in which these residues were altered to residues carrying opposite charges, and the effect on the catalytic properties, thermal lability, and susceptibility to trypsin digestion and phosphorylation by protein kinase A was determined. Most of these mutations decreased k(cat)/K(ATP) and/or k(cat)/K(Fru) (6-P) of the kinase and increased k(cat)/K(Fru 2,6-P2) of the phosphatase. These mutant enzymes were more susceptible to trypsin digestion, phosphorylation by protein kinase A, and thermal inactivation. In general, the effect was greater with amino acid residues located more distant from the N-terminus. The resulting changes were not as large as observed with the phosphorylated enzyme. Mutation of Ser22 to Pro produced large changes in the kinetic properties comparable to those of phosphorylation, suggesting that the flexible region of the N-terminus containing five serines (Ser20 to S24) is essential for the enzyme activities. These results indicated that the charged residues as well as Ser20-Ser24 in the N-terminus of the liver Fru 6-P,2-kinase:Fru 2,6-Pase are essential in the allosteric regulation and probably involved in interactions with the catalytic domains that induce a conformation that has high Fru 6-P,2-kinase and low Fru 2,6-Pase activities. Any disruption of this N-terminal interaction results in inhibition of the kinase and activation of the phosphatase.


Factors Associated With Receipt of Radiation Therapy for Rectal Cancer.
Appropriate treatment for cancer is vital to increasing the likelihood of survival; however, for rectal cancer, there are demonstrated disparities in receipt of treatment by race/ethnicity and socioeconomic status. We evaluated factors associated with receipt of appropriate radiation therapy for rectal cancer using data from the Florida Cancer Data System that had been previously enriched with detailed treatment information collected from a Centers for Disease Control and Prevention Comparative Effectiveness Research study. This treatment information is not routinely available in cancer registry data and represents a unique data resource. Using multivariable regression, we evaluated factors associated with receiving radiation therapy among rectal cancer cases stage II/III. Our sample (n=403) included cases diagnosed in Florida in 2011 who were 18 years and older. Cases clinically staged as 0/I/IV were excluded. Older age (odds ratio=0.96; 95% confidence interval, 0.94-0.97), the presence of one or more comorbidities (0.61; 0.39-0.96), and receipt of surgical intervention (0.44; 0.22-0.90) were associated with lack of radiation. In this cohort of patients, sociodemographic factors such as race/ethnicity, insurance status, and socioeconomic status, did not influence the receipt of radiation. Further research is needed, however, to understand why aging, greater comorbidity, and having surgery present a barrier to radiation therapy, particularly given that it is a well-tolerated treatment in most patients.


Remarkably low temperature optima for extracellular enzyme activity from Arctic bacteria and sea ice.
Extracellular degradative enzymes released by psychrophilic marine bacteria (growing optimally at or below 15 degrees C and maximally at 20 degrees C) typically express activity optima at temperatures well above the upper growth limit of the producing strain. In the present study, we investigated whether or not near-zero Arctic environments contain extracellular enzymes with activity optimized to temperatures lower than previously reported. By applying fluorescently tagged substrate analogues to measure leucine-aminopeptidase and chitobiase activity, the occurrence of extracellular enzymatic activity (EEA) with remarkably low temperature optima (15 degrees C) was documented in sea-ice samples. An extremely psychrophilic bacterial isolate, strain 34H, yielded an extract of cell-free protease with activity optimized at 20 degrees C, the lowest optimum yet reported for cell-free EEA from a pure culture. The use of zymogram gels revealed the presence of three proteolytic bands (between 37 and 45 kDa) in the extract and the release of the greatest quantities of the proteases when the strain was grown at -1 degrees C, suggesting a bacterial strategy for counteracting the effects of very cold temperatures on the catalytic efficiency of released enzymes. The detection of unusually cold-adapted EEA in environmental samples has ramifications not only to polar ecosystems and carbon cycling but also to protein evolution, biotechnology and bioremediation.


Identification of a putative cellular receptor for the lentivirus visna virus.
One mechanism by which viral tropism may be controlled is by the expression of a specific virus receptor on the cell surface. This paper reports the identification of a putative cellular receptor for visna virus, the prototype virus of the family Lentiviridae. Using a virus overlay protein blot assay we identified a group of polypeptides of apparent Mr 30K to 33K which interacts with visna virus and is present on permissive but not non-permissive cells. A rat polyclonal anti-ovine major histocompatibility complex (MHC) class II antigen (Ag) serum raised to immunopurified MHC class II Ag, but not preimmune serum, blocked the interaction of visna virus with these polypeptides. In an ELISA, immunopurified MHC class II Ag bound to visna virus but not to bovine parainfluenza 3 virus. Preincubation of visna virus with immunopurified soluble MHC class II Ag resulted in a marked decrease in virus-induced syncytium formation, i.e. preincubation with class II Ag inhibited infection with visna virus, but we have been unable to inhibit infection using class II Ag-specific antisera. These results suggest that ovine MHC class II Ag acts as a component of a cellular receptor for visna virus. This is of particular interest owing to the close similarities between visna virus and human immunodeficiency virus (HIV), and the relationship between MHC class II and CD4, the cellular receptor for HIV. It is also of relevance to recent reports that a growing number of viruses utilize polypeptides of the Ig supergene family as receptors.


'Ndongobacter massiliensis' gen. nov., sp. nov., a new bacterial genus isolated from a human urine sample after de novo kidney transplantation.
We report the main characteristics of 'Ndongobacter massiliensis' strain Marseille-P3170T (= CSUR P3170), which was isolated from the urine sample of a 37-year-old man who had just received a kidney transplant for genetic focal segmental glomerulosclerosis.


Inhibition of protein synthesis by N-methyl-N-nitrosourea in vivo.
1. The intraperitoneal injection of N-methyl-N-nitrosourea (100mg/kg) caused a partial inhibition of protein synthesis in several organs of the rat, the maximum effect occurring after 2-3h. 2. In the liver the inhibition of protein synthesis was paralleled by a marked disaggregation of polyribosomes and an increase in ribosome monomers and ribosomal subunits. No significant breakdown of polyribosomes was found in adult rat brains although N-methyl-N-nitrosourea inhibited cerebral and hepatic protein synthesis to a similar extent. In weanling rats N-methyl-N-nitrosourea caused a shift in the cerebral polyribosome profile similar to but less marked than that in rat liver. 3. Reaction of polyribosomal RNA with N-[(14)C]methyl-N-nitrosourea in vitro did not lead to a disaggregation of polyribosomes although the amounts of 7-methylguanine produced were up to twenty times higher than those found after administration of sublethal doses in vivo. 4. It was concluded that changes in the polyribosome profile induced by N-methyl-N-nitrosourea may reflect the mechanism of inhibition of protein synthesis rather than being a direct consequence of the methylation of polyribosomal mRNA.


Identification and characterization of a mouse cell mutant defective in the intracellular transport of glycoproteins.
We have isolated a mutant line of mouse L cells, termed gro29, in which the growth of herpes simplex virus (HSV) and vesicular stomatitis virus (VSV) is defective. The block occurs late in the infectious cycle of both viruses. We demonstrate that HSV and VSV enter gro29 cells normally, negotiate the early stages of infection, yet are impaired at a late stage of virus maturation. During VSV infection of the mutant cell line, intracellular transport of its glycoprotein (G protein) is slowed. Pulse-chase experiments showed that oligosaccharide processing is impeded, and immunofluorescence localization revealed an accumulation of G protein in a juxtanuclear region that contains the Golgi complex. We conclude that export of newly made glycoproteins is defective in gro29 cells, and speculate that this defect may reflect a lesion in the glycoprotein transport apparatus.


Spatial Resolution of Coherent Cathodoluminescence Super-Resolution Microscopy.
We investigate the nanoscale excitation of Ag nanocubes with coherent cathodoluminescence imaging spectroscopy (CL) to resolve the factors that determine the spatial resolution of CL as a deep-subwavelength imaging technique. The 10-30 keV electron beam coherently excites localized plasmons in 70 nm Ag cubes at 2.4 and 3.1 eV. The radiation from these plasmon modes is collected in the far-field together with the secondary electron intensity. CL line scans across the nanocubes show exponentially decaying tails away from the cube that reveal the evanescent coupling of the electron field to the resonant plasmon modes. The measured CL decay lengths range from 8 nm (10 keV) to 12 nm (30 keV) and differ from the calculated ones by only 1-3 nm. A statistical model of electron scattering inside the Ag nanocubes is developed to analyze the secondary electron images and compare them with the CL data. The Ag nanocube edges are derived from the CL line scans with a systematic error less than 3 nm. The data demonstrate that CL probes the electron-induced plasmon fields with nanometer accuracy.


Aptamers: problems, solutions and prospects.
Aptamers are short single-stranded oligonucleotides that are capable of binding various molecules with high affinity and specificity. When the technology of aptamer selection was developed almost a quarter of a century ago, a suggestion was immediately put forward that it might be a revolutionary start into solving many problems associated with diagnostics and the therapy of diseases. However, multiple attempts to use aptamers in practice, although sometimes successful, have been generally much less efficient than had been expected initially. This review is mostly devoted not to the successful use of aptamers but to the problems impeding the widespread application of aptamers in diagnostics and therapy, as well as to approaches that could considerably expand the range of aptamer application.


Experience-dependent specialization of receptive field surround for selective coding of natural scenes.
At eye opening, neurons in primary visual cortex (V1) are selective for stimulus features, but circuits continue to refine in an experience-dependent manner for some weeks thereafter. How these changes contribute to the coding of visual features embedded in complex natural scenes remains unknown. Here we show that normal visual experience after eye opening is required for V1 neurons to develop a sensitivity for the statistical structure of natural stimuli extending beyond the boundaries of their receptive fields (RFs), which leads to improvements in coding efficiency for full-field natural scenes (increased selectivity and information rate). These improvements are mediated by an experience-dependent increase in the effectiveness of natural surround stimuli to hyperpolarize the membrane potential specifically during RF-stimulus epochs triggering action potentials. We suggest that neural circuits underlying surround modulation are shaped by the statistical structure of visual input, which leads to more selective coding of features in natural scenes.


Sugar in mind: Untangling a sweet and sour relationship beyond type 2 diabetes.
It is widely recognised that type 2 diabetes (T2D) represents a major disease burden but it is only recently that its role in neurodegeneration has attracted more attention. This research has shown that T2D is associated with impaired cerebral health, cognitive decline and dementia. However, the impact on the brain of progressive metabolic changes associated with the pre-clinical development of the disease is less clear. The aim of this review is to comprehensively summarise how the emergence of risk factors and co-morbid conditions linked to the development of T2D impact cerebral health. Particular attention is directed at characterising how normal but elevated blood glucose levels in individuals without T2D contribute to neurodegenerative processes, and how the main risk factors for T2D including obesity, physical activity and diet modulate these effects. Where available, evidence from the animal and human literature is contrasted, and sex differences in risk and outcomes are highlighted.


A simultaneous assay method for L-glutamate and L-pyroglutamate contents in soy sauce using a 5-oxoprolinase (without ATP hydrolyzing activity).
L-Glutamine and L-glutamate, which are important flavor components in soy sauce, are converted to L-pyroglutamate during brewing. Therefore, it is necessary that the L-glutamate and L-pyroglutamate contents can be measured accurately. We developed a simultaneous assay method for L-glutamate and L-pyroglutamate by using 5-oxoprolinase (without ATP hydrolyzing activity) and glutamate oxidase. By this method, the L-pyroglutamate could be measured accurately in a range of 0.05 to 1.0 mM in the presence of 1.0 mM L-glutamate. This system is effective for process and quality controls.


The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers.
Unresolved issues with propofol include whether the pharmacokinetics are linear with dose, are influenced by method of administration (bolus vs. infusion), or are influenced by age. Recently, a new formulation of propofol emulsion, containing disodium edetate (EDTA), was introduced in the United States. Addition of EDTA was found by the manufacturer to significantly reduce bacterial growth. This study investigated the influences of method of administration, infusion rate, patient covariates, and EDTA on the pharmacokinetics of propofol. Twenty-four healthy volunteers aged 26-81 yr were given a bolus dose of propofol, followed 1 h later by a 60-min infusion. Each volunteer was randomly assigned to an infusion rate of 25, 50, 100, or 200 microg x kg(-1) x min(-1). Each volunteer was studied twice under otherwise identical circumstances: once receiving propofol without EDTA and once receiving propofol with EDTA. The influence of the method of administration and of the volunteer covariates was explored by fitting a three-compartment mamillary model to the data. The influence of EDTA was investigated by direct comparison of the measured concentrations in both sessions. The concentrations of propofol with and without EDTA were not significantly different. The concentration measurements after the bolus dose were significantly underpredicted by the parameters obtained just from the infusion data. The kinetics of propofol were linear within the infusion range of 25-200 microg x kg(-1) x min(-1). Age was a significant covariate for Volume2 and Clearance2, as were weight, height, and lean body mass for the metabolic clearance. These results demonstrate that method of administration (bolus vs. infusion), but not EDTA, influences the pharmacokinetics of propofol. Within the clinically relevant range, the kinetics of propofol during infusions are linear regarding infusion rate.


Early autoantibody screening for type 1 diabetes: a Kuwaiti perspective on the advantages of multiplexing chemiluminescent assays.
Type 1 diabetes (T1D) incidence has increased globally over the last decades, alongside other autoimmune diseases. Early screening of individuals at risk of developing T1D is vital to facilitate appropriate interventions and improve patient outcomes. This is particularly important to avoid life-threatening diabetic ketoacidosis and hospitalization associated with T1D diagnosis. Additionally, considering that new therapies have been developed for T1D, screening the population and individuals at high risk would be of great benefit. However, adopting such screening approaches may not be feasible due to limitations, such as cost, adaptation of such programs, and sample processing. In this perspective, we explore and highlight the use of multiplexing chemiluminescent assays for T1D screening and emphasize on their advantages in detecting multiple autoantibodies simultaneously, maximizing efficiency, and minimizing sample volume requirements. These assays could be extremely valuable for pediatric populations and large-scale screening initiatives, providing a cost-efficient solution with increased diagnostic accuracy and deeper insights into T1D pathogenesis. Eventually, the adoption of such screening methods can help transform T1D diagnosis, especially in countries with high T1D prevalence, such as Kuwait, which will contribute to the development of novel therapeutic interventions, positively impacting the lives of those affected by T1D and other autoimmune diseases.


Factors related to pre-operative cough strength in cardiac surgical patients: a cross-sectional study.
Pulmonary complications often arise from ineffective coughing, yet limited research exists on the determinants of cough strength in patients undergoing cardiac surgery. The aim is to explore preoperative cough strength in patients scheduled for cardiac surgery and identify factors associated with diminished cough strength. A cross-sectional study was conducted on 330 adult patients admitted for cardiac surgery at a tertiary Grade A hospital in Jiangsu Province, China between August 2022 and February 2023. Cough strength was assessed using cough peak flow, with values below 270 L/min classified as reduced cough strength. The study adhered to the STROBE guidelines. The study comprised 228 males (69.1 %) and 102 females (30.9 %), aged 23 to 81 years. Types of cardiac surgery included coronary artery bypass surgery, heart valvuloplasty, or heart valve replacement among others. The mean preoperative cough peak flow was 250.38 ± 119.71 L/min, with 60.3 % of patients exhibiting reduced cough strength. A multiple linear regression analysis identified gender, age, exercise regimen, pulmonary arterial hypertension, left ventricular ejection fraction, inspiratory capacity, and proficiency in coughing techniques as primary factors affecting cough strength. Our findings indicate an association between diminished cough strength and factors such as female gender, advanced age, absence of systematic exercise, presence of pulmonary arterial hypertension, lower left ventricular ejection fraction, reduced inspiratory capacity, and inadequate mastery of coughing techniques. Healthcare staff should prioritize regular assessment of cough strength and manage the pertinent factors to enhance preoperative coughing ability.


Caritas and job environment: a replication of Persky et al.
The purpose of this study was to replicate and expand on Persky, Nelson, Watson, and Bent (2008) study of characteristics related to nurses who were effective in Watson's Caritas framework. Previous research suggests that poorer work environments are associated with higher levels of caring. This surprising finding warrants further investigation. Registered nurses were recruited from a mid-sized community-based hospital in the Midwest portion of the United States of America (N = 20). Each completed the health environment survey (HES). Ten patients that had received primary care from the nurse completed the caring factors survey (CFS). Two hundred nurse/patient dyads were used to determine the relationship between the CFS and HES. Six of the 13 HES scales were positively associated with CFS scores. As nurses' positive perceptions of the work environment increased, patients' perceptions of caring increased. Our findings contrast Persky et al.'s. Further research is needed examining factors influencing the relationship between job environment and patient perceptions of caring.


The Dynamical Assessment of Inflammatory Biomarkers in Predicting the Outcome of Septic Patients and the Response to Antimicrobial Therapy.
To evaluate the kinetics of inflammatory biomarkers in septic patients in order to identify the most reliable predictor of unfavorable outcome. A prospective analysis of septic patients was performed. Median levels of neutrophil/lymphocyte count ratio, fibrinogen, C-reactive protein and procalcitonin were dynamically assessed and comparatively analyzed. Seventy-seven patients were included. Descendent kinetic patterns were registered for all biomarkers, except C-reactive protein. At 24 hours, neutrophil/lymphocyte count ratio significantly decreased in 42.85% of cases, procalcitonin in 37.33%, C-reactive protein in 16.12% and fibrinogen in 1.58% of cases. At 72 hours, procalcitonin decreased to one-half in 70% of cases and neutrophil/lymphocyte count ratio in 67.53% of cases. Neutrophil/lymphocyte count ratio and procalcitonin significantly decreased in the first 72 hours, while C-reactive protein increased in the first 24 hours. The proportions of patients with major decrease of baseline values were higher for neutrophil/lymphocyte count ratio and procalcitonin.


Ventilator-associated pneumonia in pediatric intensive care unit patients: risk factors and outcomes.
To determine the rates, risk factors, and outcomes of ventilator-associated pneumonia in pediatric intensive care unit (PICU) patients. A prospective cohort study was conducted at the St Louis Children's Hospital PICU on all patients who were admitted to the PICU from September 1, 1999, to May 31, 2000, except those who died within 24 hours, were > or =18 years of age, or were neonatal intensive care unit patients on extracorporeal membrane oxygenation. The primary outcome measured was the development of ventilator-associated pneumonia. Secondary outcomes were death and hospital and PICU length of stay. Multiple logistic regression analysis was performed to determine independent predictors for ventilator-associated pneumonia. There were 34 episodes of ventilator-associated pneumonia in 30 patients of 911 admissions (3.3%) and 595 (5.1%) mechanically ventilated patients. The mean ventilator-associated pneumonia rate was 11.6/1000 ventilator days. By logistic regression analysis, genetic syndrome (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.01-5.46), reintubation (OR: 2.71; 95% CI: 1.18-6.21), and transport out of the PICU (OR: 8.90; 95% CI: 3.82-20.74) independently predicted ventilator-associated pneumonia. Ventilator-associated pneumonia occurs at significant rates among mechanically ventilated PICU patients and is associated with processes of care. Additional studies are necessary to develop interventions to prevent ventilator-associated pneumonia.


GehB Inactivates Lipoproteins to Delay the Healing of Acute Wounds Infected with Staphylococcus aureus.
Staphylococcus aureus is one of the most prevalent bacteria found in acute wounds. S. aureus produces many virulence factors and extracellular enzymes that contribute to bacterial survival, dissemination, and pathogenicity. Lipase GehB is a glycerol ester hydrolase that hydrolyzes triglycerides to facilitate the evasion of S. aureus from host immune recognition. However, the role and mechanism of lipase GehB in skin acute wound healing after S. aureus infection remain unclear. In this study, we found that the gehB gene deletion mutant (USA300ΔgehB) stimulated significantly higher levels of pro-inflammatory cytokines in RAW264.7 and Toll-like receptor 2 (TLR2)-transfected HEK293 cells than the wild-type USA300 strain did. Recombinant GehB-His treated lipoprotein (Lpp) reduced stimulation of TLR2-dependent TNF-α production by RAW264.7 macrophages. GehB delayed the skin acute wound healing in BALB/c mice infected with S. aureus, while wound healing was similar in C57BL/6 TLR2-/- mice infected with either wild-type USA300 or USA300ΔgehB. In BALB/c mice, we also observed more bacterial survival, less leukocyte recruitment, lower IL-8 production, and adipocyte differentiation in USA300-infected skin acute wound tissues than those in USA300ΔgehB-challenged ones. Our data indicated that GehB inactivates lipoproteins to shield S. aureus from innate immune killing, resulting in delayed the healing of skin acute wounds infected with S. aureus.


[Interpretation of blood analysis data found after passive exposure to cannabis].
When defendants are confronted with evidence of cannabinoids in their blood suggesting consumption of cannabis they sometimes argue that this could only be due to a passive exposure. The small number of controlled studies available showed that tetrahydrocannabinol (THC), the active ingredient of cannabis, was actually found in the blood after passive exposure to cannabis smoke. The resulting blood concentrations were dependent on the applied THC doses and the size of the room in which the passive exposure occurred. However, the quantitative data indicated in the publications of the 1980s cannot be fully compared with the results of modern analytical methods. Due to the rapid distribution of THC in the body, which occurs also after passive exposure to low doses, the THC concentration in serum to be expected in a blood sample taken 1 hour after exposure is less than 1 ng/mL. For assessment of an alleged passive exposure, the metabolic THC-carboxylic acid, which is excreted more slowly, must also be taken into account. After passive exposure, similar and very low serum concentrations of THC and THC-carboxylic acid are to be expected (< 2 ng/mL), while higher blood levels suggest the deliberate consumption of a psychoactive dose.


Possibilities of the strong posterior wall of inguinal canal in women.
Three hundred and twenty-nine females aged 15-81 years (mean 51.5 years) and 1,928 males aged 17-76 years (mean 42.9 years) who presented with inguinal hernia over a ten-year period were reviewed. Combined ipsilateral direct = indirect (pantaloon) hernia appeared only from the fourth decade in both sexes with 7 (1.8 pc) and 111 (5.6 pc) cases occurring in females and males respectively. 3.5 pc of the total herniae in females and 18.6 pc in males were of primary direct type. 40 (12.2 pc) females and 270 (14 pc) males had bilateral hernia. There was a marked rise in the incidence of primary direct and bilateral hernia in males from the fourth and fifth decades. It is postulated that this is because defective collagen synthesis in the tissues of the inguinal region occurs more in males than in females.


Treatment of accidental hypothermia.
Hypothermia is an underreported cause of death in the United States. The clinical presentation of hypothermia may include neurologic, cardiovascular and metabolic abnormalities. In severely hypothermic patients, evaluation may reveal no signs of life until the patient is rewarmed. Treatment is directed at restoring normal body temperature and attending to fluid resuscitation, electrolyte disorders, cardiac arrhythmias and associated disease states or conditions. Groups at particular risk for hypothermia include outdoor workers, the homeless, trauma victims and the very young or very old. Also at risk are persons with preexisting serious illnesses and those who are taking medications or abusing drugs. Cardiac arrest, hypotension, unresponsiveness and severe hyperkalemia portend a poorer prognosis.


Telemedicine: the new must for surgery.
The vision of telesurgery comprises a multitude of new communicative elements influencing the way surgeons will treat their patients in the future. The first prerequisite for effective telecommunication is to digitize surgical data. Many medical imaging modalities provide primarily digital data sets, and digital image communication is already entering clinical practice under the labels of teleradiology and telepathology. However, for any surgical purpose, images must refer to tissues. Three-dimensional image reconstruction is warranted, and if such data shall be useful during surgery, different image sources must be combined into some virtual, multiparametric body model and matched to an intraoperatively distorted organ contour. A multitude of detail problems arise, beginning with image standards, data interfaces, data transport, image fusion, registering, contour matching, and, once the data are integrated, all the aspects of surgery-suitable data display and interaction. We refer here to several demonstration projects illustrating such a complex surgical data set and its interactive telecommunication. In all instances, telecommunication was to enable a concentration of distributed medical intelligence at the site where the patient was treated. With further technological development, such telesurgical applications will have a growing influence on patient management and surgical decision making. In the very near future, computer-aided navigation and robotic assistance, based on the same surgical data sets, will be available to all fields of surgery. How decisive the role these methods will play for specific procedures or diseases needs to be determined.


The COVID-19 pandemic and the challenge of using technology for medical education in low and middle income countries.
This article was migrated. The article was marked as recommended. The current use of technology for medical education in low and middle income countries (LMIC) during the COVID-19 pandemic is not yet reaching its potential. We provide recommendations for LMIC that has focus on a systematic framework that considers both faculty development and developing the skills of students. An enormous challenge for all medical educators, but especially in LMIC, continues to be how to maintain clinical teaching in these extraordinary times.


Microscopic and Molecular Identification of Cyclospora cayetanensis and Cystoisospora belli in HIV-Infected People in Tabriz, Northwest of Iran.
Opportunistic pathogens such as Cryptosporidium, Cystoisospora belli, and Cyclospora cayetanensis cause various gastrointestinal and non-digestive disorders in people with HIV/AIDS. These symptoms are especially severe in HIV-infected people who have a CD4+ count of less than 200 cells/mL. This study aimed to determine the prevalence of C. belli and C. cayetanensis infections among people living with HIV in Tabriz, northwest of Iran. This descriptive study was performed on 137 people with HIV who had been referred to behavioral disease counseling centers in Tabriz. Then, after receiving written consent, fecal samples were collected and evaluated for the detection of parasitic infections using direct methods and modified acid fast staining, as well as polymerase chain reaction (PCR).From the 137 fecal samples collected (98 males and 39 females, between 20 and 40 years old), 1.5% were positive for C. cayetanensis and 2.9% were positive for C. belli. Due to the prevalence of C. cayetanensis and C. belli in people with HIV in Tabriz, essential measures, including personal hygiene training for infection control and prevention, seem necessary.


[Radical prostatectomy. The surgical complications].
Study of 165 patients with prostate adenocarcinoma who underwent radical prostatectomy using a retropubic approach. Mean PSA is 19 ng/ml, mean age 63 years and median follow-up 26 months. 22 patients (13.2%) reported complications during the first month post-surgery, primarily urinary fistula of more than 5 days long in 5 patients and rectal injury in 3.49 patients (29%) reported complications after the first month, mainly urinary incontinence in 26 cases and stenosis of the urethrovesical juncture in 15. The group with early complications showed no significant differences compared to those who had none, neither in PSA (p = 0.3) or a worse pathological stage (p = 0.1), and no evidence is shown in terms of biochemical progression or in disease free progression (p = 1). Patients with urethrovesical juncture stenosis have higher mean PSA (p = 0.01), greater biochemical progression (p = 0.006), worse Gleason (p = 0.03 = and worse progression free survival (p = 0.01). Patients with stress incontinence showed no differences compared to the other groups relative to the studied factors.


Therapeutic Targets for Ankylosing Spondylitis - Recent Insights and Future Prospects.
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease belonging to the axial spondyloarthritis (axSpA), a group of diseases that affects the axial skeleton and causes severe pain and disability. An early diagnosis and appropriate treatment can reduce the severity of the disease and the risk of progression. TNF-α inhibitors demonstrated efficacy and effectiveness in axSpA patients by reducing disease activity, minimizing inflammation and improving the quality of life. More recently, new insights in pathogenesis of axSpA, including the discovery of the role of IL-23/IL-17 axis and intracellular pathways, led to the development of new biologics and small molecules that improve our therapeutic armamentarium. New alternatives are also being soon available. The aim of this paper is to narratively review the recent insights and future prospects in the treatment of AS and, more in general, axSpA.


Sensitivity and fidelity of DNA microarray improved with integration of Amplified Differential Gene Expression (ADGE).
The ADGE technique is a method designed to magnify the ratios of gene expression before detection. It improves the detection sensitivity to small change of gene expression and requires small amount of starting material. However, the throughput of ADGE is low. We integrated ADGE with DNA microarray (ADGE microarray) and compared it with regular microarray. When ADGE was integrated with DNA microarray, a quantitative relationship of a power function between detected and input ratios was found. Because of ratio magnification, ADGE microarray was better able to detect small changes in gene expression in a drug resistant model cell line system. The PCR amplification of templates and efficient labeling reduced the requirement of starting material to as little as 125 ng of total RNA for one slide hybridization and enhanced the signal intensity. Integration of ratio magnification, template amplification and efficient labeling in ADGE microarray reduced artifacts in microarray data and improved detection fidelity. The results of ADGE microarray were less variable and more reproducible than those of regular microarray. A gene expression profile generated with ADGE microarray characterized the drug resistant phenotype, particularly with reference to glutathione, proliferation and kinase pathways. ADGE microarray magnified the ratios of differential gene expression in a power function, improved the detection sensitivity and fidelity and reduced the requirement for starting material while maintaining high throughput. ADGE microarray generated a more informative expression pattern than regular microarray.