The importance of familiarity with caregiving for public caregiver stigma: Evidence from a cross-sectional study in Germany.
This study aimed to investigate the association between familiarity with caregiving and public stigma towards informal caregivers of older individuals. The sample for this Online-Survey was identified using a quota-system based on German micro census data (N=1037; aged 18 years and older, living in Germany). Familiarity with caregiving was assessed by asking whether the participant has experience in or has friends or relatives with experience in informal or professional caregiving for individuals aged 65 years or older. Public caregiver stigma was assessed by analyzing the emotional, behavioral and cognitive reactions towards caregivers as described in a vignette. Adjusted regressions analyses indicated that experience in providing informal care was associated with increased appreciative feelings and statements, and decreased social distance. Experience in providing professional care was associated with increased devaluing statements. Having friends or relatives who have experience in informal caregiving was associated with decreased social distance. Having friends or relatives who have experience in professional caregiving was associated with decreased devaluing feelings, increased appreciative feelings and decreased social distance. Results indicate that familiarity with caregiving, through one's own informal care experience or through contact with informal or professional caregivers, reduced public stigma towards informal caregivers. Moreover, experience with informal care or contact with professional caregivers increased appreciation of informal caregivers. However, increased negative stigmatizing statements were indicated among participants with experience in professional caregiving. Fostering contact and cooperation between informal caregivers and non-caregivers, as well as with professional caregivers may help reduce stigmatizing reactions.


[Effect of clonazepam and antiarrhythmic drugs on heart rate variability in patients with paroxysmal atrial fibrillation].
To study direction and intensity of autonomic changes in patients with paroxysmal atrial fibrillation (PAF) treated with clonazepam and their dynamics during antiarrhythmic therapy. Patients with nonrheumatic PAF during effective clonazepam monotherapy or ineffective antiarrhythmic therapy (n=95), untreated patients with PAF (n=22), healthy persons (n=10). Clinical cardiological and neurological examination, assessment of the state of autonomic nervous system, emotional sphere, patterns of sleep, and spectral analysis of heart rate variability (HRV). Effective monotherapy with clonazepam was associated with clinical and psychovegetative improvement, positive changes of autonomic tone and normalization of vegetative support of activity of patients with PAF. Analysis of HRV showed that ineffective (insufficiently effective) antiarrhythmic therapy was associated with stabilization of cardiac rhythm and domination of ergotropic activation which correlated with severity of psychovegetative syndrome. This could be considered as indication for supplementary use of clonazepam. Analysis of HRV confirmed expediency of the use of clonazepam in patients with PAF both as monotherapy and in combination with ineffective antiarrhythmic therapy.


Molecular beacon probes of photodamage in thymine and uracil oligonucleotides.
Molecular beacons (MB) are becoming more common as sequence-selective detectors of nucleic acids. Although they can easily detect single-base mismatches, they have never been used to directly detect DNA or RNA damage. To measure the degree of ultraviolet (UV) light damage in oligonucleotides, we report a novel MB approach for general detection of photoproducts in UV-irradiated rU17 and dT17 oligonucleotides. With monochromatic UV light irradiation at ca 280 nm under anoxic conditions, the oligonucleotide absorption decays with a single-exponential time constant of 123+/-1 min for rU17 and with double-exponential time constants of 78+/-0.5 min (99%) and 180+/-5 min (0.05%) for dT17 oligonucleotides. Under the same conditions, the MB fluorescence decays more quickly, with single-exponential time constants of 19+/-2 and 26+/-3 min for rU17 and dT17, respectively. Similar kinetics were observed with broadband UV light irradiation of oligonucleotides. The differences in the UV damage kinetics of dT17 and rU17 and their detection by absorption and fluorescence techniques will be discussed in the context of differential instabilities introduced in the nucleic acid-MB duplex by the different photoproducts formed.


Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.
DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.


EPIDEMIOLOGICAL DATA CONCERNING ONE YEAR OF A MALARIA SURVEILLANCE PILOT PROJECT IN SOUTHERN RHODESIA.
Few factual data have been published on the problem of disappearing malaria due to Plasmodium falciparum in Africa. In Southern Rhodesia a surveillance project has been under way since January 1961. The author describes malaria surveillance procedures, methods, organization and costs for the year 1962-63 and presents data relevant to a sparsely populated part of rural Africa where a surveillance visitor can cover a population of only some 3500 by monthly house-to-house visits. Through such visits, and through special surveys, an annual blood examination rate of 25% was achieved in the area at fairly low cost.It was found in the area studied, where 98% of infections are due to P. falciparum, that even Africans who have previously attained a high level of immunity will produce typical fever and associated malaria symptoms on reinfection after several years. Methods of case detection have proved adequately sensitive, despite the problem of asymptomatic carriers and despite the difficulty of obtaining true medical histories. Evidence is produced that much residual low-level transmission occurs indoors, although Anopheles gambiae are found in low density in human dwellings. Drug dosages and preventive treatment are described in detail; to reduce the number of asymptomatic carriers, single-dose presumptive treatment is advocated, at least in the last year of the attack phase. Many of the findings presented will be applicable to other African countries where malaria has been reduced to a low incidence.


The outcome of patients with hinge abduction in severe Perthes disease treated by shelf acetabuloplasty.
The management of patients with Perthes disease remains controversial. In children with hinge abduction and the potential for remodeling, we have performed a shelf acetabuloplasty, in an effort to contain the hip and allow remodeling. We report our medium-term results in a consecutive series of 27 children with severe Perthes disease and arthrographically proven hinge abduction. This is the first report in the English literature to look specifically at the results of treating patients with hinge abduction in severe Perthes disease by shelf acetabuloplasty. Twenty-seven consecutive children with unilateral Perthes disease and arthrographically proven hinge abduction were treated with a shelf acetabuloplasty. These patients have been prospectively reviewed with a clinical examination and radiographic assessment including Catterall, Salter Thompson, and Herring's lateral pillar classification. Radiological measurements included percentage acetabular cover, medial joint space, and femoral head size ratio. The mean postoperative follow-up was 62 months (range, 26-125 months). All patients were Catterall grade III or IV and lateral pillar grade B or C and had arthrographically proven hinge abduction at the time of surgery. At final follow-up, 14 hips were Stulberg grades 1 and 2; 10 hips, grade 3; and 3 hips, grades 4 and 5. The medial joint space decreased from a preoperative ratio of 1.9 to 1.4 (P = 0.002), and the percentage acetabular cover increased from 81% preoperatively to 97% postoperatively (P < 0.001). These results suggest overall good outcomes from a group of patients with severe Perthes disease as measured by the Stulberg grading when compared with historical controls. We suggest that shelf acetabuloplasty is a straight forward surgical procedure with good medium-term results in patients with severe Perthes disease who have proven hinge abduction preoperatively. Level IV case series.


Scarcity may promote cooperation in populations of simple agents.
In the study of the evolution of cooperation, resource limitations are usually assumed just to provide a finite population size. Recently, however, it has been pointed out that resource limitation may also generate dynamical payoffs able to modify the original structure of the games. Here we study analytically a phase transition from a homogeneous population of defectors when resources are abundant to the survival of unconditional cooperators when resources reduce below a threshold. To this end, we introduce a model of simple agents, with no memory or ability of recognition, interacting in well-mixed populations. The result might shed light on the role played by resource constraints on the origin of multicellularity.


Alveolar soft part sarcoma with brain metastases.
Metastatic tumors are the most common mass lesions in the brain. This case reports a rare form of sarcoma with metastasis to the brain. The appropriate management of a patient with metastatic alveolar soft part sarcoma to the brain is discussed. Author describes a 32-year-old gentleman diagnosed with primary tumor at gluteus and distant metastases at lower lobe of right lung and the brain. Histopathology proves diagnosis as alveolar soft part sarcoma. Craniotomy with excision of brain lesion was done. Repeated magnetic resonance imaging of the brain after 2 months showed rapidly growing new lesions. The next step of management was made by the oncology team as recurrence rate was high and due to multi-systemic involvement. Patient was planned for palliative chemotherapy and to be reassessed later. This case report discusses the appropriate approach to any form of brain metastases and the role of early follow-up especially after surgery for better outcome and choice of post operative management such as radiotherapy or chemotherapy or both for malignant tumors. Based on this report, it was concluded that every brain tumor patient should be frequently monitored even in the outpatient setting as most of them are metastatic and rapidly spreading. The patient should be considered for radiotherapy or chemotherapy or both after surgery if the histopathology result is suggestive of malignancy.


Fluorine-substituted benzothiadiazole-based hole transport materials for highly efficient planar perovskite solar cells with a FF exceeding 80.
Fluorine-substituted benzothiadiazole (BT) was introduced as a core structure to construct new hole transport materials. Planar perovskite solar cells with conventional materials (CH3NH3PbI3-xClx) were fabricated. The perovskite solar cells using monofluorinated BT exhibit a leading efficiency of 18.54% with a FF as high as 81%.


[Primary hyperparathyroidism in a patient with systemic lupus erythematosus].
Primary hyperparathyroidism (PHP) is a metabolic illness that results from autonomous secretion of parathyroid hormone and is one of the most common causes of hypercalcemia. We present the case of a 47-year-old female with a previous diagnosis of systemic lupus erythematosus (SLE) in whom clinical (diffuse bone pain, emotional lability, jaw tumor) and laboratory features (calcium= 13.5 mg/dL, phosphate= 1.8 mg/dL, alkaline phosphatase= 3028 U/L, PTH intact= 1472 pg/dL) prompted the diagnosis of PHP secondary to parathyroid adenoma as demonstrated by the anatomopathology. After treatment with calcitonin spray 400 UI per day, IV pamidronate 90 mg/week, and subtotal parathyroidectomy, the patient status improved with normal laboratory tests. This is the second report to describe the coexistence of these two disorders in a single patient. Although the pathophysiology of the association of PHP and SLE is not known, the recognition of this association has a practical implication since the therapeutical strategy is completely different.


Biological activity of recombinant human PDX1 protein produced from Escherichia coli.
Pancreatic and duodenum homeobox 1 (PDX1) is considered as a pivotal transcription factor that acts as a "master regulator" in pancreatogenesis and maintenance of β-cells. Earlier study has reported that PDX1 also functions as a tumor suppressor in human gastric cancer cells by inhibiting cell growth. Here, we report the bioactivity of the purified human PDX1 fusion protein using various assays like cell migration, proliferation, cell cycle analysis, and gene expression. In cancer cells, recombinant PDX1 protein reduced cell migration and proliferation, and arrested cell growth by inducing apoptosis in gastric cancer cells. In pancreatic ductal cancer cells, the application of the PDX1 protein resulted in the induction of insulin gene expression. The results of these experiments demonstrate the biological activity imparted by recombinant human PDX1 fusion protein on gastric and pancreatic cancer cells and its usefulness as a biological tool to elucidate its function in various cellular processes.


The importance of proximal and distal air bronchograms in the management of atelectasis.
Correlation of chest radiographic appearances with concurrent fibreoptic bronchoscopy in patients observed while in intensive care, and with lobar or multilobar atelectasis due to retained secretions, suggests that three levels of air bronchogram can be identified: Proximal: air is visible only to the level of the main bronchus, bronchus intermedius or lobar bronchi. Intermediate: air is visible down to the segmental bronchi. Distal: air is visible down to the subsegmental bronchi or beyond. Proximal or intermediate air bronchograms signify accumulation of secretions in central bronchi and indicate the need for fibreoptic bronchoscopy to aspirate secretions: a distal air bronchogram signifies peripheral bronchial obstruction thus precluding effective fibreoptic bronchoscopy; chest physiotherapy is then a more appropriate treatment. The proximal air bronchogram may change in extent or definition-sometimes rapidly; a receding or an increasingly poorly defined proximal air bronchogram are danger signals of centrally accumulating secretions which may lead to respiratory arrest.


A new non-centrosymmetric Gd-based borate crystal Rb7SrGd2(B5O10)3: growth, structure, and nonlinear optical and magnetic properties.
A new non-centrosymmetric borate crystal, Rb7SrGd2(B5O10)3, was successfully grown via the spontaneous nucleation technique from the Rb2O-B2O3-SrO self-flux system. It crystallizes in the trigonal system space group R32 with lattice parameters a = b = 13.4975(5) Å, c = 15.3223(8) Å, α = β = 90°, γ = 120°, and Z = 3. Its three-dimensional framework is composed of isolated GdO6 and SrO6 octahedra, RbOn (n = 6 and 8) polyhedra, and [B5O10]5- clusters. Rb7SrGd2(B5O10)3 exhibits multifunctional properties, and has both moderate second harmonic generation (SHG) responses (0.5 × KDP) and paramagnetic characteristics with μeff = 8.18μB. Thermal stability, Fourier transform infrared spectroscopy, and UV-Vis-NIR diffuse reflectance spectroscopy were performed to characterize the title compound. Its electronic band structures and density of states were also investigated via first-principles calculations.


Evidence for a force favoring GC over AT at short intronic sites in Drosophila simulans and Drosophila melanogaster.
Population genetics studies often make use of a class of nucleotide site free from selective pressures, in order to make inferences about population size changes or natural selection at other sites. If such neutral sites can be identified, they offer the opportunity to avoid any confounding effects of selection. Here, we investigate evolution at putatively neutrally evolving short intronic sites in natural populations of Drosophila melanogaster and Drosophila simulans, in order to understand the properties of spontaneous mutations and the extent of GC-biased gene conversion in these species. Use of data on the genetics of natural populations is advantageous because it integrates information from large numbers of individuals over long timescales. In agreement with direct evidence from observations of spontaneous mutations in Drosophila, we find a bias in the spectrum of mutations toward AT basepairs. In addition, we find that this bias is stronger in the D. melanogaster lineage than in the D. simulans lineage. The evidence for GC-biased gene conversion in Drosophila has been equivocal. Here, we provide evidence for a weak force favoring GC in both species, which is correlated with the GC content of introns and is stronger in D. simulans than in D. melanogaster.


Chronological metamorphosis of the auricular surface of the ilium: a new method for the determination of adult skeletal age at death.
A new method for the determination of adult skeletal age at death based upon chronological changes in the auricular surface of the ilium is presented. Formal stages have been constructed following extensive tests and refinements in observations made of such changes. Two completely "blind" tests were conducted to assess the accuracy and bias of the new method. Results show that the system is equally accurate to pubic symphyseal aging (although somewhat more difficult to apply), and also carries the advantages of a higher preservation rate for the auricular surface in archaeological populations and continued age-related change beyond the fifth decade.


Analysis of pattern reversal visual evoked potentials (PRVEP's) by spline wavelets.
In this study, the pattern-reversal visual evoked potentials (PRVEP's) collected from normal and demented subjects are investigated by applying the quadratic spline wavelet analysis. The data are decomposed into six octave frequency bands. For quantitative purposes, the wavelet coefficients in the residual waveform representing the delta-theta band activity (0-8 Hz) are explored to characterize the (N70-P100-N130) complex. Specifically, the coefficients corresponding to the location of N70, P100, and N130 peaks are investigated for their sign in order to test whether they represent a consistent (N70-P100-N130) complex in the averaged waveform. Waveforms with normal latency (N70-P100-N130) complex are observed to have positive second, negative third, and positive fourth coefficients in amplitude in their residual scale standing for the delta-theta (0-8 Hz) band activity. The method allows for the analysis of oscillatory-phase behavior of the normal and pathological PRVEP's in their delta-theta band based on a few quantitative measures consistent with the time-frequency occurrence of the major components of the evoked potential.


Cortical organization of environmental sounds by attribute.
Semantic knowledge is supported by a widely distributed neuronal network, with differential patterns of activation depending upon experimental stimulus or task demands. Despite a wide body of knowledge on semantic object processing from the visual modality, the response of this semantic network to environmental sounds remains relatively unknown. Here, we used fMRI to investigate how access to different conceptual attributes from environmental sound input modulates this semantic network. Using a range of living and manmade sounds, we scanned participants whilst they carried out an object attribute verification task. Specifically, we tested visual perceptual, encyclopedic, and categorical attributes about living and manmade objects relative to a high-level auditory perceptual baseline to investigate the differential patterns of response to these contrasting types of object-related attributes, whilst keeping stimulus input constant across conditions. Within the bilateral distributed network engaged for processing environmental sounds across all conditions, we report here a highly significant dissociation within the left hemisphere between the processing of visual perceptual and encyclopedic attributes of objects.


Maternal cell contamination of buccal smear samples in nursing neonates.
Buccal smear analysis is a non-invasive method which is being popularized by new fluorescence in situ hybridization (FISH) techniques. It is frequently used for gender identification and detection of sex chromosome aneuploidy in neonates. We attempted to determine whether or not buccal smears of nursing infants can be contaminated by maternal cells from breast feeding. FISH involving centromere specific directly labeled, multicolor probes for chromosomes X, Y and 18 were used for analysis of buccal smear samples. Buccal smear samples from 22 breast fed and 20 formula fed male neonates were analyzed in a blinded fashion. Twenty-seven percent of samples from breast fed infants had some (0.5-2.5%) XX signal pattern while the samples from formula fed infants had no XX signal pattern (difference statistically significant, p < 0.02, at 95% confidence interval). Our results indicate that breast feeding can cause maternal cell contamination of buccal smear samples that can lead to misinterpretation of results involving FISH analysis or other DNA based diagnostic studies. We have also modified the FISH technique to suit the neonates.


Smartphone-based recognition of states and state changes in bipolar disorder patients.
Today's health care is difficult to imagine without the possibility to objectively measure various physiological parameters related to patients' symptoms (from temperature through blood pressure to complex tomographic procedures). Psychiatric care remains a notable exception that heavily relies on patient interviews and self-assessment. This is due to the fact that mental illnesses manifest themselves mainly in the way patients behave throughout their daily life and, until recently there were no "behavior measurement devices." This is now changing with the progress in wearable activity recognition and sensor enabled smartphones. In this paper, we introduce a system, which, based on smartphone-sensing is able to recognize depressive and manic states and detect state changes of patients suffering from bipolar disorder. Drawing upon a real-life dataset of ten patients, recorded over a time period of 12 weeks (in total over 800 days of data tracing 17 state changes) by four different sensing modalities, we could extract features corresponding to all disease-relevant aspects in behavior. Using these features, we gain recognition accuracies of 76% by fusing all sensor modalities and state change detection precision and recall of over 97%. This paper furthermore outlines the applicability of this system in the physician-patient relations in order to facilitate the life and treatment of bipolar patients.


Metabolic fingerprinting of hard and semi-hard natural cheeses using gas chromatography with flame ionization detector for practical sensory prediction modeling.
Metabolic fingerprinting using gas chromatography with flame ionization detector (GC/FID) was used to generate a practical metabolomics-based tool for quality evaluation of natural cheese. Hydrophilic low molecular weight components, relating to sensory characteristics, including amino acids, fatty acids, amines, organic acids, and saccharides, were extracted and derivatized prior to the analysis. Data on 12 cheeses, six Cheddar cheeses and six Gouda cheeses, were analyzed by multivariate analysis. Prediction models for two sensory attributes relating to maturation, "Rich flavor" and "Sour flavor", were constructed with 4199 data points from GC/FID, and excellent predictability was validated. Chromatograms from GC/FID and gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) were comparable when the same column was used. Although GC/FID alone cannot identify peaks, the mutually complementary relationship between GC/FID and GC/MS does allow peak identification. Compounds contributing significantly to the sensory predictive models included lactose, succinic acid, L-lactic acid, and aspartic acid for "Rich flavor", and lactose, L-lactic acid, and succinic acid for "Sour flavor". Since similar model precision was obtained using GC/FID and GC/TOF-MS, metabolic fingerprinting using GC/FID, which is a relatively inexpensive instrument compared with GC/MS, is easy to maintain and operate, and is a valid alternative when metabolomics (especially using GC/MS) is to be used in a practical setting as a novel quality evaluation tool for manufacturing processes or final products.


Scanning electron microscopy of cartilage in mice with hereditary chondrodysplasia.
Mice born with hereditary, recessive chondrodysplasia (cho/cho) are dwarfed because the cartilage model upon which the endochondral osseous skeleton develops is defective. The mutant's cartilage matrix lacks cohesiveness which apparently contributes to the absence of columnar alignment of proliferating epiphyseal chondrocytes in developing tubular (long) bones. The present communication reviews our current understanding of skeletal dysplasia as it relates to defective chondrogenesis, and presents observations made with the scanning electron microscope of cellular disarray and nonuniform size and distribution of collagen fibrils which confirm the existence of a matrix defect. Autoradiographic experiments on tibial cartilage, similar to those performed on sternal cartilage, confirm the normal pattern of sulfate labeling by mutant epiphyses.


The shape of the metatarsal head as a cause of hallux abductovalgus.
The curvature of the 1st metatarsal head was evaluated on 100 radiographs by calculating the functional angle of the joint surface. This measure of curvature varied positively with the degree of hallux abductovalgus (HAV). Using measures of correlation it was found that in males, the association was linear (r2=0.39, p<0.001). In females, a linear relationship was identified only after logarithmic transformation of the data (r2=0.25, p<0.001). Comparison of the functional angle between males and females showed a significant difference (t=-5.03, df=98, p<0.001).


[Melatonin treatment of sleep disorders in disabled children].
There is a high prevalence of chronic sleep-wake cycle disorders in developmentally and neurologically disabled children. Such disorders are often resistant to hypnotic and psychotropic drugs. Administration of exogenous melatonin can have an effect upon the circadian rhythm and establish a normal sleep-wake cycle. Medline, Premedline and EBM Reviews were searched for articles on melatonin treatment of sleep-wake cycle disorders in children. Additionally, sleep was registered systematically in 15 developmentally or neurologically disabled children treated with melatonin. The search identified 75 articles of which 33 included neurologically or developmentally disabled children. Reported results generally indicate that melatonin improves sleep-wake cycle disorders in these children. However, the majority of studies were open, and knowledge about side effects and long-term effects is limited. Our own experience is in accordance with the literature; melatonin had positive effects in 13 children. Suggestions for practical use of melatonin in disabled children are presented.


C3b generation is affected by the structure of the O-antigen polysaccharide in lipopolysaccharide from salmonellae.
Salmonellae differing in the O-antigen side chain of their lipopolysaccharide were previously shown to activate the alternative pathway of complement to different extents. We now examine the generation of the major cleavage fragment of the complement component C3 (C3b) on these bacteria in a system that contains the purified components C3, B, D, and P but lacks the regulatory proteins H and I. The deposition of C3b in this system reproduces the same pattern obtained earlier with the use of whole serum, with the expected differences among the strains bearing different O-antigen. However, two distinct mechanisms for these differences in C3b generation became apparent. The intermediate activating strain showed 3 to 4 times less initial deposition of C3b than the other two strains. In contrast, the least activating strain showed adequate initial deposition but poor amplification, as shown by 2 to 3.4 lower amplification indexes as compared with those on the other two strains. Binding studies with factor B showed that decreased C3 convertase formation was responsible for the low amplification on this strain. Only 25% of the C3b bound to its surface was able to bind factor B with a high affinity, in comparison with 90% on the other two strains. No differences were found for the binding of factor H among the strains. These studies identify the molecular mechanisms by which these bacteria avoid complement activation.


Twitch contraction for identification of human muscle afferents.
A classical test to differentiate between Golgi tendon organs and muscle spindles is the twitch contraction elicited by electrical stimulation. The possibility of producing maximal twitches in the finger extensor muscles using surface stimulation over the muscle belly was investigated as well as the feasibility of the test in microneurography experiments. Electrical stimuli were applied either over the muscle in the forearm or the radial nerve in the upper arm, while the resulting torque output at single metacarpophalangeal joints was measured. The relationship between current intensity and maximal contraction force was determined and stimulus response plots were constructed over a large range of current intensities. Stimulation of the radial nerve always yielded plots with a steep and monotonous rising limb up to a plateau. It was concluded that the plateau represented maximal twitch contractions. With transcutaneous stimulation over the muscle belly, the stimulus response plots were usually more complex. However, this could be explained by force transmission through the intertendinous connections on the dorsum of the hand and by antagonist activation. It was concluded that maximal twitch contractions can readily be elicited in the human extensor digitorum muscle with nonpainful transcutaneous electrical stimulations. Moreover, maximal twitches are compatible with single unit recording from muscle afferents in microneurography experiments.


The cotton MAPK kinase GhMPK20 negatively regulates resistance to Fusarium oxysporum by mediating the MKK4-MPK20-WRKY40 cascade.
Fusarium wilt is one of the most serious diseases affecting cotton. However, the pathogenesis and mechanism by which Fusarium oxysporum overcomes plant defence responses are unclear. Here, a new group D mitogen-activated protein kinase (MAPK) gene, GhMPK20, was identified and functionally analysed in cotton. GhMPK20 expression was significantly induced by F. oxysporum. Virus-induced gene silencing (VIGS) of GhMPK20 in cotton increased the tolerance to F. oxysporum, whereas ectopic GhMPK20 overexpression in Nicotiana benthamiana reduced F. oxysporum resistance via disruption of the salicylic acid (SA)-mediated defence pathway. More importantly, an F. oxysporum-induced MAPK cascade pathway composed of GhMKK4, GhMPK20 and GhWRKY40 was identified. VIGS of GhMKK4 and GhWRKY40 also enhanced F. oxysporum resistance in cotton, and the function of GhMKK4-GhMPK20 was shown to be essential for F. oxysporum-induced GhWRKY40 expression. Together, our results indicate that the GhMKK4-GhMPK20-GhWRKY40 cascade in cotton plays an important role in the pathogenesis of F. oxysporum. This research broadens our knowledge of the negative role of the MAPK cascade in disease resistance in cotton and provides an important scientific basis for the formulation of Fusarium wilt prevention strategies.


Niastella koreensis gen. nov., sp. nov. and Niastella yeongjuensis sp. nov., novel members of the phylum Bacteroidetes, isolated from soil cultivated with Korean ginseng.
Two novel strains, GR20-10(T) and GR20-13(T), were isolated from soil using R2A medium. The soil sample was collected from a field in the Yeongju region of Korea that was cultivated with Korean ginseng. Phylogenetic analysis based on 16S rRNA gene sequences indicated that these strains formed a cluster with several uncultured bacterial clones and with Flexibacter filiformis, Flexibacter sancti, Flexibacter japonensis, Cytophaga arvensicola and Flavobacterium ferrugineum (recently reclassified as Terrimonas ferruginea) in the phylum Bacteroidetes. The level of 16S rRNA gene sequence similarity between the two novel strains was 98.9 %. Isolates GR20-10(T) and GR20-13(T) showed the highest sequence similarities to Flexibacter japonensis IFO 16041(T) (91.8 and 91.9 %, respectively) and T. ferruginea ATCC 13524(T) (90.4 and 90.6 %, respectively). The whole-cell fatty acid profiles of the two isolates were similar and their major fatty acids were 15 : 0 iso, 17 : 0 iso 3-OH and 15 : 1 iso G. The major isoprenoid quinone of both strains was MK-7. The G+C contents of GR20-10(T) and GR20-13(T) were 45.8 and 44.3 mol%, respectively. DNA-DNA hybridization (57 % DNA-DNA hybridization value) and phenotypic data indicated that strains GR20-10(T) and GR20-13(T) each belong to a separate species. On the basis of phenotypic and phylogenetic data and genomic distinctiveness, strains GR20-10(T) and GR20-13(T) represent two novel species in a novel genus in the phylum Bacteroidetes; the names Niastella koreensis gen. nov., sp. nov. (the type species; type strain GR20-10(T)=KACC 11465(T)=DSM 17620(T)) and Niastella yeongjuensis sp. nov. (type strain GR20-13(T)=KACC 11466(T)=DSM 17621(T)) are proposed.


Successful application of modified keystone flaps following skin tumor ablation.
Skin cancer and precancerous skin lesions cause significant soft-tissue defects following tumor ablation. Recently, keystone flaps have gained popularity due to their simplicity, versatility, and reliability.We evaluated the efficacy of modified keystone flaps for soft-tissue reconstruction following skin tumor ablation in 2 medical centers.We reviewed the medical records of patients who received modified keystone flaps following the removal of skin tumors from January 2017 to December 2017. The diagnosis, site, flap size, and complications were recorded.Forty-one modified keystone flaps were evaluated, and the wound dimensions ranged from 1 cm × 1 cm to 18 cm × 9.5 cm, with an average size of 9.8 cm × 6.4 cm. With our selection strategy, specific modified keystone flaps were designed for the soft-tissue defects. The flap dimensions ranged from 2.2 cm × 1 cm to 26 cm × 10 cm, with an average size of 14.3 cm × 7.5 cm. Two patients developed minor wound dehiscence (4.9%), and 1 patient developed partial flap loss (2.4%), but all of these patients healed after local wound care without the need for surgical intervention.Our selection strategy for modified keystone flaps is a feasible and reliable option for reconstruction following skin tumor excision.


Effective electron-density map improvement and structure validation on a Linux multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web Service.
Anticipating a continuing increase in the number of structures solved by molecular replacement in high-throughput crystallography and drug-discovery programs, a user-friendly web service for automated molecular replacement, map improvement, bias removal and real-space correlation structure validation has been implemented. The service is based on an efficient bias-removal protocol, Shake&wARP, and implemented using EPMR and the CCP4 suite of programs, combined with various shell scripts and Fortran90 routines. The service returns improved maps, converted data files and real-space correlation and B-factor plots. User data are uploaded through a web interface and the CPU-intensive iteration cycles are executed on a low-cost Linux multi-CPU cluster using the Condor job-queuing package. Examples of map improvement at various resolutions are provided and include model completion and reconstruction of absent parts, sequence correction, and ligand validation in drug-target structures.


Strategies used in post-operative pain assessment and their clinical accuracy.
Our knowledge about the content of strategies used by staff members in a surgical recovery unit for assessment of post-operative pain is fairly limited. The aim of the present study was to describe variations in the content of strategies used by nurses and physicians in practical clinical pain assessments and to evaluate the clinical accuracy of the strategies used. Critical care nurses (n = 30), physicians (n = 30) and postsurgical patients (n = 180) comprise the respondents. Applying a phenomenographical approach, interview data were tape-recorded during 180 clinical pain assessments. The pain assessments were related to comparative bedside pain ratings (Visual analogue Scale, VAS), both by staff members and post-operative patients. The recorded interviews were analysed to describe variations in ways of assessing pain. Pain assessment strategies were established by combining categories describing the impact of experience and categories of assessment criteria. The present observations, if included in the education of clinical staff members, could increase the understanding and thereby the quality of the pain assessment process.


Using Cell Phones for Data Collection: Benefits, Outcomes, and Intervention Possibilities with Homeless Youth.
While many homeless youth use cell phones to stay socially connected, and maintaining positive social ties can contribute to pathways out of homelessness, little is known about how using cell phones for data collection can improve these young people's lives. We conducted baseline and follow-up interviews with 150 homeless youth as well as provided them with a cell phone for 30 days to gather daily data using short message service (SMS) surveying. This paper examines youths' opinions about study participation and how they used the cell phone. Results revealed that youth liked participating in the study because the SMS texting portion, for example, made them feel that someone still cared about them, prompted them to self-reflect on their life, and allowed them to make a difference (e.g. educating the public about homelessness). Despite numerous benefits of study participation, improvements that youth discussed for future studies included changing the format of our text questions to allow for explanations and the use of higher quality phones. In terms of study phone usage, youth reported using the phone to schedule appointments, contact employers, and to keep in touch with family and friends. Finally, we highlight ways in which cell phones via SMS could be used with homeless youth to provide informational resources along with educational and employment opportunities, all of which are important intervention strategies in improving life situations for this population.


Decreased resting-state brain activity complexity in schizophrenia characterized by both increased regularity and randomness.
Schizophrenia is characterized by heterogeneous pathophysiology. Using multiscale entropy (MSE) analysis, which enables capturing complex dynamics of time series, we characterized MSE patterns of blood-oxygen-level-dependent (BOLD) signals across different time scales and determined whether BOLD activity in patients with schizophrenia exhibits increased complexity (increased entropy in all time scales), decreased complexity toward regularity (decreased entropy in all time scales), or decreased complexity toward uncorrelated randomness (high entropy in short time scales followed by decayed entropy as the time scale increases). We recruited 105 patients with schizophrenia with an age of onset between 18 and 35 years and 210 age- and sex-matched healthy volunteers. Results showed that MSE of BOLD signals in patients with schizophrenia exhibited two routes of decreased BOLD complexity toward either regular or random patterns. Reduced BOLD complexity toward regular patterns was observed in the cerebellum and temporal, middle, and superior frontal regions, and reduced BOLD complexity toward randomness was observed extensively in the inferior frontal, occipital, and postcentral cortices as well as in the insula and middle cingulum. Furthermore, we determined that the two types of complexity change were associated differently with psychopathology; specifically, the regular type of BOLD complexity change was associated with positive symptoms of schizophrenia, whereas the randomness type of BOLD complexity was associated with negative symptoms of the illness. These results collectively suggested that resting-state dynamics in schizophrenia exhibit two routes of pathologic change toward regular or random patterns, which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia.


FairSubset: A tool to choose representative subsets of data for use with replicates or groups of different sample sizes.
High-impact journals are promoting transparency of data. Modern scientific methods can be automated and produce disparate samples sizes. In many cases, it is desirable to retain identical or pre-defined sample sizes between replicates or groups. However, choosing which subset of originally acquired data that best matches the entirety of the data set without introducing bias is not trivial. Here, we released a free online tool, FairSubset, and its constituent Shiny App R code to subset data in an unbiased fashion. Subsets were set at the same N across samples and retained representative average and standard deviation information. The method can be used for quantitation of entire fields of view or other replicates without biasing the data pool toward large N samples. We showed examples of the tool's use with fluorescence data and DNA-damage related Comet tail quantitation. This FairSubset tool and the method to retain distribution information at the single-datum level may be considered for standardized use in fair publishing practices.


Distinct enzymatic properties of recombinant mouse DNA methyltransferases Dnmt3a and Dnmt3b.
Recombinant mouse Dnmt3a and Dnmt3b were expressed in sf9 cells and purified to near homogeneity. The purified Dnmt3a and Dnmt3b gave specific activities of 1.8 +/- 0.3 and 1.3 +/- 0.1 mol/h/mol enzyme towards poly(dGdC)-poly(dGdC), respectively, which were the highest among those reported. Dnmt3a or Dnmt3b showed similar K(m) values towards poly(dIdC)-poly(dIdC) and poly(dGdC)-poly(dGdC). The K(m) values for S-adenosyl-L-methionine were not affected by the methyl-group acceptors, poly(dI-dC)-poly(dIdC) and poly(dG-dC)-poly(dGdC). The results indicate that the enzymes are de novo-type DNA methyltransferases. Dnmt3a and Dnmt3b activities were inhibited by Mn(2+) and Ni(2+) and showed broad pH optima around neutral pH. Both enzymes were susceptible to sodium ions, which inhibited their activity at around physiological ionic strength. However, Dnmt3a was fully active at physiological potassium concentration, but Dnmt3b was not. Using designed oligonucleotides for the analysis of cytosine methylation, we demonstrated that, in addition to CpG, Dnmt3a methylated CpA but not CpT and CpC, and that Dnmt3b methylated CpA and CpT but scarcely CpC. The relative activity of Dnmt3b towards nonCpG sequences was higher than that of Dnmt3a. These differences in enzymatic properties of Dnmt3a and Dnmt3b may contribute to the distinct functions of these enzymes in vivo.


Ebola vaccination in the Democratic Republic of the Congo.
Following the April 2018 reemergence of Ebola in a rural region of the Democratic Republic of the Congo (DRC), the virus spread to an urban center by early May. Within 2 wk of the first case confirmation, a vaccination campaign was initiated in which 3,017 doses were administered to contacts of cases and frontline healthcare workers. To evaluate the spatial dynamics of Ebola transmission and quantify the impact of vaccination, we developed a geographically explicit model that incorporates high-resolution data on poverty and population density. We found that while Ebola risk was concentrated around sites initially reporting infections, longer-range dissemination also posed a risk to areas with high population density and poverty. We estimate that the vaccination program contracted the geographical area at risk for Ebola by up to 70.4% and reduced the level of risk within that region by up to 70.1%. The early implementation of vaccination was critical. A delay of even 1 wk would have reduced these effects to 33.3 and 44.8%, respectively. These results underscore the importance of the rapid deployment of Ebola vaccines during emerging outbreaks to containing transmission and preventing global spread. The spatiotemporal framework developed here provides a tool for identifying high-risk regions, in which surveillance can be intensified and preemptive control can be implemented during future outbreaks.


MeDEStrand: an improved method to infer genome-wide absolute methylation levels from DNA enrichment data.
DNA methylation of CpG dinucleotides is an essential epigenetic modification that plays a key role in transcription. Widely used DNA enrichment-based methods offer high coverage for measuring methylated CpG dinucleotides, with the lowest cost per CpG covered genome-wide. However, these methods measure the DNA enrichment of methyl-CpG binding, and thus do not provide information on absolute methylation levels. Further, the enrichment is influenced by various confounding factors in addition to methylation status, for example, CpG density. Computational models that can accurately derive absolute methylation levels from DNA enrichment data are needed. We developed "MeDEStrand," a method that uses a sigmoid function to estimate and correct the CpG bias from enrichment results to infer absolute DNA methylation levels. Unlike previous methods, which estimate CpG bias based on reads mapped at the same genomic loci, MeDEStrand processes the reads for the positive and negative DNA strands separately. We compared the performance of MeDEStrand to that of three other state-of-the-art methods "MEDIPS," "BayMeth," and "QSEA" on four independent datasets generated using immortalized cell lines (GM12878 and K562) and human primary cells (foreskin fibroblasts and mammary epithelial cells). Based on the comparison of the inferred absolute methylation levels from MeDIP-seq data and the corresponding reduced-representation bisulfite sequencing data from each method, MeDEStrand showed the best performance at high resolution of 25, 50, and 100 base pairs. The MeDEStrand tool can be used to infer whole-genome absolute DNA methylation levels at the same cost of enrichment-based methods with adequate accuracy and resolution. R package MeDEStrand and its tutorial is freely available for download at https://github.com/jxu1234/MeDEStrand.git .


Decreased expression of BATF2 is significantly associated with poor prognosis in oral tongue squamous cell carcinoma.
BATF2, also called SARI, is associated with several cancer types, and loss of BATF2 expression is frequently detected in aggressive and metastatic cancers. The expression of BATF2 was previously shown to slow the growth rate of malignant tumor cells injected into athymic nude mice, and decreased expression of BATF2 has been correlated to poor prognosis in hepatocellular carcinoma. However, the functional role of BATF2 in oral tongue squamous cell carcinoma (OTSCC) remains unknown. In the present study, we examined BATF2 expression in 16 fresh, paired OTSCC and adjacent non-tumor tissues, as well as in a normal tongue epithelial cell line and in 5 OTSCC cell lines by quantitative PCR and western blot analysis. We also evaluated BATF2 expression in 202 paraffin‑embedded OTSCC and 30 adjacent non-tumor samples by immunohistochemistry, and its relationship with clinicopathological features and prognosis was investigated. We found that BATF2 expression was significantly reduced in the majority of the 16 OTSCC tumor tissues and the 5 OTSCC cell lines when compared with the non-tumor tissues and the normal tongue epithelial cell line, respectively. Consistent with these results, our immunohistochemistry analysis revealed that decreased BATF2 expression was present in 124 of the 202 cases and was significantly correlated with poor tumor differentiation (P=0.002). Patients with decreased BATF2 expression showed reduced survival when compared to those with high expression (P<0.001). Multivariate analysis revealed that BATF2 expression is an independent predictor of overall survival (P=0.001). These results demonstrate that BATF2 plays a tumor-suppressor role in the development of OTSCC and that BATF2 may serve as a prognostic biomarker and potential therapeutic target for this disease.


Arabidopsis cockayne syndrome A-like proteins 1A and 1B form a complex with CULLIN4 and damage DNA binding protein 1A and regulate the response to UV irradiation.
In plants, as in animals, DNA is constantly subject to chemical modification. UV-B irradiation is a major genotoxic agent and has significant effects on plant growth and development. Through forward genetic screening, we identified a UV-B-sensitive mutant (csaat1a-3) in Arabidopsis thaliana, in which expression of CSAat1A, encoding a Cockayne Syndrome A-like protein, is reduced due to insertion of a T-DNA in the promoter region. Arabidopsis lacking CSAat1A or its homolog CSAat1B is more sensitive to UV-B and the genotoxic drug methyl methanesulfonate and exhibits reduced transcription-coupled repair activity. Yeast two-hybrid analysis indicated that both CSAat1A and B interact with DDB1A (UV-Damage DNA Binding Protein1). Coimmunoprecipitation assays demonstrated that CSAat1A and B associate with the CULLIN4 (CUL4)-DDB1A complex in Arabidopsis. A split-yellow fluorescent protein assay showed that this interaction occurs in the nucleus, consistent with the idea that the CUL4-DDB1A-CSA complex functions as a nuclear E3 ubiquitin ligase. CSAat1A and B formed heterotetramers in Arabidopsis. Taken together, our data suggest that the plant CUL4-DDB1A(CSAat1A and B) complex represents a unique mechanism to promote ubiquitination of substrates in response to DNA damage.


Monosaccharide transport across microvillous membrane of human placenta.
Transport through the microvillous membrane of the syncytium is the first step in placental transfer of nutrients. We have therefore studied glucose transport by isolated microvillous membrane vesicles. Transport occurred by selective and rapid facilitated diffusion, which was inhibited by phloridzin, phloretin, cytochalasin B, and HgCl2. Nonmediated diffusion of the substrate was found by three independent methods to be very slow. Competition studies showed that aldohexoses in the C-1 chair conformation were the preferred substrates. Transport was independent of sodium gradients and was not modulated by insulin. However, several steroids inhibited transport including estriol and progesterone, which are abundant in utero. Kinetic analysis by equilibrium exchange demonstrated a Km of 31 mM and a Vmax of 120 nmol . s-1 . mg protein-1. The Km and Vmax suggest a large capacity in relation to calculated fetal needs. In consequence of this capacity, intrasyncytial concentrations of glucose are probably maintained near those of maternal blood. Augmentation of transport at this membrane by hormones or other agents is unlikely to increase fetal supply of glucose, but down regulation by steroids may serve a regulatory function.


[Difficulties in defining and diagnosing gastroesophageal reflux: practical implications in surgery].
Today, it is difficult to set a correct definition and diagnosis of gastroesophageal reflux disease. The attempt to define it on the basis of "typical" symptoms, like heartburn and regurgitation, or "atypical" symptoms, like chronic cough, asthma, hoarseness and thoracic pain, or on the basis of endoscopic esophagitis presents notable difficulties. Moreover, the problem of a correct definition is tightly tied up to the ability to set a correct and early diagnosis. There are many diagnostics tools, but none of them is the golden standard. Today, the trend is to emphasize the role of the 24-hour pH-monitoring in diagnosing the reflux in those symptomatic patients with no visible esophagitis. However, its limit is to underline only the acid, not the duodenogastric alkaline reflux, which is also very important in the genesis of the inflammatory esophageal lesions. The esophageal manometry, however, evaluates only the mechanical state of the lower esophageal sphincter and the peristaltic function of the esophageal body but does not provide any direct information about the exposure of the esophagus to the gastric juice. The aim of this study is to analyze the problems concerning the definition and the diagnosis of the gastroesophageal reflux disease with particular attention to the practical implications on the common surgical practice, and to review some solutions reported in the literature for the difficult clinical approach to the patient with this pathology.


Comparative analysis of salivary glucose and electrolytes in diabetic individuals with periodontitis.
A high incidence of periodontal disease has been reported among diabetics, however the role of saliva in the occurrence of this oral disease in these patients is yet to be understood. To determine the effects of type-2 diabetes and periodontal disease on salivary flow rate and biochemical composition. A prospective study involving 40 adult human subjects divided equally into four groups of diabetics with periodontitis (group 1), diabetics without periodontitis (group 2), non diabetics with periodontitis (group 3) and non diabetics without periodontitis (group 4). Saliva samples were collected and analyzed for salivary glucose, total protein, calcium, sodium, potassium, chloride and bicarbonate. Salivary flow rates were also determined. Salivary glucose and potassium levels were significantly higher (P = 0.002 and 0.04 respectively) in diabetic patients regardless of periodontal disease (mean = 100.7 ± 9.33 mg/dl; 111.5 ± 32.85 mg/dl and 23.79 ± 5.19 mg/dl; 22.9 ± 6.25 mg/dl respectively) compared with non diabetic participants (mean = 80.5 ± 30.85 mg/ dl; 62.5 ± 31.89 mg/dl and 19.23 ± 5.04 mg/dl; 17.74 ± 4.68 mg/dl respectively). In contrast, there was no significant difference in saliva flow rates and levels of total protein, Na(+), Ca(++), Cl(-) and HCO3 (-)between the groups. Salivary glucose and potassium levels were significantly higher among diabetics with or without periodontitis compared with non-diabetics with or without periodontitis. However, biochemical composition of saliva in diabetic individuals has probably little role in their susceptibility to periodontitis.


A pilot intravenous cannulation team: an Irish perspective.
Peripheral intravenous cannulation (PIVC) is a potentially painful and distressing procedure for patients, and is traditionally carried out by medical personnel. A university hospital in Ireland was chosen to initiate a pilot intravenous (IV) cannulation team, to ascertain whether this procedure could be performed effectively by a team of nurses. The team was introduced to support the implementation of the European working time directive (EWTD). A team of four registered general nurses, led by a senior phlebotomist, provided PIVC. Request books were placed on each ward and data was recorded before and after each insertion. A constantly increasing percentage of first-time cannulation success is displayed from the first five months of the study. In-depth analysis on an orthopaedic ward reveal a preference for distal site insertion and routine change at 72 hours. IV teams performing IV cannulation can effectively reduce insertion rate attempts, and potentially offer a solution to the manpower issues arising as a result of implementation of the EWTD.


Factors Associated with Dietary Supplement Use among Preschool Children: Results from a Nationwide Survey in Japan.
This study was performed to reveal factors associated with dietary supplement use among Japanese preschool children in a nationwide survey. A cross-sectional, Internet survey was conducted among 2,058 mothers aged 20-40 y old who had preschool children and were registrants of a Japanese social research company in February 2013. The questionnaires assessed dietary supplement use, lifestyle and eating habits in both children and their mothers, eating awareness among mothers and the mothers' sources of health information. The study employed logistic regression analysis to evaluate the association between dietary supplement use and other variables. Dietary supplements were used by 8.0% of the children. Children who used supplements tended to be older in age, less likely to "get up cheerfully every morning," more likely to skip breakfast, eat out more frequently, and have mothers who used supplements, than children who did not use supplements. Mothers' level of education and household income were not associated with supplement use among their children. It is likely that mothers' anxiety about their children's health or unhealthy eating habits has a striking effect on supplement use among children. However, the actual dietary balance and daily rhythms of child supplement users were not irregular or unhealthy. It is necessary to give more accurate information on children's dietary habits and health to address mothers' anxiety.


An assessment of esophageal balloon use for the titration of airway pressure release ventilation and controlled mechanical ventilation in a patient with extrapulmonary acute respiratory distress syndrome: a case report.
Esophageal pressure measurement is a minimally invasive monitoring process that assesses respiratory mechanics in patients with acute respiratory distress syndrome. Airway pressure release ventilation is a relatively new positive pressure ventilation modality, characterized by a series of advantages in patients with acute respiratory distress syndrome. We report a case of a 55-year-old chilean female, with preexisting hypertension and recurrent renal colic who entered the cardiosurgical intensive care unit with signs and symptoms of urinary sepsis secondary to a right-sided obstructive urolithiasis. At the time of admission, the patient showed signs of urinary sepsis, a poor overall condition, hemodynamic instability, tachycardia, hypotension, and needed vasoactive drugs. Initially the patient was treated with volume control ventilation. Then, ventilation was with conventional ventilation parameters described by the Acute Respiratory Distress Syndrome Network. However, hemodynamic complications led to reduced airway pressure. Later she presented intraabdominal hypertension that compromised the oxygen supply and her ventilation management. Considering these records, an esophageal manometry was used to measure distending lung pressure, that is, transpulmonary pressure, to protect lungs. Initial use of the esophageal balloon was in a volume-controlled modality (deep sedation), which allowed the medical team to perform inspiratory and expiratory pause maneuvers to monitor transpulmonary plateau pressure as a substitute for pulmonary distension and expiratory pause and determine transpulmonary positive end-expiratory pressure. On the third day of mechanical respiration, the modality was switched to airway pressure release ventilation. The use of airway pressure release ventilation was associated with reduced hemodynamic complications and kept transpulmonary pressure between 0 and 20 cmH2O despite a sustained high positive end-expiratory pressure of 20 cmH2O. The application of this technique is shown in airway pressure release ventilation with spontaneous ventilation, which is then compared with a controlled modality that requires a lesser number of sedative doses and vasoactive drugs, without altering the criteria for lung protection as guided by esophageal manometry.


A theoretical analysis on characteristics of protein structures induced by cold denaturation.
Yeast frataxin is a protein exhibiting cold denaturation at an exceptionally high temperature (280 K). We show that the microscopic mechanism of cold denaturation, which has recently been suggested by us [Yoshidome and Kinoshita, Phys. Rev. E 79, 030905(R) (2009)], is also applicable to yeast frataxin. The hybrid of the angle-dependent integral equation theory combined with the multipolar water model and the morphometric approach is employed for calculating hydration thermodynamic quantities of the protein with a prescribed structure. In order to investigate the characteristics of the cold-denatured structures of yeast frataxin, we consider the entropy change upon denaturation comprising the loss of the water entropy and the gain in the protein conformational entropy. The minimum and maximum values of the conformational-entropy gain (i.e., the range within which the exact value lies) are estimated via two routes. The range of the water-entropy loss is then determined from the entropy change experimentally obtained [Pastore et al., J. Am. Chem. Soc. 129, 5374 (2007)]. We calculate the water-entropy loss upon the transition from the native structure to a variety of unfolded structures. We then select the unfolded structures for which the water-entropy loss falls within the determined range. The selection is performed at cold and heat denaturation temperatures of yeast frataxin. The structures characterizing cold and heat denaturations are thus obtained. It is found that the average values of the radius of gyration, excluded volume, and water-accessible surface area for the cold-denatured structures are almost the same as those for the heat-denatured ones. We theoretically estimate the cold denaturation temperature of yeast frataxin from the experimental data for the enthalpy, entropy, and heat-capacity changes upon denaturation. The finding is that the temperature is considerably higher than 273 K. These results are in qualitatively good accord with the experimental observations.


Functional analysis of flower development related gene GsLFY from Glycine soja.
LEAFY/FLORICAULA (LFY/FLO) is a family of plant-specific transcription factors, which plays an important role(s) in the regulation of floral organ formation and development. So far, LFY regulation on floral development in wild soybean has not been reported in the literature. In this study, the LFY gene, GsLFY, has been isolated from Glycine soja, and characterized with molecular and transgenic techniques. The cDNA for GsLFY gene is 1224 bp in length and contains an open reading frame encoding a polypeptide of 407 amino acids. Quantitative RT-PCR analysis shows that GsLFY is prominently expressed in various tissues, including roots, flowers and seeds. Among the four floral organs, GsLFY is expressed highly in sepals and stamens while weakly in the petals and carpels. Yeast two-hybrid experiments show that GsLFY possesses transactivation activity while transient expression analysis with Arabidopsis thaliana protoplasts shows that GsLFY protein is localized in the nucleus, supporting the notion that GsLFY is a transcription factor. The GsLFY transgenic tobacco plants flower about 29 days earlier than the wild-type plants, thereby providing a potential rationale for developing new soybean varieties with altered flowering time.


Prospective clinical trial of polyethylene fiber ribbon-reinforced, resin composite post-core buildup restorations.
The aim of this prospective clinical trial was to determine the outcome of polyethylene fiber ribbon-reinforced, resin composite post-and-core restorations used as endodontic buildups to support all-ceramic crowns. A total of 42 teeth (31 anterior, 11 posterior) with a mean follow-up time of 35.85 months (range, 10 to 73 months) were treated with 3-mm-wide polyethylene fiber ribbon-reinforced resin composite as post-and-core material. The posts and cores were assessed by clinical and radiographic examination. During the evaluation period, only 1 dentin-cement failure was observed as a post dislodgement after 11 months of clinical service. Performance of polyethylene fiber ribbon post and resin composite core foundation restorations provided clinically satisfactory support for all-ceramic crowns.


High expression of folate receptor alpha is associated with poor prognosis in patients with cervical cancer.
Folate receptor α (FRα) is a membrane protein expressed in various solid tumors but has limited expression in normal cells. Therefore, FRα is an attractive target for cancer treatment. This study aimed to investigate the relationship between FRα expression and the clinicopathological characteristics and survivals of cervical cancer. This retrospective study included patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. Immunohistochemical staining of FRα was performed using an anti-folate-binding protein/FBP antibody. FRα-positive staining was defined as ≥5% of tumor staining and FRα-high as ≥50% tumor staining with ≥2+ intensity. The association between FRα expression and survival was assessed using multivariate Cox regression analysis, adjusting for established prognostic factors. Overall, 123 patients were identified, and 140 tumor samples, including 17 paired primary and metastatic samples, were evaluated. As histological types, 67 patients had squamous cell carcinoma (SCC), and 56 patients had non-SCC. All primary tumors were FRα-positive. High FRα expression was observed in 25% of the cases and differed according to histology (SCC vs. non-SCC, 14.9% vs. 37.5%, p=0.004). FRα expression was significantly higher in metastatic tumors than in primary (170 [IQR, 140-205] vs. 125 [IQR, 110-150], p=0.0006). High FRα expression was significantly associated with worse overall survival (hazard ratio, 6.73; 95% confidence interval, 2.21-20.53; p=0.001). In cervical cancer, FRα expression was elevated in metastatic tumors and high expression was associated with a worse prognosis. Our study supports the development of FRα-targeted therapy for advanced cervical cancer.


"Salivary LINC00657 and miRNA-106a as diagnostic biomarkers for oral squamous cell carcinoma, an observational diagnostic study".
Early detection and diagnosis of malignant tumors is critical for improving the survival rate and treatment outcomes of oral cancer. Thus, the current prospective investigation was designed to verify the role, sensitivity, and specificity of salivary LINC00657 and miRNA-106a as diagnostic markers in oral squamous cell carcinoma patients as compared to oral lichen planus (as an example of oral potentially malignant disorders) and normal individuals, and to show LINC00657 relation to miR-106a. A total of 36 participants were included, subdivided into 3 groups: Group I: 12 patients diagnosed with oral squamous cell carcinoma (OSCC). Group II: 12 patients diagnosed with oral lichen planus (OLP). Group III: 12 systemically free individuals with no oral mucosal lesions. Unstimulated salivary samples were collected from all participants to evaluate level of LINC00657 and miR-106a in different groups using quantitative real-time PCR. OSCC showed the highest LINC00657 and lowest miR-106a fold change among included groups. Receiver Operating Characteristic (ROC) curve analysis of the two biomarkers for detecting OSCC revealed that LINC00657 had higher diagnostic accuracy (DA) (83.3%) compared to miR-106a (80.4%). As for detecting OLP, ROC analysis showed that miR-106a had higher (DA) (61%) compared to LINC00657 (52.5%). To discriminate OSCC from OLP, the diagnostic accuracy of both markers is the same (75%). Moreover, differentiating OSCC grades II and III, ROC analysis showed that miR-106a had lower (DA) (60%) compared to LINC00657 (DA) (83.3%). Salivary LINC00657 and miR-106a could be promising diagnostic markers for oral squamous cell carcinoma. Salivary LINC00657 may differentiate oral squamous cell carcinoma from oral potentially malignant disorders with considerable diagnostic accuracy. Moreover, low levels of salivary miR-106a could have the potential to indicate malignancy. The study was retrospectively registered on clinicaltrial.gov with NCT05821179 (first trial registration in 26/3/2023), date of registration: 19/4/2023.


Social experience modulates ocular dominance plasticity differentially in adult male and female mice.
Environmental factors have long been known to regulate brain plasticity. We investigated the potential influence of social experience on ocular dominance plasticity. Fully adult female or male mice were monocularly deprived for four days and kept a) either alone or in pairs of the same sex and b) either in a small cage or a large, featureless arena. While mice kept alone did not show ocular dominance plasticity, no matter whether in a cage or in an arena, paired female mice in both environmental conditions displayed a shift of ocular dominance towards the open eye. Paired male mice, in contrast, showed no plasticity in the cage, but a very strong ocular dominance shift in the arena. This effect was not due to increased locomotion, since the covered distance was similar in single and paired male mice in the arena, and furnishing cages with a running wheel did not enable ocular dominance plasticity in cage-housed mice. Confirming recent results in rats, the plasticity-enhancing effect of the social environment was shown to be mediated by serotonin. Our results demonstrate that social experience has a strong effect on cortical plasticity that is sex-dependent. This has potential consequences both for animal research and for human education and rehabilitation.


Cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg-1 in anaesthetized patients, paralysed with vecuronium.
We have studied, in adult patients, ASA I-II, the cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg-1. After induction, patients were paralysed with vecuronium and the trachea intubated. Heart rate (HR) and non-invasive mean arterial pressure (MAP) were measured every 1 min. After stabilization of HR and MAP, defined as < 3% change over three measurements, rocuronium (n = 20) or saline (n = 10) was injected at random. Mean HR increased initially from 66.6 to 72.1 beat min-1, 4 min after rocuronium, and then decreased gradually to 69.6 beat min-1, that is a net increase of 3.3 beat min-1 over 10 min (P < 0.001), whereas after saline there was a gradual decrease from 65.8 to 60.9 beat min-1 (P < 0.001) over 10 min. From the third minute, HR was significantly higher in the rocuronium group. Mean MAP decreased in both groups within 10 min to a similar extent after rocuronium and saline, that is from 74.9 to 72.1 mm Hg and from 74.7 to 72.2 mm Hg, respectively (both P < 0.001). There were no differences in MAP at any time between the rocuronium and saline groups. We conclude that an intubating dose of rocuronium, in the absence of haemodynamic effects related to paralysis itself, resulted in a limited increase in HR without change in MAP, probably because of its weak vagolytic activity.


Ipsilateral femoral head osteochondral transfers for osteochondral defects of the femoral head.
Osteochondral defects of the femoral head are rare. Several treatment options have been described, though there is currently no consensus on the appropriate management of these lesions. Five patients underwent femoral head osteochondral autograft transfer for treatment of ipsilateral femoral head osteochondral defects via surgical hip dislocation between 2011 and 2014 at our institution. The mean age of the patients was 24.8 (16-37) years. There were four females and one male. Mean follow-up was 53.8 (30-64) months. Four patients reported complete resolution of preoperative pain, return to baseline activities and were satisfied with their results. Harris hip scores improved from a mean 60.8 (30-87) to 86.6 (44-100). There was no radiographic evidence of progression of the femoral head defects. There were no operative complications. Osteochondral autograft transfer from the ipsilateral femoral head using a surgical hip dislocation demonstrated good clinical and radiographic outcomes at midterm follow-up in our cohort and may be considered a suitable option for management of these lesions in select patients. Further research and follow-up is warranted to more clearly define the indications and outcomes of this procedure.


End terminal, poly(ethylene oxide) graft layers: surface forces and protein adsorption.
Covalently grafted poly(ethylene oxide) coatings have been widely studied for use in biomedical applications, particularly for the reduction of protein and other biomolecule adsorption. However, many of these studies have not characterized the hydrated structure of the coatings. This new study uses a combination of silica colloid probe interaction force measurements using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) in order to determine the grafting density and hydrated layer structure of monomethoxy poly(ethylene oxide) aldehyde layers, covalently grafted onto amine plasma polymer surfaces, and their interactions with silica surfaces. For high grafting densities, purely repulsive interactions were measured as expected for densely grafted polymer brushes. These interactions could be described by theoretical expectations for compression of one polymer brush layer. However, at lower grafting densities, attractive interactions were observed at larger separation distances, originating from bridging interactions due to adsorption of the PEO chains on the surface of the silica colloid probe. This is a new finding indicating that the coupled PEO molecules have sufficient conformational freedom to interact strongly with an adjacent surface or, for example, protein molecules for which there is an affinity. The attractive interactions could be removed by grafting an additional PEO layer onto the silica colloid probe. Protein adsorption measurements confirmed that at high grafting densities, the amount of adsorbed protein on the PEO grafted surfaces was greatly reduced, to the order of the detection limit for the XPS technique.


Open reduction of C1-C2 subluxation with the use of C1 lateral mass and C2 translaminar screws.
Spinal cord compression secondary to a subluxation of one vertebral body over another can be achieved with reduction of the translational deformity. Intraoperative reduction of C1-C2 subluxations can be technically challenging when one uses traditional techniques (e.g., wiring and transarticular screw fixation). The popularization of C1 lateral mass and C2 pedicle screws has allowed surgeons to achieve a more complex realignment at this region of the spine. Control of both C1 and C2 with independent fixation can be used to obtain reduction. In certain instances, placement of C2 pedicle screws is not possible. The use of C2 translaminar screws (if the C2 lamina is present and suitable) is an alternative method of fixation in C2 and can be used for intraoperative reduction. A 15-year-old boy with juvenile rheumatoid arthritis presented with spinal cord compression secondary to a C1-C2 subluxation. The C2 pedicle anatomy precluded safe placement of C2 pedicle screws. An alternative method of fixation with the use of C2 translaminar screws and reduction was performed to obtain proper alignment and decompress the spinal cord. C1 lateral mass screws and C2 translaminar screws are inserted in the usual fashion. Two contoured rods, two rod holders, and two distractors, combined with C1 lateral mass screws and C2 translaminar screws, were used to achieve reduction. Concomitant distraction between the C2 translaminar screw head and the rod holder resulted in ventral translation of C2 on C1, decompressing the spinal cord. The reduction was maintained by tightening the C2 locking nut onto the rod. The use of C2 translaminar screws (if the C2 lamina is present and suitable) is an alternative method of fixation in C2. C1 lateral mass and C2 translaminar screw fixation provide a powerful means of reducing C1-C2 subluxations and maintaining alignment, achieving indirect decompression of the spinal cord.


PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulation: Applications in Rheumatic Autoimmunity.
Helper T cell activity is dysregulated in a number of diseases including those associated with rheumatic autoimmunity. Treatment options are limited and usually consist of systemic immune suppression, resulting in undesirable consequences from compromised immunity. Hedgehog (Hh) signaling has been implicated in the activation of T cells and the formation of the immune synapse, but remains understudied in the context of autoimmunity. Modulation of Hh signaling has the potential to enable controlled immunosuppression but a potential therapy has not yet been developed to leverage this opportunity. In this work, we developed biodegradable nanoparticles to enable targeted delivery of eggmanone (Egm), a specific Hh inhibitor, to CD4+ T cell subsets. We utilized two FDA-approved polymers, poly(lactic-co-glycolic acid) and polyethylene glycol, to generate hydrolytically degradable nanoparticles. Furthermore, we employed maleimide-thiol mediated conjugation chemistry to decorate nanoparticles with anti-CD4 F(ab') antibody fragments to enable targeted delivery of Egm. Our novel delivery system achieved a highly specific association with the majority of CD4+ T cells present among a complex cell population. Additionally, we have demonstrated antigen-specific inhibition of CD4+ T cell responses mediated by nanoparticle-formulated Egm. This work is the first characterization of Egm's immunomodulatory potential. Importantly, this study also suggests the potential benefit of a biodegradable delivery vehicle that is rationally designed for preferential interaction with a specific immune cell subtype for targeted modulation of Hh signaling.


Atrio-ventricular Block Following Neostigmine-Glycopyrrolate Reversal in Non-heart Transplant Patients: Case Report.
Neostigmine is the anticholinesterase drug most commonly used to reverse blockade or speed up recovery from neuromuscular blockade from nondepolarizing neuromuscular blocking drugs. Because of its cardiac muscarinic effects, prior or simultaneous administration of glycopyrrolate or atropine is usually recommended. There have been a few case reports of bradycardia, atrio-ventricular (AV) block, and cardiac arrest following neostigmine/glycopyrrolate administration to reverse neuromuscular block affecting several patients. In this report, we describe a case of 21-year-old with a history of seizure disorder and developmental delay that presented for dental surgery under general anesthesia and developed type I AV block following the simultaneous administration of neostigmine and glycopyrrolate to reverse a nondepolarizing neuromuscular block with rocuronium at the end of his surgery. We suggest that the chronic use of antiepileptic drugs in this patient in combination with neostigmine and glycopyrrolate lead to AV block in this patient. We also review similar cases reported in the literature and suggest an explanation for this observed phenomenon.


Environmental risk factors for amyotrophic lateral sclerosis: a case-control study in Canada and France.
Objective: To evaluate the association between amyotrophic lateral sclerosis (ALS) and potential environmental risk factors, especially head traumas and pesticides, in two populations from Canada and France.Methods: A case-control study was performed in tertiary-care centers. Consecutive ALS cases were recruited along with a control group from the same age distribution and region. Participants answered a phone-administered questionnaire. Head trauma exposure was censored at age of symptom onset, and a sensitivity analysis considering old head traumas that occurred more than 3 years before onset was performed. Univariate and multivariate logistic regression were used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs).Results: A total of 404 ALS cases and 381 controls completed the questionnaire. Previous head trauma was more frequently reported by cases (adjusted OR 1.50 (1.05-2.18)) with a dose-response relationship. This association was driven by a strong effect in men (adjusted OR 2.06 (1.22-3.55)) and was consistent for old traumas, but there was no association in women. For pesticides, a previous high-risk occupation was associated with ALS (adjusted OR 2.08 (1.36-3.24)), although reported occupational exposure to pesticides was not statistically significant in the multivariate model (adjusted OR 1.67 (0.97-2.97)). Past electrocution was associated with ALS (adjusted OR 1.79 (CI 1.13-2.87)), especially spinal-onset ALS. Residential exposure to pesticides, neck trauma, and welding were not associated with ALS.Conclusions: Head trauma is a risk factor for ALS in men only. Previous occupation at high risk for pesticides exposure and electrocution are also risk factors for ALS.


OASIS: an assessment tool of epidemiological surveillance systems in animal health and food safety.
The purpose of this study was to develop a standardized tool for the assessment of surveillance systems on zoonoses and animal diseases. We reviewed three existing methods and combined them to develop a semi-quantitative assessment tool associating their strengths and providing a standardized way to display multilevel results. We developed a set of 78 assessment criteria divided into ten sections, representing the functional parts of a surveillance system. Each criterion was given a score according to the prescription of a scoring guide. Three graphical assessment outputs were generated using a specific combination of the scores. Output 1 is a general overview through a series of pie charts synthesizing the scores of each section. Output 2 is a histogram representing the quality of eight critical control points. Output 3 is a radar chart representing the level reached by ten system attributes. This tool was applied on five surveillance networks.


An artificial neural network system to identify alleles in reference electropherograms.
Electropherograms are produced in great numbers in forensic DNA laboratories as part of everyday criminal casework. Before the results of these electropherograms can be used they must be scrutinised by analysts to determine what the identified data tells them about the underlying DNA sequences and what is purely an artefact of the DNA profiling process. This process of interpreting the electropherograms can be time consuming and is prone to subjective differences between analysts. Recently it was demonstrated that artificial neural networks could be used to classify information within an electropherogram as allelic (i.e. representative of a DNA fragment present in the DNA extract) or as one of several different categories of artefactual fluorescence that arise as a result of generating an electropherogram. We extend that work here to demonstrate a series of algorithms and artificial neural networks that can be used to identify peaks on an electropherogram and classify them. We demonstrate the functioning of the system on several profiles and compare the results to a leading commercial DNA profile reading system.


Effect of snoring and obstructive respiratory events on sleep architecture in adolescents.
To evaluate the effect of snoring and obstructive respiratory events on the distribution of sleep stages and arousals in a nonselected group of adolescents from the general population. Cross-sectional study. Randomly selected secondary schools in Seville, Spain. Patients A general population sample of 43 adolescents (mean [SD] age, 13.6 [1.77] years). A questionnaire for the investigation of sleep-related breathing disorders was administered. Symptoms were evaluated according to a 4-point frequency scale. Snorers answered "sometimes" or "often" to the question about snoring, and nonsnorers answered "never" or "rarely." All subjects underwent standard polysomnography at the sleep laboratory. Twenty-eight subjects were snorers; 15 were nonsnorers. No statistically significant differences were noted between both groups in the percentages of sleep stages, arousal index, awakenings, or wakefulness during sleep. Snorers showed a significantly higher number of respiratory arousals than nonsnorers (mean [SD], 1.14 [1.5] vs 0.33 [0.6], P<.05). However, neither the apnea-hypopnea index (AHI) nor the oxygen desaturation index correlated with the arousal index. Twelve snorers (27.5%) had an AHI of 2 or more; 13 nonsnorers (30.2%) had an AHI of less than 2. Snorers with some obstructive respiratory events had a significantly higher number of awakenings, a lower percentage of stage 4 sleep, and a higher number of respiratory events compared with nonsnorers. However, the total number of arousals and the arousal index were similar for both groups. Wakefulness during sleep tended to be longer in snorers than in nonsnorers although differences were not significant. The percentage of respiratory events that terminated with an arousal was greater in snorers who had an AHI of 2 or more than in nonsnorers who had an AHI of less than 2 (mean [SD], 8.4% [9.5%] vs 4.9% [11.53%], P<.05). These data indicate normal sleep architecture in the adolescents. Although snorers as well as adolescents with some polysomnographic abnormality showed a higher number of respiratory arousals than control subjects, most obstructive events did not terminate with a cortical arousal, which may suggest that adolescents share with younger children this mechanism for preserving sleep architecture.


Establishing a Multicolor Flow Cytometry to Characterize Cellular Immune Response in Chickens Following H7N9 Avian Influenza Virus Infection.
Avian influenza virus (AIV) emerged and has continued to re-emerge, continuously posing great threats to animal and human health. The detection of hemagglutination inhibition (HI) or virus neutralization antibodies (NA) is essential for assessing immune protection against AIV. However, the HI/NA-independent immune protection is constantly observed in vaccines' development against H7N9 subtype AIV and other subtypes in chickens and mammals, necessitating the analysis of the cellular immune response. Here, we established a multi-parameter flow cytometry to examine the innate and adaptive cellular immune responses in chickens after intranasal infection with low pathogenicity H7N9 AIV. This assay allowed us to comprehensively define chicken macrophages, dendritic cells, and their MHC-II expression, NK cells, γδ T cells, B cells, and distinct T cell subsets in steady state and during infection. We found that NK cells and KUL01+ cells significantly increased after H7N9 infection, especially in the lung, and the KUL01+ cells upregulated MHC-II and CD11c expression. Additionally, the percentages and numbers of γδ T cells and CD8 T cells significantly increased and exhibited an activated phenotype with significant upregulation of CD25 expression in the lung but not in the spleen and blood. Furthermore, B cells showed increased in the lung but decreased in the blood and spleen in terms of the percentages or/and numbers, suggesting these cells may be recruited from the periphery after H7N9 infection. Our study firstly disclosed that H7N9 infection induced local and systemic cellular immune responses in chickens, the natural host of AIV, and that the flow cytometric assay developed in this study is useful for analyzing the cellular immune responses to AIVs and other avian infectious diseases and defining the correlates of immune protection.


Coding algorithms for defining Charlson and Elixhauser co-morbidities in Read-coded databases.
Comorbidity measures, such as the Charlson Comorbidity Index (CCI) and Elixhauser Method (EM), are frequently used for risk-adjustment by healthcare researchers. This study sought to create CCI and EM lists of Read codes, which are standard terminology used in some large primary care databases. It also aimed to describe and compare the predictive properties of the CCI and EM amongst patients with hip fracture (and matched controls) in a large primary care administrative dataset. Two researchers independently screened 111,929 individual Read codes to populate the 17 CCI and 31 EM comorbidity categories. Patients with hip fractures were identified (together with age- and sex-matched controls) from UK primary care practices participating in the Clinical Practice Research Datalink (CPRD). The predictive properties of both comorbidity measures were explored in hip fracture and control populations using logistic regression models fitted with 30- and 365-day mortality as the dependent variables together with tests of equality for Receiver Operating Characteristic (ROC) curves. There were 5832 CCI and 7156 EM comorbidity codes. The EM improved the ability of a logistic regression model (using age and sex as covariables) to predict 30-day mortality (AUROC 0.744 versus 0.686). The EM alone also outperformed the CCI (0.696 versus 0.601). Capturing comorbidities over a prolonged period only modestly improved the predictive value of either index: EM 1-year look-back 0.645 versus 5-year 0.676 versus complete record 0.695 and CCI 0.574 versus 0.591 versus 0.605. The comorbidity code lists may be used by future researchers to calculate CCI and EM using records from Read coded databases. The EM is preferable to the CCI but only marginal gains should be expected from incorporating comorbidities over a period longer than 1 year.


Sonoelastography: musculoskeletal applications.
All participants for image samplings provided written informed consent. Conventional B-mode ultrasonography (US) has been widely utilized for musculoskeletal problems as a first-line approach because of the advantages of real-time access and the relatively low cost. The biomechanical properties of soft tissues reflect to some degree the pathophysiology of the musculoskeletal disorder. Sonoelastography is an in situ method that can be used to assess the mechanical properties of soft tissue qualitatively and quantitatively through US imaging techniques. Sonoelastography has demonstrated feasibility in the diagnosis of cancers of the breast and liver, and in some preliminary work, in several musculoskeletal disorders. The main types of sonoelastography are compression elastography, shear-wave elastography, and transient elastography. In this article, the current knowledge of sonoelastographic techniques and their use in musculoskeletal imaging will be reviewed.


Conditional data processing for single-shot spectral analysis by use of laser-induced breakdown spectroscopy.
Schemes of conditional data processing are evaluated based on either the peak-to-base ratio or the signal-to-noise ratio as a metric for analyte detection in single-shot laser-induced breakdown spectra. The analyte signal investigated is the 288.1-nm Si I emission line provided by an aerosol stream of monodisperse 2.5-microm-sized silica microspheres. Both the Si emission line and a spectral region corresponding to continuum emission are used to evaluate the statistical distribution of spectral noise. The probability of false hits is determined by evaluating various conditional processing thresholds. As the detection threshold increases, the rate of detected silica particle hits decreases along with the expected fraction of false-particle hits (i.e., spectral noise). For all threshold values the signal-to-noise ratio is found to provide a more robust metric for single-shot analyte detection compared with the peak-to-base ratio.


Preventive Effects of Collagen-Derived Dipeptide Prolyl-Hydroxyproline against Dexamethasone-Induced Muscle Atrophy in Mouse C2C12 Skeletal Myotubes.
Glucocorticoids, commonly used to manage inflammatory diseases, can induce muscle atrophy by accelerating the breakdown of muscle proteins. This research delves into the influence of Prolyl-hydroxyproline (Pro-Hyp), a collagen-derived peptide, on muscle atrophy induced with dexamethasone (DEX), a synthetic glucocorticoid, in mouse C2C12 skeletal myotubes. Exposure to DEX (10 μM) for 6 days resulted in a decrease in myotube diameter, along with elevated mRNA and protein levels of two muscle-atrophy-related ubiquitin ligases, muscle atrophy F-box (MAFbx, also known as atrogin-1) and muscle ring finger 1 (MuRF-1). Remarkably, treatment with 0.1 mM of Pro-Hyp mitigated the reduction in myotube thickness caused by DEX, while promoting the phosphorylation of Akt, mammalian target of rapamycin (mTOR), and forkhead box O3a (Foxo3a). This led to the inhibition of the upregulation of the ubiquitin ligases atrogin-1 and MuRF-1. These findings indicate the potential significance of Pro-Hyp as a promising therapeutic target for countering DEX-induced muscle atrophy.


Predictive value of regression rates following chemotherapy of small cell carcinoma of the lung.
Tumor volumes measured at the time of initial therapy, during the 28 days following treatment, and following subsequent courses of therapy for 29 patients with small cell carcinoma of the lung were determined from serially measurable roentgenographic lesions. Tumor-halving times were calculated following initial therapy, and the proportions of pretreatment tumor volumes were evaluated within 28 days after initial therapy for 26 patients. Pretreatment tumor volumes ranged from 22.5 to 485 cu cm, with a median of 87 cu cm, a log mean of 83 cu cm, and a linear mean of 113 cu cm. The tumor-halving times ranged from 4 to 86 days, with a median of 12 days, a log mean of 12 days, and a linear mean of 16 days. The reduction of tumor volume expressed as a proportion of pretreatment volume following therapy ranged between 0.02 and 0.65, with a median value of 0.22, a log mean of 0.18, and a linear mean of 0.26. Using the linear mean of 0.26 as a discriminant for survival analysis, patients with less than 0.26 had a median duration of survival of 12 months, which was significantly longer (p = 0.035) than the median survival of 8 months for patients with greater than 0.26. Tumor-halving time of 16 days was also able to separate the survival durations of 12 months of those less than 16 days compared to 8 months for greater than 16 days (p = 0.0429). Tumor regression rate, determined from two consecutive tumor volume measurements, was correlated with the tumor volume (r = 0.677; p less than 0.0001); and volume dependency of the tumor regression rate, as specified in Gompertzian kinetics, was demonstrated.


Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study.
Orthostatic hypotension has a prognostic role in determining cardiovascular and all-cause mortality. The aim of this study was to assess the prevalence of orthostatic hypotension and its association with blood pressure (BP) levels, arterial stiffness, cardiovascular and metabolic disorders and medication in individuals aged 80 years and over living in nursing home. In 994 individuals (77% women, mean age 88±5 years), the presence of orthostatic hypotension was tested according to American Autonomic Society and American Academy of Neurology guidelines. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV), peripheral to central pulse pressure amplification (PPA) and augmentation index. Cardiovascular and metabolic disorders as well as medications were recorded from patients' medical records. The prevalence of orthostatic hypotension was 18%. Treated hypertensive patients with SBP 140 mmHg or less had a lower prevalence of orthostatic hypotension than patients with SBP more than 140 mmHg (respectively, 13 vs. 23%; P < 0.001). Individuals with orthostatic hypotension exhibited higher brachial and central PP than individuals without orthostatic hypotension (respectively, 69±18 vs. 65±16 mmHg and 57±17 vs. 54±15 mmHg; P < 0.01). In these same individuals, a significant increase in augmentation index (31.1±14.0 vs. 27.2±13.6%; P < 0.01), but not in cf-PWV or in PPA, was observed. Individuals with orthostatic hypotension were treated more frequently with β-blockers and less frequently with angiotensin receptor blockers or nitrates than individuals without orthostatic hypotension (P < 0.05 for both). Contrary to the general belief, elderly individuals with well controlled BP (SBP < 140 mmHg) show lower orthostatic hypotension, thus constituting a complementary argument for efficaciously treating hypertension in these individuals.