Mortality in first 5 years in infants with functional single ventricle born in Texas, 1996 to 2003.
Infants with functional single ventricle have a high risk of death during the early years of life. Studies have reported improvement in postoperative survival, but they do not include preoperative deaths or those occurring before transfer. The purpose of this population-based study was to estimate 5-year survival in infants with functional single ventricle, to define factors associated with survival, and to estimate improvement in outcome. Patients with hypoplastic left heart syndrome, pulmonary atresia intact ventricular septum, single ventricle, and tricuspid atresia born in 1996 to 2003 were identified from the Texas Birth Defects Registry and linked to state and national birth and death vital records. We examined the effects of defect type, birth era, birth weight, gestational age, maternal race/ethnicity, extracardiac anomalies, sex, and maternal age and education on survival. Five-year survival varied by defect type: hypoplastic left heart syndrome, 38.0% (95% confidence interval, 32.6 to 43.5); single ventricle, 56.1% (95% confidence interval, 49.9 to 61.7); pulmonary atresia intact ventricular septum, 55.7% (95% confidence interval, 45.8 to 64.4); and tricuspid atresia, 74.6% (95% confidence interval, 62.4 to 83.4). The presence of extracardiac defects increased the adjusted risk of death by 84%. Non-Hispanic blacks had an adjusted risk of death that was 41% higher than that for non-Hispanic whites, and Hispanics had a 26% higher risk. Patients born in 2001 to 2003 had a 47% lower risk than those born in 1996 to 2000. This population-based study demonstrates significant improvement in overall 5-year survival, particularly in cases of hypoplastic left heart syndrome and single ventricle. Additional studies are needed to determine the factors causing racial/ethnic and regional differences in outcome.


Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic.
The mouse neurological mutant lethargic (lh) is characterized by ataxia, focal myoclonus, and absence epilepsy due to a loss-of-function mutation in the beta4 subunit of the voltage-gated calcium channel. To evaluate the role of this channel subunit in human neurological disease, we determined the chromosomal location and intron/exon structure of the human CACNB4 gene. The 1560-bp open reading frame of the CACNB4 cDNA predicts a 58-kDa protein with an amino acid sequence that is 99% identical to the rat protein. The 13 coding exons of CACNB4 span >55 kb of genomic DNA. Human cerebellar RNA contains one major CACNB4 transcript that is 9 kb in length. Expression of CACNB4 was detected in cerebellum, kidney, testis, retina, lymphoblasts, and circulating lymphocytes. Retinal transcripts were localized by in situ hybridization to ganglion cells and the inner nuclear layer. Analysis of the GeneBridge 4 radiation hybrid mapping panel localized CACNB4 to position 791 cR on human chromosome 2, in a conserved linkage group on human 2q22-q31 and mouse chromosome 2. We localized CACNB4 to the 1.3-Mb YAC clone 952F10 in Whitehead contig WC861, along with the polymorphic markers D2S2236 and D2S2299. The chromosomal linkage of three of the four beta subunit genes to homeobox gene clusters associates the evolutionary origin of the beta gene family with the events that generated the four HOX clusters early in vertebrate evolution.


Modeling glymphatic system of the brain using MRI.
The glymphatic system is functional waste clearance path from the brain parenchyma through dynamic exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF). Impairment of glymphatic waste clearance is involved in the development of neurodegenerative conditions. Despite many recent studies investigating the glymphatic system, few studies have tried to use a mathematical model to describe this system, quantitatively. In this study, we aim to model the glymphatic system from the kinetics of Gd-DTPA tracer measured using MRI in order to: 1) map the glymphatic system path, 2) derive kinetic parameters of the glymphatic system, and 3) provide quantitative maps of the structure and function of this system. In the proposed model, the brain is clustered to similar regions with respect to the profile of contrast agent (CA) density measured by MRI. Then, each region is described as a two-compartment kinetic model 'derived from' or 'clears to' its neighbors with local input function. We thus fit our model to the local cerebral regions rather than to the averaged time signal curve (TSC) of the whole brain. The estimated parameters showed distinctive differences between diabetes mellitus (DM) and control rats. The results suggest that in a typical DM brain the CSF bulk speed in the para-vasculature network is low. In addition, the resulting maps indicate that there may be increased binding and decreased absorbing of large molecules in a diabetic compared with a non-diabetic brain. The important contribution of this work was to fit the model to the local regions rather than to the averaged time signal curve (TSC) of the whole brain. This enabled us to derive quantitative maps of the glymphatic system from MRI.


Complicated deep venous insufficiency: conservative management.
An understanding of venous pathophysiology is helpful in managing deep venous insufficiency. Examination of the patient after standing for 10 minutes by searching for perforator tenderness and milking away the edema will reveal incompetent perforators. A sponge pump improves calf pumping and reduces local tissue damage from the systolic peak pressures of walking. It is an invaluable aid in treatment. The combination of high ligation of the superficial system and compression sclerotherapy for the perforators gives excellent control. Compression sclerotherapy can be readily repeated as necessary. Patients with severe deep venous insufficiency should always be advised to wear a surgical support stocking indefinitely.


The dyadic nature of bullying and victimization: testing a dual-perspective theory.
For this study, information on Who Bullies Who was collected from 54 school classes with 918 children (M age = 11) and 13,606 dyadic relations. Bullying and victimization were viewed separately from the point of view of the bully and the victim. The two perspectives were highly complementary. The probability of a bully-victim relationship was higher if the bully was more dominant than the victim, and if the victim was more vulnerable than the bully and more rejected by the class. In a bully-victim dyad, boys were more often the bullies. There was no finding of sex effect for victimization. Liking reduced and disliking increased the probability of a bully-victim relationship.


Effect of a hydroxyapatite tricalcium phosphate alloplast on osseous repair in the rat calvarium.
Bony defects caused by periodontitis are often treated by regenerative therapy using autografts and/or allografts. Alloplasts, such as hydroxyapatite or ceramics, are also used as osteoconductive materials that serve as a scaffold for new bony ingrowth. The purpose of this study was to determine the effect of hydroxyapatite tricalcium phosphate (HA-TCP) on osseous repair in the rat calvarium. Forty-four adult male Harlan Sprague-Dawley rats were assigned to one of four treatment groups: HA-TCP macroporous disk, HA-TCP microporous disk, HA-TCP granules, and demineralized freeze-dried bone (DFDB). The materials were placed into 8-mm calvarial critical-size defects (CSD). Calvariae were harvested at 10 weeks post-surgery and evaluated histomorphometrically. The DFDB group had significantly (P <0.05) more new bone formation (47%) than any other group. The HA-TCP macroporous disk group had significantly (P <0.05) more new bone formation (19.7%) than the HA-TCP microporous disk (8.5%) or HA-TCP granule (6.9%) groups. The HA-TCP macroporous disk may elicit significant new bone formation due to its rigid space-maintaining scaffold and pore size for vascular ingrowth. It is well tolerated by host tissues and may be a suitable carrier for growth factors.


Protein-binding of ascorbic acid 2. Interaction with acetylsalicylic acid.
The effect of aspirin (ASP) on the binding of ascorbic acid (AA) to bovine serum albumin (BSA) has been investigated by the method of dynamic dialysis. Scatchard plots were constructed which confirmed that binding with AA occurred in the presence of BSA. When ASP was also present, greater curvature of the plot was demonstrated indicating that less binding of AA to BSA was taking place. The limiting slopes of the plots showed that ASP displaces both primary and secondary sites previously occupied by AA and that the strengths of both primary and secondary sites increased as a result of interaction with ASP. It is concluded that primary sites for binding of AA to BSA consist of two or more types of similar binding strengths, and that secondary binding also may involve binding on two or more sites. The pathophysiological implications are discussed.


Electrophysiological Assessment of Newly Synthesized 2,3-Benzodiazepine Derivatives for Inhibiting the AMPA Receptor Channel.
Three major subtypes of ionotropic receptors regulate glutamatergic synaptic transmission, one of which is α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs). They are tetrameric, cation-permeable ionotropic glutamate receptors found across the brain. Abnormalities in AMPA receptor trafficking and synaptic assembly are linked to cognitive decline and neurological diseases such as Alzheimer's, Parkinson's, and Huntington's. The present study will investigate the effects of four novel 2,3-benzodiazepine derivatives on AMPA receptor subunits by comparing their effects on synaptic responses, desensitization, and deactivation rate in human embryonic kidney cells (HEK293T) recombinant AMPAR subunits using whole-cell patch-clamp electrophysiology. All four 2,3-BDZ compounds showed inhibitory activity against all the homomeric and heteromeric subunits tested. While the desensitization and deactivation rates in 2,3-BDZ-1 and 2,3-BDZ-2 decreased and increased, respectively, in the other two compounds (i.e., 2,3-BDZ-3 and 2,3-BDZ-4), there was no change in the desensitization or deactivation rates. These results contribute to a better understanding of AMPARs by identifying potential 2,3-BDZ drugs that demonstrate inhibitory effects on the AMPAR subunits.


Outcomes of total hip arthroplasty in calcium pyrophosphate deposition disease patients.
We aim to examine the demographics, clinical characteristics, outcomes, and resource utilization following total hip arthroplasty (THA) in patients with and without calcium pyrophosphate deposition (CPPD) disease. We queried the National Inpatient Sample database to identify patients who underwent THA between 2006 and 2014. The ICD-9 code 81.51 was used to determine the patients who underwent THA, and of those, we classified 2 groups of patients: (i) those with ICD-9 codes defining CPPD and (ii) those without any CPPD code. Data collection included patient demographics and comorbidities. Outcomes post-THA were mortality, length of stay (LOS), and costs. Associations between CPPD and specific morbidity were evaluated with chi-square tests. T tests were used for continuous variables. Among the 4,111,808 patients who underwent THA, 6198 (0.15 %) had CPPD, with a mean age of 77 years and 64.2 % were females. CPPD patients were more likely to be older (mean age 77 vs 72.7 years; p<0.001) than non-CPPD patients. The Charlson Comorbidity Index score ≥ 2 was more frequently seen in CPPD, however, the mortality post-THA was lower in the CPPD patients (0.7 % vs 1.7 %, OR 0.35, 95 % CI 0.26- 0.47). THA in CPPD patients was associated with a longer mean length of stay (LOS) (6.04 vs 5.15 days, OR 1.15, 95 % CI 1.09-1.22) while mean total charges were not statistically different between the 2 groups (p = 0.344). CPPD patients were more likely to be discharged to rehabilitation or other nursing facilities (42.5 % vs 35.3 %, p<0.001). The number of THA procedures increased in both CPPD and non-CPPD patients over time. CPPD patients who underwent THA were more likely to be older, with a greater comorbidity burden, longer LOS and discharged to a non-home setting.


Dysregulated COMT Expression in Fragile X Syndrome.
Transcriptional and proteomics analyses in human fragile X syndrome (FXS) neurons identified markedly reduced expression of COMT, a key enzyme involved in the metabolism of catecholamines, including dopamine, epinephrine and norepinephrine. FXS is the most common genetic cause of intellectual disability and autism spectrum disorders. COMT encodes for catechol-o-methyltransferase and its association with neuropsychiatric disorders and cognitive function has been extensively studied. We observed a significantly reduced level of COMT in in FXS human neural progenitors and neurons, as well as hippocampal neurons from Fmr1 null mice. We show that deficits in COMT were associated with an altered response in an assay of dopaminergic activity in Fmr1 null mice. These findings demonstrate that loss of FMRP downregulates COMT expression and affects dopamine signaling in FXS, and supports the notion that targeting catecholamine metabolism may be useful in regulating certain neuropsychiatric aspects of FXS.


Gating of local network signals appears as stimulus-dependent activity envelopes in striate cortex.
Neuronal activity often is treated as a composition of a stimulus-driven component and a second component that corrupts the signal, adding or deleting spikes at random. Standard quantitative methods such as peristimulus histograms and Fourier analysis use stimulus-locked averaging to enhance detection of the driven component of neuronal responses and de-emphasize the "noise." However, neural activity also includes bursts, oscillations, and other episodic events that standard averaging methods overlook. If this activity is stimulus independent, it can be characterized by standard power spectral analysis (or autocorrelation). But activity that is excited by (but not temporally locked to) the visual stimulus cannot be characterized by averaging or standard spectral analysis. Phase-locked spectral analysis (PLSA) is a new method that examines this "residual" activity-the difference between the individual responses to each cycle of a periodic stimulus and their average. With PLSA, residual activity is characterized in terms of temporal envelopes and their carriers. Previously, PLSA demonstrated broadband interactions between periodic visual stimuli and fluctuations in the local field potential of macaque V1. In the present study, single-unit responses (SUA) from parafoveal V1 in anesthetized macaque monkey are examined with this technique. Recordings were made from 21 neurons, 6 of which were recorded in pairs along with multiunit activity (MUA) from separate electrodes and 8 of which were recorded along with MUA from the same electrode. PLSA was applied to responses to preferred (orientation, direction, and spatial frequency) and nonpreferred drifting gratings. For preferred stimuli, all cells demonstrated broadband (1-10 Hz and higher) residual activity that waxed and waned with the stimulus cycle, suggesting that changes in the residual activity are introduced routinely by visual stimulation. Moreover, some reconstructed envelopes indicate that the residual activity was sharply gated by the stimulus cycle. Oscillations occasionally were seen in the power spectrum of single units. Phase-locked cross-spectra were determined for 3 SUA/SUA pairs and 11 SUA/MUA pairs. Residual activity in the cross-spectra was generally much less than the residual activity determined separately from each neuron. The reduction in the residual activity in the cross-spectra suggests that nearby neurons may gate inputs from distinct and relatively independent neuronal subpopulations that together generate the background rhythms of striate cortex.


A Ribbon Model for Nematic Polymer Networks.
We present a theory of deformation of ribbons made of nematic polymer networks (NPNs). These materials exhibit properties of rubber and nematic liquid crystals, and can be activated by external stimuli of heat and light. A two-dimensional energy for a sheet of such a material has already been derived from the celebrated neo-classical energy of nematic elastomers in three space dimensions. Here, we use a dimension reduction method to obtain the appropriate energy for a ribbon from the aforementioned sheet energy. We also present an illustrative example of a rectangular NPN ribbon that undergoes in-plane serpentine deformations upon activation under an appropriate set of boundary conditions.


Vasculitis of the internal carotid artery in Wegener's granulomatosis: comparison of ultrasonography, angiography, and MRI.
A 37-year old male with newly diagnosed, untreated Wegener's granulomatosis including glomerulonephritis, sinusitis, conjunctivitis, arthralgias, and positive cANCA, developed a pulsating tumor in the left submandibular region and a reversible ischemic neurologic deficit. Ultrasonography revealed both a hyperechoic wall thickening of the left proximal internal carotid artery as is known in Takayasu's arteritis and a surrounding hypoechoic region typical for perivasculitis. The wall thickening and the perivascular infiltrate could be less clearly seen by MRI. Ultrasonography, angiography, and MRI demonstrated a 3 cm long, 30%, stenosis. Angiography and MRI additionally found a more distally located kinking of the internal carotid artery that was missed by ultrasonography. Carotid artery vasculitis is a rare complication of Wegener's granulomatosis. In this case ultrasonography was superior to angiography and MRI to visualize the artery wall and the surrounding tissue, but it failed to evaluate the whole distance of the vessel.


Central adiposity after breast cancer diagnosis is related to mortality in the Health, Eating, Activity, and Lifestyle study.
We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants' waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over ~9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1: 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.


Pulse-Driven Semiconductor Gas Sensors Toward ppt Level Toluene Detection.
Improvements in the responses of semiconductor gas sensors and reductions in their detection limits toward volatile organic compounds (VOCs) are required in order to facilitate the simple detection of diseases, such as cancer, through human-breath analysis. In this study, we introduce a heater-switching, pulse-driven, micro gas sensor composed of a microheater and a sensor electrode fabricated with Pd-SnO2-clustered nanoparticles as the sensing material. The sensor was repeatedly heated and allowed to cool by the application of voltage to the microheater; the VOC gases penetrate into the interior of the sensing layer during its unheated state. Consequently, the utility factor of the pulse-driven sensor was greater than that of a conventional, continuously heated sensor. As a result, the response of the sensor to toluene was enhanced; indeed, the sensor responded to toluene at levels of 1 ppb. In addition, according to the relationship between its response and concentration of toluene, the pulse-driven sensor in this report can detect toluene at concentrations of 200 ppt and even lower. Therefore, the combination of a pulse-driven microheater and a suitable material designed to detect toluene resulted in improved sensor response, and facilitated ppt-level toluene detection. This sensor may play a key role in the development of medical diagnoses based on human breath.


Value of IL28B genotyping in patients with HCV-related mixed cryoglobulinemia: results of a large, prospective study.
HCV-related mixed cryoglobulinemia (MC) is characterized by clonal expansion of B cells producing a polyreactive natural antibody (rheumatoid factor) and interferon (IFN)-based therapy is the first therapeutic option in mild-moderate MC. Single nucleotide polymorphisms (SNPs) proximal to genes involved in the innate response (IL28B/IFN-λ gene family) are strongly associated with spontaneous and IFN-induced viral clearance in hepatitis C, but no data exist about their role in HCV-positive MC. A large cohort of patients with HCV and MC was studied to evaluate the influence of IL28B genotype on the response to treatment and/or the evolution to MC of HCV infection. The rs12979860/rs8099917 IL28B polymorphisms were analysed in 481 consecutive HCV-positive subjects (250 with MC and 231 without MC, as controls) using real-time PCR and direct sequencing. Hundred and fifteen HCV patients with MC received standard anti-HCV therapy, and the results were evaluated according to the IL28B SNP distribution. Similar IL28B SNPs allele frequencies were recorded for patients and controls. IL28B major allele homozygosis (for both SNPs tested) was tightly correlated with virological and clinical response (P = 0.002). A statistically significant association was limited to 'difficult-to-treat' (G1/4) HCV genotypes. The IL28B genotype was a strong independent predictor of response (P = 0.007, OR 6.06; CI 1.65-22.22). The IL28B genotype was confirmed to be a useful predictor of response to IFN-based therapy in patients with HCV and MC. The very close correlation between IL28B SNP distribution, virological and clinical response definitively confirmed the key role played by HCV in MC. Conversely, the IL28B genotype does not seem to influence the evolution to MC.


FELASA guidelines and recommendations.
The Federation of European Laboratory Animal Science Associations (FELASA) has been releasing guidelines and recommendations on several laboratory animal science disciplines for more than 15 y. The Working Groups producing these documents comprise specialists in each of the addressed topics, are nominated by the FELASA constituent associations, and are elected by the FELASA Board of Management. The FELASA guidelines and recommendations are not regulatory but rather are proposals based on scientific knowledge and the state of the art of laboratory animal science activities. Because they are supported by laboratory animal science associations that represent the vast majority of European professionals, these guidelines and recommendations have influenced the development of various regulatory requirements in Europe, including those related to education and training, routine laboratory animal activities, and animal health monitoring. Some reports fill existing gaps in the European legal framework or complement it. The Working Groups occasionally collaborate with other European organizations, thus enhancing the professional input and effect of the documents produced. The recently established AALAS-FELASA Liaison Body may result in future international cooperation that benefits laboratory animal science and welfare in a global context.


Effects of stem cells and granulocyte colony stimulating factor in reperfusion injury.
Bone marrow-derived stem cells have a potential capacity to differentiate and accelerate recovery in injured sites of body. Also, factors like granulocyte colony stimulating factor (GCSF) can promote their mobilization to the injured sites. We aimed to investigate the role of GCSF as an alternative therapeutic option instead of mesenchymal stem cells (MSCs) in reperfusion injury. Twenty-nine rats with induced reperfusion injury were divided into 3 groups to receive MSC, GCSF, or nothing (control). Kidney function was assessed by blood urea nitrogen and serum creatinine levels. Histological grading was performed to evaluate the extent of tubular injury and the rate of recovery. All the rats reached recovery after 14 days. Rats in the MSC group reached early functional and histological recovery compared to the controls on the 7th day of the study (P = .01 and P = .02, respectively). Compared to the control group, the GCSF group showed a more significant histological recovery on the 7th day (P = .04), but kidney function was ameliorated on the 14th day (P = .04). Both the GCSF and control groups had a significant number of CD34+ cells, which were detected by flow cytometry on the 7th day after reperfusion injury. We found therapeutic effects following administration of both MSC and GCSF which was more evident with MSC in the setting of reperfusion injury. More investigation is required to find optimal time, dose, and route of administration as well as other possible contributing factors.


DNA barcoding for the identification of mold species in bakery plants and products.
Mold identification at the species level in environmental samples is a major challenge. Molecular techniques have been widely used for fungal classification, but as most primers are genus-specific, it is laborious to identify unknown samples. In this study, a PCR-based method for the identification of mold at the species level was developed. Therefore, common sequencing primers and combinations of them, targeting specific DNA regions, were tested. Here we present a combination of eight primer pairs to identify mold within a single PCR run. The approach correctly identified mold of unknown species from samples taken at a local bakery, including Penicillium chrysogenum, Penicillium citrinum, Cladosporium sphaerospermum, Paecilomyces formosus, Rhizopus oryzae and Aspergillus niger. Results obtained from the PCR method were successfully validated by chromatographic mycotoxin and microscopy analysis. Findings highlight DNA barcoding as an appropriate tool for mold identification; however, its efficacy is essentially dependent on DNA quality and primer selection.


Unrecognised myocardial infarction and long-term risk of heart failure in the elderly: the Rotterdam Study.
To examine the association between unrecognised myocardial infarction (MI) as detected by electrocardiography and the long-term risk of heart failure. The Rotterdam Study is a prospective population-based cohort study of the general population of a suburb of the city of Rotterdam, The Netherlands. At baseline 2581 men and 3724 women aged > or =55 years were classified on the basis of electrocardiography, interview and clinical data into those with recognised MI, those with ECG-based unrecognised MI and those without MI. The participants were followed-up for incident heart failure, death or end of the study period on 12 October 2006. During a median follow-up time of 13.2 years, 823 cases of heart failure occurred, of which 403 in men. Independently of cardiovascular risk factors, recognised and unrecognised MIs yielded HRs of developing heart failure in men of 2.6 (95% CI 2.0 to 3.3) and 2.1 (95% CI 1.5 to 2.9), respectively. In women, recognised MI was associated with heart failure (HR=2.8; 95% CI 1.9 to 4.1), whereas unrecognised MI was not significantly related to the risk of heart failure (HR=1.1; 95% CI 0.7 to 1.7). Unrecognised MI detected by electrocardiography yields a long-term risk of heart failure equivalent to recognised MI in men, but is not significantly related to heart failure in women. In the light of the high incidence of both unrecognised MI and heart failure in the elderly, it may be worthwhile for both doctors and patients to improve responsiveness to typical and atypical symptoms of MI.


Elucidating the functional role of human ABHD16B lipase in regulating triacylglycerol mobilization and membrane lipid synthesis in Saccharomyces cerevisiae.
Lipids are essential biological macromolecules that play a pivotal role in various physiological processes and cellular homeostasis. ABHD16B, a member of the α/β-hydrolase domain (ABHD) superfamily protein, has emerged as a potential key regulator in lipid metabolism. However, the precise role of human ABHD16B in lipid metabolism remains unclear. In this study, we reported the overexpression of ABHD16B in Saccharomyces cerevisiae to determine its physiological relevance in lipid metabolism. Through in vivo [14C]acetate labeling experiments, we observed that overexpression of ABHD16B causes a decrease in cellular triacylglycerol (TAG) levels and a concurrent increase in phospholipid synthesis in wild-type cells. Mass spectrometry (LC-MS/MS) analysis further corroborated these findings, showing a significant decrease in TAGs with a carbon chain length of 48 and an increase in major phospholipid species, specifically 34:2, upon overexpression of ABHD16B. Confocal microscopy analysis revealed a reduction in the number of lipid droplets in strains overexpressing ABHD16B, consistent with the observed decrease in neutral lipids. Additionally, qRT-PCR analysis indicated a high phospholipid synthetic activity of ABHD16B and a potential decrease in TAG levels in wild-type yeast, possibly due to upregulation of endogenous TAG hydrolytic enzymes, as confirmed using 3tglsΔ mutant strain. Furthermore, GC-MS analysis revealed significant modifications in fatty acid composition upon ABHD16B overexpression. Collectively, our results underscore the influence of ABHD16B overexpression on TAG levels, phospholipid synthesis, lipid droplet dynamics, and fatty acid composition. These findings reveal a complex interplay between TAG hydrolysis and phospholipid synthesis, highlighting the critical involvement of ABHD16B in lipid homeostasis and providing further insights into its regulatory function in cellular lipid metabolism.


Bacterial communities associated with retail alfalfa sprouts.
Fresh produce, including salad, is increasingly implicated in foodborne outbreaks. Although studies have been carried out to detect specific human pathogens from fresh produce, the total bacterial community associated with fresh produce is poorly understood. In this study, we characterized the bacterial community associated with alfalfa sprouts, using a culture-independent method. Four retail-purchased alfalfa sprout samples were obtained from different producers, and the bacterial community associated with each sample was determined by 16S rDNA profiling. Our results indicate that alfalfa sprouts sampled in our study shared significant similarities in their bacterial communities. Proteobacteria was the dominant phylum detected from all alfalfa sprout samples, with Enterobacteriaceae, Oxalobacteraceae, Moraxellaceae, and Sphingomonadaceae as the most frequently detected families. These results indicate that growth conditions of alfalfa sprouts should be taken into consideration to prevent the proliferation of pathogenic proteobacteria such as Escherichia coli O157 and Salmonella.


Changes in acetylcholinesterase activity and muscarinic receptor bindings in mu-opioid receptor knockout mice.
Anatomical evidence indicates that cholinergic and opioidergic systems are co-localized and acting on the same neurons. However, the regulatory mechanisms between cholinergic and opioidergic system have not been well characterized. In the present study, we investigated whether there are compensatory changes of acetylcholinesterase activity and cholinergic receptors in mice lacking mu-opioid receptor gene. The acetylcholinesterase activity was determined by histochemistry assay. The cholinergic receptor binding was carried out by quantitative autoradiography using [3H]-quinuclidinyl benzilate (nonselective muscarinic receptors), N-[3H]-methylscopolamine (nonselective muscarinic receptors), [3H]-pirenzepine (M1 subtype muscarinic receptors) and [3H]-AF-DX384 (M2 subtype muscarinic receptors) in brain slices of wild-type and mu-opioid receptor knockout mice. The acetylcholinesterase activity of mu-opioid receptor knockout mice was higher than that of the wild-type in the striatal caudate putamen and nucleus accumbens, but not in the cortex and hippocampus areas. In addition, the bindings in N-[3H]-methylscopolamine and [3H]-AF-DX384 of mu-opioid receptor knockout mice were significantly lower when compared with that of the wild-type controls in the striatal caudate putamen and nucleus accumbens. However, there were no significant differences in bindings of [3H]-quinuclidinyl benzilate and [3H]-pirenzepine between mu-opioid receptor knockout and wild-type mice in the cortex, striatum and hippocampus. These data indicate that there are up-regulation of acetylcholinesterase activity and compensatory down-regulation of M2 muscarinic receptors in the striatal caudate putamen and nucleus accumbens of mu-opioid receptor knockout mice.


[Max Flesch (1852-1943): veterinary anatomist, physician and Nazi victim].
The Jewish physician Dr. med. Max Flesch, a student of the Würzburger anatomist Albert von Kölliker (1817-1905), was professor of anatomy, histology and embryology at the School of Veterinary Medicine in Bern from 1882-1887. He was the first at that school who unified the three anatomical fields in one hand. From his Institute came Oskar Rubeli (1861-1952) who was also his successor. From 1888 on Max Flesch was engaged as practitioner and later as gynaecologist. During the First World War he proved his worth as a hospital physician. After the war he most likely was working for another decade in his practice in Frankfurt before retiring in Hochwaldhausen at the Hessian Vogelsberg. During his retirement Flesch published his experiences as 1 nurse and hospital physician, respectively during the wars 1870/71 and 1914-1918. With the assumption of power by the National Socialists the living conditions for Jews in Germany radically changed; also Max Flesch became victim of the Nazi racism. Although very old he was carried off 1942 into the concentration camp Theresienstadt where he lost his life in May 1943. We owe Max Flesch honourable remembrance.


[The antiarrhythmic activity of the trimecain ammonium derivative in myocardial ischemia].
The results of experiments on cats and dogs showed that quaternidine, a quaternary ammonium derivative of trimecaine, exceeds the structural precursors (trimecaine and lidocaine), as well as the reference drugs quinidine and propranolol, in intensity of the antiarrhythmic action upon single administration on the occlusive and reperfusive arrhythmia models. The therapeutic effect of quaternidine in animals with acute myocardial ischemia lasts for about 8 h, which more than 20 times longer as compared to the duration of action of both lidocaine and trimecaine.


Estimates for local and movement-based transmission of bovine tuberculosis in British cattle.
Both badgers and livestock movements have been implicated in contributing to the ongoing epidemic of bovine tuberculosis (BTB) in British cattle. However, the relative contributions of these and other causes are not well quantified. We used cattle movement data to construct an individual (premises)-based model of BTB spread within Great Britain, accounting for spread due to recorded cattle movements and other causes. Outbreak data for 2004 were best explained by a model attributing 16% of herd infections directly to cattle movements, and a further 9% unexplained, potentially including spread from unrecorded movements. The best-fit model assumed low levels of cattle-to-cattle transmission. The remaining 75% of infection was attributed to local effects within specific high-risk areas. Annual and biennial testing is mandatory for herds deemed at high risk of infection, as is pre-movement testing from such herds. The herds identified as high risk in 2004 by our model are in broad agreement with those officially designated as such at that time. However, border areas at the edges of high-risk regions are different, suggesting possible areas that should be targeted to prevent further geographical spread of disease. With these areas expanding rapidly over the last decade, their close surveillance is important to both identify infected herds qucikly, and limit their further growth.


Doxorubicin-induced activation of protein kinase D1 through caspase-mediated proteolytic cleavage: identification of two cleavage sites by microsequencing.
Recent studies have demonstrated the importance of protein kinase D (PKD) in cell proliferation and apoptosis. Here, we report that in vitro cleavage of recombinant PKD1 by caspase-3 generates two alternative active PKD fragments. N-terminal sequencing of these fragments revealed two distinct caspase-3 cleavage sites located between the acidic and pleckstrin homology (PH) domains of PKD1. Moreover, we present experimental evidence that PKD1 is an in vitro substrate for both initiator and effector caspases. During doxorubicin-induced apoptosis, a zVAD-sensitive caspase induces cleavage of PKD1 at two sites, generating fragments with the same molecular masses as those determined in vitro. The in vivo caspase-dependent generation of the PKD1 fragments correlates with PKD1 kinase activation. Our results indicate that doxorubicin-mediated apoptosis induces activation of PKD1 through a novel mechanism involving the caspase-mediated proteolysis.


An Open-Label Discontinuation Trial of Long-Term, Off-Label Antipsychotic Medication in People With Intellectual Disability: Determinants of Success and Failure.
Although physicians are aware of the risks of prescribing long-term off-label antipsychotics in people with intellectual disability, attempts to discontinue often fail. This study aimed to identify potential determinants of successful and failed discontinuation. Long-term off-label antipsychotics were tapered in 14 weeks, with 12.5% of baseline dose every 2 weeks. Participants living in facilities offered by intellectual disability service providers, ≥6 years, with an IQ <70 were eligible to discontinue antipsychotic use, as judged by their physicians. The primary outcome was achievement of complete discontinuation at 16 weeks; changes in the Aberrant Behavior Checklist (ABC) and its 5 subscales were secondary outcomes. Potential determinants of the success or failure in discontinuing antipsychotics were psychotropic drug use and participants' living circumstances, medical health conditions, and severity of behavioral symptoms and neurologic side effects. Of 499 eligible clients, 129 were recruited. Reasons for client non-participation were clinician concerns that discontinuation might increase challenging behaviors and changes in clients' environment. Of the 129 participants, 61% had completely discontinued antipsychotics at 16 weeks, 46% at 28 weeks, and 40% at 40 weeks. ABC total scores increased in 49% of participants with unsuccessful discontinuation at 16 weeks. Autism, higher dose of antipsychotic drug, higher ABC and akathisia scores, and more-frequent worsening of health during discontinuation were associated with a lower incidence of complete discontinuation. Thus, in a selected sample of participants whom responsible clinicians had deemed discontinuation of antipsychotics could be attempted, 40% had achieved and maintained discontinuation at end of follow-up. Physicians should try to address patients' conditions that may hamper discontinuation.


The FUT2 secretor variant p.Trp154Ter influences serum vitamin B12 concentration via holo-haptocorrin, but not holo-transcobalamin, and is associated with haptocorrin glycosylation.
Vitamin B12 deficiency is common in older individuals. Circulating vitamin B12 concentration can be used to diagnose deficiency, but this test has substantial false positive and false negative rates. We conducted genome-wide association studies (GWAS) in which we resolved total serum vitamin B12 into the fractions bound to transcobalamin and haptocorrin: two carrier proteins with very different biological properties. We replicated reported associations between total circulating vitamin B12 concentrations and a common null variant in FUT2. This allele determines the secretor phenotype in which blood group antigens are found in non-blood body fluids. Vitamin B12 bound to haptocorrin (holoHC) remained highly associated with FUT2 rs601338 (p.Trp154Ter). Transcobalamin bound vitamin B12 (holoTC) was not influenced by this variant. HoloTC is the bioactive the form of the vitamin and is taken up by all tissues. In contrast, holoHC is only taken up by the liver. Using holoHC from individuals with known FUT2 genotypes, we demonstrated that FUT2 rs601338 genotype influences the glycosylation of haptocorrin. We then developed an experimental model demonstrating that holoHC is transported into cultured hepatic cells (HepG2) via the asialoglycoprotein receptor (ASGR). Our data challenge current published hypotheses on the influence of genetic variation on this clinically important measure and are consistent with a model in which FUT2 rs601338 influences holoHC by altering haptocorrin glycosylation, whereas B12 bound to non-glycosylated transcobalamin (i.e. holoTC) is not affected. Our findings explain some of the observed disparity between use of total B12 or holoTC as first-line clinical tests of vitamin B12 status.


ADAM9 is a novel product of polymorphonuclear neutrophils: regulation of expression and contributions to extracellular matrix protein degradation during acute lung injury.
A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein is stored in the gelatinase and specific granules and the secretory vesicles of human PMNs. Unstimulated PMNs express minimal quantities of surface ADAM9, but activation of PMNs with degranulating agonists rapidly (within 15 min) increases PMN surface ADAM9 levels. Human PMNs produce small quantities of soluble forms of ADAM9. Surprisingly, ADAM9 degrades several extracellular matrix (ECM) proteins, including fibronectin, entactin, laminin, and insoluble elastin, as potently as matrix metalloproteinase-9. However, ADAM9 does not degrade types I, III, or IV collagen or denatured collagens in vitro. To determine whether Adam9 regulates PMN recruitment or ECM protein turnover during inflammatory responses, we compared wild-type and Adam9(-/-) mice in bacterial LPS- and bleomycin-mediated acute lung injury (ALI). Adam9 lung levels increase 10-fold during LPS-mediated ALI in wild-type mice (due to increases in leukocyte-derived Adam9), but Adam9 does not regulate lung PMN (or macrophage) counts during ALI. Adam9 increases mortality, promotes lung injury, reduces lung compliance, and increases degradation of lung elastin during LPS- and/or bleomycin-mediated ALI. Adam9 does not regulate collagen accumulation in the bleomycin-treated lung. Thus, ADAM9 is expressed in an inducible fashion on PMN surfaces where it degrades some ECM proteins, and it promotes alveolar-capillary barrier injury during ALI in mice.


Methods for ligand-receptor assays in clinical chemistry.
This is intended to be a practical review for the clinical chemist of the laboratory procedures most commonly used to quantitate hormone receptors in various cellular fractions. These procedures include use of charcoal adsorption and hydroxylapatite for intracellular receptors and of centrifugation and filtration for membrane receptors. We discuss the use of the Scatchard analysis to establish the steroid-receptor affinity and the quantity of steroid-receptor binding sites. Both pre- and post-labeled sucrose density gradient methods are outlined. One section is devoted to the direct and indirect methods used in nuclear "exchange" assays. Basic theory underlying each assay is presented, but, more importantly, we assess the advantages and disadvantages of each procedure. On the basis of this information, one may decide which assay is best suited for a particular laboratory and (or) specimen.


Inhaled amikacin for treatment of refractory pulmonary nontuberculous mycobacterial disease.
Treatment of pulmonary nontuberculous mycobacteria, especially Mycobacterium abscessus, requires prolonged, multidrug regimens with high toxicity and suboptimal efficacy. Options for refractory disease are limited. We reviewed the efficacy and toxicity of inhaled amikacin in patients with treatment-refractory nontuberculous mycobacterial lung disease. Records were queried to identify patients who had inhaled amikacin added to failing regimens. Lower airway microbiology, symptoms, and computed tomography scan changes were assessed together with reported toxicity. The majority (80%) of the 20 patients who met entry criteria were women; all had bronchiectasis, two had cystic fibrosis and one had primary ciliary dyskinesia. At initiation of inhaled amikacin, 15 were culture positive for M. abscessus and 5 for Mycobacterium avium complex and had received a median (range) of 60 (6, 190) months of mycobacterial treatment. Patients were followed for a median of 19 (1, 50) months. Eight (40%) patients had at least one negative culture and 5 (25%) had persistently negative cultures. A decrease in smear quantity was noted in 9 of 20 (45%) and in mycobacterial culture growth for 10 of 19 (53%). Symptom scores improved in nine (45%), were unchanged in seven (35%), and worsened in four (20%). Improvement on computed tomography scans was noted in 6 (30%), unchanged in 3 (15%), and worsened in 11 (55%). Seven (35%) stopped amikacin due to: ototoxicity in two (10%), hemoptysis in two (10%), and nephrotoxicity, persistent dysphonia, and vertigo in one each. In some patients with treatment-refractory pulmonary nontuberculous mycobacterial disease, the addition of inhaled amikacin was associated with microbiologic and/or symptomatic improvement; however, toxicity was common. Prospective evaluation of inhaled amikacin for mycobacterial disease is warranted.


How sequence defines structure: a crystallographic map of DNA structure and conformation.
The fundamental question of how sequence defines conformation is explicitly answered if the structures of all possible sequences of a macromolecule are determined. We present here a crystallographic screen of all permutations of the inverted repeat DNA sequence d(CCnnnN6N7N8GG), where N6, N7, and N8 are any of the four naturally occurring nucleotides. At this point, 63 of the 64 possible permutations have been crystallized from a defined set of solutions. When combined with previous work, we have assembled a data set of 37 single-crystal structures from 29 of the sequences in this motif, representing three structural classes of DNA (B-DNA, A-DNA, and four-stranded Holliday junctions). This data set includes a unique set of amphimorphic sequence, those that crystallize in two different conformations and serve to bridge the three structural phases. We have thus constructed a map of DNA structures that can be walked through in single nucleotide steps. Finally, the resulting data set allows us to dissect in detail the stabilization of and conformational variations within structural classes and identify significant conformational deviations within a particular structural class that result from sequence rather than crystal or crystallization effects.


Inflammation Modifies the Association of Obesity with Circulating 25-Hydroxyvitamin D Levels in Cancer Survivors.
Obesity, inflammation, and circulating 25-hydroxyvitamin D (25-OHD) have distinct roles in cancer prognosis. The interplay of these factors was investigated by evaluating the associations of body mass index (BMI) with circulating 25-OHD levels in cancer survivors and determining whether associations were modified by inflammation, defined by C-reactive protein (CRP) levels. Data on cancer survivors were aggregated from the US National Health and Nutrition Examination Survey (2001-2010). Multivariable linear regression models were used to evaluate the associations of BMI with circulating 25-OHD. Analyses were stratified by CRP levels: low < 1.0 mg/L, moderate 1.0-3.0 mg/L, and high > 3.0-9.9 mg/L. Among 1,305 cancer survivors (mean age = 60.8 years, mean BMI = 28.0 kg/m2 ), circulating 25-OHD levels were 8.74 nmol/L lower (95% CI: 4.71 to 12.77) in cancer survivors with BMI ≥ 30.0 kg/m2 compared with those with BMI < 25.0 kg/m2 . This association was, however, limited to those with moderate CRP (-9.90 nmol/L, 95% CI: -16.45 to -3.36) and high CRP (-11.61 nmol/L, 95% CI: -18.71 to -5.05), but not among those with low CRP levels (-5.31 nmol/L, 95% CI:-12.66 to 2.04). A greater understanding of the interplay between 25-OHD and inflammation in cancer survivors with obesity should allow for targeted secondary prevention and help improve prognosis in these patients.


[Molecular cloning and mutation site analysis of AMPD1 gene in swine].
Adenosine monophosphate deaminase gene (AMPD1) plays an important role in the purine nucleotide cycle.The AMPD1 gene is expressed predominantly in skeletal muscles. It related with Inosine monophosphate metabolism in muscles and carcass traits. Herein the AMPD1 gene was cloned and a CDS sequence of 2 195 bp was obtained and analyzed with PCR-SSCP. chi(2) analysis showed that the distribution of genotypes among Min pig, Yorkshire and Duroc are extremely sig-nificant different (Plt;0.01).


[Cardiac rhythm and conduction disorders in polymyositis and dermatomyositis].
To assess condition of the heart in polymyositis (PM) and dermatomyositis (DM) in terms of defects in the rhythm and conductivity, we carried out ECG, 24-hour ECG monitoring, EIA measurements of KPK MB-fraction and myoglobin, echocardiography and Doppler echocardiography. Maximal frequency of arrhythmia presenting as supraventricular and ventricular extrasystole occurred in patients with acute PM/DM. Blockade of the bundle of His left anterior branch was detected most frequently in patients with acute and subacute PM-DM and in those with high serum levels of KPK MB-faction and myoglobin. Frequency of rhythmic and conductivity disorders seems unrelated to the disease duration. We registered no alterations at rest either in intracardiac hemodynamics or myocardial contractility. The study of these parameters under exercise test may provide objective information on early defects in myocardial contractility.


Oxidative stress and innate immunity responses in cigarette smoke stimulated nasal epithelial cells.
Cigarette smoke extracts (CSE) may play a significant role in diseases of the upper airway including chronic rhinosinusitis. Even short term exposure of cigarette smoke has adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking. Cigarette smoke alters toll-like receptor 4 (TLR4) expression and activation in bronchial epithelial cells. Carbocysteine is an anti-oxidant and mucolytic agent. The effects of carbocysteine on CSE induced oxidative stress and on associated innate immune and inflammatory responses in nasal epithelial cells are largely unknown. The present study was aimed to assess in CSE stimulated nasal epithelial cells (RPMI 2650) the effects of carbocysteine (10(-4)M) on: cell survival, intracellular reactive oxygen species (ROS) production, TLR4 expression, LPS binding and neutrophil chemotaxis (actin reorganization). We found that CSE increased ROS production, TLR4 expression, LPS binding and neutrophil chemotaxis and all these events were counteracted by pre-incubating CSE stimulated RPMI 2650 cells with carbocysteine. In conclusion, the present study provides compelling evidence that carbocysteine may be considered a promising therapeutic strategy in chronic inflammatory nasal diseases.


Inductive determination of allele frequency spectrum probabilities in structured populations.
We present a method for inductively determining exact allele frequency spectrum (AFS) probabilities for samples derived from a population comprising two demes under the infinite-allele model of mutation. This method builds on a labeled coalescent argument to extend the Ewens sampling formula (ESF) to structured populations. A key departure from the panmictic case is that the AFS conditioned on the number of alleles in the sample is no longer independent of the scaled mutation rate (θ). In particular, biallelic site frequency spectra, widely-used in explorations of genome-wide patterns of variation, depend on the mutation rate in structured populations. Variation in the rate of substitution across loci and through time may contribute to apparent distortions of site frequency spectra exhibited by samples derived from structured populations.


[A pathologist's radiological culture].
The authors analyze 8 papers on human radiation pathology, published in the journal "Arkhiv Patologii", which assess the quality of radiological information given in them. It turns out that pathologists have accumulated important facts on some types of pathology (thyroid cancer, diseases of different organs), but their dependence on the action of radiation requires more valid evidence. The absence of radiation doses in most papers reduces the validity of the conclusions of the articles. All possible internal and external causes of the found changes, and not just ionizing radiations should be considered while interpreting results.


The difficulties of conducting maternal death reviews in Malawi.
Maternal death reviews is a tool widely recommended to improve the quality of obstetric care and reduce maternal mortality. Our aim was to explore the challenges encountered in the process of facility-based maternal death review in Malawi, and to suggest sustainable and logically sound solutions to these challenges. SWOT (strengths, weaknesses, opportunities and threats) analysis of the process of maternal death review during a workshop in Malawi. Strengths: Availability of data from case notes, support from hospital management, and having maternal death review forms. Weaknesses: fear of blame, lack of knowledge and skills to properly conduct death reviews, inadequate resources and missing documentation. Opportunities: technical assistance from expatriates, support from the Ministry of Health, national protocols and high maternal mortality which serves as motivation factor. Threats: Cultural practices, potential lawsuit, demotivation due to the high maternal mortality and poor planning at the district level. Solutions: proper documentation, conducting maternal death review in a blame-free manner, good leadership, motivation of staff, using guidelines, proper stock inventory and community involvement. Challenges encountered during facility-based maternal death review are provider-related, administrative, client related and community related. Countries with similar socioeconomic profiles to Malawi will have similar 'pull-and-push' factors on the process of facility-based maternal death reviews, and therefore we will expect these countries to have similar potential solutions.


Re-building relationships after a spinal cord injury: experiences of family caregivers and care recipients.
Following spinal cord injury (SCI), family members are often called upon to undertake the caregiving role. This change in the nature of the relationship between the individuals with SCI and their families can lead to emotional, psychological, and relationship challenges. There is limited research on how individuals with SCI and their family caregivers adapt to their new lives post-injury, or on which dyadic coping strategies are used to maintain relationships. Thus, the objectives of this study were to obtain an in-depth understanding of 1) the experiences and challenges within a caregiving relationship post-SCI among spouses, as well as parents and adult children; and 2) the coping strategies used by caregivers and care recipients to maintain/rebuild their relationships. A qualitative descriptive approach with an exploratory design was used. Semi-structured face-to-face and telephone interviews were conducted. Thematic analysis was used to identify key themes arising from individuals with SCI's (n = 19) and their family caregivers' (n = 15) experiences. Individuals with SCI and family caregivers spoke in-depth and openly about their experiences and challenges post-injury, with two emerging themes (including subsequent sub-themes). The first theme of deterioration of relationship, which reflects the challenges experienced/factors that contributed to disintegration in a relationship post-injury, included: protective behaviours, asymmetrical dependency, loss of sex and intimacy, and difficulty adapting. The second theme of re-building/maintaining the relationship, which reflects the strategies used by dyads to adjust to the changes within the relationship brought upon by the injury, included: interdependence, shifting commonalities, adding creativity into routine, and creating a new normal. These findings should alert healthcare professionals and peer support groups as to the need for possible education and training (e.g., coping strategies, communication skills training) as well as counseling prior to discharge to assist individuals with SCI and family caregivers with adaptation to a new life post-injury.


Progranulin regulates neurogenesis in the developing vertebrate retina.
We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed-retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 77: 1114-1129, 2017.


Attenuation of chondrogenic transformation in vascular smooth muscle by dietary quercetin in the MGP-deficient mouse model.
Cartilaginous metaplasia of vascular smooth muscle (VSM) is characteristic for arterial calcification in diabetes and uremia and in the background of genetic alterations in matrix Gla protein (MGP). A better understanding of the molecular details of this process is critical for the development of novel therapeutic approaches to VSM transformation and arterial calcification. This study aimed to identify the effects of bioflavonoid quercetin on chondrogenic transformation and calcification of VSM in the MGP-null mouse model and upon TGF-β3 stimulation in vitro, and to characterize the associated alterations in cell signaling. Molecular analysis revealed activation of β-catenin signaling in cartilaginous metaplasia in Mgp-/- aortae in vivo and during chondrogenic transformation of VSMCs in vitro. Quercetin intercepted chondrogenic transformation of VSM and blocked activation of β-catenin both in vivo and in vitro. Although dietary quercetin drastically attenuated calcifying cartilaginous metaplasia in Mgp-/- animals, approximately one-half of total vascular calcium mineral remained as depositions along elastic lamellae. Quercetin is potent in preventing VSM chondrogenic transformation caused by diverse stimuli. Combined with the demonstrated efficiency of dietary quercetin in preventing ectopic chondrogenesis in the MGP-null vasculature, these findings indicate a potentially broad therapeutic applicability of this safe for human consumption bioflavonoid in the therapy of cardiovascular conditions linked to cartilaginous metaplasia of VSM. Elastocalcinosis is a major component of MGP-null vascular disease and is controlled by a mechanism different from chondrogenic transformation of VSM and not sensitive to quercetin.


Evidence of a calcium-ion-transport system in mitochondria isolated from flight muscle of the developing sheep blowfly Lucilia cuprina.
The EGTA (ethanedioxybis(ethylamine)tetra-acetic acid)-Ruthenium Red-quench technique (Reed & Bygrave, 1974a) was used to measure initial rates of Ca-2+ transport in mitochondria from flight muscle of the blowfly Lucilia cuprina. Evidence is provided for the existence in these mitochondria of a Ca-2+-transport system that has many features in common with that known to exist in rat liver mitochondria. These include requirement for energy, saturation at high concentrations of Ca-2+, a sigmoidal relation between initial rates of Ca-2+ transport and Ca-2+ concentration, a high affinity for free Ca-2+ (Km approx. 5 muM) and high affinity for the Ca-2+-transport inhibitoy, Ruthenium Red (approx. 0.03 nmol of carrier-specific binding-sites/mg of protein; Ki approx. 1.6 x 10- minus 8 M). Controlled respiration can be stimulated by Ca-2+ after a short lag-period provided the incubation medium contains KCl and not sucrose. The ability of Lucilia mitochondria to transport Ca-2+ critically depends on the stage of mitochondrial development; Ca-2+ transport is minimal in mitochondria from pharate adults, is maximal between 0 and 2h post-emergence and thereafter rapidly declines to reach less than 20% of the maximum value by about 2-3 days post-emergence. Respiration in mitochondria from newly emerged flies does not respond to added Ca-2+; that from 3-5-day-old flies is stimulated approx. 50%. Whereas very low concentrations of Ca-2+ inhibit ADP-stimulated respiration and oxidative phosphorylation in mitochondria from newly emerged flies (Ki approx. 60 ng-ions of Ca-2+/mg of protein); much higher concentrations (approx. 200 ng-ion/mg of protein) are needed to inhibit these processes in those from older flies. The potential of this system for studying the function and development of metabolite transport systems in mitochondria is discussed.


The therapeutic potential of costimulatory blockade with CTLA4Ig in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterised by joint inflammation and destruction. Controversy exists regarding the significance and exact role of activated T cells in RA. CTLA4Ig is a soluble fusion protein (cytotoxic T lymphocyte-associated antigen 4 fused to the heavy chain constant region of human IgG1), which represents the first in a new class of agents called costimulation blockers. By blocking the second signal required for optimal T-cell activation, CTLA4Ig has demonstrated efficacy in a variety of spontaneous and induced animal models of autoimmunity. A Phase II clinical study in RA showed CTLA4Ig was efficacious with an acceptable safety profile. These results suggest that activated T cells may be important in RA pathogenesis and that costimulation blockade may be a novel therapeutic approach for this disorder.


Staphylococcus lugdunensis gluteal abscess in a patient with end stage renal disease on hemodialysis.
A 57-year-old end stage renal disease patient on hemodialysis (HD) presented with sepsis secondary to right buttock abscess and overlying cellulitis. She was started on broad-spectrum antibiotic therapy and underwent incision and drainage with marked improvement. Her cultures grew methicillin-resistant Staphylococcus lugdunensis. This bacterium is more virulent than other coagulase negative staphylococci and has been implicated in causing a variety of serious infections but it has been underreported as a cause of skin infections in HD patients and possible other patient populations.


[In vitro evidence for pancreatic lineage: Ngn3 positive cells are endocrine progenitors derived from cultured islets].
Further studies have been conducted to evaluate the roles of Ngn3 in adult islet maintenance and renewal. Islets were isolated from 6 - 8 week old male C57BL/6 mice. After common bile duct cannulation, the pancreas was resected and digested in collagenase V (2.5 mg/ml). Islets were then handpicked and 10 - 12 islets were plated in 60 mm culture dish and cultivated with RPMI-1640, which contained 12.5 mmol/L HEPES, 5.2 mmol/L glucose and 2% fetal bovine serum (FBS). Islet cells were analyzed by immunocytochemistry methods for A6, insulin, glucagon, nestin, Ngn3 and 5-bromo-2'-deoxy-uridine (BrdU). The results of these studies indicated that less than 15 percent of proliferated islet cells were Ngn3 expressing cells, in which about one third of the Ngn3 positive cells co-expressed A6. The existence of Ngn3 in cultured islet cells is consistent with the results from other's findings both in embryogenesis and adult islet studies. A significant finding of our study is that the existence of A6 and Ngn3 co-expressing cells in the cultured islet. A6 is a marker for identifying bile duct epithelial cell oriented hepatic progenitor cells. Islet-derived A6 cells are possibly born in the adult pancreatic duct and migrate into islets. A6 cells co-express Ngn3 when these cells commit to endocrine lineage within the islets. More interestingly, islet-derived A6 positive cells have the potential to transdifferentiate into hepatic cells. The presence of Ngn3(+) and A6(+) cells in the cultured islets suggests that the four established islet cell types arise from a common endocrine lineage residing within the adult islets. A6 and Ngn3 are useful markers for understanding intra-islet adult stem cell lineages in our future studies. This approach may allow for significant advances in understanding the IPC proliferation and differentiation, and open the possibility of using intra-islet adult stem cells for diabetes treatment.


Conflicts between courtship and thermoregulation: the thermal ecology of amorous male garter snakes (Thamnophis sirtalis parietalis, colubridae).
Thermoregulatory behavior is an important component of daily activities for many reptiles, especially for small heliothermic (sun-basking) species that inhabit cold climates. However, the relative costs and benefits of thermoregulation depend on numerous factors, such that reptiles may sometimes accord a low priority to precise control of body temperatures. We observed and radio tracked garter snakes (Thamnophis sirtalis parietalis) in central Manitoba during the mating season (spring). Previous studies on this species have documented precise behavioral regulation of body temperatures during summer. In contrast, the courting snakes that we studied in springtime spent little time in overt thermoregulatory behavior. Body temperatures were extremely variable (both in outdoor enclosures and in the field) despite abundant opportunities for more precise thermal control. These small elongate reptiles cool so quickly (relative to the time periods needed for effective courtship) that any benefit to higher body temperatures would be transitory at best. Experiments show that hotter males are no better at obtaining matings or at detecting predators. Thus, male garter snakes concentrate on courtship rather than on basking. In the face of conflicting priorities, reptiles may often forgo precise thermoregulation because its benefits are too low, and its costs too high, compared with alternative behaviors.


Tuberculosis joint infection following total knee arthroplasty.
Delayed onset tuberculosis infection appeared in a total knee implant in a 61-year-old former coal miner. After a five-day interval the knee was salvaged by removal, aggressive debridement, suction-irrigation, and reinsertion. Antituberculosis drugs were administered immediately following surgery on the basis of the characteristic exudate and stat histologic sections showing granulomata formation. At one year follow-up examination the result was excellent. Retention of the total knee implant is a viable alternative to arthrodesis or fibrous ankylosis of the knee in such a case. Tuberculosis should be included in the differential diagnosis in patients with knee joint degenerative disease.


Role of the duplicated CCAAT box region in gamma-globin gene regulation and hereditary persistence of fetal haemoglobin.
Hereditary persistence of fetal haemoglobin (HPFH) is a clinically important condition in which a change in the developmental specificity of the gamma-globin genes results in varying levels of expression of fetal haemoglobin in the adult. The condition is benign and can significantly alleviate the symptoms of thalassaemia or sickle cell anaemia when co-inherited with these disorders. We have examined structure-function relationships in the -117 HPFH gamma promoter by analysing the effect of mutating specific promoter elements on the functioning of the wild-type and HPFH promoters. We find that CCAAT box mutants dramatically affect expression from the HPFH promoter in adult blood but have little effect on embryonic/fetal expression from the wild-type promoter. Our results suggest that there are substantial differences in the structure of the wild-type gamma promoter expressed early in development and the adult HPFH promoter. Together with previous results, this suggests that gamma silencing is a complex multifactorial phenomenon rather than being the result of a simple repressor binding to the promoter. We present a model for gamma-globin gene silencing that has significant implications for attempts to reactivate the gamma promoters in human adults by pharmacological means.


Depression in nursing homes.
Although studies have shown the prevalence of depression in nursing homes to be high, under-recognition of depression in these facilities is widespread. Use of screening tests to enhance detection of depressive symptoms has been recommended. This paper aims to provoke discussion about optimal management of depression in nursing homes. The utility of the Cornell Scale for Depression in Dementia (CSDD) is considered. CSDD data relating to residents assessed in 2008-2009 were collected from three Sydney nursing homes. CSDD scores were available from 162 residents, though raters stated they were unable to score participants on at least one item in 47 cases. Scores of 13 or more were recorded for 23% of residents in these facilities, but in most of these cases little was documented in case files to show that the results had been discussed by staff, or that they led to interventions, or that follow-up testing was arranged. Results of CSDD testing should prompt care staff (including doctors) to consider causation of depression in cases where residents are identified as possibly depressed. In particular, there needs to be discussion of how to help residents to cope with disability, losses, and feelings of powerlessness. Research is needed, examining factors that might predict response to antidepressants, and what else helps. Accreditation of nursing homes could be made to depend partly on evidence that staff regularly search for, and (if found) ensure appropriate responses to, depression.


Deep phylogeographic divergence of a migratory passerine in Sino-Himalayan and Siberian forests: the Red-flanked Bluetail (Tarsiger cyanurus) complex.
Enormous mountainous forests in Sino-Himalayans and Siberia harbor important avian biodiversity in the Northern Hemisphere. Numerous studies in last two decades have been contributed to systematics and taxonomy of passerines birds in these regions and have revealed various and complex phylogeographic patterns. A passerine species Red-flanked Bluetail Tarsiger cyanurus provided a good system to manifest such evolutionary complexity. The subspecies T. c. cyanurus and T. c. rufilatus (or/and T. c. pallidior), divergent in morphology, acoustics, and migratory strategies are allopatric in Siberia and Sino-Himalayan forests, respectively. The two taxa most likely deserve full species status but rigorous genetic analysis is missing. In this study, multilocus phylogeography based on mitochondrial DNA and Z-linked DNA reveals that T. c. cyanurus and T. c. rufilatus are reciprocally monophyletic with significant statistical support and differ with a large number of diagnostic nucleotide sites resulting substantial genetic divergence. Our finding supports the proposed split of Tarsiger cyanurus s.l. that T. cyanurus and T. rufilatus should be treated as two full species. Whether "pallidior" is a subspecies or geographical form of T. rufilatus is still uncertain. Additionally, these two forest passerine species may have diverged 1.88 (3.25-1.30) Mya, which might be shaped by geographical vicariance due to grassland and desert steppe on the central Loess Plateau during the Pliocene. Taken together, this study and further suggests another independent example of North Palearctic-Sino-Himalayan phylogeographic pattern in Palearctic birds.


The effect of haloperidol on maternal behavior in WAG/Rij rats and its consequences in the offspring.
Haloperidol treatment during pre- and post-natal period affects maternal behavior and this may have long-term effects on the offspring. We examined whether early haloperidol administration to Wistar-Albino-Glaxo dams from Rijswijk (WAG/Rij) and in Wistar control rats would affect maternal care and as a consequence, seizure susceptibility and behavior in the WAG/Rij's offspring at 3-4 months of age. Nursing dams of this well-validated genetic animal model of absence epilepsy and control dams were injected with haloperidol or saline at PPD 1 to 6. Maternal behavior was evaluated at PPD 7 to 9. Haloperidol-injected WAG/Rij dams showed more pup carryings compared with saline-injected mothers, this effect was not noticed in control Wistar dams. The offspring of haloperidol-treated WAG/Rij dams, tested during adulthood, showed heightened behavioral activity (time spent into the open arms, head dips) in the elevated plus-maze, as well as shorter spike-wave discharges (SWD) as measured in their electroencephalographic activity compared with saline-treated rats. Overall, it can be concluded that deviancies in the DA system as induced by haloperidol facilitates pup carrying/retrieval behavior in WAG/Rij rats and reduces seizure activity of the offspring in adulthood. Therefore, inter-individual differences in seizure properties and behavior in genetically predisposed animals may be due to differences in maternal behavior of the dams.


ras isoprenylation is required for ras-induced but not for NGF-induced neuronal differentiation of PC12 cells.
We have used compactin, an inhibitor of mevalonate biosynthesis, to block p21ras posttranslational modification and membrane association in PC12 cells. Previous studies have demonstrated a requirement for isoprenylation for mitogenic effects of activated p21ras in mammalian cells and for function of RAS gene products in yeast. Immunoprecipitation of [35S]methionine-labeled p21ras from PC12 cell homogenates confirmed that the processed p21ras species is missing from compactin-treated PC12 cells. Immunoprecipitation from particulate and cytosolic fractions of PC12 cells confirmed that compactin blocks p21ras membrane association: p21ras is confined to the cytosol fraction. Induction of neuronal differentiation and ornithine decarboxylase (ODCase) transcription by oncogenic p21N-ras does not occur in compactin-treated cells indicating that activity of oncogenic p21N-ras expressed in PC12 cells is abolished by compactin treatment. Thus, p21ras isoprenylation or association with the membrane appears to be required for early responses and neuronal differentiation attributable to p21ras activation. In contrast, blockade of p21ras isoprenylation and membrane association by compactin treatment did not significantly reduce PC12 cell responses to NGF. Responses examined included rapid phosphorylation of tyrosine hydroxylase, rapid induction of ODCase expression, survival in serum-free medium and neuronal differentiation. Compactin blocked growth factor-induced rapid changes in cell surface morphology but did so whether this response was induced by NGF or by EGF. These results indicate that functional p21ras is not necessary for responses to NGF which in turn implies that if a ras-dependent NGF signal transduction pathway exists, as has been previously suggested, at least one additional ras-independent pathway must also be present.


The ups and downs of mitochondrial calcium signalling in the heart.
Regulation of intramitochondrial free calcium ([Ca2+]m) is critical in both physiological and pathological functioning of the heart. The full extent and importance of the role of [Ca2+]m is becoming apparent as evidenced by the increasing interest and work in this area over the last two decades. However, controversies remain, such as the existence of beat-to-beat mitochondrial Ca2+ transients; the role of [Ca2+]m in modulating whole-cell Ca2+ signalling; whether or not an increase in [Ca2+]m is essential to couple ATP supply and demand; and the role of [Ca2+]m in cell death by both necrosis and apoptosis, especially in formation of the mitochondrial permeability transition pore. The role of [Ca2+]m in heart failure is an area that has also recently been highlighted. [Ca2+]m can now be measured reasonably specifically in intact cells and hearts thanks to developments in fluorescent indicators and targeted proteins and more sensitive imaging technology. This has revealed interactions of the mitochondrial Ca2+ transporters with those of the sarcolemma and sarcoplasmic reticulum, and has gone a long way to bringing the mitochondrial Ca2+ transporters to the forefront of cardiac research. Mitochondrial Ca2+ uptake occurs via the ruthenium red sensitive Ca2+ uniporter (mCU), and efflux via an Na+/Ca2+ exchanger (mNCX). The purification and cloning of the transporters, and development of more specific inhibitors, would produce a step-change in our understanding of the role of these apparently critical but still elusive proteins. In this article we will summarise the key physiological roles of [Ca2+]m in ATP production and cell Ca2+ signalling in both adult and neonatal hearts, as well as highlighting some of the controversies in these areas. We will also briefly discuss recent ideas on the interactions of nitric oxide with [Ca2+]m.


The pattern of completed suicides seen in Kuala Lumpur General Hospital 1999.
A study was done on 76 suicide cases managed by the Forensic Pathology Department of Hospital Kuala Lumpur (HKL) from January till December 1999 to explore the pattern of suicide and psychiatric history. The Chinese contributed 52% (n=40) of cases followed by the Indians (29%, n=22) and the Malays (12%, n=9). After the age of sixty, 84.6% of the subjects were Chinese. The common methods of suicide were poisoning (39%), hanging (34%) and jumping from height (22%). Four out of 12 case-notes traced had documented psychiatric history i.e. schizophrenia. the suicide rate for Kuala Lumpur is estimated at 7.4 per 100,000. The Indians has the highest suicide rate of 21.1 per 100,000 in keeping with other local studies. The suicide rate for the Chinese is 8.6 per 100,000, but it increased to 23 per 100,000 among the elderly Chinese. The suicide rate for Malays is 2.6 per 100,000, higher than what was cited in previous local studies. The incidence of jumping from height as a suicide method had doubled over the last 2 decades.


GW domains of the Listeria monocytogenes invasion protein InlB are required for potentiation of Met activation.
The Listeria monocytogenes protein InlB promotes intracellular invasion by activating the receptor tyrosine kinase Met. Earlier studies have indicated that the LRR fragment of InlB is sufficient for Met activation, but we show that this is not the case unless the LRR fragment is artificially dimerized through a disulphide bond. In contrast, activation of Met proceeds through monomers of intact InlB and, at physiologically relevant concentrations, requires coordinated action in cis of both InlB N-terminal LRR region and C-terminal GW domains. The GW domains are shown to be crucial for potentiating Met activation and inducing intracellular invasion, with these effects depending on association between GW domains and glycosaminoglycans. Glycosaminoglycans do not alter the monomeric state of InlB, and are likely to enhance Met activation through a receptor-mediated mode, as opposed to the ligand-mediated mode observed for the LRR fragment. Surprisingly, we find that gC1q-R, a host protein implicated in InlB-mediated invasion, specifically antagonizes rather than enhances InlB signalling, and that interaction between InlB and gC1q-R is unnecessary for bacterial invasion. Lastly, we demonstrate that HGF, the endogenous ligand of Met, substitutes for InlB in promoting intracellular invasion, suggesting that no special properties are required of InlB in invasion besides its hormone-like mimicry of HGF.


Evidence for holistic representations of ignored images and analytic representations of attended images.
According to the hybrid theory of object recognition (J. E. Hummel, 2001), ignored object images are represented holistically, and attended images are represented both holistically and analytically. This account correctly predicts patterns of visual priming as a function of translation, scale (B. J. Stankiewicz & J. E. Hummel, 2002), and left-right reflection (B. J. Stankiewicz, J. E. Hummel, & E. E. Cooper, 1998). The model also predicts that priming for attended images will generalize over configural distortions (split images), whereas priming for ignored images will not. Three experiments tested and confirmed this prediction. Split images visually primed their intact and split counterparts when they were attended but not when they were ignored, whereas intact images primed themselves whether they were attended or not. The data contribute to the growing body of evidence that 1 function of visual attention is to permit the generation of explicitly relational representations of object shape.


Chiral imprinting of diblock copolymer single-chain particles.
This Article reports the molecular imprinting of polymer single-chain particles that have a radius ∼3.7 nm. For this, the template L-phenylalanine anilide or L-ΦAA and a diblock copolymer PtBA-b-P(CEMA-r-CA) were used. Here, PtBA denotes poly(tert-butyl acrylate), and P(CEMA-r-CA) denotes a random block consisting of cinnamoyloxyethyl methacrylate (CEMA) and carboxyl-bearing (CA) units. In CHCl(3)/cyclohexane (CHX) with 64 vol % of CHX or at f(CHX) = 64%, a block-selective solvent for PtBA, PtBA-b-P(CEMA-r-CA) formed spherical micelles. The core consisted of the insoluble P(CEMA-r-CA) block and L-ΦAA, which complexed with the CA groups. Pumping slowly this micellar solution into stirred CHCl(3)/(CHX) at f(CHX) = 64% triggered micelle dissociation into single-chain micelles, which comprised presumably a solubilized PtBA tail and a collapsed P(CEMA-r-CA)/L-ΦAA head. Because the solvent reservoir was under constant UV irradiation, the photo-cross-linkable units in the P(CEMA-r-CA) head cross-linked, and the single-chain micelles were converted into cross-linked single-chain micelles or tadpoles. Synchronizing the micelle addition and photoreaction rates allowed the preparation, from this protocol, of essentially pure tadpoles at high final polymer concentrations. Imprinted tadpoles were procured after L-ΦAA was extracted from the tadpole heads. Under optimized conditions, the produced imprinted tadpoles had exceptionally high binding capacity and high selectivity for L-ΦAA. In addition, the rates of L-ΦAA release from and rebinding by the particles were high.


A deforestation-induced tipping point for the South American monsoon system.
The Amazon rainforest has been proposed as a tipping element of the earth system, with the possibility of a dieback of the entire ecosystem due to deforestation only of parts of the rainforest. Possible physical mechanisms behind such a transition are still subject to ongoing debates. Here, we use a specifically designed model to analyse the nonlinear couplings between the Amazon rainforest and the atmospheric moisture transport from the Atlantic to the South American continent. These couplings are associated with a westward cascade of precipitation and evapotranspiration across the Amazon. We investigate impacts of deforestation on the South American monsoonal circulation with particular focus on a previously neglected positive feedback related to condensational latent heating over the rainforest, which strongly enhances atmospheric moisture inflow from the Atlantic. Our results indicate the existence of a tipping point. In our model setup, crossing the tipping point causes precipitation reductions of up to 40% in non-deforested parts of the western Amazon and regions further downstream. The responsible mechanism is the breakdown of the aforementioned feedback, which occurs when deforestation reduces transpiration to a point where the available atmospheric moisture does not suffice anymore to release the latent heat needed to maintain the feedback.


Male brush-turkeys attempt sexual coercion in unusual circumstances.
Sexual coercion by males is generally understood to have three forms: forced copulation, harassment and intimidation. We studied Australian brush-turkeys, Alectura lathami, to determine whether some male behaviours towards females at incubation mounds could be classified as aggressive, whether males were attempting sexual coercion and, if so, whether the coercion was successful. We found that some male behaviours towards females were significantly more likely to be followed by the cessation of female mound activity, and hence could be classified as aggressive, while others were significantly more likely to be followed by the commencement of female mound activity, and hence could be classified as enticing. Copulation was preceded by higher rates of male enticement and by higher rates of certain types of male aggression. It therefore seemed that males were attempting sexual coercion. There was little evidence, however, that this combination of coercion and enticement was successful in obtaining copulations. While forced copulation did occur, it was infrequent, and no evidence could be found for intimidation. We conclude that harassment is the primary form of sexual coercion by male brush-turkeys. Although sexual coercion is understood to be a sub-optimal tactic, brush-turkey sexual coercion was employed as a primary tactic by dominant males who owned incubation mounds. One possible explanation for this apparent paradox is that aggression is the default solution for social conflicts in this species, and hence can be interpreted as a behavioural syndrome.


Increased susceptibility of secretor factor gene Fut2-null mice to experimental vaginal candidiasis.
Fut2-LacZ-null mice, which are a model of the human ABO and Lewis nonsecretor group, display increased susceptibility to experimental yeast vaginitis, indicating a role for alpha(1,2)fucosylated cervical glycans in mucosal defense. However, the lack of significant effect of competitive inhibition by exogenous neoglycoproteins in this study emphasizes the complexity of Candida-epithelial cell adhesion events.


Foot Angle and Loading Rate during Running Demonstrate a Nonlinear Relationship.
Vertical loading rates are typically found to be lower in forefoot compared to rearfoot strikers, promoting the idea that forefoot striking is desirable and may reduce running injury risk. However, prior work using linear models has shown that foot inclination angle (FIA) at initial contact is a poor predictor of vertical loading rate, suggesting a more complex association exists. To determine if a nonlinear model superiorly describes the relationship between FIA and average vertical loading rate (AVLR). Secondary analyses assessed the influence of sex and sport on the association between FIA and AVLR. Whole body kinematics and vertical ground reaction forces were collected for 170 healthy National Collegiate Athletic Association Division I athletes (97 males; 81 cross-country runners) during treadmill running at 2.68, 3.35, and 4.47 m·s. Foot inclination angle and AVLR were calculated for 15 strides and averaged across strides for each limb. Polynomial mixed effects models assessed linear and nonlinear trends in the relationship between FIA and AVLR across the entire sample and accounting for sex and sport participation. Average vertical loading rate was lowest at the extremes of FIA (i.e., -15°, 20°), whereas greater AVLR were observed between 5° and 10°. The cubic model resulted in a significantly better fit than the linear model (P < 0.001). Average vertical loading rate was also more variable among FIA associated with rearfoot and midfoot strike than forefoot strike. Adding sex to the model did not influence model fit; though, controlling for sport minimally improved model fit. The relationship between FIA and AVLR is best represented by a cubic model. Consequently, FIA should be treated as a continuous variable. Reducing FIA into categories may misrepresent the relationship between FIA and other gait variables.


Fall detection with body-worn sensors : a systematic review.
Falls among older people remain a major public health challenge. Body-worn sensors are needed to improve the understanding of the underlying mechanisms and kinematics of falls. The aim of this systematic review is to assemble, extract and critically discuss the information available in published studies, as well as the characteristics of these investigations (fall documentation and technical characteristics). The searching of publically accessible electronic literature databases for articles on fall detection with body-worn sensors identified a collection of 96 records (33 journal articles, 60 conference proceedings and 3 project reports) published between 1998 and 2012. These publications were analysed by two independent expert reviewers. Information was extracted into a custom-built data form and processed using SPSS (SPSS Inc., Chicago, IL, USA). The main findings were the lack of agreement between the methodology and documentation protocols (study, fall reporting and technical characteristics) used in the studies, as well as a substantial lack of real-world fall recordings. A methodological pitfall identified in most articles was the lack of an established fall definition. The types of sensors and their technical specifications varied considerably between studies. Limited methodological agreement between sensor-based fall detection studies using body-worn sensors was identified. Published evidence-based support for commercially available fall detection devices is still lacking. A worldwide research group consensus is needed to address fundamental issues such as incident verification, the establishment of guidelines for fall reporting and the development of a common fall definition.


Image coding using entropy-constrained residual vector quantization.
An entropy-constrained residual vector quantization design algorithm is used to design codebooks for image coding. Entropy-constrained residual vector quantization has several important advantages. It can outperform entropy-constrained vector quantization in terms of rate-distortion performance, memory, and computation requirements. It can also be used to design vector quantizers with relatively large vector sizes and high output rates. Experimental results indicate that good image reproduction quality can be achieved at relatively low bit rates. For example, a peak signal-to-noise ratio of 30.09 dB is obtained for the 512x512 LENA image at a bit rate of 0.145 b/p.


Extension of cox proportional hazard model for estimation of interrelated age-period-cohort effects on cancer survival.
In the frame of the Cox proportional hazard (PH) model, a novel two-step procedure for estimating age-period-cohort (APC) effects on the hazard function of death from cancer was developed. In the first step, the procedure estimates the influence of joint APC effects on the hazard function, using Cox PH regression procedures from a standard software package. In the second step, the coefficients for age at diagnosis, time period and birth cohort effects are estimated. To solve the identifiability problem that arises in estimating these coefficients, an assumption that neighboring birth cohorts almost equally affect the hazard function was utilized. Using an anchoring technique, simple procedures for obtaining estimates of interrelated age at diagnosis, time period and birth cohort effect coefficients were developed.As a proof-of-concept these procedures were used to analyze survival data, collected in the SEER database, on white men and women diagnosed with LC in 1975-1999 and the age at diagnosis, time period and birth cohort effect coefficients were estimated. The PH assumption was evaluated by a graphical approach using log-log plots. Analysis of trends of these coefficients suggests that the hazard of death from LC for a given time from cancer diagnosis: (i) decreases between 1975 and 1999; (ii) increases with increasing the age at diagnosis; and (iii) depends upon birth cohort effects.The proposed computing procedure can be used for estimating joint APC effects, as well as interrelated age at diagnosis, time period and birth cohort effects in survival analysis of different types of cancer.


The effects of the ketogenic diet for the management of type 2 diabetes mellitus: A systematic review and meta-analysis of recent studies.
To systematically review the effects of the ketogenic diet on glycaemic control, body weight, cardiovascular risk factors, and liver and kidney function in patients with type 2 diabetes. PubMed, MEDLINE, Embase, Cochrane Library and CINAHL were searched for randomised controlled trials published between 2001 and 2021 that compared the ketogenic diet to a control diet for effects on glycaemic control, body weight, cardiovascular risk factors, liver and renal function markers in adults with type 2 diabetes for >14 days. Meta-analyses using fixed or random effects models were conducted. Nineteen reports from 11 randomised controlled trials were included. Compared to the control, the ketogenic diet showed no significant difference in changes in glycaemic control or body weight, but greater increases in HDL (standardised mean difference 0.19; 95%CI 0.02-0.37; I2 = 0 %; moderate-quality evidence) and greater reductions in triglycerides (standardised mean difference -0.41; 95%CI -0.64 to -0.18; I2 = 0 %; low-quality evidence). The ketogenic diet may improve lipid profiles but showed no additional benefits for glycaemic control or weight loss compared to control diets in type 2 diabetes patients over two years.


Coverage-dependent thermodynamic analysis of the formation of water and hydrogen peroxide on a platinum model catalyst.
Understanding the selectivity of the oxygen reduction reaction, especially the formation of water versus hydrogen peroxide in fuel cells, is an ongoing challenge in electrochemistry, surface science and catalysis. In this study, we propose a comprehensive thermodynamic analysis of the reaction intermediates for the formation of water on Pt(111). Density functional theory calculations of all the elementary steps linking hydroxyl and hydroperoxyl surface species with water and hydrogen peroxide have been performed at low (1/12 ML, ML = monolayer) and high (1/4 ML) coverages. The reaction energy variation for the two competing elementary events (molecular oxygen dissociation and hydroperoxyl formation) is strongly coverage-dependent. For the direct dissociation, an increase is observed at low coverage with respect to the usual high coverage picture. The stability of the reaction intermediates is investigated from thermodynamic diagrams. At 353 K and a total pressure of 1 atm, water and hydroxyl surface species are expected to compete for adsorption on Pt(111).