[Mechanism of retention of a complete prosthesis].
Patients with full dentures often experience some problems with their dentures, one of them is retention. The retention of a full denture is a result of many factors. Some factors are of a physical nature, others of a physiological nature. The dentist has to take these factors into account while modelling the borders, flanks and basis of the prosthesis. In obtaining the best shape of those borders, flanks and basis a special emphasis is put on the border and flank modelling and the individual impression.


Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses.
Melanopsin is a novel opsin synthesized in a small subset of retinal ganglion cells. Ganglion cells expressing melanopsin are capable of depolarizing in response to light in the absence of rod or cone input and are thus intrinsically light sensitive. Melanopsin ganglion cells convey information regarding general levels of environmental illumination to the suprachiasmatic nucleus, the intergeniculate leaflet, and the pretectum. Typically, retinal ganglion cells communicate information to central visual structures by receiving input from retinal photoreceptors via bipolar and amacrine cells. Because melanopsin ganglion cells do not require synaptic input to generate light-induced signals, these cells need not receive synapses from other neurons in the retina. In this study, we examined the ultrastructure of melanopsin ganglion cells in the mouse retina to determine the type (if any) of synaptic input these cells receive. Melanopsin immunoreaction product was associated primarily with the plasma membrane of (1) perikarya in the ganglion cell layer, (2) dendritic processes in the inner plexiform layer (IPL), and (3) axons in the optic fiber layer. Melanopsin-immunoreactive dendrites in the inner (ON) region of the IPL were postsynaptic to bipolar and amacrine terminals, whereas melanopsin dendrites stratifying in the outer (OFF) region of the IPL received only amacrine terminals. These observations suggested that rod and/or cone signals may be capable of modifying the intrinsic light response in melanopsin-expressing retinal ganglion cells.


A novel therapeutic approach using the Zipper method to treat chorea in a pediatric-onset systemic lupus erythematosus patient.
Pediatric-onset systemic lupus erythematosus is among the prototypic systemic autoimmune diseases seen in children. Although the neuropsychiatric involvement rate varies during the course of the disease, it is an important cause of morbidity and mortality. The clinical picture of neuropsychiatric SLE (NPSLE) is highly variable, and neurological features can precede systemic findings, leading to some diagnostic difficulties. NPSLE requires early and aggressive immunosuppressive therapy. Some patients can be resistant to immunosuppressive therapy. Chorea is a rare manifestation that occurs in 1.2%-2% of SLE patients and can result from an immunologically mediated mechanism, antiphospholipid autoantibodies or ischemia. Herein we present the first case of pediatric-onset SLE diagnosed with central nervous system involvement and treated with Zipper method. The Zipper method is a new immunomodulation treatment. The clinical findings of the patient, which were resistant to corticosteroids and cyclophosphamide, resolved by this novel treatment.


Signatures of selection for resistance to Haemonchus contortus in sheep and goats.
Gastrointestinal nematode infection (GNI) is the most important disease affecting the small ruminant industry in U.S. The environmental conditions in the southern United States are ideal for the survival of the most pathogenic gastrointestinal nematode, Haemonchus contortus. Host genetic variation for resistance to H. contortus allows selective breeding for increased resistance of animals. This selection process increases the prevalence of particular alleles in sheep and goats and creates unique genetic patterns in the genome of these species. The aim of this study was to identify loci with divergent allelic frequencies in a candidate gene panel of 100 genes using two different approaches (frequentist and Bayesian) to estimate Fst outliers in three different breeds of sheep and goats exposed to H. contortus. Our results for sheep populations showed SNPs under selection in C3AR1, CSF3, SOCS2, NOS2, STAT5B, TGFB2 and IL2RA genes using frequentist and Bayesian approaches. For goats, SNPs in CD1D, ITGA9, IL12A, IL13RA1, CD86 and TGFB2 genes were under selection. Common signatures of selection in both species were observed in NOS2, TGFB2 and TLR4 genes. Directional selection was present in all SNPs evaluated in the present study. A total of 13 SNPs within 7 genes of our candidate gene panel related to H. contortus exposure were identified under selection in sheep populations. For goats, 11 SNPs within 7 genes were identified under selection. Results from this study support the hypothesis that resistance to H. contortus is likely to be controlled by many loci. Shared signatures of selection related to mechanisms of immune protection against H. contortus infection in sheep and goats could be useful targets in breeding programs aimed to produce resistant animals with low FEC.


Comparison of psoriasis and atopic dermatitis guidelines-an argument for aggressive atopic dermatitis management.
The development of effective systemic treatments has revolutionized the treatment of inflammatory skin diseases. The availability of safe new treatments and the understanding of psoriasis as a systemic disease with comorbidities and effects on quality of life have driven the current aggressive treatment paradigm of psoriasis. Historically the morbidity of atopic dermatitis (AD) has been dismissed, given the perception of AD as "just" a rash. Differences in the guidelines for psoriasis and AD management may suggest variations in the current conceptualization of disease severity and effects on quality of life. Published guidelines from the American Academy of Dermatology for the management of psoriasis and AD were reviewed. We recorded the similarities and differences in disease assessment and therapy. The threshold to use biologic agents for moderate to severe psoriasis highlights the aggressive nature of modern psoriasis treatment. AD guidelines include an assessment of quality of life but do not designate a disease severity threshold for systemic treatment. AD and psoriasis have a tremendous effect on quality of life. The AD guidelines have a less aggressive approach to disease management than the psoriasis guidelines. We should think critically about rapid advancement to systemic agents in AD management, especially now that more and better agents are being developed.


[The role of the cooperative effect of lipoproteins and hormones in the regulation of the lysosomal apparatus of the cell].
Cooperative effect of hydrocortisone, adrenaline and high density lipoproteins was found in initiation of the lysosomotropic induction of protein synthesis in liver tissue. Translocation of lysosomes into perinuclear area and transfer of lysosomal hydrolases into nuclei were responsible for specificity of the effect. As a result of consecutive action of carboxylic, serine and thiol proteinases activation of chromatin was induced in nuclei. These processes were inhibited by pepstatin, hordox and iodoacetamide, respectively, as well as by vinblastine--inhibitor of intracellular transport. Actinomycin D inhibited completely the elevated synthesis of RNA and protein under these conditions. The cooperative effect studied appears to be involved in physiological regeneration of liver cells under conditions of their increased functional activity.


Is C-reactive protein-albumin ratio or neutrophil-lymphocyte ratio a better indicator to predict in-hospital mortality in traumatic brain injury?
Neutrophil-lymphocyte ratio (NLR) and C-reactive protein-albumin ratio (CAR) are simple and objective markers of inflammatory responses. However, there are no studies in the literature evaluating these two markers together in traumatic brain injury (TBI). Therefore, this study aimed to examine whether CAR or NLR is a better biomarker for predicting in-hospital mortality in patients with TBI. A total of 257 consecutive patients admitted to the hospital between January 2016 and December 2021 were included in the study. The files of all patients aged >18 years with TBI were retrospectively reviewed. Clinical characteristics, Glasgow Coma Scale, and patient data during hospital stay were recorded. Definitive diagnosis was made using computed brain tomography. Routine blood tests were performed in the first 12-24 h of hospitalization. Laboratory results of patients with and without in-hospital mortality were comparatively analyzed. According to the Mann-Whitney U-test, median CRP, CAR, NLR, WBC, monocyte, neutrophil, RDW-CV, RDW-SD, and platelet values were significantly higher, whereas median albumin and RBC values were significantly lower in patients with in-hospital mortality. Student's t-test showed that the mean hemoglobin level was significantly lower in patients with in-hospital mortality compared to other patients. Univariate logistics regression model revealed that age, albumin, CRP, CAR, NLR, WBC, monocyte, neutrophil, RBC, RDW-CV, RDW-SD, and hemoglobin were the factors predicting mortality. However, in the multivariate logistic regression model, only age, albumin, CAR, and WBC were the factors predicting mortality. Areas under the curve were 0.891 for CAR (95% GA, 0.847-0.935), 0.759 for WBC (95% GA, 0.696-0.823), and 0.671 for NLR (95% GA, 0.598-0.744). The results of this study showed that CAR has better prognostic value than NLR in predicting in-hospital mortality in patients with TBI.


An efficient algorithm to compute the complete set of discrete Gabor coefficients.
The discrete Gabor (1946) transform algorithm is introduced that provides an efficient method of calculating the complete set of discrete Gabor coefficients of a finite-duration discrete signal from finite summations and to reconstruct the original signal exactly from the computed expansion coefficients. The similarity of the formulas between the discrete Gabor transform and the discrete Fourier transform enables one to employ the FFT algorithms in the computation. The discrete 1-D Gabor transform algorithm can be extended to 2-D as well.


Molecular Cloning and Expression Analysis of Enolase in the Rhipicephalus microplus (Acari: Ixodidae).
Rhipicephalus microplus is the main blooding-sucking ectoparasite of bovines and is regarded as important vectors of animal diseases such as Babesiosis. Mining protective antigens of R. microplus to develop antitick vaccine is the most potential tick control strategy. In this study, the specific primers were designed according to the conserved nucleotide sequence of enolase gene in Haemaphysalis flava, Ixodes ricinus, and Ornithodoros moubata. The fragment of enolase gene was obtained by PCR using cDNA template from fully engorged female R. microplus. The full-length cDNA of enolase gene was amplified using rapid amplification of cDNA ends (RACE). Expression pattern of enolase gene in different tissues of R. microplus was analyzed by real-time quantitative PCR (qRT-PCR). Results showed that the full-length enolase cDNA containing 2052 bp was obtained successfully. The complete cDNA included an ORF of 1305 nucleotides encoding a protein of 434 amino acids. The enolase exhibited 85.0% amino acid identity to the enolase of H. flava, 81.1% to I. ricinus enolase, and 81.3% to O. moubata enolase. qRT-PCR analysis indicated that the enolase had the highest expression in the salivary gland of R. microplus.


Analysis of monocyte subsets and toll-like receptor 4 expression in peripheral blood monocytes of women in preterm labor.
Preterm labor is associated with both localized inflammation of the uterus and elevated proinflammatory cytokines. Recently, specific roles have been suggested for distinct monocyte subsets and toll-like receptor 4 (TLR4) expression in inflammation. The aim of this study was to determine whether specific monocyte subsets and increased TLR4 expression in monocyte subsets contribute to preterm labor. The study included 30 preterm labor, 40 full-term labor and 20 pregnant women (not in labor). Four-color flow cytometry was used to examine the distribution of three monocyte subsets (CD14(+)CD16(-), CD14(high)CD16(+), and CD14(low)CD16(+)) and the TLR4 expression in each monocyte subset in each group of women. A larger percentage of CD14(high)CD16(+) cells was found in the preterm labor group than in the other groups (P=0.08, P=0.06). Women in preterm labor also showed significantly higher TLR4 expression in all monocyte subsets and increased fluorescence intensity in the CD14(+)CD16(-) and CD14(high)CD16(+) cells. Expression of TLR4 and mean fluorescence intensity on each monocyte subset were also significantly correlated. We conclude that women with preterm labor have higher CD16 monocytes, with high concomitant expression of CD14 and enhanced TLR4 expression in monocytes, and that monocyte TLR4 levels could be used as a marker to predict preterm delivery.


Older adults with disability in extreme poverty in Peru: How is their access to health care?
Disability rates increase with age. In 2012, Peruvian older adults (≥ 65 years) represented 9% of the population. Additionally, older population reported disabilities at about 5 times the rate of Peruvians between 36 and 64 years old, and 30% of older population lived in poverty. Peruvian seniors living in extreme poverty experience disabilities and the extent of their access to healthcare is unknown. This study assesses associations between disability and access to healthcare among Peruvians older individuals living in extreme poverty. Secondary analysis of a national representative population based survey that utilizes information from Peru's 2012 survey Health and Wellbeing in Older Adults (ESBAM), which includes older adults living in extreme poverty. We define disability in terms of the Activities of Daily Living (ADL disability) framework. Healthcare access was assessed as having any of Peru's available health insurance schemes combined with preventive health services (vision assessment, influenza vaccination, blood pressure assessment, diabetes screening, and cholesterol assessment). Poisson robust regression models were used to evaluate the associations among relevant variables. Prevalence Ratios and 95% confidence intervals (95%CI) were reported. Data from 3869 individuals (65 to 80 years old), of whom 1760 (45.5%) were females, were analyzed. The prevalence of ADL disability was 17.3% (95%CI: 16.0%-18.4%). In addition, more than 60% had never received any of the preventive measures evaluated, except for the blood pressure assessment. In the adjusted model, people with ADL disability had 63% less probability of having extensive insurance, compared to those without disability (p<0.05). This study shows that this Peruvian older population living in extreme poverty has limited access to healthcare services. Although there was no consistent association between ADL disability and the healthcare access, there is an urgent need to reduce the inequitable access to healthcare of this poor Peruvian older population.


Age- and sex-adjusted reference intervals for steroid hormones measured by liquid chromatography-tandem mass spectrometry using a widely available kit.
Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing. After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed. Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples. The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile. Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.


Salivary Cortisol Determination on Smartphone-Based Differential Pulse Voltammetry System.
Cortisol is commonly used as a significant biomarker of psychological or physical stress. With the accelerated pace of life, non-invasive cortisol detection at the point of care (POC) is in high demand for personal health monitoring. In this paper, an ultrasensitive immunosensor using gold nanoparticles/molybdenum disulfide/gold nanoparticles (AuNPs/MoS2/AuNPs) as transducer was explored for non-invasive salivary cortisol monitoring at POC with the miniaturized differential pulse voltammetry (DPV) system based on a smartphone. Covalent binding of cortisol antibody (CORT-Ab) onto the AuNPs/MoS2/AuNPs transducer was achieved through the self-assembled monolayer of specially designed polyethylene glycol (PEG, SH-PEG-COOH). Non-specific binding was avoided by passivating the surface with ethanolamine. The miniaturized portable DPV system was utilized for human salivary cortisol detection. A series current response of different cortisol concentrations decreased and exhibited a linear range of 0.5-200 nM, the detection limit of 0.11 nM, and high sensitivity of 30 μA M-1 with a regression coefficient of 0.9947. Cortisol was also distinguished successfully from the other substances in saliva. The recovery ratio of spiked human salivary cortisol and the variation of salivary cortisol level during one day indicated the practicability of the immunosensor based on the portable system. The results demonstrated the excellent performance of the smartphone-based immunosensor system and its great potential application for non-invasive human salivary cortisol detection at POC.


Time to be "smart"-Opportunities Arising From Smartphone-Based Behavioral Analysis in Daily Patient Care.
While pathologies of the central nervous system (CNS) are often associated with neuropsychological deficits, adequate quantification and monitoring of such deficits remains challenging. Due to their complex nature, comprehensive neuropsychological evaluations are needed, which are time-consuming, resource-intensive and do not adequately account for daily or hourly fluctuations of a patient's condition. Innovative approaches are required to improve the diagnostics and continuous monitoring of brain function, ideally in the form of a simple, objective, time-saving and inexpensive tool that overcomes the aforementioned weaknesses of conventional assessments. As smartphones are widely used and integrated in virtually every aspect of our lives, their potential regarding the acquisition of data representing an individual's behavior and health is enormous. Alterations in a patient's physical or mental health state may be recognized as behavioral deviation from the physiological range of the normal population, but also in comparison to the patient's individual baseline assessment. As smartphone-based assessment allows for continuous monitoring and therefore accounts for possible fluctuations or transiently occurring abnormalities in a patient's neurologic state, it may serve as a surveillance tool in the acute setting for early recognition of complications, or in the long-term outpatient setting to quantify rehabilitation or disease progress. This may be particularly interesting for regions of the world where healthcare resources for comprehensive clinical/neuropsychological examinations are insufficient or distances to healthcare providers are long. Here, we highlight the potential of smartphone-based behavioral monitoring in healthcare. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT03516162.


Chronic nonbacterial osteomyelitis from a tertiary care referral center.
Chronic nonbacterial osteomyelitis (CNO) is a little known autoinflammatory bone disorder primarily affecting children and sometimes young adults. Diagnosis is often delayed due to its varied and nonspecific initial symptoms. Very few cases are reported from India. The aim of this report is to increase the awareness of this disease among physicians, orthopedic surgeons, and rheumatologists. Four male patients were diagnosed with CNO in the past 3 years. The age at onset varied from 9 to 23 years with a median diagnostic delay of 3.5 years. All patients presented with recurrent bony pain with or without localized swelling over the affected bones. Two patients had previously undergone open surgical procedures with bone biopsies and three patients had received at least one course of antibiotics. Two patients responded well to nonsteroidal anti-inflammatory drugs alone, one patient required a short course of glucocorticoids, and another patient required methotrexate to control disease activity. This case series includes males, onset at a relatively later age in most, and a longer diagnostic delay. Thus, in addition to children and adolescents, CNO should be suspected in young adults presenting with recurrent bony pain with or without localized swelling.


Characterization of erythrocytic uptake and release and disposition pathways of nitrite, nitrate, methemoglobin, and iron-nitrosyl hemoglobin in the human circulation.
Nitrite-hemoglobin reactions have been studied extensively in vitro, but there is a lack of information on the kinetics of nitrite and its metabolites in humans. In this study, we developed a nine-compartment physiological pharmacokinetic model to describe the in vivo erythrocytic uptake and release and disposition pathways of nitrite, nitrate, methemoglobin, and iron-nitrosyl hemoglobin in the human circulation. Our model revealed that nitrite entered erythrocytes rapidly with a rate constant of 0.256 min(-1) (i.e., half-life = 2.71 min). The formation of iron-nitrosyl hemoglobin from nitrite, which involves the reduction of nitrite by deoxyhemoglobin to generate nitric oxide (NO) and reaction of NO with deoxyhemoglobin to form iron-nitrosyl hemoglobin, occurred rapidly as well (k = 2.02 min(-1); half-life = 0.343 min = 21 s). The disposition kinetics of methemoglobin was complex. Nitrate formation occurred primarily in erythrocytes through the nitrite-oxyhemoglobin reaction and was higher when nitrite was administered intra-arterially than intravenously. Nitrate reduction was an insignificant metabolic pathway. This study is the first to comprehensively evaluate the kinetics of nitrite and its metabolites in humans and provides unique insights into the rapid equilibrium of nitrite into erythrocytes and conversion to NO in the red cell, which is kinetically associated with vasodilation.


Managing Hepatitis C in Users of Illicit Drugs.
Persons who inject illicit drugs are the group most severely affected by the hepatitis C epidemic but the least likely to receive treatment. Controlling the epidemic will require developing strategies for effectively treating drug users. A growing number of reports have shown that a substantial proportion of drug users treated for hepatitis C can achieve sustained virologic responses even if they have psychiatric comorbidity and even if they continue to use drugs while receiving hepatitis C treatment. Successfully treating hepatitis C in injection drug users requires collaboration between those with expertise in hepatitis and those with expertise in caring for substance users. Careful attention to management of adverse effects and strong links with mental health services are important. Further research is needed to better define which patients can be successfully treated and the program elements that are critical for success. In the meantime, substantial progress can be made using current knowledge if appropriate resources are brought to bear.


[Construction of A Nomogram Prediction Model for PD-L1 Expression in Non-small Cell Lung Cancer Based on 18F-FDG PET/CT Metabolic Parameters].
In recent years, immunotherapy represented by programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunosuppressants has greatly changed the status of non-small cell lung cancer (NSCLC) treatment. PD-L1 has become an important biomarker for screening NSCLC immunotherapy beneficiaries, but how to easily and accurately detect whether PD-L1 is expressed in NSCLC patients is a difficult problem for clinicians. The aim of this study was to construct a Nomogram prediction model of PD-L1 expression in NSCLC patients based on 18F-fluorodeoxy glucose (18F-FDG) positron emission tomography/conputed tomography (PET/CT) metabolic parameters and to evaluate its predictive value. Retrospective collection of 18F-FDG PET/CT metabolic parameters, clinicopathological information and PD-L1 test results of 155 NSCLC patients from Inner Mongolia People's Hospital between September 2016 and July 2021. The patients were divided into the training group (n=117) and the internal validation group (n=38), and another 51 cases of NSCLC patients in our hospital between August 2021 and July 2022 were collected as the external validation group according to the same criteria. Then all of them were categorized according to the results of PD-L1 assay into PD-L1+ group and PD-L1- group. The metabolic parameters and clinicopathological information of patients in the training group were analyzed by univariate and binary Logistic regression, and a Nomogram prediction model was constructed based on the screened independent influencing factors. The effect of the model was evaluated by receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) in both the training group and the internal and external validation groups. Binary Logistic regression analysis showed that metabolic tumor volume (MTV), gender and tumor diameter were independent influences on PD-L1 expression. Then a Nomogram prediction model was constructed based on the above independent influences. The ROC curve for the model in the training group shows an area under the curve (AUC) of 0.769 (95%CI: 0.683-0.856) with an optimal cutoff value of 0.538. The AUC was 0.775 (95%CI: 0.614-0.936) in the internal validation group and 0.752 (95%CI: 0.612-0.893) in the external validation group. The calibration curves were tested by the Hosmer-Lemeshow test and showed that the training group (χ2=0.040, P=0.979), the internal validation group (χ2=2.605, P=0.271), and the external validation group (χ2=0.396, P=0.820) were well calibrated. The DCA curves show that the model provides clinical benefit to patients over a wide range of thresholds (training group: 0.00-0.72, internal validation group: 0.00-0.87, external validation group: 0.00-0.66). The Nomogram prediction model constructed on the basis of 18F-FDG PET/CT metabolic parameters has greater application value in predicting PD-L1 expression in NSCLC patients.


Use of Ratiometric Probes with a Spectrofluorometer for Bacterial Viability Measurement.
Assessment of microorganism viability is useful in many industrial fields. A large number of methods associated with the use of fluorescent probes have been developed, including fluorimetry, fluorescence microscopy, and cytometry. In this study, a microvolume spectrofluorometer was used to measure the membrane potential variations of Escherichia coli. In order to estimate the sensitivity of the device, the membrane potential of E. coli was artificially disrupted using an ionophore agent: carbonyl cyanide 3-chlorophenylhydrazone. The membrane potential was evaluated using two ratiometric methods: a Rhodamine 123/4',6-diamidino-2-phenylindole combination and a JC-10 ratiometric probe. These methods were used to study the impact of freezing on E. coli, and were compared with the conventional enumeration method. The results showed that it was beneficial to use this compact, easy-to-use, and inexpensive spectrofluorometer to assess the viability of bacterial cells via their membrane potential.


A New Hybrid Approach Based on Time Frequency Images and Deep Learning Methods for Diagnosis of Migraine Disease and Investigation of Stimulus Effect.
Migraine is a neurological disorder that is associated with severe headaches and seriously affects the lives of patients. Diagnosing Migraine Disease (MD) can be laborious and time-consuming for specialists. For this reason, systems that can assist specialists in the early diagnosis of MD are important. Although migraine is one of the most common neurological diseases, there are very few studies on the diagnosis of MD, especially electroencephalogram (EEG)-and deep learning (DL)-based studies. For this reason, in this study, a new system has been proposed for the early diagnosis of EEG- and DL-based MD. In the proposed study, EEG signals obtained from the resting state (R), visual stimulus (V), and auditory stimulus (A) from 18 migraine patients and 21 healthy control (HC) groups were used. By applying continuous wavelet transform (CWT) and short-time Fourier transform (STFT) methods to these EEG signals, scalogram-spectrogram images were obtained in the time-frequency (T-F) plane. Then, these images were applied as inputs in three different convolutional neural networks (CNN) architectures (AlexNet, ResNet50, SqueezeNet) that proposed deep convolutional neural network (DCNN) models and classification was performed. The results of the classification process were evaluated, taking into account accuracy (acc.), sensitivity (sens.), specificity (spec.), and performance criteria, and the performances of the preferred methods and models in this study were compared. In this way, the situation, method, and model that showed the most successful performance for the early diagnosis of MD were determined. Although the classification results are close to each other, the resting state, CWT method, and AlexNet classifier showed the most successful performance (Acc: 99.74%, Sens: 99.9%, Spec: 99.52%). We think that the results obtained in this study are promising for the early diagnosis of MD and can be of help to experts.


Training enhances attentional expertise, but not attentional capacity: Evidence from content-specific training benefits.
Cognitive training has become a billion-dollar industry with the promise that exercising a cognitive faculty (e.g., attention) on simple "brain games" will lead to improvements on any task relying on the same faculty. Although this logic seems sound, it assumes performance improves on training tasks because attention's capacity has been enhanced. Alternatively, training may result in attentional expertise-an enhancement of the ability to deploy attention to particular content-such that improvement on training tasks is specific to the features of the training context. The present study supported this attentional expertise hypothesis, showing that training benefits did not generalize fully from a trained attentional tracking task to untrained tracking tasks requiring a common attentional capacity, but differing in seemingly superficial features (i.e., retinotopic location and or motion type). This specificity suggests that attentional training benefits are linked to enhanced coordination between attentional processes and content-specific perceptual representations. Thus, these results indicate that shared attentional capacity between tasks is insufficient for producing generalized training benefits, and predict that generalization requires attentional expertise for content present in both training and outcome tasks.


S K-edge X-ray absorption spectroscopy and density functional theory studies of high and low spin {FeNO}7 thiolate complexes: exchange stabilization of electron delocalization in {FeNO}7 and {FeO2}8.
S K-edge X-ray absorption spectroscopy (XAS) is a direct experimental probe of metal ion electronic structure as the pre-edge energy reflects its oxidation state, and the energy splitting pattern of the pre-edge transitions reflects its spin state. The combination of sulfur K-edge XAS and density functional theory (DFT) calculations indicates that the electronic structures of {FeNO}(7) (S = 3/2) (S(Me2)N4(tren)Fe(NO), complex I) and {FeNO}(7) (S = 1/2) ((bme-daco)Fe(NO), complex II) are Fe(III)(S = 5/2)-NO(-)(S = 1) and Fe(III)(S = 3/2)-NO(-)(S = 1), respectively. When an axial ligand is computationally added to complex II, the electronic structure becomes Fe(II)(S = 0)-NO•(S = 1/2). These studies demonstrate how the ligand field of the Fe center defines its spin state and thus changes the electron exchange, an important factor in determining the electron distribution over {FeNO}(7) and {FeO2}(8) sites.


Browsing, Posting, and Liking on Instagram: The Reciprocal Relationships Between Different Types of Instagram Use and Adolescents' Depressed Mood.
Although studies have shown that Instagram use and young adults' mental health are cross-sectionally associated, longitudinal evidence is lacking. In addition, no study thus far examined this association, or the reverse, among adolescents. To address these gaps, we set up a longitudinal panel study among 12- to 19-year-old Flemish adolescents to investigate the reciprocal relationships between different types of Instagram use and depressed mood. Self-report data from 671 adolescent Instagram users (61% girls; MAge = 14.96; SD = 1.29) were used to examine our research question and test our hypotheses. Structural equation modeling showed that Instagram browsing at Time 1 was related to increases in adolescents' depressed mood at Time 2. In addition, adolescents' depressed mood at Time 1 was related to increases in Instagram posting at Time 2. These relationships were similar among boys and girls. Potential explanations for the study findings and suggestions for future research are discussed.


Adjudin protects rodent cochlear hair cells against gentamicin ototoxicity via the SIRT3-ROS pathway.
Hearing loss resulting from hair cell degeneration is a common disease that affects millions of people worldwide. Strategies to overcome the apparent irreversible hair cell loss in mammals become paramount for hearing protection. Here we reported that, by using a well-established gentamicin-induced hair cell loss model in vitro, adjudin, a multi-functional small molecule drug, protected cochlear hair cells from gentamicin damage. Immunohistochemistry, Western blotting and quantitative RT-PCR analyses revealed that adjudin exerted its otoprotective effects by up-regulating the level of Sirt3, a member of Sirtuin family protein located in mitochondria, which regulates reactive oxygen species (ROS) production in cochlear cells and inhibits the production of ROS and apoptotic cells induced by gentamicin. Sirt3 silencing experiments confirmed that Sirt3-ROS signaling axis mediated hair cell protection against gentamicin by adjudin, at least in part. Furthermore, adjudin's otoprotection effects were also observed in an in vivo gentamicin-injured animal model. Taken together, these findings identify adjudin as a novel otoprotective small molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in hair cell protection from ototoxic insults.


Barriers to Prevention and Timely Presentation of Diabetic Foot Ulcers: Perspectives of Patients from a High-risk Urban Population in the United States.
Diabetic foot amputation is a preventable complication that is increasing in incidence in the United States, with disparities across geography, race, ethnicity, and income. This qualitative study explored the experiences of people in a low-income urban area in the United States in preventing and obtaining care for foot ulcers. Sixteen adults with foot ulcers were identified through purposive sampling based on records of hospital stays and primary care visits. Semi-structured interviews were transcribed and analyzed for key themes. Participants described inadequate understanding of diabetic foot disease: many sought care only after developing advanced symptoms. They identified social and health system factors as barriers to timely access to care. Some participants described a realization of the seriousness of their condition and an ability to improve self-care after developing an ulcer. Patients' experiences can inform the design of amputation-reduction initiatives to achieve more desirable results, including enhanced self-management capabilities, timely access, and attention to social determinants.


Modulation transfer function measurement of a multichannel optical system.
We present a new method to measure the modulation transfer function (MTF) beyond the Nyquist frequency of a multichannel imaging system for which all the channels have parallel optical axes. Such a multichannel optical system produces a set of undersampled subimages. If the subimages contain nonredundant information, high spatial frequencies are folded between low spatial frequencies, leading to the possible extraction of frequencies higher than the Nyquist frequency. The measurement of the MTF of the multichannel system leads to the estimation of the resolution enhancement of the final image that can be obtained by applying a postprocessing algorithm to the collection of undersampled subimages. Experimental images are presented to validate this method.


New Directions for Half-Life Extension of Protein Therapeutics: The Rise of Antibody Fc Domains and Fragments.
Protein-based therapeutics has become one of the most rapidly growing and successful drug class in the clinic. However, there are still a number of key challenges that need to be addressed before the full therapeutic potential of protein drugs can be realized. Of note, many biologically active proteins have very short in vivo half-lives, a fact that has greatly hindered their clinical applications. Consequently, several different strategies including polyethylene glycol modification and fusion with Fc or albumin have been developed and implemented to prolong the serum half-life of protein therapeutics. Here we will focus on the recent advances in the development of Fc-based antibody fragments and domains and their potential use as novel half-life-extending fusion partners for protein therapeutics.


Predictors of early versus late smoking abstinence within a 24-month disease management program.
Standard smoking cessation treatment studies have been limited to 6- to 12-month follow-up, and examination of predictors of abstinence has been restricted to this timeframe. The KanQuit study enrolled 750 rural smokers across all stages of readiness to stop smoking and provided pharmacotherapy management and/or disease management, including motivational interviewing (MI) counseling every 6 months over 2 years. This paper examines differences in predictors of abstinence following initial (6-month) and extended (24-month) intervention. Baseline variables were analyzed as potential predictors of self-reported smoking abstinence at Month 6 and at Month 24. Chi-square tests, 2-sample t tests, and multiple logistic regression analyses were used to identify predictors of abstinence among 592 participants who completed assessment at baseline and Months 6 and 24. Controlling for treatment group, the final regression models showed that male gender and lower baseline cigarettes per day predicted abstinence at both 6 and 24 months. While remaining significant, the relative advantage of being male decreased over time. Global motivation to stop smoking, controlled motivation, and self-efficacy predicted abstinence at 6 months but did not predict abstinence at Month 24. In contrast, stage of change was strongly predictive of 24-month smoking status. While the importance of some predictors of successful smoking cessation appeared to diminish over time, initial lack of interest in cessation and number of cigarettes per day strongly predicted continued smoking following a 2-year program.


[Breast cancer metastases in the iris: does treatment modifies natural history of the illness?].
The 4-5% of the breast cancer patients have metastases in the eye. We present the case of a 30-year-old woman with an infiltrant duct carcinoma of the breast pT2N2M0 HER2 positive. Six months after primary radical treatment she had a systemic relapse with multiples metastatic sites, so several treatment with trastuzumab in combination with chemotherapy were started. After 4 years patient presented multiple white-coloured micronodules in the iris of the right eye. Only a 3-7.8% of ocular metastases are located in the iris. With mantenaince therapy with trastuzumab natural history of the illness has changed. Several studies had analyzed if metastases in the brain during treatment with trastuzumab have increased in comparison with the pretrastuzumab era. The infrequent presentation of metastases in the anterior uveal makes difficult to establish if it is an spontaneous fact or if it is favoured by trastuzumab treatment.


New chaos-integrated improved grey wolf optimization based models for automatic detection of depression in online social media and networks.
Depression is a psychological effect of the modern lifestyle on people's thoughts. It is a serious individual and social health problem due to the risk of suicide and loss of workforce, high chronicity, recurrence rates, and prevalence. Therefore, identification, prevention, treatment of depression, and determination of relapse risk factors are of great importance. Depression has traditionally been diagnosed using standardized scales that require clinical diagnoses or patients' subjective responses. However, these classical techniques have some limitations such as cost, uncomfortability, subjectivity, and ineffectiveness. Social media data can be simply and efficiently used for depression detection because it allows instantaneous emotional expression and quick access to various information. Some machine learning-based methods are used for detecting the depression in online social media and networks. Nevertheless, these algorithms suffer from several drawbacks, including data sparsity, dimension explosion, restricted capacity for generalization, and low performance on imbalanced data sets. Furthermore, many machine learning methods work as black-box models, and the constructed depression detection models are not interpretable and explainable. Intelligent metaheuristic optimization algorithms are widely used for different types of complex real-world problems due to their simplicity and high performance. It is aimed to remove the limitations of studies on this problem by increasing the success rate and automatically selecting the relevant features and integrating the explainability. In this study, new chaos-integrated multi-objective optimization algorithms are proposed to increase efficiency. New improved Grey Wolf Optimization algorithms have been proposed by integrating Circle, Logistic, and Iterative chaotic maps into the improved Grey Wolf Optimization algorithm. It is aimed to increase the success rate by proposing a multi-objective fitness function that can optimize the accuracy and the number of features simultaneously. The proposed algorithms are compared with different types of popular supervised machine learning algorithms and current metaheuristic algorithms that are widely and successfully used in depression detection problems. Experimental results show that the proposed models outperform machine learning methods, as evidenced by examining results with accuracy, F-measure, MCC, sensitivity, and precision measures. An accuracy value of 100% was obtained from proposed algorithms. In addition, when the confusion matrices are examined, it is seen that they exhibit a successful distribution. Although it is a new research and application area for optimization theory, promising results have been obtained from the proposed models.


Pliocene-Early Pleistocene Geological Events Structure Pacific Martens (Martes caurina).
The complex topography, climate, and geological history of Western North America have shaped contemporary patterns of biodiversity and species distributions in the region. Pacific martens (Martes caurina) are distributed along the northern Pacific Coast of North America with disjunct populations found throughout the Northwestern Forested Mountains and Marine West Coast Forest ecoregions of the West Coast. Martes in this region have been classified into subspecies; however, the subspecific designation has been extensively debated. In this study, we use genomic data to delineate conservation units of Pacific marten in the Sierra-Cascade-Coastal montane belt in the western United States. We analyzed the mitochondrial genome for 94 individuals to evaluate the spatial distribution and divergence times of major lineages. We further genotyped 401 individuals at 13 microsatellite loci to investigate major patterns of population structure. Both nuclear and mitochondrial DNA suggest substantial genetic substructure concordant with historical subspecies designations. Our results revealed that the region contains 2 distinct mitochondrial lineages: a Cascades/Sierra lineage that diverged from the Cascades/coastal lineage 2.23 (1.48-3.14 mya), consistent with orogeny of the Cascade Mountain chain. Interestingly, Pacific Martes share phylogeographic patterns similar with other sympatric taxa, suggesting that the complex geological history has shaped the biota of this region. The information is critical for conservation and management efforts, and further investigation of adaptive diversity is warranted following appropriate revision of conservation management designations.


Vergence-mediated changes in Listing's plane do not occur in an eye with superior oblique palsy.
As a normal subject looks from far to near, Listing's plane rotates temporally in each eye. Since Listing's plane relates to the control of torsional eye position, mostly by the oblique eye muscles, the current study was conducted to test the hypothesis that a patient with isolated superior oblique palsy would have a problem controlling Listing's plane. Using the three-dimensional scleral search coil technique, binocular Listing's plane was measured in four patients with congenital and in four patients with acquired unilateral superior oblique palsy during far- (94 cm) and near- (15 cm) viewing. The results were compared to previously published Listing's plane data collected under exactly the same conditions from 10 normal subjects. In patients with unilateral superior oblique palsy, either congenital or acquired, Listing's plane in the normal eye rotated temporally on near-viewing, as in normal subjects, while in the paretic eye it failed to do so. In patients with acquired superior oblique palsy, Listing's plane was already rotated temporally during far-viewing and failed to rotate any farther on near-viewing, whereas in patients with congenital superior oblique palsy Listing's plane in the paretic eye was oriented normally during far-viewing and failed to rotate any farther on near-viewing. These results suggest that the superior oblique muscle, at least in part, is responsible for the temporal rotation of Listing's plane that occurs in normal subjects on convergence.


ǂŪsigu: A mixed-method lexical study of character description in Khoekhoegowab.
Personality psychology relies heavily on evidence from North America and Europe. Lexical studies, based on the rationale that the most important psychological distinctions between people will be encoded in the natural languages, can provide input from underrepresented contexts by defining locally relevant personality concepts and their structure. We report the results of a psycholexical study in Khoekhoegowab, the most widely spoken of southern Africa's (non-Bantu) click languages. It includes the largest sample of any lexical study conducted in Sub-Saharan Africa, is the first anywhere to include qualitative interviews to systematically assess the interpretability of terms, and is one of few to rely on a more representative community sample of adults rather than students. Refinement of the survey included frequency-of-use ratings by native speakers from throughout Namibia and input on relevance to personality by those with a psychology degree. The survey was administered by interview to 622 participants by a team of 15 schoolteachers of Khoekhoegowab. The 11 dimensions of the optimal local model were labeled: Intemperance, Prosocial Diligence, Intrusive Gossip, Good Nature, Bad Temper, Predatory Aggression, Haughty Self-Respect, Vanity/Egotism, and Fear versus Courage. A Big One model of evaluation was strongly replicated. Moderate replication was found for the Big Two, Pan-Cultural Three, and a hypothesized pan-African model based on prior lexical results in 2 languages. Replication criteria were not achieved for the Big Five, Big Six, or South African Personality Inventory models. What results suggest about the local cultural context and about culturally specific aspects of the imported models are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Cellular dynamics underlying regeneration of damaged axons differs from initial axon development.
While long-distance regeneration may be limited in mammalian species, it is becoming apparent that damaged mature neurons retain some capacity for attempted regeneration and that the adult CNS is not entirely inhibitory to axon growth. Our investigations show that there are critical intrinsic features of postinjury axonal regeneration that differ from initial axon development, and that these distinct differences may account for the limited and inappropriate regenerative response that currently characterizes the mature CNS. We compared the neurochemical and dynamic characteristics of developing axons to relatively mature regenerating axons, utilizing an in vitro model of axonal transection to long-term cultured rat cortical neurons. Immunolabelling studies revealed that regenerating and developing axons have a similar localization of cytoskeletal proteins, but the tips of regenerating axons, although morphologically similar, were smaller with reduced fillopodial extension, relative to developmental growth cones. Live imaging demonstrated that regenerating axons exhibited significantly less outgrowth than developmental neurites. Furthermore, growth cones of regenerating axons had a significant reduction in pausing, considered vital for interstitial branching and pathfinding, than did developmental growth cones. In addition, unlike developing axons, the regenerating axons were unresponsive to the growth factors BDNF and GDNF. Thus, although similar in their cytoskeletal composition, the growth cones of regenerative sprouts differed from their developmental counterparts in their size, their dynamic behaviour and their ability to respond to critical growth factors. These intrinsic differences may account for the inability of post-traumatic locally sprouting axons to make accurate pathway decisions and successfully respond to trauma.


Relaxing effect of pharmacologic interventions increasing cAMP in rat heart.
The relationship between cAMP and relaxation was studied in the isolated rat heart beating at constant rate and perfused at constant coronary flow. After treatment during 1 min with different positive inotropic interventions, cyclic nucleotide levels (cAMP and cGMP) and cAMP-dependent protein kinase activity were determined in heart homogenates. Glucagon, norepinephrine, and isoproterenol increased cAMP from 0.503 +/- 0.025 pmol/mg wet wt to 1.051 +/- 0.099, 0.900 +/- 0.064, and 0.982 +/- 0.138, respectively. Simultaneously glucagon, norepinephrine, and isoproterenol increased cAMP-dependent protein kinase activity ratio from 0.21 +/- 0.02 to 0.45 +/- 0.04, 0.33 +/- 0.02, and 0.34 +/- 0.02, respectively. The ratio between maximal velocities of contraction and relaxation (+T/-T) was significantly decreased by these interventions, whereas time to peak tension (TTP) was shortened by norepinephrine and isoproterenol. High calcium, ouabain, and paired stimulation did not affect cAMP levels, TTP, or +T/-T. A striking correlation was found between cAMP-dependent protein kinase activity and relaxation induces, i.e., TTP, -T, or +T/-T (r = +/- 0.7 to -0.9). Results suggest that inotropic interventions increasing cAMP levels might be primarily affecting intracellular mechanisms causing relaxation.


Analysis of the performance of the Hartmann-Shack sensor in the human eye.
A description of a Hartmann-Shack sensor to measure the aberrations of the human eye is presented. We performed an analysis of the accuracy and limitations of the sensor using experimental results and computer simulations. We compared the ocular modulation transfer function obtained from simultaneously recorded double-pass and Hartmann-Shack images. The following factors affecting the sensor performance were evaluated: the statistical accuracy, the number of modes used to reconstruct the wave front, the size of the microlenses, and the exposure time.


Moral zombies: why algorithms are not moral agents.
In philosophy of mind, zombies are imaginary creatures that are exact physical duplicates of conscious subjects for whom there is no first-personal experience. Zombies are meant to show that physicalism-the theory that the universe is made up entirely out of physical components-is false. In this paper, I apply the zombie thought experiment to the realm of morality to assess whether moral agency is something independent from sentience. Algorithms, I argue, are a kind of functional moral zombie, such that thinking about the latter can help us better understand and regulate the former. I contend that the main reason why algorithms can be neither autonomous nor accountable is that they lack sentience. Moral zombies and algorithms are incoherent as moral agents because they lack the necessary moral understanding to be morally responsible. To understand what it means to inflict pain on someone, it is necessary to have experiential knowledge of pain. At most, for an algorithm that feels nothing, 'values' will be items on a list, possibly prioritised in a certain way according to a number that represents weightiness. But entities that do not feel cannot value, and beings that do not value cannot act for moral reasons.


The European Forum for Clinical Management: prophylaxis against the respiratory syncytial virus in infants and young children with congenital cardiac disease.
A recent, randomised, double-blind, placebo-controlled trial has demonstrated the effectiveness of palivizumab (Synagis) for prophylaxis against infection by the respiratory syncytial virus in 1,287 young children with congenital cardiac disease. Guidelines for the use of palivizumab in these children considered to be at high risk were published by the American Academy of Pediatrics, followed by similar guidelines from the British Paediatric Cardiac Association, and recommendations from a number of other individual countries, including Canada, Germany, Spain, and France. In May, 2004, further discussion was held between a group of 15 paediatric cardiologists at a European forum for clinical management held in Munich, Germany. The objective of this forum was to define optimal recommendations on prevention of infection by the respiratory syncytial virus in infants and young children with congenital cardiac disease, appropriate to the clinical needs and style of those practising in paediatrics in individual countries. Participants were invited because of their knowledge of the therapeutic area, and for their experience of using palivizumab for prophylaxis against the respiratory syncytial virus in children with congenitally malformed hearts. Measures to educate the carers of children with such congenital malformations on precautions against infection by the respiratory syncytial virus were discussed, along with the many different aspects of best practice for therapeutic prophylaxis with palivizumab. The most appropriate timing of prophylaxis, recommendations for which children are most likely to benefit from prophylaxis, and suggested protocols were among the issues covered. The recommendations resulting from the discussions are presented in this paper, as a step towards reaching consensus.


RNA sequencing using fluorescent-labeled dideoxynucleotides and automated fluorescence detection.
Although dideoxy terminated sequencing of RNA, using reverse transcriptase and oligodeoxynucleotide primers, is now a well established method, the accuracy is limited by sequence ambiguities due to unspecific chain termination events. A protocol is described which circumvents these ambiguities by using fluorescence labels tagged to dideoxynucleotides. Only chain terminations caused by dideoxynucleotides were detected while premature terminated cDNA's remain undetectable. In addition, the remaining multiple signals at nucleotide positions can be assigned to sequence heterogeneities within the RNA sequence to be determined.


The use of hyperbaric oxygen to modify the effects of recent contusion injury to the spinal cord.
Studies on the experimental spinal contusion injury in animals confirm that posttraumatic ischemia contributes to central cystic necrosis or fibrosis occurring at the level of the spinal cord lesion. Hyperbaric oxygen (HBO) modifies the degree and extent of the pathology in the spinal cord of the experimental animals. HBO has been used for 45 patients with recent spinal cord injuries. The extent of recovery in 27 patients with upper motor neuron lesions treated with adequate HBO is reported. Fifteen of the 27 patients had useful functional recovery.


Somatostatin, cortistatin and their receptors in tumours.
Somatostatin (SS) and its synthetic analogs have a role in the treatment of neuroendocrine tumours both in terms of symptoms control and antiproliferative activities. These effects are mediated by five SS receptors, widely expressed in both human neuroendocrine and non-neuroendocrine tumours, which were demonstrated to be diagnostically and therapeutically valuable targets. Cortistatin (CST), a brain cortex peptide, partially homologous to SS and having similar functions is also expressed in peripheral tissues and tumours. CST binds all SS receptors, and, differently from SS, also the ghrelin receptor GHSR1a and the CST specific receptor MrgX2. The expression profile of CST is mostly restricted to neuroendocrine tumours (gastrointestinal, pancreas, lung, parathyroid, thyroid, adrenal). In these tumours, CST probably acts via the SS or ghrelin receptor, the MrgX2 receptor being absent. Thus, in comparison to SS analogs, CST synthetic analogs may represent additional diagnostic/therapeutic tools in those tumours expressing the receptors for SS, for ghrelin or for both peptides.


The Cortical Processing of Sensorimotor Sequences is Disrupted in Writer's Cramp.
Evidence for pre-existing abnormalities in the sensory and motor systems has been previously reported in writer's cramp (WC). However, the processing of somatosensory information during motor planning has received little attention. We hypothesized that sensorimotor integration processes might be impaired partly due to a disruption in the parieto-premotor network. To test this assumption, we designed 2 nonwriting motor tasks in which subjects had to perform a 4-finger motor sequence either on the basis of sensory stimuli previously memorized (SM task) or freely generated (SG task). Brain activity was measured by combining event-related functional magnetic resonance imaging and coherency electroencephalography in 15 WC patients and 15 normal controls. The bold signal was decreased in patients in both tasks during sensory stimulation but not during movement execution. However, the EEG study showed that coherency was decreased in patients compared with controls, during the delay of the SM task and during the execution of the SG task, on both the whole network and for specific couples of electrodes. Overall, these results demonstrate an endophenotypic impairment in the synchronization of cortical areas within the parieto-premotor network during somatosensory processing and motor planning in WC patients.


Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin treatment fail to generate a calcium-mediated grp78/grp94 stress response.
grp78/grp94 induction is critical for maintaining the viability of epithelial cells and fibroblasts following treatment with thapsigargin (TG), an inhibitor of Ca2+ uptake into the endoplasmic reticulum. In contrast to these cell types, WEHI7.2 mouse lymphoma cells undergo apoptosis when treated with TG, prompting us to examine the grp78/grp94 stress response in WEHI7.2 cells. TG treatment failed to induce grp78/grp94 transcription in WEHI7.2 cells, measured by Northern hybridization and nuclear run-on assays, even if the cells were protected from apoptosis by overexpressing bcl-2. However, grp78/grp94 transcription was induced by the glycosylation inhibitor tunicamycin, suggesting that there are at least two grp78/grp94 signaling pathways, one in response to TG-induced endoplasmic reticulum Ca2+ pool depletion, which is inoperable in WEHI7.2 cells, and one in response to glycosylation inhibition, which is operable in WEHI7.2 cells. Studies of additional lymphoid lines, as well as several nonlymphoid lines, suggested a correlation between grp78/grp94 induction and resistance to apoptosis following TG treatment. In conclusion, the vulnerability of TG-treated WEHI7.2 cells to apoptosis may be due to failure to signal a grp78/grp94 stress response.


Potential benefits of amino acid supplementation for cervid performance and nutritional ecology, with special focus on lysine and methionine: A review.
Deer farming is a thriving industry for venison, velvet antlers, trophy hunting, and other by-products. Feeding and nutrition are important factors for improving production performance, especially dietary protein and amino acids (AAs), as they are the main components of all tissues. Only a few studies on AA supplementation (Lys, Met, Arg) have been performed on cervids, which show positive effects on weight gain, ADG, feed-:gain ratio, plasma AAs, carcass weight, dressing percentage, yield of high-quality muscles, storage of internal fat during winter, DM and CP digestibility, plasma protein- and fat-related metabolite concentrations, antler burr perimeter, weight, length and mineralisation, velvet antler yield, rumen volatile fatty acids, and microbiome composition. All these effects are relevant for supporting the production of cervids products, from venison to velvet or trophy antlers, as well as their general performance and well-being of captive-bred cervids. The current available information suggests that AA supplementation can be especially interesting for animals fed low protein rations, and growing animals, but should be avoided in high rations and during winter, since it may promote the accumulation of internal fat. Potential effects on milk production and the concentrations of different hormones involved in the regulation of the antler cycle should be further explored.


Registration of functional and anatomical MRI: accuracy assessment and application in navigated neurosurgery.
A procedure for acquisition, automated registration, and fusion of functional and anatomical magnetic resonance images is presented. Its accuracy is quantitatively assessed using a publicly available gold standard. A patient case is used to illustrate the technique's clinical usefulness in image-guided neurosurgery. Before and after functional MRI (fMRI) acquisition, additional anatomical images were acquired at spatial locations identical to those of the functional images (5-10 slices) for the purpose of voxel-based image registration. Registration accuracy of the anatomical volumes and high-resolution 3D MRI volumes (MP-RAGE imaging) was quantified using adapted data (8 patients) originating from the Vanderbilt Retrospective Registration Evaluation Project (NIH project 1 R01 NS33926-02). Selecting three subsets of slices from that data (5 slices/6 mm slice distance, 10 slices/3 mm distance, and 10 slices/6 mm distance), the small number of images available from fMRI acquisition was taken into account. Accuracies in registering these sparse data sets were then compared to the accuracy achieved using complete data. For clinical patient data (16 patients), fMRI images were fused with MP-RAGE images, thereby integrating anatomical images with information about the locations of functional areas. The resulting images were used for planning and navigation during tumor resections using an operating microscope (MKM, Zeiss). Quantitative analysis showed no loss of registration accuracy due to a reduced number of slices, regardless of whether 5 or 10 slices were used. For small-volume coverage in the anatomical images (thickness 24 mm), registration of one patient failed, and this could easily be identified by visual inspection. No failures were experienced when 54 mm was covered. In the clinical environment, all 16 interventions using fused fMRI and MRI data were successful. Automatic registration of functional and high-resolution anatomical MRI was found to be sufficiently accurate and reliable for use in stereotactic neurosurgery.


Additive bronchoprotective and bronchodilator effects with single doses of salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids.
We wished to evaluate whether the combination of a leukotriene receptor antagonist and long-acting beta(2)-agonist might confer additive beneficial effects in terms of bronchoprotection and bronchodilatation, in mild to moderate asthmatic patients who were suboptimally controlled on inhaled corticosteroids alone. Twelve asthmatic patients were enrolled into a single-blind, placebo-controlled, crossover study, receiving additive therapy as either of the following: (1) montelukast alone, 10 mg (ML(10)); (2) inhaled salmeterol alone, 50 microg (SM(50)); (3) ML(10) and SM(50); (4) ML(10) and inhaled salmeterol, 100 microg (SM(100)); or (5) placebo inhaler and tablet. Trough measurements were made of adenosine monophosphate (AMP) bronchial challenge (the provocative concentration of a drug [AMP] causing a fall of >/= 20% in FEV(1) [PC(20)]) as the primary end point, and spirometry, following single doses of either placebo or active treatments (12 h after salmeterol, and 24 h after monteleukast, respectively). Compared to placebo, all active treatments led to significant improvements (p < 0.05) in geometric mean AMP-PC(20): placebo, 42 mg/mL; ML(10), 106 mg/mL; SM(50), 115 mg/mL; ML(10) and SM(50), 183 mg/mL; and ML(10) and SM(100), 247 mg/mL. The effects of montelukast and salmeterol were numerically additive, with ML(10) and SM(100) being significantly different (p < 0.05) from ML(10) alone. For mean FEV(1) and forced expiratory flow rate between 25% and 75% of vital capacity, there were significant differences (p < 0.05) between both combination therapies vs ML(10) alone. Our results suggest additive benefits of a single dose of a long-acting beta(2)-agonist and leukotriene antagonist, in terms of bronchoprotection and bronchodilation. Further studies in more severe asthmatics are required to evaluate long-term clinical effects.


Drinking water as a proportion of total human exposure to volatile N-nitrosamines.
Some volatile N-nitrosamines, primarily N-nitrosodimethylamine (NDMA), are recognized as products of drinking water treatment at ng/L levels and as known carcinogens. The U.S. EPA has identified the N-nitrosamines as contaminants being considered for regulation as a group under the Safe Drinking Water Act. Nitrosamines are common dietary components, and a major database (over 18,000 drinking water samples) has recently been created under the Unregulated Contaminant Monitoring Rule. A Monte Carlo modeling analysis in 2007 found that drinking water contributed less than 2.8% of ingested NDMA and less than 0.02% of total NDMA exposure when estimated endogenous formation was considered. Our analysis, based upon human blood concentrations, indicates that endogenous NDMA production is larger than expected. The blood-based estimates are within the range that would be calculated from estimates based on daily urinary NDMA excretion and an estimate based on methylated guanine in DNA of lymphocytes from human volunteers. Our analysis of ingested NDMA from food and water based on Monte Carlo modeling with more complete data input shows that drinking water contributes a mean proportion of the lifetime average daily NDMA dose ranging from between 0.0002% and 0.001% for surface water systems using free chlorine or between 0.001% and 0.01% for surface water systems using chloramines. The proportions of average daily dose are higher for infants (zero to six months) than other age cohorts, with the highest mean up to 0.09% (upper 95th percentile of 0.3%).


Impact of balloon-occluded retrograde transvenous obliteration on management of isolated fundal gastric variceal bleeding.
Although endoscopic injection of cyanoacrylate (CA) is the only effective method for treating isolated fundal gastric variceal bleeding, the rebleeding rate is relatively high. This study investigated the efficacy of balloon-occluded retrograde transvenous obliteration (B-RTO) for management of isolated fundal gastric variceal bleeding. Patients (n = 110) with acute or recent bleeding from isolated fundal gastric varices (GV) were retrospectively studied. Acute bleeding was treated by CA injection or balloon tamponade. 44 patients underwent additional endoscopic injection of CA and ethanolamine oleate (EO) weekly until obturation of GVx from 1994 to 2002 (group A). 42 patients from 2003 to 2010 underwent B-RTO after initial hemostasis (group B). Both groups were assessed for the number of sessions required to achieve GV obturation, hospital stay, recurrent bleeding rate, morbidity and mortality. Acute gastric variceal bleeding was successfully treated in all patients by CA injection or balloon tamponade. B-RTO was successfully performed except in two patients in group B. The average number of sessions required for obturation was 3.8 for groups A and 2.2 for B (P < 0.05). Recurrent bleeding was observed in 16 and two patients in groups A and B, respectively. The cumulative non-rebleeding rate at 5 years was 58.3% and 98.1% in groups A and B, respectively. The cumulative survival rate at 5 years was 53.8% and 87.6% in groups A and B, respectively. Balloon-occluded retrograde transvenous obliteration may be superior to endoscopic injection with CA and EO for prevention of rebleeding in patients with isolated fundal GVs with a major shunt.


Listeria monocytogenes-How This Pathogen Uses Its Virulence Mechanisms to Infect the Hosts.
Listeriosis is a serious food-borne illness, especially in susceptible populations, including children, pregnant women, and elderlies. The disease can occur in two forms: non-invasive febrile gastroenteritis and severe invasive listeriosis with septicemia, meningoencephalitis, perinatal infections, and abortion. Expression of each symptom depends on various bacterial virulence factors, immunological status of the infected person, and the number of ingested bacteria. Internalins, mainly InlA and InlB, invasins (invasin A, LAP), and other surface adhesion proteins (InlP1, InlP4) are responsible for epithelial cell binding, whereas internalin C (InlC) and actin assembly-inducing protein (ActA) are involved in cell-to-cell bacterial spread. L. monocytogenes is able to disseminate through the blood and invade diverse host organs. In persons with impaired immunity, the elderly, and pregnant women, the pathogen can also cross the blood-brain and placental barriers, which results in the invasion of the central nervous system and fetus infection, respectively. The aim of this comprehensive review is to summarize the current knowledge on the epidemiology of listeriosis and L. monocytogenes virulence mechanisms that are involved in host infection, with a special focus on their molecular and cellular aspects. We believe that all this information is crucial for a better understanding of the pathogenesis of L. monocytogenes infection.


The effect of electroconvulsive therapy (ECT) on serum tryptophan metabolites.
Prior studies suggest that activation of the tryptophan catabolism via the kynurenine pathway by proinflammatory cytokines may be involved in the pathophysiology of depression. Electroconvulsive therapy (ECT) is an effective treatment for major depression (MD) with immunomodulation as one of the proposed modes of action. The aim of this study was to investigate serum concentrations of tryptophan and kynurenine pathway metabolites in MD patients and healthy controls, and to explore the effect of ECT on components of the kynurenine pathway. The study included 27 moderately to severely depressed patients referred to ECT. Blood samples were collected prior to treatment and after the completed ECT-series. Baseline samples were also collected from 14 healthy, age- and sex-matched controls. Serum concentrations of tryptophan, kynurenine, 3-hydroxykynurenine (HK), kynurenic acid (KA), xanthurenic acid (XA), anthranilic acid (AA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA), picolinic acid (Pic), pyridoxal 5'-phosphat (PLP), riboflavin, neopterin and cotinine were measured. Patients with MD had lower levels of neuroprotective kynurenine-pathway metabolites (KA, XA and Pic) and lower metabolite ratios (KA/Kyn and KA/QA) reflecting reduced neuroprotection compared to controls. The concentration of the inflammatory marker neopterin was increased after ECT, along with Pic and the redox active and immunosuppressive metabolite HAA. In this pilot study, we found increased concentrations of inflammatory marker neopterin and putative neuroprotective kynurenine metabolites HAA and Pic in MD patients after ECT. Further research in larger cohorts is required to conclude whether ECT exerts its therapeutic effects via changes in the kynurenine pathway.


Anticancer Hybrid Combinations: Mechanisms of Action, Implications and Future Perspectives.
The exponential growth of cancer cases worldwide together with recent advances concerning the pathophysiological mechanisms of the disease at the molecular level led to a paradigm shift in chemotherapy, from monotherapy to targeted drug combination regimens. However, adverse effects and the emergence of multidrug resistance (MDR) limit the effectiveness of these therapies. In this context, hybrid combinations mixing anticancer drugs and bioactive phytochemical components from medicinal plants, or even plant extracts, that can act synergistically on multiple targets and signaling pathways represent a promising approach with the potential to expand the current therapeutic arsenal. This review aims to provide a synopsis on anticancer hybrid combinations based on their multi-target mechanisms and synergistic effects from an extensive literature search focusing mainly on publications from the last ten years. In most of these combinations, the phytochemical component was shown to enhance the anticancer activity of the chemotherapeutic agent and to sensitize chemoresistant tumors in several types of cancer. Hybrid combinations, due to synergistic interactions, are also associated with less severe adverse events since lower doses can be used to achieve the same therapeutic effect. Further preclinical and clinical studies are needed, as well as the development of an adequate regulatory framework, before hybrid combination therapy can be translated into clinical practice.


Intrinsic neuroregulation of ion transport in porcine distal jejunum.
The roles of spontaneous and electrically stimulated neural activity on mucosal ion transport were examined in the distal jejunum of the pig, an omnivorous species whose digestive function bears similarities to that of humans. Serosal administration of the neuronal conduction blocker tetrodotoxin (TTX; 0.1 mumol/l), the presynaptic Ca channel blocker omega-conotoxin GVIA (0.1 mumol/l) and the ganglionic-blocking agent hexamethonium (0.1 mmol/l) decreased basal short-circuit current (Isc) across sheets of jejunal mucosa-submusa in vitro. The TTX-induced change in Isc was attributable to an increase in net Cl absorption. Electrical transmural stimulation (ETS; 300 pulses at 0.5, 3 or 10 Hz, 0.5-msec pulse width, 2.8 mA cm-2) of the mucosa-submucosa produced a frequency-dependent increase in Isc and an increase in net anion secretion. TTX, conotoxin and hexamethonium produced concentration-dependent decreases of the ETS-evoked increase in Isc, indicating that ETS depolarizes enteric neurons and suggesting that cholinergic neurons synapsing with submucosal neurons play a significant role in mediating ETS-evoked ion transport. The ETS-induced Isc appears to be mediated by neurons containing acetylcholine but not substance P or vasoactive intestinal polypeptide. These results suggest that submucosal noncholinergic neurons tonically limit Cl but not Na absorption. Electrical depolarization of submucosal neurons evokes anion secretion which appears to be mediated by cholinergic neurons as well as neurons of unknown chemical identity.


Fostering maternal and newborn care in India the Yashoda way: does this improve maternal and newborn care practices during institutional delivery?
The Yashoda program, named after a legendary foster-mother in Indian mythology, under the Norway-India Partnership Initiative was launched as a pilot program in 2008 to improve the quality of maternal and neonatal care at facilities in select districts of India. Yashodas were placed mainly at district hospitals, which are high delivery load facilities, to provide support and care to mothers and newborns during their stay at these facilities. This study presents the results from the evaluation of this intervention in two states in India. Data collection methods included in-depth interviews with healthcare providers and mothers and a survey of mothers who had recently delivered within a quasi-experimental design. Fifty IDIs were done and 1,652 mothers who had delivered in the past three months were surveyed during 2010 and 2011. A significantly higher proportion of mothers at facilities with Yashodas (55 percent to 97 percent) received counseling on immunization, breastfeeding, family planning, danger signs, and nutrition compared to those in control districts (34 percent to 66 percent). Mothers in intervention facilities were four to five times more likely to receive postnatal checks than mothers in control facilities. Among mothers who underwent cesarean sections, initiation of breastfeeding within five hours was 50 percent higher in intervention facilities. Mothers and families also reported increased support, care and respect at intervention facilities. Yashoda as mothers' aide thus seems to be an effective intervention to improve quality of maternal and newborn care in India. Scaling up of this intervention is recommended in district hospitals and other facilities with high volume of deliveries.


A randomized intervention trial of 24-wk dairy consumption on waist circumference, blood pressure, and fasting blood sugar and lipids in Japanese men with metabolic syndrome.
Dairy foods are postulated to have beneficial effects on blood pressure, body fat, serum lipids, and the incidence of type 2 diabetes. To evaluate the effects of the consumption of milk and dairy products, we performed a randomized dietary intervention trial for 24 wk in Japanese men, aged 20 to 60 y, with 2 or more components of the metabolic syndrome ( UMIN000006353). Subjects were randomized to a control group (n=98) that received dietary intervention focused on weight control supervised by registered dietitians, and a dairy-consumption group (n=102) that received both dietary intervention and regular home dairy delivery of 400 g/d for 24 wk. Co-primary endpoints included waist circumference, blood pressure, fasting blood sugar (FBS), and serum lipids. The dietary intervention decreased energy intake from 2,150 to 1,850 kcal/d in both groups (p<0.01). Mean rates of compliance with the dairy-consumption intervention were over 90%, resulting in increased calcium intake in the dairy-consumption group from 329 to 667 mg/d (p<0.01). Co-primary endpoints improved in both groups, but the degree of improvement was smaller in the dairy-consumption group (one-sided p=0.99). Subgroup analyses specified in the study protocol identified weight and leisure-time physical activity (LTPA) as significant effect modifiers. Differences in changes in systolic blood pressure compared with the control group were 28.0 mmHg (95% CI, 214.0 to 21.9, interaction; p<0.01) in the normal weight group and 25.8 mmHg (211.4 to 20.2, interaction; p=0.02) in the moderate-to-high LTPA group, indicating lower systolic blood pressure in the dairy-consumption group among participants in these subgroups. In conclusion, although effects on the co-primary endpoints of dairy consumption were not shown, dairy consumption lowered systolic blood pressure in the subgroups with normal weight and moderate-to-high LTPA and lowered FBS in the subgroup with normal weight.


Deletion of Synechocystis sp. PCC 6803 leader peptidase LepB1 affects photosynthetic complexes and respiration.
The cyanobacterium Synechocystis sp. PCC 6803 possesses two leader peptidases, LepB1 (Sll0716) and LepB2 (Slr1377), responsible for the processing of signal peptide-containing proteins. Deletion of the gene for LepB1 results in an inability to grow photoautotrophically and an extreme light sensitivity. Here we show, using a combination of Blue Native/SDS-PAGE, Western blotting and iTRAQ analysis, that lack of LepB1 strongly affects the cell's ability to accumulate wild-type levels of both photosystem I (PSI) and cytochrome (Cyt) b6f complexes. The impaired assembly of PSI and Cyt b6f is considered to be caused by the no or slow processing of the integral subunits PsaF and Cyt f respectively. In particular, PsaF, one of the PSI subunits, was found incorporated into PSI in its unprocessed form, which could influence the assembly and/or stability of PSI. In contrast to these results, we found the amount of assembled photosystem II (PSII) unchanged, despite a slower processing of PsbO. Thus, imbalance in the ratios of PSI and Cyt b6f to photosystem II leads to an imbalanced photosynthetic electron flow up- and down-stream of the plastoquinone pool, resulting in the observed light sensitivity of the mutant. We conclude that LepB1 is the natural leader peptidase for PsaF, PsbO, and Cyt f. The maturation of PsbO and Cyt f can be partially performed by LepB2, whereas PsaF processing is completely dependent on LepB1. iTRAQ analysis also revealed a number of indirect effects accompanying the mutation, primarily a strong induction of the CydAB oxidase as well as a significant decrease in phycobiliproteins and chlorophyll/heme biosynthesis enzymes.


[Pneumococcal Vaccination Coverage Rates (VCRs) Among Persons with Vaccine-Relevant Underlying Conditions and Persons Aged 60 Years and Older - An Analysis of Secondary Data from the Statutory Health Insurance (SHI) System].
In addition to standard vaccination for patients aged 60 and older, the Standing Committee on Vaccination (STIKO) recommends immunization against pneumococci for anyone at increased risk, including patients with chronic vaccine-relevant underlying conditions. In Germany, the Robert Koch Institute (RKI) regularly publishes vaccination coverage rates (VCRs) for these patient groups, without stratifying by other parameters. This study examines VCRs of patients with underlying chronic diseases, stratified by disease groups and entities, the re-vaccination rate, and VCRs in patients aged 60 years and older. This descriptive retrospective cohort study is based on a sample of about 4 million SHI-insured patients aged 16 years and older for the years 2014 to 2019, from the Institute for Applied Health Research (InGef) database. The sample is representative of age and sex distribution in the German population. Extrapolated to the total SHI-population, the overall pneumococcal VCR in patients aged 60 years and older was 45.9 % (of n= InGef standard vaccination cohort: 1 009 763). Among all at-risk patients aged 16 years and older with chronic underlying diseases, only 17.1 % had received an indicated vaccination (InGef indicated vaccination cohort: 1 379 680). Stratified by disease entity, those with underlying pulmonary emphysema had the highest VCR, at 39.0 % (of n= 28 121). Of those who received a vaccination due to an underlying chronic disease, only 23.9 % were re-vaccinated after 6 years (InGef re-vaccination cohort: 12 328). Across all vaccination cohorts, VCRs increased with age. The recommendations made by STIKO for pneumococcal vaccination based on age or an underlying chronic condition are not being implemented adequately in Germany. Although STIKO explicitly recommends vaccination from 60 years of age, the 60 to 64-year-old age group had a strikingly low VCR (13.0 % of n=268 862). Fewer than one in five patients aged 16 years and older with an underlying chronic condition had received the recommended indicated vaccination. To adequately prevent potential disease, higher vaccination rates should be targeted. This could probably be achieved through more stringent vaccination management, appropriate software solutions with vaccination reminders, monetary incentives for achieving higher vaccination rates and documentation of vaccination status in disease management programs.


Gated CNN-Transformer Network for Automatic Cardiovascular Diagnosis using 12-lead Electrocardiogram.
12-lead electrocardiogram (ECG) is a widely used method in the diagnosis of cardiovascular disease (CVD). With the increase in the number of CVD patients, the study of accurate automatic diagnosis methods via ECG has become a research hotspot. The use of deep learning-based methods can reduce the influence of human subjectivity and improve the diagnosis accuracy. In this paper, we propose a 12-lead ECG automatic diagnosis method based on channel features and temporal features fusion. Specifically, we design a gated CNN-Transformer network, in which the CNN block is used to extract signal embeddings to reduce data complexity. The dual-branch transformer structure is used to effectively extract channel and temporal features in low-dimensional embeddings, respectively. Finally, the features from the two branches are fused by the gating unit to achieve automatic CVD diagnosis from 12-lead ECG. The proposed end-to-end approach has more competitive performance than other deep learning algorithms, which achieves an overall diagnostic accuracy of 85.3% in the 12-lead ECG dataset of CPSC-2018.


Milk yield and composition of lactating cows fed steam-flaked sorghum and graded concentrations of ruminally degradable protein.
To determine the effect of various amounts of ruminally undegradable protein in the diets of lactating cows fed steam-flaked sorghum, 24 Holstein cows (90 +/- 50 d in milk) were assigned to three treatments: 0.8% urea, 6% soybean meal, or 5% fish meal. Respective percentages of ruminally undegradable protein in the diets (as a percentage of crude protein) were 30, 35, and 39%. All diets contained 37% alfalfa hay; 3 to 5% cottonseed hulls; 10 to 13% whole cottonseed; 39% steam-flaked sorghum (360 g/L); 5% of a molasses, mineral, and vitamin supplement; and the different protein supplements. Intake of dry matter was higher for cows fed urea than for cows fed soybean meal or fish meal diets. In cows that yielded more than 40 kg/d of milk (4 cows per treatment), the soybean meal and fish meal diets resulted in higher yields of milk and 3.5% fat-corrected milk and a greater efficiency of conversion of feed to milk than did the urea diet. Cows that yielded less than 40 kg/d of milk (4 cows per treatment) at the beginning of treatment tended to yield more milk when fed urea than when fed the protein supplements. Nutrient digestibilities were not greatly affected by source of N, suggesting a beneficial effect of urea supplementation on nutrient digestibilities because replacement of protein supplements with cottonseed products caused the neutral detergent fiber content of the urea diet to be about 7% higher than that of the other diets. These data show that response to ruminally undegradable protein in diets of lactating cows fed steam-flaked sorghum was related to milk yield.


Evolution of Mitral Valve Prolapse: Insights From the Framingham Heart Study.
Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking. We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 57±11 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all P<0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height ≥5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all P<0.05). NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression.


Self-harm and violent criminality among young people who experienced trauma-related hospital admission during childhood: a Danish national cohort study.
Development of a better understanding of subsequent pathways for individuals who experienced trauma during childhood might usefully inform clinicians and public health professionals regarding the causes of self-harm and interpersonal violence. We aimed to examine these risks during late adolescence and early adulthood among people admitted to hospital following injuries or poisonings during their childhood. This national cohort study included Danish people born between Jan 1, 1977, and Dec 31, 1997, and was linked to the National Patient Register and Psychiatric Central Research Register to identify all people exposed to hospital admissions for injuries or poisonings due to self-harm, interpersonal violence, or accidents before their 15th birthday. Linkage to these two registers and to the National Crime Register enabled ascertainment of self-harm and violent offending, respectively, as adverse outcomes at ages 15-35 years. Sex-specific incidence rate ratios (IRRs; relative risks) and cumulative incidence percentage values (absolute risks) were estimated. The confounding influence of parental socioeconomic status was also explored. 1 087 672 Danish people were included in this study. The prevalence of any trauma-related hospital admission was 10% (105 753 per 1 087 672; males: 64 454 [11%]; females: 44 299 [8%]) and for both sexes, accident was by far the most prevalent of the categories assessed (males: 59 011 [11%]; females: 40 756 [8%]). Similar patterns of increased risk for self-harm and violent criminality were observed in both sexes, although the IRRs were consistently and significantly larger in women (self-harm: IRR 1·94 [95% CI 1·85-2·02]; violent criminality: 2·16 [1·97-2·36]) than in men (self-harm: 1·61 [1·53-1·69]; violent criminality: 1·58 [1·53-1·63]). Confounding by parental socioeconomic status explained little of the increased risks observed. For young adult men, the highest absolute risk observed was for violent offending among individuals admitted to hospital for interpersonal violence injury during childhood (cumulative incidence 25·0% [95% CI 21·2-28·9]). For young adult women, absolute risk was highest for repeat self-harm among those admitted to hospital following self-harm during childhood (cumulative incidence 21·4% [95% CI 19·8-23·1]). More frequent trauma-related hospital admissions in childhood, and being admitted multiple times for more than one reason, conferred substantial risk increases among young people, with especially steep gradients of this nature observed among women. Trauma-related hospital admission early in life could be a useful marker for childhood distress that subsequently predicts internalised and externalised destructive behaviours among youths and young adults and might provide a timely opportunity for initiating family-oriented interventions. European Research Council.


Impact of obsessive-compulsive personality disorder symptoms in Internet users.
Internet use is pervasive in many cultures. Little is known about the impact of obsessive-compulsive personality disorder (OCPD) symptoms on impulsive and compulsive psychopathologies in people who use the Internet. Adult Internet users (N = 1,323) completed an online questionnaire quantifying OCPD symptoms, likely occurrence of select mental disorders (obsessive-compulsive disorder, attention-deficit/hyperactivity disorder [ADHD], problematic Internet use, generalized anxiety disorder), and personality questionnaires of impulsivity and compulsivity. Predictors of the presence of OCPD symptoms (endorsement of at least 4 of 8 DSM-5 criteria) were identified using binary logistic regression. In regression (P < .001, area under the curve, 0.77), OCPD symptoms were significantly associated with (in order of decreasing effect size) lower non-planning impulsivity, higher ADHD symptoms, problematic Internet use, avoidant personality disorder, female sex, generalized anxiety disorder, and some types of compulsions (checking, dressing/washing). These data suggest that OCPD symptoms, defined in terms of at least 4 of 8 DSM criteria being met, are common in Internet users. OCPD symptoms were associated with considerably higher levels of psychopathology relating to both impulsive (ADHD) and compulsive (OCD-related and problematic Internet use) disorders. These data merit replication and extension using standard in-person clinical assessments, because the current study relied on self-report over the Internet.


Severity and distribution of spasticity does not limit mobility or influence compensatory strategies following traumatic brain injury.
To determine whether the severity of lower limb spasticity had a differential effect on mobility following traumatic brain injury (TBI) and to investigate whether the distribution of lower limb spasticity influenced compensation strategies when walking. Ninety-three people attending physiotherapy for mobility limitations following TBI participated in this study. Participants were grouped according to the presence and distribution of lower limb spasticity for comparison. Mobility was measured using a 10-metre walk test and the high level mobility assessment tool. Three dimensional gait analysis was used to measure power generation and spasticity was assessed using the Tardieu scale. No significant relationship was found between the severity of lower limb spasticity and mobility limitations. There was a strong relationship between ankle power generation and mobility performance. Proximal compensation strategies did not vary significantly between groups with different distributions of lower limb spasticity. The ability to generate ankle power has a large impact on mobility outcome following TBI. Although spasticity was prevalent, the severity and distribution did not appear to impact mobility outcomes. Proximal compensation strategies were not influenced by the distribution of lower limb spasticity following TBI.