Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis revealed by organelle-specific antibodies.
Many studies have established the central involvement of the Golgi apparatus in the transport and processing of plasma membrane, lysosomal, and secreted proteins. The Golgi apparatus of neurons is also involved in the axoplasmic flow of fast-moving macromolecules and in the orthograde, retrograde, and transsynaptic transport of exogenous ligands. Markers of the Golgi apparatus, based on traditional methods of enzyme cytochemistry, are not applicable to human tissues obtained at autopsy. For that reason, the Golgi apparatus of brain cells has not been examined adequately in diseases of the human nervous system. Here we report that an antiserum raised against MG-160, a 160-kDa sialoglycoprotein of medial cisternae of the Golgi apparatus of several rat cells, is a specific and easily reproducible immunocytochemical marker of the Golgi apparatus of human neurons and other cells obtained at autopsy. Application of this probe in amyotrophic lateral sclerosis has shown a fragmentation of the Golgi apparatus in motor neurons similar to that induced by depolymerization of microtubules. We suggest that the fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis has functional implications because significant reductions of secretion of insulin and immunoglobulins have been observed in islet cells and plasma cells, respectively, treated with microtubule-disrupting agents.


A data-analytic strategy for protein biomarker discovery: profiling of high-dimensional proteomic data for cancer detection.
With recent advances in mass spectrometry techniques, it is now possible to investigate proteins over a wide range of molecular weights in small biological specimens. This advance has generated data-analytic challenges in proteomics, similar to those created by microarray technologies in genetics, namely, discovery of 'signature' protein profiles specific to each pathologic state (e.g. normal vs. cancer) or differential profiles between experimental conditions (e.g. treated by a drug of interest vs. untreated) from high-dimensional data. We propose a data-analytic strategy for discovering protein biomarkers based on such high-dimensional mass spectrometry data. A real biomarker-discovery project on prostate cancer is taken as a concrete example throughout the paper: the project aims to identify proteins in serum that distinguish cancer, benign hyperplasia, and normal states of prostate using the Surface Enhanced Laser Desorption/Ionization (SELDI) technology, a recently developed mass spectrometry technique. Our data-analytic strategy takes properties of the SELDI mass spectrometer into account: the SELDI output of a specimen contains about 48,000 (x, y) points where x is the protein mass divided by the number of charges introduced by ionization and y is the protein intensity of the corresponding mass per charge value, x, in that specimen. Given high coefficients of variation and other characteristics of protein intensity measures (y values), we reduce the measures of protein intensities to a set of binary variables that indicate peaks in the y-axis direction in the nearest neighborhoods of each mass per charge point in the x-axis direction. We then account for a shifting (measurement error) problem of the x-axis in SELDI output. After this pre-analysis processing of data, we combine the binary predictors to generate classification rules for cancer, benign hyperplasia, and normal states of prostate. Our approach is to apply the boosting algorithm to select binary predictors and construct a summary classifier. We empirically evaluate sensitivity and specificity of the resulting summary classifiers with a test dataset that is independent from the training dataset used to construct the summary classifiers. The proposed method performed nearly perfectly in distinguishing cancer and benign hyperplasia from normal. In the classification of cancer vs. benign hyperplasia, however, an appreciable proportion of the benign specimens were classified incorrectly as cancer. We discuss practical issues associated with our proposed approach to the analysis of SELDI output and its application in cancer biomarker discovery.


Predicting cognitive decline in multiple sclerosis: a 5-year follow-up study.
Cognitive decline is common in multiple sclerosis and strongly affects overall quality of life. Despite the identification of cross-sectional MRI correlates of cognitive impairment, predictors of future cognitive decline remain unclear. The objective of this study was to identify which MRI measures of structural damage, demographic and/or clinical measures at baseline best predict cognitive decline, during a 5-year follow-up period. A total of 234 patients with clinically definite multiple sclerosis and 60 healthy control subjects were examined twice, with a 5-year interval (mean = 4.9 years, standard deviation = 0.9). An extensive neuropsychological evaluation was performed at both time points and the reliable change index was computed to evaluate cognitive decline. Both whole-brain and regional MRI (3 T) measures were assessed at baseline, including white matter lesion volume, diffusion-based white matter integrity, cortical and deep grey matter volume. Logistic regression analyses were performed to determine which baseline measures best predicted cognitive decline in the entire sample as well as in early relapsing-remitting (symptom duration <10 years), late relapsing-remitting (symptom duration ≥10 years) and progressive phenotypes. At baseline, patients with multiple sclerosis had a mean disease duration of 14.8 (standard deviation = 8.4) years and 96/234 patients (41%) were classified as cognitively impaired. A total of 66/234 patients (28%) demonstrated cognitive decline during follow-up, with higher frequencies in progressive compared to relapsing-remitting patients: 18/33 secondary progressive patients (55%), 10/19 primary progressive patients (53%) and 38/182 relapsing-remitting patients (21%). A prediction model that included only whole-brain MRI measures (Nagelkerke R2 = 0.22, P < 0.001) showed cortical grey matter volume as the only significant MRI predictor of cognitive decline, while a prediction model that assessed regional MRI measures (Nagelkerke R2 = 0.35, P < 0.001) indicated integrity loss of the anterior thalamic radiation, lesions in the superior longitudinal fasciculus and temporal atrophy as significant MRI predictors for cognitive decline. Disease stage specific regressions showed that cognitive decline in early relapsing-remitting multiple sclerosis was predicted by white matter integrity damage, while cognitive decline in late relapsing-remitting and progressive multiple sclerosis was predicted by cortical atrophy. These results indicate that patients with more severe structural damage at baseline, and especially cortical atrophy, are more prone to suffer from cognitive decline. New studies now need to further elucidate the underlying mechanisms leading to cortical atrophy, evaluate the value of including cortical atrophy as a possible outcome marker in clinical trials as well as study its potential use in individual patient management.


Dystrophin Is Required for Proper Functioning of Luminance and Red-Green Cone Opponent Mechanisms in the Human Retina.
Visual information is processed in parallel pathways in the visual system. Parallel processing begins at the synapse between the photoreceptors and their postreceptoral neurons in the human retina. The integrity of this first neural connection is vital for normal visual processing downstream. Of the numerous elements necessary for proper functioning of this synaptic contact, dystrophin proteins in the eye play an important role. Deficiency of muscle dystrophin causes Duchenne muscular dystrophy (DMD), an X-linked disease that affects muscle function and leads to decreased life expectancy. In DMD patients, postreceptoral retinal mechanisms underlying scotopic and photopic vision and ON- and OFF-pathway responses are also altered. In this study, we recorded the electroretinogram (ERG) while preferentially activating the (red-green) opponent or the luminance pathway, and compared data from healthy participants (n = 16) with those of DMD patients (n = 10). The stimuli were heterochromatic sinusoidal modulations at a mean luminance of 200 cd/m2. The recordings allowed us also to analyze ON and OFF cone-driven retinal responses. We found significant differences in 12-Hz response amplitudes and phases between controls and DMD patients, with conditions with large luminance content resulting in larger response amplitudes in DMD patients compared to controls, whereas responses of DMD patients were smaller when pure chromatic modulation was given. The results suggest that dystrophin is required for the proper function of luminance and red-green cone opponent mechanisms in the human retina.


N-Terminal peptide aldehydes as electrophiles in combinatorial solid phase synthesis of novel peptide isosteres.
N-Terminal peptide aldehydes were synthesized on a solid support and utilized as electrophiles in nucleophilic reactions in order to furnish novel and diverse peptide isosteres. The aldehyde moiety of the peptide was synthesized by coupling a protected aldehyde building block to the peptide and deprotecting it quantitatively in less than 3 min. It was found that protection of the two succeeding amide nitrogens was necessary in order to avoid reaction between the aldehyde and backbone amides. The N-terminal peptide aldehydes were successfully reacted in the following way: (a) reductive amination with a large variety of amines, leading to N-alkyl-gamma-aminobutyric peptide isosteres positioned centrally in the peptide; (b) reductive amination with amino esters, leading to N-terminal 2,5-diketopiperazine peptides; (c) Horner-Wadsworth-Emmons olefination, leading to unsaturated peptide isosteres positioned centrally in the peptide; and (d) Pictet-Spengler condensations, leading to tetrahydro-beta-carbolines either positioned centrally in a peptide or fused with a diketopiperazine ring in the N-terminus of the peptide.


Hepatoprotective Activity of the Ethanolic Extract of Polygonum multiflorum Thunb. against Oxidative Stress-Induced Liver Injury.
Oxidative stress is an important pathological mechanism in various liver diseases. Polygonum multiflorum Thunb. (PM) can be used for the treatment of diseases associated with aging, hyperlipidemia, and oxidative stress in traditional Chinese medicine. In this study, we examined the hepatoprotective effects of the ethanolic extract of PM (PME) in in vitro and in vivo models. The PME induced expression of antioxidant-response-element- (ARE-) related genes in HepG2 cells showed a dose-dependent manner. Pretreatment of HepG2 cell with PME suppressed H2O2- and acetaminophen- (APAP-) induced cellular reactive oxygen species (ROS) generation and cytotoxicity. In APAP-induced mouse liver injury, pretreatment with PME also showed ability to increase the survival rate and reduce the severity of liver injury. Treatment with PME attenuated bile duct ligation-induced extrahepatic cholestatic liver injury and further increased multidrug resistance protein 4 (MRP4) and reduced organic anion-transporting polypeptide (OATP) expression. Furthermore, increased nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) was observed after treatment with PME in both in vivo models. In conclusion, the current study showed the hepatoprotective activity of PME by regulating the redox state in liver injury through Nrf2 activation and controlling hepatic bile acid homeostasis in obstructive cholestasis, through bile acid transporter expression modulation.


Synchronized and asynchronous modulation of seismicity by hydrological loading: A case study in Taiwan.
Delineation of physical factors that contribute to earthquake triggering is a challenging issue in seismology. We analyze hydrological modulation of seismicity in Taiwan using groundwater level data and GNSS time series. In western Taiwan, the seismicity rate reaches peak levels in February to April and drops to its lowest values in July to September, exhibiting a direct correlation with annual water unloading. The elastic hydrological load cycle may be the primary driving mechanism for the observed synchronized modulation of earthquakes, as also evidenced by deep earthquakes in eastern Taiwan. However, shallow earthquakes in eastern Taiwan (<18 km) are anticorrelated with water unloading, which is not well explained by either hydrological loading, fluid transport, or pore pressure changes and suggests other time-dependent processes. The moderate correlation between stacked monthly trends of large historic earthquakes and present-day seismicity implies a modestly higher seismic hazard during the time of low annual hydrological loading.


Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings.
Recruitment is often a bottleneck in secondary prevention trials in Alzheimer disease (AD). Furthermore, screen-failure rates in these trials are typically high due to relatively low prevalence of AD pathology in individuals without dementia, especially among cognitively unimpaired. Prescreening on AD risk factors may facilitate recruitment, but the efficiency will depend on how these factors link to participation rates and AD pathology. We investigated whether common AD-related factors predict trial-ready cohort participation and amyloid status across different prescreen settings. We monitored the prescreening in four cohorts linked to the European Prevention of Alzheimer Dementia (EPAD) Registry (n = 16,877; mean ± SD age = 64 ± 8 years). These included a clinical cohort, a research in-person cohort, a research online cohort, and a population-based cohort. Individuals were asked to participate in the EPAD longitudinal cohort study (EPAD-LCS), which serves as a trial-ready cohort for secondary prevention trials. Amyloid positivity was measured in cerebrospinal fluid as part of the EPAD-LCS assessment. We calculated participation rates and numbers needed to prescreen (NNPS) per participant that was amyloid-positive. We tested if age, sex, education level, APOE status, family history for dementia, memory complaints or memory scores, previously collected in these cohorts, could predict participation and amyloid status. A total of 2595 participants were contacted for participation in the EPAD-LCS. Participation rates varied by setting between 3 and 59%. The NNPS were 6.9 (clinical cohort), 7.5 (research in-person cohort), 8.4 (research online cohort), and 88.5 (population-based cohort). Participation in the EPAD-LCS (n = 413 (16%)) was associated with lower age (odds ratio (OR) age = 0.97 [0.95-0.99]), high education (OR = 1.64 [1.23-2.17]), male sex (OR = 1.56 [1.19-2.04]), and positive family history of dementia (OR = 1.66 [1.19-2.31]). Among participants in the EPAD-LCS, amyloid positivity (33%) was associated with higher age (OR = 1.06 [1.02-1.10]) and APOE ɛ4 allele carriership (OR = 2.99 [1.81-4.94]). These results were similar across prescreen settings. Numbers needed to prescreen varied greatly between settings. Understanding how common AD risk factors link to study participation and amyloid positivity is informative for recruitment strategy of studies on secondary prevention of AD.


The location of the axon initial segment affects the bandwidth of spike initiation dynamics.
The dynamics and the sharp onset of action potential (AP) generation have recently been the subject of intense experimental and theoretical investigations. According to the resistive coupling theory, an electrotonic interplay between the site of AP initiation in the axon and the somato-dendritic load determines the AP waveform. This phenomenon not only alters the shape of APs recorded at the soma, but also determines the dynamics of excitability across a variety of time scales. Supporting this statement, here we generalize a previous numerical study and extend it to the quantification of the input-output gain of the neuronal dynamical response. We consider three classes of multicompartmental mathematical models, ranging from ball-and-stick simplified descriptions of neuronal excitability to 3D-reconstructed biophysical models of excitatory neurons of rodent and human cortical tissue. For each model, we demonstrate that increasing the distance between the axonal site of AP initiation and the soma markedly increases the bandwidth of neuronal response properties. We finally consider the Liquid State Machine paradigm, exploring the impact of altering the site of AP initiation at the level of a neuronal population, and demonstrate that an optimal distance exists to boost the computational performance of the network in a simple classification task.


The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD).
Alzheimer's disease (AD) is the most common form of dementia in the older people and 7(th) leading cause of death in the United States. Deposition of amyloid-beta (Aβ) plaques, hyperphosphorylation of microtubule associated protein tau (MAPT), neuroinflammation and cholinergic neuron loss are the major hallmarks of AD. Deposition of Aβ peptides, which takes place years before the clinical onset of the disease can trigger hyperphophorylation of tau proteins and neuroinflammation, and the latter is thought to be primarily involved in neuronal and synaptic damage seen in AD. To date, four cholinesterase inhibitors or ChEI (tacrine, rivastigmine, donepezil and galantamine) and a partial NMDA receptor antagonist (memantine) are the only approved treatment options for AD. However, these drugs fail to completely cure the disease, which warrants a search for newer class of targets that would eventually lead to effective drugs for the treatment of AD. In addition to selected pharmacological agents, botanical and medicinal plant extracts are also being investigated. Apart from its culinary use, garlic (Allium sativum) is being used to treat several ailments like cancer and diabetes. Herein we have discussed the effects of a specific 'Aged Garlic Extract' (AGE) and one of its active ingredients, S-allyl-L-cysteine (SAC) in restricting several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD. Thus, based on the reported positive preliminary results reviewed herein, further research is required to develop the full potential of AGE and/or SAC into an effective preventative strategy for AD.


An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs.
HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Subtype B patients ( n = 3410) were mostly MSM (78%) and those with subtype C ( n = 810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P < 0.001). Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated.


Immunostimulation and immunoinhibition of premalignant lesions.
The immune reaction may be either stimulatory or inhibitory to tumor growth, depending upon the local ratio of immune reactants to tumor cells. A tumor-stimulatory immune response may be essential for survival of a neoplasm in vivo and for the biological progression from a premalignant lesion to a malignancy. Neither a positive nor a negative correlation between the magnitude of an immune-cell infiltrate and a cancer's prognosis can reveal whether the infiltrate was stimulating or inhibiting to the tumor's growth unless the position on the nonlinear curve that relates tumor growth to the magnitude of the immune reaction is known. This hypothesis is discussed in relation to the development of human malignant melanomas and colorectal cancers.


Is neck circumference measurement an indicator for abdominal obesity? A pilot study on Turkish Adults.
Neck circumference (NC) measurement is one of the simple screening measurements which can be used as an index of upper body fat distribution to identify obesity. The aim of this study was to determine the relationship between neck circumferences and obesity. A total 411 volunteer adults participated in this study (174 men, 237 women). A questionnaire which consisted of anthropometric measurements and demographic features was used. Patients with NC ≥37 cm for men and ≥34 cm for women require evaluation of overweight status. The percentages of the men and women with BMI ≥ 25 kg/m(2) were 55.2% and 27.0% respectively and with high neck circumferences were 85.1% and 38.8%, respectively. The percentages of the men and women with high waist circumference were 31.6% and 79.3%, respectively. In both gender there were positive significant correlations between neck circumference, body weight (men, r=0.576; women, r=0.702; p=0.000), waist circumferences (men, r=0.593; women r=0.667; p=0.000), hip circumferences (men, r=0.568; women, r=0.617; p=0.000) and BMI (men, r=0.587; women, r=0.688; p=0.000). This study indicates that NC was associated with body weight, BMI, waist and hip circumferences and waist/hip ratio for men and women. A significant association was found between NC and conventional overweight and obesity indexes. NC was associated with waist/hip ratio for men and women.


Screening and evaluation of antioxidant activity of some pyridazine derivatives.
Antioxidants are compounds that can delay, inhibit, or prevent the oxidation of materials that can be oxidized by scavenging free radicals and help in diminishing oxidative stress. They belong to different chemical classes. Recently there are studies related to pyridazinone derivatives for their antioxidant activities. Since there are evidences implicates reactive oxygen species and nitric oxide as mediators of inflammation and/or tissue damage in inflammatory and arthritic disorders it was though that compounds that have both antioxidant and anti-inflammatory activities would have been essential for the inflammatory diseases. Based on these findings a series of 2H-pyridazine-3-one and 6-chloropyridazine analogues that have anti-inflammatory activity was tested in vitro on superoxide formation and effects on lipid peroxidation were determined against alpha-tocopherol. Most of the compounds have strong inhibitory effect on superoxide anion (between 84% - 99%) at 10(- 3) M concentration. In addition, these compounds showed similar activity to alpha-tocopherol at 10(- 3) M concentrations.


Comparison of two percutaneous radiological gastrostomy tubes in the nutritional management of ALS patients.
Patient care and minimizing complications post gastrostomy have to date received little attention in ALS patients. We compare the complications associated with pigtail and mushroom type percutaneous radiological gastrostomy tubes in this patient group. Patients requiring PRG received either Wills-Oglesby or the skin level Entristar. Retrospective review of the clinical notes was performed capturing demographic data, peristomal infection, tube displacement, tube failure, nutritional status, site of disease onset, and survival. Thirty-five patients (Group 1) had the Wills-Oglesby tube of which 14 (40%) tubes required replacement. The Entristar tube was inserted in 29 patients (Group 2) where 8 (28%) required replacement (NS). The incidence of infection was significantly lower with the Entristar tube, (p<0.001). The mean time to tube removal in Group 2 was 223 days (SD 147; range 71-494 days) due to 'buried bumper syndrome'. We conclude that the Entristar skin level gastrostomy tube is associated with a reduction in peristomal infection, tube failure and blockage compared with the Wills-Oglesby tube.


Sinomenine inhibits microglial activation by Aβ and confers neuroprotection.
Neuroinflammation is an important contributor to the development of neurodegenerative diseases, including Alzheimer's disease. Thus, there is a keen interest in identifying compounds, especially from herbal sources, that can inhibit neuroinflammation. Amyloid-β (Aβ) is a major component of the amyloid plaques present in the brains of Alzheimer's disease patients. Here, we examined whether sinomenine, present in a Chinese medicinal plant, prevents oligomeric Aβ-induced microglial activation and confers protection against neurotoxicity. Oligomeric amyloid-β was prepared from Aβ(1-42). Intracellular reactive oxygen species production was determined using the dye 2',7'-dichlorodihydrofluorescin diacetate. Nitric oxide level was assessed using the Griess reagent. Flow cytometry was used to examine the levels of inflammatory molecules. BV2-conditioned medium was used to treat hippocampal cell line (HT22) and primary hippocampal cells in indirect toxicity experiments. Toxicity was assessed using MTT reduction and TUNEL assays. We found that sinomenine prevents the oligomeric Aβ-induced increase in levels of reactive oxygen species and nitric oxide in BV2 microglial cells. In addition, sinomenine reduces levels of Aβ-induced inflammatory molecules. Furthermore, sinomenine protects hippocampal HT22 cells as well as primary hippocampal cells from indirect toxicity mediated by Aβ-treated microglial cells, but has no effect on Aβ-induced direct toxicity to HT22 cells. Finally, we found that conditioned medium from Aβ-treated BV2 cells contains increased levels of nitric oxide and inflammatory molecules, but the levels of these molecules are reduced by sinomenine. Sinomenine prevents oligomeric Aβ-induced microglial activation, and confers protection against indirect neurotoxicity to hippocampal cells. These results raise the possibility that sinomenine may have therapeutic potential for the treatment of Alzheimer's diseases as well as other diseases that involve neuroinflammation.


C60 additive-assisted crystallization in CH3NH3Pb0.75Sn0.25I3 perovskite solar cells with high stability and efficiency.
The development of hybrid tin (Sn)-lead (Pb) perovskite solar cells likely tackles the toxic problem with the power conversion efficiency (PCE) exceeding 17%. However, the stability problems, e.g. hysteresis effect, degeneration and oxidation, appear to be the bottleneck that limit its further development. Here, we innovatively introduced C60 at the grain boundaries throughout the CH3NH3Pb0.75Sn0.25I3 (MAPb0.75Sn0.25I3) thin film, playing a role not only in in situ passivating the interfaces and reducing the pinholes of perovskite thin films, but also in preventing the penetration of moisture and oxygen from ambient atmosphere. Electrochemical impedance spectroscopy (EIS) illustrated that the recombination lifetime of both the bulk and surface of MAPb0.75Sn0.25I3 thin films was increased by additive incorporation of C60. Dark I-V results for the electron/hole-only devices showed that the charge trap-state density decreased with C60 additive incorporated into the hybrid Sn-Pb perovskite thin films. Importantly, the hybrid Sn-Pb perovskite solar cells modified with C60 additive were demonstrated to have superior stability and efficiency when exposed to the ambient environment without encapsulation.


Fatal Aspergillus rhinosinusitis during induction chemotherapy in a child with acute lymphoblastic leukemia.
Invasive fungal infections are a major problem in patients treated for hematologic malignancies. We report a 3-year-old girl who suffered from febrile neutropenia during induction therapy for acute lymphoblastic leukemia. Initial chest computed tomography revealed no evidence of intrapulmonary fungal lesions, however, plasma galactomannan ratio was positive. Aspergillus flavus was cultured from nasal swab and endoscopic biopsy confirmed Aspergillus rhinosinusitis. After an initially good response to voriconazole and extensive debridement, she developed late intracranial hemorrhage and infarction with fatal outcome. This case stresses the importance of early suspicion and aggressive treatment of Aspergillus rhinosinusitis in patients with febrile neutropenia.


Chest injuries of elderly postmortem human surrogates (PMHSs) under seat belt and airbag loading in frontal sled impacts: Comparison to matching THOR tests.
The goal of the study was to develop experimental chest loading conditions that would cause up to Abbreviated Injury Scale (AIS) 2 chest injuries in elderly occupants in moderate-speed frontal crashes. The new set of experimental data was also intended to be used in the benchmark of existing thoracic injury criteria in lower-speed collision conditions. Six male elderly (age >63) postmortem human subjects (PMHS) were exposed to a 35 km/h (nominal) frontal sled impact. The test fixture consisted of a rigid seat, rigid footrest, and cable seat back. Two restraint conditions (A and B) were compared. Occupants were restrained by a force-limited (2.5 kN [A] and 2 kN [B]) seat belt and a preinflated (16 kPa [A] and 11 kPa [B]; airbag). Condition B also incorporated increased seat friction. Matching sled tests were carried out with the THOR-M dummy. Infra-red telescoping rod for the assessment of chest compression (IRTRACC) readings were used to compute chest injury risk. PMHSs were exposed to a posttest injury assessment. Tests were carried out in 2 stages, using the outcome of the first one combined with a parametric study using the THUMS model to adjust the test conditions in the second. All procedures were approved by the relevant ethics board. Restraint condition A resulted in an unexpected high number of rib fractures (fx; 10, 14, 15 fx). Under condition B, the adjustment of the relative airbag/occupant position combined with a lower airbag pressure and lower seat belt load limit resulted in a reduced pelvic excursion (85 vs. 110 mm), increased torso pitch and a substantially lower number of rib fractures (1, 0, 4 fx) as intended. The predicted risk of rib fractures provided by the THOR dummy using the Cmax and PC Score injury criteria were lower than the actual injuries observed in the PMHS tests (especially in restraint condition A). However, the THOR dummy was capable of discriminating between the 2 restraint scenarios. Similar results were obtained in the parametric study with the THUMS model.


The Effects of Family Stressors on Substance Use Initiation in Adolescence.
Smoking and drinking are critical problems in adolescence that have long-term adverse impacts on health and socio-economic factors. We examine the extent to which family stresses influence the timing of initiation of smoking and drinking. Using national panel data from the National Educational Longitudinal Study (NELS) we capitalize on the survey design and use school-level fixed effects that control for the local environments, including prices of cigarettes and alcohol. In addition, we narrow our control group to classmates who will experience a similar stressor in the future. We find that a composite measure of family stressors when young increases the likelihood of initiating tobacco and alcohol use, with much of the impact attributable to parental divorce. In our baseline estimates, the composite stress measure is associated with a 30% increase in the likelihood of smoking and a 20% increase in drinking. When we control for multiple sources of confounding, the impact shrinks and remains significant for smoking but not for drinking. We conclude that studies which do not control for confounding are likely to significantly overestimate the impact of family stress on substance use. Our approach helps to move the literature forward by separating causal results from spurious associations.


Effector granules in human T lymphocytes: the luminal proteome of secretory lysosomes from human T cells.
Cytotoxic cells of the immune system have evolved a lysosomal compartment to store and mobilize effector molecules. In T lymphocytes and NK cells, the death factor FasL is one of the characteristic marker proteins of these so-called secretory lysosomes, which combine properties of conventional lysosomes and exocytotic vesicles. Although these vesicles are crucial for immune effector function, their protein content in T cells has so far not been investigated in detail. In the present study, intact membranous vesicles were enriched from homogenates of polyclonally activated T cells and initially characterized by Western blotting and electron microscopic inspection. The vesicular fraction that contained the marker proteins of secretory lysosomes was subsequently analyzed by 2D electrophoresis and mass spectrometry. The proteome analysis and data evaluation revealed that 70% of the 397 annotated proteins had been associated with different lysosome-related organelles in previous proteome studies. We provide the first comprehensive proteome map of T cell-derived secretory lysosomes with only minor contaminations by cytosolic, nuclear or other proteins. This information will be useful to more precisely address the activation-dependent maturation and the specific distribution of effector organelles and proteins in individual T or NK cell populations in future studies.


Patterns and correlates of missed nursing care in inpatient oncology units.
Missed nursing care influences the quality of hospital care, yet this problem has not been explored in the oncology setting, nor are the correlates of missed nursing care in inpatient oncology settings understood. We examined the frequency of missed care in oncology units, differences in missed care between oncology and non-oncology units, and the relationship between unit staffing and missed care. We performed secondary analysis of survey data collected in 2008 to 2009 across 9 hospitals. The MISSCARE Survey was administered to nurses and medical assistants employed in 62 units (n = 2318). Descriptive statistics and linear regression were used to examine the frequency of missed care, differences between oncology (n = 12) and non-oncology units (n=50), and the relationship between unit staffing and missed care. Oncology nursing unit personnel reported ambulation, care conference attendance, and mouth care as most frequently missed. Oncology units had significantly lower missed care than did non-oncology units (P < .05). Higher patient assignments were associated with an increase in reported missed care (P < .05). Missed care is a problem shared by inpatient oncology and non-oncology units. Missed ambulation and mouth care are worrisome, given their importance to oncology patients. Suboptimal staffing increases missed care. These data motivate quality improvement and evidence-based management. Clinicians can strategize to ensure patients receive adequate ambulation and mouth care. Managers can use our findings to support the importance of stable nurse staffing to reduce untoward patient outcomes.


Loss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis.
Loss of memory B cells occurs from the onset of HIV-1 infection and persists into the chronic stages of infection. Lack of survival of these cells, even in subjects being treated, could primarily be the consequence of an altered local microenvironment induced by HIV infection. In this study we showed that memory B cell survival was significantly decreased in aviremic successfully treated (ST) subjects compared with subjects who control viral load as a result of natural immunity (elite controller [EC]) or with uninfected control (HIV-) subjects. The lower survival levels observed in memory B cells from ST subjects were the result of disrupted IL-2 signaling that led to increased transcriptional activity of Foxo3a and increased expression of its proapoptotic target TRAIL. Notably, memory B cell survival in ST subjects was significantly enhanced by the addition of exogenous IL-2 in a Foxo3a-dependent manner. We further showed that Foxo3a silencing by siRNA resulted in decreased expression of TRAIL and apoptosis levels in memory B cells from ST subjects. Our results thus establish a direct role for Foxo3a/TRAIL signaling in the persistence of memory B cells and provide a mechanism for the reduced survival of memory B cells during HIV infection. This knowledge could be exploited for the development of therapeutic and preventative HIV vaccines.


Ring-bursting behavior en route to turbulence in narrow-gap Taylor-Couette flows.
We investigate the Taylor-Couette system where the radius ratio is close to unity. Systematically increasing the Reynolds number, we observe a number of previously known transitions, such as one from the classical Taylor vortex flow (TVF) to wavy vortex flow (WVF) and the transition to fully developed turbulence. Prior to the onset of turbulence, we observe intermittent bursting patterns of localized turbulent patches, confirming the experimentally observed pattern of very short wavelength bursts (VSWBs). A striking finding is that, for a Reynolds number larger than that for the onset of VSWBs, a new type of intermittently bursting behavior emerges: patterns of azimuthally closed rings of various orders. We call them ring-bursting patterns, which surround the cylinder completely but remain localized and separated in the axial direction through nonturbulent wavy structures. We employ a number of quantitative measures including the cross-flow energy to characterize the ring-bursting patterns and to distinguish them from the background flow. These patterns are interesting because they do not occur in the wide-gap Taylor-Couette flow systems. The narrow-gap regime is less studied but certainly deserves further attention to gain deeper insights into complex flow dynamics in fluids.


S values for 131I based on the ICRP adult voxel phantoms.
To improve the estimates of organ doses from nuclear medicine procedures using (131)I, the authors calculated a comprehensive set of (131)I S values, defined as absorbed doses in target tissues per unit of nuclear transition in source regions, for different source and target combinations. The authors used the latest reference adult male and female voxel phantoms published by the International Commission on Radiological Protection (ICRP Publication 110) and the (131)I photon and electron spectra from the ICRP Publication 107 to perform Monte Carlo radiation transport calculations using MCNPX2.7 to compute the S values. For each phantom, the authors simulated 55 source regions with an assumed uniform distribution of (131)I. They computed the S values for 42 target tissues directly, without calculating specific absorbed fractions. From these calculations, the authors derived a comprehensive set of S values for (131)I for 55 source regions and 42 target tissues in the ICRP male and female voxel phantoms. Compared with the stylised phantoms from Oak Ridge National Laboratory (ORNL) that consist of 22 source regions and 24 target regions, the new data set includes 1662 additional S values corresponding to additional combinations of source-target tissues that are not available in the stylised phantoms. In a comparison of S values derived from the ICRP and ORNL phantoms, the authors found that the S values to the radiosensitive tissues in the ICRP phantoms were 1.1 (median, female) and 1.3 (median, male) times greater than the values based on the ORNL phantoms. However, for several source-target pairs, the difference was up to 10-fold. The new set of S values can be applied prospectively or retrospectively to the calculation of radiation doses in adults internally exposed to (131)I, including nuclear medicine patients treated for thyroid cancer or hyperthyroidism.


Apolipoprotein E genotype is associated with macular pigment optical density.
Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk factors for this condition may be classified as genetic and environmental. Apolipoprotein E is putatively involved in the transport of the macular pigment (MP) carotenoids lutein (L) and zeaxanthin (Z) in serum and may also influence retinal capture of these compounds. This study was designed to investigate the relationship between macular pigment optical density (MPOD) and ApoE genotype. This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. Serum L and Z were measured by HPLC. ApoE genotyping was performed by direct polymerase chain reaction amplification and DNA nucleotide sequencing from peripheral blood. Genotype data were available on 300 of the 302 (99.3%) subjects. The mean (+/- SD) age of the subjects in this study was 47.89 +/- 11.05 (range, 21-66) years. Subjects were classed into one of three ApoE genotype groups, as follows: group 1, epsilon2epsilon2 or epsilon2epsilon3; group 2, epsilon3epsilon3; group 3, epsilon2epsilon4 or epsilon3epsilon4 or epsilon4epsilon4. All three groups were statistically comparable in terms of age, sex, body mass index, cigarette smoking, and dietary and serum levels of L and Z. There was a statistically significant association between ApoE genotype and MPOD. Subjects who had at least one epsilon4 allele had a higher MPOD across the macula than subjects without this allele (group 1 MPOD area, 0.70 +/- 0.40; group 2 MPOD area, 0.67 +/- 0.42; group 3 MPOD area, 0.85 +/- 0.46; one-way ANOVA, P = 0.014. These results suggest that ApoE genotype status is associated with MPOD. This association may explain, at least in part, the putative protective effect of the epsilon4 allele for AMD and is consistent with the view that apolipoprotein profile influences the transport and/or retinal capture of circulating L and/or Z.


Transcriptional analysis of Lactobacillus brevis to N-butanol and ferulic acid stress responses.
The presence of anti-microbial phenolic compounds, such as the model compound ferulic acid, in biomass hydrolysates pose significant challenges to the widespread use of biomass in conjunction with whole cell biocatalysis or fermentation. Currently, these inhibitory compounds must be removed through additional downstream processing or sufficiently diluted to create environments suitable for most industrially important microbial strains. Simultaneously, product toxicity must also be overcome to allow for efficient production of next generation biofuels such as n-butanol, isopropanol, and others from these low cost feedstocks. This study explores the high ferulic acid and n-butanol tolerance in Lactobacillus brevis, a lactic acid bacterium often found in fermentation processes, by global transcriptional response analysis. The transcriptional profile of L. brevis reveals that the presence of ferulic acid triggers the expression of currently uncharacterized membrane proteins, possibly in an effort to counteract ferulic acid induced changes in membrane fluidity and ion leakage. In contrast to the ferulic acid stress response, n-butanol challenges to growing cultures primarily induce genes within the fatty acid synthesis pathway and reduced the proportion of 19:1 cyclopropane fatty acid within the L. brevis membrane. Both inhibitors also triggered generalized stress responses. Separate attempts to alter flux through the Escherichia coli fatty acid synthesis by overexpressing acetyl-CoA carboxylase subunits and deleting cyclopropane fatty acid synthase (cfa) both failed to improve n-butanol tolerance in E. coli, indicating that additional components of the stress response are required to confer n-butanol resistance. Several promising routes for understanding both ferulic acid and n-butanol tolerance have been identified from L. brevis gene expression data. These insights may be used to guide further engineering of model industrial organisms to better tolerate both classes of inhibitors to enable facile production of biofuels from lignocellulosic biomass.


The Mental Health Continuum-Short Form (MHC-SF) in the Argentinean Context: Confirmatory Factor Analysis and Measurement Invariance.
The present research aimed at studying the psychometric properties of the Mental Health Continuum-Short Form (MHC-SF; Keyes, 2005) in a sample of 1,300 Argentinean adults (50% males; 50% females). Their mean age was 40.28 years old (SD = 13.59). The MHC-SF is a 14 item test that assesses three components (i.e., emotional, social, and psychological) of well-being. Convergent and divergent evidence of construct validity was assessed by conducting confirmatory factor analysis, cross-validation, factorial invariance, and correlations with external criteria. Internal consistency was studied using Cronbach's alphas. Results indicated an adequate fit of a three-dimensional model. This structure was also confirmed, and was invariant throughout sex and age. The emotional well-being scores converged with life satisfaction and positive affect measures; the psychological well-being scale had a positive association with the presence of meaning in life; and the social well-being scores showed a positive and strong correlation with an external measure of well-being. Also, all scores were negatively associated with negative affect, search of meaning in life, and presence of depression symptoms. Internal consistency was .89 for the MHC-SF. Furthermore, the findings supported the two - continua model of mental health.


The potential wind power resource in Australia: a new perspective.
Australia's wind resource is considered to be very good, and the utilization of this renewable energy resource is increasing rapidly: wind power installed capacity increased by 35% from 2006 to 2011 and is predicted to account for over 12% of Australia's electricity generation in 2030. Due to this growth in the utilization of the wind resource and the increasing importance of wind power in Australia's energy mix, this study sets out to analyze and interpret the nature of Australia's wind resources using robust metrics of the abundance, variability and intermittency of wind power density, and analyzes the variation of these characteristics with current and potential wind turbine hub heights. We also assess the extent to which wind intermittency, on hourly or greater timescales, can potentially be mitigated by the aggregation of geographically dispersed wind farms, and in so doing, lessen the severe impact on wind power economic viability of long lulls in wind and power generated. Our results suggest that over much of Australia, areas that have high wind intermittency coincide with large expanses in which the aggregation of turbine output does not mitigate variability. These areas are also geographically remote, some are disconnected from the east coast's electricity grid and large population centers, which are factors that could decrease the potential economic viability of wind farms in these locations. However, on the eastern seaboard, even though the wind resource is weaker, it is less variable, much closer to large population centers, and there exists more potential to mitigate it's intermittency through aggregation. This study forms a necessary precursor to the analysis of the impact of large-scale circulations and oscillations on the wind resource at the mesoscale.


Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer's Disease.
Alzheimer's disease (AD) is a type of incurable neurodegenerative disease that is characterized by the accumulation of amyloid-β (Aβ; plaques) and tau hyperphosphorylation as neurofibrillary tangles (NFTs) in the brain followed by neuronal death, cognitive decline, and memory loss. The high prevalence of AD in the developed world has become a major public health challenge associated with social and economic burdens on individuals and society. Due to there being limited options for early diagnosis and determining the exact pathophysiology of AD, finding effective therapeutic strategies has become a great challenge. Several possible risk factors associated with AD pathology have been identified; however, their roles are still inconclusive. Recent clinical trials of the drugs targeting Aβ and tau have failed to find a cure for the AD pathology. Therefore, effective preventive strategies should be followed to reduce the exponential increase in the prevalence of cognitive decline and dementia, especially AD. Although the search for new therapeutic targets is a great challenge for the scientific community, the roles of lifestyle interventions and nutraceuticals in the prevention of many metabolic and neurodegenerative diseases are highly appreciated in the literature. In this article, we summarize the molecular mechanisms involved in AD pathology and the possible ameliorative action of lifestyle and nutritional interventions including diet, exercise, Calorie restriction (CR), and various bioactive compounds on cognitive decline and dementia. This article will provide insights into the role of non-pharmacologic interventions in the modulation of AD pathology, which may offer the benefit of improving quality of life by reducing cognitive decline and incident AD.


The association between cord pH at birth and intellectual function in childhood.
Acidemia at birth is very common but little is known about its long-term consequences. To determine if pH at birth is related to established tests of intellectual function. School children aged 6-8, for whom obstetric data were available, who had been delivered after labour at term, and had an umbilical cord arterial pH>7.00 (i.e. that was not extremely acidemic). STUDY DESIGN/OUTCOMES: Retrospective cohort study correlating birth and arterial pH data with childhood tests for non-verbal intelligence, grammar comprehension and literacy. Relationships between pH and cognitive measures were analysed with parametric correlations. Partial correlations were used to examine these relationships, controlling for possible confounding factors. Arterial pH was significantly negatively correlated with literacy (p=0.001) and with non-verbal intelligence (p=0.033). Lower arterial pH is associated with higher scores on literacy and non-verbal intelligence tests at ages 6-8. This is unlikely to be a chance finding and is further evidence that acidemia in isolation should not be considered an adverse outcome. Further research on the relationship between labour and long-term cognitive measures is required.


Calcitonin gene-related peptide (CGRP) and migraine.
The neuropeptide calcitonin gene-related peptide (CGRP) has long been postulated to play an integral role in the pathophysiology of migraine. While clinical findings are consistent with such a role, the specific pathogenic mechanisms of CGRP in migraine have remained speculative until recently. Through advances in molecular neuroscience, the pathogenic mechanisms of CGRP in migraine have begun to be elucidated. This paper discusses the hypothesized role of CGRP in migraine and reviews recent findings on the molecular mechanisms of this neuropeptide in migraine pathophysiology. Studies in cultured trigeminal neurons demonstrate that CGRP is released from trigeminal ganglia cells, that CGRP transcription is increased under conditions mimicking neurogenic inflammation, that migraine pharmacotherapies can both reduce CGRP release and inhibit CGRP transcription, and that tumor necrosis factor-alpha (TNF-alpha), an endogenous inflammatory mediator implicated in migraine, can stimulate CGRP transcription. Together, the results suggest that, in migraine, activation of trigeminal nerves release CGRP and other peptides that cause the release of proinflammatory mediators. These mediators further increase CGRP synthesis and release over hours to days in correspondence with the 4- to 72-hour duration of a typical migraine episode. The increased CGRP synthesis and release might be mediated by activation of mitogen-activated protein kinase pathways, which, in turn, can be modulated by endogenous inflammatory substances such as TNF-alpha and affected by drugs such as sumatriptan.


Diabetes mellitus as a risk factor for stroke incidence and mortality in Mexican American older adults.
Little is known regarding diabetes mellitus as a risk factor for stroke incidence and death in older Mexican Americans. The authors studied diabetes and other potential risk factors for stroke in a sample of community-dwelling older Mexican Americans. A prospective cohort design was used that involved the Hispanic Established Population for the Epidemiologic Study of the Elderly, a longitudinal study using a weighted probability sample of Mexican Americans (aged older than 65 years) living in the southwestern United States. 3050 older Mexican American persons were originally interviewed and tested at baseline and then followed with reassessment at 2, 5, and 7 years. The incidence of stroke and stroke death were studied for the participants during a 7-year follow-up period. 690 participants were identified at baseline with diabetes. 238 participants experienced a first-time stroke during the follow-up period. 66 died as a result of a stroke. Cox proportional hazard regression analysis revealed an increased hazard ratio (HR) for stroke in persons with diabetes (HR, 1.80; 95% confidence interval [CI], 1.32 to 2.44; p <.0002) when adjusted for age, sex, body mass index, smoking, systolic blood pressure, previous heart attack, and lower extremity function. The stroke mortality rate was also higher (HR, 2.02; 95% CI, 1.04 to 3.93) for persons with diabetes when adjusted for covariates. Diabetes was associated with an increased incidence of stroke and death in older Mexican Americans, particularly those taking insulin.


Lesser-sac lavage for intraoperative detection of blunt pancreatic duct injury.
Blunt pancreatic duct injury is difficult to differentiate, especially during surgery. In terms of demonstration of pancreatic duct injury, endoscopic retrograde pancreatography (ERP) is the gold standard imaging study, however, availability can be problematic. Therefore, we have designed a method utilizing lesser-sac lavage to differentiate pancreatic duct injury. Patients sustaining blunt pancreatic trauma treated at our institution over a two-year period were retrospectively enrolled in this study. Based on computed tomography (CT), these patients were divided into two groups: deep laceration or complete transection (Group 1) and superficial laceration (Group 2). Additionally, ten patients sustaining blunt abdominal trauma who had undergone emergency laparotomy for other visceral organ injury (Group 3) and four undergoing pancreatoduodenectomy (Group 4) were selected as controls. For laparotomy in Groups 1-3, the lesser sac was opened for lavage, with 50 mL of 0.9% normal saline inserted, and 3mL of the sample fluid withdrawn at four time points (15, 30, 45 and 60 mins) with the fluid immediately replaced with 3 mL of saline. Lavage-ascites amylase (LAA) and lipase (LAL) levels were measured. Serum amylase and lipase activities were measured intraoperatively from 3mL of the patient's blood. Over the two-year study period, there were four pancreatic duct transections (Group 1), five partial pancreatic lacerations confirmed by post-ERP CT (Group 2), ten non-pancreatic traumas (Group 3), and four pancreatoduodenectomies due to pancreatic-head cancer (Group 4). The LAA and LAL for Group 1 were significantly higher than those for Group 2 or 3 at each of the four time points. The LAA and LAL ratios for Group 1 relative to Group 2 or 3 decreased gradually over time. These LAA ratios ranged from 7-13 for Group 1 to Group 2, 138-232 for Group 1 to Group 3, and 17-21 for Group 2 to Group 3. By contrast, the LAL ratio ranged from 3.0-3.4 comparing Group 1 to Group 2, 3180-29124 for Group 1 to Group 3, and 1058-8705 for Group 2 to Group 3. Using lesser-sac lavage for measurement of LAA and LA L constitutes a rapid, non-invasive and effective method for detection of pancreatic duct injury, especially transection of the main duct. LAA appears to be a better indicator for differentiation of minor (superficial laceration or side branch) or major (MPD) pancreatic injury at the first time point (15 minutes post lavage) compared to LAL. By contrast, LAL appears to be a better indicator with respect to differentiation of the injured pancreas from the normal organ at this time point.


The emotional and mental health needs of young carers: what psychiatry can do.
To review the literature on the emotional and mental health needs of young carers of parents with mental illness and the extent to which such needs are recognised and supported by professionals. Three databases were systematically searched from 2008 to 2018, and five studies met the inclusion criteria. The key findings were that young caregivers had a significantly higher dose-response mortality risk than their peers; were at increased risk of mental health difficulties, especially where the ill family member was a parent and had mental illness or misused substances; were overlooked by professionals owing to a lack of awareness; but could derive benefits from their caring role when appropriately supported. Young carers are at increased risk regarding emotional and mental health needs; this risk could be mitigated by professionals recognising the young carer's role and including them in their parent's treatment plan.


Gene duplication and neofunctionalization: POLR3G and POLR3GL.
RNA polymerase III (Pol III) occurs in two versions, one containing the POLR3G subunit and the other the closely related POLR3GL subunit. It is not clear whether these two Pol III forms have the same function, in particular whether they recognize the same target genes. We show that the POLR3G and POLR3GL genes arose from a DNA-based gene duplication, probably in a common ancestor of vertebrates. POLR3G- as well as POLR3GL-containing Pol III are present in cultured cell lines and in normal mouse liver, although the relative amounts of the two forms vary, with the POLR3G-containing Pol III relatively more abundant in dividing cells. Genome-wide chromatin immunoprecipitations followed by high-throughput sequencing (ChIP-seq) reveal that both forms of Pol III occupy the same target genes, in very constant proportions within one cell line, suggesting that the two forms of Pol III have a similar function with regard to specificity for target genes. In contrast, the POLR3G promoter--not the POLR3GL promoter--binds the transcription factor MYC, as do all other promoters of genes encoding Pol III subunits. Thus, the POLR3G/POLR3GL duplication did not lead to neo-functionalization of the gene product (at least with regard to target gene specificity) but rather to neo-functionalization of the transcription units, which acquired different mechanisms of regulation, thus likely affording greater regulation potential to the cell.


De novo reciprocal translocation t(5;6)(q13;q34) in cattle: cytogenetic and molecular characterization.
The cytogenetic analysis of a phenotypically normal bull from the Marchigiana breed revealed the presence of an abnormal karyotype due to the presence of a very long chromosome. This finding, identified in all the metaphases observed, was associated with the 2n = 60, XY karyotype, suggesting the presence of a reciprocal translocation. RBG- banding analyses identified a de novo reciprocal translocation involving BTA5 and BTA6, t(5;6)(q13;q34), while FISH analyses using cattle-specific BACs as probes enabled the confirmation and narrowed down the breakpoint regions. Array-CGH analysis also established that neither deletions nor duplications were present in the regions including the breakpoints, nor were they present elsewhere in the genome, confirming the balanced state of the translocation.


Hepatic Resection is Safe for Metachronous Hepatic Metastases from Ovarian Cancer.
To explore the efficacy of hepatic resection (HR) in a relatively unselected group of patients with ovarian cancer liver metastases (OCLM). A study was conducted between September 2000 and September 2011 on 60 ovarian cancer patients with hepatic metastases (24 solitary and 36 multiple), 40 of whom had extrahepatic metastases. HR was done in all patients provided that curative hepatic resection was feasible, and extrahepatic disease was controlled with medical and/or surgical therapy. Most patients (n=54; 90.0%) had a negative hepatic margin (R0), whereas 6 patients (10.0%) had microscopic disease at the margin (R1). The prognostic value of each study variable was assessed using log rank tests for univariate analysis and Cox proportional hazard models for multivariate analysis. The result was a median survival of 39 months and 5-year overall survival rate of 30%. Univariate analysis showed that surgery result (P=0.001), disease free interval (P=0.018) and the number of hepatic lesions (P=0.018) were significantly related to survival. Furthermore, the surgery result (P=0.004) remained significant for prognosis in multivariate analysis. For patients with OCLM, HR is safe and may provide a significant survival benefit compared with medical therapy alone. A long interval time, the number of hepatic lesions, and surgery results are key prognostic factors. Favorable outcomes can be achieved even in patients with medically controlled or surgically resectable extrahepatic disease, indicating that surgery should be considered more frequently in the multidisciplinary care of patients with OCLM.


Maternal stress retards fetal development in mice with transcriptome-wide impact on gene expression profiles of the limb.
The environment of a pregnant mother has a life-long impact on later life of offspring. Maternal stress is known to cause low birth weight and programs several physiological dysfunctions in offspring. However, the direct effects of maternal stress on the developing fetus remain largely unknown. The present study focused on the effect of chronic maternal stress on the developmental program and its molecular mechanisms. Pregnant mice were given 6-hour immobilization stress every day from 8.5 days post coitum. Fetal body weight was significantly decreased by maternal stress throughout development. Importantly, developmental events were retarded in the stressed fetuses. Around embryonic day 13.5 (E13.5), the developmental increment of somite numbers was delayed, although this difference recovered by E15.5. Limb bud formation and regression of interdigital webbing were also retarded by approximately 0.5 days. Subsequently, transcriptomes of developing limbs were analyzed by cDNA microarrays. Approximately, one-tenth of detected transcripts were significantly influenced by maternal stress. Q-PCR AQ analyses further demonstrated that the expression of a subset of limb development-associated genes, including Igf1, Aldh1a2, and Acta1, was changed in the stressed fetus. In conclusion, our findings suggest that maternal stress can retard limb and somite development in mice, with profound impacts on the developmental genetic program of limb.


Surgical margin length and location affect recurrence rates after robotic prostatectomy.
Robotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized prostate cancer, with treatment failure defined by biochemical recurrence (BCR). Open radical prostatectomy series have identified the presence of a positive surgical margin (PSM) as a predictor of long-term recurrence, a measure that is affected by the surgeon׳s skill. We evaluate the effect of PSM parameters on BCR rates from robotic-assisted laparoscopic radical prostatectomy, across 3 high-volume institutions. De-identifiable clinicopathological and histopathological data were prospectively collected for 4,001 patients with at least 3 years of follow-up. Kaplan-Meier plots and 3 statistical models were used to evaluate the effect of margin parameters on BCR, via crude rates, traditional multivariable Cox regression, and a propensity-adjusted Cox regression model. Overall, 37% of men with a PSM developed BCR compared with 10% of men with negative margins (hazard ratio [HR] = 1.81, 95% CI: 1.47-2.22). Length ≥3 mm or a multifocal positive margin was associated with a higher risk of BCR compared with negative margin cases. On multivariable Cox regression analysis of the positive margin cohort, only apical margins significantly predicted BCR relative to basal margins (HR = 2.03, 95% CI: 1.01-4.09), whereas there was no significant difference in BCR rates for posterolateral margins relative to basal margins (HR = 1.62, 95% CI: 0.84-3.11). Propensity-adjusted modeling confirmed a greater effect of apical compared with posterolateral PSM. A PSM length ≥3 mm is predictive of BCR, as is to a lesser extent multiple positive margins. In contrast to open prostatectomy series, posterolateral margins carry a smaller risk of BCR compared with apical margins.


Alcohol abstinence and mortality in a general population sample of adults in Germany: A cohort study.
Evidence suggests that people who abstain from alcohol have a higher mortality rate than those who drink low to moderate amounts. However, little is known about factors that might be causal for this finding. The objective was to analyze former alcohol or drug use disorders, risky drinking, tobacco smoking, and fair to poor health among persons who reported abstinence from alcohol drinking in the last 12 months before baseline in relation to total, cardiovascular, and cancer mortality 20 years later. A sample of residents aged 18 to 64 years had been drawn at random among the general population in northern Germany and a standardized interview conducted in the years 1996 to 1997. The baseline assessment included 4,093 persons (70.2% of those who had been eligible). Vital status and death certificate data were retrieved in the years 2017 and 2018. We found that among the alcohol-abstinent study participants at baseline (447), there were 405 (90.60%) former alcohol consumers. Of the abstainers, 322 (72.04%) had met one or more criteria for former alcohol or drug dependence or abuse, alcohol risky drinking, or had tried to cut down or to stop drinking, were daily smokers, or self-rated their health as fair to poor. Among the abstainers with one or more of these risk factors, 114 (35.40%) had an alcohol use disorder or risky alcohol consumption in their history. Another 161 (50.00%) did not have such an alcohol-related risk but were daily smokers. The 322 alcohol-abstinent study participants with one or more of the risk factors had a shorter time to death than those with low to moderate alcohol consumption. The Cox proportional hazard ratio (HR) was 2.44 (95% confidence interval (CI), 1.68 to 3.56) for persons who had one or more criteria for an alcohol or drug use disorder fulfilled in their history and after adjustment for age and sex. The 125 alcohol-abstinent persons without these risk factors (27.96% of the abstainers) did not show a statistically significant difference from low to moderate alcohol consumers in total, cardiovascular, and cancer mortality. Those who had stayed alcohol abstinent throughout their life before (42; 9.40% of the alcohol-abstinent study participants at baseline) had an HR 1.64 (CI 0.72 to 3.77) compared to low to moderate alcohol consumers after adjustment for age, sex, and tobacco smoking. Main limitations of this study include its reliance on self-reported data at baseline and the fact that only tobacco smoking was analyzed as a risky behavior alongside alcohol consumption. The majority of the alcohol abstainers at baseline were former alcohol consumers and had risk factors that increased the likelihood of early death. Former alcohol use disorders, risky alcohol drinking, ever having smoked tobacco daily, and fair to poor health were associated with early death among alcohol abstainers. Those without an obvious history of these risk factors had a life expectancy similar to that of low to moderate alcohol consumers. The findings speak against recommendations to drink alcohol for health reasons.


Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis.
The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Twenty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast(®) Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. However, comparative phase III study with larger number of patients should be done for confirmation of the efficacy of the product.


Mitochondrial changes in cidofovir therapy for BK virus nephropathy.
Polyoma (BK) virus nephropathy (BKVN) is often treated with the nucleotide analog cidofovir. An adverse effect of this drug class is proximal tubular toxicity, and ultrastructural abnormalities in proximal tubular mitochondria have been observed in patients treated with similar drugs for other viral infections. We report similar changes in biopsies from BKVN treated with cidofovir. Renal allograft biopsies showing BKVN, on which electron microscopy was performed, were categorized into 3 groups: initial diagnosis (BD), postcidofovir treatment (CT), and posttreatment with immunosuppression reduction (IR). Nineteen cases from each group were randomly selected. Mitochondrial changes were present in 6 biopsies from patients receiving CT therapy (31.5%), ranging from diffuse mitochondrial swelling to profound morphologic changes. No similar abnormalities were seen in other groups. In those with atypical mitochondria, the mean number of cidofovir doses was 2.67, with an average interval between last dose and biopsy of 2.17 weeks. CT patients without mitochondrial changes had a mean of 4.6 doses and an average interval between last dose and biopsy of 27.2 weeks. Some renal transplant patients treated with cidofovir display alterations in proximal tubular mitochondria akin to those seen with similar drugs. The findings support the mitochondrial toxicity of nucleotide analogs.


Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia.
The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C2H2 domain-containing transcription factor. Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals. We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia. Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.


Type of patients in whom biochemical recurrence after radical prostatectomy can be observed without salvage therapy.
To examine the prognosis after BCR with and without salvage therapy, including radiation and/or androgen deprivation. The study population consisted of 431 patients, all of whom underwent radical prostatectomy and developed BCR (PSA > 0.2 ng/mL). According to the two risk factors [Gleason score ≥ 8 and PSA-doubling time (DT) < 6 months], we divided the patients into two groups. The high/intermediate-risk group consisted of patients with both or one risk factor. On the other hand, patients with neither factor were in the low-risk group. We set the starting point at the timing of BCR, and the endpoints were development to castration-resistant prostate cancer (CRPC) and cancer-specific death. During the mean follow-up period of 8.3 years after BCR, CRPC was observed in 49 patients (11.4%), and 21 patients (4.9%) died due to prostate cancer. We first divided the 191 high/intermediate-risk patients according to the PSA level (PSA < 1.0 ng/mL, PSA 1.0-4.0, and PSA > 4.0 or no therapy) at the initiation of salvage therapy, including radiation and/or androgen deprivation. We found that delayed (PSA > 4.0 ng/mL) or no salvage therapy was significantly associated with CRPC and cancer-specific death. In the 240 low-risk patients, Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival or cancer-specific survival within 10 years from the timing of BCR. Observation after BCR without salvage therapy or delayed administration may be an option for low-risk patients with a Gleason score ≤ 7 and PSA-DT ≥ 6 months when their life expectancy is within 10 years.


[Knowledge about breastfeeding profits among primiparas].
Breastfeeding is the only way to nourish newborns and toddlers and it enables them to have an optimal health condition and growth. Both a child and a mother draw a lot of profits from breastfeeding. Woman's milk is perfectly balanced as far as quantity and quality is concerned. It has specific generic nourishment that ensures optimal psychological emotional and physical development of a child. Breastfeeding also protects infants from immunological problems and infections. Having the skills and knowledge about breastfeeding is the main factor that enables a smooth process of lactation. All the medical staff and midwives especially are obliged to promote breastfeeding and they should provide information as well as emotional and technical support for mums through the whole period of lactation. The aim of this thesis was to examine the level of knowledge about breastfeeding among first-time mothers. An anonymous survey was used as an analytic tool. The survey was specifically created for this research and it contained 30 questions. Majority of responders (98%) declared a will for breastfeeding. Also majority of women (94%) knew that their milk contains all the needed ingredients for proper development of their young. According to the pregnant women in labor (98%) breastfeeding is a key element in establishing an emotional connection with the child. Most of the responders knew the influence of breastfeeding on child's health. Minority of the questioned women (14%) attended birthing courses. The responders were equipped in knowledge on various levels. It proves the necessity of systematic and planned education for women. The system of lactation counseling should be an integral part of post-labor care in obstetrician clinics.


Recirculatory pharmacokinetic models of markers of blood, extracellular fluid and total body water administered concomitantly.
Pharmacokinetic models were developed to describe the disposition of markers of extracellular fluid (inulin) and total body water (antipyrine) from the moment of injection to incorporate the intravascular mixing component, determined by a marker of intravascular space (indocyanine green, ICG). The simultaneous dispositions of these markers were characterized in four halothane-anesthetized dogs. After injection of ICG, [14C]-inulin, and antipyrine into the right atrium, femoral arterial blood samples were collected every 3 sec for 1 min and less frequently to 20 min for ICG and to 360 min for inulin and antipyrine. ICG and antipyrine concentrations were measured by high-performance liquid chromatography and [14C]-inulin concentrations were measured by liquid scintillation counting. The marker concentration histories were characterized completely by fully identifiable recirculatory compartmental models. Because neither ICG nor inulin distribute beyond intravascular space before recirculation, their first-pass data were modelled simultaneously to improve confidence in central circulation model parameters. This central circulation model included an estimate of cardiac output that was retained in the recirculatory models of all markers. Three tissue compartments were identified for antipyrine, a lipid soluble marker that equilibrates with tissue (including the lung) and estimates total body water and tissue blood flow. The hydrophilic marker, inulin, diffuses into interstitial fluid so slowly that only two extravascular compartments were identified. These models may be used to determine how cardiac output and its distribution, pulmonary drug uptake, and nondistributive blood flow contribute to variability in patient response to drugs with a rapid onset of effect.


Deficiency of kappa- or lambda-type immunoglobulins.
A marked imbalance of the two light chain types of immunoglobulins was observed in two young male adults suffering from primary hypogammaglobulinemia and intrinsic factor-deficient pernicious anemia. In one patient, the kappa/lambda light chain ratio of serum immunoglobulins was 0.01; in the other, it was approximately 6 (normal value, 1.8 +/- 0.3). This light chain imbalance was found within each of the three main immunoglobulin classes. The number of mature immunoglobulin-producing cells in the bone marrow and in the mucosa of the gastrointestinal tract was reduced. The relative frequency of kappa- and lambda-producing cells in these tissues corresponded to the kappa/lambda ratio of serum immunoglobulins. However, the number of peripheral lymphocytes with membrane-associated immunoglobulins as well as the percentage distribution of blood lymphocytes with kappa- or lambda-type immunoglobulins on the membrane were within normal limits in both cases. The results suggested a hitherto unknown defect in the maturation of B-cells leading to an abnormal ratio of kappa- and lambda-type immunoglobulin-secreting cells.


Learning-Based Multi-UAV Flocking Control With Limited Visual Field and Instinctive Repulsion.
This article explores deep reinforcement learning (DRL) for the flocking control of unmanned aerial vehicle (UAV) swarms. The flocking control policy is trained using a centralized-learning-decentralized-execution (CTDE) paradigm, where a centralized critic network augmented with additional information about the entire UAV swarm is utilized to improve learning efficiency. Instead of learning inter-UAV collision avoidance capabilities, a repulsion function is encoded as an inner-UAV "instinct." In addition, the UAVs can obtain the states of other UAVs through onboard sensors in communication-denied environments, and the impact of varying visual fields on flocking control is analyzed. Through extensive simulations, it is shown that the proposed policy with the repulsion function and limited visual field has a success rate of 93.8% in training environments, 85.6% in environments with a high number of UAVs, 91.2% in environments with a high number of obstacles, and 82.2% in environments with dynamic obstacles. Furthermore, the results indicate that the proposed learning-based methods are more suitable than traditional methods in cluttered environments.


Does the evidence really suggest that we should completely revascularise bystander disease in patients with ST elevation myocardial infarction undergoing primary angioplasty? Why we still need more definitive trial data to change routine practice.
There remains considerable heterogeneity in the management of significant lesions in non culprit coronary arteries in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Three recent randomised trials have shown clinical outcome benefit in a complete revascularisation approach when compared to PPCI of the culprit artery alone. By contrast, observational data suggest that an aggressive complete revascularisation may not confer clinical benefit and may, in some cases, be harmful. Areas covered: In this review we discuss the three recent randomised trials that have advocated a complete revasculariation approach in addition to data available from registries. Expert commentary: An adequately powered, randomised controlled trial is required to answer the question of whether complete revascularisation in STEMI patients is beneficial and, if so, whether it should be ischaemia directed and whether it should be at the index procedure or staged.


Is the surgical approach beneficial to subfertile women with symptomatic extensive adenomyosis?
Our aim was to assess the role of surgical intervention for symptom control and reproductive performance improvement in the management of subfertile women with symptomatic extensive uterine adenomyosis. Sixty-five subfertile women with pathology-proven extensive uterine adenomyosis, who were treated with conservative surgery or medical treatment with 6-month gonadotrophin-releasing hormone (GnRH) agonist or combination therapy, were retrospectively reviewed and their data analyzed. Twenty-eight women received conservative surgery with/without GnRH agonist (group A), and 37 received 6-month GnRH agonist therapy only (group B). Follow-up evaluations, including subjective symptoms (a self-reported 6-point verbal numeric rating scale and an analgesic usage score for dysmenorrhea) and objective parameters (serum CA125 level, and uterine size), and clinical pregnancy and successful delivery rates were made semi-annually over the ensuing 3 or more years. The women in group A had higher serum CA125 levels, more infertile years, and a larger uterine size. Subjective symptom control and objective parameters were better in group A during the entire 36-month follow up compared with those in group B. Cumulative 3-year clinical pregnancy and successful delivery rates were significantly higher in group A, compared with those in group B (46.4% [13/28] versus 10.8% [4/37], P = 0.002, and 32.1% [9/28] versus 8.1% [3/37], P = 0.022, respectively). Conservative surgery or combination therapy provides more effective and longer durable symptom control in the management of symptomatic women with extensive uterine adenomyosis, compared with GnRH agonist alone. Reproductive performance was also better in patients treated with conservative surgery with/without GnRH agonist.


Surgical Treatment of Facial Basal Cell Carcinoma: Patient-Based Assessment of Clinical Outcome in a Prospective Cohort Study.
There are limited data on the esthetic, functional, and morphological outcomes of surgical treatment of facial basal cell carcinoma (BCC). The aim of our study was to assess the determinants of the evaluation of both the patients and the investigator of the esthetic, functional, and morphological impact of the surgical treatment of facial BCC. A prospective observational study evaluated 111 patients treated surgically for facial BCCs (n = 135 BCCs), using the Patient and Observer Scar Assessment Scale (POSAS), a validated and reliable scale designed for the evaluation of all types of scars by professionals and patients. Scar assessment rated by the patients was very good. Skin aging was associated with a better surgical outcome as evaluated by POSAS (OR = 0.30, 95% CI: 0.09-0.98; p = 0.04). Conversely, histologically infiltrative or sclerosing BCC (OR = 2.33, 95% CI: 0.95-5.71; p = 0.06) was independently associated with poorer POSAS. In terms of the investigator's evaluation, aging signs (protective factor: OR = 0.17, 95% CI: 0.04-0.73; p = 0.01), location on the H-zone of the face (risk factor: OR = 2.95, 95% CI: 1.07-8.15; p = 0.03), and histologically infiltrative or sclerosing BCC (risk factor: OR = 2.89, 95% CI: 1.01-8.29; p = 0.04) were independently associated with POSAS. Esthetic, functional, and morphological outcomes of facial BCC surgery provide high patient satisfaction overall. Taking wider margins requires specific measures to improve the surgical outcome.


Controlled release of high molecular weight hyaluronic Acid from molecularly imprinted hydrogel contact lenses.
Current dry eye treatment includes delivering comfort agents to the eye via drops, but low bioavailability and multiple administration continues to be a barrier to effective treatment. There exists a significant unmet need for devices to treat dry eye and for more comfortable contact lenses. Using molecular imprinting strategies with an analysis of biology, we have rationally designed and synthesized hydrogel contact lenses that can release hyaluronic acid (HA) at a controlled rate. Delayed release characteristics were significantly improved through biomimetic imprinting, as multiple functional monomers provided non-covalent complexation points within nelfilcon A gels without altering structural, mechanical, or optical properties. The diffusion coefficient of 1.2 million Dalton HA was controlled by varying the number and variety of functional monomers (increasing the variety lowered the HA diffusion coefficient 1.5 times more than single functional monomers, and 1.6 times more than nelfilcon A alone). HA can be delivered from a daily disposable lens at a therapeutic rate of approximately 6 microg/h for 24 h. This is the first demonstration of imprinting a large molecular weight polymer within a hydrogel and the effect of imprinting on the reptation of the long chain macromolecule from the structure.


Helicobacter pylori and gastroduodenal pathology: new threats of the old friend.
The human gastric pathogen Helicobacter pylori causes chronic gastritis, peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. It infects over 50% of the worlds' population, however, only a small subset of infected people experience H. pylori-associated illnesses. Associations with disease-specific factors remain enigmatic years after the genome sequences were deciphered. Infection with strains of Helicobacter pylori that carry the cytotoxin-associated antigen A (cagA) gene is associated with gastric carcinoma. Recent studies revealed mechanisms through which the cagA protein triggers oncopathogenic activities. Other candidate genes such as some members of the so-called plasticity region cluster are also implicated to be associated with carcinoma of stomach. Study of the evolution of polymorphisms and sequence variation in H. pylori populations on a global basis has provided a window into the history of human population migration and co-evolution of this pathogen with its host. Possible symbiotic relationships were debated since the discovery of this pathogen. The debate has been further intensified as some studies have posed the possibility that H. pylori infection may be beneficial in some humans. This assumption is based on increased incidence of gastro-oesophageal reflux disease (GERD), Barrett's oesophagus and adenocarcinoma of the oesophagus following H. pylori eradication in some countries. The contribution of comparative genomics to our understanding of the genome organisation and diversity of H. pylori and its pathophysiological importance to human healthcare is exemplified in this review.


Successful Outflow Reconstruction to Salvage Traumatic Hepatic Vein-Caval Avulsion of a Normothermic Machine Ex-Situ Perfused Liver Graft: Case Report and Management of Organ Pool Challenges.
Donor organ shortage continues to limit the availability of liver transplantation, a successful and established therapy of end-stage liver diseases. Strategies to mitigate graft shortage include the utilization of marginal livers and recently ex-situ normothermic machine perfusion devices. A 59-year-old woman with cirrhosis due to primary sclerosing cholangitis was offered an ex-situ machine perfused graft with unnoticed severe injury of the suprahepatic vasculature due to road traffic accident. Following a complex avulsion, repair and reconstruction of all donor hepatic veins as well as the suprahepatic inferior vena cava, the patient underwent a face-to-face piggy-back orthotopic liver transplantation and was discharged on the 11th postoperative day after an uncomplicated recovery. This report illustrates the operative technique to utilize an otherwise unusable organ, in the current environment of donor shortage and declining graft quality. Normothermic machine perfusion can definitely play a role in increasing the graft pool, without compromising the quality of livers who had vascular or other damage before being ex-situ perfused. Furthermore, it emphasizes the importance of promptly and thoroughly communicating organ injuries, as well as considering all reconstructive options within the level of expertise at the recipient center.


"My bitterness is deeper than the ocean": understanding internalized stigma from the perspectives of persons with schizophrenia and their family caregivers.
It is estimated that 8 million of the Chinese adult population had a diagnosis of schizophrenia. Stigma associated with mental illness, which is pervasive in the Chinese cultural context, impacts both persons with schizophrenia and their family caregivers. However, a review of the literature found a dearth of research that explored internalized stigma from the perspectives of both patients and their caregivers. We integrated data from standardized scales and narratives from semi-structured interviews obtained from eight family-dyads. Interview narratives about stigma were analyzed using directed content analysis and compared with responses from Chinese versions of the Internalized Stigma of Mental Illness Scale and Affiliated Stigma Scale. Scores from the two scales and number of text fragments were compared to identify consistency of responses using the two methods. Profiles from three family-dyads were analyzed to highlight the interactive aspect of stigma in a dyadic relationship. Our analyses suggested that persons with schizophrenia and their caregivers both internalized negative valuation from their social networks and reduced engagement in the community. Participants with schizophrenia expressed a sense of shame and inferiority, spoke about being a burden to their family, and expressed self-disappointment as a result of having a psychiatric diagnosis. Caregivers expressed high level of emotional distress because of mental illness in the family. Family dyads varied in the extent that internalized stigma were experienced by patients and caregivers. Family plays a central role in caring for persons with mental illness in China. Given the increasingly community-based nature of mental health services delivery, understanding internalized stigma as a family unit is important to guide the development of cultural-informed treatments. This pilot study provides a method that can be used to collect data that take into consideration the cultural nuances of Chinese societies.


Diagnostic features of Angle's Class II div 2 malocclusion.
A thorough knowledge of the salient features of malocclusion makes the practitioner to come to a proper diagnosis and to formulate proper mechanotherapy. It also helps to predict the prognosis, prior to the onset of treatment process. Among the various malocclusions, Class II div 2 occurs the least often. The literature review does not clearly describe the classical skeletal and dental features of Angle's Class II div 2 malocclusion. The aim of this study is to describe the unique features of Angle's Class II division 2 malocclusion. A total of 612 pre-treatment records (study models and cephalograms), with age ranging from 14 to 25 years, were obtained from the hospital records of Drs Sudha and Nageswar Rao Siddhartha Institute of Dental Sciences. Among these samples, 317 were Class II div 1 and 295 were Class II div 2. The lateral cephalograms were analyzed by using Kodak software and the arch width analysis was calculated by using digital vernier calipers. Student's t test was used for the study. On the cephalograms, the vertical skeletal measurements and few of the dental variables showed a significant difference. On the plaster models, the maxillary transverse measurements revealed a notable discrimination between the groups. Angle's Class II div 2 malocclusion has a marked horizontal growth pattern with decreased lower facial thirds, palatally inclined upper anteriors, and remarkably increased transverse maxillary arch dimensions.


Limited value of routine microalbuminuria assessment in multi-ethnic obese children.
To determine the prevalence of microalbuminuria and its association with cardiometabolic risk factors in a multi-ethnic cohort of overweight and obese children. A retrospective analysis of prospectively collected data was performed using data from 408 overweight and obese children (age 3-19 years). In addition to administering an oral glucose tolerance test, we measured anthropometric variables, plasma lipid levels, alanine aminotransferase and the urinary albumin/creatinine ratio (ACR). Microalbuminuria was defined as an ACR of between 2.5 and 25 mg/mmol in boys and 3.5 and 25 mg/mmol in girls. In total, only 11 (2.7 %) of the children analyzed presented with microalbuminuria, with no differences between ethnic groups, sex or in the prevalence of hypertension compared to the children with normoalbuminuria. After adjustment for confounders, the body mass index Z-score tended to be different between the group with microalbuminuria versus that without (3.6 vs. 3.2, respectively; P = 0.054). ACR was not associated with hypertension, impaired glucose tolerance, high triglycerides or low high-density lipoprotein-cholesterol. In a large multi-ethnic cohort of overweight and obese children, we found a low prevalence of microalbuminuria (11 children, 2.7 %), and in this small number of individuals, we found no association with any of the cardiometabolic risk factors assessed. Therefore, our data do not support the routine measurement of microalbuminuria in asymptomatic overweight and obese children and adolescents.


Do Running Activities of Adolescent and Adult Tennis Players Differ During Play?
To investigate differences in running activities between adolescent and adult tennis players during match play. Differences between winning and losing players within each age group were also examined. Forty well-trained male players (20 adolescents, 13 ± 1 y; 20 adults, 25 ± 4 y) played a simulated singles match against an opponent of similar age and ability. Running activities were assessed using portable devices that sampled global positioning system (10 Hz) and inertial-sensor (accelerometer, gyroscope, and magnetometer; 100 Hz) data. Recorded data were examined in terms of velocity, acceleration, deceleration, metabolic power, PlayerLoad, and number of accelerations toward the net and the forehand and backhand corners. Adult players spent more time at high velocity (≥4 m/s2), acceleration (≥4 m/s2), deceleration (≤-4 m/s2), and metabolic power (≥20 W/kg) (P ≤ .009, ES = 0.9-1.5) and performed more accelerations (≥2 m/s2) toward the backhand corner (P < .001, ES = 2.6-2.7). No differences between adolescent winning and losing players were evident overall (P ≥ .198, ES = 0.0-0.6). Adult winning players performed more accelerations (2 to <4 m/s2) toward the forehand corner (P = .026, ES = 1.2), whereas adult losing players completed more accelerations (≥2 m/s2) toward the backhand corner (P ≤ .042, ES = 0.9). This study shows that differences in running activities between adolescent and adult tennis players exist in high-intensity measures during simulated match play. Furthermore, differences between adolescent and adult players, and also between adult winning and losing players, are present in terms of movement directions. Our findings may be helpful for coaches to design different training drills for both age groups of players.