Recent Progress in Virtual Reality Exposure Therapy for Phobias: A Systematic Review.
This review is designed to systematically examine the available evidence about virtual reality exposure therapy's (VRET) efficacy for phobias, critically describe some of the most important challenges in the field and discuss possible directions. Evidence reveals that virtual reality (VR) is an effective treatment for phobias and useful for studying specific issues, such as pharmacological compounds and behavioral manipulations, that can enhance treatment outcomes. In addition, some variables, such as sense of presence in virtual environments, have a significant influence on outcomes, but further research is needed to better understand their role in therapeutic outcomes. We conclude that VR is a useful tool to improve exposure therapy and it can be a good option to analyze the processes and mechanisms involved in exposure therapy and the ways this strategy can be enhanced. In the coming years, there will be a significant expansion of VR in routine practice in clinical contexts.


[Spa treatment of postcholecystectomy syndrome].
In 40% cases pain and dyspepsia do not disappear after cholecystectomy made by laparotomic or laparoscopic method. The aim of the study was to introduce a new method of ultrasonic diagnosis of biliary excretion and to formulate principles of postcholecystectomy syndrome treatment depending on the dyskinesia form. The new method diagnosed 6 variants of biliary excretion: normal (7.2%), hypokinetic (42.8%), hypertonic (28.3%), hypertonic-hypokinetic (5.0%), hyperkinetic (14.5%), hypertonic-hyperkinetic (2.2%). The patients received differentiated treatment depending on the type of biliary excretion. The results of such spa treatment were much better than the results of standard therapy.


The segment as the minimal planning unit in speech production and reading aloud: evidence and implications.
Speech production and reading aloud studies have much in common, especially the last stages involved in producing a response. We focus on the minimal planning unit (MPU) in articulation. Although most researchers now assume that the MPU is the syllable, we argue that it is at least as small as the segment based on negative response latencies (i.e., response initiation before presentation of the complete target) and longer initial segment durations in a reading aloud task where the initial segment is primed. We also discuss why such evidence was not found in earlier studies. Next, we rebut arguments that the segment cannot be the MPU by appealing to flexible planning scope whereby planning units of different sizes can be used due to individual differences, as well as stimulus and experimental design differences. We also discuss why negative response latencies do not arise in some situations and why anticipatory coarticulation does not preclude the segment MPU. Finally, we argue that the segment MPU is also important because it provides an alternative explanation of results implicated in the serial vs. parallel processing debate.


Oestradiol 16 alpha-hydroxylase: a risk marker for breast cancer.
17-oxidation and 2- and 16 alpha-hydroxylation of oestradiol show important correlations with biological aspects of breast cancer in women and mice. The presence of mouse mammary tumour virus may lead to increased 16 alpha-hydroxylation. 16 alpha-hydroxyoestrone (which may be generated in an autocrine manner) forms covalent linkages with amino groups on proteins and nucleotides.


Pedunculopontine arousal system physiology - Implications for insomnia.
We consider insomnia a disorder of waking rather than a disorder of sleep. This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of insomnia, mainly representing an overactive waking drive. We determined that high frequency activity during waking and REM sleep is controlled by two different intracellular pathways and channel types in PPN cells. We found three different PPN cell types that have one or both channels and may be active during waking only, REM sleep only, or both. These discoveries point to a specific mechanism and novel therapeutic avenues for insomnia.


Job stress and mental health among nonregular workers in Korea: What dimensions of job stress are associated with mental health?
Although nonregular workers experience higher job stress, poorer mental health, and different job stress dimensions relative to regular workers, little is known about which job stress dimensions are associated with poor mental health among nonregular workers. This study investigated the association between job stress dimensions and mental health among Korean nonregular workers. Data were collected from 333 nonregular workers in Seoul and Gyeonggi Province, and logistic regression analysis was conducted. Results of the study indicated that high job insecurity and lack of rewards had stronger associations with poor mental health than other dimensions of job stress when controlling for sociodemographic and psychosocial variables. It is important for the government and organizations to improve job security and reward systems to reduce job stress among nonregular workers and ultimately alleviate their mental health issues.


Better prioritization to increase research value and decrease waste.
In a recent study published in BMC Medicine, Singh Ospina and colleagues outlined the important gaps between ongoing research and research needs in the field of endocrinology. Many recommendations from clinical practice guidelines are based on a low level of evidence, thereby resulting in research gaps. Despite the publication of around 25,000 randomized controlled trials each year, ongoing research does not cover most of these gaps. In contrast, trials are planned when sufficient data are already available for decision making, which results in redundant research and exposes patients to unnecessary risks. This lack of prioritization contributes to the enormous problem of waste in research. A systematic approach to accumulate the available body of evidence is necessary to determine when we have sufficient evidence and when we have knowledge gaps, defined as research questions with no or a low level of evidence available. Systematic registration of research gaps and their prioritization may help to organize future research. Some initiatives exist, but they need to be generalized.Please see related research: http://www.biomedcentral.com/1741-7015/13/187.


Design principles for optoelectronic applications of extraordinary light transmission effect in plasmonics nanoapertures.
The extraordinary light transmission effect (EOT) through sub-wavelength nanoapertures in opaque metal films has lead to observation of a wide variety of exciting new optical phenomena. This remarkable effect is generally related to the interaction of the light with the extended plasmonic resonances on the surface of the metal film and localized surface plasmons in the apertures. On the other hand, there is little conceptual understanding for controlling the localized surface plasmonic behavior of the individual apertures and their coupling to the extended surface plasmons. In this letter, we present an intuitive and straightforward picture of the extra-ordinary light transmission phenomena based on basic antenna principles for plasmonic excitations and coupling of these plasmonic excitations in complex nano-apertures. Our quasi-static model remarkably well explains our experimental measurements in shape anisotropic structures with unique properties controlled by adjusting the size and the geometry of the apertures. Our approach puts forward new design principles for potential applications ranging from subwavelength optoelectronics and data storage to bio/chemical sensing.


Apparent recurrence of hemolytic uremic syndrome in azathioprine-treated allograft recipients.
The present study describes 3 adult patients with hemolytic uremic syndrome (HUS) leading to chronic renal failure. Following renal transplantation, the 3 patients developed microangiopathic hemolytic anemia associated with acute rejection crises and graft failure. In 2 patients the renal histology of the transplanted kidney was consistent with HUS. It is concluded that, in adult patients, HUS may recur after renal transplantation and contribute to renal graft failure.


Effects of overfeeding naturally-mated adolescent ewes on maternal, fetal, and postnatal lamb growth.
The objective of this study was to evaluate the effects of overfeeding naturally-mated adolescent ewes (Ovis aries) on maternal, fetal, and postnatal lamb growth, hormone concentrations, and lamb carcass characteristics. Two experiments were conducted in which singleton-bearing adolescent ewes were fed a diet containing 2.72 Mcal/kg ME at a rate which met NRC gestational age requirements (MN; n = 10 in Exp. 1, n = 7 in Exp. 2) or were fed the same diet ad libitum (15% refusal rate) throughout gestation (HN; n = 7 in Exp. 1, n = 6 in Exp. 2). Ewe BW was greater (P < 0.05) for HN than MN ewes beginning on 75 d and 52 d of gestation for Exp. 1 and 2, respectively. Final BCS was greater (P ≤ 0.05) for HN than MN ewes in both experiments; 3.5 vs. 3.0, respectively, for Exp. 1, and 4.8 vs. 2.9, respectively, for Exp. 2. Fasting maternal blood insulin concentrations were greater (P ≤ 0.05) in HN ewes near term (135 d of gestation), whereas fasting maternal glucose concentrations were greater (P ≤ 0.05) during most of the second half of gestation in HN ewes, for both experiments. Gestation length did not differ (P = 0.69) between treatments in Exp. 1, but in Exp. 2, HN ewes had shorter (P = 0.01) gestation lengths (144 vs. 149 d) and had increased (P = 0.002) dystocia scores. Fetal abdominal circumference was greater (P < 0.05) in lambs from MN than HN ewes at 97 d of gestation in Exp. 1 (20.8 vs. 17.4 cm) but did not differ (P = 0.94) between treatments at 95 d of gestation in Exp. 2 (averaging 20.5 cm). There were no differences (P ≥ 0.15) in lamb BW, abdominal circumference, crown-rump length, and biparietal distance at birth; or in postnatal BW and plasma concentrations of glucose, insulin, and lactate in either experiment. There were no differences (P ≥ 0.18) in HCW, dressing percentage, LM area, fat thickness, or KPH between treatments in Exp. 2. Although there was no difference (P ≥ 0.31) between treatments in concentrations of IGF1 or IGF2 mRNA in liver samples collected at harvest, lambs from MN ewes had greater (P ≤ 0.05) concentrations of IGF1R and INSR mRNA, suggesting long-term effects of maternal diet on postnatal hepatic function. In conclusion, excess nutrition during gestation in naturally-mated adolescent ewes did not affect birth weight or postnatal performance of offspring.


Regulated gene expression in methanogens.
Methanogens form a very large and diverse group of microorganisms within the domain of the Archaea. Energy for their growth is obtained by the reduction of a variety of substrates into methane. Several genes, coding for enzymes involved in methanogenesis or in the central metabolism have been cloned and studied. The molecular features of their expression signals have been compared with bacterial and eukaryal expression signals. This indicated that the transcription process is an intermediate form between the specific processes known in Bacteria and Eukarya. The translation system that is used in Archaea is very similar with the process in Bacteria. Although the molecular features of genes and expression signals in Archaea are well-studied, investigations on the regulation of gene expression in these organisms are very scarce. In order to give insight into molecular regulatory mechanisms in methanogens, the current knowledge of regulated systems in methanogens will be reviewed in this manuscript.


Admission hyperglycemia and radiological findings of SARS-CoV2 in patients with and without diabetes.
Diabetes emerged as major risk factor for severe acute respiratory syndrome (SARS) and adverse outcome in patients with the coronavirus disease 2019 (COVID-19). Nevertheless, the role of admission hyperglycemia in patients with COVID-19 has not been well-explored, yet. With this retrospective analysis, we report for the first time that hyperglycemia on day-1 is the best predictor of radiographic imaging of SARS-CoV2, regardless of the past medical history of diabetes. Admission hyperglycemia should not be overlooked, but adequately treated to improve the outcomes of COVID-19 patients with our without diabetes.


Surgical Excision of a Symptomatic Thoracic Nerve Root Perineural Cyst Resulting in Complete Resolution of Symptoms: A Case Report.
Tarlov (perineural) cysts of the nerve root are common and usually incidental findings during magnetic resonance imaging (MRI) of the lumbosacral spine. There are a few case reports where symptomatic thoracic perineural cysts have been described in the literature. We report a case of a high thoracic nerve root perineural cyst that failed conservative therapy, requiring surgical intervention. Our patient presented with radicular symptoms involving the left hand. Imaging workup revealed a cystic lesion of the left T1 nerve root at the level of the foramen. Surgical resection resulted in significant improvement in patient symptoms, and pathology revealed a perineural cyst. We conclude that a thoracic perineural (Tarlov) cyst can be symptomatic by causing nerve root compression and can be mistaken as a nerve root sheath tumor on imaging. Surgical treatment can be curative.


Non-contingent affective outcomes influence judgments of control.
Our main goal in these experiments was to examine whether affective valence plays a role in judgments of control (JoC) in intentional action. To test this, we asked participants to completevariationsofasimple aiming task in which words appeared in place of clicked targets. The affective content of the words was manipulated during the experiments but was not contingent on participants' performance. Throughout the task, participants were periodically asked to judge their JoC.Thus, JoC judgments in this task included contributions of a well-established cue to judgments of control, task performance, and a source of affect that was not related to task performance. We found thatmetacognitions of controlvaried consistentlyacross levels of affect, with stronger judgments of being in control for conditions with positive outcome words (e.g., 'puppy') and the weaker judgments of being in control for conditions with negative outcome words (e.g.,'killer').These results suggestaffective outcomes can influence JoC, even though the outcomes are not related to performance.


Brief Report: Coordinated Modulation of Circulating miR-21 in HIV, HIV-Associated Pulmonary Arterial Hypertension, and HIV/Hepatitis C Virus Coinfection.
Dysregulation of microRNA-21 (miR-21) is independently associated with HIV infection, pulmonary arterial hypertension (PAH), and hepatitis C virus (HCV) infection. To assess the expression of miR-21 in these overlapping comorbidities, we measured plasma miR-21 in HIV with and without PAH and then stratified by concomitant HCV infection. MiR-21 was increased in HIV and HIV-PAH versus uninfected subjects, but it did not differ between these groups. HIV/HCV coinfection correlated with even higher miR-21 levels within the HIV-infected population. These data reveal specific regulation of plasma miR-21 in HIV, HIV/HCV coinfection, and PAH and suggest that miR-21 may integrate complex disease-specific signaling in the setting of HIV infection.


FUS-DDIT3 prevents the development of adipocytic precursors in liposarcoma by repressing PPARgamma and C/EBPalpha and activating eIF4E.
FUS-DDIT3 is a chimeric protein generated by the most common chromosomal translocation t(12;16)(q13;p11) linked to liposarcomas, which are characterized by the accumulation of early adipocytic precursors. Current studies indicate that FUS-DDIT3- liposarcoma develops from uncommitted progenitors. However, the precise mechanism whereby FUS-DDIT3 contributes to the differentiation arrest remains to be elucidated. Here we have characterized the adipocyte regulatory protein network in liposarcomas of FUS-DITT3 transgenic mice and showed that PPARgamma2 and C/EBPalpha expression was altered. Consistent with in vivo data, FUS-DDIT3 MEFs and human liposarcoma cell lines showed a similar downregulation of both PPARgamma2 and C/EBPalpha expression. Complementation studies with PPARgamma but not C/EBPalpha rescued the differentiation block in committed adipocytic precursors expressing FUS-DDIT3. Our results further show that FUS-DDIT3 interferes with the control of initiation of translation by upregulation of the eukaryotic translation initiation factors eIF2 and eIF4E both in FUS-DDIT3 mice and human liposarcomas cell lines, explaining the shift towards the truncated p30 isoform of C/EBPalpha in liposarcomas. Suppression of the FUS-DDIT3 transgene did rescue this adipocyte differentiation block. Moreover, eIF4E was also strongly upregulated in normal adipose tissue of FUS-DDIT3 transgenic mice, suggesting that overexpression of eIF4E may be a primary event in the initiation of liposarcomas. Reporter assays showed FUS-DDIT3 is involved in the upregulation of eIF4E in liposarcomas and that both domains of the fusion protein are required for affecting eIF4E expression. Taken together, this study provides evidence of the molecular mechanisms involve in the disruption of normal adipocyte differentiation program in liposarcoma harbouring the chimeric gene FUS-DDIT3.


Adriamycin-induced resistance to natural killer (NK)-mediated cytotoxicity.
Studies were done to determine the susceptibility of a colon carcinoma cell line, LoVo, to natural killer (NK) mediated lysis after exposure to the tumor cells to Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH). LoVo cells were exposed to ADR (0.4 micrograms/ml) for various time intervals and then tested for sensitivity to lysis by NK cells from the peripheral blood of normal donors in a sodium chromate (Cr51) release cytotoxicity assay. Exposure of tumor targets to ADR induced a resistance to NK-mediated lysis. Susceptibility to lysis decreased progressively to approximately 60% of control levels after 72 hours of ADR exposure. The induction of resistance was dependent on ADR dose, but did not magnify with doses greater than 0.4 micrograms/ml. When target cells were allowed to recover from ADR in fresh medium for 48 hours, complete reversal of the ADR effect was seen. The effect of interleukin-2 (IL-2) stimulation on the NK lysis of LoVo also was tested. IL-2-stimulated effector cells demonstrated enhanced cytotoxicity to LoVo targets and were able to overcome the ADR-induced resistance to lysis. The mechanism of resistance does not appear to be related to the altered binding of effectors to chemotherapy-treated targets, as suggested by single cell assay results.


Kidney biopsy in patients with glomerulonephritis: is the earlier the better?
Interventional diagnostic procedures are established for several diseases in medicine. Despite the KDOQI guideline recommendation for histological diagnosis of kidney disease to enable risk stratification, its optimal time point has not been evaluated. We have therefore analyzed whether histological diagnosis of glomerulonephritis (GN) at an early stage of chronic kidney disease (CKD) is associated with different outcome compared to diagnosis at a more advanced stage. A cohort of 424 consecutive patients with histological diagnosis of GN were included in a retrospective data analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy and after consecutive immunosuppressive therapy. Censored events were death, initiation of dialysis or kidney transplantation, or progression of disease, defined as deterioration of CKD stage ≥ 1 from kidney biopsy to last available kidney function measurement. Occurrence of death, dialysis/transplantation or progression of disease were associated with GFR and CKD stage at the time of kidney biopsy (p < 0.001 for all). Patients with CKD stage 1 and 2 at kidney biopsy had fewer endpoints compared to patients with a GFR of <60 ml/min (p < 0.001). Kidney function at the time point of histological GN diagnosis is associated with clinical outcome, likely due to early initiation of specific drug treatment. This suggests that selection of therapy yields greatest benefit before renal function is impaired in GN.


Crystal structure of an anhydrous form of trehalose: structure of water channels of trehalose polymorphism.
alpha, alpha-Trehalose (trehalose) is a nonreducing disaccharide of glucose and is accumulated at high concentrations in some anhydrobiotic organisms, which can survive without water for long periods and rapidly resume active metabolism upon hydration. Although it has been proposed that the intriguing mechanism of bioprotection in anhydrobiosis is conferred by a water channel, details of such a channel have yet to be revealed. We determined the crystal structure of a trehalose anhydrate to further understand the relationship between the structure of water channels and the trehalose polymorph. The space group was identical to that of the dihydrate and the lattice constants were also very similar. Among the five intermolecular hydrogen bonds between the trehalose molecules, four were preserved in the anhydrate. If dehydration of the dihydrate is slow and/or gentle enough to preserve the hydrogen bonds, transformation from the dihydrate to the anhydrate may occur. There are two different holes, hole-1 and hole-2, along one crystal axis. Hole-1 is constructed by trehalose molecules with a screw diad at its center, while hole-2 has a smaller diameter and is without a symmetry operator. Because of the screw axis at the center of hole-1, hollows are present at the side of the hole with diameters roughly equal to that of hole-1. Hole-1 and side pockets followed by hollows correspond to the positions of two water molecules of the dihydrate. The side hollows of the water channel are also observed in the water-filled hole of the dihydrate. Consequently, hole-1 is considered to be a one-dimensional water channel with side pockets. We also calculated molecular and crystal energies to examine the rapid water uptake of the anhydrate. It was demonstrated that the intermolecular interactions in the anhydrate were weaker than in the other anhydrous form, and probably also than those in amorphous trehalose. The anhydrate provides water capture for another solid form and gives protection from water uptake. These structural properties of the anhydrate may elucidate bioprotection in anhydrobiosis.


[Is atherosclerosis an autoimmunological process?].
The theories formulated to explain atherogenesis evolved from simple vessel wall lipid accumulation assumption to endothelial dysfunction with adverse vascular wall remodelling hypothesis. The theory that has been accepted lately integrates the former hypotheses and allows for introducing the local immunological activation concept. This immunological activation is initiated by negatively charged and oxidatively modified lipids (e.g. oxPAPC) and their complexes with proteins (like beta 2-GP I). Antibodies and cellular response against chaperonins: HSP 60 and their analogues from bacterial pathogens such as HSP 65, GroEi etc.) as well as release of cytokines, adhesion molecules and inflammatory mediators (CD 40/CD 40-L, IL 15, IFN gamma, IL 1 beta, TNF alpha) also take part in the process. Another important element of atherogenesis is the pathological angiogenic response within the plaque connected with the expression of angiogenic growth factors (such as VEGF, bFGF and PDGF), metallo-proteinases and local hemostasis regulators. This complex activation of local inflammatory and immunological process initiates such phenomena as development of unstable plaque, vascular remodelling, vessel lumen constriction and ischemic, thromboembolic complications of atherosclerosis.


Renal haemodynamic and tubular actions of urotensin II in the rat.
Urotensin II (UTS) is a potent vasoactive peptide that was originally identified in teleost fish. Mammalian orthologues of UTS and its receptor (UTSR) have been described in several species, including humans and rats. We have shown previously that bolus injections of UTS caused a decrease in urine flow and sodium excretion rates in parallel with marked reductions in renal blood flow (RBF) and glomerular filtration rate (GFR). The aim of this study was to determine the effect of UTS infusion at a dose that has minimal impact upon renal haemodynamics in order to identify a potential direct tubular action of UTS. Infusion of rat UTS (rUTS) at 0.6 pmol/min per 100 g body weight in male Sprague-Dawley rats, which had no effect on RBF and caused a 30% reduction in GFR, resulted in a significant increase in the fractional excretion of sodium (vehicle 2.3+/-0.6 versus rUTS 0.6 pmol 4.5+/-0.6%, P<0.05) and potassium. At the higher dose of 6 pmol/min per 100 g body weight, haemodynamic effects dominated the response. rUTS induced a marked reduction in RBF and GFR (vehicle 1.03+/-0.06 versus rUTS 6 pmol 0.31+/-0.05 ml/min per 100 g body weight, P<0.05) resulting in an anti-diuresis and anti-natriuresis, but no change in fractional excretion of sodium or potassium. Uts2d and Uts2r mRNA expression were greater in the renal medulla compared with the cortex. Together, these data support an inhibitory action of Uts2d on renal tubule sodium and potassium reabsorption in the rat, in addition to its previously described renal haemodynamic effects.


Frequent in vitro recombination in internal transcribed spacers 1 and 2 during genotyping of Pneumocystis jirovecii.
Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PCP) in immunocompromised persons. Knowledge of the transmission and epidemiology of PCP is still incipient, and investigations on these subjects are based exclusively on applications of molecular typing techniques. The polymorphic internal transcribed spacers ITS1 and ITS2 in the ribosomal DNA operon, which in the P. jirovecii genome exist as single-copy DNA, are commonly used as target loci for isolate typing. In the course of genotyping P. jirovecii in respiratory specimens from PCP patients by amplification and cloning of a large number of ITS sequences, we found mixed infections (two or more types) in 50% of the samples. In a majority of the specimens with mixed infections, we detected many ITS haplotypes (combinations of ITS1 and ITS2 types) that appeared to be products of recombination between globally common ITS haplotypes present in the same sample. Here we present results of a series of experiments showing that essentially all ITS recombinants are chimeras formed during the genotyping process. Under standard conditions, as many as 37% of the amplified sequences could be hybrid DNA artifacts. We show that by modifying PCR amplification conditions, ITS chimera formation could be largely abolished and the erroneous establishment of artifactual haplotypes avoided. The accurate assessment of genetic diversity is fundamental for a better understanding of the epidemiology and biology of P. jirovecii infections.


Non-Stoichiometric Amorphous Indium Selenide Thin Films as a Buffer Layer for CIGS Solar Cells with Various Temperatures in Rapid Thermal Annealing.
The conventional structure of most of copper indium gallium diselenide (Culn(1-x)Ga(x)Se2, CIGS) solar cells includes a CdS thin film as a buffer layer. Cd-free buffer layers have attracted great interest for use in photovoltaic applications to avoid the use of hazardous and toxic materials. The RF magnetron sputtering method was used with an InSe2 compound target to prepare the indium selenide precursor. Rapid thermal annealing (RTA) was conducted in ambient N2 gas to control the concentration of volatile Se from the precursor with a change in temperature. The nature of the RTA-treated indium selenide thin films remained amorphous under annealing temperatures of ≤ 700 degrees C. The Se concentration of the RTA-treated specimens demonstrated an opposite trend to the annealing temperature. The optical transmittance and band gap energies were 75.33% and 2.451-3.085 eV, respectively, and thus were suitable for the buffer layer. As the annealing temperature increased, the resistivity decreased by an order-of-magnitude from 10(4) to 10(1) Ω-cm. At lower Se concentrations, the conductivity abruptly changed from p-type to n-type without crystallite formation in the amorphous phase, with the carrier concentration in the order of 10(17) cm(-3).


Effect of dietary resveratrol supplementation on meat quality, muscle antioxidative capacity and mitochondrial biogenesis of broilers.
The naturally occurring polyphenol resveratrol has been acknowledged with many beneficial biological effects. The aim of this study was to evaluate the influence of dietary resveratrol supplementation on meat quality, muscle antioxidative capacity and mitochondrial biogenesis of broilers. One hundred and eighty 21-day-old male Cobb broilers were randomly assigned to two groups and fed on a 0 mg kg-1 or 400 mg kg-1 resveratrol-supplemented diet for 21 days. Then, chickens were slaughtered and pectoralis major muscle (PM) samples were collected for analysis. The results showed that resveratrol not only tended to increase (P < 0.10) PM pH24h but also significantly decreased (P < 0.05) PM L*45min , pH decline, drip loss and lactate content. Meanwhile, PM total antioxidative capacity and catalase activity were significantly increased (P < 0.05) by resveratrol, while malondialdehyde content was decreased (P < 0.10). Moreover, resveratrol significantly increased (P < 0.05) PM peroxisome proliferator-activated receptor γ coactivator 1α and nuclear respiratory factor 1 mRNA levels, along with increased (P < 0.05) citrate synthase activity. Resveratrol can be used as a feed additive to improve meat quality of broilers, which may be associated with improved muscle antioxidative status and mitochondrial biogenesis. © 2017 Society of Chemical Industry.


Morphological changes induced in the pig kidney by extracorporeal shock wave lithotripsy: nephron injury.
While shock wave lithotripsy (SWL) is known to cause significant damage to the kidney, little is known about the initial injury to cells along the nephron. In this study, one kidney in each of six juvenile pigs (6-7 weeks old) was treated with 1,000 shock waves (at 24 kV) directed at a lower pole calyx with an unmodified HM-3 lithotripter. Three pigs were utilized as sham-controls. Kidneys were fixed by vascular perfusion immediately after SWL or sham-SWL. Three of the treated kidneys were used to quantitate lesion size. Cortical and medullary samples for light (LM) and transmission electron microscopy (TEM) were taken from the focal zone for the shock waves (F2), the contralateral kidney, and the kidneys of sham-SWL pigs. Because preservation of the tissue occurred within minutes of SWL, the initial injury caused by the shock waves could be separated from secondary changes. No tissue damage was observed in contralateral sham-SWL kidneys, but treated kidneys showed signs of injury, with a lesion of 0.2% +/- 0.1% of renal volume. Intraparenchymal hemorrhage and injury to tubules was found at F2 in both the cortex and medulla of SWL-treated kidneys. Tubular injury was always associated with intraparenchymal bleeding, and the range of tissue injury included total destruction of tubules, focal cellular fragmentation, necrosis, cell vacuolization, and membrane blebbing. The initial injury caused by SWL was cellular fragmentation and necrosis. Cellular vacuolization, membrane blebbing, and disorganization of apical brush borders appear to be secondary changes related to hypoxia.


Frontal lobe atrophy in motor neuron diseases.
Neuronal degeneration in the precentral gyrus alone cannot account for the occurrence of spastic paresis in motor neuron diseases. To look for more extensive cortical atrophy we measured MRIs of the upper parts of the frontal and parietal lobes in 11 sporadic cases of classical amyotrophic lateral sclerosis (ALS), eight patients with primary lateral sclerosis (PLS) and an age- and sex-matched group of 49 neurologically normal people. None of the patients had overt dementia or other mental diseases. In PLS there is progressive spastic paresis but in contrast to ALS there is no lower motor neuron degeneration. The surface area of the precentral gyri and the amount of underlying white matter in PLS were consistently approximately 75% of the normal size. By contrast, there was some shrinkage of the precentral gyri in some of the ALS patients but the mean measurements for the group did not differ significantly from the controls. Anterior to the precentral sulci, the cortical surface area in PLS was approximately 85% of that of the controls, with correspondingly reduced white matter. In ALS the cortical surface areas of the anterior frontal lobes did not differ from those of the controls, but the amount of underlying white matter was reduced almost as much in ALS as it was in PLS. The measured changes in the frontal lobes suggest that in PLS there is simultaneous atrophy of the primary, premotor and supplementary motor areas of the cortex, with consequent degeneration of corticospinal and corticoreticular axons descending through the underlying white matter. These changes could account for the progressive upper motor neuron syndrome. In ALS, with no significant frontal cortical atrophy, the shrinkage of the white matter may be due to degeneration of axons projecting to the frontal cortex from elsewhere. Deprivation of afferents could explain the diminution of motor functions of the frontal lobes in ALS and also the changes in word fluency, judgement and attention that can be detected by appropriate testing in some patients with the disease. Incidental observations include slightly larger parietal lobes but no difference in the frontal lobes in men as compared with women. There was also a small but significant decrease in size of the normal frontal lobes with age. The latter change was much smaller than the atrophy seen in patients with ALS and PLS.


Predecessors of the giant 1960 Chile earthquake.
It is commonly thought that the longer the time since last earthquake, the larger the next earthquake's slip will be. But this logical predictor of earthquake size, unsuccessful for large earthquakes on a strike-slip fault, fails also with the giant 1960 Chile earthquake of magnitude 9.5 (ref. 3). Although the time since the preceding earthquake spanned 123 years (refs 4, 5), the estimated slip in 1960, which occurred on a fault between the Nazca and South American tectonic plates, equalled 250-350 years' worth of the plate motion. Thus the average interval between such giant earthquakes on this fault should span several centuries. Here we present evidence that such long intervals were indeed typical of the last two millennia. We use buried soils and sand layers as records of tectonic subsidence and tsunami inundation at an estuary midway along the 1960 rupture. In these records, the 1960 earthquake ended a recurrence interval that had begun almost four centuries before, with an earthquake documented by Spanish conquistadors in 1575. Two later earthquakes, in 1737 and 1837, produced little if any subsidence or tsunami at the estuary and they therefore probably left the fault partly loaded with accumulated plate motion that the 1960 earthquake then expended.


Cardiac autonomic responses after resistance exercise in treated hypertensive subjects.
The aim of this study was to assess and to compare heart rate variability (HRV) after resistance exercise (RE) in treated hypertensive and normotensive subjects. Nine hypertensive men [HT: 58.0 ± 7.7 years, systolic blood pressure (SBP) = 133.6 ± 6.5 mmHg, diastolic blood pressure (DBP) = 87.3 ± 8.1 mmHg; under antihypertensive treatment] and 11 normotensive men (NT: 57.1 ± 6.0 years, SBP = 127 ± 8.5 mmHg, DBP = 82.7 ± 5.5 mmHg) performed a single session of RE (2 sets of 15-20 repetitions, 50% of 1 RM, 120 s interval between sets/exercise) for the following exercises: leg extension, leg press, leg curl, bench press, seated row, triceps push-down, seated calf flexion, seated arm curl. HRV was assessed at resting and during 10 min of recovery period by calculating time (SDNN, RMSSD, pNN50) and frequency domain (LF, HF, LF/HF) indices. Mean values of HRV indices were reduced in the post-exercise period compared to the resting period (HT: lnHF: 4.7 ± 1.4 vs. 2.4 ± 1.2 ms(2); NT: lnHF: 4.8 ± 1.5 vs. 2.2 ± 1.1 ms(2), p < 0.01). However, there was no group vs. time interaction in this response (p = 0.8). The results indicate that HRV is equally suppressed after RE in normotensive and hypertensive individuals. These findings suggest that a single session of RE does not bring additional cardiac autonomic stress to treated hypertensive subjects.


Stapled hemorrhoidopexy. Complications and 2-year follow-up.
Stapled hemorrhoidopexy (SH) presents a number of complications which differ from those of traditional haemorrhoidectomy (Milligan-Morgan, diathermy haemorrhoidectomy). The follow-up shows better symptom control than other surgical techniques. Four hundred and forty-nine patients with haemorrhoids of all degrees and mucosal rectal prolapse were treated at our institution over a five-year period (1999-2004). Patients were assessed by structural interview to assess their symptoms before and after surgery, and surgical and functional outcome was assessed at 1, 3, 6, 12 and 24 months. A visual analog scale was used for postoperative pain scoring. Patient's satisfaction is the best response to all criticism. Bleeding in the early postoperative period occurred in 3.9% of all patients and in 7 cases (1.5%) reoperation was necessary. Urge to defecate, although present in 14% of patients, disappears in a few weeks. Severe pain, when present, may depend on technical failure or learning curve. Complete or incomplete recurrence occurred in 10 cases (2.2%). We had one case of rectovaginal fistula in a young woman. In 3 cases we underestimated the extent of the mucosal prolapse and the patients were reoperated on by stapled transanal rectal resection after one (2 patients) and two years. Stapled hemorrhoidopexy is a significantly less painful operation and offers significant advantages in terms of hospital stay and symptom control in the long term, making for a significantly earlier return to work. The complications are similar to those of other techniques and are easily resolved. The unusual complications described (rectal perforation, pelvic sepsis, rectovaginal fistulas) might suggest that the operation should be performed by experienced colorectal surgeons who are familiar with the technique and aware of the possible complications.


A note on the self-similar solutions to the spontaneous fragmentation equation.
We provide a method to compute self-similar solutions for various fragmentation equations and use it to compute their asymptotic behaviours. Our procedure is applied to specific cases: (i) the case of mitosis, where fragmentation results into two identical fragments, (ii) fragmentation limited to the formation of sufficiently large fragments, and (iii) processes with fragmentation kernel presenting a power-like behaviour.


Modulation of cholinergic neurotransmission in guinea-pig airways by opioids.
1. Opioid receptors have been localised on sensory fibres in the vagus nerve and opioids have previously been shown to inhibit non-adrenergic, non-cholinergic (NANC) neurotransmission in guinea-pig bronchi in vitro and in vivo. We have now investigated whether an inhibitory effect could be demonstrated on cholinergic neurotransmission. 2. Electrical field stimulation (EFS) (8 Hz, 0.5 ms, 40 V for 20 s) produced only a rapid, cholinergic response in the upper trachea but in the lower trachea and main bronchi a cholinergic response which was atropine-sensitive and a longer lasting NANC contraction that was atropine-insensitive was demonstrated. This slow contraction could be blocked by tetrodotoxin and capsaicin pretreatment. 3. [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAMGO), a selective mu-opioid receptor agonist, inhibited the cholinergic response to EFS at 8 Hz in a dose-dependent manner in main bronchi (IC50 = 113 nM with a maximal inhibition of 35.7 +/- 5.6% 10 microM, n = 5). In the lower trachea, DAMGO inhibited the cholinergic response to a similar extent (inhibition of 35.8 +/- 3.5% at 10 microM, n = 5). However, DAMGO had no effect on the contractile response to exogenously applied acetylcholine in the main bronchi. By contrast, opioids had no inhibitory effect on cholinergic neurotransmission in the upper trachea. DAMGO (1 microM) inhibited the cholinergic response to EFS in a frequency-dependent manner in the main bronchi with greater inhibition at lower frequencies of stimulation. 4. The delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) significantly inhibited the cholinergic component of the constrictor response to EFS at 8 Hz in the bronchi but at the highest dose used (10 microM). U-50,488H, a Kappa-receptor agonist, had no inhibitory effect on the cholinergic constrictor component in the main bronchi (10microM). 5. DAMGO also inhibited the NANC responses to EFS in the main bronchi in a dose-dependent manner (with an IC50 = 36 nm and a maximal inhibition of 63.4 + 8.3%, at 1 microM, n = 5). DAMGO had no effect on contractile responses to exogenously applied substance P (SP). DPDPE (10 microM) was less effective in inhibition of the NANC bronchoconstriction with a maximal inhibition of 29.2 + 4.2% (n = 7), and U-50,488H (1O microM) had no inhibitory effect. 6. After capsaicin pretreatment, which depleted sensory nerves of neuropeptides, the inhibitory effect of DAMGO (1 microM) on cholinergic constriction in main bronchi at 8 Hz was only 13.4 + 1.9% (n = 13) compared with 32.9 + 4.0% (n = 9) inhibition in vehicle-treated controls (P < 0.001). 7. Opioids may reduce the cholinergic neural responses in airways partly via an inhibitory action on excitatory NANC nerves and partly by a direct effect on cholinergic neurotransmission. The opioid receptor involved is of the mu-opioid receptor subtype.


Antitumoral activity of the mithralog EC-8042 in triple negative breast cancer linked to cell cycle arrest in G2.
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer. Despite response to chemotherapy, relapses are frequent and resistance to available treatments is often observed in the metastatic setting. Therefore, identification of new therapeutic strategies is required. Here we have investigated the effect of the mithramycin analog EC-8042 (demycarosil-3D-β-D-digitoxosyl mithramycin SK) on TNBC. The drug caused a dose-dependent inhibition of proliferation of a set of TNBC cell lines in vitro, and decreased tumor growth in mice xenografted with TNBC cells. Mechanistically, EC-8042 caused an arrest in the G2 phase of the cell cycle, coincident with an increase in pCDK1 and Wee1 levels in cells treated with the drug. In addition, prolonged treatment with the drug also causes apoptosis, mainly through caspase-independent routes. Importantly, EC-8042 synergized with drugs commonly used in the therapy of TNBC in vitro, and potentiated the antitumoral effect of docetaxel in vivo. Together, these data suggest that the mithralog EC-8042 exerts an antitumoral action on TNBC cells and reinforces the action of standard of care drugs used in the therapy of this disease. These characteristics, together with a better toxicology profile of EC-8042 with respect to mithramycin, open the possibility of its clinical evaluation.


Design and Application of Toxic and Harmful Gas Monitoring System in Fire Fighting.
In recent years, fire accidents in petrochemical plant areas and dangerous goods storage ports in China have shown a trend of frequent occurrence. Toxic and harmful gases are diffused in the scenes of these accidents, which causes great difficulties for fire fighting and rescue operations of fire fighting forces, and consequently, casualties of firefighters often occur. In order to ensure the safety of firefighters in such places, this paper designs a monitoring system of toxic and harmful gases specially used in fire fighting and rescue sites of fire forces, and establishes the transmission network, monitoring terminal and data processing software of the monitoring system of toxic and harmful gases, establishing the danger model of the monitoring area of toxic and harmful gas-monitoring terminal, and the danger model of fire fighters' working area, fusing the field toxic and harmful gas data, terminal positioning data, and field environmental data, designing the data structure of the input data set and the network structure of the RNN cyclic neural network model, and realizing the dynamic early warning of toxic and harmful gases on site.


Surgical treatment of the cardiometabolic syndrome and obesity.
Prevalence of overweight and obesity has reached a pandemic proportion worldwide and is increasingly contributing to premature morbidity and mortality. Lifestyle changes including behavioral modification, exercise, different dietary plans, and medications have very poor outcome on long-term weight loss. Bariatric surgery has shown to be very effective for morbidly obese patients. Surgery in these patients not only decreases their body weight but also may improve comorbid conditions associated with obesity. These patients on average lose 61% of excess body weight depending on the procedure performed. Diabetes, hyperlipidemia, and hypertension are normalized in these patients by 77%, 70%, and 62%, respectively. Patients need to be selected carefully for surgical treatment of obesity and have to be monitored closely over the long term for nutritional deficiencies and other complications.


You Don't Have to Be Infected to Suffer: COVID-19 and Racial Disparities in Severe Maternal Morbidity and Mortality.
Both coronavirus disease 2019 (COVID-19) and maternal mortality disproportionately affect minorities. However, direct viral infection is not the only way that the former can affect the latter. Most adverse maternal events that end in hospitals have their genesis upstream in communities. Hospitals often represent a last opportunity to reverse a process that begins at a remove in space and time. The COVID-19 pandemic did not create these upstream injuries, but it has brought them to national attention, exacerbated them, and highlighted the need for health care providers to move out of the footprint of their institutions. The breach between community events that seed morbidity and hospitals that attempt rescues has grown in recent years, as the gap between rich and poor has grown and as maternity services in minority communities have closed. COVID-19 has become yet another barrier. For example, professional organizations have recommended a reduced number of prenatal visits, and the platforms hospitals use to substitute for some of these visits are not helpful to people who either lack the technology or the safe space in which to have confidential conversations with providers. Despite these challenges, there are opportunities for departments of obstetrics and gynecology. Community-based organizations including legal professionals, health-home coordinators, and advocacy groups, surround almost every hospital, and can be willing partners with interested departments. COVID-19 has made it clearer than ever that it is time to step out of the footprint of our institutions, and to recognize that the need to find upstream opportunities to prevent downstream tragedies. KEY POINTS: · COVID-19 will exacerbate disparities in perinatal outcomes.. · The virus, per se, is not the pandemic's biggest threat to the health of minority women.. · The solution to maternal mortality cannot be found within the walls of hospitals..


Treatment integrity in a home-based pre-reading intervention programme.
Treatment integrity is an underexposed issue in the phonological awareness intervention research. The current study assessed the integrity of treatment of the families (N = 32) participating in the experimental condition of a home-based pre-reading intervention study. The participating kindergartners were all genetically at risk for developing dyslexia. Two aspects of treatment integrity, the number of lessons completed (quantity) and the quality of the administration of the programme (observed in a videotaped session), were investigated. The level of treatment integrity turned out to be 66% when completion of all lessons was taken as quantitative criterion, and about 74% when quality of the parent-child interaction was assessed. The two measures could predict the pre-reading skills at the end of kindergarten. Together they accounted for 43% of the variance in this dependent variable. Together with pre-reading scores at the pre-test the total predicted variance was 87%. The number of lessons completed still contributed 12% to the prediction after controlling for pre-test scores. The results indicated that treatment integrity indeed appears to be an important aspect of treatment outcome and should therefore be included in intervention studies.


Accumulation of nonesterified fatty acids causes the sustained energetic deficit in kidney proximal tubules after hypoxia-reoxygenation.
Kidney proximal tubules exhibit decreased ATP and reduced, but not absent, mitochondrial membrane potential (Deltapsi(m)) during reoxygenation after severe hypoxia. This energetic deficit, which plays a pivotal role in overall cellular recovery, cannot be explained by loss of mitochondrial membrane integrity, decreased electron transport, or compromised F1F0-ATPase and adenine nucleotide translocase activities. Addition of oleate to permeabilized tubules produced concentration-dependent decreases of Deltapsi(m) measured by safranin O uptake (threshold for oleate = 0.25 microM, 1.6 nmol/mg protein; maximal effect = 4 microM, 26 nmol/mg) that were reversed by delipidated BSA (dBSA). Cell nonesterified fatty acid (NEFA) levels increased from <1 to 17.4 nmol/mg protein during 60- min hypoxia and remained elevated at 7.6 nmol/mg after 60 min reoxygenation, at which time ATP had recovered to only 10% of control values. Safranin O uptake in reoxygenated tubules, which was decreased 85% after 60-min hypoxia, was normalized by dBSA, which improved ATP synthesis as well. dBSA also almost completely normalized Deltapsi(m) when the duration of hypoxia was increased to 120 min. In intact tubules, the protective substrate combination of alpha-ketoglutarate + malate (alpha-KG/MAL) increased ATP three- to fourfold, limited NEFA accumulation during hypoxia by 50%, and lowered NEFA during reoxygenation. Notably, dBSA also improved ATP recovery when added to intact tubules during reoxygenation and was additive to the effect of alpha-KG/MAL. We conclude that NEFA overload is the primary cause of energetic failure of reoxygenated proximal tubules and lowering NEFA substantially contributes to the benefit from supplementation with alpha-KG/MAL.


A Comprehensive Characterization of the TI-LGAD Technology.
Pixelated low-gain avalanche diodes (LGADs) can provide both precision spatial and temporal measurements for charged particle detection; however, electrical termination between the pixels yields a no-gain region, such that the active area or fill factor is not sufficient for small pixel sizes. Trench-isolated LGADs (TI-LGADs) are a strong candidate for solving the fill-factor problem, as the p-stop termination structure is replaced by isolated trenches etched in the silicon itself. In the TI-LGAD process, the p-stop termination structure, typical of LGADs, is replaced by isolating trenches etched in the silicon itself. This modification substantially reduces the size of the no-gain region, thus enabling the implementation of small pixels with an adequate fill factor value. In this article, a systematic characterization of the TI-RD50 production, the first of its kind entirely dedicated to the TI-LGAD technology, is presented. Designs are ranked according to their measured inter-pixel distance, and the time resolution is compared against the regular LGAD technology.


Framing breastfeeding and formula-feeding messages in popular U.S. magazines.
Media framing of infant feeding has the ability to influence knowledge and views of the barriers, benefits, and solutions inherent in breastfeeding or formula-feeding. This study examined how seven popular U.S. parenting, general women's, and African American magazines framed breastfeeding and formula-feeding messages to determine whether a sense-making approach was used and the extent to which visual images portrayed feeding practices. Analysis included 615 articles published from 1997 to 2003 that referred to infant feeding. Text and images were analyzed. The magazines provided more information on breastfeeding than formula feeding. Parenting magazines included more advice than barriers or benefits. African American magazines presented more breastfeeding benefits, and general women's magazines contained the least infant-feeding information. Messages were focused on individualized breastfeeding barriers and advice, seldom covered social and environmental issues, and placed much of the responsibility of infant feeding on the mother, while the role of social and partner support was diminished. Bottle-feeding images were nearly as common as breastfeeding images. Findings can be used by public health practitioners to increase the likelihood of reaching certain target audiences through popular magazines.


COMPARISON BETWEEN FOUR USUAL METHODS OF IDENTIFICATION OF Candida SPECIES.
Infection by Candida spp. is associated with high mortality rates, especially when treatment is not appropriate and/or not immediate. Therefore, it is necessary to correctly identify the genus and species of Candida. The aim of this study was to compare the identification of 89 samples of Candida spp. by the manual methods germ tube test, auxanogram and chromogenic medium in relation to the ID 32C automated method. The concordances between the methods in ascending order, measured by the Kappa index were: ID 32C with CHROMagar Candida(κ = 0.38), ID 32C with auxanogram (κ = 0.59) and ID 32C with germ tube (κ = 0.9). One of the species identified in this study was C. tropicalis,which demonstrated a sensitivity of 46.2%, a specificity of 95.2%, PPV of 80%, NPV of 81.1%, and an accuracy of 80.9% in tests performed with CHROMagar Candida;and a sensitivity of 76.9%, a specificity of 96.8%, PPV of 90.9%, NPV of 91%, and an accuracy of 91% in the auxanogram tests. Therefore, it is necessary to know the advantages and limitations of methods to choose the best combination between them for a fast and correct identification of Candida species.


Hospital Inpatient Stays for Autistic Youth and Youth With Other Disabilities.
Addressing health care needs is complex in autistic youth for many reasons. Increased inpatient care that has been noted in this population, particularly for ambulatory care sensitive conditions (ACSCs), may be a marker of inadequate primary and outpatient care. This study used data from hospital inpatient discharges from the National Inpatient Sample 2017. The prevalence, average length of stay, and the average cost per day of the 10 most common principal diagnoses for index stay were calculated for autistic youth and youth with mental, behavioral, and other neurodevelopmental disabilities (MBND), ages 0 to 17. Of every 1000 inpatient stays, 7.3 were for autistic youth and 65.2 for youth with MBND. The rate varied by US region and zip code-level household income. The most common diagnosis associated with stays in autistic youth was mood disorders, as in youth with MBND. Nearly all top 10 principal diagnoses for autistic youth were for ACSCs. The highest average cost per day for autistic youth was for physical injuries ($4320 per day), and the longest stays were for schizophrenia (14 days). High occurrence of ACSCs in autistic youth suggests that primary care may not adequately address health and mental health needs. Clinical complexity and autism characteristics may be impacting care received in the hospital. Additional considerations need to explore and examine care complexity, racial and ethnic disparities, and the large portion of Medicaid-covered youth. Strategies for the provision of care to these vulnerable populations are of great concern.


Molecular-Level Understanding of Surface Roughness Boosting Segregation Behavior at the ZIF-8/Ionic Liquid Interfaces.
Here, we perform a series of classical molecular dynamics simulations for two different [HEMIM][DCA] and [BMIM][BF4] ionic liquids (ILs) on the ZIF-8 surface to explore the interfacial properties of metal-organic framework (MOFs)/IL composite materials at the molecular level. Our simulation results reveal that the interfacial structures of anions and cations on the ZIF-8 surface are dominated by the surface roughness due to the steric hindrance, which is extremely different from the driving mechanism based on solid-ion interactions of ILs on flat solid surfaces. At the ZIF-8/IL interfaces, the open sodalite (SOD) cages of the ZIF-8 surface can block most of the large-size cations outside and significantly boost the segregation behavior of anions and cations. In comparison with the [BMIM][BF4] IL, the [HEMIM][DCA] IL has much more anions entering into the open SOD cages owing to the combination of stronger ZIF-8-[DCA]- interactions and more ordered arrangement of [DCA]- anions on the ZIF-8 surface. Furthermore, more and stronger ZIF-8-[BF4]- hydrogen bonds (HBs) are found to exist on the cage edges than the ZIF-8-[DCA]- HBs, further preventing [BF4]- anions from entering into SOD cages. By more detailed analyses, we find that the hydrophobic interaction has an important influence on the interfacial structures of the side chains of [HEMIM]+ and [BMIM]+ cations, while the π-π stacking interaction plays a key role in determining the interfacial structures of the imidazolium rings of both cations. Our simulation results in this work provide a molecular-level understanding of the underlying driving mechanism on segregation behavior at the ZIF-8/IL interfaces.


Majorana fermion induced resonant Andreev reflection.
We describe experimental signatures of Majorana fermion edge states, which form at the interface between a superconductor and the surface of a topological insulator. If a lead couples to the Majorana fermions through electron tunneling, the Majorana fermions induce resonant Andreev reflections from the lead to the grounded superconductor. The linear tunneling conductance is 0 (2e(2)/h) if there is an even (odd) number of vortices in the superconductor. Similar resonance occurs for tunneling into the zero mode in the vortex core. We also study the current and noise of a two-lead device.


Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity.
Here, we disrupted the p70 S6 kinase (p70(s6k)) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70(s6k-/-) cells proliferated at a slower rate than parental cells, suggesting that p70(s6k) has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70(s6k-/-) cells, indicating that other events inhibited by the drug, independent of p70(s6k), also are important for both cell proliferation and the action of rapamycin. In p70(s6k-/-) cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70(s6k-/-) cells, indicating that these events proceed independently of p70(s6k) activity. This study localizes the function of p70(s6k) to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.


Weighted multiplicity adjustments for animal carcinogenicity tests.
Sparse data is a difficulty in the analysis of animal carcinogenicity data: it is difficult to detect effects when the background tumor rates are low. The widely used "Haseman rule" and its variants provide more power to tests with low background rates, while maintaining a degree of control over the global false positive rate. In this article we explore the use of these rules, finding global error rates that are unacceptably high for many animal carcinogenicity studies. We provide alternative weighting methods that correct the deficiencies of the Haseman rule, and apply them to carcinogenicity data from a pharmaceutical company.


Exploring the Pathophysiologic Cascade Leading to Osteoclastogenic Activation in Gaucher Disease Monocytes Generated via CRISPR/Cas9 Technology.
Gaucher disease (GD) is caused by biallelic pathogenic variants in the acid β-glucosidase gene (GBA1), leading to a deficiency in the β-glucocerebrosidase (GCase) enzyme activity resulting in the intracellular accumulation of sphingolipids. Skeletal alterations are one of the most disabling features in GD patients. Although both defective bone formation and increased bone resorption due to osteoblast and osteoclast dysfunction contribute to GD bone pathology, the molecular bases are not fully understood, and bone disease is not completely resolved with currently available specific therapies. For this reason, using editing technology, our group has developed a reliable, isogenic, and easy-to-handle cellular model of GD monocytes (GBAKO-THP1) to facilitate GD pathophysiology studies and high-throughput drug screenings. In this work, we further characterized the model showing an increase in proinflammatory cytokines (Interleukin-1β and Tumor Necrosis Factor-α) release and activation of osteoclastogenesis. Furthermore, our data suggest that GD monocytes would display an increased osteoclastogenic potential, independent of their interaction with the GD microenvironment or other GD cells. Both proinflammatory cytokine production and osteoclastogenesis were restored at least, in part, by treating cells with the recombinant human GCase, a substrate synthase inhibitor, a pharmacological chaperone, and an anti-inflammatory compound. Besides confirming that this model would be suitable to perform high-throughput screening of therapeutic molecules that act via different mechanisms and on different phenotypic features, our data provided insights into the pathogenic cascade, leading to osteoclastogenesis exacerbation and its contribution to bone pathology in GD.


Minimum free energy path of ligand-induced transition in adenylate kinase.
Large-scale conformational changes in proteins involve barrier-crossing transitions on the complex free energy surfaces of high-dimensional space. Such rare events cannot be efficiently captured by conventional molecular dynamics simulations. Here we show that, by combining the on-the-fly string method and the multi-state Bennett acceptance ratio (MBAR) method, the free energy profile of a conformational transition pathway in Escherichia coli adenylate kinase can be characterized in a high-dimensional space. The minimum free energy paths of the conformational transitions in adenylate kinase were explored by the on-the-fly string method in 20-dimensional space spanned by the 20 largest-amplitude principal modes, and the free energy and various kinds of average physical quantities along the pathways were successfully evaluated by the MBAR method. The influence of ligand binding on the pathways was characterized in terms of rigid-body motions of the lid-shaped ATP-binding domain (LID) and the AMP-binding (AMPbd) domains. It was found that the LID domain was able to partially close without the ligand, while the closure of the AMPbd domain required the ligand binding. The transition state ensemble of the ligand bound form was identified as those structures characterized by highly specific binding of the ligand to the AMPbd domain, and was validated by unrestrained MD simulations. It was also found that complete closure of the LID domain required the dehydration of solvents around the P-loop. These findings suggest that the interplay of the two different types of domain motion is an essential feature in the conformational transition of the enzyme.


Exploring the functional impact of mutational drift in LRRK2 gene and identification of specific inhibitors for the treatment of Parkinson disease.
Parkinson's disease (PD) is a disorder of the central nervous system that is caused due to the death of the dopaminergic neurons in the region of the brain called substantia nigra. Mutations in LRRK2 genes are associated with disease condition and it's been reported as crucial factor for drug resistance. Identification of deleterious mutations and studying the structural and functional impact of such mutations may lead to the identification of potential selective inhibitors. In this study, we analyzed 52 PD associated mutations, among that 20 were identified as highly deleterious. The deleterious mutations G2019S and I2020T in the kinase domain were playing a key role in causing resistance to drug levedopa. Molecular docking analyses have been performed to understand the binding affinity of levodapa with LRRK2 in wild and mutant condition. Molecular docking results show that levedopa binds differentially and obtained less number of hydrogen bonds in compared with wild type LRRK2. In addition, molecular dynamics simulations were performed to study the efficacy of docked complexes and it was observed that the efficacy of the mutant complexes (G2019S-Levodopa and I2020T-Levodopa) affected in the presence of mutation. Finally, through virtual screening approach specific inhibitors SCHEMBL6473053 and SCHEMBL1278779 have been identified that could potentially inhibit LLRK2 mutants G2019S and I2020T respectively. Over all this computational investigation correlates the impact of genotypic modulation in structure and function of drug target which enhanced in the identification of precision medicine to treat PD.


Machine learning to predict curative multidisciplinary team treatment decisions in oesophageal cancer.
Rising workflow pressures within the oesophageal cancer (OC) multidisciplinary team (MDT) can lead to variability in decision-making, and health inequality. Machine learning (ML) offers a potential automated data-driven approach to address inconsistency and standardize care. The aim of this experimental pilot study was to develop ML models able to predict curative OC MDT treatment decisions and determine the relative importance of underlying decision-critical variables. Retrospective complete-case analysis of oesophagectomy patients ± neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) between 2010 and 2020. Established ML algorithms (Multinomial Logistic regression (MLR), Random Forests (RF), Extreme Gradient Boosting (XGB)) and Decision Tree (DT) were used to train models predicting OC MDT treatment decisions: surgery (S), NACT + S or NACRT + S. Performance metrics included Area Under the Curve (AUC), Accuracy, Kappa, LogLoss, F1 and Precision -Recall AUC. Variable importance was calculated for each model. We identified 399 cases with a male-to-female ratio of 3.6:1 and median age of 66.1yrs (range 32-83). MLR outperformed RF, XGB and DT across performance metrics (mean AUC of 0.793 [±0.045] vs 0.757 [±0.068], 0.740 [±0.042], and 0.709 [±0.021] respectively). Variable importance analysis identified age as a major factor in the decision to offer surgery alone or NACT + S across models (p < 0.05). ML techniques can use limited feature-sets to predict curative UGI MDT treatment decisions. Explainable Artificial Intelligence methods provide insight into decision-critical variables, highlighting underlying subconscious biases in cancer care decision-making. Such models may allow prioritization of caseload, improve efficiency, and offer data-driven decision-assistance to MDTs in the future.


The inhibition of growth and angiogenesis in heterotransplanted esophageal carcinoma via intratumoral injection of arsenic trioxide.
To investigate the antitumor action of arsenic trioxide (As2O3) by intratumoral injection into solid tumors, tumor growth inhibition (TGI) and angiogenesis of heterotransplanted esophageal carcinoma in mice was carried out. The cultured human esophageal carcinoma cells were inoculated into both laterals of the abdominal wall of severe combined immunodeficient (SCID) mice. When both lateral tumors had grown to about 10x8x5 mm(3), the right tumors were treated with an intratumoral injection of As2O3 in dosage of 1, 5 and 10 microg per day, respectively, for 10 days sequentially. Left tumors were treated with PBS (phosphate buffer solution) as control. The weight of transplanted tumor masses were measured and counted for TGI. The tissue of tumor, liver, kidney, heart, lung and brain was examined histopathologically and tumor tissues were examined by light- or electron-microscope. Ki-67 and CD34 were assessed by immunohistochemistry and positive nuclei of Ki-67 and microvessel density (MVD) labeled by CD34 were measured. The results revealed that on the 20th day after the first injection, As2O3-treated tumors were suppressed markedly as compared with the contrarily situated tumor, accompanied by a marked apoptosis and necrosis in tumor cells. The tissue of liver, kidney, heart, lung and brain was unaffected by As2O3. MVD in tumor tissue was decreased in the right side tumor with the significant difference in the 5 micro g and 10 micro g group (p<0.01). TGI was 5.80 (p>0.05), 58.66 (p<0.01) and 73.97% (p<0.01) in the 1, 5 and 10 micro g groups respectively, but 2.21% (p>0.05) in the control group. Conclusively, a repeated administration of As2O3 (5 and 10 microg x 10) induced an increase of tumor growth inhibition and decrease of angiogenesis in the solid tumor in tumor progressive periods. These results suggest that intra-tumoral injection of As2O3 may be investigated as a modality to treat some solid tumors.


Successful desensitization to fixed drug eruption: the presence of CD25+CD4+ T cells in the epidermis of fixed drug eruption lesions may be involved in the induction of desensitization.
Fixed drug eruption (FDE) is a distinct type of drug-induced eruption, in which intraepidermal CD8+ T cells in the lesional skin are the final effector cells in the epidermal injury of FDE. Desensitization is a unique approach for the management of drug eruption, which has been reported to be effective in treating FDE. However, the mechanisms underlying desensitization to FDE are quite unknown. We reported a case of successful desensitization to allopurinol-induced FDE. To clarify the mechanisms underlying desensitization to FDE, we examined the phenotype of T cells in the epidermis of FDE lesions before and after desensitization using flow cytometry. The overwhelming majority of intraepidermal T cells in the FDE lesion before desensitization consisted of CD8+ T cells, whereas a significant number of CD25+CD4+ T cells were present in the epidermis of FDE lesions after desensitization. The presence of CD25+CD4+ T cells in the epidermis of FDE lesions may be involved in the induction of desensitization to FDE.


The nurse practitioner role in the NICU as perceived by parents.
The aim of this study was to understand and describe the nature of nurse practitioner care delivery in the newborn intensive care unit (NICU) as perceived by parents of critically ill neonates. This qualitative study used a phenomenologic approach to answer the research question: "What is the lived experience of parents whose babies were cared for by a nurse practitioner in the NICU? Consistent with phenomenologic methods, eight parents were asked: "What was it like for you to have a nurse practitioner care for you and your baby?" Parents whose babies had within the last 8 months spent at least 2 weeks in the NICU and had been discharged to home were asked to participate by letter. Consent of interested parents was obtained and interviews were conducted in the parents' homes. All interviews were audiotaped and transcribed. In addition to being able to effectively manage the medical care of the complex neonate, nurse practitioners were consistently perceived as: "being positive and reassuring," "being present," "caring," "translating information," and "making parents feel at ease." Nurse practitioners working in the NICU can feel validated by the fact that they are clearly appreciated by parents. Inclusion of NPs in the NICU care team enhances the care provided to infants and their families.


Oilfield water treatment by electrocoagulation-reverse osmosis for agricultural use: effects on germination and early growth characteristics of sunflower.
This study aims to evaluate the effects of oilfield water (OW), treated by a hybrid process of electrocoagulation and reverse osmosis (EC-RO), on seed germination and early growth characteristics of sunflower (Heliantus annus L.). In the EC step, tests were conducted with 28.6 A m-2 current density and 4 min. reaction time. In the RO step, the system was operated with 1 L min-1 constant flow and 2 MPa, 2.5 MPa and 3 MPa feed pressures. In all feed pressures, RO polymeric membranes achieved very high removals of chemical oxygen demand (up to 89%) and oils and greases (100%) from EC-treated effluent. In best feed pressure (2.5 MPa), turbidity, total dissolved salts, electrical conductivity, salinity, toxic ions and sodium adsorption ratio values attained internationally recognized standards for irrigation water. Using EC-RO (feed pressure:2.5 MPa) treated OW, germinated sunflower seeds percentage (86 ± 6%), speed of germination (30 ± 2) and biomass production (49 ± 5 mg) were statistically similar to control (distilled water) results. Vigor index average values obtained using OW treated by EC-RO (3871)were higher than that obtained by OW water treated by EC (3300). The results of this study indicate that EC-RO seems to be a promising alternative for treatment of OW aiming sunflower crops irrigation, since the use of this treated effluent did not affect adversely seed germination and seedling development, and improved seedling vigor. Furthermore, OW treatment by EC-RO reduces sodium levels into acceptable standards values avoiding soil degradation.


Massage therapy after cardiac surgery.
Cardiac surgery presents a life-saving and life-enhancing opportunity to hundreds of thousands of patients each year in the United States. However, many patients face significant challenges during the postoperative period, including pain, anxiety, and tension. Mounting evidence demonstrates that such challenges can impair immune function and slow wound healing, in addition to causing suffering for the patient. Finding new approaches to mitigate these challenges is necessary if patients are to experience the full benefits of surgery. Massage therapy is a therapy that has significant evidence to support its role in meeting these needs. This paper looks at the data surrounding the use of massage therapy in cardiac surgery patients, with a special focus on the experience at Mayo Clinic.


Connective tissue lipoatrophic panniculitis.
A 23 years old girl with a past history of sero-positive oligoarticular juvenile idiopathic arthritis developed nodules and depressed scars over face and limbs. Biopsy from the lesion revealed mixed panniculitis. She responded to steroids and hydroxychloroquine but has residual lipoatrophic scars needing reconstructive surgery.


Nearly resonant multidimensional systems under a transient perturbative interaction.
We analyze the response of a classical system with N>or=2 internal degrees of freedom satisfying R<or=(N-1) approximated resonance conditions to an external perturbative transient interaction. Under certain assumptions on the system internal frequencies and on the coupling interaction, we show the precise N-R adiabatic invariants and obtain an estimate of the span of the domain defined by the intersecting resonances. The results are illustrated considering a system of three anharmonic oscillators transiently coupled by an explicitly time-dependent interaction, and applied to the low energy vibro-rotationally inelastic collisions between two diatomic molecules.


Membrane potential and endocytic activity control disintegration of cell-cell adhesion and cell fusion in vinculin-injected MDBK cells.
Cell fusion occurs during fertilization and in the formation of organs such as muscles, placenta, and bones. We have developed an experimental model for epithelial cell fusion which permits analysis of the processes during junction disintegration and formation of polykaryons (Palovuori and Eskelinen [2000] Eur. J. Cell. Biol. 79: 961-974). In the present work, we analyzed the process in detail. Cell fusion was achieved by microinjecting into the cytoplasm of kidney epithelial Madin-Darby bovine kidney (MDBK) cells TAMRA-tagged vinculin, which incorporated into lateral membranes, focal adhesions and nucleus, and, prior fusion, induced internalization of actin, cadherin and plakoglobin to small clusters in cytoplasm. Injected vinculin was still visible at lateral membranes after removal of junctional proteins indicating that it was tightly associated and perturbed the cell-cell contact sites resulting in membrane fragmentation. Injection of active Rac together with vinculin induced accumulation of cadherin to the membranes, but did not affect vinculin-membrane association. However, it hampered cell fusion probably by supporting adherens junctions. In order to stop endocytosis, we lowered intracellular pH of vinculin-injected cells to 5.5 with the aid of nigericin in KCl buffer. In acidified cells, injected vinculin delineated lateral membranes as thick layers, cadherin remained in situ, and cell fusion was completely inhibited. Since this treatment also leads to cell depolarization, we checked the vinculin incorporation in a KCl solution containing nigericin at neutral pH. In these circumstances, both endogenous and injected vinculin delineated lateral membranes as very thin discontinuous layers, but still fusion was hampered most likely due to perturbation in the initial vinculin-membrane association. We suggest that vinculin might function as a sensor of the environment triggering cell fusion during development in circumstances where membrane potential and local and transient pH gradients play a role.


Somogyi effect in patient with hypopituitarism.
A patient with diabetes mellitus and hypopituitarism developed the Somogyi effect that was characterized by insulin-induced hypoglycemia and rebound insulin-resistant hypoglycemia. This compensatory insulin-resistant hyperglycemia has generally been ascribed to the release of anterior hypophyseal hormones; however, our findings suggest that factors other than anterior hypophyseal hormones are involved.


Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: diagnosis using minilavage samples.
Over a 30-month period, we evaluated 74 patients with acquired immunodeficiency syndrome (AIDS) for suspected opportunistic pulmonary infection. All had abnormal findings on chest roentgenogram. Sixty patients (81%) were found to have Pneumocystis carinii pneumonia (PCP). We assessed the yield of various diagnostic methods, and found that bronchoalveolar lavage samples obtained by the instillation of 20 to 50 ml of normal saline (minilavage) contained detectable organisms in 51 of 53 patients (sensitivity of 96%) when the samples were embedded in plastic, cut in thick sections (1 micron), stained with toluidine blue O, and evaluated by light microscopy. In comparison, the diagnostic yield was 94% for lung biopsy, 85% for touch preparation of lung tissue, 32% for bronchial washing, and 14% for brush biopsy. It is significant that minilavage samples embedded in plastic were positive in all seven patients who did not have transbronchial lung biopsy because they were at high risk for complications. We conclude that the process of embedding minilavage samples in plastic and evaluating thick sections stained with toluidine blue O is a sensitive method of diagnosing PCP in patients with AIDS.


The association of Red cell distribution width and in-hospital mortality in older adults admitted to the emergency department.
The objective of the study was to test the hypothesis that elevated red cell distribution width (RDW) at admission increases the risk of mortality in older patients admitted to the emergency department (ED). We performed a retrospective analysis of patients admitted to the ED between May 2013 and October 2013. We included patients who were older than 65 years who visited the ED with any medical problems. Baseline RDW values were measured at the time of admission to the ED. The primary outcome was all-cause in-hospital mortality. Multivariate logistic analysis was performed. A total of 1,990 patients were finally included in this study. The mean age was 75 years (SD 7), and 936 (47 %) subjects were male. The in-hospital mortality rate was 3.76 % (74 patients). RDW values higher in non-survivors than in survivors (15.9 ± 2.5 vs. 13.8 ± 1.7, p < 0.001). Multivariate logistic analysis showed that RDW was associated with all-cause in-hospital mortality after adjusting for other confounding factors. RDW value at admission is an independent predictor of all-cause in-hospital mortality among patients older than 65 years. After adjustment for multiple confounders, the all-cause in-hospital mortality rate increased by 21.8% for each 1% increase in RDW. These results show that RDW at admission is associated with in-hospital mortality among patients older than 65. Thus, RDW at admission may represent a surrogate marker of disease severity. We caution against using these findings to aid clinical decision-making process until they are externally validated.


CRISPR-Mediated Integration of Large Gene Cassettes Using AAV Donor Vectors.
The CRISPR/Cas9 system has recently been shown to facilitate high levels of precise genome editing using adeno-associated viral (AAV) vectors to serve as donor template DNA during homologous recombination (HR). However, the maximum AAV packaging capacity of ∼4.5 kb limits the donor size. Here, we overcome this constraint by showing that two co-transduced AAV vectors can serve as donors during consecutive HR events for the integration of large transgenes. Importantly, the method involves a single-step procedure applicable to primary cells with relevance to therapeutic genome editing. We use the methodology in primary human T cells and CD34+ hematopoietic stem and progenitor cells to site-specifically integrate an expression cassette that, as a single donor vector, would otherwise amount to a total of 6.5 kb. This approach now provides an efficient way to integrate large transgene cassettes into the genomes of primary human cells using HR-mediated genome editing with AAV vectors.


The prevalence of antibodies of Brucella abortus, Dermatophilus congolensis and bovine leukaemia virus in Nigerian slaughter cattle.
In a pilot survey to compare the relative prevalence of three diseases in apparently healthy White Fulani Zebu (WFZ) cattle slaughtered in Nigeria, sera from 80 randomly selected animals with no significant gross lesions on ante mortem and post mortem inspection were examined for antibodies to Brucella abortus, Dermatophilus congolensis and bovine leukaemia virus. Of the samples screened, 5.0, 8.8 and 2.0% showed serological evidence for brucellosis, cutaneous streptothricosis and bovine leukosis respectively.


How children and adults produce and perceive uncertainty in audiovisual speech.
We describe two experiments on signaling and detecting uncertainty in audiovisual speech by adults and children. In the first study, utterances from adult speakers and child speakers (aged 7-8) were elicited and annotated with a set of six audiovisual features. It was found that when adult speakers were uncertain they were more likely to produce fillers, delays, high intonation, eyebrow movements, and "funny faces." The basic picture for the child speakers was somewhat similar, in that the presence of certain audiovisual cues correlated with uncertainty, but the differences were relatively small and less often significant. In the second study both adult and child judges watched responses from adult and child speakers selected from the first study to find out whether they were able to correctly estimate a speakers' level of uncertainty. It was found that both child and adult judges gave more accurate scores for answers from adult speakers than from child speakers and that child judges overall provided less accurate scores than adult judges.


New technology for deep light distribution in tissue for phototherapy.
Photodynamic therapy is one of several techniques developed for phototherapy for solid cancers and hematologic malignancies. Photodynamic therapy is a treatment that utilizes a molecular energy exchange between visible light and a photosensitive drug, which results in the production of 1O2, a highly reactive cytocidal oxygen species. The effect is limited to the region where light and drug are combined so that malignant tissue is destroyed and the usual side effects associated with standard cancer therapies are avoided. The light component of photodynamic therapy is customarily generated via dye-pumped or diode lasers. The cost and the complexity of lasers have seriously limited the clinical use of photodynamic therapy for malignancies. A new device technology, based on light-emitting diodes, has been developed (Light Sciences Corporation, Issaquah, WA) that allows light production inside the target tissue. This new technology will expand the current range of indications that are treatable with photodynamic therapy to include moderate- and large-volume refractorytumors. Conventional photodynamic therapy utilizes the delivery of intense light for seconds or minutes. The new approach differs from conventional photodynamic therapy in that it combines a novel interstitial light delivery system with prolonged photoactivation of photosensitive drugs. Prolonging photoactivation time in order to deliver a higher light dose results in an amplification effect, whereby the repeated activation of each photosensitive drug molecule leads to the generation of many thousands of 1O2 molecules. The production of overwhelming numbers of these powerful oxidants in individual cells and the vascular supply of tumors leads to irreversible damage and death of the targeted lesions. Results of preclinical studies have indicated a significant correlation between increased duration of photoactivation and increased volume and depth of photodynamic therapy-induced necrosis. The new developments will enable photodynamic therapy to be used effectively against refractory bulky disease as frontline therapy or in combination with chemotherapy, radiation therapy, or biologics. Perhaps most promising, many patients with advanced refractory disease may now be relieved of symptoms or may return to the treatable population.


Effect of cam resection depth on clinical outcomes after primary hip arthroscopy.
The amount of resection or the starting point of the resection on the femoral head for cam lesions in femoroacetabular impingement (FAI) is controversial. The purpose of this study was to study the effect of postoperative resection depth, and resection arc ratio of cam lesion on the frequency of achieving substantial clinical benefit (SCB), patient acceptable state (PASS) in modified Harris Hip Score (mHHS) and Hip Outcome Score Activity of Daily Living (HOSADL), 2 years postoperatively. All patients who underwent first-time hip arthroscopy for FAI with a 2-year follow-up were included in this study. Patient-reported outcomes included the mHHS, HOSADL, and visual analogue scale for pain (Pain VAS). Radiological parameters such as alpha angletraditional (αT), alpha anglecartilage (αC), resection arc ratio (% alpha anglecartilage-alpha angletraditional/360°), resection depth (''D''mm) and resection depth ratio 'D%' (D/femoral head diameter %) were measured using the 45° Dunn view. We identified 26 patients (27 hips) with 2-year follow-up. There were 10 female and 16 male patients. The mean age of the patients was 33 ± 12 years.Higher frequency of achieving SCB threshold for mHHS was related to labrum repair (73% vs. debridement '27%' p = 0.03), lower preoperative αT (64° vs. 76°, p = 0.04), lower preoperative mHHS (54 vs. 81, p < 0.001) and higher preoperative VAS scores (8 vs. 7, p = 0.02). Higher frequency of reaching PASS threshold for mHHS was associated with lower αC (82°vs. 92° p:0.02), lower RA (8% vs. 11%, p = 0.03), lower D (2.8 mm vs. 4.5 mm p:0.03), lower D% (4.7% vs. 8.4% p = 0.04) and higher postoperative mHHS (97 vs. 82 p < 0.001). A higher frequency of achieving SCB for HOSADL was related to lower D% (5% vs. 10.5%, p = 0.04).Cam resection depth affects the frequency of achieving clinically meaningful scores and resection depth less than 6% of the femoral head diameter seems to be appropriate for optimal results. The starting point of resection on head cartilage needs to be <90° when alpha angle is used for reference.


Dinitrogenase with altered substrate specificity results from the use of homocitrate analogues for in vitro synthesis of the iron-molybdenum cofactor.
The in vitro synthesis of the iron-molybdenum cofactor (FeMo-co) of nitrogenase requires homocitrate (2-hydroxy-1,2,4-butanetricarboxylic acid). Homocitrate is apparently synthesized by the nifV gene product. In the absence of homocitrate, no FeMo-co is formed in vitro, as determined from coupled C2H2 reduction assays and the lack of 99Mo label incorporation into apodinitrogenase. Several organic acids were tested for their ability to replace homocitrate in the FeMo-co synthesis system. With appropriate homocitrate analogues, aberrant forms of FeMo-co are synthesized that exhibit altered substrate specificity and inhibitor susceptibility. Homoisocitrate (1-hydroxy-1,2,4-butanetricarboxylic acid) and 2-oxoglutarate facilitated the incorporation of 99Mo into apodinitrogenase in the FeMo-co synthesis system, yielding a dinitrogenase that effectively catalyzed the reduction of protons but not C2H2 or N2. Citrate also promoted the incorporation of 99Mo into apodinitrogenase, and the resulting holodinitrogenase reduced protons and C2H2 effectively but not N2. In addition, proton reduction from this enzyme was inhibited by CO. The properties of the homodinitrogenase formed in the presence of citrate were reminiscent of those of the Klebsiella pneumoniae NifV- dinitrogenase. We also observed low rates of HD formation from NifV- dinitrogenase compared to those from the wild-type enzyme. No HD formation was observed with the dinitrogenase activated in vitro in the presence of citrate. We propose that in vivo NifV- mutants utilize citrate for FeMo-co synthesis.


Enteric Infection at Flare of Inflammatory Bowel Disease Impacts Outcomes at 2 Years.
Outcomes of inflammatory bowel disease (IBD) following flare complicated by enteric infection (EI) are limited by follow-up duration and insufficient assessment of the role of non-Clostridioides difficile pathogens. We compared 2-year IBD outcomes following flare with and without EI. We performed a retrospective cohort study of adults evaluated with stool PCR testing for IBD flare. Subjects were stratified by presence of EI at flare and were matched for age, sex, and date to those without EI. The primary outcome was a composite of steroid-dependent IBD, colectomy, and/or IBD therapy class change/dose escalation at 2 years. Additional analyses were performed by dividing the EI group into C. difficile infection (CDI) and non-CDI EI, and further subdividing non-CDI EI into E. coli subtypes and other non-CDI EI. We identified 137 matched subjects, of whom 62 (45%) had EI (40 [29%] CDI; 17 [12%] E. coli). Enteric infection at flare was independently associated with the primary outcome (adjusted odds ratio, 4.14; 95% confidence interval [CI], 1.62-11.5). After dividing EI into CDI and non-CDI EI, only CDI at flare was independently associated with the primary outcome (adjusted odds ratio, 4.04; 95% CI, 1.46-12.6). After separating E. coli subtypes from non-CDI EI, E. coli infection and CDI at flare were both independently associated with the primary outcome; other EI was not. Enteric infection at flare-specifically with CDI-is associated with worse IBD outcomes at 2 years. The relationship between E. coli subtypes at flare and subsequent IBD outcomes requires further investigation.


Hyoscine butylbromide: a useful premedicant.
The actions of intravenous hyoscine butylbromide (Buscopan) and atropine sulphate on reduction of upper respiratory tract secretions during anaesthesia are compared. Hyoscine butylbromide has a significantly more powerful action.


Consolidation trend design based on Young's modulus of clarithromycin single crystals.
The key aim of this study was to determine single mechanical properties of clarithromycin polymorphic forms in order to select some of them as more suitable for the tableting process. For this purpose, AFM single-point nanoindentation was used. The Young's moduli of clarithromycin polymorphs were substantially different, which was consistent with the structural variations in their packing motifs. The presence of the adjacent layers, which can easily slide over each other due to the low energy barrier (the lowest Young's modulus was 0.25 GPa) resulted in better bulk compressibility (the highest Heckel coefficient) of clarithromycin Form I. We also addressed the importance of tip geometry screening because the stress during the force mode often results in tip apex fracture. Even the initial manufacture of the diamond-coated tips can result in defects such as double-apex tips.


Relaxation Behavior by Time-Salt and Time-Temperature Superpositions of Polyelectrolyte Complexes from Coacervate to Precipitate.
Complexation between anionic and cationic polyelectrolytes results in solid-like precipitates or liquid-like coacervate depending on the added salt in the aqueous medium. However, the boundary between these polymer-rich phases is quite broad and the associated changes in the polymer relaxation in the complexes across the transition regime are poorly understood. In this work, the relaxation dynamics of complexes across this transition is probed over a wide timescale by measuring viscoelastic spectra and zero-shear viscosities at varying temperatures and salt concentrations for two different salt types. We find that the complexes exhibit time-temperature superposition (TTS) at all salt concentrations, while the range of overlapped-frequencies for time-temperature-salt superposition (TTSS) strongly depends on the salt concentration (Cs) and gradually shifts to higher frequencies as Cs is decreased. The sticky-Rouse model describes the relaxation behavior at all Cs. However, collective relaxation of polyelectrolyte complexes gradually approaches a rubbery regime and eventually exhibits a gel-like response as Cs is decreased and limits the validity of TTSS.


[Clinical features and genome-wide copy number variation analysis in 60 children with early-onset epileptic encephalopathies of unknown cause].
To study the clinical features of early-onset epileptic encephalopathies (EEEs) of unknown cause, and to identify pathogenic microdeletion/microduplication of EEEs by genome-wide analysis of copy number variations (CNVs). The clinical data of 60 children diagnosed with unexplained EEEs between July 2012 and April 2013 were obtained and analyzed. Specimens were collected from the selected children and their parents. Single nucleotide polymorphism array was used to detect genome-wide CNVs, and fluorescence in situ hybridization was performed to verify the results and analyze the source of the parents, further to identify suspected pathogenic CNVs of EEEs. Among the 60 children with unexplained EEEs, 34 were diagnosed with West syndrome, 3 with Ohtahara syndrome, 3 with Dravet syndrome, and 20 with unclassified EEEs. In total, 77% of the patients were associated with moderate to severe mental retardation. Head imaging test implied that 35% of the patients had brain dysplasia or astrophy. Among 54 patients, 17% showed microcephalus. After treatment, 28 patients had clinical seizures under control, 16 out of control, 5 dead, and 1 lost to follow-up. Genome-wide analysis of CNVs showed that 7 pathogenic or suspected pathogenic CNVs were present in 5 patients. EEEs of unknown cause are associated with high phenotypic heterogeneity and poor prognosis. Genome-wide CNVs analysis can demonstrate pathogenic or suspected pathogenic CNVs. This research expands the gene bank of EEEs and improves the understanding about possible etiology of unexplained EEEs. The results provide a reference for genetic counseling regarding reproduction in the patient's family.


The biophysics of a critical phenomenon: colonization and sedimentation of the photosynthetic bacteria Rubrivivax gelatinosus.
In response to environmental changes, the photosynthetic bacterium Rubrivivax gelatinosus (Rvx.) can switch from a planktonic lifestyle to a phototrophic biofilm. Like in critical phenomena, the colonization and sedimentation of the cells is abrupt and hard to predict causally, and the underlying biophysics of the mechanisms involved is not known. Herein, we report basic experimental observations and quantitative explanations as keys to understanding microbial turnover of aggregates. (1) The moment of sedimentation can be controlled by the height of the tube of cultivation, by the concentrations of externally added Ficoll (a highly branched polymer) and/or of internally produced polysaccharides (constituents of the biofilm). (2) The observed translational diffusion coefficient of the planktonic bacteria is the sum of diffusion coefficients coming from random Brownian and twitching movements of the bacteria and amounts to 14 (μm)2/s. (3) This value drops hyperbolically with the association number of the cell aggregates and with the concentration of the exopolysaccharides in the biofilm. In the experiments described herein, their effects could be separated. (4) The critical conditions of colonization and sinking of the cells will be achieved if the height of the tube meets the scale height that is proportional to the ratio of the diffusion coefficient and the net mass of the bacterium. The decisive role of the web-like structure of a biofilm, the organization of bacteria from loose cooperativity to solid aggregation, and the possible importance of similar controls in other phototrophic microorganisms are discussed.