Effectiveness of Music in Enhancing Nutrition Education Outcomes Among Adolescents.
To determine the effectiveness of healthy eating songs (HES) in improving adolescents' healthy eating knowledge, attitude, and practice. Pretest-posttest quasi-experimental nonequivalent group design. Students from 2 of the selected schools (n = 37 and n = 35) received nutrition education using conventional classroom instruction and HES, whereas the other 2 (n = 30 and n = 31) received theirs using conventional classroom instruction only. Ibadan, Nigeria. A total of 133 students selected from 4 junior secondary schools participated in the study. Changes in healthy eating knowledge, attitude, and practice at the school level. Independent t tests were used for analyzing summary data, whereas the linear mixed model was used to analyze the fixed effects of predictor variables at P < 0.05. Nutrition education had a significant effect on knowledge (F = 65.7, P < 0.001), attitude (F = 85.2, P < 0.001), and practice (F = 131.5, P < 0.001). Improvement in knowledge, attitude, and practice was observed in both groups. However, the intervention group performed better than the comparison group in knowledge (95% confidence interval [CI], -0.1 to 2.8), attitude (95% CI, 1.7-9.7), and practice (95% CI, 2.8-5.8). Geographical location had a significant effect on knowledge (F = 7.1, P = 0.005). Interaction effect of treatment and geographical location was significant on knowledge and attitude of students. The use of HES may be an effective way of improving adolescents' healthy eating knowledge, attitude, and practice. However, testing culturally appropriate HES in more diverse audiences is warranted.


Evaluation of bone marrow mesenchymal stem cell standard cryopreservation procedure efficiency.
Mesenchymal stem cells are obtained from a variety of sources, particularly bone marrow. These cells have great potential for clinical research due to their potential to regenerate tissue. As is well known, the cryopreservation process can store any cell type, particularly blood cells, for an indeterminate time. The aim of this study was to analyze the efficiency of standard cryopreservation procedures for adult mesenchymal stem cells from bone marrow. Mononuclear stem cells isolated from 10 Wistar male rats were cultivated for 4 weeks to obtain mesenchymal stem cells. The parameters considered in this study were trypan blue exclusion test and annexin V conjugated with 7-amino-actinomycin for flow cytometry before cryopreservation in liquid nitrogen vapor phase for 1 month and after thawing. The viabilities determined by the trypan blue exclusion test were 94.76% and 90.58%, and the flow cytometry assay (annexin V conjugated with 7-amino-actinomycin) were 85.52% and 66.25%, before cryopreservation and after thawing, respectively. Standard procedures for cryopreservation were not efficient for those cells. The flow cytometry assay was more sensitive than the trypan blue exclusion test to demonstrate nonviability.


Synthetic studies towards a new scaffold, spirobicycloimidazoline.
A new scaffold consisting of a carbocycle and a substituted imidazoline in an orthogonal arrangement was synthesized as a potential specific inhibitor of glycosidases. The spirobicycloimidazoline, (5R,6R,7R,8R)-8-(hydroxymethyl)-2-phenyl-1,3-diazaspiro[4.4]non-1-ene-6,7-diol, was synthesized from methyl 2-O-p-methoxybenzyl-3,4-di-O-benzyl-alpha/beta-D-gluco-6-enopyranoside via (1R,2S,3S,4R,5S)-3,4-bis(benzyloxy)-2-(4-methoxybenzyloxy)-5-vinyl-cyclopentanol. The ring contraction of the 6-enopyranoside in the presence of zirconocene equivalent ('Cp(2)Zr') reagent gave exclusively the corresponding cyclopentanol without cleavage of the PMB protecting group. In the course of the study, a new alpha-mannosidase inhibitor, (1R,2R,3R,5R)-5-amino-3-hydroxymethyl-cyclopentane-1,2-diol, was also discovered.


Relationships Among Daytime Napping and Fatigue, Sleep Quality, and Quality of Life in Cancer Patients.
The relationships among napping and sleep quality, fatigue, and quality of life (QOL) in cancer patients are not clearly understood. The aim of the study was to determine whether daytime napping is associated with nighttime sleep, fatigue, and QOL in cancer patients. In total, 187 cancer patients were recruited. Daytime napping, nighttime self-reported sleep, fatigue, and QOL were assessed using a questionnaire. Objective sleep parameters were collected using a wrist actigraph. According to waking-after-sleep-onset measurements, patients who napped during the day experienced poorer nighttime sleep than did patients who did not (t = -2.44, P = .02). Daytime napping duration was significantly negatively correlated with QOL. Patients who napped after 4 PM had poorer sleep quality (t = -1.93, P = .05) and a poorer Short-Form Health Survey mental component score (t = 2.06, P = .04) than did patients who did not. Fatigue, daytime napping duration, and sleep quality were significant predictors of the mental component score and physical component score, accounting for 45.7% and 39.3% of the variance, respectively. Daytime napping duration was negatively associated with QOL. Napping should be avoided after 4 PM. Daytime napping affects the QOL of cancer patients. Future research can determine the role of napping in the sleep hygiene of cancer patients.


The frequency of mucosal-associated invariant T cells is selectively increased in dermatitis herpetiformis.
Mucosal-associated invariant T (MAIT) cells are a novel subset of innate-like T-cells that are enriched in mucosal tissues. Their presence in human skin has only recently been recognised. We describe the expression of skin-tropic molecules on human skin MAIT cells at steady state and investigate their contribution to various dermatoses with known T-cell involvement. To examine the expression of skin-tropic molecules by MAIT cells at steady state, we performed a flow cytometric analysis of blood and skin samples from healthy donors. To investigate any potential wider contribution of MAIT cells to skin disease, we examined psoriasis, alopecia areata and dermatitis herpetiformis biopsies using immunofluorescent staining to identify the proportion of T-cells expressing MAIT cell surface markers. We found that MAIT cells constituted a small population of T-cells in normal human skin, similar to the percentage found in peripheral blood. Like other skin T-cells, skin MAIT cells expressed high levels of the skin-associated markers, cutaneous lymphocyte antigen and CD103. In psoriasis and alopecia areata the proportion of MAIT cells was similar to that found in normal skin, but in dermatitis herpetiformis it was significantly elevated. The expression of skin-tropic molecules by skin MAIT cells is consistent with their resident status in normal human skin. Our results suggest that MAIT cells may play a role in the pathogenesis of dermatitis herpetiformis.


Isolation and characterization of HIV-2ben obtained from a patient with predominantly neurological defects.
A HIV-2 strain named HIV-2ben was isolated from peripheral blood lymphocytes of a patient who, since 1984, had developed neurological symptoms such as Raynaud's syndrome, followed by paresthesia of extremities and ataxia, and finally paraparesis of the legs and incontinence. This new isolate could be distinguished from HIV-2rod by antibody-binding epitopes, peptide maps of core p24 and p18 polypeptides and restriction endonuclease cleavage pattern.


Bioinformatic analyses of integral membrane transport proteins encoded within the genome of the planctomycetes species, Rhodopirellula baltica.
Rhodopirellula baltica (R. baltica) is a Planctomycete, known to have intracellular membranes. Because of its unusual cell structure and ecological significance, we have conducted comprehensive analyses of its transmembrane transport proteins. The complete proteome of R. baltica was screened against the Transporter Classification Database (TCDB) to identify recognizable integral membrane transport proteins. 342 proteins were identified with a high degree of confidence, and these fell into several different classes. R. baltica encodes in its genome channels (12%), secondary carriers (33%), and primary active transport proteins (41%) in addition to classes represented in smaller numbers. Relative to most non-marine bacteria, R. baltica possesses a larger number of sodium-dependent symporters but fewer proton-dependent symporters, and it has dimethylsulfoxide (DMSO) and trimethyl-amine-oxide (TMAO) reductases, consistent with its Na(+)-rich marine environment. R. baltica also possesses a Na(+)-translocating NADH:quinone dehydrogenase (Na(+)-NDH), a Na(+) efflux decarboxylase, two Na(+)-exporting ABC pumps, two Na(+)-translocating F-type ATPases, two Na(+):H(+) antiporters and two K(+):H(+) antiporters. Flagellar motility probably depends on the sodium electrochemical gradient. Surprisingly, R. baltica also has a complete set of H(+)-translocating electron transport complexes similar to those present in α-proteobacteria and eukaryotic mitochondria. The transport proteins identified proved to be typical of the bacterial domain with little or no indication of the presence of eukaryotic-type transporters. However, novel functionally uncharacterized multispanning membrane proteins were identified, some of which are found only in Rhodopirellula species, but others of which are widely distributed in bacteria. The analyses lead to predictions regarding the physiology, ecology and evolution of R. baltica.


Partial amino acid sequence of erythrocyte carbonic anhydrase from tiger shark.
1. A partial primary structure (197 residues) of carbonic anhydrase from tiger shark (Galeocerdo cuvieri) erythrocytes has been determined. 2. The amino acid sequence of the enzyme is identical to those of human cytoplasmic carbonic anhydrases (CA I-III) by as much as 52-60%. 3. It is shown that tiger shark CA most closely resembles the CA II isoenzyme of amniotes. 4. Isoelectric focusing and inhibition studies on carbonic anhydrase from dogfish (Squalus acanthias) blood and muscle indicate the presence of the same isoenzyme in shark blood and muscle.


The long transcript of lncRNA TMPO-AS1 promotes bone metastases of prostate cancer by regulating the CSNK2A1/DDX3X complex in Wnt/β-catenin signaling.
The second most common male cancer is prostate cancer (PCa), which has a high tendency for bone metastasis. Long non-coding RNAs, including TMPO-AS1, play a crucial role in PCa progression. However, TMPO-AS1's function in PCa bone metastasis (BM) and its underlying molecular mechanisms are unclear. Herein, we found that the long transcript of TMPO-AS1 (TMPO-AS1L) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1L correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1L promoted, whereas downregulated TMPO-AS1L inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1L was demonstrated to act as a scaffold, that strengthened the interaction of casein kinase 2 alpha 1 (CSNK2A1) and DEAD-box helicase 3 X-linked (DDX3X), and activated the Wnt/β-catenin signaling pathway, thus promoting BM of PCa. Moreover, upregulation of TMPO-AS1L in PCa resulted from transcription elongation modulated by general transcription factor IIF subunit 2 (GTF2F2). Collectively, our study provides critical insights into the role of TMPO-AS1L in PCa BM via Wnt/β-catenin signaling, identifying TMPO-AS1L as a candidate marker of PCa bone metastasis prognosis and therapeutic target.


Silicone intubation: an alternative to dacryocystorhinostomy.
Silicone intubation is an alternative to dacryocystorhinostomy in selected patients who have epiphora and obstruction of the nasolacrimal system. Silicone tubing may be passed through the nasolacrimal system and left in place for a prolonged period of time. In many instances, this obviates the need for a dacryocystorhinostomy. If the intubation is not completely successful, a dacryocystorhinostomy can always be carried out at a later date.


Effects of putative neurotransmitters on neuronal activity in monkey auditory cortex.
The effects of the putative neurotransmitters norepinephrine (NE), gamma-aminobutyric acid (BAGA), and acetylcholine (ACh) were tested on auditory cortex neurons which were activated acoustically by species-specific vocalizations in awake squirrel monkeys. Five-barrel glass electrodes were used to record the activity single neurons in the superior temporal gyrus and to apply NE, GABA, or ACh microiontophoretically. Poststimulus time histograms and raster displays of neuronal responses to the vocalizations were computed before, during, and after iontophoresis. Dose-dependent inhibition of spontaneous and vocalization-evoked discharge rates was seen with NE and GABA. Generally, excitation was observed with ACh. A given dose of NE or GABA reduced spontaneous activity by a greater proportion than it reduced activity evoked by the vocalizations. During excitatory responses, segments with lower discharge rates were reduced proportionately more than segments with higher discharge rates. Usually, response 'pattern' was not altered by iontophoresis of any of the substances. However, in some cases the differential inhibition of slow activity produced by NE or GABA did result in a 'patern' change. The demonstration that small amounts of locally applied NE and GABA substantially alter the specific neuronal activation produced by vocalizations provides additional evidence that these agents may function as neurotransmitters in this neocortical area and offers clues about their functional significance.


Role of fatty acids in growth-promoting effect of serum albumin on hamster cells in vitro.
Dialyzed serum albumin had considerable growth-promoting effect on cultivated hamster cells. This effect was virtually lost on removal of the fatty acids, and it was completely restored by recombination of the fatty acid-free albumin with the isolated and purified fatty acids. The role of albumin itself appeared to be largely that of a carrier of fatty acids, protecting the cells against toxic effects of fatty acids in free solution. This conclusion was based on two observations: Fatty acids in the absence of albumin were growth-inhibitory except in extremely dilute solutions, and beta-lactoglobulin, a protein possessing, like albumin, the ability to bind and release fatty acids, could replace albumin in the presence of fatty acids with similar growth-promoting effect. Examination of individual molecular types of fatty acids showed that all unsaturated acids tested were growth-promoting, whereas the saturated acids were growth-inhibiting, with the exception of stearic acid in low concentrations. Although the possibility of a mitotic triggering effect was not excluded, the fatty acids presumably stimulated growth by providing substrate for cellular metabolism, since there was a direct relationship between the degree of growth stimulation and the duration of exposure of cells to the fatty acids.


The impact and mechanism of high-speed rail on energy efficiency: an empirical analysis based on 285 cities of China.
Improving energy efficiency is an important measure of environmental governance. At present, studies on the impact of high-speed rail on energy efficiency need to be further studied. This paper constructs panel data of 285 cities at prefecture-level and above in China from 2003 to 2017, and uses the difference-in-difference (DID) to study the impact of high-speed railway on urban energy efficiency. Based on the theories of "factor flow," "knowledge spillover," and "center-periphery," this paper discusses the influence mechanism and heterogeneity of high-speed railway on energy efficiency. The empirical results show that high-speed railway can significantly improve energy efficiency, and the conclusion is still valid after parallel trend test, propensity score matching and difference-in-difference (PSM-DID) test, and instrumental variable method. The results remained true after a series of robustness tests. Mechanism analysis shows that high-speed railway can improve energy efficiency by promoting industrial structure upgrading, technological innovation, and market integration. Analysis of heterogeneity shows that the promotion effect of high-speed railway on energy efficiency is greater in central and western cities and core cities. This study provides useful enlightenment for optimizing China's high-speed rail construction planning and seizing the opportunity of high-speed rail development to improve energy efficiency.


Estrogen dramatically decreases albumin mRNA levels and albumin synthesis in Xenopus laevis liver.
The levels of albumin mRNA in Xenopus laevis liver were measured at various times after injection of estradiol using two different methods involving hybridization of cloned albumin cDNA to total liver RNA. The absolute levels of albumin mRNA fell by more than 95% during the first 4 days following estrogen treatment, then slowly returned to normal levels over the following 12 days. Albumin synthesis paralleled the albumin mRNA levels during the first 8 days after injection; but, 16 and 32 days after injection, albumin synthesis again decreased while albumin mRNA remained at normal levels. The time courses of the effects of estrogen on albumin and vitellogenin mRNA levels were different. Whereas albumin mRNA levels were minimal 4 days after estradiol injection, vitellogenin mRNA levels were maximal 8 days after injection.


An introduction to the structure and function of inflammatory mediators for clinicians.
As is apparent from a brief overview of some of the more important mediators involved in perinatal physiology and disease states, basic science research has provided many clinically relevant observations that, as discussed in other articles in this issue, have resulted in the discovery and development of clinically effective medications used daily in the care of the gravid mother and her fetus or neonate. In addition, an excellent base for the understanding of the mechanisms of the physiology of the maternal-fetal-placental unit has been established via extensive general and more focused research involving mediators.


A Response Surface Model to Predict and Experimentally Tune the Chemical, Magnetic and Optoelectronic Properties of Oxygen-Doped Boron Nitride.
Porous boron nitride (BN), a combination of hexagonal, turbostratic and amorphous BN, has emerged as a new platform photocatalyst. Yet, this material lacks photoactivity under visible light. Theoretical studies predict that tuning the oxygen content in oxygen-doped BN (BNO) could lower the band gap. This is yet to be verified experimentally. We present herein a systematic experimental route to simultaneously tune BNO's chemical, magnetic and optoelectronic properties using a multivariate synthesis parameter space. We report deep visible range band gaps (1.50-2.90 eV) and tuning of the oxygen (2-14 at.%) and specific paramagnetic OB3 contents (7-294 a.u. g-1 ). Through designing a response surface via a design of experiments (DOE) process, we have identified synthesis parameters influencing BNO's chemical, magnetic and optoelectronic properties. We also present model prediction equations relating these properties to the synthesis parameter space that we have validated experimentally. This methodology can help tailor and optimise BN materials for heterogeneous photocatalysis.


Long-term clinical and hemodynamic results of molsidomine treatment in patients with refractory heart failure.
In this report we describe the clinical and hemodynamic response of refractory cardiac failure to molsidomine. In the first part of the study the hemodynamic effects of a single oral dose of 2 or 4 mg of molsidomine were compared with placebo control in 23 patients. In the second phase the dose 8 to 24 mg/24 hours was used in nine patients with functional class III or IV symptoms over an average period of 28 months (range 7 to 42 months); a hemodynamic control study was performed. These data demonstrate that molsidomine has a hemodynamic effect on pulmonary artery pressure for 5 to 6 hours, that the peak effect is reached between 1 and 1 1/2 hours after oral intake, and that the clinical and hemodynamic benefits of molsidomine may be maintained in the long term in patients with particularly severe cardiac failure. The conditions of seven patients were clinically improved with treatment; significant reductions in mean right atrial, pulmonary artery, and pulmonary capillary pressures were observed.


Temperature sensitivities of metazoan and pre-metazoan Src kinases.
Homologous enzymes from different species display functional characteristics that correlate with the physiological and environmental temperatures encountered by the organisms. In this study, we have investigated the temperature sensitivity of the nonreceptor tyrosine kinase Src. We compared the temperature dependencies of c-Src and two Src kinases from single-celled eukaryotes, the choanoflagellate Monosiga brevicollis and the filasterean Capsaspora owczarzaki. Metazoan c-Src exhibits temperature sensitivity, with high activity at 30 °C and 37 °C. This sensitivity is driven by changes in substrate binding as well as maximal velocity, and it is dependent on the amino acid sequence surrounding tyrosine in the substrate. When tested with a peptide that displays temperature-dependent phosphorylation by c-Src, the enzymatic rates for the unicellular Src kinases show much less variation over the temperatures tested. The data demonstrate that unicellular Src kinases are temperature compensated relative to metazoan c-Src, consistent with an evolutionary adaptation to their environments.


[The passage from infancy to adolescence and modern family. The role of pediatricians and psychologists].
Currently, the debate on family difficulties during the passage of their children to adolescence gives the responsibility of a positive result in this evolutive process to both children and parents, because their interaction is a common construction, in which they have a role in selecting tools and goals. The pediatrician and the psychologist may give help the family in this critical period for their children.


Influence of guide wire removal on tip location in peripherally inserted central catheters (PICCs): a retrospective cross-sectional study.
The aim of this study was to identify the prevalence of peripherally inserted central catheter (PICC) malposition and the influence of guide wire removal on tip location in PICCs and determine whether related factors, including age, sex, side of insertion and brand of catheter, influence the PICC tip location. Single-centre research institute in China recruiting patients from the hospital. A total of 837 adult patients with inserted PICCs were recruited from October 2016 to May 2017. This was a cross-sectional study aiming to identify the prevalence of PICC malposition and the influence of guide wire removal on tip location in PICCs. A linear regression model and a variance of factorial design analysis were performed. The PICC tip location was documented on a postinsertion chest X-ray. Multivariable analyses were performed based on the following related factors: age, sex, side of insertion and brand of catheter. The tip location moved a mean of 17.4 mm among the 837 included patients. The prevalence of PICC malposition was 83.6% (700/837), while 16.4% (137/837) of PICCs remained in correct location. The mean movement caused by guide wire removal without an adjusted tail end was (-1.95±26.90) mm. The difference between tail end adjustment movement and actual tip position movement in each PICC was (33.0±17.1) mm in type C, which was significantly higher than the findings for type A (12.8±13.3) mm and type B (12.9±12.7) mm. PICC malposition is a frequent event. Different catheter brands were associated with different ranges of movement in tip location after guide wire removal. The age and sex of the patients and the insertion side did not influence the extent of movement.


Biogenesis of vacuolar membrane glycoproteins of yeast Saccharomyces cerevisiae.
To investigate the biogenesis of the yeast vacuole, we have sought novel marker proteins localized to the vacuolar membrane. Glycoproteins were prepared from vacuolar membrane vesicles by concanavalin A-Sepharose column chromatography and used to raise monoclonal antibodies. The antibodies obtained recognize several vacuolar proteins that have N-linked oligosaccharide chains. A set of the antibodies reacts with a vacuolar glycoprotein with a major molecular species of 72 kDa (vgp72), which appears to associate peripherally with the vacuolar membrane. The biosynthesis of vgp72 has been examined in detail by pulse-chase experiments and by analyses using various secretory mutants (sec18, sec7, and sec1) and a vacuolar protease mutant (pep4). vgp72 first appears in the endoplasmic reticulum as a 74-kDa species and is quickly modified in the Golgi apparatus to two distinct species: a 79-kDa form, and a heterogeneously glycosylated form (90-150 kDa). Subsequently, both species are proteolytically processed in the vacuole giving rise to a 72-kDa species as well as heavily glycosylated form. Thus, the biogenesis of vgp72 utilizes the early part of the secretory pathway as is the case of vacuolar soluble enzymes. A unique feature is that two species that are different in the extent of glycosylation appear to follow the same destination to the vacuolar membrane.


Psychiatric disorders of abused women at a shelter.
Thirty physically abused women were randomly selected from the population of a local women's shelter and evaluated by psychiatric interview and psychiatric rating scales. High prevalences of major depression disorder (37%) and PTSD (47%) were determined. Furthermore, these disorders were found to be positively associated. These results suggest the need for immediate availability of psychiatric services at such shelters along with further study of their populations and possible intervention strategies.


Rhythms in the biting behaviour of a mosquito Armigeres subalbatus.
The biting cycle of Armigeres subalbatus is distinctly crepuscular, exhibiting two peaks of activity, a smaller one at dawn and a larger one at dusk. The biting cycle is entrained to natural light-dark cycles and the time interval from dawn to dawn or dusk to dusk peaks is exactly 24 h and from dawn to dusk or dusk to dawn is about 12 h measured at 50% level. This rhythm manifests itself day after day without any marked qualitative change.The rate of change of light intensity may determine the onset of crepuscular biting. The sudden increase (up to ca. 17 lx) or decrease (down to ca. 4 lx) in the intensity of ambient light at the time of sunrise or sunset coincides with the peak of the biting activity.The density of the population of the host-seeking females fluctuates in relation to the phases of the moon, increasing with the full moon phase and decreasing with the new moon phase.Even though the density of the population is greater outdoors than indoors both at ground levels and in the first floor, the peak of activity occurs at the same time in all the places. A vertical stratification of biting activity was also noticed.


Purification, crystallisation and X-ray diffraction study of fully functional laccases from two ligninolytic fungi.
Laccase isozymes from the white-rot basidiomycete fungi Trametes versicolor and Pycnoporus cinnabarinus were purified to apparent iso-electric homogeneity and crystallised. T. versicolor laccase crystallises in two crystal forms, both with the orthorhombic space group P2(1)2(1)2(1), which diffract to 1.9 and 2.95 A resolution, respectively. The crystals of P. cinnabarinus laccase belong to the monoclinic space group C2 and diffract to at least 2.2 A resolution. All the laccase crystals are suitable for X-ray structure determination and contain a full complement of copper ions.


Differential expression of fibronectin in a rat histiocytoma: possible role of fibronectin in tumor cell adhesion.
The specific role of fibronectin in tumor cells has been investigated using the transplantable histiocytic tumor line AK-5 [A. Khar (1986) J. Natl. Cancer Inst. 76, 871]. These cells, capable of growth as both ascites and solid tumors in rats, can be separated into four subpopulations by buoyant density centrifugation on Percoll. These subpopulations are shown to contain different amounts of fibronectin on the cell surface when studied by immunofluorescent staining followed by cytofluorometric analysis. Cells which contain high amounts of fibronectin can grow both as ascites and as solid tumors while those cells which contain low amounts of fibronectin cannot grow as solid tumors but can grow as ascitic tumors. Pretreatment of high-fibronectin-containing cells with anti-fibronectin antibody abolished their capacity to grow as solid tumors; however, the cells retained their capacity to grow as ascitic tumors. These results have been discussed with reference to the specific role of fibronectin in tumor-forming cells.


Prognostic value of myocardial perfusion scintigraphy in diabetic patients and without coronary lesion.
To determine the prognostic value of myocardial perfusion scintigraphy-gated SPECT in patients with diabetes mellitus and without obstructive coronary artery disease. This retrospective study included consecutive patients undergoing adenosine stress-rest myocardial perfusion imaging (MPI) by 99mTc-tetrofosmin between 2009 and 2011. The patients had diabetes mellitus and coronary angiography without significant coronary lesions. In total, 37 diabetic patients (female/male: 20/17; mean age: 65.2 (range: 40-78). 29 non-diabetic patients were included wich are matched with the group of diabetic patients with positive MPI. The group of non-diabetic patients had scintigraphy with myocardial ischemia and without angiographic lesions. A 36-month clinical follow-up was performed, and major cardiac events were recorded. In 78.3% (29/37) of diabetic patients the scintigraphic study showed myocardial ischemia, while it was negative in the 21.7%. The cardiac event rate in both groups was 6%. In diabetics with a myocardial perfusion study with myocardial ischemia, there were 3 major cardiac events. In diabetic patients with negative study had no cardiac event. In the non-diabetic control group the cardiac events rate was 3.4% (1/29). In diabetic patients without obstructive coronary disease, myocardial perfusion study can be predictor of cardiac events. A negative study can be an indicator of a better cardiovascular prognosis.


Noninvasive imaging diagnosis of sinusoidal obstruction syndrome: a pictorial review.
Sinusoidal obstruction syndrome (SOS) is a rare liver disorder due to hepatic vascular injury. Its rapid and accurate diagnosis is crucial for patient survival. SOS is often established clinically, based on Baltimore, modified Seattle, or European Society for Blood and Marrow Transplantation (EBMT) criteria. Unfortunately, such criteria are not highly specificity and fail to provide a timely, reliable differential diagnosis. The use of noninvasive imaging techniques, such as ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), has recently grown in this setting, some key imaging features offering diagnostic improvement. This review provides a synopsis of current noninvasive imaging techniques used for this purpose, summarizing accurate and reliable diagnostic features of SOS.


Light at night disrupts diel patterns of cytokine gene expression and endocrine profiles in zebra finch (Taeniopygia guttata).
Increased exposure to light pollution perturbs physiological processes through misalignment of daily rhythms at the cellular and tissue levels. Effects of artificial light-at-night (ALAN) on diel properties of immunity are currently unknown. We therefore tested the effects of ALAN on diel patterns of cytokine gene expression, as well as key hormones involved with the regulation of immunity, in zebra finches (Taeniopygia guttata). Circulating melatonin and corticosterone, and mRNA expression levels of pro- (IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines were measured at six time points across 24-h day in brain (nidopallium, hippocampus, and hypothalamus) and peripheral tissues (liver, spleen, and fat) of zebra finches exposed to 12 h light:12 h darkness (LD), dim light-at-night (DLAN) or constant bright light (LLbright). Melatonin and corticosterone concentrations were significantly rhythmic under LD, but not under LLbright and DLAN. Genes coding for cytokines showed tissue-specific diurnal rhythms under LD and were lost with exposure to LLbright, except IL-6 in hypothalamus and liver. In comparison to LLbright, effects of DLAN were less adverse with persistence of some diurnal rhythms, albeit with significant waveform alterations. These results underscore the circadian regulation of biosynthesis of immune effectors and imply the susceptibility of daily immune and endocrine patterns to ALAN.


Ligand binding characteristics of the Ku80 von Willebrand domain.
The N-terminal von Willebrand domain of Ku80 supports interactions with a Ku binding motif (KBM) that has been identified in at least three other DNA repair proteins: the non-homologous end joining (NHEJ) scaffold APLF, the modulator of retrovirus infection, MRI, and the Werner syndrome protein (WRN). A second, more recently identified Ku binding motif present in XLF and several other proteins (KBMX) has also been reported to interact with this domain. The isolated Ku80 von Willebrand antigen domain (vWA) from Xenopus laevis has a sequence that is 60% identical with the human domain, is readily expressed and has been used to investigate these interactions. Structural characterization of the complexes formed with the KBM motifs in human APLF, MRI, and WRN identify a conserved binding site that is consistent with previously-reported mutational studies. In contrast with the KBM binding site, structural studies indicate that the KBMX site is occluded by a distorted helix. Fluorescence polarization and 19F NMR studies of a fluorinated XLF C-terminal peptide failed to indicate any interaction with the frog vWA. It was hypothesized that availability of this binding site is conditional, i.e., dependent on specific experimental conditions or other repair factors to make the site available for binding. Modulating the fraction of KBMX-accessible binding site mutationally demonstrated that the more open site is capable of binding the KBMXXLF motif peptide. It is suggested that the conditional nature of KBMX binding limits formation of non-productive complexes so that activation-dependent site availability can more optimally support advancing the synapsis process.


Is the use of biosensor in monitoring food quality experiencing an uplift trend over the last 30 years?: A bibliometric analysis.
Recently, there has been intense competition among food industries worldwide as they strive to fulfill the ever-growing consumer expectations regarding both the quantity and quality of food. The increasing demand for high-quality food has motivated researchers and academics to constantly innovate and develop real-time and precise tools for monitoring food quality. One such tool that has emerged is biosensors, which have already been widely investigated; however, no bibliometric reviews have discussed biosensor use holistically, comprehensively, and objectively. Therefore, this review aimed to analyze the trend of biosensor publications for monitoring food quality based on the number of documents published from 1991 to 2021, analyze the contribution of various journals, institutions, and cooperation between countries, highlight the most influential authors and articles, and predict the development of this topic. The Method used in this study is bibliometric analysis which consists of four stages, namely data mining from the Scopus database which are limited to data for the last 30 years (1991-2021), refining data, data visualization and interpretation data. There are 604 articles obtained from Scopus and visualization shows that biosensor use for monitoring food quality has significantly increased in the past three decades. Biosensors and Bioelectronics is the leading journal in publishing manuscripts on the topic of biosensors. In terms of the largest contribution, China produced the highest number of publications on related topics, while the United States has the highest collaborations between countries. Moreover, Whitcombe MJ has the most influential articles, while Wang S had the largest number of outputs. The frequently used keywords are "biosensors," "food safety," and "food analysis." These results are important references to determine the state of the art and directions for further investigations.


Lipid peroxidation and lung ultrastructural changes in an experimental model of leukocyte-mediated pulmonary injury.
The aim of this study was to study ultrastructural changes and lipid peroxidation in rabbits lung after massive complement activation and leukocyte aggregation. A prolonged and massive leukocyte activation was induced by intraperitoneal inoculation of zymosan suspected in paraffin. Fifteen animals (group 3) were given 0.6 g/kg of zymosan, 22 animals (group 2) received 1 g/kg, and 11 rabbits (group 1) were treated with paraffin alone and served as controls. An acute mortality rate of 40% was observed in group 3 and of 68% in group 2. Surviving animals were studied for 10 days. In these animals a marked decrease in circulating granulocytes and a progressive decline in arterial PO2 were recorded (PO2 on day 10 in group 2 animals was 51.94 +/- 4.26, p less than 0.01). Microscopic and ultrastructural evaluation revealed sequestration of granulocytes in the pulmonary microvasculature. Studies of lung homogenates demonstrated increased levels of lipid peroxide derivative malondialdehyde (group 2 rabbits, 1624 +/- 638; group 1, 795 +/- 57 pm/mg pt, p less than .001) and decreased levels of the tissue antioxidant alpha-tocopherol. The results of this study are compatible with the hypothesis of leukocyte-mediated injury through production of oxygen radicals.


Purification and characterization of a new peptide antibiotic produced by a thermotolerant Bacillus licheniformis strain.
A Bacillus licheniformis strain, 189, isolated from a hot spring environment in the Azores, Portugal, strongly inhibited growth of Gram-positive bacteria. It produced a peptide antibiotic at 50 degrees C. The antibiotic was purified and biochemically characterized. It was highly resistant to several proteolytic enzymes. Additionally, it retained its antimicrobial activity after incubation at pH values between 3.5 and 8; it was thermostable, retaining about 85% and 20% of its activity after 6 h at 50 degrees C and 100 degrees C, respectively. Its molecular mass determined by mass spectrometry was 3249.7 Da.


Cracking addiction the second time around: reconsolidation of drug-related memories.
One of the greatest challenges in the understanding and treatment of addiction is cue-elicited relapse to drug use. The present findings of Miller and Marshall and Lee et al. reported in this issue of Neuron demonstrate that retrieved drug-related memories undergo reconsolidation and thus suggest that these maladaptive associations may be more labile than previously thought.


Proteomic and glycomic analyses of a lung-specific protein surfactant protein-D.
In order to verify the protein enriched from pooled human sera to be a lung-specific protein surfactant protein-D (SP-D), we performed peptide mass fingerprinting (PMF)-based protein identification. MASCOT search results of the obtained PMF unequivocally demonstrated that it is identical to human SP-D. Meanwhile, we performed MALDI-QIT-TOF mass spectrometry-based N-glycomic analysis of the recombinant human SP-D produced in murine myeloma cells. The obtained mass spectra of N-glycans from the recombinant SP-D demonstrated that the recombinant protein is almost exclusively modified with core-fucosylated N-glycans [1].


Physico-chemical characterization and enzymatic functionalization of Enteromorpha sp. cellulose.
Although green macro-algae represent a renewable and highly abundant biomass, they remain poorly exploited in terms of carbohydrate polymers compared to red and brown ones and other lignocellulosic materials. In this study, cellulose from the green macro-algae Enteromorpha sp. was isolated, physico-chemically characterized and enzymatically functionalized. The cellulose content was about 21.4% (w/w). FTIR analyses indicated an absence of acetyl or uronic esters confirming the absence of hemicellulose contamination. The 36% crystallinity index of the extracted cellulose revealed a high amorphous character as determined by X-ray diffraction. The moisture adsorption isotherms and specific surface measurements were respectively 42.87g/100g and 8.34m(2)/g. The Enteromorpha sp. cellulose was first enzymatically saccharified by a commercial cellulase preparation from Aspergillus niger with a hydrolysis yield of 70.4%. Besides, it was successfully functionalized based on the transglycosylation mechanism of the same enzymatic preparation, to produce highly added-value biosurfactants (butyl-glucoside) with a concentration of 8mM.


Case-control study of endophthalmitis after cataract surgery comparing scleral tunnel and clear corneal wounds.
To study the possible association between clear corneal incision with or without placement of a suture during cataract extraction and postoperative endophthalmitis. Retrospective, comparative, case-controlled study. Thirty-eight patients treated for culture-positive, acute post-cataract surgery endophthalmitis, and 371 randomly selected control patients who underwent uncomplicated cataract surgery in the referring community were studied. Incision type and use of suture during cataract surgery of endophthalmitis patients were compared with the controls. The data were analyzed using logistic regression methods. Of the 38 patients with endophthalmitis, 17 patients (45%) had clear corneal incisions and 21 patients (55%) had a scleral tunnel incision. In 371 controls, 76 patients (20%) had clear corneal incisions and 295 patients (80%) had scleral tunnel incisions. Clear corneal incision was associated with a threefold greater risk of endophthalmitis than was scleral tunnel incision (Odds Ratio, 3.36, 95% Confidence Interval = 1.67 to 6.78). The type of incision was significant (chi(2) = 11.53, P =.0007); a clear corneal incision was more frequently associated with endophthalmitis. A subgroup analysis revealed that the presence or absence of a suture was not significant (chi(2) = 1.31, P =.2524). In this retrospective, case-controlled study, clear corneal incisions were found to be a statistically significant risk factor for acute post-cataract surgery endophthalmitis when compared with scleral tunnel incisions.


Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats.
To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats. Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting. Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05). KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.


Fine structure of rabbit ear chondrocytes in vitro and after autotransplantation.
Chondrocytes were isolated enzymatically from rabbit ear cartilage, grown in vitro or as autotransplants for 1, 2 or 5 weeks and then examined by transmission electron microscopy. A confluent monolayer formed rapidly in vitro and the cells later grew in multiple overlapping layers, producing thick sheets of cartilaginous tissue. The cells retained a normal structure throughout the period of observation and, like the chondrocytes in intact cartilage, showed numerous microfilaments, and extensive granular endoplasmic reticulum and a prominent Golgi complex. Large amounts of intercellular matrix were laid down in vitro consisting of thin collagen fibrils, small rounded or polygonal granules believed to represent proteoglycans and patches and fibres of elastin. Chondrocytes in intramuscular autotransplants reconstituted an elastic cartilage. The exogenous origin of the cells in the transplants was verified by labeling of the lysosomes by exposure of the cells to colloidal thorium dioxide particles prior to injection. Structurally, the cells and the matrix of the transplants conformed to the above description. Accumulations of elastin-like material were sometimes observed in the Golgi vacuoles of the cells. Extracellularly, such conglomerates aggregated in connection with bundles of microfibrils, building up mature elastic fibres with a dense amorphous structure. The culture and transplant systems characterized here provide suitable experimental models for studies on development, growth and aging of elastic cartilage, including various aspects of the formation and turnover of elastic fibres and other macromolecular matrix components.


Clinical values of common biomarkers for efficacy monitoring of antibiotics in early-onset neonatal sepsis.
To investigate the clinical values of the common biomarkers including blood routine (B-Rt), C-reactive protein (CRP), serum amyloid A (SAA) and procalcitonin (PCT) for efficacy monitoring of antibiotics in early-onset neonatal sepsis (EONS). The clinical and laboratory data of 78 neonates with confirmed EONS in the neonatal intensive care unit (NICU) of our center from July 1, 2019 to June 30, 2020 were retrospectively analyzed. All the subjects were treated with cefotiam (50 mg/kg q12h) and augmentin (30 mg/kg q12h) within 12 hours after birth. Blood samples were collected 0-12 hours after birth for blood culture, measurements of B-Rt, CRP and SAA. Subsequently, blood sampling was performed at intervals of 12-24, 24-48, 48-96, and 96-144 hours for measurements of B-Rt, CRP, SAA and PCT. Statistical analyses were performed in the SPSS 20.0 software package. P value of <0.05 was considered statistically significant. WBC count showed no significant change among different intervals (12-24, 24-48, 48-96, and 96-144 hours); in contrast, NEU%, CRP, SAA and PCT significantly differed across all intervals. SAA had sensitivities of 75.86%, 93.1%, 44.83%, and 3.45%, respectively; specificities of 100% across all intervals; and AUCs of 0.879 (P<0.0001), 0.966 (P<0.0001), 0.724 (P<0.0001), and 0.500, respectively (P=1). PCT had sensitivities of 100%, 100%, 79.31%, and 51.72%, respectively; specificities of 100% across all intervals; and AUCs of 1 (P<0.0001), 1 (P<0.0001), 0.793 (P<0.0001), and 0.517 (P>0.8551), respectively. WBC count, NEU% and CRP showed no clinical significance for any intervals for efficacy monitoring of antibiotic treatment. SAA and PCT had similar monitoring values at 12-24 and 24-48 hours. SAA is thus more valuable than PCT for efficacy monitoring of antibiotics at the 48-96 and even at the 96-144 hours intervals in EONS.


Estimation of stature from somatometry of skull.
In order to investigate the possibility of estimating stature from somatometry of the skull, we carried out a study on 124 Japanese cadavers (comprising 77 males and 47 females) that had been autopsied at our laboratory between July 1986 and June 1991. Somatometry of the skull was performed on diameter (distance between glabella and external protuberance) and circumference (length around the skull through two points: the glabella and the external protuberance). The regression equations calculated were as follows: stature in males = (diameter + circumference) x 1.35 + 70.6 (standard error of estimate (S.E.) = 6.96 cm); stature in females = circumference x 1.28 + 87.8 (S.E. = 6.59 cm); stature in both sexes = (diameter + circumference) x 1.95 + 25.2 (S.E. = 7.95 cm). These S.E.s appear to be larger than those obtained for other parts of the body. However, in cases where identification is required by means of only the skull, this method could prove useful.


Effect of a controlled high-fat versus low-fat diet on insulin sensitivity and leptin levels in African-American and Caucasian women.
African-American women have been shown to be more insulin-resistant than age- and weight-matched Caucasian women, but the reasons for this difference are unclear. The purpose of the present study was to determine whether experimental manipulation of dietary fat intake has differential effects by race on insulin sensitivity (S(I)) in 20 African-American and 11 Caucasian women. Additionally, leptin levels before and after 3 weeks of an isocaloric high-fat ([HF] 50% fat, 35% carbohydrate, and 15% protein) or low-fat ([LF] 20% fat, 55% carbohydrate, and 15% protein) diet were compared. African-American and Caucasian women did not differ significantly in the body mass index (BMI) or percentage body fat at baseline. S(I) (adjusted for BMI) decreased on the HF diet and increased on the LF diet in both races combined relative to the baseline control (control, 2.42 +/- 0.22; HF, 2.29 +/- 0.22; LF, 2.75 +/- 0.21 x 10(-4) min(-1)/microU x mL; main effect of diet, P = .04). There was a 6% decrease in S(I) on the HF diet compared with the control in women of both races, while the LF diet increased S(I) by 6% in African-American and 20% in Caucasian women. Leptin levels increased by 14% on the HF versus control diet in African-Americans (35.2 +/- 3.0 v 30.8 +/- 3.0 ng/mL, P < .01), but did not change with diet in Caucasian women. Glucose and insulin administration had no effect on leptin levels. We conclude that a HF diet consumed over several weeks reduces S(I) in healthy women of both races; however, the magnitude of increase in S(I) on a LF diet is greater in Caucasian women. The HF diet significantly increased leptin levels in African-American women, although there were no other influences of diet, insulin, or race on serum leptin.


Synthesis of benzo[c]quinolizin-3-ones: selective non-steroidal inhibitors of steroid 5 alpha-reductase 1.
A short and efficient synthesis of novel benzo[c]quinolizin-3-one derivatives is described. The synthesis is based on the tandem Mannich-Michael cyclization between 2-silyloxy-1,3-butadienes and a N-t-Boc iminium ion. The prepared derivatives are selective inhibitors of human steroid 5 alpha-reductase isoenzyme 1, thus having potential application as drugs for treatment of male pattern baldness and other DHT-dependent skin disorders.


[Ultra-Wide Field Retinal Imaging and Angiography in the Differential Diagnosis and Therapeutic Decisions in Vascular Diseases of the Peripheral Retina].
Investigation of vascular diseases of the peripheral retina requires imaging procedures that allow a comprehensive view of the periphery, as well as reproducible pictures. In particular, ultra-wide field fluorescence angiography facilitates diagnosis, therapeutic decisions and follow-up examinations. While vasculopathies such as Coats disease and familiar exudative vitreoretinopathy are diagnosed within the first and second decade of life, patients' compliance during fundus imaging is typically reduced within this age range. Compared to the repeated imaging procedures for composite formation, ultra-wide field imaging has significantly reduced recording time. Nevertheless, current imaging systems are not able to map the entire retina in scaled proportions. Therefore, the imaging frame must be guided by patients' gaze onto the affected retinal area. Moreover, the medical photographer must be aware of the clinical setting and the region of interest. Hence, previous detailed funduscopy by trained ophthalmologists will remain indispensable.


Reanalysis of the role of pronase treatment of B cells in the flow cytometric crossmatch assay: Fc receptor is not the primary target.
Pronase, a mixture of nonspecific bacterial proteases, is used to pretreat human lymphocytes to prevent false-positive B cell results in the flow cytometric crossmatch (FCXM) assay. The target of pronase has been reported to be B cell-expressed Fc receptors, which nonspecifically bind IgG. As pronase use in FCXM can induce other complications, including degradation of HLA leading to inappropriate FCXM results, and false-positive T cell results when testing serum from HIV-positive patients, we tested whether specifically blocking Fc receptor CD32 could replace pronase. Anti-CD32 mAb 6C4 was superior to pronase for blocking binding of aggregated IgG to B cells. However, 6C4 was unable to replace pronase in clinical FCXM, as it did not prevent false-positive B cell FCXM results, or enhance sensitivity of the assay. We conclude that the functional targets of pronase in the FCXM assay are poorly understood, and that B cell-expressed Fc receptor plays an insignificant role.


Chlamydia trachomatis infections--the Royal Women's Hospital experience.
During the 18-month period from December 1, 1985 to May 31, 1987 Chlamydia trachomatis was the most-common sexually-transmitted agent to be identified at the Royal Women's Hospital, Melbourne. It was isolated from 4% of all specimens for which such culture was requested and was found five-times more frequently than was Neisseria gonorrhoeae. A review of the clinical presentation and the management of the 100 public patient for this period whose cervical specimens were found to give positive results for the presence of chlamydiae revealed that 77% of the women were less than 25 years of age, 78% of the women were single and 65% of the women were nulliparous. Thirty-five women were asymptomatic carriers of chlamydiae. Of the remaining 65 patients with symptoms, 46% experienced pelvic pain, 39% experienced a vaginal discharge and 26% experienced irregular bleeding. The importance of abnormal bleeding is emphasized. In patients who presented for therapeutic abortions, morbidity occurred in 19% of those who were carriers of Chl. trachomatis; accordingly, screening for chlamydiae as routine is recommended in such patients. Furthermore, because of the risk of pelvic inflammatory disease and its consequences, it is important not only to treat female patients in whom chlamydiae have been isolated, but also to treat and to follow-up their sexual partners simultaneously.


Re-imagining fMRI for awake behaving infants.
Thousands of functional magnetic resonance imaging (fMRI) studies have provided important insight into the human brain. However, only a handful of these studies tested infants while they were awake, because of the significant and unique methodological challenges involved. We report our efforts to address these challenges, with the goal of creating methods for awake infant fMRI that can reveal the inner workings of the developing, preverbal mind. We use these methods to collect and analyze two fMRI datasets obtained from infants during cognitive tasks, released publicly with this paper. In these datasets, we explore and evaluate data quantity and quality, task-evoked activity, and preprocessing decisions. We disseminate these methods by sharing two software packages that integrate infant-friendly cognitive tasks and eye-gaze monitoring with fMRI acquisition and analysis. These resources make fMRI a feasible and accessible technique for cognitive neuroscience in awake and behaving human infants.


Usefulness of Q-wave area for threshold-based stratification of global left ventricular myocardial infarct size.
Left ventricular (LV) infarct size affects prognosis after acute myocardial infarction (AMI). Delayed enhancement cardiac magnetic resonance (DE-CMR) provides accurate infarct quantification but is unavailable or contraindicated in many patients. This study tested whether simple electrocardiography (ECG) parameters can stratify LV infarct size. One hundred fifty-two patients with AMI underwent DE-CMR and serial 12-lead ECG. Electrocardiograms were quantitatively analyzed for multiple aspects of Q-wave morphology, including duration, amplitude, and geometric area (QWAr) summed across all leads except aVR. Patients with pathologic Q waves had larger infarcts measured by DE-CMR or enzymes (both p <0.001), even after controlling for infarct distribution by CMR or x-ray angiography. Comparison between early (4 ± 0.4 days after AMI) and follow-up (29 ± 6 days) ECG demonstrated temporal reductions in Q-wave amplitude (1.8 ± 1.4 vs 1.6 ± 1.6 mV; p = 0.03) but not QWAr (41 ± 38 vs 39 ± 43 mV•ms; p = 0.29). At both times, QWAr augmented stepwise with DE-CMR quantified infarct size (p <0.001). QWAr increased markedly at 10% LV infarct threshold, with differences more than threefold on early ECG (59 ± 39 vs 18 ± 20 mV•ms; p <0.001) and nearly fivefold (59 ± 46 vs 13 ± 16 mV•ms; p <0.001) on follow-up. Diagnostic performance compared with a 10% infarction cutoff was good on early (area under the curve = 0.84) and follow-up (area under the curve = 0.87) ECG. Optimization of sensitivity (95% to 98%) enabled QWAr to exclude affected patients with 90% to 94% negative predictive value at each time point. In conclusion, LV infarct size is accompanied by stepwise increments in Q-wave morphology, with QWAr increased three- to fivefold at a threshold of 10% LV infarction. Stratification based on QWAr provides excellent negative predictive value for exclusion of large (≥10%) LV infarct burden.


Pancake ready mix enriched with dehydrated squash pulp (Cucurbita moschata): formulation and shelf life.
The objective of this study was to evaluate the physicochemical, sensory and texture characteristics of pancakes which contained dehydrated squash pulp (10 and 30 g/100 g of ready mix pancake). For this, first the physicochemical characteristics as well as the thermal and functional properties of dehydrated squash pulp (DSP) were determined. Then, the stability of the pancake ready mix was evaluated, through its physical-chemical and microbiological properties, during a storage period of 3 weeks, at 25, 40 and 50 °C. Finally, shelf life was estimated by means of two predictive methods (reaction kinetics and microbiological method). Results showed that DSP presented a high dietary fiber content (30.02 g/100 g), total carotenoids (452.04 µg/g), and phenolic compounds (415 ± 9.19 mg GAE/100 g), high swelling power, low solubility and emulsifying capacity. The formulation with the highest acceptance was that containing 10% dehydrated squash pulp (DSP-10), which obtained a shelf life of 5.39 weeks (28 °C) (reaction kinetics) and 33.51 weeks (microbiological method).


An improved dual-domain network for metal artifact reduction in CT images using aggregated contextual transformations.
Objective. Metal artifact reduction (MAR) remains a challenging task due to the difficulty of removing artifacts while preserving anatomical details of the tissue. Although current dual-domain networks have shown promising performance in MAR, they heavily rely on the image domain, which can be too smooth and lose important information in the metal-affected area. To address this problem, we propose an improved dual domain network framework.Approach. We enhance sinogram completion performance by utilizing an aggregated contextual transformations network in the sinogram domain. Furthermore, we utilizea prior-projection-based linearized correction method to obtain images with beam-hardening artifacts removed, which are incorporated into the input of the image post-processing network to assist in training the image domain network. Finally, we train the sinogram domain network and the image domain network separately to their respective convergences.Main results. In experiments conducted on a simulated dataset, our method achieves the best average RMSE of 25.1, SSIM of 0.973, and PSNR of 42.1, respectively.Significance. The proposed method is capable of preserving tissue structures near metallic objects while eliminating metal artifacts from the reconstructed images. Related codes will be released athttps://github.com/Corinna-China/AOTDudoNet.


Structure of an amorphous calcium carbonate phase involved in the formation of Pinctada margaritifera shells.
Some mollusc shells are formed from an amorphous calcium carbonate (ACC) compound, which further transforms into a crystalline material. The transformation mechanism is not fully understood but is however crucial to develop bioinspired synthetic biomineralization strategies or accurate marine biomineral proxies for geoscience. The difficulty arises from the simultaneous presence of crystalline and amorphous compounds in the shell, which complicates the selective experimental characterization of the amorphous fraction. Here, we use nanobeam X-ray total scattering together with an approach to separate crystalline and amorphous scattering contributions to obtain the spatially resolved atomic pair distribution function (PDF). We resolve three distinct amorphous calcium carbonate compounds, present in the shell of Pinctada margaritifera and attributed to: interprismatic periostracum, young mineralizing units, and mature mineralizing units. From this, we extract accurate bond parameters by reverse Monte Carlo (RMC) modeling of the PDF. This shows that the three amorphous compounds differ mostly in their Ca-O nearest-neighbor atom pair distance. Further characterization with conventional spectroscopic techniques unveils the presence of Mg in the shell and shows Mg-calcite in the final, crystallized shell. In line with recent literature, we propose that the amorphous-to-crystal transition is mediated by the presence of Mg. The transition occurs through the decomposition of the initial Mg-rich precursor into a second Mg-poor ACC compound before forming a crystal.


Biofeedback therapy in the treatment of bladder overactivity, vesico-ureteral reflux and urinary tract infection.
Voiding disorders are commonly encountered in paediatric urology practice. Urinary incontinence often leads to the impairment of self-esteem but can also cause renal damage, when recurrent urinary tract infection (UTI) or vesico-ureteral reflux (VUR) exists. The aim of this study was to assess the efficacy of a biofeedback training program in children with a long history of voiding disorders. Between 1998 and 2002, 60 children with voiding disorders without neuropathic disease, aged 5-14, were treated. There were 48 girls and 12 boys. The main symptoms were daytime incontinence for 90%, urge syndrome for 78%, and night-time incontinence for 60%. UTIs were noted in 62% of the children, for 37% of them in association with a VUR. Ten weekly sessions were planned for all the children. They were given instructions on toilet behaviour and posture, and pelvic floor training. They had to supervise their voiding frequency and liquid intake at home using a chart. Biofeedback procedure used surface perineal electrodes. The exercises focused on relaxation of the perineum. The first results were recorded 6 months after the last session: 96% of the children with daytime incontinence and 83% of the children with night-time incontinence were cured or improved; 84% of the children were free from infection and VUR was cured in 50% of cases. After a mean follow-up of 21 months, 8% of the children with daytime incontinence and 33% with night-time incontinence relapsed, with a significant difference between primary and secondary enuresis. A breakthrough UTI was observed in 19% of cases. This non-invasive training program was effective in the treatment of daytime incontinence, UTI and VUR. There was an improvement in secondary but not primary enuresis. To prevent relapse, additional support sessions seem to be necessary.


Equipping pharmacists for delivering pharmaceutical care to seniors: a qualitative systematic review of Asian seniors' social support.
Pharmacists must cater to seniors' needs and communicate better in delivering pharmaceutical care. However, pharmaceutical care for seniors is unique since they commonly depend on support from their social environment. Our study aimed to collect perceptions and experiences of Asian seniors regarding social support. A qualitative systematic review of peer-reviewed articles between January 2012 and January 2022 was conducted using PubMed, Scopus, Academic Search Complete via EBSCOhost, ProQuest, and Google Scholar. Selected studies were extracted, and thematic synthesis was performed. A total of 23 qualitative studies with diverse rigor were included in this review. Themes that emerged around perceptions and experiences of social support were (1) family orientation, (2) having faith in religion, (3) the importance of the elderly providing support, (4) taboos, (5) elderly self-reliance, (6) elderly fear of being a burden, and (7) differences on perceptions and experiences regarding social support. A discussion on how these results may contribute to pharmacy practice is provided. This study reviews the available social support for seniors and highlights its importance for pharmacists.


Poo Matters! A scoping review of the impact of constipation on epilepsy.
Epilepsy is a common neurological disorder which frequently presents with co-morbid physical health conditions, including constipation. However, the nature of the relationship between the two conditions has not been well defined. To quantify constipation's relationship with epilepsy and anti-seizure medication (ASM). A scoping review registered on PROSPERO (CRD42022320079) with suitable search terms was conducted and reported in accordance with PRISMA guidance. CINAHL, Embase, PsycInfo and MEDLINE electronic databases were searched by an information specialist. The Joanna Briggs Institute (JBI) critical appraisal tools alongside the Oxford Centre for Evidence Based Medicine (OCEBM) levels of evidence were used to assist in assessing relevance, quality, and results of the included publications. Nine articles selected for inclusion in the review. The prevalence of irritable bowel syndrome (including constipation) was reported to be up to five times more frequent in people with epilepsy (PWE). Functional constipation was reported in 36% of PWE. Constipation was found to be the second most common co-morbid condition in children with epilepsy. Two studies found constipation to precede seizures. Constipation was reported as a common side effect of ASMs in PWE. Two studies rated OCEBM level 2 the remaining level 3. Our findings suggest a higher prevalence of constipation in PWE. Co-occurring multimorbidity and resulting polypharmacy adds further complexity to the process of establishing aetiology of constipation in PWE. Potential contributory aetiological factors for constipation such as neurodevelopmental and genetic disorders, ASM side effects and the epilepsy itself require better understanding and research.


Long-term needle litterfall of a Scots pine Pinus sylvestris stand: relation to temperature factors.
Needle litterfall of a Scots pine was caught over 24 years (1962-1986) with litter-traps in a Scots pine stand in southeastern Finland. The age of the trees averaged 111 years in 1962. The stand was naturally recruited and only minor silvicultural treatments occurred during its history. Litterfall showed great year-to-year variation, the minimum being 18 g/m2 (in 1968) and maximum 213 g/m2 (in 1973). There was no overall trend in the amount of litterfall, and the age of the stand was thus not important in determining the needle fall. We used time domain time series analysis (ARIMA) and standard climatic data (temperature, precipitation) to investigate the relationship of litterfall to climatic factors. Mean July temperature was clearly correlated with needle litterfall. High temperature in July coincided with enhanced litterfall in the same and the next year. Litterfall enhanced litterfall in the same and the next year. Litterfall increased also after high temperatures during March-April, but only in the same year. In addition to these the litterfall had a 4-year self-dependency. This is approximately the same as the mean longevity of needles in the study area. Altogether the time series model we propose covers about 90% of the variance of the original time series.


Healthcare services for Japanese elderly long-staying in Thailand from the perspective of the patient and healthcare providers: a survey study.
Long-stay refers to a long visit abroad by retired middle-aged and older people. This study describes the attitudes/opinions of elderly Japanese long-staying subjects and healthcare providers in Thailand. Two cross-sectional questionnaire surveys were conducted in Chiang Mai Province, Thailand. Questionnaires were sent to a sample recruited from a self-help group of Japanese elders in Thailand (n = 68) and to Thai healthcare providers (n = 101). About half of the Japanese subjects routinely used a Thai medical service, although only 15% had been admitted to the hospital. Half of the Japanese subjects thought the quality of Thai medical services was high. Many elderly Japanese subjects were unable to speak either English or Thai, leading to communication difficulties. About 80% of healthcare professionals found no difference between caring for elderly Japanese subjects and people from Thailand. Most healthcare providers agreed that Japanese language training should be available to medical staff as translators were not always available. Healthcare providers agreed with the Thai government policy promoting long-stays. The most recognized obstacle in caring for Japanese long-stay elderly was the language barrier. More research on Japanese elders staying abroad is needed to promote effective communication between Japanese elderly and other ethnic healthcare professionals.


Estrogen receptor 1 inhibits the progression of hepatocellular carcinoma via positively regulating lncRNA maternally expressed gene 3 under high glucose conditions.
Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) is crucial in the association of diabetes mellitus (DM) and hepatocellular carcinoma (HCC), and estrogen receptor 1 (ESR1) plays an essential role in various cancers. However, the underlying regulatory effect of ESR1/lncRNA MEG3 on HCC with DM remains unclear. This study explored the regulatory effect of ESR1/lncRNA MEG3 on HCC cell progression. Bioinformatics analysis was used to predict the promoter sequence of lncRNA MEG3 using UCSC (http://genome.ucsc.edu/), followed by luciferase reporter and RNA immunoprecipitation (RIP) assays to verify the specific combination between ESR1 and lncRNA MEG3 promoter. After cotransfection with ESR1, ESR1 siRNA or lncRNA MEG3 RNA, CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) and colony formation assays were used to evaluate the cell proliferation capacity. Cell apoptosis was assessed using flow cytometry analysis. Next, wound healing and Transwell assays were conducted to examine cell invasiveness and migration. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were performed to quantify the expression of ESR1 or lncRNA MEG3. ESR1 might be the transcription factor (TF) of lncRNA MEG3, and ESR1 bound with lncRNA MEG3 promoter. Overexpression of ESR1 repressed the proliferation, migration and invasion of HepG2 cells, and promoted apoptosis of HepG2 cells under high glucose conditions. Silencing ESR1 decreased lncRNA MEG3 expression in HepG2 cells but enhanced proliferation, migration and invasion. Meanwhile, a rescue assay demonstrated that silencing lncRNA MEG3 reversed the inhibitory effect of ESR1 on HepG2 cell progression. ESR1 inhibits HCC cell progression through positively regulating lncRNA MEG3, and the results provide a promising strategy for HCC management.


Role of Oak Coumarins in the Taste of Wines and Spirits: Identification, Quantitation, and Sensory Contribution through Perceptive Interactions.
During barrel aging, wines and spirits undergo sensory changes as a result of the release of aroma and taste molecules. Among the nonvolatile compounds, various coumarins have already been identified in oak wood but their sensory role remained unclear. In this study, the presence of coumarins in oak wood extract, wine, and spirits was first assessed by targeted screening. Fraxetin was identified for the first time in these matrices. After development and validation of a liquid chromatography-high-resolution mass spectrometry quantitation method, esculetin, scopoletin, fraxetin, umbelliferone, 4-methylumbelliferone, and coumarin were assayed in various wines and spirits. The concentrations measured were generally below the gustatory detection thresholds determined in wines and spirits. Nevertheless, by adding a mixture of coumarins in wines and spirits, a significant increase in bitterness was observed, thus demonstrating their potential contribution to the taste of wines and spirits through perceptive interactions.


[A 74 year old patient with recurrent shock caused by hypopituitarism].
This article analyzes the case of a 74 year old patient who was hospitalized four times with recurrent complaints, which consisted of hypothermia, hypotension, weakness, and a hyponatremia, and were always caused by an underlying acute infection. Laboratory results showed an hypothyroidism, a secondary adrenal insufficiency, a secondary hypogonadism, and a growth hormone deficiency, which led to a diagnosis of pituitary dysfunction. Magnetic resonance imaging of the brain showed an 'empty sella', a non-visualization of the pituitary gland caused by an herniation of a supra-sellar cistern into the pituitary fossa. Considering the lack of an underlying pituitary tumor, a treatment consisting of partial hormonal substitution was started, eventually resulting in the full recovery of the patient.


Zinc transporter 8 haploinsufficiency protects against beta cell dysfunction in type 1 diabetes by increasing mitochondrial respiration.
Zinc transporter 8 (ZnT8) is a major humoral target in human type 1 diabetes (T1D). Polymorphic variants of Slc30A8, which encodes ZnT8, are also associated with protection from type 2 diabetes (T2D). The current study examined whether ZnT8 might play a role beyond simply being a target of autoimmunity in the pathophysiology of T1D. The phenotypes of NOD mice with complete or partial global loss of ZnT8 were determined using a combination of disease incidence, histological, transcriptomic, and metabolic analyses. Unexpectedly, while complete loss of ZnT8 accelerated spontaneous T1D, heterozygosity was partially protective. In vivo and in vitro studies of ZnT8 deficient NOD.SCID mice suggested that the accelerated disease was due to more rampant autoimmunity. Conversely, beta cells in heterozygous animals uniquely displayed increased mitochondrial fitness under mild proinflammatory conditions. In pancreatic beta cells and immune cell populations, Zn2+ plays a key role as a regulator of redox signaling and as an independent secondary messenger. Importantly, Zn2+ also plays a major role in maintaining mitochondrial homeostasis. Our results suggest that regulating mitochondrial fitness by altering intra-islet zinc homeostasis may provide a novel mechanism to modulate T1D pathophysiology.


A proposed method to predict preterm birth using clinical data, standard maternal serum screening, and cholesterol.
The objective of the study was to create a predictive model for preterm birth (PTB) from available clinical data and serum analytes. Serum analytes and routine pregnancy screening plus cholesterol and corresponding health information were linked to birth certificate data for a cohort of 2699 Iowa women with serum sampled in the first and second trimester. Stepwise logistic regression was used to select the best predictive model for PTB. Serum screening markers remained significant predictors of PTB, even after controlling for maternal characteristics. The best predictive model included maternal characteristics, first-trimester total cholesterol, total cholesterol change between trimesters, and second-trimester alpha-fetoprotein and inhibin A. The model showed better discriminatory ability than PTB history alone and performed similarly in subgroups of women without past PTB. Using clinical and serum screening data, a potentially useful predictor of PTB was constructed. Validation and replication in other populations, and incorporation of other measures that identify PTB risk, like cervical length, can be a step toward identifying additional women who may benefit from new or currently available interventions.


Genome-wide association study identifies an NLR gene that confers partial resistance to Magnaporthe oryzae in rice.
Because of the frequent breakdown of major resistance (R) genes, identification of new partial R genes against rice blast disease is an important goal of rice breeding. In this study, we used a core collection of the Rice Diversity Panel II (C-RDP-II), which contains 584 rice accessions and are genotyped with 700 000 single-nucleotide polymorphism (SNP) markers. The C-RDP-II accessions were inoculated with three blast strains collected from different rice-growing regions in China. Genome-wide association study identified 27 loci associated with rice blast resistance (LABRs). Among them, 22 LABRs were not associated with any known blast R genes or QTLs. Interestingly, a nucleotide-binding site leucine-rich repeat (NLR) gene cluster exists in the LABR12 region on chromosome 4. One of the NLR genes is highly conserved in multiple partially resistant rice cultivars, and its expression is significantly up-regulated at the early stages of rice blast infection. Knockout of this gene via CRISPR-Cas9 in transgenic plants partially reduced blast resistance to four blast strains. The identification of this new non-strain specific partial R gene, tentatively named rice blast Partial Resistance gene 1 (PiPR1), provides genetic material that will be useful for understanding the partial resistance mechanism and for breeding durably resistant cultivars against blast disease of rice.


Adsorption isotherms of homologous alkyldimethylbenzylammonium bromides on sodium montmorillonite.
The adsorption of homologous alkyldimethylbenzylammonium bromides, [C(6)H(5)CH(2)N(CH(3))(2)R]Br, on sodium montmorillonite from aqueous NaCl solutions at room temperature has been studied. R stands for the methyl-, butyl-, hexyl-, octyl-, decyl-, and dodecyl-group, and the corresponding ammonium cations will be denoted as C1+, C4+, C6+, C8+, C10+, and C12+, respectively. C1+, the reference cation, attains the plateau region of adsorption at a level close to the cation exchange capacity (CEC) of the clay. The chain-length dependence on adsorptivity of the homologous cations exhibits an unexpected peculiarity. In the case of short-chain homologues of C1+ their adsorption onto sodium montmorillonite decreases in the order C1+>C4+>C6+. This behavior is due, presumably, to the growing steric hindrances at the surface of clay, which occur because of the limited area available for the bulky organic cations at the exchange sites. These limitations appear to be out-balanced in the case of higher homologues for which the increasingly growing hydrophobic effects lead to the expected sequence of adsorptivity of the cations, i.e., C1+<C8+<C10+<C12+. The extent of adsorption of the long-chain homologous cations at the plateau region exceeds the CEC value and indicates the commencement of formation of a bilayer or admicelle. As expected, the adsorption data for the short-chain homologues fit fairly well to the Langmuir isotherm, whereas the data for the C10+ and C12+ cations show an increasing departure from linearity of the corresponding plots. Results of X-ray analysis of organo-clays fully loaded with C1+, C4+, and C12+ cations suggest that in the case of short-chain homologues, the ammonium cations lay flatly and interact relatively strongly with the montmorillonite packet surface, whereas the long-chain homologue forms an interdigitated system of coiled hydrocarbon chains.


The formation and stability of methyl phosphotriesters in the DNA of rat tissues after treatment with the carcinogen N,N-dimethylnitrosamine.
Following the injection i.p. of N,N-dimethylnitrosamine (DMN) into Chester Beatty (CB) hooded, female rats (2 mg/kg) measurable concentrations of methyl phosphotriesters were found in the DNA of liver, lung and kidney but not in spleen, thymus or brain. In lung and kidney these lesions were stable for at least 14 days but in liver there was a steady loss (t 1/2 9-11 days). Administering the same total dose in 10 weekly injections produced the same concentration of phosphotriesters in lung and kidney DNA as the single injection but in liver only half of the concentration induced by the single injection was found. It was calculated that the half-life of methyl phosphotriesters in the liver DNA of animals given repetitive injections was of the order of 6 weeks.


Temporal variations of perfluoroalkyl substances and polybrominated diphenyl ethers in alpine snow.
The occurrence and temporal variation of 18 perfluoroalkyl substances (PFASs) and 8 polybrominated diphenyl ethers (PBDEs) in the European Alps was investigated in a 10 m shallow firn core from Colle Gnifetti in the Monte Rosa Massif (4455 m above sea level). The firn core encompasses the years 1997-2007. Firn core sections were analyzed by liquid chromatography-tandem mass spectrometry (PFASs) and gas chromatography-mass spectrometry (PBDEs). We detected 12 PFASs and 8 PBDEs in the firn samples. Perfluorobutanoic acid (PFBA; 0.3-1.8 ng L(-1)) and perfluorooctanoic acid (PFOA; 0.2-0.6 ng L(-1)) were the major PFASs while BDE 99 (<MQL-4.5 ng L(-1)) and BDE 47 (n.d.-2.6 ng L(-1)) were the major PBDEs. This study demonstrates the occurrence of PFASs and PBDEs in the European Alps and provides the first evidence that PFASs compositions may be changing to PFBA-dominated compositions.


Size-dependent surface activity of rutile and anatase TiO2 nanocrystals: facile surface modification and enhanced photocatalytic performance.
The size-dependent surface activity of titania was illustrated through the formation of ultrafine nanocrystals with clean surfaces. It was demonstrated that, when the size of the nanocrystals was small enough, their surface activity could be significantly enhanced, as evidenced by the formation of transparent macroassemblies, their increased dispersity in various solvents, the facile modification of their surface by organic molecules at room temperature, their strong visible-light absorption through coordination with peroxide, and highly enhanced photocatalytic performance.


[Cranial and facial sutures: embryological aspects, anatomy and effects on orthopedic treatment].
In this work, the AA. have related the principal suture of the skull and the face, analysing the embryonal, functional and anatomic aspects, with particular reference to the times of end of growth and ossification. Furthermore, the AA. had explained the orthopedic appliances which influence, with their action, the activity of specific suture, emphasizing the growth period in which they are more efficient in the correction of the various dentofacial disharmonies.


Intestinal burying of the jejunal-tube of a PEG-J levodopa-carbidopa release system for Parkinson's disease. Successful endoscopic management.
Levodopa-carbidopa intestinal gel (LCIG) continuous infusion into the jejunum through a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J) is an alternative therapy for Parkinson's disease (PD) patients, with a very poor control of their symptoms on regular oral medications (Hoehn-Yahr stage IV). Around 62.2 % of patients present procedure and device-related adverse effects (AE), with an 8.2 % rate of mayor complications.


IgG-coated erythrocytes augment the lipopolysaccharidestimulated increase in serum tumor necrosis factor-alpha.
Previous studies have shown that the injection of IgG-coated erythrocytes (EIgG) caused an increase in the mortality rate due to bacterial lipopolysaccharide (LPS). This observation led to the present evaluation of the effect of EIgG on the LPS-stimulated increase in serum tumor necrosis factor-alpha (TNF-alpha) levels and TNF-alpha secretion by macrophages. The prior injection of EIgG augmented the increase in LPS-stimulated serum TNF-alpha levels ninefold at 1 h after LPS. Serum TNF-alpha levels were augmented when LPS was injected 2 or 6 h after EIgG but not at 0.5 or 12 h after EIgG. Complement activation caused by EIgG may contribute to the priming for TNF-alpha, because activation of complement with cobra venom factor caused a threefold augmentation of the LPS-stimulated serum TNF-alpha levels. Isolated macrophages that had ingested EIgG or were adherent to immobilized IgG showed augmented TNF-alpha secretion in response to LPS. Thus clearance of immune complexes from the blood can augment the LPS-stimulated increase in serum TNF-alpha levels that is due, in part, to complement activation and signaling via FcgammaR.


Co-expression network analysis of human tau-transgenic mice reveals protein modules associated with tau-induced pathologies.
Abnormally accumulated tau protein aggregates are one of the hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD). In order to investigate proteomic alteration driven by tau aggregates, we implemented quantitative proteomics to analyze disease model mice expressing human MAPT P301S transgene (hTau-Tg) and quantified more than 9,000 proteins in total. We applied the weighted gene co-expression analysis (WGCNA) algorithm to the datasets and explored protein co-expression modules that were associated with the accumulation of tau aggregates and were preserved in proteomes of AD brains. This led us to identify four modules with functions related to neuroinflammatory responses, mitochondrial energy production processes (including the tricarboxylic acid cycle and oxidative phosphorylation), cholesterol biosynthesis, and postsynaptic density. Furthermore, a phosphoproteomics study uncovered phosphorylation sites that were highly correlated with these modules. Our datasets represent resources for understanding the molecular basis of tau-induced neurodegeneration, including AD.


Proof of concept for a banding scheme to support risk assessments related to multi-product biologics manufacturing.
A banding scheme theory has been proposed to assess the potency/toxicity of biologics and assist with decisions regarding the introduction of new biologic products into existing manufacturing facilities. The current work was conducted to provide a practical example of how this scheme could be applied. Information was identified for representatives from the following four proposed bands: Band A (lethal toxins); Band B (toxins and apoptosis signals); Band C (cytokines and growth factors); and Band D (antibodies, antibody fragments, scaffold molecules, and insulins). The potency/toxicity of the representative substances was confirmed as follows: Band A, low nanogram quantities exert lethal effects; Band B, repeated administration of microgram quantities is tolerated in humans; Band C, endogenous substances and recombinant versions administered to patients in low (interferons), intermediate (growth factors), and high (interleukins) microgram doses, often on a chronic basis; and Band D, endogenous substances present or produced in the body in milligram quantities per day (insulin, collagen) or protein therapeutics administered in milligram quantities per dose (mAbs). This work confirms that substances in Bands A, B, C, and D represent very high, high, medium, and low concern with regard to risk of cross-contamination in manufacturing facilities, thus supporting the proposed banding scheme.


Advances in Biomarkers for Risk Stratification in Barrett's Esophagus.
Dysplasia currently is the primary biomarker used to risk stratify patients with Barrett's esophagus, but dysplasia has a number of considerable limitations in this regard. Thus, investigators over the years have explored innumerable alternative molecular biomarkers for risk stratification in Barrett's esophagus. This report focuses only on those biomarkers that appear most promising based on the availability of multiple published studies corroborating good results, and on the commercial availability of the test. These promising biomarkers include p53 immunostaining, TissueCypher, BarreGEN, and wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS3D).


Cell membrane-based biomimetic vehicles for effective central nervous system target delivery: Insights and challenges.
Central nervous system (CNS) disorders, including brain tumor, ischemic stroke, Alzheimer's disease, and Parkinson's disease, threaten human health. And the existence of the blood-brain barrier (BBB) hinders the delivery of drugs and the design of drug targeting delivery vehicles. Over the past decades, great interest has been given to cell membrane-based biomimetic vehicles since the rise of targeting drug delivery systems and biomimetic nanotechnology. Cell membranes are regarded as natural multifunction biomaterials, and provide potential for targeting delivery design and modification. Cell membrane-based biomimetic vehicles appear timely with the participation of cell membranes and nanoparticles, and raises new lights for BBB recognition and transport, and effective therapy with its biological multifunction and high biocompatibility. This review summarizes existing challenges in CNS target delivery and recent advances of different kinds of cell membrane-based biomimetic vehicles for effective CNS target delivery, and deliberates the BBB targeting mechanism. It also discusses the challenges and possibility of clinical translation, and presents new insights for development.


Effect of CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor on pulmonary ventilation derived by 3D phase-resolved functional lung MRI in cystic fibrosis patients.
To investigate whether 3D phase-resolved functional lung (PREFUL)-MRI parameters are suitable to measure response to elexacaftor/tezacaftor/ivacaftor (ETI) therapy and their association with clinical outcomes in cystic fibrosis (CF) patients. Twenty-three patients with CF (mean age: 21; age range: 14-46) underwent MRI examination at baseline and 8-16 weeks after initiation of ETI. Morphological and 3D PREFUL scans assessed pulmonary ventilation. Morphological images were evaluated using a semi-quantitative scoring system, and 3D PREFUL scans were evaluated by ventilation defect percentage (VDP) values derived from regional ventilation (RVent) and cross-correlation maps. Improved ventilation volume (IVV) normalized to body surface area (BSA) between baseline and post-treatment visit was computed. Forced expiratory volume in 1 second (FEV1) and mid-expiratory flow at 25% of forced vital capacity (MEF25), as well as lung clearance index (LCI), were assessed. Treatment effects were analyzed using paired Wilcoxon signed-rank tests. Treatment changes and post-treatment agreement between 3D PREFUL and clinical parameters were evaluated by Spearman's correlation. After ETI therapy, all 3D PREFUL ventilation markers (all p < 0.0056) improved significantly, except for the mean RVent parameter. The BSA normalized IVVRVent was significantly correlated to relative treatment changes of MEF25 and mucus plugging score (all |r| > 0.48, all p < 0.0219). In post-treatment analyses, 3D PREFUL VDP values significantly correlated with spirometry, LCI, MRI global, morphology, and perfusion scores (all |r| > 0.44, all p < 0.0348). 3D PREFUL MRI is a very promising tool to monitor CFTR modulator-induced regional dynamic ventilation changes in CF patients. 3D PREFUL MRI is sensitive to monitor CFTR modulator-induced regional ventilation changes in CF patients. Improved ventilation volume correlates with the relative change of mucus plugging, suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement. • 3D PREFUL MRI-derived ventilation maps show significantly reduced ventilation defects in CF patients after ETI therapy. • Significant post-treatment correlations of 3D PREFUL ventilation measures especially with LCI, FEV1 %pred, and global MRI score suggest that 3D PREFUL MRI is sensitive to measure improved regional ventilation of the lung parenchyma due to reduced inflammation induced by ETI therapy in CF patients. • 3D PREFUL MRI-derived improved ventilation volume (IVV) correlated with MRI mucus plugging score changes suggesting that reduced endobronchial mucus is predominantly responsible for regional ventilation improvement 8-16 weeks after ETI therapy.


Neonatal onset of mitochondrial disorders in 129 patients: clinical and laboratory characteristics and a new approach to diagnosis.
Mitochondrial disorders (MD) may manifest in neonates, but early diagnosis is difficult. In this study, clinical and laboratory data were analyzed in 129 patients with neonatal onset of MD to identify any association between specific mitochondrial diseases and their symptoms with the aim of optimizing diagnosis. Retrospective clinical and laboratory data were evaluated in 461 patients (331 families) with confirmed MD. The neonatal onset of MD was reported in 28% of the patients. Prematurity, intrauterine growth retardation and hypotonia necessitating ventilatory support were present in one-third, cardiomyopathy in 40%, neonatal seizures in 16%, Leigh syndrome in 15%, and elevated lactate level in 87%. Hyperammonemia was observed in 22 out of 52 neonates. Complex I deficiency was identified in 15, complex III in one, complex IV in 23, complex V in 31, combined deficiency of several complexes in 53, and PDH complex deficiency was identified in six patients. Molecular diagnosis was confirmed in 49 cases, including a newborn with a 9134A>G mutation in the MTATP6 gene, which has not been described previously. The most significant finding is the high incidence of neonatal cardiomyopathy and hyperammonemia. Based on our experience, we propose a diagnostic flowchart applicable to critically ill neonates suspicious for MD. This tool will allow for the use of direct molecular genetic analyses without the need for muscle biopsies in neonates with Alpers, Barth, MILS and Pearson syndromes, SCO1, SCO2, TMEM70, ATP5E, SUCLG1 gene mutations and PDH complex deficiency.


Transcriptome and metabolome analyses of Shatian pomelo (Citrus grandis var. Shatinyu Hort) leaves provide insights into the overexpression of the gibberellin-induced gene CcGASA4.
The gibberellic acid (GA)-stimulated Arabidopsis (GASA) gene family is highly specific to plants and plays crucial roles in plant growth and development. CcGASA4 is a member of the GASA gene family in citrus plants; however, the current understanding of its function in citrus is limited. We used CcGASA4-overexpression transgenic citrus (OEGA) and control (CON) plants to study the role of CcGASA4 in Shatian pomelo. The RNA sequencing (RNA-seq) analysis showed that 3,522 genes, including 1,578 upregulated and 1,944 downregulated genes, were significantly differentially expressed in the CON versus OEGA groups. The Gene Ontology enrichment analysis showed that 178 of the differentially-expressed genes (DEGs) were associated with flowers. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were enriched in 134 pathways, including "plant-pathogen interaction", "MAPK signaling pathway-plant", "phenylpropane biosynthesis", "plant hormone signal transduction", "phenylalanine, tyrosine and tryptophan biosynthesis", and "flavonoid and flavonol biosynthesis". The most significantly-enriched pathway was "plant-pathogen interaction", in which 203 DEGs were enriched (126 DEGs were upregulated and 78 were downregulated). The metabolome analysis showed that 644 metabolites were detected in the OEGA and CON samples, including 294 differentially-accumulated metabolites (DAMs; 83 upregulated versus 211 downregulated in OEGA compared to CON). The metabolic pathway analysis showed that these DAMs were mainly involved in the metabolic pathways of secondary metabolites, such as phenylpropanoids, phenylalanine, flavone, and flavonol biosynthesis. Thirteen flavonoids and isoflavones were identified as DAMs in OEGA and CON. We also discovered 25 OEGA-specific accumulated metabolites and found 10 that were associated with disease resistance. CcGASA4 may therefore play a functional role in activating the expression of MAPK signaling transduction pathway and disease resistance genes, inhibiting the expression of auxin- and ethylene-related genes, and activating or inhibiting the expression of brassinosteroid biosynthesis- and abscisic acid-related genes. CcGASA4 may also play a role in regulating the composition and abundance of flavonoids, isoflavones, amino acids, purines, and phenolic compounds. This study provides new insights into the molecular mechanisms of action of CcGASA4 in citrus plants.