Effect of alkaline and alkaline-photocatalytic pretreatment on characteristics and biogas production of rice straw.
To overcome recalcitrant nature and investigate enhancement of biogas production of rice straw (RS), it was subjected to pretreatment under mild conditions. Alkaline pretreatment using sodium hydroxide (NaOH), photocatalytic pretreatment utilizing titania nanoparticles (TiO2 NPs) and alkaline-photocatalytic pretreatment was used to disrupt the lignocellulose complex. As compared to raw RS, maximum biogas and methane enhancement due to alkaline pretreatment was observed for 1.5% w/v NaOH pretreated RS which was 50 and 71% respectively. Photocatalytic pretreatment of RS at 0.25 g/L TiO2 increased biogas and methane yield by 30 and 36% respectively. However, maximum biogas and methane enhancement was observed for alkaline-photocatalytic pretreatment at 1.5% w/v NaOH-0.25 g/L TiO2 which was 74 and 122% respectively. Comparatively high enhancements were observed during alkaline-photocatalytic combined pretreatment due to increased cellulose and decreased lignin content. Moreover, the experimental data obtained from the experiments were validated using a non-linear kinetic model.


Promoting an equitable and supportive school climate in high schools: the role of school organizational health and staff burnout.
In response to persistent racial disparities in academic and behavioral outcomes between Black and White students, equitable school climate has drawn attention as a potential target for school reform. This study examined differences in Black and White students' experiences of school climate and explored whether indicators of school organizational health and staff burnout moderated differences in students' school experiences by race. Utilizing hierarchical linear modeling with a sample of 18,397 Black students (n=6228) and White students (n=12,169) and 2391 school staff in 53 schools, we found a consistent pattern of racial inequalities, such that Black students reported less positive experiences than White students across three indicators of school climate (caring γ=-0.08, p<.001; equity γ=-0.05, p=.007; and engagement γ=-0.05, p<.001). In addition, we found significant, positive associations between aggregated staff-report of school organizational health and student-reported school climate (e.g., staff affiliation and student-perceived equity, γ=0.07, p<.001). Surprisingly, a number of school organizational health indicators were more strongly associated with positive perceptions of school climate among White students than Black students, translating into greater racial disparities in perceived school climate at schools with greater organizational health (e.g., supportive leadership by race on student-perceived engagement, γ=-0.03, p=.042). We also found negative associations between staff-reported burnout and students' experience of equity, such that the racial gap was smaller in schools with high ratings of burnout (γ=0.04, p=.002). These findings have implications for educators and education researchers interested in promoting school social contexts that equitably support student engagement and success.


Presence of central veins and susceptibility weighted imaging for evaluating lesions in multiple sclerosis and leukoaraiosis.
The process of demyelination in multiple sclerosis (MS) is reflected in lesions of the central nervous system (CNS), which are found in an abundance of different diseases and are frequently radiographically indistinguishable. Our aim was to determine whether the perivenous distribution of MS lesions identified on susceptibility weighted images (SWI) could be used as a specific radiographic sign for MS, and also to determine whether the visibility of the central vein (CV) is affected by the activity of MS lesions. We retrospectively examined 34 subjects with MS and 19 subjects with ischemic lesions, which underwent a 3T MRI investigation. According to FLAIR and T2-weighted sequences the lesions were categorized regarding location. The presence of CVs was determined on SWI. Gadolinium enhanced T1-weighted sequence was included for the evaluation of MS lesion activity. A total load of 601 MS and 204 ischemic lesions was identified. We found significantly more lesions with CVs in the group with ischemic lesions compared to the group with MS lesions (p<0.001). Similarly, significantly more supratentorial peripheral ischemic lesions had CVs (p=0.011), whereas in supratentorial periventricular and intratentorial lesions we found no significant difference between the two groups (p=0.377 and p=0.615). Comparing the active and inactive MS lesions regarding CVs, we found no significant difference between the groups (p=0,472). We can conclude that the presence of a CV is not a specific radiographic sign for MS. CVs can also be identified in lesions caused by various other diseases.


Study on cyanidin metabolism in petals of pink-flowered strawberry based on transcriptome sequencing and metabolite analysis.
Pink-flowered strawberry is a promising new ornamental flower derived from intergeneric hybridization (Fragaria × Potentilla) with bright color, a prolonged flowering period and edible fruits. Its flower color ranges from light pink to red. Pigment compounds accumulated in its fruits were the same as in cultivated strawberry fruits, but different from that in its flowers. However, the transcriptional events underlying the anthocyanin biosynthetic pathway have not been fully characterized in petal coloration. To gain insights into the regulatory networks related to anthocyanin biosynthesis and identify the key genes, we performed an integrated analysis of the transcriptome and metabolome in petals of pink-flowered strawberry. The main pigments of red and dark pink petals were anthocyanins, among which cyanidins were the main compound. There were no anthocyanins detected in the white-flowered hybrids. A total of 50,285 non-redundant unigenes were obtained from the transcriptome databases involved in red petals of pink-flowered strawberry cultivar Sijihong at three development stages. Amongst the unigenes found to show significant differential expression, 57 were associated with anthocyanin or other flavonoid biosynthesis, in which they were regulated by 241 differentially expressed members of transcription factor families, such as 40 MYBs, 47 bHLHs, and 41 NACs. Based on a comprehensive analysis relating pigment compounds to gene expression profiles, the mechanism of flower coloration was examined in pink-flowered strawberry. A new hypothesis was proposed to explain the lack of color phenotype of the white-flowered strawberry hybrids based on the transcriptome analysis. The expression patterns of FpDFR and FpANS genes corresponded to the accumulation patterns of cyanidin contents in pink-flowered strawberry hybrids with different shades of pink. Moreover, FpANS, FpBZ1 and FpUGT75C1 genes were the major factors that led to the absence of anthocyanins in the white petals of pink-flowered strawberry hybrids. Meanwhile, the competitive effect of FpFLS and FpDFR genes might further inhibit anthocyanin synthesis. The data presented herein are important for understanding the molecular mechanisms underlying the petal pigmentation and will be powerful for integrating novel potential target genes to breed valuable pink-flowered strawberry cultivars.


Cell penetrating peptide functionalized perfluorocarbon nanoemulsions for targeted cell labeling and enhanced fluorine-19 MRI detection.
A bottleneck in developing cell therapies for cancer is assaying cell biodistribution, persistence, and survival in vivo. Ex vivo cell labeling using perfluorocarbon (PFC) nanoemulsions, paired with 19 F MRI detection, is a non-invasive approach for cell product detection in vivo. Lymphocytes are small and weakly phagocytic limiting PFC labeling levels and MRI sensitivity. To boost labeling, we designed PFC nanoemulsion imaging probes displaying a cell-penetrating peptide, namely the transactivating transcription sequence (TAT) of the human immunodeficiency virus. We report optimized synthesis schemes for preparing TAT co-surfactant to complement the common surfactants used in PFC nanoemulsion preparations. We performed ex vivo labeling of primary human chimeric antigen receptor (CAR) T cells with nanoemulsion. Intracellular labeling was validated using electron microscopy and confocal imaging. To detect signal enhancement in vivo, labeled CAR T cells were intra-tumorally injected into mice bearing flank glioma tumors. By incorporating TAT into the nanoemulsion, a labeling efficiency of ~1012 fluorine atoms per CAR T cell was achieved that is a >8-fold increase compared to nanoemulsion without TAT while retaining high cell viability (~84%). Flow cytometry phenotypic assays show that CAR T cells are unaltered after labeling with TAT nanoemulsion, and in vitro tumor cell killing assays display intact cytotoxic function. The 19 F MRI signal detected from TAT-labeled CAR T cells was 8 times higher than cells labeled with PFC without TAT. The peptide-PFC nanoemulsion synthesis scheme presented can significantly enhance cell labeling and imaging sensitivity and is generalizable for other targeted imaging probes.


Evolution of cytokine responses: IL-1beta directly affects intracellular Ca2+ concentration of teleost fish leukocytes through a receptor-mediated mechanism.
In this work we studied the biological activities of recombinant IL-1beta from the teleosts sea bass (Dicentrarchus labrax) and rainbow trout (Oncorhynchus mykiss) by investigating the effects induced on intracellular Ca2+ concentrations ([Ca2+]i) of spleen leucocytes. Splenocytes were loaded with the Ca2+-permeant Fura-2AM, and then stimulated with rIL-1beta. The emitted fluorescence was read for 5 min at 1 min intervals on a dual excitation fluorescence fluorimeter. Results showed that rIL-1beta induced in both species a rise in [Ca2+]i, and a subsequent decrease until 5 min after stimulation. The stimulating effect was dose-dependent in both species reaching a plateau at 200 ng/ml of rIL-1beta, was abolished by heat-treatment of rIL-1beta, and affected in a dose-dependent fashion by treatment of leucocytes with trypsin. These features suggested a functional IL-1 receptor was involved in the binding. The observed rise in [Ca2+]i was not detected in human PBMC and was species-specific, since rIL-1beta from sea bass, trout, and human were unable to interfere each other in the assay. Moreover, incubation of splenocytes with rIL-1beta induced a rapid tyrosine phosphorylation of a 24 kDa polypeptide in both species. This work represents the first evidence of a direct effect on [Ca2+]i induced by IL-1beta and suggests that in the evolution of IL-1 activities, teleost fishes display a peculiar IL-1-associated behaviour that is lacking in mammals.


Gene editing and modulation for Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by loss of dystrophin protein, encoded by the DMD gene. DMD manifests early in childhood as difficulty walking, progresses to loss of ambulation by the teens, and leads to death in early adulthood. Adeno-associated virus-vectorized gene therapies to restore dystrophin protein expression using gene replacement or antisense oligonucleotide-mediated pre-mRNA splicing modulation have emerged, making great strides in uncovering barriers to gene therapies for DMD and other genetic diseases. While this first-generation of DMD therapies are being evaluated in ongoing clinical trials, uncertainties regarding durability and therapeutic efficacy prompted the development of new experimental therapies for DMD that take advantage of somatic cell gene editing. These experimental therapies continue to advance toward clinic trials, but questions remain unanswered regarding safety and translatable efficacy. Here we review the advancements toward treatment of DMD using gene editing and modulation therapies, with an emphasis on those nearest to clinical applications.


Disorders of eating behavior: correlation between hypothalamo-pituitary-thyroid function and psychopathological aspects.
Altered pituitary-thyroid (PT) function (TSH, FT4, FT3 plasma levels) was correlated with symptoms of Eating Disorders (ED) in 137 patients (65 ANR, 12 ANP, 19 ANBP, 26 BN, 8 EDNOS-AN, 7 EDNOS-BN) and 30 controls. PT hormone concentrations were assessed by immunofluorimetry and psychopathology by EDI-2 and HSCL-90. Values of TSH were decreased in ANP, BN, EDNOS-AN, of T4 in ANR, ANP, AN-BP, of T3 in ANR, ANP, ANBP, BN, EDNOS-AN, EDNOS-BN. TSH values correlated negatively with ineffectiveness in BN and EDNOS-AN, and with depression in EDNOS-AN. FT4 values correlated positively with perfectionism in ANR, ANP and ANBP, with interoceptive awareness in EDNOS-AN, and negatively with depression in EDNOS-AN and with body dissatisfaction in EDNOS-BN. FT3 values correlated positively with perfectionism in ANBP and BN, with ineffectiveness in ANR and ANP, with depression in EDNOS-AN, with hostility in ANR and EDNOS-BN, with interpersonal sensibility in ANP, with somatization in EDNOS-BN, and negatively with interpersonal distrust in EDNOS-AN. Prospective studies are needed to confirm whether or not altered PT parameters correlate with ED symptoms during the course of the diseases.


Cryo-EM structure of mammalian RNA polymerase II in complex with human RPAP2.
Nuclear import of RNA polymerase II (Pol II) involves the conserved factor RPAP2. Here we report the cryo-electron microscopy (cryo-EM) structure of mammalian Pol II in complex with human RPAP2 at 2.8 Å resolution. The structure shows that RPAP2 binds between the jaw domains of the polymerase subunits RPB1 and RPB5. RPAP2 is incompatible with binding of downstream DNA during transcription and is displaced upon formation of a transcription pre-initiation complex.


How stealthy are PEG-PLA nanoparticles? An NIR in vivo study combined with detailed size measurements.
Detailed in vivo and ex vivo analysis of nanoparticle distribution, accumulation and elimination processes were combined with comprehensive particle size characterizations. The in vivo fate of near infrared (NIR) nanoparticles in nude mice was carried out using the Maestro™ in vivo fluorescence imaging system. Asymmetrical field flow field fractionation (AF4) coupled with multi-angle laser light scattering (MALLS), photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) were employed for detailed in vitro characterization. PEG-PLA block polymers were synthesized and used for the production of defined, stable, nontoxic nanoparticles. Nanoparticle analysis revealed narrow size distribution; AF4/MALLS permitted further accurate size evaluation. Multispectral fluorescence imaging made it possible to follow the in vivo fate non-invasively even in deep tissues over several days. Detailed fluorescence ex vivo imaging studies were performed and allowed to establish a calculation method to compare nanoparticle batches with varying fluorescence intensities. We combined narrow-size distributed nanoparticle batches with detailed in vitro characterization and the understanding of their in vivo fate using fluorescence imaging, confirming the wide possibilities of the non-invasive technique and presenting the basis to evaluate future size-dependent passive tumor accumulation studies.


Short duration of dual antiplatelet therapy following complex percutaneous coronary intervention: A systematic review and meta-analysis.
The optimal composition and duration of antiplatelet therapy after complex percutaneous coronary intervention (PCI) remains unclear. We conducted a meta-analysis to compare 1-3 months of dual antiplatelet therapy (DAPT) followed by monotherapy vs. 12 months of DAPT. MEDLINE/PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were queried for studies comparing 1-3 months of DAPT followed by monotherapy vs. 12 months of DAPT in the outcomes of complex PCI from inception through January 2023. Outcomes of interest included major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, target vessel revascularization, and stroke. Compared to 12 months, 1-3 months of dual antiplatelet therapy had a weak association with less major bleeding (OR 0.67; 95 % CI, 0.44-1.00; p = 0.05; I2 = 28 %). There were no significant differences between the shorter and longer antiplatelet therapy in terms of all-cause mortality (OR 0.83; 95 % CI, 0.59-1.16; p = 0.21; I2 = 17 %), cardiovascular mortality (OR 0.87; 95 % CI, 0.53-0.42; p = 0.50; I2 = 0), MI (OR 0.97; 95 % CI, 0.69-1.35; p = 0.82; I2 = 32 %), stent thrombosis (OR 1.17, 95 % CI, 0.77-1.76; p = 0.38; I2 = 0 %), target vessel revascularization (OR 1.05, 95 % CI, 0.58-1.89; p = 0.82; I2 = 64 %), or stroke (OR 1.10, 95 % CI, 0.55-2.17; p = 0.37; I2 = 7 %);. Among patients undergoing complex PCI, DAPT for 1-3 months may be associated with less major bleeding but similar rates of cardiovascular events (death, MI, stroke, stent thrombosis, and revascularization) compared to DAPT for 12 months.


Nosocomial pneumonia: a cost-of-illness analysis.
We investigated incremental cost of nosocomial pneumonia (NP) from the perspective of a hospital and health insurance funds. The incremental cost was determined by calculating total costs for pneumonia patients and controls using prospective and retrospective matched-pairs analysis with 29 and 37 matched pairs, respectively. Compared to controls, patients who developed pneumonia had to be on artificial ventilation 5 days longer, needed markedly more intensive care with 6.55 additional days in intensive care. Excess cost per pneumonia patient amounted to DM 14,606 (95% CI: DM 5,285-23,927) from the hospital's perspective and to DM 7,988 (95% CI: DM 5,281-10,894) according to statutory insurance charges. According to the retrospective anaLysis carried out on the neurosurgical and neurological intensive care wards, pneumonia patients were ventiLated 5 days longer than patients without pneumonia, needed more intensive care over 30 days and had an additional 14.03 days of intensive care and 10.14 more days in hospital. Excess cost per patient was DM 29,610 (95% CI: DM 23,054-36,174) from the hospitals perspective and DM 18,000 (95% CI: 14,885-21,020) according to the statutory insurance criteria. The study gives insight into the structure of incremental cost caused by NP and shows that based on a conservative cost calculation the incremental cost per NP patient is higher for the hospital than for health insurance funds which indicates a significant financial deficit for the hospital. Antibiotics and microbiology together only contribute 6.8% to incremental cost. Therefore in a cost saving initiative their close relationship to length of hospitalization must be considered.


The LH/FSH ratio has little use in diagnosing polycystic ovarian syndrome.
The luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is often requested to help diagnose polycystic ovarian syndrome (PCOS) despite a recent consensus recommending against its use. This study aimed to compare the variability of the LH/FSH ratio in PCOS with that of normal menstruating women over a full cycle in order to establish the diagnostic utility, or otherwise, of the test. Twelve women with PCOS and 11 matched controls had blood collected at four-day intervals on 10 consecutive occasions over a complete menstrual cycle. The median LH/FSH ratio for individual subjects did not differ significantly between the PCOS and the non-affected group (1.6 versus 1.2, P = 0.14). Only 7.6% of samples from PCOS patients had an LH/FSH ratio above three, compared with 15.6% of samples from normal subjects. This study confirms that measurement of the LH/FSH ratio is of limited use in the diagnosis of PCOS.


Minimally invasive surfactant therapy for moderate to late premature neonates with respiratory distress syndrome born in a non-tertiary unit.
Minimally invasive surfactant therapy (MIST) is used to deliver exogenous surfactant to preterm neonates with respiratory distress syndrome. The objective of this study was to review the use of MIST in moderate to late preterm neonates born in a non-tertiary unit. A retrospective review was conducted of neonates receiving MIST in a non-tertiary unit. MIST was considered in neonates requiring continuous positive airway pressure ≥ 6 cm H2 O and fraction of inspired oxygen ≥ 0.35. The Hobart method was used to deliver exogenous surfactant. The primary outcome was improvement in respiratory function. Secondary outcomes include intubation and transfer to a tertiary unit. Between 2016 and 2020, 23 infants were treated with MIST. The median gestational age was 33+5 ± 2.7 weeks and mean age of surfactant administration was 6.6 ± 3.6 h. Surfactant administration resulted in a reduction in median fraction of inspired oxygen from 0.3 to 0.21 at 4 h post MIST (P value: 0.001), and a reduction in median positive end-expiratory pressure (PEEP) from 7 to 6 cm H2 O at 24 h post MIST (P value: 0.003). Continuous positive airway pressure support was required for a median period of 3.5 days following MIST. There was respiratory improvement in 52 and 65% of neonates at 4 and 24 h, respectively, following MIST. The incidence of intubation was 13% and transfer to a tertiary unit was 44%. Use of MIST at this unit improved respiratory outcomes in moderate to late preterm neonates with respiratory distress syndrome. This procedure was well tolerated with few adverse events. Further research evaluating the efficacy of MIST in other non-tertiary units is warranted.


Placebo effect of nitrate monotherapy for myocardial ischemia.
Nitrate monotherapy was assessed by treadmill exercise stress testing in 18 patients with significant but relatively asymptomatic myocardial ischemia who were receiving no other antianginal therapy. In addition, prolonged ambulatory electrocardiographic monitoring was performed in 7 patients with demonstrable ischemia during baseline monitoring. After baseline assessment, 5 treatment periods were used in a random order (each of 1 week duration), incorporating 2 dose levels of transdermal nitrate (10 and 20 mg/24 hours) and isosorbide dinitrate (ISDN) (30 and 60 mg/day in divided doses) with a 10-hour nitrate-free interval every 24 hours, as well as a placebo period using a double-blind technique. All treatment periods (including placebo) showed a significant (p < 0.01) 45 to 69% prolongation in the time to 1 mm ST depression during exercise. Paired baseline times of 231 +/- 28 and 233 +/- 30 seconds increased to 367 +/- 37 seconds with 30 mg/day of ISDN, 393 +/- 37 seconds with 60 mg/day of ISDN, 381 +/- 31 seconds with 10 mg/day of transdermal nitrate, and 372 +/- 33 seconds with 20 mg/day of transdermal nitrate. The value for placebo was 342 +/- 29 seconds, which was not significantly different from active treatment (p > 0.1). Some patients appeared to individually respond to > or = 1 nitrate preparation significantly more than to placebo, but this appeared to be unpredictable and largely independent of dosage level and route of administration. There was a qualitatively similar but statistically insignificant reduction in total ischemic time during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)


IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts.
Insulin-like growth factor (IGF) signaling is critical for osteoblast development and IGF binding protein (IGFBP)-4 is one of the principle IGFBPs expressed by osteoblasts. Release of bound IGF via proteolytic degradation of IGFBP-4 is likely to be critical for osteoblast development. We have investigated whether IGF-sensitive, IGFBP-4 degradation in mouse MC3T3-E1 osteoblasts is due to the metzincin pregnancy-associated plasma protein (PAPP)-A. Degradation of IGFBP-4 by PAPP-A or MC3T3-E1 conditioned medium was enhanced by IGF-II but inhibited by mutation of basic residues at or near the PAPP-A cleavage site in IGFBP-4. Furthermore, immunodepletion of PAPP-A from MC3T3-E1 conditioned medium abolished IGFBP-4 degradation. We also found that PAPP-A messenger RNA was expressed throughout differentiation of MC3T3-E1 cells. These results demonstrate for the first time that PAPP-A is the IGFBP-4 protease in MC3T3-E1 cells, a widely used model for osteoblast development, and that PAPP-A may regulate IGF release throughout osteoblast differentiation.


Twin pregnancy after ICSI in a patient with ovarian cancer complicated with maternal hepatitis C: case report.
Fertility sparing surgery was carried out for an epithelial ovarian cancer patient. After adjuvant chemotherapy, she underwent assisted reproduction and gave birth to twins. She was given alpha-Interferon therapy for hepatitis C during pregnancy.


Immunofluorescent detection of actin and myosin in healing gingival epithelium.
Indirect immunofluorescent labeling shows a sequential increase in detectable epithelial cell actin and myosin during wound repair migration and maturation. While actin shows a substantial increase between pre-wound and migration levels, the relative detectable myosin is omnipresent at apparently high levels, and it increases only slightly during active migration.


Inhibition of nitrification by low oxygen concentrations in an aerated treatment pond system with biofilm promoting mats.
Inhibition of nitrification in the presence of low oxygen concentrations (below 1.2 mg/L) and temperature dependency at oxygen saturation levels were observed in an aerated treatment pond system with biofilm promoting mats in two parallel ponds for remediation of ammonium, methyl tertiary butyl ether (MTBE), and benzene-contaminated groundwater. Within the first 18 months, at an average oxygen concentration of 0.7 +/- 0.5 mg/L along the ponds, no significant decrease of ammonium or significant formation of nitrification products were observed. After increasing the aeration to oxygen saturation levels, the ammonium removal increased up to a maximum of 27%, with concomitant formation of nitrite and nitrate (up to 26 and 0.6 mM). The subsequent reduction of aeration in one pond to the previous level resulted in a definitive stop of nitrification, while, in the other pond, nitrification was well-correlated with the water temperature, reaching up to 45% ammonium removal.


Increased vascular permeability in the rabbit iris induced by prostaglandin E1. An electron microscopic study using lanthanum as a tracer in vivo.
Prostaglandin E1 (PGE1) (25 micrograms) was applied topically to the eyes of albino rabbits, and lanthanum was used as an electron microscopic tracer to study possible vascular permeability changes in the iris of these eyes. Lanthanum was injected directly into the blood circulation 15 min after application of the PG, and the eyes were enucleated 30 to 60 min later. PGE1 was found to induce increased vascular permeability. Heavy deposits of the tracer were found in the walls of iridial venules, especially between the endothelium and its basement lamina. The highest concentration of lanthanum was found in close relation to the interendothelial clefts. Occasionally, gaps between neighbouring endothelial cells were observed. In control eyes, not treated with PG, no extravasation of the tracer was found. The study indicates that the iridial blood vessels contribute to the production of the plasmoid aqueous humour induced by PGE1 in the rabbit eye.


Cellular battle against endoplasmic reticulum stress and its adverse effect on health.
The endoplasmic reticulum (ER) is a dynamic organelle and a reliable performer for precisely folded proteins. To maintain its function and integrity, arrays of sensory and quality control systems enhance protein folding fidelity and resolve the highest error-prone areas. Yet numerous internal and external factors disrupt its homeostasis and trigger ER stress responses. Cells try to reduce the number of misfolded proteins via the UPR mechanism, and ER-related garbage disposals systems like ER-associated degradation (ERAD), ER-lysosome-associated degradation (ERLAD), ER-Associated RNA Silencing (ERAS), extracellular chaperoning, and autophagy systems, which activates and increase the cell survival rate by degrading misfolded proteins, prevent the aggregated proteins and remove the dysfunctional organelles. Throughout life, organisms must confront environmental stress to survive and develop. Communication between the ER & other organelles, signaling events mediated by calcium, reactive oxygen species, and inflammation are linked to diverse stress signaling pathways and regulate cell survival or cell death mechanisms. Unresolved cellular damages can cross the threshold limit of their survival, resulting in cell death or driving for various diseases. The multifaceted ability of unfolded protein response facilitates the therapeutic target and a biomarker for various diseases, helping with early diagnosis and detecting the severity of diseases.


Creatine phosphate (Neoton) as an additive to St. Thomas' Hospital cardioplegic solution (Plegisol). Results of a clinical study.
Experimentally, creatine phosphate (CP) added to St. Thomas' Hospital cardioplegic solution (STH) improved post-ischaemic recovery of cardiac function in the rat heart. We investigated the effect of adding CP (10.0 mmol/l) to STH. Fifty open-heart surgery patients were randomized into control (STH) and treated (STH + CP) groups (25 per group). Patients underwent (a) monitoring for peri- and postoperative arrhythmias (48-h Holter monitoring). (b) quantitative birefringence assessment of intraoperative myocardial protection in left and right ventricular biopsies sampled at start of bypass (pre-isch.), end of bypass (end-isch.) and after 10 min reperfusion (post-isch.), and (c) measurement of serum creatine kinase-MB isozyme (CK-MB) values for up to 4 days postoperatively; results were assessed with respect to (d) haemodynamics and postoperative clinical outcome. Inotropic support (adrenaline) was required in three patients (12%) from each group; no patient died. All patients required defibrillation, and the number of direct current shocks required for sinus rhythm was the same in each group. The occurrence and incidence of reperfusion-induced arrhythmias were the same in both groups. Serum CK and CK-MB values were similar throughout the sampling period in both groups of patients; one patient in the control group had raised CK-MB levels postoperatively, but perioperative infarction was not indicated by the electrocardiogram.(ABSTRACT TRUNCATED AT 250 WORDS)


Chemical and mechanical accelerated and long-term stability evaluation of sunscreen formulation containing grape seed extract.
Sunscreens and catechins from grape seed extract (GSE) are sensitive to various environmental factors and undergo certain changes over time that might affect the effectiveness of the final product. To this date, effects of thermal storage conditions have not been sufficiently addressed to guarantee the long-term stability of sunscreen formulations. To study the chemical and mechanical accelerated and long-term stability of sunscreen formulation containing GSE at the Climatic Zone IVb conditions. Stability studies were performed for 6 months for accelerated stability study at 30°C ± 2 and 50°C ± 2, 75 ± 5% relative humidity; and long-term stability study at 5°C ± 5. The quantification of constituents of three formulations: sunscreen with GSE, cream with UV filters only, and cream with GSE only was performed by high-performance liquid chromatography. In vitro spectrophotometry was used to determine changes in sun protection effectiveness through SPF and UVAPF values. Mechanical stability was evaluated by textural and rheological analyzes. All tested formulations were less stable at high-temperature conditions. The contents of catechin (С) and epicatechin (EC) in sunscreen with GSE were reduced to 37% and 50% at 50°C, respectively, whereas UV filters appeared to be stable. However, despite the significant reduction in catechins over time, polyphenols in GSE remained unchanged at different stored conditions. The SPF values and water resistance of sunscreen with GSE were maintained throughout the study. A current in vitro study has shown that sunscreen with GSE is a value-added anti-aging ingredient in sunscreen formulation because its polyphenolic composition as well as SPF values and water resistance were maintained under all temperature conditions over time.


Core needle biopsy. A useful adjunct to fine-needle aspiration in select patients with palpable breast lesions.
Fine-needle aspiration (FNA) biopsy is an established, highly accurate method for diagnosing palpable breast lesions. However, in some cases a definitive diagnosis cannot be made by FNA alone, either due to the inherent limitations of cytology itself or the ability to obtain adequate material for diagnosis. This study evaluated the usefulness of a supplemental core needle biopsy performed by a cytopathologist in conjunction with an FNA biopsy in select patients. Twelve patients with palpable breast lesions underwent the combined FNA/core needle biopsy procedure during the study period from March 1995 through March 1996. All 12 patients first had an FNA aspiration that was preliminarily evaluated by the FNA cytopathologist while the patient was at the clinic. If the cytopathologist was unable to render a definitive diagnosis of the lesion type or if a repeat FNA was requested by the clinician because of a previous non-definitive FNA result, a core needle biopsy was then performed. When the FNA and the core needle biopsies were reviewed together, a correct definitive diagnosis was made in 10 of the 12 cases. In contrast, review of the FNA material alone yielded a correct definitive diagnosis in only five cases. The supplemental core needle biopsy was found to be especially useful in: 1) providing a definitive diagnosis of infiltrating carcinoma in those cases in which the FNA diagnosis was reported as "suspicious;" 2) providing ample tissue for ancillary studies; and 3) differentiating a phyllodes tumor from a fibroadenoma. It is the authors' opinion that the FNA cytopathologist is the physician best qualified to perform the combined FNA/core needle biopsy procedure should he/she deem it necessary.


A comparison of vascularized and nonvascularized bone grafts for reconstruction of mandibular continuity defects.
This study compared vascularized and nonvascularized bone grafts for the reconstruction of segmental defects of the mandible. The results in 39 patients having vascularized bone grafts (38 fibulas and one iliac crest) and 29 patients having nonvascularized bone grafts (26 iliac crest [22 corticocancellous block grafts, four cancellous bone grafts in a tray] and three rib grafts) for segmental mandibular reconstruction were evaluated in terms of overall success rate, total number of surgeries performed, total blood loss, total number of hospital days, and total number of hours in the operating room. Of 39 vascularized bone grafts, two failed (95% success rate), whereas of 29 nonvascularized bone grafts, seven failed (76% success rate). Failure for the nonvascularized bone grafts was closely correlated to the length of the defect. Nonvascularized bone graft patients underwent an average of one more surgical procedure for total reconstruction than vascularized bone graft patients, including osseointegrated implants. However, vascularized bone graft patients spent a mean of over 14 additional days in the hospital for all of their reconstructive procedures and an additional 3 hours in the operating room as compared with nonvascularized bone graft patients. Blood loss was similar in both groups (1,100 mL). Only 20% to 24% of patients in each treatment group have completed reconstruction to include osseointegrated implants. The success rate for vascularized bone grafting is high and is the treatment of choice when primary reconstruction is required, when the patient has been previously irradiated, or when simultaneous replacement of soft tissue is required. Vascularized bone grafts are also the treatment of choice for mandibular replacements over 9 cm in length. Nonvascularized bone grafts create a better contour and bone volume for facial esthetics and subsequent implant insertion, and may be the treatment of choice for secondary reconstruction of defects less than 9 cm in length.


Genotype-phenotype relationships in an investigation of the role of proteases in abdominal aortic aneurysm expansion.
The aim of the study was to investigate the effect of functional polymorphisms in promoters of matrix metalloproteinase (MMP) 2, MMP-3, MMP-9, MMP-12 and plasminogen activator inhibitor (PAI) 1 genes on the growth rate of small abdominal aortic aneurysms (AAA). Some 455 individuals with a small AAA (4.0-5.5 cm) were monitored for aneurysm growth by ultrasonography (mean follow-up 2.6 years). They also provided a DNA sample for analysis of the -1306 C > T, -1171 5A > 6A, -1562 C > T, -82 A > G and -675 4G > 5G alleles of MMP-2, MMP-3, MMP-9, MMP-12 and PAI-1, respectively. Mean linear AAA growth rates were calculated by flexible modelling; the sample size was sufficient to detect variants that influenced the growth rate by 25 per cent. For MMP-2, MMP-9 and MMP-12 genotypes, growth rates were similar to the mean linear growth rate of 3.08 mm per year. For MMP-3, growth rates were 3.05 (for 5A5A), 3.19 (for 5A6A) and 2.90 (for 6A6A) mm per year. For PAI-1, patients with 4G4G, 4G5G and 5G5G genotypes had growth rates of 3.18, 2.92 and 3.47 mm per year, respectively, for aneurysms with a baseline diameter of 45.1, 44.6 and 46.2 mm. The increased growth rate for patients with PAI-1 5G5G genotype was not statistically significant (P = 0.061), although these patients had the lowest plasma PAI-1 concentrations (P = 0.018). There was no evidence that any specific MMP polymorphism had a clinically significant effect on AAA expansion. The plasminogen system may have a small but clinically significant role in AAA development. Much larger studies would be needed to evaluate genes of smaller effect.


Spo0M: structure and function beyond regulation of sporulation.
In this mini-review, we present a perspective on the recent findings relating Spo0M structure and function that will stimulate and guide further studies in the characterization of this interesting protein. Cell division and sporulation constitute two of the best studied processes in the model organism Bacillus subtilis; however, there are many missing pieces in the giant regulatory puzzle that governs the independent and shared networks between them. Spo0M is a little studied protein that has been related to both, cell division and sporulation, but its biochemical function and its direct interactions have not been yet defined. Structural analysis of Spo0M revealed the presence of an arrestin-like domain and an FP domain (a dimerization domain present in proteasome elements), motifs more commonly found in eukaryotic proteins. The aim of this perspective is to present open questions regarding the functional and structural features of Spo0M that make this protein a good candidate for the ancestor of arrestins in bacteria and an important element in developmental and differentiation processes of Bacillus subtilis.


[Personal experiences with transplantation of antigenically compatible cornea. Preliminary report].
Ten corneae from donors selected in respect of partial compatibility of the HLA antigens were transplanted in the period October 1988--October 1989. The grafting was performed in 10 patients with leukomas included in the group of maximal risk (5+). In 9 patients the leukomas were due to ocular burns (chemical in 8 patients and thermal in 1 patient). In 1 patient, a 74 years old man the grafting was performed in the single eye with Salzman's corneal dystrophy with a simultaneous cataract extraction. During observation, which lasted 2 to 12 months 6 grafts remained transparent, 1--partly opacified. Not any transplant did totally opacify.


A systematic review of public health-aligned recommendations for preparing physical education teacher candidates.
Since Sallis and McKenzie's seminal article in 1991 outlining physical education's role in public health, increased attention has been given to promoting youth physical activity in schools. The present study systematically reviewed the literature from 1991 to 2013 to identify recommendations for the preparation of physical education teacher candidates (PETCs) from a public health perspective. Eight online databases (e.g., Educational Resources Information Center, Google Scholar) served as data sources for the study. Multiple combinations of key terms (e.g., physical education teacher education [PETE], public health, health-oriented) were used to identify relevant literature meeting search criteria. A content analysis was used to identify 47 distinct recommendations from 25 included articles and to synthesize these recommendations into major areas of focus. Three major areas of focus were identified: (a) candidate profile (e.g., PETCs should be physically active and fit role models), (b) candidate knowledge (e.g., PETCs should know about behavior change theories), and (c) candidate skills (e.g., PETCs should be able to advocate for school-based physical activity). This review can serve as a blueprint for PETE programs seeking to align professional preparation with public health goals.


Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: hematologic recovery and costs. A randomized, controlled trial.
Previous studies have suggested that peripheral blood stem cell (PBSC) transplantation has an advantage over autologous bone marrow transplantation. To compare the hematologic recovery and costs associated with PBSC transplantation with those associated with autologous bone marrow transplantation in patients receiving high-dose chemotherapy for solid tumors or lymphomas. Multicenter, randomized, controlled clinical trial. French Federation of Cancer Centers, located in cancer facilities or public hospitals with transplantation units. Children and adults with solid tumors or lymphomas who were candidates for high-dose chemotherapy. Bone marrow or filgrastim-mobilized PBSCs. The major and point was the duration of thrombocytopenia (platelet count < 50 x 10(9)/L). An economic evaluation of both types of transplantation was done prospectively to measure costs and cost-effectiveness. 129 patients entered the trial; 64 had PBSC transplantation, and 65 had bone marrow transplantation. The median duration of thrombocytopenia was 16 days in the PBSC group and 35 days in the bone marrow group (P < 0.001). All of the other clinical end points studied (time to last platelet transfusion, duration of granulocytopenia, number of transfusion episodes, and duration of hospitalization) favored PBSC transplantation. A cost analysis showed that total cost was decreased by 17% in adults and 29% in children with PBSC transplantation; thus, PBSC transplantation was clearly more cost-effective than bone marrow transplantation for both platelet and granulocyte recovery. Transplantation of PBSCs is associated with more rapid hematologic recovery than is bone marrow transplantation after high-dose chemotherapy for solid tumors or lymphomas. Furthermore, global costs are lower and cost-effectiveness ratios are better with PBSC transplantation.


Staging, recurrence and follow-up of uterine cervical cancer using MRI: Updated Guidelines of the European Society of Urogenital Radiology after revised FIGO staging 2018.
The recommendations cover indications for MRI examination including acquisition planes, patient preparation, imaging protocol including multi-parametric approaches such as diffusion-weighted imaging (DWI-MR), dynamic contrast-enhanced imaging (DCE-MR) and standardised reporting. The document also underscores the value of whole-body 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) and highlights potential future methods. In 2019, the ESUR female pelvic imaging working group reviewed the revised 2018 FIGO staging system, the up-to-date clinical management guidelines, and the recent imaging literature. The RAND-UCLA Appropriateness Method (RAM) was followed to develop the current ESUR consensus guidelines following methodological steps: literature research, questionnaire developments, panel selection, survey, data extraction and analysis. The updated ESUR guidelines are recommendations based on ≥ 80% consensus among experts. If ≥ 80% agreement was not reached, the action was indicated as optional. The present ESUR guidelines focus on the main role of MRI in the initial staging, response monitoring and evaluation of disease recurrence. Whole-body FDG-PET plays an important role in the detection of lymph nodes (LNs) and distant metastases. • T2WI and DWI-MR are now recommended for initial staging, monitoring of response and evaluation of recurrence. • DCE-MR is optional; its primary role remains in the research setting. • T2WI, DWI-MRI and whole-body FDG-PET/CT enable comprehensive assessment of treatment response and recurrence.


Does route of delivery affect maternal and perinatal outcome in women with eclampsia? A randomized controlled pilot study.
The route of delivery in eclampsia is controversial. We hypothesized that adverse maternal and perinatal outcomes may not be improved by early cesarean delivery. This was a randomized controlled exploratory trial carried out in a rural teaching institution. In all, 200 eclampsia cases, carrying ≥34 weeks, were allocated to either cesarean or vaginal delivery. Composite maternal and perinatal event rates (death and severe morbidity) were compared by intention-to-treat principle. Groups were comparable at baseline with respect to age and key clinical parameters. Maternal event rate was similar: 10.89% in the cesarean arm vs 7.07% for vaginal delivery (relative risk, 1.54; 95% confidence interval, 0.62-3.81). Although the neonatal event rate was less in cesarean delivery-9.90% vs 19.19% (relative risk, 0.52; 95% confidence interval, 0.25-1.05)-the difference was not significant statistically. A policy of early cesarean delivery in eclampsia, carrying ≥34 weeks, is not associated with better outcomes.


A hybrid constrained coral reefs optimization algorithm with machine learning for optimizing multi-reservoir systems operation.
The continuous growing demand for water, prolonged periods of drought, and climatic uncertainties attributed mainly to climate change mean surface water reservoirs more than ever need to be managed efficiently. Several optimization algorithms have been developed to optimize multi-reservoir systems operation, mostly during severe dry/wet seasons, to mitigate extreme-events consequences. Yet, convergence speed, presence of local optimums, and calculation-cost efficiency are challenging while looking for the global optimum. In this paper, the problem of finding an efficient optimal operation policy in multi-reservoir systems is discussed. The complexity of the long-term operating rules and the reservoirs' upstream and downstream joint-demands projected in recursive constraints make this problem formidable. The original Coral Reefs Optimization (CRO) algorithm, which is a meta-heuristic evolutionary algorithm, and two modified versions have been used to solve this problem. Proposed modifications reduce the calculation cost by narrowing the search space called a constrained-CCRO and adjusting reproduction operators with a reinforcement learning approach, namely the Q-Learning method (i.e., the CCRO-QL algorithm). The modified versions search for the optimum solution in the feasible region instead of the entire problem domain. The models' performance has been evaluated by solving five mathematical benchmark problems and a well-known continuous four-reservoir system (CFr) problem. Obtained results have been compared with those in the literature and the global optimum, which Linear Programming (LP) achieves. The CCRO-QL is shown to be very calculation-cost-effective in locating the global optimum or near-optimal solutions and efficient in terms of convergence, accuracy, and robustness.


Erratum.
In R. Jeffrey Smith's article "Beggs takes a leave of absence at NASA" (News and Comment, 20 Dec., p. 1363), NASA acting administrator William R. Graham was incorrectly identified as "Thomas Graham."


Molecular cloning of the chicken gizzard telokin gene and cDNA.
Telokin is a protein which consiste of the C-terminal portion of smooth muscle myosin light chain kinase (MLCK) (M. Ito, R. Dabrowska, V. Guerriero, Jr., and D. J. Hartshone (1989) J. Biol. Chem. 264, 13971-13974). In this study, the chicken gizzard telokin cDNA and gene were cloned and analyzed. The telokin cDNA coded 157 amino acid residues which were completely identical to the C-terminal portion of the amino acid sequence of chicken gizzard MLCK. The telokin gene was coded in a 6.3-kb EcoRI genomic fragment and it consisted of three exons. The 5'-leader sequence of the telokin cDNA and genomic sequence revealed that the telokin gene was included in the MLCK gene and the transcription started in the intronic sequence of the MLCK gene. The analysis of the telokin gene suggests that the telokin expression was under the control of an independent promotor. Northern blotting and the reverse transcriptase-polymerase chain reaction methods revealed that telokin was expressed not only in chicken gizzard but also in chicken heart, lung, intestine, and skeletal muscle although the levels of the expression in the latter were much less than that in the gizzard.


Ectomesenchymal chondromyxoid tumor of the anterior tongue: a rare case.
Ectomesenchymal chondromyxoid tumor is a rare tumor seen in the anterior dorsal aspect of the tongue. Diagnosis of this lesion without a prediagnosis clinically is made only with histopathological findings including the immunohistochemical examinations. However, diverse results are being reported in the literature with keratin staining. While glial fibrillary acid protein positiveness maintain being a fixed repeating feature, we emphasized for our case of a 28-year-old Caucasian woman having the findings of qualities supporting the ectomesenchymal origin of the mentioned tumor.


[Proper use of apixaban: an outline for clinical practice].
Apixaban is a direct inhibitor of coagulation factor Xa. Superior efficacy over aspirin and antivitamin K has been shown in the prevention of stroke and systemic embolism during non-valvular atrial fibrillation with a more favorable safety profile, even though the risk of hemorrhage cannot be ignored, considering its mechanism of action. The recommended dose is 5mg twice daily which can be reduced to 2.5mg depending on the individual risk. Apixaban is also indicated for the treatment of venous thromboembolism but reimbursement has not yet been accepted in France for this indication. As with all direct oral anticoagulants, no routine biological monitoring is required, nevertheless their use may have an impact on all coagulation tests, eventually hampering interpretation. In particular clinical circumstances where a measure of anticoagulant efficacy is deemed necessary, specific assay of anti-Xa activity is appropriate, the result being expressed as concentration of the anticoagulant used. It is therefore necessary to state the name of the medicine for which the assay is requested. With these new anticoagulants, management of hemorrhagic events can be more difficult due to the lack of a specific antidote. Pro-hemostatic substances have exhibited efficacy in animal models but results are still insufficiently documented in clinical practice. Local or locoregional hemostasis measurements, when possible, are an essential factor in the treatment of hemorrhagic events.


Prevention of in vitro and in vivo acute ischemic neuronal damage by (2S)-1-(4-amino-2,3,5-trimethylphenoxy)-3-{4-[4-(4-fluorobenzyl) phenyl]-1-piperazinyl}-2-propanol dimethanesulfonate (SUN N8075), a novel neuroprotective agent with antioxidant properties.
(2S)-1-(4-Amino-2,3,5-trimethylphenoxy)-3-{4-[4-(4-fluorobenzyl) phenyl]-1-piperazinyl}-2-propanol dimethanesulfonate (SUN N8075) is a novel antioxidant with neuroprotective properties. We examined whether SUN N8075 inhibited the neuronal damage resulting from permanent focal cerebral ischemia, and examined its neuroprotective properties in vivo and in vitro mechanism. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion in mice, and the resulting infarction, brain swelling, and neurological deficits were evaluated after 24 h or 72 h. Brain damage was assessed histochemically using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and antibody recognizing 4-hydroxynonenal histidine adduct (4-HNE). In the in vitro study, we examined the effects of SUN N8075 on 1) lipid peroxidation in mouse brain homogenates and 2) cell viability and caspase-3 protease activity under a hypoxic insult or FeSO(4) in rat cultured cerebrocortical neurons. SUN N8075 administered either 10 min before or at 1 h after the occlusion reduced both infarction size and neurological deficits. SUN N8075 reduced brain swelling when administered 10 min before, 1 h, or 3 h after occlusion. Furthermore, only pretreatment (administered 10 min before) decreased infarct volume and brain swelling at 72 h after middle cerebral artery occlusion. SUN N8075 reduced the number of TUNEL-positive cells and decreased the level of oxidative damage, as assessed by immunopositive staining to 4-HNE. SUN N8075 inhibited lipid peroxidation, leakage of lactate dehydrogenase, caspase-3 activation induced by in vitro hypoxia, and the neuronal damage induced by in vitro FeSO(4) exposure. These findings indicate that SUN N8075 has neuroprotective effects against acute ischemic neuronal damage in mice and may prove promising as a therapeutic drug for stroke.


Semantic integration during metaphor comprehension in Asperger syndrome.
Previous research indicates severe disabilities in processing figurative language in people diagnosed on the autism spectrum disorders. However, this aspect of language comprehension in Asperger syndrome (AS) specifically has rarely been the subject of formal study. The present study aimed to examine the possibility that in addition to their pragmatic deficits, the difficulties in the comprehension of metaphors in AS may be explained by deficient linguistic information processing. Specifically, we aimed to examine whether a deficient semantic integration process underlies the difficulties in metaphor comprehension frequently experienced by persons with AS. The semantic integration process of sixteen AS participants and sixteen matched controls was examined using event related potentials (ERPs). N400 amplitude served as an index for degree of effort invested in the semantic integration process of two-word expressions denoting literal, conventional metaphoric, and novel metaphoric meaning, as well as unrelated word pairs. Large N400 amplitudes for both novel and conventional metaphors demonstrated the greater difficulties in metaphor comprehension in the AS participants as compared to controls. Findings suggest that differences in linguistic information processing cause difficulties in metaphor comprehension in AS.


miR-584-5p Inhibits Osteosarcoma Progression by Targeting Connective Tissue Growth Factor.
Background: miR-584-5p is a critical regulator in the progression of multiple cancers. However, its specific role and downstream targets in osteosarcoma are unclear. This research investigated the roles and underlying mechanisms of miR-769-5p and the Hippo pathway in osteosarcoma cells. Materials and Methods: RT-qPCR, CCK-8 and EdU and colony formation, wound-healing and transwell chamber, flow cytometry, and Western blot assay detected the expression of miR-584-5p and CTGF, cell proliferation, migration, invasion apoptosis and protein expression. Result: Their study illuminated that miR-584-5p overexpression repressed osteosarcoma cell migration/invasion and proliferation and facilitated apoptosis. Mechanistically, miR-584-5p targets negatively regulated connective tissue growth factor (CTGF). miR-584-5p inhibited osteosarcoma cell metastasis by regulating CTGF. In addition, miR-584-5p inactivated the Hippo pathway through CTGF in osteosarcoma. Conclusion: miR-584-5p inhibits osteosarcoma cell proliferation, migration, and invasion and promotes apoptosis by targeting CTGF, indicating that miR-584-5p acts as a promising diagnostic and predictive biomarker for osteosarcoma.


The association between paternal childcare involvement and postpartum depression and anxiety among Chinese women-a path model analysis.
Depression and anxiety are among the most common morbidities during the perinatal period. Very few studies have been conducted to examine the association between paternal childcare involvement and postpartum depression (PPD) and anxiety (PPA) in East Asian cultures. This study aims to examine the association between fathers' involvement in childcare and mothers' mental health and explores the potential mediating effects of the mother and child's health among a national sample of Chinese women. This is a cross-sectional, self-administered online survey of maternal women (N = 778) within 1 year after childbirth in China. The questionnaire comprised of sociodemographics, fathers' childcare involvement, child and mother's physical health, and mothers' postpartum mental health status. A path analysis model was constructed to examine the correlation between paternal childcare involvement and maternal depression and anxiety within 1-year postpartum. The mediating effect of the mother and child's physical health was also explored in the model. Paternal involvement in childcare was significantly associated with lower PPD (β = - .36, p < 0.001) and PPA (β = - .29, p < 0.001) levels of mothers after covariates were adjusted. Furthermore, women's physical health partially mediated the association between paternal involvement and PPD, and child's health partially mediated the association between paternal involvement and PPA and PPD. Our findings emphasize the essential role of father's childcare involvement and the need to promote culturally tailored intervention programs, which may improve the mental health status among Chinese postpartum mothers.


Differential metabolic markers associated with primary open-angle glaucoma and cataract in human aqueous humor.
We aimed to identify metabolic biomarkers and investigate the metabolic alterations in relation to primary open-angle glaucoma (POAG) and cataract in human aqueous humor. Sixteen POAG patients undergoing surgical treatments and 24 patients undergoing cataract surgeries were included in this case-control study. We performed the metabolomic analysis of aqueous humor samples using a non-targeted gas chromatography coupled to time-of-flight mass spectrometer. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacities of each metabolite marker. Databases including the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were utilized to search for the potential pathways of metabolites. Aqueous humor metabolomic profiles could well distinguish POAG from controls. Fourteen metabolic biomarkers were identified as potential aqueous humor biomarkers for POAG, yielding AUC values from 0.62 to 0.86. In pathway analysis, Biotin metabolism was highly impacted, implying that these metabolic markers play important roles in the regulation of this pathway. This study identified valuable metabolic biomarkers and pathways that may facilitate an improved understanding of the POAG pathogenesis. The finding holds translational value in the development of new therapeutic measures for POAG.


Efficacy and Safety of Quantum Molecular Resonance Electrotherapy in Patients with Aqueous-Deficient, Evaporative and Mixed-Type Dry Eye: A Randomized Interventional Study.
To evaluate the efficacy and safety of Quantum Molecular Resonance (QMR) treatment in patients with severe dry eye disease (DED), as well as its effects on aqueous-deficient (ADDE), evaporative (EDE), and mixed (MDE) dry eye. In this prospective, interventional study, 81 patients were randomly allocated to received four treatment sessions of QMR at 1-week intervals (Rexon-Eye®, Resono Ophthalmic, Trieste, Italy) (QRM group) or tear substitute four times daily, containing 0.15% sodium hyaluronate and 3% trehalose (Thealoz Duo®, Thea Pharma, France) (SH-TH group). Outcome measures included ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), tear breakup time (TBUT), non-invasive breakup time (NIBUT), corneal fluorescein staining (CFS), lipid layer thickness (LLT), tear film osmolarity (OSM), and meibomian gland dysfunction (MGD) grade, which were assessed at baseline and 1-month and 3-month follow-up. The QMR group achieved better improvements than the SH-TH group in OSDI and SANDE questionnaires, NIBUT, LLT, and CFS. The mean differences between the groups were as follows: OSDI (- 12.4 ± 0.25 points, P = 0.01), SANDE (10.6 ± 1.7 points, P = 0.01), NIBUT (2 ± 0.25 s, P = 0.01), LLT (18.7 ± 0.7 nm, P = 0.01), and CFS (1.2 ± 0.1 points, P = 0.02). In subgroups analysis, QMR treatment demonstrated a beneficial role to improve DED symptoms and signs in ADDE, EDE, and MDE. QMR is an effective and well-tolerated treatment that seems to improve DED symptoms and signs in patients with severe DED. However, further studies are needed to confirm this. ClinicalTrials.gov identifier NCT06119386.


Does gestational diabetes mellitus increase the risk of cardiovascular disease? A Mendelian randomization study.
In recent years, epidemiological studies have revealed the relationship between gestational diabetes mellitus (GDM) and cardiovascular disease (CVD). In this study, we utilized Mendelian randomization (MR) to investigate the potential causal impact of GDM on cardiovascular disease for the first time. We retrieved summary statistics from published genome-wide association studies. MR was first performed using significant SNPs extracted from the eighth data release of the FinnGen study. Next, a replication analysis for coronary artery disease (CAD) was conducted in another European ancestry population to validate our findings. Finally, mediation analysis was carried out to assess potential mediation effects. Our data analysis revealed that genetically predicted GDM was significantly associated with increased CAD risk (OR 1.10, 95% CI 1.02-1.18, p 0.006). Replication analysis confirmed a significant genetic association between GDM and CAD (OR 1.07, 95% CI 1.02-1.12, p 0.003) in another European ancestry population. Mediation analysis indicated no significant mediation effect by type 2 diabetes mellitus (T2DM) on the GDM-CAD relationship (mediation effect β [95% CI]: 0.005 [-0.003, -0.017]). Women with a prior history of GDM face an elevated risk of future CAD. This increased risk of CAD cannot be solely attributed to the subsequent onset of diabetes. Regular CAD risk assessment and primary prevention strategies are of paramount importance for women with a history of GDM.


Insulin-like growth factor I (IGF-I) in healthy children, adolescents and adults as determined by a radioimmunoassay specific for the synthetic 53-70 peptide region.
A radioimmunoassay (RIA) specific for the synthetic 53-70 peptide region of human insulin-like growth factor I (IGF-I) was used to determine IGF-I in the serum of 191 healthy newborns, children and adolescents and in 26 adults. The results compare favourably with reported values obtained using RIA systems for the native IGF-I molecule. Intra- and inter-assay CV were 3.3 and 7.2% respectively. In childhood, mean +/- SD IGF-I levels rise from 6.0 +/- 3.5 nmol/l in newborns to 16.5 +/- 4.0 nmol/l at 8-11 years in both sexes. At the onset of puberty, IGF-I levels in females (24.9 +/- 6.6 nmol/l) are significantly (P greater than 0.005) higher than in males (17.2 +/- 4.2 nmol/l). With further pubertal development IGF-I levels continue to rise, reaching peak values at pubertal stage P4 (40.6 +/- 4.5 nmol/l in males, 42.8 +/- 5.1 nmol/l in females) and decline thereafter to lower values during adulthood: 16.5 +/- 5.8 nmol/l (males) and 24.2 +/- 7.0 nmol/l (females) (P greater than 0.001). In pubertal males, IGF-I correlates significantly with height (r = 0.66, P less than 0.001), bone age (r = 0.69, P less than 0.001) and growth velocity (r = 0.64, P = 0.025) as well as with testosterone levels (r = 0.69, P less than 0.001). In pubertal females a significant correlation is found between IGF-I and height (r = 0.55, P less than 0.020). The ready availability of a simple, precise and reproducible IGF-I RIA, should contribute much to evaluating the importance of IGF-I measurements in normal growth and in the diagnosis and therapy of various growth disorders.


Scorched mussels (BIVALVIA: MYTILIDAE: BRACHIDONTINAE) from the temperate coasts of South America: phylogenetic relationships, trans-Pacific connections and the footprints of Quaternary glaciations.
This study addresses aspects of the phylogeny and phylogeography of scorched mussels (BIVALVIA: MYTILIDAE: BRACHIDONTINAE) from southern South America (Argentina and Chile), as well as their ecophylogenetic implications. Relationships were inferred from sequences of two nuclear (28S and 18S) and one mitochondrial (COI) genes, using Bayesian and maximum likelihood analyses. Our results indicate that the monophyletic BRACHIDONTINAE include three well supported clades: [i] Brachidontes Swainson (=Hormomya Mörch), [ii] Ischadium Jukes-Browne+Geukensia van de Poel, and [iii] Austromytilus Laseron+Mytilisepta Habe (usually considered a member of the SEPTIFERINAE)+Perumytilus Olsson. Species of clade [iii] are distributed along the temperate coasts of the Pacific Ocean. Available evidence supports divergence between Austromytilus (Australia) and Perumytilus (South American) following the breakup of Australian, Antarctic and South American shelves. Four brachidontins occur in southern South America: Brachidontes rodriguezii (d'Orbigny), B. granulatus (Hanley), and two genetically distinct clades of Perumytilus. The latter are confined to the Chile-Peru (North Clade) and Magellanic (South Clade) Biogeographic Provinces, respectively warm- and cold-temperate. The South Clade is the only brachidontin restricted to cold-temperate waters. Biogeographic considerations and the fossil record prompted the hypothesis that the South Clade originated from the North Clade by incipient peripatric differentiation, followed by isolation during the Quaternary glaciations, genetic differentiation in the non-glaciated coasts of eastern Patagonia, back-expansion over southern Chile following post-LGM de-glaciation, and development of a secondary contact zone between the two clades in south-central Chile. Evidence of upper Pleistocene expansion of the South Clade parallels similar results on other organisms that have colonized coastal ecosystems from eastern Patagonia since the LGM, apparently occupying free ecological space. We emphasize that the assembly of communities cannot be explained solely in terms of environmental drivers, as history also matters.


Surveillance for colonic carcinoma in ulcerative colitis.
To evaluate the efficacy of surveillance colonoscopy with biopsy for the detection of high-grade dysplasia (HGD) or colonic carcinoma in patients with chronic ulcerative colitis, we undertook a retrospective review of 248 patients who underwent 370 examinations (mean duration of disease 12 yr). High-grade dysplasia or carcinoma was found in 24 examinations in 16 patients, with a mean duration of disease of 16 yr. There were 15 patients with HGD. Nine patients had HGD alone, 6 had HGD and carcinoma, and 1 had carcinoma without HGD. The overall incidence of HGD was 6%. Dysplasia-associated lesions or mass were the most consistent indicators of carcinoma, the combination being present in four instances. Of the 7 patients with cancer, 6 were recognized by colonoscopy, and 1 patient with negative visual endoscopic findings was discovered using surveillance biopsies. The conclusions of this study are that dysplasia is a reliable histopathologic marker and correlates with the presence of cancer in chronic ulcerative colitis; the absence of dysplasia correlates with the absence of cancer. The presence of dysplasia-associated lesions or mass with HGD is the strongest indication for operation. This study supports the use of surveillance colonoscopy in managing high-risk ulcerative colitis patients.


Long-term performance of implants with moderately rough anodized surface supporting single-tooth restorations: A retrospective analysis with an up to 15-year follow-up.
This retrospective study aimed to evaluate long-term clinical and radiologic performance of anodized surface implants supporting single implant restorations. Patients who received at least one anodized surface implant for a single-tooth restoration between 2003 and 2004 in the Brånemark clinic (Göteborg, Sweden) were included in the study. The assessed outcomes included implant survival, biological and technical complications, as well as marginal bone levels (MBL) based on radiographs. Baseline data on patient demographics, implant placement, and surgery details were also collected. The cumulative survival rate (CSR) was calculated using the Kaplan-Meier survival analysis. The study included 97 patients with 129 implants. Mean patient age at the time of implant placement was 31.7 ± 16.4 years. All implants were placed in a two-stage approach with delayed loading. The last follow-up visit was on average 13.4 ± 4.8 years after implant insertion. Three implants failed, yielding the implant-level 15-year CSR of 97.4%. Majority of the implants had no biological (70.5%) nor technical (81.4%) complications. The mean MBL was -1.0 ± 0.7 mm (n = 101) at prosthetic placement and -1.8 ± 1.0 mm (n = 80) at the last follow-up, while the mean marginal bone loss (MBL) from prosthetic placement to last follow-up was 0.6 ± 1.1 mm (n = 65). Moderately rough anodized implants have shown favorable long-term outcomessingle-tooth indication, with high survival and a low rate of technical complications. Furthermore, long-term studies are needed to present longitudinal data on peri-implantitis.


One-Stage Soft Tissue Reconstruction Following Sarcoma Excision: A Personalized Multidisciplinary Approach Called "Orthoplasty".
Background and Objectives. Wide surgical resection is a relevant factor for local control in sarcomas. Plastic surgery is mandatory in demanding reconstructions. We analyzed patients treated by a multidisciplinary team to evaluate indications and surgical approaches, complications and therapeutic/functional outcomes. Methods. We analyzed 161 patients (86 males (53%), mean age 56 years) from 2006 to 2017. Patients were treated for their primary tumor (120, 75.5%) or after unplanned excision/recurrence (41, 25.5%). Sites included lower limbs (36.6%), upper limbs (19.2%), head/neck (21.1%), trunk (14.9%) and pelvis (8.1%). Orthoplasty has been considered for flaps (54), skin grafts (42), wide excisions (40) and other procedures (25). Results. At a mean follow-up of 5.3 years (range 2-10.5), patients continuously showed no evidence of disease (NED) in 130 cases (80.7%), were alive with disease (AWD) in 10 cases (6.2%) and were dead with disease (DWD) in 21 cases (13.0%). Overall, 62 patients (38.5%) developed a complication (56 minor (90.3%) and 6 major (9.7%)). Flap loss occurred in 5/48 patients (10.4%). The mean Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) was 74.8 ± 14 and 79.1 ± 13, respectively. Conclusions. Orthoplasty is a combined approach effective in management of sarcoma patients, maximizing adequate surgical resection, limb salvaging and functional recovery. One-stage reconstructions are technically feasible and are not associated with increased risk of complications.


A maternal effect mutation leading to deficiencies of organs and homeotic transformations in the adults ofDrosophila.
The temperature sensitive mutationfs(l)h is characterized at the restrictive temperature of 29°C by both a maternal effect responsible for the early embryonic lethality and pupal zygotic lethality. The two phenotypes are inseparable and map at a short deletion in the X chromosome (7Dl, 7D5-6). At semipermissive temperatures, hemizygous mutant females produce adults with morphological defects, such as organ deficiencies and homeotic transformations of haltere to wing and third leg to second leg. These defects depend on the maternal genotype and are governed by an early temperature sensitive period, which covers the end of oogenesis and the first hours of embryogenesis. Furthermore, this maternal effect mutation interacts with some dominant mutations of the bithorax system. These properties suggest thatfs(l)h is somehow involved in segmental determination.


Liquid chromatography--electrospray ionisation mass spectrometry method for the determination of escitalopram in human plasma and its application in bioequivalence study.
A novel liquid chromatographic--electrospray ionisation mass spectrometric (LC--ESI-MS) method has been developed for the determination of escitalopram, an antidepressant in human plasma using paroxetine as internal standard. The method involved liquid--liquid extraction of the analyte from human plasma with a mixture of diethyl ether and dichloromethane (70:30, v/v). The chromatographic separation was achieved within 7.0 min by using 2.0 mM ammonium acetate (pH 5.0)--acetonitrile (54:46, v/v) as mobile phase and a ODS YMCAQ 150 mm x 4.6 mm analytical column; the flow-rate was 1.0 ml/min. Ion signals m/z 325.0 and 330.0 for escitalopram and internal standard, were measured in the positive mode. A detailed validation of the method was performed as per USFDA guidelines and the standard curves were found to be linear in the range of 1.0-200 ng/ml with a mean correlation coefficient more than 0.99. The absolute recovery was more than 75% for both escitalopram and internal standard. The method was simple, sensitive, precise, accurate and was successfully applied to the bioequivalence study of escitalopram in healthy, male, human subjects.


Health and Safety in a Family Child Care Network: An Analysis of Violation Data of Routine, Full Unannounced Inspections.
To analyze how engagement with a staffed family child network is associated with compliance on health and safety regulations among family day care (FDC) homes. Publically available data on health and safety inspection violations on FDC homes were merged with engagement data from a staffed family child network. Descriptive analysis, logistic regression, and latent class analysis were used. Network FDC homes, compared to non-network FDC homes, were less likely to have health and safety violations in the areas of Child/Family/Staff Documentation (43.1% vs. 53.6%, p = 0.001) and Indoor Safety (36.0% vs. 42.6%, p = .041). Controlling for area median income and for decades since obtaining license, network FDC homes had fewer violations, fewer violation categories, and less variety of violation categories. Additionally, FDC homes which were not engaged with the staffed family child network but were in the city or town in which the network offered services, performed better compared to FDC homes in cities or towns without network resources. The better compliance among network FDC homes and among FDC homes in cities and towns where the network offers services, suggests that the network is having positive effects on health and safety quality in FDC homes. A staffed child care network may be a means to improve child care quality and may be a means of improving educational and health outcomes for children.


Cardiac manifestations of the antiphospholipid syndrome.
The antiphospholipid syndrome has been associated with multiple cardiac abnormalities. The earliest reports were of valvular disease, including verrucous endocarditis, as well as valvular thickening and insufficiency. Subsequently, antiphospholipid antibodies were implicated in coronary artery disease manifested by premature myocardial infarction and coronary artery bypass graft occlusion. In addition, there have been rare reports of intracardiac thrombi and diffuse cardiomyopathy in association with antiphospholipid antibodies. In this review, we discuss the nature and prevalence of the cardiac manifestations of the antiphospholipid antibody syndrome as well as some of the proposed pathophysiologic mechanisms. We also provide examples from our own experience. The expanding spectrum of cardiac disease associated with antiphospholipid antibodies suggests an important role for these antibodies in certain types of cardiac pathology.


Benzodiazepine use and mortality of incident dialysis patients in the United States.
Benzodiazepines and other omega-receptor agonists are frequently used for sleep and anxiety disorders. We studied the rates, correlates, and safety of individual benzodiazepines and zolpidem use from the records of 3690 patients in a national cohort of Dialysis Morbidity and Mortality Study Wave 2 data. We assessed drug utilization and an association between drug use and all-cause mortality. Overall, 14% of incident dialysis patients used a benzodiazepine or zolpidem. Women, Caucasians, current smokers, and patients with chronic obstructive pulmonary disease were more likely to use these drugs, whereas patients with cerebrovascular disease were less likely to use these drugs. In adjusted analyses, benzodiazepine or zolpidem use was associated with a 15% higher mortality rate. Chronic obstructive pulmonary disease significantly modified this association, suggesting that these patients were at higher risk. No association was found between benzodiazepine use and greater risk for hip fracture. We conclude that benzodiazepine or zolpidem use is common in incident dialysis patients and may be associated with greater mortality. Further studies are needed to elucidate the safety of these drugs in the dialysis population, which may lead to cautious and restrictive utilization of omega-receptor agonists in dialysis patients.


Metabolic and clinical consequences of changing from high-glucose to high-fat regimens in parenterally fed newborn infants.
To evaluate the metabolic and clinical consequences of changing from high-glucose to high-fat regimens during initiation of parenteral nutrition, we performed 22 studies in 11 newborn infants (birth weight (mean +/- SD) 2.54 +/- 0.54 kg, gestational age 37 +/- 3 weeks, postnatal age 8 +/- 3 days) maintained in a constant thermal environment. In a paired design, two isoproteinic (2.4 +/- 0.2 gm/kg/day) and isocaloric (64 +/- 6 kcal/kg/day) regimens differing by source of energy (high glucose vs high lipid) were infused on consecutive days. Environmental and body temperatures were recorded during a 4-hour period, and 24-hour urinary excretions of catecholamines, nitrogen, and C peptide were measured. Despite constant incubator and average skin temperatures, the rectal and interscapular temperatures rose significantly when the high-glucose regimen was changed to a high-lipid regimen. The specific locations of these changes in body temperature suggested brown fat activation. A significant drop in nitrogen retention (63 +/- 9% vs 56 +/- 10%) during the lipid infusion could be further evidence of a metabolic adaptation to the rapid change in energy substrates.


Catheter dislodgement: a cause of failure of intraarterial vasopressin infusions to control gastrointestinal bleeding.
Catheter dislodgement is a major cause of technical failures in intraarterial vasopressin therapy for gastrointestinal bleeding. Ten such cases were observed in the past five years. In seven patients catheter dislodgement led to recurrent bleeding during vasopressin infusion. In one patient aortic infusion of vasopressin caused recurrent bleeding and reversible acrocyanosis of the feet, and in two patients vasopressin infusion into the left renal artery resulted in chest pain and hematuria. Catheter dislodgement should be suspected if bleeding that was initially controlled recurs during vasopressin infusion.


Genome-wide screening for prognosis-predicting genes in early-stage non-small-cell lung cancer.
In early-stage non-small-cell lung cancer (NSCLC), a substantial proportion of patients can be cured by surgery. Development of distant metastases is the most frequent cause of therapeutic failure. The possibility to accurately predict a patient's risk for developing distant metastasis would help to identify patients that are candidates for further intervention such as conventional adjuvant chemotherapy or experimental drugs. Current molecular biology techniques allow the genome-wide screening for differentially expressed genes; and adequate bioinformatics approaches are developed at a rapid pace to improve prognosis prediction. Genes associated with metastasis do not necessarily play a role in disease pathogenesis but rather reflect the activation of specific signal-transduction pathways that are associated with enhanced migration and invasion capability. In our own work, we have identified several genes (e.g. thymosin beta-4, elF4A1), including a novel non-coding RNA (MALAT-1) to be expressed at significantly higher levels in stage-I and stage-II NSCLC primary tumours that subsequently metastasised. As a consequence, patients with high-level expression of these genes were shown to have significantly worse survival compared to patients with low-level expression of these genes. These data support the hypothesis that gene-expression patterns in primary tumours determine the tumours' likelihood to metastasise. In the near future, this information will be used for tailored therapy approaches for patients with early-stage NSCLC.


T cells play an essential role in anti-F1 mediated rapid protection against bubonic plague.
Plague, which is initiated by Yersinia pestis infection, is a fatal disease that progresses rapidly and leads to high mortality rates if not treated. Antibiotics are an effective plague therapy, but antibiotic-resistant Y. pestis strains have been reported and therefore alternative countermeasures are needed. In the present study, we assessed the potential of an F1 plus LcrV-based vaccine to provide protection shortly pre- or post-exposure to a lethal Y. pestis infection. Mice vaccinated up to one day before or even several hours after subcutaneous challenge were effectively protected. Mice immunized one or three days pre-challenge were protected even though their anti-F1 and anti-LcrV titers were below detection levels at the day of challenge. Moreover, using B-cell deficient μMT mice, we found that rapidly induced protective immunity requires the integrity of the humoral immune system. Analysis of the individual contributions of vaccine components to protection revealed that rF1 is responsible for the observed rapid antibody-mediated immunity. Applying anti-F1 passive therapy in the mouse model of bubonic plague demonstrated that anti-F1 F(ab')(2) can delay mortality, but it cannot provide long-lasting protection, as do intact anti-F1 molecules. Fc-dependent immune components, such as the complement system and (to a lesser extent) neutrophils, were found to contribute to mouse survival. Interestingly, T cells but not B cells were found to be essential for the recovery of infected animals following passive anti-F1 mediated therapy. These data extend our understanding of the immune mechanisms required for the development of a rapid and effective post-exposure therapy against plague.


Effect of synthetic chicken vasoactive intestinal peptide on pancreatic blood flow and on exocrine and endocrine secretions of the pancreas in dogs.
This study was undertaken to determine the effect of synthetic chicken vasoactive intestinal peptide (VIP) on pancreatic blood flow, exocrine and endocrine secretions of the pancreas, and biliary secretion in dogs. The effect of synthetic chicken VIP on pancreatic blood flow and systemic arterial pressure was identical to that of natural chicken VIP in dogs. The present study demonstrated that synthetic chicken VIP induces significant increases in pancreatic blood flow, pancreaticobiliary secretion, and blood levels of insulin and glucose in dogs. Both the volume of pancreatic juice and blood levels of insulin were increased in consonance with the increase of pancreatic blood flow. This study suggests that the stimulatory effects of synthetic chicken VIP on exocrine and endocrine secretions of the pancreas may be related to the increased pancreatic blood flow elicited by synthetic chicken VIP.


Zebrafish unplugged reveals a role for muscle-specific kinase homologs in axonal pathway choice.
En route to their target, pioneering motor growth cones repeatedly encounter choice points at which they make pathway decisions. In the zebrafish mutant unplugged, two of the three segmental motor axons make incorrect decisions at a somitic choice point. Using positional cloning, we show here that unplugged encodes a homolog of muscle-specific kinase (MuSK) and that, unlike mammalian MuSK, unplugged has only a limited role in neuromuscular synaptogenesis. We demonstrate that unplugged is transiently expressed in cells adjacent to the choice point and that unplugged signaling before the arrival of growth cones induces changes in the extracellular environment. In addition, we find that the unplugged locus generates three different transcripts. The splice variant 1 (SV1) isoform lacks the extracellular modules essential for agrin responsiveness, and signaling through this isoform mediates axonal pathfinding, independent of the MuSK downstream component rapsyn. Our results demonstrate a new role for MuSK homologs in axonal pathway selection.


A multidimensional model of resilience: Family, community, national, global and intergenerational resilience.
This paper aims to unpack the empirical and theoretical complexity that surrounds 'resilience', with particular attention to its application to war-affected children and youth. We expand current conceptual frameworks to adopt a more inclusive and intergenerational approach that accounts for the added layers of national, global and intergenerational resilience, arguing for greater recognition of the shared or relational nature of resilience. We introduce a multidimensional model of resilience that integrates the macro- and micro-level to include resilience-enabling systems at the family, community, national, global and intergenerational levels. The purpose of this conceptual framework is to provide a more holistic and integrative model that combines both bottom-up and top-down approaches to cultivating resilience, highlighting the power of interconnections across interrelated systems and social structures. Using the case example of post-genocide Rwanda and the experiences of children born of genocidal rape, we apply our multidimensional model to illustrate concrete examples of resilience-enabling systems at the family, community, national, global and intergenerational levels. Our proposed multidimensional model as applied to youth born of genocidal rape in Rwanda reveals key gaps in their surrounding social ecological systems, highlighting the importance of coordinated and mutually-reinforcing efforts to engender resilience across all dimensions concurrently. We conclude with a set of policy and practice implications, directions for future research, and lessons-learned on how best to champion the resilience of this unique and important population of children.


Efficacy and Safety of a Balanced Salt Solution Versus a 0.9% Saline Infusion for the Prevention of Contrast-Induced Acute Kidney Injury After Contrast-Enhanced Computed Tomography.
We aimed to elucidate whether a balanced salt solution decreases the occurrence of contrast-induced acute kidney injury (CI-AKI) after contrast-enhanced computed tomography (CE-CT) as compared to 0.9% saline solution. A randomized clinical trial. The study was performed in 14 tertiary hospitals in South Korea. Patients with estimated glomerular filtration rates (eGFRs) < 45 or <60 mL/min/1.73 m2 and additional risk factors (age ≥ 60 years or diabetes) who were undergoing scheduled CE-CT were included from December 2016 to December 2018. An open-label intervention was performed. The study group received a balanced salt solution and the control group received 0.9% saline solution as prophylactic fluids for CE-CT. The primary outcome was CI-AKI, defined by creatinine level elevation ≥ 0.5 mg/dL or 25% from baseline within 48 to 72 hours after CE-CT. Secondary outcomes included AKI defined based on the KDIGO (Kidney Disease: Improving Global Outcomes) guideline, eGFR changes, death, or requiring dialysis within 6 months after CE-CT. 493 patients received the study fluids. The control and study groups included 251 and 242 patients, respectively. The occurrence of CI-AKI in the study (10 [4.2%]) and control (17 [6.8%]) groups was not significantly different (P = 0.27). No significant difference was present for the secondary outcomes; AKI by the KDIGO definition (study: 19 [7.9%], control: 27 [10.8%]; P = 0.33), death/dialysis (study: 11 [4.7%], control: 9 [3.7%]; P = 0.74), and eGFR changes (study: 0.1 ± 0.2 mg/dL, control: 0.3 ± 2.8 mg/dL; P = 0.69). This study failed to meet target enrollment. The risk for CI-AKI was similar after administration of a balanced salt solution and after use of 0.9% saline solution during CE-CT in higher-risk patients. This study was funded by CJ Healthcare (CS2015_0046). Registered at ClinicalTrials.gov with study number NCT02799368.


Beta-phased Ni(OH)2 nanowall film with reversible capacitance higher than theoretical Faradic capacitance.
β-Ni(OH)(2) was constructed into a three-dimensional mesoporous film on Ni foam with ultra-thin (∼6 nm) primary nanowalls showing ultrahigh specific capacitance (2675 F g(-1)) and excellent cycling performance (>96% for 500 cycles). The capacitance was higher than theoretical value possibly due to the combination of Faradic and electrical double-layer capacitances.


MMP13 Expression Is Increased Following Mutant α-Synuclein Exposure and Promotes Inflammatory Responses in Microglia.
α-Synuclein is a 140-amino acid protein that readily misfolds and is associated with the Lewy body pathology found in sporadic and genetic forms of Parkinson's disease. We and others have shown that wild-type α-synuclein is a damage-associated molecular pattern that directly elicits a proinflammatory response in microglia through toll-like receptor activation. Here we investigated the direct effect of oligomeric mutant α-synuclein (A53T) on microglia morphology and activation. We found that misfolded A53T increased quantitative measures of amoeboid cell morphology, NFκB nuclear translocation and the expression of prototypical proinflammatory molecules. We also demonstrated that A53T increased expression of MMP13, a matrix metalloproteinase that remodels the extracellular matrix. To better understand the role of MMP13 in synucleinopathies, we further characterized the role of MMP13 in microglial signaling. We showed exposure of microglia to MMP13 induced a change in morphology and promoted the release of TNFα and MMP9. Notably, IL1β was not released indicating that the pathway involved in MMP13 activation of microglia may be different than the A53T pathway. Lastly, MMP13 increased the expression of CD68 suggesting that the lysosomal pathway might be altered by this MMP. Taken together this study shows that mutant α-synuclein directly induces a proinflammatory phenotype in microglia, which includes the expression of MMP13. In turn, MMP13 directly alters microglia supporting the need for multi-target therapies to treat Parkinson's disease patients.


Fluctuation and relaxation analysis of monazomycin-induced conductance in black lipid membranes.
Fluctuation and relaxation analyses were performed on monazomycin-induced conductance of lipid bilayer membranes. With both methods a slow (sec) and a fast (msec) current component are apparent; however, the amplitude of the slow, voltage-dependent process is greater than that of the fast component in the step relaxation experiment and less in the fluctuation experiment. The fluctuation analysis showed principally a rapid voltage-dependent process which appears to be related to the multistate character of the conducting channel. The experimental results are interpreted in terms of a simplified kinetic model which is used to calculate relaxation and noise amplitudes.


A PHD inhibitor prevents changes in the phosphoproteome and capillary rarefaction by CsA: treatment option for CKD?
Labes et al. analyze the phosphoproteome in a mouse model of chronic cyclosporine A nephrotoxicity and detect significant changes in the angiogenic pathway. Furthermore, they observe reduced hemoglobin levels and capillary rarefaction in the kidney. The authors show that coadministration of the hypoxia-inducible factor prolyl hydroxylase inhibitor daprodustat almost completely prevents changes of the phosphoproteome and capillary rarefaction, suggesting that prolyl hydroxylase domain enzyme inhibitors may preserve microvasculature of the kidney, which is commonly impaired in chronic kidney disease.


QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice: an approach based on behavioral and biochemical investigations.
Previous studies in our laboratory examined the antidepressant potential of 3-methoxy-N-p-tolylquinoxalin-2-carboxamide (QCM-4), a 5-HT3 receptor antagonist in acute and chronic rodent models of depression. The aim of present study was to investigate the effect of QCM-4 on chronic unpredictable mild stress (CUMS) induced depression in obese mice using behavioral based battery tests and biochemical assessments. Depressive behavior was induced in obese mice by subjecting to different stress procedures for 28 days. The results indicated that the CUMS induced severe depressive behavior in obese mice as demonstrated by a significant decreased sucrose consumption, increased immobility time in forced swim test (FST) and tail suspension test (TST), decreased percent entries and time in open arm in elevated plus maze (EPM). Moreover, CUMS significantly increased the plasma glucose, total cholesterol, triglycerides and total proteins in obese mice. Chronic treatment with QCM-4 (2 mg/kg po) and standard drug escitalopram (10 mg/kg po) significantly reversed the depressive behavioral changes (increased sucrose consumption, decreased immobility time in FST and TST, and increased the percent entries and time in open arm in EPM) and biochemical alterations (reversed the raised levels of plasma glucose, total cholesterol, triglycerides and total proteins) in obese mice subjected to CUMS. No alteration was observed in the locomotor score in obese mice. In conclusion, the results of the present study suggested that QCM-4 attenuated the depression co-morbid with obesity in mice subjected to CUMS which to some extent is mediated by reversing the "insulin resistance" or "altered plasma glucose" in obese mice.


Endoscopic Treatments Following Bariatric Surgery.
Weight regain after bariatric surgery is common and can be managed with surgical interventions or less morbid endoscopic techniques. These endoscopic approaches target structural postoperative changes that are associated with weight regain, most notably dilation of the gastrojejunal anastomosis aperture. Purse string suture placement, as well as argon plasma coagulation application to the anastomosis, may result in significant and durable weight loss. Furthermore, various endoscopic approaches may be used to safely and effectively manage other complications of bariatric surgery that may result in poor weight loss or weight regain after surgery, including fistula formation.


Effects of short-chain fatty acids on cell volume regulation and chloride transport in the rat distal colon.
Superfusion of isolated crypts from rat colon with sodium butyrate-containing solutions induced an amiloride-sensitive swelling of the cells at the upper one-third of the crypt. In HCO3(-)-containing buffer, swelling was followed by regulatory volume decrease, which was inhibited by K+ and C- channel blockers and inhibitors of leukotriene synthesis. Whole-cell patch-clamp recordings revealed that butyrate induced a membrane depolarization, which was dependent on Cl- and was accompanied by an increase in membrane inward current, indicating an increase in Cl- conductance. Membrane outward (K+) current, however, behaved inconsistently, suggesting an activation of swelling-induced K+ currents, but an inhibition of pH-sensitive K+ currents due to the cellular acidification. Cell-attached patch-clamp recordings showed an activation of basolateral Cl- channels by butyrate. The lipoxygenase inhibitor, NDGA (nordihydroguaiaretic acid), inhibited the butyrate response and even reversed it into a slight hyperpolarization indicating that the butyrate-induced Cl- channels, but not the K+ channels, are stimulated by a leukotriene. Short-chain fatty acids concentration-dependently decreased short-circuit current (Isc). The decrease in Isc was diminished by a Cl- channel blocker, NPPB (5-nitro-2-[3-phenylpropylamino]-benzoate), and a lipoxygenase inhibitor, NDGA. Butyrate stimulated the mucosa to serosa fluxes (Jms) of Na+ and Cl-. The effect on J(ms)Cl was blocked by NPPB or NDGA. The stimulation of J(ms)Cl correlated with the degree of metabolism of the short-chain fatty acid. Consequently, two factors seem to be responsible for the stimulation of Cl- absorption by short-chain fatty acids: (a) the intracellular production of HCO3- during the oxidation of short-chain fatty acids as substrate for the apical Cl-/HCO3- exchanger, and (b) the activation of volume-sensitive basolateral Cl- channels.