Factors affecting pupal survival and eclosion in the pine beauty moth, Panolis flammea (D&S).
The proportion of adult Panolis flammea emerging from the overwintering pupae was markedly affected by pupation substrate, waterlogging, temperature and relative humidty. Pupae which had spent the winter in needle litter had a significantly greater survival rate than those in either soil or peat.The greater the length of time spent waterlogged the greater the mortality rate of P. flammea pupae. At temperatures of-20° C, there was 100% pupal mortality within 24 h of exposure.Pupal weight loss was proportional to the length of time spent as a pupa. Female pupae lost proportionately more weight than male pupae. Pupae of both sexes lost more weight at a low relative humidity than at a high relative humidity. At low relative humidities female pupal mortality was higher than that of male pupae.


Brushite-coated Mg-Nd-Zn-Zr alloy promotes the osteogenesis of vertebral laminae through IGF2/PI3K/AKT signaling pathway.
Biodegradable magnesium (Mg) alloys have been extensively investigated in orthopedic implants due to their suitable mechanical strength and high biocompatibility. However, no studies have reported whether Mg alloys can be used to repair lamina defects, and the biological mechanisms regulating osteogenesis are not fully understood. The present study developed a lamina reconstruction device using our patented biodegradable Mg-Nd-Zn-Zr alloy (JDBM), and brushite (CaHPO4·2H2O, Dicalcium phosphate dihydrate, DCPD) coating was developed on the implant. Through in vitro and in vivo experiments, we evaluated the degradation behavior and biocompatibility of DCPD-JDBM. In addition, we explored the potential molecular mechanisms by which it regulates osteogenesis. In vitro, ion release and cytotoxicity tests revealed that DCPD-JDBM had better corrosion resistance and biocompatibility. We found that DCPD-JDBM extracts could promote MC3T3-E1 osteogenic differentiation via the IGF2/PI3K/AKT pathway. The lamina reconstruction device was implanted on a rat lumbar lamina defect model. Radiographic and histological analysis showed that DCPD-JDBM accelerated the repair of rat lamina defects and exhibited lower degradation rate compared to uncoated JDBM. Immunohistochemical and qRT-PCR results showed that DCPD-JDBM promoted osteogenesis in rat laminae via IGF2/PI3K/AKT pathway. This study shows that DCPD-JDBM is a promising biodegradable Mg-based material with great potential for clinical applications.


Cryoprotective effect of water-tailored trehalose-based natural deep eutectic solvents on frozen-thawed mirror carp (Cyprinus carpio L.) surimi.
The inhibitory effect of water-tailored natural deep eutectic solvents (NADES) constructed from citric acid and trehalose with different amounts on the quality deterioration and oxidation of frozen-thawed (F-T) mirror carp (Cyprinus carpio L.) surimi was studied. NADES was obtained by citric acid to trehalose and the effect of moisture addition (v/v) on the structure, physicochemical, and anti-freezing capacity of NADES was assessed. NADES + 10 % H2O has relatively low viscosity (25 %) and strong freezing resistance. However, a 50 % H2O addition leads to the disappearance of the hydrogen bond. The addition of NADES effectively inhibits water loss, migration, and mechanical damage on F-T surimi. An inhibitory effect of 4 % (w/w) NADES on oxidation was verified by a decrease in carbonyl contents (17.4 %, 8.63 %) and TBARS (37.9 %, 15.2 %) of surimi compared with control (P < 0.05) and sucrose + sorbitol after 5F-T cycles, suggesting the potential of NADES as a cryoprotectant for the food industry.


Macropinocytosis and Cell Migration: Don't Drink and Drive….
Macropinocytosis is a nonspecific mechanism by which cells compulsively "drink" the surrounding extracellular fluids in order to feed themselves or sample the molecules therein, hence gaining information about their environment. This process is cell-intrinsically incompatible with the migration of many cells, implying that the two functions are antagonistic. The migrating cell uses a molecular switch to stop and explore its surrounding fluid by macropinocytosis, after which it employs the same molecular machinery to start migrating again to examine another location. This cycle of migration/macropinocytosis allows cells to explore tissues, and it is key to a range of physiological processes. Evidence of this evolutionarily conserved antagonism between the two processes can be found in several cell types-immune cells, for example, being particularly adept-and ancient organisms (e.g., the social amoeba Dictyostelium discoideum). How macropinocytosis and migration are negatively coupled is the subject of this chapter.


Antidyskinetic effect of magnesium sulfate in MPTP-lesioned monkeys.
The antiparkinsonian action of an NMDA receptor antagonist, magnesium sulfate (50, 100, and 200 mg/kg), alone and in association with levodopa was explored in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian and control rhesus monkeys. At the three doses tested, magnesium sulfate decreased levodopa-induced dyskinesia [cumulative dyskinetic scores after levodopa: 129 +/- 13; after levodopa and magnesium sulfate: 65 +/- 14 (50 mg/kg), P < 0.001; 64 +/- 10 (100 mg/kg), P < 0.001; 66 +/- 21 (200 mg/kg), P < 0.001, compared to levodopa administration alone]. These results show that magnesium sulfate importantly reduces levodopa-induced dyskinesia.


Single-Well Injection-Drift Test to Estimate Groundwater Velocity.
A simple algebraic equation is presented here to estimate the magnitude of groundwater velocity based on data from a single-well injection-drift test thereby eliminating the time-consuming and costly extraction phase. A volume of tracer-amended water was injected by forced-gradient into a single well followed by monitoring of the conservative solute tracers under natural-gradient conditions as their upgradient portions drifted back through the well. The breakthrough curve data from the single well during the drift phase was analyzed to determine the mean travel times of the tracers. The estimated mean upgradient travel distance back through the single well and the mean travel times of the tracers were used in a simple algebraic equation to estimate groundwater velocity. The groundwater velocity based on the single-well injection-drift test was estimated to be approximately 0.64 ft per day. Two transects of observation wells were used to monitor the natural-gradient tracer transport downgradient of the injection well. The one-dimensional, or dual-well, transport of the tracer from the injection well to the nearest downgradient observation well indicated that the groundwater velocity was 0.55 ft per day. The two-dimensional, or multi-well, transport of the center of mass of the tracers indicated that the groundwater velocity was 0.60 ft per day; the dual- and multi-well results were in excellent agreement with those from the single-well and validated the simple algebraic equation. The new single-well method presented here is relatively simple, rapid, and does not require an extraction phase.


Experimental demonstration of a continuously variant fractional fourier transformer.
We demonstrate that an off-axis illuminated hemispherical-rod microlens acts as a fractional Fourier transformer with a continuously varying degree of fractionality. A complete theoretical treatment of the device as well as experimental results are presented.


Interpretation of red cell survival data for in vivo compatibility testing: a normal value study.
Short-term survival studies are sometimes required to determine the compatibility of donor red cells. The results of these studies are generally expressed as per cent survival at 60 min. The present study was undertaken to investigate the potential for more sophisticated data analytical techniques to improve sensitivity. In one group of eight healthy male volunteers, autologous red cells were labelled with 51chromium and injected immediately, while in a second group, red cells were stored for 5 d prior to injection. In both groups, eight to 10 samples were collected in the first 6 h and another 10-12 samples over the next 4 weeks. Estimation of the 60 min per cent survival was insufficiently sensitive to detect 'physiological' haemolysis following injection of 5-d-old autologous blood. Regression analysis of 6 h survival data, however, demonstrated significantly higher red cell clearance rates in these cases than in those receiving fresh cells, with a mean 24 h loss of 3.3% of activity. The upper limit for the 6 h red cell clearance rate was 1.63%/h after fresh autologous blood and 2.43%/h after 5-d-old blood. The significance of these findings is discussed and a protocol suggested for the analysis of short-term red cell survival data.


Augmentation of tendon-to-bone healing with a magnesium-based bone adhesive.
Healing of an anterior cruciate ligament graft in a bone tunnel occurs by formation of fibrous scar tissue, which is weaker than the normal fibrocartilaginous insertion. We hypothesized that a magnesium-based bone adhesive would improve tendon-to-bone healing in a rabbit anterior cruciate ligament reconstruction model. Controlled laboratory study. Thirty-five New Zealand White rabbits underwent bilateral anterior cruciate ligament reconstructions with semitendinosus autografts. A total of 12.5 g of bone adhesive was placed in the intraosseous tunnel around the graft in one limb, while the tunnels in the contralateral limb received no implant. Sixteen animals each were sacrificed at 3 weeks and at 6 weeks (12 biomechanical testing/4 histology). Outcomes included semiquantitative histologic analyses for new cartilage formation and fibrous tissue formation in the tendon-bone interface, microcomputed tomography to quantify new bone formation along the bone tunnel, and biomechanical testing of load-to-failure and stiffness. Three animals were sacrificed at time 0 to confirm adequate tunnel fill with the bone adhesive on microcomputed tomography. All specimens had adequate tunnel fill with the bone adhesive at time 0. Application of the bone adhesive resulted in more cartilage formation and less fibrous tissue formation at the tendon-bone interface at 6 weeks compared with controls (P < .05). There was significantly more bone formation in the tibia of the treated limbs at 6 weeks (P = .01). The load-to-failure was significantly higher in the treated group at 6 weeks (71.8 +/- 31.8 N vs 43.4 +/- 14.8 N; P = .04). There were no differences in stiffness at either time point, and there were no differences at 3 weeks in any outcome variable. The magnesium-based bone adhesive improves tendon-to-bone healing based on histologic and biomechanical testing at 6 weeks in a rabbit model of anterior cruciate ligament reconstruction. Further studies are needed to investigate the clinical potential of this bone adhesive to enhance healing and decrease recovery time in soft-tissue ligament reconstruction.


Diagnostic value of [ 68 Ga]Ga-Pentixafor versus [ 18 F]FDG PET/CTs in non-small cell lung cancer: a head-to-head comparative study.
In this study, we aimed to compare the diagnostic value of [ 68 Ga]Ga-Pentixafor and [ 18 F]FDG PET/CT in the evaluation of non-small cell lung cancer (NSCLC) patients. Patients with pathology-proven NSCLC were prospectively included. Patients underwent [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT within 1 week. All suspicious lesions were interpreted as benign or malignant, and the corresponding PET/CT semi-quantitative parameters were recorded. A two-sided P -value <0.05 was considered significant. Twelve consecutive NSCLC patients (mean age: 60 ± 7) were included. All patients underwent both [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT scans with a median interval of 2 days. Overall, 73 abnormal lesions were detected, from which 58 (79%) were concordant between [ 18 F]FDG and [ 68 Ga]Ga-Pentixafor PET/CT. All primary tumors were clearly detectable in both scans visually. Also, [ 68 Ga]Ga-Pentixafor PET/CT demonstrated rather comparable results with [ 18 F]FDG PET/CT scan in detecting metastatic lesions. However, malignant lesions demonstrated significantly higher SUVmax and SUVmean in [ 18 F]FDG PET/CT ( P -values <0.05). Regarding the advantages, [ 68 Ga]Ga-Pentixafor depicted two brain metastases that were missed by [ 18 F]FDG PET/CT. Also, a highly suspicious lesion for recurrence on [ 18 F]FDG PET/CT scan was correctly classified as benign by subsequent [ 68 Ga]Ga-Pentixafor PET/CT. [ 68 Ga]Ga-Pentixafor PET/CT was concordant with [ 18 F]FDG PET/CT in detecting primary NSCLC tumors and could visualize the majority of metastatic lesions. Moreover, this modality was found to be potentially helpful in excluding tumoural lesions when the [ 18 F]FDG PET/CT was equivocal, as well as in detecting brain metastasis where [ 18 F]FDG PET/CT suffers from poor sensitivity. However, the count statistics were significantly lower.


Label-free and sensitive strategy for microRNAs detection based on the formation of boronate ester bonds and the dual-amplification of gold nanoparticles.
MicroRNAs (miRNAs), regulating gene expression by translational repression or degradation of messenger RNAs, are believed to be important for cancer diagnosis and prognosis serving as reliable molecular biomarkers. Simple, sensitive, and cost-effective assays for miRNAs are therefore in urgent demand. The main difference in the structure of RNA versus DNA is the presence of a hydroxyl group at the 2' position of the ribose sugar in RNA, which makes the RNA molecule contain cis-diol at the end of the chain. Hydrophilic boronic acids are well known to form covalent bonds with cis-diols. In this work, we reported a label-free and sensitive method for the detection of miRNAs based on the formation of boronate ester covalent bonds and the dual-amplification of gold nanoparticles (AuNPs). Specifically, miRNAs were captured by the pre-immobilized DNA probes at the gold electrode, and derivatized with 4-mercaptophenylboronic acid (MBA)-capped AuNPs (MBA-AuNPs) through the formation of tight covalent bonds between the boronic acids of MBA-AuNPs and diols of miRNAs. Electrochemically active dopamine (DA)-capped AuNPs (DA-AuNPs) were then attached by the anchored MBA-AuNPs via the interaction of boronic acids and DA tags, which facilities the amplified voltammetric detection of miRNAs. Analytical merits (e.g., sensitivity, reproducibility, storage stability, dynamic range, and selectivity) were addressed. We believe that the results will be valuable for the development of biosensor for the detection of miRNAs in a biological matrix.


FCGR3B gene frequencies and FCGR3 variants in a Chinese population from Zhejiang Province.
The human neutrophil antigens HNA-1a, -1b and -1c play an important role in immune neutropenia. The frequencies of the coding FCGR3B genes were determined in different populations. New FCGR3B variants were also found in some populations. This study investigated the FCGR3B gene frequencies and FCGR3 variants in a Chinese population compared with the results of Northern Germans and African Blacks (Uganda). Our results show that the gene frequencies in 413 healthy Chinese individuals from Zhejiang Province were 0.565 for FCGR3B*1, 0.430 for FCGR3B*2 and 0.00 for FCGR3B*3. The genotype frequency of FCGR3B(null) was 0.48% (2/413). Sequencing of FCGR3 revealed that in seven out of 19 Chinese individuals, cloned and sequenced DNA fragments that exhibited variants caused by single nucleotide exchanges at one or more of the polymorphic positions 141, 147, 227, 266 and 277 in exon 3 also existed in this Chinese population. From the present study, it is concluded that the FCGR3B*1 gene is more frequent in a Chinese population from Zhejiang Province than the FCGR3B*2 gene, and the FCGR3B*3 gene seems to be absent, which is in contrast to studies in the white populations. Gene variants caused by single nucleotide exchanges were found in addition to the well-known forms, but the reason for this remains unclear.


Effect of vanadate on protein phosphorylation and on acid phosphatase activity in the canine prostate.
To evaluate the possible role of intracellular phosphatases in the local regulation of prostatic functions, the effect of sodium orthovanadate (VO4), an inhibitor of phosphotyrosyl protein phosphatases, was studied on both protein phosphorylation and acid phosphatase activity. Secretory and non-secretory epithelial cells were isolated from normal and metaplastic prostates and incubated with [32P]phosphate in the presence and in the absence of VO4; the phosphoproteins were separated by electrophoresis and the gels were either directly submitted to autoradiography or after an alkali treatment to reveal those proteins enriched in phosphotyrosine. Prior to alkali treatment, several phosphoproteins were evidenced and in less than half of the cell preparations a slight increase in labeling intensity under vanadate (less than 75%) was observed in two phosphoproteins, p57 and p44. After alkali treatment: (1) the effect of VO4 on p57 remained in the order of 44-45% and it was restricted to less than half of non-secretory cell preparations; (2) its effect on p44 was intensified (134-207%) and observed in all cell types and in more than 80% of all preparations; and (3) in half of non-secretory cell preparations from metaplastic glands, an effect of VO4 on p35 (127%) became evident. In all instances, with normal and/or metaplastic prostates, protein phosphorylation activity, either total or alkali-resistant and in the presence or in the absence of VO4, was always higher in non-secretory epithelial cells as compared to secretory cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Self-wetting triphase photocatalysis for effective and selective removal of hydrophilic volatile organic compounds in air.
Photocatalytic air purification is widely regarded as a promising technology, but it calls for more efficient photocatalytic materials and systems. Here we report a strategy to introduce an in-situ water (self-wetting) layer on WO3 by coating hygroscopic periodic acid (PA) to dramatically enhance the photocatalytic removal of hydrophilic volatile organic compounds (VOCs) in air. In ambient air, water vapor is condensed on WO3 to make a unique tri-phasic (air/water/WO3) system. The in-situ formed water layer selectively concentrates hydrophilic VOCs. PA plays the multiple roles as a water-layer inducer, a surface-complexing ligand enhancing visible light absorption, and a strong electron acceptor. Under visible light, the photogenerated electrons are rapidly scavenged by periodate to produce more •OH. PA/WO3 exhibits excellent photocatalytic activity for acetaldehyde degradation with an apparent quantum efficiency of 64.3% at 460 nm, which is the highest value ever reported. Other hydrophilic VOCs like formaldehyde that are readily dissolved into the in-situ water layer on WO3 are also rapidly degraded, whereas hydrophobic VOCs remain intact during photocatalysis due to the "water barrier effect". PA/WO3 successfully demonstrated an excellent capacity for degrading hydrophilic VOCs selectively in wide-range concentrations (0.5-700 ppmv).


Sharp 3-Ended Metallic Foreign Body in an Infant Hypopharynx.
Foreign body ingestion is common in infants and children, but they can pose a difficult situation and a diagnostic problem if the foreign body is embedded in the soft tissues of the pharynx. To the best of our knowledge, this is the first case reported with such an unusually shaped foreign body having three sharp ends embedded at two different locations in the hypopharynx of a kid such small in age giving rise to respiratory as well as feeding problem. Secondly, a sharp foreign body penetrating arytenoid causing its swelling and inflammation, thus compromising the glottic opening and producing stridor is a rare phenomenon. We present a case of a 9 months old male infant who presented in ENT emergency with complaints of vomiting, refusal to accept solid as well as liquid feed for 5 days and sudden onset of abnormal grunting sounds on breathing for 1 day. Chest examination revealed intercostal retractions with decreased air entry bilaterally and conducted sounds in chest on auscultation. Abdomen examination revealed no abnormalities, and routine blood and urine investigations were also within normal limits. A metallic foreign body with three sharp ends was visualized in the neck X-ray, the retrieval of which by rigid hypopharyngoscopy relieved the symptoms.


Kinetics of assembly and decay of complement components on Escherichia coli O111:B4 preparation of stable intermediates.
The preparation of bacterial intermediates bearing complement components at various steps of the complement sequence was investigated by suspending immunoglobulin M-opsonized Escherichia coli O111:B4 cells in complement-deficient sera at different temperatures and ionic strengths. The optimal conditions for the formation of the intermediates at Tmax were found to be an ionic strength of 0.091 mu and a temperature of 37 degrees C, except for BAC142, which could be formed equally well at room temperature. In contrast to all the other intermediates, which, once formed at Tmax, were stable in the presence of the whole serum, BAC142 decayed with a half-life of 10 min due to the lability of bound C2. Washing with a buffer of either 0.091 or 0.046 mu did not affect the bacterial intermediates, with the exception of BAC1-3 formed either in the presence of C5-deficient serum or with purified C3 added to BAC142. All the intermediates were found to be stable after incubation in 0.091-mu buffer for 30 min at 37 degrees C.


Determinants of occupational hazards knowledge and safety practices among textile workers in Karachi, Pakistan: a cross sectional study.
To determine the factors associated with good knowledge and safe practices regarding occupational hazards among textile workers. The cross-sectional study was conducted in Karachi from September 2015 to February 2016, and comprised male workers from seven textile mills. A 45-item structured questionnaire was developed and pretested in Urdu, the local language. One part of the questionnaire comprised 31 items related to good knowledge, and the other part comprised 14 items related to safe practices. Data was analysed using SPSS 19. Of the 300 subjects, 123(41%) were aged 18-27 years, 183(63%) were educated, 184(61.3%) worked more than eight hours daily, 170(57%) were employed in the weaving section and 164(55%) as machine operators. Besides, 231(77%) had good knowledge, and 62(21%) reported safe practices. Educated workers were more likely (p<0.05), and machine operators were less likely (p<0.05) to have good knowledge, while educated workers, those in the spinning section and those working less than 8-hours daily (p<0.05) were more likely to report safe practices. There was a high knowledge level, but a wide gap in adopting safety practices, which indicates need for focused interventions targeting high-risk workers and regulation of working hours.


Production of monoclonal antibodies and development of an ELISA for solamargine.
The ratio of hapten and bovine serum albumin in an antigen conjugate was determined by matrix-assisted laser desorption/ionization mass spectrometry. A hybridoma secreting monoclonal antibodies against solamargine was produced by fusing splenocytes immunized with a solamargine-bovine serum albumin conjugate with HAT-sensitive mouse myeloma cell line, P3-X63-Ag8-653. Extensive cross-reaction of anti-solamargine antibodies against solasonine appeared. Aglycone of solamargine, solasodine cross-reacted with anti-solamargine antibodies resulting in a 43.8% cross-reaction. Insignificant cross-reaction appeared with tomatine (2.06%). The full measuring range of the assay extends from 57.5 pmol ml(-1) to 11.5 nmol ml(-1) of solamargine.


Antimicrobial properties of some West African medicinal plants iv. Antimicrobial activity of xylopic acid and other constituente of the fruits of Xylopia aethiopica (Annonaceae).
Xylopic acid and four other isolates from the fresh ripe fruits of Xylopia aethiopica a common ingredient in several Ghanaian folklore medicines and foods, have been examined for antimicrobial activity against five micro-organisms, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Xylopic acid and two other diterpene isolates were found to have antimicrobial properties.


Fuzi decoction ameliorates pain and cartilage degeneration of osteoarthritic rats through PI3K-Akt signaling pathway and its clinical retrospective evidence.
Osteoarthritis (OA) is a difficult disease but the clinic lacks effective therapy. As a classic formula of traditional Chinese medicine (TCM), Fuzi decoction (FZD) has been clinically applied for treating OA-related syndromes, but its anti-OA efficacy and mechanism remain unclear. To experimentally and clinically determine the anti-OA efficacy of FZD and clarify the underlying mechanism. UPLC/MS/MS was applied to identify the main components of FZD. A monoiodoacetate (MIA)-induced OA rat model was employed to evaluate the in vivo efficacy of FZD against OA, by using pain behavior assessment, histopathological observation, and immunohistochemical analysis. Primary rat chondrocytes were isolated to determine the in vitro effects of FZD by using cell viability assay, wound healing assay, and real-time PCR (qPCR) analysis on anabolic/catabolic mRNA expressions. RNA sequencing (RNA-seq) and network pharmacology analysis were conducted and the overlapping data were used to predict the mechanism of FZD, followed by verification with qPCR and Western blot assays. Finally, a retrospective analysis was performed to confirm FZD's efficacy and safety in OA patients. The UPLC/MS/MS result showed that FZD contained atractylenolide I, benzoylhypaconitine, benzoylmesaconitine, benzoylaconitine, hypaconitine, mesaconitine, aconitine, lobetyolin, paeoniflorin, and pachymic acid. The in vivo data showed that FZD restored the cartilage degeneration in MIA-induced OA rats by ameliorating pain behavior parameters, recovering histopathological alterations, benefitting cartilage anabolism (up-regulating Col2 expression), and suppressing catabolism (down-regulating MMP13 and Col10 expressions). The in vitro data showed that FZD increased cell viability and wound healing capacity of chondrocytes, and restored the altered expressions of anabolic and catabolic genes of chondrocytes. The overlapping results of RNA-seq and network pharmacology analysis suggested that PI3K/Akt signaling mediated the anti-OA mechanism of FZD, which was verified by qPCR and Western blot experiments. Clinically, the anti-OA efficacy and safety of FZD were confirmed by the retrospective analysis on OA patients. The scientific innovation of this study was the determination of anti-OA efficacy of FZD by experimental and clinical evidence and the discovery of its mechanism by integrated RNA-seq, network pharmacology, and molecular experiments, which suggests FZD as a promising TCM agency for OA treatment.


Liposomally-entrapped ATP: improved efficiency against experimental brain ischemia in the rat.
ATP was entrapped inside negatively charged liposomes composed of sulfatide, in order to improve its penetration into the brain and to reduce its degradation into other tissues. These liposomes were prepared according to an original method allowing a satisfying stability of the formulation. Liposomally entrapped ATP was administered intracerebroventricularly to rats submitted to brain ischemic episodes by both carotid artery clamping and systemic blood pressure lowering (during 3 minutes every 15 minutes). Such treatment importantly increases the number of ischemic episodes before brain silence appeared. So, this paper allows new perspectives in the administration of drugs into the brain.


Effects of eccentric overload training on patellar tendon and vastus lateralis in three days of consecutive running.
The analysis of structural changes in patellar tendon and muscle of healthy subjects in response to mechanical loads provides useful insight into the mechanism underlying overuse injuries. Changes produced in tendon and muscles structures after eccentric overload training and three consecutive running days were examined. Twenty healthy subjects were recruited and divided into two groups. One group (ECC) performed eccentric overload squat training (six weeks). After such training, the ECC group performed three running sessions on consecutive days, as did the control group (CONT). The structure of their patellar tendons and vastus lateralis muscles was quantified using ultrasound and Doppler imaging. Images were obtained before and after eccentric training for the ECC group and on every day of running performance for both groups. After eccentric training, the ECC group experienced an increase in cross-sectional area (CSA) of patellar tendon (P=0.012). After every day of running, the ECC group experienced a decrease in CSA (P=0.027). In the CONT group, after one day of running a significant increase was observed in anteroposterior width of their patellar tendon (P=0.028), as well as a decrease in pennation angle of vastus lateralis muscle (P=0.028) within three days of running sessions. Eccentric overload training brought about changes in the patellar tendon consistent with an improvement in the quality of the tissue. The ECC group in our study showed a more normalised pattern than the CONT group in the running performance, in agreement with previous research. Level 3, controlled trial.


Electrocardiographic aspects of skin diving.
Electrocardiographic (ECG) aspects of skin diving were monitored by means of continuous ECG recording in a pool 15 m deep. Ten regularly trained divers with different levels of experience divid a minimum of three consecutive times, holding their beath, reaching depths of 6 m, 9 m, and 12 or 15 m. The water temperature was 28 degrees C. During the ascending part of these dives, bradycardia was observed in all skin-divers. Minimal heart rate correlated negatively with the diver's experience (number of dives previously performed). In six divers cardiac arrhythmia was observed. Atrial arrhythmias were sometimes isolated occurrences, but more frequently they were multiple. Ventricular arrhythmias tended to be bigeminal. Apparently, forced expiration through the snorkel when surfacing precipitated these rhythmic disorders.


Antiphytopathogenic activity of the bioluminescent mushroom Neonothopanus nambi against root-rot disease.
Aurisin A (1) and the culture medium of the luminescent mushroom Neonothopanus nambi showed antifungal activity against Phytophthora palmivora, which causes the root-rot disease of Monthong durian, in a preliminary greenhouse experiment. Moreover, a new natural product, neonambiquinone B (2), was isolated. Their structures were elucidated by mass, IR and extensive analysis of their 1D and 2D NMR spectroscopic data. The results demonstrated that the culture medium of N. nambi is a promising potential for their agricultural applications.


A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat or human term myometrium.
Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP's inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8×10-6M and 0.9×10-3M) and human myometrial contractions (EC50 16.3×10-6M and 1.1×10-3M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.


Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma.
(1) Background: Upfront treatment consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has relevantly contributed to achieving durable remissions following induction treatment in multiple myeloma (MM) patients. The optimization of HDCT regimens can, therefore, essentially contribute to improving the depth and duration of tumor remissions. To date, melphalan at 200 mg/m2 is the standard HDCT regimen for fit MM patients. In our previous work, we showed promising efficacy and safety results for treosulfan (14 g/m2) and melphalan (200 mg/m2) (TreoMel) in acute myeloid leukemia (AML) patients receiving ASCT. Based on these data, TreoMel became the standard of care for fit MM patients at our institution. (2) Methods: We identified 115 consecutive MM patients who underwent consolidation with TreoMel between 01/2020 and 08/2022 at the University Hospital of Bern. We analyzed the safety and efficacy data, as well as the treosulfan pharmacokinetics, correlating them with tumor responses. (3) Results: A complete response (CR) rate of 84% was achieved, which is comparable to the CR rate reported for the quadruplet combination. The median PFS was 30 months (95% CI: 20.4-not reached), and the 31-month OS rate was 83%. The median area under the curve (AUC) for treosulfan was 952.5 mg*h/L (range: 527.4-1781.4), and the median peak level was 332.3 mg/L (range: 168-554). The treosulfan pharmacokinetics showed no significant correlation with MM responses after HDCT and ASCT. However, female patients had a significantly higher AUC (p = 0.007) and peak value (p = 0.001), and the higher values were associated with longer hospitalizations. (4) Conclusions: Treatment consolidation with TreoMel HDCT demonstrated a promising efficacy and safety profile in our cohort of MM patients and deserves further investigation in prospective studies.


Impact of South Carolina's Medicaid fluoride varnish reimbursement policy on children's receipt of fluoride varnish in medical and dental settings.
We estimated the effect of South Carolina's (SC) Medicaid fluoride varnish (FV) reimbursement policy on children's receipt of fluoride varnish in medical (MFV) and dental (DFV) settings. We obtained data from SC Medicaid enrollment and claims files for children ≤ 47 months of age across State Fiscal Years (SFY) 2008-2013 and created a panel dataset of 52,841 children representing 126,464 child-years of observation. Pooled multivariate logistic regression models were estimated to identify factors associated with a higher likelihood of a child receiving one or more MFV or DFV treatments. The FV rates per child-year were 1 percent for physicians and 23 percent for dentists, respectively. The child-year rate for receipt of FV from both a physician and a dentist was less than one-third of one percent. A policy designed to increase access to FV treatments from physicians and dentists for children up to forty-seven months of age was not successful for physicians; however, the positive findings for dentists were promising.


Effects of a multiple health behavior change intervention for colorectal cancer survivors on psychosocial outcomes and quality of life: a randomized controlled trial.
Multiple health behavior change can ameliorate adverse effects of cancer. The purpose of this study was to determine the effects of a multiple health behavior change intervention (CanChange) for colorectal cancer survivors on psychosocial outcomes and quality of life. A total of 410 colorectal cancer survivors were randomized to a 6-month telephone-based health coaching intervention (11 sessions using acceptance and commitment therapy strategies focusing on physical activity, weight management, diet, alcohol, and smoking) or usual care. Posttraumatic growth, spirituality, acceptance, mindfulness, distress, and quality of life were assessed at baseline, 6 and 12 months. Significant intervention effects were observed for posttraumatic growth at 6 (7.5, p < 0.001) and 12 months (4.1, p = 0.033), spirituality at 6 months (1.8, p = 0.011), acceptance at 6 months (0.2, p = 0.005), and quality of life at 6 (0.8, p = 0.049) and 12 months (0.9, p = 0.037). The intervention improved psychosocial outcomes and quality of life (physical well-being) at 6 months with most effects still present at 12 months. ( ACTRN12608000399392).


Small echogenic renal masses: how often is computed tomography used to confirm the sonographic suspicion of angiomyolipoma?
Although renal angiomyolipoma (AML) has a typical ultrasound appearance, many authorities suggest that a computed tomography (CT) scan be obtained to confirm the diagnosis because small echogenic renal cell carcinomas can simulate AML. Our study evaluates the actual follow-up in such patients and factors that may affect whether CT confirmation is recommended or obtained. From 1986 through 1992, 36 patients had an ultrasound diagnosis of probable renal AML (well-circumscribed, homogenously echogenic mass). In each case the patient's age, symptoms, ultrasound results and recommendations, and imaging follow-up were recorded. CT confirmation of the sonographic diagnosis was recommended in only 11 of 36 (31%) patients. Only 7 of these 11 patients actually underwent CT, 5 of whom had the diagnosis confirmed by CT detection of intratumoral fat. Ten of 23 patients (43%) over 50 years of age had CT recommended, whereas only 1 of 13 (8%) patients under age 50 years did (P < 0.05). CT confirmation was recommended for 5 of 13 (38%) lesions greater than 10 mm and for 6 of 23 (26%) smaller masses. None of the 9 patients under age 50 years with small masses (less than 10 mm) had CT recommended. Although many authorities recommend CT to confirm the sonographic diagnosis of renal AML, this algorithm is rarely followed in everyday clinical practice, especially in patients under age 50 years with masses less than 10 mm.


Patterns of indoor radon concentrations, radon-hazard potential, and radon testing on a small geographic scale in Utah.
Currently, there are no publicly-available estimates of indoor radon concentration at scales smaller than the county. Radon-hazard potential soil maps that reflect underlying geologic factors can be created at small geographic scale and linked to residential and census data. We determined the association between residential radon tests and high radon-hazard potential soil at the residential and block group levels using a large Utah-based dataset. We also identified characteristics of block groups with limited tests in the dataset. We geocoded a dataset of residential radon tests obtained from 2001 to 2017 by a statewide educational program. We linked each location to maps of radon-hazard potential soil, the Environmental Protection Agency's (EPA) county radon zones. We also calculated the number of tests conducted in each block group and linked block groups to demographic data from the 2020 United States census. Log-linear and logistic models identified the association between residential home test results and 1) radon-hazard potential soil of each residence, 2) percent of residences on high radon-hazard potential soils in block groups, and 3) EPA's radon zones. We compared demographic characteristics among block groups with ≥5 or <5 residential tests in our dataset. Approximately 42% of homes in the dataset tested ≥4 pCi/L. We found significant positive associations for residential radon test results with 1) residential location on high radon-hazard potential soil and 2) block groups with >0% of residences on high radon-hazard potential soil. EPA radon zones were not associated with residential test results. Block groups with <5 tests had higher than the statewide median percentage of Hispanic residents (OR = 2.46, 95% CI = 1.89-3.21) and were located in rural counties. Radon-hazard potential soil has a significant association with residential home radon tests. More efforts are needed to improve radon testing in block groups that are rural and have greater percentages of racial minorities.


Current consensus on the management of primary sclerosing cholangitis.
Guidelines for the management of primary sclerosing cholangitis (PSC) have recently been published by both the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD). The current review focuses on the management of PSC, based on these guidelines. There is no established medical therapy for PSC. The role for UDCA in slowing the disease progression and improving survival is as yet unclear, and there are no specific recommendations for the general use of UDCA in this condition. Guidelines recommend that dominant bile duct strictures with significant cholestasis should be treated with biliary dilatation, with or without stenting. Prospective studies to define type, duration, optimal frequency and long-term effects of endoscopic therapy are needed. Liver transplantation is recommended for end stage disease and has excellent results. PSC patients with dysplasia in biliary brush cytology specimens should also be considered for transplantation. There is no evidence-based algorithm for the follow-up of PSC patients, but some regular investigations are recommended (surveillance colonoscopies in patients with IBD and ultrasound to detect gallbladder mass lesions).


A fuzzy model of glucose regulation.
We present a detailed glucose regulation model using fuzzy inference system (FIS) descriptions of hormonal control action and the familiar Michaelis-Menten (M-M) kinetic description for glucose transport. The fuzzy M-M model is compared and contrasted with a well-known comprehensive glucose model. The two models give similar results for glucose response, endogenous glucose production, and total uptake. The fuzzy M-M model features a renal subsystem that provides 25% of the endogenous glucose production. The work demonstrates the successful application of fuzzy logic and fuzzy inference to biological modelling. The flexibility of fuzzy inference, a linguistic description technique, permits conceptually simple statements about nonlinear processes.


Phylogenetic and structural information on glyceraldehyde-3-phosphate dehydrogenase (G3PDH) in Plasmodium provides functional insights.
Plasmodium is dependent on glycolysis for ATP production. The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (G3PDH) plays an important role in glycolysis and is, therefore, a potential target for antimalarial drug development. The g3pdh gene of nine Plasmodium species was sequenced from genomic DNA and the type and origin determined by phylogenetic analysis. Substitutions were analyzed over a wide phylogenetic spectrum in relation to the known three-dimensional structures of the P. falciparum and human proteins. Substitutions were found within the functional domains (Rossman NAD+-binding and catalytic domains). A number of replacements within the adenosyl-binding surfaces were found to be conserved within the Chromoalveolates, others in the Apicomplexa, and still others within the genus Plasmodium, all of which were different from the human sequence. These sites may prove to be of functional importance and provide insights for drug-targeting studies, as have other regions examined in Leishmania and Toxoplasma G3PDH research.


Histamine H2 receptor mediates postsynaptic excitation and presynaptic inhibition in submucous plexus neurons of the guinea-pig.
Intracellular recordings were made from submucous plexus neurons of the guinea-pig cecum maintained in vitro. Histamine (0.3-10 microM) produced a dose-dependent membrane depolarization (congruent to 13 mV with 3 microM) in about 28% of the cells tested; most of these cells showed a prominent calcium-activated potassium conductance (AH cells). The depolarization was due primarily to an inactivation of potassium conductance which is available at the resting membrane potential of -60 mV. Peak amplitude of the fast excitatory postsynaptic potential was depressed by histamine (0.1-10 microM) in a dose-dependent manner (congruent to 62% depression with 1 microM). This was observed even in those cells in which histamine did not produce any membrane depolarizations (mostly S cells). The depression of the fast excitatory postsynaptic potential resulted from the presynaptic inhibition of acetylcholine release. Histamine also reduced the amplitude of the non-cholinergic, presumably peptidergic, slow excitatory postsynaptic potential by suppressing peptide release from presynaptic nerve terminals. Peak amplitude of the adrenergic inhibitory synaptic potential was not depressed by histamine suggesting that histamine receptors are not present on presynaptic terminals of sympathetic nerve fibres. Both postsynaptic and presynaptic actions of histamine were blocked by cimetidine or ranitidine but not by pyrilamine implying that H2 receptors are involved.


Blunt cardiac rupture in a patient with a history of total correction of tetralogy of Fallot.
A 35-year-old man with a history of total correction of tetralogy of Fallot (TOF) fell down while riding a bike and experienced blunt cardiac rupture. His vital signs were stable because the bleeding was limited by an adhesion caused by the previous operation. Chest computed tomography clearly displayed the ruptured points, and an emergency operation was performed. Because a pneumothorax was suspected, a cardiopulmonary bypass was established with a femorofemoral bypass while the patient was conscious before artificial ventilation was initiated. Two ruptured points were detected on the anterior wall of the right ventricle and were repaired by suturing. The patient recovered and was discharged without any major complications 40 days after the operation. This is the first published case of blunt cardiac rupture after total correction of TOF.


Bacteria involved in biodegradation of creosote PAH - A case study of long-term contaminated industrial area.
Polycyclic aromatic hydrocarbons (PAH) contained in creosote oil are particularly difficult to remove from the soil environment. Their hydrophobic character and low bioavailability to soil microorganisms affects their rate of biodegradation. This study was performed on samples of soil that were (for over forty years) subjected to contamination with creosote oil, and their metagenome and physicochemical properties were characterized. Moreover, the study was undertaken to evaluate the biodegradation of PAHs by autochthonous consortia as well as by selected bacteria strains isolated from long-term contaminated industrial soil. From among the isolated microorganisms, the most effective in biodegrading the contaminants were the strains Pseudomonas mendocina and Brevundimonas olei. They were able to degrade more than 60% of the total content of PAHs during a 28-day test. The biodegradation of these compounds using AT7 dispersant was enhanced only by Serratia marcescens strain. Moreover, the addition of AT7 improved the effectiveness of fluorene and acenaphthene biodegradation by Serratia marcescens 6-fold. Our results indicated that long-term contact with aromatic compounds induced the bacterial strains to use the PAHs as a source of carbon and energy. We observed that supplementation with surfactants does not increase the efficiency of hydrocarbon biodegradation.


Reconstruction of intractable ulcer of the knee joint in Werner's syndrome with free latissimus dorsi myocutaneous flap.
The authors report the successful treatment of an intractable ulcer of the right knee in a patient with Werner's syndrome, using a free latissimus dorsi myocutaneous flap transfer.


On the moral status of hominins.
This article evaluates the moral status of hominins, and obligations we may have towards them. In exploring these ethical considerations, I consider one of the most recent hominin finds: the 'graveyard' of Homo naledi in the Dinaledi caves at the Cradle of Humankind in South Africa. I argue that findings about H. naledi establish a pro tanto duty not to excavate their remains.


microRNA-148a in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Cardiomyocyte Apoptosis in Atrial Fibrillation by Inhibiting SMOC2.
Exosomes-related microRNAs (miRNAs) have been considered to be the significant biomarkers contributing to the development of atrial fibrillation (AF). We observed the implicit mechanism of exosomes-miR-148a derived from bone marrow mesenchymal stem cells (BMSCs) in AF. The AF cell and mice models were established firstly. QRT-PCR and Western blot analysis were applied to detect the expression of miR-148a, SPARC-associated modular calcium-binding protein 2 (SMOC2), Bcl-2, Bax, and caspase-3. BMSCs were separated from healthy mice and exosomes were obtained from BMSCs. BMSCs were transfected with mimics and inhibitor, and HL-1 cells were treated with mimics and pcDNA3.1. MTT assay were used to detect cell viability of cells. Flow cytometric analysis and TUNEL analysis were used for detecting cell apoptosis of cells. In our study, exosomes derived from BMSCs inhibited the development of AF, and miR-148a acted a vital role in this segment. SMOC2 was a target gene of miR-148a and promoted apoptosis of HL-1 cells. Additionally, miR-148a mimics decreased cellular apoptosis, eliminated SMOC2 expression, and elevated Bcl-2 expression in AF-treated cells. Collectively, miR-148a overexpressed in BMSC-exosomes restrained cardiomyocytes apoptosis by inhibiting SMOC2.


Characterisation of five novel HLA-G alleles with coding DNA base changes.
We identified five novel human leukocyte antigen-G alleles with protein-modifying mutations in Caucasian and/or African populations.


Alcohol consumption: risks and benefits.
Alcohol has had a long and complicated role in human society and health. Excessive use of alcohol causes enormous morbidity and mortality worldwide, but the health effects of alcohol use within recommended guidelines are diverse and complex. Established effects include increased high-density lipoprotein cholesterol and antithrombotic activity, providing plausible mechanisms for the observed association of moderate drinking with lower risk of coronary heart disease but higher risk of hemorrhagic stroke. However, moderate drinking increases sex steroid hormone levels and may interfere with folate metabolism, both of which are potential mechanisms for the observed associations of moderate drinking with several forms of cancer, particularly breast and colorectal. Genetic susceptibility to the effects of alcohol on cancer and coronary heart disease also differs across the population. Recommendations regarding moderate drinking must be individualized to reflect the potentially competing effects of alcohol on several chronic diseases.


Liver haemostasis using microbubble-enhanced ultrasound at a low acoustic intensity.
To explore the haemostatic effects of microbubble-enhanced ultrasound (MEUS) at a very low acoustic intensity on the bleeding liver of rabbits. Liver incisions made on 20 rabbits were treated with a pulsed therapeutic ultrasound transducer. The transducer was operated at 831 KHz with an acoustic intensity of 0.4 W/cm(2). The treatment was coordinated with intravenous injection of microbubbles. Ultrasound only and sham treatment served as the controls. Visual bleeding score and 10-min bleeding volume were evaluated for haemostatic efficacy. Contrast-enhanced ultrasound (CEUS) was performed to assess the liver perfusion. Nine treated livers were harvested for acute histological examination. Regarding the bleeding incisions made on rabbit livers, the haemorrhage stopped immediately after 2 min of MEUS treatment but bleeding continued in the controls treated by ultrasound or microbubble injection alone. The bleeding scores and the 10-min haemorrhagic volumes dropped significantly in the MEUS group compared with those of the controls (p < 0.01). The mechanism of MEUS haemostasis appears to involve the extensive swelling of hepatocytes and the haemorrhage of the portal area, which formed a joint compression on the regional liver circulation. Low acoustic intensity MEUS might provide a novel method for liver haemostasis. • This animal experiment demonstrates a novel method of controlling hepatic haemorrhage • The treatment uses therapeutic ultrasound during enhancement with intravenous microbubbles • This combined therapy was more effective than ultrasound or intravenous microbubbles alone • More work is required with larger animals before potential human trials.


Endothelial Cell Membrane Sensitivity to Shear Stress is Lipid Domain Dependent.
Blood flow-associated shear stress causes physiological and pathophysiological biochemical processes in endothelial cells that may be initiated by alterations in plasma membrane lipid domains characterized as liquid-ordered (l(o)), such as rafts or caveolae, or liquid-disordered (l(d)). To test for domain-dependent shear sensitivity, we used time-correlated single photon counting instrumentation to assess the photophysics and dynamics of the domain-selective lipid analogues DiI-C(12) and DiI-C(18) in endothelial cells subjected to physiological fluid shear stress. Under static conditions, DiI-C(12) fluorescence lifetime was less than DiI-C(18) lifetime and the diffusion coefficient of DiI-C(12) was greater than the DiI-C(18) diffusion coefficient, confirming that DiI-C(12) probes l(d), a more fluid membrane environment, and DiI-C(18) probes the l(o) phase. Domains probed by DiI-C(12) exhibited an early (10 s) and transient decrease of fluorescence lifetime after the onset of shear while domains probed by DiI-C(18) exhibited a delayed decrease of fluorescence lifetime that was sustained for the 2 min the cells were subjected to flow. The diffusion coefficient of DiI-C(18) increased after shear imposition, while that of DiI-C(12) remained constant. Determination of the number of molecules (N) in the control volume suggested that DiI-C(12)-labeled domains increased in N immediately after step-shear, while N for DiI-C(18)-stained membrane transiently decreased. These results demonstrate that membrane microdomains are differentially sensitive to fluid shear stress.


Effect of oral captopril on premature ventricular complexes in patients with preserved left ventricular systolic function: a randomized clinical trial.
Some studies have suggested that angiotensin-converting enzyme (ACE) inhibition in patients with heart failure is associated with a decrease in frequency of spontaneous premature ventricular complexes (PVCs). It is not clear whether such a finding represents a primary effect of ACE inhibition or, instead, a secondary result of treatment of heart failure. For a primary drug effect to be present, PVC suppression during ACE inhibition should also occur in patients with preserved left ventricular systolic function. We therefore undertook a randomized double-blind placebo-controlled crossover clinical trial to assess the effect of oral captopril (50 mg. b.i.d.) on ventricular arrhythmia frequency in 11 patients with > 30 PVCs/h (during a 48-h ambulatory recording) and a left ventricular ejection fraction of > or = 45% (measured by radionuclide multigated acquisition scan). Pharmacologic activity of the administered drug was evidenced by an increase in median plasma renin activity to 2.4 ng/AI/ml/h from a value of 1.1 ng/AI/ml/h during placebo (p = 0.001) and an 8.5 +/- 10.3 drop in mean diastolic blood pressure during captopril versus placebo (p < 0.03). During captopril treatment, a mean of 491 +/- 378 PVCs/h were observed compared with 389 +/- 169 PVCs/h during placebo, a nonsignificant difference. There was also no significant change in left ventricular ejection fraction, plasma catecholamines, or serum potassium during captopril treatment. Thus, ACE inhibition in patients with preserved left ventricular systolic function fails to suppress ventricular ectopic activity. Extrapolated to patients with heart failure, our observations argue against a primary PVC suppressive action of ACE inhibitors but do not rule out possible secondary antiarrhythmic effects of these agents.


Tristerix tetrandrus (Loranthaceae) and its host-plants in the Chilean matorral: patterns and mechanisms.
Interactions between a Chilean mistletoe, quintral (Tristerix tetrandrus, Loranthaceae) and its potential host plants were studied at a site with mediterranean type climate. The results show that the distribution of T. tetrandrus is related to the behavior of avian dispersers, which feed on its fruit, and evacuate the seeds at random in the field, but the distribution is also influenced bymicroenvironmental conditions, survival of seedlings is hampered at drier locations. The infection capacity of the seeds is increased after birds have eliminated the fruit coat.Survival of T. tetrandrus seeds differed depending on the species to which they were attached experimentally. Seeds germinated, and plants developed on Colliguaya odorifera and Kageneckia oblonga, previously reported as susceptible to infection. Survival was significantly higher on C. odorifera, although in the field it is infected less frequently than K. oblonga. In species on which no T. tetrandrus has been previously reported, resistance to infection might be ascribed to different mechanisms: in Quillaja saponaria, differentiation of cork layers apparently prevents penetration by haustoria; in Lithraea caustica haustoria enter the cortex and phloem, but no further development ensues. K. oblonga seldom bears more than one T. tetrandrus plant. Experimental inoculations showed that significantly more seeds developed into plants on K. oblonga individuals not previously infected with quintral, suggesting that they become resistant to infection.


Scarabaeus cristatus (Coleoptera: Scarabaeidae) as intermediate host of Physocephalus dromedarii (Nematoda: Spirocercidae)--a contribution to the epidemiology of camel physocephalidosis.
In UAE, camel Physocephalus dromedarii was diagnosed for the first time in 2011 in dromedaries from a farm that previously had imported animals from foreign countries. The large scarab beetle, Scarabaeus cristatus, was found to be the major intermediate host for this parasite in Dubai. A total of 638 specimens of S. cristatus were collected and examined for the presence of third-stage larvae of nematode larvae at two sites in the Dubai Emirate (Emirates Industry for Camel Milk and Products and horse endurance training track) within a distance of 15 km. Third-stage larvae of P. dromedarii were detected in 94 and 97 % of beetles collected from the territory of the camel milk farm and the endurance training track, respectively. In addition to third-stage larvae, 264 beetles contained second-stage larvae. Only four beetles were infected with other than P. dromedarii larvae. The average larval burden in beetles from camel milk farm was significantly higher compared to those in beetles collected from the other site (1538 vs. 697). Comparison of larval burdens in juvenile and adult beetles collected at the camel milk farm showed a significantly higher intensity in adult specimens (501 vs. 1734) while in beetles found on the horse endurance track, larval burdens were comparable (548 vs. 858). The results suggest that S. cristatus become infected at the camel milk farm, and in search for other sources of food, they fly to places where they were found feeding on feces of other animals.


Validation of diagnostic algorithm to differentiate between tuberculous meningitis and acute bacterial meningitis.
Discrimination between tuberculous and acute bacterial meningitis is difficult by clinical features alone and laboratory methods may only supplement the clinical suspicion. We aimed to validate the diagnostic criteria by Thwaites et al. [1] and construct our own diagnostic predictors based on the clinical and laboratory features. 380 patients of acute bacterial meningitis (ABM) and 210 patients of tuberculous meningitis (TBM) were enrolled retrospectively from June 2004 to June 2007 and prospectively from July 2007 to September 2008. HIV positive patients were excluded. Detailed history, clinical examination CSF analysis, haematological, biochemical investigations and imaging was performed in all patients. Factors associated with the diagnosis of TBM in the present study included rural area of residence, longer duration of disease, presence of clear CSF, lower percentage of CSF neutrophils, presence of diplopia and hemiparesis. On validation, age did not appear as a significant factor in our population. The diagnostic algorithm from our study group had a sensitivity of 95.71% and specificity of 97.63%. The diagnostic criterion has a fair validation in our population when the age factor is excluded. The rule is useful in HIV negative patients with low CSF sugar and negative organism yield in the CSF.


Copper-catalyzed cross coupling reaction of sulfonyl hydrazides with 3-aminoindazoles.
A novel Cu-catalyzed radical-radical cross coupling reaction of 3-aminoindazoles with sulfonyl hydrazides has been disclosed, enabling the production of diverse 1,3-substituted aminoindazoles in good yields. This methodology is distinguished by readily available starting materials, wide substrate scope and operational simplicity. In addition, a gram-scale reaction has been well demonstrated.


Association of intimate partner physical and sexual violence with unintended pregnancy among pregnant women in Peru.
To examine the associations between lifetime physical and/or sexual intimate partner violence (IPV) with pregnancy intent among pregnant women in Lima, Peru. A total of 2167 women who delivered at the Instituto Nacional Materno Perinatal, Lima, Peru were interviewed during the postpartum recovery period. Logistic regression was used to estimate multivariable adjusted odds ratios and 95% confidence intervals. Lifetime physical or sexual violence (40.0%) and unintended pregnancies (65.3%) were common in the study population. Compared with non-abused women, abused women had a 1.63-fold increased risk for unintended pregnancy. Unintended pregnancy risk was 3.31-fold higher among women who experienced both physical and sexual abuse compared with non-abused women. The prevalence and severity of physical violence during pregnancy was greater among women with unintended pregnancies compared with women with planned pregnancies. The findings indicate the need to include IPV screening and treatment in prenatal care and reproductive health settings.


Effects of thyroid hormones on human breast cancer cell proliferation.
The involvement of estrogens in breast cancer development and growth has been well established. However, the effects of thyroid hormones and their combined effects with estrogens are not well studied. We investigated the response of human breast cancer cells to thyroid hormone, particularly the role of T3 in mediating cell proliferation and gene expression. We demonstrated that 17beta-estradiol (E2) or triiodothyronine (T3) promoted cell proliferation in a dose-dependent manner in both MCF-7 and T47-D cell lines. The E2- or T3-dependent cell proliferation was suppressed by co-administration of the ER antagonist ICI. We also demonstrated that T3 could enhance the effect of E2 on cell proliferation in T47-D cells. Using an estrogen response element (ERE)-mediated luciferase assay, we determined that T3 was able to induce the activation of ERE-mediated gene expression in MCF-7 cells, although the effects were much weaker than that induced by E2. These results suggest that T3 can promote breast cancer cell proliferation and increase the effect of E2 on cell proliferation in some breast cancer cell lines and thus that T3 may play a role in breast cancer development and progression.


Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19.
To explore ABO blood group distribution and clinical characteristics in patients with COVID-19. The clinical data of 187 patients with COVID-19 seen between January 20, 2020 and March 5, 2020 at the First Hospital of Changsha were retrospectively analyzed. The differences in the ABO blood group distribution between COVID-19 patients and the control group (1991 cases) were analyzed. The relationship between blood type and clinical characteristics was analyzed. Of the 187 patients with COVID-19, 69 had type A (36.90%), 63 had type B (33.69%), 41 had type O (21.92%), and 14 had type AB blood (7.49%). The proportion of patients with type A blood in the COVID-19 group was significantly higher than that in the control group (36.90% vs. 27.47%, P = 0.006), while the proportion of patients with type O blood in the COVID-19 group was significantly lower than that in the control group (21.92% vs. 30.19%, P = 0.018). The risk of COVID-19 was higher for individuals with blood group A than for those with blood group O (OR = 1.849, 95% CI = 1.228-2.768, P = 0.003). The risk of COVID-19 was higher for patients with blood group A than for those with a blood group other than A (OR = 1.544, 95% CI = 1.122-2.104, P = 0.006). Patients with blood group O had a lower risk of COVID-19 than non-O blood group patients (OR = 0.649, 95% CI = 0.457-0.927, P = 0.018). The ABO blood group distribution was related to COVID-19 status. Patients with blood group A had an increased risk for infection with SARS-CoV-2, whereas blood group O was associated with a decreased risk, indicating that certain ABO blood groups were correlated with SARS-CoV-2 susceptibility. Blood type was related to some clinical characteristics of patients with COVID-19.


Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats.
There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P<0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P<0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P<0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens.


Co-Doped Mn3 O4 Nanocubes via Galvanic Replacement Reactions for Photocatalytic Reduction of CO2 with High Turnover Number.
The synthesis of Co-doped Mn3 O4 nanocubes was achieved via galvanic replacement reactions for photo-reduction of CO2 . Co@Mn3 O4 nanocubes could efficiently photo-reduce CO2 to CO with a remarkable turnover number of 581.8 using [Ru(bpy)3 ]Cl2 ⋅ 6H2 O as photosensitizer and triethanolamine as sacrificial agent in acetonitrile and water. The galvanic replaced Co species are homogeneously distributed at the outer surface of Mn3 O4 , providing catalytic active sites during CO2 reduction reactions, which facilitate the separation and migration of photogenerated charge carriers, further benefiting the outstanding photocatalytic performance of CO2 reduction. Density functional theory calculations revealed that the decreasing of conduction band maximum in Co@Mn3 O4 was beneficial to the electron attachment from the excited sensitized molecule, which promoted photocatalytic reduction of CO2 .


Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers.
Obsessive-Compulsive Disorder (OCD) is a prevalent and severe clinical condition whose hallmarks are excessive, unwanted thoughts (obsessions) and repetitive behaviors (compulsions). The onset of symptoms generally occurs during pre-adult life and typically affects subjects in different aspects of their life's, compromising social and professional relationships. Although robust evidence suggests a genetic component in the etiopathogenesis of OCD, the causes of the disorder are still not completely understood. It is thus of relevance to take into account how genes interact with environmental risk factors, thought to be mediated by epigenetic mechanisms. We here provide an overview of genetic and epigenetic mechanisms of OCD, focusing on the modulation of key central nervous system genes, in the attempt to suggest possible disease biomarkers.


Abnormal dynamic resting-state brain network organization in auditory verbal hallucination.
Auditory-verbal hallucinations (AVH) are a key symptom of schizophrenia. Recent neuroimaging studies examining dynamic functional connectivity suggest that disrupted dynamic interactions between brain networks characterize complex symptoms in mental illness including schizophrenia. Studying dynamic connectivity may be especially relevant for hallucinations, given their fluctuating phenomenology. Indeed, it remains unknown whether AVH in schizophrenia are directly related to altered dynamic connectivity within and between key brain networks involved in auditory perception and language, emotion processing, and top-down control. In this study, we used dynamic connectivity approaches including sliding window and k-means to examine dynamic interactions among brain networks in schizophrenia patients with and without a recent history of AVH. Dynamic brain network analysis revealed that patients with AVH spent less time in a 'network-antagonistic' brain state where the default mode network (DMN) and the language network were anti-correlated, and had lower probability to switch into this brain state. Moreover, patients with AVH showed a lower connectivity within the language network and the auditory network, and lower connectivity was observed between the executive control and the language networks in certain dynamic states. Our study provides the first neuroimaging evidence of altered dynamic brain networks for understanding neural mechanisms of AVH in schizophrenia. The findings may inform and further strengthen cognitive models of AVH that aid the development of new coping strategies for patients.


Palladium-Catalyzed Asymmetric Arylation of C(sp(3))-H Bonds of Aliphatic Amides: Controlling Enantioselectivity Using Chiral Phosphoric Amides/Acids.
Enantioselective arylation of secondary β-C(sp(3))-H bonds of 8-aminoquinoline amides was realized with a palladium catalyst. Chiral phosphoric amides and acids were used for the first time to control the stereoselectivity at the C-H bond cleavage step in the C-H activation reactions.


Evaluation of thiamethoxam and imidacloprid as seed treatments to control European corn borer and Indianmeal moth (Lepidoptera: Pyralidae) larvae.
Efficacy of thiamethoxam (Cruiser) and imidacloprid (Gaucho) were evaluated as seed treatments for controlling European corn borer, Ostrinia nubilalis (Hübner) and Indianmeal moth, Plodia interpunctella (Hübner) larvae in stored grain. At approximately 22-26 degrees C, all fifth instar European corn borers died after two or 4 d of exposure to corn treated with 250 and 500 ppm thiamethoxam, respectively, while mortality of larvae exposed for two and 4 d on corn treated with 6.3-937.5 ppm imidacloprid did not exceed 48% at any concentration. At 29 degrees C, all nondiapausing fifth instars were killed after 3, 4, and 6-d exposure to 400, 300 and 200-ppm thiamethoxam, respectively, while survival increased at successively lower concentrations of 100, 50, 25, and 12.5 ppm. At 29 degrees C, the LC50 decreased from 85.9 to 7.2 ppm as the duration of exposure on treated corn increased from 2 to 6 d. All second and third instar Indianmeal moth larvae died after a 5 d exposure period to corn grain treated with thiamethoxam at 50 ppm or higher, but as the larvae aged, higher concentrations and longer exposure periods were required to give 100% mortality of each larval instar. Similar results were obtained when larval Indianmeal moths were exposed on corn treated with imidacloprid, or on sorghum treated with thiamethoxam. Mature wandering phase fifth instars were the most tolerant larval stage of the Indianmeal moth.


HMGB1/RAGE axis accelerates the repair of HUVECs injured by pathological mechanical stretching via promoting bFGF expression.
During hypertension-induced endothelial dysfunction, periodic mechanical stretching (MS) activates related inflammatory pathways and leads to endothelial damage, but the underlying mechanisms remain unknown. The present study aimed to determine the injury of HUVECs caused by overstretching and the role of HMGB1-RAGE pathway in HUVECs after injury. Human umbilical vein endothelial cells (HUVECs) were cultured and seeded in BioFlex™ plates (six wells). Cells were exposed to 5% (physiological state) and 20% (pathological state) mechanical stretch at 1 Hz for 12 or 24 h in a Flexcell-5000™, with unstretched cells serving as controls. It was found that excessive MS can inhibit cell viability, proliferation, and tube-forming ability resulting in disordered cell arrangement and orientation, slowing cell migration. All these changes cause endothelial damage compared to physiological MS. Endothelial cells (ECs) promote cell migration and self-repair after injury by increasing the High-mobility group box 1 (HMGB1) expression. Experiments and protein prediction networks have shown that HMGB1 can also promote the expression of downstream protein bFGF by binding to receptor for advanced glycation end products (RAGE). Interestingly, VEGF protein expression did not change significantly during this repair process, implying that bFGF replaces the role of VEGF in vascular endothelial repair. The present study demonstrates that in the context of endothelial injury caused by excessive MS, the HMGB1/RAGE/bFGF pathway is activated and promotes endothelial repair after injury. Therefore, understanding these mechanisms will help find new therapies for diseases such as hypertension, atherosclerosis, and aneurysm formation.


Horseradish peroxidase-catalyzed aerobic oxidation of indole-3-acetic acid. II. Oxygen uptake and chemiexcitation.
Light emission from the horseradish peroxidase-catalyzed aerobic or anaerobic oxidation of indole-3-acetic acid has been investigated under opposite extreme conditions of enzyme/substrate ratio. The O2-dependent chemiluminescent processes represent a minor part of the total oxygen consumption. Superoxide is involved in chemiexcitation as is evident from the observed inhibitory effect of superoxide dismutase. At high enzyme/substrate ratio, only a part of the emission is dependent on superoxide ion; at low ratio the dependence is extensive. At high ratio, some of the emission is independent of superoxide and O2. The identical quenching effects of D- and L-tryptophan are consistent with the formation of the quenching species only in bulk solution. The similarity of the emission spectra under extreme conditions indicates that the same main emitters are formed. This is also supported by the effect of quenchers. Possibly some of the emitters originate in the oxidative cleavage of the 2,3-double bond of the indole ring.


A multicenter evaluation of the role of mechanical bowel preparation in pediatric colostomy takedown.
In response to studies in adults that have failed to demonstrate a benefit for mechanical bowel preparation in colonic surgery, we sought to evaluate the utility of mechanical bowel preparation in a multicenter, retrospective study of children who underwent colostomy takedown. The records of 272 children who underwent colostomy takedown at 3 large children's hospitals were reviewed, and the utilization of mechanical bowel preparation and perioperative antibiotics was noted. Length of stay and the incidences of wound, anastomotic, and other complications were compared. A polyethylene glycol bowel prep was administered to 187 children. All subjects received perioperative, intravenous antibiotics, and 52% of those with bowel preps received preoperative oral antibiotics. Subjects in the bowel prep group had a significantly higher incidence of wound infection (P = .04) and longer length of stay (P = .05). Oral antibiotics did not affect outcome. The use of a mechanical bowel preparation in children before colostomy takedown was associated with a greater risk for wound infection, no protection from other complications, and a longer length of stay. This suggests that bowel preparation may be safely omitted in many children who undergo colonic surgery, thereby reducing cost and discomfort.


Wearable technologies for health research: Opportunities, limitations, and practical and conceptual considerations.
One of the most notable limitations of laboratory-based health research is its inability to continuously monitor health-relevant physiological processes as individuals go about their daily lives. As a result, we have generated large amounts of data with unknown generalizability to real-world situations and also created a schism between where data are collected (i.e., in the lab) and where we need to intervene to prevent disease (i.e., in the field). Devices using noninvasive wearable technology are changing all of this, however, with their ability to provide high-frequency assessments of peoples' ever-changing physiological states in daily life in a manner that is relatively noninvasive, affordable, and scalable. Here, we discuss critical points that every researcher should keep in mind when using these wearables in research, spanning device and metric decisions, hardware and software selection, and data quality and sampling rate issues, using research on stress and health as an example throughout. We also address usability and participant acceptability issues, and how wearable "digital biomarker" and behavioral data can be integrated to enhance basic science and intervention studies. Finally, we summarize 10 key questions that should be addressed to make every wearable study as strong as possible. Collectively, keeping these points in mind can improve our ability to study the psychobiology of human health, and to intervene, precisely where it matters most: in peoples' daily lives.


Norsesquiterpenoids and triterpenoids from strawberry cv. Falandi.
Falandi is a common strawberry (Fragaria × ananassa Duch.) cultivar in southern China. Further study of the chemical constituents in Falandi fruit led to the isolation of nine norsesquiterpenoids and three triterpenoids. Falandioside D (1) and falandins A (2) and B (3) were new norsesquiterpenoids, and the others excluding tormentic acid (11) were found in strawberry for the first time. Compounds 1 and 11 exhibited potent α-glucosidase inhibitory activity with the half maximal inhibitory concentration (IC50) values of 565.0 and 27.4 μM in comparison to acarbose (619.9 μM). Compounds 3, 7 (blumenol C glucoside), and 11 showed cytotoxicity against human nasopharyngeal carcinoma cell line CNE1 with the IC50 values of 57.6, 56.4, and 36.0 μM, respectively. Among new compounds, 1 showed 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging capacity (IC50=36.2 μM). These results suggested that non-phenolic constituents were also involved in the antidiabetic, antitumour, and antioxidant effects of strawberry fruit.


The Conditions Favoring Between-Community Raiding in Chimpanzees, Bonobos, and Human Foragers.
Chimpanzees, bonobos, and human foragers share a fission-fusion social system and a mating system of joint male resource defense polygyny. Within-community skew in male strength varies among and within species. In this study, we extend a mathematical model of within-group male coalition formation among primates to derive the conditions for between-community conflicts in the form of raids. We show that the main factor affecting the presence of successful raiding is the likelihood of major discrepancies in party strength, which are set by party size distributions (and thus community size) and the skew in strength. This study confirms the functional similarities between the raiding of chimpanzees and human foragers, and it supports the "imbalance of power" hypothesis for raiding. However, it also proposes two amendments to this model. First, the absence of raiding in bonobos may be attributable more to potential female involvement in defense against raids, which increases the size of defensive coalitions. Second, the model attributes some of the raiding in humans to major contrasts in instantaneous fighting ability created by surprise raids on unarmed victims; it also draws attention to the distinction between minor raids and major raids that involve multiple bands of the same community.


Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo[2,3-a]carbazole derivatives.
Development of potent and selective Pim kinase inhibitors has recently emerged as an important field for the design of new anti-cancer drugs. We report the synthesis of new N-10-substituted pyrrolo[2,3-a]carbazole derivatives and their evaluation as Pim kinase inhibitors. Moreover, in vitro antiproliferative activity of these compounds was evaluated toward a human fibroblast primary culture and three human solid cancer cell lines (PA1, PC3 and DU145). Compounds 3, 7 and 10 showed inhibitory potencies toward Pim-1 and Pim-3 in the nanomolar range. Additionally, dimethylamino analog 10 also demonstrated interesting sub-micromolar antiproliferative activities toward the cell lines tested.


Renal failure in sick hypertensive premature infants receiving captopril therapy.
A retrospective study of nine sick premature infants with chronic lung disease who received captopril for control of systemic hypertension (systolic blood pressure (BP) greater than 113 mm Hg) was carried out to determine efficacy of therapy and associated complications. All nine infants had markedly elevated peripheral renin values, 134.3 +/- 128.1 ng/mL/hr (mean +/- SD). Five infants had abnormal renal sonographic and perfusion scans with evidence of renal artery thrombosis, parenchymal disease, or both. Captopril therapy (0.3 mg/kg) was instituted at a postnatal age of 123 +/- 108 days. After the initial dose, the systolic BP decreased significantly in all infants, the decrease ranging from 21% to 58% of the pretreatment value. Dosage was subsequently halved in all infants. Seventeen episodes of unpredictable decreases in BP more than 40% from baseline occurred during the reduced maintenance therapy. Four infants had a total of seven episodes during which the BP decreased by 57 +/- 10% from baseline; this decrease persisted for 17 +/- 6 hours and was unresponsive to volume reexpansion and inotropic therapy. All seven episodes were accompanied by oliguria (urine output less than 1 mL/kg/hr) that persisted for 18 +/- 12 hours. These episodes were accompanied by neurologic signs (subtle seizures, lethargy, and/or apnea) within 18 +/- 6 hours after the onset of oliguria. The remaining five infants had a total of 13 episodes of decreased BP of 50 +/- 8% of baseline, which were of significantly shorter duration and responded to volume reexpanders, inotropic therapy, or both and were unaccompanied by oliguria. These data suggest the need for close observation of BP in infants receiving maintenance captopril therapy.


Range of Risk Factor Levels, Risk Control, and Temporal Trends for Nephropathy and End-stage Kidney Disease in Patients With Type 1 and Type 2 Diabetes.
To investigate trends, optimal levels for cardiometabolic risk factors, and multifactorial risk control in diabetic nephropathy and end-stage kidney disease (ESKD) in patients with diabetes and matched control subjects. This study included 701,622 patients with diabetes from the Swedish National Diabetes Register and 2,738,137 control subjects. Trends were analyzed with standardized incidence rates. Cox regression was used to assess excess risk, optimal risk factor levels, and risk according to the number of risk factors, in diabetes. ESKD incidence among patients with and without diabetes initially declined until 2007 and increased thereafter, whereas diabetic nephropathy decreased throughout follow-up. In patients with diabetes, baseline values for glycated hemoglobin, systolic blood pressure (SBP), triglycerides, and BMI were associated with outcomes. Hazard ratio (HR) for ESKD for patients with type 2 diabetes who had all included risk factors at target was 1.60 (95% CI 1.49-1.71) compared with control subjects and for patients with type 1 diabetes 6.10 (95% CI 4.69-7.93). Risk for outcomes increased in a stepwise fashion for each risk factor not at target. Excess risk for ESKD in type 2 diabetes showed a HR of 2.32 (95% CI 2.30-2.35) and in type 1 diabetes 10.92 (95% CI 10.15-11.75), compared with control. Incidence of diabetic nephropathy has declined substantially, whereas ESKD incidence has increased. Traditional and modifiable risk factors below target levels were associated with lower risks for outcomes, particularly notable for the causal risk factors of SBP and HbA1c, with potential implications for care.


p95-APP1 links membrane transport to Rac-mediated reorganization of actin.
Motility requires protrusive activity at the cellular edge, where Rho family members regulate actin dynamics. Here we show that p95-APP1 (ArfGAP-putative, Pix-interacting, paxillin-interacting protein 1), a member of the GIT1/PKL family, is part of a complex that interacts with Rac. Wild-type and truncated p95-APP1 induce actin-rich protrusions mediated by Rac and ADP-ribosylation factor 6 (Arf6). Distinct p95-APP1-derived polypeptides have different distributions, indicating that p95-APP1 cycles between the cell surface and endosomes. Our results show that p95-APP1 functionally interacts with Rac and localizes to endosomal compartments, thus identifying p95-APP1 as a molecular link between actin organization, adhesion, and membrane transport during cell motility.


Towards virtual surgery in oral cancer to predict postoperative oral functions preoperatively.
Our aim was to develop a dynamic virtual model of the oral cavity and oropharynx so that we could incorporate patient-specific factors into the prediction of functional loss after advanced resections for oral cancer. After a virtual resection, functional consequences can be assessed, and a more substantiated decision about treatment can be made. In this study we used a finite element model of the tongue, which can be implemented in the total virtual environment in the future. We analysed the movements and changes in volume, and the effects of changes in the material variables, to mimic scar tissue. The observed movements were in accordance with descriptions of in vivo movements. Affected movements caused by the mimicked scar tissue were also similar to expectations. Some changes in volume were measured, particularly in individual elements. We have taken the first steps in the development of a finite element model of the tongue. Now, refinement is necessary to make the model suitable for future use in virtual surgery.


Effectiveness of the "Trisquel" board game intervention program for patients with schizophrenia spectrum disorders.
Schizophrenia spectrum disorders present emotional, cognitive and/or behavioural alterations relat- ed to daily functioning. Therefore, it is necessary to develop intervention programs focused on the improvement of these constructs. The aim of this work is to analyse the effect of the intervention program "Trisquel" on cognitive functioning, symptomatologic perception and psychosocial functioning.


Sexual dysfunction in men with multiple sclerosis--a comprehensive pilot-study into etiology.
Ideally, the etiological diagnosis of sexual dysfunction in patients with multiple sclerosis is established on the basis of both objective and subjective tests. Accordingly, we assessed sexual function in 16 male patients with multiple sclerosis and complaints of sexual dysfunction by means of subjective data from interviews and questionnaires and objective data, obtained from (psycho)physiological tests. Psychophysiological investigation consisted of measurement of sleep erections and of erectile response to visual erotic stimulation and penile vibration. Urodynamic investigation was used to assess the neurological status of the genital tract. Sixteen male patients with clinically definite multiple sclerosis, complaints of sexual dysfunction and a steady heterosexual relationship participated in the study. The majority of patients had no abnormalities in the objective tests. Only one (1 out of 15) patient showed disturbed sleep-erections, and four (4 out of 12) other patients showed signs of neurological dysfunction of the genital tract. In our patient-group, disturbed sleep erections and abnormal findings on urodynamic investigation appeared unrelated to the complaint of erectile dysfunction. Sexual function was related to psychological factors, decreased general sensitivity, and motor impairment.


HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey.
Behçet disease (BD) is predominantly found between East Asia and the Mediterranean basin along the historic Silk Road. HLA-B51 is known to be strongly associated with BD. We investigated the association between HLA-B51 and the ocular manifestations of BD among various ethnic groups. A literature survey was conducted, and 18 articles written in English were reviewed. A strong correlation was found between HLA-B51 and ocular lesions in the entire cohort discussed in the reviewed articles (OR = 1.76, p = 0.000057). HLA-B51 was shown to have a strong association with ocular manifestations of BD patients in East-Eurasian (OR = 2.40, p = 0.0030) and Middle-Eurasian (OR = 1.87, p = 0.0045), but not in West-Eurasian (OR = 1.28, p = 0.35) areas. This correlation seemed to become stronger towards the east. A meta-analysis showed that the correlation became stronger towards the east along the Silk Road. The study results may facilitate understanding of the etiology and characteristics of BD.


Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects.
CD23 plays a role in the regulation of IgE production and allergy-induced immune and inflammatory responses. A novel anti-CD23 monoclonal antibody, lumiliximab, is a potential therapeutic antibody recently demonstrated to be safe in human beings. This study investigated the effects of lumiliximab on allergen-induced immune responses from atopic subjects compared with blocking HLA-DR and costimulatory molecules, CD80 and CD86. Allergen-stimulated PBMCs from atopic subjects were pretreated with lumiliximab or antibodies to CD80, CD86, and HLA-DR. Cultures were analyzed for cell proliferation and IL-1beta, TNF-alpha, and IL-5 cytokine secretion. An allergen-specific T-cell line was developed and analyzed for lymphocyte proliferation in response to allergen with or without lumiliximab. Lumiliximab's effect on CD86 expression was evaluated by flow cytometry in the U937 monocytic cell line. Lumiliximab reduced allergen-induced PBMC proliferation by 50% (n = 6; P = .006). In addition, cultures pretreated with lumiliximab had a reduction in the proinflammatory cytokines IL-1beta (P < .003) and TNF-alpha (P = .05) and the T(H)2 cytokine IL-5 (P = .002). Blocking CD86 resulted in greater reduction in proliferation than lumiliximab (P = .003) but similar effects in cytokine secretion. The anti-CD80 blocking antibody had no effect on cytokine production but did reduce proliferation. Furthermore, the addition of lumiliximab to cytokine stimulated U937 cells reduced surface expression of CD86 (P = .012). These results indicate that the anti-CD23 mAb, lumiliximab, may be involved in modulating antigen presenting cells and reducing TH2-type immune responses. The use of this antibody may provide clinical benefit for treating allergic diseases.


Impact of income inequality and other social determinants on suicide rate in Brazil.
To analyze whether income inequality and other social determinants are associated with suicide rate in Brazil. This study used panel data from all 5,507 Brazilian municipalities from 2000 to 2011. Suicide rates were calculated by sex and standardized by age for each municipality and year. The independent variables of the regression model included the Gini Index, per capita income, percentage of individuals with up to eight years of education, urbanization, average number of residents per household, percentage of divorced people, of Catholics, Pentecostals, and Evangelicals. A multivariable negative binomial regression for panel data with fixed-effects specification was performed. The Gini index was positively associated with suicide rates; the rate ratio (RR) was 1.055 (95% CI: 1.011-1.101). Of the other social determinants, income had a significant negative association with suicide rates (RR: 0.968, 95% CI: 0.948-0.988), whereas a low-level education had a positive association (RR: 1.015, 95% CI: 1.010-1.021). Income inequality represents a community-level risk factor for suicide rates in Brazil. The decrease in income inequality, increase in income per capita, and decrease in the percentage of individuals who did not complete basic studies may have counteracted the increase in suicides in the last decade. Other changes, such as the decrease in the mean residents per household, may have contributed to their increase. Therefore, the implementation of social policies that may improve the population's socioeconomic conditions and reduce income inequality in Brazil, and in other low and middle-income countries, can help to reduce suicide rates.


Immune evasion and chronological decrease in titer of neutralizing antibody against SARS-CoV-2 and its variants of concerns in COVID-19 patients.
Many variants of SARS-CoV-2 have emerged, and decreased neutralizing antibodies after vaccination and breakthrough infections have become a problem. The importance of monitoring titers of neutralizing antibodies is getting higher. We enrolled 146 COVID-19 patients, who were thought to be infected with Wuhan-hu-1 or D614G strains, and examined the time course of neutralizing titers against six concerning strains (Wuhan-hu-1, Alpha, Beta, Gamma, Kappa, and Delta) using newly developed ELISA. The acquisition of neutralizing titer was positively associated with disease severity. Immune evasions were observed approximately 20 to 30% for Alpha, Kappa, and Delta variant, and 40 to 45% for Beta and Gamma variant. The titers against all strains decreased over time, and interestingly, while titers against Wuhan-hu-1 decreased by 23%, those to Delta variant decreased by 70%. Our simple, cost-effective, and non-hazardous system will be applicable to process numerous samples, such as monitoring titers against prevalent strains after infection or vaccination.


Outcomes of simultaneous endoscopic submucosal dissection for synchronous multiple gastric neoplastic lesions: a retrospective comparative study.
Simultaneous endoscopic submucosal dissection (ESD) is occasionally used in synchronous multiple gastric neoplastic lesions (SMGL). Therefore, we aim to evaluate the safety and efficacy of simultaneous ESD for SMGL compared with ESD for single lesions. A total of 1058 patients who received ESD from November 2006 to September 2019 were retrospectively evaluated in this study, including 997 single gastric epithelial lesions treated by single ESD (unifocal group) and 125 SMGL from 61 patients treated by simultaneous ESD (multifocal group). The mean procedure time was 49.2 ± 41.30 min and 89.5 ± 66.33 min in unifocal group and multifocal group, respectively (p < 0.001). There was no significant difference in postoperative stenosis rate (1.0% vs. 0.0%, p = 1.000), intraoperative bleeding (endoscopic resection bleeding-c3 grade) rate (0.5% vs. 1.6%, p = 0.696), postoperative bleeding rate (1.3% vs. 0.0%, p = 0.461), and perforation rate (0.9% vs. 1.6%, p = 0.449) between the two groups. In addition, en block resection rate (p = 0.825), complete resection rate (p = 0.856) and curative resection rate (p = 0.709) were comparable between the two groups. During the follow-up, the local recurrence rate per patient: p = 0.363; per lesion: p = 0.235) was not significantly different between the two groups, however, the cumulative incidence of metachronous lesions after treatment was significantly higher in the multifocal group than the other group (10.0% vs. 3.2%, p = 0.004). Simultaneous ESD is safe and effective in the treatment of SMGL. However, separate ESD is recommended for SMGL with longer procedure time. Besides, the metachronous gastric neoplastic lesions should be paid attention to during follow-up.