Percutaneous intraluminal downsizing of systemic-to-pulmonary artery shunts: a novel application of the Diabolo stent technique-Case series and description of the technique.
This article aims to describe the feasibility of a novel application of the Diabolo stent technique for percutaneous downsizing of systemic-to-pulmonary artery shunts in patients with pulmonary overcirculation. Pulmonary overcirculation can lead to systemic hypoperfusion, impaired systemic oxygen delivery, and hemodynamic instability especially in patients with single-ventricle physiology. Different medical and surgical strategies to treat pulmonary overcirculation have been reported so far, but no percutaneous approach amenable to further adjustment over time has been described. Retrospective review of patients who underwent percutaneous intraluminal reduction of a systemic-to-pulmonary artery shunt with a covered stent in a Diabolo "hour-glass" configuration. From July 2018 to February 4, 2019, consecutive patients underwent trans-catheter downsizing of a systemic-to-pulmonary artery shunt. The median age was 3.3 years (range 0.7-5.7 years). All patients had symptomatic pulmonary overflow despite maximal medical therapy. All patients underwent successful implantation of a covered stent in a Diabolo "hour-glass" configuration without any complications. Successful reduction in pulmonary overcirculation was noted in all patients with a decrease of mean pulmonary artery pressure from a median of 29 mmHg (range 25-32 mmHg) to a median of 21 mmHg (range 14-27 mmHg). Percutaneous intraluminal downsizing of systemic-to-pulmonary artery shunts with a covered stent in a Diabolo configuration is safe and feasible. With this technique, the pulmonary blood flow can be adjusted in a physiologic closed-chest condition and further regulated over time.


Eccentric plantar-flexor torque deficits in participants with functional ankle instability.
Inversion ankle sprains can lead to a chronic condition called functional ankle instability (FAI). Limited research has been reported regarding isokinetic measures for the plantar flexors and dorsiflexors of the ankle. To examine the isokinetic eccentric torque measures of the ankle musculature in participants with stable ankles and participants with functionally unstable ankles during inversion, eversion, plantar flexion, and dorsiflexion. Case-control study. Athletic training research laboratory. Twenty participants with a history of "giving way" were included in the FAI group. Inclusion criteria for the FAI group included a history of at least 1 ankle sprain and repeated episodes of giving way. Twenty participants with no prior history of ankle injury were included in the control group. Isokinetic eccentric torque was assessed in each participant. Isokinetic eccentric testing was conducted for inversion-eversion and plantar-flexion-dorsiflexion movements. Peak torque values were standardized to each participant's body weight. The average of the 3 trials for each direction was used for statistical analysis. A significant side-by-group interaction was noted for eccentric plantar flexion torque (P < .01). Follow-up t tests revealed a significant difference between the FAI limb in the FAI group and the matched limb in the control group. Additionally, a significant difference was seen between the sides of the control group (P = .03). No significant interactions were identified for eccentric inversion, eversion, or dorsiflexion torques (P > .05). A deficit in plantar flexion torque was identified in the functionally unstable ankles. No deficits were identified for inversion, eversion, or dorsiflexion torque. Therefore, eccentric plantar flexion strength may be an important contributing factor to functional ankle instability.


Cervical Disc Replacement.
Anterior cervical disc replacement (arthroplasty) has gained momentum over the past 2 decades. The ball-and-socket prosthesis design of arthroplasty has been shown to simulate normal motion in all 3 rotation planes at the level of surgery and replicates physiologic motion. Anterior cervical discectomy and fusion has been shown to be a safe and effective surgery over decades; cervical disc replacement counters some secondary effects owing to its preservation of segmental mobility, the potential to reduce adjacent segment degeneration, and the lack of plating or harvesting bone graft. The literature is growing in support of the success and longevity of arthroplasty.


Palmitate uptake in calcium tolerant, adult rat myocardial single cells--evidence for an albumin mediated transport across sarcolemma.
The dependence of (1-14C)-palmitate uptake in adult rat heart single cells on albumin was investigated. The apparent initial rate of palmitate uptake vs total palmitate concentration exhibited saturation kinetics, provided the concentration ratio of palmitate vs albumin was kept constant. However, if total palmitate was increased at constant albumin concentrations, the dependence of the initial rate on palmitate concentration was linear. Within the concentration range of total palmitate investigated in this study, the concentration of free palmitate remained almost constant. These results favour the hypothesis, that palmitate uptake in rat myocardium may be mediated by an albumin dependent sarcolemmal transport system.


Parallel solid-phase synthesis of mucin-like glycopeptides.
The glycopeptide, Ac-Pro-Thr(alpha-D-GalNAc)-Thr(alpha-D-GalNAc)-Thr(alpha-d-GalNAc)-Pro-Leu-Lys-NH(2) (1), which features three consecutive O-glycosylated Thr residues and mimics a portion of mucin 2, has been prepared by solid-phase synthesis. Seven related, partially glycosylated peptides (2-8) were synthesized as well. This suite of molecules allowed a systematic analysis of synthetic protocols. N(alpha)-(9-Fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl)-L-threonine pentafluorophenyl ester [Fmoc-L-Thr(Ac(3)-alpha-D-GalN(3))-OPfp] was used as a building block that coupled efficiently when used in a relatively low molar excess, that is, approximately 1.5 equiv, with N,N-dimethylformamide (DMF) as the solvent. For conversion of the azido group to the N-acetyl function, direct treatment with thioacetic acid was preferred over a two-step procedure involving reduction with dithiothreitol (DTT) followed by N-acetylation. Effective O-deacetylation of 1-8 in solution was achieved by treatment with sodium methoxide (10-15 mM; approximately 5 equiv) in methanol. On-resin deacetylation techniques were also examined, using sodium methoxide (6-10 mM) in DMF-methanol (17:3) (for 4 and 11) or hydrazine (70 mM) in methanol (for 8). The more convenient on-resin technique in DMF-methanol gave yields similar to solution conditions, and promises to be widely useful for solid-phase glycopeptide synthesis. HPLC profiles showed that free glycopeptides elute earlier than the corresponding O-acetylated derivatives, and that retention times vary systematically with the number of sugar moieties. (1)H NMR studies carried out in water showed an increase in conformational organization of glycopeptides with increased density of glycosylation.


Antioxidative and immunological activities of ophiopogon polysaccharide liposome from the root of Ophiopogon japonicus.
The antioxidative and immunoregulatory activities of ophiopogon polysaccharide liposome (OPL) were investigated. The results demonstrated that the radical-scavenging activity increased along with the increasing of OPL concentrations, and the scavenging capability of OPL was slightly stronger than ophiopogon polysaccharide (OP) in vitro. In vivo, OPL at high and medium doses could significantly improve the levels of SOD and GSH-Px, and decrease the levels of MPO, XOD and MDA compared with OP. In addition, OPL could not only significantly enhance the splenocyte proliferation and the proportion of CD4(+) and CD8(+) T cells, but also improve the levels of cytokines, antigen-specific antibody titers and immune organ index in the mice immunized with OVA compared with OP. These results indicated that the antioxidative and immunoregulatory activities of OP were significantly enhanced after encapsulated with liposome. Therefore, OPL would be expected to exploit into a new-type of functional food as both medicine and food.


Forensic medicine and human rights.
The forensic scientist is used to evaluate lesions with regard to their age, the weapon used, the seriousness, etc. Based on a material of examinations of alleged victims of torture some of the types of lesions are discussed. The importance of being strictly objective and using a scientific approach is stressed. The Committee of Concerned Forensic Scientists and Physicians for the Documentation of Human Rights Abuses (CCFS) was formed in 1984. The aims and the work of the committee are described.


The teleost fish medaka (Oryzias latipes) as genetic model to study gravity dependent bone homeostasis in vivo.
Long-term space flight and microgravity result in bone loss that can be explained by reduced activity of bone-forming cells (osteoblasts) and/or an increase in activity of bone resorbing cells (osteoclasts). Osteoprotegerin (OPG) has been shown to regulate the balance between osteoblast and osteoclast cell numbers and is involved in maintaining constant bone mass under normal gravitational conditions. The small bony fish medaka (Oryzias latipes) has attracted increasing attention as a genetic model system to study normal embryonic developmental and pathological processes. To analyze the molecular mechanisms of bone formation in this small vertebrate, we have isolated two opg genes, opgl and opg2, from medaka. Our phylogenetic analysis reveals that both genes originated from a common ancestor by fish-specific gene duplication and represent the orthologs of the mammalian opg gene. Both opg genes are differentially expressed during embryonic and larval development, in adult tissues and in cultured primary osteoblast-like cells. Furthermore, we have characterized the opg2 promoter region and identified consensus binding sites for the transcription factor core-binding-factor-1A (CBFA1). In mammals, CBFA1 has been shown to be a regulator of opg expression and to be essential for several steps during osteoblast differentiation. Here we show that sequence and expression domains of opg, cbfal and a member of the dlx gene family are highly conserved between medaka and higher vertebrates. This suggests that not only single genes but entire genetic networks for bone formation are conserved between teleosts and mammals. These findings will open medaka fish as a genetic model to monitor bone formation under different gravity conditions in a living whole animal allowing the identification of novel factors involved in bone homeostasis.


Advances in platinum cancer chemotherapy. Advances in the design of cisplatin analogues.
In the past 4 years substantial progress has been made in the development of platinum cancer chemotherapy. A number of drug candidates have undergone clinical trials and one 'second generation' platinum drug, carboplatin, has been approved for use in the treatment of ovarian and small cell lung cancer. This review covers the major developments since the last international conference on Platinum Chemotherapy in Vermont, and attempts to highlight the primary factors that appear to be influencing the synthesis and screening of potential third generation platinum drugs. A predominant feature in the evaluation of analogues has been the emphasis on chelating diamine complexes, in particular those of diaminocyclohexane, which show activity in L1210 tumours that are resistant to cisplatin, and the use of a wide range of carboxylate ligands as a means of circumventing solubility and toxicity problems inherent in the parent compounds. There has also been an increased effort in studies relating to complexes containing mixed amines and functionalised amines, building on the assumption, which remains valid to date, that two amines are a necessary requirement for anti-tumour activity. Efforts have also been made to address the use of complexes containing biologically active ligands, and the concept of targeting compounds to specific organs and formulating drugs to achieve more specific activity or controlled release of drugs with lower toxicities. These may provide a viable route to drugs that can be administered more easily, for example by an oral route, or show a different spectrum of activity. However, it may prove difficult to adequately characterise these more complex systems. The major problem encountered in evaluating cisplatin analogues, as with other prospective cancer drugs, is finding reproducible anti-tumour screens that are predictive of the behaviour of the drugs in the clinic. Progress is being made in the development of sensitive and resistant human tumour xenograft lines and this area should be monitored with interest, as it may provide a key to the development of a future platinum drug, hopefully with a wider range of activity than either cisplatin or carboplatin.


Influence of a pre-operative enteral supplement on functional activities of peripheral leukocytes from patients with major surgery.
Following severe trauma or major surgery patients develop functional alterations of host defense mechanisms which contribute an enhanced susceptibility towards microbial infections. Several studies have demonstrated that a specialized nutritional regimen may improve immune functions. We analyzed leukocyte functions from 40 patients undergoing major upper gastrointestinal surgery in a randomized placebo-controlled double-blind study. Patients were divided into two groups, one received 5 days pre-operatively an orally given experimental supplement enriched with omega-3-fatty acids, arginine, and ribonucleic acid (RNA), the other an isocaloric, control supplement. The experimental group generated significantly more leukotriene B(5) (LTB(5)) as compared to the control group. In contrast, the capacity to generate leukotriene B(4) (LTB(4)) as well as the synthesis of interleukin-8 (IL-8) was not significantly different in both groups. Additionally, lymphocyte/monocyte proliferation was analyzed and donor specific heterogeneities were observed; but no significant differences were found between the two nutritional regimens.


Image, context and transition: smoking in mid-to-late adolescence.
This paper explores 16-19-year-old Scottish smokers' experiences and attitudes towards smoking and their understandings of the ways in which this transitional period impacts on their smoking behaviour. The study involved 49 qualitative interviews conducted mostly in friendship pairs. Interviewees also completed a brief smoking questionnaire. The paper highlights the salience of social context in smoking initiation and maintenance, and the role of smoking across a range of social spheres. Interviewees described how transitions from school to work, further education or un/employment, impacted on their smoking. Smoking was perceived to be an important 'lubricant' for social relations, and marker of an acceptable identity in familiar and new contexts which acted to reinforce and increase smoking. In contrast, smoking restrictions at home, work and/or educational settings were felt to moderate consumption. This has implications for cessation programmes for older adolescents who have been relatively ignored by tobacco control. The study also suggests that if smoke-free policies were extended to all workplaces, this would have a particular impact on smoking amongst older adolescents by hindering the transition from social to regular smoking.


Multivariate analysis of prognostic factors in regional cutaneous metastases of extremity melanoma.
In 135 patients with regional cutaneous recurrence of extremity melanoma, the prognostic significance of 12 clinical and pathologic variables was analyzed in four alternative Cox stepwise regression models and by single variable analysis. A highly significant fit of the regression (P less than 0.01) identified four factors that particularly influenced survival: the presence of intradermal or mixed (as opposed to purely subcutaneous) metastases (P less than 0.001), sex (P = 0.032), excision of regional cutaneous metastases with or without perfusion (P = 0.033), and the presence of subcutaneous metastases (P = 0.201). Not predictive of survival were age at diagnosis; site of primary; anatomic location, number, size, or distance from the primary of the regional cutaneous metastases; time since primary treatment; number of positive regional lymph nodes; and single- or triple-drug perfusion.


Serum levels of insulin, IGF-1, and IGFBP-1 in pre-eclampsia and eclampsia.
To investigate whether the serum concentrations of insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women with mild pre-eclampsia, severe pre-eclampsia, and eclampsia. In this prospective study, we investigated 20 mild pre-eclamptic, 20 severe pre-eclamptic, and 20 eclamptic patients in the third trimester. The control group consisted of 20 healthy pregnant women. Serum levels of insulin, IGF-1, and IGFBP-1 were measured. In patients with eclampsia, serum levels of IGF-1 were lower, and IGFBP-1 were higher, respectively, than control and other study groups (P<0.001) The values of IGF-1 in mild pre-eclampsia and severe pre-eclampsia were lower compared with control groups (both P<0.01), but there were no differences between mild and severe pre-eclampsia. The serum levels of IGFBP-1 in severe pre-eclampsia were higher compared with control groups (P<0.01), but there was no statistical difference between mild pre-eclampsia and other groups. IGF-1 was lower, and IGFBP-1 was higher in pre-eclamptic and eclamptic patients than controls, these alterations were related to the severity of pre-eclampsia.


Nutrient intakes and sources of fiber among children with low and high dietary fiber intake: the 2016 feeding infants and toddlers study (FITS), a cross-sectional survey.
Increasing dietary fiber intake in children may improve overall diet quality. The purpose of this study was to compare nutrient intakes and sources of fiber between young children with low and high fiber intakes utilizing data from the Feeding Infants and Toddlers Study (FITS) 2016. The FITS 2016 was a nationwide, cross sectional survey of caregivers designed to assess food and nutrient intakes, feeding behaviors, and dietary patterns among infants and young children living in the U.S. Energy adjusted macro and micronutrient intakes (nutrients/1000 kcals) of children with energy adjusted fiber intakes (g/1000 kcals) in the highest quartile were compared to those in the lowest quartile with paired t-tests. Sources of fiber for each quartile were ranked according to percent of total fiber intake. Children with fiber intakes in the highest quartile had significantly lower intakes of total fat (mean difference ranged from 7.4-9.6 g, p < 0.0005) and saturated fat (mean difference ranged from 4 to 5.8 g, p < 0.0005), and significantly higher intakes of vitamin B-6 (mean difference ranged from 0.3-0.4 mg, p < 0.0005), magnesium (mean difference ranged from 57.2-61.8 mg, p < 0.0005), iron (mean difference ranged from 2.2-3.7 mg, p < 0.0005), and potassium (mean difference ranged from 318.2 mg to 446.1 mg, p < 0.0005) compared to children in the lowest quartile across all age groups. Children in the highest quartile had higher intakes of nut butters, legumes, fruits, and vegetables and consumed a greater percentage of grains as whole grains than those in the lowest quartile. Encouraging intake of fruits, vegetables, legumes, nut butters, and at least 75% of grains as whole grains may help young children improve dietary fiber intake and overall diet quality.


Zeta potentials (ζ) of metal oxide nanoparticles: A meta-analysis of experimental data and a predictive neural networks modeling.
Zeta potential is usually measured to estimate the surface charge and the stability of nanomaterials, as changes in these characteristics directly influence the biological activity of a given nanoparticle. Nowadays, theoretical methods are commonly used for a pre-screening safety assessments of nanomaterials. At the same time, the consistency of data on zeta potential measurements in the context of environmental impact is an important challenge. The inconsistency of data measurements leads to inaccuracies in predictive modeling. In this article, we report a new curated dataset of zeta potentials measured for 208 silica- and metal oxide nanoparticles in different media. We discuss the data curation framework for zeta potentials designed to assess the quality and usefulness of the literature data for further computational modeling. We also provide an analysis of specific trends for the datapoints harvested from different literature sources. In addition to that, we present for the first time a structure-property relationship model for nanoparticles (nano-SPR) that predicts values of zeta potential values measured in different environmental conditions (i.e., biological media and pH).


Correlates of anxiety, hostility, depression, and psychosocial adjustment in parents of NICU infants.
The birth of a premature or critically ill infant can result in debilitating parental responses. This study identifies correlates of parental anxiety, hostility, depression, and psychosocial adjustment so that nurses can identify parents likely to need special attention or intervention. An explanatory, correlational design was used. The study involved 469 parents (mothers = 299, 65 percent; mean age 29.1 +/- 6.8 years) of infants hospitalized in five Level III NICUs. The main outcomes were those variables which correlated with the independent variables and included: parent status (mother or father), ethnicity, employment status, and education. Parents experienced high levels of anxiety, hostility, and depression. Poorer family functioning, lower levels of social support, and lower perceived control were associated with higher levels of anxiety, hostility, and depression and with poorer adjustment. Parental status (mother or father), ethnicity, employment status, and education were significantly related to parental responses.


Proline-Rich Peptides with Improved Antimicrobial Activity against E. coli, K. pneumoniae, and A. baumannii.
Proline-rich antimicrobial peptides (PrAMPs) are promising agents to combat multi-drug resistant pathogens due to a high antimicrobial activity, yet low cytotoxicity. A library of derivatives of the PrAMP Bac5(1-17) was synthesized and screened to identify which residues are relevant for its activity. In this way, we discovered that two central motifs -PIRXP- cannot be modified, while residues at N- and C- termini tolerated some variations. We found five Bac5(1-17) derivatives bearing 1-5 substitutions, with an increased number of arginine and/or tryptophan residues, exhibiting improved antimicrobial activity and broader spectrum of activity while retaining low cytotoxicity toward eukaryotic cells. Transcription/translation and bacterial membrane permeabilization assays showed that these new derivatives still retained the ability to strongly inhibit bacterial protein synthesis, but also acquired permeabilizing activity to different degrees. These new Bac5(1-17) derivatives therefore show a dual mode of action which could hinder the selection of bacterial resistance against these molecules.


A prospective randomized comparison between laparoscopic and laparotomic approaches in women with early stage endometrial cancer: a focus on the quality of life.
This study was undertaken to compare the quality of life (QoL) in women with early stage endometrial cancer treated with 2 different surgical approaches. Eighty-four women with clinical stage I endometrial cancer were enrolled in a prospective randomized controlled trial design and treated with laparoscopic or laparotomic approach. Another 40 women matched for demographic characteristics were studied as controls. In patients, before and after surgery, and in their matched controls, QoL was evaluated by using the Short-Form Healthy Survey (SF-36) and the climacteric symptoms using the Kupperman Index (KI). After randomization, no difference was detected in data recorded between the groups. At entry, QoL was similar in both treatment groups but significantly (P < .05) worse in comparison with controls. Throughout the study, QoL was significantly (P < .05) higher in laparoscopic group versus laparotomic group. After KI adjustment our data did not change. In early stage endometrial cancer, the laparoscopic approach provides significant benefits compared with laparotomy in terms of QoL.


Tris(hy-droxy-meth-yl)methanaminium trifluoro-acetate.
In the crystal structure of the title salt, C(4)H(12)NO(3) (+)·C(2)F(3)O(2) (-), N-H⋯O and O-H⋯O hydrogen bonds link the ions, forming a complex three-dimensional network.


Brominated derivatives from the Chinese sponge Pseudoceratina sp.
Chemical examination of the marine sponge Pseudoceratina sp. resulted in the isolation and characterization of two new dibromotyrosine-derived metabolites (1-2), and a new histamine-derived alkaloid (3), along with eight known dibromotyrosine based products. Their structures were elucidated on the basis of IR, 1D and 2D NMR, and MS spectral data analyses.


Circular dichroism spectra of purified cytochromes P-450 from rabbit liver microsomes.
Circular dichroism (CD) spectra were measured for cytochromes P-450 (P-450) purified from phenobarbital- and 3-methylcholanthrene-induced rabbit liver microsomes. No striking difference in alpha-helix content was seen between phenobarbital-induced P-450 (PB P-450) (50%), phenobarbital-induced P-448 (PB P-448) (40%) and 3-methylcholanthrene-induced P-448 (MC P-448) (45--50%) in terms of ultraviolet CD spectra. Strong negative CD spectra associated with 3-methylcholanthrene transitions for MC P-448 in the near-ultraviolet region (250--310 nm) and weaker negative CD spectra associated with Soret transitions for PBP-448 ([theta] = 50 000) and MCP-448 ([theta] = 160 000), indicated that structures of these preparations are strikingly different from each other. Reduction of P-450 and P-448 led to a remarkable decrease of the Soret CD trough, suggesting that reduction was accompanied by a striking conformational change in the vicinity of the heme. Since CO complexes of reduced P-450 and P-448 showed a CD trough and an S-shaped CD, respectively, associated with the absorption peak at 450 nm, the heme vicinities are remarkably different from each other. The CD spectra in the visible region are also discussed. It was noticed that P-420, the denatured form of P-450, exhibited no CD spectra in the Soret and visible regions.


Surface chemistry of graphene tailoring the activity of digestive enzymes by modulating interfacial molecular interactions.
As a kind of novel functional material, graphene-related nanomaterials (GRMs) have great potentials in industrial and biomedical applications. Meanwhile, the production and wide application of GRMs will increase the risk of unintended or intentional oral exposure to human beings, attracting safety concerns about their biological fates and toxicological effects. The normal enzymatic activity of digestive enzymes is essential for the proper functioning of the gastrointestinal tract system. However, whether and how orally entered GRMs and their surface groups affect digestive enzymes' activity are still scarce. In this paper, we systematically studied the effects of graphene oxide (GO), graphene modified with hydroxyl groups (OH-G), carboxyl groups (COOH-G), and amino groups (NH2-G) on enzymatic activity of three typical digestive enzymes (pepsin, trypsin, and α-pancreatic amylase). The results showed that the activity of trypsin and α-pancreatic amylase could be greatly changed after GRMs incubation in a surface chemistry dependent manner, while the activity of pepsin was not affected. To elucidate the mechanisms at the molecular level, the interactions between trypsin and GRMs were studied by spectrometry, thermophoresis, and computational simulation approaches, and the key roles of surface chemistry of GRMs in tailoring the activity of trypsin were finally figured out. GO allosterically inhibited trypsin's activity in the non-competitive manner because of the conformation transition induced by the intensive interactions. COOH-G could effectively hamper enzymatic activity of trypsin in the competitive manner by blocking the active catalytic pocket. As for NH2-G and OH-G, they had little impact on the activity of trypsin due to the weak binding affinity or limited conformational change. Our findings not only indicate surface chemistry plays an important role in tailoring the effects of GRMs on the activity of digestive enzymes but also provide new insights for understanding the oral safety of nanomaterials from daily products and the environment.


Inhibitory effects of N-methyl-D-aspartate (NMDA) and α1-adrenergic receptor antagonist ifenprodil on human Kv1.5 channel.
Ifenprodil has been known to reduce cardiac contractility and cerebral vasodilation by antagonizing α1-adrenergic and N-methyl D-aspartate receptor-mediated intracellular signals. This study aimed to investigate the direct effect of ifenprodil on the human voltage-gated Kv1.5 channel (hKv1.5) by using a Xenopus oocyte expression system and a two-microelectrode voltage clamp technique. The amplitudes of hKv1.5 currents, including peak and steady state, were suppressed in a concentration-dependent manner (IC50; 43.1 and 35.5 μM, respectively) after 6 min of ifenprodil treatment. However, these effects were ~ 80% reversed by washout, suggesting that ifenprodil directly inhibited the hKv1.5 independent of membrane receptors or intracellular signals. The inhibition rate of steady state showed voltage dependence, wherein the rates increased according to test voltage depolarization. Ifenprodil reduced the time constants of hKv1.5 inactivation but has higher effects on activation. hKv1.5 inhibition by ifenprodil showed use dependency because the drug more rapidly reduced the current at the higher activation frequencies, and subsequent reduction in frequency after high activation frequency caused a partial channel block relief. Therefore, ifenprodil directly blocked the hKv1.5 in an open state and accelerated the time course of the channel inactivation, which provided a biophysical mechanism for the hKv1.5 blocking effects of ifenprodil.


Interleukin-1beta stimulates early myogenesis of mouse C2C12 myoblasts: the impact on myogenic regulatory factors, extracellular matrix components, IGF binding proteins and protein kinases.
The purpose of the study was to examine the mechanisms important for early myogenesis in mouse C2C12 myogenic cells exposed to interleukin-1beta. Cyclin A and cyclin B1 were increased by interleukin-1beta (1 ng/ml), but the level of cyclin D1 and total DNA content was unaffected. Fusion index and the rate of protein synthesis was increased in the presence of IL-1beta, but these effects were limited to 3-day-treatment. IL-1beta increased the level of MyoD, myogenin and MHC on the 3rd day of differentiation, without altering the content of the active form of myostatin, as well as it augmented the level of fibronectin, integrin beta1 and full length 100 kDa form of ADAM12. IL-1beta caused a decrease in IGFBP-4 and IGFBP-6 levels and a marked increase in IGFBP-5. The phosphorylation of PKB and ERK1/2 and the cellular content of p38 were elevated by IL-1beta. We conclude that the myogenic effect of IL-1beta was limited to the onset of myoblast fusion and was associated with: i) increase in the level of myogenic transcription factors i.e. MyoD and myogenin expression, ii) modification of extracellular matrix assembly and signaling, manifested by an increase in fibronectin, integrin-beta1 and ADAM12 content, iii) drop in IGFBP-4 and IGFBP-6, and an increase in IGFBP-5, that could alter the local IGF-1 bioavailability, and iv) increase in phosphorylation of PKB and ERK1/2, and the expression of p38 kinase, leading to activation of intracellular pathways essential for myogenic differentiation.


How Cu(II) binding affects structure and dynamics of α-synuclein revealed by molecular dynamics simulations.
We report accelerated molecular dynamics simulations of α-Synuclein and its complex with two Cu(II) ions bound to experimentally determined binding sites. Adding two Cu(II) ions, one bound to the N-terminal region and one to the C-terminus, decreases size and flexibility of the peptide while introducing significant new contacts within and between N-terminus and non-Aβ component (NAC). Cu(II) ions also alter the pattern of secondary structure within the peptide, inducing more and longer-lasting elements of secondary structure such as β-strands and hairpins. Free energy surfaces, obtained from reweighting the accelerated molecular dynamics boost potential, further demonstrate the restriction on size and flexibility that results from binding of copper ions.


The effect of thermocycling on the bonding of different restorative materials to access opening through porcelain fused to metal restorations.
Porcelain fused to metal (PFM) crowns provide the best treatment option for teeth that have a large or defective restoration. More than 20% of teeth with PFM crowns or bridges require non-surgical root canal treatment (NSRCT). This may be due to the effect of restorative procedures and the possible leakage of bacteria and or their by-products, which leads to the demise of the tooth pulp. Thus, this study was planned to compare the ability of the restorative materials to seal perforated PFM specimens. The study evaluates the ability of amalgam, composite or compomer restorative materials to close perforated PFM specimen's in-vitro. Ninety PFM specimens were constructed using Ni-Cr alloys and feldspathic porcelain, and then they were divided into 3 groups: amalgam (A), composite + Exite adhesive bond (B) and compomer + Syntac adhesive bond (C). All the PFM samples were embedded in an acrylic block to provide complete sealing of the hole from the bottom side. After the aging period, each group was further divided into 3 equal subgroups according to the thermocycling period (one week for 70 cycles, one month for 300 cycles and three months for 900 cycles). Each subgroup was put into containers containing dye (Pelikan INK), one maintained at 5℃ and the other at 55℃, each cycle for 30 sec time. The data obtained was analyzed by SPSS, 2006 using one way ANOVA test and student t-test and significant difference level at (P<.01). The depth of dye penetration was measured at the interfaces of PFM and filling materials using Co-ordinate Vernier Microscope. The lowest levels of the dye penetration for the three groups, as well as subgroups were during the first week. The values of dye leakage had significantly increased by time intervals in subgroups A and C. It was seen that amalgam showed higher leakage than composite while compomer showed the lowest level of leakage.


Environmental conditions affecting the strength of induced resistance against mites in cotton.
Spider mites (Tetranychus urticae) were raised on cotton plants that had been damaged by a previous bout of mite feeding (T. turkestani) and on control plants that were previously not exposed to mites. The effect of induced plant responses upon mite populations was variable ranging from a 4-fold reduction in population growth to no difference at all. The strength of induced resistance was greatest when the population growth of mites was low for other, unknown, reasons. When mite population growth on control plants was great, the effects of induced resistance were diminished.Mite population growth was inversely related to levels of initial damage caused by previous feeding. There was no evidence of a damage threshold that needed to be exceeded before induced resistance became effective. Increased levels of initial damage were not associated with morphological changes in the plants.


Endoscopy in patients receiving radiation therapy to the thorax.
Radiation therapy for thoracic malignancies is often complicated by radiation-induced esophagitis. Symptoms of radiation esophagitis are nonspecific and include dysphagia, odynophagia, and chest pain. Patients receiving radiation therapy are also at risk for infectious esophagitis, which can be indistinguished clinically from radiation-induced esophagitis. We retrospectively reviewed data on patients who had esophagitis symptoms during or after thoracic radiation therapy and were referred for upper endoscopy. We sought to determine how often infectious esophagitis or cancer was present, as compared to radiation-induced esophagitis alone. Twenty-four upper endoscopies were performed on 16 patients over a three-year period to evaluate esophagitis symptoms. Forty-four percent of the patients endoscoped had infectious esophagitis or recurrent cancer diagnosed by endoscopy. No complications occurred from the procedures. Esophagoscopy is a safe procedure that should be considered, to exclude infection or cancer, in patients who develop esophagitis symptoms during or after thoracic radiation.


In vivo metabolic activity of the suprachiasmatic nuclei: non-uniform intranuclear distribution of 14C-labeled deoxyglucose uptake.
Anatomical techniques have shown that the suprachiasmatic nuclei (SCN) are organized into distinct dorsomedial and ventrolateral subdivisions. As a functional correlate to this morphological organization, the intranuclear distribution of SCN glucose utilization was mapped using the autoradiographic 14C-labeled deoxyglucose method. In nocturnal rats and diurnal squirrel monkeys injected with the tracer during the light portion of the light-dark cycle, the middle of the SCN was metabolically more active than its rostral or caudal ends. No obvious dorsomedial/ventrolateral parcellation of SCN functional activity was disclosed. The rostrocaudal metabolic contour persisted unchanged in the absence of external light and resembled the 3-dimensional shape of the SCN (the highest metabolic activity was generally found at the largest cross-sectional area). This result is discussed with respect to its implications for the generation of circadian rhythmicity by the endogenous pacemaker in the SCN.


Lethal respiratory course and additional features expand the phenotypic spectrum of PIEZO2-related distal arthrogryposis type 5.
Distal arthrogryposes (DA) are a group of conditions presenting with multiple congenital contractures in the distal joints. The 10 types of DA are distinguished by different extra-articular manifestations. Heterozygous gain-of-function variants in PIEZO2 are known to cause a spectrum of DA conditions including DA type 3, DA type 5, and possibly Marden Walker syndrome, which are usually distinguished by the presence of cleft palate (DA3), ptosis and restriction in eye movements (DA5), and specific facial abnormalities and central nervous system involvement, respectively. We report on a boy with a recurrent de novo heterozygous PIEZO2 variant in exon 20 (NM_022068.3: c.2994G > A, p.(Met998Ile); NM_001378183.1: c.3069G > A, p.(Met1023Ile)), who presented at birth with DA and later developed respiratory insufficiency. His phenotype broadly fits the PIEZO2 phenotypic spectrum and potentially extends it with novel phenotypic features of pretibial linear vertical crease, immobile skin, immobile tongue, and lipid myopathy.


The structure of Klebsiella pneumoniae K108 capsular polysaccharide is similar to Escherichia coli colanic acid.
The clinical isolate of Klebsiella pneumoniae 1333/P225 was revealed as containing a KL108 K. pneumoniae K locus for capsule biosynthesis. The gene cluster demonstrated a high level of sequence and arrangement similarity with that of the E. coli colanic acid biosynthesis gene cluster. The KL108 gene cluster includes a gene of WcaD polymerase responsible for joining oligosaccharide K units into capsular polysaccharide (CPS), acetyltransferase, pyruvyltransferasefive and genes for glycosyltransferases (Gtrs), four of which have homologues in genetic units of the colanic acid synthesis. The fifth Gtr is specific to this cluster. The work involved the use of sugar analysis, Smith degradation and one- and two-dimensional 1H and 13C NMR spectroscopy to establish the structure of the K108 CPS. The CPS repetitive K unit is composed of branched pentasaccharide with three monosaccharides in the backbone and a disaccharide side chain. The main chain is the same as for colanic acid but the side chain differs. Two bacteriophages infecting K. pneumoniae strain 1333/P225 were isolated and structural depolymerase genes were determined; depolymerases Dep108.1 and Dep108.2 were cloned, expressed and purified. It was demonstrated that both depolymerases specifically cleave the β-Glcp-(1→4)-α-Fucp linkage between K108 units in the CPS.


Early seasonal development of brain song control nuclei in male blue tits.
In songbirds, the seasonal growth of the song system is generally thought to be controlled by the spring increase in plasma levels of testosterone and/or related changes in singing activity. Here we report an extremely early seasonal growth (before February) of the song control nuclei HVC and RA in Corsican blue tits (Parus caeruleus) indicating that the vernal development of these nuclei occurs well before the vernal increase in plasma testosterone, testes size and song activity. The development of HVC and RA occurred simultaneously in two populations that are known to breed consistently 1 month apart as an adaptation to heterogeneous landscapes (predominance of broad-leaved deciduous versus evergreen oak trees). The unidentified environmental and/or physiological cues controlling the plasticity in the song system must therefore differ, at least in part, from those affecting other morphological and physiological traits controlling reproduction.


An Injectable Containing Morphine, Ropivacaine, Epinephrine, and Ketorolac Is Not Cytotoxic to Articular Cartilage Explants From Degenerative Knees.
The purpose of this study was to determine the effects of a multidrug injectate containing morphine, ropivacaine, epinephrine, and ketorolac, commonly referred to as the "Orthococktail," on cartilage tissue viability and metabolic responses using an established in vitro model. With institutional review board approval and informed patient consent, tissues normally discarded after total knee arthroplasty (TKA) were recovered. Full-thickness cartilage explants (n = 72, Outerbridge grade 1 to 3) were created and bisected. Paired explant halves were treated with either 1 mL Orthococktail or 1 mL of saline and cultured for 8 hours at 37°C, with 0.5 mL of the treatment being removed and replaced with tissue culture media every hour. Explants were cultured for 6 days, and media were changed and collected on days 3 and 6. After day 6, tissues were processed for cell viability, weighed, and processed for histologic grading. Outcome measures were compared for significant differences between treated and untreated samples. There were no significant differences in cartilage viability between control and Orthococktail-treated samples across a spectrum of cartilage pathologies. Orthococktail treatment consistently resulted in a significant decrease in the release of PGE2, MCP-1, MMP-7, and MMP-8 on day 3 of culture and PGE2, MMP-3, MMP-7, and MMP-8 on day 6 of culture, compared with saline controls. The results of the present study indicate that an Orthococktail injection composed of morphine, ropivacaine, epinephrine, and ketorolac is associated with a transient decrease in degradative and inflammatory mediators produced by more severely affected articular cartilage and may mitigate perioperative joint pain such that postoperative narcotic drug use could be reduced. The Orthococktail solution used in this study may be a safe intraoperative, intra-articular injection option for patients undergoing joint arthroplasty and other joint preservation surgical procedures.


Investigation of self-etching dentin primers.
In order to simplify the dentin bonding procedures by combining the dentin cleansing and dentin primer steps, we investigated the efficacy of the four acidic monomers--monomethacryloxyethyl succinate (MES), dimethacryloxyethyl phosphate (DMEP), tertiary butylacrylamide sulfonic acid (TBAS), and 4-methacryloxyethyl trimellitic anhydride (4-META), diluted in 35% hydroxyethyl methacrylate (HEMA) solution--by measuring the maximum contraction gap of the visible-light-curing composite (Silux 3M, St. Paul, MN, USA) in the cylindrical dentin cavity mediated by the bonding agent (Clearfil New Bond, Kuraray Co., Osaka, Japan). More than five of the ten specimens which were pre-treated with an aqueous mixture of 35% HEMA and four functional monomers at the concentrations of 0.1 M, 0.2 M, and 0.3 M showed a complete marginal adaptation, and this result was the same as in the control group in which the cavities were cleansed and pre-treated with 0.5 M EDTA and 35% HEMA, respectively. Moreover, the procedures were simpler. Therefore, these four monomers are considered to be effective as self-etching primers.


Dimethylarginine dimethylaminohydrolase-1 mediates inhibitory effect of interleukin-10 on angiotensin II-induced hypertensive effects in vascular smooth muscle cells of spontaneously hypertensive rats.
In hypertension studies, anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to prevent angiotensin II (Ang II)-induced vasoconstriction and regulate vascular function by down-regulating pro-inflammatory cytokine and superoxide production in vascular cells. However, little is known about the mechanism behind the down-regulatory effect of IL-10 on Ang II-induced hypertensive mediators. In this study, we demonstrated the effects of IL-10 on expression of dimethylarginine dimethylaminohydrolase (DDAH)-1, a regulator of NO bioavailability, as well as the down-regulatory mechanism of action of IL-10 in relation to Ang II-induced hypertensive mediator expression and cell proliferation in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). IL-10 increased DDAH-1 but not DDAH-2 expression and increased DDAH activity. Additionally, IL-10 attenuated Ang II-induced DDAH-1 inhibition in SHR VSMCs. Increased DDAH activity due to IL-10 was mediated mainly through Ang II subtype II receptor (AT2 R) and AMP-activated protein kinase (AMPK) activation. DDAH-1 induced by IL-10 partially mediated the inhibitory action of IL-10 on Ang II-induced 12-lipoxygenase (LO) and endothelin (ET)-1 expression in SHR VSMCs. In addition, the inhibitory effect of IL-10 on proliferation of Ang II-induced VSMCs was mediated partially via DDAH-1 activity. These results suggest that DDAH-1 plays a potentially important role in the anti-hypertensive activity of IL-10 during Ang II-induced hypertension.


Accidental finding of COVID-associated mucormycosis (CAM) in a patient presenting as toothache: A case report and review of literature.
Mucormycosis is an angio-invasive rapidly progressing fungal infection, usually reported in immunocompromised individuals. We present a case of COVID-associated mucormycosis in a patient with a presenting symptom of toothache in the maxilla with a possible mild case of COVID-19. Coronavirus-associated mucormycosis (CAM) had reached epidemic status, especially during the second wave of COVID-19. It was especially prevalent in India with a large mortality rate. Mucormycosis, particularly the rhinocerebral type is seen to be greatly associated with COVID-19, especially in patients with altered immunity. Uncontrolled diabetes, chronic kidney disease, immunocompromised patients, malignant hematological diseases, etc. are the major risk factors of CAM, precipitated by the injudicious use of corticosteroids for the treatment of COVID-19. CAM may often present in the maxillofacial region which warrants that dental clinicians be aware of the clinical presentation, diagnostic guidelines, and appropriate management measures for the disease. This report is one such case of CAM involving the posterior maxilla in a middle-aged individual with mild COVID-19 symptoms.


Role of Surgery for Metastatic Melanoma.
Complete surgical resection of metastatic melanoma has a known survival benefit. Treatment of metastatic melanoma, however, has become increasingly complex with the introduction of targeted treatments and immune checkpoint inhibitors. Integration of systemic medical therapy and surgical resection has shown promising results, with significantly improved long-term survivals. Results from current clinical trials are awaited to help further delineate the sequence and combination of systemic therapy and surgery.


Association between herpes simplex virus 1 exposure and the risk of depression in UK Biobank.
Herpes simplex virus-1 (HSV-1) infection is reported to be associated with depression. But limited efforts were made to investigate the relationship between HSV-1 infection and the risk of depression, especially from the genetic perspective. In UK Biobank cohort, linear and logistic regression analyses were first performed to test the association of HSV-1 seropositivity/antibody with depression, including depression status (N = 2951) and Patient Health Questionnaire (PHQ) score (N = 2839). Using individual genotypic and phenotypic data from the UK Biobank, genome-wide environmental interaction study (GWEIS) was then conducted by PLINK2.0 to evaluate gene × HSV-1 interacting effect on the risk of depression. Finally, gene set enrichment analysis was conducted to identify the biological pathways involved in the observed gene × HSV-1 interaction for depression. In UK Biobank cohort, significant associations were observed between depression status and HSV-1 (odds ratio [OR] = 1.09; 95% confidence interval [CI], 1.02-1.16; P = 2.40 × 10-2 for HSV-1 antibody and OR = 1.28; 95% CI, 1.12-1.47, P = 2.59 × 10-3 for HSV-1 seropositivity). GWEIS revealed four significant gene × HSV-1 interaction signals for PHQ score (all P < 5.0 × 10-8 ) and the leading loci was SULF2 (rs6094791, P = 8.60 × 10-9 ). Pathway analyses identified 21 pathways for PHQ score and 19 for depression status, including multiple neural development- and immune-related ones, such as KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION (false discovery rate [FDR] = 3.18 × 10-2 ) for depression and LU_AGING_BRAIN_UP (FDR = 4.21 × 10-2 ) for PHQ score. Our results suggested that HSV-1 was associated with the risk of depression, which was modulated by the several genes that were related to the nerve development or immune function.


Analyses of crop water use and environmental performance of small private irrigation along the white Volta basin of Northern Ghana.
Small private irrigation (SPI) is a farmer-initiated irrigation which has the potential to increase the contribution of the overall irrigation sector to global food security. However, there is no much information about these systems for effective policies for regulation. This study compared the resource use productivities and environmental impacts of SPI systems to those of a government-led irrigation scheme (GIS) in Northern Ghana. The results showed that land productivity was higher in the SPI than in the GIS. Productivity per unit cultivated area was 2571.00 US$/ha under SPI while that of the GIS was 676.00 US$/ha. Output per unit command area was also two times higher in the SPI than in the GIS; that is 2571.00 US$/ha and 1113.00 US$/ha for SPI and GIS respectively. For water productivity, output per unit irrigation supply was 0.33 US$/m3 and 0.08US$/m3 for SPI and GIS respectively while output per unit water consumed by ET was 0.60 US$/m3 for SPI and 0.06 US$/m3 for the GIS. The results implied that the SPI schemes performed better in land and water productivities compared with the GIS which is attributed to higher yields and the selection of high valued crops by farmers under SPI. However, both irrigation system types at the time of this study did not cause significant deterioration to the water bodies and surrounding environment as the biochemical oxygen demand (BOD) values of nearby water bodies were less than 3.0-5.0 mg/l, which is considered as acceptable levels for drinking water by World Health Organisation (WHO) while salinity levels were also within acceptable limits (<750 μS/cm). With appropriate policies to regulate and provide support systems to the SPI, these systems may increase the overall agricultural productivity and improve job creation for the teeming unemployed youth and women in the savannah agroecological zone of Ghana.


Cardiorenal actions of endothelin, Part II: Effects of cyclooxygenase inhibitors.
The effects of cyclooxygenase inhibitors (meclofenamate and indomethacin) on endothelin-induced changes in renal function were evaluated in pentobarbital anesthetized female rats. Two groups (n = 5/group) of rats were evaluated: one group received a continuous intravenous infusion of meclofenamate (0.03 mg kg-1 min-1) and the second group received a bolus injection of indomethacin (5 mg/kg). Following surgery, rats were allowed 60 min to stabilize and 3 X 20 min control clearances collected. Endothelin-1 (100 eta kg-1 min-1) was then added into the infusate for 30 min. Neither meclofenamate nor indomethacin caused significant changes on endothelin-induced systemic vasoconstriction; blood pressure increased from 107 +/- 3 to 136 +/- 2 mmHg (p less than 0.01) with endothelin alone, from 103 +/- 6 to 135 +/- 6 mmHg (p less than 0.01) with endothelin plus meclofenamate, and from 105 +/- 6 to 131 +/- 10 mmHg (p less than 0.01) with endothelin plus indomethacin. Similarly, endothelin-induced decreases in glomerular filtration rate (GFR) were not affected by either meclofenamate or indomethacin; GFR decreased from 2.7 +/- 0.2 to 0.8 +/- 0.3 ml/min (p less than 0.01) with endothelin alone, from 2.3 +/- 0.5 to 0.7 +/- 0.4 ml/min (p less than 0.01) with endothelin plus meclofenamate, and from 2.6 +/- 0.4 to 0.6 +/- 0.4 ml/min (p less than 0.01) with endothelin plus indomethacin. Baseline excretion rates of sodium, potassium and urine volume were also not affected by the inhibitors of cyclooxygenase. These data demonstrate that, under the conditions of the current study, endothelin-induced changes in renal and cardiovascular function are not affected by inhibiting prostaglandin production.


Fabrication of selective and sensitive chemical sensor probe based on ternary nano-formulated CuO/MnO2/Gd2O3 spikes by hydrothermal approach.
In this approach, thin spikes (NSs) of ternary nano-formulated mixed CuO/MnO2/Gd2O3 were synthesized by the hydrothermal approach for efficient detection of 3-methoxyphenyl hydrazine (3-MPHyd) chemical from various environmental samples. The NSs were systematically characterized by using XPS, EDS, TEM, FTIR, UV/vis, and XRD. The fabricated NSs onto the glassy carbon electrode (GCE) was successfully applied for the selective and sensitive detection of 3-MPHyd in the phosphate buffer system (PBS), which displayed the highest sensitivity, good selectivity with ultra-trace detection limit, high stability, good reproducibility, and quick response time. The real environmental samples were tested for validation from stand point of the ternary doped nanomaterials for sensing in the practical applications using by electrochemical method.


Esophageal motility in progressive systemic sclerosis (PSS). Comparison of cine-radiographic and manometric evaluation.
The evaluation of structural and functional abnormalities of the esophagus by manometry (using perfused tubes) and cine-radiography were compared in 25 subjects with progressive systemic sclerosis (PSS). Motility by both procedures was definitely abnormal in 19 subjects and normal in 3. The remaining 3 subjects had abnormal motility on manometry, coupled with cine-esophagrams interpreted as normal. Many structural abnormalities not demonstrated by manometry were identified by cine-radiography. Therefore, the initial diagnostic examination of motility in PSS should be the cine-esophagram.


Interleukin-33 induces interleukin-17F in bronchial epithelial cells.
IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.


Amide signal intensities may be reduced in the motor cortex and the corticospinal tract of ALS patients.
The aim of the study is to assess amide concentration changes in ALS patients compared with healthy controls by using quantitative amide proton transfer (APT) and multiparameter magnetic resonance imaging, and testing its correlation with clinical scores. Sixteen ALS patients and sixteen healthy controls were recruited as part of the Canadian ALS Neuroimaging Consortium, and multimodal magnetic resonance imaging was performed at 3 T, including APT and diffusion imaging. Lorentz fitting was used to quantify the amide effect. Clinical disability was evaluated using the revised ALS functional rating scale (ALSFRS-R), and its correlation with image characteristics was assessed. The diagnostic performance of different imaging parameters was evaluated with receiver operating characteristic analysis. Our results showed that the amide peak was significantly different between the motor cortex and other gray matter territories within the brain of ALS patients (p < 0.001). Compared with controls, amide signal intensities in ALS were significantly reduced in the motor cortex (p < 0.001) and corticospinal tract (p = 0.046), while abnormalities were not detected using routine imaging methods. There was no significant correlation between amide and ALSFRS-R score. The diagnostic accuracy of the amide peak was superior to that of diffusion imaging. This study demonstrated changes of amide signal intensities in the motor cortex and corticospinal tract of ALS patients. • The neurodegenerative disease amyotrophic lateral sclerosis (ALS) has a lack of objective imaging indicators for diagnosis and assessment. • Analysis of amide proton transfer imaging revealed changes in the motor cortex and corticospinal tract of ALS patients that were not visible on standard magnetic resonance imaging. • The diagnostic accuracy of the amide peak was superior to that of diffusion imaging.


[Impact of the COVID-19 pandemic on the care of major trauma patients: analysis from the TraumaRegister DGU®].
The treatment of major trauma patients requires intensive care capacity, which is a critical resource particularly during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, the aim of this study was to analyze the impact on major trauma care considering the intensive care treatment of COVID-19 positive patients. Demographic, prehospital, and intensive care treatment data from the TraumaRegister DGU® of the German Trauma Society (DGU) in 2019 and 2020 were analyzed. Only major trauma patients from the state of Bavaria were included. Inpatient treatment data of COVID-19 patients in Bavaria in 2020 were obtained using IVENA eHealth. In total, 8307 major trauma patients were treated in the state of Bavaria in the time period investigated. The number of patients in 2020 (n = 4032) compared to 2019 (n = 4275) was not significantly decreased (p = 0.4). Regarding COVID-19 case numbers, maximum values were reached in the months of April and December with more than 800 intensive care unit (ICU) patients per day. In the critical period (> 100 patients with COVID-19 on ICU), a prolonged rescue time was evident (64.8 ± 32.5 vs. 67.4 ± 30.6 min; p = 0.003). The length of stay and ICU treatment of major trauma patients were not negatively affected by the COVID-19 pandemic. The intensive medical care of major trauma patients could be ensured during the high-incidence phases of the COVID-19 pandemic. The prolonged prehospital rescue times show possible optimization potential of the horizontal integration of prehospital and hospital.


The use of the PAPNET automated cytological screening system for the diagnosis of oral squamous carcinoma.
The automated PAPNET screening system has been developed to recognize abnormal cells in cervical smears. Given that the oral mucosa sheds cells resembling superficial and intermediate cells of the cervix, the aim of this study was to assess whether the PAPNET system could be used to detect dysplastic cells in oral mucosal smears. Sixty-two oral smears from 27 patients were examined by both light microscopy and using the PAPNET system from clinically abnormal and normal areas by two pathologists. The clinically abnormal sites were also biopsied for histological analysis. There was 100% correlation between the manual and PAPNET screening results. Cytological interpretation of oral smears by both manual and PAPNET screening methods correctly diagnosed squamous cell carcinoma in 14/23 (61%) of patients who had all been confirmed by biopsy. The nine patients with false-negative cases could be attributed to poor smear technique and preparation. The PAPNET system can be used to identify abnormal cells in oral smears and, as such, may have an application for screening those populations at high risk of oral cancer--provided that adequate tuition is given in smear technique.


Cataract secondary to electrical shock from a Taser gun.
A 35-year-old man presented with traumatic iritis, angle-recession glaucoma, and a retinal dialysis secondary to blunt trauma from a Taser gun in the right eye and a unique electrical cataract in the left eye. Taser guns, which can also function as stun guns, can lead to electrical cataract formation. Given the increasing use of Taser guns by law enforcement and citizens, blunt mechanical and electrical sequelae of Taser gun injuries should be recognized.


Indium-Catalyzed Reductive Dithioacetalization of Carboxylic Acids with Dithiols: Scope, Limitations, and Application to Oxidative Desulfurization.
In this study an InI3-TMDS (1,1,3,3-tetramethyldisiloxane) reducing system effectively catalyzed the reductive dithioacetalization of a variety of aromatic and aliphatic carboxylic acids with 1,2-ethanedithiol or 1,3-propanedithiol leading to the one-pot preparation of either 1,3-dithiolane derivatives or a 1,3-dithiane derivative. Also, the intact indium catalyst continuously catalyzed the subsequent oxidative desulfurization of an in situ formed 1,3-dithiolane derivative, which led to the preparation of the corresponding aldehydes.


Calcium-binding proteins in the cerebellar cortex of the bottlenose dolphin and harbour porpoise.
Studying the distribution of Ca2+-binding proteins allows one to discover specific neuron chemotypes involved in the regulation of the activity of various neural elements. While extensive data exist on Ca2+-binding proteins in the nervous system, in particular, in the cerebellar cortex of terrestrial mammals, the localization of these proteins in the cerebellar cortex of marine mammals has not been studied. We studied the localization of calretinin, calbindin, and parvalbumin immunoreactivity in the cerebellar cortex of the bottlenose dolphin Tursiops truncates and harbour porpoise Phocoena phocoena. In both species, most Purkinje cells were calbindin-immunoreactive, while calretinin and parvalbumin were expressed in a small portion of Purkinje cells. In addition, calretinin-immunoreactive unipolar brush and granule cells and calbindin- and parvalbumin-immunoreactive basket, stellate, and Golgi cells were observed. Calretinin-immunoreactive corticopetal (mossy and climbing) fibers were found. Based on the length of the primary dendrite, short-, middle-, and long-dendrite unipolar brush cells could be distinguished. The validity of this classification was supported using cluster analysis suggesting the presence of several natural types of these cells. The distribution of Ca2+-binding proteins in the cerebellar cortex of the cetaceans studied was generally similar to that reported for terrestrial mammals, suggesting that this trait is evolutionarily conservative in mammals.


Perceived discrimination among Maghrebi users of health services in Tarragona (Spain).
Discrimination in health services for reasons of nationality or ethnicity is not a rare occurrence. This work aims to qualitatively analyse the perceived discrimination among Maghrebi community in Tarragona (Spain) with regard to the healthcare services they receive. A qualitative study was carried by means of 12 semi-structured interviews and 10 focus groups with Maghrebi adults living in Tarragona. The scope of the study was public health services in the area. A content analysis was performed using open coding. Our results show that perceived discrimination is greater than actual discrimination because the deficiencies of the healthcare system are often interpreted as unfairness. However, our subjects also recounted incidents of clear discrimination against Maghrebi users of the healthcare system. The tendency to feel discriminated against is the culmination of an interaction between the group's low self-esteem and locals' often negative sentiments towards the group. We suggest addressing the shortcomings of the healthcare system in order to reduce this level of perceived discrimination and thus improve patient satisfaction. To improve this group's self-esteem and change how they are perceived, public policies should be put into effect which promote social inclusion and the respect for Maghrebis' rights as people, with actions taken on both fronts: in the host society and within the Maghrebi community itself. Furthermore, an active role for the patient with regard to his or her rights should be encouraged in order to minimize abuse from professionals and to facilitate institutional control of individual actions.


Calcium metabolism in olive ridley turtle eggs during embryonic development.
Analyses of calcium, magnesium, sulphur, potassium and phosphorus content of the eggshell, yolk-albumen and embryos of olive ridley turtle, Lepidochelys olivacea, have been carried out at various stages of embryonic development. Calcium is the major inorganic constituent in the egg (shell and yolk-albumen) and embryos. Other elements are present either in trace or in minute trace amounts. The egg contents (yolk and albumen) provide only 40% of the embryonic calcium requirement of the hatchling. The remaining 60% is provided by the eggshell. The eggshell also undergoes a similar reduction in its calcium content from laying to hatching. Elements other than calcium present in the yolk-albumen are sufficient for normal embryonic development. The movement of calcium from the eggshell to the embryo starts at about the 40th day of development at 29.5 degrees C. Birds, turtles and crocodiles use their eggshell as the secondary source of embryonic calcium requirement. This dependence on the eggshell varies in different groups which is highest in birds and lowest in crocodiles.


Accuracy of a new low-flow sidestream capnography technology in newborns: a pilot study.
To evaluate the accuracy of a new low-flow sidestream capnography technology and analyze components of the capnogram in mechanically ventilated newborns with and without pulmonary disease. Twenty patients were prospectively identified. Eligible infants were mechanically ventilated and had an indwelling arterial catheter. Two groups were identified: newborns who were receiving mechanical ventilation for pulmonary diseases, and newborns who were receiving postoperative mechanical ventilation for nonpulmonary conditions. End-tidal CO(2) (PetCO(2)) was measured for 1-minute pre- and post-arterial blood sampling, and PetCO(2) and PaCO(2) were compared for each patient. Eight quantitative waveform parameters were also measured on all patients. Newborns in the pulmonary group (n=13) (persistent pulmonary hypertension of the newborn/meconium aspiration syndrome, respiratory distress syndrome, pneumonia) and newborns in the control group (n=7) were matched for birth weight, gestational age, and postnatal age. PetCO(2)-PaCO2 Gradient values were higher in the pulmonary group (7.4+/-3.3 mm Hg) than controls (3.4+/-2.4 mm Hg). Four waveform parameters (ascending slope, alveolar angle, alpha angle, descending angle) were identified, which independently differentiated patients with pulmonary disease from controls. Low-flow capnography with Microstream technology accurately measured alveolar CO(2) in newborns without pulmonary disease, as demonstrated by normal PetCO(2)-PaCO(2) gradients. The measured PetCO(2)-PaCO(2) gradient, as expected, was significantly higher in newborns with pulmonary disease. We also identified four quantitative waveform parameters that may be useful in differentiating between mechanically ventilated newborn patients with and without lung disease.


Nucleosomes and flipons exchange energy to alter chromatin conformation, the readout of genomic information, and cell fate.
Alternative non-B-DNA conformations formed under physiological conditions by sequences called flipons include left-handed Z-DNA, three-stranded triplexes, and four-stranded i-motifs and quadruplexes. These conformations accumulate and release energy to enable the local assembly of cellular machines in a context specific manner. In these transactions, nucleosomes store power, serving like rechargeable batteries, while flipons smooth energy flows from source to sink by acting as capacitors or resistors. Here, I review the known biological roles for flipons. I present recent and unequivocal findings showing how innate immune responses are regulated by Z-flipons that identify endogenous RNAs as self. Evidence is also presented supporting important roles for other flipon classes. In these examples, the dynamic exchange of energy between flipons and nucleosomes enables rapid switching of genetic programs without altering flipon sequence. The increased phenotypic diversity enabled by flipons drives their natural selection, with adaptations evolving faster than is possible by codon mutation alone.


Echocardiographic diagnosis of bland thrombus on an aortic valve.
Echocardiography is a valuable modality for imaging thrombi and vegetations. Although patients with systemic lupus erythematosus may develop Libman-Sacks endocarditis, in which punctate verrucous plaques are found histologically on valvular endocardial tissue, these lesions are ordinarily too small for ultrasonic imaging. We describe a patient with systemic lupus erythematosus complicated by systemic embolization, who had a large mobile aortic valve thrombus, which was discovered with the aid of echocardiography and was confirmed by surgical resection.


Signed and unsigned effects of prediction error on memory: Is it a matter of choice?
Adaptive decision-making is governed by at least two types of memory processes. On the one hand, learned predictions through integrating multiple experiences, and on the other hand, one-shot episodic memories. These two processes interact, and predictions - particularly prediction errors - influence how episodic memories are encoded. However, studies using computational models disagree on the exact shape of this relationship, with some findings showing an effect of signed prediction errors and others showing an effect of unsigned prediction errors on episodic memory. We argue that the choice-confirmation bias, which reflects stronger learning from choice-confirming compared to disconfirming outcomes, could explain these seemingly diverging results. Our perspective implies that the influence of prediction errors on episodic encoding critically depends on whether people can freely choose between options (i.e., instrumental learning tasks) or not (Pavlovian learning tasks). The choice-confirmation bias on memory encoding might have evolved to prioritize memory representations that optimize reward-guided decision-making. We conclude by discussing open issues and implications for future studies.


The phenotypic equilibrium of cancer cells: From average-level stability to path-wise convergence.
The phenotypic equilibrium, i.e. heterogeneous population of cancer cells tending to a fixed equilibrium of phenotypic proportions, has received much attention in cancer biology very recently. In the previous literature, some theoretical models were used to predict the experimental phenomena of the phenotypic equilibrium, which were often explained by different concepts of stabilities of the models. Here we present a stochastic multi-phenotype branching model by integrating conventional cellular hierarchy with phenotypic plasticity mechanisms of cancer cells. Based on our model, it is shown that: (i) our model can serve as a framework to unify the previous models for the phenotypic equilibrium, and then harmonizes the different kinds of average-level stabilities proposed in these models; and (ii) path-wise convergence of our model provides a deeper understanding to the phenotypic equilibrium from stochastic point of view. That is, the emergence of the phenotypic equilibrium is rooted in the stochastic nature of (almost) every sample path, the average-level stability just follows from it by averaging stochastic samples.


Malignant papillary mesothelioma of the tunica vaginalis testes: cutaneous metastases showing pagetoid epidermal invasion.
Malignant papillary mesothelioma of the tunica vaginalis testis is an extremely rare tumor arising from the mesothelium of the tunica vaginalis. A total of 14 cases have been reported, with only two exhibiting cutaneous metastases. We present a third case of cutaneous metastases arising from this unusual tumor. In addition, this is the first reported case of the occurrence of pagetoid epidermal invasion in this condition.


Antiulcer drugs and gastric mucosal integrity. Effects of misoprostol, 16,16-dimethyl PGE2, and cimetidine on hemodynamics and metabolic rate in canine gastric mucosa.
Although prostaglandins (PGs) of the E series have gastric antisecretory and cytoprotective properties, many have different effects on the barrier integrity of the gastric mucosa. The direct effect of antiulcer drugs on gastric mucosal blood flow, mucosal barrier permeability, and metabolic rate have not been adequately studied. These factors are important in the defense of the gastric mucosa. Part of the difficulty relates to the possible influence of gastric mucosal blood flow on gastric acid secretion. To rule out this confounding factor, omeprazole can be used to reveal the true pharmacologic effects of these antiulcer drugs independent of the effect of gastric secretion per se. The study examined the effects of 16,16-dimethyl PGE2 (dmPGE2), misoprostol, and cimetidine on gastric mucosal blood flow, oxygen consumption, potential difference (PD), electrolytes, and fluid flux using the ex vivo gastric chamber dog model. The PGs were administered intraluminally with an isotonic acid solution; cimetidine was administered by arterial infusion. None of the drug treatments had any significant effect on mean systemic arterial pressure, arterial blood gases, body temperature, or oxygen consumption. dmPGE2 significantly (P less than 0.001) decreased PD and enhanced the electrolytes (Na+, K+) and fluid flux across the mucosa (P less than 0.05). Misoprostol significantly increased gastric mucosal blood flow (P less than 0.02) and fluid efflux but decreased PD values. Cimetidine did not have any significant effects on barrier or metabolic functions of the stomach. These results suggest that a considerable difference exists in the pharmacology of gastric antisecretory drugs in relation to their effect on several factors affecting gastric mucosal integrity.


Medical management of brain tumor patients.
Brain tumors can present challenging medical problems. Seizures, peritumoral edema, venous thromboembolism, fatigue, and cognitive dysfunction can complicate the treatment of patients who have primary or metastatic brain tumors. Effective medical management results in decreased morbidity and mortality and improved quality of life for affected patients.


SF-Assemblin genes in Paramecium: phylogeny and phenotypes of RNAi silencing on the ciliary-striated rootlets and surface organization.
Cilia emanate from basal bodies just underneath the cell membrane. Basal bodies must withstand torque from the ciliary beat and be appropriately spaced for cilia to beat in metachronal waves. Basal body rootlets provide stability for motile cilia. Paramecium has three. Our focus is on the largest one, the striated rootlet (SR). Paramecium basal bodies align in straight rows. Previously we found a potential role for the SR in this alignment. Here we present a phylogeny of the Paramecium homologs of the SF-Assemblin gene of the SR of Chlamydomonas, and the organization of these genes. We describe the phenotypes from RNA interference (RNAi) silencing of genes and gene groups. Phenotypes of the RNAi depletions were characterized by immunofluorescence (IF), electron microscopy, and mass spectrometry. We found 30 genes for Paramecium SF-Assemblin homologs (SFA) organized into 13 Paralog Groups (further categorized in five Structural Groups). Representatives of Paralog Groups were found in the SRs. Silencing the transcripts of any of the Structural Groups correlates with misaligned rows of basal bodies, SRs, and cortical units. The silencing of Structural Groups was key and gave us the ability to systematically disrupt SR structures and cell surface organization. Silencing of SFA genes and Paralog Groups shows no effects on the SR or the cell surface organization. Silencing of the larger Structural Groups has an enormous impact on rows of basal bodies, SRs and cortical units, and SR striations, and length. Misaligned basal bodies have cilia causing the cells to swim in abnormal paths.


TNF-α potentiates glutamate-induced spinal cord motoneuron death via NF-κB.
Besides glutamate excitotoxicity, the neuroinflammatory response is emerging as a relevant contributor to motoneuron loss in amyotrophic lateral sclerosis (ALS). In this regard, high levels of circulating proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) have been shown both in human patients and in animal models of ALS. The aim of this work was to study the effects of TNF-α on glutamate-induced excitotoxicity in spinal cord motoneurons. In rat spinal cord organotypic cultures chronic glutamate excitotoxicity, induced by the glutamate-uptake inhibitor threohydroxyaspartate (THA), resulted in motoneuron loss that was associated with a neuroinflammatory response. In the presence of TNF-α, THA-induced excitotoxic motoneuron death was potentiated. Co-exposure to TNF-α and THA also resulted in down-regulation of the astroglial glutamate transporter 1 (GLT-1) and in increased extracellular glutamate levels, which were prevented by nuclear factor-kappaB (NF-κB) inhibition. Furthermore, TNF-α and THA also cooperated in the induction of oxidative stress in a mechanism involving the NF-κB signalling pathway as well. The inhibition of this pathway abrogated the exacerbation of glutamate-mediated motoneuron death induced by TNF-α. These data link two important pathogenic mechanisms, excitotoxicity and neuroinflammation, suggested to play a role in ALS and, to our knowledge, this is the first time that TNF-α-induced NF-κB activation has been reported to potentiate glutamate excitotoxicity on motononeurons.


Detection of circulating tumor-associated antigen depends on the domains recognized by the monoclonal antibodies used: N-terminal trimmed EpCAM-levels are much higher than untrimmed forms.
The measurement of tumor-associated proteins is of high diagnostic value in the follow-up of cancer patients. Most tests ignore that various forms of the protein can exist; especially in epithelial cancers and the soluble receptors they produce. We choose EpCAM as model-antigen to analyze whether tests recognizing different domains of the protein give different results in patients' sera. EpCAM-reactive autoantibodies are present in the sera of patients with colorectal carcinoma, however little is known about the existence and possible relevance of circulating soluble EpCAM protein. Most monoclonal EpCAM-antibodies recognize the first EGF-like repeat and fail to detect N-terminal trimmed protein. We developed a novel ELISA to determine the concentration of serum EpCAM with mAbs recognizing the second EGF-like repeat. In 59 healthy controls, EpCAM concentrations ranged from 232 to 8893ng/ml (mean 1525ng/ml). Levels of EpCAM in 412 patients with adenocarcinoma were somewhat higher with concentrations ranging from 176 to 36,259ng/ml (mean 1971ng/ml). In direct comparison, the untrimmed protein specific ELISA detected lower levels and frequencies as compared to the EGFII-specific ELISA. Only sera with less than 1μg/ml circulating EGFII-EpCAM (66% of the sera) contained EpCAM-specific IgG antibodies. The absence of IgG antibodies in the sera with more than 1μg/ml circulating EpCAM was not due to immune complex formation. Anti-EpCAM IgA and IgM antibodies did not show such a correlation. It will be important to assess whether the presence of high levels of circulating EGFII-EpCAM is associated with side effects in patients given immunotherapy.


Lipopolysaccharide-induced hyperalgesia of intracranial capsaicin sensitive afferents in conscious rats.
Migraineous and non-migraineous headache is reported to be at highest intensity after an infection. This study investigated whether activation of the immune system can induce hyperalgesia in intracranial capsaicin sensitive afferents. The effects of intraperitoneal injected lipopolysaccharides (LPS) on behavior and c-fos expression in the trigeminal nucleus caudalis layer I, II (TNC I,II) elicited by intracisternally applied capsaicin were studied. Low concentrations of LPS potentiated capsaicin-induced immobilization behavior without affecting c-fos expression in the TNC I,II. Large amounts of LPS however increased the number of capsaicin-induced c-fos positive cells in the TNC I,II. These effects of LPS on capsaicin sensitive afferents are probably mediated by cytokines that act at peripheral vagal nerves, central brain regions or via direct actions of cytokines on capsaicin sensitive afferent nerve terminals. The hyperalgesic action of LPS on intracranial trigeminal and possibly other capsaicin sensitive afferents of the head may explain why different types of infections are accompanied by headache and why migraineous and non-migraineous headache is of highest intensity after an infection.


Design and synthesis of indolo[2,3-a]quinolizin-7-one inhibitors of the ZipA-FtsZ interaction.
The binding of FtsZ to ZipA is a potential target for antibacterial therapy. Based on a small molecule inhibitor of the ZipA-FtsZ interaction, a parallel synthesis of small molecules was initiated which targeted a key region of ZipA involved in FtsZ binding. The X-ray crystal structure of one of these molecules complexed with ZipA was solved. The structure revealed an unexpected binding mode, facilitated by desolvation of a loosely bound surface water.


Transferrin receptor 2 is a potential novel therapeutic target for β-thalassemia: evidence from a murine model.
β-thalassemias are genetic disorders characterized by anemia, ineffective erythropoiesis, and iron overload. Current treatment of severe cases is based on blood transfusion and iron chelation or allogeneic bone marrow (BM) transplantation. Novel approaches are explored for nontransfusion-dependent patients (thalassemia intermedia) who develop anemia and iron overload. Here, we investigated the erythropoietin (EPO) receptor partner, transferrin receptor 2 (TFR2), as a novel potential therapeutic target. We generated a murine model of thalassemia intermedia specifically lacking BM Tfr2: because their erythroid cells are more susceptible to EPO stimulation, mice show improved erythropoiesis and red blood cell morphology as well as partial correction of anemia and iron overload. The beneficial effects become attenuated over time, possibly due to insufficient iron availability to sustain the enhanced erythropoiesis. Germ line deletion of Tfr2, including haploinsufficiency, had a similar effect in the thalassemic model. Because targeting TFR2 enhances EPO-mediated effects exclusively in cells expressing both receptors, this approach may have advantages over erythropoiesis-stimulating agents in the treatment of other anemias.


Rho GTPases as key transducers of proliferative signals in g1 cell cycle regulation.
Mitogenic growth factor- and integrin-dependent signaling pathways cooperate to control the proliferation of nontransformed cells. As integral mediators of these networks, the Rho family of GTPases play a pivotal role in G1 cell cycle progression, primarily through regulation of cyclin D1 expression, as well as the levels of the cyclin-dependent kinase inhibitors p21cip1 and p27kip1. Such dual control of both the critical positive and negative regulators of G1 progression make the Rho GTPases prime candidates to target the autonomous proliferation which typifies cancer cells. Cyclin D1 has been identified as an important oncogene and the cdk inhibitors as tumor suppressors in human breast carcinogenesis. Evidence pointing to the potential role of Rho-dependent pathways and their interaction with oncogenic Ras in contributing to such cell cycle abnormalities that characterize human breast cancer is also presented.


Cultivation and stable operation of aerobic granular sludge at low temperature by sieving out the batt-like sludge.
Aerobic granules were successfully cultivated at 10 °C with relatively low strength substrate. Stable granules coexisted with the batt-like sludge (BLS) were obtained in 60 days. After removing the BLS, nutrient removal performance was greatly improved and stable removal efficiencies of 99% phosphorous, 98% ammonia and 60% TN were achieved. The bacterial community structure revealed that it was an unclassified-Comamonadaceae genus dominant in the BLS, which represented for low relative abundance in mature granules. Overgrowth of unclassified-Comamonadaceae genus was considered to be the key factor for inhibiting the performance of granules. The final configuration of granules was dominated by DPAO genus Flavobacterium and polysaccharide nutritional genus Chryseolinea. This study showed that stable aerobic granules with superior performance under low temperature could be successfully cultivated by sieving out the BLS.


A person-centered approach to resilience against bullying victimization in adolescence: Predictions from teacher support and peer support.
There is ample evidence that bullying victimization typically has deleterious effects on the developmental outcomes of adolescents, while little research attention has been paid to those who show "resilient" despite the stress associated with being bullied. This study aimed to identify such a group according to the severity of exposure to bullying victimization and psychological adaptation in terms of negative (i.e., depressive symptoms) as well as positive (i.e., subjective well-being) aspects, and to examine their associations with interpersonal sources in school ecology (i.e., teacher support and peer support) using a short-term longitudinal design. Latent profile analysis was performed on a sample of 2339 adolescents in junior high schools (Mage = 12.97 ± 0.58 years, 51.1 % boys). The presence of a resilient (8.0 %) profile was identified, along with three other distinct profiles: normative (59.2 %), vulnerable (29.0 %), and adverse (3.8 %). Despite experiencing bullying victimization of comparable severity, adolescents who reported more teacher support and peer support were more likely to classify to the "Resilient" profile. A broader range of malleable resource factors should be considered to enhance a nuanced understanding of what resource factors contribute to resilience. Multiple reporting sources should be applied to overcome information bias. And the results need to be verified across different cultural contexts, age groups, and regions. These findings add a new contribution to the literature by highlighting the utility of a person-centered approach in the field of victimization resilience studies and the important roles of teacher and peer support against bullying victimization. Future prevention and early intervention could consider support from teachers and peers as potentially robust and malleable targets.


Experimental data used to validate the FE model of the structural performance of two flexible pipes laid in a single trench.
The objective of the article is to describe the methodology followed to validate the finite element model for the new method of setting pipes in a separate sewer system, using one trench to accommodate the storm pipe over the sanitary pipe "doi.org/10.1016/j.tust.2019.103019" (Abbas et al., 2019). A physical model was established in the Liverpool John Moores University (LJMU) lab to test the structural performance of two PVC pipes buried in one trench. The results of the physical model were used to validate an FE model using the same material properties and boundary conditions used in the physical model. The validation process allowed the FE model to be upgraded to a 3D FE full-scale model for testing the novel method used to place the separate sewer system.


Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4.
In a prospective screening program for type I diabetes mellitus, we identified a unique family in which several members (mother and three siblings) expressed an unusual set of HLA-DR alleles (DR2+, DR3/4-) and were in different phases of immunologically mediated islet beta cell dysfunction. Immunologic and/or clinical manifestations of type I diabetes were absent in all siblings not sharing both HLA haplotypes in common with the proband. This article illustrates: the clinical utility of prospective family screening for predictive markers, such as islet cell antibodies, progressive autoimmune beta cell destruction can occur in the absence of the "high-risk" alleles HLA-DR3 and DR4, and HLA identity with the proband, rather than specific HLA alleles, i.e., presence of DR3, DR4 and absence of DR2, is an essential factor.


Cartography of the multiple formal systems of molecular autopoiesis: from the biology of cognition and enaction to anticipation and active inference.
A rich literature has grown up over the years that bears with autopoiesis, which tends to assume that it is a model, a theory, a principle, a definition of life, a property, refers to self-organization or even to hastily conclude that it is hylomorphic, hylozoist, in need of reformulation or to be overcome, making its status even more unclear. Maturana insists that autopoiesis is none of these and rather it is the causal organization of living systems as natural systems (NS) such that when it stops, they die. He calls this molecular autopoiesis (MA), which comprises two domains of existence: that of the self-producing organization (self-fabrication) and that of the structural coupling/enaction (cognition). Like all-NS in the universe, MA is amenable to be defined in theoretical terms, i.e. encoded in mathematical models and/or formal systems (FS). Framing the multiple formal systems of autopoiesis (FSA) into the Rosen's modeling relation (a process of bringing into equivalence the causality of NS and the inferential rules of FS), allows a classification of FSA into analytical categories, most importantly Turing machine (algorithmic) vs non-Turing machine (non-algorithmic) based, and FSA with a purely reactive mathematical image as cybernetic systems, i.e. feedbacks based, or conversely, as anticipatory systems making active inferences. It is thus the intent of the present work to advance the precision with which different FS may be observed to comply (preserve correspondence) with MA in its worldly state as a NS. The modeling relation between MA and the range of FS proposed as potentially illuminating their processes forecloses the applicability of Turing-based algorithmic computational models. This outcome indicates that MA, as modelled through Varela's calculus of self-reference or more especially through Rosen's (M,R)-system, is essentially anticipatory without violating structural determinism nor causality whatsoever, hence enaction may involve it. This quality may capture a fundamentally different mode of being in living systems as opposed to mechanical-computational systems. Implications in different fields of biology from the origin of life to planetary biology as well as in cognitive science and artificial intelligence are of interest.


Dietary supplements and related products: a brief summary.
We were gratified by the interest expressed in publishing a large number of presentations from the NIDA organized Workshop on "Natureceuticals (Natural Products), Nutraceuticals, Herbal Botanicals, Psychoactives: Drug Discovery and Drug-Drug Interactions". The number of manuscripts received necessitated two volumes of proceedings. In this brief summary of the second volume, we present an introduction to the roles of organizations such as National Center for Complementary and Alternate Medicine and Office of Dietary Supplements, both at the National Institutes of Health, and the Food and Drug Administration. These agencies are involved in research and regulation of dietary supplements and related products. Next, a brief summary of each of the fifteen articles is provided. The first four articles are related to regulatory and standardization aspects: issues related to botanicals (Khan); USP and dietary supplements (Srinivasan); dietary supplement reference materials (Sander et al.); and proposed cGMPs and the scientific basis behind the proposed regulations by FDA (Melethil). The next three articles relate to the methodologies employed in research: LC/MS for the pharmacokinetic analysis polyphenols from dietary supplements (Barnes et al.); proteomic analysis of grape seed extract (Kim et al.); and a nematode model, C. elegans, in Alzheimer's and ginkgo biloba extract for mechanistic studies; another model, a hepatocyte tissue culture model for drug herbal interaction, is reviewed later and presented by Venkataramanan. The next four chapters are on specific dietary supplements: green tea and the polyphenolic catechins (Zaveri); curcumin (Maheswari et al.); tocotrienols (alpha-tocotrienol, Sen and Roy), gamma-tocotrienol (Sree Kumar et al.). This topic is followed by drug interaction studies: in vitro and in vivo assessment methodologies (Venkataramanan); flavonoid-drug interactions (Morris); MDR and CYP3A4-mediated drug-herb interaction (Pal and Mitra); and evidence-based examination of drug-herb interaction (Chavez and Chavez).


Achilles tendon material properties are greater in the jump leg of jumping athletes.
The Achilles tendon (AT) must adapt to meet changes in demands. This study explored AT adaptation by comparing properties within the jump and non-jump legs of jumping athletes. Non-jumping control athletes were included to control limb dominance effects. AT properties were assessed in the preferred (jump) and non-preferred (lead) jumping legs of male collegiate-level long and/or high jump (jumpers; n=10) and cross-country (controls; n=10) athletes. Cross-sectional area (CSA), elongation, and force during isometric contractions were used to estimate the morphological, mechanical and material properties of the ATs bilaterally. Jumpers exposed their ATs to more force and stress than controls (all p≤0.03). AT force and stress were also greater in the jump leg of both jumpers and controls than in the lead leg (all p<0.05). Jumpers had 17.8% greater AT stiffness and 24.4% greater Young's modulus in their jump leg compared to lead leg (all p<0.05). There were no jump versus lead leg differences in AT stiffness or Young's modulus within controls (all p>0.05). ATs chronically exposed to elevated mechanical loading were found to exhibit greater mechanical (stiffness) and material (Young's modulus) properties.