Relationship between the presence of unerupted mandibular third molars and fractures of the mandibular condyle.
Previous studies have shown that the presence of unerupted mandibular third molars predisposes the mandible to angle fractures. This study attempted to relate the presence of unerupted mandibular third molars with the incidence of condyle fractures. The authors compared the proportion of fractures in 439 patients who had unerupted third molars or no unerupted third molars. Fractures at the condylar region showed a significantly higher incidence in patients without unerupted third molars than in those patients with unerupted third molars. This study provides solid clinical evidence to suggest that the removal of unerupted mandibular third molars predisposes the mandible to condyle fractures.


Malmö Treatment Referral and Intervention Study (MATRIS)—effective referral from syringe exchange to treatment for heroin dependence: a pilot randomized controlled trial.
Syringe exchange has been suggested as a potential conduit to treatment for drug dependence, but this has never been documented in Europe. The primary aim was to compare the effectiveness of strength-based case management intervention (CMI) against referral only to facilitate treatment attendance in a syringe exchange programme. We also assessed the effectiveness of a syringe exchange programme for referral of heroin-dependent patients to evidence-based treatment with methadone or buprenorphine (buprenorphine-naloxone). Single-site, two-group randomized controlled trial. The syringe exchange programme in Malmö, Sweden and an out-patient clinic (research treatment facility) for maintenance treatment, situated outside the hospital area and run by Malmö Addiction Centre. Heroin-dependent patients willing to participate (n = 75) were referred to maintenance treatment and randomized to either a strength-based case management intervention aiming to facilitate referral (n = 36) or to referral-only (n = 39). The intervention group received an appointment for maintenance treatment and a CMI adjusted to individual patient needs. The CMI was semi-structured, assessing the patients' strengths and needs and identifying what practical help they might need to get to the appointment for maintenance treatment. The control group received an appointment for maintenance treatment. The primary outcome was treatment entry. Among patients who turned up for recruitment interview and randomization, the percentage of patients who started treatment was 95% in the intervention group and 94% in the control group. Treatment entry was unrelated to intervention status [unadjusted odds ratio (OR) = 0.92 (0.12–6.89), P = 1.00 and adjusted OR = 0.96 (0.12–7.83)]. A randomized controlled trial in a syringe exchange programme showed no evidence that a strength-based case management intervention improved attendance for treatment over referral alone. Attendance rates were high in both groups.


Primary leiomyosarcoma of the pulmonary artery: diagnostic and surgical implications.
Primary pulmonary trunk sarcoma is a rare and highly lethal disease. A case of multicentric pulmonary trunk leiomyosarcoma with right and left main pulmonary artery involvement, mimicking massive pulmonary embolism, is described. The importance of a timely diagnosis and of radical surgical excision is discussed.


Ethanol increases the sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA in short-term hepatocyte incubations.
The sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA was increased in mitochondria isolated from rat hepatocytes incubated with ethanol. This effect was mimicked by incubation of hepatocytes with acetaldehyde or by preincubation of isolated mitochondria with malonyl-CoA. Both ethanol and acetaldehyde increased the intracellular concentration of malonyl-CoA. Results suggest that the ethanol-induced elevation of intracellular malonyl-CoA levels may be responsible for the enhanced sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA.


An intensive medical care network led to successful living-donor liver transplantation in late-onset hepatic failure with disseminated Staphylococcus aureus infection.
Here, we describe a 42-year-old male patient with late-onset hepatic failure (LOHF) due to acute-onset autoimmune hepatitis. At first, his response to steroid therapy was good, but hepatitis relapsed during steroid pulse therapy. Deterioration of liver function caused LOHF, and LOHF has a poor prognosis, particularly when it is complicated by infection. Systemic infection by Staphylococcus aureus resulted in a skin rash and septic pulmonary embolism, and is an absolute contraindication for liver transplantation (LT). In this treatment network, hepatologists and a transplant surgeon cooperated to overcome severe infection and their efforts led to successful transplantation. On-line hemodiafiltration is an indispensable treatment option for acute liver failure. Infection control is crucial for LT and an intensive medical care network led to successful living-donor LT.


Characterizing the collagen stabilizing effect of crosslinked chitosan nanoparticles against collagenase degradation.
Antibacterial and chelating properties of chitosan has been widely studied for various dental applications. To characterize the interaction between chitosan-nanoparticles (CSnp) and collagen, and understand their stabilizing effect against collagenase degradation for dentin matrix stabilization. Phase-1: a single Type I collagen-fibril model was used to study the interaction with CSnp along with carbodiimides crosslinking treatment. Degradation of the crosslinked fibrils was studied with bacterial collagenase enzyme and monitored using Fourier Transform Infrared (FTIR) spectroscopy, turbidity measurement (400nm), ninhydrin assay and Atomic Force Microscopy (AFM). Interaction of CSnp with collagenase and Type I collagen, were evaluated using SDS-PAGE, and proteolytic cleavage potential of a synthetic peptide. Phase-2: degradation of dentin collagen crosslinked with/without CSnp was evaluated using FTIR, ninhydrin assay and Scanning Electron Microscopy (SEM). Glutaraldehyde crosslinking was used as a positive control. Both native collagen-fibrils and dentin collagen after crosslinking showed higher resistance to collagenase degradation, as observed in turbidity measurements and FTIR spectra. AFM images showed the interaction of CSnp with single collagen-fibril and crosslinked collagen resisted collagenase degradation up to 54h. The collagen and collagenase both formed complexes with CSnp resulting in thickening of bands and reduction in collagen degradation. CSnp treated collagenase showed significantly reduced cleavage of the fluorescent peptides. Dentin collagen was coated with CSnp following crosslinking with significant increase in resistance to collagenase degradation. Crosslinked CSnp on collagen stabilized and enhanced the resistance of dentin matrix against bacterial collagenase degradation due to non-specific interaction with both collagen and collagenase.


Genotypic, phenotypic, and pathogenic characterization of the soil isolated Acinetobacter courvalinii.
Most of the human gene homologs are found in Caenorhabditis elegans. As a wide variety of micro-organisms present in the environment is pathogens, so, C. elegans could be a useful model to track future infectious disease. With this knowledge, in this study, we isolated Acinetobacter courvalinii from the soil and characterized its pathogenicity for the first time. For the isolation, we used Glucose-Yeast extract-Ethanol-Calcium carbonate medium. To this aim, we evaluated the resistivity of bacteria against several stressful microenvironments. As we observed, A. courvalinii JP_A1001 shown highly tolerance against the acidic environment (pH 3-7), resistant against up to 0.2% of phenol content, and survived in the medium supplemented with 0.3% of bile salt. In addition, the bacteria were also resistant against several antibiotics showing the property of multidrug-resistant bacteria. Moreover, the isolated bacteria have shown the biofilm formation ability within 60 h. Further, we found that incubation of C. elegans with A. courvalinii JP_A1001 decreased the body movement and increased the free radical generation which remarkably influenced the life expectancy of C. elegans compared to E. coli OP50. Therefore, we concluded that A. courvalinii JP_A1001 found in the soil could be a future threat as a pathogen to public health.


Myelin basic protein: structural characterization of spherulites formation and preventive action of trehalose.
Myelin basic protein (MBP) is one of the main protein components of central nervous system that as shown in our work, under appropriate condition, forms spherulites. The structural and morphological features of these elements and the ability of trehalose to decrease or completely avoid their formation have been clarified with different but complementary techniques. The FTIR spectra provided compelling evidence for the presence of a small amount of elements organized in secondary structures such as helices and sheets. Polarized optical microscope observations show the presence of spherulites with an average size ranged from 41 to 61 μm, characterized by non-birifrangent core. The fluorescence data supply useful informations that are consistent with the presence of a molecular exclusion effect, following interaction of the disaccharide with protein that involves the environment around the single tryptophan residue. Moreover, study of protein conformational states by SDS-PAGE, let us to state that trehalose completely avoid autocatalytic cleavage properties of MBP up to 4 days of incubation at 37 °C and pH 7.4.


The role of Transcription Factor IIH complex in nucleotide excision repair.
DNA damage occurs throughout life from a variety of sources, and it is imperative to repair damage in a timely manner to maintain genome stability. Thus, DNA repair mechanisms are a fundamental part of life. Nucleotide excision repair (NER) plays an important role in the removal of bulky DNA adducts, such as cyclobutane pyrimidine dimers from ultraviolet light or DNA crosslinking damage from platinum-based chemotherapeutics, such as cisplatin. A main component for the NER pathway is transcription factor IIH (TFIIH), a multifunctional, 10-subunit protein complex with crucial roles in both transcription and NER. In transcription, TFIIH is a component of the pre-initiation complex and is important for promoter opening and the phosphorylation of RNA Polymerase II (RNA Pol II). During repair, TFIIH is important for DNA unwinding, recruitment of downstream repair factors, and verification of the bulky lesion. Several different disease states can arise from mutations within subunits of the TFIIH complex. Most strikingly are xeroderma pigmentosum (XP), XP combined with Cockayne syndrome (CS), and trichothiodystrophy (TTD). Here, we summarize the recruitment and functions of TFIIH in the two NER subpathways, global genomic (GG-NER) and transcription-coupled NER (TC-NER). We will also discuss how TFIIH's roles in the two subpathways lead to different genetic disorders.


Scleral buckling in 2 1/2- to 11-month-old premature infants with retinal detachment associated with acute retrolental fibroplasia.
The authors' experience over the past five years in the cryosurgical management of retinal detachment in ten eyes of eight premature infants with retrolental fibroplasia, whose ages at the time of detachment surgery ranged from 2 1/2 months to 11 months with an average of 5 1/2 months, is reported. Postoperative follow-up, ranging from eight to 61 months, has revealed that scleral buckling was successful in six eyes (60%). The ERG responses are slow to become established postoperatively, and VER testing is of questionable value in these cases.


The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis.
Histone chaperones affect chromatin structure and gene expression through interaction with histones and RNA polymerase II (PolII). Here, we report that the histone chaperone Spt6 counteracts H3K27me3, an epigenetic mark deposited by the Polycomb Repressive Complex 2 (PRC2) and associated with transcriptional repression. By regulating proper engagement and function of the H3K27 demethylase KDM6A (UTX), Spt6 effectively promotes H3K27 demethylation, muscle gene expression, and cell differentiation. ChIP-Seq experiments reveal an extensive genome-wide overlap of Spt6, PolII, and KDM6A at transcribed regions that are devoid of H3K27me3. Mammalian cells and zebrafish embryos with reduced Spt6 display increased H3K27me3 and diminished expression of the master regulator MyoD, resulting in myogenic differentiation defects. As a confirmation for an antagonistic relationship between Spt6 and H3K27me3, inhibition of PRC2 permits MyoD re-expression in myogenic cells with reduced Spt6. Our data indicate that, through cooperation with PolII and KDM6A, Spt6 orchestrates removal of H3K27me3, thus controlling developmental gene expression and cell differentiation.


Adherence to early pulmonary rehabilitation after COPD exacerbation and risk of hospital readmission: a secondary analysis of the COPD-EXA-REHAB study.
Early pulmonary rehabilitation after exacerbation of chronic obstructive pulmonary disease (COPD) has previously been shown to reduce the risk of hospital admission and improve physical performance and quality of life. However, the impact of attendance at early rehabilitation programmes has not been established. To evaluate the impact of increasing attendance to pulmonary rehabilitation on the risk of hospital admission, physical performance and quality of life in patients attending an early rehabilitation programme after an exacerbation of COPD. This study was a secondary exploratory analysis of the randomised controlled trial COPD-EXA-REHAB study, involving patients hospitalised with an exacerbation of COPD. The COPD-EXA-REHAB study compared early pulmonary rehabilitation, starting within 2 weeks after an exacerbation, with standard treatment, that is, the same programme starting 2 months later. The present analysis included only the 70 patients allocated to early pulmonary rehabilitation. At 1-year follow-up, we found an association between the number of sessions attended and a reduction in hospital admissions (incidence rate ratio 0.93 (95% CI 0.88 to 0.99), p=0.02), corresponding to a 7% reduction for each session attended. Similarly, at 2-month follow-up, physical performance was positively associated with sessions attended: the mean Incremental Shuttle Walk Test result improved by 8 m with each session (95% CI 2.54 to 13.56, p=0.005) and the Endurance Shuttle Walk Test result by 44 s (95% CI 18.41 to 68.95, p=0.001). Quality of life, assessed using the COPD Assessment Test, was not significantly associated with the number of attended sessions, with the average score increasing by 0.15 points with each session (95% CI -0.35 to 0.65, p=0.55). Increased attendance at early pulmonary rehabilitation after exacerbation of COPD was associated with reduced risk of hospital admission and improved physical performance.


α-Arrestins and Their Functions: From Yeast to Human Health.
α-Arrestins, also called arrestin-related trafficking adaptors (ARTs), constitute a large family of proteins conserved from yeast to humans. Despite their evolutionary precedence over their extensively studied relatives of the β-arrestin family, α-arrestins have been discovered relatively recently, and thus their properties are mostly unexplored. The predominant function of α-arrestins is the selective identification of membrane proteins for ubiquitination and degradation, which is an important element in maintaining membrane protein homeostasis as well as global cellular metabolisms. Among members of the arrestin clan, only α-arrestins possess PY motifs that allow canonical binding to WW domains of Rsp5/NEDD4 ubiquitin ligases and the subsequent ubiquitination of membrane proteins leading to their vacuolar/lysosomal degradation. The molecular mechanisms of the selective substrate's targeting, function, and regulation of α-arrestins in response to different stimuli remain incompletely understood. Several functions of α-arrestins in animal models have been recently characterized, including redox homeostasis regulation, innate immune response regulation, and tumor suppression. However, the molecular mechanisms of α-arrestin regulation and substrate interactions are mainly based on observations from the yeast Saccharomyces cerevisiae model. Nonetheless, α-arrestins have been implicated in health disorders such as diabetes, cardiovascular diseases, neurodegenerative disorders, and tumor progression, placing them in the group of potential therapeutic targets.


Steam vaporizers: A danger for paediatric burns.
Steam vaporizers are used to humidify air in dry environments. They are marketed to moisten children's airway secretions and thus to help relieve symptoms associated with upper respiratory tract infections. Unfortunately the steam emitted from the unit can also pose a significant risk of burns to children. Our study aimed to ascertain patterns of injury and treatment outcomes from steam burns resulting from these devices. Potential preventative measures are discussed. Children who had sustained vaporizer scald burns were identified at the outpatient burns clinic over a 10-month period (November 2014-August 2015). Medical records were reviewed retrospectively and data collected on pattern of injury, management and outcomes. Ten children were treated for vaporizer steam burns over the study period. The mean age was 1.6 years and 8 (80%) patients were male. Operative intervention was undergone in 5 (50%) cases; four acutely and one as a secondary reconstructive procedure. Hand burns accounted for 8 (80%) of cases. Steam vaporizers can cause significant burns in the paediatric population. Toddlers were most at risk, frequently sustaining hand burns that underwent skin grafting. Greater public awareness of the danger is indicated and measures to prevent such injuries should be addressed by appropriate authorities.


DNA damage induced by hypochlorite and hypobromite with reference to inflammation-associated carcinogenesis.
Hypohalites (OCl-, OBr-) are formed at inflammation sites as antimicrobial agents. OCl- is also used for the disinfection of water supplies and the association of drinking chlorinated water with cancer risk is pointed out. In this study, OCl- itself induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, while OBr- damaged DNA only when glutathione (GSH) was added. OCl- caused oxidative DNA damage more efficiently than OBr-/GSH. In experiment with 32P-labeled DNA fragments, OCl- strongly caused piperidine-labile sites at guanine residues than piperidine-inert 8-oxodG, whereas OBr-/GSH caused no piperidine-labile sites. Endogenous OCl- may play a role in genotoxicity close to the site of inflammation.


A tabletability change classification system in supporting the tablet formulation design via the roll compaction and dry granulation process.
In this paper, the material library approach was used to uncover the pattern of tabletability change and related risk for tablet formulation design under the roll compaction and dry granulation (RCDG) process. 31 materials were fully characterized using 18 physical parameters and 9 compression behavior classification system (CBCS) parameters. Then, each material was dry granulated and sieved into small granules (125-250 μm) and large granules (630-850 μm), respectively. The compression behavior of granules was characterized by the CBCS descriptors, and were compared with that of ungranulated powders. The relative change of tabletability (CoTr) index was used to establish the tabletability change classification system (TCCS), and all materials were classified into three types, i.e. loss of tabletability (LoT, Type I), unchanged tabletability (Type II) and increase of tabletability (Type III). Results showed that approximately 65% of materials presented LoT, and as the granules size increased, 84% of the materials exhibited LoT. A risk decision tree was innovatively proposed by joint application of the CBCS tabletability categories and the TCCS tabletability change types. It was found that the LoT posed little risk to the tensile strength of the final tablet, when Category 1 or 2A materials, or Category 2B materials with Type II or Type III change of tabletability were used. Formulation risk happened to Category 2C or 3 materials, or Category 2B materials with Type I change of tabletability, particularly when high proportions of these materials were involved in tablet formulation. In addition, the risk assessment results were verified in the material property design space developed from a latent variable model in prediction of tablet tensile strength. Overall, results suggested that a combinational use of CBCS and TCCS could aid the decision making in selecting materials for tablet formulation design via RCDG.


Collagenase and elastase in the serum of adjuvant arthritic rats.
Collagenase and elastase activities in the serum of adjuvant arthritic rats declined with time as the disease progressed and did not parallel increases in alpha 1-macroglobulin or alpha 2-acute phase globulin levels. The fall in collagenase and elastase activities was accompanied by a decline in serum alpha 1-proteinase inhibitor levels. It was concluded that the fall in collagenase and elastase activities in serum was due to inactivation by serum anti-proteases.


A rare presentation of tricuspid valve thrombus in a normal heart.
A young woman presented with a presumptive diagnosis of tricuspid valve tumor in a structurally normal heart. She was recently started on oral progesterone for menorrhagia related to uterine fibroids. She underwent an excision of the mass attached to the tricuspid valve, which was found to be an organized thrombus. We suggest a clinical approach to this problem.


Atrial fibrillation in heart failure: prognostic significance and management.
AF in Heart Failure. Atrial fibrillation and congestive heart failure are commonly occurring cardiac disorders that often exist concomitantly. The prognostic significance of the presence or absence of atrial fibrillation, as an independent risk factor, in patients with heart failure remains controversial. Antiarrhythmic drugs with good hemodynamic profiles and neutral effects on survival are preferred treatments for converting atrial fibrillation and maintaining sinus rhythm. Other standard therapies for congestive heart failure, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers also have a role in the treatment of these coexisting disease states. The article presents an overview of atrial fibrillation in patients with heart failure and reviews the prevalence, prognostic significance, and efficacy of various antiarrhythmic agents for the conversion and maintenance of sinus rhythm.


Successful outcome of ergocryptine-induced pregnancies in twenty-one women with prolactin-secreting pituitary adenomas.
The natural history of prolactin-secreting adenomas is not known. For this reason, optimal therapy for women harboring these adenomas who desire to conceive is also unknown. Argument can be found to favor surgical excision, radiation therapy, prolactin-suppressing chemotherapy, and clinical observation. In a large series of women with prolactin-secreting pituitary adenomas, 21 have conceived and delivered healthy infants, all of whom had ergocryptine-induced prolactin suppression as the sole form of therapy. Endocrinologic, neurologic, biochemical, and radiologic assessment failed to demonstrate any obvious growth of the pituitary adenoma, except for slight enlargement of the sella turcica in one patient who delivered twins. The failure to demonstrate any worsening of the clinical state may reflect the fact that no large tumors were included in this series, only small but definite microadenomas found on sellar tomography. All of the various modalities of therapy must be considered with each patient, but this series suggests that ergocryptine treatment with careful clinical follow-up is relatively safe in patients with small pituitary tumors.


Intercellular water exchanges trigger soliton-like waves in multicellular systems.
Oscillations and waves are ubiquitous in living cellular systems. Generations of these spatiotemporal patterns are generally attributed to some mechanochemical feedbacks. Here, we treat cells as open systems, i.e., water and ions can pass through the cell membrane passively or actively, and reveal a new origin of wave generation. We show that osmotic shocks above a shock threshold will trigger self-sustained cell oscillations and result in long-range waves propagating without decrement, a phenomenon that is analogous to the excitable medium. The traveling wave propagates along the intercellular osmotic pressure gradient, and its wave speed scales with the magnitude of intercellular water flows. Furthermore, we also find that the traveling wave exhibits several hallmarks of solitary waves. Together, our findings predict a new mechanism of wave generation in living multicellular systems. The ubiquity of intercellular water exchanges implies that this mechanism may be relevant to a broad class of systems.


Computed tomographic and angiographic demonstration of gastroduodenal artery pseudoaneurysm in a pancreatic pseudocyst.
The complementary use of computed tomography and angiography in two patients with bleeding gastroduodenal artery pseudoaneurysm associated with pancreatic pseudocyst is presented.


Reaction chain modeling of denitrification reactions during a push-pull test.
Field quantitative estimation of reaction kinetics is required to enhance our understanding of biogeochemical reactions in aquifers. We extended the analytical solution developed by Haggerty et al. (1998) to model an entire 1st order reaction chain and estimate the kinetic parameters for each reaction step of the denitrification process. We then assessed the ability of this reaction chain to model biogeochemical reactions by comparing it with experimental results from a push-pull test in a fractured crystalline aquifer (Ploemeur, French Brittany). Nitrates were used as the reactive tracer, since denitrification involves the sequential reduction of nitrates to nitrogen gas through a chain reaction (NO3(-)→NO2(-)→NO→N2O→N2) under anaerobic conditions. The kinetics of nitrate consumption and by-product formation (NO2(-), N2O) during autotrophic denitrification were quantified by using a reactive tracer (NO3(-)) and a non-reactive tracer (Br(-)). The formation of reaction by-products (NO2(-), N2O, N2) has not been previously considered using a reaction chain approach. Comparison of Br(-) and NO3(-) breakthrough curves showed that 10% of the injected NO3(-) molar mass was transformed during the 12 h experiment (2% into NO2(-), 1% into N2O and the rest into N2 and NO). Similar results, but with slower kinetics, were obtained from laboratory experiments in reactors. The good agreement between the model and the field data shows that the complete denitrification process can be efficiently modeled as a sequence of first order reactions. The 1st order kinetics coefficients obtained through modeling were as follows: k1=0.023 h(-1), k2=0.59 h(-1), k3=16 h(-1), and k4=5.5 h(-1). A next step will be to assess the variability of field reactivity using the methodology developed for modeling push-pull tracer tests.


Using Tongue Depressors as a Technique to Aid Cord Localization During Collagenase Injection For Dupuytren Disease.
Collagenase injections are used as a minimally invasive treatment for Dupuytren contracture of the palm and fingers, with good published success. Most complications are related to injection-site swelling, pain, and ecchymosis. However, the risk of flexor tendon and digital nerve injury can occur when injecting cords that cause proximal interphalangeal joint contractures. In addition, poor localization and incorrect injection of the solution into cords may result in an incomplete correction. We describe a technique to improve visualization and isolation of Dupuytren cords using a tongue depressor.


Magnetic resonance imaging evaluation of myocardial perfusion and viability in congenital and acquired pediatric heart disease.
This study examined the feasibility and potential clinical utility of magnetic resonance imaging (MRI) evaluation of myocardial perfusion (first-pass contrast enhancement) and viability (myocardial delayed enhancement) in 30 patients with congenital and acquired pediatric heart disease. Good agreement was found between MRI evaluation of myocardial perfusion and viability and analysis of segmental wall motion as well as coronary angiography (n = 10) and single photon emission computed tomography (n = 6).


Correction: Prognostic Value of Lactate and Central Venous Oxygen Saturation after Early Resuscitation in Sepsis Patients.
[This corrects the article DOI: 10.1371/journal.pone.0153305.].


Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling.
Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10-8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10-7, OR = 0.707; TYK2: pburden = 6.17 × 10-4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.


Effect of surface treatments on bond durability of zirconia-reinforced lithium silicate ceramics: An in vitro study.
The influence of surface treatments on the bond durability of zirconia-reinforced lithium silicate ceramics (ZLS) is unclear. The purpose of this in vitro study was to evaluate the effect of different surface treatments on the bond durability of zirconia-reinforced lithium silicate ceramic after long-term thermocycling. Five computer-aided design and computer-aided manufacturing (CAD-CAM) dental ceramic blocks, including 2 zirconia-reinforced lithium silicate ceramic materials (Vita Suprinity/VS and Cetra Duo/CD), 2 commonly used glass-ceramic materials (e.max CAD/EM and Empress CAD/EP), and 1 yttria-stabilized zirconia (Y-TZP, Zenostar/ZS) were tested. Rectangular ceramic blocks were divided into 6 groups and subjected to different surface treatments: group Control (no treatment), group Uni (universal adhesive), group HF (hydrofluoric acid), group CoJet, group HF+Uni (HF and universal adhesive), and group CoJet+Uni (CoJet and universal adhesive). Subsequently, the specimens were cemented to composite resin blocks, sectioned into rectangular microbars of approximately 2×2×12 mm in size, and assigned to 2 groups with and without 100 000 thermal cycles (n=15 per group). The microtensile bond strength (μTBS) test was performed using a universal testing machine. Failure modes were observed with a stereomicroscope and scanning electron microscope (SEM). Three-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons was performed to evaluate the effects of surface treatments, ceramics, and thermocycling on μTBS (α=.05). The μTBS (MPa) was affected by the surface treatment (P<.001), ceramic type (P<.001), and thermocycling (P<.001). The bond strength after HF etching and universal adhesive treatment was highest in glass-ceramic groups (VS, CD, EP, and EM), while CoJet combined with universal adhesive indicated the highest bond strength in the ZS group before (34.3 ±4.2 MPa) and after thermocycling (16.0 ±2.9 MPa). No significant differences for μTBS were found among ZLS (VS and CD), lithium disilicate ceramic group (EM), and leucite-based ceramic group (EP, P>.05), but they demonstrated better bond strength than zirconia (ZS group, P<.01) after thermocycling. Adhesive failure increased in all groups, and the cohesive failure of glass-ceramic decreased after thermocycling. ZLS showed similar μTBS with traditional glass-ceramics, including lithium disilicate ceramic and leucite-based ceramic, and more durable bonding than zirconia to resist thermocycling. Moreover, the combination of HF and universal adhesive treatments was the most effective method for ZLS among all the different surface treatments in this study.


Infant cynomolgus monkeys exposed to denosumab in utero exhibit an osteoclast-poor osteopetrotic-like skeletal phenotype at birth and in the early postnatal period.
RANKL is a key regulator of bone resorption and osteoclastogenesis. Denosumab is a fully human IgG2 monoclonal antibody that inhibits bone resorption by binding and inhibiting the activity of RANKL. To determine the effects of denosumab on pre- and postnatal skeletal growth and development, subcutaneous injections of 0 (control) or 50 mg/kg/month denosumab were given to pregnant cynomolgus monkeys from approximately gestation day (GD) 20 until parturition (up to 6 doses). For up to 6 months postpartum (birth day [BD] 180/181), evaluation of the infants included skeletal radiographs, bone biomarkers, and oral examinations for assessment of tooth eruption. Infant bones were collected at necropsy for densitometry, biomechanical testing, and histopathologic evaluation from control and denosumab-exposed infants on BD1 (or within 2 weeks of birth) and BD181, and from infants that died or were euthanized moribund from BD5 to BD69. In all denosumab-exposed infants, biomarkers of bone resorption and formation were markedly decreased at BD1 and BD14 and slightly greater at BD91 vs. control, then similar to control values by BD181. Spontaneous long bone fractures were detected clinically or radiographically in 4 denosumab-exposed infants at BD28 and BD60, with evidence of radiographic healing at ≥BD60. In BD1 infants exposed to denosumab in utero, radiographic evaluations of the skeleton revealed decreased long bone length; a generalized increased radio-opacity of the axial and appendicular skeleton and bones at the base of the skull with decreased or absent marrow cavities, widened growth plates, flared/club-shaped metaphysis, altered jaw/skull shape, and reduced jaw length; and delayed development of secondary ossification centers. Densitometric evaluations in these infants demonstrated a marked increase in bone mineral density at trabecular sites, but cortical bone mineral density was decreased. Histologically, long bone cortices were attenuated and there was an absence of osteoclasts. Bones with active endochondral ossification consisted largely of a dense network of retained primary spongiosa with reduced marrow space consistent with an osteopetrotic phenotype. A minimal increase in growth plate thickness largely due to the expansion of the hypertrophic zone was present. Retained woven bone was observed in bones formed by intramembranous ossification, consistent with absence of bone remodeling. These changes in bone tissue composition and geometry were reflected in reduced biomechanical strength and material properties of bones from denosumab-exposed infants. Material property changes were characterized by increased tissue brittleness reflected in reductions in calculated material toughness at the femur diaphysis and lack of correlation between energy and bone mass at the vertebra; these changes were likely the basis for the increased skeletal fragility (fractures). Although tooth eruption was not impaired in denosumab-exposed infants, the reduced growth and increased bone density of the mandible resulted in dental abnormalities consisting of tooth malalignment and dental dysplasia. Radiographic changes at BD1 persisted at BD28, with evidence of resumption of bone resorption and remodeling observed in most infants at BD60 and/or BD90. In 2 infants euthanized on BD60 and BD69, there was histologic and radiographic evidence of subphyseal/metaphyseal bone resorption accompanied by multiple foci of ossification in growth plates that were markedly increased in thickness. In infants necropsied at BD181, where systemic exposure to denosumab had been below limits of quantitation for approximately 3months, there was largely full recovery from all bone-related changes observed earlier postpartum, including tissue brittleness. Persistent changes included dental dysplasia, decreased bone length, reduced cortical thickness, and decreased peak load and ultimate strength at the femur diaphysis. In conclusion, the skeletal and secondary dental effects observed in infant monkeys exposed in utero to denosumab are consistent with the anticipated pharmacological activity of denosumab as a monoclonal antibody against RANKL and inhibitor of osteoclastogenesis. The resulting inhibition of resorption impaired both bone modeling and remodeling during skeletal development and growth. The skeletal phenotype of these infant monkeys resembles human infants with osteoclast-poor osteopetrosis due to inactivating mutations of RANK or RANKL.


Are Bombax buonopozense and Bombax malabaricum possible nutraceuticals for age management?
Human longevity and healthy ageing though controversial require extended investigations. Some studies have shown that ageing can be managed by reducing the amounts of free radicals the cells are exposed to. Oxidative stress has been shown to be combated by antioxidants and plant sources are known to generate antioxidants that are efficacious and low in toxicity. This review aims to enlighten on antioxidants from Bombax buonopozense and Bombax malabaricum for prevention, reversal or delay of age-related diseases. Furthermore, it advocates for more studies to enable the shift from research to commercial applications of the antioxidants as nutraceuticals in age management.


Equity and trends in general practitioners' allocation in China: based on ten years of data from 2012 to 2021.
General practitioners (GP) are the gatekeepers of residents' health, 2021 is the 10th year of the establishment of the GP system in China. This study aims to assess the equity and trends of GP allocation in China from 2012 to 2021, summarize the efforts and progress of GPs in China during the decade, predict the development trend of GPs in mainland China in the next 5 years to provide a reference for regional health planning and rational allocation of GPs in China. Data from 2012 to 2021 on GPs in 22 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in mainland China (excluding Hong Kong, Macao, and Taiwan) are collected by us. Gini coefficient, Lorenz curve and health resource agglomeration degree (HRAD) were used to analyze the equity of the allocation of GPs in China from different dimensions, a Grey prediction model was used to forecast the number of GPs in 2022-2026. The number of GPs in mainland China increased from 109 794 to 434 868 from 2012 to 2021, with 3.08 GPs per 10 000 people in 2021. The Gini coefficient of GPs allocation by population in China decreased from 0.312 to 0.147 from 2012 to 2021, while the Gini coefficient of geographic dimension remained between 0.700 and 0.750. Compared with the degree of curvature of the Lorenz curve in the geographic dimension, the degree of curvature of the population and economic dimension were smaller. In 2021, the HRAD in the Eastern region was 4.618, the Central region was 1.493, with different degrees of imbalance among regions, the HRAD/PAD (population agglomeration degree) in the Eastern, Central and Western regions were 1.196, 0.880 and 0.821, respectively. GPs in the Eastern region is still concentrated, while the Central and Western regions were at a similar level, GPs were more scarce. The GM (1,1) model predicts that the number of GPs in mainland China will reach about 720 000 in 2026, the number of GPs per 10 000 people will reach 4.9. After a decade of development, the number of GPs in China has increased significantly. It has reached the goal of the GP system when it was first established. However, the equity of the geographical dimension, both in terms of Gini coefficient and HRAD, has great differences between different regions. The average Gini coefficient at the geographic dimension is 0.723. The average HRAD index was 4.969 in the East and 0.293 in the West. The Western region has the problem of insufficient GP allocation in both population and geographical dimension. In the future, the number of GPs in China will continue to grow rapidly with the support of policies. The "2030" goal, proposed in 2018, is expected to be achieved by 2026. Due to certain factors (such as COVID-19), the actual situation may be different from the predicted results.


Oxidative biomarkers in leaf tissue of barley seedlings in response to aluminum stress.
Cellular responses to Al-stress in Hordeum vulgare seedling bioassay were evaluated with an objective to identify the possible biomarkers in leaf tissue that would be best suited to biomonitor aluminum (Al) in the environment. Germinating seeds were treated with different concentrations of AlCl(3) at pH 4.5 for 12h. Al-uptake and accumulation in root and leaf, generation of reactive oxygen species (ROS: O(2)(-), H(2)O(2) and ()OH), cell death, activity of antioxidant enzymes: catalase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, lipid peroxidation, protein oxidation, DNase activity and DNA damage were measured in leaf tissue of the seedlings on day 6 after treatment. The above parameters assessed in leaf tissue that followed a dose-response exhibited significant correlation with concentration of Al(3+) in experimental solution as well as in root tissue. The findings underscored the sensitivity as well as potential of Hordeum vulgare seedling bioassay for biomonitoring of Al in the ambient environment.


Placental accumulation of 57Co-vitamin B12 in mice studied by light- and electron-microscopic autoradiography.
Pregnant C57BL mice on day 18 of gestation were injected with 0.114 micrograms cyanocobalamin-57Co and killed either 40 min or 3 h later. Radioactivity measurements showed that the placenta was the organ with the highest concentration. Light- and electron-microscopic autoradiography of the placental labyrinth showed heavy accumulation of radioactivity in the second (middle) trophoblastic cell layer in the barriers between the maternal and fetal circulations. Silver grains were mainly associated with the folded plasma membrane deep in the cytoplasm or with vesicles, indicating a cellular uptake by pinocytosis. The cytosolic accumulations present may be derived from cellular metabolic sites, such as that of protein synthesis.


From Lockdown to Slow Release: Pediatric Dental Services during COVID-19 Pandemic-Emergency Preparedness and Impact on Future.
The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has led to global pandemic raising significant challenges to the healthcare professionals due to its high transmission rate via droplet spread or direct contact. Pediatric dentists play an important role in the healthcare system by managing dental emergencies in children while taking special measures to practice universal infection control in this COVID-19 pandemic. However, data are limited pertaining to the prevalence, etiology, and treatment provided to children at pediatric dental emergency services during the COVID-19 lockdown period. To assess the effect of the COVID-19 pandemic lockdown period on Pediatric Dental Emergency Services. A retrospective study was conducted using data of patients aged 0-14 years who visited the Pediatric Dental Emergency Services, during the COVID-19 lockdown period from March 23, 2020, to August 31, 2020. Information regarding age, gender, time of presentation, chief complaint, and treatment were collected and analyzed. This study revealed that dental emergencies in the pediatric dental services were predominantly related to dental pain (54.49%) followed by an abscess (12.35%), traumatic dental injuries (8.42%), and swelling (8.42%). A 5-year-old was the most prevalent age-group who reported dental emergencies. Dental pain was the most common chief complaint of patients reporting during the COVID-19 pandemic. However, the recent state of affairs obligates the need to strike a balance between the safety of the healthcare professionals and providing optimum dental care to the patients requiring emergency intervention. While dental emergencies are unforeseeable, increasing community awareness about proper at-home care routines and utilizing regular dental preventive measures can potentially reduce the number of emergency visits. Goswami M, Gogia M, Bhardwaj S. From Lockdown to Slow Release: Pediatric Dental Services during COVID-19 Pandemic-Emergency Preparedness and Impact on Future. Int J Clin Pediatr Dent 2021;14(3):398-402.


Trend of gastric cancer incidence and death rate in adolescents and young adults: A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database.
Less attentions are paid into the adolescents and young adults (AYAs) diagnosed with gastric cancer (GC). Our study aims to explore incidence rate trend, death rate trend, and prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in AYAs with GC. A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database was performed. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) with 95% confidence interval (CI) for incidence and death rate trends. Prognostic factors for OS and CSS were investigated using Cox proportional hazard model and gray test, respectively, with results shown as hazard ratio (HR) with 95% CI. Although no statistical significance, incidence rate trend showed a tendency to an increase in AYAs (AAPC = 0.2, 95% CI: -0.2-0.6). All-cause death rate trends were declined both in AYAs and middle-aged and elderly people (MAEP), with AAPC value of -0.6 (95% CI: -0.8 to -0.5) and -0.5 (95% CI: -0.6 to -0.4), respectively. AYAs had a lower risk of all-cause death (HR: 0.87, 95% CI: 0.84-0.90) but a higher risk of GC-specific death (HR: 1.11, 95% CI: 1.07-1.15) than MAEP. Chemotherapy (HR: 1.27, 95% CI: 1.16-1.40) and intraoperative radiation (HR: 2.89, 95% CI: 1.13-7.37) were, respectively, identified as risk factors for worse OS and CSS in AYAs. AYAs had a higher risk of GC-specific death, indicating more attention should be paid into AYAs with GC.


Mechanochemical Preparations of Anion Coordinated Architectures Based on 3-Iodoethynylpyridine and 3-Iodoethynylbenzoic Acid.
The halogen bond has previously been explored as a versatile tool in crystal engineering and anion coordination chemistry, with mechanochemical synthetic techniques having been shown to provide convenient routes towards cocrystals. In an effort to expand our knowledge on the role of halogen bonding in anion coordination, here we explore a series of cocrystals formed between 3-iodoethynylpyridine and 3-iodoethynylbenzoic acid with halide salts. In total, we report the single-crystal X-ray structures of six new cocrystals prepared by mechanochemical ball milling, with all structures exhibiting C≡C-I⋅⋅⋅X- (X=Cl, Br) halogen bonds. Whereas cocrystals featuring a pyridine group favoured the formation of discrete entities, cocrystals featuring a benzoic acid group yielded an alternation of halogen and hydrogen bonds. The compounds studied herein were further characterized by 13C and 31P solid-state nuclear magnetic resonance, with the chemical shifts offering a clear and convenient method of identifying the occurrence of halogen bonding, using the crude product obtained directly from the mechanochemical ball milling. Whereas the 31P chemical shifts were quickly able to identify the occurrence of cocrystallization, 13C solid-state NMR was diagnostic of both the occurrence of halogen bonding and of hydrogen bonding.


Clone and expression of mutant M-CSF and its receptor from human leukemic cell line J6-1.
Macrophage colony-stimulating factor (M-CSF) plays important roles in hematopoietic and immunologic systems. Some isoforms or mutations have been demonstrated including membrane-bound and cellular M-CSF, which associated with some leukemia, lymphoma and other solid tumors. We previously reported that the M-CSF-like membrane-associated factor (MAF-J6-1) and its receptor was found from human leukemic cell line J6-1. In this report, the cDNA of MAF-J6-1 and its receptor were cloned. The cDNA sequence of MAF-J6-1 shows a 768bp open reading frame (ORF) with 99.2% homology to m-M-CSF, but six site mutations, including two synonymous mutations and four missense mutations. The cDNA of MAF-J6-1-R has a 2916bp ORF shared 99.6% homology with M-CSF-R, but 13 site mutations, including six synonymous mutations and seven missense mutations. At the same time, a 1662bp mutant s-M-CSF cDNA, which has 10 site mutations including three synonymous mutations and seven missense mutations, was cloned from J6-1 cells. The cDNAs of MAF-J6-1 and MAF-J6-1-R were inserted into a mammalian expression plasmid pTARGET and were expressed in COS-7 cells that demonstrated by their specific MAb. COS-7 cells transfected with MAF-J6-1-R show obvious protein tyrosine kinase (PTK) activity. Our present work shows that MAF-J6-1 and its receptor are mutations of M-CSF and its receptor.


Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with DNA polymerase α-primase.
The molecular mechanisms that drive the infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the causative agent of coronavirus disease 2019 (COVID-19)-are under intense current scrutiny to understand how the virus operates and to uncover ways in which the disease can be prevented or alleviated. Recent proteomic screens of the interactions between viral and host proteins have identified the human proteins targeted by SARS-CoV-2. The DNA polymerase α (Pol α)-primase complex or primosome-responsible for initiating DNA synthesis during genomic duplication-was identified as a target of nonstructural protein 1 (nsp1), a major virulence factor in the SARS-CoV-2 infection. Here, we validate the published reports of the interaction of nsp1 with the primosome by demonstrating direct binding with purified recombinant components and providing a biochemical characterization of their interaction. Furthermore, we provide a structural basis for the interaction by elucidating the cryo-electron microscopy structure of nsp1 bound to the primosome. Our findings provide biochemical evidence for the reported targeting of Pol α by the virulence factor nsp1 and suggest that SARS-CoV-2 interferes with Pol α's putative role in the immune response during the viral infection.


Sequence-dependent cleavage site selection by RNase Z from the cyanobacterium Synechocystis sp. PCC 6803.
Biosynthesis of transfer RNA requires processing from longer precursors at the 5'- and 3'-ends. In eukaryotes, in archaea, and in those bacteria where the 3'-terminal CCA sequence is not encoded, 3' processing is carried out by the endonuclease RNase Z, which cleaves after the discriminator nucleotide to generate a mature 3'-end ready for the addition of the CCA sequence. We have identified and cloned the gene coding for RNase Z in the cyanobacterium Synechocystis sp. PCC 6803. The gene has been expressed in Escherichia coli, and the recombinant protein was purified. The enzymatic activity of RNase Z from Synechocystis has been studied in vitro with a variety of substrates. The presence of C or CC after the discriminator nucleotide modifies the cleavage site of RNase Z so that it is displaced by one and two nucleotides to the 3'-side, respectively. The presence of the complete 3'-terminal CCA sequence in the precursor of the tRNA completely inhibits RNase Z activity. The inactive CCA-containing precursor binds to Synechocystis RNase Z with similar affinity than the mature tRNA. The properties of the enzyme described here could be related with the mechanism by which CCA is added in this organism, with the participation of two separate nucleotidyl transferases, one specific for the addition of C and another for the addition of A. This work is the first characterization of RNase Z from a cyanobacterium, and the first from an organism with two separate nucleotidyl transferases.


The pathology of Cysticercus tenuicollis infection in goats.
The pathology of Cysticercus tenuicollis in goats was studied on Days 7, 15, 30 and 60 post-infection. The characteristic gross lesions on the 15th day of infection included accumulation of a large quantity of serofibrinous fluid in the peritoneal and thoracic cavities and a large number of small-sized cysts floating in the fluid of the peritoneal cavity. Large circular brown to red areas with alternate areas of haemorrhages also appeared on the liver surface and in the parenchyma due to migrating C. tenuicollis. The microscopic lesions in the liver included cyst-like channels with a mass of fibrin and erythrocytes. Hepatic cells were mostly degenerated with focal areas of parenchymal destruction. Sinusoids were dilated and the bile ducts revealed degenerative changes. Lungs of animals killed on Day 15, revealed focal areas of emphysema and haemorrhages with lodged larvae of C. tenuicollis. Pleura appeared oedematous. Alveoli showed the presence of serous exudate.


Ca2+ releasing effect of perezone on adrenal cortex mitochondria.
Ca2+ energy-coupled transport was analized in adrenal cortex mitochondria using the sesquiterpenic drug perezone. Perezone promotes Ca2+ efflux by inducing collapse of the membrane potential and oxidation of pyridine nucleotides. The effect of perezone on mitochondrial Ca2+ release follows a dose-response relationship and is dependent of the reduction of the drug. These data suggest that perezone may produce a cytotoxic effect through an impairment in Ca2+ homeostasis.


New antimalarial targets: the example of glucose transport.
In order for a novel drug target to attract attention it must be shown to be essential for parasite survival. In addition, it is desirable that a novel target provides some molecular and functional basis for the development of selective inhibitors. In this respect the pathway for transport of glucose to the parasite in Plasmodium falciparum has attracted increasing interest as a target for antimalarial chemotherapy. In particular, the plasmodial hexose transporter, PfHT, known to mediate transport of this essential substrate to the parasite has been a promising candidate for development of inhibitors. The article summarises the steps involved in development of this parasite protein as a drug target. Details of PfHT identification, functional characterisation and its validation as a drug target by using a selective inhibitor are discussed. The potential use of a robust system to screen libraries of compounds in a high-throughput format, in pursuit of an inhibitor of PfHT is also described. In conclusion PfHT represents one example of a rational approach in the drug discovery process to structure-base design of drugs.


Clostridium difficile and One Health.
For over four decades, Clostridium difficile has been a significant enteric pathogen of humans. It is associated with the use of antimicrobials that generally disrupt the microbiota of the gastrointestinal tract. Previously, it was thought that C. difficile was primarily a hospital-acquired infection; however, with the emergence of community-associated cases, and whole-genome sequencing suggesting the majority of the hospital C. difficile infection (CDI) cases are genetically distinct from one another, there is compelling evidence that sources/reservoirs of C. difficile outside hospitals play a significant role in the transmission of CDI. To review the 'One Health' aspects of CDI, focusing on how community sources/reservoirs might be acting as a conduit in the transfer of C. difficile between animals and humans. The importance of a One Health approach in managing CDI is discussed. A literature search was performed on PubMed and Web of Science for relevant papers published from 1 January 2000 to 10 July 2019. We present evidence that demonstrates transmission of C. difficile in hospitals from asymptomatic carriers to symptomatic CDI patients. The source of colonization is most probably community reservoirs, such as foods and the environment, where toxigenic C. difficile strains have frequently been isolated. With high-resolution genomic sequencing, the transmission of C. difficile between animals and humans can be demonstrated, despite a clear epidemiological link often being absent. The ways in which C. difficile from animals and humans can disseminate through foods and the environment are discussed, and an interconnected transmission pathway for C. difficile involving food animals, humans and the environment is presented. Clostridium difficile is a well-established pathogen of both humans and animals that contaminates foods and the environment. To manage CDI, a One Health approach with the collaboration of clinicians, veterinarians, environmentalists and policy-makers is paramount.


Prevalence, incidence and remission of urinary incontinence in women: longitudinal data from the Norwegian HUNT study (EPINCONT).
To determine incidence and remission of UI as well as changes in UI prevalence in the Norwegian EPINCONT surveys. The EPINCONT surveys were conducted in the county of Nord-Trøndelag, Norway, as part of two large cross-sectional health surveys (HUNT2 and HUNT3) in 1995 - 1997 (EPINCONT1 (E1)), and 2006 - 2008 (EPINCONT2 (E2)). EPINCONT collected information about prevalence of UI, as well as information about type and severity of UI. A 16% relative increase in UI prevalence was found in 11 years. The women who answered E2 were significantly older, had a higher BMI and higher prevalence of diseases such as asthma, diabetes and angina compared with the women who answered E1. Crude UI prevalence increased between the studies. Changes in known risk factors for UI such as age, BMI, weight and parity could explain some of the relative increase in prevalence, and were also found to be associated with either incidence of UI, remission of UI or both.


A long terminal repeat retrotransposon of Schizosaccharomyces japonicus integrates upstream of RNA pol III transcribed genes.
Transposable elements (TEs) are common constituents of centromeres. However, it is not known what causes this relationship. Schizosaccharomyces japonicus contains 10 families of Long Terminal Repeat (LTR)-retrotransposons and these elements cluster in centromeres and telomeres. In the related yeast, Schizosaccharomyces pombe LTR-retrotransposons Tf1 and Tf2 are distributed in the promoter regions of RNA pol II transcribed genes. Sequence analysis of TEs indicates that Tj1 of S. japonicus is related to Tf1 and Tf2, and uses the same mechanism of self-primed reverse transcription. Thus, we wondered why these related retrotransposons localized in different regions of the genome. To characterize the integration behavior of Tj1 we expressed it in S. pombe. We found Tj1 was active and capable of generating de novo integration in the chromosomes of S. pombe. The expression of Tj1 is similar to Type C retroviruses in that a stop codon at the end of Gag must be present for efficient integration. 17 inserts were sequenced, 13 occurred within 12 bp upstream of tRNA genes and 3 occurred at other RNA pol III transcribed genes. The link between Tj1 integration and RNA pol III transcription is reminiscent of Ty3, an LTR-retrotransposon of Saccharomyces cerevisiae that interacts with TFIIIB and integrates upstream of tRNA genes. The integration of Tj1 upstream of tRNA genes and the centromeric clustering of tRNA genes in S. japonicus demonstrate that the clustering of this TE in centromere sequences is due to a unique pattern of integration.


Clinical application of carbon nanoparticles in lymphatic mapping during colorectal cancer surgeries: A systematic review and meta-analysis.
To investigate the overall performance of carbon nanoparticles (CNs) for detecting lymph nodes (LNs) and node metastasis during colorectal cancer surgery. The English and Chinese literature was searched until 29 April 2020. Studies were included if they were randomized controlled trials (RCTs) for colorectal resection and LN dissection that compared the use of CNs with a blank control in colorectal cancer surgery. Quality assessment and data extraction were performed, and a meta-analysis was conducted using ReviewManager 5.3 and Stata 15.1 software. A total of 17 RCTs comprising 1241 patients were included for analysis. Compared with the outcomes of the blank controls, the use of CNs resulted in an average of 5.21 more LNs per patient (weighted mean difference = 5.21, 95% confidence interval [CI] = 4.14-6.29, p < 0.001) and a 68% higher detection rate of micro LNs (relative risk [RR] = 1.68, 95% CI = 1.38-2.04, p < 0.001). In addition, more metastatic LNs were identified in stained nodes (RR = 1.56, 95% CI = 1.40-1.75, p < 0.001), but the total detection rate of metastatic nodes did not differ between the groups. CN is an effective lymphatic tracer in colorectal cancer surgeries. Further studies with larger sample sizes are needed to validate these findings.


Caspase-2 and microRNA34a/c regulate lidocaine-induced dorsal root ganglia apoptosis in vitro.
Epidural administration of lidocaine may cause neurotoxicity in spinal cord dorsal root ganglia neurons (DRGNs). In this study, we explored the underling mechanisms of apoptotic pathways of lidocaine-induced apoptosis in DRGNs. Neonatal rat DRGNs were treated with lidocaine to induced apoptosis in vitro. Western blot showed caspase- (casp-) 2/3/9 proteins were all upregulated by lidocaine in DRGNs. However, inhibition of casp-2 protected lidocaine-induced apoptosis in DRGNs, whereas Casp3/9 inhibition did not. The possible upstream epigenetic regulators of casp-2, microRNA-34 (miR-34) family, including miR-34a/b/c, were evaluated by dual-luciferase reporter assay and qRT-PCR. We found miR-34a/c, but not miR-34b, were down-regulated in lidocaine-induced DRGN apoptosis. Subsequent upregulation of miR-34 family showed miR-34a/c were able to inhibit casp-2 and protect lidocaine-induced apoptosis in DRGNs, whereas miR-34b did not. Thus, out study shows that casp-2, in association with miR-34a/c was actively involved in lidocaine-induced apoptosis in DRGNs. Inhibiting casp-2 or upregulating miR-34a/c may provide novel meanings to protect local anesthetic-induced neurotoxicity.


Synthesis and properties of vinyl monomer/enzyme conjugates. Conjugation of L-asparaginase with N-succinimidyl acrylate.
Monomer conjugation of an enzyme followed by copolymerization with free monomer is a useful method of enzyme immobilization. L-asparaginase was conjugated with N-succinimidyl acrylate. Analysis of the conjugated enzyme via isoelectric focusing showed that a molar ratio of 9.5 free monomers per enzyme was needed during the conjunction for each vinyl group bound. Only 3% of the enzyme activity was lost per vinyl group added, and conjugation of an average of four monomers per enzyme thermally destabilized the enzyme only at temperatures above 50 degrees C. Activity of the enzyme at physiological temperatures was relatively unaffected.


Negative effects of ADAMTS-7 and ADAMTS-12 on endplate cartilage differentiation.
The roles of ADAMTS-7 and ADAMTS-12 in disc degeneration have not been previously examined. The purpose of this study was to examine the expression of ADAMTS-7 and ADAMTS-12 in the endplate cells isolated from patients with degenerative disc disease and to see whether they are associated with the pathological change of endplate. Sixty-four degenerated lumbar endplate specimens were obtained from the patients with degenerative disc disease categorized as type Modic I or II in magnetic resonance imaging (MRI) and 12 nondegenerative specimens as control (vertebra burst fracture patients without degenerative change in MRI) during surgical procedures. The expression of ADAMTS-7 and ADAMTS-12 was examined by real-time PCR and Western blotting. A statistically significant increase in mRNA expression of ADAMTS-7 and ADAMTS-12 was observed in the endplate cells in degenerative discs compared with nondegenerative discs. The corresponding protein levels of ADAMTS-7 and ADAMTS-12 had the same expression patterns. Moreover, ADAMTS-7 and ADAMTS-12 down-regulated the expression of Col II, Sox9, and Col X the marker genes for chondrogenesis. Our results indicate that ADAMTS-7 and ADAMTS-12 appear to be potent negative regulators of endplate cartilage development.


Sanitary implications associated with the use of eutrophic freshwater.
This review presents the problem of eutrophication of lakes whose waters are used also for potable use. The indirect negative impact of algal blooms as well as the direct consequences of the overgrowth of toxic Cyanophyta are considered. Problems for water treatment plants processing eutrophic raw water are exposed. Basic treatment will not easily remove algae or their by-products and increased use of chlorine will give rise to high levels of chlorinated by-products such as THM. Possible alternatives and improvements are suggested for the treatment of poor quality raw water to obtain high quality drinking water.


Demonstration of spontaneously dividing male fetal cells in maternal blood by negative magnetic cell sorting and fish.
We investigated a case of massive feto-maternal bleeding by using negative magnetic cell sorting (MACS) and fluorescent in situ hybridization (FISH). A 37-year-old pregnant woman had an uncomplicated amniocentesis for advanced maternal age at 16 weeks' gestation. The fetal karyotype was 46,XY. At 19 weeks' gestation, she had a minor car accident and slight vaginal bleeding. A subsequent Kleihauer-Betke test showed a 140 ml feto-maternal haemorrhage. Serial sonographic examinations indicated a normal fetus and placenta. We performed FISH analysis on maternal peripheral blood at 25 weeks. Anti-CD45 and MACS were used to deplete maternal leucocytes, enriching the proportion of fetal nucleated erythrocytes present. The isolated cells were analysed by using dual-colour FISH with X and Y specific probes. Approximately 65,800 nucleated cells were obtained after MACS depletion. A total of 234 cells were analysed by FISH. The results revealed that 70 of the nucleated cells (30 per cent) were male with one X and one Y signal. Among these cells, six male metaphases were observed in spontaneously dividing cells.


Galactose-particle receptor on liver macrophages. Quantitation of particle uptake.
Liver macrophages have been shown previously to bind and ingest gold particles coated with asialoglycoproteins via a N-acetyl-D-galactosamine / D-galactose-specific lectin (Kolb-Bachofen, V., Schlepper-Schäfer, J., Vogell, W. and Kolb, H. (1982) Cell 29, 859-866). We present here a quantitative analysis of lectin-dependent particle endocytosis. We used a conjugate of asialofetuin with colloidal gold as ligand, the cellular uptake of which could be followed by spectrophotometry. Freshly isolated Kupffer cells from the rat liver ingest asialofetuin at a rate of approx. 4200 particles/cell per min. Uptake is inhibited by saccharides related in structure to D-galactose and depends on the presence of Ca2+. The rate of endocytosis is zero below 10 degrees C, shows a modest increase until 20 degrees C and a steep increase between 20 and 37 degrees C. Uptake is energy-dependent and strongly inhibited by cytochalasin B but only slightly by colchicine.


[About of 82 obstetrical astro-articular injuries of the new-born (excepting brachial plexus palsies). Limits of initial therapeutic aggression and follow-up of evolution, particulary concerning traumatic separation of upper femoral epiphysis (author's transl)].
Obstetrical fracture has not a bad character, because of quick healing and, above all, because of extraordinary modelling by growth. The authors record 33 fractures of long bones which confirm this good prognosis. 20 birth fractures of the clavicule associated with brachial plexus palsies are recorded on account of their pathogenic, diagnostic and therapeutic intricacies. Prognosis of obstetrical traumatic separation of the epiphysis (epiphysiolysis) would be more preoccupying. This feeling is not given off the series of 28 observations recorded which conern 13 upper humeral, 6 lower humeral epiphysis, 1 of 6 upper femoral and 1 lower femoral epiphysis, of upper and lower of tibia. Diagnosis is not so easy, helped, if necessary, by arthrography. The clinical aspect of "pseudo-dislocation" associated with periostal callus, early appearing (about on the 10th day) rectifies diagnosis. Early treatment, as little aggressive as possible, (essentially orthopedic management by tractions along the axis of limb, giving up an anatomy as close as possible to normality) avoids sequellae, not existing at shoulder nor elbow and, if they exist, extremely decreased at hip, and the surgical management of which is always delayed. Initially good result of one birth dislocation of cervical spine, precedently recorded is considerably impaired.


MicroRNA‑92a promotes cell proliferation, migration and survival by directly targeting the tumor suppressor gene NF2 in colorectal and lung cancer cells.
Inactivation of the tumor suppressor protein Merlin leads to the development of benign nervous system tumors in neurofibromatosis type2 (NF2). Documented causes of Merlin inactivation include deleterious mutations in the encoding neurofibromin2 gene (NF2) and aberrant Merlin phosphorylation leading to proteasomal degradation. Rare somatic NF2 mutations have also been detected in common human malignancies not associated with NF2, including colorectal and lung cancer. Furthermore, tumors without NF2 mutations and with unaltered NF2 transcript levels, but with low Merlin expression, have been reported. The present study demonstrated that NF2 is also regulated by microRNAs (miRNAs) through direct interaction with evolutionarily conserved miRNA response elements (MREs) within its 3'‑untranslated region (3'UTR). Dual‑Luciferase assays in human colorectal carcinoma (HCT116) and lung adenocarcinoma (A549) cells revealed downregulation of NF2 by miR‑92a‑3p via its wild‑type 3'UTR, but not NF2‑3'UTR with mutated miR‑92a‑3p MRE. HCT116 cells overexpressing miR‑92a‑3p exhibited significant downregulation of endogenous NF2 mRNA and protein levels, which was rescued by co‑transfection of a target protector oligonucleotide specific for the miR‑92a‑3p binding site within NF2‑3'UTR. miR‑92a‑3p overexpression in HCT116 and A549 cells promoted migration, proliferation and resistance to apoptosis, as well as altered F‑actin organization compared with controls. Knockdown of NF2 by siRNA phenocopied the oncogenic effects of miR‑92a overexpression on HCT116 and A549 cells. Collectively, the findings of the present study provide functional proof of the unappreciated role of miRNAs in NF2 regulation and tumor progression, leading to enhanced oncogenicity.


Fully integrated colorimetric sensor based on transparency substrate for salbutamol determination.
A facile colorimetric method based on a typical redox reaction was first developed for the determination of salbutamol (SAL) using a low-cost and portable transparency-based analytical device (TAD). The TAD was simply fabricated by wax-printing onto a transparent polymer-based substrate to create the hydrophobic barriers and the colorimetric reaction zones where the color changes could be easily observed with the naked eye. Potassium permanganate (KMnO4), a common oxidizing agent, was deliberately used as a colorimetric reagent for SAL. Once SAL reacted with KMnO4 in the acidified system, it could undergo oxidation and the color of KMnO4 subsequently changed from light pink to orange. The color change corresponding to the SAL concentration could be clearly observed at the TAD sensor. In addition, the reaction color could be recorded using a digital camera and then analyzed by ImageJ for quantitative analysis. Under the optimized conditions, the developed method together with the TAD sensor exhibited high efficiency for SAL determination with linearity ranging from 0.5 to 40 mg·L-1 and a limit of detection (LOD) of 0.05 mg·L-1. •This proposed TAD-based colorimetric method using permanganate as color reagent showed excellent performance in SAL detection with good accuracy and high precision.


Health and ecotoxicological risk assessment for human and aquatic organism exposure to polycyclic aromatic hydrocarbons in the Baiyangdian Lake.
Seasonal and regional distributions of 17 polycyclic aromatic hydrocarbons (PAHs) in surface waters from four different main water functional regions of the Baiyangdian Lake were analyzed through GC/MS/MS during spring and summer season. The aim was to identify their possible pollution sources and evaluate their health risk for human and ecotoxicological risk for aquatic organisms. Results showed that the range of total PAH concentration is 35.38-88.06 ng/L (average 46.57 ng/L) in spring and 25.64-301.41 ng/L (average 76.23 ng/L) in summer. PAH contamination was observed slightly lower in the summer season from the pollution characteristics of water bodies in most areas of the Baiyangdian Lake, and the levels of PAH pollution in the water body of urban residential regions and rural residential regions were relatively higher than those in tourist regions and low human disturbance regions. Source analysis based on diagnostic ratios confirmed that combustion sources and petroleum sources were two main sources for PAHs entering into the waters of the Baiyangdian Lake. Human health risk assessment showed that PAHs in surface waters from the Baiyangdian Lake will not cause a potential non-carcinogenic risk to local residents and the carcinogenic risk could mostly be accepted, but the potential lifetime carcinogenic risk for infants in rural residential regions should be concerned about. Urban residential regions and rural residential regions were subject to higher cumulative non-carcinogenic and carcinogenic risk when compared to the other functional regions. Ecotoxicological risk assessment found a moderate risk to aquatic organisms presented by individual PAH and a low risk by total PAHs, and PAHs in the water body of urban residential regions and rural residential regions also have relatively higher harm effects to aquatic organisms compared with the other two functional regions. This study revealed the pollution characteristics of PAHs and their possible sources in waters of the Baiyangdian Lake, clarified its correlation to regional anthropogenic activities, and provided corresponding risk management strategies for human and aquatic organisms.


Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy.
The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin-layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of GEM-loaded neutral and cationic SVAs was tested in human alveolar basal epithelial (A549) and colorectal cancer (CaCo-2) cells. GEM-loaded cationic SVAs increased the anticancer activity in A549 and CaCo-2 cells relative to free drug, neutral SVAs, and CLs. In vivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentrations in lung tissue than neutral SVAs and CLs. Cationic SVAs may therefore serve as an innovative future therapy for pulmonary carcinoma.


Copper (II) Acylhydrazinates. Their Synthesis and Characterization.
Acylhydrazine derived furanyl and thienyl Schiff bases and their Cu(II) complexes have been prepared and characterized on the basis of their physical, spectral and analytical data. The preferred enolic form of the Schiff base function as a tetradentate ligand during coordination to the metal ion yielding a square planar complex. The Schiff bases and their complexes with different anions were tested for their antibacterial activity against bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa andKlebsiella pneumonae.


Combined thoraco-laparoscopic hepatectomy concomitant with resection of the diaphragm for solitary peritoneal seeding from cervical cancer: A case report.
Combined thoraco-laparoscopic resection can aid in precise resection of an invasive tumor of the diaphragm. A 44-year-old woman was referred to our department for resection of solitary peritoneal seeding from cervical cancer following systemic chemotherapy. The tumor was located in the right diaphragm with an ill-defined border of the liver. Combined thoraco-laparoscopic resection was proposed. Laparoscopy portrayed that the right diaphragm was partially attached to the liver, and the depth of tumor invasion to the diaphragm was ambiguous. Observation from the thoracic cavity indicated a white-colored distortion following the location of peritoneal seeding. Partial resection and repair of the diaphragm were made using the thoracoscopic-assisted approach, followed by laparoscopic hepatectomy. The postoperative course was uneventful, and pathological findings revealed that peritoneal metastases of the diaphragm and surgical margin was negative for cancer. Combined thoraco-laparoscopic resection can cover the drawbacks of each approach and is among the options for minimally invasive surgery for invasive tumor of the diaphragm.


How do we make health impact assessment fit for purpose?
Progress has been made in recent years in the process of health impact assessment (HIA), including community involvement. The technical side is less well developed. A minimum requirement is that there should be some consistency or robustness, so that the outcome of an HIA does not depend just on who happens to carry it out, that it is not easily swayed by the vested interests that typically surround any project, and that it can withstand legal challenge. Validity is an important criterion, as well as repeatability, as the latter can be achieved merely by propagating errors. All types of evidence should be considered legitimate, including qualitative and quantitative methods. The quality of evidence, and its generalisability, need to be carefully assessed; we should leave behind the divisive discourse around "positivism". Typically there is less information on the links from interventions (policies or projects) to changes in determinants of health than there is on the immediate precursors of health and ill-health. A practical question is, how the best existing knowledge can be made available to HIA practitioners. Other issues are more tractable than is often thought, e.g. that an HIA has to be able to trade off positive and negative impacts to different groups of people, and that the complexity of social causation prevents clear analysis of cause and effect.


Identification of genetic loci that overlap between schizophrenia and metabolic syndrome.
Patients with schizophrenia (SCZ) frequently exhibit an elevated risk of metabolic syndrome (MetS), which may lead to a worse clinical outcome. Even though these two phenotypes are genetically linked, little is known about their shared genetic determinants. Here, we investigated whether SCZ and MetS share genetic risk factors. To examine the genetic overlap between the two disorders, we applied a comprehensive genetic overlap analysis by integrating GWAS data for SCZ (n = 320,404) and MetS (n = 291,107) at the genome, genetic variants, and gene levels. At the genome level, we observed polygenic overlap between SCZ and MetS by utilizing LDSC (rg=-0.09, P = 1 × 10-4) and GNOVA (rho=-0.04, P = 1.39 × 10-8) analysis. At the SNP level, we performed conjunctional FDR (conjFDR) analysis to identify genetic variants simultaneously associated with two phenotypes. Based on conjFDR < 0.05, we identified 22 loci shared between SCZ and MetS. At the gene level, we further demonstrated that SCZ- and MetS-inferred gene expression overlapped across 49 GTEx tissues and highlighted the PCCB and KCTD13 genes as putative mediators of the genetic association. Overall, these findings shed novel light on the association between SCZ and MetS, and potentially enhance our knowledge of the high comorbidity and genetic processes that overlap between the two disorders.


Bond angle effects on microtensile bonds: laboratory and FEA comparison.
To test the hypothesis that there is a reduction in bond strength when a microtensile load is applied to adhesive junctions prepared at 10, 20 and 30 degrees to the usual perpendicular interface. To evaluate the effect of bond angle and adhesive layer thickness on stress levels within the adhesive joint utilizing FEA. Twenty-four non-carious third molars were selected, occlusal enamel removed and polished perpendicular to the long axis of the tooth. The Clearfil SE Bond and Single Bond were applied on the dentin. A 4 mm resin restoration, Z 100, was built up. The teeth were sectioned at 10 degrees, 20 degrees and 30 degrees to the bonding interface (n = 3). The control (n = 3) group had all cuts parallel to the tooth longitudinal axis (0 degrees bond angle). The bond values were calculated in MPa and Two-Way ANOVA and Tukey test applied. FEA was performed (1 mm/side square specimens) to obtain the maximum principal stress (MPS) in the microtensile-model for each bond angle and for varying adhesive thickness from 20 microm to 200 microm for each group. The bond strength results diminish as the angle on the interface increased (P<0.05) for Clearfil SE Bond between 0 (control) and 30 degrees, and for Single Bond between 0 (control) and 10, 20, and 30 degrees. The hypothesis can be fully accepted for Single Bond and partially accepted for Clearfil SE Bond. For the FEA, there was a trend toward decreasing MPS as the bond angle increased, while the MPS for each angled group increased with adhesive layer thickness. The MPS results for angled interfaces, exhibited the same trend as the lab values. FEA results indicated an MPS increase with increased adhesive thickness.


Do ward sisters have influence over care?
The role of the ward sister has changed significantly since modern nursing began in the 19th century. This article looks at the history of the ward sister, explores the impact of political and professional changes on the role and discusses how ward sisters can help maintain the quality of care in today's NHS.


Electrophysiological indicators of inhibitory control deficits in depression.
Ample evidence from behavioral and brain imaging studies suggests that inhibitory control is impaired in depression, though the precise nature of this impairment is unclear. The purpose of the present study was to examine potential deficits in three aspects of inhibitory control - conflict monitoring, conflict resolution, and overt behavioral inhibition - in the context of depressive symptoms. Depressed (n=15) and non-depressed (n=15) participants completed a stop-signal reaction time (SSRT) task while electroencephalography (EEG) data were recorded. EEG results indicate that depression impacts only the conflict resolution phase of inhibitory control, with higher levels of depressive and reflective pondering symptoms associated with poorer conflict resolution. Findings have clear implications for treatments of depression, many of which do not currently target the inhibitory control deficits present in this disorder.


Liver enzymes and fibrosis markers in patients with non-alcoholic fatty liver disease and concomitant chronic viral hepatitis.
The impact of non-alcoholic fatty liver disease (NAFLD) on patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has yet to be determined. In this retrospective, cross-sectional analysis, untreated chronic HBV, hepatitis B e-antigen (HBeAg)-positive patients with NAFLD had similar liver biochemistry and FIB-4 values as age-, gender-, and viral-load-matched HBeAg-positive patients without NAFLD. Among HBeAg-negative patients with NAFLD, although liver biochemistry findings were similar, mean FIB-4 values were significantly lower (0.98, SD 1.46, versus 1.51, SD 4.04, respectively; p < 0.05) and the percentage of patients with FIB-4 values in keeping with advanced fibrosis or cirrhosis was less (0.3% versus 3.9%, p < 0.015) than that of matched HBeAg-negative patients without NAFLD. Chronic HCV-infected patients with NAFLD had higher mean serum aminotransferase values than those without NAFLD (123 U/L, SD 247, versus 90 U/L, SD 128, respectively; p < 0.05). These results suggest that NAFLD adversely affects chronic HCV infections but not HBV infections.


Proteomic identification of mitochondrial targets involved in andrographolide sodium bisulfite-induced nephrotoxicity in a rat model.
Our previous works have indicated that the mitochondrion is the primary target of nephrotoxicity induced by andrographolide sodium bisulfate (ASB), but the mechanisms of ASB-induced nephrotoxicity have remained largely unknown. In this study, proteomic analysis was used to explore the changes in the renal mitochondrial proteome in SD rats after treatment with ASB. SD rats were intraperitoneally administered with ASB (100, 600mg/kg/d) for 7 days. Renal impairment was evaluated by pathological observation. Two-dimensional gel electrophoresis (2-DE), as well as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS), was applied for the identification of mitochondrial protein and was validated by Western blotting. Protein-protein interactions were analyzed using a Web-based bioinformatics tool (STRING, version 9.1). Rat kidneys exhibited histopathological changes after treatment with ASB, and 13 proteins were significantly changed, including ES1 protein homolog, heat shock cognate 71kDa protein, peroxiredoxin-1 (Prdx1), cytochrome C oxidase subunit 5B (COX5B), prohibitin (PHB), threonine-tRNA ligase, pyruvate dehydrogenase E1 component subunit beta (PDH-β), voltage-dependent anion-selective channel protein 2 (VDAC2), voltage-dependent anion-selective channel protein 1 (VDAC1), adenylate kinase 2 (KAD2) and others. These data demonstrated that the expression levels of several proteins significantly changed in the mitochondria, and these proteins could be candidate biomarkers for ASB-induced nephrotoxicity.


The pharmacodynamic effects of a lower-lipid emulsion of propofol: a comparison with the standard propofol emulsion.
Using a randomized, double-blind protocol design, we compared a new lower-lipid emulsion of propofol (Ampofol) containing propofol 1%, soybean oil 5%, and egg lecithin 0.6% with the most commonly used formulation of propofol (Diprivan) with respect to onset of action and recovery profiles, as well as intraoperative efficacy, when administered for induction and maintenance of general anesthesia as part of a "balanced" anesthetic technique in 63 healthy outpatients. Anesthesia was induced with sufentanil 0.1 microg/kg (or fentanyl 1 microg/kg) and propofol 2 mg/kg IV and maintained with a variable-rate propofol infusion, 120-200 microg x kg(-1) x min(-1). Onset times to loss of the eyelash reflex and dropping a syringe were recorded. Severity of pain on injection, speed of induction, intraoperative hemodynamic variables, and electroencephalographic bispectral index values were assessed. Recovery times to opening eyes and orientation were noted. The results demonstrated that there were no significant differences between Ampofol and Diprivan with respect to onset times, speed of induction, anesthetic dose requirements, bispectral index values, hemodynamic variables, recovery variables, or patient satisfaction. However, the incidence of pain on injection was more frequent in the Ampofol group (26% versus 6%, P < 0.05). We conclude that Ampofol is equipotent to Diprivan with respect to its anesthetic properties but was associated with a more frequent incidence of mild pain on injection. The pharmacodynamic profile of a lower-lipid containing emulsion of propofol (Ampofol) was compared with Diprivan when administered for induction and maintenance of general anesthesia. This preliminary study demonstrated that the two formulations of propofol were equivalent with respect to their induction and maintenance properties. However, Ampofol was associated with a more frequent incidence of pain on injection.


S-allylmercaptocysteine inhibits mucin overexpression and inflammation via MAPKs and PI3K-Akt signaling pathways in acute respiratory distress syndrome.
Cytokine storm is an important cause of acute respiratory distress syndrome and multiple organ failure. Excessive secretion and accumulation of mucins on the surface of airway cause airway obstruction and exacerbate lung infections. MUC5AC and MUC5B are the main secreted mucins and overexpressed in various inflammatory responses. S-allylmercaptocysteine, a water-soluble organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. The aim of this work was to investigate the therapeutic effects of SAMC on mucin overproduction and inflammation in 16HBE cells and LPS-induced ARDS mice. Results show that SAMC treatment ameliorated inflammatory cell infiltration and lung histopathological changes in the LPS-induced ARDS mice. SAMC also inhibited the expressions of MUC5AC and MUC5B, decreased the production of pro-inflammatory markers (IL-6, TNF-α, CD86 and IL-12) and increased the production of anti-inflammatory markers (IL-10, CD206 and TGF-β). These results confirm that SAMC had potential beneficial effects on suppressed hyperinflammation and mucin overexpression. Furthermore, SAMC exerted the therapeutic effects through the inhibition of phosphorylation of MAPKs and PI3K-Akt signaling pathways in the 16HBE cells and mice. Overall, our results demonstrate the effects of SAMC on the LPS-induced mucin overproduction and inflammation both in the 16HBE cells and mice.


Parity and body weight in the United States: differences by race and size of place of residence.
In women, parity has been studied in relation to body weights. This study examined whether and how relationships between parity and body weight differ by race and size of place of residence, adjusting for sociodemographic factors (age, income, education, working status, and marital status) and health behaviors (alcohol consumption, birth control pills, diet, physical activity, and smoking). A U.S. national sample of 3398 white and black women from the Third National Health and Nutrition Examination Survey was used to study the relationships using multiple linear regression analysis. The parity-weight relationships varied by race and size of place of residence. After adjusting for the covariates, significant relationships between parity and body weight were found only in black women in metropolitan areas and white women in non-metropolitan areas. Compared with women with no children, white women with two children living in non-metropolitan areas tended to have lower BMIs, whereas black women in metropolitan areas with one or two children showed higher BMIs. Overall, the parity-weight relationships in these groups of women were not strong or linear. The parity-weight relationships of black women in non-metropolitan areas warrant further examination.


A mutation designed to alter crystal packing permits structural analysis of a tight-binding fluorescein-scFv complex.
The structure of the scFv fragment FITC-E2, obtained from a naive phage antibody scFv library derived from human donors, was determined at 2.1 A resolution in the free form and at 3.0 A in the complexed form. The wild-type (wt) scFv binds fluorescein with a K(D) of 0.75 nM. The free scFv readily crystallizes by compacting its 18 amino acid-long CDR-H3, partially occluding the binding site and further blocking access by binding to the "bottom" of a neighboring scFv molecule with a cluster of exposed aromatic residues within CDR-H3. Only upon mutating one of the residues involved in this dominant crystal contact, an exposed tryptophan in the middle of CDR-H3, crystals of the complex could be obtained. A series of alanine mutants within the putative antigen binding site, covering a range of binding affinities, were used to relate macroscopic thermodynamic and kinetic binding parameters to single-molecule disruption forces measured by AFM. The effects of the mutations on the binding properties, particularly on the fraction of binding-competent molecules within the population, cannot be fully explained by changes in the strength of local interactions. The significant conformational change of CDR-H3 between the free and the liganded form illustrates the plasticity of the binding site. An accompanying study in this issue by Curcio and colleagues presents the molecular dynamics simulation of the forced unbinding experiments and explores possible effects of the mutations on the unbinding pathway of the hapten.


Characterization of laryngeal muscle stem cell survival and proliferation.
Laryngeal muscle and skeletal muscle stem cells (MSC) have been shown to differ in physiological basal activity and responsiveness to stimuli. Given these differences, it is the purpose of this investigation to characterize the in vitro proliferation and survival of laryngeal and skeletal MSC to determine whether intrinsic differences exist that may account for differences noted in vivo. Basic science experiment utilizing rat MSC. Cultures of both laryngeal and skeletal MSC were harvested and equal numbers from both groups were expanded under similar conditions, quantifying cellular population to determine proliferation rate for each population. Increased proliferative potential was confirmed using Western blot analysis of extracellular signal-regulated kinase phosphorylation. As per standard survival assay protocol, cultures were placed in serum-deprived medium and cell survival was assessed by terminal uridine deoxynucleotidyl transferase-mediated dUTP nick end labeling assay at 72 hours. Our results demonstrated increased proliferation of laryngeal MSC relative to the skeletal MSC when cultured under similar conditions. Western blot demonstrated increased activation of the proliferation pathway, extracellular signal-regulated kinase, in the laryngeal group. There was no detectable difference in the MSC survival between the two groups. Compared with skeletal MSC, laryngeal MSC demonstrate increased proliferation and regenerative capacity. This may explain some of the differences in physiological role and responses involved in each cell population's tissue of origin.


Areca nut procyanidins ameliorate streptozocin-induced hyperglycemia by regulating gluconeogenesis.
Hepatic gluconeogenesis is a major contributor to blood glucose in diabetes mellitus. Our previous study indicated that areca nut extract enriched with catechin-based procyanidins from oligomers to polymers gave rise to anti-inflammatory effects in vitro and in vivo. Here we have surveyed the molecular features of areca nut procyanidins (ANPs) using quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) and the resulting mass spectrum accurately described ANP from monomer to hexadecamer. Furthermore, the potential of ANP in terms of blood glucose homeostasis was explored using cyclic adenosine monophosphate (cAMP)/dexamethasone stimulated primary mouse hepatocytes and multiple low dose streptozocin (MLD-STZ) treated mice. With the primary hepatocytes, ANP dose-dependently inhibited gluconeogenesis and reduced the mRNA expression of two gluconeogenic key enzymes, phosphoenol-pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Intragastrically feeding of 10mg/kg ANP for 4weeks reduced the levels of fasting blood glucose, PEPCK and G6Pase in MLD-STZ mice. In additional, the level of 5'-AMP-activated protein kinase (AMPK) expression showed a trend towards being restored in the ANP treated MLD-STZ-mice. This study indicated that ANP has the potential to improve hyperglycemia by regulating gluconeogenic related kinases in MLD-STZ-mice.


Nitric oxide controls feeding behavior in the chicken.
To investigate the effect of nitric oxide (NO) on food intake in the chicken, L-NG-nitro-arginine methyl ester HCl (L-NNA), an inhibitor of NO synthase, was applied. When i.p. administered, L-NNA significantly inhibited the food intake of broiler chickens in a dose response manner. Food ingestion was also depressed by the i.c.v. injection of L-NNA in a dose response fashion. The effect of L-NNA was attenuated by i.c.v. administration of L-arginine. These results suggest that central NO may control feeding behavior in the chicken.