Chronotoxicity of Acrylamide in Mice Fed a High-Fat Diet: The Involvement of Liver CYP2E1 Upregulation and Gut Leakage.
Acrylamide (ACR) is produced under high-temperature cooking of carbohydrate-rich foods via the Maillard reaction. It has been reported that ACR has hepatic toxicity and can induce liver circadian disorder. A high fat diet (HFD) could dysregulate liver detoxification. The current study showed that administration of ACR (100 mg/kg) reduced the survival rate in HFD-fed mice, which was more pronounced when treated during the night phase than during the day phase. Furthermore, ACR (25 mg/kg) treatment could cause chronotoxicity in mice fed a high-fat diet, manifested as more severe mitochondrial damage of liver during the night phase than during the day phase. Interestingly, HFD induced a higher CYP2E1 expressions for those treated during the night phase, leading to more severe DNA damage. Meanwhile, the expression of gut tight junction proteins also significantly decreases at night phase, leading to the leakage of LPSs and exacerbating the inflammatory response at night phase. These results indicated that a HFD could induce the chronotoxicity of ACR in mice liver, which may be associated with increases in CYP2E1 expression in the liver and gut leak during the night phase.


Species difference in cholesteryl ester cycle and HDL-induced cholesterol efflux from macrophage foam cells.
The species difference in the turnover rates of the cholesteryl ester (CE) cycle in macrophage foam cells (MFC) was examined in mice and rats. MFC were induced by acetyl-LDL and pulsed with [3H]oleate, followed by a chase with [14C]oleate. The replacement of the initial amount of cholesteryl [3H]oleate by cholesteryl [14C]oleate within 24 hours was 63% in mouse MFC, whereas it was 33% in rat MFC. The corresponding replacement in rabbit MFC was < 10%. In addition, HDL removed 41% of the CE mass from mouse MFC but only 22% from rat MFC. HDL-induced CE reduction from mouse MFC was enhanced by 40% by the inhibitor for acyl-coenzyme A:cholesterol acyltransferase (58-035), whereas the enhancing effect was not observed with rat MFC. These results indicate that the rate of CE turnover may serve as a critical factor to determine the capacity of MFC to respond to HDL-induced CE reduction, suggesting the possibility that the species difference in the turnover rates of the CE cycle in MFC might explain, in part, the species difference in susceptibility to experimental atherosclerosis.


Simultaneous projections from prefrontal cortex to dopaminergic and serotonergic nuclei.
Derangements of the prefrontal cortex (PFC) and of brainstem monoaminergic systems occur in depression and schizophrenia. Anatomical and functional evidence supports a PFC control of the brainstem monoaminergic systems. Similarly, the PFC contains a high density of monoamine receptors for which antipsychotic drugs exhibit high affinity. This raises the possibility that pathological or drug-induced changes in PFC may subsequently alter monoaminergic activity. Recent data indicate that a substantial proportion of PFC pyramidal neurons projecting to the ventral tegmental area (VTA) or the dorsal raphe nucleus (DR) express the 5-HT2A receptor mRNA, which suggests that atypical antipsychotic drugs affect serotonergic and dopaminergic function by targeting PFC 5-HT2A receptors. Using electrophysiological and tract-tracing techniques we examined whether PFC pyramidal neurons projecting to DR are segregated from those projecting to the VTA. Sequential electrical stimulation of these nuclei in anaesthetized rats evoked antidromic potentials from both areas in the same pyramidal neurons of the medial PFC (60%, n=30). A similar percentage of dual DR+VTA projection neurons (50%) was obtained using the reciprocal collision test (n=85). Similarly, tracer application (Fluoro-Gold in VTA and cholera toxin B in DR, or vice versa) retrogradely labelled pyramidal neurons in PFC projecting to VTA (81±18), to DR (52±9) and to both nuclei (31±4, n=5 rats). Overall, these results indicate that the PFC may simultaneously coordinate the activity of dopaminergic and serotonergic systems within a short temporal domain, supporting a concerted modulation of the ascending serotonergic and dopaminergic activity during antipsychotic drug treatment.


Discovery of novel 5-methyl-1H-pyrazole derivatives as potential antiprostate cancer agents: Design, synthesis, molecular modeling, and biological evaluation.
Androgen receptor (AR) signaling functions as a core driving force for the progression of prostate cancer (PCa), and AR has been proved to be an effective therapeutic target even for castration-resistant prostate cancer (CRPC). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e, leading to the discovery of a series of 5-methyl-1H-pyrazole derivatives. AR reporter gene assay revealed compounds A13 and A14 as potent AR antagonists. Some of the compounds in this series inhibited growth of PCa LNCaP cells more efficiently than enzalutamide. A13 and A14 also showed improved metabolic stability compared with 10e in human liver microsomes.


Thermal stability of the functional ingredients, glucosylated benzophenones and xanthones of honeybush (Cyclopia genistoides), in an aqueous model solution.
Thermal stability of the benzophenones, 3-β-d-glucopyranosyl-4-β-d-glucopyranosyloxyiriflophenone (1), 3-β-d-glucopyranosylmaclurin (2) and 3-β-d-glucopyranosyliriflophenone (3), and the xanthones, mangiferin (4) and isomangiferin (5), was assessed separately in an aqueous model solution (pH 5) to delineate their major degradation products and mechanism(s). Degradation followed first-order reaction kinetics and the temperature-dependence of the respective reaction rate constants complied with the Arrhenius equation. The stability of the compounds increased in the order 2>4>3>5>1. 4-O-Glucosylation significantly stabilised 1 against degradation compared to 3, enediol B-ring functionality of 2 decreased stability compared to 3 and position of glucosylation affected the stability of the xanthones with 5 being more stable than 4. The xanthone nucleus (C-ring) conferred higher stability to 4 and 5 compared to their benzophenone analogue 2. Cyclisation of 2 to 4 and 5 would underestimate their degradation in mixtures. Other reactions were isomerisation, dimerisation, acetylation and hydrolysis.


Creative Strengths-Based Approaches to Health Promotion: Perspectives From Graduate Training Experiences.
The authors met during a career development experience where they discussed the commonalities of their successes and challenges conducting creative strengths-based health promotion research with underserved communities during their graduate and postgraduate training. They identified changes to health promotion pedagogy that they would like to see in the future. These include understanding both the strengths and the challenges of creative strengths-based health promotion research conducted with underserved communities, ensuring that reflexivity and flexibility is a component of the process, developing support networks for trainees, understanding personal limitations to effect change, and supporting self-care. They hope that trainees and health education programs will learn from their experiences.


Computational analysis of the effects of reduced temperature on thrombin generation: the contributions of hypothermia to coagulopathy.
Hypothermia, which can result from tissue hypoperfusion, body exposure, and transfusion of cold resuscitation fluids, is a major factor contributing to coagulopathy of trauma and surgery. Despite considerable efforts, the mechanisms of hypothermia-induced blood coagulation impairment have not been fully understood. We introduce a kinetic modeling approach to investigate the effects of hypothermia on thrombin generation. We extended a validated computational model to predict and analyze the impact of low temperatures (with or without concomitant blood dilution) on thrombin generation and its quantitative parameters. The computational model reflects the existing knowledge about the mechanistic details of thrombin generation biochemistry. We performed the analysis for an "average" subject, as well as for 472 subjects in the control group of the Leiden Thrombophilia Study. We computed and analyzed thousands of kinetic curves characterizing the generation of thrombin and the formation of the thrombin-antithrombin complex (TAT). In all simulations, hypothermia in the temperature interval 31°C to 36°C progressively slowed down thrombin generation, as reflected by clotting time, thrombin peak time, and prothrombin time, which increased in all subjects (P < 10(-5)). Maximum slope of the thrombin curve was progressively decreased, and the area under the thrombin curve was increased in hypothermia (P < 10(-5)); thrombin peak height remained practically unaffected. TAT formation was noticeably delayed (P < 10(-5)), but the final TAT levels were not significantly affected. Hypothermia-induced fold changes in the affected thrombin generation parameters were larger for lower temperatures, but were practically independent of the parameter itself and of the subjects' clotting factor composition, despite substantial variability in the subject group. Hypothermia and blood dilution acted additively on the thrombin generation parameters. We developed a general computational strategy that can be used to simulate the effects of changing temperature on the kinetics of biochemical systems and applied this strategy to analyze the effects of hypothermia on thrombin generation. We found that thrombin generation can be noticeably impaired in subjects with different blood plasma composition even in moderate hypothermia. Our work provides mechanistic support to the notion that thrombin generation impairment may be a key factor in coagulopathy induced by hypothermia and complicated by blood plasma dilution.


Expression of B-cell translocation gene 2 protein in normal human tissues.
The antiproliferative B-cell translocation gene 2 (BTG2(TIS21/PC3)) is emerging as an important regulator of cell cycle dynamics. BTG2(TIS21/PC3) expression increases in response to the induction of DNA damage, cell differentiation, cell quiescence, cell contact, and as part of a positive feedback mechanism in response to growth stimulation. The objective of the present study was to provide further insight into the biological function of BTG2(TIS21/PC3) by determining the expression levels and cellular localization of BTG2(TIS21/PC3) in a spectrum of normal human tissues and to determine the proliferative indices (based on Ki-67 staining) and apoptotic indices (based on TUNEL assay) in those cell populations where BTG2(TIS21/PC3) was differentially expressed. Highest levels of BTG2(TIS21/PC3) expression were seen in kidney proximal tubules, lung alveolar bronchial epithelium and in the basal cell layer of prostate acini. BTG2(TIS21/PC3) was expressed at significantly different levels within the different epithelial populations of the kidney (proximal vs distal tubules) and prostate (acinar basal cells vs lumenal cells). Moderate levels of expression were seen in the acinar cells of breast and pancreas and in the mucosal epithelium of the intestine. Low levels of expression were seen in neurons, hepatocyctes, the zona granulosa of the ovary, round spermatids and thyroid follicles. Our results therefore indicate an imperfect correlation between the terminally differentiated phenotype and BTG2(TIS21/PC3) expression, but no correlation between basal cellular proliferative or apoptotic indices and BTG2(TIS21/PC3) expression levels.


Review of some pharmacokinetic and pharmacodynamic properties of anti-infective medicines administered to the koala (Phascolarctos cinereus).
Although koalas are iconic Australian animals, no pharmacokinetic studies of any first-line medicines used to treat diseased or injured koalas had been published prior to 2010. Traditionally, medicine dosages suggested for this species underwent linear extrapolation from those recommended for domesticated species. The koala, a specialist folivore whose natural diet consists of almost exclusively Eucalyptus spp. foliage has anatomical and physiological adaptations for detoxifying their diet which also affect medicine pharmacokinetic profiles. This review addresses aspects of medicine absorption, clearance, and other indices (such as medicine binding to plasma proteins) of enrofloxacin/marbofloxacin and chloramphenicol used for the systemic treatment of chlamydiosis, and fluconazole ± amphotericin, and posaconazole for the treatment of cryptococcosis. Based on observations from published studies, this review includes suggestions to improve therapeutic outcomes when administering medicines to diseased koalas.


P2y receptor-mediated angiogenesis via vascular endothelial growth factor receptor 2 signaling.
Pathological as well as physiological angiogenesis is known to be regulated by such factors as nucleotides and Vascular Endothelial Growth Factor (VEGF). Activated P2Y nucleotide receptors have been observed to associate and transactivate VEGF Receptor 2 (VEGFR2), suggesting a cooperation between nucleotide and VEGF signaling in angiogenesis. P2YR mediated VEGFR2 signaling therefore may be important in describing the angiogenic signaling of nucleotides such as ATP. Here, we provide evidence that supports the notion of P2YR-VEGFR2 signaling. The significant angiogenic effect of P2Y1/2 receptor agonists (100 microM ATP and 10 microM 2MS-ATP) on endothelial cell tubulogenesis was suppressed back to near control levels upon addition of 1 microM SU1498 (specific VEGFR2 tyrosine kinase inhibitor). We believe that this P2YR-VEFGR2 signaling is an important component of pathological, as well as physiological angiogenesis.


Sleep-related eating disorder and its associated conditions.
Sleep-related eating disorder (SRED) is a condition characterized by recurrent episodes of eating at the transition from night-time sleep to arousal. SRED patients describe eating in an out-of-control manner with preference for high-caloric foods and sometimes with inedible or toxic items. Level of consciousness during SRED episodes ranges from partial consciousness to dense unawareness typical of somnambulistic episodes. SRED is sometimes associated with psychotropic medication, in particular sedative hypnotics, and other sleep disorders, including parasomnias, narcolepsy, and restless legs syndrome. Night eating syndrome (NES) is another important condition in the disordered night-time eating spectrum showing hyperphagia episodes at full arousal from nocturnal sleep without accompanying amnesia. NES could be considered an abnormality in the circadian rhythm of meal timing with a normal circadian timing of sleep onset. The two conditions often overlap and possibly share a common pathophysiology. Studies have suggested that central nervous system serotonin modulation may lead to an effective treatment of NES, while the anti-seizure medication topiramate may be an effective SRED treatment.


Comparison of Extracorporeal Shock Wave Therapy versus Manual Lymphatic Drainage on Cellulite after Liposuction: A Randomized Clinical Trial.
Cellulite is associated with variations in the skin appearance with cottage cheese, mattress-like, or orange peel. The most common areas for these lesions are the posterior or upper thighs and buttocks and mainly affect females after puberty. The objective of the study was to determine whether extracorporeal shock wave therapy (ESWT) or manual lymphatic drainage (MLD) is more effective for the reduction of the grade of cellulite after liposuction. This study is a single-blinded randomized controlled clinical trial. Thirty females with grade 3 cellulite were randomly distributed into two groups equal in number (n = 15), group A was equipped to ESWT and group B was equipped to MLD. The cellulite grading scale was used to assess cellulite grade, and the skinfold caliper was used to assess the thickness of subcutaneous fat. The assessment was carried out before and four weeks after starting the treatment. Both groups received topical retinol twice daily for four weeks; in addition, group A received ESWT, while group B received MLD, two times/week for 4 weeks. The mean values of the skinfold caliper in group A decreased by 24.4% and in group B by 15.38% with a significant difference between the two groups (p < 0.001). Also, the mean values of the cellulite grading scale decreased significantly after treatment in group A compared with the mean values of group B (p < 0.001). There was more reduction in the grade of cellulite and thickness of subcutaneous fat in the ESWT group than the MLD group after liposuction.


Orotidine-Containing RNA: Implications for the Hierarchical Selection (Systems Chemistry Emergence) of RNA.
The prebiotic synthesis of canonical nucleobases from HCN is a cornerstone for the RNA world hypothesis. However, their role in the primordial pathways to RNA is still debated. The very same process starting from HCN also gives rise to orotic acid, which (via orotidine) plays a crucial role in extant biology in the de novo synthesis of uridine and cytidine, the informational base-pairs in RNA. However, orotidine itself is absent in RNA. Given the prebiotic and biological relevance of orotic acid vis-à-vis uracil, we investigated orotidine-containing RNA oligonucleotides and show that they have severely compromised base-pairing properties. While not unexpected, these results suggest that the emergence of extant RNA cannot just be a consequence of the plausible prebiotic formation of its chemical constituents/building blocks. In combination with other investigations on alternative prebiotic nucleobases, sugars, and linkers, these findings imply that the selection of the components of extant RNA occurred at a higher hierarchical level of an oligomer/polymer based on its functional properties-pointing to a systems chemistry emergence of RNA from a library of precursors.


Diagnostic Efficacy of Carotid Ultrasound for Predicting the Risk of Perioperative Hypotension or Fluid Responsiveness: A Meta-Analysis.
Despite the acceptance of carotid ultrasound for predicting patients' fluid responsiveness in critical care and anesthesia, its efficacy for predicting hypotension and fluid responsiveness remains unclear in the perioperative setting. Electronic databases were searched from inception to May 2023 to identify observational studies focusing on the use of corrected blood flow time (FTc) and respirophasic variation in carotid artery blood flow peak velocity (ΔVpeak) for assessing the risks of hypotension and fluid responsiveness. Using FTc as a predictive tool (four studies), the analysis yielded a pooled sensitivity of 0.82 (95% confidence interval (CI): 0.72 to 0.89) and specificity of 0.94 (95% CI: 0.88 to 0.97) for the risk of hypotension (area under curve (AUC): 0.95). For fluid responsiveness, the sensitivity and specificity of FTc were 0.79 (95% CI: 0.72 to 0.84) and 0.81 (95% CI: 0.75 to 0.86), respectively (AUC: 0.87). In contrast, the use of ΔVpeak to predict the risk of fluid responsiveness showed a pooled sensitivity of 0.76 (95% CI: 0.63 to 0.85) and specificity of 0.74 (95% CI: 0.66 to 0.8) (AUC: 0.79). The current meta-analysis provides robust evidence supporting the high diagnostic accuracy of FTc in predicting perioperative hypotension and fluid responsiveness, which requires further studies for verification.


G72/G30 genes and schizophrenia: a systematic meta-analysis of association studies.
Schizophrenia may result from a neurotransmission hypofunction of glutamatergic and N-methyl-d-aspartate (NMDA) receptors. Linkage disequilibrium mapping has identified several promising and novel positional candidates, including the G72/G30 and d-amino-acid oxidase (DAAO) genes. Since the first positive association report, many subsequent studies have attempted to replicate the association but the results have been mixed. To try to resolve this inconsistency and to elucidate the relationship between the important glutamate-related genes and schizophrenia, the current meta-analysis has combined samples involving 16 polymorphisms covering all published case-control and family-based association studies up to October 2005. The results suggest that there is weak evidence of association between the G72/G30 genes and schizophrenia.


[Enhanced hydrolysis of excess sludge by external enzymes].
The effects of external enzymes to enhance excess sludge hydrolysis were investigated. Protease and alpha-amylase were added singly and in combination, and it was found that external enzymes can enhance sludge hydrolysis. When treated with single enzyme, alpha-amylase had higher efficiency than protease, SCOD/TCOD rose from 16.3% to 22.3% and VSS reduction improved from 39.8% to 54.24% at the optimal dosage of 60 mg/g (calculated by addition of enzyme in TS). Furthermore, mixture enzymes showed better hydrolysis efficiency than single enzyme. The highest VSS reduction was observed at an enzyme mixture ratio of 1:3 with protease and amylase when the hydrolysis temperature was 50 degrees C, and the VSS reduction achieved 68.43%. Correspondingly, the concentration of reducing sugar and NH4+ -N rose from 37.29, 47.60 mg/L to 177.8, 143.43 mg/L, respectively. According to the kinetic and enzymatic analysis of hydrolysis process, sludge hydrolysis within prior 4 h was consistent with first-order reaction dynamic. During the hydrolysis, both protease and amylase activity rose gradually, the highest activity observed were 2.57 U/mL and 4.64 U/mL at 4h after hydrolysis. Thereafter, the enzyme activity decreased.


Suicide case with multiple injuries with sharp objects.
The work of forensic - medical expert examination of the corpse at the place of its discovery and further research in the morgue often there are certain difficulties associated with the solution of a number of issues, including the establishment of a kind of death. Bringing the case demonstrates that, during the initial examination of the corpse to the place of its discovery the presence of multiple injuries on the body of a different nature, as a rule, initially suggest investigators to suspect that the murder occurred. But further questioning around him lately those studying survey data and scene study results allowed the corpse to make objective conclusions.


Effects of avermectin residues in cattle dung on dung beetle (Coleoptera: Scarabaeidae) reproduction and survival.
Scarabaeine dung beetles feeding on dung from cattle treated with an injection of avermectin at a therapeutic dose to control internal parasites, show larval mortality, mortality of immature adults, reduced egg production, and inhibited ovariole development for periods of 1-4 weeks following treatment. In winter rainfall regions of Australia, feeding by newly emerged adults of an introduced species, Onthophagus binodis, resulted in shredding of cattle dung between December and May. Production of brood masses and eggs resulted in dung being buried from September to November. Feeding by newly emerged adults of a native species, Onthophagus ferox, resulted in dung being buried in May and June, and production of brood masses for breeding resulted in dung burial between September and November. There are thus 2-6 months of the year when injection of cattle with avermectin would affect mortality of newly emerged beetles, and 3 months of the year when avermectin treatment of cattle would affect dung beetle oviposition or larval survival. Beetles were attracted to fresh dung for 2-4 days, and most had left the pad within a week. There are no data to indicate the effects of avermectin residues in dung on dung beetle populations and on beetle fitness. Tests should be done to determine if avermectins in slow release devices have a greater effect on dung beetles than injections, and to determine what effects both have on dung beetle populations.


Deferoxamine Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis and Activating the Nrf2 Pathway.
Objective: Osteoarthritis (OA) is a common disease with a complex pathology including mechanical load, inflammation, and metabolic factors. Chondrocyte ferroptosis contributes to OA progression. Because iron deposition is a major pathological event in ferroptosis, deferoxamine (DFO), an effective iron chelator, has been used to inhibit ferroptosis in various degenerative disease models. Nevertheless, its OA treatment efficacy remains unknown. We aimed to determine whether DFO alleviates chondrocyte ferroptosis and its effect on OA and to explore its possible mechanism. Methods: Interleukin-1β (IL-1β) was used to simulate inflammation, and chondrocyte ferroptosis was induced by erastin, a classic ferroptosis inducer. A surgical destabilized medial meniscus mouse model was also applied to simulate OA in vivo, and erastin was injected into the articular cavity to induce mouse knee chondrocyte ferroptosis. We determined the effects of DFO on ferroptosis and injury-related events: chondrocyte inflammation, extracellular matrix degradation, oxidative stress, and articular cartilage degradation. Results: IL-1β increased the levels of ROS, lipid ROS, and the lipid peroxidation end product malondialdehyde (MDA) and altered ferroptosis-related protein expression in chondrocytes. Moreover, ferrostatin-1 (Fer-1), a classic ferroptosis inhibitor, rescued the IL-1β-induced decrease in collagen type II (collagen II) expression and increase in matrix metalloproteinase 13 (MMP13) expression. Erastin promoted MMP13 expression in chondrocytes but inhibited collagen II expression. DFO alleviated IL-1β- and erastin-induced cytotoxicity in chondrocytes, abrogated ROS and lipid ROS accumulation and the increase in MDA, improved OA-like changes in chondrocytes, and promoted nuclear factor E2-related factor 2 (Nrf2) antioxidant system activation. Finally, intra-articular injection of DFO enhanced collagen II expression in OA model mice, inhibited erastin-induced articular chondrocyte death, and delayed articular cartilage degradation and OA progression. Conclusion: Our research confirms that ferroptosis occurs in chondrocytes under inflammatory conditions, and inhibition of chondrocyte ferroptosis can alleviate chondrocyte destruction. Erastin-induced chondrocyte ferroptosis can stimulate increased MMP13 expression and decreased collagen II expression in chondrocytes. DFO can suppress chondrocyte ferroptosis and promote activation of the Nrf2 antioxidant system, which is essential for protecting chondrocytes. In addition, ferroptosis inhibition by DFO injection into the articular cavity may be a new OA treatment.


Separation of C2-naphthalenes by gas chromatography x fourier transform infrared spectroscopy (GC x FT-IR): two-dimensional separation approach.
A two-dimensional separation approach involving gas chromatography (GC) and Fourier transform infrared spectroscopy (FT-IR) is used to separate C2-naphthalene isomers at or near baseline resolution. In addition to GC separation, the FT-IR also plays an important role in the separation, as well as its traditional role of detection and identification. This two-dimensional separation approach for the analysis of a C2-naphthalene isomeric mixture is a good example of separation design based on molecular difference and the characteristics of an analytical instrument. The details of this two-dimensional separation are discussed, along with the advantages and limitations of this approach. While two-(or multiple-)dimensional separations have demonstrated superior capabilities in the characterization of complex, largely unknown mixtures, the development of GCxFT-IR illustrates the applicability of this analytical approach in the separation of simpler but still challenging, mixtures. The GCxFT-IR results have extended this approach toward its application to the analysis of samples of more complicated composition.


The voltage-gated sodium channel, para, limits Anopheles coluzzii vector competence in a microbiota dependent manner.
The voltage-gated sodium channel, para, is a target of DDT and pyrethroid class insecticides. Single nucleotide mutations in para, called knockdown resistant or kdr, which contribute to resistance against DDT and pyrethroid insecticides, have been correlated with increased susceptibility of Anopheles to the human malaria parasite Plasmodium falciparum. However, a direct role of para activity on Plasmodium infection has not yet been established. Here, using RNA-mediated silencing, we provide in vivo direct evidence for the requirement of wild-type (wt) para function for insecticide activity of deltamethrin. Depletion of wt para, which is susceptible to insecticide, causes deltamethrin tolerance, indicating that insecticide-resistant kdr alleles are likely phenocopies of loss of para function. We then show that normal para activity in An. coluzzii limits Plasmodium infection prevalence for both P. falciparum and P. berghei. A transcriptomic analysis revealed that para activity does not modulate the expression of immune genes. However, loss of para function led to enteric dysbiosis with a significant increase in the total bacterial abundance, and we show that para function limiting Plasmodium infection is microbiota dependent. In the context of the bidirectional "enteric microbiota-brain" axis studied in mammals, these results pave the way for studying whether the activity of the nervous system could control Anopheles vector competence.


[Attenuation rules and germicidal efficacy of ozoneted water].
To determine initial concentrations of ozonated water under different temperatures, attenuation rules of ozonated water under the room temperature (25 ℃), and to inspect the effects of ozonated water under different concentrations on common microorganisms. Methods: The online test method and the plate cultivation method were employed to check the concentrations and killing rates on common microorganisms of ozonated water produced by HZ-2601 B Ozone Water Generating Instrument. Results: The initial concentrations of ozonated water at 20, 25, 30, 35, and 40 ℃ were 4.38, 4.26, 3.12, 2.76, and 1.31 mg/L, respectively. The ozonated water was rapidly attenuated at first 10 min. The concentration of ozonated water still remained at 1.06 mg/L and 0.37 mg/L at 25 and 30 ℃ after 30 min. The average killing rates for Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Candida albicans in 1.0 mg/L ozonated water for 1 min were 99%, 100%, 100%, 100%, and 100%, respectively. The average killing rates of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans in 0.3 mg/L ozonated water for 1 min were 100%, 100%, 100%, 95%, and 92%, respectively. Conclusion: The initial concentrations of ozonated water produced by HZ-2601 B Ozone Water Generating Instrument decrease with the increase of temperature. Ozonated water under 20-30 ℃ has good sterilization effect on common microorganisms.


Efficient generation of goats with defined point mutation (I397V) in GDF9 through CRISPR/Cas9.
The recent emergence of the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9 system has attracted significant attention for its potential to improve traits of agricultural importance. However, most applications in livestock species to date have depended on aberrant DNA repair to generate frameshifting indels. Whether this genomic engineering technique involving homology-dependent repair (HDR) can be used to introduce defined point mutations has been less explored. Previously, we reported a G→A point mutation (g.231A>G, p.Val397Ile) in the growth differentiation factor 9 (GDF9) gene that has a large effect on the litter size of cashmere goats. In the present study we report that by co-injecting synthesised RNAs and single-stranded oligo deoxynucleotide (ssODN) donor sequences into goat zygotes, we successfully introduced defined point mutations resulting in single amino acid substitutions in the proteins as expected. The efficiency of this precise single-nucleotide substitution in newborn kids was as high as 24% (4/17), indicating that ssODN-directed HDR via zygote injection is efficient at introducing point mutations in the goat genome. The findings of the present study further highlight the complex genome modifications facilitated by the CRISPR/Cas9 system, which is able to introduce defined point mutations. This represents a significant development for the improvement of reproduction traits in goats, as well as for validating the roles of specific nucleotides in functional genetic elements in large animals.


Unique disialosyl gangliosides from salmon kidney: characterization of V3alphaFuc, IV3betaGalNAc, II3(alphaNeuAc)2-Gg4Cer and its analogue with 4-O-acetyl-N-acetylneuraminic acid.
Four unidentified acidic glycolipids (X3-X6) were isolated from the kidney of the Pacific salmon on an anion exchange column and by high performance liquid chromatography using a silica bead (Iatrobeads) column. Based on methylation analysis, chemical and enzymatic degradation, proton nuclear magnetic resonance spectroscopy and mass spectrometry, the glycon structure of X5 and X6 was identified as a unique disialosyl fucosyl-N-acetylgalactosaminyl ganglio-N-tetraose:Fucalpha3GalNAcbeta3Galbeta3GalNAcbeta4[NeuAcalpha8NeuAcalpha3] Galbeta4Glcbeta1Cer. NMR showed that X3 and X4 were analogues of X5 and X6 and contained O-acetyl groups on C4 of the outer N-acetylneuraminic acid, first disialosyl gangliosides containing 4-O-acetyl-N-acetylneuraminic acid. The ceramides of X3 and X5 contained predominantly C24: 1, and X4 and X6 contained saturated fatty acids (C14: 0, C16: 0 and C18: 0), whereas the long chain base was exclusively sphingenine. The concentrations of X3 and X4 were 0.13 and 0.16 nmol/g of kidney respectively and those of X5 and X6, were 0.07 nmol/g each.


Validating the Brain Injury Guidelines: Results of an American Association for the Surgery of Trauma prospective multi-institutional trial.
Brain Injury Guidelines (BIG) was developed to effectively use health care resources including repeat head computed tomography (RHCT) scan and neurosurgical consultation in traumatic brain injury (TBI) patients. The aim of this study was to prospectively validate BIG at a multi-institutional level. This is a prospective, observational, multi-institutional trial across nine Levels I and II trauma centers. Adult (16 years or older) blunt TBI patients with a positive initial head computed tomography (CT) scan were identified and categorized into BIG 1, 2, and 3 based on their neurologic examination, alcohol intoxication, antiplatelet/anticoagulant use, and head CT scan findings. The primary outcome was neurosurgical intervention. The secondary outcomes were neurologic worsening, RHCT progression, postdischarge emergency department visit, and 30-day readmission. A total of 2,432 patients met the inclusion criteria, of which 2,033 had no missing information and were categorized into BIG 1 (301 [14.8%]), BIG 2 (295 [14.5%]), and BIG 3 (1,437 [70.7%]). In BIG 1, no patient worsened clinically, 4 of 301 patients (1.3%) had progression on RHCT with no change in management, and none required neurosurgical intervention. In BIG 2, 2 of 295 patients (0.7%) worsened clinically, and 21 of 295 patients (7.1%) had progression on RHCT. Overall, 7 of 295 patients (2.4%) would have required upgrade from BIG 2 to 3 because of neurologic examination worsening or progression on RHCT, but no patient required neurosurgical intervention. There were no TBI-related postdischarge emergency department visits or 30-day readmissions in BIG 1 and 2 patients. All patients who required neurosurgical intervention were BIG 3 (280 of 1,437 patients [19.5%]). Agreement between assigned and final BIG categories was excellent ( κ = 99%). In this cohort, implementing BIG would have decreased CT scan utilization and neurosurgical consultation by 29% overall, with a 100% reduction in BIG 1 patients and a 98% reduction in BIG 2 patients. Brain Injury Guidelines is safe and defines the management of TBI patients by trauma and acute care surgeons without the routine need for RHCT and neurosurgical consultation. Therapeutic/Care Management; Level III.


A New Feature-Enhanced Speckle Reduction Method Based on Multiscale Analysis for Ultrasound B-Mode Imaging.
Effective speckle reduction in ultrasound B-mode imaging is important for enhancing the image quality and improving the accuracy in image analysis and interpretation. In this paper, a new feature-enhanced speckle reduction (FESR) method based on multiscale analysis and feature enhancement filtering is proposed for ultrasound B-mode imaging. In FESR, clinical features (e.g., boundaries and borders of lesions) are selectively emphasized by edge, coherence, and contrast enhancement filtering from fine to coarse scales while simultaneously suppressing speckle development via robust diffusion filtering. In the simulation study, the proposed FESR method showed statistically significant improvements in edge preservation, mean structure similarity, speckle signal-to-noise ratio, and contrast-to-noise ratio (CNR) compared with other speckle reduction methods, e.g., oriented speckle reducing anisotropic diffusion (OSRAD), nonlinear multiscale wavelet diffusion (NMWD), the Laplacian pyramid-based nonlinear diffusion and shock filter (LPNDSF), and the Bayesian nonlocal means filter (OBNLM). Similarly, the FESR method outperformed the OSRAD, NMWD, LPNDSF, and OBNLM methods in terms of CNR, i.e., 10.70 ± 0.06 versus 9.00 ± 0.06, 9.78 ± 0.06, 8.67 ± 0.04, and 9.22 ± 0.06 in the phantom study, respectively. Reconstructed B-mode images that were developed using the five speckle reduction methods were reviewed by three radiologists for evaluation based on each radiologist's diagnostic preferences. All three radiologists showed a significant preference for the abdominal liver images obtained using the FESR methods in terms of conspicuity, margin sharpness, artificiality, and contrast, p<0.0001. For the kidney and thyroid images, the FESR method showed similar improvement over other methods. However, the FESR method did not show statistically significant improvement compared with the OBNLM method in margin sharpness for the kidney and thyroid images. These results demonstrate that the proposed FESR method can improve the image quality of ultrasound B-mode imaging by enhancing the visualization of lesion features while effectively suppressing speckle noise.


[Suicidal ideations and suicide attempts after starting on aripiprazole, a new antipsychotic drug].
In 5 patients, 3 women aged 30, 32 and 41 years and 2 men aged 36 and 56 years, serious side effects developed after starting aripiprazole, a new antipsychotic drug. 2 patients had not been treated with antipsychotic drugs before, while in 3 there was a switch in antipsychotic treatment. The side effects consisted primarily oftroubling feelings ofagitation, akathisia, insomnia and dysphoria. 3 of the patients made a suicide attempt and 2 developed suicidal thoughts. The patients had not previously attempted suicide and the suicidal thoughts disappeared after discontinuation ofaripiprazole. Suicidal tendencies have not been reported before as a side effect ofaripiprazole.


Calcium-independent desmosomes of keratinocytes are hyper-adhesive.
Desmosomes in tissues are resistant to disruption by chelation of extracellular calcium. It has been suggested that this represents a hyper-adhesive state of these intercellular junctions that is crucial for the maintenance of epidermal integrity. Desmosomes change to a lower affinity, calcium-dependent adhesive state when cells are cultured at low density or when an intact epithelial cell sheet is wounded. Here we demonstrate that cells of the immortalized human keratinocyte line HaCaT acquire calcium-independent desmosomes in confluent culture. An adhesion assay shows that HaCaT cells with calcium-independent desmosomes are more cohesive than cells with calcium-dependent desmosomes. This assay relates directly to desmosomal adhesion because it involves splitting of the desmosomal adhesive material. Moreover, the difference in adhesiveness between calcium-dependent and calcium-independent desmosomes involves no quantitative change in the known protein composition of desmosomes. Instead, switching between the two adhesive states can be achieved by activation or inhibition of protein kinase C (PKC), suggesting a direct effect of PKC signalling on desmosomal adhesion. These results provide direct support for the concept of hyper-adhesiveness in desmosomes.


Metastatic bone cancer as a recurrence of early gastric cancer -- characteristics and possible mechanisms.
The surgical outcome of most early gastric cancer (EGC) is usually satisfactory. Some cases show bone metastasis even though the depth of cancer invasion is confined to the mucosa. The most frequent site for recurrence of EGC is the liver. Cases of EGC with bone metastasis are reviewed to clarify the clinicopathological characteristics of EGC giving rise to bone metastasis. Possible mechanisms and risk factors underlying this rare condition are proposed. Forty-six cases of bone metastasis from EGC are reviewed from published reports and meeting proceedings in Japan. This investigation suggests that risk factors for bone metastasis from EGC include depressed-type signet-ring cell carcinoma, poorly differentiated carcinoma, and/or the likely involvement of lymph node metastasis, even though the cancer is confined to the gastric mucosa. The risk factors do not include recurrence of EGC in the liver. We speculate that the mechanism of bone metastasis from EGC is via lymphatic channels and systemic circulation. Post-operative follow-up of cases should consider the development of bone metastasis from EGC. We propose the use of elevated alkaline phosphatase levels for the detection of bone metastasis and recommend bone scintigraphy in positive cases.


Targeting the TSH receptor in thyroid cancer.
Recent advances in the arena of theranostics have necessitated a re-examining of previously established fields. The existing paradigm of therapeutic thyroid-stimulating hormone receptor (TSHR) targeting in the post-surgical management of differentiated thyroid cancer using levothyroxine and recombinant human thyroid-stimulating hormone (TSH) is well understood. However, in an era of personalized medicine, and with an increasing awareness of the risk profile of longstanding pharmacological hyperthyroidism, it is imperative clinicians understand the molecular basis and magnitude of benefit for individual patients. Furthermore, TSHR has been recently re-conceived as a selective target for residual metastatic thyroid cancer, with pilot data demonstrating effective targeting of nanoparticles to thyroid cancers using this receptor as a target. This review examines the evidence for TSHR signaling as an oncogenic pathway and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases. Priorities for further research are highlighted.


Medicines optimization for patients with chronic kidney disease in the outpatient setting: the role of the clinical pharmacist.
Medicines optimization (MO) in patients with chronic kidney disease (CKD) is at high risk at transition points of different ambulatory care levels such as nephrologists in outpatient clinics and general practitioners (GPs). We examined if adding a clinical pharmacist to the therapeutic team promotes implementation of nephrologists' drug therapy recommendations by GPs' and reduces drug-related problems (DRPs). A prospective, controlled intervention study was conducted in the nephrology outpatient clinic of the Klinikum Fulda, Germany. The control and intervention phases took place successively. Patients with CKD stage 3-5 and at least one concomitant disease, for example, arterial hypertension or type-2 diabetes were recruited consecutively in three subgroups (naive, 1 contact, ≥2 contacts with nephrologist) from June 2015 to May 2019. GPs' acceptance and frequency of DRPs without (control group [CG]) and with (intervention group [IG]) pharmacist's interventions were compared after 6 months. Interventions include educational training events for GPs between control- and intervention phase, medication therapy management and pharmaceutical patient counselling. In total, 256 patients (CG = 160, IG = 96) were recruited into the study. GPs' acceptance of nephrologists' medication recommendations increased significantly among naive patients and those with one prior contact with the nephrologist (CG/IG: naive = 72.8%/95.5%, 1 contact = 81.1%/94.4%; P < 0.001). DRPs per patient were significantly reduced in all subgroups (P < 0.001). Interdisciplinary collaboration between the nephrologist, GPs and clinical pharmacist resulted in better MO for patients with CKD.


Spectral sensitivity and wavelength discrimination of the human peripheral visual field.
Spectral sensitivity and wavelength discrimination are determined along the nasal horizontal meridian of the human peripheral retina. The target size as a function of eccentricity is varied according to a particular cortical magnification factor. Spectral sensitivity is measured by flicker photometry parameterized for the flicker frequency (10-20 Hz) and is found to be independent of the eccentricity (0-80 degrees) for 20-Hz flicker photometry after correction of the foveal spectral sensitivity for macular pigment absorption. This 20-Hz function is chosen as being representative for the peripheral luminous-efficiency function and is used in the wavelength-discrimination experiments. The peripheral retina can perform wavelength discrimination up to an eccentricity of 80 degrees. If field-size scaling according to the eccentricity-dependent cone density, the cortical magnification factor, or the reciprocal of the interganglion cell distance is applied, then wavelength-discrimination performance from 8 degrees to 80 degrees eccentricity is roughly the same. Foveal wavelength discrimination is considerably better than peripheral wavelength discrimination.


[Treatment of developmental disorders--principles, methods and indication].
In a review article, the basic principles of special education and therapies for children with developmental disabilities are discussed. Physiotherapy, occupational therapy, speech therapy and psychomotor therapy are the most widely used treatment methods. In addition there are many preschool programs of special schools. The essence of all these activities (infant stimulation, parent education, and home based services) should have the aim to challenge active and self-guided movements or plays which have the highest likelihood to effect an improvement and success of early intervention. Perhaps one of the most important goals of early intervention programmes is to stimulate comprehension the parents and the families and capabilities of their children.


The significance of cutaneous immunoglobulin deposits in lupus erythematosus and NZB/NZW F1 hybrid mice.
In 50 to 60 percent of patients with systemic lupus erythematosus (SLE), a band of immunoglobulins beneath the epidermis of visibly normal skin. This highly specific finding has been used as a diagnostic test (Lupus Band Test) for SLE. Similar immunoglobulin deposits are found in an inbred strain of New Zealand mice which spontaneously develop an autoimmune disease with many features of SLE. Subepidermal immunoglobulin deposits are found most frequently in SLE patients with proliferative glomerulonephritis, hypocomplementemia, and serum antibodies to native DNA (anti-nDNA). When anti-nDNA levels are suppressed by cyclophosphamide, these deposits disappear. The subepidermal accumulation of immunoglobulin in SLE patients and in the mouse model apparently depends on the presence of antibody to native DNA. It is proposed that serum anti-nDNA precipitates with nDNA which is released locally from epidermal nuclear breakdown.


[Invasion by trichinae in the patient hospitalized with suspicion of occupational borreliosis: a case report].
Diagnosis of occupational infectious diseases gives rise to a number of problems in the practice of occupational medicine. Similar symptoms of many infections, including parasitic diseases, can limit the range of applied diagnostic and certification procedures only to diseases induced by pathogenic agents or exposures occurring in the occupational environment. In some cases this makes difficult or even impossible to explain a real cause of patients' complaints. We present a case report on the patient with suspected occupational borreliosis. Due to many diagnostic doubts during hospitalization, including long term presence of some clinical manifestations reported by the patient, which could occur in the course of borreliosis and also suggest earlier infection by trichinae, a wider span of specialist examinations was applied. Finally, the invasion of trichinae was diagnosed and later confirmed by serologic tests.


Detection and typing of human papillomavirus by e6 nested multiplex PCR.
A nested multiplex PCR (NMPCR) assay that combines degenerate E6/E7 consensus primers and type-specific primers was evaluated for the detection and typing of human papillomavirus (HPV) genotypes 6/11, 16, 18, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 56, 58, 59, 66, and 68 using HPV DNA-containing plasmids and cervical scrapes (n = 1,525). The performance of the NMPCR assay relative to that of conventional PCR with MY09-MY11 and GP5+-GP6+ primers, and nested PCR with these two primer sets (MY/GP) was evaluated in 495 cervical scrapes with corresponding histologic and cytologic findings. HPV prevalence rates determined with the NMPCR assay were 34.7% (102 of 294) in the absence of cervical intraepithelial neoplasia (CIN 0), 94.2% (113 of 120) in the presence of mild or moderate dysplasia (CIN I/II), and 97.8% (44 of 45) in the presence of severe dysplasia (CIN III). The combination of all four HPV detection methods applied in the study was taken as "gold standard": in all three morphological subgroups the NMPCR assay had significantly (P < 0.0001) higher sensitivities than the MY09-MY11 and GP5+-GP6+ assays and sensitivities comparable or equal to those of the MY/GP assay. All 18 HPV genotypes investigated were detected among the clinical samples. The ratio of high- to low-risk HPV genotypes increased from 4:1 (80 of 103) in CIN 0 to 19:1 (149 of 157) in CIN I to III. Multiple infections were detected in 47.9% (124 of 259) of the patients. In conclusion, the novel NMPCR method is a sensitive and useful tool for HPV DNA detection, especially when exact HPV genotyping and the identification of multiple HPV infections are required.


How do we target the factors that maintain anorexia nervosa? A behaviour change taxonomical analysis.
All psychological treatments for anorexia nervosa appear to have equal (albeit modest) effects. This may be explained because they target similar processes. Although different psychological treatments have been developed for anorexia nervosa treatment, their taxonomical components have not been compared. This study undertook a taxonomical analysis of behaviour change techniques (BCTs), using the CALO-RE analysis tool, from the manuals of Enhanced Cognitive Behavioural Therapy (CBT-E), Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA), Family Based Therapy (FBT), Specialist Supportive Clinical Management (SSCM), and Focal Psychodynamic Psychotherapy (FPT). The highest number of BCTs were found in FPT (72,5%), and the lowest were in SSCM (30%). The other interventions had a similar range of BCTs which mainly focused on goal planning (FBT (50%), CBT-E (47.5%), MANTRA (42.5%)). Modelling, shaping, and training communication, self-monitoring, and fear arousal were the less commonly used BCTs across manuals. Manualized psychological interventions for people with anorexia nervosa share a substantial number of behaviour change techniques which might explain their similar levels of effectiveness. New strategies may be needed in order to improve outcomes.


Molecular evolution of the proopiomelanocortin system in Barn owl species.
Examination of genetic polymorphisms in outbred wild-living species provides insights into the evolution of complex systems. In higher vertebrates, the proopiomelanocortin (POMC) precursor gives rise to α-, β-, and γ-melanocyte-stimulating hormones (MSH), which are involved in numerous physiological aspects. Genetic defects in POMC are linked to metabolic disorders in humans and animals. In the present study, we undertook an evolutionary genetic approach complemented with biochemistry to investigate the functional consequences of genetic polymorphisms in the POMC system of free-living outbred barn owl species (family Tytonidae) at the molecular level. Our phylogenetic studies revealed a striking correlation between a loss-of-function H9P mutation in the β-MSH receptor-binding motif and an extension of a poly-serine stretch in γ3-MSH to ≥7 residues that arose in the barn owl group 6-8 MYA ago. We found that extension of the poly-serine stretches in the γ-MSH locus affects POMC precursor processing, increasing γ3-MSH production at the expense of γ2-MSH and resulting in an overall reduction of γ-MSH signaling, which may be part of a negative feedback mechanism. Extension of the γ3-MSH poly-serine stretches ≥7 further markedly increases peptide hormone stability in plasma, which is conserved in humans, and is likely relevant to its endocrine function. In sum, our phylogenetic analysis of POMC in wild living owls uncovered a H9P β-MSH mutation subsequent to serine extension in γ3-MSH to 7 residues, which was then followed by further serine extension. The linked MSH mutations highlight the genetic plasticity enabled by the modular design of the POMC gene.


pi protein- and ATP-dependent transitions from 'closed' to 'open' complexes at the gamma ori of plasmid R6K.
R6K-encoded pi protein can bind to the seven, 22 bp tandem iterons of the gamma origin. In this work, we use a variant of pi, His-pi.F107S, that is hyperactive in replication. In vitro, His-pi.F107S-dependent local DNA melting (open complex formation) occurs in the absence of host proteins (IHF/HU or DnaA) and it is positioned in the A + T-rich region adjacent to iterons. Experiments described here examine the effects of ATP, Mg2+ and temperature on the opening reaction. We show that the opening of the gamma origin can occur in the presence of ATP as well as AMP-PCP (a non-hydrolyzable ATP analog). This suggests that, for gamma origin, ATP hydrolysis may be unnecessary for open complex formation facilitated by His-pi.F107S. In the absence of ATP or Mg2+, His-pi.F107S yielded data suggestive of distortions in the iteron attributable to DNA bending rather than DNA melting. Our findings also demonstrate that ATP and pi stimulate open complex formation over a wide range of temperatures, but not at 0 degrees C. These and other results indicate that ATP and/or Mg2+ are not needed for His-pi.F107S binding to iterons and that ATP effects an allosteric change in the protein bound to gamma origin.


Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization.
Bronchopulmonary dysplasia (BPD) and pulmonary emphysema, both significant global health problems, are characterized by a loss of alveoli. Vascular endothelial growth factor (VEGF) is a trophic factor required for endothelial cell survival and is abundantly expressed in the lung. We report that VEGF blockade decreases lung VEGF and VEGF receptor 2 (VEGFR-2) expression in newborn rats and impairs alveolar development, leading to alveolar simplification and loss of lung capillaries, mimicking BPD. In hyperoxia-induced BPD in newborn rats, air space enlargement and loss of lung capillaries are associated with decreased lung VEGF and VEGFR-2 expression. Postnatal intratracheal adenovirus-mediated VEGF gene therapy improves survival, promotes lung capillary formation, and preserves alveolar development in this model of irreversible lung injury. Combined VEGF and angiopoietin-1 gene transfer matures the new vasculature, reducing the vascular leakage seen in VEGF-induced capillaries. These findings underscore the importance of the vasculature in what is traditionally thought of as an airway disease and open new therapeutic avenues for lung diseases characterized by irreversible loss of alveoli through the modulation of angiogenic growth factors.


Insights into properties and energetics of iron-sulfur proteins from simple clusters to nitrogenase.
Some of the principal physical features of iron-sulfur clusters in proteins are analyzed, including metal-ligand covalency, spin polarization, spin coupling, valence delocalization, valence interchange and small reorganization energies, with emphasis on recent spectroscopic and theoretical work. The current state of structural, spectroscopic, and computational knowledge for the iron-sulfur clusters in the nitrogenase iron and iron-molybdenum proteins is examined by comparison and contrast to 'simpler' ironclusters. The differing interactions of the nitrogenase iron and iron-molybdenum clusters compared with those of other iron-sulfur clusters with the protein and solvent environment are also explored.


Screening program of prostate cancer at Tokai University Hospital: characterization of prostate-specific antigen measurement.
A total of 67,214 men participated in screening for prostate cancer (PC) using serum prostate-specific antigen (PSA) from April 1996 to March 2003 at Tokai University Hospital. In 3.5% (2330 / 67,214) of the men, an elevated PSA level (> 4.0 ng/ml) was found and 68.1% (1586/2330) of these subjects were examined at our Urological Outpatient Clinic. Re-testing of PSA showed that 8.4% (133/1586) had a normal level. Needle biopsy of the prostate was performed in 45.2% (633/1453) of the remaining men. As a result, 142 PCs were found and the detection rate was 0.2% (142 / 67,214). The age of the patients with PC was over 50 years. During this period, 135 individuals with voiding dysfunction were also diagnosed as having PC. Comparison of the patients detected by screening with those found at the outpatient clinic revealed significant differences of the age (64.8 vs. 71.9 years, p < 0.0001), serum PSA level (14.6 vs. 154.9 ng/ml, p < 0.0001), and clinical stage (p < 0.0001). In conclusion, a health screening program that includes serum PSA testing is useful for detection of PC at an earlier stage and in younger individuals. We recommend that all men aged 50 years or older undergo testing for PSA to detect PC at an early stage.


Global analysis of DNA methylation in young (J1) and senescent (J2) Gossypium hirsutum L. cotyledons by MeDIP-Seq.
DNA methylation is an important epigenetic modification regulating gene expression, genomic imprinting, transposon silencing and chromatin structure in plants and plays an important role in leaf senescence. However, the DNA methylation pattern during Gossypium hirsutum L. cotyledon senescence is poorly understood. In this study, global DNA methylation patterns were compared between two cotyledon development stages, young (J1) and senescence (J2), using methylated DNA immunoprecipitation (MeDIP-Seq). Methylated cytosine occurred mostly in repeat elements, especially LTR/Gypsy in both J1 and J2. When comparing J1 against J2, there were 1222 down-methylated genes and 623 up-methylated genes. Methylated genes were significantly enriched in carbohydrate metabolism, biosynthesis of other secondary metabolites and amino acid metabolism pathways. The global DNA methylation level decreased from J1 to J2, especially in gene promoters, transcriptional termination regions and regions around CpG islands. We further investigated the expression patterns of 9 DNA methyltransferase-associated genes and 2 DNA demethyltransferase-associated genes from young to senescent cotyledons, which were down-regulated during cotyledon development. In this paper, we first reported that senescent cotton cotyledons exhibited lower DNA methylation levels, primarily due to decreased DNA methyltransferase activity and which also play important role in regulating secondary metabolite process.


[Computed tomography of the retroperitoneum following nephrectomy for renal cell carcinoma].
CT of the retroperitoneum in 70 patients (98 scans) who had undergone previous nephrectomy for renal cell carcinoma was reviewed. The interval between surgical operation and CT scanning were 15 days-7 years. In 59 cases (84%), CT scans were performed within the first 2 years. After nephrectomy, the emptied renal fossae were filled with adjacent organs, such as colon (27), small intestine (21), liver (14), inferior vena cava (3), adrenal gland (2) on the right side, and spleen (28) small intestine (33), colon (15), tail of pancreas (11), adrenal gland (2) on the left. In 47 cases, where CT scans were done within 4 months after operation, there were abscess/hematoma (8) and soft tissue thickening caused by post-operative edema and or inflammation (6). Most of the early post-operative complications gradually reduced in size in the follow-up scans. Local recurrences or metastases were detected by CT scan in 15 cases, with recurrence at the excision site (5), renal bed (6), adrenal gland (4), retroperitoneal lymph nodes (7) and contralateral kidney (1). 7 patients had solitary lesions and 8 patients had multiple recurrences. In 2 patients, local recurrences were detected by routine follow-up CT scanning. In 4 cases, recurrences were proved by surgery, and the others by clinical follow-up. Local recurrences were assessed within 2 years in 10/15 cases (67%), and 4 cases within 6 months. 9 cases had venous thrombosis (IVC 9, renal vein 3), the size of which was reduced after radiotherapy in 1 case. CT is the most preferred imaging technique in evaluating post-nephrectomy patients for renal cell carcinoma.


Maribavir inhibits Epstein-Barr virus transcription through the EBV protein kinase.
Maribavir (MBV) inhibits Epstein-Barr virus (EBV) replication and the enzymatic activity of the viral protein kinase BGLF4. MBV also inhibits expression of multiple EBV transcripts during EBV lytic infection. Here we demonstrate, with the use of a BGLF4 knockout virus, that effects of MBV on transcription take place primarily through inhibition of BGLF4. MBV inhibits viral genome copy numbers and infectivity to levels similar to and exceeding levels produced by BGLF4 knockout virus.


Effect of hypertriglyceridemia on left ventricular global longitudinal strain in patients with coronary heart disease in Jilin Province, China: a cross-sectional study.
Using speckle tracking technology to investigate the effect of hypertriglyceridemia on the global longitudinal strain(GLS) of the left ventricle in patients with coronary heart disease in the early stage, and to explore the value of myocardial strain in early identification of cardiac dysfunction in patients with coronary heart disease in the pre-heart failure stage. A cross-sectional study of 138 participants was conducted in Jilin Province, China. Basic clinical, biochemical, and echocardiographic data were obtained for all patients. Myocardial strain parameters were compared between the hypertriglyceridemia and normal triglyceride level groups and the effect of hypertriglyceridemia on early left ventricular global longitudinal strain impairment in coronary heart disease patients was evaluated. The overall longitudinal strain of the left ventricle was smaller in the hypertriglyceridemia group than in the normal triglyceride group. After the multivariate Logistic regression model adjusting for the influence of confounding factors, the results remained stable. The risk of impairment of global longitudinal strain of the left ventricle in patients with coronary heart disease is positively correlated with triglyceride levels, and hypertriglyceridemia maybe an independent risk factor affecting early cardiac dysfunction in the pre-heart failure stage of patients with coronary heart disease.


The Role of Health Care Transformation for the Chinese Dream: Powering Economic Growth, Promoting a Harmonious Society.
After having successfully expanded health insurance coverage, China now faces the challenge of building an effective and efficient delivery system to serve its large and aging population. The country finds itself at a crossroads-it can emulate the models of Western countries with their well-known limitations, or embark on an ambitious endeavor to create an innovative and sustainable model. We recommend that China choose the second option and design and implement a health care system based on population health management principles and sophisticated health information technology. Taking this path could yield a triple dividend for China: Health care will contribute to the growth of service sector employment, stimulate domestic demand by unlocking savings, and enable China to export its health system development capabilities to other emerging economies, mirroring its success in building other critical infrastructure. These forces can help turn the Chinese Dream into a reality.


Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.
Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.


[A case of recurrent breast cancer that responded to bevacizumab].
We report a case of a 59-year-old woman who was forced to undergo mastectomy of the right breast (Rt Bt) plus axillary lymph node (Ax) dissection for right breast cancer at another hospital. The pathological diagnosis was invasive ductal carcinoma( scirrhou[s sci], pT2N2M0, Stage IIIA, estrogen recepto[r ER[]+], progesterone recepto[r PgR[]+], human epidermal growth factor receptor-2[HER2][2+]). Although no recurrence was observed after postoperative adjuvant chemotherapy and endocrine therapy, skin metastasis on the left back and pleuritis carcinomatosa were detected at our hospital 9 years and 6 months after the operation. Thereafter, bone metastasis, contralateral lymph node metastasis, and frequent occurrence of hepatic metastasis were sequentially detected. The patient was treated with chemotherapy (a total of 4 regimens) and endocrine therapy in addition to radiation therapy for lymph node metastasis over a period of approximately 2 years and 3 months; however, disease control was poor. Therefore, combined chemotherapy with paclitaxel and bevacizumab was initiated from February 2012. Soon after the initiation of combination therapy, the serum carcinoembryonic antigen (CEA) level gradually reduced and computed tomography (CT) revealed that the multiple-organ metastases had remarkably reduced in size. The response was classified as a clinical partial response (cPR). Although adverse events such as peripheral neuropathy, nose bleeding, and high blood pressure were observed, these were all of lesser that Grade 2 severity. The efficacy of chemotherapy was noted for 11 months.


Medicaid managed care and STDs: missed opportunities to control the epidemic.
We examined the extent to which selected Medicaid managed care organizations (MCOs) promoted certain prevention and control services for sexually transmitted diseases (STDs) and the potential influence of health plans and medical groups on the delivery of STD care by primary care providers (PCPs) in seven large U.S. cities. Low-cost clinical services were routinely performed by PCPs, but higher-cost services were less often provided. Lack of organizational priority to promote STD prevention and control is a major barrier even for those MCOs that serve this high-risk, low-income population. Stronger incentives and legally binding provisions in Medicaid contracts are needed to promote adherence to standards of STD care.


Transposed arteriovenous fistulae: do the results justify the effort?
Transposed arteriovenous fistulae have been utilized in clinical scenarios where simple arteriovenous fistulae have failed or their construction was not possible for anatomical reasons. Despite variability in published reports, transposed arteriovenous fistulae have acceptable patency rates and outperform prosthetic arteriovenous grafts in patency, frequency of intervention to maintain patency, and complication rates.


Design Strategies for Cellular Nanosponges as Medical Countermeasures.
The interest in using therapeutic nanoparticles to bind with harmful molecules or pathogens and subsequently neutralize their bioactivity has grown tremendously. Among various nanomedicine platforms, cell membrane-coated nanoparticles, namely, "cellular nanosponges," stand out for their broad-spectrum neutralization capability challenging to achieve in traditional countermeasure technologies. Such ability is attributable to their cellular function-based rather than target structure-based working principle. Integrating cellular nanosponges with various synthetic substrates further makes their applications exceptionally versatile and adaptive. This review discusses the latest cellular nanosponge technology focusing on how the structure-function relationship in different designs has led to versatile and potent medical countermeasures. Four design strategies are discussed, including harnessing native cell membrane functions for biological neutralization, functionalizing cell membrane coatings to enhance neutralization capabilities, combining cell membranes and functional cores for multimodal neutralization, and integrating cellular nanosponges with hydrogels for localized applications. Examples in each design strategy are selected, and the discussion is to highlight their structure-function relationships in complex disease settings. The review may inspire additional design strategies for cellular nanosponges and fulfill even broader medical applications.


Bottle-brush polymers as an intermediate between star and cylindrical polymers.
We present a theoretical study of a single bottle-brush molecule, which consists of multiarmed polymer stars grafted densely onto a stiff backbone. Mean-field approximation and a variational approach are used to calculate the dominant trajectories of the grafted chains, the shape of the molecule, and the segment density distribution around the backbone. All these properties are calculated for an arbitrary relationship between the size of the backbone and that of a grafted star. Hence cylindrical comb copolymer brushes and spherically symmetric polymer stars are considered as the limiting cases of the present problem.


Association of Clinical Factors with the Costs of Kidney Transplantation in the Current Era.
BACKGROUND Kidney transplantation is reported to save costs compared to maintenance dialysis. We analyzed the current actual costs of kidney transplantation compared to dialysis, and analyzed risk factors for higher costs after transplantation. MATERIAL AND METHODS Altogether, 338 kidney transplant recipients between 2009 and 2014 were included in this study. All individual-level cost data from specialized health care and data from all reimbursed medication and travel costs were acquired from official records. Cost data were compared before and after transplantation within the same patients starting from dialysis initiation and continued until the end of follow-up at the end of 2015. RESULTS Total annual costs were median 53 275 EUR per patient in dialysis, 59 583 EUR for the first post-transplantation year (P<0.001), and 12 045 EUR for the subsequent years (P<0.001 compared to dialysis). Median costs for specialized health care were 36 103 EUR/year per patient during dialysis, compared to median 51 640 EUR for the first post-transplantation year (P<0.001 compared to dialysis), whereas the median costs for the subsequent years declined to median 4895 EUR/year (P<0.001 compared to dialysis). The median annual costs for drug treatments and travel reimbursements during dialysis were higher compared to after transplantation (P<0.001). Delayed graft function and highly sensitized status were independent risk factor for higher costs during the first the post-transplantation year. CONCLUSIONS After the first posttransplant year the costs of a kidney transplant patient for the health care system are <1/3 of the costs seen during dialysis treatment. Delayed graft function and previous sensitization were associated with increased costs post-transplantation.


Treatment of free-flowing tuberculous pleurisy with intrapleural urokinase.
Patients with loculated tuberculous pleurisy (TBP) treated with urokinase suffer less from residual pleural thickening (RPT) than those treated with simple drainage. However, the role of intrapleural urokinase in free-flowing TBP patients remains unclear. A total of 318 patients with presumed TBP were screened. The final 171 patients who participated in the study were randomly allocated to the urokinase group (n = 86) and the control group (n = 85). Personalised doses of urokinase were infused via a catheter. This procedure was repeated every 24 h until the volume of pleural fluid obtained was less than 50 ml after three injections. Changes in lung function and pleural thickening were recorded and compared between both groups periodically for 24 weeks. Seven patients (9.1%) had restrictive functional sequelae in the control group, while no patient in the urokinase group suffered from sequelae (P < 0.05). The incidence of RPT (⩾10 mm) was 0 for the urokinase group and 9.1% for the control group (P < 0.05). A lower percentage of patients treated with intrapleural urokinase had blunted costophrenic angle than controls (5.1% vs.19.5%, P < 0.05). Patients with free-flowing TBP treated with urokinase suffered less from RPT than those treated with drainage.


Biodegradation of anionic surfactants by Alcaligenes faecalis, Enterobacter cloacae and Serratia marcescens strains isolated from industrial wastewater.
Pseudo-persistent organic pollutants, such as anionic surfactants (AS), are nowadays among the more complex problems that threaten the aquatic environments and other environmental compartments. The present work describes the identification and efficiency of a consortium, isolated from Algerian industrial wastewater, to remove three anionic surfactants (i.e., sodium dodecylbenzenesulfonate (SDBS), sodium dodecyl sulfate (SDS) and sodium lauryl ether sulfate (SLES)). The genetic analysis of 16S rRNA indicated that these strains are Alcaligenes faecalis, Enterobacter cloacae and Serratia marcescens. Under aerobic conditions, pH 7.0 and optimum temperature of 30 °C, the mixed consortium allowed to degrade 85.1% of initial SDBS amount after 144 h of incubation with half-life of 20.8 h. While E. cloacae and S. marcescens pure strains eliminated 46% and 41% less SDBS respectively. Evenly, SDS was degraded at only 23.71% by A. faecalis strain. However, the degradation capacity of SDS by the consortium was very high (94.2%) with a half-life of 9.8 h. The SLES anionic surfactant showed a lower biodegradation by the consortium (47.53%) due to the presence of ether oxide units in the chemical structure of SLES which induced toxicity to the medium. The investigation of the biodegradation of this type of organic pollutants by microorganisms has recently become a key issue for the environmental protection area.


Recurrent severe anion gap metabolic acidosis secondary to episodic ethylene glycol intoxication.
Acute ethylene glycol toxicity and its attendant metabolic derangement is a well described clinical entity. Recurrent severe anion gap metabolic acidosis consequent to episodic ingestion of ethylene glycol has not been previously reported. We present a patient who developed severe anion gap metabolic acidosis with no osmolar gap and hypokalemia, consequent to episodic ethylene glycol ingestion. Modest artifactual elevation of the serum lactic acid level and rapid response to intravenous bicarbonate infusion may serve as diagnostic clues. Consideration of these aberrant features should be included in the clinical assessment of severe anion gap metabolic acidosis.


Development of mandibular osteoradionecrosis in rats: Importance of dental extraction.
To develop an animal model of mandibular osteoradionecrosis (ORN) using a high-energy radiation source (as used in human therapeutics) and to assess the role of tooth extraction on ORN development. Ten animals were irradiated with a single 35- or 50-Gy dose. Three weeks later, the second left mandibular molar was extracted from three animals in each group. Nine weeks after irradiation, the animals were euthanized, with an injection of contrast agent in the bloodstream to highlight vascularization. Mandibles were harvested and studied using micro-CT, histology, tartrate-resistant acid phosphatase activity and scanning electron microscopy. This study demonstrates that a single 50-Gy dose associated with molar extraction is necessary for ORN development. In these conditions, absence of healing of the mucosa and bone, dental effects, fibrosis, an increase in osteoclast activity and a decrease in vascularization were observed. We also determined that molar extraction increases the impact of the cellular effects of radiation. The mandibular ORN animal model was validated after 50-Gy irradiation and molar extraction. The results of this study therefore support an animal ORN model and tissue engineering strategies will now be developed to regenerate bone for patients with head and neck cancer.


Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.
Activation of T cells through the engagement of the T cell receptors (TCRs) with specific peptide-MHC complexes on antigen presenting cells (APCs) is the major determinant for their proliferation, differentiation and display of effector functions. To assess the role of quantity and quality of peptide-MHC presentation in eliciting T cell activation and suppression functions, we genetically engineered human T cells with two TCRs that recognize HLA-A*0201-restricted peptides derived from either HIV or melanoma antigens. The engineered-TCRs are highly functional in both CD8(+) and CD4(+) T cells as assessed by the upregulation of activation markers, induction of cytokine secretion and cytotoxicity. We further demonstrated that engineered-TCRs can also be expressed on naïve human T cells, which are stimulated through APCs presenting specific peptides to induce T cell proliferation and acquire effector functions. Furthermore, regulatory T cells (Tregs) ectopically expressing the engineered-TCRs are activated in an antigen-specific fashion and suppress T cell proliferation. In this system, the inhibitory activity of peptide-stimulated Tregs require the presence of dendritic cells (DCs) in the culture, either as presenters or as bystander cells, pointing to a critical role for DCs in suppression by Tregs. In conclusion, the engineered-TCR system reported here advances our ability to understand the differentiation pathways of naïve T cells into antigen-specific effector cells and the role of antigen-specific signaling in Treg-mediated immune suppression.


Responses of mesangial cells of autoimmune mice to cytokines.
Glomerulonephritis is one of the most important complications of SLE. The genesis of the renal lesions in this disorder is determined by a cascade of events that leads to mesangial cell proliferation as one of the hallmarks of the kidney disease. The current study examines the postulate that there may be intrinsic abnormalities in the mesangial cells of the autoimmune host which predisposes it to develop nephritis. It investigates the possibility that growth responses of mesangial cells of the autoimmune MRL/MpJ-lpr/lpr mice are different from those of their congenic normal MRL/MpJ-(+)/+ (MRL-(++)) counterparts when cultured with various cytokines. To test this possibility, growth responses of mesangial cells as assessed by [3H]TdR uptake were measured when these cells were cultured with epidermal growth factor, platelet-derived growth factor, transforming growth factor-beta, and 1,25-dihydroxy vitamin D3. Epidermal growth factor stimulated the growth of mesangial cells of both strains of mice equally, but platelet-derived growth factor appeared to elicit a more pronounced proliferative response from mesangial cells of the autoimmune mice. In regard to inhibitory substances tested, mesangial cells of autoimmune MRL-lpr mice appeared to be relatively insensitive to the suppressive effects of transforming growth factor-beta and 1,25-dihydroxy vitamin D3. Collectively, the response profile of mesangial cells of the MRL-lpr mice suggests that these cells have a tendency to proliferate when they are acted on by cytokines, so that they may be more susceptible to develop the proliferative lesions seen in the nephritis of SLE.


Targeting Oncoproteins for Degradation by Small Molecule-Based Proteolysis-Targeting Chimeras (PROTACs) in Sex Hormone-Dependent Cancers.
Sex hormone-dependent cancers, including breast, ovary, and prostate cancer, contribute to the high number of cancer-related deaths worldwide. Steroid hormones promote tumor occurrence, development, and metastasis by acting on receptors, such as estrogen receptors (ERs), androgen receptors (ARs), and estrogen-related receptors (ERRs). Therefore, endocrine therapy targeting ERs, ARs, and ERRs represents the potential and pivotal therapeutic strategy in sex hormone-dependent cancers. Proteolysis-targeting chimeras (PROTACs) are a novel strategy that can harness the potential of the endogenous ubiquitin-proteasome system (UPS) to target and degrade specific proteins, rather than simply inhibiting the activity of target proteins. Small molecule PROTACs degrade a variety of proteins in cells, mice, and humans and are an emerging approach for novel drug development. PROTACs targeting ARs, ERs, ERRs, and other proteins in sex hormone-dependent cancers have been reported and may overcome the problem of resistance to existing endocrine therapy and receptor antagonist treatments. This review briefly introduces the PROTAC strategy and summarizes the progress on the development of small molecule PROTACs targeting oncoproteins in sex hormone-dependent cancers, focusing on breast and prostate cancers.


Iron nitrosyls of a pentadentate ligand containing a single carboxamide group: syntheses, structures, electronic properties, and photolability of NO.
Three iron complexes of a pentadentate ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy(3)H, H is the dissociable amide proton) have been synthesized. All three species, namely, two nitrosyls [(PaPy(3))Fe(NO)](ClO(4))(2) (2) and [(PaPy(3))Fe(NO)](ClO(4)) (3) and one nitro complex [(PaPy(3))Fe(NO(2))](ClO(4)) (4), have been structurally characterized. These complexes provide the opportunity to compare the structural and spectral properties of a set of isostructural [Fe-NO](6,7) complexes (2 and 3, respectively) and an analogous genuine Fe(III) complex with an "innocent" sixth ligand ([(PaPy(3))Fe(NO(2))](ClO(4)), 4). The most striking difference in the structural features of 2 and 3 is the Fe-N-O angle (Fe-N-O = 173.1(2) degrees in the case of 2 and 141.29(15) degrees in the case of 3). The clean (1)H NMR spectrum of 2 in CD(3)CN reveals its S = 0 ground state and confirms its [Fe-NO](6) configuration. The binding of NO at the non-heme iron center in 2 is completely reversible and the bound NO is photolabile. Mössbauer data, electron paramagnetic resonance signal at g approximately 2.00, and variable temperature magnetic susceptibility measurements indicate the S = (1)/(2) spin state of the [Fe-NO](7) complex 3. Analysis of the spectroscopic data suggests Fe(II)-NO(+) and Fe(II)-NO(*) formulations for 2 and 3, respectively. The bound NO in 3 does not show any photolability. However, in MeCN solution, it reacts rapidly with dioxygen to afford the nitro complex 4, which has also been synthesized independently from [(PaPy(3))Fe(MeCN)](2+) and NO(2)(-). Nucleophilic attack of hydroxide ion to the N atom of the NO ligand in 2 in MeCN in the dark gives rise to 4 in high yield.


High-risk fertility behaviours among women of reproductive ages in the Democratic Republic of the Congo: Prevalence, correlates, and spatial distribution.
High-risk fertility behaviour remains a major public health in the Democratic Republic of the Congo, like other sub-Saharan Africa countries, especially because Total Fertility Rate (TFR) is very high in the country, estimated at 6.6 children. Despite the commendable progress in reducing maternal deaths in the region, sub-Saharan Africa is still lagging very behind compared with other regions. Yet, high-risk fertility behaviours are pivotal to improve maternal and child health. This study aims to assess geographical variations of, and to identify risk factors associated with high-risk fertility behaviours among married women in the Democratic Republic of the Congo using the 2013-14 Demographic and Health Survey. Overall, 11,497 married women were selected from a nationally representative using a two-stage sampling design. Standard logistic regressions were performed to identify individual- and household/community-level factors associated with high-risk fertility behaviours. Additionally, interactions between women's age and education, and urban residence were tested. Bernoulli based spatial scan statistics were used to identify the presence of high-risk fertility behaviours spatial clusters using Kulldorff's SaTScan version 9.6 software. ArcGIS 10.7 was used to visualize the spatial variations of high-risk fertility behaviours. Geographically weighted regression (GWR) analysis was employed using Multiscale GWR version 2.0 software. Findings indicated that more than two-third of married women exhibited high-risk fertility behaviours in the Democratic Republic of the Congo. Multivariate logistic regression showed that education was negatively and significantly associated with the odds of high-risk fertility behaviours. In contrast, women's age significantly increased the odds of high-risk fertility behaviours. Interactions between urban residence and women's education and age confirmed the urban advantage identified from previous studies. Finally, high-risk fertility behaviours were highly clustered in the Northeastern provinces of the country. The study showed that there were significant geographical variations of high-risk fertility behaviours across provinces in the Democratic Republic of the Congo. The paper also identified significant-high hot spots of high-risk fertility behaviours in the Northeastern provinces of the country. To reduce high-risk fertility behaviours, and ultimately improve maternal and child outcomes in the country, policymakers and health planners need to strategically address these inequalities. Finally, this paper highlighted the persistent needs of country-specific studies due to differences across sub-Saharan African countries in terms of social development and cultures.


Preliminary observations on the BK 8518 mandible from Baringo, Kenya.
A newly discovered adult hominid mandible (BK 8518) from Baringo, Kenya, is described and assessed. The corpus, many of the tooth crowns, and most of the left ascending ramus are preserved. The teeth are heavily and asymmetrically worn. Compared with BK 67 (the 1966 mandible) the body of BK 8518 is more robust; the internal symphyseal buttressing is more pronounced; the M3s have seven cusps and exceed the M2s in size. There are no compelling reasons, however, to attribute the two mandibles to different taxa and, in view of the lack of any comprehensive taxonomic diagnosis for Homo erectus, "erectus-like," and habiline mandibular remains, the new specimen is also best regarded as Homo sp. indet. (aff. erectus).


Paracoccusacridae sp. nov., isolated from the insect Acrida cinerea living in deserted cropland.
A Gram-stain-negative, aerobic, rod-shaped, non-motile bacterial strain, designated SCU-M53T, was isolated from the insect Acrida cinerea. Phylogenetic analysis on the basis of 16S rRNA gene sequences showed that strain SCU-M53T belonged to the genus Paracoccus, having Paracoccus chinensisNBRC 104937T (97.04 % 16S rRNA gene sequence similarity) and Paracoccus niistensis KCTC 22789T (96.70 %) as the most closely related phylogenetic neighbours. Growth occurred at 10-40 °C (optimum 25-30 °C), pH 5.0-10.0 (optimum pH 6.5-7.5) and with 0-4 % (w/v) NaCl (optimum 0-1 % NaCl). The fatty acids of strain SCU-M53T were C18 : 1ω7c, C18 : 0, C16 : 0, C14 : 0 3-OH, C14 : 0 and C10 : 0 3-OH. The polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, an unknown aminolipid, two unknown phospholipids and two unknown lipids. The isoprenoid quinone was ubiquinone-10. The DNA G+C content was 60.6 mol%. Strain SCU-M53T exhibited 36.5 and 28.6 % DNA-DNA relatedness to P. chinensis NBRC 104937T and P. niistensis KCTC 22789T, respectively. According to these results, strain SCU-M53T represents a novel species of the genus Paracoccus, for which the name Paracoccus acridae sp. nov. is proposed. The type strain is SCU-M53T (=KCTC 42932T=CGMCC 1.15419T).


Tessellating the Latent Space for Non-Adversarial Generative Auto-Encoders.
Non-adversarial generative models are relatively easy to train and have less mode collapse than adversarial models. However, they are not very accurate in approximating the target distribution in latent space because they don't have a discriminator. To this end, we develop a novel divide-and-conquer model called Tessellated Wasserstein Auto-Encoders (TWAE) which has less statistical error in approximating the target distribution. TWAE tessellates the support of the target distribution into a given number of regions using the centroidal Voronoi tessellation (CVT) technique and designs data batches according to the tessellation instead of random shuffling for accurate computation of discrepancy. Theoretically, we demonstrate that the error in estimating the discrepancy decreases as the number of samples n and the regions m of the tessellation increase at rates of [Formula: see text] and [Formula: see text], respectively. TWAE is very flexible to different non-adversarial metrics and can significantly enhance their generative performance in terms of Fréchet inception distance (FID) compared to existing ones. Furthermore, numerical results demonstrate that TWAE is competitive to the adversarial model and shows powerful generative ability.


3D 3C-SiC/Graphene Hybrid Nanolaminate Films for High-Performance Supercapacitors.
High-performance supercapacitors feature big and stable capacitances and high power and energy densities. To fabricate high-performance supercapacitors, 3D 3C-SiC/graphene hybrid nanolaminate films are grown via a microwave plasma-assisted chemical vapor deposition technique. Such films consist of 3D alternating structures of vertically aligned 3C-SiC and graphene layers, leading to high surface areas and excellent conductivity. They are further applied as the capacitor electrodes to construct electrical double layer capacitors (EDLCs) and pseudocapacitors (PCs) in both aqueous and organic solutions. The capacitance for an EDLC in aqueous solutions is up to 549.9 µF cm-2 , more than 100 times higher than that of an epitaxial 3C-SiC film. In organic solutions, it is 297.3 µF cm-2 . The pseudocapacitance in redox-active species (0.05 Fe(CN)6 3-/4- ) contained aqueous solutions is as high as 62.2 mF cm-2 . The capacitance remains at 98% of the initial value after 2500 charging/discharging cycles, indicating excellent cyclic stability. In redox-active species (0.01 m ferrocene) contained organic solutions, it is 16.6 mF cm-2 . Energy and power densities of a PC in aqueous solution are 11.6 W h kg-1 and 5.1 kW kg-1 , respectively. These vertically aligned 3C-SiC/graphene hybrid nanolaminate films are thus promising electrode materials for energy storage applications.


Immunogenetics of collagen-induced arthritis in rats.
CIA can be viewed as a multifactorial animal model of experimentally-induced autoimmunity that is targeted to joint tissues and under multiple gene control. Thus, although induction of CIA requires immune reactivity to type II collagen, a high immune response to type II collagen is not pathognomonic of CIA, indicating that determinant specificity is of crucial importance. Also, both RT1-linked and non-RT1-linked gene directed functions are involved in the final clinical response to immunization with type II collagen. RT1-linked control is likely exerted at the level of Class II (Ia) molecules (as it is in mice) with inherent selectivity of arthritogenic vs non-arthritogenic epitopes for presentation to the immune response system; non-RT1-linked control may reflect genes controlling T-cell receptors, immunoglobulin subtypes or complement components. There is also evidence that the effects of potentially pathological anti-collagen autoimmunity may in some strains be muted or even obviated by other non-RT1 gene controlled traits that are not directly related to the immune system. These general conclusions are in close accord with those of other investigators who have carefully conducted extensive and in-depth studies of the immunogenetics of CIA in mice. CIA is obviously not an exact model of any one of the more common rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus. In fact, it is more closely analogous to polychondritis and some of the other sero-negative connective tissue diseases. However, CIA remains an extremely useful model in attempts to understand the genetic and environmental factors which influence a specific and definable autoimmune process--anti-collagen reactivity. In turn, autoimmunity to collagen, and to other autoantigens, is a contributing or complicating aspect of most of the diverse human rheumatic disease syndromes which have been identified to date. The characteristics of the CIA model in rats which have been discussed in this article, i.e., genetically controlled variations in incidence, severity, rate of progression and expression of clinical disease, are also characteristic of the human rheumatic disease patient population. Likewise, the probable contribution of multiple genes to these syndromes is recognized. Continued investigation of the CIA model can be expected to yield important information that can be used to better understand its human counterparts.


Design, synthesis, and initial evaluation of high-affinity technetium bombesin analogues.
Potent antagonists of bombesin-like peptides have shown great potential for applications in cancer therapy. A 99mTc-labeled agent capable of identifying patients who could benefit from these emerging therapies would have a great impact on patient management. This study involves the synthesis and initial evaluation of technetium diaminedithiolate analogues derived from the potent bombesin analogue Pyr-Gln-Lys-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 (Lys3-bombesin). We coupled two diaminedithiol (DADT) bifunctional chelating agents (BCAs 1 and 2) to the Lys3 residue at the N-terminal region that is not required for binding to the receptor. 99mTc labeling was performed by ligand exchange on addition of [99mTc]glucoheptonate to a solution of the adduct at room temperature. Two products were obtained from each adduct on analysis by HPLC. The major to minor product ratios of the 99mTc-labeled analogues were 3:1 for products from BCA 1 and 9:1 for the products from BCA 2. Macroscopic amounts of the 99Tc analogues were similarly prepared using [99Tc]glucoheptonate. In this case, the major to minor ratios were 2:1 for the products from both BCAs. For initial evaluation of the binding of the Tc-labeled peptides to bombesin receptors, the 99Tc analogues were used in vitro in competitive binding assays in rat brain cortex membranes against [125I-Tyr4]bombesin. Results of the in vitro assays showed that the inhibition constants (Ki) of the major and minor products were 3.5+/-0.7 and 3.9+/-1.5 nM, respectively, for the products from BCA 1; and 7.4+/-2.0 and 5.2+/-1.5 nM for the products derived from BCA 2, respectively. The high affinity exhibited by these technetium analogues is an indication of their potential for use in non-invasive in vivo biochemical characterization of cancers that possess receptors for bombesin.