Thievery, home ranges, and nestmate recognition inEctatomma ruidum.
Thievery of food items among colonies of a ponerine ant,Ectatomma ruidum was common; nonnestmates in colonies or near the colony entrances receive incoming food items and carry them to their own colony. In our study area 7 of 10 colonies were victimized by thief ants. Colonies have discrete home ranges and home range size is correlated with the number of workers in the colony. Worker ants discriminate nestmates from non-nestmates when non-nestmates are presented at colony entrances, but individuals from different colonies were not observed to engage in agonistic interactions away from nest entrances. Non-nestmates gain entrance to colonies when the entrance is unguarded. Many instances of non-nestmates being removed from colonies by residents were observed. The costs and benefits of theft under these circumstances are considered.


Comparison of tendon-bone healing between a newly developed ultrasound device and the conventional metallic drill in a rabbit MCL reconstruction model.
Ligament reconstructive surgeries demand tunnel creation using an over-drilling technique, though this technique has some problems such as metallic particle liberation or difficulties in tunnel creation other than circular cross-section. Recently, a new ultrasound (US) device for bone excavation to overcome these problems was developed. This study aimed to compare the tendon-bone healing in tunnels created using the new US device to that created using the conventional drill in a rabbit model. A total of 72 rabbits underwent a reconstruction for the anterior half of the medial collateral ligament (MCL) using a half of the patellar tendon. For the femoral tunnel creation, a new US device was used in 36 rabbits (US group), while a conventional metallic drill was used for the remaining 36 rabbits (DR group). At 4, 8, and 12 weeks postoperatively, biomechanical (n = 10) and histological (n = 2) evaluations were performed. The ultimate failure load was almost equivalent between the US and DR groups at each period (US/DR; 4 weeks, 50.0 ± 12.8 N/43.4 ± 18.9 N, p = 0.62; 8 weeks, 78.6 ± 11.5 N/77.3 ± 29.9 N, p = 0.92; and 12 weeks: 98.9 ± 33.5 N/102.2 ± 38.3 N, p = 0.80). Pull-out failure from the femoral tunnel was only observed in two rabbits in the US group and one rabbit in the DR group at 4 weeks postoperatively. At 8 and 12 weeks, all specimens had a mid-substance tear. The collagen fiber continuity between tendon and bone occurred 8 weeks postoperatively in both groups and no histological difference was recognized throughout the evaluation period. The tunnels created using the new US device and the conventional drill had equivalent biomechanical and histological features in tendon-bone healing. The bone excavation technology by the new US device may be applicable in ligament reconstructive surgeries.


Clonally related Burkholderia contaminans among ventilated patients without cystic fibrosis.
We investigated a cluster of 10 Burkholderia cepacia complex-positive cultures among ventilated patients and those with a tracheostomy in an acute care hospital. Isolates from 5 patients had outbreak-strain-related Burkholderia contaminans. Isolates of B. cepacia complex unrelated to the outbreak strain were cultured from a sink drain. The investigation identified practices that might have led to contamination of patient respiratory care supplies with tap water, which might have contributed to the cluster.


Heterogeneous response of individual multicellular tumour spheroids to immunotoxins and ricin toxin.
The cytoreductive effects of anti-transferrin receptor (anti-TfnR) immunotoxins (ITs) and of ricin toxin against tumour micromasses have been evaluated in a multicellular tumour spheroid (MTS) model. More than 600 (656) MTSs obtained with human breast carcinoma (MCF7) or rat glioblastoma (9L) cell lines were treated individually with ITs or toxin and the effects induced by the treatment were measured for each MTS as volume variation vs time by applying the Gompertz growth model. Two dose-dependent patterns of MTS growth were observed in MTSs of both cell lines in response to IT or toxin treatment: (1) complete inhibition of MTS growth ('sterilisation'); and (2) partial/complete inhibition ('heterogeneous response'). Within the range of IT or toxin concentrations resulting in partial inhibition of MTS growth, the sensitivity of treated MTSs was extremely heterogeneous (the cytoreductive effects varying between 0.1 and 4 logs of cells killed for a given IT or toxin concentration). Analysis of the post-treatment regrowth kinetics indicated that treated non-sterilised and control MTSs reached the same final limiting volumes. However, the doubling time estimated for the surviving cells of treated MCF7 and 9L MTSs ranged between 15 and 50 h, indicating that each MTS had individual growing potential. In conclusion, our results indicate that at substerilising IT concentrations individual heterogenicity of MTSs may greatly influence the cytoreductive potential of ITs. An implication of our study is that the efficacy of an IT treatment in eradicating disseminated micrometastases may not be predictable a priori. The MTS model that we describe in this paper may help in dissecting out factors limiting the effect of ITs in three-dimensional tumours.


Role of protein kinase C β₂ in relaxin-mediated inhibition of cardiac fibrosis.
Relaxin is a pleiotropic hormone owing endogenous antifibrosis effect on numerous organs. We demonstrated relaxin's inhibitive effect on cardiac fibrosis previously. The aim of this study was to investigate the role of protein kinase C (PKC) β2 in relaxin's action under high glucose conditions. Cardiac fibroblasts (CFs) were isolated, exposed to high glucose and incubated with recombinant human relaxin (rhRLX). Western blot analysis revealed a relaxin-mediated decrease in total expression and translocation of PKCβ2, showing downregulation of PKCβ2 is involved in relaxin's action. Blocking PKCβ2 pathway with ruboxistaurin accelerated rhRLX-mediated inhibition in both proliferation of CFs and deposition of collagen. In conclusion, relaxin can inhibit high glucose-associated cardiac fibrosis partly through PKCβ2 pathway. Further work should be done to fully understand intracellular mechanisms of relaxin's action to accelerate its clinical use.


The 3Rs Concept: Time to Change How We Evaluate the Efficacy of Anthelmintics in Companion Animals.
Experimental infections are required by current guidelines for investigating the efficacy of anthelmintics in dogs and cats. Recently, alternatives to experimental infections and the sacrificing of research dogs and cats have been evaluated, and novel conceptual investigations and methods of examination have been explored. Several of these approaches could potentially be used in efficacy studies for anthelmintics in dogs and cats. Here, we provide food for thought towards using new tools for evaluating the efficacy of anthelmintics in companion animals, for promoting the value of field trials, and for updating the existing guidelines for the efficacy testing of anthelmintics in dogs and cats.


Effect of Phlorotannins from Brown Seaweeds on the In Vitro Digestibility of Pig Feed.
Phlorotannins have been reported to have positive effects on pig health, including improved gut health and digestibility. In this study, we investigate the effect of phenolics found in two brown seaweeds, Ascophyllum nodosum and Fucus serratus, on in vitro dry matter digestibility of seaweeds and commercial pig feed. Phlorotannin extracts and whole seaweeds were supplemented into pig feed to test their effect on digestibility. Solid-phase extraction was used to purify the phenolics to phlorotannins. The results showed a slight decrease in the digestibility of pig feed that was found to be significant when phlorotannin extracts were added from either seaweed. However, when whole A. nodosum was added to the pig feed, the effect on digestibility was less pronounced. Specifically, no significant difference in digestibility was observed at inclusion rates up to 5%, and thereafter results varied. A difference in digestibility was also observed in the same species at the same inclusion rate, collected from different seasons. This suggests that other compounds, e.g., polysaccharides, are having an effect on digestibility when whole seaweeds are supplemented to animal feed. This research has also highlighted the need to base supplementation on phenolic concentration as opposed to a standardised percentage inclusion of seaweeds to ensure that digestibility is not adversely affected.


Meningioma of the third ventricle.
A case of meningioma of the third ventricle is described. The tumor was completely removed using a transcallosal approach.


Spatial and temporal variation in carbon isotope discrimination in prairie graminoids.
We present the results of a 5-year examination of variation in the stable carbon isotope composition (δ) of three C3 graminoid species from a Sandhills prairie: Agropyron smithii, Carex heliophila and Stipa comata. Although consistent species-specific patterns for mean δ were seen, there was also significant and substantial among-year and within-season variation in δ. A smaller contribution to variation in δ came from topographic variation among sampling sites. Effects of species, year, season and topography contribute to variation in δ in an additive manner. An association between climate and δ exists that is consistent with previous work suggesting that δ reflects the interplay between photosynthetic gas exchange and plant water relations. Within the growing season, the time over which δ integrates plant response to the environment ranges from days to months.


Damage effects of bisphenol A against sepsis induced acute lung injury.
In addition to oxidative damage, sepsis can cause multiple organ dysfunction and poses a life-threatening threat. In addition to severe tissue damage, hypotension, and multiple organ failure, sepsis can cause high morbidity and mortality. It is the lungs that are most vulnerable in abdominal sepsis, with impaired oxygen and nutrient exchange occurring in the pulmonary microcirculation. However, the etiology of sepsis and the link between sepsis and lung injury has not been elucidated. In this work, by exploring the data from the GEO and CTD database, a gene association study was conducted to determine whether sepsis-induced lung injury is caused by BPA. Further analysis demonstrated that MMP9, CEBPA, CYP1B1, CTSD, FKBP5, DGAT2, HP, TIMP2, ARG1 and MGST1 may play an important role in sepsis-induced lung injury. Finally, the single-cell RNA sequence demonstrated that CEBPA is mainly enriched in lung epithelial cells and epithelial cells, whereas CYP1B1 is closely related to basal cells, macrophages, and interstitial cells. In order to maintain lung function, epithelial and alveolar macrophages as well as other lung cells are important. When the lung epithelium is activated for a prolonged period of time, barrier function may be compromised and tissue damage may result, aggravating the lung injury. By using the animal model, we successfully simulated the model of sepsis lung injury. The HE staining demonstrated the rats with BPA-treated septic lung injury showed more alveolar structure to be disordered, pulmonary interstitial edema to be evident, and red blood cells as well as inflammatory cells. For PCR assay, the results demonstrated that the expression level of CEBPA is higher in the lung samples with sepsis compared with the normal samples of the lung. In order to evaluate the expression level of CEBPA and CYP1B1 in lung tissue, we then performed the PCR assay. For CYP1B1, the results demonstrated that the expression level of CYP1B1 in lung samples with sepsis is lower than in normal lung samples. In total, BPA may be a potential contributing factor to sepsis-induced lung injury.


Experience with Endeavor stent implantations.
Restenosis is the most common disadvantage of percutaneous coronary interventions. The incidence of restenosis can be lowered with the use of stents. After the use of stents, 'in-stent' restenosis can occur. To avoid it drug-eluting stents were developed, but the occurrence of stent thrombosis is higher than observed in case of bare-metal stents. Endeavor is a new zotarolimus-eluting stent developed to reduce the stent thrombosis. In a prospective study we aimed to follow-up our patients regarding the incidence of in-stent restenosis, stent thrombosis, and clinical end points after Endeavor stent implantation. Endeavor stents have been implanted in patients undergoing coronary angiography with the following indications: complex lesions susceptible to restenosis and after recanalization of chronic total occlusions. Endeavor stent implantations were successfully performed in 99 patients and has been successful in 98% of cases, two stents could not be implanted because of technical difficulties. Significant restenosis was observed in eight patients (8.1%). Subacute stent thrombosis (within 10 days) occurred in two patients (2.0%). Any late stent thrombosis was not observed. Our registry affirmed the results of the Endeavor I trial in a population with more severe and longer coronary stenosis. We can conclude that the Endeavor stent is suitable for implantation in complex, longer coronary lesions. Our long-term follow-up data do not prove those opinions which prefer bare-metal stent implantation in all patients because of the late adverse events of the drug-eluting stents.


Hospital discharges and 30-day case fatality for drug poisoning: a Danish population-based study from 1979 to 2002 with special emphasis on paracetamol.
To examine the number of hospital discharges and 30-day case fatalities due to drug poisoning based on data from a Danish County Hospital Discharge Registry from 1979 to 2002. All patients with a hospital discharge diagnosis of drug poisoning were identified and separated into groups taking: (1) opioid analgesics; (2) non-opioid analgesics; (3) anxiolytics; (4) antidepressants; (5) antipsychotics; or (6) non-specified. Paracetamol and salicylate were analysed separately. From 1994 to 2001, the total amount of drugs sold in the county was identified from a national drug database. A total of 13,432 patients with a median age 41.5 years at discharge of whom 59% were females accounted for 20,249 discharges for drug poisoning. The overall number of discharges remained essentially stable around 170 discharges per 100,000 inhabitants per year. From the mid-1990's, paracetamol became the most frequently used drug in poisoning with the largest increase in female teenagers. Thirty-day case fatality in poisoning with opioids was 3.6% compared with around 1% in other drug categories. For most drug categories, a sale of around 80,000 defined daily doses was associated with one hospital discharge due to drug poisoning. The overall number of hospital discharges remained stable and seems primarily related to amount of drugs available. With almost 10 years delay, the easier access to paracetamol was followed by an increase in hospitalisation due to poisoning with paracetamol. However, although the majority of hospitalisations were found in the younger age group, the highest mortality was seen among the elderly.


Melatonin mitigates type 1 diabetes-aggravated cerebral ischemia-reperfusion injury through anti-inflammatory and anti-apoptotic effects.
Cerebral ischemia and diabetes mellitus (DM) are common diseases that often coexist and interact with each other. DM doubles the risk of ischemic stroke, and cerebral ischemia causes stress-induced hyperglycemia. Most experimental stroke studies used healthy animals. Melatonin is neuroprotective against cerebral ischemia-reperfusion injury (CIRI) in non-DM, normoglycemic animals through anti-oxidant effect, anti-inflammation, and anti-apoptosis. Previous studies have also reported a negative correlation between hyperglycemia and urinary melatonin metabolite. The present study investigated the effects of type 1 DM (T1DM) on CIRI in rats and the role of melatonin against CIRI in T1DM animals. Our results revealed that T1DM aggravated CIRI, leading to greater weight loss, increased infarct volume, and worse neurological deficit. T1DM aggravated the post-CIRI activation of nuclear factor kappa B (NF-κB) pathway and increase in pro-apoptotic markers. A single intraperitoneal injection of melatonin at 10 mg/kg given 30 min before ischemia onset attenuated CIRI in T1DM rats, resulting in less weight loss, decreased infarct volume, and milder neurological deficit when compared with the vehicle group. Melatonin treatment achieved anti-inflammatory and anti-apoptotic effects with reduced NF-κB pathway activation, reduced mitochondrial cytochrome C release, decreased calpain-mediated spectrin breakdown product (SBDP), and decreased caspase-3-mediated SBDP. The treatment also led to fewer iNOS+ cells, milder CD-68+ macrophage/microglia infiltration, decreased TUNEL+ apoptotic cells, and better neuronal survival. T1DM aggravates CIRI. Melatonin treatment is neuroprotective against CIRI in T1DM rats via anti-inflammatory and anti-apoptotic effects.


Evaluations of alleged torture and ill treatment in Thailand: A collection of forensic medical evidence by non-medical evaluators.
Forensic medical evidence plays a critical role in the investigation and documentation of torture and ill treatment, as well as in civil reparation cases and in state monitoring mechanisms, especially if conducted on a timely basis by qualified, impartial experts. Detainees in many countries, such as Thailand, face significant barriers to access medical personnel while in custody or independent, non-governmental or impartial forensic experts. This study summarizes an effective method of collecting forensic medical evidence of torture and ill treatment by non-medical evaluators under conditions of limited access to detainees. The aim of the study was to determine the feasibility to render an expert opinion based on such documentation. We reviewed 49 non-medical forensic evaluations of alleged torture and ill treatment conducted by 11 attorneys or legal representatives in Southern Thailand between March and October 2011. Forty-four non-medical evaluations (90%) had sufficient information for the authors to formulate an opinion between the alleged abuse and the documented findings and to make a statement as to the level of consistency between them. Of these 44 evaluations, the authors determined that in 28 (70%) cases, the documented findings were highly consistent with the alleged abuse and in 13 (30%) cases, the documented findings were consistent with the alleged abuse. The study shows that non-medical evaluations conducted by attorneys and legal advocates can be a resource when individuals are denied access to forensic medical expertise. The results of a non-medical evaluation interpreted by an expert can have great evidentiary value when courts are reluctant to entertain writs of protection, such as a habeas corpus, or when states are reluctant to meet their obligations to pursue formal forensic evaluations.


Impact of different oral treatments on the composition of the supragingival plaque microbiome.
Dental plaque consists of a diverse microbial community embedded in a complex structure of exopolysaccharides. Dental biofilms form a natural barrier against pathogens but lead to oral diseases in a dysbiotic state. Using a metaproteome approach combined with a standard plaque-regrowth study, this pilot study examined the impact of different concentrations of lactoperoxidase (LPO) on early plaque formation, and active biological processes. Sixteen orally healthy subjects received four local treatments as a randomized single-blind study based on a cross-over design. Two lozenges containing components of the LPO-system in different concentrations were compared to a placebo and Listerine®. The newly formed dental plaque was analyzed by mass spectrometry (nLC-MS/MS). On average 1,916 metaproteins per sample were identified, which could be assigned to 116 genera and 1,316 protein functions. Listerine® reduced the number of metaproteins and their relative abundance, confirming the plaque inhibiting effect. The LPO-lozenges triggered mainly higher metaprotein abundances of early and secondary colonizers as well as bacteria associated with dental health but also periodontitis. Functional information indicated plaque biofilm growth. In conclusion, the mechanisms on plaque biofilm formation of Listerine® and the LPO-system containing lozenges are different. In contrast to Listerine®, the lozenges led to a higher bacterial diversity.


Fouling behaviors are different at various negative potentials in electrochemical anaerobic membrane bioreactors with conductive ceramic membranes.
Membrane fouling remains a critical challenge to the practical application of anaerobic membrane bioreactor (AnMBR). To address this challenge, a conductive ceramic membrane was prepared for fouling control in AnMBR. By using the conductive membranes, the anti-fouling performances were enhanced about 3 times at potentials below -1.0 V vs Ag/AgCl compared to the conventional AnMBR. The particle size distributions and the electric field calculations suggest that such an enhancement was mainly attributed to the increased particle sizes of foulants in the supernatant and the electric field forces. Moreover, the scanning electron microscope and confocal laser scanning microscope results show that the conductive membrane at -1.0 V could increase the porosity of the gel layer on the surface, whereas the conductive membrane at -2.0 V could inhibit the activity of adhering bacteria. Surprisingly, membrane fouling of electrically-assisted AnMBR (AnEMBR) at -0.5 V was increased, which was attributed to a dense biofilm-like structure formation. Such a result is contrary to the conventional cognition that negative potential could mitigate the membrane fouling. Overall, this work supplements the understanding of the anti-fouling effects of the electric field in AnEMBR, and provides supplementary information for the engineering application of AnEMBR.


Report of severe accidental baclofen intoxication in a healthy 4-year-old boy and review of the literature.
The number of reports on baclofen intoxication has increased in recent years. Here we report the case of a 4-year-old boy in deep coma who was referred to the pediatric intensive care unit. The patient was intubated and mechanically ventilated. A computerized tomography scan without contrast showed a collapsed appearance of the ventricular system suggesting diffuse cerebral edema. A multichannel electroencephalogram registered 6 h after admission showed a very slow and ample continuous pattern, without structure, nonreactive to stimulations, expressing diffuse and severe nonspecific cerebral pain. A targeted analysis to determine the baclofen plasma levels was performed. Test results of plasma samples were highly positive for baclofen (2009 ng/mL). Following 36 h of mechanical ventilation, the patient rapidly regained consciousness and recovered normal neurological behavior. The present case demonstrates the importance of considering baclofen overdosage in cases of deep coma with areflexia, and emphasizes the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member. A review of the literature on pediatric baclofen overdose is included.


Fractionated grid therapy in treating cervical cancers: conventional fractionation or hypofractionation?
To evaluate the conventionally fractionated and hypofractionated grid therapy in debulking cervical cancers using the linear quadratic (LQ) model. A Monte Carlo technique was used to calculate the dose distribution of a commercially available grid in a 6-MV photon beam. The LQ model was used to evaluate the therapeutic outcome of both the conventionally fractionated (2 Gy/fraction) and hypofractionated (15 Gy/fraction) grid therapy regimens to debulk cervical cancers with different LQ parameters. The equivalent open-field dose (EOD) to the cancer cells and therapeutic ratio (TR) were defined by comparing grid therapy with the open debulking field. The clinical outcomes from 114 patients were used to verify our theoretical model. The cervical cancer and normal tissue cell survival statistics for grid therapy in two regimens were calculated. The EODs and TRs were derived. The EOD was only a fraction of the prescribed dose. The TR was dependent on the prescribed dose and the LQ parameters of both the tumor and normal tissue cells. The grid therapy favors the acutely responding tumors inside radiosensitive normal tissues. Theoretical model predictions were consistent with the clinical outcomes. Grid therapy provided a pronounced therapeutic advantage in both the hypofractionated and conventionally fractionated regimens compared with that seen with single fraction, open debulking field regimens, but the true therapeutic advantage exists only in the hypofractionated grid therapy. The clinical outcomes and our study indicated that a course of open-field radiotherapy is necessary to control tumor growth fully after a grid therapy.


A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells.
The quiescence of radial neural stem cells (rNSCs) in adult brain is regulated by environmental stimuli. However, little is known about how the neurogenic niche couples the external signal to regulate activation and transition of quiescent rNSCs. Here, we reveal that long-term excitation of hippocampal dentate granule cells (GCs) upon voluntary running leads to activation of adult rNSCs in the subgranular zone and thereby generation of newborn neurons. Unexpectedly, the role of these excited GC neurons in NSCs depends on direct GC-rNSC interaction in the local niche, which is through down-regulated ephrin-B3, a GC membrane-bound ligand, and attenuated transcellular EphB2 kinase-dependent signaling in the adjacent rNSCs. Furthermore, constitutively active EphB2 kinase sustains the quiescence of rNSCs during running. These findings thus elucidate the physiological significance of GC excitability on adult rNSCs under external environments and indicate a key-lock switch regulation via cell-cell contact for functional transition of rNSCs.


Management of cavernous hemangioma of the liver.
Cavernous hemangioma of the liver was diagnosed in 12 of 60 patients (20 percent) evaluated for surgery of neoplastic liver disease. All were female, from 29 to 77 years old. Six patients presented with abdominal pain and seven had taken estrogens. Indications for surgery included uncertain diagnosis, symptoms, large lesion greater than or equal to 6 cm, and hypoproliferative anemia. Three right lobectomies, one left lateral segmentectomy, one open biopsy, and one right trisegmentectomy were performed. There were no deaths, one subphrenic abscess, and one bile leak. The remaining seven patients were observed and at 2 to 6 years post operatively had followed a benign course. Resectional therapy may be considered for superficial large or symptomatic lesions in the appropriate patient, but most hepatic hemangiomas follow a benign course.


Determination of polychlorinated biphenyls in transformer oil using various adsorbents for solid phase extraction.
Various adsorbents for a solid phase extraction (SPE) method were used to study their ability to separate PCBs from transformer oil to rapidly determine their sub-ppm concentration in the transformer oil. Approximately 90% of the transformer oil could be removed from the PCBs by using a hydrophilic-lipophilic balanced copolymer (HLB) adsorbent, but the recovery of deca-chlorobiphenyl (deca-CB) used as a surrogate was only 24.5% due to lose during this cleanup process. The use of a silica adsorbent gave good results with 89.9% recovery of the deca-CB. The recovery of Aroclor 1242 and 1260 were 95.4 and 90.3% on silica, and 98.9 and 83.5% on HLB, respectively. Acid treatment was an essential step in removing the ambiguous interference peaks to help identify the PCBs. A decreased sensitivity of the electron capture detection (ECD) for PCBs was observed due to the presence of the remaining trace oil after the workup procedure. This loss in sensitivity was allowed for by using tetrachloroxylene as an internal standard, and this was found to be reliable for the criteria of quality control by employing an experiment in which LCS was spiked with 2mg/l of Aroclor 1260 and analyzed each day over a 25 day period. The MDL for the analytical method established in this study is 0.05 mg/l.


Arginine-carboxylated pullulan, a potential antibacterial material for food packaging.
Pullulan possesses excellent film-forming properties and oxygen isolation capabilities. However, it exhibits limited antibacterial properties and poor water resistance, thereby hindering its application in the field of food preservation. In this study, we synthesized D-arginine-succinic anhydride-pullulan (Arg-SA-Pul) by carboxylating pullulan and subsequently grafting it with D-arginine. The antimicrobial test demonstrated that Arg-SA-Pul exhibited comparable antibacterial activity against Escherichia coli and Staphylococcus aureus. Using Arg-SA-Pul as the primary material and glycerol as the plasticizer, we fabricated an antibacterial film via the tape casting method. The film's light transmittance, water solubility, and water vapor permeability were evaluated. Compared to the natural pullulan film, the Arg-SA-Pul film exhibited lower vapor permeability. Additionally, we conducted preservation tests on cherries by coating them with the Arg-SA-Pul film. The results demonstrated that the Arg-SA-Pul film exhibited a significant preservation effect on cherries and effectively delayed their ripening and senescence. In the future, the Arg-SA-Pul film could be employed as a bacteriostatic preservation material to extend the shelf life of fruits.


Uracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUG1.
Both a DNA lesion and an intermediate for antibody maturation, uracil is primarily processed by base excision repair (BER), either initiated by uracil-DNA glycosylase (UNG) or by single-strand selective monofunctional uracil DNA glycosylase (SMUG1). The relative in vivo contributions of each glycosylase remain elusive. To assess the impact of SMUG1 deficiency, we measured uracil and 5-hydroxymethyluracil, another SMUG1 substrate, in Smug1 -/- mice. We found that 5-hydroxymethyluracil accumulated in Smug1 -/- tissues and correlated with 5-hydroxymethylcytosine levels. The highest increase was found in brain, which contained about 26-fold higher genomic 5-hydroxymethyluracil levels than the wild type. Smug1 -/- mice did not accumulate uracil in their genome and Ung -/- mice showed slightly elevated uracil levels. Contrastingly, Ung -/- Smug1 -/- mice showed a synergistic increase in uracil levels with up to 25-fold higher uracil levels than wild type. Whole genome sequencing of UNG/SMUG1-deficient tumours revealed that combined UNG and SMUG1 deficiency leads to the accumulation of mutations, primarily C to T transitions within CpG sequences. This unexpected sequence bias suggests that CpG dinucleotides are intrinsically more mutation prone. In conclusion, we showed that SMUG1 efficiently prevent genomic uracil accumulation, even in the presence of UNG, and identified mutational signatures associated with combined UNG and SMUG1 deficiency.


TRIM29 facilitates the epithelial-to-mesenchymal transition and the progression of colorectal cancer via the activation of the Wnt/β-catenin signaling pathway.
Tripartite Motif 29 (TRIM29) has been newly identified as being implicated in cancer progression. However, the biological role and molecular mechanism of TRIM29 in the invasion and metastasis of colorectal cancer (CRC) remain to be determined. The expression levels of TRIM29 and β-catenin in CRC patient specimens were detected by immunohistochemistry. Recombinant lentivirus vectors containing the TRIM29 gene and its small hairpin interfering RNAs were constructed and transduced into CRC cells. Wound-healing and Transwell assays were performed to evaluate the migration and invasion abilities of CRC cells in vitro. Hepatic metastasis models in nude mice were established to validate the function of TRIM29 in vivo. Moreover, the expressions of epithelial-to-mesenchymal transition (EMT)-associated proteins were detected by qRT-PCR and Western blotting in CRC cells. Finally, Western blotting, qRT-PCR, luciferase reporter assays, and immunofluorescence assays were used to explore the molecular mechanisms of TRIM29 in CRC progression. Increased TRIM29 expression positively correlated with lymph node metastasis and β-catenin expression in patient CRC tissues. Overexpression of TRIM29 promoted invasion and metastasis of CRC cells in vitro and in vivo by regulating EMT, whereas the knockdown of TRIM29 had the opposite effect. Further mechanistic studies suggest that TRIM29 can activate the Wnt/β-catenin signaling pathway via up-regulating CD44 expression in colorectal cancer. TRIM29 induces EMT through activating the Wnt/β-catenin signaling pathway via up-regulating CD44 expression, thus promoting invasion and metastasis of CRC.


The rare mantis shrimp Areosquilla indica (Hansen, 1976) (Crustacea, Stomatopoda) from the Great Barrier Reef: first Australian records of the genus and species.
The rare mantis shrimp genus Areosquilla is recorded from Australia for the first time based on nine specimens of A. indica (Hansen, 1926) collected from the Great Barrier Reef. Morphological variation beyond that observed in previous accounts is reported. The present record and other recent discoveries bring the Australian stomatopod fauna to 152 species and 68 genera.


[Study on the protective effect of xinkang oral liquid on the isoproterenol-induced ischemic myocardial damage in rats].
To study the protective effect of Xinkang oral liquid on the ischemic myocardial damage. Ischemic myocardial damage model was obtained by i.p. 85 mg/kg isoproterenol. The level of superoxide dismutase (SOD), malondialdehyde (MDA), creatine kinase (CK), lactic dehydrogenase (LDH) in the serum and endothelin (ET) in the plasma were detected. The level of ET, MDA, CK, LDH of Xinkang oral liquid group was much lower than that of model group (P < 0.01). The SOD activity was higher than that of model group (P < 0.01). The level of Xinkang oral liquid group was lower than that of Shuxin oral liquid group. The SOD activity of Xinkang oral liquid group was much higher than that of Shuxin oral liquid group (P < 0.01). Xinkang oral liquid can prevent the myocardium from ischemic damage.


FLT3 mutation status is a predictor of early death in pediatric acute promyelocytic leukemia: a report from the Children's Oncology Group.
FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL). Diagnostic specimens from 104 pediatric APL patients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM). FLT3/Mut status was correlated with disease characteristics and clinical outcome for patients treated on CALGB C9710 (n = 50). Forty-two of the 104 patients (40%) had either FLT3/ITD (n = 28, 27%) or FLT3/ALM (n = 15, 14%). Median diagnostic WBC count was 23,400 cells/µl vs. 3,600 cells/µl for those with and without FLT3/Mut (P < 0.001), and similar results for the cohort of 50 patients treated on C9710 (P < 0.001). In patients treated on C9710, presence of a FLT3 mutation was highly correlated with diagnostic WBC count >10,000 (P = 0.004), microgranular variant histology (P = 0.035), and a lower remission rate (P = 0.009). In patients who received ATRA (C9710 or CCG-2911, n = 8), those with FLT3/Mut had an induction death rate of 30% (7/23) compared to 3% (1/35) in FLT3/WT patients (P = 0.005). In patients with high WBC counts (>10,000), those with FLT3/Mut had a significantly higher risk of induction death versus FLT3/WT patients (47% vs. 0%, P = 0.05). FLT3/Mut was not associated with adverse outcome in those who survived induction therapy. FLT3/Mut are prevalent in pediatric APL and are associated with high WBC count and increased induction death. This study provides further evidence for testing APL patients for FLT3/Mut and the potential role for FLT3 inhibitors in this disease.


Oxidation of glyceraldehyde-3-phosphate dehydrogenase enhances its binding to nucleic acids.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a protein with various activities far from its enzymatic function. Here, we showed that the oxidation of SH-groups of the active site of GAPDH enhanced its binding with total transfer RNA or with total DNA. Both NAD and NADH-the cofactors of GAPDH-inhibited the GAPDH-RNA (DNA) interaction, though NAD was much less effective than NADH in the case of oxidized GAPDH. Oxidation of GAPDH strongly decreased its affinity to NAD but not to NADH. Immobilized tetramers of GAPDH dissociated into dimers during the incubation with total RNA but not DNA. The staining of HeLa cells with monoclonal antibodies specific to dimers, monomers or the denatured form of GAPDH revealed the condensation of non-native forms of GAPDH in the nucleus. The role of oxidation of GAPDH in the regulation of the quaternary structure of the enzyme and in its interaction with nucleic acids is discussed.


Spectrum of Nondystrophic Skeletal Muscle Channelopathies in Children.
The nondystrophic skeletal muscle channelopathies are a group of disorders caused by mutations of various voltage-gated ion channel genes, including nondystrophic myotonia and periodic paralysis. We identified patients with a diagnosis of muscle channelopathy from our neuromuscular database in a tertiary care pediatric center from 2005 to 2015. We then performed a retrospective review of their medical records for demographic characteristics, clinical features, investigations, treatment, and follow-up. Thirty-three patients were identified. Seventeen had nondystrophic myotonia. Seven of them had chloride channelopathy (four Becker disease and three Thomsen disease). Warm-up phenomenon and muscle hypertrophy were common clinical manifestations in this subgroup. Ten patients had sodium channelopathy (four paramyotonia congenita and six other sodium channel myotonia). Stiffness of the facial muscles was an important presenting symptom, and eyelid myotonia was a common clinical finding in this subgroup. The majority of these patients had electrical myotonia. Mexiletine was effective in controlling the symptoms in patients who had received treatment. Sixteen children had periodic paralysis (four hyperkalemic periodic paralysis, eight hypokalemic periodic paralysis, and four Andersen-Tawil syndrome). Acetazolamide was commonly used to prevent paralytic attacks and was found to be effective. Nondystrophic muscle channelopathies present with diverse clinical manifestations (myotonia, muscle hypertrophy, proximal weakness, swallowing difficulties, and periodic paralysis). Cardiac arrhythmias are potentially life threatening in Andersen-Tawil syndrome. Timely identification of these disorders is helpful for effective symptomatic management and genetic counseling.


A new compressed sensing cine cardiac MRI sequence with free-breathing real-time acquisition and fully automated motion-correction: A comprehensive evaluation.
The purpose of this study was to compare a new free-breathing compressed sensing cine (FB-CS) cardiac magnetic resonance imaging (CMR) to the standard reference multi-breath-hold segmented cine (BH-SEG) CMR in an unselected population. From January to April 2021, 52 consecutive adult patients who underwent both conventional BH-SEG CMR and new FB-CS CMR with fully automated respiratory motion correction were retrospectively enrolled. There were 29 men and 23 women with a mean age of 57.7 ± 18.9 (standard deviation [SD]) years (age range: 19.0-90.0 years) and a mean cardiac rate of 74.6 ± 17.9 (SD) bpm. For each patient, short-axis stacks were acquired with similar parameters providing a spatial resolution of 1.8 × 1.8 × 8.0 mm3 and 25 cardiac frames. Acquisition and reconstruction times, image quality (Likert scale from 1 to 4), left and right ventricular volumes and ejection fractions, left ventricular mass, and global circumferential strain were assessed for each sequence. FB-CS CMR acquisition time was significantly shorter (123.8 ± 28.4 [SD] s vs. 267.2 ± 39.3 [SD] s for BH-SEG CMR; P < 0.0001) at the penalty of a longer reconstruction time (271.4 ± 68.7 [SD] s vs. 9.9 ± 2.1 [SD] s for BH-SEG CMR; P < 0.0001). In patients without arrhythmia or dyspnea, FB-CS CMR provided subjective image quality that was not different from that of BH-SEG CMR (P = 0.13). FB-CS CMR improved image quality in patients with arrhythmia (n = 18; P = 0.002) or dyspnea (n = 7; P = 0.02), and the edge sharpness was improved at end-systole and end-diastole (P = 0.0001). No differences were observed between the two techniques in ventricular volumes and ejection fractions, left ventricular mass or global circumferential strain in patients in sinus rhythm or with cardiac arrhythmia. This new FB-CS CMR addresses respiratory motion and arrhythmia-related artifacts without compromising the reliability of ventricular functional assessment.


Glucagon changes substrate preference in gluconeogenesis.
Fasting hyperglycemia in diabetes mellitus is caused by unregulated glucagon secretion that activates gluconeogenesis (GNG) and increases the use of pyruvate, lactate, amino acids, and glycerol. Studies of GNG in hepatocytes, however, tend to test a limited number of substrates at nonphysiologic concentrations. Therefore, we treated cultured primary hepatocytes with three identical substrate mixtures of pyruvate/lactate, glutamine, and glycerol at serum fasting concentrations, where a different U-13C- or 2-13C-labeled substrate was substituted in each mix. In the absence of glucagon stimulation, 80% of the glucose produced in primary hepatocytes incorporated either one or two 13C-labeled glycerol molecules in a 1:1 ratio, reflecting the high overall activity of this pathway. In contrast, glucose produced from 13C-labeled pyruvate/lactate or glutamine rarely incorporated two labeled molecules. While glucagon increased the glycerol and pyruvate/lactate contributions to glucose carbon by 1.6- and 1.8-fold, respectively, the glutamine contribution to glucose carbon was increased 6.4-fold in primary hepatocytes. To account for substrate 13C carbon loss during metabolism, we also performed a metabolic flux analysis, which confirmed that the majority of glucose carbon produced by primary hepatocytes was from glycerol. In vivo studies using a PKA-activation mouse model that represents elevated glucagon activity confirmed that most circulating lactate carbons originated from glycerol, but very little glycerol was derived from lactate carbons, reflecting glycerol's importance as a carbon donor to GNG. Given the diverse entry points for GNG substrates, hepatic glucagon action is unlikely to be due to a single mechanism.


Sex differences and effects of the estrous stage on hippocampal-prefrontal theta communications.
Effective communication between the mammalian hippocampus and neocortex is essential to certain cognitive-behavioral tasks critical to survival in a changing environment. Notably, functional synchrony between local field potentials (LFPs) of the ventral hippocampus (vHPC) and the medial prefrontal cortex (mPFC) within the theta band (4-12 Hz) underlies innate avoidance behavior during approach-avoidance conflict tasks in male rodents. However, the physiology of vHPC-mPFC communications in females remains unestablished. Furthermore, little is known about how mPFC subdivisions functionally interact in the theta band with hippocampal subdivisions in both sexes in the absence of task demand. Given the established roles of biological sex and gonadal hormone status on innate avoidance behaviors and neuronal excitability, here, we characterize the effects of biological sex and female estrous stage on hippocampal-prefrontal (HPC-mPFC) theta signaling in freely moving female and male rats. LFPs from vHPC, dorsal hippocampus (dHPC), mPFC-prelimbic (PrL), and mPFC-infralimbic (IL) were simultaneously recorded during spontaneous exploration of a familiar arena. Data suggest that theta phase and power in vHPC preferentially synchronize with PrL; conversely, dHPC and IL preferentially synchronize. Males displayed greater vHPC-PrL theta synchrony than females, despite similar regional frequency band power and inter-regional coherence. Additionally, several significant estrous-linked changes in HPC-mPFC theta dynamics were observed. These findings support the hypothesis that HPC-mPFC theta signaling is sensitive to both biological sex and female estrous stage. These findings establish novel research avenues concerning sex as a biological variable and effects of gonadal hormone status on HPC-mPFC network activity as it pertains to threat evaluation biomarkers.


Clinical outcome of silent myocardial ischemia.
Asymptomatic coronary artery disease can be detected by an abnormal electrocardiogram at rest, by a positive exercise test result unaccompanied by pain, or by the demonstration of silent ischemic episodes during daily activities. However, the clinical outcome of patients with silent myocardial ischemia has not yet been clearly defined. In a study of 356 patients with documented coronary disease--211 of whom had previous myocardial infarction--the prognostic information of spontaneous ST-segment depression was found to be independent of that associated with a positive exercise test result, ejection fraction, and extent of arteriographically documented coronary artery disease. Patients with asymptomatic ischemia had a higher coronary event rate than those without ischemia. Cardiac event rates followed a similar pattern for patients with silent, symptomatic and mixed ischemia--whether or not there was previous myocardial infarction.


The comparability of bispectral index and state entropy index during maintenance of sufentanil-sevoflurane-nitrous oxide anesthesia.
Manufacturers recommend maintaining Bispectral (BIS) or Spectral Entropy (State Entropy, SE) indexes between 40 and 60 during the maintenance of anesthesia. We compared these indexes during this period. Data were obtained from 58 patients receiving sufentanil-sevoflurane-nitrous oxide anesthesia. The anesthesiologist was blinded to BIS and SE. Artifact-free concurrent BIS and SE values (7792 pairs), automatically recorded at 1-min intervals, were compared using Bland-Altman analysis, Kappa coefficient for agreement and crude proportion of agreement. The occurrence of errors of judgment (Type 1 defined as one parameter <40 and the other >60, or Type 2 defined as BIS and SE values on different sides of a threshold [40 or 60]) was also counted. Bias was -2 with limits of agreement of -18 and 9. Kappa BIS/SE obtained from all patients was 0.537 +/- 0.147; crude agreement >0.80 was observed in 45% of patients. Type 1 number of errors of judgment corresponded to two instances. Median and interquartile values of Type 2 number of errors of judgment were 4.5 [3.0-6.0] when considering a difference between BIS and SE more than 5. Although limits of agreement between BIS and SE were large, Kappa value moderate, and crude agreement <0.80 in more than half of the patients, making completely contradictory decisions (e.g., deepening the anesthetic based on one parameter and lightening it based upon the other) would have been exceptional. More common would have been a risk of error between no change versus increasing or decreasing anesthetic depth.


Enhanced expression of neurotensin/neuromedin N mRNA and products of NT/NMN precursor processing in neonatal rats.
Intestinal levels of immunoreactive neurotensin (iNT) and neuromedin N (iNMN), as well as mRNA for the NT/NMN precursor, were elevated during the suckling period in rats. While transient expression of NT/NMN was observed at 1-5 days of age in the proximal small intestine and colon, NT/NMN levels in the ileum increased to peak at 10-20 days of age and then decreased to adult levels. The levels of these peptides were not elevated in the central nervous system and pituitary over this time period. Chromatographic analyses of jejunoileal extracts indicated that large molecular forms of iNT and iNMN were present, constituting approximately 1.3% of total iNT and approximately 56% of total iNMN, respectively. Treatment of the large forms with pepsin, which is known to generate the fully immunoreactive peptides, NT(3-13), NT(4-13), and NMN, increased immunoreactivity tenfold (iNT) and 1.2-fold (iNMN). Thus, large forms actually constituted approximately 13% (iNT) and approximately 60% (iNMN). Based upon its physicochemical properties, large molecular iNMN was tentatively identified as a 125 residue peptide with NMN at its C-terminus [i.e., rat prepro-NT/NMN(23-147)]. The properties of large molecular iNT were most similar to those predicted for the entire precursor [i.e., rat prepro-NT/NMN(23-169)]. These results indicate a) that enhanced expression of NT/NMN occurs in a tissue-specific manner in rats during the suckling period; b) that the pattern of precursor processing in intestine yields primarily NT and a large molecular form of NMN.


Cabazitaxel's ototoxicity: An animal study and histopathologic research.
Chemotherapeutic agents can have both serious side effects and ototoxicity, which can be caused by direct toxic effects or by metabolic derangement by the agents. Cabazitaxel (CBZ) is a next-generation semi-synthetic taxane derivative that is effective in both preclinical models of human tumors that are sensitive or resistant to chemotherapy and in patients suffering from progressive prostate cancer despite docetaxel treatment. The primary aim of this study is to investigate the ototoxicity of CBZ in a rat model. : A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups. CBZ (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to Groups 2, 3, and 4 at doses of 0.5, 1.0, and 1.5 mg/kg/week, respectively, for 4 consecutive weeks; Group 1 received only i.p. saline at the same time. At the end of the study, the animals were sacrificed and their cochlea removed for histopathological examination. : Intraperitoneal administration of CBZ exerted an ototoxic effect on rats, and the histopathological results became worse in a dose-dependent manner (P < 0.05). : Our findings suggest that CBZ may be an ototoxic agent and can damage the cochlea. More clinical studies should be conducted to understand its ototoxicity.


X-linked inhibitor of apoptosis (XIAP) inhibits c-Jun N-terminal kinase 1 (JNK1) activation by transforming growth factor beta1 (TGF-beta1) through ubiquitin-mediated proteosomal degradation of the TGF-beta1-activated kinase 1 (TAK1).
Active NF-kappaB renders malignant hepatocytes refractory to the growth inhibitory and pro-apoptotic properties of transforming growth factorbeta1 (TGF-beta1). NF-kappaB counteracts TGF-beta1-induced apoptosis through up-regulation of downstream target genes, such as XIAP and Bcl-X(L), which in turn inhibit the intrinsic pathway of apoptosis. In addition, induction of NF-kappaB by TGF-beta1 inhibits JNK signaling, thereby attenuating TGF-beta1-induced cell death of normal hepatocytes. However, the mechanism involved in the negative cross-talk between the NF-kappaB and JNK pathways during TGF-beta1 signaling has not been determined. In this study, we have identified the XIAP gene as one of the critical mediators of NF-kappaB-mediated suppression of JNK signaling. We show that NF-kappaB plays a role in the up-regulation of XIAP gene expression in response to TGF-beta1 treatment and forms a TGF-beta1-inducible complex with TAK1. Furthermore, we show that the RING domain of XIAP mediates TAK1 polyubiquitination, which then targets this molecule for proteosomal degradation. Down-regulation of TAK1 protein expression inhibits TGF-beta1-mediated activation of JNK and apoptosis. Conversely, silencing of XIAP promotes persistent JNK activation and potentiates TGF-beta1-induced apoptosis. Collectively, our findings identify a novel mechanism for the regulation of JNK activity by NF-kappaB during TGF-beta1 signaling and raise the possibility that pharmacologic inhibition of the NF-kappaB/XIAP signaling pathway might selectively abolish the pro-oncogenic activity of TGF-beta1 in advanced hepatocellular carcinomas (HCCs) without affecting the pro-apoptotic effects of TGF-beta1 involved in normal liver homeostasis.


Acquisition of mands, tacts, and intraverbals through sign exposure in an individual with autism.
Many children with autism communicate through the use of alternative communication systems, such as sign language. Limited research has been conducted on the situations under which sign language will be acquired across verbal operants without direct teaching. The purpose of the current study was to evaluate exposure to sign language on the acquisition of signed mands, tacts, and intraverbals in a male child with autism. Results indicated fast acquisition of mands, tacts, and intraverbals without direct teaching. Results are discussed in the context of future research investigating exposure without direct teaching in individuals who communicate with alternative communication systems.


Implementation of specimen banking concepts in developing countries. First trial--Sri Lanka.
The necessity to establish a small scale Environmental Specimen Bank projects in tropical countries is stressed. An example from Sri Lanka demonstrates the needs, the benefits and the prospects of such an integrated research project.


Ocular relapse in acute myeloid leukemia (M4) with normal bone marrow.
A patient with the rare occurrence of ocular relapse of acute myeloid leukemia (AML) M4 while the bone marrow was normal is reported in this paper. A 47-year-old woman with AML was treated with chemotherapy and went successfully into remission. Four months later, she presented with pain, redness, and a mass over the left eye. The ocular relapse involved the subconjunctival space and anterior chamber of the left eye and, presumably, the left lacrimal gland. There were also multiple subcutaneous nodules on both of her forearms. Incisional biopsy from the subconjunctival lesion was performed. Histopathological examination of the specimen showed diffuse blast cell infiltration. Her bone marrow was still in remission. Although exceedingly rare, ocular extramedullary relapse in AML M4 heralds bone marrow recurrence and, despite intensive chemotherapy, the prognosis is dismal.


Upside-down spleen as cause of suprarenal mass.
An upside-down configuration of the spleen can be mistaken for a left suprarenal mass. A radioisotopic liver-spleen scan will demonstrate a characteristic appearance of the spleen with its hilus superiorly and its convex border medially and adjacent to the kidney. When a left suprarenal mass is identified, we advocate the liver-spleen scan as the first step in the diagnostic workup. If the typical configuration is found, no further studies are necessary.


Epidemiological investigations on viral hepatitis in preschool and school communities. Note I. Prevalence and incidence of viral hepatitis and the role of the community in transmission.
A transversal and longitudinal epidemiological follow up was undertaken of the viral hepatitis cases occurring in two types of children communities (kindergartens and schools). The role of organized communities in the spread of hepatitis viruses and the contribution of external factors to the maintenance of hepatitis endemicity are discussed.


Bone imaging in the assessment of en bloc osteocutaneous autotransplantation.
A patient is presented who sustained an avulsed portion of the mandible and all soft tissues of the floor of the oral cavity, requiring an autogenous en bloc transplant to replace the avulsed tissues. The clinical role of bone imaging in assessing the patency of the microvasculature and viability of the vascularized osteocutaneous graft is discussed, and the criticality of the time of image acquisition in prognosticating the success of the transplantation is emphasized.


Effect of urbanization on soil methane and nitrous oxide fluxes in subtropical Australia.
Increasing population densities and urban sprawl are causing rapid land use change from natural and agricultural ecosystems into smaller, urban residential properties. However, there is still great uncertainty about the effect that urbanization will have on biogeochemical C and N cycles and associated greenhouse gas (GHG) budgets. We aimed to evaluate how typical urbanization related land use change in subtropical Australia affects soil GHG exchange (N2 O and CH4 ) and the associated global warming potential (GWP). Fluxes were measured from three land uses: native forest, a long-term pasture, and a turf grass lawn continuously over two years using a high-resolution automated chamber system. The fertilized turf grass had the highest N2 O emissions, dominated by high fluxes >100 g N2 O-N day-1 immediately following establishment though decreased to just 0.6 kg N2 O-N ha-1 in the second year. Only minor fluxes occurred in the forest and pasture, with the high aeration of the sandy topsoil limiting N2 O emissions while promoting substantial CH4 uptake. Native forest was consistently the strongest CH4 sink (-2.9 kg CH4 -C ha-1 year-1 ), while the pasture became a short-term CH4 source after heavy rainfall when the soil reached saturation. On a two-year average, land use change from native forest to turf grass increased the non-CO2 GWP from a net annual GHG sink of -83 CO2 -e ha-1 year-1 to a source of 245 kg CO2 -e ha-1 year-1 . This study highlights that urbanization can substantially alter soil GHG exchange by altering plant soil water use and by increasing bulk density and inorganic N availability. However, on well-drained subtropical soils, the impact of urbanization on inter-annual non-CO2 GWP of turf grass was low compared to urbanized ecosystems in temperate climates.


Patients with pheochromocytoma exhibit low aldosterone renin ratio-preliminary reports.
Plasma renin activity (PRA) is generally increased in patients with pheochromocytoma (PCC) due to low circulating plasma volume and activation of β-1 adrenergic receptor signaling. However, there has been no study on the aldosterone renin ratio (ARR) in patients with PCC. To elucidate the issue, this study aimed to determine the PRA, plasma aldosterone concentration (PAC), and ARR in patients with PCC and compare them with those in patients with subclinical Cushing's syndrome (SCS) and non-functioning adrenal adenoma (NFA). In this retrospective single-center, cross-sectional study, 67 consecutive patients with adrenal tumors (PCC (n = 18), SCS (n = 18), and NFA (n = 31)) diagnosed at Kobe University Hospital between 2008 and 2014 were enrolled. PRA was significantly higher in patients with PCC than in those with SCS and NFA (2.1 (1.3 ~ 2.8) vs. 0.7 (0.5 ~ 1.8) and 0.9 (0.6 ~ 1.4) ng/mL/h; p = 0.018 and p = 0.025). Although PACs were comparable among the three groups, ARR was significantly lower in patients with PCC than in those with SCS and NFA (70.5 (45.5 ~ 79.5) vs. 156.0 (92.9 ~ 194.5) and 114.9 (90.1 ~ 153.4); p = 0.001 and p < 0.001). Receiver operating characteristic curve analysis demonstrated that, in differentiating PCC from NFA, PRA > 1.55 ng/mL/h showed a sensitivity of 70.0% and specificity of 80.6%. Interestingly, ARR < 95.4 showed a sensitivity of 83.3% and specificity of 86.7%, which were higher than those in PRA. ARR decreased in patients with PCC, which was a more sensitive marker than PRA. Further study is necessary to understand the usefulness of this convenient marker in the detection of PCC. This study was not registered because of the retrospective analysis.


Ranibizumab in Myopic Choroidal Neovascularization: A Subgroup Analysis by Ethnicity, Age, and Ocular Characteristics in RADIANCE.
To assess the impact of ethnicity, age, and ocular characteristics on ranibizumab efficacy in myopic choroidal neovascularization (CNV). In this post hoc subgroup analysis from the phase III RADIANCE study, best-corrected visual acuity (BCVA) outcomes and treatment exposure were analyzed in 105 patients treated with ranibizumab 0.5 mg. Baseline categories included ethnicity, age, baseline BCVA, lesion area, CNV lesion area, refraction sphere, axial length, subretinal fluid, and location of CNV. At month 12, the mean change in BCVA was numerically higher in East-Asians than in Caucasians (17.0 vs. 14.1 letters). The median number of injections varied with ethnicity (East-Asians vs. Caucasians: 2 vs. 3), baseline BCVA (highest vs. lowest: 1 vs. 4), CNV lesion area and lesion area (largest vs. smallest: 5 vs. 1 and 5 vs. 2). East-Asians showed numerically higher BCVA gains than Caucasians. The number of injections varied across subgroups, emphasizing the need for individualized treatment.


SSU71, encoding the largest subunit of TFIIF, is located on the right arm of chromosome VII in Saccharomyces cerevisiae.
SSU71 (TFG1) is an essential nuclear gene encoding the largest subunit of the yeast general transcription factor TFIIF. The SSU71 gene was physically mapped to the right arm of chromosome VII, physically linked to QCR9, by hybridization of the cloned gene to CHEF and lambda clone grid blots. This assignment was confirmed by genetic mapping. A search of the nucleotide sequence databases revealed that SSU71 is immediately adjacent to the TYS1 gene, which encodes tRNA(Tyr) synthetase. TYS1 was reported previously to lie on chromosome XV based on sequence overlap with the adjacent UBR1 gene. The mapping data reported here established that TYS1 and UBR1 do not lie on chromosome XV; rather the SSU71-TYS1-UBR1 gene cluster lies on the right arm of chromosome VII, physically linked to QCR9 and genetically linked to ade3 and ser2.


Phacoemulsification, capsulorhexis, and intraocular lens power prediction accuracy.
Phacoemulsification with capsulorhexis reduces the surgical variability and may result in a more predictable refractive outcome. To evaluate the prediction accuracy with current IOL power prediction formulas, we reviewed a retrospective series of 628 phacoemulsification cases, including 148 short (< 22 mm) and 80 long (> 25 mm) eyes. Using the Binkhorst II formula and the manufacturer's recommended anterior chamber depth (ACD) values, the mean absolute refractive prediction error was 0.56 diopters (D). This error could be reduced to 0.51 D by retrospectively optimizing the ACD values for each lens type. Under similar least error conditions, the mean error was 0.51 D with the SRK/T formula and 0.47 D with the Olsen formula (P < .01). The Binkhorst formula overestimated the refraction in short eyes and underestimated the refraction in long eyes. The SRK/T and the Olsen formula were unbiased with the axial length. We hypothesize that the high prediction accuracy may be partially explained by a more predictable pseudophakic ACD with the current surgical technique.


Subbasal nerve fiber regeneration after LASIK and LASEK assessed by noncontact esthesiometry and in vivo confocal microscopy: prospective study.
To evaluate recovery of the corneal subbasal nerve plexus and corneal sensitivity after myopic laser in situ keratomileusis (LASIK) and laser-assisted subepithelial keratectomy (LASEK). Manchester Centre for Vision, Royal Eye Hospital, Manchester, United Kingdom. Thirty LASEK patients and 20 LASIK patients had slit-scanning confocal microscopy and noncontact corneal esthesiometry preoperatively and 1, 3, and 6 months after surgery. Images of the subbasal nerve plexus were analyzed using customized software to evaluate nerve regeneration. Central corneal sensitivity decreased significantly 1 month after LASEK and LASIK and returned to normal levels after 3 months. Corneal subbasal nerve fiber density, nerve branch density, nerve fiber length, and nerve fiber width decreased significantly 1 month after LASIK and had not returned to the preoperative levels by 6 months. Nerve fiber tortuosity decreased significantly 1 month after LASEK and returned to the preoperative levels 3 months after surgery. There were no significant differences in nerve fiber tortuosity before and after LASIK. Neither corneal sensitivity nor nerve fiber morphology was different between the 2 groups at any postoperative visit. Corneal sensitivity and subbasal nerve morphology were adversely affected by LASEK and LASIK. Corneal sensitivity recovered 3 months after the procedure, but subbasal nerves were still abnormal after 6 months. Despite the different forms of surgical trauma to corneal nerves with LASIK and LASEK, there was no apparent difference in the time course of recovery of corneal structure and function.


If a joint is hot it's not the time: health professionals' views on developing an intervention to promote physical activity in rheumatoid arthritis.
The study aimed to explore the views of health professionals on (i) physical activity in people who have rheumatoid arthritis (RA) and (ii) the design of an intervention to promote physical activity in this population. We used a qualitative methodology and conducted 14 interviews (rheumatologists n = 7, physiotherapist n = 4, clinical nurse specialists n = 3). Interviews were transcribed verbatim and analyzed using thematic analysis. Three key themes were generated: "Personal opinions", "Supporting physical activity" and "An ideal world". Although health professionals viewed physical activity as important, recommending it to people who have RA was largely based on persons' disease status rather than empirical evidence. Resources were highlight as a key challenge to interventions in clinical practice. Supporting physical activity through provision of information, goal setting and monitoring was also discussed. Health professionals believe physical activity is important for people who have RA, although there is uncertainty regarding physical activity recommendations for this population. Thus, there is scope to increase health professionals' knowledge of recent evidence. Views varied on how an intervention to promote physical activity should be delivered, but consideration of barriers to delivery in clinical practice is important. Implications for Rehabilitation Physical activity is an important aspect of disease management for people who have rheumatoid arthritis. Health professionals need to acknowledge the "mixed messages" received by people who have RA about being physically active thus further education for health professionals is suggested to standardize physical activity advice in clinical practice. Health professionals may benefit from education about behavior change theory and techniques. When designing future physical activity interventions consideration of the practical challenges of implementing research in a clinical setting is necessary.


Familial resemblance of bone mineral density (BMD) and calcaneal ultrasound attenuation: the BMD in mothers and daughters study.
The familial resemblance in bone mineral density (BMD) and calcaneal broadband ultrasound attenuation (BUA) was examined in 207 mother-daughter pairs. Mothers were participants in the Study of Osteoporotic Fractures. Three groups of daughters were recruited based on their maternal history of "fracture," "low BMD" without fracture (< 0.58 g/cm2, t-score < -2.5), and "normal BMD" without fracture (> 0.67 g/cm2, t-score > -1.6). Data on other potentially heritable factors known to influence BMD and BUA were also collected. BMD was measured at the hip, spine, whole body, and calcaneus. Calcaneal BUA was assessed using the Walker-Sonix UBA 575. Total hip and femoral neck BMD were significantly lower (5.0-8.0%, p < 0.017) among daughters, in particular premenopausal daughters, of mothers with established osteoporosis ("fracture" or "low BMD") compared with daughters of mothers at lower risk of osteoporosis ("normal BMD"). BUA did not differ across daughter groups. Lifestyle characteristics (dietary calcium, smoking, physical activity) were not highly correlated in mothers and daughters. Height, weight, and body composition were significantly correlated within mother-daughter pairs and could be a potential mechanism by which BMD is inherited. Among pre- and postmenopausal daughters, heritability estimates ranged from 50-63% and 34-48%, respectively. Heritability for calcaneal BUA (53%) was evident among postmenopausal daughters only. In conclusion, familial association in BMD was strongest among premenopausal daughters. Estimates of heritability suggest that maternal BMD and BUA are important independent predictors of BMD and BUA among daughters, reinforcing the importance of prevention and early intervention among women with a positive family history of osteoporosis.


Concurrent Cholecystectomy Is Associated with a Lower Risk of Recurrence after Curative Resection in Early-Stage Hepatocellular Carcinoma: A 10 Year Observational Single-Center Study.
Cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC). However, there is little information about the impact of cholecystectomy on the outcome of HCC. To evaluate the long-term effect of concurrent cholecystectomy on recurrence and overall survival in HCC after curative hepatectomy. We retrospectively enrolled 857 patients with BCLC stage 0 or A HCC who underwent primary resection from January 2001 to June 2016. The impact of concurrent cholecystectomy on overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox's proportional hazards models after one-to-one propensity score matching (PSM). Of the 857 patients, 539 (62.9%) received concurrent cholecystectomy (cholecystectomy group) and 318 (37.1%) did not (non-cholecystectomy group). During the mean follow-up period of 75.0 months, 471 (55.0%) patients experienced recurrence, and 321 (37.5%) died. RFS and OS were not significantly different between the groups. After PSM, a total of 298 patients were enrolled in each group. RFS was significantly higher in the cholecystectomy than non-cholecystectomy group (p = 0.044). In multivariate analysis, age (p = 0.022), serum AFP (p = 0.008), liver cirrhosis (p < 0.001), diabetes (p = 0.004), tumor number (p = 0.005), tumor size (p = 0.002), histological grade (p = 0.001), microvascular invasion (p < 0.001) and cholecystectomy (p = 0.021) were independent risk factors for HCC recurrence. However, there were no significant differences in OS between the cholecystectomy and non-cholecystectomy groups. Concurrent cholecystectomy may reduce recurrence in early-stage HCC after curative resection. Further studies are needed to validate our results.


Shell selection and utilization in a terrestrial hermit crab, Coenobita compressus (H. Milne Edwards).
Shell utilization and shell selection studied in the tropical terrestrial hermit crab, Coenobita compressus (H. Milne Edwards). Three major shell related variables are examined; shell size, shell species, and shell condition. Nerita scabricosta (Lamarck) is the most commonly occupied shell, and it is also preferred over other shell species. Coenobita in the field are usually found in smaller than the preferred size of shell, and the difference between utilized and preferred shells is most pronounced in relatively small individuals. Shell size preference differs significantly between similarly sized crabs collected at different sites. There is also a preference for shells which have previously been used by other Coenobita individuals. This preference is due to shell modification by Coenobita, which increases the effective size of the shell. It is argued that the fitness of most sexually mature individuals is probably unaffected by the supply of new shells, since these are too small to be utilized. It is possible that the interaction of adult Coenobita for shells may be better described as mutualism than as competition. This illustrates the fact that a significant difference between utilized and preferred resources need not imply competition for those resources. Results indicate that the nature of intraspecific competition and population regulation in at least this terrestrial hermit crab is significantly different from these processes in marine hermit crabs.


Multicomplex-based pharmacophore-guided 3D-QSAR studies of N-substituted 2'-(aminoaryl)benzothiazoles as Aurora-A inhibitors.
Aurora-A has been known as one of the most important targets for cancer therapy, and some Aurora-A inhibitors have entered clinical trails. In this study, combination of the ligand-based and structure-based methods is used to clarify the essential quantitative structure-activity relationship of known Aurora-A inhibitors, and multicomplex-based pharmacophore-guided method has been suggested to generate a comprehensive pharmacophore of Aurora-A kinase based on a collection of crystal structures of Aurora-A-inhibitor complex. This model has been successfully used to identify the bioactive conformation and align 37 structurally diverse N-substituted 2'-(aminoaryl)benzothiazoles derivatives. The quantitative structure-activity relationship analyses have been performed on these Aurora-A inhibitors based on multicomplex-based pharmacophore-guided alignment. These results may provide important information for further design and virtual screening of novel Aurora-A inhibitors.


Interaction of T7 RNA polymerase with DNA in an elongation complex arrested at a specific psoralen adduct site.
We have probed the interaction of T7 RNA polymerase with DNA in an elongation complex arrested by a site specifically placed psoralen diadduct or furanside monoadduct using DNase I footprinting techniques. The psoralen derivative, HMT (4'-hydroxy-methyl-4,5',8-trimethylpsoralen), was first placed at a specific site in the middle of a chemically synthesized double-stranded DNA fragment containing a T7 RNA polymerase promoter at one end. The psoralen molecule was photochemically attached either to 2 adjacent thymidine residues on opposite strands as a diadduct or to only 1 thymidine residue on the coding strand as a furan-side monoadduct. Using these psoralen-modified DNAs as templates for transcription, we found that T7 RNA polymerase was blocked at the psoralen adduct site and that the arrested elongation complex protected about 15 nucleotides upstream from the adduct on the coding strand and 20 nucleotides around the adduct on the noncoding strand from DNase I digestion. The two psoralen-modified DNA templates yielded identical RNA transcripts and DNase I footprints. In contrast, T7 polymerase protected only the coding strand from -20 to +8 in the initiation complex. These results suggest that the RNA polymerase undergoes a marked conformational change upon converting from an initiation complex to an elongation complex.


A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site.
HIV infection of chimpanzees results in a chronic viremia unaccompanied by the ultimately fatal immunodeficiency that marks HIV infection in man. We show here that expression of HIV envelope proteins allows syncytium formation between cells expressing human but not chimpanzee or macaque CD4. We find that the CD4 sequences regulating cell fusion lie outside the recognized virus binding site; in the simplest exchange, chimpanzee CD4 bearing human residue 87 supports syncytium formation, while human CD4 bearing chimpanzee residue 87 does not. Neither the equilibrium nor the forward rate constants for HIV-CD4 association are affected by substitution at position 87. Infection of human cells expressing chimpanzee CD4 is insensitive to lysosomotropic agents, suggesting that viral penetration under these circumstances does not require endocytosis. The benign course of HIV infection in chimpanzees may reflect the failure of the host to support direct cell to cell transmission of the virus.


Hepatodiaphragmatic portosystemic shunt in cirrhosis.
A case of an unusual form of hepatodiaphragmatic portosystemic shunt arising from the periphery of left posterosuperior portal vein branch, running beneath the inferior aspect of left hemidiaphragm and draining into the left lateral abdominal wall is demonstrated and assessed with digital subtraction portography, maximum-intensity-projection images reconstructed from helical CT during arterial portography and pulsed Doppler sonography with flow velocity measurement. This is a reported case of this unusual intrahepatic portosystemic shunt and discussion on the utility of current radiological techniques.


Trends in the Use of Sedative-Hypnotics, Opioids, and Neuromuscular Blockers in Hospitalized Patients During the COVID-19 Pandemic: Observational Retrospective Study.
The coronavirus disease 2019 (COVID-19) pandemic has increased the use of drugs administered for mechanical ventilation, leading to shortages in some countries. The aim was to identify trends in the consumption of sedatives, hypnotics, neuromuscular blockers, and opioids used for anesthetic induction and deep sedation in hospitals in Colombia. This was a descriptive, longitudinal, and retrospective study with monthly follow-up of sedative, hypnotic, opioid, and neuromuscular blocker dispensing in 20 clinics and hospitals from January to November 2020. The frequencies of use of each drug and variations in the institutions and intensive care units (ICUs) were identified. A total of 1,252,576 units of the analyzed drugs were delivered to 79,094 treated patients, 55.0% of whom were women (n = 43,521). The drugs with the greatest increase in consumption were rocuronium (1058% variation in March-November) and propofol (511%). The consumption of midazolam and vecuronium initially increased, but by the end of the study period, it decreased. Among drugs dispensed only in ICUs, 920,170 units were delivered (73.5% of the drugs dispensed during the study), and the most often dispensed drugs were fentanyl (n = 251,519; 27.3% of the drugs used in the ICU) and midazolam (5 mg/5 mL) solution (n = 188,568; 20.5%). Specifically in the ICU, the drugs with the greatest increase in use were rocuronium (19,709%), propofol (2622%), and ketamine (2591%). Rapid changes in the use of drugs were evident, which demonstrates the need for closer cooperation among treating physicians, service providers, pharmaceutical managers, and state institutions to maintain a sufficient and timely supply of critical drugs in this type of contingency.


Neurology of volition.
Neurological disorders of volition may be characterized by deficits in willing and/or agency. When we move our bodies through space, it is the sense that we intended to move (willing) and that our actions were a consequence of this intention (self-agency) that gives us the sense of voluntariness and a general feeling of being "in control." While it is possible to have movements that share executive machinery ordinarily used for voluntary movement but lack a sense of voluntariness, such as psychogenic movement disorders, it is also possible to claim volition for presumed involuntary movements (early chorea) or even when no movement is produced (anosognosia). The study of such patients should enlighten traditional models of how the percepts of volition are generated in the brain with regard to movement. We discuss volition and its components as multi-leveled processes with feedforward and feedback information flow, and dependence on prior expectations as well as external and internal cues.


Simultaneous improvements in antibacterial and flame retardant properties of PET by use of bio-nanotechnology for fabrication of high performance PET bionanocomposites.
Recently, attentions to the applications of biotechnology and nanotechnology in the polymer industries have been greater than before. Hybrid nanocomposites containing multi-type of nano structures are widely established, but application of biotechnology for in-situ embedment of nanoparticles in polymer matrix is rarely reported. In this study, poly (ethylene terephthalate) (PET) based ternary bionanocomposites containing modified chitosan (phosphorylated chitosan) and nanosilver particles were prepared by simple eco-friendly method. Chitosan was selected as a biopolymer with respect to the biological activity and compatibility with PET. Phosphorylation of chitosan was achieved in order to introduce the phosphorus moieties as a flame retardant agent in PET matrix by using chemical approach. Also a cost-effective and environmentally friendly method was used for the in-situ fabrication and decoration of silver nanoparticles on to phosphorylated chitosan in PET matrix. Effects of the hybrid system (phosphorylated chitosan and silver nanoparticles) on the morphology, thermal behavior and antibacterial properties of the PET samples were investigated by different methods. The microstructure and homogeneity of the samples were analyzed by studying of dispersion of nanoparticles in PET via scanning electron microscopy. The antibacterial properties of PET nanocomposites can be improved by insertion of silver nanoparticles into the bulk of polymer matrix. Obtained results indicated that the PET/phosphorylated chitosan/silver nanocomposites showed a significantly higher growth inhibition rate compared with the PET and PET/phosphorylated chitosan blend. Also the flame retardant properties of PET nanocomposites were drastically enhanced.


Prediction of 3-Year Survival in Patients with Cognitive Impairment Based on Demographics, Neuropsychological Data, and Comorbidities: A Prospective Cohort Study.
Based on readily available demographic data, neuropsychological assessment results, and comorbidity data, we aimed to develop and validate a 3-year survival prediction model for patients with cognitive impairment. In this prospective cohort study, 616 patients with cognitive impairment were included. Demographic information, data on comorbidities, and scores of the Mini-Mental State Examination (MMSE), Instrumental Activities of Daily Living (IADL) scale, and Neuropsychiatric Inventory Questionnaire were collected. Survival status was determined via telephone interviews and further verified in the official death register in the third year. A 7:3 ratio was used to divide patients into the training and validation sets. Variables with statistical significance (p < 0.05) in the single-factor analysis were incorporated into the binary logistic regression model. A nomogram was constructed according to multivariate analysis and validated. The final cohort included 587 patients, of whom 525 (89.44%) survived and 62 (10.56%) died. Younger age, higher MMSE score, lower IADL score, absence of disinhibition, and Charlson comorbidity index score ≤ 1 were all associated with 3-year survival. These predictors yielded good discrimination with C-indices of 0.80 (0.73-0.87) and 0.85 (0.77-0.94) in the training and validation cohorts, respectively. According to the Hosmer-Lemeshow test results, neither cohort displayed any statistical significance, and calibration curves displayed a good match between predictions and results. Our study provided further insight into the factors contributing to the survival of patients with cognitive impairment. Our model showed good accuracy and discrimination ability, and it can be used at community hospitals or primary care facilities that lack sophisticated equipment.


Association of Alzheimer's disease and Chlamydophila pneumoniae.
This paper critically reviews the association of infection by Chlamydophila pneumoniae (C. pneumoniae) and Alzheimer's disease (AD). The aging population has increased interest in finding the cause of AD, but studies have yielded contradictory results that are likely due to varying diagnostic tools and different uses of diagnostic tests. Knowledge of AD's characteristics, risk factors, and hypothesized etiologies has expanded since Alois Alzheimer's initial description of AD. Epidemiologic and projection studies provide incidence estimates of AD through a two-stage method: (1) primary diagnosis of dementia by cognitive testing such as Mini-Mental State Examination (MMSE), and (2) clinical diagnosis of AD through criteria such as National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Cross-sectional studies yield prevalence estimates of infection by C. pneumoniae by detecting immunoglobulins through laboratory tests such as microimmunofluorescence (MIF). Studies examining the association of C. pneumoniae and AD are limited, but brain autopsy provides information about presence, proximity to areas associated with AD, and bacterial load. Standardization of diagnostic techniques would allow for better comparability of studies, but uncertainty about the best method of diagnosis of infection by C. pneumoniae and AD may call for revised or novel diagnostic tools.


[The dystocias of the start of labour and their treatment with a beta sympatho-mimetic drug (author's transl)].
The authors have studied 106 cases of dystocia of the start of labour, which is defined as an abnormal increase in the length of the time of dilatation before the cervix reaches three centimetres dilated, in spite of contractions that apparently are of good quality. The contractions can be stopped by a beta sympatho-mimetic drug (Ritodrine) easily and the immediate problem is resolved, in that the woman is allowed a rest during which she can recover for a few hours. The labour starts off after this normally, but the percentage of Caesarean sections is very high (26.4 per cent) because in fact these dystocias of the start of labour are often associated with disproportion or a poorly flexed posterior position. There has been no serious secondary effect of the treatment nor any ill effects observed on the fetuses.


Optimization of ultrasonic-assisted polysaccharide extraction from Hyperici Perforati Herba using response surface methodology and assessment of its antioxidant activity.
This study performed a comprehensive investigation of Hyperici Perforati Herba polysaccharide (HPHP) regarding the development and optimization of extraction methods, elucidation of structure and characteristics, and determination of antioxidant activities. An ultrasonic-assisted extraction method, which offered advantages in terms of the extraction yield and energy efficiency, was developed by response surface analysis. The following optimum conditions were determined: a crushing degree at 65 mesh, ultrasonic time at 50 min and temperature of 43 °C. Through enzyme-mediated deproteination via the Sevag method, activated carbon depigmentation, and DEAE-52 and Sephadex G-100 column elution, three HPHPs were obtained, and their monosaccharides mainly included mannose, galactose, glucose and arabinose. The molar weights were 8.347, 1.199 and 22.426 kDa, respectively. The HPHP structures were an amorphous aggregate of spherical-like shapes with a rough surface of pores and crevices, which presented characteristic Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectra of polysaccharides. Their main glucosidic linkage is the α-type configuration. Moreover, HPHPs exhibited strong scavenging activity for DPPH·, ABTS·+, OH· and O2·- radicals; good ferric reducing power; and effective protection against oxidative damage in human cells. Overall, the results of this work underpinned a fundamental understanding of HPHPs, thus providing a potential antioxidant for further research and development.


Histological Evaluation of Bone Regeneration Using Hydroxyapatite Based Bone Substitute Derived from Antler: An Animal Study.
Guided bone regeneration (GBR) is considered as a prerequisite in some cases of implant dentistry. For this purpose, bone materials are commonly used. Calcium compounds and Ca-P based materials like hydroxyapatite (HA, Ca10 (PO4)6(OH)2), due to their similarity with the human bone, can be used as graft materials for bone regeneration. This study aimed to evaluate biocompatibility of antler xenograft and compare the osteoconduction effects of antler xenograft with Cerabone in regeneration of calvarium bony defects of rabbits. Five defects with a diameter of 6 mm and a depth of 3 mm were prepared in the calvarium of four rabbits. Thereafter, two defects were randomly grafted with antler xenograft, two defects were filled with Cerabone, and one defect remained as the untreated group. Histological evaluations, including measuring percentage of new regenerated bone and the amounts of osteoblast, osteoclast, and osteocyte cells, were also performed. To do statistical analyses, paired t-test, chi-square, and Fisher tests were applied. The percentage of new bone formation was significantly higher in antler xenograft (73.33%) and in Cerabone (48.91%) compared to the untreated group (18.91%). The amounts of osteocytes and osteoblasts were obtained as 3.52 ± 0.17 and 2.41 ± 0.24 in the Antler xenograft and as 2.57 ± 0.29 and 2.31 ± 0.32 in the Cerabone group, respectively. Bone marrow formation were significantly higher in antler xenograft (6.66 ± 5.34) and Cerabone (1.99 ± 3.17) compared to the untreated group. According to this pilot study, results of using antler xenograft as an osteoconductive materials in regeneration of rabbit calvarial defects are comparable with Cerabone. Although more clinical studies are needed.


The preventive effect of garlicin on a porcine model of myocardial infarction reperfusion no-reflow.
To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI). Twenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA). Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01). Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.


Transcriptomics reveal high regulatory diversity of drought tolerance strategies in a biennial oil crop.
Spring droughts are expected to become more frequent in Central Europe as a result of climate change. Their coincidence with flowering of biennial crops like winter oilseed rape (Brassica napus) can cause major impact for yield development. However, no data is available on the diversity of genetic regulation of drought tolerance during this stage under realistic conditions. Here, we assessed the phenotypic plasticity of drought response for eight diverse B. napus accessions under field-like conditions and linked their stress response to gene and miRNA expression during early and late stress. We observed highly diverse responses, both on the phenotypic and on the gene expression level. Our data suggest that drought tolerant accessions have more effective molecular protection mechanisms like ROS scavenging, source/sink ratio and regulation of developmental timing, compared to otherwise phenotypically similar accessions. Bna.MAP3K13.C05 expression was found to be protective independently of the tolerance mechanism, indicating cross-talk to nitrogen signaling. Moreover, we identified putative miRNA genes in the B. napus genome which respond to stress and may also be involved in protective mechanisms, representing possible breeding targets.


How does nintedanib overcome cancer drug-resistant mutation of RET protein-tyrosine kinase: insights from molecular dynamics simulations.
Targeted drug therapies represent a therapeutic breakthrough in the treatment of human cancer. However, the emergence of acquired resistance inevitably compromises therapeutic drugs. Rearranged during transfection (RET) proto-oncogene, which encodes a receptor tyrosine kinase, is a target for several kinds of human cancer such as thyroid, breast, and colorectal carcinoma. A single mutation L881V at the RET kinase domain was found in familial medullary thyroid carcinoma. Nintedanib can effectively inhibit the RET L881V mutant, whereas its analog compound 1 is unable to combat this mutant. However, the underlying mechanism was still unexplored. Here, molecular dynamics (MD) simulations, binding free energy calculations, and structural analysis were performed to uncover the mechanism of overcoming the resistance of RET L881V mutant to nintedanib. Energetic analysis revealed that the L881V mutant remained sensitive to the treatment of nintedanib, whereas it was insensitive to the compound 1. Structural analysis further showed that the distribution of K758, D892, and N879 network had a detrimental effect on the binding of compound 1 to the L881V mutant. The obtained results may provide insight into the mechanism of overcoming resistance in the RET kinase.


Preactivated thiolated nanoparticles: A novel mucoadhesive dosage form.
Within this study a novel form of mucoadhesive nanoparticles (NPs) exhibiting a prolonged residence time on mucosal tissues was developed. In order to achieve this goal a new thiomer was synthesized by the covalent attachment of the amino acid l-cysteine ethyl ester to poly(acrylic acid) (100 kDa). The free thiol groups were in the following preactivated with the aromatic thiol bearing ligand 2-mercaptonicotinic acid (2-MNA) and the amount of coupled l-cysteine ethyl ester as well as the amount of attached 2-MNA was determined. Based on this, preactivated thiomer NPs were prepared by ionic gelation with polyethylenimine (PEI). The resulting NPs were characterized regarding size and zeta potential. Furthermore their mucoadhesive properties were investigated via rheological measurements with porcine intestinal mucus and via determination of the particles' mucosal residence time. Results showed that 1666.74 μmol l-cysteine ethyl ester and 603.07 μmol 2-MNA could be attached per gram polymer. NPs were in a size range of 112.67-252.84 nm exhibiting a zeta potential of -29 mV. Thiolated NPs only led to a 2-fold increase in mucus viscosity whereas preactivated NPs showed a 6-fold higher mucus viscosity than unmodified NPs. The mucosal residence time of thiolated NPs was 1.6-fold prolonged and that of preactivated NPs even 4.4-fold higher compared to unmodified particles. Accordingly, preactivated thiolated NPs providing a prolonged residence time on mucosal membranes could be a promising dosage form for various applications.


Serum levels of testosterone and luteinizing hormone in patients with chronic renal disease.
Androgen metabolism has been studied in 33 patients (17 males, 16 females) with chronic renal disease not undergoing dialysis treatment. The mean value of serum testosterone was reduced in both sexes, whereas that of serum leteinizing hormone (LH) was elevated in the males. The parameters became increasingly pathological with decreasing renal function. There was no correlation between serum testosterone and serum LH, indicating an inadequate hypothalamic-pituitary response to the testicular dysfunction. The clinical significance of this relative hypoandrogenaemia is obscure. A possible relation to the anaemia and bone disease of chronic renal failure is discussed.


Risk factors and prevention for spinal cord injury from diving in swimming pools and natural sites in Quebec, Canada: a 44-year study.
Diving is the most frequent cause of spinal cord injury (SCI) from recreation and sport in Canada. This study was done to identify risk factors for SCI from diving in the province of Quebec. An interview survey was done for a target population of 203 subjects with a SCI from diving treated in the two specialized rehabilitation centers in Quebec during 1961-2004. Telephone interviews of consenting individuals were used to collect pertinent personal, equipment, and environmental factors for each incident. Response was 44% (89/203); 92% were male and 85% <35 years old. Only 37% were aware prior to injury of the risk of SCI from diving, and only 33% had received water safety training. Swimming pools were the site of 51% (n=45) and natural bodies of water for 49% (n=44). 87% (n=39) of pools were single-unit home pools and 57% (n=26) above-ground. Depth indicators were absent for 100% of above-ground and 74% of in-ground pools. For SCI in in-ground pools, 63% resulted from striking the up-slope between deep and shallow ends. For dives at natural sites, a dock or wharf was the most frequent location, 36% (n=16). In 52% of pools and 79% of natural sites, depth was <1.4m (4.6ft). Signs prohibiting diving were absent in 96% of above-ground and 89% of in-ground pools. Alcohol was reported in 47% of SCIs. The target for prevention of diving SCI is male youths and young adults. Above-ground pools are too shallow and small for diving. Deep ends of many in-ground pools are excessively shallow and short since many SCIs resulted from striking the up-slope. Prevention of SCI from diving needs to focus on education of potential victims, pool vendors and manufacturers, and regulations for safety norms in private pools. Water safety should highlight diving as a high-risk activity, and emphasize that most home pools and natural sites are unsafe. Safer evidence-based pool designs and more effective warnings need to be implemented.