Development of endocrine pathways in the regulation of calcium homeostasis.
The mammalian fetus is maintained hypercalcaemic relative to its mother by the action of a calcium pump believed to be located at the basement membranes of the epithelial cells of the fetal chorion. It has recently been demonstrated that the activity of this putative pump is stimulated by a new fetal hormone, parathyroid hormone-related protein, described originally as the product of a human BEN cell line which was derived from a lung tumour associated with hypercalcaemia of malignancy. Whereas the circulating level of immunoreactive parathyroid hormone in the fetus is very low, in keeping with the hypercalcaemia, the plasma concentrations of bioactive parathyroid hormone and parathyroid hormone-related protein can be measured using a sensitive cytochemical bioassay and the separate concentrations assessed by pre-incubation with appropriate antisera. The total plasma concentration of both hormones is inversely related to the prevailing calcium ion concentration but the set point of parathyroid hormone-related protein is probably higher than that for parathyroid hormone. Probably as a result of the hypercalcaemia, the circulating concentration of calcitonin is also higher than in maternal plasma and may serve to limit bone resorption to favour net bone accretion as part of the overall growth of the fetus. Vitamin D and its most active metabolite, 1,25(OH)2D, can pass across the placenta in either direction, in contrast to most peptide hormones. In addition to the supply of some 1,25(OH)2D by the mother to her fetus, the fetal placenta and fetal kidneys can all synthesize 1,25(OH)2D. The relative concentrations circulating in maternal and fetal plasma pools vary with the species, presumably as a result of differing importance of the three sources of supply to the fetus and the relative concentrations of vitamin D-binding protein circulating in mother and fetus. The importance of parathyroid hormone-related protein derived from fetal parathyroid glands has been clearly demonstrated in the fetal sheep. Such animals develop rickets following the removal of their parathyroid glands, despite the demonstration of this substance in fetal placental membranes. However, the relative importance of the parathyroid glands versus the placenta and its membranes as the principal source of parathyroid hormone-related protein remains to be elucidated and may vary with species.


Immunological effect of PM2.5 on cytokine production in female Wistar rats.
To investigate the immunological effect of PM2.5 on cytokine production in female Wistar rats. Female Wistar rats were given 0.3 mg, 0.75 mg, 2 mg, 5 mg of PM2.5 per 0.5 mL saline, respectively. Saline was used as the negative control. TNF-alpha and IL-6 levels in the branchoalveolar lavage were measured by ELISA, and mRNA expression levels in lung tissue were detected by RT-PCR. Alveolar macrophages were collected for testing phogacytic function. Exposure to PM2.5 stimulated TNF-alpha production in a dose-dependent manner (P < 0.05), However, no statistically significant difference was found. No time-dependent change in TNF-a and IL-6 production was found. TNF-alpha and IL-6 mRNA expressions were induced by PM2.5-exposure. The phagocytic rate (PR) was significantly decreased by PM2.5 treatment. PM2.5 exposure increases inflammation response of the lung in a dose-dependent manner. Moreover, tissue injury induced by PM2.5 may be related to altered production of cytokines. PMz2.5 may impair the phagocytic activity of alveolar macrophages.


The diversity of KIR gene in Chinese Northern Han population and the impact of donor KIR and patient HLA genotypes on outcome following HLA-identical sibling allogeneic hematopoietic stem cell transplantation for hematological malignancy in Chinese people.
Killer cell immunoglobulin-like receptors (KIRs) are members of a group of molecules that specifically recognize HLA class I ligands and are found on subsets of human lymphopoetic cells. The number of KIR loci can vary between individuals, resulting in a heterogeneous array of possible KIR genes. The range of observed profiles has been explained by the occurrence of two haplotype families termed A and B, which can be distinguished on the basis of certain KIR sequences. Immunogenetic analysis of different ethnic populations shows significant differences in terms of the distribution for group A and group B haplotypes. Recently, attention has been focused on the role of killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus-host direction between donor and recipient in allogeneic hematopoietic stem-cell transplantation (ASCT). The goal of this study was to study the frequency of specific KIR genes in Chinese Northern Han population and evaluate the role of KIR-ligand mismatch in Chinese HLA-identical sibling hematopoietic stem cell transplantation patients with hematological malignancy. Here genomic DNA from 150 Northern Chinese Han individuals was typed for the presence or absence of KIR genes. Seventy-four allogeneic stem cell transplantation donor/recipient pairs were typed for HLA-A, B, C and KIR. Sixteen KIR genes were observed in the population, and framework genes 3DL3, 3DP1, 2DL4, and 3DL2 were present in all individuals. Twenty-two different genotypes were found. Group A haplotypes outnumbered group B haplotypes in frequency by approximately 3:1, with individuals having two group A haplotypes accounting for 51.9% (78/150). We observed that 57 out of 74 (77.3%) donor-recipient pairs could be characterized by lack of recipient HLA ligand for donor KIR. We observed that 36 out of 45 (80%) donor-recipient HLA-identical sibling transplant pairs could be characterized by lack of recipient HLA ligand for donor KIR. Cumulative incidence analysis of aGVHD in patients undergoing HLA-identical sibling hematopoietic stem cell transplantation in this study demonstrated a decreased incidence of severe aGVHD in patients lacking HLA ligand for donor-inhibitory KIR2DL1 (31.4 vs. 70%, P = 0.029). And also in AML (acute myeloid leukemia) patients lacking HLA ligand for donor-inhibitory KIR and KIR2DL1 (17.6 vs. 75%, P = 0.03). Our data demonstrated that the Chinese Han population is distinct in KIR gene frequencies and putative KIR haplotypes in comparison to some other populations. Almost all allogeneic donors could be characterized as having an inhibitory KIR for each of the three known class I ligands. KIR and KIR2DL1 mismatch is associated with lower aGVHD in Chinese after HLA-identical sibling hematopoietic stem cell transplantation.


Case Report: Passive Handstand Promotes Cerebrovascular Elasticity Training and Helps Delay the Signs of Aging: A 40-Year Follow-Up Investigation.
There are no long-term (>10 years) follow-up evaluations of the effects of handstand exercise or studies on the use of equipment for passive handstand exercise. To report a 40-year follow-up investigation of a Chinese man who has been practicing passive handstand for 40 years. This observational investigation was conducted in Guizhou Province, China. A (currently) 66-year-old Chinese man who had been practicing passive handstand exercise for 40 years was followed up. Physical and auxiliary examinations were carried out to determine the effects of long-term passive handstand exercise on the human body. The participant's cerebrovascular, spinal health, mental health, and visual acuity as well as the presence of facial aging were examined. His cerebral vessels were healthy, he appeared younger than his peers, his cervical spondylosis improved, and his mental state and cognitive function were good. Long-term passive handstand exercise can promote cerebrovascular elasticity training and delay signs of aging. We recommend promoting this passive handstand exercise to the public.


Ordinal regression models for zero-inflated and/or over-dispersed count data.
Count data commonly arise in natural sciences but adequately modeling these data is challenging due to zero-inflation and over-dispersion. While multiple parametric modeling approaches have been proposed, unfortunately there is no consensus regarding how to choose the best model. In this article, we propose a ordinal regression model (MN) as a default model for count data given that this model is shown to fit well data that arise from several types of discrete distributions. We extend this model to allow for automatic model selection (MN-MS) and show that the MN-MS model generates superior inference when compared to using the full model or more traditional model selection approaches. The MN-MS model is used to determine how human biting rate of mosquitoes, known to be able to transmit malaria, are influenced by environmental factors in the Peruvian Amazon. The MN-MS model had one of the best fit and out-of-sample predictive skill amongst all models. While A. darlingi is strongly associated with highly anthropized landscapes, all the other mosquito species had higher mean biting rates in landscapes with a lower fraction of exposed soil and urban area, revealing a striking shift in species composition. We believe that the MN and MN-MS models are valuable additions to the modelling toolkit employed by environmental modelers and quantitative ecologists.


Potential use of native fruits waste from Argentina as nonconventional sources of cosmetic ingredients.
Collagenase, hyaluronidase, elastase, and tyrosinase enzymes are overexpressed and overactive in the skin aging process and hydrolyze the components of the dermal extracellular matrix (ECM) of the skin; these enzymes produce the clinical framework of aging, which includes skin dryness, hyperpigmentation, wrinkles, and inelasticity. The aim of this study was to explore the potential use of waste from two Argentine native fruits, namely Ziziphus mistol, and red and orange varieties of Solanum betaceum, as sources of bioactive compounds. Phenolic enriched extracts (PEE) from waste of Z. mistol and S. betaceum were obtained, and their total contents of phenolics and flavonoids were evaluated. The bioactive properties of the extracts were analyzed by measuring their antioxidant capacity and the inhibitory activity on collagenase, hyaluronidase, elastase, and tyrosinase enzymes. The increased ability to inhibit the collagenase was demonstrated by the PEE of Z. mistol seeds and peel, while the enzyme elastase was mostly inhibited by extracts of S. betaceum skin. Z. mistol seed extract was the most active to inhibit hyaluronidase, reaching 96% inhibition at a concentration of 100 μg GAE/mL. The most active extracts to inhibit the tyrosinase enzyme were obtained from the peel of two varieties of chilto fruits, orange and red, and the mistol seed. The results obtained suggest that Z. mistol and S. betaceum waste may be considered as a source of bioactive phenolics. Here, Argentine native fruits waste is presented as a most promising alternative in cosmetic products, with future uses such as hydrogels, creams, or lotions.


A qualitative exploration of motivations and barriers for community leisure organisations' engagement with the Jooay™ mobile app.
Participation in leisure activities is key to the physical and mental health of children and adolescents with disabilities. The Jooay™ mobile app aims to link children and adolescents with disability to participation opportunities in their community. This study explored the perspectives of community leisure organisations and their motivations and perceived barriers to be listed as a leisure service on Jooay™. Twenty representatives of community leisure organisations in metropolitan Perth, Western Australia were interviewed. Vroom's Expectancy Theory was used to shape the semi-structured interview guides. Data were analysed with thematic analysis using an inductive open coding approach. Four key themes pertaining to motivations and barriers to registration with Jooay™ were developed: Building reputation; Collaboration; Ability to deliver accessible leisure services; and Usability of Jooay™. Multiple motivating factors for registering on Jooay™ were identified including positive financial implications, meeting corporate social responsibilities, building collaborative stakeholder partnerships, and building organisational confidence and awareness of disability through supportive partnerships. Environmental and organisational barriers to inclusion were highlighted. Findings will inform future promotion of the features and benefits of Jooay™ to engage community leisure organisations. This may increase the number of accessible leisure services listed within the app, providing a greater selection of community leisure activities in which children and adolescents with disability can participate.IMPLICATIONS FOR REHABILITATIONCommunity leisure organisations would be motivated to engage with the JooayTM app, provided the right supports are in place for them.Additional benefits of registering on JooayTM may include positive financial implications, meeting corporate social responsibilities, building collaborative stakeholder partnerships, and building disability confidence and awareness through supportive partnerships.Ongoing education and support is needed for community leisure organisations regarding; disability awareness, competency, and capacity to deliver leisure services in inclusive and equitable ways. This will enable them to increase their accessibility for children with disabilities, particularly for non-disability-specific leisure organisations.Information about leisure services on the Jooay™ app builds capacity in the community to identify diverse access needs of children and young people with disabilities and the most effective strategies to address them.


Cigarette smoking and the risk of nasopharyngeal carcinoma: a meta-analysis of epidemiological studies.
The role of cigarette smoking as an independent risk factor for patients with nasopharyngeal carcinoma (NPC) is controversial. We attempted to provide evidence of a reliable association between cigarette smoking and the risk of NPC. Meta-analysis. PubMed online and the Cochrane Library of relevant studies published up to February 2016. All studies had to evaluate the relationship between NPC and cigarette smoking with never smokers as the reference group. The primary outcome was the adjusted OR, RR or HR of NPC patients comparing smoking with never-smoking; the second was the crude OR, RR or HR. We identified 17 case-control studies and 4 cohort studies including 5960 NPC cases and 429 464 subjects. Compared with never smokers, current smokers and ever smokers had a 59% and a 56% greater risk of NPC, respectively. A dose-response relationship was identified in that the risk estimate rose by 15% (p<0.001) with every additional 10 pack-years of smoking, and risk increased with intensity of cigarette smoking (>30 cigarettes per day). Significantly increased risk was only found among male smokers (OR, 1.36; 95% CI 1.15 to 1.60), not among female smokers (OR, 1.58; 95% CI 0.99 to 2.53). Significantly increased risk also existed in the differentiated (OR, 2.34; 95% CI 1.77 to 3.09) and the undifferentiated type of NPC (OR, 1.15; 95% CI 0.90 to 1.46). Moreover, people who started smoking at younger age (<18 years) had a greater risk than those starting later for developing NPC (OR, 1.78; 95% CI 1.41 to 2.25). Cigarette smoking was associated with increased risk of NPC, especially for young smokers. However, we did not find statistical significant risks of NPC in women and in undifferentiated type, which might warrant further researches.


Impact of a multifaceted community-based falls prevention program on balance-related psychologic factors.
To assess the impact of a multifaceted falls prevention program including exercise and educational components on perceived balance and balance confidence among community-dwelling seniors. Quasi-experimental design. Community-based organizations. Two hundred community-dwelling adults aged 60 years and over recruited by community-based organizations. A 12-week multifaceted falls prevention program including 3 components (a 1-hour group exercise class held twice a week, a 30-minute home exercise module to be performed at least once a week, a 30-minute educational class held once a week). Perceived balance and balance confidence. Multivariate analysis showed that the program was successful in increasing perceived balance in experimental participants. However, balance confidence was not improved by program participation. A multifaceted community-based falls prevention program that was successful in improving balance performance among community-dwelling seniors also had a positive impact on perceived balance. However, the program did not improve participants' balance confidence. These results suggest that balance confidence has determinants other than balance and that new components and/or modifications of existing components of the program are required to achieve maximal benefits for seniors in terms of physical and psychologic outcomes.


A Model of Advocacy to Inform Action.
The need for effective advocacy on the part of health professionals has never been greater. The recent COVID-19 pandemic has made the connection between human health and social conditions clear, while highlighting the limitations of biomedical interventions to address those conditions. Efforts to increase the frequency and effectiveness of advocacy activities by health professionals have been hampered by the lack of a practical framework to define and develop advocacy competencies among trainees as well as to plan and execute advocacy activities. The authors of this article propose a framework which defines advocacy as occurring across three domains of influence (practice, community, and government) using three categories of advocacy skills (policy, communication, and relationships). When these skills are successfully applied in the appropriate domains of influence, the resulting change falls into three levels: individual, adjacent, and structural. The authors assert that this framework is immediately applicable to a broad variety of health professionals, educators, researchers, organizations, and professional societies as they individually and collectively seek to improve the health and well-being of those they care for.


Photoelectron imaging and photoelectron labeling.
Photoelectron imaging involves the photoejection of low-energy electrons from a specimen surface exposed to UV light. The electrons are then accelerated and focused by an electron-optics system in much the same way fluorescent light is focused in an optical microscope. Thus, photoelectron imaging is the electron-optical analog of fluorescence microscopy. In combination with photoemissive labels it serves to extend the range of studies possible by fluorescence, for example in work on cell surfaces and internal structures of cells that have been exposed by detergent extraction of membranes.


Selection of cells with different chromosomal localizations of the amplified c-myc gene during in vivo and in vitro growth of the breast carcinoma cell line SW 613-S.
The c-myc gene is amplified in the human breast carcinoma cell line SW 613-S. At early in vitro passages, the extra copies of the gene were mainly localized in double minute chromosomes (DMs), as shown by in situ hybridization with a biotinylated c-myc probe. However, cells without DMs were also present in which the c-myc genes were found integrated into any of several distinct chromosomes (mainly 7q+, 4 and 4q+, and 1). When this cell line was propagated in vitro, the level of c-myc amplification decreased because cells with DMs and a high amplification level were lost and replaced by cells without DMs and having a low amplification level. On the contrary, when early passage SW 613-S cells were grown in vivo, as subcutaneous tumours in nude mice, cells with numerous DMs and a high level of c-myc amplification were selected for. In one cell line (SW 613-Tu1) established from such a tumour, the DM-containing cells were substituted at late passages for cells with a high number of c-myc copies integrated within an abnormally banded region, at band 17q24 of a 17q+ chromosome. When only cells with integrated genes were present, this cell line was still highly tumorigenic indicating that the localization of the c-myc genes in DMs was not required for these cells to be tumorigenic in nude mice. Furthermore, cells of the secondary tumours induced by SW 613-Tu1 did not contain any DMs showing that in vivo growth did not promote the release of integrated c-myc copies into DMs.


Pulmonary Artery Denervation for Patients With Residual Pulmonary Hypertension After Pulmonary Endarterectomy.
Pulmonary artery denervation (PADN) procedure has not been applied to patients with residual chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA). This study sought to assess the safety and efficacy of PADN using remote magnetic navigation in patients with residual CTEPH after PEA. Fifty patients with residual CTEPH despite medical therapy at least 6 months after PEA, who had mean pulmonary artery pressure ≥25 mm Hg or pulmonary vascular resistance (PVR) > 400 dyn‧s‧cm-5 based on right heart catheterization were randomized to treatment with PADN (PADN group; n = 25) using remote magnetic navigation for ablation or medical therapy with riociguat (MED group; n = 25). In the MED group, a sham procedure with mapping but no ablation was performed. The primary endpoint was PVR at 12 months after randomization. Key secondary endpoint included 6-min walk test. After PADN procedure, 2 patients (1 in each group) developed groin hematoma that resolved without any consequences. At 12 months, mean PVR reduction was 258 ± 135 dyn‧s‧cm-5 in the PADN group versus 149 ± 73 dyn‧s‧cm-5 in the MED group, mean between-group difference was 109 dyn‧s‧cm-5 (95% confidence interval: 45 to 171; p = 0.001). The 6-min walk test distance was significantly increased in the PADN group as compared to distance in the MED group (470 ± 84 m vs. 399 ± 116 m, respectively; p = 0.03). PADN in patients with residual CTEPH resulted in substantial reduction of PVR at 12 months of follow-up, accompanied by improved 6-min walk test.


Optimisation of the protocol for detection of Aeromonas species in ready-to-eat salads, and its use to speciate isolates and establish their prevalence.
Aeromonas spp. are detected in more than 500 cases of gastrointestinal infection each year in England and Wales. This study aimed to identify their prevalence in ready-to-eat salads, which are a potential source of aeromonas infection. The protocol for isolation of mesophilic Aeromonas spp. from salads was optimised. Using the improved method, Aeromonas spp were isolated from 19 of 25 samples (25 g) of ready-to-eat salad products. Aeromonas organisms were counted, isolates were identified to species level, and the effect of pH on colonisation of salads was assessed. Aeromonas was present at high levels in six salads (> or = 100 cfu/g). The major species present in salads was Aeromonas caviae, but A.hydrophila and A.sobria, which have more pathogenic potential, were also isolated. It is hoped that this study will help to assess the risk to public health of aeromonas in salads.


Epididymal lymphoma: report of two cases and imaging findings.
Epididymal lymphoma is a very rare tumor that is difficult to differentiate radiologically from other paratesticular tumors. Most cases of epididymal lymphoma are secondary involvement of the epididymis in patients with testicular lymphoma. However, isolated epididymal lymphoma is very rare. We herein report two cases of isolated epididymal lymphoma with different imaging findings. Patient 1 was a 52-year-old man who presented with a painless scrotal mass. Patient 2 was a 65-year-old man who presented with painless scrotal swelling. Ultrasound (US) demonstrated different imaging findings: US in patient 1 showed a well-defined round mass in the tail of the epididymis with hypervascularity confined to the epididymis, while US in patient 2 showed diffuse infiltrative enlargement with hypervascularity confined to the epididymis. Orchiectomy performed in both patients revealed diffuse large B-cell lymphoma confined to the epididymis.


Oral THC produces minimal behavioral alterations in preadolescent rats.
Although the oral route has traditionally been used for THC administration during the perinatal period in the rat, most studies administering THC during the postnatal period utilize intraperitoneal (ip) administration. In an effort to utilize the same route of administration in both prenatal and postnatal studies, we administered Delta-9-tetrahydrocannabinol (THC) in sesame oil by gavage during postnatal days 22-40 (equivalent to childhood to early adolescence) to male and female rats. We quantified behavior 40 min after administration in the Accuscan activity monitor on days 22, 29 and 40. In addition, we examined active and passive avoidance behaviors in treated adults. Acutely, THC had subtle effects on activity when measured during the period of drug administration and minimal effects on avoidance behaviors examined up to 140 days of age. Since several groups have found that lower doses of THC administered intraperitoneally to periadolescent rats do produce behavioral alterations, we suspect that the inordinately slow absorption of the drug via the oral route may be responsible for the paucity of significant findings in our study. Therefore, oral administration of THC, particularly under conditions of mild food deprivation, may lead to sub-psychoactive concentrations of the drug within the brain.


Effects of the molecular weight of hyaluronan on the conformation and release kinetics of self-assembled 5-fluorouracil-loaded lysozyme-hyaluronan colloidal nanoparticles.
Lysozyme (LYS) and hyaluronan with low (HA1: 3 kDa), medium (HA2: 120 kDa), and high (HA3: 1200 kDa) molecular weights were used to fabricate lysozyme-hyaluronan colloidal nanoparticles using a green self-assembly method. Fourier transform infrared spectroscopy indicated that hydrogen bonding, hydrophobic and electrostatic interactions promoted the formation of the colloidal nanoparticles. The hydrophobic area of prepared colloidal nanoparticles was quantified using a pyrene fluorescent probe, and the results showed that the LYS-HA3 nanoparticles had the strongest hydrophobic capacity. Furthermore, 5-fluorouracil (5-Fu) was used to evaluate encapsulation performance, demonstrating that the LYS-HA3 nanoparticles had the highest encapsulation ability (>90 %). All prepared 5-Fu-loaded lysozyme-hyaluronan (5-Fu@LYS-HA) colloidal nanoparticles exhibited excellent long-term storage stability at 4 °C for 60 days. Cellular uptake and in vitro release results indicated that the LYS-HA2 nanoparticles exhibited the highest cellular uptake efficiency, and the LYS-HA3 nanoparticles had the best slow-release effect, while the release process was mainly controlled by the combination of Fickian diffusion and structural relaxation, respectively. This study demonstrates the influence of molecular weight on the conformational and structural properties of colloidal nanoparticles, which has implications for the design of insoluble drug self-assembly systems.


A muscarinic agonist-stimulated chloride efflux pathway is associated with fluid secretion in rat parotid acinar cells.
Cl- efflux from rat parotid acinar cells was stimulated by the muscarinic-cholinergic agonist carbachol (K0.5 approximately 1 microM). Carbachol application resulted in a rapid (T1/2 less than 10 sec.) and dramatic (approximately 50%) loss of intracellular Cl- followed by a much slower (T1/2 approximately 2 min) recovery to approximately 70% of original acinar Cl- content. Diphenylamine-2-carboxylate (1 mM), a putative Cl- channel blocker, blunted the initial Cl- loss and enhanced the subsequent recovery of Cl- content, while bumetanide (0.1 mM) blocked Cl- recovery with no effect on Cl- loss. Calculation of the rate of salivary secretion from measurements of sustained stimulated acinar Cl- release in vitro, yielded a value of 14 microliters/gland/min, in excellent agreement with previously published in vivo data. These results demonstrate that Cl- loss via this efflux pathway can account for fluid secretion from the rat parotid gland.


Suboccipital telovelar approach for microsurgical resection of a hemorrhagic brainstem cavernous malformation in an infant - how I do it.
The resection of brainstem cavernous malformations pose an extreme neurosurgical challenge, especially in infants as very few cases are reported in the literature. The optimal management still needs to be defined, demanding a tailored approach on an individual basis. Herein, we report our management and surgical technique for the resection of hemorrhagic pontine cavernous malformation in a 9-month-old infant through a suboccipital telovelar approach. The resection of hemorrhagic brainstem cavernomas is feasible and safe even in selected infant patients. The timing and the microsurgical technique are of paramount importance for the prevention of postoperative deficits.


Complete or Incomplete Revascularization for ST-Segment Elevation Myocardial Infarction: The PRAMI Trial to COMPLETE.
Many patients presenting with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (CAD). Following successful primary percutaneous coronary intervention (PCI) of culprit lesion, whether to routinely revascularize nonculprit lesions or treat them medically has been debated. Recently, the large-scale, multinational COMPLETE trial definitively established benefit of routine, staged, angiographically guided nonculprit lesion PCI in reducing hard clinical outcomes, including the composite of death from cardiovascular causes or new myocardial infarction, with no major safety concerns. A strategy of complete revascularization with routine nonculprit lesion PCI in suitable lesions should be standard of care in STEMI with multivessel CAD.


Histamine activates proenkephalin A mRNA but not phenylethanolamine N-methyltransferase mRNA expression in cultured bovine adrenal chromaffin cells.
The effects of histamine on the regulation of proenkephalin A (ProEnk A) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression were examined in cultures of bovine adrenal chromaffin cells. Prolonged incubation with histamine resulted in a concentration-dependent increase in the levels of ProEnk A mRNA with little effect on the levels of PNMT mRNA. The activation of ProEnK A mRNA by histamine followed a slow time course, reaching 2-3 fold basal levels after 48 h incubation. This activation was antagonized by the H1-antagonist mepyramine but not by the H2-antagonist cimetidine indicating involvement of H1-histamine receptors. The histamine-induced activation of ProEnK mRNA was blocked by the RNA synthesis inhibitor actinomycin D, suggesting that the novo synthesis of ProEnkA mRNA is a requirement for activation. In the presence of the calcium channel blocker D600, the histamine-induced increase in ProEnk A mRNA was greatly reduced, though not abolished. Prolonged incubation with histamine also caused a substantial release of catecholamines and opioid peptides from these cells. These results suggest that the synthesis and release of opioid peptides is controlled by histamine via H1-receptors. The differential effects of histamine on ProEnk A mRNA and PNMT mRNA expression suggest that different regulatory mechanisms are called upon to regulate the synthesis of opioid peptides and adrenaline in response to stimulation of the chromaffin cells.


Epigallocatechin-3-gallate activates the AMP-activated protein kinase signaling pathway to reduce lipid accumulation in canine hepatocytes.
Epigallocatechin-3-gallate (EGCG) plays a crucial role in hepatic lipid metabolism. However, the underlying regulatory mechanism of hepatic lipid metabolism by EGCG in canine is unclear. Primary canine hepatocytes were treated with EGCG (0.01, 0.1, or 1 μM) and BML-275 (an AMP-activated protein kinase [AMPK] inhibitor) to study the effects of EGCG on the gene and protein expressions associated with AMPK signaling pathway. Data showed that treatment with EGCG had greater activation of AMPK, as well as greater expression levels and transcriptional activity of peroxisome proliferator activated receptor-α (PPARα) along with upregulated messenger RNA (mRNA) abundance and protein abundance of PPARα-target genes. EGCG decreased the expression levels and transcriptional activity of sterol regulatory element-binding protein 1c (SREBP-1c) along with downregulated mRNA abundance and protein abundance of SREBP-1c target genes. Of particular interest, exogenous BML-275 could reduce or eliminate the effects of EGCG on lipid metabolism in canine hepatocytes. Furthermore, the content of triglyceride was significantly decreased in the EGCG-treated groups. These results suggest that EGCG might be a potential agent in preventing high-fat diet-induced lipid accumulation in small animals.


Robot-Aided Training of Propulsion During Walking: Effects of Torque Pulses Applied to the Hip and Knee Joints During Stance.
We sought to evaluate the effects of the application of torque pulses to the hip and knee joint via a robotic exoskeleton in the context of training propulsion during walking. Based on our previous study, we formulated a set of conditions of torque pulses applied to the hip and knee joint associated with changes in push-off posture, a component of propulsion. In this work, we quantified the effects of hip/knee torque pulses on metrics of propulsion, specifically hip extension (HE) and normalized propulsive impulse (NPI), in two experiments. In the first experiment, we exposed 16 participants to sixteen conditions of torque pulses during single strides to observe the immediate effects of pulse application. In the second experiment, we exposed 16 participants to a subset of those conditions for 200 strides to quantify short-term adaptation effects. During pulse application, NPI aligned with the expected modulation of push-off posture, while HE was modulated in the opposite direction. The timing of the applied pulses, early or late stance, was crucial, as the effects were often in the opposite direction when changing timing condition. Extension torque applied at late stance increased HE in both experiments - range of change in HE: (2.9 ± 0.4 deg, 7.7 ± 1.0 deg), . The same conditions resulted in a negative change in NPI only in the single pulse experiment - change in NPI for knee torque: -3.0 ± 0.4 ms, - and no significant change for hip torque. Also, knee extension and flexion torque during early and late stance, respectively, increased NPI during single pulse application - range of change in NPI: (3.8, 4.6) ± 0.8 ms, . During repeated pulse application, NPI increased for late stance flexion torque - range of change in NPI: (4.5 ± 0.7 ms, 4.8 ± 0.8 ms), , but not late stance extension torque. After exposure, we observed positive after-effects in HE in three conditions - range of change in HE: (2.0 ± 0.3 deg, 3.7 ± 0.7 deg) - and significant positive after-effects in NPI for early stance flexion torques - change in NPI: (2.7 ± 0.6 ms, ). These results indicate that positive propulsive after-effects can be achieved through repeated exposure to torque pulses.


Comparative studies of pig platelet membrane proteins.
The proteins and glycoproteins of pig platelet membranes have been studied using gel electrophoretic techniques. A nomenclature is suggested from the apparent molecular weights estimated by one-dimensional electrophoresis. Isoelectric focusing showed that the majority of the proteins are in the 4.0-7.0 pH range. Subunits have been inferred from oligoproteins by two-dimensional, reduced-nonreduced, electrophoresis techniques. High resolution two dimensional electrophoresis combining isoelectric focusing and sodium dodecyl sulphate allows the observations of 60 polypeptide bands. An identification of some of those bands based on a correlation from reported human blood platelet membrane proteins is presented for comparison.


Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo.
The flavolignan silibinin was studied for its ability to restore drug sensitivity to EGFR-mutant NSCLC xenografts with epithelial-to-mesenchymal transition (EMT)-driven resistance to erlotinib. As a single agent, silibinin significantly decreased the tumor volumes of erlotinib-refractory NSCLC xenografts by approximately 50%. Furthermore, the complete abrogation of tumor growth was observed with the co-treatment of erlotinib and silibinin. Silibinin fully reversed the EMT-related high miR-21/low miR-200c microRNA signature and repressed the mesenchymal markers SNAIL, ZEB, and N-cadherin observed in erlotinib-refractory tumors. Silibinin was sufficient to fully activate a reciprocal mesenchymal-to-epithelial transition (MET) in erlotinib-refractory cells and prevent the highly migratogenic phenotype of erlotinib-resistant NSCLC cells. Given that the various mechanisms of resistance to erlotinib result from EMT, regardless of the EGFR mutation status, a water-soluble, silibinin-rich milk thistle extract might be a suitable candidate therapy for upcoming clinical trials aimed at preventing or reversing NSCLC progression following erlotinib treatment.


Diffuse Lewy body disease.
Diffuse Lewy body disease, also called dementia with Lewy bodies (DLB), is defined as progressive dementia and pathological Lewy bodies distributed in the central and autonomic nervous systems. The clinical features are dementia, cognitive fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder (RBD). Confirmatory techniques include dopamine transporter imaging, meta-iodobenzylguanidine (MIBG) myocardial scintigraphy, and polysomnography. The pathology finding in DLB is misfolded alpha-synuclein, the main component of Lewy bodies, propagating in the central nervous system. This may interrupt the acetylcholine pathway and activate an inflammatory response. Mutations of several genes have been found in patients with DLB, including SNCA, GBA, and APOE. The differential diagnosis of DLB and Parkinson's disease with dementia (PDD) is a debated issue. Clinical features distinguishing DLB from PDD include the timing of dementia and visual hallucinations, responses to dopaminergic agents and anti-psychotics, and imaging findings. As to the management of DLB, cholinesterase inhibitors are the Level-A recommendation for treating dementia in DLB patients and also are beneficial for treating visual hallucinations and psychotic symptoms. Dopamine agonists have the risk of inducing psychotic symptoms, while levodopa should be used carefully for motor symptoms. Melatonin and clonazepam are effective in controlling RBD. Several other treatment methods are undergoing trials, including pimavanserine, nilotinib, psychological interventions, and behavior therapy.


Natural history of generalized motor seizures: A retrospective analysis.
This study aims to characterize the natural history of generalized motor seizures through longitudinal stratification of patient-reported clinical seizures into high, medium and low rates of generalized motor seizures (also known as generalized tonic-clonic seizures or GTCs). From 2007 to 2018, 1.4 million seizures were recorded by 12,402 SeizureTracker.com users that met inclusion/exclusion criteria. The number of GTCs per year since the first seizure diary entry was calculated for each user and categorized as: Low (0 GTCs/year), Medium (1-2 GTCs/year), or High (>3 GTCs/year) GTC rates. Kaplan-Meier survival curves for the time until exiting the initial category were computed. There was a global difference between risk groups (p < 0.01). Further pairwise log rank tests revealed a difference between each pair of risk groups (p < 0.01). At 3 years, 40.8% of people initially presenting with high GTC rates remained in their initial category, while 77.3% of people initially presenting with low GTC rates remained in their initial category. A patient with a low rate of GTCs is likely to remain at low risk for future GTCs, whereas higher GTC rate patients (at least one GTC/year) may leave their initial risk stratification. Thus, yearly re-assessment may be prudent when considering risk of further GTCs. Given the association between higher yearly rates of GTCs with increased SUDEP risk and morbidity in epilepsy, further validation of these findings is important for prognostication.


Global hotspots and trends in interactions of microplastics and heavy metals: a bibliometric analysis and literature review.
Microplastics (MPs) are identified as emerging contaminants; however, their interactions with heavy metals in the environment have not been well elucidated. Here, the research progress, hotspots, and trends in the interactions of MPs and heavy metals were analyzed at a global scale using a bibliometric analysis combined with a literature review. We comprehensively searched the Web of Science Core Collection database from 2008 to July 5, 2022. A total of 552 articles published in 124 journals were selected, which came from 70 countries and 841 institutions. The most contributing journals, countries, institutions, and authors were identified. Visualization methods were used to identify high co-citation references and hot keywords in the 552 articles. Evolutionary and cluster analyses of hot keywords suggested several research hotspots in the co-contamination of MPs and heavy metals, including their toxicity and bioaccumulation, the adsorption and desorption behaviors, the environmental pollution and risk assessment, and their detection and characterization. Based on the current research status, several directions of priority are recommended to understand the interactions between MPs and heavy metals and their potential risks. This article can help recognize the current research status and future directions in this field.


Modeling the Risk of Entry, Establishment, Spread, Containment, and Economic Impact of Tilletia indica, the Cause of Karnal Bunt of Wheat, Using an Australian Context.
ABSTRACT Modeling techniques were developed to quantify the probability of Tilletia indica entering and establishing in Western Australia (WA), and to simulate spread, containment, and the economic impact of the pathogen. Entry of T. indica is most likely to occur through imports of bulk grain or fertilizer (0.023 +/- 0.017 entries per year and approximately 0.009 +/- 0.009 establishments per year). Entry may also occur through straw goods, new or second-hand agricultural machinery, and on personal effects of travelers who have visited regions with infected plants. The combined probability of entry and establishment of T. indica, for all pathways of entry, is about one entry every 25 years and one establishment every 67 years. Alternatively, sensitivity analysis does show that increases in quarantine funding can reduce the probability of entry to about one entry every 50 years and less than one establishment every 100 years. T. indica is spread efficiently through contaminated farm machinery, seed and soil, rain, air currents, and animals. Depending on the rate of spread of the pathogen and the amount of resources allocated for detection, the time until first detection could range from 4 to 11 years and the economic impact could range from 8 to 24% of the total value of wheat production in WA.


Sub-basal Corneal Nerve Plexus Analysis Using a New Software Technology.
To study sub-basal corneal nerve plexus (SCNP) parameters by in vivo corneal confocal microscopy using a new software technology and examine the effect of demographics and diabetes mellitus (DM) on corneal nerves morphology. A Confoscan 4 (Nidek Technologies) was used in this cross-sectional study to image the SCNP in 84 right eyes at the Miami Veterans Affairs eye clinic. Images were analyzed using a new semiautomated nerve analysis software program (The Corneal Nerve Analysis tool) which evaluated 9 parameters including nerve fibers length (NFL) and nerve fibers length density (NFLD). The main outcome measure was the examination of SCNP morphology by demographics, comorbidities, and HbA1c level. Interoperator and intraoperator reproducibility were good for the 9 parameters studied (Intraclass Correlations [ICCs] 0.73-0.97). Image variability between two images within the same scan was good for all parameters (ICC 0.66-0.80). Older individuals had lower SCNP parameters with NFL and NFLD negatively correlating with age (r=-0.471, and -0.461, respectively, P<0.01 for all). Patients with diabetes had lower mean NFLD 10987.6 μm/mm (±3,284.6) and NFL 1,289.5 μm/frame (±387.2) compared with patients without diabetes (mean NFLD 15077.1 μm/mm [±4,261.3] and NFL 1750.0 μm/frame [±540.7]) (P<0.05 for all). HbA1c levels in patients with diabetes were inversely correlated with NFL and NFLD (r= -0.568, and -0.569, respectively, P<0.05 for all). The Corneal Nerve Analysis tool is a reproducible diagnostic software technique for the analysis of the SCNP with confocal microscopy. Older age, DM, and higher level of HbA1c were associated with a significant reduction in SCNP parameters.


Exploratory analysis of early toxicity of sunitinib in advanced hepatocellular carcinoma patients: kinetics and potential biomarker value.
Sunitinib--a multitargeted tyrosine kinase inhibitor--can modulate circulating inflammatory factors in cancer patients that may be relevant for hepatocellular carcinoma (HCC) progression. However, a recent phase III study of sunitinib in HCC was halted due to its toxicity. Here, we studied the early kinetics of adverse events after sunitinib, and explored their association with circulating proteins and clinical outcome in advanced HCC in a single-arm phase II study. Toxicity was evaluated every two weeks during the first cycle of therapy. Biomarker changes from baseline were tested after adjusting for multiple comparisons. Correlation between toxicities and overall survival (OS) or time-to-tumor progression (TTP) was evaluated in a Cox model using log-transformed levels or change in biomarkers, after stratifying by stage and adjusting for baseline level. Myeloid and lymphoid blood cell counts decreased by 20% to 50% after sunitinib treatment (P < 0.05 for all). The extent of the early decrease in neutrophils and monocytes, and the development of nonhematologic toxicities (i.e., skin toxicities), were significantly associated with both OS and TTP (P < 0.05). Changes in circulating cells significantly associated with specific changes in plasma biomarkers (i.e., changes in platelets with changes in VEGF-C and soluble-VEGFR3; changes in neutrophils with changes in IL-8, TNF-α, and soluble-VEGFR2). The adverse effects of sunitinib, particularly on the hematopoietic system, may be rapid and appear directly related to its activity in HCC. This exploratory study suggests that early hematopoietic toxicities may potentially predict outcome in advanced HCC after sunitinib treatment.


Effect of calcitonin gene-related peptide on glucose and gastric inhibitory polypeptide-stimulated insulin release from cultured newborn and adult rat islet cells.
Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide that is present in peripheral cells of islets and in nerves around and within islets. CGRP can inhibit insulin secretion in vitro and in vivo. Whether the inhibitory action of CGRP is mediated by somatostatin or by nerve terminals is, however, not known. The objective of this study was to examine the effect of CGRP on insulin secretion, using cultured newborn and adult rat islet cells which did not contain nerve terminals. In adult rat islet cells, CGRP (10(-10) to 10(-8) M) significantly inhibited glucose-stimulated and gastric inhibitory polypeptide (GIP)-potentiated insulin secretion, but in newborn rat islet cells, CGRP did not inhibit glucose-stimulated insulin secretion. Inhibition of glucose-stimulated and GIP-potentiated insulin release was dependent on the glucose concentration during the prestimulation period. CGRP did not stimulate release of somatostatin. These findings suggest that rat CGRP can act directly on beta-cells through a specific receptor that is absent in newborn rat beta-cells.


Synthesis, crystal structure and DNA cleavage activities of copper(II) complexes with asymmetric tridentate ligands.
Two asymmetric tridentate copper(II) complexes, [Cu(dppt)Cl(2)].0.25H(2)O (1) (dppt=3-(1,10-phenanthrolin-2-yl)-5,6-diphenyl-as-triazine) and [Cu(pta)Cl(2)] (2) (pta=3-(1,10-phenanthrolin-2-yl)-as-triazino[5,6-f]acenaphthylene), have been prepared and characterized by elemental analysis, IR and Fast atomic bombardment mass spectra. Complex 1 has also been structurally characterized. The complexes exist as distorted square pyramid with five co-ordination sites occupied by the tridentate ligand and the two chlorine anions. DNA interaction studies suggest that the ligand planarity of the complex has a significant effect on DNA binding affinity increasing in the order [Cu(dppt)Cl(2)]< [Cu(pta)Cl(2)]. In the presence of ascorbate or glutathione, the two complexes are found to cause significant cleavage of double-strand pBR 322 DNA and [Cu(pta)Cl(2)] exhibited the higher cleaving efficiency.


Evolution, characterization, and immune response function of long-chain acyl-CoA synthetase genes in rainbow trout (Oncorhynchus mykiss) under hypoxic stress.
Long-chain acyl-CoA synthetases (Acsls), members of the acyl-activating enzyme superfamily, haves been systematically characterized in mammals and certain fishes, but the research on their involvement in reproductive development and hypoxic stress response in rainbow trout remains limited. In this study, we investigated the acsl gene structure and physical and chemical characteristics and the evolutionary relationship among acsl genes using the NCBI/Ensembl database. Using hypoxia treatment experiment, acsl gene expression in various organs and its regulation were investigated. A total of 11 acsl genes were identified in rainbow trout. Phylogenetic analyses found that acsl genes in rainbow trout were clustered into two clades: acsl3/4 and acsl1/2/5/6, and the additional gene duplication observed resulted from the third round of genome duplication unique to teleosts. Multiple sequence alignment and conserved motif analyses showed that the sequence of acsl proteins was highly conserved. Real-time quantitative PCR (RT-qPCR) showed that the acsl genes were highly expressed in immune tissues (liver and head kidney). Under hypoxia, the expression of acsl genes was upregulated, suggesting that they enhance the tolerance to hypoxia and are involved in the immune response in rainbow trout. Our study provides valuable insights into teleost evolution and effects of hypoxia on biological immunity and form a basis for further research on the functional characteristics of acsl genes.


The magnesium, calcium, sodium, potassium and chloride contents of the term human placenta.
The ion content of the human term placenta was determined. When ordered decreasingly according to their placental content, the series of ions was: Na greater than Cl greater than K greater than Ca greater than Mg. These levels, plotted as a function of the tissue dry weight, showed an exponential distribution. Using Cl as an extracellular marker, Na and K cellular concentrations were evaluated. The equilibrium potentials derived from these values were very different from the measured syncytial membrane potential or from the value usually recorded in non-innervated tissues.


Clinical reliability of zirconium abutment in implant restorations in the English and Korean literature.
This study aimed to evaluate the mechanical, biological, and esthetic stability of a zirconium abutment according to evidence-based dentistry. An electronic search was performed. Domestic studies were found using the keywords "zirconia abutments" and "zirconium abutment" in KMbase, KoreaMed, and the National Assembly Library, and international studies were found using the same keywords in PubMed. All identified studies were divided by evidence level from the viewpoint of the research type utilizing the evidence-based review manual. A total of 102 domestic studies (with Korean language) were found, and 9 of these studies were selected. In these nine studies, 3 had evidence level 3 and 6 had evidence level 4. A total of 97 international studies (with English language) were found, and 19 were selected. Among these 19 studies, 5 had evidence level 2 and 7 had evidence level 3, whereas the remainder had evidence level 4. According to the studies, zirconium abutments are mechanically, biologically, and esthetically stable, but the evidence level of these studies is low, and the follow-up duration is no longer than 5 years. All examined studies verified the mechanical stability of zirconium abutments for a period no longer than 5 years. Therefore, a long-term clinical observation is needed. Zirconium abutments are thought to be biologically stable, but they are not superior to titanium abutments. As the esthetic stability of such abutments had a low evidence level in the studies that examined here, a much higher evidence level is needed.


A case of cardiac rupture subsequent to myocardial infarction diagnosed in emergency room.
A 72-year-old woman was transferred to the emergency room because of left anterior chest pain with cold sweating. Electrocardiography revealed recent anterior myocardial infarction. Echocardiography showed akinesis of the mid-ventricular septum to the apex by apical view, a small amount of pericardial effusion and collapse of the right ventricular wall, indicating cardiac tamponade, by subcostal view. These echocardiographic findings strongly suggested cardiac rupture subsequent to the myocardial infarction. Emergent operation was successfully performed to repair the ruptured left ventricle.


Computer simulation of the coagulation of suspended solids - The applicability of the Müller-Smoluchowski theory.
The results of studies carried out using a computer programme simulating the coagulation of suspensions containing spherical sol particles and spherical coagulant particles are reported. The influence of the degree of dispersion of the system on the coagulation reaction kinetics was investigated. The obtained results of kinetic studies were tested in the light of classical Müller-Smoluchowski equations. The influence of the physical properties of the coagulant, such as size, density and mass, on the coagulation rate was tested. It was found that within the range described in this paper, the rate of the simulated coagulation process fulfils both the kinetic equation of a first-order reaction, and the kinetic equation of a second-order reaction. Within the tested range, a significant influence of the mass and size of the coagulant on the coagulation rate was ascertained. The kinetic Müller-Smoluchowski dependence is fulfilled in a broader range of the degree of dispersion, when the coagulant particle mass and the sol particle mass are equal. When the particle mass increases with an increase in the particle radius, the coagulation rate increases faster that it would result from the Müller's dependence.


Brain damage by mild metabolic derangements in methylmalonic acidemia.
Methylmalonic acidemia caused by an l-methylmalonyl-CoA mutase deficiency. The mut(0) type is associated with significant mortality and morbidity, but tandem mass spectrometry has made early detection possible. Five patients were identified through newborn screening for elevated propionylcarnitine (C3-carnitine) levels. These patients received a positive screening result at a median age of 10 days (range, 5-18 days). When treated at a median age of 11 days (range, 3-50 days), 2 patients were asymptomatic, and only one was significantly acidotic (pH <7.2), but all had various degrees of hyperammonemia (range, 127-1,244 mumol/L). Magnetic resonance imaging of the brain was performed in 4 patients shortly after diagnosis, and the results were all abnormal. Four patients were followed. There was no further metabolic decompensation after the initial episodes, but their mean developmental quotient was only 50. These results suggest that early hyperammonemia can lead to significant brain damage in methylmalonic acidemia. Therefore, treatment of this disease in newborns must be more aggressive.


Regio- and stereoselective copper-catalyzed β-borylation of allenoates by a preactivated diboron.
A mild and efficient copper-catalyzed borylation of electron deficient allenoates using an sp(2)-sp(3) mixed hybridized diboron regioselectively installs a boron moiety on the β-position with exclusive (Z)-double bond geometry.


Feasibility of Surgical Resection After Induction Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapy for N2 Lung Adenocarcinomas.
Prognosis of patients with stage IIIA-N2 lung adenocarcinoma is still not optimistic. The aim of this study was to evaluate safety, feasibility, and outcomes of surgery after induction epidermal growth factor receptor-tyrosine kinase inhibitor therapy in a clinical trial setting. Fourteen patients with IIIA-N2 lung adenocarcinoma and epidermal growth factor receptor mutation received erlotinib induction followed by surgery in a phase II clinical trial. Perioperative outcomes and survival results were compared with a control group of 15 patients receiving neoadjuvant chemotherapy during the same time period. Thirteen patients showed partial response to induction, whereas 16 patients remained stable. Serum carcinoembryonic antigen level in the erlotinib group was significantly higher than in the chemotherapy group before treatment but was reduced to similar levels after induction. Operation time, blood loss, resection extents, complete resection rates, postoperative drainage, complication rates, and length of hospital stay were all comparable between the 2 groups. Thoracoscopic resection was accomplished in 78.6% of patients in the erlotinib group and 80.0% of patients in the chemotherapy group (P = .924) but was higher in patients who responded to induction than those who did not (92.3% vs 68.8%, P = .119). A resection extent greater than lobectomy and incomplete resections were only seen in stable disease after induction. No significant difference was detected in 1-year and 3-year overall or disease-free survivals between the 2 groups. Pulmonary resection is safe and feasible after induction treatment with erlotinib for stage IIIA-N2 lung adenocarcinomas. Better surgical and oncologic outcomes may be expected in patients who respond to effective induction therapies.


Rapid screening of urine specimens for bacteriuria by the cellenium system.
This study evaluated the performance of the Cellenium 160 US urine screening system in comparison to that of the semiquantitative culture method. The performance characteristics of the Cellenium system for all clinically significant uropathogens were 89.5% sensitivity, 94.4% specificity, 97.1% negative predictive value, and 81% positive predictive value.


Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes.
Clostridium difficile infection (CDI) occurs due to a dysbiosis in the colon. The appendix is considered a 'safe house' for gut microbiota and may help repopulate gut flora of patients with CDI. To study the impact of prior appendectomy on the severity and outcomes of CDI. We retrospectively reviewed data of 1580 patients with CDI, admitted to our hospital between 2008 to 2018. Patients were grouped based on the presence or absence of the appendix. The primary aim was to (1) assess all-cause mortality and (2) the severity of CDI. Severity was defined as per the Infectious Diseases Society of America criteria. Logistic regression, and propensity score analysis using inverse probability of treatment weights (IPTW) was performed. Of the 1580 patients, 12.5% had a history of appendectomy. There was no statistical difference in mortality between patients with a prior appendectomy or without (13.7% vs 14%, P = 0.877). However, a history of appendectomy affected the severity of CDI [odds ratio (OR) = 1.32, 95% confidence interval: 1.01-1.75]. On IPTW, this association remained significant (OR = 1.59, P < 0.05). On multivariable analysis of secondary outcomes, prior appendectomy was also associated with toxic megacolon (OR = 5.37, P < 0.05) and colectomy (OR = 2.77, P < 0.05). Prior appendectomy may affect the severity of CDI, development of toxic megacolon and the eventual need for colectomy. Since treatment of CDI is governed by its severity, stronger antibiotic regimens or earlier use of fecal microbiota transplant may be a viable option for patients with prior appendectomy.


A squaraine and Hg(2+)-based colorimetric and "turn on" fluorescent probe for cysteine.
A novel squaraine derivative (SQ-1) was synthesized and characterized for the determination of cysteine. Binding with Hg(2+) as a fluorescent quencher to SQ-1 leads to absorption and emission turn-off. More significantly, the SQ-1-Hg(2+) complex exhibits a dual-channel chromofluorogenic responses to biologically important cysteine with a high sensitivity and selectivity over other natural amino acids, along with a low detection limit of 36.7 nM.


Two varieties of the onset of atrial fibrillation studied by monophasic action potential recording.
Two types of the initiation of atrial fibrillation are demonstrated in the continuous recordings of right atrial monophasic action potentials. In the first way, more common, atrial fibrillation takes place suddenly after an an extrasystolic atrial beat, in the second one it develops gradually after atrial tachycardia. In the first type the micro reentry starts from the beginning, in the second type only after sustained focal atrial tachycardia.


The alpha-glucosidase inhibitor miglitol increases hepatic CYP7A1 activity in association with altered short-chain fatty acid production in the gut of obese diabetic mice.
Bile acids (BAs) have been shown to contribute to glucose and energy homeostasis. We have recently reported that miglitol, an alpha-glucosidase inhibitor, increases fecal BA excretion and ameliorate insulin resistance and obesity in mice. The aim of this study was to clarify the mechanisms by which miglitol affects BA metabolism. The expression of genes regulating BA metabolism, gut microbiome and short-chain fatty acids (SCFA) were examined. NSY mice, representing an obese type 2 diabetic model, were fed with a high-fat diet with or without miglitol for 4 weeks. The expression of BA-related genes in the liver and the lower intestine were measured. Alterations in fecal microbiome, fecal SCFA along with plasma lipid levels were also evaluated. Miglitol significantly increased fecal BA secretion and markedly upregulated the mRNA expression, protein levels and enzyme activity of hepatic cholesterol 7α-hydroxylase, a rate-limiting enzyme of BA synthesis. In the intestine, miglitol treatment significantly suppressed the mRNA expression of apical sodium-dependent bile acid transporter and ATP-binding cassette transporter G5 and G8. In fecal microbiome, the prevalence of prevotella was remarkably reduced and that of clostridium subcluster XIVa was increased by miglitol. Miglitol elevated formic and n-butyric acids along with total SCFA concentration in feces, while succinic acid was decreased. There was no change in plasma total cholesterol levels. Collectively, miglitol may affect BA metabolism via enhanced CYP7A1 activity resulting from at least in part the alterations in gut microbiome and SCFA production in obese diabetic mice.


Intestinal Tract Microbe Communities Associated with Horseshoe Crabs from Beibu Gulf, China.
Until now, there has been little research on the intestinal microbial community of horseshoe crabs. To fill this gap, we investigated the microbiome composition of the Chinese horseshoe crab, Tachypleus tridentatus, and the mangrove horseshoe crab, Carcinoscorpius rotundicauda. We sequenced the 16S rRNA gene of intestinal bacterial species and compared the microbial community structure and diversity. Next, we show that the total effective bacterial sequence was 36,865 reads, and the average annotated operational taxonomic unit (OTU) number was 240. Through hierarchical clustering analysis and principal coordinate analysis samples from two horseshoe crab species, we found that the intestinal flora of the same horseshoe crab species was relatively concentrated, while the microbiome of a different horseshoe crab species were significantly separated. Cluster analysis showed that two samples, one from Chinese horseshoe crabs and one from mangrove horseshoe crabs, had similar microbial community structure, while other samples were relatively discrete. The gut microbiota of the mangrove horseshoe crab were dominated by the phyla Tenericutes (42.71%), Firmicutes (24.27%), and Proteobacteria (20.39%), while the top three phyla in the Chinese horseshoe crab intestinal tract were Tenericutes (57.19%), Proteobacteria (22.14%), and Bacteroidetes (7.38%). To intuitively understand the similarity and overlap of the OTU composition of each group, we performed Venn diagram analysis. The two species shared 284 OTUs, accounting for 81.8% of the total. This indicates that although there is high similarity between mangrove and Chinese horseshoe crab in gastrointestinal microbial community structure, there are also some differences, which deserve further discussion.


Chronic recurrent multifocal osteomyelitis--report of eight patients.
The authors undertook a retrospective review of the clinical records and radiologic findings of eight children with chronic, recurrent multifocal osteomyelitis (CRMO). This disease is a recognized clinicopathologic entity with typical radiographic findings, mostly in the metaphyses of the long bones. The diagnosis is one of exclusion without pathognomonic findings. The patients were treated with non-steroidal anti-inflammatory drugs. There was no evidence of altered bone growth or abnormal joint development. It is concluded that CRMO is a distinct clinical entity that is different from acute or subacute bacterial osteomyelitis. Recognition of this condition is important to avoid treatment with antibiotics and repeated operations.


PKC-delta/c-Src-mediated EGF receptor transactivation regulates thrombin-induced COX-2 expression and PGE(2) production in rat vascular smooth muscle cells.
The thrombin/proteinase-activated receptors (PARs) have been shown to regulate smooth muscle cell proliferation, migration, and vascular maturation. Thrombin up-regulates expression of several proteins including cyclooxygenase (COX)-2 in vascular smooth muscle cells (VSMCs) and contributes to vascular diseases. However, the mechanisms underlying thrombin-regulated COX-2 expression in VSMCs remain unclear. Western blotting, RT-PCR, and EIA kit analyses showed that thrombin induced the expression of COX-2 mRNA and protein and PGE(2) release in a time-dependent manner, which was attenuated by inhibitors of PKC (GF109203X and rottlerin), c-Src (PP1), EGF receptor (EGFR; AG1478) and MEK1/2 (U0126), or transfection with dominant negative mutants of PKC-delta, c-Src or extracellular regulated kinase (ERK) and ERK1 short hairpin RNA interference (shRNA). These results suggest that transactivation of EGFR participates in COX-2 expression induced by thrombin in VSMCs. Accordingly, thrombin stimulated phosphorylation of ERK1/2 which was attenuated by GF109203X, rottlerin, PP1, GM6001, CRM197, AG1478, or U0126, respectively. Furthermore, this up-regulation of COX-2 mRNA and protein was blocked by selective inhibitors of AP-1 and NF-kappaB, curcumin and helenalin, respectively. Moreover, thrombin-stimulated activation of NF-kappaB, AP-1, and COX-2 promoter activity was blocked by the inhibitors of c-Src, PKC, EGFR, MEK1/2, AP-1 and NF-kappaB, suggesting that thrombin induces COX-2 promoter activity mediated through PKC(delta)/c-Src-dependent EGFR transactivation, MEK-ERK1/2, AP-1, and NF-kappaB. These results demonstrate that in VSMCs, activation of ERK1/2, AP-1 and NF-kappaB pathways was essential for thrombin-induced COX-2 gene expression. Understanding the regulation of COX-2 expression and PGE(2) release by thrombin/PARs system on VSMCs may provide potential therapeutic targets of vascular inflammatory disorders including arteriosclerosis.


[Effect of stimulation and destruction of the amygdaloid body on the ovaries of sexually mature and immature female rats].
Experiments were conducted on sexually-mature and infantile female rats; changes in the ovaries and the uterus after the stimulation and destruction of the amygdaloid nuclei were studied. A possible mechanism of the influences exerted by the amygdaloid nuclei on the ovaries is discussed.


The effect of phosphorylation on arrestin-rhodopsin interaction in the squid visual system.
Invertebrate visual opsins are G protein-coupled receptors coupled to retinoid chromophores that isomerize reversibly between inactive rhodopsin and active metarhodopsin upon absorption of photons of light. The squid visual system has an arrestin protein that binds to metarhodopsin to block signaling to Gq and activation of phospholipase C. Squid rhodopsin kinase (SQRK) can phosphorylate both metarhodopsin and arrestin, a dual role that is unique among the G protein-coupled receptor kinases. The sites and role of arrestin phosphorylation by SQRK were investigated here using recombinant proteins. Arrestin was phosphorylated on serine 392 and serine 397 in the C-terminus. Unphosphorylated arrestin bound to metarhodopsin and phosphorylated metarhodopsin with similar high affinities (Kd 33 and 21 nM respectively), while phosphorylation of arrestin reduced the affinity 3- to 5-fold (Kd 104 nM). Phosphorylation of metarhodopsin slightly increased the dissociation of arrestin observed during a 1 hour incubation. Together these studies suggest a unique role for SQRK in phosphorylating both receptor and arrestin and inhibiting the binding of these two proteins in the squid visual system. Invertebrate visual systems are inactivated by arrestin binding to metarhodopsin that does not require receptor phosphorylation. Here we show that squid rhodopsin kinase phosphorylates arrestin on two serines (S392,S397) in the C-terminus and phosphorylation decreases the affinity of arrestin for squid metarhodopsin. Metarhodopsin phosphorylation has very little effect on arrestin binding but does increase arrestin dissociation.


Insights into the mechanism of persulfate activation with biochar composite loaded with Fe for 2,4-dinitrotoluene degradation.
Iron in biochar composite loaded with Fe (Fex@biochar) is crucial for persulfate activation. However, the iron dosages-driven mechanism linked to the speciation, electrochemical property, and persulfate activation with Fex@biochar remains ambiguous. We synthesized and characterized a series of Fex@biochar and evaluated its catalytic performance in 2,4-dinitrotoluene removal experiments. With increasing FeCl3 dosage, iron speciation in Fex@biochar changed from γ-Fe2O3 to Fe3O4, and the variation in functional groups was as follows: Fe-O, aliphatic C-O-H, O-H, aliphatic C-H, aromatic CC or CO, and C-N. The electron accepting capacity of Fex@biochar increased as the FeCl3 dosage increased from 10 to 100 mM but decreased at 300 and 500 mM FeCl3. 2,4-dinitrotoluene removal first increased and subsequently decreased, reaching 100% in the persulfate/Fe100@biochar system. The Fe100@biochar also showed good stability and reusability for PS activation, verified by five test cycles. The mechanism analysis indicated that the iron dosage altered the Fe (Ⅲ) content and electron accepting capacity of Fex@biochar during pyrolysis, further controlling persulfate activation and 2,4-dinitrotoluene removal. These results support the preparation of eco-friendly Fex@biochar catalysts.


Vaccination of yeast sensitive individuals: review of safety data in the US vaccine adverse event reporting system (VAERS).
The preparation of recombinant hepatitis B vaccines involves using cellular cultures of Saccharomyces cerevisiae, otherwise known as baker's yeast. Prior to vaccine licensure, clinical trials were performed to address whether residual yeast proteins in the vaccines could induce anaphylaxis, including testing for IgE anti-yeast antibody levels. 1-2% of subjects had anti-yeast IgE antibodies before immunization, but demonstrated no significant rise in IgE after HBV. We searched reports in the Vaccine Adverse Event Reporting System (VAERS) for those that mentioned a history of allergy to yeast and then reviewed the adverse events described in these reports for potential anaphylactic reactions. Probable anaphylaxis was defined as the presence of one or more dermatologic symptoms and one or more respiratory, gastrointestinal, or cardiovascular symptoms with onset within 4 h of Hepatitis B vaccination. Possible anaphylaxis was defined in one of two ways: (1) cases that described dermatologic or respiratory symptoms (but not both) occurring within 4h of vaccination; or (2) cases that described one or more dermatologic and/or respiratory symptoms occurring 4-12 h post vaccination. Among the 107 reports of pre-existing "yeast allergies," 11 reports described probable or possible anaphylaxis after HBV. Four additional cases were described after other vaccines. The majority of vaccinees who met the case definitions and had a history of yeast allergies were female, ages ranged from 10 to 64, and symptom onset ranged from 15 min to 5 h after vaccination. No deaths were reported. The small number of reports to VAERS may be partly due to health care professionals observing current contraindications by not vaccinating yeast sensitive individuals. Nevertheless, yeast associated anaphylaxis after HBV in sensitized patients appears to be a rare event.


Metabolic mapping in mammalian retina: a biochemical and 3H-2-deoxyglucose autoradiographic study.
It has long been known that mammalian retinas metabolize glucose aerobically to lactic acid and carbon dioxide. The classical view holds that glucose is the primary substrate for energy metabolism in all retinal cells, and that photoreceptor cells have the highest rates of glycolysis and respiration. A different and more recent view is that the Müller cells are the principal, if not sole aerobic producers of lactate, which then serves as the primary fuel for the mitochondria in photoreceptor cells and other retinal neurons. In this paper, we have examined these two competing hypotheses in rat and guinea pig retinas by identifying the cellular sites of glucose uptake and phosphorylation via hexokinase by means of autoradiographic studies with 3H-2-deoxyglucose (3H-2DG). The rat retina serves as a vascular model and the guinea pig retina serves as an avascular model. Rat and guinea pig eyecups were incubated in oxygenated, bicarbonate-buffered media containing glucose in the presence of labeled and unlabeled 2DG. Biochemical measurements of lactate production and ATP content were made on rat retinas incubated with different concentrations of glucose and 2DG in order to establish the optimal condition for conducting the autoradiographic studies with 3H-2DG. The optimal substrate concentrations were 1mM glucose and 0.25 mM 2DG. Results showed that following incubation of dark-adapted rat eyecups for 1 hr in media containing 1mM glucose/0.25 mM 2DG and supplemented with 3H-2DG, the label was distributed throughout all the layers of the retina, from the ganglion cell layer to the retinal pigment epithelium, with denser label associated with the outer retina (photoreceptors) relative to the density of label in the inner retina, as evaluated by counts of silver grains in individual retinal layers. Exposure of rat eyecups to light did not alter the relative distribution of label, but did increase total grain counts by 70%. However, uptake of labeled 2DG, as measured by scintillation counting of radioactivity in trichloroacetic acid extracts, was not significantly different between light- and dark-adapted rat retinas. In guinea pig eyecups, labeled 2DG was distributed throughout all the retinal layers. Addition of 10mM lactate or pyruvate to the glucose/2DG media produced no measurable change in the density or distribution of label in the eyecups. Measurements of the activity of hexokinase in rat retinas revealed that this enzyme was present in both the mitochondrial and cytosolic fractions. The present results suggest that as long as the availability of ambient glucose is adequate, retinal neurons use glucose, rather than glial-derived lactate, as the major substrate for the production of high energy phosphates.


Evolution, synthesis and SAR of tripeptide alpha-ketoacid inhibitors of the hepatitis C virus NS3/NS4A serine protease.
N-terminal truncation of the hexapeptide ketoacid 1 gave rise to potent tripeptide inhibitors of the hepatitis C virus NS3 protease/NS4A cofactor complex. Optimization of these tripeptides led to ketoacid 30 with an IC50 of 0.38 microM. The SAR of these tripeptides is discussed in the light of the recently published crystal structures of a ternary tripetide/NS3/NS4A complexes.


Skeletal requirements for optimal growth hormone replacement in the transitional years.
In addition to its well-established effects on linear growth in childhood and adolescence, growth hormone (GH) has both direct and indirect actions on bone remodelling and homeostasis. In this review, the discussion begins with the influence of childhood-onset growth hormone deficiency (CO-GHD) on bone mineral accretion. The limitations of methods of assessing bone mineral density (BMD) are highlighted and specific influential factors, which affect peak bone mass achievement and therefore skeletal health in later life, are evaluated.


TMT-HCC: a tool for text mining the biomedical literature for hepatocellular carcinoma (HCC) biomarkers identification.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. New insights into the pathogenesis of this lethal disease are urgently needed. Chromosomal copy number alterations (CNAs) can lead to activation of oncogenes and inactivation of tumor suppressors in human cancers. Thus, identification of cancer-specific CNAs will not only provide new insight into understanding the molecular basis of tumor genesis but also facilitate the identification of HCC biomarkers using CNA. This paper presents the TMT-HCC system; it is a tool for text mining the biomedical literature for hepatocellular carcinoma (HCC) biomarkers identification. TMT-HCC provides researchers with a powerful way to identify and discern molecular biomarkers of HCC to inform diagnosis, prognosis, and treatment driver genes with causal roles in carcinogenesis is to detect genomic regions that under frequent alterations in cancers (CNAs). TMT-HCC also extracts protein-protein interactions from the full text of the scientific papers. The results provided that the integration of genomic and transcriptional data offers powerful potential for identifying novel cancer genes in HCC pathogenesis.


Catalytic generation of arynes and trapping by nucleophilic addition and iodination.
A fair exchange: in the title reaction, alkynyllithium serves as an initiator for benzyne generation through an iodine-lithium exchange. When performed in the presence of stoichiometric amounts of a nucleophile, the generated benzyne undergoes attack by lithio nucleophiles to generate aryllithium, which is then iodinated by iodoalkyne to give the iodoarenes 1.


A polyketide synthase, BbpksP, contributes to conidial cell wall structure and UV tolerance in Beauveria bassiana.
Conidial pigments of filamentous fungi play vital roles in fungal biotic/abiotic stress tolerance and are usually synthesized by polyketide synthases or other pigment synthesis proteins. Beauveria bassiana, an important insect pathogenic fungus used worldwide for pest biocontrol, produces white conidia on artificial media, while no conidial pigment has been observed or reported in it. However, real-time PCR and promoter-report analyses reveal a polyketide gene of B. bassiana (named BbpksP), homologous to melanin synthesis genes, is specifically expressed in aerial conidia. We show that deletion of BbpksP does not result in changes in conidial yield, germination rate or colony radial growth; however, the defect impairs conidial cell wall structure. A dense electron layer appears in the outer edge of the cell envelope in wild-type conidia, as observed by TEM, but this dense layer is absent in the ΔBbpksP mutant. The lack of BbpksP gene also reduces the UV-B tolerance of B. bassiana conidia. Bioassay reveals that deletion of BbpksP decreased virulence of B. bassiana against Galleria mellonella larvae via topical infection. These data indicate that the product(s) of BbpksP contributes to the integrity of the B. bassiana conidial cell wall and further affects the tolerance of UV-B stress and insecticidal activity.


[Studies on chemical constituents in herbs of Dracocephalum moldavica II].
To study the chemical constituents of Dracocephalum moldavica. The compounds were isolated by using RA polystyrene resin, polyamide and silica gel column chromatography, The structures of the compounds were elucidated on the basis of physic-chemical properties and spectra data. Six compounds were identified as syringaresinol4-O-beta-D-monoglucoside (I), sy-ringaresinol-4,4'-O-bis-beta-D-glucoside (II), kaempferol-3-O-beta-D-(6"-O-p-coumaroyl)-galactopyranoside (III), 2"-p-coumarylastragalin (IV), takakin-8-O-beta-D-glucopyranoside (V), beta-daucosterol (VI). Compounds I-V were obtained from genus Dracocephalum for the first time.


Cohort study of near-miss maternal mortality and subsequent reproductive outcome.
To determine the aetiology and outcome of near-miss mortality in obstetrical patients and the subsequent reproductive outcome where fertility is conserved. Retrospective cohort study of 51,576 women delivered at a University teaching hospital of whom 50 required transfer for critical care. Over the 12 year study period 1988-1999, 50 women required transfer for intensive care (0.97/1000) and there were three maternal deaths (5.8/100,000). The main indications for transfer were hypertensive disease (32%), haemorrhage (24%) and maternal cardiac disease (24%). The perinatal mortality rate was 14%. Thirty two women conserved their fertility potential and 16 had subsequent healthy liveborn children. This study of near-miss maternal mortality reminds us of the need for continuing vigilance in the provision of obstetrical care. The successful reproductive outcome highlights the resilience of many women to adverse events in pregnancy but the high loss of fertility potential reflects the physical and psychological morbidity incurred.


Distal degenerative sensory neuropathy in a long-term type 2 diabetes rat model.
Peripheral neuropathy associated with type 2 diabetes (DPN) is not widely modeled. We describe unique features of DPN in type 2 diabetic Zucker diabetic fatty (ZDF) rats. We evaluated the structural, electrophysiological, behavioral, and molecular features of DPN in ZDF rats and littermates over 4 months of hyperglycemia. The status of insulin signaling transduction molecules that might be interrupted in type 2 diabetes and selected survival-, stress-, and pain-related molecules was emphasized in dorsal root ganglia (DRG) sensory neurons. ZDF rats developed slowing of motor sciatic-tibial and sensory sciatic digital conduction velocity and selective mechanical allodynia with preserved thermal algesia. Diabetic sural axons, preserved in number, developed atrophy, but there was loss of large-calibre dermal and small-calibre epidermal axons. In diabetic rats, insulin signal transduction pathways in lumbar DRGs were preserved or had trends toward upregulation: mRNA levels of insulin receptor beta-subunit (IRbeta), insulin receptor substrate (IRS)-1, and IRS-2. The numbers of neurons expressing IRbeta protein were also preserved. There were trends toward early rises of mRNA levels of heat shock protein 27 (HSP27), the alpha2delta1 calcium channel subunit, and phosphatidylinositol 3-kinase in diabetes. Others were unchanged, including nuclear factor-kappaB (NF-kappaB; p50/p105) and receptor for advanced glycosylation endproducts (RAGE) as was the proportion of neurons expressing HSP27, NF-kappaB, and RAGE protein. ZDF type 2 diabetic rats develop a distal degenerative sensory neuropathy accompanied by a selective long-term pain syndrome. Neuronal insulin signal transduction molecules are preserved.


Evolution and Distribution of Teleost myomiRNAs: Functionally Diversified myomiRs in Teleosts.
Myosin heavy chain (MYH) genes belong to a multigene family, and the regulated expression of each member determines the physiological and contractile muscle properties. Among these, MYH6, MYH7, and MYH14 occupy unique positions in the mammalian MYH gene family because of their specific expression in slow/cardiac muscles and the existence of intronic micro(mi) RNAs. MYH6, MYH7, and MYH14 encode miR-208a, miR-208b, and miR-499, respectively. These MYH encoded miRNAs are designated as myomiRs because of their muscle-specific expression and functions. In mammals, myomiRs and host MYHs form a transcription network involved in muscle fiber-type specification; thus, genomic positions and expression patterns of them are well conserved. However, our previous studies revealed divergent distribution and expression of MYH14/miR-499 among teleosts, suggesting the unique evolution of myomiRs and host MYHs in teleosts. Here, we examined distribution and expression of myomiRs and host MYHs in various teleost species. The major cardiac MYH isoforms in teleosts are an intronless gene, atrial myosin heavy chain (amhc), and ventricular myosin heavy chain (vmhc) gene that encodes an intronic miRNA, miR-736. Phylogenetic analysis revealed that vmhc/miR-736 is a teleost-specific myomiR that differed from tetrapoda MYH6/MYH7/miR-208s. Teleost genomes also contain species-specific orthologs in addition to vmhc and amhc, indicating complex gene duplication and gene loss events during teleost evolution. In medaka and torafugu, miR-499 was highly expressed in slow/cardiac muscles whereas the expression of miR-736 was quite low and not muscle specific. These results suggest functional diversification of myomiRs in teleost with the diversification of host MYHs.


Both NKCC1 and anion exchangers contribute to Cl⁻ accumulation in postnatal forebrain neuronal progenitors.
Neuronal progenitors are continuously generated in the postnatal rodent subventricular zone and migrate along the rostral migratory stream to supply interneurons in the olfactory bulb. Nonsynaptic GABAergic signaling affects the postnatal neurogenesis by depolarizing neuronal progenitors, which depends on an elevated intracellular Cl(-) concentration. However, the molecular mechanism responsible for Cl(-) accumulation in these cells still remains elusive. Using confocal Ca(2+) imaging, we found that GABA depolarization-induced Ca(2+) increase was either abolished by bumetanide, a specific inhibitor of the Na(+) -K(+) -2Cl(-) cotransporter, or reduced by partial replacement of extracellular Na(+) with Li(+) , in the HEPES buffer but not in the CO(2)/HCO₃⁻ buffer. GABA depolarization-induced Ca(2+) increase in CO(2)/HCO₃⁻ buffer was abolished by a combination of bumetanide with the anion exchanger inhibitor DIDS or with the carbonic anhydrase inhibitor acetozalimide. Using gramicidin-perforated patch-clamp recording, we further confirmed that bumetanide, together with DIDS or acetozalimide, reduced the intracellular chloride concentration in the neuronal progenitors. In addition, with BrdU labeling, we demonstrated that blocking of the Na(+) -K(+) -2Cl(-) cotransporter, but not anion exchangers, reduced the proliferation of neuronal progenitors. Our results indicate that both the Na(+) -K(+) -2Cl(-) cotransporter and anion exchangers contribute to the elevated intracellular chloride responsible for the depolarizing action of GABA in the postnatal forebrain neuronal progenitors. However, the Na(+) -K(+) -2Cl(-) cotransporter displays an additional effect on neuronal progenitor proliferation.


SH3P2 suppresses osteoclast differentiation through restricting membrane localization of myosin 1E.
Osteoclasts are multinucleated cells responsible for bone resorption. Src homology 3 (SH3) domain-containing protein-2 (SH3P2)/osteoclast-stimulating factor-1 regulates osteoclast differentiation, but its exact role remains elusive. Here, we show that SH3P2 suppresses osteoclast differentiation. SH3P2 knockout (KO) mice displayed decreased femoral trabecular bone mass and enhanced localization of osteoclasts on the tibial trabecular bone surface, suggesting that SH3P2 suppresses bone resorption by osteoclasts. Osteoclast differentiation based on cellular multinuclearity induced by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) was enhanced in bone marrow-derived macrophages lacking SH3P2. RANKL induced SH3P2 dephosphorylation, which increased the association of actin-dependent motor protein myosin 1E (Myo1E) with SH3P2 and thereby prevented Myo1E localization to the plasma membrane. Consistent with this, Myo1E in the membrane fraction increased in SH3P2-KO cells. Together with the attenuated osteoclast differentiation in Myo1E knocked down cells, SH3P2 may suppress osteoclast differentiation by preventing their cell-to-cell fusion depending on Myo1E membrane localization.


Characterization of a nitrate-inducible transcriptional repressor NIGT1 provides new insights into DNA recognition by the GARP family proteins.
The GARP domain is a single Myb-related DNA-binding domain found in plant transcription factors. Proteins containing the GARP domain (GARP family proteins) are suggested to be involved in the regulation of various physiological processes through their interactions with ostensibly different DNA sequences. Our recent study on a nitrate-inducible gene encoding a GARP family protein, referred to as NIGT1 (Nitrate-Inducible, GARP-type Transcriptional Repressor 1), not only suggests a previously unidentified role for the GARP family proteins in higher plants but also provides a hypothesis for why NIGT1 can show dual specificity on DNA binding and why respective GARP family proteins can recognize very different DNA sequences.


Carnitine concentration during the development of human tissues.
The different carnitine storage patterns in developing human tissues (skeletal muscle, liver and brain) were demonstrated. The carnitine concentration was high in the skeletal muscle and liver relative to other tissues during preterm gestation, and the skeletal muscle carnitine concentration increased with growth. On the other hand, the brain carnitine concentration was low. The brain contained a larger proportion of acylcarnitine than of free carnitine from midgestation, while the skeletal muscle and liver contained larger concentrations of free carnitine than of acylcarnitine. These different carnitine concentrations and composition patterns in the skeletal muscle, liver and brain may be related to maturation of the potential carnitine reserve and to metabolic functions, such as fatty acid utilization and the reservoir of acetyl units, in each developmental tissue.


Effect of microsomal enzyme modulators on N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS)-induced nephrotoxicity in the Fischer 344 rat.
We have previously reported that phenobarbital (PB) pretreatment enhances and piperonyl butoxide (PIBX) pretreatment or cobalt chloride (CoCl2) pretreatment decreases the nephrotoxicity induced by the model nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) in the Fischer 344 rat. The objective of this study was to determine the effect of a microsomal enzyme inducer (PB) or microsomal enzyme inhibitor (PIBX or CoCl2) on a single intraperitoneal (i.p.) injection of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS, 0.05, 0.1 or 0.2 mmol/kg), a nephrotoxicant metabolite of NDPS, or vehicle (sesame oil, 2.5 ml/kg). Renal function was monitored at 24 and 48 h post-NDHS for PB pretreated rats and at 24 h only for PIBX and CoCl2 pretreated rats, due to lethality at 48 h in PIBX pretreated rats. PB pretreatment potentiated the renal toxicity induced by a non-toxic dose of NDHS (0.05 mmol/kg), inducing diuresis and elevated proteinuria, hematuria, glucosuria, blood urea nitrogen (BUN) concentration and kidney weight. PB pretreatment also enhanced some monitored renal effects of a toxic dose (0.1 mmol/kg) of NDHS, including reduced organic ion transport by renal cortical slices. PIBX and CoCl2 pretreatments did not markedly affect the increased kidney weight, proteinuria, glucosuria, BUN concentration or altered organic ion transport induced by NDHS (0.2 mmol/kg) treatment. We conclude that PB potentiates NDHS-induced nephrotoxicity via a mechanism not influenced by CoCl2 or PIBX.


Prevention of post-operative nausea and vomiting in children--a prospective randomized double-blind study.
Post-operative nausea and vomiting (PONV) are common complications related to surgery and anaesthesia. The aim of this study was to assess whether sevoflurane, with or without the use of an antiemetic such as ondansetron, increases or not the incidence of PONV in children. One hundred and ten children, 2 months to 14 years undergoing inguinal hernia, hypospadias and penile deformity repair, were randomly allocated into one of two groups, according to whether they received ondansetron or placebo (47 vs. 63). Induction and maintenance of anaesthesia was with Sevoflurane in both groups. Regional anaesthesia was performed on all children (inguinal nerve, penile or caudal block). No opioids were used. In post-operative period, children were assessed for PONV, every 4 h for the first 24 h. Vomiting was very low in both groups (8 cases: 7.3%). No significant statistical difference of post-operative nausea (p = 0.296) and vomiting (p = 0.462) (Fisher's exact test) was found between the group that received ondansetron and the placebo group. We found that the use of ondansetron did not change the incidence of PONV, the avoidance of opioids and the adequate analgesia may contribute to this. Post-operative oral intake of liquid, (within the first 4 h), increases the risk for PONV.


Aloe vera for preventing radiation-induced skin reactions: a systematic literature review.
To systematically review and critically appraise the evidence for effectiveness of Aloe vera gel for radiation-induced skin reactions. Major biomedical databases and specialist complementary and alternative medicine databases were searched. Additionally, efforts were made to identify unpublished and ongoing research. Relevant research was systematically categorised by study type and appraised according to study design. Clinical commentaries were obtained for each study included in the review. One earlier systematic review on Aloe vera for a variety of conditions was located. Five published randomised-controlled trials (RCTs) were found, along with two additional RCTs that are not published. No non-RCTs, uncontrolled studies or qualitative studies were found. There is no evidence from clinical trials to suggest that topical Aloe vera is effective in preventing or minimising radiation-induced skin reactions in cancer patients. Further methodologically rigorous, sufficiently powered research studies should be conducted to evaluate the effectiveness of currently used and novel therapies for the prevention, minimisation and management of radiation-induced skin reactions.


Fucodendropeptides induce changes in cells of the immune system in food allergic patients via DC-SIGN receptor.
Food allergy induced by lipid transfer proteins (LTPs) of Rosacea fruit family, such as peach, is becoming an important health problem in the Mediterranean area. Current treatments, such as allergen specific immunotherapy (AIT) with allergenic extracts show promising, but in many cases, they need an improvement in homogeneity, availability and induction of tolerant responses. Peptide-based vaccines containing adjuvants, such as carbohydrates for C-type lectin receptors (CLRs) are presented as an alternative approach. In this work, we have prepared fucosylated glycodendropeptides (GDPs) functionalized with Pru p 3 peptides via click chemistry. These GDPs, DnFuc9Prup3, induced changes in moDC maturation and lymphocyte proliferation in food allergic patients, indicating specific recognition via DC-SIGN receptor. From these data, D4Fuc9Prup3 can be considered a promising candidate for specific immunotherapy development.


Clinical outcomes of treatment for spinal cord compression due to primary non-Hodgkin lymphoma.
Primary non-Hodgkin lymphoma of the spine (PNHLS) with spinal cord compression is an extremely rare disease in clinical practice. The optimal treatment options for this disease have been controversial and pose a challenge for the clinicians. To provide some useful insight into the treatments, outcomes, and prognostic factors of PNHLS. Retrospective analysis. The authors collected 40 patients' data with primary non-Hodgkin lymphoma at the mobile spine, and these patients presented with spinal cord compression as a first symptom between 1998 and 2010. The posttreatment neurologic status, general status, local recurrence, and survival were noted according to the telephone calls, letters, or follow-up visits in the outpatient department. Multidisciplinary treatments, including surgical intervention, chemotherapy, and radiotherapy, were performed in this series. Follow-ups regarding treatment outcomes, local recurrence, and survival rates were carried out and analyzed. The prognostic factors including age, neurologic status, general status, vertebrae involvement, and treatment outcomes were determined. The median age of the patients was 52 years (range, 13-79 years). After treatments, 30 patients (75%) reached a complete remission (CR). The 5-year overall survival (OS) of all patients was 72.9%. Patients who were younger than 60 years, with single vertebra involvement, or had CR after treatment had higher 5-year OS (p<.05). In multivariate analysis, CR after treatment and involvement of a single vertebra were identified as favorable prognostic factors for OS. Patients with PNHLS with neurologic compression had distinct clinical features. Regarding treatment, the authors emphasized the importance of multidisciplinary management and the optimal operating juncture. Patients with excellent response to the treatment and single vertebra involvement had better survival.