miR-382-5p promotes cell invasion in hepatocellular carcinoma by targeting PTEN to activate PI3K/Akt signaling pathway.
This study aimed at investigating miR-382-5p expression in tissues and cell lines with hepatocellular carcinoma (HCC), its effects on the invasion of HCC cells, and related mechanisms. miR-382-5p expression in HCC tissues, adjacent tissues, cell lines of normal hepatic cells, and HCC cells were detected by qRT-PCR, indicating its upregulation or downregulation in HCC cell lines (Hep3B and HCCLM3). The effect of miR-382-5p on cell invasion was observed by the Transwell experiment. The targeting relationship of miR-382-5p and the phosphatase and tensin homolog (PTEN) was analyzed using bioinformatics tools and the luciferase reporter gene assay. The correlation between miR-382-5p and PTEN was analyzed with Spearman correlation analysis. PTEN expression was observed after upregulation and downregulation of miR-382-5p expression. The effect of miR-382-5p on the expression of key proteins in PI3K/Akt signaling pathway was determined by Western blot. miR-382-5p expression was upregulated in both HCC tissues and cell lines (both P<0.05). Upregulation or downregulation of miR-382-5p significantly promoted or inhibited the invasion of cell lines, Hep3B, and HCCLM3. The luciferase reporter gene assay confirmed that PTEN is a target of miR-382-5p. The expressions of miR-382-5p and PTEN were negatively correlated (r=-0.742, P<0.001). Upregulation of PTEN expression by plasmid transfection can reverse the invasive effect of miR-382-5p on HCC cells. Upregulation of miR-382-5p can activate PI3K/Akt signaling pathway, and downregulation of miR-382-5p can inhibit PI3K/Akt signaling pathway. miR-382-5p can activate the PI3K/Akt signaling pathway by targeting PTEN and promote HCC cell invasion.


Presence of the N-methyl-D-aspartic acid R1 glutamatergic receptor subunit in the lumbosacral spinal cord of male rats.
The lumbosacral spinal cord contains neurones that control the lower urogenital and digestive tracts. Spinal neurones respond to activation from the periphery and supraspinal nuclei. Glutamate, acting through a variety of receptors, is an established transmitter of excitatory pathways to the spinal cord. Using immunohistochemical methods, we reveal the presence of the N-methyl-D-aspartic acid R1 (NMDAR1) glutamatergic receptor subunit in the lumbosacral spinal network that controls urogenital and digestive functions: the dorsal horn; the area around the central canal including the dorsal grey commissure; the sacral parasympathetic nucleus; and pudendal motoneurones. A complete thoracic spinal section did not alter labelling. Using retrograde labelling techniques, we identify sacral preganglionic neurones and pudendal neurones that are NMDAR1 immunoreactive. Glutamate, acting at NMDA receptors, can therefore co-ordinate the activity of the autonomic and somatic outflows to the pelvic organs.


Large-scale N-glycoproteome map of rat brain tissue: simultaneous characterization of insoluble and soluble protein fractions.
The large-scale N-glycosylation analysis is critical for biomedical research, since a variety of diseases are found to be associated with glycoproteins. By a combination of glycoprotein analysis in insoluble protein fraction solubilized with 1% v/v 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM BF(4)) and those in soluble fraction, a total number of 462 non-redundant N-glycoprotein groups, including 316 transmembrane glycoproteins, were successfully identified. Correspondingly, 849 unique N-glycosites were confidently recognized. The data set could provide a support for the further in-depth research of brain N-glycosylation, such as for the discovery of candidate drug targets and biomarkers.


Complex preference relationships between native and non-native angiosperms and foraging insect visitors in a suburban greenspace under field and laboratory conditions.
The introduction and spread of non-native flora threatens native pollinators and plants. Non-native angiosperms can compete with native plants for pollinators, space, and other resources which can leave native bees without adequate nutritional or nesting resources, particularly specialist species. In the current study, we conducted flower preference experiments through field observations and controlled binary choice tests in an artificial arena to determine the impact of field vs. laboratory methods on flower preferences of native bees for native or non-native flowers within their foraging range. We conducted counts of insect pollinators foraging on the flowers of three plant species in a suburban green belt including one native (Arthropodium strictum) and two non-native (Arctotheca calendula and Taraxacum officinale) plant species. We then collected native halictid bees foraging on each of the three plant species and conducted controlled binary tests to determine their preferences for the flowers of native or non-native plant species. In the field counts, halictid bees visited the native plant significantly more than the non-native species. However, in the behavioural assays when comparing A. strictum vs. A. calendula, Lasioglossum (Chilalictus) lanarium (Family: Halictidae), bees significantly preferred the non-native species, regardless of their foraging history. When comparing A. strictum vs. T. officinale, bees only showed a preference for the non-native flower when it had been collected foraging on the flowers of that plant species immediately prior to the experiment; otherwise, they showed no flower preference. Our results highlight the influence that non-native angiosperms have on native pollinators and we discuss the complexities of the results and the possible reasons for different flower preferences under laboratory and field conditions.


Fibroblast dysfunction is a key factor in the non-healing of chronic venous leg ulcers.
Chronic age-related degenerative disorders, including the formation of chronic leg wounds, may occur due to aging of the stromal tissues and ensuing dysfunctional cellular responses. This study investigated the impact of environmental-driven cellular aging on wound healing by conducting a comprehensive analysis of chronic wound fibroblast (CWF) behavior in comparison with patient-matched healthy skin normal fibroblasts (NF). The dysfunctional wound healing abilities of CWF correlated with a significantly reduced proliferative life span and early onset of senescence compared with NF. However, pair-wise comparisons of telomere dynamics between NF and CWF indicated that the induction of senescence in CWF was telomere-independent. Microarray and functional analysis suggested that CWFs have a decreased ability to withstand oxidative stress, which may explain why these cells prematurely senescence. Microarray analysis revealed lower expression levels of several CXC chemokine genes (CXCL-1, -2, -3, -5, -6, -12) in CWF compared with NF (confirmed by ELISA). Functionally, this was related to impaired neutrophil chemotaxis in response to CWF-conditioned medium. Although the persistence of non-healing wounds is, in part, due to prolonged chronic inflammation and bacterial infection, our investigations show that premature fibroblast aging and an inability to correctly express a stromal address code are also implicated in the disease chronicity.


Allogeneic haematopoietic stem cell transplantation for myelofibrosis: prognostic indicators and the role of JAK2V617F measurable-residual disease monitoring by droplet-digital polymerase chain reaction.
Relapse after allogeneic haematopoietic stem cell transplantation (HSCT) is one of the key determinants of outcome in myelofibrosis (MF) and remains an important unmet need. In this retrospective single-centre study, we evaluated 35 consecutive patients with MF receiving allogeneic HSCT. At 30 days post-HSCT, full donor chimerism was achieved in 31 patients (88.6%). The median time to neutrophil engraftment was 16.8 (10-42) days and the median time to platelet engraftment was 26 (12-245) days. Four patients (11.4%) experienced primary graft failure. With a median duration of follow-up of 33 (1-223) months, with the 5-year overall survival (OS) and progression-free survival (PFS) were 51.6% and 46.3%, respectively. Relapse after HSCT (P < 0.001), leucocyte count ≥ 18 × 109/L at HSCT (P = 0.003) and accelerated/blast phase disease at HSCT (P < 0.001) were significantly associated with worse OS. Age at HSCT ≥ 54 years (P = 0.01), mutated ETV6 (P = 0.03), leucocyte count ≥ 18 × 109/L (P = 0.02), accelerated/blast phase MF (P = 0.001), and grade 2-3 bone marrow reticulin fibrosis at 12 months post-HSCT (P = 0.002) were significantly associated with worse PFS. JAK2V617F MRD ≥ 0.047 [sensitivity 85.7%; positive predictive value (PPV) 100%; AUC 0.984; P = 0.001] at 6 months and JAK2V617F MRD ≥ 0.009 (sensitivity 100%; PPV 100%; AUC 1.0; P = 0.001) at 12 months were highly predictive of post-HSCT relapse. Inferior OS and PFS were significantly associated with detectable JAK2V617F MRD at 12 months (P = 0.003 and P = 0.0001, respectively).


Choanal polyp originating from the middle turbinate.
Choanal polyps usually originate from the maxillary sinus. Unusual origins such as the sphenoid sinus, ethmoid sinus, nasal septum and hard and soft palate have been reported in the literature. Herein, we report a rare case of choanal polyp originating from the middle turbinate that was removed by an endoscopic surgery technique. The computed tomographic findings are described and the literature is reviewed.


A Randomized Trial of Single-Dose Oral Dexamethasone Versus Multidose Prednisolone for Acute Exacerbations of Asthma in Children Who Attend the Emergency Department.
In acute exacerbations of asthma in children, corticosteroids reduce relapses, subsequent hospital admission, and the need for ß2-agonist bronchodilators. Prednisolone is the most commonly used corticosteroid, but prolonged treatment course, vomiting, and a bitter taste may reduce patient compliance. Dexamethasone has a longer half-life and has been used safely in other acute pediatric conditions. We examine whether a single dose of oral dexamethasone is noninferior to prednisolone in the emergency department (ED) treatment of asthma exacerbations in children, as measured by the Pediatric Respiratory Assessment Measure (PRAM) at day 4. We conducted a randomized, open-label, noninferiority trial comparing oral dexamethasone (single dose of 0.3 mg/kg) with prednisolone (1 mg/kg per day for 3 days) in patients aged 2 to 16 years and with a known diagnosis of asthma or at least 1 previous episode of ß2-agonist-responsive wheeze who presented to a tertiary pediatric ED. The primary outcome measure was the mean PRAM score (range of 0 to 12 points) performed on day 4. Secondary outcome measures included requirement for further steroids, vomiting of study medication, hospital admission, and unscheduled return visits to a health care practitioner within 14 days. There were 245 enrollments involving 226 patients. There was no difference in mean PRAM scores at day 4 between the dexamethasone and prednisolone groups (0.91 versus 0.91; absolute difference 0.005; 95% CI -0.35 to 0.34). Fourteen patients vomited at least 1 dose of prednisolone compared with no patients in the dexamethasone group. Sixteen children (13.1%) in the dexamethasone group received further systemic steroids within 14 days after trial enrollment compared with 5 (4.2%) in the prednisolone group (absolute difference 8.9%; 95% CI 1.9% to 16.0%). There was no significant difference between the groups in hospital admission rates or the number of unscheduled return visits to a health care practitioner. In children with acute exacerbations of asthma, a single dose of oral dexamethasone (0.3 mg/kg) is noninferior to a 3-day course of oral prednisolone (1 mg/kg per day) as measured by the mean PRAM score on day 4.


Subcutaneous fat in normal and diseased states: 2. Anatomy and physiology of white and brown adipose tissue.
White and brown adipose tissues, both present to some degree in all mammals, represent counter actors in energy metabolism. One of the primary functions of white adipocytes is to store excess energy as lipid, which is then mobilized to other tissues in response to metabolic needs that arise in times of food shortage. White adipocyte physiology can be grouped into 3 main categories with potentially overlapping mechanisms: lipid metabolism, glucose metabolism, and endocrine functions. Brown adipocytes, on the other hand, use accumulated lipid from food primarily as a source for chemical energy that can then be released from the cell in the form of heat. Recently, new discoveries about the significance of brown fat have sparked interest in this organ as a potential tool in the fight against obesity in adult humans. A basic overview of the anatomy and physiology of adipose tissue, with particular emphasis on the differences between white and brown fat, is presented.


A preliminary study to identify locomotor-cognitive dual tasks that reveal persistent executive dysfunction after mild traumatic brain injury.
To identify different combinations of physical (level, obstacle avoidance, stepping down) and cognitive (visual, mental) demands within a locomotor navigational context that best discriminates between persons with mild traumatic brain injury (MTBI) and control subjects for an eventual clinical tool to assess residual executive dysfunction. Group comparison study. Rehabilitation facility. Volunteer sample (N=14) of persons with MTBI (n=7) (6 women; age, 20±1.6 y) and a comparison group (n=7) of subjects without neurologic problems (6 women; age, 22.4±1.4 y). Not applicable. Gait speed (m/s) and dual-task cost calculated as the relative change in gait speed from single (no cognitive task) to dual tasks for the same gait condition. There were significant interactions between groups and cognitive tasks and between groups and cognitive and physical tasks for gait speed. Specifically, the MTBI group walked slower than control subjects in the dual-task conditions when stepping over an obstacle combined with each cognitive task. When gait speed was measured as dual-task costs, group differences were more evident, except for stepping down. These preliminary results suggest that both absolute gait speed and calculated dual-task costs during the combination of stepping over an obstacle with a simultaneous cognitive task are sensitive to revealing executive dysfunction in persons with MTBI. Gait speed can be easily measured in the clinic to provide important information to make diagnoses and decide about return to play or function. Continued work building on these preliminary results is needed toward the development of a clinical tool.


Evidence for two putative holin-like peptides encoding genes of Bacillus pumilus strain WAPB4.
An open reading frame encoding a 71-amino acid BhlA bacteriocin-related holin-like peptide was present upstream of 86-amino acid holin-like peptide, xhlB, encoding gene in the genome of Bacillus pumilus strain WAPB4. Analysis of BhlA using TMHMM server suggested one putative transmembrane domain at the N-terminal part and a number of highly charged amino acid residues at the C-terminal part. XhlB of B. pumilus strain WAPB4 composed of two putative transmembrane domains separated by a β-turn, and numerous charged residues in the C-terminus. The dual start motifs were found in both BhlA and XhlB. Structural analysis of their sequence revealed features characteristic for holin. To analyze the effect of BhlA on bacteria cell, its ORF was cloned and expressed in Escherichia coli BL21(DE3). Expression of holin-like peptide, BhlA, was found to be toxic to the host cell. The site of action of BhlA is on the cell membrane and caused bacterial death by cell membrane disruption as clearly demonstrated by transmission electron microscopy or TEM.


Meclonazepam analogues as potential new antihelmintic agents.
New analogues of the potent antihelmintic meclonazepam were prepared and evaluated against Schistosoma mansoni. The biological data suggests substitution at positions 2 and 4 of meclonazepam could provide promising analogues for prophylactic and therapeutic activity against S. mansoni.


Cumulative interfraction interval analysis of influence of time and interruptions on radiotherapy results in oral cancers.
To present a new approach to analyze the influence of time and interruptions in fractionated radiotherapy, in terms of cumulative interfraction intervals (CIFIs), that is, the interval between nonsuccessive fractions of radiotherapy. The subjects were 142 patients with epidermoid cancer of the buccal mucosa-gingiva-palate region treated by 60 Gy in 25 fractions during 5 weeks. The influence of CIFI between the first and sixth, eleventh, sixteenth, and twenty-first fractions (CIFI(1-6), CIFI(1-11), CIFI(1-16), and CIFI(1-21), respectively), as well as overall treatment time on local control, was analyzed by Kaplan-Meier calculation of the primary relapse-free survival and Mann-Whitney U testing of the difference in various CIFIs between the tumors that recurred (recurred group) and those that did not (controlled group). Only CIFI(1-11) influenced local control significantly, with the 5-year primary relapse-free survival rate being 67.9%, 48.4%, and 32.6% in those with CIFI(1-11) of <14, 14, and >14 days (p = 0.0181). The median CIFI(1-11) in the controlled group was significantly lower than that in the recurred group (14 days vs. 15 days; p = 0.0037). Interruptions during the first 11 fractions, including planned weekend gaps, decrease the effect of radiotherapy, possibly because of successful tumor cell repopulation during the protracted interfraction intervals. The analysis of time in terms of CIFI rather than overall treatment time appears to be a promising area for research.


Refined three-dimensional solution structure of insect defensin A.
Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure-activity relationship and forms the basis for understanding its antibiotic activity at the molecular level. We describe a refined model of the three-dimensional structure of defensin A derived from an extensive analysis of 786 inter-proton nuclear Overhauser effects. The backbone fold involves an N-terminal loop and an alpha-helical fragment followed by an antiparallel beta-structure. The helix and the beta-structure are connected by two of the three disulphide bridges present in defensin A, forming a so-called 'cysteine-stabilized alpha beta' (CS alpha beta) motif. The N-terminal loop, which is locally well defined, can occupy different positions with respect to the other moieties of the molecule. The CS alpha beta motif, which forms the core of the defensin A structure, appears to be a common organization for several families of small proteins with toxic properties. The distribution of amino acid side chains in the protein structure creates several hydrophobic or hydrophilic patches. This leads us to propose that the initial step in the action of positively charged defensin A molecules with cytoplasmic membranes may involve interactions with acidic phospholipids.


Antimicrobial susceptibility and invasive ability of Staphylococcus aureus isolates from mastitis from dairy backyard systems.
Fifteen (15) backyard farms were investigated to determine the antimicrobial susceptibility and invasion ability of S. aureus isolates from cows with subclinical mastitis in México. A total of 106 cows were sampled and 31 S. aureus isolates were recovered. S. aureus isolates were resistant to penicillin class antibiotics and susceptible to gentamicin and cetyltrimethylammonium bromide. STA9 and STA13 isolates were resistant to erythromycin (MIC > 25 microg/ml) and lincomycin (STA13, MIC > 25 microg/ml; STA9, MIC > 100 microg/ml). STA9 isolate harbors the erm(B) and msr(A) genes, whereas STA13 isolate harbors the erm(C) gene. STA9 and STA13 isolates contains the lnu(A) gene. Only 5 isolates (STA11, STA13, STA14, STA15 and STA21) were able to internalize in bovine mammary epithelial cells. These results indicate that S. aureus isolates from dairy backyard farms showed differences in the antimicrobial susceptibility patterns and invasion ability in bovine mammary epithelial cells. This kind of evaluations should be performed in different dairy regions, since resistance patterns and isolate diversity vary on a per-region basis.


Internal ATP is the only energy requirement for the translocation of precursor proteins across chloroplastic membranes.
The energy requirements for the import of nuclear-encoded proteins into isolated chloroplasts have been reinvestigated. We have shown that, in contrast to protein import into mitochondria, the translocation of the precursors to ferredoxin, plastocyanin (prPC) and the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (prSS) across all chloroplastic membranes is independent of a protonmotive force and requires only ATP. This extends previous works in which investigations were limited to prSS and demonstrates that our results are probably general to all chloroplastic protein precursors. Our results are particularly interesting for the import of prPC, since in addition to the two envelope membranes, this protein must traverse the energy-transducing thylakoid membranes en route to its proper location in the thylakoid lumen. This lack of involvement of a protonmotive force, specifically of a transmembrane electric potential, demonstrates that separate mechanisms operate during the import of proteins into chloroplasts and mitochondria. We also examined the question of whether ATP is utilized inside or outside of chloroplasts during protein import. Previous attempts to resolve this question have resulted in conflicting answers. We found, by two independent approaches, that ATP for protein import is utilized inside chloroplasts. The implications of these results on the possible mechanisms of protein import into chloroplasts are discussed.


Influenza classification from short reads with VAPOR facilitates robust mapping pipelines and zoonotic strain detection for routine surveillance applications.
Influenza viruses represent a global public health burden due to annual epidemics and pandemic potential. Due to a rapidly evolving RNA genome, inter-species transmission, intra-host variation, and noise in short-read data, reads can be lost during mapping, and de novo assembly can be time consuming and result in misassembly. We assessed read loss during mapping and designed a graph-based classifier, VAPOR, for selecting mapping references, assembly validation and detection of strains of non-human origin. Standard human reference viruses were insufficient for mapping diverse influenza samples in simulation. VAPOR retrieved references for 257 real whole-genome sequencing samples with a mean of >99.8% identity to assemblies, and increased the proportion of mapped reads by up to 13.3% compared to standard references. VAPOR has the potential to improve the robustness of bioinformatics pipelines for surveillance and could be adapted to other RNA viruses. VAPOR is available at https://github.com/connor-lab/vapor. Supplementary data are available at Bioinformatics online.


Effect of inhibitory amino acid antagonists on IPSPs induced in lumbar motoneurons upon stimulation of the nucleus reticularis gigantocellularis during active sleep.
The present study was performed to generate data implicating glycine or gamma-aminobutyric acid as neurotransmitter candidates mediating the IPSPs which are recorded in lumbar motoneurons following electrical stimulation of the nucleus reticularis gigantocellularis (NRGc) during the atonia of active sleep. Accordingly, intracellular records were obtained from lumbar motoneurons in unanesthetized, normally respiring cats during naturally occurring states of active sleep, while inhibitory amino acid antagonists were microiontophoretically released next to the recorded cell. Electrical stimuli, applied to the NRGc during active sleep under drug-free conditions, evoked inhibitory postsynaptic potentials (IPSPs) in all of the lumbar motoneurons which were examined. These NRGc-induced IPSPs exhibited an average latency-to-onset of 26.6 +/- 1.3 ms, a latency-to-peak of 42.5 +/- 1.3 ms, an average amplitude of 3.9 +/- 0.4 mV and a duration of 34.4 +/- 2.1 ms. Strychnine, when applied microiontophoretically, abolished or markedly suppressed these NRGc-induced IPSPs. In contrast, the microiontophoretic application of picrotoxin or bicuculline methiodide failed to block these IPSPs. To the extent that strychnine may be considered to be a specific antagonist of glycine, the present results suggest that glycine (or a structurally related amino acid) participates in the generation of NRGc-induced IPSPs during the atonia of active sleep.


Intratubular and peritubular capillary hydrostatic and oncotic pressures after chronic renal sympathectomy in the anaesthetized rat.
The possible role of peritubular capillary physical forces in the diuretic-natriuretic effects of chronic renal denervation was investigated in Inactin-anaesthetized nondiuretic control (C) and unilaterally denervated (D) rats. Micropuncture techniques were combined with measurement of intratubular and peritubular capillary hydrostatic pressures and afferent and efferent arteriolar plasma oncotic pressures were determined, as well. Compared to data of C rats and of innervated kidneys, marked denervation diuresis and natriuresis were seen without changes in GFR. Both late proximal and early distal (F/P)In values were significantly lower in D kidneys with similar SNGFR. Afferent (pia) and efferent (pi e) arteriolar oncotic pressures were unchanged by denervation (C-pi a = 23.3 +/- 0.79, pi e = 29.9 +/- 0.87 mm Hg; D-pi a = 23.2 +/- 0.94, pi e = 29.8 +/- 1.04 mm Hg). Proximal intratubular hydrostatic pressure was moderately but significantly higher in D kidneys (C = 11.9 +/- 0.5, D = 13.7 +/- 0.3 mm Hg, P less than 0.01), while peritubular capillary pressures were: efferent arteriole (C = 13.9 +/- 0.5, D = 13.4 +/- 0.6 mm Hg, NS). It is concluded that the tubular effects of chronic renal sympathectomy are not dependent on changes in Starling forces of the peritubular environment.


Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function.
Recent advances in pluripotent stem cell research have provided investigators with potent sources of cardiogenic cells. However, tissue engineering methodologies to assemble cardiac progenitors into aligned, 3-dimensional (3D) myocardial tissues capable of physiologically relevant electrical conduction and force generation are lacking. In this study, we introduced 3D cell alignment cues in a fibrin-based hydrogel matrix to engineer highly functional cardiac tissues from genetically purified mouse embryonic stem cell-derived cardiomyocytes (CMs) and cardiovascular progenitors (CVPs). Procedures for CM and CVP derivation, purification, and functional differentiation in monolayer cultures were first optimized to yield robust intercellular coupling and maximize velocity of action potential propagation. A versatile soft-lithography technique was then applied to reproducibly fabricate engineered cardiac tissues with controllable size and 3D architecture. While purified CMs assembled into a functional 3D syncytium only when supplemented with supporting non-myocytes, purified CVPs differentiated into cardiomyocytes, smooth muscle, and endothelial cells, and autonomously supported the formation of functional cardiac tissues. After a total culture time similar to period of mouse embryonic development (21 days), the engineered cardiac tissues exhibited unprecedented levels of 3D organization and functional differentiation characteristic of native neonatal myocardium, including: 1) dense, uniformly aligned, highly differentiated and electromechanically coupled cardiomyocytes, 2) rapid action potential conduction with velocities between 22 and 25 cm/s, and 3) significant contractile forces of up to 2 mN. These results represent an important advancement in stem cell-based cardiac tissue engineering and provide the foundation for exploiting the exciting progress in pluripotent stem cell research in the future tissue engineering therapies for heart disease.


Biomechanical and adhesion comparison of linea alba prophylactic reinforcement with coated and uncoated three-dimensional T-shaped mesh in rabbits.
Incisional hernia (IH) is a frequent complication of median laparotomy. The use of prophylactic mesh to reduce IH incidence has gained increasing attention. We hypothesized that in an animal model, linea alba prophylactic reinforcement with a three-dimensional T-shaped polypropylene mesh results in greater abdominal wall resistance. Study was performed in 27 rabbits. After abdominal midline incision, animals were divided into three groups according to the laparotomy closure method used: (1)3D T-shaped coated mesh; (2)3D T-shaped uncoated mesh; and (3) closure without mesh. After 4 months, each animal's abdominal wall was resected and tensiometric tests were applied. Results included IH occurrence, adhesions to the mesh, and wound complications. There was no significant difference between the groups in maximum tensile strength (p=0.250) or abdominal wall elongation under maximum stress (p=0.839). One rabbit from the control group developed IH (p=1.00). Small intestine and colon adhesions occurred only in the uncoated mesh group (p<0.001) and the degree of adhesions was higher in this group compared to the coated mesh group (p<0.05). Use of the current 3D T-shaped prophylactic mesh model did not result in a significant difference in tensiometric measurements when compared with simple abdominal wall closure in rabbits.


Is glucose the sole source of tissue browning in diabetes mellitus?
Reactions between glucose and protein are held to be responsible for the protein 'browning' reactions which occur in diabetes mellitus. In vitro, however, the formation of such novel protein fluorophores is dependent upon the metal-catalysed oxidation of the monosaccharide (glucose 'autoxidation'). Since other small oxidisable molecules are capable of 'browning' proteins via similar metal-catalysed oxidative mechanisms we suggest that protein modification in diabetes may not be restricted to reactions with monosaccharides but may also include other small autoxidisable molecules.


Bedside insertion of inferior vena cava filters.
Certain types of injuries make a patient more at risk for the development of a DVT or PE. Because the condition of such patients is critical, the treatment options are limited, and special attention is required so as not to cause further harm. Bedside procedures that preclude the need to transport a patient to another department offer clear advantages. By describing a tested clinical procedure--percutaneous insertion of the IVC filter--trauma nurses can gain a better understanding of how to prepare the patient, expedite the process, and provide ongoing nursing management.


Surgical rehabilitation for anophthalmic sockets devoid of orbital implant.
To determine the necessity of rehabilitative surgical procedures for no implant anophthalmic sockets, and predictive factors of corrective operations after secondary orbital implantation. Nineteen unilateral anophthalmic patients without orbital implant were included. The distance of eyebrow, upper eyelid margin, and lower eyelid margin from the horizontal medial canthal line (BM, UM, and LM, respectively) was measured using photographs. The anophthalmic orbit anatomy was compared with that of the healthy side using CT scans. Five (26.3%) patients showed satisfactory results with the secondary implantation alone. Fourteen (74%) patients needed additional surgeries for ptosis, shallow inferior fornix, enophthalmos, or lower eyelid malposition. Separated superior muscle complex and prominent intermuscular septum connecting the levator and the lateral rectus muscles were noticeable in CT scans. Predictive factors for ptosis surgery included longer BM (p = 0.04), shorter distance from the superior orbital wall to the upper margin of the prosthesis (p < 0.01), and a longer height of the prosthesis (p = 0.04). Most patients needed multiple operations after secondary implantation for rehabilitation. Additional ptosis operation may be required for patients with a high brow on the anophthalmic side, a vertically long prosthesis, and an impinged prosthesis against the superior orbital wall.


Exploring the potential of thermophilic anaerobic co-digestion between agro-industrial waste and water hyacinth: operational performance, kinetic study and degradation pathway.
Anaerobic co-digestion (co-AD) of agro-industrial waste, namely, palm oil mill effluent (POME) and sugarcane vinasse (Vn), with water hyacinth (WH) as co-substrate was carried out in two separate Anaerobic Suspended Growth Closed Bioreactors (ASGCBs) under thermophilic (55 °C) conditions. The highest chemical oxygen demand (COD) and soluble COD reduction in co-AD of POME-WH (78.61%, 78.86%) is slightly higher than co-AD of Vn-WH (75.75%, 78.24%). However, VFA reduction in co-AD of POME-WH (96.41%) is higher compared to co-AD of Vn-WH (85.94%). Subsequently, biogas production peaked at 13438 mL/day values and 16122 mL/day for co-AD of POME-WH and Vn-WH, respectively. However, the methane content was higher in the co-AD of POME-WH (72.04%) than in the co-AD of Vn-WH (69.86%). Growth yield (YG), maximum specific substrate utilization rate (rx,max) and maximum specific biomass growth rate (μmax) are higher in co-AD of POME-WH, as supported by the higher mixed liquor volatile suspended solids (MLVSS) and COD reduction efficiency compared to co-AD of Vn-WH. However, methane yield ([Formula: see text]) reported in the co-AD of POME-WH and Vn-WH are 0.2748 and 0.3112 L CH4/g CODreduction, respectively, which suggests that WH is a more suitable co-substrate for Vn compared to POME.


SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells.
Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation and depolarization-induced rises in intracellular Ca2+. Here we show that tomosyn, which suppresses insulin exocytosis by binding syntaxin1A, does so in a manner which requires its SUMOylation. Glucose-dependent de-SUMOylation of tomosyn1 at K298 releases syntaxin1A and controls the amplification of exocytosis in concert with a recently-identified tomosyn1-interacting partner; the Ca2+-binding protein secretagogin, which dissociates from tomosyn1 in response to Ca2+-raising stimuli and is required for insulin granule trafficking and exocytosis downstream of Ca2+ influx. Together our results suggest that tomosyn acts as a key signaling hub in insulin secretion by integrating signals mediated by metabolism-dependent de-SUMOylation and electrically-induced entry of Ca2+ to regulate the availability of exocytotic proteins required for the amplification of insulin secretion.


Magnetic resonance imaging of the active second stage of labour: proof of principle.
To prove that magnetic resonance imaging of foetal anatomy during the active second stage of vaginal delivery is feasible. Initially, five pregnant volunteers around the 30th week of gestation were examined in an open MRI. Based on the findings, one vaginal delivery was acquired under real-time imaging. To monitor the birth status during image acquisition, an MR-compatible wireless cardiotocography (CTG) system was built. Single-shot sequence parameters were optimised to compensate motion artefacts during labour. Safety requirements to monitor the birth process under real-time MR imaging were met. High-resolution MR images were acquired immediately before and after delivery. In one patient, TSE single-shot cinematic sequences of the active second stage of labour were obtained. All sequences were adapted to tolerate movement of the mother and infant, as well as residual noise from the CTG. Furthermore, the MR imaging during labour showed only minor image artefacts. CTG-monitored acquisition of MRI series during the active second stage of delivery is feasible. Image quality should allow various further studies to improve models for birth simulation as well as potential investigation of obstructed labour and obstetric complications.


A model of troponin-I in complex with troponin-C using hybrid experimental data: the inhibitory region is a beta-hairpin.
We present a model for the skeletal muscle troponin-C (TnC)/troponin-I (TnI) interaction, a critical molecular switch that is responsible for calcium-dependent regulation of the contractile mechanism. Despite concerted efforts by multiple groups for more than a decade, attempts to crystallize troponin-C in complex with troponin-I, or in the ternary troponin-complex, have not yet delivered a high-resolution structure. Many groups have pursued different experimental strategies, such as X-ray crystallography, NMR, small-angle scattering, chemical cross-linking, and fluorescent resonance energy transfer (FRET) to gain insights into the nature of the TnC/TnI interaction. We have integrated the results of these experiments to develop a model of the TnC/TnI interaction, using an atomic model of TnC as a scaffold. The TnI sequence was fit to each of two alternate neutron scattering envelopes: one that winds about TnC in a left-handed sense (Model L), and another that winds about TnC in a right-handed sense (Model R). Information from crystallography and NMR experiments was used to define segments of the models. Tests show that both models are consistent with available cross-linking and FRET data. The inhibitory region TnI(95-114) is modeled as a flexible beta-hairpin, and in both models it is localized to the same region on the central helix of TnC. The sequence of the inhibitory region is similar to that of a beta-hairpin region of the actin-binding protein profilin. This similarity supports our model and suggests the possibility of using an available profilin/actin crystal structure to model the TnI/actin interaction. We propose that the beta-hairpin is an important structural motif that communicates the Ca2+-activated troponin regulatory signal to actin.


Identification of angiotensin-converting enzyme 2 (ACE2) protein as the potential biomarker in SARS-CoV-2 infection-related lung cancer using computational analyses.
COVID-19 is a pandemic that began to spread worldwide caused by SARS-CoV-2. Lung cancer patients are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 enters into the host by the ACE2 receptor. Thus, ACE2 is the key to understand the mechanism of SARS-CoV-2 infection. However, the lack of knowledge about the biomarker of COVID-19 warrants the development of ACE2 biomarkers. The analysis of ACE2 expression in lung cancer was performed using The Cancer Genome Atlas (TCGA). Therefore, we investigated the prognosis, clinical characteristics, and mutational analysis of lung cancer. We also analyzed the shared proteins between the COVID-19 and lung cancer, protein-protein interactions, gene-miRNAs, gene-transcription factors (TFs), and the signaling pathway. Finally, we compared the mRNA expression of ACE2 and its co-expressed proteins using the TCGA. The up-regulation of ACE2 in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) was found irrespective of gender and age. We found the low survival rate in high expression of ACE2 in lung cancer patients and 16 mutational positions. The functional assessment of targeted 12,671, 3107, and 29 positive genes were found in COVID-19 disease, LUAD, and LUSC, respectively. Then, we identified eight common genes that interact with 20 genes, 219 miRNAs, and 16 TFs. The common genes performed the mRNA expression in lung cancer, which proved the ACE2 is the best potential biomarker compared to co-expressed genes. This study uncovers the relationship between COVID-19 disease and lung cancer. We identified ACE2 and also its co-expressed proteins are the potential biomarker and therapy as the current COVID-19 disease and lung cancer.


Development of a curated Hershberger database.
A systematic literature review was conducted to identify Hershberger bioassays for ∼3200 chemicals including those used to validate the OECD/US EPA guideline assay, US EPA's chemicals screened for endocrine activity, and the library of chemicals run in US EPA 's ToxCast in vitro assays. For 134 chemicals that met pre-defined criteria, experimental results were extracted into a database used to characterize uncertainty in results and evaluate the concordance of the Hershberger assay with other in vivo rodent studies that measure androgen-responsive endpoints. Of 25 chemicals tested in >1 Hershberger study, 28% had disagreements between studies (i.e. ≥1 positive and ≥1 negative study), and of the 65 chemicals tested in Hershberger studies and other in vivo studies with androgen-responsive endpoints, 43% indicated disagreements, though in some cases these may be explained by differences in study designs or physiology of the animal model. Ultimately, 49 chemicals were identified with reproducible androgen pathway responses confirmed in ≥2 in vivo rodent studies that could be considered reference chemicals useful for validating alternative methods.


Publications from clinical trials: process, conflict of interest and the evidence base.
The aim of this study is to review the issues of publication of clinical trials with consideration of ethics and the incomplete evidence base. We review clinical trials and issues of communications and ethics. Several case studies of notable public health researchers will be discussed. Many of the major breakthroughs of public health practice, including the works of John Snow would not have been published under modern guidelines for scientific communication. The research-publication system of modern health care poses many challenges for editors. Journal editors need to include a balance of different types of studies where insufficient randomised controlled trials are available. Clinical trials are a reliable source of evidence for health care practitioners. Journals need to uphold the integrity of the information provided by randomised controlled trials (RCTs) and synthesise and communicate health information. At the same time, editors must assess non-RCT evidence and be vigilant for many of the other potential problems in health and medical communication.


Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer.
The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. Here, we investigate the relationship of ColXα1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting. A total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColXα1 was performed on whole tumor sections. Associations between ColXα1expression, clinical pathological features, and outcomes were analyzed. ColXα1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColXα1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColXα1 expressing (HR = 2.1; 95% CI = 1.2-3.9) tumors of older patients (> = 58 years) (HR = 5.3; 95% CI = 1.7-17) with higher stage (HR = 2.6; 95% CI = 1.3-5.2). Similarly, DFS was lower in ColXα1 expressing (HR = 1.8; 95% CI = 1.6-5.7) tumors of older patients (HR = 3.2; 95% CI = 1.3-7.8) with higher stage (HR = 2.7; 95% CI = 1.6-5.7) and low TILs. In low PR+ tumors, higher ColXα1 expression was associated with poorer prognosis. ColXα1 expression is associated with poor disease free survival and overall survival in ER+/HER2+ breast cancer. This study provides further support for the prognostic utility of ColXα1 as a breast cancer associated stromal factor that predicts response to chemotherapy.


Mechanism of induction of class I major histocompatibility antigen expression by murine leukemia virus.
Alterations in expression of major histocompatibility complex (MHC) antigens on tumor cells clearly correlate with the tumorgenicity and metastatic potential of those cells. These changes in the biological behavior of the tumor cells are presumably secondary to resulting changes in their susceptibility to immune recognition and destruction. Murine leukemia viruses (MuLV) exert regulatory effects on class I genes of the MHC locus. MuLV infection results in substantial increases in cell surface expression of all three class I MHC antigens. These viral effects on MHC antigen expression profoundly influence immune-mediated interaction with the infected cells, as assessed by cytotoxic T lymphocyte recognition and killing. Control of class I MHC and beta-2 microglobulin genes by MuLV takes place via a trans-acting molecular mechanism. MuLV controls expression of widely separated endogenous cellular MHC genes, transfected xenogeneic class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to a bacterial reporter gene. These findings indicate that MuLV exerts its effects on MHC expression via a trans mechanism. The MuLV-responsive sequences on the MHC genes appear to lie within 1.2 kilobases upstream of the initiation codon for those genes.


Abiotic environmental factors override phytoplankton succession in shaping both free-living and attached bacterial communities in a highland lake.
Bacterial communities are an important part of biological diversity and biogeochemical cycling in aquatic ecosystems. In this study, the relationship amongst the phytoplankton species composition and abiotic environmental factors on seasonal changes in the community composition of free-living and attached bacteria in Lake Erhai were studied. Using Illumina high-throughput sequencing, we found that the impact of environmental factors on both the free-living and attached bacterial community composition was greater than that of the phytoplankton community, amongst which total phosphorus, Secchi disk, water temperature, dissolved oxygen and conductivity strongly influenced bacterial community composition. Microcystis blooms associated with subdominant Psephonema occurred during the summer and autumn, and Fragilaria, Melosira and Mougeotia were found at high densities in the other seasons. Only small numbers of algal species-specific bacteria, including Xanthomonadaceae (Proteobacteria) and Alcaligenaceae (Betaproteobacteria), were tightly coupled to Microcystis and Psephonema during Microcystis blooms. Redundancy analysis showed that although the composition of the bacterial communities was controlled by species composition mediated by changes in phytoplankton communities and abiotic environmental factors, the impact of the abiotic environment on both free-living and attached bacterial community compositions were greater than the impact of the phytoplankton community. These results suggest that the species composition of both free-living and attached bacterial communities are affected by abiotic environmental factors, even when under strong control by biotic factors, particularly dominant genera of Microcystis and Psephonema during algal blooms.


Viscosity & SO2-sensitive dual colorimetric effect fluorescent sensor enabled imaging detection within plant onion and biological system.
The biological microenvironment includes important parameters such as viscosity, polarity, temperature, oxygen content and pH. In particular, abnormal cell viscosity is associated with the development of major diseases. Sulphur dioxide (SO2) serves not only as an essential atmospheric pollutant but also an influential signalling molecule in biological cells, predisposing individuals to increased respiratory disease. In this work, we designed and synthesized a novel fluorescent probe CouCN-V&S with dual response to micro environmental viscosity and SO2. The probe monitored viscosity and SO2 separately through dual emission channels with a difference of 135 nm. The probe responded sensitively to SO2 (<1s) and exhibited satisfactory immunity to interference and pH stability. The probe was successfully applied to imaging cellular, intra-zebrafish viscosity and SO2 changes. Interestingly, we took onion epidermal cells as model and explored the capability of probe CouCN-V&S to image SO2 in plant cells for the first time.


A Stress-Induced Martensitic Transformation in Aged Ti49Ni51 Alloy after High-Velocity Impact.
The effects of a high-velocity impact on the microstructure, phase transformation and mechanical property of aged Ti49Ni51 alloy are investigated. The transformation behavior and microstructure along the impact direction after impact emerge with regionalization characteristics, including a deformed region near the crater (0-4 mm) and an un-deformed region of the distal crater (5-6 mm). Stress-induced martensite is the main deformation mechanism in the deforming region of aged Ti49Ni51 alloy under high-velocity impact.


Clinico-radiological characteristics, histo-pathological features and long-term survival outcomes in central neurocytoma: A single-institutional audit.
Central neurocytoma is a rare benign brain tumor that typically arises from the subependymal lining of the lateral ventricles in young adults and is generally associated with excellent survival following neurosurgical excision alone. This is a retrospective clinical audit of biopsy-proven neurocytoma registered between 2004 and 2019 at a single institution in India. All time-to event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Any p-value <0.05 was considered statistically significant. A total of 66 patients with neurocytoma were included in the descriptive analysis. Median age of study cohort was 31 years with equitable gender ratio. Majority (83%) of tumors were intraventricular, lateral ventricle being the commonest location. Following maximal safe resection, patients were generally kept on close clinico-radiological surveillance. Most patients (80%) had typical World Health Organization (WHO) grade II neurocytoma with remaining 20% showing histological atypia and/or high-grade features. Outcome analysis was restricted to 35 patients with relevant treatment details and adequate follow-up information. Six patients experienced recurrent/progressive disease with 2 documented deaths. At a median follow up of 52 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 93.3% and 96.8% respectively. Three patients developed delayed recurrence (>5-years after initial diagnosis) underscoring the importance of long-term follow-up. Atypical/high-grade histology was associated with inferior survival that may stand to benefit with upfront adjuvant radiotherapy. This represents the largest single-institution series of central neurocytoma and demonstrates excellent outcomes with adequate surgical resection alone, reserving radiotherapy for large residual tumor, recurrent disease, and/or atypical high-grade histology.


Preferences of different tick species for human hosts in Turkey.
The ticks removed from the patients who applied to the hospitals in Istanbul and neighboring cities, Turkey, with the complaint of tick bite were examined in this study, on account of their species, biological stages, attachment sites on the body, and the age of the affected patients. A total of 16,969 ticks were identified. Encountered species were as follows: 33.6 % Ixodes spp. immature, 25.3 % Hyalomma spp. immature, 24.3 % I. ricinus, 9.5 % Rhipicephalus sanguineus gr., 3.2 % R. bursa, 2.2 % Hyalomma marginatum, 1.96 % Haemaphysalis adults, 1.66 % Hyalomma aegyptium, 0.52 % Dermacentor marginatus, 0.39 % Rhipicephalus spp. nymphs, 0.12 % Dermacentor spp. nymphs, 0.11 % Haemaphysalis spp. nymphs, 0.09 % Hyalomma scupense, and 0.03 % Hyalomma excavatum. The distribution of attachment sites of the species and instars showed significant differences. Furthermore, age data of the patients also revealed that certain tick species were more common within certain age groups.


Application of a computer program for genetic typing of classical swine fever virus isolates from Germany.
The commercial software program HLA SequiTyper (Amersham Pharmacia Biotech), designed originally for human leukocyte antigen typing, was adapted for rapid typing of classical swine fever (CSF) virus isolates. The program compares new sequence data with those stored in a database file and calculates the most probable assignment. For generating the CSF virus sequence database, 150 bp of the 5' nontranslated genomic region (5'-NTR) from 88 German classical swine fever virus isolates from outbreaks between 1984 and 1997 were solid-phase sequenced directly after RT-PCR amplification. Sequence alignments showed that they all belonged to the previously defined genetic group 2. Within this group, six different subgroups could be distinguished, and were designated according to the geographic location where they are either still endemic or where they appeared most commonly. The advantage of using the HLA SequiTyper program is that it reads directly the sequence files as generated by the ALF sequencer (Amersham Pharmacia Biotech), making any manipulations unnecessary. In addition, a constant quality control of the raw sequence data can be achieved, as more than one sequence from the same isolate can be evaluated at once. Using this approach, new CSF isolates can be typed within 2 days.


Reduction of infarct size by cell-permeable oxygen metabolite scavengers.
The timely restoration of blood flow to severely ischemic myocardium limits myocardial infarct size. However, experimental studies demonstrate that the myocardial salvage achieved is suboptimal because of additional injury that occurs during reperfusion, due in part to the generation of reactive oxygen metabolites. Initially, superoxide (O2-) was considered to be the central mediator of reperfusion injury. While there are several potential pathways of O2- generation in reperfused myocardium, O2- is poorly reactive toward tissue biomolecules. However, O2-, in the presence of redox-active metals such as iron, generates .OH or hydroxyl-like species that are highly reactive with cell constituents. Thus, while O2- may initiate reaction sequences leading to myocardial injury, it may not be the actual injurious agent. In vitro studies suggest that oxygen metabolite injury occurs at intracellular sites and involves iron-catalyzed processes. Consistent with this mechanism, extracellular oxygen metabolite scavengers have not convincingly reduced infarct size. However, treatment around the time of reperfusion, after ischemia is well established, with cell-permeable scavengers of .OH reduce infarct size. Results with these cell-permeable agents suggest that in the intact animal during regional ischemia and reperfusion, oxygen metabolite injury also occurs at intracellular sites. Cell-permeable scavenger agents are a promising class of drugs for potential clinical use, though further experimental and toxicologic studies are required.


Case reports: Tantalum debris dispersion during revision of a tibial component for TKA.
Porous tantalum nonmodular tibial components for TKA were introduced in 1999. We revised three well-fixed tantalum tibial trays. For removal, we used osteotomes and revision oscillating saw blades. Removal of the components was laborious and resulted in generation of abundant tantalum debris that seeded the periarticular soft tissues despite meticulous protection with gauze. The retained metallic debris that is visible on postoperative radiographs has the potential for generation of third-body wear. We alert the orthopaedic community about this phenomenon and recommend minimizing the use of motorized revision instruments for removal of trabecular metal implants.


DC-52, a novel antitumor antibiotic. 2. Isolation, physico-chemical characteristics and structure determination.
DC-52, C18H22N2O4, is a new antitumor antibiotic produced by Streptomyces melanovinaceus nov. sp. The structure of DC-52 has been determined by consideration of spectral data. It has the novel skeleton, 8,11-iminoazepinoisoquinoline.


Quantitative differential phase contrast imaging in an LED array microscope: errata.
This errata corrects typos found in the derived transfer functions in [Opt. Express23, 11394 (2015)10.1364/OE.23.011394].


Association between leisure-time physical activity and the built environment in China: Empirical evidence from an accelerometer and GPS-based fitness app.
To reexamine the relationship between leisure-time physical activity (LTPA) and the built environment (BE), this paper takes advantage of the massive amount of data collected by an accelerometer and GPS-based fitness mobile app. Massive LTPA data from more than 3 million users were recorded by Codoon in 500m by 500m grid cells and aggregated to 742 natural cities in mainland China. Six BE indicators were quantified using GIS at the city scale. Robust regression analysis was used to estimate the correlation between LTPA and BE. Five of six BE indicators-connectivity, road density, land use mix, points of interest density, and density of parks and squares-were significantly, positively, independently, and linearly related to LTPA in the regression analysis. The study obtains findings that are consistent with the previous literature but also provides novel insights into the important role of POI density in encouraging LTPA, as well as how the relationship between LTPA and BE varies by time of day. The study also sheds light on the embrace of new technology and new data in public health and urban studies.


Discovery of imidazoleisoindole derivatives as potent IDO1 inhibitors: Design, synthesis, biological evaluation and computational studies.
Indoleamine-2,3-dioxygenase-1 (IDO1) is an attractive target for cancer immunotherapy. Herein, a series of novel imidazoleisoindole derivatives were prepared and evaluated for their ability to inhibit IDO1. Among these, derivative 11r was the most active compound with nanomolar potency in the Hela cell-based assay, while showed negligible cellular toxicity. UV-visible spectra study demonstrated that compounds 11p and 11r bound to IDO1 and coordinated with the heme iron. Furthermore, they could significantly promote T cell proliferation, increase IFN-γ production, and reduce the numbers of Foxp3+ regulatory T cells. Finally, induced fit docking (IFD) and quantum mechanics/molecular mechanics (QM/MM) calculation were performed to understand the interactions of these compounds to IDO1 protein, which provided a comprehensive guide for further structural modification and optimization.


Metabolic effects of glucose, medium chain triglyceride and long chain triglyceride feeding before prolonged exercise in rats.
The purpose of this study was to test the hypothesis that oral ingestion of lipids could increase endurance by slowing the rate of glycogen depletion. Trained rats were killed after a 2 h run on a rodent treadmill, following an intragastric infusion of water, glucose, medium chain triglycerides (MCT) or long chain triglycerides (LCT). Glucose and triglycerides were administered in equicaloric concentrations (50 kJ). The results show that oral ingestion of lipids (MCT or LCT) did not reduce glycogen depletion in liver, heart or skeletal muscle after exercise whereas the fat diet increased muscle and heart glycogen stores in resting conditions. In contrast, glucose feeding induced a significant sparing effect on endogenous carbohydrate utilization and reduced physical exercise lipolysis. These data indicated, firstly, that enhanced lipid availability induced by a single lipid meal before exercise was not able to modify the glycogen depletion occurring after exercise and, secondly, that the glucose/fatty acid cycle was not effective in these conditions. The comparison between lipids indicated that the effect on glycogen use of MCT did not differ from that of LCT, and did not seem to be of any particular importance during physical exercise.


Wound Healing Effectivity of the Ethanolic Extracts of Ageratum conyzoides L. Leaf (White and Purple Flower Type) and Centella asiatica and Astaxanthin Combination Gel Preparation in Animal Model
The study's objective was to determine the wound healing activity of the combination of ethanolic extracts of Ageratum conyzoides L. leaf (white and purple), Centella asiatica, and astaxanthin gel preparation. For in-gel preparation, three different formulas of gelling agents, namely carbopol 934 (1%), hydroxypropyl methylcellulose (HPMC) (9%), and natirum-carboxymethylcellulose (Na-CMC) (4%), were employed. Then, the organoleptic, pH, spreadability, and viscosity of the formulas were evaluated. To determine wound healing activity, six treatments, including negative control (placebo), positive control (bioplacenton), BP5 (A. conyzoides L. leaf ethanolic extract of white flower type 5%, C. asiatica L. Urb leaf ethanolic extract 2.5%, astaxanthin 0.05%), BU5 (A. conyzoides L. leaf ethanolic extract of purple flower type 5%, C. asiatica L. Urb leaf ethanolic extract 2.5%, astaxanthin 0.05%), BU10 (A. conyzoides L. leaf ethanolic extract of purple flower type 10%, C. asiatica L. Urb leaf ethanolic extract 5%, and astaxanthin 0.1%), and BP10 (A. conyzoides L. leaf ethanolic extract of white flower type 10%, C. asiatica L. Urb leaf ethanolic extract 5%, and astaxanthin 0.1%) were evaluated. All treatments were applied to an incision wound (1.5 cm). Measurement of the wound length was conducted daily for 14 days. The results showed that the carbopol 934 (1%) gelling agent formula was better than HPMC and Na-CMC. Meanwhile, the percentages of wound healing activity for negative, positive, BP5, BU5, BU10, and BP10 groups were 72.51%, 69.36%, 70.14%, 81.70%, 86.54%, and 80.21%, respectively. The BU5 and BU10 showed significant activity (p<0.05) compared with positive and negative controls. BU10 provided the best wound healing activity and can be developed as a commercial product.


[Analysis on the status of anemia among children under 3 years old in 10 provinces in western China].
To analyze the status of anemia among children under 3 years old from western China based on the data gathered from the project area. 9616 children under 3 years old and their families were investigated, using stratified random sampling method in 46 counties in western China. To measure the content of haemoglobin by cyanmethemoglobin and hemocue, under the diagnostic criterion as 110 g/L for child aged 6 months to 6 years old, proposed by WHO and UNICEF. The overall prevalence of anemia among child under 3 years old in ten provinces was 33.8%. Prevalence of anemia varied along with age differences. The peak of anemia prevalence was 12-18 months. The related risk of anemia between mother and child was 3.271. Data from logistic regression showed that mother being anemic, cooking with iron pan, cooking for child separate from adults and gender had statistical significance to their children's anemia. The feasible measures should be developed to reduce the prevalence of anemia.


Beware of Neglect of Non-COVID Patients in COVID Era.
Clerk AM. Beware of Neglect of Non-COVID Patients in COVID Era. Indian J Crit Care Med 2021;25(8):837-838.


The complete structure of the trifoliin A lectin-binding capsular polysaccharide of Rhizobium trifolii 843.
The complete structure of the acidic, extracellular, capsular polysaccharide of Rhizobium trifolii 843 has been elucidated by a combination of chemical, enzymic, and spectroscopic methods, confirming an earlier proposed sugar sequence and assigning the locations of the acyl substituents. The polysaccharide was depolymerized by a lyase into octasaccharide units which were uniform in carbohydrate composition and linkage. These units also contained a uniform distribution of acetyl and pyruvic acetal [O-(1-carboxyethylidene)] groups, and half of them were further acylated with D-3-hydroxybutanoyl groups. A much smaller proportion (less than 5%) of the oligomers was further acylated by a second D-3-hydroxybutanoyl group. The locations of the subtituents were determined chemically and by J-correlated, 1H-n.m.r. spectroscopy, proton nuclear Overhauser effect (n.O.e.) measurements, double-rd structure of the carbohydrate chain were determined by methylation analysis using g.l.c.-m.s. fast-atom-bombardment mass spectrometry, and n.m.r. studies on the reduced, deacylated oligomer. Structural studies were supplemented by n.m.r. analyses on the original polymer. The oligosaccharides were found to be branched octasaccharides with four sugar residues in each branch, and the carbohydrate sequence agreed well with that expected from earlier work. In the abbreviated sequence and structure (1a), the sugar residues are labelled "a" through "h". The main chain (a-d) is composed of a 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid group (a) that is linked to O-4 of a 3-O-acetyl-D-glucosyluronic acid residue (b) which is beta-linked to O-4 of a D-glucosyl residue (c). Residue c is beta-linked to O-4 of the branching D-glucose residue (d). The side chain consists of a substituted D-galactosyl group (h) which is beta-linked to O-3 of residue 9 of a beta-(1----4)-linked D-glucose trisaccharide (fragment e-f-g). The reducing end of the resulting tetrasaccharide (e-f-g-h) is beta-linked to O-6 of the branching D-glucose residue (d). In the native polymer, this branching residue is alpha-linked to O-4 of the modified D-glucuronic acid residue (a) which is the unsaturated sugar in the oligomer. A small proportion of the O-2 atoms of the acetylated D-glucosyluronic acid residues is acetylated because of ester migration. The two terminal sugars (g and h) of the branch chain bear 4,6-O-(1-carboxyethylidene) groups. The D-galactosyl groups of half of the oligomers are acylated by D-3-hydroxybutanoyl groups at O-3.(ABSTRACT TRUNCATED AT 400 WORDS)


Are large dinners associated with excess weight, and does eating a smaller dinner achieve greater weight loss? A systematic review and meta-analysis.
There are suggestions that large evening meals are associated with greater BMI. This study reviewed systematically the association between evening energy intake and weight in adults and aimed to determine whether reducing evening intake achieves weight loss. Databases searched were MEDLINE, PubMed, Cinahl, Web of Science, Cochrane Library of Clinical Trials, EMBASE and SCOPUS. Eligible observational studies investigated the relationship between BMI and evening energy intake. Eligible intervention trials compared weight change between groups where the proportion of evening intake was manipulated. Evening intake was defined as energy consumed during a certain time - for example 18.00-21.00 hours - or self-defined meal slots - that is 'dinner'. The search yielded 121 full texts that were reviewed for eligibility by two independent reviewers. In all, ten observational studies and eight clinical trials were included in the systematic review with four and five included in the meta-analyses, respectively. Four observational studies showed a positive association between large evening intake and BMI, five showed no association and one showed an inverse relationship. The meta-analysis of observational studies showed a non-significant trend between BMI and evening intake (P=0·06). The meta-analysis of intervention trials showed no difference in weight change between small and large dinner groups (-0·89 kg; 95 % CI -2·52, 0·75, P=0·29). This analysis was limited by significant heterogeneity, and many trials had an unknown or high risk of bias. Recommendations to reduce evening intake for weight loss cannot be substantiated by clinical evidence, and more well-controlled intervention trials are needed.


Duplex sequencing provides detailed characterization of mutation frequencies and spectra in the bone marrow of MutaMouse males exposed to procarbazine hydrochloride.
Mutagenicity testing is an essential component of health safety assessment. Duplex Sequencing (DS), an emerging high-accuracy DNA sequencing technology, may provide substantial advantages over conventional mutagenicity assays. DS could be used to eliminate reliance on standalone reporter assays and provide mechanistic information alongside mutation frequency (MF) data. However, the performance of DS must be thoroughly assessed before it can be routinely implemented for standard testing. We used DS to study spontaneous and procarbazine (PRC)-induced mutations in the bone marrow (BM) of MutaMouse males across a panel of 20 diverse genomic targets. Mice were exposed to 0, 6.25, 12.5, or 25 mg/kg-bw/day for 28 days by oral gavage and BM sampled 42 days post-exposure. Results were compared with those obtained using the conventional lacZ viral plaque assay on the same samples. DS detected significant increases in mutation frequencies and changes to mutation spectra at all PRC doses. Low intra-group variability within DS samples allowed for detection of increases at lower doses than the lacZ assay. While the lacZ assay initially yielded a higher fold-change in mutant frequency than DS, inclusion of clonal mutations in DS mutation frequencies reduced this discrepancy. Power analyses suggested that three animals per dose group and 500 million duplex base pairs per sample is sufficient to detect a 1.5-fold increase in mutations with > 80% power. Overall, we demonstrate several advantages of DS over classical mutagenicity assays and provide data to support efforts to identify optimal study designs for the application of DS as a regulatory test.


Patient satisfaction and postoperative pain with different postoperative therapy regimens after standardized cataract surgery: a randomized intraindividual comparison.
The purpose of this study was to evaluate if administration of artificial tears of high or low-viscosity improve cataract patients' satisfaction and postoperative pain after cataract surgery. Thirty consecutive patients undergoing bilateral cataract surgery under topical anesthesia were enrolled prospectively. Administration of the following postoperative therapies was randomized: for all participants, one eye was treated with "instant vision" (IV) therapy alone (IV-alone), i.e., this eye remained uncovered. In group 1 (n = 11), the second eye received IV therapy with Hylo-Comod(®) (HC) eye drops; in group 2 (n = 9), IV with Vidisic(®) (VS) eye drops; in group 3 (n = 10), an ointment bandage (OB). Postoperative satisfaction, pain scores, visual acuity, intraocular pressure, tear break-up time and postoperative corneal changes were compared. Group 1: No clear preference was observed for any of the methods concerning subjective satisfaction. Group 2: 100% of patients preferred IV + VS therapy. Group 3: Patients' postoperative satisfaction with OB therapy was 89%. Concerning postoperative pain perception, no significant differences were found between IV therapy alone and the IV-combination therapies. Significant differences in pain perception (P < 0.042) were measured between IV and OB in the first 8 h postoperatively. Ten hours postoperatively and beyond, there were no significant differences in pain scores (P > 0.05). Pain perception was significantly lower with OB when compared to IV-alone or IV-combination therapies using artificial tears. This result was verified by OB's 89% patient satisfaction level. Low-viscosity artificial tears showed no significant subjective benefits for the patients; patient satisfaction was greatest (100%) with a high-viscosity tear substitute.


Prenatal MRI assessment of mediastinal shift angle as a feasible and effective risk stratification tool in isolated right-sided congenital diaphragmatic hernia.
To develop a mediastinal shift angle (MSA) measurement method applicable to right-sided congenital diaphragmatic hernia (RCDH) in fetal MRI and to validate the predictive value of MSA in RCDH. Twenty-seven fetuses with isolated RCDH and 53 controls were included in our study. MSA was measured on MRI axial image at the level of four-chamber view of the fetal heart. The angle between the sagittal midline landmark line and the left boundary landmark line touching tangentially the lateral wall of the left ventricle was used to quantify MSA for RCDH. Appropriate statistical analyses were performed to determine whether MSA can be regarded as a valid predictive tool for postnatal outcomes. Furthermore, predictive performance of MSA was compared with that of lung area to head circumference ratio (LHR), observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected TFLV (O/E TFLV). MSA was significantly higher in the RCDH group than in the control group. MSA, LHR, O/E LHR, TFLV, and O/E TFLV were all correlated with postnatal survival, pulmonary hypertension (PH), and extracorporeal membrane oxygenation (ECMO) therapy (p < 0.05). Value of the AUC demonstrated good predictive performance of MSA for postnatal survival (0.901, 95%CI: (0.781-1.000)), PH (0.828, 95%CI: (0.661-0.994)), and ECMO therapy (0.813, 95%CI: (0.645-0.980)), which was similar to O/E TFLV but slightly better than TFLV, O/E LHR, and LHR. We developed a measurement method of MSA for RCDH for the first time and demonstrated that MSA could be used to predict postnatal survival, PH, and ECMO therapy in RCDH. Newly developed MRI assessment method of fetal MSA in RCDH offers a simple and effective risk stratification tool for patients with RCDH. • We developed a measurement method of mediastinal shift angle for right-sided congenital diaphragmatic hernia for the first time and demonstrated its feasibility and reproducibility. • Mediastinal shift angle can predict more prognostic information other than survival in right-sided congenital diaphragmatic hernia with good performance. • Mediastinal shift angle can be used as a simple and effective risk stratification tool in right-sided congenital diaphragmatic hernia to improve planning of postnatal management.


Long-term results of fourth ventriculo-cisternostomy in complex versus simplex atresias of the fourth ventricle outlets.
Twelve cases of atresia of the fourth ventricle outlets are presented and they are classified into 2 types: simplex versus complex. Fourth ventriculo-cisternostomy is the treatment of choice. Based on the surgical experiences in simplex cases, new technical modifications were developed to make it applicable to the complex cases as well. The advantages and limitations of such operative approaches over other conventional shunt procedures are compared and the long-term postoperative results are listed. Hopefully, the surgical intervention described here may have opened a reasonable method for treating certain cases of the trapped fourth ventricle as a special variant of the complex atresia type. It is important to realize that knitted tubes are categorically unqualified for the surgical use like this.


Sheng Yang He.
Interview with Sheng Yang He, who studies the molecular biology of plant-pathogen interactions at Michigan State University.


Simultaneous production of casein and mammary tumor virus in mouse mammary epithelial cells grown on floating collagen gels.
Simultaneous production of casein and mammary tumor virus (MTV) was analyzed in monolayer cultures of mammary epithelial cells from pregnant BALB/cfC3H mice. A comparison of the 2 cell culture substrata, plastic culture dish and floating collagen gel, showed that the latter supported a much higher degree of simultaneous casein and MTV production in the presence of insulin, cortisol and prolactin in serum-free culture medium. Importance of floating collagen gel was further shown by delaying the flotation of gels. When the release of gels was delayed, there were concomitant delays in the increase of casein and MTV production. These results indicate that hormones, nature of substratum and flotation regulate the degree of differentiation of mammary epithelial cells in vitro.


The number of microspheres in Y90 radioembolization directly affects normal tissue radiation exposure.
In Y90 radioembolization, the number of microspheres infused varies by more than a factor of 20 over the shelf-life of the glass radioembolization device. We investigated the effect of the number of Y90 microspheres on normal liver tissue. Healthy pigs received lobar radioembolization with glass Y90 microspheres at 4, 8, 12, and 16 days post-calibration, representing a > 20× range in the number of microspheres deposited per milliliter in tissue. Animals were survived for 1-month post-treatment and the livers were explanted and scanned on a micro CT system to fully characterize the microscopic distribution of individual microspheres. A complete 3D microdosimetric evaluation of each liver was performed with a spatially correlated analysis of histopathologic effect. Through whole-lobe microscopic identification of each microsphere, a consistent number of microspheres per sphere cluster was found at 4, 8, and 12 days postcalibration, despite an 8-fold increase in total microspheres infused from days 4 to 12. The additional microspheres instead resulted in more clusters formed and, therefore, a more homogeneous microscopic absorbed dose. The increased absorbed-dose homogeneity resulted in a greater volume fraction of the liver receiving a potentially toxic absorbed dose based on radiobiologic models. Histopathologic findings in the animals support a possible increase in normal liver toxicity in later treatments with more spheres (i.e., ≥ day 12) compared to early treatments with less spheres (i.e., ≤ day 8). The microdosimetric evidence presented supports a recommendation of caution when treating large volumes (e.g., right lobe) using glass 90Y microspheres at more than 8 days post-calibration, i.e., after "2nd week" Monday. The favorable normal tissue microscopic distribution and associated low toxicity of first week therapies may encourage opportunities for dose escalation with glass microspheres and could also be considered for patients with decreased hepatic reserve.


[Dental state in patients with head and neck cancers].
In France, in 2005, there were approximately 16,000 new cases of head and neck cancer. These cancers have an unfavourable prognosis: the survival rates at 3 and 10 years are 50% and 10% respectively. The consumption of alcohol and tobacco is the most important risk factor; in some countries HPV infection was identified as a risk factor of head and neck tumours. Furthermore, a poor oral hygiene seems to raise this risk. We found many decay and periodontium problems in patients with an upper aerodigestive tract cancer. An evaluation of dental state is necessary before any cancer treatment. Treatments by radiotherapy engender noxious effects: hypocellular, hypovascularization, hypoxie of the irradiated tissues, which lead to immediate and chronically oral complications such as mucositis, fibrosis, xerostomia, decay, or osteoradionecrosis. An oral follow-up of these patients can prevent these complications, or reduce the severity of oral complications, and promote a good oral state.


Bad company: Microenvironmentally mediated resistance to targeted therapy in melanoma.
This review will focus on the role of the tumor microenvironment (TME) in the development of drug resistance in melanoma. Resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment, a phenomenon that is often attributed to the incredible plasticity of melanoma cells but may also depend on the TME. The TME is unique in its cellular composition-it contains fibroblasts, immune cells, endothelial cells, adipocytes, and among others. In addition, the TME provides "non-homeostatic" levels of oxygen, nutrients (hypoxia and metabolic stress), and extracellular matrix proteins, creating a pro-tumorigenic niche that drives resistance to MAPKi treatment. In this review, we will focus on how changes in the tumor microenvironment regulate MAPKi resistance.


Influence of Neighborhood Social and Natural Environment on Prostate Tumor Histology in a Cohort of Male Health Professionals.
Adverse neighborhood social and natural (green space) environments may contribute to the etiology of prostate cancer (CaP), but mechanisms are unclear. We examined associations between neighborhood environment and prostate intratumoral inflammation in 967 men diagnosed with CaP with available tissue samples from 1986-2009 in the Health Professionals Follow-up Study. Exposures were linked to work or residential addresses in 1988. We estimated indices of neighborhood socioeconomic status (nSES) and segregation (Index of Concentration at the Extremes (ICE)) using US Census tract-level data. Surrounding greenness was estimated using seasonal averaged Normalized Difference Vegetation Index (NDVI) data. Surgical tissue underwent pathological review for acute and chronic inflammation, corpora amylacea, and focal atrophic lesions. Adjusted odds ratios (aORs) for inflammation (ordinal) and focal atrophy (binary) were estimated using logistic regression. No associations were observed for acute or chronic inflammation. Each interquartile-range increase in NDVI within 1,230 m of the participant's work or home address (aOR = 0.74, 95% confidence interval (CI): 0.59, 0.93), in ICE-income (aOR = 0.79, 95% CI: 0.61, 1.04), and in ICE-race/income (aOR = 0.79, 95% CI: 0.63, 0.99) was associated with lower odds of postatrophic hyperplasia. Interquartile-range increases in nSES (aOR = 0.76, 95% CI: 0.57, 1.02) and ICE-race/income (aOR = 0.73, 95% CI: 0.54, 0.99) were associated with lower odds of tumor corpora amylacea. Histopathological inflammatory features of prostate tumors may be influenced by neighborhood.


NR1D1::MAML1 epithelioid and spindle cell sarcoma mimicking pseudomyogenic hemangioendothelioma in core biopsy: A case report and review of the literature.
Epithelioid and spindle cell sarcomas with NR1D1::MAML1/2 gene fusions are rare and emerging entities. Only six cases of NR1D1-rearranged mesenchymal tumors have previously been reported in the literature; they are often characterized by an epithelioid morphology, at least focal pseudogland formation, prominent cytoplasmic vacuoles, and focal to diffuse immunohistochemical expression of keratin. We herein report the first case of an NR1D1::MAML1 epithelioid and spindle cell sarcoma with dual immunohistochemical expression of ERG and FOSB, mimicking a pseudomyogenic hemangioendothelioma (PHE) on core biopsy. The sarcoma arose in the left forearm of a 64-year-old man. Initial biopsy showed a mesenchymal neoplasm composed of epithelioid and spindle cells dispersed in myxoid stroma with scattered stromal neutrophils. The morphologic features, combined with the dual immunohistochemical expression of ERG and FOSB, initially mimicked PHE, representing an important potential diagnostic pitfall. The patient subsequently underwent a radical resection, which showed a much more diffuse epithelioid appearance with nested architecture and pseudogland formation. Next-generation sequencing was performed on the resection specimen, which revealed an NR1D1::MAML1 gene fusion, confirming the final diagnosis. Given the fully malignant potential of this tumor, knowledge and recognition of this rare entity are essential to ensure proper management, prevent misdiagnosis, and further characterize the clinical course of this emerging entity. Comprehensive molecular testing can help to identify these rare tumors and exclude the possibility of epithelioid mimics, including PHE.


Interactive effects of stress, dietary restraint, and disinhibition on appetite.
Previous laboratory studies of disinhibited eating in response to stress have had varied outcomes. Since recent research implies that disinhibited eating might be observed when using the Thre-Factor Eating Questionnaire restraint (TFEQ-R) measure when scores on the TFEQ disinhibition (TFEQ-D) scale were also used, the present study investigated the disinhibitory effects of stress on eating in women classified using both TFEQ-R [high R (HR) vs. low R (LR)] and TFEQ-D [high D (HD) vs. low D (LD)] scores. Twenty women in each restraint (R) or disinhibition (D) combination were tested in either a stress or no-stress condition followed by a test lunch. Women classified as LR-HD consumed more than the other groups in the no-stress condition and reduced intake in response to stress, whereas HR-HD and LR-LD both ate more in the stress than no-stress conditions. HD consumed more sweet foods regardless of stress, whereas HR ate less savoury foods than LR. Mood data confirmed the success of the stress manipulation on affective state and also suggested that HD were more responsive to stress. Overall, these data imply that tendency to overeat, as measured by the TFEQ-D scale, is a better predictor than restraint in predicting short-term eating in response to stress.


The effect of massage on cellular immunity, endocrine and psychological factors in women with breast cancer -- a randomized controlled clinical trial.
The purpose of this study was to examine the effect of repeated effleurage massage treatments compared with a visit control group on circulating lymphocytes by studying the number and activity of peripheral blood NK cells, CD4+ and CD8+ T cells in women with breast cancer. Furthermore, the effect of repeated effleurage massage treatments on the levels of cortisol in saliva and oxytocin in plasma as well as degree anxiety, depression and quality of life was studied. A single centre, prospective, randomized, controlled trial. The study was conducted in a radiation department, in a hospital in south-western Sweden. Twenty-two women (mean age=62) with breast cancer undergoing radiation were included in this study. The patients were randomly assigned to effleurage massage therapy (20 min of effleurage on ten occasions) or to control visits (ten 20-minute visits). Blood samples were collected before the first and last massage/control visit for analysis of peripheral blood NK, T cells and oxytocin. Saliva was analysed for cortisol. In addition, the patients completed the Hospital Anxiety and Depression Scale, Life Satisfaction Questionnaire and Spielbergers State Trait Anxiety Inventory prior to the first and last massage/control visit. Effleurage massage treatment had no significant effect on the number, frequencies or activation state of NK cells or CD4+ or CD8+ T cells. Furthermore, no significant changes between groups were detected on cortisol and oxytocin concentrations, anxiety, depression or quality of life. Significant effect of effleurage massage on cellular immunity, cortisol, oxytocin, anxiety, depression or quality of life could not be demonstrated in this study. Several possible explanations to the results of this study are discussed.


Transcranial contrast-enhanced ultrasonography with Sonazoid in semiquantitative evaluation of brain perfusion.
To semiquantitatively evaluate brain perfusion by transcranial contrast-enhanced ultrasonography (TCEUS) using Sonazoid. We performed TCEUS in 11 healthy volunteers and seven patients with occlusive cerebrovascular disease involving the anterior circulation. After recording first-pass perfusion images on one side of the head and flush-replenishment (FR) images on both sides, we measured the time from arrival to peak (TAP) and peak intensity (PI) at first pass. Using the FR method, plateau value (A) and rise rate (β) of intensity (I) were obtained from the curve I(t) = A(1 - e (-β*t) ). In the patients, TAP was longer and PI was smaller in middle cerebral artery (MCA) areas than in posterior cerebral artery (PCA) areas on the ipsilesional side of the head (p < 0.05). A and β were smaller in MCA areas than in PCA areas on the ipsilesional side of the head (p < 0.05), while these parameters showed no apparent differences between MCA and PCA areas in the volunteers. TCEUS with Sonazoid allows effective semiquantitative evaluation of brain perfusion.


Progressive multifocal leukoencephalopathy (PML) following autologous peripheral blood stem cell transplantation for multiple myeloma.
PML should be considered in patients with neurological symptoms following MM and in those who are immunosuppressed. Symptoms are diverse and often rapidly progressing. Prompt referral and early involvement of the multidisciplinary team are crucial.


Photocatalytic degradation of aqueous pollutants using silica-modified TiO(2).
Photocatalytic degradation (PCD) of several aqueous pollutants was investigated using a porous silica-coated titanium dioxide (SiO(2)-TiO(2)) photocatalyst. Several cationic, neutral and anionic pollutants were tested. The results indicate that modifying the surface properties of TiO(2) using silica significantly enhances the PCD rate of the cationic pollutants. The rate enhancement decreased with an increase in substrate concentration, especially for the quaternary amines, and was attributed to the decrease in initial adsorption. However, no significant rate-increase resulted for acetate and phenol. Results suggest that the increased presence of cationic pollutants at the catalyst surface caused the rate enhancement.


Association of interleukin-10 gene promoter polymorphism in spontaneous abortions: a family-based triad study.
The present study is a triad study designed to determine the co-relation of IL-10 -819C/T promoter polymorphism with the risk of spontaneous abortions. A total of 50 families with spontaneous abortions and 60 families with medically terminated pregnancies were considered for the present study. Fetal tissue of less than 20 weeks of gestation along with peripheral blood from all the couples was collected in this study. A standard amplification refractory mutation system-polymerase chain reaction was carried out to determine the IL 10 genotype in all the subjects. Odd's ratio and their respective 95% confidence intervals were used to determine the strength of association between IL-10 promoter gene polymorphism and spontaneous abortions. The study revealed a statistically significant association of IL-10 -819C/T polymorphism between the two family groups among fetuses (p=0.0000003) and mothers (p=0.0000001). No significant difference was observed in the genotype distribution of IL-10 among fathers. An increased frequency of TT genotype and T allele was observed in spontaneously aborted fetuses and their mothers compared to respective controls. In conclusion, IL-10 C -819T gene promoter polymorphism may act as a major genetic regulator in the etiology of spontaneous abortions.


Automated left heart chamber volumetric assessment using three-dimensional echocardiography in Chinese adolescents.
Several studies have reported the accuracy and reproducibility of HeartModel for automated determination of three-dimensional echocardiography (3DE)-derived left heart volumes and left ventricular (LV) ejection fraction (LVEF) in adult patients. However, it remains unclear whether this automated adaptive analytics algorithm, derived from a 'training' population, can encompass adequate echo images in Chinese adolescents. The aim of our study was to explore the accuracy of HeartModel in adolescents compared with expert manual three-dimensional (3D) echocardiography. Fifty-three Chinese adolescent subjects with or without heart disease underwent 3D echocardiographic imaging with an EPIQ system (Philips). 3D cardiac volumes and LVEF obtained with the automated HeartModel program were compared with manual 3D echocardiographic measurements by an experienced echocardiographer. There was strong correlation between HeartModel and expert manual 3DE measurements (r = 0.875-0.965, all P < 0.001). Automated LV and left atrial (LA) volumes were slightly overestimated when compared to expert manual measurements, while LVEF showed no significant differences from the manual method. Importantly, the intra- and inter-observer variability of automated 3D echocardiographic model was relatively low (<1%), surpassing the manual approach (3.5-17.4%), yet requiring significantly less analyzing time (20 ± 7 vs 177 ± 30 s, P < 0.001). Simultaneous quantification of left heart volumes and LVEF with the automated HeartModel program is rapid, accurate and reproducible in Chinese adolescent cohort. Therefore, it has a potential to bring 3D echocardiographic assessment of left heart chamber volumes and function into busy pediatric practice.


Contents of second peak in the circadian variation of acute myocardial infarction in the Japanese population.
Circadian variation has been accepted as a factor in acute myocardial infarction (AMI). An increased incidence of cardiac events in the morning has been reported for a long time. Recent reports have indicated that the onset of AMI shows two peaks, which occur in the morning and evening. It has also been demonstrated that circadian pattern of AMI may vary with sex and age. We investigated 522 consecutive patients who underwent primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI) between 2000 and 2010. The patients were classified into 3 age groups: younger (≤59 years old), intermediate (60-79 years old), and older (≥80 years old). Clinical data were investigated, including the age and sex, angiographic characteristics, and time of onset of STEMI. There were two peaks in the onset of STEMI throughout the day, which were at 7:00-10:00 and 19:00-21:00 h, among all patients (male and female). Stratified analysis showed that older females formed the main part of the second peak. There were two peaks in the onset of STEMI in a Japanese population in Tokyo. The second peak was significantly dominated by the older female group. Age and gender influenced the second peak in the circadian variation of AMI in a Japanese population in Tokyo.


Hemostasis in Laryngeal Surgery.
The larynx is a highly vascularized organ supplied by the superior and inferior laryngeal arteries. Both microphonosurgery and external laryngeal surgery require excellent hemostasis. Topical agents including adrenalin and fibrin-based products as well as surgical instrumentation, such as coagulation devices or in some cases embolization, are in the surgeon's armamentarium and facilitate efficient and successful surgery.


DNA vaccination boosts Bacillus Calmette-Guérin protection against mycobacterial infection in zebrafish.
Despite the widespread use of the current Bacillus Calmette-Guérin (BCG) vaccine, tuberculosis is still a major cause of morbidity and mortality worldwide. Vaccination with BCG does not prevent a Mycobacterium tuberculosis infection, nor does it inhibit the reactivation of latent tuberculosis. Here, we show that adult zebrafish are modestly and variably protected from a mycobacterial infection by BCG vaccination. An intraperitoneal (i.p.) BCG vaccination was associated with enhanced survival upon a high-dose (20,000 bacteria) Mycobacterium marinum infection. In addition, BCG-vaccinated fish were more able to restrict a low-dose (30 bacteria) intraperitoneal infection with M. marinum, as indicated by lower bacterial loads at six weeks post infection (wpi). However, the vaccination could not completely prevent an infection. A qRT-PCR analysis comparing BCG-vaccinated and unvaccinated fish upon a mycobacterial infection indicated that the induction of Tumor necrosis factor (TNF) was more modest in vaccinated fish. The partial protection gained by BCG could be boosted by a DNA vaccine combining Ag85B, ESAT6 and a resuscitation-related gene RpfE, suggesting that this combination of antigens could be useful for a future BCG booster vaccine. We conclude that zebrafish is a useful early-phase preclinical model for studying subunit vaccines designed for boosting the effects of BCG.


OsCpn60α1, encoding the plastid chaperonin 60α subunit, is essential for folding of rbcL.
Chaperonins are involved in protein-folding. The rice genome encodes six plastid chaperonin subunits (Cpn60) - three α and three β. Our study showed that they were differentially expressed during normal plant development. Moreover, five were induced by heat stress (42°C) but not by cold (10°C). The oscpn60α1 mutant had a pale-green phenotype at the seedling stage and development ceased after the fourth leaf appeared. Transiently expressed OsCpn60α1:GFP fusion protein was localized to the chloroplast stroma. Immuno-blot analysis indicated that the level of Rubisco large subunit (rbcL) was severely reduced in the mutant while levels were unchanged for some imported proteins, e.g., stromal heat shock protein 70 (Hsp70) and chlorophyll a/b binding protein 1 (Lhcb1). This demonstrated that OsCpn60α1 is required for the folding of rbcL and that failure of that process is seedling-lethal.


Influence of progressive addition lenses on reading posture in myopic children.
To determine the influence of single-vision lenses (SVLs) and progressive addition lenses (PALs) on the near vision posture of myopic children based on their near phoria. Sixty-two myopic children were assigned to wear SVLs followed by PALs. Eighteen children were esophoric (greater than +1), 18 were orthophoric (-1 to 1) and 26 were exophoric (less than -1) at near. Reading distance, head tilt and ocular gaze angles were measured using an electromagnetic system after adaptation to each lens type. The lens type did not influence reading distance or head tilt angle (p>0.05 for both), but ocular gaze angle decreased significantly with the PALs (F=9.25, p=0.004). With the PALs, exophoric children exhibited significantly increased head tilt angle (p=0.003) and reduced ocular gaze angle (p=0.004) compared with esophoric children. Near non-exophoric children exhibited similar eye and head postures when wearing SVLs and PALs, whereas exophoric children exhibited reduced ocular gaze angle (t=-3.18, p=0.04) with PALs compared with SVLs. Using PALs for reading, the mean addition power employed by esophoric children was significantly greater than exophoric children (p=0.04). The lens type and the near phoria state affected near vision posture. During reading, myopic esophoric children used a lower portion of their PALs compared with exophoric children, resulting in greater addition power. These results may partially explain why myopic children with near esophoria exhibited superior treatment effects in myopia control trials using PALs.