Giant magnetoresistance in organic spin-valves.
A spin valve is a layered structure of magnetic and non-magnetic (spacer) materials whose electrical resistance depends on the spin state of electrons passing through the device and so can be controlled by an external magnetic field. The discoveries of giant magnetoresistance and tunnelling magnetoresistance in metallic spin valves have revolutionized applications such as magnetic recording and memory, and launched the new field of spin electronics--'spintronics'. Intense research efforts are now devoted to extending these spin-dependent effects to semiconductor materials. But while there have been noteworthy advances in spin injection and detection using inorganic semiconductors, spin-valve devices with semiconducting spacers have not yet been demonstrated. pi-conjugated organic semiconductors may offer a promising alternative approach to semiconductor spintronics, by virtue of their relatively strong electron-phonon coupling and large spin coherence. Here we report the injection, transport and detection of spin-polarized carriers using an organic semiconductor as the spacer layer in a spin-valve structure, yielding low-temperature giant magnetoresistance effects as large as 40 per cent.


There is no simple adequate sampling scheme for estimating the myelinated fibre size distribution in human peripheral nerve: a statistical ultrastructural study.
Morphometric studies of peripheral nerves (PN) usually involve some sampling of the myelinated fibres (MF). In order to scrutinize the statistical properties of the sampling processes in common use and the reliability of the resulting estimates, a quantitative analysis of human superficial peroneal nerves from 8 different normal subjects was undertaken at the ultrastructural level, both in terms of MF spatial distribution and of their size distribution. This study used sampling rates involving more than 10% of the whole myelinated fibre population observed in each nerve fascicle. However, in nearly all the fascicles evaluated, the sampling fluctuations are so high that neither the number of axons nor their diameter distribution can be assessed with enough accuracy. A systematic study of the myelinated fibres shows that the spatial distribution of their size is not uniform. This marked heterogeneity in the MF size distribution imposes measurement of large enough samples (500 or 600 MFs usually represent about one-half or two-thirds of the whole MF population) in a way to secure a reliable enough estimate of the density and size distributions. However, the practical usefulness of sampling schemes requiring more than one-half of the whole MF population in a nerve fascicle, is questionable.


The phase relationship between the circadian rhythms of locomotor activity and circulating melatonin in the pigeon (Columba livia).
The phase relationship between the circadian rhythms of locomotor activity and circulating melatonin levels under LD 12:12 and constant dim light conditions (LLdim) was examined in pigeons. Our new radioimmunoassay technique had sufficient sensitivity to detect the concentration of melatonin from a small quantity of plasma, which enabled us to measure locomotor activity simultaneously with circulating melatonin rhythms from each individual pigeon. The relationship of phase between the two circadian rhythms in LLdim was the same as in LD. The rhythms of locomotor activity and melatonin levels free-run but maintain the relation of 180 degrees out of phase in LLdim. These results do not contradict the hypothesis that melatonin may entrain the circadian rhythm of locomotor activity in the pigeon.


Low cerebral blood flow: a risk factor in the neonate.
Among 19 infants in whom cerebral blood flow had been determined a few hours after birth, four died during the first days or weeks after birth, all with massive intracranial hemorrhage. The other infants were examined at 9 to 12 1/2 months of age by means of clinical neurologic evaluation, developmental psychologic assessment (Cattell), EEG, and cranial computed tomography. Six of the ten infants who had had CBF of 20 ml/100 gm/minute or less had developed cerebral atrophy as demonstrated at autopsy or by CT scan, none with neonatal flows above 20 had done so. Only one in the low flow group had developed completely normally, whereas abnormal development was found in only a minority of the high flow group. No other neonatal observation had such a clear relationship to later development. It is concluded that CBF of 20 or less during the first hours of life is critical.


A biologically active parathyroid hormone-like substance secreted by an adenosquamous carcinoma of the transverse colon.
Recently, controversy has emerged as to whether paraneoplastic hypercalcemia in nonparathyroid tumors is due to ectopic production of a parathyroid hormone (PTH)-like substance. A sensitive DNA hybridization technique was unable to reveal PTH mRNA in a collection of such tumors. However, there is growing evidence that squamous differentiation of tumors favors the expression of PTH-like substances. We report the case of a 41-year-old woman with an adenosquamous carcinoma of colonic origin associated with severe hypercalcemia. The squamous component of liver metastases showed immunoreactivity with two different PTH antisera, suggesting the production of a PTH-like substance.


Different intracellular signalling properties induced by human and porcine growth hormone.
Growth hormone (GH) is reportedly species-specific. Primate growth hormone can trigger non-primate growth hormone receptor (GHR), but primates GHR cannot be activated by non-primate GH. However, it is also unclear that why primate GH and non-primate GH have different biological activities. Thus, we analysed primate growth hormone (human growth hormone (hGH)) or non-primate GH (porcine growth hormone (pGH))-induced intracellular signalling in 3T3-F442A cells and rat hepatocytes in a dose- and time-dependent manner to explore the different biological activities between them. The results revealed that both hGH and pGH can activate Janus kinase 2 (JAK2), Signal transducers and activators of transcription 1, 3 and 5 (STATs 1, 3 and 5) and extracellular signal-regulated kinase 1/2 (ERK1/2). There were no significant differences in JAK2 or ERK1/2 tyrosine phosphorylation after hGH and pGH treatment, but there were different between hGH and pGH in STAT/1/3/5 tyrosine phosphorylation, and JAK2, STAT/1/3/5 tyrosine phosphorylation was time-dependent and dose-dependent, whereas ERK1/2 was not. Both hGH and pGH demonstrated similar kinetics for STATs 1, 3 and 5 phosphorylation, but the pGH-mediated tyrosine phosphorylation was weaker than that mediated by hGH. Our observations indicated that the levels of main signalling proteins phosphorylation triggered by hGH or pGH were not exactly the same, which may explain the different biological activities showed by primate GH and non-primate GH.


Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
Integrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East Asians (Biobank Japan) and 377,441 Europeans (UK Biobank). We identify ten cancer risk variants including five pleiotropic associations (e.g., rs2076295 at DSP on 6p24 associated with lung cancer and rs2525548 at TRIM4 on 7q22 nominally associated with six cancers). Quantifying shared heritability among the cancers detects positive genetic correlations between breast and prostate cancer across populations. Common genetic components increase the statistical power, and the large-scale meta-analysis of 277,896 breast/prostate cancer cases and 901,858 controls identifies 91 newly genome-wide significant loci. Enrichment analysis of pathways and cell types reveals shared genetic backgrounds across said cancers. Focusing on genetically correlated cancers can contribute to enhancing our insights into carcinogenesis.


Inhibition of return: a graphical meta-analysis of its time course and an empirical test of its temporal and spatial properties.
Immediately after a stimulus appears in the visual field, there is often a short period of facilitated processing of stimuli at or near this location. This period is followed by one in which processing is impaired, rather than facilitated. This impairment has been termed inhibition of return (IOR). In the present study, the time course of this phenomenon was examined in two ways. (1) A graphical meta-analysis plotted the size of the effect as a function of the stimulus onset asynchrony (SOA) of the two stimuli. This analysis showed that IOR is impressively stable for SOAs of 300-1,600 msec. It also showed that the literature does not provide any clear sense of the duration of IOR. (2) An empirical approach was, therefore, taken to fill this gap in our knowledge of IOR. In three experiments, IOR was tested using SOAs between 600 and 4,200 msec. IOR was robust for approximately 3 sec and appeared to taper off after this point; the observed duration varied somewhat as a function of the testing conditions. In addition, for the first second, the degree of inhibition was inversely related to distance of the target from the original stimulus, but for the next 2 sec this spatial distribution was not observed. Theories of the mechanisms and function of IOR must conform to these spatial and temporal properties.


Do differences in innervation result in different post-synaptic responses to exogenous agonists?
1. The pharmacological reactivity of the epididymal and prostatic portions of the rat vas deferens to BaCl2, phenylephrine and carbachol were recorded by isometric and isotonic technique. 2. The maximum response induced by the three agonists were similar at the epidiymal end, while at the prostatic portion phenylephrine produced a response 80% lower than that of barium and carbachol. 3. The pD2 value to agonists and the sensitivity to calcium channel blockers were lower at the prostatic end. 4. The data suggest that not only the pharmacological reactivity of the prostatic and epididymal portions differs, but also that the activity of the prostatic portion is much more reduced to alpha 1-agonists.


Neuropilin-2 promotes lineage plasticity and progression to neuroendocrine prostate cancer.
Neuroendocrine prostate cancer (NEPC), a lethal subset of prostate cancer, is characterized by loss of AR signaling and resulting resistance to AR-targeted therapy during neuroendocrine transdifferentiation, for which the molecular mechanisms remain unclear. Here, we report that neuropilin 2 (NRP2) is upregulated in both de novo and therapy-induced NEPC, which induces neuroendocrine markers, neuroendocrine cell morphology, and NEPC cell aggressive behavior. NRP2 silencing restricted NEPC tumor xenograft growth. Mechanistically, NRP2 engages in reciprocal crosstalk with AR, where NRP2 is transcriptionally inhibited by AR, and in turn suppresses AR signaling by downregulating the AR transcriptional program and confers resistance to enzalutamide. Moreover, NRP2 physically interacts with VEGFR2 through the intracellular SEA domain to activate STAT3 phosphorylation and subsequently SOX2, thus driving NEPC differentiation and growth. Collectively, these results characterize NRP2 as a driver of NEPC and suggest NRP2 as a potential therapeutic target in NEPC.


Monoclonal antibody uptake in B-cell lymphomas: experimental studies in nude mouse xenografts.
Accumulation of radiolabelled monoclonal antibodies (mAb) in human B-lymphoma xenografts was found to result in two distinct patterns. The basic elements leading to these patterns were elucidated by autoradiographic and immunohistological analysis applied to the nude mouse xenografts BJAB and OCI.LY1. With BJAB, accumulation occurred exclusively in peripheral cell layers of the lymphoma nodule, while central areas were not accessible irrespective of mAb dose. This feature was the consequence of an inefficient transport across intratumoral vessels together with peripheral mAb supply through a subcapsular pseudosinus. With OCI.LY1, intratumoral vessels showed generalized leakiness. Furthermore, interstitial transport was operative to a fair extent, such that in early images multiple sites of mAb extravasation were obvious, which coalesced during the course of prolonged uptake. The pattern of peripheral mAb uptake resulted in a low overall tumour uptake, while multifocal uptake yielded substantial accumulation values.


Pedunculated liposarcoma of the esophagus: a first case report.
A large pedunculated myxoid liposarcoma of the cervical esophagus is presented. Because of its long pedicle, the presenting symptoms were primarily respiratory rather than digestive. The tumor lent itself to local excision rather than esophageal resection, given the absence of involvement of its pedicle and the resultant wide margin of excision. Review of the literature did not disclose a similar case.


The inducible trimethylamine-N-oxide reductase of Escherichia coli K12: biochemical and immunological studies.
The inducible trimethylamine-N-oxide reductase which migrates on non-denaturing polyacrylamide gels with an RF of 0.22, has been purified from the soluble fraction of wild-type E. coli K12. The molecular weight of the purified enzyme estimated by molecular-sieve chromatography is about 230,000. It is composed of two subunits of molecular weight 110,000. Antiserum specific for the enzyme has been produced. Gel filtration on Sephadex G-200 of the soluble fraction gave two peaks of trimethylamine-N-oxide reductase, one with an Mr of 230,000 and an RF of 0.22, and another with an Mr of 120,000 and an RF of 0.36. Since the anti-trimethylamine-N-oxide reductase serum recognises the two forms and shows a single subunit with an Mr of 110,000, we conclude that in E. coli there is a single inducible trimethylamine-N-oxide reductase which can exist as a dimer or a monomer. Other immunological studies with anti-trimethylamine-N-oxide reductase serum on crude extracts prepared from cells grown in the absence of inducer showed that the constitutive trimethylamine-N-oxide reductase was not recognised by the antiserum. The same analyses carried out on a tor mutant (defective in the structural gene of the inducible enzyme) confirmed without ambiguity that the constitutive enzyme is immunologically distinct from the inducible enzyme. In the same way, using the anti-trimethylamine-N-oxide reductase serum, rocket immunoelectrophoresis analyses were able to show that the inducible apoenzyme is not regulated by the fnr gene product and that molybdate does not seem necessary for the synthesis or stabilisation of this enzyme.


An artificial anchor domain: hydrophobicity suffices to stop transfer.
A hydrophobic sequence of 23 contiguous, uncharged residues anchors the coliphage f1 gene III protein (pIII) to the Escherichia coli cytoplasmic membrane; mutations removing this domain allow secretion of the protein to the periplasm. Multiple copies of an oligonucleotide encoding the hydrophobic repeat, Leu-Ala-Leu-Val, were introduced into genes for secreted forms of pIII. Artificial domains of 16 or more hydrophobic residues function to anchor the protein. Pronase protection experiments demonstrate that the new sequences act to halt transfer of the protein across the membrane, thus specifying a transmembrane topology. Relocating the hydrophobic domain within the polypeptide chain predictably alters the resultant protein/membrane topology. Repeats of a polar sequence were inserted with no effect on secretion. Furthermore, an unrelated hydrophobic sequence, uncovered by a gene III frameshift mutation, acts to anchor the protein. We conclude that function simply reflects hydrophobicity and not some more subtle feature of structure or sequence.


Neck Muscle and Head/Neck Kinematic Responses While Bracing Against the Steering Wheel During Front and Rear Impacts.
Drivers often react to an impending collision by bracing against the steering wheel. The goal of the present study was to quantify the effect of bracing on neck muscle activity and head/torso kinematics during low-speed front and rear impacts. Eleven seated subjects (3F, 8 M) experienced multiple sled impacts (Δv = 0.77 m/s; apeak = 19.9 m/s2, Δt = 65.5 ms) with their hands on the steering wheel in two conditions: relaxed and braced against the steering wheel. Electromyographic activity in eight neck muscles (sternohyoid, sternocleidomastoid, splenius capitis, semispinalis capitis, semispinalis cervicis, multifidus, levator scapulae, and trapezius) was recorded unilaterally with indwelling electrodes and normalized by maximum voluntary contraction (MVC) levels. Head and torso kinematics (linear acceleration, angular velocity, angular rotation, and retraction) were measured with sensors and motion tracking. Muscle and kinematic variables were compared between the relaxed and braced conditions using linear mixed models. We found that pre-impact bracing generated only small increases in the pre-impact muscle activity (< 5% MVC) when compared to the relaxed condition. Pre-impact bracing did not increase peak neck muscle responses during the impacts; instead it reduced peak trapezius and multifidus muscle activity by about half during front impacts. Bracing led to widespread changes in the peak amplitude and timing of the torso and head kinematics that were not consistent with a simple stiffening of the head/neck/torso system. Instead pre-impact bracing served to couple the torso more rigidly to the seat while not necessarily coupling the head more rigidly to the torso.


The effect of the National Health Insurance Scheme (NHIS) on health service delivery in mission facilities in Ghana: a retrospective study.
In 2004, Ghana began implementation of a National Health Insurance Scheme (NHIS) to minimize out-of-pocket expenditure at the point of use of service. The implementation of the scheme was accompanied by increased access and use of health care services. Evidence suggests most health facilities are faced with management challenges in the delivery of services. The study aimed to assess the effect of the introduction of the NHIS on health service delivery in mission health facilities in Ghana. We conceptualised the effect of NHIS on facilities using service delivery indicators such as outpatient and inpatient turn out, estimation of general service readiness, revenue and expenditure, claims processing and availability of essential medicines. We collected data from 38 mission facilities, grouped into the three ecological zones; southern, middle and northern. Structured questionnaires and exit interviews were used to collect data for the periods 2003 and 2010. The data was analysed in SPSS and MS Excel. The facilities displayed high readiness to deliver services. There were significant increases in outpatient and inpatient attendance, revenue, expenditure and improved access to medicines. Generally, facilities reported increased readiness to deliver services. However, challenging issues around high rates of non-reimbursement of NHIS claims due to errors in claims processing, lack of feedback regarding errors, and lack of clarity on claims reporting procedures were reported. The implementation of the NHIS saw improvement and expansion of services resulting in benefits to the facilities as well as constraints. The constraints could be minimized if claims processing is improved at the facility level and delays in reimbursements also reduced.


Disorganized functional architecture of amygdala subregional networks in obsessive-compulsive disorder.
A precise understanding of amygdala-centered subtle networks may help refine neurocircuitry models of obsessive-compulsive disorder (OCD). We applied connectivity-based parcellation methodology to segment the amygdala based on resting-state fMRI data of 92 medication-free OCD patients without comorbidity and 90 matched healthy controls (HC). The amygdala was parcellated into two subregions corresponding to basolateral amygdala (BLA) and centromedial amygdala (CMA). Amygdala subregional functional connectivity (FC) maps were generated and group differences were evaluated with diagnosis-by-subregion flexible factorial ANOVA. We found significant diagnosis × subregion FC interactions in insula, supplementary motor area (SMA), midcingulate cortex (MCC), superior temporal gyrus (STG) and postcentral gyrus (PCG). In HC, the BLA demonstrated stronger connectivity with above regions compared to CMA, whereas in OCD, the connectivity pattern reversed to stronger CMA connectivity comparing to BLA. Relative to HC, OCD patients exhibited hypoconnectivity between left BLA and left insula, and hyperconnectivity between right CMA and SMA, MCC, insula, STG, and PCG. Moreover, OCD patients showed reduced volume of left BLA and right CMA compared to HC. Our findings characterized disorganized functional architecture of amygdala subregional networks in accordance with structural defects, providing direct evidence regarding the specific role of amygdala subregions in the neurocircuitry models of OCD.


Adhesive systems: composites, dentine bonding agents and glass ionomers.
The urge by manufacturers to develop new and better materials can often leave the dentist confused as to how they work. This article seeks to describe these materials simply and how they can best be made to work; it may also help practitioners to ask representatives leading questions when presented with the latest product.


[Study on the preparation of curcumin inclusion complex and its stability].
To prepare the curcumin inclusion complex and study its stability. Beta-cyclodextrin (beta-CD) was chosen as inclusion material and orthogonal design method was used. UV-Vis spectrophotometer was used to determine the solubility and content of different samples. They were placed under conditions of light and the solution containing Fe(3+) to determine their stability. The optimum preparation procedure were : curcumin and beta-cyclodextrin feed molar ratio of 1: 1, the concentration of ethanol was 40%, 40 degrees C inclusion temperature and 1 h reaction time. Inclusion complex prepared under eptimal condition is stable.


An ensemble learning approach to identify pastured poultry farm practice variables and soil constituents that promote Salmonella prevalence.
Animal sourced foods including contaminated poultry meat and eggs contribute to human non-typhoidal salmonellosis, a foodborne zoonosis. Prevalence of Salmonella in pastured poultry production systems can lead to contamination of the final product. Identification of farm practices that affect Salmonella prevalence is critical for implementing control measures to ensure the safety of these products. In this study, we developed predictive models based predominantly on deep learning approaches to identify key pre-harvest management variables (using soil and feces samples) in pastured poultry farms that contribute to Salmonella prevalence. Our ensemble approach utilizing five different machine learning techniques predicts that physicochemical parameters of the soil and feces (elements such as sodium (Na), zinc (Zn), potassium (K), copper (Cu)), electrical conductivity (EC), the number of years that the farms have been in use, and flock size significantly influence pre-harvest Salmonella prevalence. Egg source, feed type, breed, and manganese (Mn) levels in the soil/feces are other important variables identified to contribute to Salmonella prevalence on larger (≥3 flocks reared per year) farms, while pasture feed and soil carbon-to-nitrogen ratio are predicted to be important for smaller/hobby (<3 flocks reared per year) farms. Predictive models such as the ones described here are important for developing science-based control measures for Salmonella to reduce the environmental, animal, and public health impacts from these types of poultry production systems.


Structural and functional analysis of native peroxiredoxin 2 in human red blood cells.
Peroxiredoxin 2, a typical 2-Cys peroxiredoxin, is the third most abundant protein in erythrocytes. It is understood that the physiologically functional state of peroxiredoxin 2 is the monomer, and that its role in scavenging low levels of H(2)O(2) results in the formation of disulfide-linked dimers, which are reversibly reduced to monomers by the thioredoxin-thioredoxin reductase system. Additionally, peroxiredoxins are highly susceptible to sulfinic acid formation through reactions with various peroxides. This overoxidized form, which is thought to convert peroxiredoxins into molecular chaperones and to be accompanied by a transition to polymeric forms, can be reversed by sulfiredoxins. However, physiological conformational changes and the antioxidant role of erythrocyte peroxiredoxin 2 are still unclear because there is low sulfiredoxin and thioredoxin-thioredoxin reductase activity in erythrocytes. In this study, we examined the structural and redox states of peroxiredoxin 2 in fresh hemolysates and estimated the activities of native and overoxidized peroxiredoxin 2 purified from red blood cells to clear the physiological roles of peroxiredoxin 2 in erythrocyte. Our findings demonstrate that native peroxiredoxin 2 exists as high molecular weight (>160 kDa) oligomers and that decamers or higher order molecular weight oligomers (260-460 kDa) have peroxidase activity. We further showed that peroxiredoxin 2 oligomers, which were predominantly composed of monomers in the reduced form, exert a chaperone activity equal to that of overoxidized peroxiredoxin 2 polymers. These results provide the novel insight that redox-active peroxiredoxin 2 functions in human red blood cells as high molecular weight oligomers that possess peroxidase and chaperone activities.


Enteral migration of a Pezzer tube after a feeding jejunostomy: report of a case.
We herein report a rare complication of the migration of a feeding jejunostomy tube through the entire intestine. A surgical Stamm jejunostomy was performed in a patient with an unresectable gastric cancer using a 28-F silicone catheter with a mushroom tip (Pezzer catheter). The catheter was suture-fixed to the skin, family members were given instructions regarding tube feeding and tube care, and the patient was discharged to home care. Two months later, he presented because of the "disappearance" of the tube. A clinical examination revealed a mature jejunostomy tract, skin erosion at the site where the suture was placed, and absence of the tube. There were no signs of intestinal obstruction or peritonitis. Abdominal X-ray examination showed the catheter inside the jejunum. The patient was treated conservatively with serial radiographs showing rapid tube migration through the intestine, and the tube was eliminated spontaneously 5 days later. An awareness of this complication and its appropriate treatment is important given the widespread use of enteral nutrition.


Role of somatosensory evoked potentials in predicting outcome during thoracoabdominal aortic repair.
Clinical utility of somatosensory evoked potentials (SSEP) in descending thoracic and thoracoabdominal aortic repair is debated. We reviewed our practical experience with SSEP in descending thoracic and thoracoabdominal aortic repairs. Between January 2000 and April 2005, we used SSEP monitoring in 444 patients (270 thoracoabdominal aorta and 174 descending thoracic aorta). Median age was 68 years; 36% were female. Only changes of spinal origin were analyzed. Changes were classified as (1) no change, (2) transient changes that returned to baseline by the end of the procedure, or (3) persistent changes that did not return to baseline by the end of the procedure. Somatosensory evoked potential changes occurred in 87 (19.6%) patients; 22 (25%) of these did not return to baseline. Immediate neurologic deficit occurred in 8 of 444 patients (1.8%); five deficits (5 of 87; 5.8%) occurred in patients with SSEP changes, compared with three deficits (3 of 357; 0.8%) in patients without changes. Odds ratio for this comparison was 7.2 (p < 0.002). Somatosensory evoked potential was a poor screening tool for neurologic deficit, with a sensitivity of 62.5% and specificity 81.2%. Negative predictive value was 99.2%, indicating a very low event probability in the absence of SSEP changes. Delayed neurologic deficit occurred in 3.2% and was not related to SSEP changes. Somatosensory evoked potential changes were also associated with increased 30-day mortality and low glomerular filtration rate. Intraoperative SSEP monitoring was reliable in ruling out spinal injury in descending thoracic and thoracoabdominal aortic repair, but had a low sensitivity. It did not predict delayed neurologic deficit. Spinal SSEP change was an independent predictor of mortality and correlated with low preoperative glomerular filtration rate.


Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy.
To determine whether developmental synaptic pruning defects in epileptic C1q-knockout (KO) mice are accompanied by postsynaptic abnormalities in dendrites and/or spines. Immunofluorescence staining was performed on biocytin-filled layer Vb pyramidal neurons in sensorimotor cortex. Basal dendritic arbors and their spines were reconstructed with NEUROLUCIDA software, and their morphologic characteristics were quantitated in Neuroexplorer. Seven to nine completely filled pyramidal neurons were analyzed from the wild-type (WT) and C1q KO groups. Compared to WT controls, KO mice showed significant structural modifications in their basal dendrites including (1) higher density of dendritic spines (0.60 ± 0.03/μm vs. 0.49 ± 0.03/μm dendritic length in WT, p < 0.05); (2) remarkably increased occurrence of thin spines (0.26 ± 0.02/μm vs. 0.14 ± 0.02/μm dendritic length in control, p < 0.01); (3) longer dendritic length (2,680 ± 159 μm vs. 2,119 ± 108 μm in control); and (4) increased branching (22.6 ± 1.9 vs. 16.2 ± 1.3 in WT at 80 μm from soma center, p < 0.05; 12.4 ± 1.4 vs. 8.2 ± 0.6 in WT at 120 μm from soma center, respectively, p < 0.05). Dual immunolabeling demonstrated the expression of putative glutamate receptor 2 (GluR2) on some thin spines. These dendritic alterations are likely postsynaptic structural consequences of failure of synaptic pruning in the C1q KO mice. Failure to prune excessive excitatory synapses in C1q KO mice is a likely mechanism underlying abnormalities in postsynaptic dendrites, including increased branching and alterations in spine type and density. It is also possible that seizure activity contributes to these abnormalities. These structural abnormalities, together with increased numbers of excitatory synapses, likely contribute to epileptogenesis in C1q KO mice.


Microbiological and compositional status of Turkish white cheese.
Results of the chemical and microbiological examination of 38 Turkish white cheese samples are presented. On average, the cheese was characterized by a high moisture and salt content, 58.18 and 3.56%, respectively, and a pH of 4.68. Significant variation was found in these compositional factors, indicating the extreme diversity of manufacturing practices. Microbiological analysis revealed the presence of high numbers of coliforms, faecal coliforms and Escherichia coli, extremely high numbers of faecal streptococci, and a low level and incidence of Staphylococcus aureus, Salmonella and Clostridium perfringens were not isolated from the samples. There was no correlation between the levels of coliforms, faecal coliforms, E. coli and enterococci, suggesting that the enterococci count in Turkish white cheese may not be a good indicator of sanitary practices.


Treatment of posterior and anterior urethral trauma.
To assess the occurrence and treatment of posterior urethral (most often caused by traffic accidents and comprising half of all cases of urinary tract traumas) and anterior urethral injury (usually iatrogenic during catheterization or cystoscopy, or caused by blunt trauma, e.g. straddle injury or penetrating trauma). The records and details of patients with posterior and anterior urethral trauma were analysed from 61 urological departments in Poland between 1995 and 1999. During the 5-year period there were 268 cases of posterior and 255 of anterior urethral injury; for the former, most occurred during traffic accidents, and of the latter 206 were iatrogenic (during catheterization or cystoscopy), of which 48 were accompanied by perineal injury. The posterior injuries were isolated or involved many organs, mainly pelvic bones. Both types of injuries were diagnosed using ascending urethrography, voiding cysto-urethrography and urethroscopy/endoscopy. Treatment for posterior injuries included cystostomy alone or cystostomy with abdominal drainage or perineal drainage; some patients also had their urethra reconstructed. The treatment for anterior injuries was conservative in 193 patients and surgical in 62. The early detection and appropriate surgical treatment of posterior and anterior urethral injury is crucial for the recovery of urethral function, and avoids many complications.


Generating highly reflective and conductive metal layers through a light-assisted synthesis and assembling of silver nanoparticles in a polymer matrix.
The development of metalized surfaces exhibiting mirror properties and/or electric conductivity without heavy equipments and with low metal charge is a big challenge in view of many industrial applications. We report herein on the photo-assembling of silver nanoparticles (AgNPs) in a polymer matrix, carried out within minutes from an acrylate monomer and silver nitrate at room temperature, under air and without any solvents. The top surface of the material gets converted into a continuous silver thin film and a depthwise concentration gradient of AgNPs is created in the polymer, which images the absorption profile of the actinic UV light in the reactive formulation. This specific assembling of the silver@polymer coating induces excellent reflective and conductive properties. The conductance was observed to strongly increase with increasing the exposure from 3 to 30 min due to the formation of a more and more compact metal film. This coating strategy works with a variety of substrates (textile, paper, glass, wood, plastic and stainless steel). Moreover, on flexible surfaces such as textile, the flexibility was preserved. The possibility to use this kind of nanomaterial as a printing ink, with a much lower metal concentration (3 to 5 wt.%) than concurrent inks, was also demonstrated.


Estimation of aneurysm wall stresses created by treatment with a shape memory polymer foam device.
In this study, compliant latex thin-walled aneurysm models are fabricated to investigate the effects of expansion of shape memory polymer foam. A simplified cylindrical model is selected for the in-vitro aneurysm, which is a simplification of a real, saccular aneurysm. The studies are performed by crimping shape memory polymer foams, originally 6 and 8 mm in diameter, and monitoring the resulting deformation when deployed into 4-mm-diameter thin-walled latex tubes. The deformations of the latex tubes are used as inputs to physical, analytical, and computational models to estimate the circumferential stresses. Using the results of the stress analysis in the latex aneurysm model, a computational model of the human aneurysm is developed by changing the geometry and material properties. The model is then used to predict the stresses that would develop in a human aneurysm. The experimental, simulation, and analytical results suggest that shape memory polymer foams have potential of being a safe treatment for intracranial saccular aneurysms. In particular, this work suggests oversized shape memory foams may be used to better fill the entire aneurysm cavity while generating stresses below the aneurysm wall breaking stresses.


[Dependence of the efficacy of slowing on the localization of inhibitory synapses on neuronal dendrites. Mathematical modeling].
In the case of somatic inhibition the maximum efficiency of inhibition is observed when exciting inputs are situated distal of the long dendrite. For fibres of a medium length simultaneous inhibition in the soma and the distal end is more efficient. Excitant synapsis near the soma produce the best inhibition only at some fixed distance. This effect can explain the morphological fact of rarefaction of synaptic contacts near soma.


Differential cytokine profiling in Chagasic patients according to their arrhythmogenic-status.
Chagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by heart failure and sudden death. Identifying which factors are involved in evolution and treatment response is actually challenging. Thus, the aim of this work was to determine the Th1/Th17 (IL-6, IL-2, TNF, IL-17 and IFN-γ) and Th2 (IL-4 and IL-10) serum profile in Venezuelan Chagasic patients stratified according amiodarone treatment, hypertension and arrhythmias. Sera from 38 chagasic patients were analyzed to determine the level of cytokines by Multiplexed Bead-Based Immunoassays. ANOVA test was applied to determine differences for each group. Additionally, a Linear Discriminant Analysis (LDA) was applied to observe the accuracy of different cytokines to discriminate between the groups. The levels of several cytokines were significantly higher in the high-risk of sudden death and untreated group. LDA showed that IL-2, IFN-γ and IL-10 were the best cytokines for discriminating between high-risk of sudden death and untreated patients versus low-risk of sudden death, treated and control groups. High IL-2 levels seem to identify patients with high-risk of sudden death and seems adequate as treatment efficacy marker. To our knowledge, this is the first report about the anti-inflammatory role of the amiodarone in Chagas disease, suggesting an inmunomodulatory effect that may be exploited as coadjutant therapy in chronic Chagas disease.


Co- or Ni-modified Sn-MnOx low-dimensional multi-oxides for high-efficient NH3-SCR De-NOx: Performance optimization and reaction mechanism.
NH3-SCR performances were explored to the relationship between structure morphology and physio-chemical properties over low-dimensional ternary Mn-based catalysts prepared by one-step synthesis method. Due to its strong oxidation performance, Sn-MnOx was prone to side reactions between NO, NH3 and O2, resulting in the generation of more NO2 and N2O, here most of N2O was driven from the non-selective oxidation of NH3, while a small part generated from the side reaction between NH3 and NO2. Co or Ni doping into Sn-MnOx as solid solution components obviously stronged the electronic interaction for actively mobilization and weakened the oxidation performance for signally reducing the selective tendency of side reactions to N2O. The optimal modification resulted in improving the surface area and enhancing the strong interaction between polyvalent cations in Co/Ni-Mn-SnO2 to provide more surface adsorbed oxygen, active sites of Mn3+ and Mn4+, high-content Sn4+ and plentiful Lewis-acidity for more active intermediates, which significantly broadened the activity window of Sn-MnOx, improved the N2 selectivity by inhibiting N2O formation, and also contributed to an acceptable resistances to water and sulfur. At low reaction temperatures, the SCR reactions over three catalysts mainly obeyed the typical Elye-rideal (E-R) routs via the reactions of adsorbed l-NHx (x = 3, 2, 1) and B-NH4+ with the gaseous NO to generate N2 but also N2O by-products. Except for the above basic E-R reactions, as increasing the reaction temperature, the main adsorbed NOx-species were bidentate nitrates that were also active in the Langmuir-Hinshelwood reactions with adsorbed l-NHx species over Co/Ni modified Mn-SnO2 catalyst.


Ventricular fibrillation in a patient with unsuspected mitral valve prolapse and a prolonged Q-T interval.
Mitral valve prolapse is a common cardiac abnormality associated with arrhythmias and sudden death. In most instances it can be diagnosed on the basis of physical findings. Those patients who are symptomatic or who display electrocardiographic abnormalities appear to be most susceptible to arrhythmias and, therefore, may be at increased risk for anaesthesia. Because the syndrome is relatively common and may present a very innocent clinical picture, anaesthetists should be aware of this condition and the problems it may present. A case of mitral valve prolapse syndrome associated with ventricular fibrillation on induction of anaesthesia is reported. The symptoms and pathophysiology of the disorder are reviewed and the potential problems and the anaesthetic management are discussed.


Precordial ST-segment continuum: A variant of the de Winter sign.
The vast majority of patients with acute occlusion of the proximal left anterior descending coronary artery (LAD) suffer frank ST-elevation myocardial infarction (STEMI). In contrast, a small but not insignificant minority presents with an electrocardiographic (ECG) pattern termed the "de Winter sign." The de Winter sign is characterized by upsloping ST depression followed by tall and peaked T waves in the precordial leads. The purpose of this report is to present two cases of acute obstruction of a large wrap-around LAD where the ECGs simultaneously displayed diagnostic criteria both for STEMI and the de Winter sign. We provide possible explanations for this hitherto undescribed phenomenon.


Erectile function after permanent prostate brachytherapy.
To determine the incidence of potency preservation after permanent prostate brachytherapy using a validated patient-administered questionnaire and to evaluate the effect of multiple clinical and treatment parameters on penile erectile function. Four hundred twenty-five patients underwent permanent prostate brachytherapy from April 1995 to October 1999. Two hundred nine patients who were potent before brachytherapy and who at the time of the survey were not receiving hormonal therapy were mailed the specific erectile questions of the International Index of Erectile Function (IIEF) questionnaire with a self-addressed stamped envelope. The questionnaire consisted of 5 questions, with a maximal score of 25. Of the 209 patients, 181 (87%) completed and returned the questionnaire. The mean and median follow-up was 40.4 +/- 14.9 and 40.6 months, respectively (range 19-75). Preimplant erectile function was assigned using a three-tiered scoring system (2 = erections always or nearly always sufficient for vaginal penetration; 1 = erections sufficient for vaginal penetration but considered suboptimal; 0 = the inability to obtain erections and/or erections inadequate for vaginal penetration). Postimplant potency was defined as an IIEF score >/=11. The clinical parameters evaluated for erectile function included patient age, preimplant potency, clinical T-stage, pretreatment prostate-specific antigen level, Gleason score, elapsed time after implantation, hypertension, diabetes mellitus, and tobacco consumption. Treatment parameters included radiation dose to the prostate gland, use of hormonal manipulation, use of supplemental external beam radiotherapy (EBRT), choice of isotope, prostate volume, and planning volume. The efficacy of sildenafil citrate in brachytherapy-induced erectile dysfunction (ED) was also evaluated. Pretreatment erectile function scores of 2 and 1 were assigned to 125 and 56 patients, respectively. With a 6-year follow-up, 39% of patients maintained potency after prostate brachytherapy, with a plateau on the potency preservation curve. Postimplant preservation of potency (IIEF >/=11) correlated with preimplant erectile function (50.4% vs. 13.2% for preimplant scores of 2 and 1, respectively, p <0.001), patient age (57.4%, 38.2%, and 21.9% for patients <60, 60-69, and >/=70 years old, respectively, p <0.004), use of supplemental EBRT (52.0% vs. 26.4% for patients without and with EBRT, p <0.001), and a history of diabetes mellitus (41.4% vs. 0% for patients without and with diabetes, respectively, p = 0.017). In multivariate analysis, clinical stage, radiation dose to the prostate gland, hormonal manipulation, choice of isotope, history of hypertension, and tobacco consumption had no effect on the ultimate preservation of potency. Only the preimplant potency score, use of supplemental EBRT, and diabetes maintained statistical significance. Sixty-two patients used sildenafil, with 53 (85%) reporting a favorable response. When potent patients were grouped with the ED patients who used sildenafil, the 6-year actuarial rate of potency preservation was 92%. Including the 70 impotent patients who never used sildenafil, the actuarial 6-year rate of potency preservation with and without pharmacologic support was 54% and 39%, respectively. Our results suggest that brachytherapy-induced ED is more common than previously reported and may be the result of obtaining patient information by means of a validated quality-of-life instrument by mail and not by personal interview. In multivariate analysis, only pretreatment potency, supplemental EBRT, and diabetes maintained statistical significance. Most patients with brachytherapy-induced ED responded favorably to sildenafil. Although the 6-year actuarial incidence of potency preservation was 39%, 52% of patients not receiving supplemental EBRT maintained potency. In addition, with pharmacologic support, 92% of patients maintained potency.


Highly Selective Electrocatalytic CuEDTA Reduction by MoS2 Nanosheets for Efficient Pollutant Removal and Simultaneous Electric Power Output.
Electrocatalytic reduction of ethylenediamine tetraacetic acid copper (CuEDTA), a typical refractory heavy metal complexation pollutant, is an environmental benign method that operates at mild condition. Unfortunately, the selective reduction of CuEDTA is still a big challenge in cathodic process. In this work, we report a MoS2 nanosheet/graphite felt (GF) cathode, which achieves an average Faraday efficiency of 29.6% and specific removal rate (SRR) of 0.042 mol/cm2/h for CuEDTA at - 0.65 V vs SCE (saturated calomel electrode), both of which are much higher than those of the commonly reported electrooxidation technology-based removal systems. Moreover, a proof-of-concept CuEDTA/Zn battery with Zn anode and MoS2/GF cathode is demonstrated, which has bifunctions of simultaneous CuEDTA removal and energy output. This is one of the pioneer studies on the electrocatalytic reduction of heavy metal complex and CuEDTA/Zn battery, which brings new insights in developing efficient electrocatalytic reduction system for pollution control and energy output.


Analysis of polychlorinated biphenyls (PCBs) in dairy products by modified QuEChERS/GC-QqQ-MS/MS method: A risk assessment study.
Polychlorinated biphenyls (PCBs) are harmful chemicals that are persistent in the environment and can accumulate in the food chain. The purpose of the present research was to assess non-dioxin-like polychlorinated biphenyls (NDL-PCBs) in some dairy products (yogurt, doogh, and kashk) using modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) technique and gas chromatography-triple-quadrupole mass spectrometry (GC-QqQ-MS/MS) method and risk assessment study. The LOQs (limit of quantifications), LODs (limit of detections), recovery, and RSD for the PCB analytes were 0.180-0.360, 0.06-0.12 ng/g fat, 97.45-102.63%, and 6.33-8.86%, respectively. The results revealed that the mean concentrations of Ʃ6-NDL-PCBs in samples were 15.17 ± 3.44 ng/g fat, which was lower than the standard level established by European Union (EU, 40 ng/g fat). The maximum mean level was PCB 180 (9.98 ± 2.04 ng/g fat) and the minimum mean level of PCBs in samples was PCB 28 (0.09 ± 0.06 ng/g fat). Also, results showed that kashk samples had a maximum mean level of 6-NDL-PCBs (18.66 ± 2.42 ng/g fat) and doogh samples had a minimum mean level of 6-NDL-PCBs (12.21 ± 2.22 ng/g fat). The mean level of 6-NDL-PCBs in yogurt samples was 14.65 ± 2.02 ng/g fat. The heat map results showed the correlation between the spectral indices of 6-NDL-PCBs in different dairy products. According to the Monte Carlo method, risk assessment was done using calculating the Estimated Daily Intake (EDI) and Incremental Life Cancer Risk (ILCR). The EDI values of 6 NDL-PCBs based on the 95th percentile in yogurt, doogh, and kashk were 14.3, 1.49, and 0.5 ng/kg.day, respectively. Considering that the contaminant level in the samples is lower than the EU limit, it can be concluded that dietary exposure to 6 NDL-PCBs may not pose a risk to the health of consumers.


The impact of composition on the physical properties and evaporative mass transfer of a PCE-diesel immiscible liquid.
The impact of immiscible-liquid composition on mass transfer between immiscible liquid and vapor phases was evaluated for a complex mixture of chlorinated solvents and petroleum hydrocarbons. A mixture of tetrachloroethene and diesel was discovered at a site in Tucson, Arizona. Partitioning of tetrachloroethene into a layer of diesel has been observed, with resultant concentrations of tetrachloroethene up to approximately 15% by weight. The density, viscosity, surface tension, and interfacial tension were measured for tetrachloroethene-diesel mixtures with tetrachloroethene fractions ranging from 7% to 32%, and the results indicated that immiscible-liquid composition did impact the physical properties of the tetrachloroethene-diesel mixture. The results of batch phase-partitioning experiments were compared to predictions based on Raoult's Law, and the analysis indicated that immiscible-liquid/vapor and immiscible-liquid/water partitioning were both essentially ideal. Flow-cell experiments were conducted to characterize steady-state tetrachloroethene removal from the tetrachloroethene-diesel mixture via vapor extraction. The effluent concentrations for the experiment conducted with free-phase immiscible liquid were comparable to equilibrium values. Conversely, the effluent concentrations were significantly lower for the experiment wherein a residual saturation of immiscible liquid was distributed within sand. The lower concentrations for the latter experiment were attributed to dilution effects associated with a nonuniform distribution of immiscible liquid within the flow cell.


Solitary neurofibroma of the vagus nerve in the aortopulmonary window masquerading as a developmental cyst.
A rare case of solitary neurofibroma of the vagus nerve in the aortopulmonary window masquerading as a developmental cyst is reported. Its computed tomographic characteristics and magnetic resonance imaging are described and correlated with pathologic findings. Although the features of such imaging modalities are quite characteristic for a neurofibroma, its differentiation from "atypical" developmental cysts may be difficult.


Speech considerations in prosthodontic rehabilitation of the glossectomy patient.
A knowledge of normal articulation is needed before the prosthodontist can assess the compensatory articulation used by glossectomy patients. The amount and portion of tongue resected is directly correlated with speech intelligibility. The loss of the tip of the tongue is more critical to intelligibility than a hemiglossectomy. Partial glossectomy speakers can often use the residual tongue stump to perform adaptive movements that approximate normal movements and should be treated as an articulation problem. The compensatory articulation used by the total glossectomy patient was reviewed. The prosthodontic management of patients with partial tongue resection often includes lowering the palatal vault, while the management of the total glossectomy patient usually requires a mandibular tongue prosthesis. These prostheses can be refined with the use of multiview videofluoroscopy, videotaping, and spectrographic analysis.


Relative blood loss and operative time can predict length of stay following orthognathic surgery.
The aim of this study was to investigate the length of stay (LOS) following orthognathic surgery and thereby to establish a benchmark. The secondary aim was to identify predictors of postoperative LOS following orthognathic surgery. Patients were treated consecutively during the period 2010 to 2012. Inclusion criteria were (1) patient age ≥18 years, and (2) surgery involving a three-piece Le Fort I osteotomy, or a bilateral sagittal split osteotomy (BSSO), or bimaxillary surgery. A total of 335 patients were included. The following data were recorded: height, weight, body mass index (BMI), age, sex, operative time, intraoperative blood loss, and type of surgery. LOS was defined as the duration of time from date of surgery to date of discharge. The average LOS was 1.3 days following Le Fort I osteotomy, 1.3 days following BSSO, and 1.8 days following bimaxillary surgery. In the multivariate regression model (R(2)=0.11), predictors of a prolonged LOS were operative time (P<0.001) and relative blood loss (P=0.002). No significant effect of age, BMI, sex, or treatment on LOS was observed. The short duration of LOS found in this study supports the possibility of increasing outpatient pathways for selected patients.


Community empowerment: the alternative resources movement in Quebec.
In order to achieve true community participation in mental health care, a redistribution of decision-making power is needed. Currently, this power is almost exclusively in the hands of psychiatric institutions and the state. Community participation would require greater representation from community organizations. This paper describes the history of the alternative resources movement in Quebec. This movement has challenged the health care system and promoted innovative therapeutic approaches. In this process, community organizations have been faced with the difficult task of gaining more power while maintaining strong links with the communities they serve.


Physical function, body mass index, and fitness outcomes in children, adolescents, and emerging adults with craniopharyngioma from proton therapy through five years of follow-up.
Children diagnosed with craniopharyngioma are vulnerable to adverse health outcomes. Characterization of body mass index (BMI), physical function, and cardiopulmonary fitness in those treated with proton radiotherapy (PRT) will serve to design interventions to improve outcomes. Ninety-four children with craniopharyngioma completed physical function testing prior to PRT and annually for 5 years. For each outcome, age- and sex-specific z-scores were calculated using normative values. Participants with z-scores > 1.5 or < - 1.5 were classified as impaired. Those with z-scores > 2.0 or < - 2.0 were classified as significantly impaired. Descriptive statistics were used to describe study outcomes and change in prevalence of impairments from 2 to 5 years after treatment. Nearly half of participants [45.2%, 95% confidence interval (CI) 39.4, 51.0] had mean BMI z-scores > 1.5 at baseline, with prevalence increasing to 66.7% (95% CI 61.5, 71.9) at 5 years. More than half of participants (54.2%, 95% CI 48.4, 60.0) had knee extension strength z-scores < - 1.5 at baseline, with prevalence increasing to 81.3% (95% CI 77.7, 84.9) at 5 years. BMI and knee extension strength had the largest proportion of participants impaired at both 2 and 5 years (53.2% and 62.3%, respectively). Resting heart rate had the highest proportion of participants not impaired at 2 years but became impaired at 5 years (26.6%). Children with craniopharyngioma have BMI and fitness abnormalities at diagnosis and continue 5 years after treatment. This cohort may benefit from interventions designed to improve BMI, strength, and resting indicators of cardiopulmonary fitness.


Surgeons' experience and interaction effect in randomized controlled trials regarding new surgical procedures.
The most reliable information on any type of medical intervention is provided through the results of randomized controlled trials (RCTs). However, RCTs comparing a new surgical technique with an older one may provide inaccurate conclusions when surgeons participating in the study have disparate experience with the new technique. In this case, the surgeon-to-surgeon variability may confound the outcome and lead to a significant interaction effect between surgeon and surgical technique. Subsequently the RCT design does not ensure the same outcome probability among patients assigned to the group undergoing the new technique. Overlooking the interaction effect may be responsible for inaccurate conclusions, which are usually unfavorable with regard to the new technique. We discuss how this interaction effect could be involved in conclusions provided by several RCTs that compared laparoscopic hysterectomy to vaginal hysterectomy. We demonstrate how this interaction may be revealed using a hypothetical RCT whose data was reasonably presumed on the basis of literature data.


The miR-143/145 cluster induced by TGF-β1 suppresses Wilms' tumor 1 expression in cultured human podocytes.
Transforming growth factor (TGF)-β1 contributes to podocyte injury in various glomerular diseases, including diabetic kidney disease, probably at least in part by attenuating the expression of Wilms' tumor 1 (WT1). However, the precise mechanisms remain to be defined. We performed miRNA microarray analysis in a human podocyte cell line cultured with TGF-β1 to examine the roles of miRNAs in podocyte damage. The microarray analysis identified miR-143-3p as the miRNA with the greatest increase following exposure to TGF-β1. Quantitative RT-PCR confirmed a significant increase in the miR-143-3p/145-5p cluster in TGF-β1-supplemented cultured podocytes and demonstrated upregulation of miR-143-3p in the glomeruli of mice with type 2 diabetes. Ectopic expression of miR-143-3p and miR-145-5p suppressed WT1 expression in cultured podocytes. Furthermore, inhibition of Smad or mammalian target of rapamycin signaling each partially reversed the TGF-β1-induced increase in miR-143-3p/145-5p and decrease in WT1. In conclusion, TGF-β1 induces expression of miR-143-3p/145-5p in part through Smad and mammalian target of rapamycin pathways, and miR-143-3p/145-5p reduces expression of WT1 in cultured human podocytes. miR-143-3p/145-5p may contribute to TGF-β1-induced podocyte injury.NEW & NOTEWORTHY This study by miRNA microarray analysis demonstrated that miR-143-3p expression was upregulated in cultured human podocytes following exposure to transforming growth factor (TGF)-β1. Furthermore, we report that the miR-143/145 cluster contributes to decreased expression of Wilms' tumor 1, which represents a possible mechanism for podocyte injury induced by TGF-β1. This study is important because it presents a novel mechanism for TGF-β-associated glomerular diseases, including diabetic kidney disease (DKD), and suggests potential therapeutic strategies targeting miR-143-3p/145-5p.


[Tumor budding in colorectal cancer-Information for clinical use and instructions for practical evaluation].
Some patients with high-risk colorectal cancer show a worse prognosis within the same UICC stage. Therefore, the identification of additional risk factors is necessary to find the best treatment for these patients. In which settings can tumor budding help the clinical decision-making process for treatment planning and how should scoring be performed? Evaluation of current publications on tumor budding with an emphasis on practical grading and potential problems in the determination of tumor budding. Tumor budding is a significant risk factor for worse clinical outcome of colorectal cancer and can influence clinical decision-making in pT1 and stage II colorectal cancer. A scoring method was standardized by the ITBCC 2016 and is feasible in everyday practice. Challenges in assessment can be addressed by increasing awareness of potential problem cases.


Development and characterization of trans-anethole-containing solid lipid microparticles: antiinflammatory and gastroprotective effects in experimental inflammation.
The present study prepared, optimized, and characterized solid lipid microparticles that contained trans-anethole (SLMAN), evaluated their antiinflammatory activity in acute and chronic inflammation models, and investigated their effects on the gastric mucosa in arthritic rats. The microparticles were obtained by a hot homogenization process and characterized by physicochemical analyses. The acute inflammatory response was induced by an intradermal injection of 0.1 ml of carrageenan solution (200 μg) in the hind paw. The rats were treated orally with a single dose of SLMAN 1 h before induction of the inflammatory response. The chronic inflammatory response was induced by the subcutaneous application of 0.1 ml of complete Freund's adjuvant suspension (500 µg) in the hind paw. SLMAN was orally administered, starting on the day of arthritis induction, and continued for 21 days. The results showed that SLMAN was obtained with good encapsulation efficiency. Treatment with SLMAN at doses of 25 and 50 mg/kg was as effective as trans-anethole (AN) at a dose of 250 mg/kg on acute and chronic inflammatory responses. Histological analyses showed that treatment with SLMAN did not aggravate lesions in the gastric mucosa in arthritic rats. These results indicated that treatment with SLMAN at a dose that was 5-10 times lower than non-encapsulated AN exerted an inhibitory effect on acute and chronic inflammatory responses, suggesting the better bioavailability and efficacy of microencapsulated AN without aggravating lesions in the gastric mucosa in arthritic rats.


Using Surveillance With Near-Real-Time Alerts During a Cluster of Overdoses From Fentanyl-Contaminated Crack Cocaine, Connecticut, June 2019.
In 2019, Connecticut launched an opioid overdose-monitoring program to provide rapid intervention and limit opioid overdose-related harms. The Connecticut Statewide Opioid Response Directive (SWORD)-a collaboration among the Connecticut State Department of Public Health, Connecticut Poison Control Center (CPCC), emergency medical services (EMS), New England High Intensity Drug Trafficking Area (HIDTA), and local harm reduction groups-required EMS providers to call in all suspected opioid overdoses to the CPCC. A centralized data collection system and the HIDTA overdose mapping tool were used to identify outbreaks and direct interventions. We describe the successful identification of a cluster of fentanyl-contaminated crack cocaine overdoses leading to a rapid public health response. On June 1, 2019, paramedics called in to the CPCC 2 people with suspected opioid overdose who reported exclusive use of crack cocaine after being resuscitated with naloxone. When CPCC specialists in poison information followed up on the patients' status with the emergency department, they learned of 2 similar cases, raising suspicion that a batch of crack cocaine was mixed with an opioid, possibly fentanyl. The overdose mapping tool pinpointed the overdose nexus to a neighborhood in Hartford, Connecticut; the CPCC supervisor alerted the Connecticut State Department of Public Health, which in turn notified local health departments, public safety officials, and harm reduction groups. Harm reduction groups distributed fentanyl test strips and naloxone to crack cocaine users and warned them of the dangers of using alone. The outbreak lasted 5 days and tallied at least 22 overdoses, including 6 deaths. SWORD's near-real-time EMS reporting combined with the overdose mapping tool enabled rapid recognition of this overdose cluster, and the public health response likely prevented additional overdoses and loss of life.


Factors Associated with Adoption and Adoption Intentions of Nonparental Caregivers.
Data from the 2011-2012 National Survey of Children's Health and the 2013 National Survey of Children in Nonparental Care were used to fit a multinomial logistic model comparing three groups to those who never considered adoption: those who ever considered, but are not currently planning adoption; those planning adoption; and those who adopted. Adoption may be more likely when the caregiver is a nonkin foster parent, a foster care agency was involved, and/or financial assistance is available. Those with plans to adopt but who have not adopted may face adoption barriers such as extreme poverty, lower education and being unmarried.


Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4-10 brain metastases: A nonrandomized controlled trial.
There is no randomized evidence comparing whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases. This prospective nonrandomized controlled single arm trial attempts to reduce the gap until prospective randomized controlled trial results are available. We included patients with 4-10 brain metastases and ECOG performance status ≤ 2 from all histologies except small-cell lung cancer, germ cell tumors, and lymphoma. The retrospective WBRT-cohort was selected 2:1 from consecutive patients treated within 2012-2017. Propensity-score matching was performed to adjust for confounding factors such as sex, age, primary tumor histology, dsGPA score, and systemic therapy. SRS was performed using a LINAC-based single-isocenter technique employing prescription doses from 15-20Gyx1 at the 80% isodose line. The historical control consisted of equivalent WBRT dose regimens of either 3Gyx10 or 2.5Gyx14. Patients were recruited from 2017-2020, end of follow-up was July 1st, 2021. 40 patients were recruited to the SRS-cohort and 70 patients were eligible as controls in the WBRT-cohort. Median OS, and iPFS were 10.4 months (95%-CI 9.3-NA) and 7.1 months (95%-CI 3.9-14.2) for the SRS-cohort, and 6.5 months (95%-CI 4.9-10.4), and 5.9 months (95%-CI 4.1-8.8) for the WBRT-cohort, respectively. Differences were non-significant for OS (HR: 0.65; 95%-CI 0.40-1.05; P =.074) and iPFS (P =.28). No grade III toxicities were observed in the SRS-cohort. This trial did not meet its primary endpoint as the OS-improvement of SRS compared to WBRT was non-significant and thus superiority could not be proven. Prospective randomized trials in the era of immunotherapy and targeted therapies are warranted.


Electron Holes in G-Quadruplexes: The Role of Adenine Ending Groups.
The study deals with four-stranded DNA structures (G-Quadruplexes), known to undergo ionization upon direct absorption of low-energy UV photons. Combining quantum chemistry calculations and time-resolved absorption spectroscopy with 266 nm excitation, it focuses on the electron holes generated in tetramolecular systems with adenine groups at the ends. Our computations show that the electron hole is placed in a single guanine site, whose location depends on the position of the adenines at the 3' or 5' ends. This position also affects significantly the electronic absorption spectrum of (G+)● radical cations. Their decay is highly anisotropic, composed of a fast process (<2 µs), followed by a slower one occurring in ~20 µs. On the one hand, they undergo deprotonation to (G-H2)● radicals and, on the other, they give rise to a reaction product absorbing in the 300-500 nm spectral domain.


Estimating distribution and retention of mercury in three different soils contaminated by emissions from chlor-alkali plants: part I.
Mercury emissions from chlor-alkali plants have been past and present sources of soil contamination with Hg. Here we calculate net mercury (Hg) deposition to soils in the vicinity (100-1000-m downwind) of three-chlor alkali plants. Calculations were based on spatial distribution patterns of Hg concentrations in soils, which were extrapolated by kriging. Moreover, we investigated to what extent Hg deposition depends on the elevation of receptors and canopy throughfall. Mercury concentrations in soil exceed background values up to a factor of 56 and show enrichment factors between 2 and 5.8 calculated from the median Hg concentration. Net deposition rates range between 2356 and 8952 microg m(-2) year(-1), which is up to 224-fold the background values. Net deposition of Hg to soils at the three sites varies between 1.2 and 2.4% of total emitted Hg. Highest deposition rates were found at sites with extended elevated or forested areas. Here, Hg concentrations in soils increased by a factor of up to 7.3 in elevated (+180 m) forest areas compared to non-elevated grassland soils.


Efficacy of Vitamin C Supplements in Prevention of Cancer: A Meta-Analysis of Randomized Controlled Trials.
Previous randomized controlled trials (RCTs) have reported inconsistent findings regarding the association between vitamin C supplementation and the risk of cancer. We performed a meta-analysis of RCTs to investigate the efficacy of vitamin C supplements for prevention of cancer. We searched the PubMed, EMBASE, and Cochrane Library databases in November 2014 using common keywords related to vitamin C supplements and cancer. Among 785 articles, a total of seven trials were identified, which included 62,619 participants; 31,326 and 31,293 were randomized to vitamin C supplementation and control or placebo groups, respectively, which were included in the final analysis. A fixed-effects meta-analysis of all seven RCTs revealed no significant association between vitamin C supplementation and cancer (relative risk, 1.00; 95% confidence intervals, 0.95-1.05). Similarly, subgroup meta-analysis by dose of vitamin C administered singly or in combination with other supplements, follow-up period, methodological quality, cancer mortality, gender, smoking status, country, and type of cancer also showed no efficacy of vitamin C supplementation for cancer prevention. This meta-analysis shows that there is no evidence to support the use of vitamin C supplements for prevention of cancer.


Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming.
Mammalian parental genomes contribute differently to early embryonic development. Before activation of the zygotic genome, the maternal genome provides all transcripts and proteins required for the transition from a highly specialized oocyte to a pluripotent embryo. Depletion of these maternally-encoded transcripts frequently results in failure of preimplantation embryonic development, but their functions in this process are incompletely understood. We found that female mice lacking NLRP2 are subfertile because of early embryonic loss and the production of fewer offspring that have a wide array of developmental phenotypes and abnormal DNA methylation at imprinted loci. By demonstrating that NLRP2 is a member of the subcortical maternal complex (SCMC), an essential cytoplasmic complex in oocytes and preimplantation embryos with poorly understood function, we identified imprinted postzygotic DNA methylation maintenance, likely by directing subcellular localization of proteins involved in this process, such as DNMT1, as a new crucial role of the SCMC for mammalian reproduction.


Four-year biochar study: Positive response of acidic soil microenvironment and citrus growth to biochar under potassium deficiency conditions.
Biochar has direct or indirect effects on soil microorganisms, but the changes in soil metabolism are rarely monitored and analyzed. In addition, the potassium (K) effect of biochar has not attracted much attention. This study set up a four-year experiment with acid soil and citrus as the test soil and plants, respectively. The long-term effects of biochar on the acid soil microenvironment and citrus growth were explored from soil properties (nutrient contents, microbial communities, and metabolites) and citrus growth (nutrient contents, reactive oxygen species (ROS), and root endophytes). The results showed that the four-year amendment of biochar in acid soil was very significant, in which the soil pH was increased by 1 unit, organic matter and cation exchange capacity (CEC) increased by 120.77% and 16.21%, respectively. Biochar improved the K availability of soil by increasing the number and metabolic activity of Azotobacter and Pseudomonas, and finally effectively alleviated the K deficiency of citrus. From the perspective of available K content, 2% biochar reduced the 20% conventional K application rate. The pH, organic matter, and cation exchange capacity (CEC) were the most important factors affecting the bacterial community structure, while the fungal community was more sensitive to the change in the nutrient environment. Biochar mainly stimulated the progress of soil metabolism by affecting the metabolic activity of bacterial communities. Biochar application increased some of the beneficial bacteria in the soil, i.e., the relative abundance of Pseudarthrobacter increased by 700 times. However, biochar and exogenous K did not significantly affect arbuscular mycorrhizal fungi (AMF) and endophytic bacteria in citrus roots. In general, biochar has a long-term and positive response to the acidic soil microenvironment and citrus growth, as well as promotion value in the agricultural field.


Printable food: the technology and its application in human health.
Millions of Americans suffer from diseases and conditions that require careful control of their diet as part of treatment. The current solution is to have each person customize their own food choices. Food production automation can enable consumer specific data to be easily integrated into the food as it is being prepared. This would improve the quality and utility of the food without a cognitive burden on the consumer. 3D Printing is an ideal family of technologies for enabling such mass customization of food. Current efforts in 3D printing food are focused on improving the artistic quality of food in the short term and consumer health in the long term.


The influence of information structuring and health literacy on recall and satisfaction in a simulated discharge communication.
We investigated the effects of information structuring and its potential interaction with pre-existing medical knowledge on recall in a simulated discharge communication. 127 proxy-patients (i.e. students) were randomly assigned to one of four conditions. Video vignettes provided identical information, differing in means of information structuring only: The natural conversation (NC) condition was not explicitly structured whereas the structure (S) condition presented information organised by chapter headings. The book metaphor (BM) and the post organizer (PO) conditions also presented structured information but in addition included a synopsis, either at the beginning or at the end of discharge communication, respectively. Proxy-patients' recall, perception of quality and pre-existing medical knowledge were assessed. Information structuring (conditions: S, BM, PO) did not increase recall in comparison to NC, but pre-existing medical knowledge improved recall (p < .01). An interaction between medical knowledge and recall in the BM condition was found (p = .02). In comparison to the NC, proxy-patients in all information structuring conditions more strongly recommended the physician (p < .001). Structured discharge communication complemented by the BM is beneficial in individuals with lower pre-existing medical knowledge. The lower pre-existing medical knowledge, the more recipients will profit from information structuring with the BM.


Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington's disease mice.
Motor slowing, forebrain white matter loss, and striatal shrinkage have been reported in premanifest Huntington's disease (HD) prior to overt striatal neuron loss. We carried out detailed LM and EM studies in a genetically precise HD mimic, heterozygous Q140 HD knock-in mice, to examine the possibility that loss of corticostriatal and thalamostriatal terminals prior to striatal neuron loss underlies these premanifest HD abnormalities. In our studies, we used VGLUT1 and VGLUT2 immunolabeling to detect corticostriatal and thalamostriatal (respectively) terminals in dorsolateral (motor) striatum over the first year of life, prior to striatal projection neuron pathology. VGLUT1+ axospinous corticostriatal terminals represented about 55% of all excitatory terminals in striatum, and VGLUT2+ axospinous thalamostriatal terminals represented about 35%, with VGLUT1+ and VGLUT2+ axodendritic terminals accounting for the remainder. In Q140 mice, a significant 40% shortfall in VGLUT2+ axodendritic thalamostriatal terminals and a 20% shortfall in axospinous thalamostriatal terminals were already observed at 1 month of age, but VGLUT1+ terminals were normal in abundance. The 20% deficiency in VGLUT2+ thalamostriatal axospinous terminals persisted at 4 and 12 months in Q140 mice, and an additional 30% loss of VGLUT1+ corticostriatal terminals was observed at 12 months. The early and persistent deficiency in thalamostriatal axospinous terminals in Q140 mice may reflect a development defect, and the impoverishment of this excitatory drive to striatum may help explain early motor defects in Q140 mice and in premanifest HD. The loss of corticostriatal terminals at 1 year in Q140 mice is consistent with prior evidence from other mouse models of corticostriatal disconnection early during progression, and can explain both the measurable bradykinesia and striatal white matter loss in late premanifest HD.


Endoscopic stenting versus operative gastrojejunostomy for malignant gastric outlet obstruction.
Malignant gastric outlet obstruction represents a terminal stage in pancreatic cancer. Between 5% and 25% of patients with pancreatic cancer ultimately experience malignant gastric outlet obstruction. The aim in palliating patients with malignant gastric outlet obstruction is to reestablish an oral intake by restoring gastrointestinal continuity. This ultimately improves their quality of life in the advanced stages of cancer. The main drawback to operative bypass is the high incidence of delayed gastric emptying, particularly in this group of patients with symptomatic obstruction. This study aimed to compare surgical gastrojejunostomy and endoscopic stenting in palliation of malignant gastric outlet obstruction, acknowledging the diversity and heterogeneity of patients with this presentation. This retrospective study investigated patients treated for malignant gastric outlet obstruction from December 1998 to November 2008 at Nepean Hospital, Sydney, Australia. Endoscopic duodenal stenting was performed under fluoroscopic guidance for placement of the stent. The operative patients underwent open surgical gastrojejunostomy. The outcomes assessed included time to diet, hospital length of stay (LOS), biliary drainage procedures, morbidity, and mortality. Of the 45 participants in this study, 26 underwent duodenal stenting and 19 had operative bypass. Comparing the stenting and operative patients, the median time to fluid intake was respectively 0 vs. 7 days (P < 0.001), and the time to intake of solids was 2 vs. 9 days (P = 0.004). The median total LOS was shorter in the stenting group (11 vs. 25 days; P < 0.001), as was the median postprocedure LOS (5 vs. 10 days; P = 0.07). Endoscopic stenting is preferable to operative gastrojejunostomy in terms of shorter LOS, faster return to fluids and solids, and reduced morbidity and in-hospital mortality for patients with a limited life span.


Unscheduled DNA-synthesis in UV-irradiated spleen lymphocytes of the rat after whole-body X-irradiation.
Unscheduled DNA-synthesis of UV-irradiated spleen lymphocytes of the rat is inhibited in a dose-dependent manner by total-body X-irradiation. The reaction is observed immediately after exposure and reaches its maximum within 8--16 h. Doses of some rads are detectable. Following sublethal X-irradiation (250 rad), regeneration takes 4--6 weeks. Analogous results have been obtained in rats treated with 2,4,6-triethyleneimino-1,3,5-triazine. Regardless of the action mechanisms, it is concluded from the present results that the inhibition of the unscheduled incorporation of thymidine-3H in splenic lymphocytes is a very sensitive, though not specific expression of impairment of the lymphatic system.


Effects of a mindfulness-based weight loss intervention in adults with obesity: A randomized clinical trial.
To determine whether adding mindfulness-based eating and stress management practices to a diet-exercise program improves weight loss and metabolic syndrome components. In this study 194 adults with obesity were randomized to a 5.5-month program with or without mindfulness training and identical diet-exercise guidelines. Intention-to-treat analyses with multiple imputation were used for missing data. The primary outcome was 18-month weight change. Estimated effects comparing the mindfulness to control arm favored the mindfulness arm in (a) weight loss at 12 months, -1.9 kg (95% CI: -4.5, 0.8; P = 0.17), and 18 months, -1.7 kg (95% CI: -4.7, 1.2; P = 0.24), though not statistically significant; (b) changes in fasting glucose at 12 months, -3.1 mg/dl (95% CI: -6.3, 0.1; P = 0.06), and 18 months, -4.1 mg/dl (95% CI: -7.3, -0.9; P = 0.01); and (c) changes in triglyceride/HDL ratio at 12 months, -0.57 (95% CI: -0.95, -0.18; P = 0.004), and 18 months, -0.36 (95% CI: -0.74, 0.03; P = 0.07). Estimates for other metabolic risk factors were not statistically significant, including waist circumference, blood pressure, and C-reactive protein. Mindfulness enhancements to a diet-exercise program did not show substantial weight loss benefit but may promote long-term improvement in some aspects of metabolic health in obesity that requires further study.


Self-regulated learning strategies used in surgical clerkship and the relationship with clinical achievement.
Self-regulated learning indicates students' skills in controlling their own learning. Self-regulated learning, which a context-specific process, emphasizes autonomy and control. Students gain more autonomy with respect to learning in the clinical years. Examining the self-regulated learning skills of students in this period will provide important clues about the level at which students are ready to use these skills in real-life conditions. The self-regulated learning strategies used by medical students in surgical clerkship were investigated in this study and their relation with clinical achievement was analyzed. The study was conducted during the surgery clerkship of medical students. The participation rate was 94% (309 students). Motivated Strategies for Learning Questionnaire (MSLQ), a case-based examination, Objective Structured Clinical Examination (OSCE), and tutor evaluations for assessing achievement were used. The relationship between the Motivated Strategies for Learning Questionnaire scores of the students and clinical achievement was analyzed with multilinear regression analysis. The findings showed that students use self-regulated learning skills at medium levels during their surgery clerkship. A relationship between these skills and OSCE scores and tutor evaluations was determined. OSCE scores of the students were observed to increase in conjunction with increased self-efficacy levels. However, as students' beliefs regarding control over learning increased, OSCE scores decreased. No significant relationship was defined between self-regulated learning skills and case-based examination scores. We observed that a greater self-efficacy for learning resulted in higher OSCE scores. Conversely, students who believe that learning is a result of their own effort had lower OSCE scores.


COL11A1 Polymorphisms Are Associated with Primary Angle-Closure Glaucoma Severity.
PLEKHA7 and COL11A1 were genotyped for single-nucleotide polymorphisms (SNPs) to investigate the possible association of these two genes with primary angle-closure glaucoma (PACG) and disease severity. A total of 51 PACG cases and 51 normal controls were recruited. Twelve SNPs in the PLEKHA7 (rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) and COL11A1 (rs1676484, rs3753841, rs12138977, rs2126642, and rs2622848) genes were genotyped by direct Sanger sequencing. Distributions of allele frequencies and genotype frequencies in cases and controls, as well as in mild, moderate, and severe subgroups, were compared based on mean defect (MD ≤ 6.00 dB, 6 dB < MD ≤ 12 dB, and MD > 12 dB were considered mild, moderate, and severe, respectively). Independent Student's t-tests and chi-square tests were used to compare characteristics of PACG cases and controls. Chi-square tests were used to compare the distribution of allele frequencies in cases and controls and in MD-based subgroups with various degrees of glaucoma severity. Binary logistic regression was used to compare the distribution of genotype frequencies and calculate odds ratios (OR) with confidence intervals (CI). Three of the 12 SNPs in COL11A1, rs1676486 (P=0.026, OR = 2.089, 95% CI = 1.092-3.996), rs3753841 (P=0.036, OR = 1.886, 95% CI = 1.038-3.426), and rs12138977 (P=0.024, OR = 2.133, 95% CI = 1.104-4.123) were found to have a significant association with PACG. Furthermore, in the subgroup analysis, rs1676486 (P=0.018, OR = 2.416, 95% CI = 1.284-4.544; P=0.011, OR = 2.119, 95% CI = 1.204-3.729), rs12138977 (P=0.009, OR = 2.158, 95% CI = 1.287-3.618; P=0.006, OR = 1.962, 95% CI = 1.239-3.106), and rs3753841 (P=0.007, OR = 2.550, 95% CI = 1.344-4.839) showed statistically significant differences between moderate/severe groups and controls. Our data suggested that COL11A1 rs1676484, rs3753841, and rs12138977 polymorphisms may be of value for further study as potential gene-dependent risk factors for developing PACG. Moreover, COL11A1 rs1676484 and rs12138977 polymorphisms might be associated with PACG disease severity.


Cytotoxic pyridine alkaloids from a marine-derived fungus Arthrinium arundinis exhibiting apoptosis-inducing activities against small cell lung cancer.
Small cell lung cancer (SCLC) is a kind of high-grade neuroendocrine carcinoma, which is characterized by a higher proliferative rate, earlier metastasis and more poor outcomes compared to non-small cell lung cancer (NSCLC). Under the guidance of MS/MS based molecular networking, three undescribed pyridone alkaloids, namely, arthpyrones M-O (1-3), together with two known pyridone derivatives, arthpyrones C (4) and G (5), were isolated from a sponge-derived Arthrinium arundinis. Their structures were determined through extensive spectroscopic analysis, ECD calculations, and X-ray single-crystal diffraction. Arthpyrone M (1) possessed a novel cage structure bearing an ether bridge functionality rarely reported in this class of metabolites. All isolated compounds were evaluated for their cytotoxicities against five cancer cell lines. As a result, compounds 1-5 showed cytotoxicity against some or all of the five cancer cell lines with IC50 values ranging from 0.26 to 6.43 μM. Among them, arthpyrone O (3) not only exhibited potent efficacy against the proliferative activity of SCLC cells and induced apoptosis in vitro, but also significantly inhibited the growth of xenograft tumor based on SCLC cells in vivo, which indicated 4-hydroxy-2-pyridone alkaloids might been revised as privileged scaffolds in drug discovery.


Use of chitosan and chitosan-derivatives to remove arsenic from aqueous solutions--a mini review.
Arsenic removal has become a relevant concern due to the final confirmation of its behaviour as chronic human carcinogen, corresponding to an ever-increasing contamination of water, soil and crops in many parts of the world. Developing easily accessible removal strategies is therefore a primary environmental matter. Chitosan and chitosan derivatives show good adsorption performances against arsenic removal and are considered low cost products, easily obtainable. This review provides a summary of recent advances of the application of these compounds in the area of sorption sciences for arsenate and arsenite removal from water, focusing on equilibrium and kinetic mechanisms.


First report of two thioredoxin homologues in crustaceans: molecular characterization, genomic organization and expression pattern in swimming crab Portunus trituberculatus.
Previously, we had reported two homologues of the thioredoxin (Trx) super-family (PtTrx1 and PtTrx2) identified from eyestalk and haemocytes cDNA library of swimming crab Portunus trituberculatus, respectively. It was the first report of two thioredoxin homologues from the same crustacean species. Here, we focused on the molecular characterization, genomic organization and expression pattern of PtTrx1 and PtTrx2. The full-length cDNA sequences of PtTrx1 and PtTrx2 were 739 and 1300 bp, encoding 105 and 133 amino acids, respectively. They both had a conserved CGPC active site and highly similar tertiary structures, which containing four β-sheets and four α-helixes. Specifically, PtTrx2 was encoded by a nuclear gene and its cellular localization was targeted to mitochondria by an N-terminal mitochondrial pre-sequence. Sequence analysis revealed PtTrx1 and PtTrx2 were encoded by different genomic locus. As the first analyzed genomic structure of PtTrxs in crustaceans, two introns with microsatellites were found in the open reading frame region of these genes. Quantitative real-time PCR analysis revealed the mRNA expression of PtTrx1 transcripts were mainly detected in gill, while, PtTrx2 in eyestalk and gill. The temporal expression levels of PtTrxs transcripts in haemocytes showed different expression patterns after challenge with Vibrio alginolyticus, Micrococcus luteus and Pichia pastoris. These results together indicate that PtTrxs should be involved in the responses to pathogen challenge of P. trituberculatus.


Effect of glycosaminoglycans on the detection of antibodies to collagen in synovial fluid.
Antibodies to collagen in the synovial fluid of RA patients were determined by radioimmuno assay using 14-C-labeled collagen and by passive hemagglutination with collagen coated erythrocytes. The effect of various glycosaminoglycans, possibly present in synovial fluid, on these two assays was investigated. None of the glycosaminoglycan preparations tested significantly changed either antibody titers or the amount of 14-C-radioactivity precipitated in radioimmunoassay. Digestion of the synovial fluid with chondroitinase ABC likewise had no effect on the results. It is therefore concluded that the glycosaminoglycans present in synovial fluid do not interact with native or denatured collagen under the experimental conditions existing in the determination of antibodies to collagen.


Liver histology in ICU patients dying from sepsis: a clinico-pathological study.
To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. Liver biochemistries were increased in the majority of patients before death. Histology of liver biopsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholangitis/cholangiolitis in 20% of patients. Mixed hepatitic/cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was observed in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was associated with increased hospitalization in the ICU prior death (P=0.026). Features of hepatitis and steatosis are the main histological findings in the liver in the majority of patients dying from sepsis.


Corrigendum: Genome-wide identification of genes encoding cystathionine beta synthase domain-containing proteins in wheat and its relationship with anther male sterility under heat stress.
[This corrects the article DOI: 10.3389/fpls.2022.1061472.].


Reversible modification of mitochondrial ADP/ATP translocases by paired Legionella effector proteins.
Adenosine diphosphate (ADP) ribosylation is a reversible posttranslational modification involved in the regulation of numerous cellular processes. Prototype ADP ribosyltransferases (ARTs) from many pathogenic bacteria are known to function as toxins, while other bacterial ARTs have just recently emerged. Recent studies have shown that bacteria also possess enzymes that function as poly-ADP ribose (ADPr) glycohydrolases (PARGs), which reverse poly-ADP ribosylation. However, how bacteria manipulate host target proteins by coordinated reactions of ARTs and ADPr hydrolases (ARHs) remains elusive. The intracellular bacterial pathogen Legionella pneumophila, the causative agent of Legionnaires' disease, transports a large array of effector proteins via the Dot/Icm type IV secretion system to host cells. The effector proteins, which mostly function as enzymes, modulate host cellular processes for the bacteria's benefit. In this study, we identified a pair of L. pneumophila effector proteins, Lpg0080 and Lpg0081, which function as an ART and an ARH, respectively. The two proteins were shown to coordinately modulate mitochondrial ADP/adenosine triphosphate (ATP) translocases (ANTs) by their enzymatic activities to conjugate ADPr to, and remove it from, a key arginine residue. The crystal structures of Lpg0081 and the Lpg0081:ADPr complex indicated that Lpg0081 is a macroD-type ARH with a noncanonical macrodomain, whose folding topology is strikingly distinct from that of the canonical macrodomain that is ubiquitously found in eukaryotic PARGs and ARHs. Our results illustrate that L. pneumophila has acquired an effector pair that coordinately manipulate mitochondrial activity via reversible chemical modification of ANTs.


Low anxiety males display higher degree of salt sensitivity, increased autonomic reactivity, and higher defensiveness.
Psychological parameters such as heightened anxiety and defensiveness are associated with increased cardiovascular morbidity and mortality. Autonomic dysfunction is considered to be an important pathogenetic pathway. Little research has been done regarding potential links between emotional factors and salt sensitivity. The aim of the present study was to determine whether subjects with different levels of trait anxiety differ in the degree of salt sensitivity and autonomic reactivity to a mental stress task. Seventy-two young normotensive men were phenotyped for salt sensitivity and underwent a standardized mental stress test and psychological assessment. According to their trait anxiety test scores, they were classified as low-, moderate- or high-anxiety subjects. A measure of defensiveness was used to assess self-deceptive tendencies. Low-anxiety subjects displayed a higher degree of salt sensitivity compared to moderate- and high-anxiety subjects (P < 0.001), increased heart rate (HR) and electrodermal responses to the stressor compared to moderate-anxiety subjects (P < 0.01 and P < 0.05 respectively) and elevated levels of self-deception compared to moderate- and high-anxiety subjects (P < 0.001). Low-anxiety subjects were characterized by a higher degree of salt sensitivity and increased autonomic responsiveness. Defensiveness was also shown to be elevated in this group and might be the underlying psychological trait explaining these findings. Future research on the associations of anxiety and cardiovascular risk should implement measurement of defensiveness in order to identify these subjects at potential risk for cardiovascular disease despite self-reports of low anxiety.


Identifying Restriction Factors for Hemorrhagic Fever Viruses: Dengue and Junín.
Host restriction factors are cellular components that interfere with viral multiplication. They are up-regulated and expressed upon viral infection and in consequence their activity is specific. So far several important restriction factors have been described against diverse viruses. The cellular antiviral mechanisms defined include proteins with the ability to interfere with early steps of viral replication and others that have been shown to block viral morphogenesis. However, other strategies by which the antiviral action is exerted still remain elusive. An additional interesting matter is how viruses also developed ways to by-pass these host-specific obstacles. Thus, unusual cell localization or re-localization represents a frequent virus choice to evade the cellular surveillance. In the present chapter, we summarize methods to identify cell restriction factors, their antiviral activity, and possible subcellular locations where their activity can take place.