Pathogenesis of necrotizing enterocolitis: modeling the innate immune response.
Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants. The pathophysiology is likely secondary to innate immune responses to intestinal microbiota by the premature infant's intestinal tract, leading to inflammation and injury. This review provides an updated summary of the components of the innate immune system involved in NEC pathogenesis. In addition, we evaluate the animal models that have been used to study NEC with regard to the involvement of innate immune factors and histopathological changes as compared to those seen in infants with NEC. Finally, we discuss new approaches to studying NEC, including mathematical models of intestinal injury and the use of humanized mice.


LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway.
Osteoarthritis (OA) is a joint disease that causes great pain to patients and imposes a tremendous burden on the world's medical resources. Regulatory noncoding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), play an important role in OA progression. Here, we identified differential expression of transcription factor LEF1 that increased circRNA circRNF121 levels in normal and OA cartilage tissues. The expression of LEF1 and circRNF121 was positively associated with Mankin's scores. Alteration of circRNF121 mediated the degradation of extracellular mechanisms (ECM), apoptosis, and proliferation of chondrocytes. MiR-665 was identified as a direct regulatory target of circRNF121 and MYD88. Functional analysis showed that circRNF121 and MYD88 modulated ECM degradation, apoptosis, and proliferation of chondrocytes, which could be reversed by miR-665. MYD88 regulated the activity of the NF-кB signaling pathway by circRNF121 via sponging miR-665. Collectively, these data indicated that LEF1 impacted OA progression by modulating the circRNF121/miR-665/MYD88 axis via NF-кB pathway. Our research proposed a new molecular mechanism for the development of OA, and provided a prospective therapeutic target for OA.


An elderly patient presenting with hip pain following a fall: an unusual presentation of necrotising fasciitis.
Necrotising fasciitis (NF) is a rapidly progressive soft tissue infection involving necrosis of subcutaneous tissues. Early surgical intervention reduces mortality, but initial clinical findings are often non-specific and can delay the diagnosis. An 80-year-old patient, presented to our emergency department with pain in her left hip and mild bruising following a fall. An x-ray, requested to investigate a possible hip fracture, in fact demonstrated air in the subcutaneous tissues. She rapidly deteriorated and soon developed blood-filled blisters, crepitus and fixed staining of the skin. She underwent urgent debridement of involved tissues in theatre confirming the diagnosis of NF. The presence of subcutaneous emphysema on plain radiograph as in this case, is extremely specific to the diagnosis of NF. Although other imaging modalities can aid diagnosis these remain as an adjunct rather than a definitive diagnostic tool and should not delay surgical intervention based on clinical findings.


Catalytic hydrothermal conversion of carboxymethyl cellulose to value-added chemicals over metal-organic framework MIL-53(Al).
Catalytic hydrolysis of biomass over solid catalysts can be one of the most efficient pathways for a future sustainable society dependent on cellulose biomass. In this work metal-organic framework MIL-53(Al) without any functionalization was directly employed as an efficient heterogeneous catalyst for the hydrolysis of carboxymethyl cellulose (CMC) to 5-hydroxymethyl-furaldehyde (5-HMF) in aqueous phase. A 5-HMF molar yield of 40.3% and total reducing sugar (TRS) molar yield of 54.2% were obtained with water as single solvent at 473 K for 4 h. The catalyst could be reused three times without losing activity to a greater extent. With the remarkable advantages such as the use of water as single solvent and MIL-53(Al) as a novel heterogeneous green catalyst, the work provides a new platform for the production of value added chemicals and liquid fuels from biomass.


Stimulus-evoked glutamate release is diminished by acute exposure to uranium in vitro.
Uranium is used in civilian applications, in the manufacture of nuclear fuel, and by the military for munitions and armament, but little information is available on its neurotoxicity. Neurological dysfunctions have been observed after chronic exposure in both animals and humans, but the actions of acute exposure on amino acid neurotransmission have not been investigated. The following study was performed to examine the effects of uranyl ion (UO(2)(+2)) on hippocampal glutamatergic and GABAergic function as possible bases for the neurotoxicity and to assess the direct effects on the exocytotic process. Nominal UO(2)(+2) concentrations were applied to superfused hippocampal synaptosomes to permit estimation of the metal's potency on endogenous transmitter release in the presence and absence of Ca(+2). K(+)-evoked glutamate release was diminished in the range of 10 nM-316 microM UO(2)(+2), resulting in an IC(50) of 1.92 microM. In contrast, the potency of UO(2)(+2) to decrease stimulated GABA release was reduced, producing an IC(50) approximately 2.6 mM. In the absence of Ca(+2) in the superfusion medium there was no systematic change in the magnitude of glutamate or GABA release, suggesting that UO(2)(+2) does not possess Ca(+2)-mimetic properties. The inhibitory potency of UO(2)(+2) on glutamate release is similar to the potencies of other multivalent metal ions, suggesting by inference an action exerted on voltage-sensitive Ca(+2) channels. The bases for the reduced potency to inhibit GABA release is not known, but differential sensitivity to other heavy metals has been reported for glutamate and GABA neurotransmission. These findings indicate a profile of neurotoxicity not unlike that of other metal ions, and indicate the importance of extending subsequent studies to chronic exposure models.


Single-center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia.
The BCL-2 inhibitor venetoclax (ven) has revolutionized the treatment of acute myeloid leukemia (AML) in elderly adults, leading to its recent FDA approval for this population in combination regimens. Although extensive data exist for adult myeloid malignancies, there are limited preclinical data on the efficacy and/or dosing of venetoclax for pediatric myelodysplastic syndrome (MDS) or AML and thus little information to guide use of this regimen in pediatric patients. Our objective was to describe our single-center experience with venetoclax in combination with the hypomethylating agent 5-azacitidine (aza) in pediatric patients with MDS or AML. We conducted a retrospective chart review of patients treated at Children's Hospital Colorado prior to March 2020 with at least one cycle of ven/aza. Patients were included if between the ages of 1 and 25 years with a diagnosis of high-grade MDS or AML. AML patients had relapsed or primary refractory disease or were deemed poor candidates for standard chemotherapy. Eight patients received ven/aza, two for high-grade MDS and six for AML. Ven/aza was well tolerated by all patients. The most common adverse events seen with this regimen were gastrointestinal and hematologic. Morphologic responses were seen in six patients including both patients with MDS. All four AML responders became minimal residual disease negative. Three responders have thus far proceeded to allogeneic hematopoietic stem cell transplant following ven/aza. Our clinical experience suggests that ven/aza is a safe and promising regimen that should be further explored with late-phase clinical trials.


The effect of cortical repetitive transcranial magnetic stimulation on cognitive event-related potentials recorded in the subthalamic nucleus.
We studied whether the cognitive event-related potentials (ERP) in the subthalamic nucleus (STN) are modified by the modulation of the inferior frontal cortex (IFC) and the dorsolateral prefrontal cortex (DLPFC) with repetitive transcranial magnetic stimulation (rTMS). Eighteen patients with Parkinson's disease who had been implanted with a deep brain stimulation (DBS) electrode were included in the study. The ERPs were recorded from the DBS electrode before and after the rTMS (1 Hz, 600 pulses) over either the right IFC (10 patients) or the right DLPFC (8 patients). The ERPs were generated by auditory stimuli. rTMS over the right IFC led to a shortening of ERP latencies from 277 +/- 14 ms (SD) to 252 +/- 19 ms in the standard protocol and from 296 +/- 17 ms to 270 +/- 20 ms in the protocol modified by a higher load of executive functions (both P < 0.01). The application of rTMS over the DLPFC and the sham stimulation over the IFC showed no significant changes. The shortening of ERP latency after rTMS over the right IFC reflected the increase in the speed of the cognitive process. The rTMS modulation of activity of the DLPFC did not influence the ERP. Connections (the IFC-STN hyperdirect pathway) with the cortex that bypass the BG-thalamocortical circuitries could explain the position of the STN in the processing of executive functions.


Locomotor activity of rats in open field after microinjection of procaine into superior colliculus or underlying reticular formation.
Whereas large lesions of the superior colliculus in rats increase locomotor activity in the open field, bilateral collicular microinjections of muscimol (an agonist of the inhibitory neurotransmitter GABA) have been reported to reduce open-field activity. This difference might be due to muscimol's acting on a subpopulation of collicular neurones, or to some feature of the microinjection technique. The issue was investigated by observing open-field behavior after reversible lesions produced by bilateral microinjections of the local anaesthetic procaine (10-300 micrograms in 0.5 microliter) into midbrain sites. Injections of procaine into the superior colliculus produced effects similar to those reported after muscimol injections: both locomotor activity and other exploratory responses were suppressed, with the rats spending much of their time motionless in an alert posture. In contrast, animals with injections of procaine into the mesencephalic reticular formation (MRF) ventral to the superior colliculus resembled rats given large collicular lesions: they showed very striking increases in locomotor activity, while their rearing and exploratory head movements were reduced. It is suggested that in some experiments large collicular lesions may have increased locomotor activity in the open field because they invaded underlying MRF. However, it is also possible that in rodents the acute effects of collicular inactivation, as assessed by microinjection of muscimol or procaine, are different from the chronic effects that are observed in experiments with electrolytic or radiofrequency lesions.


Activation of MAP kinase by insulin and vanadate in adipocytes from young and old rats.
Vanadate has insulin-like effects in adipocytes without stimulating insulin receptor kinase activity. However, it activates IRS-1 associated PI 3-kinase, suggesting that it mimics insulin effects by stimulating signaling elements downstream of PI 3-kinase. Here we analysed the stimulation of MAPK by insulin and vanadate and observed that both elicit a rapid 3.5-4 fold activation which is abolished by wortmannin and PD98059. Simultaneous addition of insulin and vanadate does not result in an additive effect neither on MAPK nor in MEK. Whereas insulin action is transient, vanadate stimulation lasts up to 20 min. In insulin-resistant adipocytes from old rats, insulin stimulates poorly MAPK, whereas a normal activation is achieved with vanadate. We conclude that: (a) insulin and vanadate use a common signaling pathway from PI 3-kinase to MEK and MAPK; (b) vanadate but not insulin, elicits a sustained activation of both enzymes; (c) this pathway is functional in old rat adipocytes.


Boron neutron capture in prostate cancer cells.
A modified enhanced thermal neutron beam (METNB) assembly at Fermilab was used to irradiate borylphenylalanine (BPA) treated human prostate cancer cells, DU 145. Acceptable cellular uptake levels of BPA and no BPA cytotoxicity were observed. In the absence of BPA, the relative biological effectiveness (RBE) of the METNB was determined to be 2.3-4.8 times greater than gamma rays. An additional 1.2 or 1.4 fold relative enhancement from boron neutron capture (RE(BNC)) was observed for METNB irradiated DU 145 cells treated with 4.9 or 12mM BPA, respectively. The additional cell killing of the BPA loaded DU 145 cells by the METNB at Fermilab is evidence for a BNC enhanced cell killing.


The LncRNA H19/miR-1-3p/CCL2 axis modulates lipopolysaccharide (LPS) stimulation-induced normal human astrocyte proliferation and activation.
Reactive astrocyte proliferation post SCI (spinal cord injury) leads to the formation of glial scars, thus hindering axon regeneration and SCI repair, during which the activation of astrocytes plays a central role. This study attempted to identify the lncRNA-miRNA-mRNA network which exerts a critical effect on normal human astrocyte (NHA) activation and proliferation during SCI inflammation. Herein, lncRNA H19 expression was increased by LPS in NHAs, and H19 was positively correlated with CCL2. H19 silencing in NHAs significantly attenuated the promoting effects of LPS stimulation on NHA proliferation and activation as manifested by inhibited cell viability and DNA synthesis capacity, reduced NHA activation markers, and reduced inflammatory factor concentrations (CCL2, IL-6, and TNF-α). miR-1-3p directly bound to H19 and the CCL2 3'UTR. miR-1-3p overexpression also attenuated the promoting effects of LPS stimulation on NHA proliferation and activation. H19 relieved miR-1-3p-induced inhibition of CCL2 expression by acting as a ceRNA. The inhibition of miR-1-3p could significantly reverse the effects of H19 silencing on NHA proliferation and activation, suggesting that the H19/miR-1-3p axis regulates the proliferation and activation of NHAs via CCL2. In conclusion, lncRNA H19, miR-1-3p, and CCL2 form a lncRNA-miRNA-mRNA axis that modulates NHA proliferation and activation in vitro.


crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans.
We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.


Plant lectins: targeting programmed cell death pathways as antitumor agents.
Lectins, a group of highly diverse, carbohydrate-binding proteins of non-immune origin that are ubiquitously distributed in plants, animals and fungi, are well-characterized to have numerous links a wide range of pathological processes, most notably cancer. In this review, we present a brief outline of the representative plant lectins including Ricin-B family, proteins with legume lectin domains and GNA family that can induce cancer cell death via targeting programmed cell death pathways. Amongst these above-mentioned lectins, we demonstrate that mistletoe lectins (MLs), Ricin, Concanavalin A (ConA) and Polygonatum cyrtonema lectin (PCL) can lead to cancer cell programmed death via targeting apoptotic pathways. In addition, we show that ConA and PCL can also result in cancer cell programmed death by targeting autophagic pathways. Moreover, we summarize the possible anti-cancer therapeutic implications of plant lectins such as ConA, Phaseolus vulgaris lectin (PHA) and MLs that have been utilized at different stages of preclinical and clinical trials. Together, these findings can provide a comprehensive perspective for further elucidating the roles of plant lectins that may target programmed cell death pathways in cancer pathogenesis and therapeutics. And, this research may, in turn, ultimately help cancer biologists and clinicians to exploit lectins as potential novel antitumor drugs in the future.


Curcumin effects on blood lipid profile in a 6-month human study.
Studies in animals and a short-term human study have suggested that curcumin, a polyphenolic compound concentrated in the curry spice turmeric, decreases serum cholesterol concentration. However, no controlled human trials have examined the effect of curcumin on cholesterol. This study investigated the effects of consuming curcumin on the serum lipid profile in men and women. Elderly subjects (n=36) consumed 4 g/d curcumin, 1g/d curcumin, or placebo in a 6-month, randomized, double-blind trial. Plasma curcumin and its metabolites were measured at 1 month, and the serum lipid profile was measured at baseline, 1 month, and 6 months. The plasma curcumin concentration reached a mean of 490 nmol/L. The curcumin concentration was greater after capsule than powder administration. Consumption of either dose of curcumin did not significantly affect triacylglycerols, or total, LDL, and HDL cholesterol over 1 month or 6 months. However, the concentrations of plasma curcumin and serum cholesterol were positively and significantly correlated. Curcumin consumption does not appear to have a significant effect on the serum lipid profile, unless the absorbed concentration of curcumin is considered, in which case curcumin may modestly increase cholesterol.


Trends and Outcomes in Pediatric Patients Undergoing Scoliosis Repair: A Population-Based Study.
Although surgery represents the only definitive treatment for congenital scoliosis, comprehensive information regarding trends in perioperative complications, particularly in the pediatric setting, is lacking. We sought to identify trends in and factors associated with perioperative complications following pediatric scoliosis surgery. In this retrospective cohort study, patients below the age of 21 years undergoing a scoliosis repair procedure were identified from the Premier Healthcare database (2006-2016). The primary outcomes of interest were any complication, cardiopulmonary complications, blood transfusions, intensive care unit (ICU) admission, length of stay (LOS), and cost of hospitalization. Trends in these outcomes over time were analyzed. Multivariable logistic regression models were run to identify factors associated with each of the perioperative outcomes. In the full cohort of 9351 scoliosis patients, 17% experienced any complication, 12% of which were cardiopulmonary in nature, 42% required blood transfusions, and 62% were admitted to the ICU. Median LOS was 5 days (interquartile range [IQR], 4-6) and median cost was $56,375 (IQR, $40,053-$76,311). Annual incidence of complications and blood transfusions as well as LOS and cost decreased significantly throughout the study period. The most consistently observed factors associated with complications were younger age, high comorbidity burden, low institutional case volume, and hospital teaching status. Although the incidence of the studied adverse outcomes in scoliosis surgery has decreased over time, this study shows it remains relatively high (17%). The associations demonstrated help clarify factors associated with complications and may be useful in guiding interventions to improve outcomes.


Conservative treatment of hepatic portal venous gas resulting from non-occlusive mesenteric ischemia: a case report.
A 73-year-old man with severe intellectual disability, malnutrition, and hypoalbuminemia presented to our hospital after experiencing vomiting following dinner. Electrocardiography revealed a sinus rhythm. Plain abdominal radiography showed branching radiolucency in the liver. Abdominal computed tomography (CT) revealed branching gaseous foci of low density in the portal vein and its tributaries, suggesting the presence of hepatic portal venous gas (HPVG). Abdominal contrast-enhanced CT showed a segmental lack of contrast enhancement in the intestinal wall despite the absence of vascular occlusion in the main trunk and branches of the mesenteric artery. The patient was diagnosed with non-occlusive mesenteric ischemia (NOMI) accompanied by HPVG. Peripheral parenteral nutrition, antibiotic treatment, and human serum albumin were administered. The HPVG disappeared approximately 20 h after hospitalization. Intravascular dehydration associated with hypoalbuminemia was considered to be the cause of NOMI; the latter improved through the early correction of dehydration and hypoalbuminemia. The presence of HPVG is usually considered a diagnostic clue in patients with abdominal catastrophe and is associated with high mortality. However, the current case demonstrates the pitfalls of assessing the severity of the underlying condition based solely on the presence of HPVG.


Molecular characterization and expression of cyclic nucleotide gated ion channels 19 and 20 in Arabidopsis thaliana for their potential role in salt stress.
Cyclic nucleotide gated ion channels (CNGCs) in plants have very important role in signaling and development. The study reports role of CNGC19 and CNGC20 in salt stress in A. thaliana. In-silico, genome wide analysis showed that CNGC19 and CNGC20 are related to salt stress with maximum expression after 6 h in A. thaliana. The position of inserted T-DNA was determined (in-vivo) through TAIL-PCR for activation tagged mutants of CNGC19 and CNGC20 under salt stress. The expression of AtCNGC19 and AtCNGC20 after cloning under 35S promoter of expression vectors pBCH1 and pEarleyGate100 was determined in A. thaliana by real-time PCR analysis. Genome wide analysis showed that AtCNGC11 had lowest and AtCNGC20 highest molecular weight as well as number of amino acid residues. In-vivo expression of AtCNGC19 and AtCNGC20 was enhanced through T-DNA insertion and 35S promoter in over-expressed plants under high salt concentration. AtCNGC19 was activated twice in control and about five times under 150 mM NaCl stress level, and expression value was also higher than AtCNGC20. Phenotypically, over-expressed plants and calli were healthier while knock-out plants and calli showed retarded growth under salinity stress. The study provides new insight for the role of AtCNGC19 and AtCNGC20 under salt stress regulation in A. thaliana and will be helpful for improvement of crop plants for salt stress to combat food shortage and security.


H-reflex study in normal children and patients with cerebral palsy.
The H-reflex was studied in 53 children with cerebral palsy, and the results were compared with those obtained for 56 normal control subjects. Pairs of identical stimuli were delivered and the time course of recovery of the amplitude of the H-reflex was determined. Recovery of the H-reflex was increased in the normal control group aged 0 to 12 mos compared to that in the normal control group aged 1 to 9 yrs, especially at interstimulus intervals from 100 to 800 msec. In children with spasticity, marked recoveries of the H-reflex were observed in both age groups, 0 to 12 mos and 1 to 9 yrs, compared to those in normal controls. In the cases of athetosis, recovery of the H-reflex was also marked. In children with ataxia, it was not pronounced and similar to that in normal controls. From these findings, an H-reflex study was considered to be useful for evaluation of central nervous system function in childhood.


Strain-Engineered Nano-Ferroelectrics for High-Efficiency Piezocatalytic Overall Water Splitting.
Developing nano-ferroelectric materials with excellent piezoelectric performance for piezocatalysts used in water splitting is highly desired but also challenging, especially with respect to reaching large piezo-potentials that fully align with required redox levels. Herein, heteroepitaxial strain in BaTiO3 nanoparticles with a designed porous structure is successfully induced by engineering their surface reconstruction to dramatically enhance their piezoelectricity. The strain coherence can be maintained throughout the nanoparticle bulk, resulting in a significant increase of the BaTiO3 tetragonality and thus its piezoelectricity. Benefiting from high piezoelectricity, the as-synthesized blue-colored BaTiO3 nanoparticles possess a superb overall water-splitting activity, with H2 production rates of 159 μmol g-1 h-1 , which is almost 130 times higher than that of the pristine BaTiO3 nanoparticles. Thus, this work provides a generic approach for designing highly efficient piezoelectric nanomaterials by strain engineering that can be further extended to various other perovskite oxides, including SrTiO3 , thereby enhancing their potential for piezoelectric catalysis.


Gastric proton pump with two occluded K+ engineered with sodium pump-mimetic mutations.
The gastric H+,K+-ATPase mediates electroneutral exchange of 1H+/1K+ per ATP hydrolysed across the membrane. Previous structural analysis of the K+-occluded E2-P transition state of H+,K+-ATPase showed a single bound K+ at cation-binding site II, in marked contrast to the two K+ ions occluded at sites I and II of the closely-related Na+,K+-ATPase which mediates electrogenic 3Na+/2K+ translocation across the membrane. The molecular basis of the different K+ stoichiometry between these K+-counter-transporting pumps is elusive. We show a series of crystal structures and a cryo-EM structure of H+,K+-ATPase mutants with changes in the vicinity of site I, based on the structure of the sodium pump. Our step-wise and tailored construction of the mutants finally gave a two-K+ bound H+,K+-ATPase, achieved by five mutations, including amino acids directly coordinating K+ (Lys791Ser, Glu820Asp), indirectly contributing to cation-binding site formation (Tyr340Asn, Glu936Val), and allosterically stabilizing K+-occluded conformation (Tyr799Trp). This quintuple mutant in the K+-occluded E2-P state unambiguously shows two separate densities at the cation-binding site in its 2.6 Å resolution cryo-EM structure. These results offer new insights into how two closely-related cation pumps specify the number of K+ accommodated at their cation-binding site.


Pesticide mixture toxicity assessment through in situ and laboratory approaches using embryo-larval stages of the pacific oyster (Magallana gigas).
Worsened state of oysters in French Arcachon Bay, demand an investigation of possible causes. This study evaluated the effects of an environmentally relevant mixture of five common pesticides on the early-life stages of the Pacific oyster (Magallana gigas). Laboratory assays with artificial mixture and in situ transplantation were complementarily used to investigate a series of sublethal endpoints. The laboratory exposure revealed developmental toxicity at 0.32 μg/L, which corresponds to mixture concentrations in Arcachon Bay. Downregulation of some gene transcriptions was observed at environmental level. No difference in larvae development was revealed among the three sites in Arcachon Bay. This study was the first to evaluate locomotion of oyster larvae exposed in situ. Suspected poor water quality in the inner part of Arcachon Bay was reflected by impairment at the molecular level. In conclusion, current concentrations of the tested pesticides in Arcachon Bay hinder larval development and affect several biological functions.


Visible-light-driven photocatalytic PVDF-TiO2/CNT/BiVO4 hybrid nanocomposite ultrafiltration membrane for dairy wastewater treatment.
Enhancing the performance of polymeric membranes by nanomaterials has become of great interest in the field of membrane technology. The present work aimed to fabricate polyvinylidene fluoride (PVDF)-hybrid nanocomposite membranes and modify them with TiO2 and/or BiVO4 nanoparticles and/or carbon nanotubes (CNTs) in various ratios. Their photocatalytic performance under visible light was also investigated. All modified PVDF membranes exhibited higher hydrophilicity (lower contact angle of water droplets) than that of the neat membrane used as a reference. The membranes were characterized by using bovine serum albumin (BSA) as model dairy wastewater. The hybrid membranes had better antifouling properties as they had lower irreversible filtration resistance than that of the neat membrane. Hybrid PVDF membranes containing TiO2/CNT/BiVO4 showed the highest flux and lowest irreversible resistance during the filtration of the BSA solution. PVDF-TiO2/BiVO4 had the highest flux recovery ratio under visible light (70% for the PVDF mixed with 0.5% TiO2 and 0.5% BiVO4). The hydrophilicity of membrane surfaces increased with the incorporation of nanoparticles, preventing BSA to bind to the surface. This resulted in a slight decrease in BSA and chemical oxygen demand rejections, which were still above 97% in all cases.


Biological implications of gap junction structure, distribution and composition: a review.
Traditionally, all gap junctions have been considered to be identical in structure and function throughout the animal kingdom. Functions ascribed to these membrane specializations have been fundamental and have not been thought to differ significantly with respect to their mechanism of action. More recent studies support the view, however, that structural and compositional diversity may reflect significant functional differences between gap junctions in different classes of tissue but no clear and definitive patterns have yet emerged. This review does not attempt to comprehensively analyze the totality of the vast gap junction and coupling literature but focuses instead upon those recent observations which raise new questions related to the biological activities of gap junctions in different tissues.


lncRNA lnc-POP1-1 upregulated by VN1R5 promotes cisplatin resistance in head and neck squamous cell carcinoma through interaction with MCM5.
Cisplatin resistance is a major therapeutic challenge in advanced head and neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the key signaling pathway for cisplatin resistance in HNSCC cells. Vomeronasal type-1 receptor 5 (VN1R5) was identified as a cisplatin resistance-related protein and was highly expressed in cisplatin-resistant HNSCC cells and tissues. The long noncoding RNA (lncRNA) lnc-POP1-1 was confirmed to be a downstream target induced by VN1R5. VN1R5 transcriptionally regulated lnc-POP1-1 expression by activating the specificity protein 1 (Sp1) transcription factor via the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. VN1R5 promoted cisplatin resistance in HNSCC cells in a lnc-POP1-1-dependent manner. Mechanistically, lnc-POP1-1 bound to the minichromosome maintenance deficient 5 (MCM5) protein directly and decelerated MCM5 degradation by inhibiting ubiquitination of the MCM5 protein, which facilitated the repair of DNA damage caused by cisplatin. In summary, we identified the cisplatin resistance-related protein VN1R5 and its downstream target lnc-POP1-1. Upon upregulation by VN1R5, lnc-POP1-1 promotes DNA repair in HNSCC cells through interaction with MCM5 and deceleration of its degradation.


Cryopreservation of marrow and stromal progenitor cells: use of long-term liquid culture as a measure of the recovery of renewable hematopoietic and stromal cells.
Long-term liquid culture was used to assess the broad functional integrity of murine bone marrow after cryopreservation. Cryopreserved and thawed marrow contained not only renewable hematopoietic stem cells, but also stromal progenitor cells capable of transferring the hematopoietic microenvironment to liquid culture. Long-term liquid culture may be a superior method of assessing the functional potential of cryopreserved marrow when compared to stem cell assays alone.


Estrogen facilitates fear conditioning and increases corticotropin-releasing hormone mRNA expression in the central amygdala in female mice.
Estrogens exert important actions on fear and anxiety-like behavior both in humans and non-human animals. Currently, the mechanisms underlying estrogenic modulation of fear are not known. However, evidence suggests that estrogens may exert their influence on fear within the amygdala. The purpose of the present study was to examine effects of estrogen on fear conditioning. Specifically, the present study examined whether long-term estrogen treatment in ovariectomized female mice via Silastic capsule implantation would facilitate both contextual and cued fear conditioning. In a separate set of experiments, we then examined whether estrogen treatment in ovariectomized female mice would modulate corticotropin-releasing hormone (CRH) gene expression within the amygdala. Long-term estrogen treatment facilitated both contextual and cued fear. Ovariectomized mice treated with estrogen froze significantly more to a context as well as to a discrete auditory cue. In addition, estrogen treatment significantly increased CRH mRNA expression within the central nucleus of the amygdala as measured by in situ hybridization and quantitative PCR. These data raise the possibility that estrogens could influence fear responses in females through their actions in the amygdala.


Cell states beyond transcriptomics: Integrating structural organization and gene expression in hiPSC-derived cardiomyocytes.
Although some cell types may be defined anatomically or by physiological function, a rigorous definition of cell state remains elusive. Here, we develop a quantitative, imaging-based platform for the systematic and automated classification of subcellular organization in single cells. We use this platform to quantify subcellular organization and gene expression in >30,000 individual human induced pluripotent stem cell-derived cardiomyocytes, producing a publicly available dataset that describes the population distributions of local and global sarcomere organization, mRNA abundance, and correlations between these traits. While the mRNA abundance of some phenotypically important genes correlates with subcellular organization (e.g., the beta-myosin heavy chain, MYH7), these two cellular metrics are heterogeneous and often uncorrelated, which suggests that gene expression alone is not sufficient to classify cell states. Instead, we posit that cell state should be defined by observing full distributions of quantitative, multidimensional traits in single cells that also account for space, time, and function.


Assessment of myocardial perfusion during cold stress using thallium-201 scintigraphy in diabetic patients with abnormal changes in left ventricular function during cold stress.
Eleven type-I (insulin-dependent) diabetic patients with abnormal changes in left ventricular function in response to cold stress (CS) were investigated to try and determine the cause of these abnormal responses. Resting M-mode echocardiography demonstrated that all 11 patients had normal left ventricular dimensions and wall motion, thereby excluding overt cardiomyopathy. Thallium-201 scintigraphy was used to assess myocardial perfusion during CS and eight patients were found to have perfusion defects during stress which persisted in four. It is possible that CS unmasks evidence of myocardial ischemia but it is also possible that the abnormal responses to CS reflect altered vasomotor reactivity in the diabetic patient, producing coronary spasm. Left ventricular function may be influenced by many factors in diabetes and an abnormal CS test may not necessarily indicate structural disease. Such tests, however, may help in the further understanding of the pathophysiology of heart disease in diabetes.


Studies on the effects of dietary zinc dose on 65Zn absorption in vivo and on the effects of Zn status on 65Zn absorption and body loss in young rats.
Weanling male rats were maintained on diets containing 5, 10, 20, 40, 80 or 160 mg zinc/kg for 14 d. On day 15 they received 65Zn either by intraperitoneal injection or in a test meal containing 20 mg Zn/kg. After dosing, the rats were again maintained on the diets they had received previously. Whole-body 65Zn retention was measured immediately after dosing and daily for a further 9 d. From regression analysis of the semi-logarithmic plots of 65Zn retention from 0 to 192 h after 65Zn administration, the true extent of 65Zn absorption and the biological half-life (t1/2) of body 65Zn stores were calculated. At the end of the experiment, the rats were killed and the entire small intestines of some rats from each group were rapidly flushed out to remove food and faecal residues, frozen in liquid nitrogen and stored under an atmosphere of N2 at -20 degrees before separation of cytosolic Zn-binding fractions by gel filtration on Sephadex G-75. The results suggest that rats which received diets that were either deficient (5 mg Zn/kg), marginal (10 mg Zn/kg) or adequate (20-80 mg Zn/kg) in Zn achieved homeostatic regulation of body Zn by changes in both the extent of Zn absorption and excretion. However, when Zn supply was excessive, increasing from 80 to 160 mg Zn/kg, no further changes were seen in Zn absorption, and homeostatic control appeared to be effected entirely by changes in rates of body Zn loss. Gel chromatography of intestinal cytosol on Sephadex G-75 revealed that Zn was associated with two major fractions. The first (peak 1) had a molecular weight (MW) greater than 75 kdaltons and the second (peak 2), a MW of approximately 10 kdaltons and was assumed to be metallothionein. There was no obvious relation between the amount of Zn bound to peak 1 and dietary Zn content. In contrast, the amount of Zn recovered in peak 2 increased linearly with increasing dietary Zn content. Comparisons between the effect of dietary Zn content on Zn bound to peak 2 and 65Zn retention may, depending on the range of Zn intakes, indicate possible roles for intestinal metallothionein in the control of Zn absorption or excretion. A study of the effects of dietary dose of 65Zn on the extent of 65Zn absorption in rats of normal Zn status indicated a possible biphasic relation. At low doses (5-40 mg Zn/kg) 65Zn absorption appeared to exhibit a curvilinear response to increasing 65Zn dose, indicating possibly a saturable process.(ABSTRACT TRUNCATED AT 400 WORDS)


Development of atropine sulphate nasal drops and its pharmacokinetic and safety evaluation in healthy human volunteers.
The increased use of organophosphate (OP) insecticides and the ever increasing possibility of terror groups using nerve agents underscore the need to develop effective and safe antidotes against OP poisoning. While intramuscular administration of nerve gas antidotes like atropine sulphate has certain lacunae, intravenous route is neither practical nor feasible in the field conditions for mass casualties. The objective was to develop a novel atropine sulphate nasal drop formulation, evaluate and characterize it using scintigraphy and to carry out safety-efficacy study in human volunteers with a view to obtain early pharmacological effects in comparison to the existing options, particularly the conventional intramuscular route. Permeability studies were done using atropine sulphate solution containing variable amount of chitosan. Radiometric method was developed for scintigraphy studies while standard spectroscopy was used for the quantification of atropine sulphate in fluids. Concentration of atropine sulphate in nasal drops to produce therapeutic concentration in blood was calculated. Six volunteers (age range 18-53 years) were administered the formulation delivering 6mg of atropine sulphate each. Bioavailability and atropinization were noted serially. Based on the results of in vitro, human scintigraphy and analytical data, 1% atropine sulphate-0.5% chitosan was chosen as the final nasal formulation. Human bioavailability curve was created which showed that the therapeutic concentration of the drug in blood was reached within 5min with nasal drops suggesting that drug delivery through the nasal route is significantly better than the intramuscular route. Unpaired t-test between the means of baseline value of heart rate and that of each time interval showed that increase in heart rate of all the volunteers became significant at 15min (P<0.01) and extremely significant at 30min (P<0.001). Correlation was evident from 5min (c>0.7). Pupil diameter showed maximal increase at 30min (P<0.01). This novel product, 1% atropine sulphate-0.5% chitosan nasal drops might be a safe and efficacious emergency treatment of organophosphorous poisoning with several advantages over the present management, including early atropinization and capability of mass treatment in least amount of time.


Biochemical characterization and membrane fluidity of membranous vesicles isolated from boar seminal plasma.
Mammalian seminal plasma contains membranous vesicles (MV), which differ in composition and origin. Among these particles, human prostasomes and equine prostasome-like MV have been the most studied. The aim of the present work is to characterize the biochemical composition and membrane fluidity of MV isolated from boar seminal plasma. The MV from boar seminal plasma were isolated by ultracentrifugation and further purification by gel filtration on Sephadex G-200. The MV were examined by electron microscopy (EM), amount of cholesterol, total phospholipid, protein content, and phospholipid composition were analyzed. Membrane fluidity of MV and spermatozoa were estimated from the electron spin resonance (ESR) spectra of the 5-doxilstearic acid incorporated into the vesicle membranes by the order parameter (S). The S parameter gives a measure of degree of structural order in the membrane and is defined as the ratio of the spectral anisotropy in the membranes to the maximum anisotropy obtained in a rigidly oriented system. The S parameter takes into consideration that S = 1 for a rapid spin-label motion of about only one axis and S = 0 for a rapid isotropic motion. Intermediate S values between S = 0 and S = 1 represents the consequence of decreased membrane fluidity. The EM revealed the presence of bilaminar and multilaminar electron-dense vesicles. Cholesterol to phospholipid molar ratio from the isolated MV was 1.8. Phospholipid composition showed a predominance of sphingomyelin. The S parameter for porcine MV and for boar spermatozoa was 0.73 +/- 0.02 and 0.644 +/- 0.008, respectively, with the S for MV being greater (p < 0.001) than the S for spermatozoa. The high order for S found for boar MV was in agreement with the greater cholesterol/phospholipids ratio and the lesser ratio for phosphatidylcholine/sphingomyelin. Results obtained in the present work indicate that MV isolated from boar semen share many biochemical and morphological characteristics with equine prostasome-like MV and human prostasomes. The characteristics of the porcine MV of the seminal plasma, however, differed from those of boar sperm plasma membranes.


[Clinical simulation for quality improvement in the care of postpartum haemorrhage].
To analyse and redesign the care process for patients with severe post-partum haemorrhage using simulation and a human factors approach. The project was developed between June 2016 and May 2017. The working group was created following the participatory leadership method and included professionals with knowledge and position to influence the organisation. The existing process and clinical protocols were reviewed. An in situ simulation was used to observe team performance in the hospital recovery room. Information was expanded through an open and structured interview with professionals selected for their experience in the subject matter. Task analysis was used to document the process, and a failure mode and effects analysis was made to assess system vulnerabilities. Results were mapped using a flow chart. The analysis identified six groups of people working on different tasks, their activities and sequence of action, the importance of naming an explicit coordinator, the way in which information is disseminated and transformed, and the stages where it is necessary to share information and make key clinical decisions. The existing clinical protocols and the aids established in order to use the available resources were integrated, including blood draws and haemostatic agents, as well as an administration guide. The analysis of the patient care process in post-partum haemorrhage using in situ simulation with a human factors perspective, including an analysis of the interaction between professionals and the system where they work, established a detailed and personalised map of the components that determine how work flows through the organisation.


Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study.
The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories. Observational cohort study. Adults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753). 2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events. Adjudicated ASCVD events after the year 1 study visit. We calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death. There were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively. Data on whether participants were taking a maximally tolerated statin dosage were unavailable. The 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin.


Long-term treated HIV infection is associated with platelet mitochondrial dysfunction.
HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. Here, we studied platelet mitochondrial DNA content (mtDNApl) and mitochondrial function in people living with HIV (PLHIV) and related this to platelet function. In a cohort of 208 treated PLHIV and 56 uninfected controls, mtDNApl was quantified, as well as platelet activation, platelet agonist-induced reactivity and inflammation by circulating factors and flow cytometry. In a subgroup of participants, the metabolic activity of platelets was further studied by mitochondrial function tests and the Seahorse Flux Analyzer. PLHIV had significantly lower mtDNApl compared to controls (8.5 copies/platelet (IQR: 7.0-10.7) vs. 12.2 copies/platelet (IQR: 9.5-16.6); p < 0.001), also after correction for age, sex and BMI. Prior zidovudine-use (n = 46) was associated with a trend for lower mtDNApl. PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. MtDNApl correlated positively with both platelet parameters and correlated negatively with inflammatory marker sCD163. Mitochondrial function tests in a subgroup of participants confirmed the presence of platelet mitochondrial respiration defects. Platelet mitochondrial function is disturbed in PLHIV, which may contribute to platelet dysfunction and subsequent complications. Interventions targeting the preservation of normal platelet mitochondrial function may ultimately prove beneficial for PLHIV.


Effects of soil properties and long aging time on the toxicity of exogenous antimony to soil-dwelling springtail Folsomia candida.
The most existing studies on the toxicity of antimony (Sb) were performed in limited types of soil and after short aging time. Effects of soil properties and long aging time on chronic toxicity of Sb(III) and Sb(V) to model organism Folsomia candida were studied in the laboratory studies. The results showed that after the Sb(V)-treated soils were aged for 365 d, the Sb exhibited no toxicity to survival and reproduction even at the nominal highest concentration of 12,800 mg kg-1 in ten types of soils with distinct differences in soil properties. In the Sb(III)-treated ten soils aged only for 30 d, the concentrations causing 50% mortality (LC50) and concentrations inhibiting 50% reproduction (EC50) were 1288-3219 mg kg-1 and 683-1829 mg kg-1, respectively. The LC50 were higher than the highest test concentration and the EC50 significantly increased by 2.24-6.16 fold after the Sb(III)-treated soils were aged for 150 d, and soil pH was the most important single factor explaining the variance in aging effects. After the aging time was 365 d, similar with Sb(V)-treated soils, no toxicity were observed in the most Sb(III)-treated soils, indicating the increasing aging effects with aging time. Regression analysis indicated that the OM and pH were the most important single factor predicting Sb toxicity to reproduction in Sb(III)-treated soils aged for 30 and 150 d, respectively.


Does Religiosity Reduce Narcissistic Personality Disorder? Examining the Case of Muslim University Students.
The purpose of this study was to examine the influences of religiousness on the prevalence of Narcissistic Personality Disorder (NPD) among young adults. Prevalence of three forms of Allportian religious orientation, three forms of quest religious orientation and seven symptoms of NPD were examined through self-reported measures. 618 randomly selected Muslim students from the four public sector Pakistani universities participated in the study. Three research instruments comprising Religious Orientation Scale developed by Gorsuch and McPherson, Quest Scale developed by Batson and Schoenrade and Narcissistic Personality Inventory developed by Raskin and Terry were used to collect the data. All subscales demonstrated more than .70 Cronbach Alpha Coefficients. The findings demonstrate comparatively higher presence of intrinsic, extrinsic personal and extrinsic social religious orientations among the Pakistani Muslim young adults. The presence of NPD symptoms remains higher among the participants too. The study concludes that the religious orientations significantly explain the variances in the prevalence of NPD symptoms among the Muslim university students with the direct effects of intrinsic and extrinsic personal religious orientations and indirect effects of quest religious orientations.


[Morphology versus prognosis in renal cell carcinoma a statistical approach].
In a group of 102 selected cases of renal cell carcinoma which at various periods after nephrectomy terminated fatally, age, sex, and 23 gross and/or histologic tumor characteristics were examined, subclassified, and evaluated. An attempt was made to correlate these parameters statistically to postoperative survival time. A newly developed and programmed statistical method, i.c. "dichotomic variance analysis", proved to be superior to both multiple regression and cluster analysis. Using infiltrative-destructive tumor growth, polymorphy, and chromatin density of tumor cell nuclei, extension of renal vein invasion, age and sex, as the only 6 required out of 25 distinguished tumor parameters, this statistical multivariate method comprised 7 distinctive groups of different mean geometrical postoperative survival time, obviously corresponding to 7 tumor types of increasing degree of malignancy. By step-wise dichotomic splitting of tumor groups it therefore was possible to delinate schematically some of the complex connections between the criteria or variables of prognostic significance. Conceivable sources of errors possibly influencing reproducibility and practical applicability of the presented dichotomic variance analysis in evaluating prognostic criteria in renal cell carcinoma are discussed.


Mitotic recombination and segregation of satellites in Bloom's syndrome.
Mitotic recombination in satellite stalks--a phenomenon often difficult to distinguish from satellite association--was studied in a sister and a brother with Bloom's syndrome. Segregation after recombination was analyzed in the lymphocytes of the sister who had Q-bright satellites. Her cells varied greatly both in regard to the acrocentrics which displayed Q-bright satellites and the number of such satellites per cell. In 58 cells a total of 31 different patterns were seen. In 83 cells of 6 controls who also had Q-bright satellites on at least one acrocentric chromosome, not one cell was found in which the pattern differed from that characteristic of the person. Obviously exchanges between satellite stalks in patients with Bloom's syndrome are fairly frequent (estimated lower limit 6/1000) and very rare in persons who do not have this syndrome (estimated 0.1/1000).


Cytology and intrinsic organization of the perihypoglossal nuclei in the cat.
The morphology of the neurons in the perihypoglossal nuclei (nucleus prepositus, nucleus intercalatus, and nucleus of Roller) of the cat was studied in normal Nissl material, and by intracellular injection of horseradish peroxidase. The neurons in the nucleus prepositus were morphologically heterogeneous. Many of the cells in the ventromedial part of the caudal prepositus had relatively large somata, and complex dendritic trees which arose from numerous proximal dendrites and ramified extensively in the ventromedial aspect of the prepositus. These neurons had thick axons which typically did not give rise to local collaterals. The cells in the dorsolateral part of the caudal prepositus tended to have small somata, and dendritic trees which arborized in that region of the nucleus. The axons of these small cells frequently gave rise to local collaterals which terminated in the prepositus. Most of the cells in the prepositus had medium-sized somata and relatively few dendrites which branched in an isodendritic manner and extended for long distances, frequently leaving the nucleus. These "principal" prepositus neurons had axons which arborized unilaterally, and often gave rise to collaterals which terminated in either the ipsilateral or contralateral prepositus. The neurons in the nucleus of Roller and nucleus intercalatus which were intracellularly injected with horseradish peroxidase resembled the multidendritic and small prepositus cells, respectively. The intrinsic connectivity of the perihypoglossal nuclei was also studied by injecting horseradish peroxidase or 3H-leucine into the prepositus nucleus. The results of these experiments suggest that the perihypoglossal nuclei are highly interconnected bilaterally, although the large cells in the ventromedial prepositus and the nucleus of Roller contribute little to these intrinsic connections, and are not major recipients of intrinsic inputs. On the other hand, the magnitude of the reciprocal connections between the prepositus and the nucleus intercalatus suggests that they are functionally related.


Separation and characterization of liposomes using asymmetric flow field-flow fractionation with online multi-angle light scattering detection.
Liposomes, mainly formed by phospholipids and cholesterol that entrapped different compounds, were separated and characterized using asymmetric flow field-flow fractionation (AF4) coupled with a multi-angle light scattering detector (MALS). AF4 allows the separation of liposomes according to their hydrodynamic size, and the particle size can be estimated directly by their elution time. Besides, different synthesized liposome suspensions of liposomes with different species encapsulated in different places in liposomes were prepared with analytical purposes to be studied. These liposomes were: empty liposomes (e-Ls), magnetoliposomes (MLs) with Fe3O4@AuNPs-C12SH inside the lipid bilayer, and long-wavelength fluorophores encapsulated into the aqueous cavity of liposomes (Ls-LWF). The optimization process of the variables that affect the fractionation has been established. The separation effectiveness has been compared with the results achieved with a photon-correlation spectroscopy analyzer based on dynamic light scattering (DLS) and transmission electron microscopy (TEM), used in self-assembly structures characterization. In all cases, three different classes of liposomes have been obtained; two are commonly appaired in all studied samples, while only a third class is characteristic for each of the liposomes. This mean that the proposed methodology could be used for identifying liposomes according to the encapsulated material.


Asthma Remission by Age at Diagnosis and Gender in a Population-Based Study.
Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seemingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce. To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission. In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was categorized by age at diagnosis to early- (0-11 years), intermediate- (12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months. Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, significant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.37-3.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD. Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission.


Upregulation of Systemic Inflammatory Pathways Following Anterior Cruciate Ligament Injury Relates to Both Cartilage and Muscular Changes: A Pilot Study.
In conjunction with cartilage breakdown, muscle maladaptation including atrophy and increased fibrosis have been observed in the quadriceps following anterior cruciate ligament (ACL) injury. Previously observed upregulated muscle-related proteins in the synovial fluid following ACL rupture allude to cellular communication between the joint and muscle. Therefore, the purpose of this study was to determine whether muscle-related analytes are differentially expressed in the serum. Sixteen patients with an acute ACL tear participated in this IRB-approved study. Serum was obtained at two different time points at a mean of 6 and 14 days post-injury, and serum was analyzed by a highly multiplexed assay of 1,300 proteins. Pathway analysis using DAVID was performed; genes included met three criteria: significant change between the two study time points using a paired t test, significant change between the two study time points using a Mann-Whitney non-parametric test, and significant Benjamini post hoc analysis. Twelve analytes significantly increased between time points. Proteins chitinase-3-like protein 1 (p = 0.01), insulin-like growth factor binding protein 1 (p = 0.01), insulin-like growth factor binding protein 5 (p = 0.02), renin (p = 0.004), and lymphotoxin alpha 1: beta 2 (p = 0.03) were significantly upregulated in serum following acute ACL injury. The current results confirm the inflammatory pattern previously seen in the synovial fluid thought to play a role in the progression of post-traumatic osteoarthritis after ACL injury, and this data also provides further insights into important communication between the joint and quadriceps group, whose function is important in long term health. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:387-392, 2020.


Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease.
Microglial phagocytosis is an energetically demanding process that plays a critical role in the removal of toxic protein aggregates in Alzheimer's disease (AD). Recent evidence indicates that a switch in energy production from mitochondrial respiration to glycolysis disrupts this important protective microglial function and may provide therapeutic targets for AD. Here, we demonstrate that the translocator protein (TSPO) and a member of its mitochondrial complex, hexokinase-2 (HK), play critical roles in microglial respiratory-glycolytic metabolism and phagocytosis. Pharmacological and genetic loss-of-function experiments showed that TSPO is critical for microglial respiratory metabolism and energy supply for phagocytosis, and its expression is enriched in phagocytic microglia of AD mice. Meanwhile, HK controlled glycolytic metabolism and phagocytosis via mitochondrial binding or displacement. In cultured microglia, TSPO deletion impaired mitochondrial respiration and increased mitochondrial recruitment of HK, inducing a switch to glycolysis and reducing phagocytosis. To determine the functional significance of mitochondrial HK recruitment, we developed an optogenetic tool for reversible control of HK localization. Displacement of mitochondrial HK inhibited glycolysis and improved phagocytosis in TSPO-knockout microglia. Mitochondrial HK recruitment also coordinated the inflammatory switch to glycolysis that occurs in response to lipopolysaccharide in normal microglia. Interestingly, cytosolic HK increased phagocytosis independent of its metabolic activity, indicating an immune signaling function. Alzheimer's beta amyloid drastically stimulated mitochondrial HK recruitment in cultured microglia, which may contribute to microglial dysfunction in AD. Thus, targeting mitochondrial HK may offer an immunotherapeutic approach to promote phagocytic microglial function in AD.


Pediatric reference intervals for 19 biologic variables in healthy children.
We defined age- and sex-specific reference intervals for 19 biologic variables in serum samples from healthy children, 1 to 22 years of age, using common laboratory equipment. Upper and lower reference intervals were defined as the estimated 2.5 and 97.5 percentiles of the distribution. For variables (y) that varied with age, the relationship of y to age was modeled with polynomial regression. Parametric percentile estimates specific to each age were then calculated as the predicted y value +/- 1.96 . SD, in which SD = the standard deviation of the residuals. For variables not associated with age, the nonparametric 2.5 and 97.5 sample percentiles were used to define the reference intervals. No significant age or sex differences were found for serum sodium, total protein, glucose, direct bilirubin, or albumin. Potassium, chloride, and urea showed constant values in children that were higher than adult values in the case of potassium and chloride and lower than adult values in the case of urea. No sex-related differences were seen for these analytes. Creatinine, uric acid, and bicarbonate showed an upward trend in values with increasing age, whereas aspartate aminotransferase, phosphorus, and total and ionized calcium showed a downward trend with increasing age. Sex-related differences were noted for these analytes. The immunoglobulins (IgG, IgA, and IgM) showed an upward trend with increasing age, with no sex-related differences except for IgM in children.


The role of perinatal psychiatry access programs in advancing mental health equity.
This editorial presents: 1) a review of Perinatal Psychiatry Access Programs as an integrated care model with potential for promoting perinatal mental health equity; and 2) a summary of how the model has been and can be further adapted to help achieve perinatal mental health equity in geographically diverse settings. Within the editorial, we highlight Access Programs as a promising model for promoting perinatal mental health equity. This editorial is supported by original descriptive data on the Lifeline for Moms National Network of Perinatal Psychiatric Access Programs. Descriptive data is additionally provided on three statewide Access Programs. The Access Program model, and the accompanying Network of Access Programs, is a multi-level approach demonstrating promise in reducing perinatal mental health inequities. Access Programs demonstrate potential to implement interventions to address well-documented inequities in perinatal mental healthcare access at the patient-, clinician-, practice-, community-, and policy-levels. For Access Programs to leverage their potential to advance perinatal mental health equity, systematic efforts are needed that include partnership with impacted communities and implementation teams.


[Correlation between the in vivo dynamics of redox processes and neuronal electrical activity in response to angiotensin II and cyclic AMP].
The biologically active substances induced mostly similar changes of the restorative equivalents level whereas the pattern of equivalents varied in neuronal activity of the mammal brain cortex. The effects of angiotensin II and cAMP on neuronal activity were different. The data obtained suggest that the angiotensin II effect on neurons is actualized both through the cAMP system and through other molecular mechanisms.


Synaptic expression of the high-affinity kainate receptor subunit KA2 in hippocampal cultures.
Non-N-methyl-D-aspartate glutamate receptors are responsible for fast excitatory neurotransmission in the mammalian CNS. These receptors are rapidly activated and desensitized in the presence of glutamate, and are often further subdivided into alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid and kainate receptors based on their selective agonists. Non-NMDA glutamate receptors are composed of multiple subunits which recently have been cloned, and studies on the recombinant glutamate receptors have helped clarify the distinctions between AMPA and kainate-preferring glutamate receptors. Although the subunits which make up both AMPA and kainate receptors have a widespread distribution, most currents recorded in vivo are characteristic of recombinant AMPA receptors. To help clarify the functional role of high-affinity kainate receptors, we have characterized the expression of a high-affinity kainate receptor subunit, KA2, in cultured hippocampal neurons. Using immunocytochemistry, we found that KA2 was expressed in hippocampal neurons at all times during the development of the cells in culture, and the subunit was enriched in dendritic spines after about 14 days. The subcellular distribution of KA2 paralleled that of the AMPA receptor subunit GluR1, with the AMPA and kainate subunits being colocalized at all times in culture. The enriched KA2 immunoreactivity co-localized with the synaptic vesicle protein synaptophysin at the resolution of light microscopy, indicating synaptic localization of KA2. Although the kainate subunit KA2 co-localized with the AMPA subunit GluR1, co-immunoprecipitation experiments demonstrated a direct interaction between the AMPA receptor subunits GluR1 and GluR2/3, but not between GluR1 and the kainate subunits GluR6/7 or KA2. We therefore, conclude that both AMPA and kainate receptor subunits are enriched in the same dendritic spines, yet do not combine to form receptor complexes.


Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents.
Polyunsaturated fatty acids such as docosahexaenoic acid (DHA), linolenic acid, and linoleic acid were linked to the C-2' position of the second-generation taxoids that could overcome MDR caused by overexpressed ABC transporters. The new conjugates, tested in vivo, exhibited strong activity against drug-resistant colon cancer and drug-sensitive ovarian cancer xenografts in mice. Two of the new conjugates, DHA-SB-T-1214 and DHA-SB-T-1213, were found to achieve the total regression of drug-resistant and drug-sensitive tumors, respectively, in the animal models with substantially reduced systemic toxicity.


Increases in compulsivity, inflammation, and neural injury in HIV transgenic rats with escalated methamphetamine self-administration under extended-access conditions.
The abuse of stimulants, such as methamphetamine (METH), is associated with treatment non-compliance, a greater risk of viral transmission, and the more rapid clinical progression of immunological and central nervous system human immunodeficiency virus (HIV) disease. The behavioral effects of METH in the setting of HIV remain largely uncharacterized. We used a state-of-the-art paradigm of the escalation of voluntary intravenous drug self-administration in HIV transgenic (Tg) and wildtype rats. The rats were first allowed to self-administer METH under short-access (ShA) conditions, which is characterized by a nondependent and more "recreational" pattern of METH use, and then allowed to self-administer METH under long-access (LgA) conditions, which leads to compulsive (dependent) METH intake. HIV Tg and wildtype rats self-administered equal amounts of METH under ShA conditions. HIV Tg rats self-administered METH under LgA conditions following a 4-week enforced abstinence period to model the intermittent pattern of stimulant abuse in humans. These HIV Tg rats developed greater motivation to self-administer METH and self-administered larger amounts of METH. Impairments in function of the medial prefrontal cortex (mPFC) contribute to compulsive drug and alcohol intake. Gene expression profiling of the mPFC in HIV Tg rats with a history of escalated METH self-administration under LgA conditions showed transcriptional evidence of increased inflammation, greater neural injury, and impaired aerobic glucose metabolism than wildtype rats that self-administered METH under LgA conditions. The detrimental effects of the interaction between neuroHIV and escalated METH intake on the mPFC are likely key factors in the greater vulnerability to excessive drug intake in the setting of HIV.


Streptococcus gallolyticus subspecies pasteurianus bacteremia accompanied by acute pancreatitis.
While Streptococcus gallolyticus subsp. gallolyticus has a well-known association with colorectal cancer, an epidemiological association between S. gallolyticus subsp. pasteurianus (SGSP) and hepatobiliary diseases has been suggested. Here we described a case of gallstone pancreatitis and SGSP bacteremia in which species-identification by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) helped to diagnose the biliary etiology. A 61-year-old Japanese man without history of alcohol consumption was hospitalized for acute pancreatitis. His past medical history included endoscopically treated familial adenomatous polyposis. A blood culture grew gram-positive cocci, identified to be SGSP by MALDI-TOF MS. A contrast-enhanced computed tomography scan showed pancreatic enlargement and increased fatty tissue concentration around the perirenal and pararenal space. He was diagnosed with acute pancreatitis and subsequently recovered after appropriate antimicrobial therapy and supportive care. Subsequent magnetic resonance cholangiopancreatography showed gallstones in the gallbladder neck, suggesting the cause of the acute pancreatitis. Seven months after admission, cholecystectomy was performed for cholelithiasis. This case highlights that the identification of subspecies enabled by MALDI-TOF MS supports the diagnosis of the underlying etiology from the microbiological point of view.


Portal vein recanalisation alone to treat severe portal hypertension in non-cirrhotic patients with chronic extrahepatic portal vein obstruction.
We aimed to evaluate long-term outcome of patients with chronic non-cirrhotic extrahepatic portal vein obstruction (CNC-EHPVO) who underwent portal vein recanalisation (PVR) without transjugular intrahepatic portosystemic shunt (TIPS) insertion and to determine factors predicting PVR failure and stent occlusion. This retrospective monocentric study included all patients who underwent PVR without TIPS insertion in the context of CNC-EHPVO between the years 2000 and 2019. Primary patency was defined by the absence of a complete stent occlusion on follow-up imaging. A total of 31 patients underwent PVR with a median follow-up of 52 months (24-82 months). Indications were gastrointestinal bleeding (n = 13), abdominal pain attributed to CNC-EHPVO (n = 7), prior to abdominal surgery (n = 4), and others (n = 7). Technical success was obtained in 27 patients. PVR failure was associated with extension within the intrahepatic portal veins (p = 0.005) and recanalisation for abdominal pain (p = 0.02). Adverse events occurred in 6 patients with no mortality. Anticoagulation was administered in 21 patients after technical success of PVR. In patients with technical success, 5-year primary patency was 73% and was associated with improved muscle mass (p = 0.007) and decreased spleen volume (p = 0.01) at 1 year. Furthermore, 21 (78%) patients with PVR technical success were free of portal hypertension complication at 5 years. PVR without TIPS insertion was feasible and safe in selected patients with CNC-EHPVO and portal hypertension with past or expected complications. Primary patency at 5 years was obtained in 3 of 4 patients with technical success of PVR and was associated with a control of complications of CNC-EHPVO. PVR was associated with improvement of sarcopenia and decreased spleen volume at 1 year. Patients with chronic obstruction of the portal vein and without cirrhosis or malignancy can develop complications related to the high pressure in the venous system. The present study reports long-term favourable outcome of patients in whom the obstruction was treated with stents.


An auto real-time jump tagging system for exploring stereotyped jumping behavior in mice.
The jump is one of the common stereotyped behavior in rodents which can be found in certain types of disease models, such as addiction. It can be easily identified by the human eye. However, it is difficult to be tagged in real-time by manual operation, which limits the detailed exploration of its neural mechanisms with the new techniques, such as fiber photometry recording. Here we introduced an auto real-time jump tagging system (Art-JT system) to record the jump based on online monitoring the pressure changes of the floor in which the mouse is free exploring. Meanwhile, the Art-JT system can send the digital signal of the jump timing to the external device for tagging the events in the fiber photometry system. We tested it with the mice induced by Naloxone precipitated withdrawal jumping and found that it could accurately record the jump events and provide several detailed parameters of the jump. We also confirmed that the jump was correlated with the medial prefrontal cortex and primary motor cortex neuronal activities by combining the Art-JT system, GCaMP6 mice, and fiber photometry system. Our results suggested that the Art-JT system may be a powerful tool for recording and analyzing jumps efficiently and helping us to understand stereotyped behavior.


Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study.
This study's primary purpose was to determine whether earlier findings suggesting an association between sporadic Creutzfeldt-Jakob disease (sCJD), a transmissible spongiform encephalopathy of humans and specific dietary components could be replicated. The a priori hypotheses were that consumption of (i) foods likely to contain organ tissue and (ii) raw/rare meat are associated with increased sCJD risk. Population-based case-control study. Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 4 years. An 11-state case-control study of pathologically confirmed, definite sCJD cases, matched controls, and a sample of control-surrogates was conducted. Ninety-six percent (106/110) of the case data was obtained in 1991-1993, prior to variant CJD publicity. Using control self-responses, consumption of hot dogs, sausage, pepperoni, kielbasa, "other" canned meat, poultry liver, any stomach/intestine, beef stomach/intestine, any organ tissue, and beef organ tissue was individually associated with increased sCJD risk; odds ratios (OR) ranged from 2.4 to 7.2 (0.003 <p<0.025). Rare/raw meat consumption was associated with sCJD (OR=2.0; p<0.05). Greater consumption of hot dogs, bologna, salami, sausage, pepperoni and kielbasa was associated with significantly higher risk. The OR for gizzard consumption was 7.6, p<0.04. Bologna, salami, any liver, beef liver and pork stomach/intestine were marginally associated with sCJD: ORs ranged from 1.7 to 3.7; 0.05 <p< 0.10. Brain consumption was not associated with an elevated risk. Analyses using control-surrogate data indicate that use of the control self-responses did not bias the results away from the null hypothesis. The a priori hypotheses were supported. Consumption of various meat products may be one method of transmission of the infectious agent for sCJD.


Contrast enhanced ultrasound (CEUS) applications in neurosurgical and neurological settings - New scenarios for brain and spinal cord ultrasonography. A systematic review.
Contrast-enhanced ultrasound (CEUS) is a real-time, feasible technique. Both intraoperatively and bedside, it satisfies the need for serial assessment and easy performability. Initially employed in neuro-oncology, it has recently overcome this first application. We aimed to evaluate the literature and give a comprehensive view of its use in the fields listed below. A systematic review of all pertinent literature was performed via PubMed access according PRISMA P guidelines. Studies not involving human adults and not reporting original data were excluded. Cross-check of references of selected articles was performed to complete bibliographical research. 67 articles were then grouped by field of application: Oncology (26 articles) further subdivided in a) cranial tumors (23 articles) and b) spinal tumors (3 articles); Vascular (31 articles), divided in three sections: a) aneurysms, AVMs and AVFs surgery (6 articles), b) cerebral perfusion assessment and acute stroke patients management (15 articles), c) carotid plaques treatment (10 articles); TBI (2 articles); Pediatrics (4 articles); Peripheral nerve surgery (2 articles) and others (2 articles). CEUS versatility across the aforementioned areas was analyzed, underlining its complementarity to other well-settled imaging techniques. This review is focused on reporting CEUS advantages and disadvantages, suggesting a further broadening of the already numerous applications.


[Ultrasound and CT imaging formation of hepatic metastases: microangiographic study. Preliminary report (author's transl)].
The authors discuss the echographic and CT imaging of hepatic metastases relying on a comparative experimental echographic, CT, microangiographic and histologic study on isolated livers. They stress the role of the vascular pattern in the ultrasound and CT imaging formation.


Relaxation behavior of polyethylene welded joints.
The paper presents results of the investigation of structure relaxation and thermal properties of PE-80 and PE-100 polyethylene hot-tool butt welds. It was found that a weld with the re-crystallized crystalline structure is formed during the welding of dissimilar types of polyethylene. It is shown that within a long period (1 year) the relaxation occurs not only in amorphous but also in the crystalline phase (crystalline α-form transforms into mixed αβ-form), with respective changes in polyethylene properties.


Retinal development in humans: the roles of differential growth rates, cell migration and naturally occurring cell death.
The distribution of ganglion cells throughout the retinal ganglion cell layer is non-uniform in adult mammals. This paper reviews some of our data describing the development of retinal ganglion cell topography in the human fetus. Results indicated that early in the fetal period the distribution of cells in the ganglion cell layer is almost uniform, but by the end of gestation there is a gradient in cell density of about 10:1 (central:peripheral). Peripheral retina grows more rapidly than the central retina prior to about 23 weeks gestation, but this differential growth rate apparently has little effect on the development of a centro-peripheral density gradient. The gradient appears between about 18 and 30 weeks gestation, and during this period there appears to be a greater rate of cell death in the ganglion cell layer of the peripheral retina. Cell density at the developing fovea is less than the perifoveal cell density at all ages, suggesting that ganglion cells migrate from foveal into perifoveal regions throughout the fetal period.


Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification.
Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca2+]i) is one of the factors predicted to regulate cornification, the dynamics of [Ca2+]i in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca2+]i in mouse skin. [Ca2+]i was elevated in basal cells on the second time scale in three spatiotemporally distinct patterns. The transient elevation of [Ca2+]i also occurred at the most apical granular layer at a single cell level, and lasted for approximately 40 min. The transient elevation of [Ca2+]i at the granular layer was followed by cornification, which was completed within 10 min. This study demonstrates the tightly regulated elevation of [Ca2+]i preceding the cornification of epidermal keratinocytes, providing possible clues to the mechanisms of cornification.


Flatness and boundness of photonic drumhead surface state in a metallic lattice.
Nodal chain (NC) semi-metals have the degeneracy of interlacing rings in their band structure in momentum space. With the projection of degenerate rings towards crystal boundaries, there is a special type of surface dispersion appearing at surface Brillouin zone and termed drumhead surface state (DSS). Previously, experimental investigations on photonic NC and DSS have been done on metallic photonic crystals at microwave frequencies. However, far-field detection of DSS and its coupling to radiative modes in free space have not been studied. In the work, we analyze the photonic DSS in a metallic lattice by angle-resolved far-field reflection measurement and numerical simulation at terahertz (THz) frequencies, and reveal its flatness and boundness in band structure, even in the radiation continuum. Particularly, the DSS band can be tuned being from negatively dispersive via flat to positively dispersive by a single surface parameter, and the DSS at Γ point in surface Brillouin zone is in fact a symmetry-protected bound state in the continuum. Our results might have some potential applications towards THz photonics.


Factor XII protects neurons from apoptosis by epidermal and hepatocyte growth factor receptor-dependent mechanisms.
Factor XII (FXII) is a serine protease that participates in the intrinsic coagulation pathway. Several studies have shown that plasma FXII exerts a deleterious role in cerebral ischemia and traumatic brain injury by promoting thrombo-inflammation. Nevertheless, the impact of FXII on neuronal cell fate remains unknown. We investigated the role of FXII and FXIIa in neuronal injury and apoptotic cell death. We tested the neuroprotective roles of FXII and FXIIa in an experimental model of neuronal injury induced by stereotaxic intracerebral injection of N-methyl-D-aspartic acid (NMDA) in vivo and in a model of apoptotic death of murine primary neuronal cultures through serum deprivation in vitro. Here, we found that exogenous FXII and FXIIa reduce brain lesions induced by NMDA injection in vivo. Furthermore, FXII protects cultured neurons from apoptosis through a growth factor--like effect. This mechanism was triggered by direct interaction with epidermal growth factor (EGF) receptor and subsequent activation of this receptor. Interestingly, the "proteolytically" active and two-chain form of FXII, FXIIa, exerts its protective effects by an alternative signaling pathway. FXIIa activates the pro-form of hepatocyte growth factor (HGF) into HGF, which in turn activated the HGF receptor (HGFR) pathway. This study describes two novel mechanisms of action of FXII and identifies neurons as target cells for the protective effects of single and two-chain forms of FXII. Therefore, inhibition of FXII in neurological disorders may have deleterious effects by preventing its beneficial effects on neuronal survival.


Korean Red Ginseng attenuates ultraviolet-mediated inflammasome activation in keratinocytes.
Keratinocytes form a physical barrier and act as an innate immune cell in skin. Keratinocytes secrete pro-inflammatory cytokines, such as interleukin (IL)-1β, resulting from inflammasome activation when exposed to ultraviolet (UV) irradiation. Korean Red Ginseng extracts (RGE) have been well-studied as modulators of inflammasome activation in immune cells, such as macrophages. In the study, we elucidated the role of RGE on the UV-mediated inflammasome activation in keratinocytes compared with that in macrophages. Human skin keratinocyte cells (HaCaT), human epidermal keratinocytes (HEK), human monocyte-like cells (THP-1), and mouse macrophages were treated with RGE or a saponin fraction (SF) or non-saponin fraction (NS) of RGE before and after UV irradiation. The secretion levels of IL-1β, as an indicator of inflammasome activation, were analyzed. The treatment of RGE or SF in macrophages after UV irradiation inhibited IL-1β secretion, but similar treatment in HaCaT cells did not. However, the treatment of RGE or SF in HaCaT cells in the presence of poly I:C, a toll-like receptor (TLR) 3 ligand, before UV exposure elicited the inhibition of the IL-1β secretion. The inhibition was caused by the disruption by RGE or SF of the TLR mediating up-regulation of the pro-IL-1β and NLRP3 genes during the priming step. RGE and its saponins inhibit IL-1β secretion in response to UV exposure in both keratinocytes and macrophages. In particular, RGE treatment interrupted only the priming step in keratinocytes, although it did attenuate both the priming and activation steps in macrophages.


[Recurrent breast cancer to the sternum 15 years after radical mastectomy and primary lung cancer; report of a case].
We reported a successful operative case of solitary metastasis in the sternum 15 years after radical operation for a breast cancer and a primary lung cancer. The patient was a 59-year-old woman who was admitted for skin ulcer and tumor of the anterior chest wall. Histological diagnosis by skin biopsy was metastasis of breast cancer. Concurrently, chest computed tomography (CT) revealed a coin lesion with slight spiculation at the right lower lobe. Because histological diagnosis by the partial resection of the right lower lobe was primary lung cancer, we performed right lower lobectomy. Twenty-four days after the operation, subtotal sternal resection was carried out. She is alive and well without any complaints.


Myotoxicity of telbivudine in pre-existing muscle damage.
It is unknown if telbivudine causes muscle damage only in patients with pre-existing muscle pathology. A 27 yo male of African origin received telbivudine for hepatitis B during 3 months. Three weeks after initiation of the drug he developed myalgia, and tiredness. Creatine-kinase increased from 278 U/l (n, <170 U/l) at baseline to 3243 U/l. Shortly after discontinuation of telbivudine muscle symptoms and hyper-CK-emia disappeared. The findings suggest that pre-existing muscle damage favored the myotoxic effect of telbivudine. Telbivudine appears to cause accelerated muscle toxicity if given to patients who already have muscle damage. Patients under telbivudine should be closely monitored for muscular side effects and those with pre-existing muscle damage should not receive the drug.


A Motorcyclist-Injury Severity Analysis: A Comparison of Single-, Two-, and Multi-Vehicle Crashes Using Latent Class Ordered Probit Model.
Motorcycle crashes increasingly become a high proportion of the overall motorized vehicle fatalities. However, limited research has been conducted to compare the injury severity of single-, two- and multi-vehicle crashes involving a motorcycle. This study aims to investigate the effects of rider characteristics, road conditions, pre-crash situations, and crash features on motorcycle severities with respect to different numbers of vehicles involved. The crash data used was obtained through a comprehensive Motorcycle Crash Causation Study (MCCS) by the Federal Highway Administration. An anatomic injury severity indicator, the New Injury Severity Score (NISS), is utilized to calculate a total score as the sum of squared the abbreviated injury scale scores of each of the rider's three most severe injuries. A hybrid approach integrating Latent Class Clustering (LCC) and Ordered Probit (OP) models was used to uncover the unobserved heterogeneity and to explore the major factors which significantly affect the injury severities resulting from single-, two- and multi-vehicle crashes involving a motorcycle. The results show that the significant differences in severity exist between different numbers of vehicles involved. More importantly, they also indicate dividing motorcycle crashes into homogeneous classes before modelling helps to discover insightful information. Pre-speed of the motorcycle is found to be a main factor associated with serious and critical injuries in most types of crashes. Findings of the study provide specific and insightful countermeasures targeting at the contributing factors of motorcycle crashes.


[Not Available].
To evaluate the effectiveness of interventions aimed at reducing inappropriate hospital use, identified with diagnosis-independent and explicit criteria methods. Systematic review of the literature to identify evaluative studies of interventions for reducing inappropriate hospìtal use, followed by a narrative synthesis of their characteristics and results. Works were included in English, French or Spanish languages, with experimental, quasi-experimental or observational designs, and with or without group control. We found 15 evaluative studies (2 randomised clinical trials, 8 quasi-experimental with control group and 5 with beforeafter without control group designs), the majority of them carried out in the United States (3 in Spain). The heterogeneity in hospital characteristics, hospitalisation units, patients characteristics, sampling unit, instruments, and presentation of results limited the quantitative synthesis. Feedback and administrative interventions were the most common. All the studies except 2 were positive, showing reductions in several outcomes (percentage of inappropriate stays, inappropriate admissions or inappropriate stays in the day previous to discharge, and in the length of stay). Intensive interventions that combined educational, feedback, self-assesment and administrative components showed the best results. The literature review suggests that several interventions are effective to reduce inappropriate hospital use, particularly if they are direct, active, reach the doctors and combine several components.


Sustainable resource production for manufacturing bioactives from micro- and macroalgae: Examples from harvesting and cultivation in the Nordic region.
Micro- and macroalgae are a great and important source of raw material for manufacturing of bioactives and ingredients for food, feed, cosmetics, or pharmaceuticals. Macroalgae (or seaweeds) have been harvested locally from wild stocks in smaller volumes for a long time, and a production chain based on cultivated seaweed for the harvest of considerably larger amounts is in progress for several species. Microalgae and cyanobacteria such as Spirulina have been produced in "backyard ponds" for use in food and feed also for a long time, and now we see the establishment of large production plants to control the cultivation process and increase the production yields. There is also a shift from harvesting or cultivation centered in warmer, sunnier areas to increasing exploitation of natural resources in temperate to boreal regions. In locations with strong seasonal variations in solar irradiance and temperatures, we need to develop procedures to maximize the biomass production in the productive seasons and ensure efficient stabilization of the biomass for year-round processing and product manufacturing. Industrialized biomass production and large-scale manufacturing of bioactives also mean that we must employ sustainable, cost-effective, and environmentally friendly processing methods, including stabilization and extraction methods such as ensiling and subcritical water extraction (SWE) and advanced analytic tools to characterize the products. These topics are focus areas of the Nordic Centre of Excellence (NCoE) NordAqua, and here we present a review of current activities in the field of micro- and macroalgae biomass production sectors illustrated with some of our experiences from the NordAqua consortium.


Effects of selective histamine receptor antagonists on skin responses to intradermal bradykinin in healthy volunteers.
The effects of chlorpheniramine and cimetidine on the cutaneous responses to intradermal injections of bradykinin were investigated in a randomized, double-blind, placebo-controlled, cross-over study. Chlorpheniramine significantly attenuated the increase in cutaneous blood flow and erythema induced by bradykinin but not the weal response. Cimetidine was without influence on these parameters and the effects of the combined therapy of chlorpheniramine and cimetidine were not significantly different from those due to chlorpheniramine alone. These results suggest that the cutaneous vasodilator effect of bradykinin is in part due to histamine release acting on histamine H1-receptors.


Response evaluation of bone metastasis in prostate cancer: Preliminary comparison of computerized bone scan index versus standardized clinical criteria.
The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria. Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent. Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses. Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.


[Change in blood rheological properties in response to graded physical exertion in patients with ischemic heart disease and persons at risk].
Blood rheologic properties were investigated before and after rationed exercise in 26 patients exhibiting risk factors unattended by atherosclerotic signs, 33 coronary patients and 26 normal subjects. Hemorheologic changes in response to bicycle ergometry were shown to depend largely on the efficiency of cardiac performance and be more marked in coronary patients and those exhibiting risk factors, as compared to normal subjects. In addition, the erythrocyte aggregation coefficient increased significantly during rationed exercise in coronary and risk-factor patients, in contrast to normal subjects. It is suggested that disorders of blood viscosity and erythrocyte aggregation, developing in part of coronary and risk-factor patients, may be conducive to the progress of atherosclerosis and coronary heart disease.