Study of environmental health problems in Korea using integrated environmental health indicators.
We have investigated the usefulness of environmental health indicators for the evaluation of environmental health in Korea. We also assessed the association between environmental contamination and health outcomes by integrating indicators into a composite measure. We selected health-related environmental indicators and environment-related health status indicators. The data were obtained from published statistical data from the period 2008-2009. Both synthesized measures of environmental indicators and health status indicators were calculated using Strahll's taxonometric methods. The range of values determined by this method is 0-1, with higher values representing a better situation in the given area. The study area consisted of 16 large administrative areas within Korea. The arithmetic mean of the synthesized measure of environmental indicators was 0.348 (SD = 0.151), and that of the synthesized measure of health status indicators was 0.708 (SD = 0.107). The correlation coefficient between the synthesized measures of environmental indicators and health status indicators was 0.69 (95% CI: 0.28-0.88). Comparisons between local communities based on integrated indicators may provide useful information for decision-makers, allowing them to identify priorities in pollutant mitigation policies or in improvement actions for public health. Integrated indicators are also useful to describe the relationships between environmental contamination and health effects.


Plasma membrane Ca2+ release-activated Ca2+ channels with a high selectivity for Ca2+ identified by patch-clamp recording in rat liver cells.
Repetitive waves of increased cytoplasmic Ca2+ concentration play a central role in the process by which hormones regulate liver function. Maintenance of these Ca2+ waves requires Ca2+ inflow through store-operated Ca2+ channels. The properties and mechanism(s) of activation of these channels are not well understood. Store-operated Ca2+ channels (SOCs) in the H4-IIE rat liver cell line were studied by whole-cell patch clamping. Depletion of Ca2+ in intracellular stores by intracellular perfusion with either inositol 1,4,5-trisphosphate (InsP(3)) or thapsigargin in the presence of 10 mmol/L ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid (EGTA), or with 10 mmol/L EGTA alone, activated an inward current that reversed at a membrane potential above +40 mV. In physiologic extracellular medium, this inward current was carried exclusively by Ca2+ and was blocked by a variety of di- and trivalent cations. In the absence of extracellular Ca2+ and Mg2+, the inward current was carried by monovalent cations. This current was 10 to 30 times larger than that observed in the presence of extracellular Ca2+, and permitted the detection of single-channel events that corresponded to a single-channel conductance of about 40 pS. Both the Ca2+ and Na+ inward currents were blocked by the calmodulin antagonist, N-(6-amino hexyl)-5-chloro-1-naphthalenesulphonamide (W7), but not by calmidazolium or calmodulin-dependent protein kinase II fragment 290-309. It is concluded that liver cells possess plasma membrane Ca2+ channels that have a high selectivity for Ca2+, are activated by a decrease in the concentration of Ca2+ in intracellular stores through a mechanism that is unlikely to involve calmodulin, and are involved in re-filling intracellular Ca2+ stores during Ca2+ signaling.


PTEN-Induced Putative Kinase 1 Dysfunction Accelerates Synucleinopathy.
Mutations in PTEN-induced putative kinase 1 (PINK1) cause autosomal recessive Parkinson's disease (PD) and contribute to the risk of sporadic PD. However, the relationship between PD-related PINK1 mutations and alpha-synuclein (α-syn) aggregation-a main pathological component of PD-remains unexplored. To investigate whether α-syn pathology is exacerbated in the absence of PINK1 after α-syn preformed fibril (PFF) injection in a PD mouse model and its effects on neurodegeneration. In this study, 10-week-old Pink1 knockout (KO) and wildtype (WT) mice received stereotaxic unilateral striatal injection of recombinant mouse α-syn PFF. Then, α-syn pathology progression, inflammatory responses, and neurodegeneration were analyzed via immunohistochemistry, western blot analysis, and behavioral testing. After PFF injection, the total α-syn levels significantly increased, and pathological α-syn was markedly aggregated in Pink1 KO mice compared with Pink1 WT mice. Then, earlier and more severe neuronal loss and motor deficits occurred. Moreover, compared with WT mice, Pink1 KO mice had evident microglial/astrocytic immunoreactivity and prolonged astrocytic activation, and a higher rate of protein phosphatase 2A phosphorylation, which might explain the greater α-syn aggravation and neuronal death. The loss of Pink1 function accelerated α-syn aggregation, accumulation and glial activation, thereby leading to early and significant neurodegeneration and behavioral impairment in the PD mouse model. Therefore, our findings support the notion that PINK1 dysfunction increases the risk of synucleinopathy.


[Assessment of unresectability of pancreatic carcinoma by enhanced-CT and selective angiography].
One of the major limitations of curative resection in the patients with pancreatic cancer is local tumor extension to the major vessels surrounding pancreas. Therefore the assessment of the involvement of major arteries surrounding pancreas by tumor before operation is very important for the judgement of respectability of pancreatic carcinoma. This study was designed to assess the clinical value of contrast-enhanced CT(CECT) and selective angiography (SAG) in predicting the unresectability of patients with pancreatic cancer. From Aug 7, 1996 to Aug 12, 2000, 67 patients with pancreatic ductal adenocarcinoma proved pathologically were retrospectively analyzed. Of these patients, 31 and 54 patients were treated with CECT and SAG, respectively. The involvement of major vessels surrounding pancreas in CECT and SAG were assessed by operator according to specific criterias, which were compared with finding in operation. Finally, the accuracy of the method was assessed. Among 31 cases who were treated with CECT, 13 were judged unresectable by CECT; and 12 were found unresectable during operation, with predict value of 91%. Among 54 cases who were treated with SAG, 28 were judged unresectable by SAG; and 23 were found unresectable during operation, with predict value of 82%. The sensitivity, specificity, and predict value of CECT and SAG were 60%, 91%, 92%, and 77%, 79%, 82%, respectively. The sensitivity, specificity, and predict value of CECT combined with SAG were 91%, 100%, 100%, respectively. Enhanced CT and SAG are useful in assessing the unresectability of pancreatic carcinoma, the combination of two ways can improve the sensitivity, specificity and predict value.


Mechanistic evaluation of arsenite oxidation in TiO2 assisted photocatalysis.
We report herein a detailed assessment of the roles of O2, H2O2, *OH, and O2-* in the TiO2 assisted photocatalytic oxidation (PCO) of arsenite. Although both arsenite, As(III), and arsenate, As(V), adsorb extensively onto the surface of TiO2, past studies relied primarily on the analysis of the arsenic species in solution, neglecting those adsorbed onto the surface of TiO2. We used extraction and analyses of the arsenic species adsorbed onto the surface of the TiO2 to illustrate that the oxidation of As(III) to As(V) occurs in an adsorbed state during TiO2 PCO. The TiO2 photocatalytic oxidation (PCO) of surface adsorbed As(III) in deoxygenated solutions with electron scavengers, Cu2+, and polyoxometalates (POM) yields oxidation rates that are comparable to those observed under oxygen saturation, implying the primary role of oxygen is as a scavenger of the conduction band electron. Pulse radiolysis and competition kinetics were employed to determine a rate constant of 3.6 x 10(6) M(-1) s(-1) for the reaction of As(III) with O2-*. Transient absorption studies of adsorbed hydroxyl radicals, generated by subjecting colloidal TiO2 to radiolytic conditions, provide convincing evidence that the adsorbed hydroxyl radical (TiO2+*OH) plays the central role in the oxidation with As(III) during TiO2 assisted photocatalysis. Our results suggest the reaction of superoxide anion radical does not contribute in the conversion of As(III) when compared to the reaction of As(III) with *OH radical during TiO2 PCO.


Hypercalcemia and acute renal failure in milk-alkali syndrome: a case report.
Historically, the milk-alkali syndrome developed as an adverse reaction to the Sippy regimen of milk, cream and alkaline powders as treatment for peptic ulcer disease. The classic description includes hypercalcemia, metabolic alkalosis, and renal failure. Over the past 20 years, milk-alkali syndrome has had a resurgence, as consumption of supplements containing calcium has increased. A 46-year-old man presented to the emergency department after outpatient labs to evaluate his fatigue. He was found to have acute renal failure and hypercalcemia (total serum calcium was 15.9 mg/dL). Subsequent laboratory evaluation excluded both hyperparathyroidism and malignancy as causes. A detailed history led to the diagnosis of milk-alkali syndrome. With hydration and cessation of calcium carbonate ingestion, his renal function and serum calcium levels returned to normal. Physicians should have a high index of suspicion for milk-alkali syndrome in patients with hypercalcemia. Milk-alkali syndrome is no longer a merely a historical curiosity; it is currently the third most common cause of hypercalcemia.


Multiple myocardial bridges causing severe ischaemia in adolescent with pulmonary stenosis.
Myocardial bridges are often asymptomatic but may need therapy when causing ischaemia. They have rarely been reported in children or in association with CHD, where symptomatology may be mistakenly attributed to the CHD. We report a case of multiple myocardial bridges causing ischaemia in an adolescent with pulmonary stenosis and discuss management.


Using genetic relatedness to understand heterogeneous distributions of urban rat-associated pathogens.
Urban Norway rats (Rattus norvegicus) carry several pathogens transmissible to people. However, pathogen prevalence can vary across fine spatial scales (i.e., by city block). Using a population genomics approach, we sought to describe rat movement patterns across an urban landscape and to evaluate whether these patterns align with pathogen distributions. We genotyped 605 rats from a single neighborhood in Vancouver, Canada, and used 1,495 genome-wide single nucleotide polymorphisms to identify parent-offspring and sibling relationships using pedigree analysis. We resolved 1,246 pairs of relatives, of which only 1% of pairs were captured in different city blocks. Relatives were primarily caught within 33 meters of each other leading to a highly leptokurtic distribution of dispersal distances. Using binomial generalized linear mixed models, we evaluated whether family relationships influenced rat pathogen status with the bacterial pathogens Leptospira interrogans, Bartonella tribocorum, and Clostridium difficile, and found that an individual's pathogen status was not predicted any better by including disease status of related rats. The spatial clustering of related rats and their pathogens lends support to the hypothesis that spatially restricted movement promotes the heterogeneous patterns of pathogen prevalence evidenced in this population. Our findings also highlight the utility of evolutionary tools to understand movement and rat-associated health risks in urban landscapes.


The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo.
Aurora kinases regulate key stages of mitosis including centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. Aurora A and B kinase overexpression has also been associated with various human cancers, and as such, they have been extensively studied as novel antimitotic drug targets. Here, we characterize the Aurora kinase inhibitor CCT137690, a highly selective, orally bioavailable imidazo[4,5-b]pyridine derivative that inhibits Aurora A and B kinases with low nanomolar IC(50) values in both biochemical and cellular assays and exhibits antiproliferative activity against a wide range of human solid tumor cell lines. CCT137690 efficiently inhibits histone H3 and transforming acidic coiled-coil 3 phosphorylation (Aurora B and Aurora A substrates, respectively) in HCT116 and HeLa cells. Continuous exposure of tumor cells to the inhibitor causes multipolar spindle formation, chromosome misalignment, polyploidy, and apoptosis. This is accompanied by p53/p21/BAX induction, thymidine kinase 1 downregulation, and PARP cleavage. Furthermore, CCT137690 treatment of MYCN-amplified neuroblastoma cell lines inhibits cell proliferation and decreases MYCN protein expression. Importantly, in a transgenic mouse model of neuroblastoma that overexpresses MYCN protein and is predisposed to spontaneous neuroblastoma formation, this compound significantly inhibits tumor growth. The potent preclinical activity of CCT137690 suggests that this inhibitor may benefit patients with MYCN-amplified neuroblastoma.


The impact of standing wave effects on transcranial focused ultrasound disruption of the blood-brain barrier in a rat model.
Microbubble-mediated disruption of the blood-brain barrier (BBB) for targeted drug delivery using focused ultrasound shows great potential as a therapy for a wide range of brain disorders. This technique is currently at the pre-clinical stage and important work is being conducted in animal models. Measurements of standing waves in ex vivo rat skulls were conducted using an optical hydrophone and a geometry dependence was identified. Standing waves could not be eliminated through the use of swept frequencies, which have been suggested to eliminate standing waves. Definitive standing wave patterns were detected in over 25% of animals used in a single study. Standing waves were successfully eliminated using a wideband composite sharply focused transducer and a reduced duty cycle. The modified pulse parameters were used in vivo to disrupt the BBB in a rat indicating that, unlike some other bioeffects, BBB disruption is not dependent on standing wave conditions. Due to the high variability of standing waves and the inability to correctly estimate in situ pressures given standing wave conditions, attempts to minimize standing waves should be made in all future work in this field to ensure that results are clinically translatable.


Anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts.
Activated cardiac apoptosis was found in hearts from hypertensive animals, but little information regarding the effects of exercise training on cardiac apoptosis in hypertension is available. The purpose of this study was to evaluate the anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts. 28 spontaneously hypertensive rats were divided into sedentary group (SHR) or underwent running exercise on treadmill for 1 h/day, 5 sessions/wk, for 12 wk (SHR-EX). Fourteen age-matched Wistar Kyoto rats served as a sedentary normotensive group (WKY). After exercise training or sedentary status, the excised hearts were measured by hemotoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) assay, and Western blotting. Fewer TUNEL-positive apoptotic cells were in SHR-EX groups than those in SHR. Protein levels of Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathways), as well as Bid, t-Bid, Bad, p-Bad, Bak, cytochrome c, activated caspase 9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the SHR-EX group compared with the SHR group. Protein levels of IGF-1, IGF-1R, p-PI3K, p-Akt, p-Bad, and Bcl2 (cardiac pro-survival pathway) become more activated in SHR-EX groups than SHR and WKY. Exercise training prevented hypertension-enhanced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced cardiac pro-survival pathway in rat models. Our findings demonstrate new therapeutic effects of exercise training on hypertensive hearts for preventing apoptosis and enhancing survival.


Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.
Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α-IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α-IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.


MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission.
The modification of proteins by the small ubiquitin-like modifier (SUMO) is known to regulate an increasing array of cellular processes. SUMOylation of the mitochondrial fission GTPase dynamin-related protein 1 (DRP1) stimulates mitochondrial fission, suggesting that SUMOylation has an important function in mitochondrial dynamics. The conjugation of SUMO to its substrates requires a regulatory SUMO E3 ligase; however, so far, none has been functionally associated with the mitochondria. By using biochemical assays, overexpression and RNA interference experiments, we characterized the mitochondrial-anchored protein ligase (MAPL) as the first mitochondrial-anchored SUMO E3 ligase. Furthermore, we show that DRP1 is a substrate for MAPL, providing a direct link between MAPL and the fission machinery. Importantly, the large number of unidentified mitochondrial SUMO targets suggests a global role for SUMOylation in mitochondrial function, placing MAPL as a crucial component in the regulation of multiple conjugation events.


Synthesis and mutagenicity of trans-dihydrodiol metabolites of benzo[b]naphtho[2,1-d]thiophene.
The syntheses of potentially important metabolites of benzo[b]naphtho[2,1-d]thiophene ([2,1]BNT)--trans-1,2-dihydroxy-1,2-dihydrobenzo[b]naphtho[2,1- d]thiophene ([2,1]BNT-1,2-diol) and trans-3,4-dihydroxy-3,4-dihydrobenzo[b]naphtho[2,1-d]thiophene ([2,1]BNT-3,4-diol)--are described. The syntheses involved preparation of the appropriate 1-(3-benzo[b]-thiopheneyl)-2-(methoxyphenyl)ethylenes followed by photocyclization to methoxy-[2,1]BNTs, hydrolysis to hydroxy-[2,1]BNTs, oxidation to [2,1]BNT-diones, and NaBH4 reduction. The dihydrodiols were tested for mutagenicity in Salmonella typhimurium TA 100 with activation; [2,1]BNT-3,4-diol, which can form a bay region diol epoxide, was as mutagenic as [2,1]BNT whereas [2,1]BNT-1,2-diol was inactive. These results suggest that the metabolic activation of [2,1]BNT proceeds partially via formation of a bay region diol epoxide.


Fibroblast transgelin and smooth muscle SM22alpha are the same protein, the expression of which is down-regulated in many cell lines.
In this report we investigate the expression and relationship of transgelin (Tg), a transformation and shape-change sensitive actin gelling protein found in fibroblasts and smooth muscle [Shapland et al., 1988: J. Cell. Biol. 107:153-161; Shapland et al., 1993: J. Cell. Biol. 121:1065-1073], to SM22alpha, a smooth muscle protein of unknown function [Lees-Millar et al., 1987: J. Biol. Chem. 262:2988-2993; Solway et al., 1995: J. Biol. Chem. 270:13460-13469]. To clarify their relationship we have cloned and sequenced the cDNA encoding Tg from cultures of rat embryo fibroblasts. The sequences of fibroblast Tg and the smooth muscle isoform SM22 are identical [Prinjha et al., 1994: Cell Motil. Cytoskeleton 28:243-255; Shanahan et al., 1993: Circ. Res. 73:193-204; Solway et al., 1995]. These data, coupled with our immunoblot analysis and previous observations [Shapland et al., 1988; Shapland et al., 1993], demonstrate that Tg expression is not restricted to smooth muscle since this protein is also present in normal mesenchymal cells. However, we also show that Tg, although present in secondary cultures of mouse and rat embryo fibroblasts, is absent in many apparently normal fibroblast cell lines. Tg down-regulation may therefore be an early and sensitive marker for the onset of transformation. A functional role for Tg is unlikely to directly involve Ca2+ since it neither contains a functional EF hand nor binds 45Ca2+.


A Two-Translocator Model for the Transport of 2-Oxoglutarate and Glutamate in Chloroplasts during Ammonia Assimilation in the Light.
This study examines the transport of 2-oxoglutarate (2-OG) and other dicarboxylates during ammonia assimilation in illuminated spinach chloroplasts. The transport of all dicarboxylates examined was strongly inhibited by NH(4)Cl preincubation in the light. Treatment with NH(4)Cl caused a rapid depletion of the endogenous glutamate pool and a corresponding increase in endogenous glutamine content. The inhibition of transport activity by NH(4)Cl was apparently linked to its metabolism in the light because inhibition of glutamine synthetase activity by the addition of l-methionine sulfoximine or carbonylcyanide-m-chlorophenylhydrazone abolished this affect. Measurements of endogenous metabolite pools showed that malate was most rapidly exchanged during the uptake of all exogenous dicarboxylates examined. Depending on the exogenous substrates used, the apparent half-times of efflux measured for endogenous malate, aspartate and glutamate were 10, 10 to 30, and 15 to 240 seconds, respectively. The transport of 2-OG was also inhibited by malate. But chloroplasts preincubated with malate in the presence or absence of NH(4)Cl were found to have high transport activity similar to untreated chloroplasts. A two-translocator model is proposed to explain the stimulation of 2-OG transport as well as the stimulation of (NH(3), 2-OG)-dependent O(2) evolution by malate (KC Woo, CB Osmond 1982 Plant Physiol 69: 591-596) in isolated chloroplasts. In this model the transport of 2-OG on the 2-OG translocator and glutamate on the dicarboxylate translocator is coupled to malate counter-exchange in a cascade-like manner. This results in a net 2-OG/glutamate exchange with no net malate transport. Thus, during NH(3) assimilation the transport of 2-OG into and the export of glutamate out of the chloroplast occurs via the 2-OG and the dicarboxylate translocators, respectively.


A combined quantitative mass spectrometry and electron microscopy analysis of ribosomal 30S subunit assembly in E. coli.
Ribosome assembly is a complex process involving the folding and processing of ribosomal RNAs (rRNAs), concomitant binding of ribosomal proteins (r-proteins), and participation of numerous accessory cofactors. Here, we use a quantitative mass spectrometry/electron microscopy hybrid approach to determine the r-protein composition and conformation of 30S ribosome assembly intermediates in Escherichia coli. The relative timing of assembly of the 3' domain and the formation of the central pseudoknot (PK) structure depends on the presence of the assembly factor RimP. The central PK is unstable in the absence of RimP, resulting in the accumulation of intermediates in which the 3'-domain is unanchored and the 5'-domain is depleted for r-proteins S5 and S12 that contact the central PK. Our results reveal the importance of the cofactor RimP in central PK formation, and introduce a broadly applicable method for characterizing macromolecular assembly in cells.


A sign for the early detection of medullary sclerosis.
The radiographic image of a normal bone has a continuous radiopaque boundary of variable thickness and a relatively radiolucent interior. Normally, the endosteal edge of this boundary line is well defined. However, this edge may be obscured in diseases that induce medullary new bone formation. The use of this sign for the early detection of medullary sclerosis is demonstrated by specific examples.


Uptake of immunoreactive leukocyte elastase-inhibitor complexes in macrophage-like cells in abscesses.
Leukocyte elastase was demonstrated immunohistochemically not only in PMN-leukocytes in subcutaneous abscesses but also in scattered macrophage-like cells which in addition contained immunoreactive alpha 1-proteinase inhibitor (alpha 1PI) and alpha 2-macroglobulin (alpha 2M). These cells were located mainly in the marginal region of the abscess. It is concluded that the intracellular deposits in the macrophage-like cells represent phagocytized elastase and/or elastase-alpha 1PI and elastase-alpha 2M complexes. A contributing, local production of the inhibitor is, however, not excluded by the present findings.


Review of 14 drowning publications based on the Utstein style for drowning.
The Utstein style for drowning (USFD) was published in 2003 with the aim of improving drowning research. To support a revision of the USFD, the current study aimed to generate an inventory of the use of the USFD parameters and compare the findings of the publications that have used the USFD. A search in Pubmed, Embase, the Cochrane Library, Web of Science and Scopus was performed to identify studies that used the USFD and were published between 01-10-2003 and 22-03-2015. We also searched in Pubmed, Embase, the Cochrane Library, Web of Science, and Scopus for all publications that cited the two publications containing the original ILCOR advisory statement introducing and recommending the USFD. In total we identified 14 publications by groups that explicitly used elements of the USFD for collecting and reporting their data. Of the 22 core and 19 supplemental USFD parameters, 6-19 core (27-86%) and 1-12 (5-63%) supplemental parameters were used; two parameters (5%) have not been used in any publication. Associations with outcome were reported for nine core (41%) and five supplemental (26%) USFD parameters. The USFD publications also identified non-USFD parameters related to outcome: initial cardiac rhythm, time points and intervals during resuscitation, intubation at the drowning scene, first hospital core temperature, serum glucose and potassium, the use of inotropic/vasoactive agents and the Paediatric Index of Mortality 2-score. Fourteen USFD based drowning publications have been identified. These publications provide valuable information about the process and quality of drowning resuscitation and confirm that the USFD is helpful for a structured comparison of the outcome of drowning resuscitation.


Improved survival after acute myocardial infarction complicated by cardiogenic shock with circulatory support and transplantation: comparing aggressive intervention with conservative treatment.
The prognosis for patients with myocardial infarction has steadily improved, but remains poor for those developing cardiogenic shock. Utilization of re-vascularization, mechanical circulatory support and transplantation in these patients may improve survival. We retrospectively analyzed the clinical outcome of 138 consecutive patients at the Cleveland Clinic from 1992 to 1998 who met the criteria for cardiogenic shock after acute myocardial infarction. All patients received intensive medical therapy and intra-aortic balloon pump support. Forty-three patients received intensive medical therapy (conservative group) and 95 patients were treated aggressively (aggressive group). The aggressive group comprised patients who were treated with percutaneous intervention/coronary artery bypass grafting (n = 77, re-vascularization group), and patients who received circulatory support/cardiac transplantation (n = 18). The baseline demographics and angiographic and hemodynamic features were comparable for the two groups. The in-hospital mortality rate was significantly reduced in the aggressive group compared with the conservative group (54% vs 81%, p = 0.002). The in-hospital mortality rate of the circulatory support/transplant group was markedly reduced compared with the conservative group (33% vs 81%, p < 0.001), and was also significantly lower than that of the re-vascularization group (33% vs 63%, p= 0.03). The aggressive group had a markedly improved 5-year survival compared with the conservative group (30% vs 6.2%, p = 0.003). These data suggest that an aggressive strategy, particularly left ventricular assist device support as a bridge to heart transplantation, may improve survival in post-myocardial infarction patients with cardiogenic shock.


Gicerin, a cell adhesion molecule, participates in the histogenesis of retina.
Gicerin is a novel cell adhesion molecule that belongs to the immunoglobulin superfamily. Gicerin protein adheres to neurite outgrowth factor (NOF), an extracellular matrix protein in the laminin family, and also exhibits homophilic adhesion. Heterophilic adhesion of gicerin to NOF is thought to play an active role in neurite outgrowth of developing retinal cells in vitro. In this study, we examined the adhesion activity of gicerin during the retinal development of Japanese quail using an antibody directed against gicerin, to elucidate the biological importance of gicerin in retinal histogenesis. Immunohistochemical and Western blot analysis showed that gicerin was highly expressed in the developing retina but suppressed in the mature retina. The aggregation of neural retinal cells from 5-day embryonic quail retina was significantly inhibited when incubated with a polyclonal antibody to gicerin, suggesting that gicerin protein participates in the adhesion of neural retinal cells of the developing retina. Furthermore, histogenesis of retina both in the organ cultures and in ovo embryos was severely disrupted by incubation with a gicerin antibody. These findings provide evidence that gicerin plays an important role in retinal histogenesis.


Optimal method for early detection of cardiac disorders in thalassemia major patients: magnetic resonance imaging or echocardiography?
Heart failure resulting from myocardial iron deposition is the most important cause of death in β-thalassemia major (TM) patients. Cardiac T2*magnetic resonance imaging (MRI), echocardiography, and serum ferritin level serve as diagnostic methods for detecting myocardial iron overload. In this study, we aimed to evaluate the relationship between the above-mentioned methods. T2*MRI and echocardiographic measurement of left ventricular (LV) systolic and diastolic function were performed in 63 patients. Serum ferritin level was measured. The relationships between all assessments were evaluated. There were 40 women and 23 men with a mean age of 23.7±5.1 years (range, 15-35 years). There was no statistically significant correlation between serum ferritin level and LV systolic and diastolic function (P=0.994 and P=0.475, respectively). T2*MRI results had a significant correlation with ferritin level; 63.6% of patients with serum ferritin level >2,000 ng/mL had abnormal cardiac MRI, while none of the patients with ferritin level <1,000 ng/mL had abnormal cardiac MRI (P=0.001). There was no significant correlation between MRI findings and LV systolic function (P=1.00). However, we detected a significant difference between LV diastolic function and cardiac siderosis (P=0.03). MRI findings are a good predictor of future cardiac dysfunction, even in asymptomatic TM patients; however, diastolic dysfunction may happen prior to cardiac siderosis in some patients, and echocardiography is able to diagnose this diastolic dysfunction while T2*MRI shows normal findings.


Training effects of combined resistance and proprioceptive neck muscle exercising.
To investigate training effects of two different resistance and proprioceptive exercising concepts of neck muscles. Twenty-six healthy women participated in a randomized pilot trial. The test persons were randomized to two different neck-training programs (resistance training (RT) and proprioceptive resistance training (PRT)). They performed a standardized training program for the duration of ten weeks two times weekly. The neck strength, the cross-sectional area of three neck muscle groups (1. sternocleidomastoid muscles; 2. multifidus and semispinalis cervicis muscles; 3. semispinalis capitis and splenius muscles) and the proprioceptive capability evaluated by the dynamic joint repositioning error (DJRE) of the head were assessed pre- and post-intervention. Strength gain did not differ significantly between the two resistance training groups (PRT group: 8.2% to 29.3%; RT group: 1.4% to 19.8%). Change of hypertrophy of all neck muscle groups was significantly (p< 0.001 to p=0.013) greater in the PRT group (18.9% to 32.3%) than in the RT group (1.5% to 12.9%). The DJRE deteriorated with 35% in the RT group and did not change in PRT group (-2.0%). In combination with resistance training, proprioceptive training led to a significantly higher muscle hypertrophy and didn't effect a significant deterioration of the proprioceptive capability compared to isolated resistance training.


Modeling the optical properties of self-organized arrays of liquid crystal defects.
Local full Mueller matrix measurements in the Fourier plane of a microscope lens were used to determine the internal anisotropic ordering in periodic linear arrays of smectic liquid crystal defects, known as 'oily streaks'. We propose a single microstructure-dependent model taking into account the anisotropic dielectric function of the liquid crystal that reproduces the smectic layers orientation and organization in the oily streaks. The calculated Mueller matrix elements are compared to the measured data to reveal the anchoring mechanism of the smectic oily streaks on the substrate and evidence the presence of new type of defect arrangement. Beyond the scientific inquiry, the understanding and control of the internal structure of such arrays offer technological opportunities for developing liquid-crystal based sensors and self-assembled nanostructures.


Relaxant effects of alpha-human atrial natriuretic peptide on venous smooth muscle.
1 The present study has examined the relaxant effects of alpha-human atrial natriuretic peptide (alpha-hANP) and sodium nitroprusside on dog saphenous vein ring preparations; responses were tested on a background of tone corresponding to 30% and 80% of maximal contraction. Also tested on the lower background of tone were the responses to carbachol, M&B 22,948, forskolin and 3-isobutyl-1-methylxanthine (IBMX). The vascular responses to alpha-hANP and carbachol were also examined in dog splenic artery ring preparations. 2 On a background of tone corresponding to 30% of maximal contraction, both alpha-hANP and sodium nitroprusside were found to relax venous ring preparations with IC50 values of 6 x 10(-8) and 2 x 10(-7) M, respectively. When the background of tone was raised to 80% of maximal contraction, the relaxant effect of sodium nitroprusside was significantly reduced and that of alpha-hANP became almost completely abolished; the IC50 value for sodium nitroprusside in these experimental conditions was 2 x 10(-6) M. 3 The cGMP phosphodiesterase inhibitor M&B 22,948 was found to produce a concentration-dependent relaxation, with an IC50 value of 2 x 10(-6)M in saphenous vein rings with a background of tone corresponding to 30% of maximal contraction. By contrast, saphenous vein rings were found to be insensitive to carbachol. Forskolin and IBMX were also found to produce concentration-dependent relaxing responses of venous preparations, with IC50 values of 2 x 10(-7) and 7 x 10(-7) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulation of Senescence in Carnation (Dianthus caryophyllus): Effect of Abscisic Acid and Carbon Dioxide on Ethylene Production.
Abscisic acid hastened senescence of carnation flowers and this was preceded by stimulation of accelerated ethylene production. Carbon dioxide delayed the onset of autocatalytic ethylene production in flowers regardless of treatment with abscisic acid. Flowers exhibited a low and transient climacteric of ethylene production without wilting while in 4% carbon dioxide and underwent accelerated ethylene production culminating in wilting when removed from carbon dioxide. Hypobaric ventilation, which lowers ethylene to hyponormal levels within tissues, extended flower longevity and largely negated enhancement of senescence by abscisic acid. Supplementing hypobarically ventilated flowers with ethylene hastened senescence irrespective of abscisic acid treatment. Collectively, the data indicate that abscisic acid hastens senescence of carnations largely as a result of advancing the onset of autocatalytic ethylene production.


[Surgical treatment for hilar cholangiocarcinoma of Bismuth-Corlette type IV].
To investigate the surgical treatment for hilar cholangiocarcinoma(HCCA) of Bismuth-Corlette type IV. The clinical data of 73 HCCA patients admitted in Southwest Hospital, the Third Military Medical University from January 2002 to December 2008 were analyzed retrospectively. There were 41 males and 32 females, aged from 30 to 84 years old (averaged, 56.8 years old). All patients were diagnosed as hilar mass with hilar biliary obstruction by B-ultrasound, CT, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography or percutaneous transhepatic cholangiography, and confirmed by pathological examination in intra-operation and post-operation. Diagnosis of all patients were according to Bismuth-Corlette type IV. Fifteen cases underwent percutaneous transhepatic cholangial drainage, stents were implanted in 8 patients. Simple internal drainage was performed on 25 of the 73 patients and 4 with palliative resection. Radical resection was performed on 19 patients. The radical resection rate of HCCA were 26.0%. The 1, 3 years of survival rates were 36.8%, 10.5% respectively. The 1 year survival rate was 6.3% in drainage group. Radical resection is the potentially curative treatment for HCCA, a sufficient, reasonable use of internal and external drainage would improve the patient's quality of life.


Adenylate cyclase activity not found in soybean hypocotyl and onion meristem.
Tissue, homogenates, and purified cell fractions prepared from hypocotyls of a dicot, soybean (Glycine max), and meristematic tissue of a monocot, onion (Allium cepa), were examined critically for evidence of adenylate cyclase activity. Three assay methods were used: chemical analysis, isotope dilution analysis, and enzyme cytochemistry. In both crude extracts or whole tissue, as well as purified membranes, with or without auxin, no adenylate cyclase was detected by any of the three methods.For plasma membranes, the specific activity was less than 1/40 or 1/25,000 that of rat liver plasma membranes, depending on the assay procedure, i.e. below the limits of detection. Using comparable methods, we could detect neither cyclic adenosine 3':5'-monophosphate nor the phosphodiesterase responsible for its degradation in either purified membranes or homogenates. The results suggest that hormone responses in plants are not generally mediated by a mechanism involving the obligate production of cyclic adenosine 3':5'-monophosphate by a plasma membrane associated adenylate cyclase.


Clinical trials in neonatal sepsis.
Antibiotic licensing studies remain a problem in neonates. The classical adult clinical syndrome-based licensing studies do not apply to neonates, where sepsis is the most common infection. The main obstacle to conducting neonatal antibiotic trials is a lack of consensus on the definition of neonatal sepsis itself and the selection of appropriate endpoints. This article describes the difficulties of the clinical and laboratory definitions of neonatal sepsis and reviews the varying designs of previous neonatal sepsis trials. The optimal design of future trials of new antibiotics will need to be based on pharmacokinetic/pharmacodynamic parameters, combined with adequately powered clinical studies to determine safety and efficacy.


Do mental events cause neural events analogously to the probability fields of quantum mechanics?
If non-material mental events, such as the intention to carry out an action, are to have an effective action on neural events in the brain, it has to be at the most subtle and plastic level of these events. In the first stage of our enquiry an introduction to conventional synaptic theory leads on to an account of the manner of operation of the ultimate synaptic units. These units are the synaptic boutons that, when excited by an all-or-nothing nerve impulse, deliver the total contents of a single synaptic vesicle, not regularly, but probabilistically. This quantal emission of the synaptic transmitter molecules (about 5000-10 000) is the elementary unit of the transmission process from one neuron to another. In the second stage this refined physiological analysis leads on to an account of the ultrastructure of the synapse, which gives clues as to the manner of its unitary probabilistic operation. The essential feature is that the effective structure of each bouton is a paracrystalline presynaptic vesicular grid with about 50 vesicles, which acts probabilistically in vesicular (quantal) release. In the third stage it is considered how a non-material mental event, such as an intention to move, could influence the subtle probabilistic operations of synaptic boutons. On the biological side, attention is focused on the paracrystalline presynaptic vesicular grids as the targets for non-material mental events. On the physical side, attention is focused on the probabilistic fields of quantum mechanics which carry neither mass nor energy, but which nevertheless can exert effective action at microsites. The new light on the mind-brain problem came from the hypothesis that the non-material mental events, the 'World 2' of Popper, relate to the neural events of the brain (the 'World 1' of matter and energy) by actions in conformity with quantum theory. This hypothesis that mental events act on probabilistic synaptic events in a manner analogous to the probability fields of quantum mechanics seems to open up an immense field of scientific investigation both in quantum physics and in neuroscience.


Analysis of an adaptive lead weighted ResNet for multiclass classification of 12-lead ECGs.
Background. Twelve lead ECGs are a core diagnostic tool for cardiovascular diseases. Here, we describe and analyse an ensemble deep neural network architecture to classify 24 cardiac abnormalities from 12 lead ECGs.Method. We proposed a squeeze and excite ResNet to automatically learn deep features from 12-lead ECGs, in order to identify 24 cardiac conditions. The deep features were augmented with age and gender features in the final fully connected layers. Output thresholds for each class were set using a constrained grid search. To determine why the model made incorrect predictions, two expert clinicians independently interpreted a random set of 100 misclassified ECGs concerning left axis deviation.Results. Using the bespoke weighted accuracy metric, we achieved a 5-fold cross-validation score of 0.684, and sensitivity and specificity of 0.758 and 0.969, respectively. We scored 0.520 on the full test data, and ranked 2nd out of 41 in the official challenge rankings. On a random set of misclassified ECGs, agreement between two clinicians and training labels was poor (clinician 1:κ= -0.057, clinician 2:κ= -0.159). In contrast, agreement between the clinicians was very high (κ= 0.92).Discussion. The proposed prediction model performed well on the validation and hidden test data in comparison to models trained on the same data. We also discovered considerable inconsistency in training labels, which is likely to hinder development of more accurate models.


Surgical Aspects of Recurrent Inguinal Hernia in Adults.
Surgeons occasionally encounter a case of recurrent hernia in adult patients after the primary repair, and these cases are challenging to manage appropriately. This study was conducted to describe the clinical nature of recurrent inguinal hernia, compare the results of management, and identify the relationship between the specific risk factors and the occurrence of recurrent hernia. Retrospectively reviewed 58 patients who underwent the inguinal herniorrhaphy for recurrent hernia in a single institution. Analyzed clinical characteristics of recurrent hernia and tried to verify the relationship between smoking, obesity, and occurrence of recurrent hernia. Recurrent inguinal hernia was 13.5 per cent of all hernia repairs in the study period. Most of the recurrence was the first event (74.1%) and showed an interval to recurrence with a mean duration of 40.7 months. There was no significant difference in procedure time, development of postoperative complications, and duration of hospital stay according to the procedure. Compromise of smoker and overweight was significantly higher in the recurrent group (P < 0.05). Surgeons should be aware of the increased risk for recurrence in adult inguinal hernia patients when they smoke or are overweight (body mass index ≥ 25 kg/m2), also it needs to follow-up during the adequate period.


Detection of drug-resistant Klebsiella pneumoniae in Chinese hares (Lepus sinensis).
We investigated an outbreak of acute pneumonia among adult Chinese hares (Lepus sinensis) and diarrhea among juvenile hares in Hebei Province, China, in 2012. Diagnosis was based on necropsy examination, microbial characteristics, biochemical identification, and nucleotide sequence analysis. The isolated bacteria from tissue samples of dead hares were identified as Klebsiella pneumoniae ssp. pneumoniae (K. pneumoniae). This K. pneumoniae was resistant to the antimicrobials imipenem, meropenem, penicillin, and vancomycin, but was highly sensitive to cefepime, cotrimoxazole, and enrofloxacin. Klebsiella pneumoniae is an important opportunistic pathogen, which often causes nosocomial infections in immunocompromised patients. However, the emergence of drug-resistant K. pneumoniae in hares indicates the existence of increasing risk of pathogen transmission between humans and wildlife. Given the close association between wildlife, livestock, and humans, it is important to identify epidemiologic factors associated with infection in these hares to minimize the risk of K. pneumoniae transmission.


Dedifferentiated epithelial-myoepithelial carcinoma of the parotid gland with aberrant expression of prostate specific antigen: a case report.
This report describes a rare case of dedifferentiated epithelial-myoepithelial carcinoma (EMCa) of the parotid gland. The tumor had 2 distinct components; a well-differentiated EMCa comprising of ductal and myoepithelial cells with low nuclear grade and low proliferation index. The second component showed a completely different morphology comprising of sheets and clusters of poorly differentiated cells with high nuclear grade and proliferative activity. The dedifferentiation was associated with an accelerated clinical course. Dedifferentiated EMCa is extremely rare with only 8 cases reported in the English literature. An unusual feature, hitherto not described in this tumor is the aberrant expression of prostate-specific antigen in the dedifferentiated component. In male patients, this may cause diagnostic confusion with metastatic prostate carcinoma.


Chronic volar distal radioulnar joint instability: joint capsular plication to restore function.
Volar instability of the distal radioulnar joint (DRUJ) is uncommon, and there is little written about it. The purpose of this study is to describe a new procedure to treat volar DRUJ instability and to present the outcomes of patients who received this unique surgical repair at a minimum of 1 year follow-up. We performed a retrospective case series of 6 consecutive patients treated with a volar and dorsal capsular plication procedure by an upper extremity specialist surgeon at a teaching hospital between April 1999 and October 2004. We evaluated measures, including wrist range of motion, grip strength, radiographs, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and Patient-Rated Wrist Evaluation (PRWE), at final follow-up. Five of 6 patients had resolution of pain and instability symptoms. The average difference in range of motion between operative and contralateral sides was -7 degrees flexion, 2 degrees extension, 4 degrees radial deviation, 2 degrees ulnar deviation, -17 degrees supination and -2 degrees pronation. Average grip strength measured 83% of the uninjured side. The average DASH score was 13.5 (range 0-46.7), and the average PRWE score was 26.7 (range 0-70). One patient had a low ulnar neuropathy, which resolved. One patient fractured the temporary DRUJ stabilization screw and had radiographic evidence of nonbridging heterotopic ossification. Joint capsular plication for DRUJ has not yet been described in the literature. It is less elaborate in that it does not require a tendon graft with bone tunnels. The results at an average 16.5 months postoperatively are promising.


Thioredoxin-like Activity of Thylakoid Membranes: THIOREDOXIN CATALYZING THE REDUCTIVE INACTIVATION OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE OCCURS IN BOTH SOLUBLE AND MEMBRANE-BOUND FORM.
The inactivation of pea leaf chloroplast glucose-6-phosphate dehydrogenase by dithiothreitol can be catalyzed by thioredoxin-like molecules that are present in chloroplasts. This thioredoxin activity occurs predominantly as a soluble species, but washed thylakoid membranes also exhibit some thioredoxin-like activity. The membrane-associated thioredoxin can be extracted by treatment with the detergent Triton X-100. The solubilized thioredoxin appears to have a molecular size similar to that of the soluble thioredoxin which catalyzes the same reaction. The thylakoid-bound activity constitutes only about 5% of the total chloroplast thioredoxin activity. The thioredoxin occurring in the membrane fraction cannot, however, be ascribed to the trapping of stroma since less than 0.1% of three stromal marker enzymes are found in the same thylakoid extract.


[Long-term follow-up of childhood low-risk ALL patients treated with SCMC-ALL-2005 protocol].
To evaluate the long-term efficacy of SCMC-ALL-2005 protocol in treatment of low-risk childhood acute lymphoblastic leukemia (ALL). From May 1, 2005 to April 30, 2009, 387 patients enrolled into SCMC-ALL-2005 protocol. Based on the characteristics of cell morphology, immunology, cytogenetics and molecular biology and treatment response, 158 patients were fit into the low-risk treatment group. All the cases were registered in pediatric oncology network database (POND). The clinical characteristics and outcome were analyzed. Until December 31, 2012, the 5-year event free survival (EFS) and overall survival (OS) is (77.76±3.37)% and (89.55±2.83)%, respectively. Median follow-up time is 5.33 y (3.75-7.70 y). Five patients (3.16%) died of complication, all of them were severe infections. Twenty-seven patients (17.09%) relapsed, including 13 bone marrow relapse (8.23%), 5 testis relapse (5.32% of boys, 2 of unilateral and 3 bilateral), 6 central nerve system relapse (CNS, 3.80%), 1 relapse in both bone marrow and CNS, 1 relapse in both bone marrow and testis, and 1 right ovary and fallopian tube relapse. Relapse is related to positive minimal residual disease. Two cases (1.27%) occurred second tumors, 4 patients (2.53%) gave up treatment in complete remission without special reasons. The EFS and life quality of SCMC-ALL-2005 protocol in the treatment of childhood low-risk ALL is satisfactory. The treatment-related mortality rate is lower, and the long-term EFS is higher than that of XH-99 protocol.


Genetic factors of reaction time performance: DRD4 7-repeat allele associated with slower responses.
Twin studies indicate substantial inherited components in cognitive abilities. One of the most extensively studied candidate genes of cognitive functioning is the dopamine D4 receptor gene (DRD4), which has been suggested to be related to attentional disorders. Based on reaction time data of 245 Caucasians participating in different cognitive tasks, slower responses characterized the group with the 7-repeat allele. This effect was present in both sexes and was not because of fatigue. To our knowledge, this is the first report on significant association (P = 0.0001) between the DRD4 variable number of tandem repeat (VNTR) polymorphism and response latencies in a non-clinical adult sample. Other studied dopaminergic polymorphisms did not show an association with reaction time. These results illustrate that speed-of-performance measures derived from multiple reaction time tasks using standardization procedures could be promising tools to detect unique genetic effects in the background of cognitive abilities.


Purification in high yield and characterisation of the galactose-specific lectin from the seeds of snake gourd (Trichosanthes anguina).
The galactose-specific lectin present in the seeds of snake gourd (Trichosanthes anguina) was purified in high yield by affinity chromatography on cross-linked guar gum. The purified snake gourd seed lectin (SGSL) yielded a single symmetrical peak on gel filtration with an M(r) of 62 kDa and gave a single band in PAGE under non-denaturing conditions. In SDS-PAGE, SGSL gave a single band of M(r) 53 kDa in the absence of beta-mercaptoethanol, and two bands of M(r) 32 and 23 kDa in its presence, indicating that the lectin is a heterodimer in which the subunits are linked by a disulphide bridge. The lectin gave a single precipitin line in immunodiffusion experiments with antiserum raised against the purified SGSL. No cross-reactivity was found between SGSL and antiserum raised against the Momordica charantia lectin and vice versa, suggesting that the two lectins are antigenically dissimilar. Haemagglutination-inhibition data show that Me beta D-Gal is the best monosaccharide inhibitor of SGSL and indicate that an equatorial hydroxyl at C-2 and axial hydroxyl at C-4 in the pyranose form are important binding loci for the lectin.


Radioiodine (131I) therapy in a child with autism spectrum disorder: A complex and demanding task.
In January 2017, an 11.5-year-old male child with autism was referred for radioiodine (RAI) therapy post total thyroidectomy for papillary thyroid carcinoma. The treatment required swallowing a RAI capsule and remaining isolated (48-72 h). Initially, obstacles to a successful treatment seemed insurmountable as he had complex needs and behavioral issues due to his autism, mild intellectual disability, and family environment. His mother was adamant that he would not be able to swallow the capsule and comply with the required isolation period. A multidisciplinary team was formed to explore options for successful treatment. Each option considered had its own risks and challenges. Behavioral therapy was considered to be the only possible option. It was pursued with regular, frequent contact between the child, his parents, and members of the team for counseling and behavioral modification, familiarization of the child with the staff, procedures, trial visits, and admission. The patient was successfully treated in October 2017.


[Adrenocorticotropin receptor in familial glucocorticoid deficiency].
Recent studies have revealed the presence of four subtypes for the melanocortin receptor (MC-R). Among these MC-Rs, MC2-R is considered to be an adrenocorticotropin (ACTH) receptor because its expression is almost localized in the adrenal cortex. Five Japanese patients with ACTH unresponsiveness were examined as to whether they have mutations in the putative ACTH receptor. Among these patients, there are two groups of siblings, each of which consists of two individuals. The coding region of the ACTH receptor gene was amplified by polymerase chain reaction and directly sequenced on both strands, however, no point mutation was found in any of the five patients, suggesting that familial glucocorticoid deficiency, caused by the mutated ACTH receptor, may be rare.


Bone metastasis in hepatocellular carcinoma. A report of five cases and a review of the literature.
Hepatocarcinoma occurs frequently throughout the world. Bone metastases are rare although incidence has increased because of progress in diagnosis and treatment. The authors report 5 cases of bone metastases and review the literature. The spine is the most frequent localization of bone metastases. Radiotherapy is the treatment of choice for this lesion. Surgery should be used to prevent and treat complications such as nerve compression and pathologic fracture, only if the coagulative pattern and the conditions of the patient allow it. The authors recommend the use of long intramedullary nailing when localization of the disease is in the femur, with prophylactic stabilization of the neck in diaphyseal metastasis.


When, where, and how to intervene? Trade-offs between time and costs in coastal nutrient management.
Policies and regulations designed to address nutrient pollution in coastal waters are often complicated by delays in environmental and social systems. Social and political inertia may delay implementation of cleanup projects, and even after the best nutrient pollution management practices are developed and implemented, long groundwater travel times may delay the impact of inland or upstream interventions. These delays and the varying costs of nutrient removal alternatives used to meet water quality goals combine to create a complex dynamic decision problem with trade-offs about when, where, and how to intervene. We use multi-objective optimization to quantify the trade-offs between costs and minimizing the time to meet in-bay nutrient reduction goals represented as a Total Maximum Daily Load (TMDL). We calculate the impact of using in-bay (in-situ) nutrient removal through shellfish aquaculture relative to waiting for traditional source control to be implemented. We apply these methods to the Three Bays Watershed in Cape Cod, Massachusetts. In gross benefit terms, not accounting for any social costs, this equates to an average value of 37¢ (2035 TMDL target date) and 11¢ (2060 TMDL target date) per animal harvested over the plan implementation period. Our results encourage the consideration of alternative and in-situ approaches to tackle coastal pollution while traditional source control is implemented and its effects realized over time.


Identification of a 'snapshot' of co-expressed angiogenic markers in laser-dissected vessels from unstable carotid plaques with targeted arrays.
Angiogenesis is a feature of the atherogenic process, with intimal neovascularisation arising from vessels in the adventitia, adjacent to a plaque. Immature, leaky blood vessels from unstable plaques proliferate abnormally and, being poorly invested with smooth muscle cells, may contribute to instability of the plaque by facilitation of inflammatory cell infiltration and haemorrhagic complications. We used laser-capture microdissection to isolate angiogenic areas of the extracellular matrix (containing CD105/flt-1-positive, fragile thin-walled vessels) and non-angiogenic vascular areas (CD105-negative, with smooth muscle cell covering) of complicated endarterectomy plaques, and specifically designed angiogenesis-TaqMan real-time PCR microarrays to identify gene expression. Important pro-angiogenic components, including Notch-3, delta-like-4 (DLL4), Tie-2, angiopoietin-1 (Angio-1) and receptor for advanced glycation end products (RAGE), and one anti-angiogenic factor, endostatin, were up-regulated in these regions. Immunohistochemistry demonstrated localisation within intimal, active (CD105-positive) microvessels and co-localisation of Notch-3 and DLL4/Tie-2 and Angio-1 in the same vessels indicating multiple/synergistic signalling mechanisms associated with vessel development. These data, although providing only a snapshot of information, demonstrate that plaque vascularisation occurs in the presence of multiple angiogenically active factors. Knowledge of their combined effects could help in the formulation of novel therapeutics designed to stabilise or prevent their formation in the treatment of atherosclerosis.


Towards digital health equity - a qualitative study of the challenges experienced by vulnerable groups in using digital health services in the COVID-19 era.
The COVID-19 pandemic has given an unprecedented boost to already increased digital health services, which can place many vulnerable groups at risk of digital exclusion. To improve the likelihood of achieving digital health equity, it is necessary to identify and address the elements that may prevent vulnerable groups from benefiting from digital health services. This study examined the challenges experienced by vulnerable groups in using digital health services during the COVID-19 pandemic. Qualitative descriptive design was utilized. Semi-structured interviews were conducted between October 2020 and May 2021. The participants (N = 74) were older adults, migrants, mental health service users, high users of health services, and the unemployed. Qualitative content analysis with both inductive and deductive approach was used to analyze the data. Challenges related to the use of digital health services were interpreted through digital determinants of health from the Digital Health Equity Framework. For most of the participants the access to digital health services was hampered by insufficient digital, and / or local language skills. The lack of support and training, poor health, as well as the lack of strong e-identification or suitable devices also prevented the access. Digital services were not perceived to be applicable for all situations or capable of replacing face-to-face services due to the poor communication in the digital environment. Fears and the lack of trust regarding digital platforms were expressed as well as concerns related to the security of the services. Contact with a health care professional was also considered less personal and more prone to misunderstandings in the digital environment than in face-to-face services. Finally, digital alternatives were not always available as desired by participants, or participants were unaware of existing digital services and their value. Several development needs in the implementation of digital health services were identified that could improve equal access to and benefits gained from digital services in the future. While digital health services are increasing, traditional face-to-face services will still need to be offered alongside the digital ones to ensure equal access to services.


Acyl-CoA:cholesterol acyltransferase inhibitor avasimibe reduces atherosclerosis in addition to its cholesterol-lowering effect in ApoE*3-Leiden mice.
The present study investigated whether the ACAT inhibitor avasimibe can reduce atherogenesis independently of its cholesterol-lowering effect in ApoE*3-Leiden mice. Two groups of 15 female ApoE*3-Leiden mice were put on a high-cholesterol (HC) diet; 1 group received 0.01% (wt/wt) avasimibe mixed into the diet. The HC diet resulted in a plasma cholesterol concentration of 18.7+/-2.6 mmol/L. Addition of avasimibe lowered plasma cholesterol by 56% to 8.1+/-1.2 mmol/L, caused mainly by a reduction of and composition change in VLDL and LDL. In a separate low-cholesterol (LC) control group, plasma cholesterol was titrated to a level comparable to that of the avasimibe group (10.3+/-1.4 mmol/L) by lowering the amount of dietary cholesterol. After 22 weeks of intervention, atherosclerosis in the aortic root area was quantified. Treatment with avasimibe resulted in a 92% reduction of lesion area compared with the HC control group. Compared with the LC control, avasimibe reduced lesion area by 78%. After correction for the slight difference in cholesterol exposure between the LC control and avasimibe groups, the effect of avasimibe on lesion area (73% reduction) remained highly significant. In addition, monocyte adherence to the endothelium, free cholesterol accumulation, and lesion severity were reduced by avasimibe treatment. Treatment with avasimibe potently lowered plasma cholesterol levels in ApoE*3-Leiden mice and considerably reduced atherosclerotic lesion area in addition to its cholesterol-lowering effect. Because monocyte adherence to the endothelium and lesion severity were also reduced by avasimibe, treatment with avasimibe may result in higher plaque stability and therefore a reduced risk of plaque rupture.


Circulatory effects of desflurane.
The cardiovascular properties of desflurane and some other inhalational anaesthetics are outlined and compared, and the way in which they may be effectively used in clinical practice is considered. Desflurane appears to offer some advantages compared with currently available anaesthetics. Its effects on left ventricular function are moderate and the solubility of the agent in blood and tissue is remarkably less than isoflurane, enflurane, or halothane.


Phenotypic and molecular epidemiology of Acinetobacter baumannii strains isolated in Rabta Hospital, Tunisia.
Acinetobacter baumannii (A. baumannii) is often implicated in hospital outbreaks in Tunisia. It's a significant opportunistic pathogen that is usually associated with serious underlying diseases such as pneumoniae, meningitis and urinary tract infections. The aim of this prospective study was to evaluate the global state of its endemicity and the antibiotic resistance evolution. The possibility of nosocomial transmission of one or more epidemic strain(s) was investigated by means of 3 methods: biotyping, antibiotyping and Random Amplified Polymorphic DNA analysis (RAPD). MIC for imipenem by Ellipsometer-test strip (E-TEST). The presence of metallo-beta-lactamases (MBL) was detected according to the double synergy test of EDTA and imipenem disks. A. baumannii strains were mainly localized in intensive care (52.2%) and surgery units (23.6%). Among 224 strains that were studied, 4 biotypes were delineated with a predominance of biotype1. Resistance to beta-lactams was mostly associated with the production of cephalosporinases and penicilinases (84.3%). 45% of strains were resistant to imipenem which were associated with MBL production. RAPD gave 5 genomic groups. This study demonstrates the epidemic behaviour airborne spread of A. baumannii in hospital wards. The multiresistance was often responsible for failure of antibiotics therapy. The prevention of nosocomial infection and severe hygiene controls must be performed.


Biological stoichiometry of growth in Drosophila melanogaster.
We examined the relationship between growth rate, C:N:P stoichiometry, and nucleic acid content in Drosophila melanogaster. The "Growth Rate Hypothesis" predicts that N and P contents per unit body mass will be high during ontogenetic stages characterized by rapid growth, reflecting the large requirement for P-rich ribosomal RNA during these periods. The ratio of RNA:DNA also is predicted to change with changes in growth rate. Growth is rapid in early D. melanogaster larvae, slowing considerably just prior to pupation. As predicted, a positive relationship was found between growth rate and N and P content, but not C. Thus, body C:P and N:P ratios declined with increasing growth rate. The relationship between RNA content and growth rate also was positive. Additionally, the fraction of total body P contributed by ribosomal RNA increased with increasing growth rate.


[The rat model of erectile dysfunction caused by cavernous nerve injury].
To identify rat cavernous nerve and establish a rat model of erectile dysfunction (ED) caused by injury of cavernous nerve. Twenty rats were undergone dissections. Cavernous nerves were identified with the aid of operating microscope and confirmed by electrical stimulation. Then, 42 experimental rats were randomized into 3 groups, including sham operated controls, unilateral and bilateral cavernous nerve ablation groups. Three weeks after surgery, rat models were evaluated with Apomorphine Test. The major pelvic ganglion lies on either side of the dorsolateral lobes of the prostate. It includes 2 inflows, one called hypogastric nerve and another is pelvic nerve. The largest outflow is termed as cavernous nerve. Stimulus parameters which could induce obvious penile erection were 5 volts, frequency of 20 Hertz and duration of 5 milliseconds. Three weeks after surgery, apomorphine could induce penile erection of each rat in controls with mean (2.57 +/- 1.40) erections in 30 minutes, while there were no erections (0.00 +/- 0.00) either in unilateral or bilateral group. The rat of larger ganglion and its cavernous nerve can be easily identified, obvious response to electrical stimulation, low cost of animal purchase, easy housing and availability made rat as an ideal animal for establishing ED model caused by cavernous nerve injury. In addition, our study showed in the early period of cavernous nerve injury, either unilateral or bilateral, all rats lost their erectile function.


Quantitative genetics and functional-structural plant growth models: simulation of quantitative trait loci detection for model parameters and application to potential yield optimization.
Prediction of phenotypic traits from new genotypes under untested environmental conditions is crucial to build simulations of breeding strategies to improve target traits. Although the plant response to environmental stresses is characterized by both architectural and functional plasticity, recent attempts to integrate biological knowledge into genetics models have mainly concerned specific physiological processes or crop models without architecture, and thus may prove limited when studying genotype x environment interactions. Consequently, this paper presents a simulation study introducing genetics into a functional-structural growth model, which gives access to more fundamental traits for quantitative trait loci (QTL) detection and thus to promising tools for yield optimization. The GREENLAB model was selected as a reasonable choice to link growth model parameters to QTL. Virtual genes and virtual chromosomes were defined to build a simple genetic model that drove the settings of the species-specific parameters of the model. The QTL Cartographer software was used to study QTL detection of simulated plant traits. A genetic algorithm was implemented to define the ideotype for yield maximization based on the model parameters and the associated allelic combination. By keeping the environmental factors constant and using a virtual population with a large number of individuals generated by a Mendelian genetic model, results for an ideal case could be simulated. Virtual QTL detection was compared in the case of phenotypic traits--such as cob weight--and when traits were model parameters, and was found to be more accurate in the latter case. The practical interest of this approach is illustrated by calculating the parameters (and the corresponding genotype) associated with yield optimization of a GREENLAB maize model. The paper discusses the potentials of GREENLAB to represent environment x genotype interactions, in particular through its main state variable, the ratio of biomass supply over demand.


Actin in wound-healing of rabbit corneal endothelium. I. Study by immunoperoxidase method.
The distribution of actin in the rabbit cornea was examined by the indirect immunoperoxidase method using mouse monoclonal anti-actin IgM and goat anti-mouse IgM serum conjugated with peroxidase, which was stained with 4-chloronaphthol. Flat preparation of the cornea was made and the actin distribution was examined in the normal endothelium and also during wound-healing of the endothelium that took place after transcorneal freezing. In the normal cornea, the epithelial, stromal and endothelial cells contained actin in the cytoplasm. Diffuse actin staining in the endothelial cytoplasm was observed in the flat preparation of the normal endothelium. After endothelial damage, the cells adjacent to the damaged area showed a fiber-like staining of actin around the nucleus; this occurred 12 to 24 hours after the freezing. Punctate staining was seen on the 2nd day, and the intensity of the staining was maximum on the 3rd day when the wound was completely covered. On the 3rd day, fibroblast-like cells were encountered and a long fiber-like staining of actin was seen in the cytoplasm, but the staining disappeared on the 4th day. The long fiber-like and punctate staining reappeared on the 14th day. Normal staining pattern was recovered on the 28th day. These findings suggest that actin production was accelerated in the endothelial cells during the wound-healing, and that this productive activity returned to normal levels as healing was completed.


Data-driven approach to generating achievable dose-volume histogram objectives in intensity-modulated radiotherapy planning.
To propose a method of intensity-modulated radiotherapy (IMRT) planning that generates achievable dose-volume histogram (DVH) objectives using a database containing geometric and dosimetric information of previous patients. The overlap volume histogram (OVH) is used to compare the spatial relationships between the organs at risk and targets of a new patient with those of previous patients in a database. From the OVH analysis, the DVH objectives of the new patient were generated from the database and used as the initial planning goals. In a retrospective OVH-assisted planning demonstration, 15 patients were randomly selected from a database containing clinical plans (CPs) of 91 previous head-and-neck patients treated by a three-level IMRT-simultaneous integrated boost technique. OVH-assisted plans (OPs) were planned in a leave-one-out manner by a planner who had no knowledge of CPs. Thus, DVH objectives of an OP were generated from a subdatabase containing the information of the other 90 patients. Those DVH objectives were then used as the initial planning goals in IMRT optimization. Planning efficiency was evaluated by the number of clicks of the "Start Optimization" button in the course of planning. Although the Pinnacle(3) treatment planning system allows planners to interactively adjust the DVH parameters during optimization, planners in our institution have never used this function in planning. The average clicks required for completing the CP and OP was 27.6 and 1.9, respectively (p <.00001); three OPs were finished within a single click. Ten more patient's cord + 4 mm reached the sparing goal D(0.1cc) <44 Gy (p <.0001), where D(0.1cc) represents the dose corresponding to 0.1 cc. For planning target volume uniformity, conformity, and other organ at risk sparing, the OPs were at least comparable with the CPs. Additionally, the averages of D(0.1cc) to the cord + 4 mm decreased by 6.9 Gy (p <.0001); averages of D(0.1cc) to the brainstem decreased by 7.7 Gy (p <.005). The averages of V(30 Gy) to the contralateral parotid decreased by 8.7% (p <.0001), where V(30 Gy) represents the percentage volume corresponding to 30 Gy. The method heralds the possibility of automated IMRT planning.


Analysis of results of surgical treatment in Crohn's disease.
Crohn's disease is a non-specific, chronic inflammatory disorder affecting any part of alimentary tract. Patients receiving proper medication require surgery in 70-90% of cases. Analysis of results of surgical treatment in Crohn's disease in patients treated at the Medical University of Wrocław and an attempt to elaborate the optimal surgical strategy in Crohn's disease was the aim of the study. The medical documentation of 52 patients with confirmed diagnosis of Crohn's disease was analysed, focusing on the course of the disease before surgery linked with its localization, duration and medical treatment. Then indications for surgery, type of surgical procedure performed and perioperative morbidity and mortality were discussed. Thirteen patients had urgent surgery. Thirty-nine patients had planned surgery. The most common procedure was ileocecal resection or right hemicolectomy. In 36 cases the postoperative course was uncomplicated. The most common surgical complication was wound infection. Pneumonia was the most common general complication. Fatal cases occured in elderly patients with long-term and severely complicated disease. The optimal timing of surgery is extremely difficult and remains non-standardized. Key decisions are often established intraoperatively and they require considerable surgeon experience, patient's awareness and close cooperation of surgeons and gastroenterologists.


Accumulation of CVIET Pfcrt allele of Plasmodium falciparum in placenta of pregnant women living in an urban area of Dakar, Senegal.
Chemoprophylaxis is recommended during pregnancy to reduce the risk of placental infection. However, in areas with increasing drug resistance, it can trigger selection of resistant parasites in the placenta and increase the frequency of placental malaria. The objective of this study was to analyse the selection of drug-resistant parasites in the placenta in an area where chloroquine was still recommended as prophylaxis. We analysed the polymorphism of parasites from matched placental and venous blood samples at the time of delivery from women in Dakar. Polymorphism of the isolates was studied using nested PCR typing of MSA1 and MSA2 genes, and full sequence of PfCRT exon 2. Of 692 women recruited at delivery, 72 had placental malaria. Two Pfcrt exon 2 genotypes were found, and 86% of the placentas had monoallelelic CVIET infection compared with 39% that had peripheral blood infection. Mixed parasite populations of CVIET/CVMNK occurred in 53% of the peripheral blood samples but only in 7% of the infected placentas. This selection of CVIET in placenta was not related to a decreased polymorphism of the parasites, as a large diversity of MSA1 and MSA2 was found in both placenta and venous blood. This diversity confirms that a multiplicity of circulation isolates can occur at low parasite transmission. msp1 and msp2 genotyping revealed mostly distinct populations of parasites in venous and placental blood. These data suggest that, even in low transmission areas, diverse parasite populations can accumulate in the placenta during pregnancy despite strong selection at the PfCRT locus due to chemoprophylaxis with chloroquine.


Manganese (Mn) oxidation increases intracellular Mn in Pseudomonas putida GB-1.
Bacterial manganese (Mn) oxidation plays an important role in the global biogeochemical cycling of Mn and other compounds, and the diversity and prevalence of Mn oxidizers have been well established. Despite many hypotheses of why these bacteria may oxidize Mn, the physiological reasons remain elusive. Intracellular Mn levels were determined for Pseudomonas putida GB-1 grown in the presence or absence of Mn by inductively coupled plasma mass spectrometry (ICP-MS). Mn oxidizing wild type P. putida GB-1 had higher intracellular Mn than non Mn oxidizing mutants grown under the same conditions. P. putida GB-1 had a 5 fold increase in intracellular Mn compared to the non Mn oxidizing mutant P. putida GB-1-007 and a 59 fold increase in intracellular Mn compared to P. putida GB-1 ∆2665 ∆2447. The intracellular Mn is primarily associated with the less than 3 kDa fraction, suggesting it is not bound to protein. Protein oxidation levels in Mn oxidizing and non oxidizing cultures were relatively similar, yet Mn oxidation did increase survival of P. putida GB-1 when oxidatively stressed. This study is the first to link Mn oxidation to Mn homeostasis and oxidative stress protection.


Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.
Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting antibody uptake in brain. Nevertheless, there are limited data on the therapeutic properties including safety liabilities that will enable successful development of TfR-based therapeutics. We evaluate TfR/BACE1 bispecific antibody variants in mouse and show that reducing TfR binding affinity improves not only brain uptake but also peripheral exposure and the safety profile of these antibodies. We identify and seek to address liabilities of targeting TfR with antibodies, namely, acute clinical signs and decreased circulating reticulocytes observed after dosing. By eliminating Fc effector function, we ameliorated the acute clinical signs and partially rescued a reduction in reticulocytes. Furthermore, we show that complement mediates a residual decrease in reticulocytes observed after Fc effector function is eliminated. These data raise important safety concerns and potential mitigation strategies for the development of TfR-based therapies that are designed to cross the blood-brain barrier.


Why some adults with intellectual disability consult their general practitioner more than others.
This research identifies factors affecting why some adults with intellectual disability (AWIDs) consult their general practitioner (GP) more than others. Little is known about these factors, despite AWIDs having higher health needs and reduced longevity. Current barriers to accessing health care need to be understood and overcome to achieve improved health outcomes. A secondary analysis of data obtained from a stratified randomised sample of AWIDs participating in a cluster randomised trial of hand held health records. The number of GP consultations was obtained retrospectively for the year preceding initial health interviews from GP records. AWIDs and their carers were given separate health interviews using identical/adapted questions where possible. Two hundred and one AWIDs and or their carers from 40 practices participated (response rate 64.6%) with GP consultation data extracted for 187 AWIDs. Overall consulting levels were low, 3.2 per annum for women and 2.2 for men. Increased age, gender (women) and type of carer (paid) were all significantly associated with increased consultations. Carers reporting health problems, medications reported by AWIDs, medications recorded in GP records, and pain reported by AWIDs were also significant factors affecting consultations to GP practices after adjustment for age and type of carer. Overall consultation rates were lower than expected, and affected by age, gender and type of carer. Targeted interventions are needed to improve attendance and promote health.


Temporal effects of ouabain on in-vitro development of mouse zygotes.
Ouabain is a specific inhibitor of Na(+)-K(+)-ATPase, an enzyme which controls the intracellular Na+ and K+ levels. In this study, in-vitro fertilized zygotes from a hybrid mouse strain were used to examine the temporal effects of 50 microM ouabain on embryonic development in vitro during the preimplantation period. A higher incidence of blastocyst formation at the end of the culture period was found when embryos were cultured in the presence of ouabain from 22 to 46 h post-insemination, or any other period that included this time period. When zygotes from randomly bred mice were used, inhibition of Na(+)-K(+)-ATPase with ouabain clearly promoted development through the 2-cell block in vitro. As Na(+)-K(+)-ATPase is the most important regulator of intracellular electrolyte concentrations in mammalian cells, these results suggest that an ionic imbalance exists in embryos cultured in conventional media which can be positively influenced by inhibiting this enzyme.


Isolation of elastic tissue microfibrils derived from cultured cells of calf ligamentum nuchae.
Cells cultured from calf ligamentum nuchae produce extracellular microfibrils identical to those of intact elastic tissue as determined by ultrastructural appearance, degradative enzyme susceptibilities and amino acid composition. A method to isolate large amounts of the microfibrillar component using fluorescein mercuric acetate is described. The cultures do not appear to synthesize the amorphous component, elastin, in that radioactive desmosine and isodesmosine were not detected after incubating cultures with labeled lysine nor was elastin seen ultrastructurally.


Km typing with PCR: application to population screening.
The immunoglobulin kappa light chain (IgK) locus may play a significant role in the pathology of both infectious and autoimmune diseases. Most of the work on IgK genetics has been conducted using immunological techniques for allelic typing and sequence analysis. This is restricted by availability of reagents and can be both expensive and time-consuming. PCR primers were designed to amplify the kappa constant gene (Ck), and four allele-specific oligonucleotides (ASOs) were used to distinguish the alleles in the amplified PCR products. Direct sequencing of PCR products was performed to confirm that the primers specifically amplified the Ck region and the ASOs differentiated the Km alleles. Sequencing of an average of 209 nucleotides of DNA from 50 individuals revealed no variation except at codon 191, which is known to be involved in a frequent polymorphism. An analysis of 347 different individual DNAs from 10 human populations was conducted to determine Km allelic frequencies within these populations and to apply this type of data collection to population studies.


Global Trends and Hotspots in Research on Rehabilitation Robots: A Bibliometric Analysis From 2010 to 2020.
Background: In recent years, with the development of medical science and artificial intelligence, research on rehabilitation robots has gained more and more attention, for nearly 10 years in the Web of Science database by journal of rehabilitation robot-related research literature analysis, to parse and track rehabilitation robot research hotspot and front, and provide some guidance for future research. Methods: This study employed computer retrieval of rehabilitation robot-related research published in the core data collection of the Web of Science database from 2010 to 2020, using CiteSpace 5.7 visualization software. The hotspots and frontiers of rehabilitation robot research are analyzed from the aspects of high-influence countries or regions, institutions, authors, high-frequency keywords, and emergent words. Results: A total of 3,194 articles were included. In recent years, the research on rehabilitation robots has been continuously hot, and the annual publication of relevant literature has shown a trend of steady growth. The United States ranked first with 819 papers, and China ranked second with 603 papers. Northwestern University ranked first with 161 publications. R. Riener, a professor at the University of Zurich, Switzerland, ranked as the first author with 48 articles. The Journal of Neural Engineering and Rehabilitation has the most published research, with 211 publications. In the past 10 years, research has focused on intelligent control, task analysis, and the learning, performance, and reliability of rehabilitation robots to realize the natural and precise interaction between humans and machines. Research on neural rehabilitation robots, brain-computer interface, virtual reality, flexible wearables, task analysis, and exoskeletons has attracted more and more attention. Conclusions: At present, the brain-computer interface, virtual reality, flexible wearables, task analysis, and exoskeleton rehabilitation robots are the research trends and hotspots. Future research should focus on the application of machine learning (ML), dimensionality reduction, and feature engineering technologies in the research and development of rehabilitation robots to improve the speed and accuracy of algorithms. To achieve wide application and commercialization, future rehabilitation robots should also develop toward mass production and low cost. We should pay attention to the functional needs of patients, strengthen multidisciplinary communication and cooperation, and promote rehabilitation robots to better serve the rehabilitation medical field.


Enhancement of microhomology-mediated genomic rearrangements by transient loss of mouse Bloom syndrome helicase.
Bloom syndrome, an autosomal recessive disorder of the BLM gene, confers predisposition to a broad spectrum of early-onset cancers in multiple tissue types. Loss of genomic integrity is a primary hallmark of such human malignancies, but many studies using disease-affected specimens are limited in that they are retrospective and devoid of an appropriate experimental control. To overcome this, we devised an experimental system to recapitulate the early molecular events in genetically engineered mouse embryonic stem cells, in which cells undergoing loss of heterozygosity (LOH) can be enriched after inducible down-regulation of Blm expression, with or without site-directed DNA double-strand break (DSB) induction. Transient loss of BLM increased the rate of LOH, whose breakpoints were distributed along the chromosome. Combined with site-directed DSB induction, loss of BLM synergistically increased the rate of LOH and concentrated the breakpoints around the targeted chromosomal region. We characterized the LOH events using specifically tailored genomic tools, such as high-resolution array comparative genomic hybridization and high-density single nucleotide polymorphism genotyping, revealing that the combination of BLM suppression and DSB induction enhanced genomic rearrangements, including deletions and insertions, whose breakpoints were clustered in genomic inverted repeats and associated with junctional microhomologies. Our experimental approach successfully uncovered the detailed molecular mechanisms of as-yet-uncharacterized loss of heterozygosities and reveals the significant contribution of microhomology-mediated genomic rearrangements, which could be widely applicable to the early steps of cancer formation in general.


Non-standard O(2) consumption-temperature curves during rest and isometric exercise in human skeletal muscle.
The present work was aimed at measuring intramuscular oxygen consumption (O(2)) as a function of temperature (T), in human forearm, during rest and aerobic isometric exercise (4% of the maximal voluntary contraction, MVC). Based upon results from in vitro experiments performed on isolated mitochondria of animal species, it was hypothesised that, during isometric exercise, the O(2)-T curve should display a maximum for some 'optimal' T. Intramuscular T and measurements were performed using a combined deep body temperature/near infrared probe during muscle cooling. At rest, O(2) increased non-linearly and monotonically as a function of T (n=8). O(2) increased approximately 2 times when going from 26 to 36 degrees C. A log(O(2))-T plot or a log(O(2))-1/T did not linearise the data. During isometric contraction, O(2) values at 26.8+/-0.6, 28.6+/-0.9, 31.9+/-0.9 and 35.9+/-0.9 degrees C were 3.04+/-1.26, 7.60+/-1.64, 4.43+/-1.95, and 6.64+/-1.37 micromol 100 g(-1) min(-1), respectively (n=6). The O(2) value at 28.6 degrees C was significantly higher (P<0.05) than that at 26.8 and 31.9 degrees C. The 'sudden' O(2) change at 28.6 degrees C is compatible with the phenomenon observed at the mitochondrial level.


Incidental experiences of regulatory fit and the processing of persuasive appeals.
This article examines how the subjective experiences of "feeling right" from regulatory fit and of "feeling wrong" from regulatory non-fit influence the way people process persuasive messages. Across three studies, incidental experiences of regulatory fit increased reliance on source expertise and decreased resistance to counterpersuasion, whereas incidental experiences of regulatory non-fit increased reliance on argument strength and increased resistance to counterpersuasion. These results suggest that incidental fit and non-fit experiences can produce, respectively, more superficial or more thorough processing of persuasive messages. The mechanisms underlying these effects, and the conditions under which they should and should not be expected, are discussed.


Interstitial rejection, vascular rejection, and diffuse thrombosis of renal allografts. Predisposing factors, histology, immunohistochemistry, and relation to outcome.
Histological and immunohistochemical analyses were made of biopsy specimens from 50 consecutive patients who experienced putative graft rejection. The mean age of the patients was 44.5 years (range, 17-69 years) and 26 were men. There were 67 evaluable allograft specimens, which were grouped according to the histological diagnosis: group 1, acute tubulointerstitial rejection (n = 42); group 2, acute vascular rejection (n = 18); and group 3, diffuse thrombosis (n = 7). Over a follow-up period of 21-57 months, the mean number of rejection episodes was 1.7, 2.8, and 3.3 in groups 1, 2, and 3, respectively. Allograft loss occurred in 7 out of 30, 10 out of 16, and 4 out of 4 patients in groups 1, 2, and 3, respectively. The following histological parameters differed significantly (P < 0.05) among the groups: interstitial edema, congestion of peritubular capillaries, glomerular thrombosis, and glomerular ischemia (group 3 > group 2 > group 1). Interstitial bleeding was seen more often in group 2 and 3 tissues than in group 1 specimens (P < 0.01). Immunohistochemical analyses showed that vascular rejection was associated with WT14 staining for monocytes and macrophages around the tubuli and with interstitial deposition of complement factor 3. With regard to serology, positive anti-endothelial cell antibody-dependent cellular cytotoxicity was associated with vascular rejection and thrombosis of the graft in all patients tested, and with graft loss in 75%. Pre-existent positive anti-IgG immunofluorescence on peritubular capillaries in pretransplant biopsy specimens incubated with patient serum was found in only 3 of the 50 patients, but was associated with graft loss in 2 of the 3. Cytomegalovirus infection was associated with a higher percentage of graft loss. There were significant intergroup differences in panel reactive antibodies before transplantation (P < 0.001), with higher titers in groups 2 and 3. The findings in relation to interstitial rejection are compatible with cellular rejection, while the data on vascular rejection support a humorally mediated pathogenesis.


Factors affecting the utilization of antenatal care among women of reproductive age in Nurpur Shahan.
Antenatal care is important for the prevention of maternal and foetal mortality and morbidity. The purpose of this study was to determine the frequency of utilization of antenatal care and to identify the factors that affect it. A cross sectional survey was conducted in the community of Nurpur Shahan, Islamabad, Pakistan in January 2010 using a structured questionnaire. Included were 390 women of reproductive age who were questioned about their knowledge of antenatal care and its utilization. The frequency of utilization of antenatal care was (84.4%). Among those who never used the antenatal care, permission to use the facility and ignorahce were the main reasons. Education of both the wife and husband with this regard must be worked upon.


Synthesis of High-Performance CSA Cements as Low Carbon OPC Alternative.
Starting from natural raw materials, cements based calcium sulphoaluminate (CSA) clinkers have been successfully obtained as an eco-friendly alternative to ordinary Portland cement. CSA-based cements with ye'elimite as the main phase have been produced over the years and are widely used today. In this regard, the present paper considers the study of hydration processes for CSA pastes prepared with a water/cement ratio of 0.5 according to the EN-197 standard and their characterization by thermal analysis (DTA-TG), X-ray diffraction analysis (XRD), and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). A mechanical strength of 60.9 MPa was the greatest achieved for mortars hardened for 28 days.


How frequently do patients with multiple sclerosis use complementary and alternative medicine?
The purpose of the study was to examine the prevalence and characteristics of the utilisation of complementary and alternative medicine (CAM) by patients with multiple sclerosis (MS). Cross-sectional study using a semi-structured interview. One hundred and fifty-four MS patients were examined by interview to collect sociodemographic and disease-related variables as well as aspects of their usage of CAM. The investigation was completed by data from neurological examination. Reported utilisation of CAM by MS patients. At the time of the investigation 61.7% (n = 95) of the MS patients reported that they were currently using CAM. Most of the therapies utilised (90.3%; n = 205) were complementary and only 9.7% (n = 22) were alternative choices. Users of complementary medicine were more severely affected by the disease than non-users, but no sociodemographic differences between users and non-users were found. Concerning the efficacy of CAM, 65.8% (n = 146) of MS patients reported improvement, 32.9% (n = 73) no influence, and 1.3% (n = 3) worsening of their condition. 4.5% (n = 10) of the CAM therapies were accompanied by slight side-effects. A large proportion of MS patients use unconventional treatments, yet clinical studies on the efficacy of CAM in these cases have not been undertaken. Therefore, further research on their motivation and on objective effects of CAM is required.