[A case of post-cardiac arrest syndrome presenting with lateralized periodic discharges evolving to a cyclic seizure pattern on electroencephalogram].
A 53-year-old man with hypertension experienced sudden cardiopulmonary arrest. Ambulance crews detected ventricular fibrillation that responded to defibrillation. Cardiopulmonary resuscitation resulted in return of spontaneous circulation (ROSC) after 30 minutes. At admission to our hospital, he was in a comatose state. Therapeutic hypothermia was performed for two days with other supportive care. However, despite these therapies, he remained comatose, and a diagnosis of post-cardiac arrest syndrome (PCAS) was made. On the sixth hospital day, an electroencephalogram (EEG) showed lateralized periodic discharges (LPDs) in the right occipital area evolving to electrographic seizures. Over roughly 15 minutes, this evolution process repeated 10 times, demonstrating a cyclic seizure pattern. Intravenous administration of 10 mg diazepam resulted in temporal attenuation of the high-amplitude discharges followed by LPDs re-emergence accompanying a low-amplitude fast rhythm on the background activity (LPDs+). Antiepileptic drugs administration was continued, along with supportive care. He opened his eyes on the 11th hospital day, after which his general conditions showed a good recovery. He was discharged on the 30th day without any sequelae.


Water transformation in the media of biofilters controlled by Rhodococcus fascians in treating an ethyl acetate-contaminated airstream.
Biofilters do not provide much water for bacteria to grow. To use them efficiently and properly, it is essential to understand the kinetics of water transformation and to control moisture levels. This study aims to clarify whether the metabolism of microorganisms will improve the water-holding capacity of media or will intensify drying. This experiment was conducted in duplicate, that is, both with and without bacterial inoculation. Both the constant water content mode and the declining water content mode show that microbial growth in a log phase will enhance drying. In contrast, the bacteria growing in a logarithmic decline phase will improve water-holding capacity. Basically, water evaporation can result from the latent heat obtained from microbial respiration or from the physical temperature difference between the unsaturated air and the wet media. Two ways that biofilters can gain water are from water incorporated into bacteria cells and from water obtained from the oxidation of volatile organic compounds (VOCs).


Oxytocin and vasopressin: distinct receptors in myometrium.
The binding characteristics of [3H]oxytocin [( 3H]OT) and [3H]lysine vasopressin [( 3H]LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas [3H]OT was found to bind to a single class of sites with high affinity [Kd, 1.5 +/- 0.4 (+/- SEM) nM] and low capacity [maximum binding (Bmax), 34 +/- 6 fmol/mg protein], [3H]LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for [3H]OT and [3H]LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for [3H]LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin.


Fatty acid concentration, proximate composition, and mineral composition in fishbone flour of Nile Tilapia.
Nile tilapia (Oreochormis niloticus) fishbone is a fish part with unknown composition. After elaboration of flour fishbone of tilapia it was analysede. The results in 100 g of flour were: moisture (14.2%), protein (40.8%), total lipids (25.3%), and ash (18.3%), and mineral (in 100 g) was 2715.9 mg (calcium), 1.3 mg (iron), and 1132.7 mg (phosphorus). A total of 22 fatty acids were detected in fishbone flour total lipids (TL), being the major ones in (g) of total lipids: 16:0 (208.5 mg); 18:1n-9 (344.3 mg); and 18:2n-6 (109.6 mg). The concentration of linolenic acid--LNA (18:3n-3); eicopentaenoic acid--EPA (20:5n-3), and docosahexaenoic acid--DHA (22:6n-3) were (29.9 mg), (3.3 mg), and (12.9 mg), respectively. The content to saturated (SFA) were (296.2 mg), monounsaturated (MUFA) 415.0 mg, and polyunsaturated (PUFA) 175.6 mg. The ratio PUFA:MUFA:SFA was 1:2.4:1.7, and the ratio omega-6/omega-3 fatty acids were 2.8. The last is within the recommended values. The results show low concentrations of omega-3 fatty acids in flour. The value caloric and calcium, iron, phosphorus, and protein content the fishbone flour of tilapia may results a valuable alternative food in the human diet.


Overexpression of miR-155 in clear-cell renal cell carcinoma and its oncogenic effect through targeting FOXO3a.
MicroRNA-155 (miR-155) is overexpressed in numerous human cancer types and has an oncogenic role. Previous study has revealed that miR-155 serves an important role in the progression of clear-cell renal cell carcinoma (ccRCC); however, the underlying mechanism was not completely clarified. The present study aimed to investigate the biological role of miR-155 in ccRCC and the underlying molecular mechanisms. The expression of miR-155 in 20 ccRCC and adjacent normal kidney tissues was determined by PCR. After downregulation of miR-155 expression by miR-155 inhibitor, cell growth was assessed by MTT and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cell invasion and migration was detected by wound healing and Transwell assays. Furthermore, forkhead box O3a (FOXO3a) mRNA and protein expression were detected by PCR and immunoblotting. The expression of FOXO3a in 20 ccRCC tissues was also examined by immunohistochemistry. The expression of miR-155 was upregulated in ccRCC tissues compared to that in adjacent normal tissues. Inhibition of miR-155 significantly suppressed the proliferation, colony formation, migration and invasion, and induced G1 arrest and apoptosis of ccRCC cells in vitro. Moreover, inhibition of miR-155 significantly upregulated FOXO3a expression, and miR-155 expression was inversely correlated with FOXO3a expression in ccRCC tissues. In conclusion, miR-155 may have an important role in the genesis of ccRCC through targeting FOXO3a and may be a potential target for ccRCC therapy.


Auxosporulation in Paralia guyana MacGillivary (Bacillariophyta) and Possible New Insights into the Habit of the Earliest Diatoms.
Diatoms are one of the most ecologically important aquatic micro-eukaryotes. As a group unambiguously recognized as diatoms, they seem to have appeared relatively recently with a limited record of putative remains from oldest sediments. In contrast, molecular clock estimates for the earliest possible emergence of diatoms suggest a considerably older date. Depending on the analysis, Paralia and Leptocylindrus have been recovered within the basal molecular divergences of diatoms. Thus these genera may be in the position to inform on characters that the earliest diatoms possessed. Here we present auxospore development and structure of initial and post-auxospore cells in a representative of the ancient non-polar centric genus Paralia. Their initial frustules showed unusual, but not unprecedented, spore-like morphology. Similarly, initial frustules of Leptocylindrus have been long considered resting spores and a unique peculiarity of this genus. However, even though spore-like in appearance, initial cells of Paralia readily resumed mitotic divisions. In addition, Paralia post-auxospore cells underwent several rounds of mitoses in a multi-step process of building a typical, "perfect" vegetative valve. This degree of heteromorphy immediately post-auxosporulation is thus far unknown among the diatoms. A spore-related origin of diatoms has already been considered, most recently in the form of the "multiplate diploid cyst" hypothesis. Our discovery that the initial cells in some of the most ancient diatom lineages are structurally spore-like is consistent with that hypothesis because the earliest diatoms may be expected to look somewhat similar to their ancestors. We speculate that because the earliest diatoms may have appeared less diatom-like and more spore-like, they could have gone unrecognized as such in the Triassic/Jurassic sediments. If correct, diatoms may indeed be much older than the fossil record indicates, and possibly more in line with some molecular clock predictions.


Laboratory tests for defining bactericidal activity as predictors of antibiotic efficacy in the treatment of endocarditis due to Staphylococcus aureus in rabbits.
The validity of laboratory tests that define bactericidal activity to predict antimicrobial efficacy was studied in rabbits with endocarditis due to Staphylococcus aureus, both nafcillin-nontolerant (NT) and nafcillin-tolerant (T). Infected rabbits were treated with nafcillin, clindamycin, chloramphenicol, or no drug (control) for up to 11 days; dosage was designed so that peak antibiotic serum concentration/minimal inhibitory concentration ratios were approximately 50. During treatment, peak and trough serum concentration/minimal bactericidal concentration ratios and peak and trough titers of serum bactericidal antibacterial activity were determined. The rank order of efficacy, as defined by survival, eradication of bacteremia, and sterilization of cardiac vegetations, was nafcillin = clindamycin greater than chloramphenicol greater than control, both adjusted and unadjusted for the challenge strain of S. aureus. Bactericidal activity (observed only with nafcillin plus S. aureus NT) was associated with lower bacterial counts in vegetations at four days but was otherwise unrelated to therapeutic outcome.


Safety signals and human anxiety: a fear-potentiated startle study.
The effect of a safety signal on the magnitude of anticipatory anxiety was investigated using the fear-potentiated startle reflex paradigm in humans. The amplitude of the acoustic startle reflex was measured during the anticipation of unpleasant electric shocks ("threat") and during "safe" conditions. Threat and safe conditions were signaled by three different colored lights. Two lights signaled safe conditions (safe 1, safe 2) and the other light signaled the threat condition (threat). In phase I, the lights alternated, each presentation consisting of one colored light. In phase II, the lights were presented alone or in the two combinations of safe 1 (or safe 2) + threat and safe 1 + safe 2. In both phases, the contingency between the lights and the shock was explained to the subjects. It was emphasized that no shock could be administered when the safe 1 and threat light were simultaneously presented in phase II. Subjects' belief and understanding of the instructions were verified. In Phase I, startle was increased in the threat-alone compared to the safe-alone condition, reflecting increased anticipatory anxiety in the threat-alone condition. In phase II, startle in the safe + threat condition was smaller than in the threat-alone condition, but was larger than in the safe + threat. These results were interpreted as suggesting that the threat signal was still able to elicit anticipatory anxiety despite the fact that it was no longer associated with a threat.


Electrospray ionization mass spectrometric detection of low polar compounds by adding NaAuCl4.
Liquid chromatography electrospray ionization mass spectrometry (LC/ESI/MS) has been widely used for various analyses. However, it is difficult to use LC/ESI/MS for the analysis of low polar compounds, such as polycyclic aromatic hydrocarbons. It is well known that AuCl4- ion decomposes to AuCl3 by heating, and AuCl3 is a strong π-electrophilic Lewis acid. Low polar compounds (pyrene, benzo[a]pyrene, perylene, benzo[ghi]perylene, dibenzothiophene and p-dimethoxybenzene) were detected by ESI/MS in the positive ion mode by adding NaAuCl4 . The low polar compound interacts with AuCl3 formed at the ESI interface, and undergoes electron transfer to AuCl3 . The radical cation of the low polar compound was then detected by MS. In addition, the LC/ESI/MS determination of polycyclic aromatic hydrocarbons by the post-column addition of NaAuCl4 was studied. © 2016 The Authors Journal of Mass Spectrometry Published by John Wiley & Sons Ltd.


Transitions regulating the timing of cytokinesis in embryonic cells.
Anaphase, mitotic exit, and cytokinesis proceed in rapid succession, and while mitotic exit is a requirement for cytokinesis in yeast, it may not be a direct requirement for furrow initiation in animal cells. In this report, we physically manipulated the proximity of the mitotic apparatus (MA) to the cell cortex in combination with microinjection of effectors of the spindle checkpoint and CDK1 activity to determine how the initiation of cytokinesis is coupled to the onset of anaphase and mitotic exit. Whereas precocious contact between the MA and the cell surface advanced the onset of cytokinesis into early anaphase A, furrowing could not be advanced prior to the metaphase-anaphase transition. Additionally, while cells arrested in anaphase could be induced to initiate cleavage furrows, cells arrested in metaphase could not. Finally, activation of the mitotic checkpoint in one spindle of a binucleate cell failed to arrest cytokinesis induced by the control spindle but did inhibit the formation of furrows between the arrested MA and the control, nonarrested MA. Our experiments suggest that the competence of the mitotic apparatus to initiate cytokinesis is not dependent on cyclin degradation but does require anaphase-promoting complex (APC) activity and, thus, inactivation of the mitotic checkpoint.


Temporal aspects of excitation-contraction coupling in airway smooth muscle.
In airway smooth muscle (ASM), ACh induces propagating intracellular Ca2+ concentration ([Ca2+]i) oscillations (5-30 Hz). We hypothesized that, in ASM, coupling of elevations and reductions in [Ca2+]i to force generation and relaxation (excitation-contraction coupling) is slower than ACh-induced [Ca2+]i oscillations, leading to stable force generation. When we used real-time confocal imaging, the delay between elevated [Ca2+]i and contraction in intact porcine ASM cells was found to be approximately 450 ms. In beta-escin-permeabilized ASM strips, photolytic release of caged Ca2+ resulted in force generation after approximately 800 ms. When calmodulin (CaM) was added, this delay was shortened to approximately 500 ms. In the presence of exogenous CaM and 100 microM Ca2+, photolytic release of caged ATP led to force generation after approximately 80 ms. These results indicated significant delays due to CaM mobilization and Ca2+-CaM activation of myosin light chain kinase but much shorter delays introduced by myosin light chain kinase-induced phosphorylation of the regulatory myosin light chain MLC20 and cross-bridge recruitment. This was confirmed by prior thiophosphorylation of MLC20, in which force generation occurred approximately 50 ms after photolytic release of caged ATP, approximating the delay introduced by cross-bridge recruitment alone. The time required to reach maximum steady-state force was >15 s. Rapid chelation of [Ca2+]i after photolytic release of caged diazo-2 resulted in relaxation after a delay of approximately 1.2 s and 50% reduction in force after approximately 57 s. We conclude that in ASM cells agonist-induced [Ca2+]i oscillations are temporally and spatially integrated during excitation-contraction coupling, resulting in stable force production.


The involvement of caspases in the process of nuclear removal during lens fiber cell differentiation.
The terminal differentiation of lens fiber cells involves elimination of their organelles, which must occur while still maintaining their functionality throughout a lifetime. Removal of non-nuclear organelles is accomplished through induction of autophagy following the spatiotemporal suppression of the PI3K/Akt signaling axis. However, blocking this pathway is not alone sufficient to induce removal of fiber cell nuclei. While the final steps in fiber cell nuclear elimination are highlighted by the appearance of TUNEL-positive nuclei, which are associated with activation of the lens-specific DNaseIIβ, there are many steps in the process that precede the appearance of double stranded DNA breaks. We showed that this carefully regulated process, including the early changes in nuclear morphology resulting in nuclear condensation, cleavage of lamin B, and labeling by pH2AX, is reminiscent of the apoptotic process associated with caspase activation. Multiple caspases are known to be expressed and activated during lens cell differentiation. In this study, we investigated the link between two caspase downstream targets associated with apoptosis, ICAD, whose cleavage by caspase-3 leads to activation of CAD, a DNase that can create both single- and double-stranded DNA cleavages, and lamin B, a primary component of the nuclear lamina. We discovered that the specific inhibition of caspase-3 activation prevents both lamin B and DNA cleavage. Inhibiting caspase-3 did not prevent nuclear condensation or removal of the nuclear membrane. In contrast, a pan-caspase inhibitor effectively suppressed condensation of fiber cell nuclei during differentiation. These studies provide evidence that caspases play an important role in the process of removing fiber cell nuclei during lens differentiation.


Effects of the nitric oxide donor sodium nitroprusside on intracellular pH and contraction in hypertrophied myocytes.
We compared the effects of the nitric oxide donor sodium nitroprusside (SNP) on intracellular pH (pHi), intracellular calcium concentration ([Ca2+]i) transients, and cell contraction in hypertrophied adult ventricular myocytes from aortic-banded rats and age-matched controls. pHi was measured in individual myocytes with SNARF-1, and [Ca2+]i transients were measured with indo 1 simultaneously with cell motion. Experiments were performed at 37 degrees C in myocytes paced at 0.5 Hz in HEPES-buffered solution (extracellular pH = 7.40). At baseline, calibrated pHi, diastolic and systolic [Ca2+]i values, and the amplitude of cell contraction were similar in hypertrophied and control myocytes. Exposure of the control myocytes to 10(-6) mol/L SNP caused a decrease in the amplitude of cell contraction (72 +/- 7% of baseline, P < .05) that was associated with a decrease in pHi (-0.10 +/- 0.03 U, P < .05) with no change in peak systolic [Ca2+]i. In contrast, in the hypertrophied myocytes exposure to SNP did not decrease the amplitude of cell contraction or cause intracellular acidification (-0.01 +/- 0.01 U, NS). The cGMP analogue 8-bromo-cGMP depressed cell shortening and pHi in the control myocytes but failed to modify cell contraction or pHi in the hypertrophied cells. To examine the effects of SNP on Na(+)-H+ exchange during recovery from intracellular acidosis, cells were exposed to a pulse and washout of NH4Cl. SNP significantly depressed the rate of recovery from intracellular acidosis in the control cells compared with the rate in hypertrophied cells. SNP and 8-bromo-cGMP cause a negative inotropic effect and depress the rate of recovery from intracellular acidification that is mediated by Na(+)-H+ exchange in normal adult rat myocytes. In contrast, SNP and 8-bromo-cGMP do not modify cell contraction or pHi in hypertrophied myocytes.


Gametogenesis in the freshwater prawn, Macrobrachium lamerrii.
Histological changes of the female and male gonads were studied and their relation to reproductive cycle is described. Ovary showed distinct changes during the course of its reproductive cycle. Maturational changes did not occur simultaneously in all follicles of the ovary. Regression of ovary during the non breeding season with a number of degenerating oocytes was observed. The seasonal changes in spermatogenesis revealed that growth in the testes appeared to be less than in the case of females.


Cross-sectional study of the relationship between trait emotional intelligence and career adaptability of Chinese youths.
Young people often experience dramatic changes, both psychologically and physically, as they are transiting from students to working adults. However, there is still a lack of empirical studies on the relationship between the trait emotional intelligence and the career adaptability of youths in the Asia-Pacific region. This research examines that relationship in Chinese youths in Hong Kong. Cross-sectional data (N = 500) was collected from two universities in 2019 and 2020. The 2019 sample was made up of 256 Chinese university students (117 males, 139 females; ages 21-25). The 2020 sample included 244 Chinese university students (132 males, 112 females; ages 21-25). The participants were asked to complete the Wong and Law Emotional Intelligence Scale (WLEIS) to evaluate their emotional intelligence in the domains of self-emotion appraisal, other people's emotion appraisal, regulation of emotion, and use of emotion. Participants completed the Career Adapt-Abilities Scale (CAAS) to assess their career adaptability in the areas of concern, control, curiosity, and confidence. All domains of trait emotional intelligence were positively associated with career adaptability. Multiple Regression analysis showed that self-emotion appraisal and appraisal of other people's emotional were the most predictive factors in terms of career adaptability. Together, these two dimensions of emotional intelligence explain 12.5%, 26.2%, 13.4% and 69.4% respectively of the variance in students' concern, control, curiosity, and confidence in relation to career adaptability. The results highlight the importance of emotional intelligence in career adaptability. It is thus of value to study further whether career adaptability of young people may improve if emotional intelligence is incorporated into the student curriculum. The findings offer valuable insights for educators and teachers who are responsible for well-rounded development of students, and will thereby foster healthy lifestyles, stable emotional well-being and greater career adaptability in adolescents.


The Physical Oceanography of Ice-Covered Moons.
In the outer solar system, a growing number of giant planet satellites are now known to be abodes for global oceans hidden below an outer layer of ice. These planetary oceans are a natural laboratory for studying physical oceanographic processes in settings that challenge traditional assumptions made for Earth's oceans. While some driving mechanisms are common to both systems, such as buoyancy-driven flows and tides, others, such as libration, precession, and electromagnetic pumping, are likely more significant for moons in orbit around a host planet. Here, we review these mechanisms and how they may operate across the solar system, including their implications for ice-ocean interactions. Future studies should continue to advance our understanding of each of these processes as well as how they may act together in concert. This interplay also has strong implications for habitability as well as testing oceanic hypotheses with future missions. Expected final online publication date for the Annual Review of Marine Science, Volume 16 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis.
The direct involvement of Clostridium difficile in the lesional tissue of pseudomembranous colitis has not been demonstrated; the organism's effects have been assumed to be strictly toxin mediated. Because C. difficile cytotoxin may be found incidentally in the intestinal lumina of asymptomatic infants, the role of the organism in a variety of pediatric intestinal diseases is uncertain. The authors studied seven cases of fatal pediatric pseudomembranous colitis in which the presence of C. difficile was uniformly demonstrable in lesional tissues with the use of both an intestinal spore stain and a specific immunostain. The patients had either underlying Hirschsprung's disease or hematologic malignancy; the striking pathologic features peculiar to these patients were altered mucosal mucin and immunologic barriers in the former group and neutropenia in the latter. Two patients had demonstrable circulating cytotoxin in serum or ascitic fluid, and C. difficile was identified invading colonic mucosa or submucosa. Such phenomena did not occur in control pediatric patients with multiple other intestinal lesions. Altered host factors may be responsible for the intestinal invasion of C. difficile and its systemic toxin circulation in cases of fatal pediatric pseudomembranous colitis.


Factors regulating condylar cartilage growth under repeated load application.
Mechanical loading can influence the biological behavior of the bone-associated cells leading to adaptive changes in skeletal mass and architecture. SOX9 and PTHrP genes are known to regulate chondrocyte differentiation and delay maturation, ultimately control the endochondral bone formation. To investigate the effects of repeated mechanical loading on bone, 280 Sprague-Dawley rats were used in this experiment. The animals were randomly allocated into experimental and control groups. Repeated mechanical loading was applied through a bite-jumping device in the experimental group. The experimental animals were sacrificed on 10 different time points together with the matched control. Total RNA was extracted from the mandibular condylar cartilage for PTHrP and SOX9 genes quantification using real-time RTPCR. Results showed that PTHrP expression was increased and reached a peak level on the seventh day after mechanical loading was given. Repeated mechanical loading triggered a significant increase of PTHrP expression leading to another peak increment. The expression of SOX9 was highly correlated with the PTHrP expression, and its pattern of expression was similar to that of PTHrP after repeated mechanical loading. In conclusions, repeated mechanical loading on the condyle triggers the expression of PTHrP and SOX9, which in turn promotes condylar cartilage growth.


Effects of a novel class III antiarrhythmic agent, NIP-142, on canine atrial fibrillation and flutter.
The effects of a new benzopyran derivative, NIP-142, on atrial fibrillation (AF) and flutter (AFL) and on electrophysiological variables were studied in the dog. NIP-142 (3mg/kg) was administered intravenously to pentobarbital-anesthetized beagles during vagally-induced AF and during AFL induced after placement of an intercaval crush. Isolated canine atrial tissues were studied using standard microelectrode technique. NIP-142 terminated AF in 5 of 6 dogs after an increase in fibrillation cycle length (CL) and prevented reinitiation of AF in all 6 dogs. NIP-142 terminated AFL in all 6 dogs without any appreciable change in flutter CL, and prevented reinitiation of AFL in all 6 dogs. NIP-142 prolonged atrial effective refractory periods (11+/-5%, 3+/-3%, 12+/-3%, and 10+/-5% from the baseline value at basic CLs of 150, 200, 300, and 350ms, respectively) without changes in intraatrial conduction time. The prolongation of the atrial effective refractory period was greater in the presence of vagal stimulation. NIP-142 decreased action potential phase-1 notch and increased phase-2 plateau height without making any changes in the action potential duration, although it did reverse carbachol-induced shortening of the action potential duration. In conclusion, NIP-142 is effective in treating AFL and vagally-induced AF by prolonging atrial refractoriness.


From Ebola to COVID-19: emergency preparedness and response plans and actions in Lagos, Nigeria.
Lagos state is the industrial nerve centre of Nigeria and was the epicentre of the 2014 Ebola outbreak in Nigeria as it is now for the current Coronavirus Disease (COVID-19) outbreak. This paper describes how the lessons learned from the Ebola outbreak in 2014 informed the emergency preparedness of the State ahead of the COVID-19 outbreak and guided response. Following the Ebola outbreak in 2014, the Lagos State government provided governance by developing a policy on emergency preparedness and biosecurity and provided oversight and coordination of emergency preparedness strategies. Capacities for emergency response were strengthened by training key staff, developing a robust surveillance system, and setting up a Biosafety Level 3 laboratory and biobank. Resource provision, in terms of finances and trained personnel for emergencies was prioritized by the government. With the onset of COVID-19, Lagos state was able to respond promptly to the outbreak using the centralized Incident Command Structure and the key activities of the Emergency Operations Centre. Contributory to effective response were partnerships with the private sectors, community engagement and political commitment. Using the lessons learned from the 2014 Ebola outbreak, Lagos State had gradually prepared its healthcare system for a pandemic such as COVID-19. The State needs to continue to expand its preparedness to be more resilient and future proof to respond to disease outbreaks. Looking beyond intra-state gains, lessons and identified best practices from the past and present should be shared with other states and countries.


[Change in visual evoked potential by radiotherapy of nasopharyngeal carcinoma].
To study the effect of radiotherapy of nasopharyngeal carcinoma on visual evoked potential (VEP). VEP of 63 patients with nasopharyngeal carcinoma were tested before, at the end of, half a year, one year, 2 years and 3 years after their radiotherapy. Within the male group, one year after radiotherapy, the latency of VEP was significantly delayed than that before and at the end of radiotherapy, while the amplitude was decreased significantly. Two years after radiotherapy, the latency of VEP was significantly delayed more than that before radiotherapy. However there was no significant difference among VEP at the end of, half a year and 3 years after radiotherapy. Within the female group, 2 years after radiotherapy, the latency of VEP was significantly delayed than that before radiotherapy. Three years after radiotherapy, the latency of VEP was significantly delayed than that before, at the end of, half a year and one year after radiotherapy. There was no significant difference in VEP amplitudes before and after radiotherapy. Within the male group, the abnormal delay of VEP latency mostly happens one or two years after radiotherapy. Within the female group, the significant delay of VEP latency happens at the end of radiotherapy and lasts for 3 years, while the VEP amplitude does not change significantly during the 3 years after radiotherapy. The result indicates that the sustained radiation damage within the female visual nerve system starts at the end of radiotherapy, but to a lesser degree. It was shown that radiotherapy of nasopharyngeal carcinoma certainly damages the visual nerve system, though there is sex difference in the impairment.


Efficacy of ECT for Agitation in Dementia: A Case Report.
A patient with vascular dementia had severe, unremitting agitation that was refractory to conventional therapies and put her life in jeopardy. She had a dramatic response to bilateral electroconvulsive therapy (ECT), with longitudinal follow-up demonstrating that her behavioral symptoms lapsed predictably when maintenance ECT was delayed.


Trophoblastic invasion of the uterine epithelium in Calomys callosus (Rodentia, Cricetidae).
Implantation sites in the uterus of the cricetid rodent Calomys callosus were examined by light and electron microscopy at several points during day 4 of pregnancy to determine the changes occurring in the trophoblast and epithelial cells during the early blastocyst-endometrial relationship, particularly the epithelial removal phase. By morning, the blastocysts had already lodged in the antimesometrial region of the uterine crypts and the embryo-maternal interaction was limited to sparse contacts between the epithelial microvilli and the trophoblast surface. A few dense and altered epithelial cells were present. Three zones could be distinguished in the stromal region. In the subepithelial area, the stromal cells showed features similar to those found in other rodents during the early decidualization process. Effective epithelial invasion by the trophoblast occurred only in the evening, although at noon, apposition and attachment phases were identifiable. During invasion, the trophoblast processes were first seen insinuating between the epithelial cells, projecting towards the basal lamina, and finally replacing these cells. The epithelial cells in contact with the invading trophoblast exhibited severe disorganization similar to that found during the process of cell death by apoptosis. The removal of such cells occurred by trophoblast phagocytosis. Once in contact with the basal lamina, the trophoblast rapidly spread out both mesometrially and antimesometrially, phagocytosing the remaining epithelial cells. Trophoblast processes were also seen penetrating the basal lamina. Given that the epithelium breached and phagocytosed by the trophoblast habitually displays degenerative characteristics, we consider the mechanisms that might be involved in epithelial cell death and in the removal of the uterine epithelium, and the participation of the trophoblast in both these events.


Effects of a benzimidazole compound on monooxygenase activities.
A retinoid-type benzimidazole compound (benzimidazole-tetranaphthalene, BITN) was synthesized and its effects on hepatic cytochrome P450 (CYP) dependent ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD) enzyme activities were determined in rats in vitro. In vitro addition of BITN in 10(-3) M concentration to the reaction medium caused inhibitions in EROD (94%) and PROD (82%) activities. With the same concentration (10(-3) M) all-trans-retinoic acid (RA) was able to inhibit EROD activity 65% and PROD activity 59% whereas buthylated hydroxytoluen (BHT) inhibited EROD and PROD activities 73% and 62%, respectively. The specific inhibitors of EROD activity (caffeine) and PROD activity (SKF 525A) at 10(-3) M concentration inhibited the corresponding enzymes 33% and 77%, respectively. Thus, these results reveal that the BITN has a stronger inhibitory effect than RA, BHT, caffeine and SKF 525 A on the enzyme activities. Since these enzymes (EROD, CYP 1A1/2 and PROD, CYP2B1) activate polycyclic hydrocarbons, aromatic amines and aliphatic halogenated hydrocarbons to their ultimate mutagenic or carcinogenic forms, and are effective in producing reactive oxygen species such as superoxide, hydroxyl radical and hydrogen peroxide, the new compound, BITN, appears to have a greater anticarcinogenic and antioxidant potential than RA and BHT.


Optimization of copper removal from aqueous solutions in a continuous electrochemical cell divided by cellulosic separator.
Copper, as an inseparable part of many industrial discharges, threatens both public and environmental health. In this work, an electrochemical cell utilizing a cellulosic separator was used to evaluate Cu removal using graphite anodes and stainless steel cathodes in a continuous-flow mode reactor. In the experimental matrix, Cu concentration (1-5 mg L-1), electrolysis time (20-90 min), and current intensity (0.1-0.4 A) were employed. Results showed that the maximum removal efficiency of copper was obtained as 99%. The removal efficiency was independent of initial copper concentration and directly related to electrolysis time and current intensity. Energy consumption was more dependent on current intensity than electrolysis time. Under optimal conditions (75.8 min electrolysis time, 0.18 A current intensity, and 3 mg L-1 copper concentration), the removal efficiency was obtained as 91% while 7.05 kWh m-3 electrical energy was consumed. The differences between the actual and predicted data under optimal conditions were 0.42% for copper removal and 0.23% for energy consumption, which signify the performance and reliability of the developed models. The results exhibited the suitability of the electrochemical reduction for copper removal from aqueous solutions, which was facilitated under alkaline conditions prevailing in the cathodic compartment due to applying a cell divided by a cellulosic separator.


The effects of enalapril maleate and cold stress exposure on tyrosine hydroxylase activity in some rat tissues.
Enalapril is a highly specific and competitive inhibitor of angiotensin-I converting enzyme (ACE) and thus belongs to the category of ACE inhibitors. The beneficial effects of ACE inhibitors appear to result primarily from the suppression of the plasma renin-angiotensin-aldesterone system. This study was designed to detect the effects of enalapril maleate and cold stress on tyrosine hydroxylase (TH) activity in adrenal medulla, heart and hypothalamus in rat. In cold stress treatment (exposed to 8 degrees C cold for 48 h) TH activity was found to be raised significantly (p < 0.05) in adrenal medulla, hypothalamus and heart tissues. In the adrenal medulla, hypothalamus and heart tissues, TH activity of enalapril maleate treated rats (10 mg kg(-1) body weight) group was not raised significantly (p > 0.05). Following intraperitoneal injection of enalapril maleate (10 mg kg(-1) body weight) the rats were exposed to 8 degrees C cold for 48 h. After cold stress and enalapril maleate treatment no statistically significant change in tyrosine hydroxylase activity was detected in adrenal medulla, hypothalamus or heart (p > 0.05). The results of our studies show that enalapril maleate blocks the effect of cold stress on the regulation of TH activity.


Resolved: Low-dose prednisone is indicated as a standard treatment in patients with rheumatoid arthritis.
It is known and has been repeatedly demonstrated that low doses of prednisone or prednisolone (10 mg daily or 5 mg bid) will control most of the inflammatory features of early polyarticular rheumatoid arthritis (Table 2). Also, low doses of prednisolone are known to retard the bony damage of rheumatoid arthritis, and thus these are the original disease-modifying antirheumatic drugs. Glucocorticoids are potent antiinflammatory and immunosuppressive agents by virtue of their repression of the genomic expression by transcriptional interference, inhibiting such proinflammatory proteins as COX-2, IL-1, IL-2, IL-6, TNFalpha, and adhesion molecules. Nature has produced an ideal antiinflammatory and immunosuppressive agent, namely glucocorticoids, and it is up to us to use it in appropriate situations (e.g., active early inflammatory polyarticular rheumatoid arthritis) and in low doses, frequently daily divided doses. Low doses of glucocorticoids (prednisone or prednisolone) accomplish everything NSAIDs or COX-2 inhibitors accomplish but with more antiinflammatory effects, fewer side effects, and much less expense. It is certainly possible (but not precisely tested) that low doses of prednisone (prednisolone) enhance the effects of other DMARDs, including anti-TNF agents. The side effects of low-dose glucocorticoids are minimal. By using concomitant calcium and vitamin D and monitoring bone status with DEXA scans, the osteopenia potential of low doses of prednisone will be minimal. The use of low-dose prednisone without NSAIDs will put the patient at very little risk for stomach ulceration and bleeding.


Regulation of apical transporter of L-DOPA in human intestinal Caco-2 cells.
The present study examined the nature of the apical inward L-3,4-dihydroxyphenylalanine (L-DOPA) transporter in human intestinal epithelial Caco-2 cells, and whether protein kinases modulate the activity of this transporter. The apical inward transfer of L-DOPA was promoted through an energy-dependent and sodium-insensitive transporter (Km=33 microM; Vmax=2932 pmol/mg protein/6 min). This transporter was insensitive to N-(methylamino)-isobutyric acid, but competitively inhibited by 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH; IC50=83 microM). The organic cation inhibitor decynium 24 failed to affect the accumulation of L-DOPA, whereas the organic anion inhibitor 4,4'-diisothiocynatostilbene-2,2'-disulphonic acid (DIDS) competitively inhibited L-DOPA uptake (IC50=83 microM). However, the apical-to-basal and basal-to-apical transepithelial transport and the cell accumulation of [3H]-PAH was close to that of [14C]-sorbitol and insensitive to DIDS (300 microM). Modulators of protein kinase A (PKA) [cyclic adenosine monophosphate (cAMP), forskolin, H-89 and cholera toxin], protein kinase G (PKG) [cyclic guanosine monophosphate (GMP), zaprinast, LY 83583 and sodium nitroprusside] and protein kinase C (PKC) (phorbol 12,13-dibutirate and chelerythrine) failed to affect the accumulation of L-DOPA. The Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-DOPA uptake (IC50s of 53 and 252 microM, respectively), but the rise of intracellular Ca2+ by A23187 (1 microM) and thapsigargin (1 microM) played no role on L-DOPA uptake. It is concluded that Caco-2 cells take up L-DOPA over the apical cell border through the sodium-independent and pH-sensitive L-type amino acid transporter.


Liver resection for colorectal liver metastases in older patients.
Seventy-six percentages of patients with a newly diagnosed colorectal carcinoma are between 65 and 85 years old. A substantial proportion will develop liver metastases, for which resection is the only potential curative treatment. This study was conducted to investigate both the feasibility, and short- and long-term outcomes of liver resection for colorectal liver metastases in elderly patients. Between August 1990 and April 2007 data were prospectively collected on patients over 70 years of age who underwent a liver resection for colorectal liver metastases in a single centre. One hundred and eighty-one liver resections were performed in 178 consecutive patients (median age 74 years). Thirty-four patients (18.8%) received neoadjuvant chemotherapy (all FOLFOX) prior to liver surgery and the majority (57.5%) of liver resections involved more than two Couinaud's segments. Median hospital stay was 13 days, 70 (38.5%) patients had postoperative complications, and overall in hospital mortality was 4.9% (9 patients). Overall- and disease-free survival rates at 1, 3 and 5 years were 86.1%, 43.2% and 31.5% and 65.8%, 26% and 16%, respectively. In multivariate analysis: T3 primary staging; major liver resections; more than three liver lesions; and the occurrence of postoperative complications were associated with inferior overall survival. Liver resection for colorectal liver metastases in elderly patients is safe and may offer long-time survival to a substantial percentage of patients. We strongly recommend considering senior patients for surgical treatment whenever possible.


Competencies drive decision making.
Staff nurses, using the Nursing Interventions Classification, selected the core competencies, performance criteria and interventions relevant to their practice. A performance-based approach highlights performance outcomes and previous experience. A preceptor and self-directed learning activities help apply the knowledge in the work setting.


Speech perception by infants: categorization based on nasal consonant place of articulation.
This study examined the ability of six-month-old infants to recognize the perceptual similarity of syllables sharing a phonetic segment when variations were introduced in phonetic environment and talker. Infants in a "phonetic" group were visually reinforced for head turns when a change occurred from a background category of labial nasals to a comparison category of alveolar nasals . The infants were initially trained on a [ma]-[na] contrast produced by a male talker. Novel tokens differing in vowel environment and talker were introduced over several stages of increasing complexity. In the most complex stage infants were required to make a head turn when a change occurred from [ma,mi,mu] to [na,ni,nu], with the tokens in each category produced by both male and female talkers. A " nonphonetic " control group was tested using the same pool of stimuli as the phonetic condition. The only difference was that the stimuli in the background and comparison categories were chosen in such a way that the sounds could not be organized by acoustic or phonetic characteristics. Infants in the phonetic group transferred training to novel tokens produced by different talkers and in different vowel contexts. However, infants in the nonphonetic control group had difficulty learning the phonetically unrelated tokens that were introduced as the experiment progressed. These findings suggest that infants recognize the similarity of nasal consonants sharing place of articulation independent of variation in talker and vowel context.


Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer's disease by meta-analysis and adaptive boosting ensemble learning.
Blood circulating microRNAs that are specific for Alzheimer's disease (AD) can be identified from differentially expressed microRNAs (DEmiRNAs). However, non-reproducible and inconsistent reports of DEmiRNAs hinder biomarker development. The most reliable DEmiRNAs can be identified by meta-analysis. To enrich the pool of DEmiRNAs for potential AD biomarkers, we used a machine learning method called adaptive boosting for miRNA disease association (ABMDA) to identify eligible candidates that share similar characteristics with the DEmiRNAs identified from meta-analysis. This study aimed to identify blood circulating DEmiRNAs as potential AD biomarkers by augmenting meta-analysis with the ABMDA ensemble learning method. Studies on DEmiRNAs and their dysregulation states were corroborated with one another by meta-analysis based on a random-effects model. DEmiRNAs identified by meta-analysis were collected as positive examples of miRNA-AD pairs for ABMDA ensemble learning. ABMDA identified similar DEmiRNAs according to a set of predefined criteria. The biological significance of all resulting DEmiRNAs was determined by their target genes according to pathway enrichment analyses. The target genes common to both meta-analysis- and ABMDA-identified DEmiRNAs were collected to construct a network to investigate their biological functions. A systematic database search found 7841 studies for an extensive meta-analysis, covering 54 independent comparisons of 47 differential miRNA expression studies, and identified 18 reliable DEmiRNAs. ABMDA ensemble learning was conducted based on the meta-analysis results and the Human MicroRNA Disease Database, which identified 10 additional AD-related DEmiRNAs. These 28 DEmiRNAs and their dysregulated pathways were related to neuroinflammation. The dysregulated pathway related to neuronal cell cycle re-entry (CCR) was the only statistically significant pathway of the ABMDA-identified DEmiRNAs. In the biological network constructed from 1865 common target genes of the identified DEmiRNAs, the multiple core ubiquitin-proteasome system, that is involved in neuroinflammation and CCR, was highly connected. This study identified 28 DEmiRNAs as potential AD biomarkers in blood, by meta-analysis and ABMDA ensemble learning in tandem. The DEmiRNAs identified by meta-analysis and ABMDA were significantly related to neuroinflammation, and the ABMDA-identified DEmiRNAs were related to neuronal CCR.


Mini-subvastus versus medial parapatellar approach in total knee arthroplasty.
We compared short-term clinical results of the mini-subvastus approach with the standard parapatellar approach for total knee arthroplasty. Can one gain adequate access through the mini-subvastus approach without exceeding operating time, incurring additional complications, and maintaining correct implant geometry? In a prospective, observer-blinded study, 120 consecutive patients having total knee arthroplasty were operated on by one surgeon using either the mini-subvastus approach without patella eversion or the standard parapatellar approach with patella eversion. Patients were matched according to age, gender, body mass index, knee flexion, deformity, and pre-existing high tibial osteotomy. The mini-subvastus approach was technically more demanding. Reduced access and visibility prolonged the tourniquet time by an average of 15 minutes and led to two intraoperative complications. Patients in the mini-subvastus group lost on average 100 mL less blood and had better pain scores on day one [visual analogue scale (VAS): mean 2.4 versus 3.89]. They reached 90 degrees knee flexion earlier (2.8 versus 4.5 days), and an active straight-leg raise earlier (3.2 versus 4.1 days). Their average flexion at 30, 60 and 90 days was slightly better (100 degrees , 110 degrees , and 112 degrees versus 94 degrees , 106 degrees , and 109 degrees ). All patients including those with complications had good results with good component geometry and leg alignment. The mini-subvastus approach offers early but short-lived benefits for patients at the expense of a longer operation and a higher risk of complications. Therapeutic study, Level II-1 (prospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.


Explanation-based learning in infancy.
In explanation-based learning (EBL), domain knowledge is leveraged in order to learn general rules from few examples. An explanation is constructed for initial exemplars and is then generalized into a candidate rule that uses only the relevant features specified in the explanation; if the rule proves accurate for a few additional exemplars, it is adopted. EBL is thus highly efficient because it combines both analytic and empirical evidence. EBL has been proposed as one of the mechanisms that help infants acquire and revise their physical rules. To evaluate this proposal, 11- and 12-month-olds (n = 260) were taught to replace their current support rule (that an object is stable when half or more of its bottom surface is supported) with a more sophisticated rule (that an object is stable when half or more of the entire object is supported). Infants saw teaching events in which asymmetrical objects were placed on a base, followed by static test displays involving a novel asymmetrical object and a novel base. When the teaching events were designed to facilitate EBL, infants learned the new rule with as few as two (12-month-olds) or three (11-month-olds) exemplars. When the teaching events were designed to impede EBL, however, infants failed to learn the rule. Together, these results demonstrate that even infants, with their limited knowledge about the world, benefit from the knowledge-based approach of EBL.


[Blood 7-ketocholesterol level, clinical features and gene mutation analysis of 18 children with Niemann-Pick disease type C].
To investigate 7-ketocholesterol (7-KC) level in the blood, clinical features and gene mutation of Niemann-Pick disease type C (NPC). Eighteen patients diagnosed as NPC in Shanghai Xinhua Hospital seen from February 2013 to October 2014 were enrolled in this study. They included 13 males and 5 females and aged from 5 months to 21 years. The plasma 7-KC concentrations, clinical features and gene mutations of NPC patients were reviewed retrospectively. Fourteen NPC patients had neurological symptoms with the age of neurological onset from 1 year to 16 years. In seven cases the disease was early-infantile subtype, in 1 late-infantile subtype, in five juvenile subtype and in one adult subtype. The 7-KC value in the plasma of NPC patients was higher than the normal range, (348.5±168.7) μg/L in the early-infantile subtype, 150.6 μg/L in the late-infantile subtype, (145.0±46.3) μg/L in the juvenile subtype, and 32.0 μg/L in the adult subtype, respectively, additionally, four NPC patients had no observable neuropsychiatric disability when confirmed to be NPC by genetic testing, with the plasma 7-KC value (345.6±134.2) μg/L; 16 of 18 patients had splenomegaly or hepatosplenomegaly. Among 18 patients, 34 different mutations in the NPC1 gene were identified including 27 reported mutations, 1 novel small deletion 3609_3610delAC, five novel exonic point mutations, c. 3683T>C(M1228T), c. 3679A>T(R1227W), c. 1070C>T(S357L), c. 1456A>C(N486H) and c. 1142G>A(W381X) and 1 novel intronic mutation c. 881+ 3A>G. The 7-KC levels in the blood of patient was remarkably increased, and there was a tendency that 7-KC levels inversely correlated with the age of neurological onset. Most NPC patient had splenomegaly or hepatosplenomegaly. Among 18 patients, 34 different mutations in the NPC1 gene were identified including seven novel mutations, which enriched the gene mutation spectrum.


Crosslinking of a Single Poly(ionic liquid) by Water into Porous Supramolecular Membranes.
Reversible regulation of membrane microstructures via non-covalent interactions is of considerable interest yet remains a challenge. Herein, we discover a general one-step approach to fabricate supramolecular porous polyelectrolyte membranes (SPPMs) from a single poly(ionic liquid) (PIL). The experimental results and theoretical simulation suggested that SPPMs were formed by a hydrogen-bond-induced phase separation of a PIL between its polar and apolar domains, which were linked together by water molecules. This unique feature was capable of modulating microscopic porous architectures and thus the global mechanical property of SPPMs by a rational design of the molecular structure of PILs. Such SPPMs could switch porosity upon thermal stimuli, as exemplified by dynamically adaptive transparency to thermal fluctuation. This finding provides fascinating opportunities for creating multifunctional SPPMs.


Deep Friction Massage Versus Steroid Injection in the Treatment of Lateral Epicondylitis.
The aim of the study was to determine the efficacy of deep friction massage in the treatment of lateral epicondylitis by comparing outcomes with a control group treated with splinting and therapy and with an experimental group receiving a local steroid injection. A randomized clinical trial was conducted to compare outcomes after recruitment of consecutive patients presenting with lateral epicondylitis. Patients were randomized to receive one of 3 treatments: group 1: splinting and stretching, group 2: a cortisone injection, or group 3: a lidocaine injection with deep friction massage. Pretreatment and posttreatment parameters of visual analog scale (VAS) pain ratings, Disabilities of the Arm, Shoulder and Hand (DASH) scores, and grip strength were measured. Outcomes were measured at early follow-up (6-12 weeks) and at 6-month follow-up. There was a significant improvement in VAS pain score in all treatment groups at early follow-up. DASH score and grip strength improved in the cortisone injection group and the deep friction massage group at early follow-up; these parameters did not improve in the splinting and stretching group. At 6-month follow-up, only patients in the deep friction massage group demonstrated a significant improvement in all outcome measures, including VAS pain score, DASH score, and grip strength. Deep friction massage is an effective treatment for lateral epicondylitis and can be used in patients who have failed other nonoperative treatments, including cortisone injection.


Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001.
Because the causes of most lymphoid neoplasms remain unknown, comparison of incidence patterns by disease subtype may provide critical clues for future etiologic investigations. We therefore conducted a comprehensive assessment of 114,548 lymphoid neoplasms diagnosed during 1992-2001 in 12 Surveillance, Epidemiology, and End Results (SEER) registries according to the internationally recognized World Health Organization (WHO) lymphoma classification introduced in 2001. Cases coded in International Classification of Diseases for Oncology, Second Edition (ICD-O-2), were converted to ICD-O-3 for WHO subtype assignment. Age-specific and age-adjusted rates were compared by sex and race (white, black, Asian). Age-adjusted trends in incidence were estimated by sex and race using weighted least squares log-linear regression. Diverse incidence patterns and trends were observed by lymphoid neoplasm subtype and population. In the elderly (75 years or older), rates of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma increased 1.4% and 1.8% per year, respectively, whereas rates of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) declined 2.1% per year. Although whites bear the highest incidence burden for most lymphoid neoplasm subtypes, most notably for hairy cell leukemia and follicular lymphoma, black predominance was observed for plasma cell and T-cell neoplasms. Asians have considerably lower rates than whites and blacks for CLL/SLL and Hodgkin lymphoma. We conclude that the striking differences in incidence patterns by histologic subtype strongly suggest that there is etiologic heterogeneity among lymphoid neoplasms and support the pursuit of epidemiologic analysis by subtype.


Expression of Wilms tumor 1 gene distinguishes vascular malformations from proliferative endothelial lesions.
Vascular malformations and hemangiomas, which are endothelial lesions of childhood, may result in considerable morbidity because they can cause discomfort and functional impairment and have a negative affect on the patient's appearance. Although vascular malformations may initially appear very similar to hemangiomas, they have distinct clinical courses. Infantile hemangiomas progress through 3 stages: proliferative, involuting, and involuted. The proliferative phase is characterized by clinical growth. Once hemangiomas reach their maximum size, they begin to regress or involute. Histologically, this stage is characterized by endothelial apoptosis. Finally, the involuted stage of the hemangioma occurs when the original lesion is replaced by a connective tissue remnant. In contrast to hemangiomas, vascular malformations do not involute but continue to enlarge as the patient grows. The biochemical differences between hemangiomas, which involute, and vascular malformations, which do not involute, are not well understood. We found that the transcription factor encoded by the Wilms tumor 1 (WT1) gene is expressed in the endothelium of hemangiomas but not in vascular malformations. Defects in WT1 signaling may underlie the inability of malformation endothelial cells to undergo physiologic apoptosis and remodeling. The availability of WT1 staining in hospital laboratories may allow the clinician to distinguish hemangiomas from vascular malformations and thus to give appropriate therapy to the patient.


Preparation of 2,4,5-Trisubstituted Oxazoles through Iodine-mediated Aerobic Oxidative Cyclization of Enaminones.
A novel approach to trisubstituted oxazoles has been developed that is based upon an iodine-mediated aerobic oxidative cyclization of enaminone derivatives. This transition-metal-free procedure was highly efficient and involved the removal of four hydrogen atoms under mild conditions.


Reaching the covert, fragile side of patients: the case of narcissistic personality disorder.
A multifaceted self allows selection of those sides that are most suited to a situation and an interpersonal context, thus improving adaptation. Patients suffering from personality disorders display a limited range of self-aspects, and their relationships are stereotyped and maladaptive. Another problem is that some of these sides scarcely reach consciousness and usually remain in the background. In the case of narcissistic personality disorder (NPD) the self-part that is fragile is unlikely to reach consciousness, so that people suffering from this disorder are impervious and detached. We present a case of a psychotherapist working with a woman suffering from NPD by facilitating the emergence of the fragile part of her self, hidden by angry and scornful characters. We demonstrate, moreover, how reaching such a self-part is associated with an improvement in the patient's interpersonal relationships outside the consulting room.


Prognostic significance of loss of a chromosome 17p and p53 gene mutations in blast crisis of chronic myelogenous leukaemia.
In 31 cases of chronic myelogenous leukaemia (CML) we examined the prognostic significance of chromosomal loss of a 17p and p53 mutations at the onset of blast crisis (BC). p53 mutations were closely related to a shortened survival in CML-BC (P < 0.005 by the logrank test), whereas loss of a 17p by itself was not a poor prognostic indicator. The prognostic significance of loss of a 17p, however, emerged when combined with its predominance in the metaphases analysed. This predominance might easily and rapidly be screened by polymerase chain reaction-based analysis in about half of the cases.


[A nidulans bronchial aspergillosis after treatment of low-grade lymphoma with fludarabine].
Pulmonary aspergillosis is a common complication in neutropenic patients. The most important fungus is Aspergillus fumigatus. We report a case of invasive pulmonary aspergillosis due to Aspergillus nidulans secondary to fludarabine therapy. There are few cases of pulmonary aspergillosis due to Aspergillus nidulans (one chronic necrotizing pulmonary aspergillosis, one aspergilloma). Fludarabine induces a marked decreased of CD4 lymphocyte count responsible for opportunistic infections. It is the first case of aspergillosis after fludarabine therapy and the occurrence of such infection must be considered after purine analog therapy.


Comparison of sisomicin and gentamicin in bacteriuric patients with underlying diseases of the urinary tract.
Sisomicin and gentamicin (2 mg/kg) were administered in a random fashion to patients with bacteriuria superimposed on abnormalities of the urinary tract. Cure was achieved in a similar number of patients in both groups, but superinfection and reinfection with resistant microorganisms was more frequent in patients receiving gentamicin. Untoward side effects were not frequent in this series, especially if the serious underlying urological disease of most patients is taken into consideration. The susceptibility of the causative pathogens to the antibiotic administered and the severity of the underlying disease were the most important factors in the outcome.


Insulin in w/o/w multiple emulsions: biological activity after oral administration in normal and diabetic rats.
In this work the biological effects of two w/o/w multiple emulsions composed of the soybean oil (EHS) or medium-chain triglycerides (ETCM), containing insulin, were studied. The release mechanism of insulin from multiple emulsions proposed in our previous in-vitro investigations was confirmed by subcutaneous administration. This mechanism is the swelling-breakdown phenomenon which occurs when the emulsions are diluted under hypo-osmotic condition. The biological effect after oral administration, evaluated in two experimental protocols, single administration in normal and diabetic rats and short-term treatment in diabetic rats, shows that in diabetic rats small amounts of biologically active insulin were absorbed from these emulsions. In these experiments no significant difference between EHS and ETCM was found.


Genetic regulation of the quinic acid utilization (QUT) gene cluster in Aspergillus nidulans.
A large number of quinic acid non-utilizing qut mutants of Aspergillus nidulans deficient in the induction of all three quinic acid specific enzymes have been analysed. One class the qutD mutants, are all recessive and are non-inducible at pH 6.5 due to inferred deficiency in a quinate ion permease. Two regulatory genes have been identified. The QUTA gene encodes an activator protein since most qutA mutants are recessive and non-inducible although a few fully dominant mutants have been found. The QUTR gene encodes a repressor protein since recessive mutations are constitutive for all three enzyme activities. Rare dominant non-inducible mutants which revert readily to yield a high proportion of constitutive strains are inferred to be qutR mutants defective in binding the inducer. The gene cluster has been mapped in the right arm of chromosome VIII in the order: centromere - greater than 50 map units - ornB - 12 map units - qutC (dehydratase)-0.8 map units-qutD (permease), qutB (dehydrogenase), qutE (dehydroquinase), qutA (activator)-4.4 map units - qutR (repressor)-20 map units - galG. This organization differs from that of the qa gene cluster in Neurospora crassa, particularly in the displacement of qutC and qutR.


Altered Brain Functional Activity in Infants with Congenital Bilateral Severe Sensorineural Hearing Loss: A Resting-State Functional MRI Study under Sedation.
Early hearing deprivation could affect the development of auditory, language, and vision ability. Insufficient or no stimulation of the auditory cortex during the sensitive periods of plasticity could affect the function of hearing, language, and vision development. Twenty-three infants with congenital severe sensorineural hearing loss (CSSHL) and 17 age and sex matched normal hearing subjects were recruited. The amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo) of the auditory, language, and vision related brain areas were compared between deaf infants and normal subjects. Compared with normal hearing subjects, decreased ALFF and ReHo were observed in auditory and language-related cortex. Increased ALFF and ReHo were observed in vision related cortex, which suggest that hearing and language function were impaired and vision function was enhanced due to the loss of hearing. ALFF of left Brodmann area 45 (BA45) was negatively correlated with deaf duration in infants with CSSHL. ALFF of right BA39 was positively correlated with deaf duration in infants with CSSHL. In conclusion, ALFF and ReHo can reflect the abnormal brain function in language, auditory, and visual information processing in infants with CSSHL. This demonstrates that the development of auditory, language, and vision processing function has been affected by congenital severe sensorineural hearing loss before 4 years of age.


DpiA binding to the replication origin of Escherichia coli plasmids and chromosomes destabilizes plasmid inheritance and induces the bacterial SOS response.
The dpiA and dpiB genes of Escherichia coli, which are orthologs of genes that regulate citrate uptake and utilization in Klebsiella pneumoniae, comprise a two-component signal transduction system that can modulate the replication of and destabilize the inheritance of pSC101 and certain other plasmids. Here we show that perturbed replication and inheritance result from binding of the effector protein DpiA to A+T-rich replication origin sequences that resemble those in the K. pneumoniae promoter region targeted by the DpiA ortholog, CitB. Consistent with its ability to bind to A+T-rich origin sequences, overproduction of DpiA induced the SOS response in E. coli, suggesting that chromosomal DNA replication is affected. Bacteria that overexpressed DpiA showed an increased amount of DNA per cell and increased cell size-both also characteristic of the SOS response. Concurrent overexpression of the DNA replication initiation protein, DnaA, or the DNA helicase, DnaB-both of which act at A+T-rich replication origin sequences in the E. coli chromosome and DpiA-targeted plasmids-reversed SOS induction as well as plasmid destabilization by DpiA. Our finding that physical and functional interactions between DpiA and sites of replication initiation modulate DNA replication and plasmid inheritance suggests a mechanism by which environmental stimuli transmitted by these gene products can regulate chromosomal and plasmid dynamics.


Intervertebral anticollision constraints improve out-of-plane translation accuracy of a single-plane fluoroscopy-to-CT registration method for measuring spinal motion.
The study aimed to propose a new single-plane fluoroscopy-to-CT registration method integrated with intervertebral anticollision constraints for measuring three-dimensional (3D) intervertebral kinematics of the spine; and to evaluate the performance of the method without anticollision and with three variations of the anticollision constraints via an in vitro experiment. The proposed fluoroscopy-to-CT registration approach, called the weighted edge-matching with anticollision (WEMAC) method, was based on the integration of geometrical anticollision constraints for adjacent vertebrae and the weighted edge-matching score (WEMS) method that matched the digitally reconstructed radiographs of the CT models of the vertebrae and the measured single-plane fluoroscopy images. Three variations of the anticollision constraints, namely, T-DOF, R-DOF, and A-DOF methods, were proposed. An in vitro experiment using four porcine cervical spines in different postures was performed to evaluate the performance of the WEMS and the WEMAC methods. The WEMS method gave high precision and small bias in all components for both vertebral pose and intervertebral pose measurements, except for relatively large errors for the out-of-plane translation component. The WEMAC method successfully reduced the out-of-plane translation errors for intervertebral kinematic measurements while keeping the measurement accuracies for the other five degrees of freedom (DOF) more or less unaltered. The means (standard deviations) of the out-of-plane translational errors were less than -0.5 (0.6) and -0.3 (0.8) mm for the T-DOF method and the R-DOF method, respectively. The proposed single-plane fluoroscopy-to-CT registration method reduced the out-of-plane translation errors for intervertebral kinematic measurements while keeping the measurement accuracies for the other five DOF more or less unaltered. With the submillimeter and subdegree accuracy, the WEMAC method was considered accurate for measuring 3D intervertebral kinematics during various functional activities for research and clinical applications.


Characterization of chaperonin 10 (Cpn10) from the intestinal human pathogen Entamoeba histolytica.
Entamoeba histolytica is the causative agent of amoebiasis, a poverty-related disease that kills an estimated 100 000 people each year. E. histolytica does not contain "standard mitochondria", but harbours mitochondrial remnant organelles called mitosomes. These organelles are characterized by the presence of mitochondrial chaperonin Cpn60, but little else is known about the functions and molecular composition of mitosomes. In this study, a gene encoding molecular chaperonin Cpn10--the functional partner of Cpn60--was cloned, and its structure and expression were characterized, as well as the cellular localization of its encoded protein. The 5' untranslated region of the gene contains all of the structural promoter elements required for transcription in this organism. The amoebic Cpn10, like Cpn60, is not significantly upregulated upon heat-shock treatment. Computer-assisted protein modelling, and specific antibodies against Cpn10 and Cpn60, suggest that both proteins interact with each other, and that they function in the same intracellular compartment. Thus, E. histolytica appears to have retained at least two of the key molecular components required for the refolding of imported mitosomal proteins.


IL-17A-producing T cells are associated with the progression of lung adenocarcinoma.
Accumulating evidence has shown that T cells are crucial in shaping the tumor microenvironment and regulating tumor development. However, the roles of IL-17A‑producing T cells (IL-17A+CD4+ Th17, IL-17A+CD8+ Tc17 and IL-17A+ γδT17 cells) and related cytokines in the progression of lung cancer (LC) remain uncertain. Here, we found that the frequencies of both Th17 and γδT17 cells in the peripheral blood of patients with lung adenocarcinoma (LA) were higher than those in healthy controls (HCs), whereas the frequency of Tc17 cells in the patients with LA was decreased. In addition, the frequencies of circulating Th17 and γδT17 cells, but not Tc17 cells, were positively associated with tumor invasion and metastasis. Furthermore, the major source of IL-17A production was Th17 cells, followed by Tc17 and γδT17 cells, in peripheral blood from patients with LA and HCs; but the percentages of Th17 and γδT17 cells in total intracellular IL-17A+ cells obtained from the patients with LC were higher than those from HCs. Moreover, the protein and corresponding mRNA levels of IL-17A, IL-23, IL-1β, and TGF-β1 were much higher in the patients with LA than those in HCs, and the levels of IL-17A in patients were positively correlated with numbers of both Th17 and γδT17 cells, but not Tc17 cells. Finally, the frequencies of circulating Th17 and γδT17 cells, along with the levels of IL-17A, IL-23, IL-1β, and TGF-β1 were decreased in the patients with LA after tumor resection, whereas the frequency of circulating Tc17 cells was inversely increased in these patients. Our findings indicate that Th17, Tc17, γδT17 cells, and IL-17A-associated cytokines contribute to the development of LA and thus represent promising targets for therapeutic strategies.


[Centralisation of acute stroke care is not better].
There is no evidence that centralisation of acute stroke care will lead to more performance of thrombolysis, in the Netherlands, to a reduction in the 'door-to-needle' time or a better outcome after stroke. The implementation of far-reaching changes in acute stroke care in the Netherlands would be dangerous, and would not lead to better and cheaper, but to worse and more expensive care.


4: Acute community-acquired meningitis and encephalitis.
Acute meningitis and encephalitis are medical emergencies that require prompt assessment (usually by cerebral imaging and lumbar puncture) and treatment; specialist consultation is recommended. In acute meningitis, early administration of antibiotics can be life-saving (usually high-dose penicillin and/or a third-generation cephalosporin); antibiotics may be needed before referral to hospital. Emergence of penicillin and cephalosporin resistance in Streptococcus pneumoniae has necessitated more complex antibiotic regimens that include vancomycin or rifampicin for empirical treatment of meningitis. Adjunctive dexamethasone therapy may be of benefit in children with Haemophilus influenzae meningitis; there is no controlled evidence of its benefit in adults, but it could be considered in those with raised intracranial pressure. In possible encephalitis, empirical therapy with intravenous aciclovir should be given to cover herpes simplex virus (HSV) until the cause is established; HSV encephalitis may be fatal and leaves up to 50% of survivors with long-term sequelae.


The association between the two more common genetic causes of spermatogenic failure: a 7-year retrospective study.
Chromosomal abnormalities and Y chromosome microdeletions are considered to be the two more common genetic causes of spermatogenic failure. However, the relationship between chromosomal aberrations and Y chromosome microdeletions is still unclear. This study was to investigate the incidence and characteristics of chromosomal aberrations and Y chromosome microdeletions in infertile men, and to explore whether there was a correlation between the two genetic defects of spermatogenic failure. A 7-year retrospective study was conducted on 5465 infertile men with nonobstructive azoospermia or oligozoospermia. Karyotype analysis of peripheral blood lymphocytes was performed by standard G-banding techniques. Y chromosome microdeletions were screened by multiplex PCR amplification with six specific sequence-tagged site (STS) markers. Among the 5465 infertile men analyzed, 371 (6.8%) had Y chromosome microdeletions and the prevalence of microdeletions in azoospermia was 10.5% (259/2474) and in severe oligozoospermia was 6.3% (107/1705). A total of 4003 (73.2%) infertile men underwent karyotyping; 370 (9.2%) had chromosomal abnormalities and 222 (5.5%) had chromosomal polymorphisms. Karyotype analysis was performed on 272 (73.3%) patients with Y chromosome microdeletions and 77 (28.3%) had chromosomal aberrations, all of which involved sex chromosomes but not autosomes. There was a significant difference in the frequency of chromosomal abnormalities between men with and without Y chromosome microdeletions (P< 0.05).


[Acute aspiration and trismus due to tetanus].
Tetanus is a worldwide health problem, causing the deaths of approximately 1,000,000 people every year. In Germany, about 15 infections are reported annually. The initial symptoms often develop in the head and neck region. As a result, some patients are referred to the otorhinolaryngologist. We report on a 83 year old female who suffered from recurrent aspiration and trismus. She had acquired a small injury on her lower leg 2 weeks earlier; protective antibody levels did not exist. The neurophysiological examination showed a result typical of tetanus. The patient received tetanus immunoglobulin, metronidazole and benzodiazepines. Due to respiratory problems, tracheotomy and ventilation became necessary. Elderly people often lack protective antibody levels against tetanus. If typical symptoms are manifest, tetanus has to be considered as a possibility. A complete history, including recent injuries and past vaccinations, should be compiled.


Molecular Origins of Deformation in Amorphous Methane Hydrates.
Water and methane can stay together under low temperature and high pressure in the forms of liquid solutions and crystalline solids. From liquid and gaseous states to crystalline solids or the contrary processes, amorphous methane hydrates can occur in these evolution scenarios. Herein, mechanical properties of amorphous methane hydrates are explored for the first time to bridge the gap between mechanical responses of monocrystalline and polycrystalline methane hydrates. Our results demonstrate that mechanical properties of amorphous methane hydrates are strongly governed by our original proposed order parameter, namely, normalized hydrogen-bond directional order parameter. Followed by this important achievement, a multistep deformation mechanism core is proposed to explain mechanical properties of amorphous methane hydrates. Through an extensive detailed analysis of amorphous methane hydrates, our simulation results not only greatly enlarge our fundamental understanding for mechanical responses of amorphous methane hydrates in geological systems but also offer a fresh perspective in structure-property topics of solid materials in future science and technology.


Causal role of Helicobacter pylori in peptic ulcer relapse.
Helicobacter pylori has been shown to infect the gastric mucous layer of almost all patients with duodenal ulcer disease, as well as that of most patients with gastric ulcer disease. Recent studies have suggested that the eradication of H. pylori affects the natural history of duodenal ulcer disease such that the rate of relapse decreases markedly. We evaluated the relationship between H. pylori infection and peptic ulcer relapse in a Japanese population following a prospective study. Seven of 18 (38.9%) gastric ulcer patients positive for H. pylori relapsed by the end of 1 year, whereas only 1 of 9 (11.1%) gastric ulcer patients without H. pylori developed ulcer relapse (P < 0.05). Relapse rates of duodenal ulcer patients negative for H. pylori were significantly lower than those positive for H. pylori within 1 year (0% vs 66.7%; P < 0.01). The effects of anti-H. pylori drugs on the eradication of H. pylori were examined in 50 patients with peptic ulcers. Eradication rates with a proton pump inhibitor (PPI) alone (omeprazole 20 mg) showed the lowest values (4 of 13; 30.8%). The rates were: 44.4% for amoxicillin alone (4 of 9); 70% for triple therapy consisting of amoxicillin, metronidazole, and bismuth subnitrate (14 of 20); and 87.5% for concomitant therapy of the PPI plus amoxicillin (7 of 8). Reinfection rates of H. pylori within 1 year after eradication of this organism were distinctly higher in the PPI alone group (80%) than in other groups (18.2%-32.4%).(ABSTRACT TRUNCATED AT 250 WORDS)


A new acoustic lens material for large area detectors in photoacoustic breast tomography.
We introduce a new acoustic lens material for photoacoustic tomography (PAT) to improve lateral resolution while possessing excellent acoustic acoustic impedance matching with tissue to minimize lens induced image artifacts. A large surface area detector due to its high sensitivity is preferable to detect weak signals in photoacoustic mammography. The lateral resolution is then limited by the narrow acceptance angle of such detectors. Acoustic lenses made of acrylic plastic (PMMA) have been used to enlarge the acceptance angle of such detectors and improve lateral resolution. However, such PMMA lenses introduce image artifacts due to internal reflections of ultrasound within the lenses, the result of acoustic impedance mismatch with the coupling medium or tissue. A new lens is proposed based on the 2-component resin Stycast 1090SI. We characterized the acoustic properties of the proposed lens material in comparison with commonly used PMMA, inspecting the speed of sound, acoustic attenuation and density. We fabricated acoustic lenses based on the new material and PMMA, and studied the effect of the acoustic lenses on detector performance comparing finite element (FEM) simulations and measurements of directional sensitivity, pulse-echo response and frequency response. We further investigated the effect of using the acoustic lenses on the image quality of a photoacoustic breast tomography system using k-Wave simulations and experiments. Our acoustic characterization shows that Stycast 1090SI has tissue-like acoustic impedance, high speed of sound and low acoustic attenuation. These acoustic properties ensure an excellent acoustic lens material to minimize the acoustic insertion loss. Both acoustic lenses show significant enlargement of detector acceptance angle and lateral resolution improvement from modeling and experiments. However, the image artifacts induced by the presence of an acoustic lens are reduced using the proposed lens compared to PMMA lens, due to the minimization of internal reflections. The proposed Stycast 1090SI acoustic lens improves the lateral resolution of photoacoustic tomography systems while not suffering from internal reflection-induced image artifacts compared a lens made of PMMA.


The novel competitive N-methyl-D-aspartate (NMDA) antagonist CGP 37849 preferentially induces phencyclidine-like behavioral effects in kindled rats: attenuation by manipulation of dopamine, alpha-1 and serotonin1A receptors.
The novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) was found to produce a phencyclidine (PCP)-like behavioral syndrome (ataxia, locomotion, stereotypies) in amygdala-kindled rats, whereas the amphetamine-like behavioral alterations of the syndrome (locomotion, stereotypies) were only infrequently seen in nonkindled rats. In dose-response experiments in kindled and nonkindled rats, behavioral effects were scored using a ranked intensity scale, and the behaviors and behavioural scores determined after CGP 37849 were compared with those determined after i.p. administration of the noncompetitive NMDA receptor antagonist dizocilpine maleate (MK-801). In kindled rats, 20 mg/kg of CGP 37849 produced about the same scores for hyperlocomotion and head weaving as 0.1 mg/kg of MK-801. Kindled rats exhibited higher behavioral scores than nonkindled rats, especially in the case of CGP 37849. The behavioral effects produced by CGP 37849 in kindled rats were almost indistinguishable from the PCP-like behavioral effects induced by MK-801, indicating that CGP 37849 indeed produces a PCP-like pattern of behavior in kindled rats. Hyperlocomotion and head weaving induced by CGP 37849 in kindled rats could be attenuated or totally prevented by pretreatment with ipsapirone, a partial agonist/antagonist at postsynaptic 5-hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype. Furthermore, these behavioural effects were attenuated or blocked by the dopamine antagonist haloperidol and the alpha-1 adrenoceptor antagonist, prazosin. The data demonstrate that kindling induces a hypersensitivity to PCP-like behavioral effects of competitive and noncompetitive NMDA receptor antagonists, which could relate to the recent finding of increased function of NMDA receptors following kindling.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential effects of prostaglandin F2 alpha and of prostaglandins E1 and E2 on cyclic 3',5'-monophosphate production and intracellular calcium mobilization in avian uterine smooth muscle cells.
The effects of prostaglandins (PGs) E1 (PGE1), E2 (PGE2) and F2 alpha (PGF2 alpha) on cyclic 3',5'-adenosine monophosphate (cAMP) production and intracellular Ca mobilization were examined in smooth muscle cells of chicken uterus grown in primary culture. At subnanomolar concentrations, both PGE1 and PGE2 significantly suppressed cAMP levels. However, at higher concentrations (0.1-100 microM), both agonists caused a dose-related increase in cAMP production. PGF2 alpha, on the other hand, had no effect on cAMP production. Forskolin (1-100 microM), which also stimulated cAMP production in a dose-dependent fashion, potentiated the effects of both PGE1 and PGE2. In digitonin-permeabilized uterine cells preloaded with 45Ca2+, the addition of PGF2 alpha caused a biphasic 45Ca2+ efflux. There was a small but significant 45Ca2+ release (10.0 +/- 1.5%) within 30 s (rapid phase), followed by a larger one (32.0 +/- 2.0%) within 5 min (slow phase). PGE2, at doses above 1 nM (which significantly increased cAMP accumulation), promoted 45Ca2+ sequestration. This action of PGE2 was observed as early as 1 min and was complete by 5 min. In addition, 0.001 nM PGE2 (a dose that was ineffective on 45Ca2+ mobilization) enhanced PGF2 alpha-induced 45Ca2+ mobilization from 22.5 +/- 5% to 57.0 +/- 3.5%. These results show that PGs of the E series have distinctly different effects on cAMP production and intracellular Ca mobilization. PGF2 alpha action may be linked directly to intracellular Ca mobilization, whereas the effects of PGE may be exerted at multiple sites depending on its local concentration. At low concentrations, its action may be mediated by the suppression of cAMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Recurrent Nausea and Vomiting in a Pregnant Woman with Chronic Marijuana Use.
Cannabinoid hyperemesis syndrome is a condition characterized by chronic cannabis use and cyclic episodes of nausea, vomiting, and abdominal pain, relieved by compulsive bathing. The syndrome is likely to be underdiagnosed in pregnant women due to its similarity with hyperemesis gravidarum in the presentation. We report a 20-year-old pregnant woman with multiple admissions for recurrent nausea and vomiting who was observed to be taking frequent hot showers. Without other identifiable causes, she was diagnosed with cannabinoid hyperemesis syndrome and managed with antiemetics and abstinence. Abstinence from cannabis use is highly recommended in pregnant women due to its potential harm in fetal development and stimulation of intractable nausea and vomiting. Recognizing the symptoms and proper history taking prompt early diagnosis, allowing timely and adequate treatment.


Convergent regulation of neuronal differentiation and Erk and Akt kinases in human neural progenitor cells by lysophosphatidic acid, sphingosine 1-phosphate, and LIF: specific roles for the LPA1 receptor.
The bioactive lysophospholipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) have diverse effects on the developing nervous system and neural progenitors, but the molecular basis for their pleiotropic effects is poorly understood. We previously defined LPA and S1P signaling in proliferating human neural progenitor (hNP) cells, and the current study investigates their role in neuronal differentiation of these cells. Differentiation in the presence of LPA or S1P significantly enhanced cell survival and decreased expression of neuronal markers. Further, the LPA receptor antagonist Ki16425 fully blocked the effects of LPA, and differentiation in the presence of Ki16425 dramatically enhanced neurite length. LPA and S1P robustly activated Erk, but surprisingly both strongly suppressed Akt activation. Ki16425 and pertussis toxin blocked LPA activation of Erk but not LPA inhibition of Akt, suggesting distinct receptor and G-protein subtypes mediate these effects. Finally, we explored cross talk between lysophospholipid signaling and the cytokine leukemia inhibitory factor (LIF). LPA/S1P effects on neuronal differentiation were amplified in the presence of LIF. Similarly, the ability of LPA/S1P to regulate Erk and Akt was impacted by the presence of LIF; LIF enhanced the inhibitory effect of LPA/S1P on Akt phosphorylation, while LIF blunted the activation of Erk by LPA/S1P. Taken together, our results suggest that LPA and S1P enhance survival and inhibit neuronal differentiation of hNP cells, and LPA1 is critical for the effect of LPA. The pleiotropic effects of LPA may reflect differences in receptor subtype expression or cross talk with LIF receptor signaling.


Inspiratory muscle training in Morquio's syndrome: a case study.
We reported a case of MPS IV A presented with dyspnea on exertion and respiratory muscle weakness. The patient underwent inspiratory muscle training (IMT) using threshold loading for 18 weeks. After 6 weeks of initial IMT, aerobic exercise training consisting of walking was added to the treatment program. Inspiratory muscle strength increased 70%, and 6-minute walk test (6MWT) distance increased to 47 m. With the inclusion of aerobic exercise training, additional increases in inspiratory muscle strength (7%) and 6MWT distance (26.5 m) were obtained. Exertional dyspnea improved from severe to slight after 6 weeks of IMT, and to very slight after additional 12 weeks of combined aerobic training and IMT. Health-related quality of life improved especially in social function, emotional function, vitality, and physical role. In conclusion, inspiratory muscles can be trained with the improvement of muscle strength in a patient with Morquio's syndrome.


Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replication.
We initially identified lens epithelium-derived growth factor/p75 (LEDGF/p75) as a binding partner of human immunodeficiency virus type 1 (HIV-1) integrase. To investigate the role of LEDGF/p75 in HIV replication and its potential as a new antiviral target, we stably overexpressed two different fragments containing the integrase binding domain (IBD) of LEDGF/p75 fused to enhanced green fluorescent protein (eGFP). HIV-1 replication was severely inhibited by overexpression of the eGFP-IBD fusion proteins, while no inhibition was observed in cell lines overexpressing the interaction-deficient D366A mutant. Quantitative PCR pinpointed the block to the integration step, whereas nuclear import was not affected. Competition of the IBD fusion proteins with endogenous LEDGF/p75 for binding to integrase led to a potent defect in HIV-1 replication in both HeLaP4- and MT-4-derived cell lines. A previously described diketo acid-resistant HIV-1 strain remained fully susceptible to inhibition, suggesting that this strategy will also work in patients who harbor strains resistant to the current experimental integrase inhibitors. These data support LEDGF/p75 as an important cofactor for HIV replication and provide proof of concept for the LEDGF/p75-integrase interaction as a novel target for treating HIV-1 infection.


Efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids: an observational single-center study.
To evaluate treatment response of uterine fibroids after ultrasound guided high-intensity focused ultrasound (USgHIFU) with a special focus on fibroid size and characterization based on Funaki classification scheme, as well as clinical response to treatment of leading fibroid-associated symptoms. Uterine fibroids treated by USgHIFU were assigned to Funaki type 1-3 based on T2-w-MRI. Differences in size, non-perfused volume ratio (NPVR) and volume reduction over time were determined using T1-/T2-w MRI sequences and contrast-enhanced sonography. Treatment effects on three leading fibroid-associated symptoms were also evaluated. Measurements were compared by mixed model, Bland-Altman's plot and Spearman's correlation. In this prospective single-center study, 35 patients with 44 symptomatic uterine fibroids were treated by USgHIFU (n = 22, n = 12 and n = 10 assigned to Funaki type 1, 2 and 3, respectively). NPVRs of Funaki type 1 and 2 fibroids were significantly higher compared to type 3 (p = .0023). A significant fibroid shrinkage was observed independent of Funaki type compared to baseline: 38.8 ± 26.9%, 46.7 ± 30.3% and 54.5 ± 29.3% at 3, 6 and 12 months, respectively (each p < .05). Moreover, patients experienced a significant improvement of fibroid-associated hypermenorrhea (3.9 ± 1.3 vs. 2.3 ± 1.3), pressure in the pelvic area (3.5 ± 1.3 vs. 2.1 ± 0.9) and frequent urination (2.8 ± 1.5 vs. 1.9 ± 0.8) one year post-procedure (each p < .05), regardless of fibroid Funaki type. Following USgHIFU, a significant shrinkage of uterine fibroids and improvement of leading fibroid-associated symptoms were demonstrated regardless of the Funaki type.


Returning to the present moment: Thinking about one's childhood increases focus on the hedonistic present.
Children seem to live more in the present moment than adults. But is it possible to make the present time perspective more available among adults? Four experiments demonstrated that activating childhood selves can lead adults to be more embedded in the hedonistic present. Studies 1 and 2 showed that recalling memories from childhood, either in an open-ended or a structured form, increased participants' focus on the hedonistic present. Study 3 showed that this effect also occurred after an implicit childhood manipulation. Study 4 revealed that taking the perspective of a child significantly increased orientation to the hedonistic present, compared to taking the perspective of an adult. The effects of activation of childhood selves were not mediated by mood, nostalgia, impatience, concentration, difficulty of the task, enjoyment connected with the task, or involvement in the task. Evaluation of one's childhood and tendency to relive childhood memories did not affect the results.


Reactivated thyroid hormone receptor β attenuates anaplastic thyroid cancer (ATC) stem cell activity.
Anaplastic thyroid cancer (ATC) is one of the most aggressive solid cancers in humans, with limited treatment options. Recent studies suggest that cancer stem cell (CSC) activity contributes to therapeutic resistance and recurrence of ATC. We show that the expression of the endogenous thyroid hormone receptor β gene (THRB) is silenced in ATC and demonstrate that the exogenously expressed TRβ suppresses CSC activity. Decitabine is one of the demethylation agents to treat myelodysplastic syndrome and acute myeloid leukemia patients and is currently in clinical trials for hematopoietic malignancies and solid tumors. We aim to show that the re-expression of the endogenous THRB gene by decitabine can attenuate CSC activity to block ATC tumor growth. We treated ATC cell lines derived from human ATC tumors (11T and 16T cells) with decitabine and evaluated the effects of the reactivated endogenous TRβ on CSC activity in vitro and in vivo xenograft models. We found that treatment of 11T and 16T cells with decitabine reactivated the expression of endogenous TRβ, as evidenced by western blot and immunohistochemical analyses. The expressed TRβ inhibited cell proliferation by arresting cells at the S phase, increased apoptotic cell death by upregulation of cleaved caspase-3, and markedly suppressed the expression of CSC regulators, including cMYC, ALDH, SOX2, CD44, and β-catenin. Decitabine also inhibited xenograft tumor growth by suppressing CSC activity, inhibiting cancer cell proliferation, and increasing apoptosis. Our findings suggest that re-expression of the endogenous TRβ is a novel therapeutic approach for ATC via suppression of CSC activity.


Ablation of osteopontin suppresses N-methyl-N-nitrosourea and Helicobacter pylori-induced gastric cancer development in mice.
Several clinical studies have reported increased expression of osteopontin (OPN) in various types of human cancer, including gastric cancer. However, the precise mechanisms underlying tumor development remain unclear. In the present study, we investigated the pathogenic roles of OPN in Helicobacter pylori-induced gastric cancer development. Wild-type (WT) and OPN knockout (KO) mice were treated with N-methyl-N-nitrosourea (MNU) and infected with H.pylori. Mice were killed 50 weeks after treatment, and stomach tissues were assessed by histopathological examination, immunohistochemistry, quantitative real-time RT-PCR and western blotting. To clarify the carcinogenic effects of OPN, we also conducted an in vitro study using AGS human gastric cancer cell line and THP-1 human monocytic cell line. The overall incidence of gastric tumors was significantly decreased in OPN KO mice compared with WT mice. Apoptotic cell death was significantly enhanced in OPN KO mice and was accompanied by upregulation of signal transducer and activator of transcription 1 (STAT1) and inducible nitric oxide synthase (iNOS). In vitro study, OPN suppression also caused STAT1 upregulation and iNOS overexpression in AGS and THP-1 cells, which resulted in apoptosis of AGS cells. In addition, a negative correlation was clearly identified between expression of OPN and iNOS in human gastric cancer tissues. Our data demonstrate that loss of OPN decreases H.pylori-induced gastric carcinogenesis by suppressing proinflammatory immune response and augmenting STAT1 and iNOS-mediated apoptosis of gastric epithelial cells. An important implication of these findings is that OPN actually contributes to the development of gastric cancer.