[Sinus histiocytosis with massive lymphadenopathy--a disseminated form of the Rosai-Dorfman syndrome].
A 20 year-old black male presented with a generalized lymphadenopathy, skin papules with maximum involvement of the head and trunk region, and elevated temperature. Ultrasound, CT and bone scans revealed infiltration of the kidneys and bones. Surgical specimens of the cervical lymph nodes showed massive infiltration of sinuses by histiocytes with engulfed lymphocytes and granulocytes in their cytoplasm. A similar finding was found in the excised dermis and nasopharyngeal mucosa. Immunohistochemical investigations showed a strong positive reaction of sinusoidal macrophages with anti S100 protein, anti alpha-1 antitrypsin and alpha-1 antichymotrypsin antibodies, negative CD1a. The engulfed granulocytes were positive with lysozyme and MAC387 antibodies; lymphocytes reacted with antilymphocytic antibodies L26, HLADR, UCHL-1 and OPD4 only rarely, possibly due to alterations of their cell membranes in the cytoplasmic environment of histiocytes. Occasional plasma cells were also entrapped in the macrophages. The best results were obtained with CD3 antibody which showed focal predominance of phagocytosed T cells. These findings confirm a nonselective nature of the emperipolesis. In situ hybridization with probes EBER and BHLF against Epstein-Barr virus sequences was negative. The pacient was treated by multidrug chemotherapy with a moderate regression of the infiltrates. The symptoms of the disease persisted for 10 months from the treatment start but further course of the disease is uncertain. The patients is lost to follow up.


An Orthogonal Multi-input Integration System to Control Gene Expression in Escherichia coli.
In many biotechnological applications, it is useful for gene expression to be regulated by multiple signals, as this allows the programming of complex behavior. Here we implement, in Escherichia coli, a system that compares the concentration of two signal molecules, and tunes GFP expression proportionally to their relative abundance. The computation is performed via molecular titration between an orthogonal σ factor and its cognate anti-σ factor. We use mathematical modeling and experiments to show that the computation system is predictable and able to adapt GFP expression dynamically to a wide range of combinations of the two signals, and our model qualitatively captures most of these behaviors. We also demonstrate in silico the practical applicability of the system as a reference-comparator, which compares an intrinsic signal (reflecting the state of the system) with an extrinsic signal (reflecting the desired reference state) in a multicellular feedback control strategy.


Homogeneously Staining Regions (HSR) in Chromosome 1 of the House Mouse: Synapsis and Recombination at Meiosis.
Amplified sequences constitute a large part of mammalian genomes. A chromosome 1 containing 2 large (up to 50 Mb) homogeneously staining regions (HSRs) separated by a small inverted euchromatic region is present in many natural populations of the house mouse (Mus musculus musculus). The HSRs are composed of a long-range repeat cluster, Sp100-rs, with a repeat length of 100 kb. In order to understand the organization and function of HSRs in meiotic chromosomes, we examined synapsis and recombination in male mice hetero- and homozygous for the HSR-carrying chromosome using FISH with an HSR-specific DNA probe and immunolocalization of the key meiotic proteins. In all homozygous and heterozygous pachytene nuclei, we observed fully synapsed linear homomorphic bivalents 1 marked by the HSR FISH probe. The synaptic adjustment in the heterozygotes was bilateral: the HSR-carrying homolog was shortened and the wild-type homolog was elongated. The adjustment was reversible: desynapsis at diplotene was accompanied by elongation of the HSRs. Immunolocalization of H3K9me2/3 indicated that the HSRs in the meiotic chromosome retained the epigenetic modification typical for C-heterochromatin in somatic cells. MLH1 foci, marking mature recombination nodules, were detected in the proximal HSR band in heterozygotes and in both HSR bands of homozygotes. Unequal crossing over within the long-range repeat cluster can cause variation in size of the HSRs, which has been detected in the natural populations of the house mouse.


The impact of obesity on illness absence and productivity in an industrial population of petrochemical workers.
Examine employee illness absence and the economic impact of overweight and obesity in a petrochemical industry workforce. A 10-year follow-up (1994-2003) of 4153 Shell Oil Company employees was conducted. Absence frequency rates and average number of workdays lost were calculated for normal weight, overweight, and obese employees with and without the presence of additional risk factors. The study also assessed the change in overweight and obesity prevalence in the study population and estimated the current and future economic impact of these conditions. Overall, obese employees were 80% more likely to have absences (24.0 vs. 13.3 per 100 employees) and were absent 3.7 more days (7.7 vs. 4.0 days) per year compared with those employees with normal body weights. Among employees with no additional risk factors, overweight employees lost more than 1.5 times more days (4.2 vs. 2.6 days) per year, and obese employees more than 2.5 times more days (7.2 vs. 2.6 days) compared with their normal-weight colleagues. Similarly, absence frequency attributable to cardiovascular disease significantly increased among employees with one or two additional risk factors present, such as smoking, high blood pressure, or hypercholesterolemia. The direct cost of illness absence from overweight and obesity for this study population was $1,873,500. Furthermore, 31% of the total illness absence was attributable to overweight and obesity in 1994, and the percentage had risen to 36% by 2003. The economic impact to employers is great and will continue to rise unless measures are taken, particularly to reduce the number of employees moving from overweight to obesity with time.


[Diabetic tractional retinal detachment].
Diabetic tractional retinal detachment is a severe complication in diabetic retinopathy. The decision for a surgical intervention has to consider the spontaneous course of the disease, intraoperative and postoperative complications and the expected functional results. An extramacular tractional detachment can remain stable for a long time and can be observed as long as the centre of the macula is not threatened. Traction to the macula can cause oedema and reduced vision, even if the macula itself is not detached. In these cases vitreous surgery can improve vision. Retinal breaks due to tractional membranes can cause a traction-rhegmatogenous retinal detachment which is usually rapidly progressive and requires early surgery. For cases with tractional detachment of the macula there is no alternative to surgery. In cases with long-standing and complete tractional detachment with severe retinal ischaemia the functional prognosis even after anatomically successful surgery is poor and it may be better not to operate.


[Changes in dietary habits and selected cardiovascular risk factors of the Warsaw population over the 5-year observation period (1993-97/98)].
The aim of the study was to characterise changes in dietary habits and cardiovascular risk factors of the Warsaw cohort population over a 5-year observation period. Two Warsaw population samples (249 men and 259 women), aged 35-64, were surveyed in 1993 and resurveyed in years 1997/98. Over a five-year observation period, daily dietary cholesterol decreased from 363 mg to 319 mg in men and from 263 mg to 232 mg in women, the percentage of energy from fat decreased from 38.8% to 34.7% in men and from 37.1% to 31.2% in women, the percentage of energy from saturated fatty acids from 13.6% to 11.7% and from 12.9% to 10.5% respectively. These changes resulted in a significant reduction in atherogenicity of the average diet as expressed by Keys score. Intakes of vitamins B1 and B2, calcium, magnesium and iron was consistently below Recommended Dietary Allowances (RDA) for the Polish population. Participants of both genders consumed significantly greater amounts of total bread (35%), milk (50%) and butcher meat products (22%). In the same time increase of HDL-cholesterol level (average of 2.0 mg/dl in men and 3.1 mg/dl in women) and decrease of LDL-cholesterol by 5 mg/dl in men was noted.


Evolution of human lifespan: Past, future, and present.
The only satisfactory general theory for understanding the biology of aging is that provided by evolutionary genetics. The central theoretical result of the evolutionary theory of aging is that aging is caused by a fall in the force of natural selection, beginning at the time of the onset of reproduction and continuing until the cessation of reproduction. This formal result has been tested using breeding experiments in which the force of natural selection is altered in replicated laboratory populations. As predicted by the evolutionary theory of aging, such experiments can readily postpone aging. A recent advance has been the discovery of late-life mortality plateaus in human and other populations. These can be predicted theoretically from the late-life plateau in the force of natural selection, when it remains at or near zero. It is virtually certain that human lifespan has substantially increased over its last few million years of evolution. Evolutionary theory can explain this increase in terms of decreased ecological vulnerability resulting from increased brain size. The immediate future of human evolution is unlikely to see extensive genetic increases in lifespan, given the experimental data on rates of change in lifespan with experimental populations. But, evolutionary research suggests that there are few fundamental biological barriers to the extension of human lifespan, only practical barriers. Am. J. Hum. Biol. 10:409-420, 1998. © 1998 Wiley-Liss, Inc.


Natural low-molecular mass organic compounds with oxidase activity as organocatalysts.
Organocatalysts, low-molecular mass organic compounds composed of nonmetallic elements, are often used in organic synthesis, but there have been no reports of organocatalysts of biological origin that function in vivo. Here, we report that actinorhodin (ACT), a natural product derived from Streptomyces coelicolor A3(2), acts as a biocatalyst. We purified ACT and assayed its catalytic activity in the oxidation of L-ascorbic acid and L-cysteine as substrates by analytical methods for enzymes. Our findings were as follows: (i) oxidation reactions producing H2O2 proceeded upon addition of ACT to the reaction mixture; (ii) ACT was not consumed during the reactions; and (iii) a small amount (catalytic amount) of ACT consumed an excess amount of the substrates. Even at room temperature, atmospheric pressure, and neutral pH, ACT showed catalytic activity in aqueous solution, and ACT exhibited substrate specificity in the oxidation reactions. These findings reveal ACT to be an organocatalyst. ACT is known to show antibiotic activity, but its mechanism of action remains unknown. On the basis of our results, we propose that ACT kills bacteria by catalyzing the production of toxic levels of H2O2. We also screened various other natural products of bacterial, plant, and animal origins and found that several of the compounds exhibited catalytic activity, suggesting that living organisms produce and use these compounds as biocatalysts in nature.


Do we need new trials of procalcitonin-guided antibiotic therapy?
Using biomarkers as a guide to tailor the duration of antibiotic treatment in respiratory infections is an attractive hypothesis assessed in several studies. Recent work aiming to summarize the evidence assessed the effect of a procalcitonin (PCT)-guided antibiotic treatment on outcomes in acute lower respiratory tract infections (LRTI), suggesting that significant reductions in antibiotic duration occur when using a PCT-guided algorithm. However, controversial evidence also suggested PCT-guided algorithms were associated with increased antibiotic duration and increased incidence of Clostridium difficile, without any impact on mortality, in real-world settings. So, although using PCT-guided antibiotic stewardship is promising, after more than a decade of randomized controlled trials on this topic the evidence in its favor is still less than compelling due to limitations in trial design, not taking into consideration fundamental aspects of PCT biology, and the absence of evidence-based antimicrobial duration in intervention and control groups. In this commentary we highlight some questions and limitations of primary PCT study data that might impact interpretation and clinical use of PCT at the bedside.


Differential Impact of miR-21 on Pain and Associated Affective and Cognitive Behavior after Spared Nerve Injury in B7-H1 ko Mouse.
MicroRNAs (miRNAs) are increasingly recognized as regulators of immune and neuronal gene expression and are potential master switches in neuropathic pain pathophysiology. miR-21 is a promising candidate that may link the immune and the pain system. To investigate the pathophysiological role of miR-21 in neuropathic pain, we assessed mice deficient of B7 homolog 1 (B7-H1), a major inhibitor of inflammatory responses. In previous studies, an upregulation of miR-21 had been shown in mouse lymphocytes. Young (8 weeks), middle-aged (6 months), and old (12 months) B7-H1 ko mice and wildtype littermates (WT) received a spared nerve injury (SNI). We assessed thermal withdrawal latencies and mechanical withdrawal thresholds. Further, we performed tests for anxiety-like and cognitive behavior. Quantitative real time PCR was used to determine miR-21 relative expression in peripheral nerves, and dorsal root ganglia (DRG) at distinct time points after SNI. We found mechanical hyposensitivity with increasing age of naïve B7-H1 ko mice. Young and middle-aged B7-H1 ko mice were more sensitive to mechanical stimuli compared to WT mice (young: p < 0.01, middle-aged: p < 0.05). Both genotypes developed mechanical and heat hypersensitivity (p < 0.05) after SNI, without intergroup differences. No relevant differences were found after SNI in three tests for anxiety like behavior in B7-H1 ko and WT mice. Also, SNI had no effect on cognition. B7-H1 ko and WT mice showed a higher miR-21 expression (p < 0.05) and invasion of macrophages and T cells in the injured nerve 7 days after SNI without intergroup differences. Our study reveals that increased miR-21 expression in peripheral nerves after SNI is associated with reduced mechanical and heat withdrawal thresholds. These results point to a role of miR-21 in the pathophysiology of neuropathic pain, while affective behavior and cognition seem to be spared. Contrary to expectations, B7-H1 ko mice did not show higher miR-21 expression than WT mice, thus, a B7-H1 knockout may be of limited relevance for the study of miR-21 related pain.


Deferred Versus Immediate Stenting in Patients With ST-Segment Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis.
A number of studies have evaluated the efficacy of deferred stenting vs immediate stenting in patients with ST-segment elevation myocardial infarction, but the findings were not consistent across these studies. This meta-analysis aims to assess optimal treatment strategies in patient with ST-segment elevation myocardial infarction. We searched the PubMed, EMBASE, and the Cochrane Library for studies that assessed deferred vs immediate stenting in patients with ST-segment elevation myocardial infarction. Nine studies including 1456 patients in randomized controlled trials and 719 patients in observational studies were included in the meta-analysis. No significant differences were observed in the incidence of no- or slow-reflow between deferred stenting and immediate stenting in randomized controlled trials (odds ratio [OR] 0.51, 95%CI 0.17-1.53, P=0.23, I2=70%) but not in observational studies (OR 0.13, 95%CI 0.06-0.31, P<0.0001, I2=0%). Deferred stenting was associated with an increase in long-term left ventricular ejection fraction (weighted mean difference 1.90%, 95%CI 0.77-3.03, P=0.001, I2=0%). No significant differences were observed in the rates of major adverse cardiovascular events (OR 0.53, 95%CI 0.27-1.01, P=0.06 [randomized OR 0.98, 95%CI 0.73-1.30, P=0.87, I2=0%; nonrandomized OR 0.30, 95%CI 0.15-0.58, P=0.0004, I2=0%]), major bleeding (OR=0.1.61, 95%CI 0.70-3.69, P=0.26, I2=0%), death (OR=0.78, 95%CI 0.53-1.15, P=0.22, I2=0%), MI (OR=0.97, 95%CI 0.34-2.78, P=0.96, I2=35%) and target vessel revascularization (OR 0.97, 95%CI 0.40-2.37, P=0.95, I2=24%), between deferred and immediate stenting. Compared with immediate stenting, a deferred-stenting strategy did not reduce the occurrence of no- or slow-reflow, death, myocardial infarction, or repeat revascularization compared with immediate stenting in patients with ST-segment elevation myocardial infarction, but showed an improved left ventricular function in the long term.


Chloroplast-associated molecular patterns as concept for fine-tuned operational retrograde signalling.
Chloroplasts compose about one-quarter of the mesophyll cell volume and contain about 60% of the cell protein. Photosynthetic carbon assimilation is the dominating metabolism in illuminated leaves. To optimize the resource expenditure in these costly organelles and to control and adjust chloroplast metabolism, an intensive transfer of information between nucleus-cytoplasm and chloroplasts occurs in both directions as anterograde and retrograde signalling. Recent research identified multiple retrograde pathways that use metabolite transfer and include reaction products of lipids and carotenoids with reactive oxygen species (ROS). Other pathways use metabolites of carbon, sulfur and nitrogen metabolism, low molecular weight antioxidants and hormone precursors to carry information between the cell compartments. This review focuses on redox- and ROS-related retrograde signalling pathways. In analogy to the microbe-associated molecular pattern, we propose the term 'chloroplast-associated molecular pattern' which connects chloroplast performance to extrachloroplast processes such as nuclear gene transcription, posttranscriptional processing, including translation, and RNA and protein fate. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.


Single Diastereomer of a Macrolactam Core Binds Specifically to Myeloid Cell Leukemia 1 (MCL1).
A direct binding screen of 100 000 sp(3)-rich molecules identified a single diastereomer of a macrolactam core that binds specifically to myeloid cell leukemia 1 (MCL1). A comprehensive toolbox of biophysical methods was applied to validate the original hit and subsequent analogues and also established a binding mode competitive with NOXA BH3 peptide. X-ray crystallography of ligand bound to MCL1 reveals a remarkable ligand/protein shape complementarity that diverges from previously disclosed MCL1 inhibitor costructures.


Heart block and acute kidney injury due to hyperparathyroidism-induced hypercalcemic crisis.
We describe a patient who presented with multi-system organ failure due to extreme hypercalcemia (serum calcium 19.8 mg/dL), resulting from primary hyperparathyroidism. He was found to have a 4.8 cm solitary atypical parathyroid adenoma. His course was complicated by complete heart block, acute kidney injury, and significant neurocognitive disturbances. Relevant literature was reviewed and discussed. Hyperparathyroidism-induced hypercalcemic crisis (HIHC) is a rare presentation of primary hyperparathyroidism and only a small minority of these patients develop significant cardiac and renal complications. In cases of HIHC, a multidisciplinary effort can facilitate rapid treatment of life-threatening hypercalcemia and definitive treatment by surgical resection. As such, temporary transvenous cardiac pacing and renal replacement therapy can provide a life-saving bridge to definitive parathyroidectomy in cases of HIHC.


An excimer-based, turn-on fluorescent sensor for the selective detection of diphosphorylated proteins in aqueous solution and polyacrylamide gels.
Protein phosphorylation is a ubiquitous post-translational modification, which often acts as a switch to proteins' activation and is frequently perturbed in diseases. Although many general phospho-protein detection tools are available, none of them offers information about the relative spatial arrangement of phosphorylated residues. Specifically, proximally phosphorylated residues are hallmarks of certain activated disease-relevant proteins. We herein report the first turn-on fluorescent sensor for the selective detection of proximally phosphorylated protein sites, suitable for application in both aqueous solutions and polyacrylamide gels.


Time course of tolerance to the performance benefits of caffeine.
The ergogenic effect of acute caffeine ingestion has been widely investigated; however, scientific information regarding tolerance to the performance benefits of caffeine, when ingested on a day-to-day basis, is scarce. The aim of this investigation was to determine the time course of tolerance to the ergogenic effects of a moderate dose of caffeine. Eleven healthy active participants took part in a cross-over, double-blind, placebo-controlled experiment. In one treatment, they ingested 3 mg/kg/day of caffeine for 20 consecutive days while in another they ingested a placebo for 20 days. Each substance was administered daily in an opaque unidentifiable capsule, and the experimental trials started 45 min after capsule ingestion. Two days before, and three times per week during each 20-day treatment, aerobic peak power was measured with an incremental test to volitional fatigue (25 W/min) and aerobic peak power was measured with an adapted version of the Wingate test (15 s). In comparison to the placebo, the ingestion of caffeine increased peak cycling power in the incremental exercise test by ~4.0 ±1.3% for the first 15 days (P<0.05) but then this ergogenic effect lessened. Caffeine also increased peak cycling power during the Wingate test on days 1, 4, 15, and 18 of ingestion by ~4.9 ±0.9% (P<0.05). In both tests, the magnitude of the ergogenic effect of caffeine vs. placebo was higher on the first day of ingestion and then progressively decreased. These results show a continued ergogenic effect with the daily ingestion of caffeine for 15-18 days; however, the changes in the magnitude of this effect suggest progressive tolerance.


Quantum selection of order in an XXZ antiferromagnet on a Kagome lattice.
Selection of the ground state of the kagome-lattice XXZ antiferromagnet by quantum fluctuations is investigated by combining nonlinear spin-wave and real-space perturbation theories. The two methods unanimously favor q=0 over sqrt[3]×sqrt[3] magnetic order in a wide range of the anisotropy parameter 0≤Δ≲0.72. Both approaches are also in accord on the magnitude of the quantum order-by-disorder effect generated by topologically nontrivial, looplike spin-flip processes. A tentative S-Δ phase diagram of the model is proposed.


Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer's disease and mild cognitive impairment subtypes.
Neuropsychiatric disorders are common in cognitively impaired older persons, and associated with institutionalization and caregiver stress in Alzheimer's disease (AD). Few studies have compared the occurrence of both psychiatric disorders and neuropsychiatric symptoms in patients with AD and mild cognitive impairment (MCI) subtypes. We aimed to investigate the frequency of psychiatric disorders and neuropsychiatric symptoms in AD and MCI patients, compared to controls. We included 245 outpatients of a memory clinic in Rome, Italy (119 AD; 68 multidomain-MCI; 58 amnestic-MCI) and 107 controls. Categorical disorders of depression and apathy were diagnosed with structured interviews. Symptoms were evaluated with the Neuropsychiatric Inventory (NPI). The odds ratios (OR) of patients having neuropsychiatric symptoms compared to controls were calculated with logistic regression, adjusted for sociodemographic and clinical variables. A large proportion of AD (49.6%) and multidomain-MCI (44.1%) patients had depression disorder. Apathy disorder was common in AD (51.3%) but less frequent in amnestic-MCI (6.9%) and multidomain-MCI (14.7%). AD patients were three times more likely to have depression disorders (OR = 3.0, CI = 1.1-7.6) or apathy (OR = 16.9, CI = 4.6-61.8) compared to amnestic-MCI, and seven times more likely to have apathy disorder than multidomain-MCI (OR = 7.5, CI = 3.0-19.2). After apathy and depression, the most prevalent neuropsychiatric symptoms in AD and MCI were anxiety, agitation, irritability, night-time behaviors, and appetite disturbances. There was an increasing prevalence of many neuropsychiatric symptoms with increasing severity of cognitive syndromes. Clinicians should consider the relevance of neuropsychiatric disorders and symptoms in patients with cognitive disturbances, and incorporate a thorough psychiatric examination in the evaluation of patients.


Robust hippocampal responsivity during retrieval of consolidated associative memory.
A contentious point in memory research is whether or not the hippocampus plays a time-limited role in the consolidation of declarative memories. A widely held view is that declarative memories are initially encoded in the hippocampus, then transferred to the neocortex for long-term storage. Alternate views argue instead that the hippocampus continues to play a role in remote memory recall. These competing theories are largely based on human amnesic and animal lesion/inactivation studies. However, in vivo electrophysiological evidence supporting these views is scarce. Given that other studies examining the role of the hippocampus in remote memory retrieval using lesion and imaging techniques in human and animal models have provided mixed results, it would be particularly useful to gain insight at the in vivo electrophysiological level. Here we report hippocampal single-neuron and theta activity recorded longitudinally during acquisition and remote retrieval of trace eyeblink conditioning. Results from conditioned rabbits were compared to those obtained from yoked pseudo-conditioned control rabbits. Results reveal continued learning-specific hippocampal activity one month after initial acquisition of the task. Our findings yield insight into the normal physiological responses of the hippocampus during memory processes and provide compelling in vivo electrophysiological evidence that the hippocampus is involved in both acquisition and retrieval of consolidated memories.


Diagnosis and monitoring of childhood asthma.
Diagnosis of asthma is clinical, however due to varied presentations in childhood both under and over diagnosis are possible. A good number of cases may not present with wheeze but may have a cough variant asthma. Episodic symptoms of airflow obstruction and reversibility are two very important features of asthma. Many congenital (Cystic fibrosis) and acquired conditions (foreign body) may cause wheezing in childhood and should be ruled out clinically or by specific investigations. Spirometry and peak expiratory flow rates help in objective assessment and are good tools for monitoring chronic patients. Total IgE has no role in diagnosis. There is now emphasis on co-management of asthma and patient/parents should be trained to keep symptoms records and wherever possible peak flow records. They should also be taught proper interpretation of readings for stepping up therapy in case of worsening.


Case report: SLC6A1 mutations presenting with isolated absence seizures: description of 2 novel cases.
We report the clinical and EEG data of two patients harboring heterozygous SLC6A1 mutations, who presented with typical absence seizures at 3 Hz spike and wave as well as with mild cognitive disability. Neuroradiological and other laboratory investigations were normal. Our observations suggest that SLC6A1 mutations can be suspected in children with typical absences as the only seizure type, especially if associated with, even mild, cognitive deficits.


The use of monoclonal antibodies against human chorionic gonadotropin for immunoperoxidase staining of normal placenta, pituitary gland, and pituitary adenomas.
A monoclonal mouse antibody to human chorionic gonadotropin (hCG) was used in a modified unlabeled antibody enzyme-bridge staining method to demonstrate the localization of hCG in normal human placenta, pituitary gland, and six pituitary chromophobe adenomas. Mouse ascitic fluid containing monoclonal antibody could be diluted up to 1:500,000 for detection of hCG in the syncytiotrophoblast, whereas no staining was observed in the pituitary or adenomas even with high antibody concentrations (dilutions from 1:500 upward). Nonspecific background staining was negligible. These results demonstrate that monoclonal antibodies are suitable for immunohistochemical localization of antigens in tissues.


[First isolation of the yeast Saccharomyces paradoxus in Western Siberia].
Two ascomycetous yeast strains have been isolated near Novosibirsk from oak exudate. The strains have been identified as Saccharomyces paradoxus Bachinskaya based on the results of biochemical tests. The conspecificity of the isolates with S. paradoxus was confirmed by electrophoretic karyotyping and restriction analysis of the ITS region of its rDNA. This first isolation of S. paradoxus in Siberia provides evidence for the continuity of its natural habitats.


The pesticide dieldrin disrupts proteins related to oxidative respiration and mitochondrial stress in the central nervous system.
Quantitative proteins analysis was carried out in the hypothalamus of zebrafish following dietary exposure to the legacy pesticide dieldrin. Data were collected using iTRAQ labeling methodology and data were acquired using a hybrid quadrupole Orbitrap (Q Exactive) MS system (Thermo Fisher Scientific, Bremen, Germany). There were 3941 proteins identified in the hypothalamus of zebrafish, and these proteins comprised 23 unique expression patterns for proteins based on the three doses of dieldrin. There were 226 proteins that were regulated in one or more doses of dieldrin and 3715 proteins that were not affected. Thus, 5.7% of the proteins detected responded to the treatment. Many proteins that were differentially expressed were those found in, or associated with, the mitochondria. The proteomics data described in this article is associated with a research article, "Transcriptomic and proteomic analysis implicates the immune system and mitochondria as molecular targets of dieldrin in the zebrafish (Danio rerio) central nervous system" (A.M. Cowie, K.I. Sarty, A. Mercer, J. Koh, K.A. Kidd, C.J. Martyniuk, submitted) [1], and serves as a resource for researchers working in the field of pesticide exposures and protein biomarkers.


Design of the radiation shielding for the time of flight enhanced diagnostics neutron spectrometer at Experimental Advanced Superconducting Tokamak.
A radiation shielding has been designed to reduce scattered neutrons and background gamma-rays for the new double-ring Time Of Flight Enhanced Diagnostics (TOFED). The shielding was designed based on simulation with the Monte Carlo code MCNP5. Dedicated model of the EAST tokamak has been developed together with the emission neutron source profile and spectrum; the latter were simulated with the Nubeam and GENESIS codes. Significant reduction of background radiation at the detector can be achieved and this satisfies the requirement of TOFED. The intensities of the scattered and direct neutrons in the line of sight of the TOFED neutron spectrometer at EAST are studied for future data interpretation.


Always look beyond the stones: hyperoxaluria overlooked.
We report a case which demonstrates the disastrous consequences of late diagnosis of hyperoxaluria in a 24-year-old woman with nephrocalcinosis, a staghorn calculus and recurrent urinary tract infections. Her initial management at another hospital included multiple percutaneous nephrostomies and lithropsies. Metabolic screening was not undertaken. Hyperoxaluria was finally diagnosed by elevated urine oxalate (1.235 mmol/24 h) and renal biopsy, by which time there was already significant reduction of renal function. A diagnosis of hyperoxaluria type I was confirmed by liver biopsy. Despite starting pyridoxine and crystallization inhibitors, her renal function deteriorated, requiring hemodialysis and she was referred for combined liver-renal transplantation. Clinical clues of primary hyperoxaluria type I are a positive family history or presentation with severe renal stones at an unusually early age. Irrespective of the above, all patients with first presentation of renal calculi should undergo metabolic screening, including urine oxalate.


Broad dual-band temporal compressive imaging with optical calibration.
For applications such as remote sensing and bio-imaging, images from multiple bands can provide much richer information compared to a single band. However, most multispectral imaging systems have difficulty in acquiring images for high-speed moving objects. In this paper, we use a DMD-based temporal compressive imaging (TCI) system to obtain high-speed images of moving objects over a broad dual-band spectral range, in the visible and the near-infrared (NIR) bands simultaneously. To deal with the degraded reconstruction caused by the optics, four nonuniform calibration strategies are studied, which can also be implemented into other compressive imaging systems. Moving objects covered by paint or through a diffuser are reconstructed to demonstrate the superior performance of the calibrated broad dual-band TCI system.


Management of a rare combination of avulsion and intrusive luxation: A case report.
In traumatic dental injury, concomitant occurrence of avulsion and intrusive luxation is exceptional. This is because the vectors of forces responsible for both avulsive and intrusive injuries are in different directions. The present case report reviews the management of a rare combination of avulsion in right maxillary lateral incisor (tooth #12) and intrusive luxation in right maxillary central incisor (tooth #11) in a 22-year-old Asian male. Clinical and radiographic evaluation was done at 12-month follow-up. Various treatment modalities and complications associated with both avulsion and intrusion are also discussed in the paper.


A review of mitigating strategies to improve the thermal environment and thermal comfort in urban outdoor spaces.
Urban open space provides various benefits to citizens, but the thermal environment of this space is impacted by global warming and urban heat islands. A growing number of studies have been conducted on strategies for improving the urban thermal environment and attracting more people to outdoor spaces. This paper reviews the mechanisms and cooling effects of four major mitigation strategies, namely, changing the urban geometry, planting vegetation, using cool surface, and incorporating bodies of water. Our review found that on summer days these four strategies yielded a median reduction in air temperature of 2.1 K, 2.0 K, 1.9 K, and 1.8 K, respectively. In terms of integrated effect on thermal comfort, changing the urban geometry provided the greatest improvement, with the largest reduction in physiologically equivalent temperature (PET) in summer (median ΔPET = 18.0 K). The use of vegetation and water bodies reduced the median PET by 13.0 K and 4.6 K, respectively. However, some simulation studies found that reflective surface led to higher PET in summer because of the increased amount of reflected solar radiation. The mitigation strategies improved the urban thermal environment to a greater extent in hotter and drier climates. Vegetation, cool surface, and water bodies provided less cooling in compact urban spaces than in open areas. The results that we reviewed can be used by designers and planners seeking to create thermally comfortable urban open spaces.


Development of a virtual Z(eff) diagnostic for the W7-X stellarator.
For the W7-X stellarator a diagnostic system for measurement of local Z(eff) values from the visible bremsstrahlung continuum is foreseen. The method is based on passive, absolute measurement of the bremsstrahlung intensity along several lines of sight. In order to eliminate the spurious impact of other radiation sources of different spectral intensity distribution than the bremsstrahlung, like the line radiation, it is intended to spectrally resolve the detected radiation, e.g., by use of microspectrometers. The visible bremsstrahlung background can be extracted by making use of the 1/lambda(2) dependence of its intensity (expressed in unit Wm(3) sr nm) in the high temperature plasmas by using Bayesian data analysis techniques. In a second step, the local values of Z(eff) as a function of the effective plasma radius are derived by inversion, using different regularization methods, of the line-integrated bremsstrahlung signals with the knowledge of the magnetic flux surfaces. Inversion of the full model based on statistical methods allows taking into account all conceivable uncertainties accompanying Z(eff) measurement and provides uncertainties of the local Z(eff) values and valuable information on other uncertain parameters of the model. In this paper we show the first steps in developing a virtual Z(eff) diagnostic for W7-X which allows the optimization of the statistical model as well as of the future diagnostic setup.


Analysis of calcium and lead in calcium supplements by inductively coupled plasma-atomic emission spectrometry and graphite furnace atomic absorption spectrophotometry.
A method was developed to analyze various calcium supplements for Ca and Pb content. The analysis involves a dry ash of the supplements followed by wet digestion. The Pb is determined by graphite furnace atomic absorption spectrophotometry (GFAAS). Analysis of Ca is by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Ca supplements fortified with Pb at levels ranging from 0.25 to 10.0 micrograms/g yielded recoveries ranging from 82.7 +/- 4.2 to 105.0 +/- 1.7%. To test accuracy, the method was applied to National Institute of Standards and Technology standard reference materials (NIST SRMs) 1572 citrus leaves and 1486 bone meal. GFAAS analysis of SRM 1572 averaged 13.1 +/- 0.6 micrograms Pb per g (certificate value, 13.3 +/- 2.4 micrograms Pb per g), and analysis of SRM 1486 averaged 1.34 +/- 0.11 micrograms Pb per g (certificate value, 1.335 +/- 0.014 micrograms Pb per g). ICP-AES analysis of SRM 1572 averaged 3.12 +/- 0.01% Ca (certificate value, 3.15 +/- 0.10% Ca by weight), and analysis of SRM 1486 averaged 27.63 +/- 0.27% Ca (certificate value, 26.58 +/- 0.24% Ca). The method's limit of quantitation (LOQ), on supplement Ca basis and a 1 g sample, averaged 0.75 micrograms Pb per 1 g Ca for supplements containing 9 to 35% Ca by weight. At a Pb level of 0.663 micrograms/g Ca, the reproducibility relative standard deviation (RSDr) averaged 7.3% and the repeatability relative standard deviation (RSDR) averaged 8.0%. It is recommended that the method be studied collaboratively.


Evaluation of Bioactive Glass and Low Viscosity Resin as Orthodontic Enamel Sealer: An In Vitro Study.
The study aimed to evaluate the effect of applying fluoride bioactive glass (FBAG) and Alpha-Glaze® (resin sealer) on the shear bond strength of orthodontic brackets to enamel bonded by Transbond XT, brushing−abrasion durability, and their protective effect against simulated cariogenic acidic attack. Materials include 135 extracted premolars that were divided into three groups—FBAG, Alpha-Glaze, and control. The shear bond strength test was measured using an Instron Universal Testing Machine. The brushing abrasion challenge took place with a tooth-brushing simulator. Transmitted light microscopy examinations were performed after the specimens were demineralized for 4 days. The results show that the shear bond strength values of the three groups did not report any statistically significant differences: FBAG (28.1 ± 5.5 Mpa), Alpha-Glaze (32.5 ± 7.4 Mpa), and control (30.7 ± 6.5 Mpa) p < 0.05. The Adhesive Remenant Index (ARI) study showed chipping of enamel in 6.6% of Alpha-Glaze and control specimens and 40% of specimens had their enamel surface covered with resin. Furthermore, 30% of the FBAG and 100% of the Alpha-Glaze sealer specimens resisted the abrasion test. In conclusion, FBAG can serve as an orthodontic-sealer capable of protecting the enamel surface surrounding orthodontic brackets. However, the Alpha-Glaze sealer did not offer the capability of protecting the enamel.


Predictors of problem gambling remission in adults: A Canadian longitudinal study.
Remission from problem gambling (PG) continues to be a priority of clinicians and researchers. Data from cross-sectional studies indicate that some correlates are more predictive of PG, and existing longitudinal studies have exclusively examined risk factors that predict emergence of PG. This study's objective is to fill in the remaining pieces of the puzzle by identifying factors that might facilitate remission from PG. A stratified sample of 10,199 Canadian adult gamblers were recruited from an online panel. Respondents who screened positively for PG at baseline and completed a follow-up assessment 1 year later (n = 468) were assessed on a series of modifiable gambling, psychosocial, mental health, and substance use variables. A forward stepwise logistic regression was conducted to identify the strongest predictors of remission from PG at follow-up. A Least Absolute Shrinkage and Selection Operator regression was also conducted to confirm the most relevant predictors. Out of 75 candidate variables, 10 were retained by the regression model. Two were related to cessation of specific gambling activities, two were related to gambling motivations, two were psychosocial in nature, two were related to substance use while gambling, and one was related to remission from a mental health disorder. The final and strongest predictor was PG severity at baseline. Although PG remission predictors were mostly gambling-related, psychosocial aspects may also be targeted by stakeholders aiming to reduce PG. Ceasing to use tobacco while gambling and diversifying leisure activities may be promising targets. Other mental health and substance use predictors may still possibly be relevant, but only for a subset of people with PG. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Effect of Nutrition on Statural Growth .
In children, proper growth and development are often regarded as a surrogate marker for good health. A complex system controls the initiation, rate, and cessation of growth, and thus gives a wonderful example of the interactions between genetics, epigenetics, and environmental factors (especially stress and nutrition). Malnutrition is considered a leading cause of growth attenuation in children. This review summarizes our current knowledge regarding the mechanisms linking nutrition and skeletal growth, including systemic factors, such as insulin, growth hormone, insulin-like growth factor-1, fibroblast growth factor-21, etc., and local mechanisms, including mTOR, miRNAs, and epigenetics. Studying the molecular mechanisms regulating skeletal growth may lead to the establishment of better nutritional and therapeutic regimens for more effective linear growth in children with malnutrition and growth abnormalities. .


Role of healthcare in Korean long-term care insurance.
With the rapid aging of the population, Korea introduced public long-term care insurance for older people in 2008. The long-term care insurance was designed as a separate scheme from the national health insurance, with eligibility qualifications and the certification process based on functional disability, benefits and coverage of community-based and institutional care, and a financing structure through multi-party contributions. Delivering appropriate health services to long-term care beneficiaries who manifest a high prevalence of comorbid chronic conditions with rising healthcare costs, however, presents a particular challenge. The lack of coordination between the health and long-term care sectors, limited consideration of physicians' assessments in the certification process, inadequate provision of health services in long-term care facilities, and overlapping and inefficient use of care resources act as barriers to providing comprehensive healthcare for older beneficiaries. Through active participation in the long-term care system, health professionals can help older patients navigate through the complex long-term care terrain to obtain quality healthcare.


Development of an in vitro model for the analysis of bovine endometrium using simple techniques.
This study aimed to develop an in vitro model for the analysis of the bovine endometrium. Immunofluorescent staining revealed that the hetero-spheroids and the cultured explants showed almost similar structure in the localization of bovine endometrial epithelial cells and endometrial stromal cells, except the glandular-like structure of the epithelial cells inside the explants. Gelatin zymography revealed that the hetero-spheroids did not express matrix metalloproteinases (MMPs) after 4 days of culture, but strong MMP expressions were observed in the cultured explants until 7 days of culture. Additionally, expression of progesterone receptor (PR), estrogen receptor alpha (ERα), type I interferon receptor 1 (IFNAR1) and 2 (IFNAR2) messenger RNA was observed both in the homo- and hetero-spheroids. The expression of oxytocin receptor (OTR) mRNA in E2 and E2+P4 (1,3,5(10)-Estratrien-3, 17β-diol + 4-Pregnen-3, 20-dinone) treated groups were significantly (P < 0.05) higher than that of the control group of spheroids. In case of cultured explants, the expression of PR and OTR mRNA were significantly (P < 0.05) higher in E2 treated groups compared to the control groups. Hepatocyte growth factor (HGF) mRNA expression was also higher in P4 treated groups at 10 days in culture (P < 0.05). In a nutshell, the in vitro model developed in this study for the analysis of the endometrium may provide a new platform for extensive research on bovine endometrial function.


Simultaneous Discrimination of Cys/Hcy and GSH With Simple Fluorescent Probe Under a Single-Wavelength Excitation and its Application in Living Cells, Tumor Tissues, and Zebrafish.
Owing to the important physiological sits of biothiols (Cys, Hcy, and GSH), developing accurate detection methods capable of qualitative and quantitative analysis of biothiols in living systems is needed for understanding the biological profile of biothiols. In this work, we have designed and synthesized a 4'-hydroxy-[1,1'-biphenyl]-4-carbonitrile modified with NBD group-based fluorescent probe, BPN-NBD, for sensitive detection of Cys/Hcy and GSH by dual emission signals via a single-wavelength excitation. BPN-NBD exhibited an obvious blue fluorescence (λmaxem = 475 nm) upon the treatment with GSH and reacted with Cys/Hcy to give a mixed blue-green fluorescence (λmaxem = 475 and 545 nm). Meanwhile, BPN-NDB performed sufficient selectivity, rapid detection (150 s), high sensitivity (0.011 µM for Cys, 0.015 µM for Hcy, and 0.003 µM for GSH) and could work via a single-wavelength excitation to analytes and had the ability to image Cys/Hcy from GSH in living MCF-7 cells, tumor tissues, and zebrafish by exhibiting different fluorescence signals. Overall, this work provided a powerful tool for thiols visualization in biological and medical applications.


A two-year randomized weight loss trial comparing a vegan diet to a more moderate low-fat diet.
The objective was to assess the effect of a low-fat, vegan diet compared with the National Cholesterol Education Program (NCEP) diet on weight loss maintenance at 1 and 2 years. Sixty-four overweight, postmenopausal women were randomly assigned to a vegan or NCEP diet for 14 weeks, and 62 women began the study. The study was done in two replications. Participants in the first replication (N = 28) received no follow-up support after the 14 weeks, and those in the second replication (N = 34) were offered group support meetings for 1 year. Weight and diet adherence were measured at 1 and 2 years for all participants. Weight loss is reported as median (interquartile range) and is the difference from baseline weight at years 1 and 2. Individuals in the vegan group lost more weight than those in the NCEP group at 1 year [-4.9 (-0.5, -8.0) kg vs. -1.8 (0.8, -4.3); p < 0.05] and at 2 years [-3.1 (0.0, -6.0) kg vs. -0.8 (3.1, -4.2) kg; p < 0.05]. Those participants offered group support lost more weight at 1 year (p < 0.01) and 2 years (p < 0.05) than those without support. Attendance at meetings was associated with improved weight loss at 1 year (p < 0.001) and 2 years (p < 0.01). A vegan diet was associated with significantly greater weight loss than the NCEP diet at 1 and 2 years. Both group support and meeting attendance were associated with significant weight loss at follow-up.


Smartphones in medicine: emerging practices in an academic medical center.
Advances in mobile phone technology now provide a myriad of resources to physicians' fingertips. However, the medical profession continues to struggle with potential for misuse of these devices. There is a need for better understanding of physicians' uses of smartphones in order to establish guidelines for appropriate and professional behavior. The purpose of the current study was to survey physicians' and medical students' practices concerning smartphone use in the healthcare setting. Physicians and medical students were asked to complete anonymous surveys regarding uses of smartphones within the past month in various healthcare settings. Overall, the participants reported distinctly different patterns in the uses they made of their phones in different settings (P<.001), with most individuals engaging in most behaviors while on break but few using their smartphones while with patients or during procedures. It appears that physicians and medical students make decisions about using their smartphones according to some combination of three considerations: degree of relevance to patient care, the appropriateness of the behavior in front of patients, and the issue of how disruptive that behavior may be.


Incorporation of realistic delivery limitations into dynamic MLC treatment delivery.
The clinical implementation of IMRT involves the use of a number of complex software-based systems, typically including an inverse planning system, a leaf sequencer, and a computer-controlled treatment delivery system. The inverse planning system determines the desired fluence patterns, the leaf sequencer translates those fluence maps into leaf trajectories, and the control system delivers those trajectories. While verification of intensity-modulated treatment fields has focused primarily on the dosimetric aspects of delivery, accurate delivery of the intended fluence distribution is dependent upon both the leaf sequencer and delivery control systems. Leaf sequencing algorithms typically do not incorporate many control system limitations, and this can lead to discrepancies between planned and delivered sequences. In this work, simple and complex fields were sequenced for the dynamic sliding window technique using different leaf speeds and tolerance settings to identify various limitations of the accelerator control system. This work was conducted on a Varian 2100 EX equipped with a Millennium 120 leaf MLC. The identified limitations were then incorporated into the sequencing algorithm using a limiting leaf velocity (less than the maximum leaf velocity), the leaf position tolerance, and the communications delay in the control system. Collision avoidance in leaf pairs was found to depend on a control system-enforced minimum gap between leaves and led to acceleration effects. By incorporating these effects into the leaf sequencing algorithm, dynamic sliding-window leaf sequences were produced which did not require beam interruptions or dose rate modulations for the parameter values used in calculating the sequence (dose rate, tolerance, leaf speed, and total monitor units). Incorporation of control system limitations into the leaf sequencing algorithm results in IMRT fields that are delivered with the prescribed constant dose rate, require less time to deliver, and have well-defined, calculable transmission dose characteristics.


The base-to-base induced-tropia prism test for detection of amblyopia: a pilot study.
To investigate the accuracy of the base-to-base prism test (BBPT), which entails inducing an esotropia with the use of base-in prisms before each eye, in the diagnosis of amblyopia. Participants were consecutive patients recruited from a pediatric ophthalmology practice who were able to perform logMAR acuity testing. All participants underwent an orthoptic examination, including logMAR visual acuity testing, and a sensorimotor evaluation. Patients with an interocular difference of 2 or more lines were considered to have amblyopia. Fixation preference was assessed by use of both the vertical fixation test and the BBPT. The agreement between the BBPT and visual acuity was analyzed and compared with the agreement between the vertical fixation test and visual acuity. Fifty-one consecutive patients aged 4 to 17 (mean, 9.8 years; SD ± 3.4) were included, of whom 11 were diagnosed with amblyopia. Kappa analysis showed moderate but significant agreement between the BBPT and logMAR (κ = 0.453, p = 0.001), whereas the vertical fixation test demonstrated only a fair agreement (κ = 0.254, p = 0.061). The overall sensitivity for the BBPT was 72.7% (95% confidence interval [95% CI], 43.4%-90.3%) but only 40% for the vertical fixation test (95% CI, 16.8%-69.7%). For the BBPT, specificity was 80% (95% CI, 65.2%-89.5%); for the vertical fixation test, 78% (95% CI, 63.3%-88.0%). The BBPT appears to be more sensitive than the vertical fixation test for detecting amblyopia in our patient population. The 2 tests had similar specificity.


Hematocrit and coronary heart disease.
Hematocrit values of patients with acute myocardial infarction have been reported by some workers to be higher than those found in controls; this has been denied by others. In these reported studies important postural, postprandial, age and stress effects have not been considered. In the present investigation hematocrits of healthy and coronary subjects were determined under the same "standard basal" conditions, in the morning hours, fasting or after a light breakfast, and in sitting position; patients studied had no acute illness or distress. A mean hematocrit of 49.1 +/- 2.4% was observed in 66 men with chronic coronary disease and of 46.8 +/- 3.2% in 68 healthy controls of the same age and sex, the difference being highly significant. The increased hematocrit and plasma viscosity in coronary patients creates significantly higher whole blood viscosity than that observed in healthy controls. This hemodynamic factor may be responsible for the development of clinical symptoms of coronary heart disease and possibly of the basic vascular disease itself.


Exploring the proteins and metabolites associated with male antennae responses to female exposure of Antheraea pernyi (Lepidoptera: Saturniidae) moths.
Detection of sex pheromones of insects relies on the antennae. The female pheromone signal transmission in the male antennae ultimately initiates the courtship and mating behaviors of males. To investigate the proteins and metabolites involved in this neural transduction, integrative proteomics and metabolomics analysis including tandem mass tag (TMT) proteomic quantification and liquid chromatography tandem mass spectrometry (LC/MS)-based metabolomics was adopted for comparing proteomic and metabolic changes between the antennae of male moths following stimulation by females and the non-stimulated males of Antheraea pernyi (Guérin-Méneville, Lepidoptera: Saturniidae) in this study. A total of 92 differentially expressed proteins (DEPs) containing 52 upregulated and 40 downregulated proteins and 545 differentially expressed metabolites (DEMs) including 218 upregulated and 327 downregulated metabolites were identified from the antennae of female-stimulated male moths based on the proteome and metabolome data, respectively. Bioinformatics analysis was performed for the 45 DEPs and 160 DEMs, including Gene Ontology (GO), Clusters of Orthologous Groups (COG), and Kyoto Encylopaedia of Genes and Genomes (KEGG) enrichment analysis and Human Metabolome Database (HMDB) annotation. A number of DEPs and DEMs related to neural transmission of female pheromone signals in the male antennae of A. pernyi were screened, including tyrosine hydroxylase, cryptochrome-1, tachykinin, arylalkylamine N-acetyltransferase, cadherin-23, glutathione S-transferase delta 3, tyramine, tryptamine, n-oleoyl dopamine, n-stearoyl dopamine, and n-stearoyl tyrosine. The altered expression levels of those proteins or metabolites were speculated involved in regulating the neuron activity for enhanced transmission of neural impulses and continuous perception, reception, and transduction of female pheromone signals. Our findings yielded novel insights into the potential mechanisms in the antennae of male A. pernyi responding to female attraction.


Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine.
Asthma was the most common comorbidity of patients hospitalized with 2009 H1N1 influenza. We sought to assess the immunogenicity and safety of an unadjuvanted, inactivated 2009 H1N1 vaccine in patients with severe versus mild-to-moderate asthma. We conducted an open-label study involving 390 participants (age, 12-79 years) enrolled in October-November 2009. Severe asthma was defined as need for 880 μg/d or more of inhaled fluticasone equivalent, systemic corticosteroids, or both. Within each severity group, participants were randomized to receive intramuscularly 15 or 30 μg of 2009 H1N1 vaccine twice 21 days apart. Immunogenicity end points were seroprotection (hemagglutination inhibition assay titer ≥40) and seroconversion (4-fold or greater titer increase). Safety was assessed through local and systemic reactogenicity, asthma exacerbations, and pulmonary function. In patients with mild-to-moderate asthma (n = 217), the 2009 H1N1 vaccine provided equal seroprotection 21 days after the first immunization at the 15-μg (90.6%; 95% CI, 83.5% to 95.4%) and 30-μg (95.3%; 95% CI, 89.4% to 98.5%) doses. In patients with severe asthma (n = 173), seroprotection 21 days after the first immunization was 77.9% (95% CI, 67.7% to 86.1%) and 94.1% (95% CI, 86.8% to 98.1%) at the 15- and 30-μg doses, respectively (P = .004). The second vaccination did not provide further increases in seroprotection. Participants with severe asthma who are older than 60 years showed the lowest seroprotection (44.4% at day 21) with the 15-μg dose but had adequate seroprotection with 30 μg. The 2 dose groups did not differ in seroconversion rates. There were no safety concerns. Monovalent inactivated 2009 H1N1 pandemic influenza vaccine was safe and provided overall seroprotection as a surrogate of efficacy. In patients older than 60 years with severe asthma, a 30-μg dose might be more appropriate.


An Unusual Case of Aortic Stenosis in Systemic Sclerosis.
Systemic sclerosis is a connective tissue disorder that frequently involves the heart. All cardiac structures can be involved but aortic valve involvement is rare. We report a case of an 83-year-old man with a history of systemic sclerosis presenting with shortness of breath. A transthoracic echocardiogram revealed severe aortic stenosis that could not be explained by other causes. These patients often pose challenges in management as they are not surgical candidates. Transaortic valvular implantation is a viable option for these patients.


Phenytoin-isoniazid interaction: a kinetic approach to management.
A case of phenytoin-isoniazid drug interaction is reported. Pharmacokinetic evaluation was performed on the basis of two different phenytoin serum concentrations obtained on two different dosage regimens. Whereas Vmax was found to be in the normal range, the patient's Km was increased five-fold. The literature regarding this interaction is reviewed. This case illustrates the usefulness of pharmacokinetic methods in the management of phenytoin-isoniazid interaction.


The proliferative role of insulin and the mechanism underlying this action in human breast cancer cell line MCF-7.
To explore the proliferative role of insulin and the potential mechanism in human breast cancer cell line MCF-7. MCF-7 cells were treated with different concentrations of insulin. Morphological observation and methylthiazolyltetrazolium (MTT) assay were used to detect the proliferation of MCF-7 cells. The expression of insulin receptor mRNA was detected by RT-PCR, with or without mitogen activated kinase (MAPK) signals blocked by their inhibitors: SP600125, the inhibitor of Jun N-terminal kinase (JNK), and PD98059, the inhibitor of extracellular signal-regulated (ERK1/2). Insulin increased the proliferation of MCF-7 cells in a concentration-independent manner. Western blotting implicated that 100 nM insulin induced activation of JNK and ERK. The expression of phosphorylated JNK was detected within 5 min after insulin treatment and sustained for an hour, while ERK was activated later than JNK, at the 30th min after insulin treatment. Then we reevaluated the proliferative effect promoted by insulin after MAPK signaling pathway was blocked by its inhibitors. The results showed that after inhibiting the activities of JNK and ERK, the proliferative effect of insulin was also attenuated. Western blot results showed that, while blocking the MAPK signaling pathway, 10 μM (ERK pathway inhibitor) could significantly inhibit phosphorylated activation of ERK1/2 with 200 nM insulin at 30 min, while no obvious inhibition with 20 μM SP600125 (JNK pathway inhibitor) of phosphorylated activation of ERK1/2 was noticed. It seems that insulin can stimulate the proliferation of MCF-7 cells in vitro. MAPK signal transduction pathway involves the proliferative effect, which also regulates the expression of insulin receptor, mediates and amplifies the insulin signaling pathway.


Women's attitudes to screening for neural tube defects.
The attitudes of 2254 pregnant and 262 other women to serum alpha-fetoprotein (AFP) screening for neural tube defects (NTDs) were investigated, the former by interview and the latter by questionnaires to which 228 replies were received. Over 97 per cent of the pregnant women wanted to be included in such a screening programme. Ninety-six per cent of other women who completed the questionnaire were in favour of national screening for NTDs but 14 per cent of them were uncertain about the action they would take if the test were positive.


Botanicals With Dermatologic Properties Derived From First Nations Healing: Part 2-Plants and Algae.
Plants and algae have played a central role in the treatment of skin conditions in both traditional First Nations healing and in modern dermatology. The objective of this study was to examine the evidence supporting the dermatological use of seaweed, witch hazel, bearberry, and mayapple. Four plants and algae used in traditional First Nations treatments of skin disease were selected based on expert recommendations. Several databases were searched to identify relevant citations without language restrictions. Seaweed has potential clinical use in the treatment of acne and wrinkles and may be incorporated into biofunctional textiles. Witch hazel is an effective and well-tolerated treatment of inflammation and diaper dermatitis. Bearberry leaves contain arbutin, a skin-lightening agent that is an alternative for the treatment of hyperpigmentation. Mayapple contains podophyllotoxin, a treatment for condyloma accuminata, molluscum contagiosum, and recalcitrant palmoplantar warts. Common plants and algae are replete with bioactive agents that may have beneficial effects on the skin. Further research will open the door to new and innovative products in the future. Limitations of this study include that the scope of our study is limited to 4 plants and algae, a small sample of the breadth of plants used by First Nations for dermatological treatments.


Cycloalkane and cycloalkene C-H bond dissociation energies.
Both C-H bond dissociation energies for cyclobutene were measured in the gas phase (BDE = 91.2 +/- 2.3 (allyl) and 112.5 +/- 2.5 (vinyl) kcal mol-1) via a thermodynamic cycle by carrying out proton affinity and electron-binding energy measurements on 1- and 3-cyclobutenyl anions. The results were compared to those for an acyclic model compound, cis-2-butene, and provide the needed information to experimentally establish the heat of formation of cyclobutadiene. Chemically accurate G3 and W1 calculations also were carried out on cycloalkanes, cycloalkenes, and selected reference compounds. It appears that commonly cited bond energies for cyclopropane, cyclobutane, and cyclohexane are 3 to 4 kcal mol-1 too small and their pi bond strengths, as given by BDE1 - BDE2, are in error by up to 8 kcal mol-1.


Identification and mapping of Sr46 from Aegilops tauschii accession CIae 25 conferring resistance to race TTKSK (Ug99) of wheat stem rust pathogen.
Mapping studies confirm that resistance to Ug99 race of stem rust pathogen in Aegilops tauschii accession Clae 25 is conditioned by Sr46 and markers linked to the gene were developed for marker-assisted selection. The race TTKSK (Ug99) of Puccinia graminis f. sp. tritici, the causal pathogen for wheat stem rust, is considered as a major threat to global wheat production. To address this threat, researchers across the world have been devoted to identifying TTKSK-resistant genes. Here, we report the identification and mapping of a stem rust resistance gene in Aegilops tauschii accession CIae 25 that confers resistance to TTKSK and the development of molecular markers for the gene. An F2 population of 710 plants from an Ae. tauschii cross CIae 25 × AL8/78 were first evaluated against race TPMKC. A set of 14 resistant and 116 susceptible F2:3 families from the F2 plants were then evaluated for their reactions to TTKSK. Based on the tests, 179 homozygous susceptible F2 plants were selected as the mapping population to identify the simple sequence repeat (SSR) and sequence tagged site (STS) markers linked to the gene by bulk segregant analysis. A dominant stem rust resistance gene was identified and mapped with 16 SSR and five new STS markers to the deletion bin 2DS5-0.47-1.00 of chromosome arm 2DS in which Sr46 was located. Molecular marker and stem rust tests on CIae 25 and two Ae. tauschii accessions carrying Sr46 confirmed that the gene in CIae 25 is Sr46. This study also demonstrated that Sr46 is temperature-sensitive being less effective at low temperatures. The marker validation indicated that two closely linked markers Xgwm210 and Xwmc111 can be used for marker-assisted selection of Sr46 in wheat breeding programs.


Liver engraftment potential of hepatic cells derived from patient-specific induced pluripotent stem cells.
Human induced pluripotent stem cells (iPSCs) are potential renewable sources of hepatocytes for drug development and cell therapy. Differentiation of human iPSCs into different developmental stages of hepatic cells has been achieved and improved during the last several years. We have recently demonstrated the liver engraftment and regenerative capabilities of human iPSC-derived multistage hepatic cells in vivo. Here we describe the in vitro and in vivo activities of hepatic cells derived from patient specific iPSCs, including multiple lines established from either inherited or acquired liver diseases, and discuss basic and clinical applications of these cells for disease modeling, drug screening and discovery, gene therapy and cell replacement therapy.


Gene expression profiles of mRNA, lncRNA, miRNA, and circRNA and their clinical implications in chronic rhinosinusitis with nasal polyps.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with complex pathophysiology and therapeutic strategies. Moreover, the molecular mechanisms underlying the pathogenesis of CRSwNP are incompletely understood. This study aimed to investigate the transcriptomic characteristics, ceRNA networks, and whether these molecular markers play a role in the occurrence and development of CRSwNP. Following RNA sequencing, a ceRNA network was predicted and constructed based on the sequencing results and multiple databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease ontology (DO) were applied to analyze the potential mechanisms in relation to the pathogenesis of CRSwNP. CIBERSORT was used to evaluate the immune cell infiltration levels in CRSwNP. The candidate genes of differentially expressed (DE) mRNA, DE-lncRNA, DE-miRNA, and DE-circRNA were verified by RT-qPCR, and the back-splice junction of circRNA was verified using Sanger sequencing. The clinical significance of differentially expressed genes was analyzed with correlation test and receiver operating characteristic curve. We identified 716 DE-mRNA, 230 DE-lncRNA, 42 DE-miRNA, and 46 DE-circRNA, and GO and KEGG enrichment analyses indicated that they were involved in multiple biological pathways, predominantly those associated with immunity and inflammation. DO analysis revealed CRSwNP is associated with diseases such as gastroesophageal reflux and allergic reactions. High expression of circ_0021727 was significantly and positively correlated with several important clinical indicators, and the area under the curve was 0.741. This study provides transcriptomic characteristics, which are potential biomarkers or therapeutic targets for the diagnosis and treatment of CRSwNP.


Paradoxical Induction of ALOX15/15B by Cortisol in Human Amnion Fibroblasts: Implications for Inflammatory Responses of the Fetal Membranes at Parturition.
Inflammation of the fetal membranes is an indispensable event of parturition, with increasing prostaglandin E2 (PGE2) synthesis as one of the ultimate products that prime labor onset. In addition to PGE2, the fetal membranes also boast a large capacity for cortisol regeneration. It is intriguing how increased PGE2 synthesis is achieved in the presence of increasing amounts of classical anti-inflammatory glucocorticoids in the fetal membranes at parturition. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) synthesized by lipoxygenase 15/15B (ALOX15/15B) has been shown to enhance inflammation-induced PGE2 synthesis in amnion fibroblasts. Here, we examined whether glucocorticoids could induce ALOX15/15B expression and 15(S)-HETE production to promote PGE2 synthesis in amnion fibroblasts at parturition. We found that cortisol and 15(S)-HETE abundance increased parallelly in the amnion at parturition. Cortisol induced ALOX15/15B expression and 15(S)-HETE production paradoxically in amnion fibroblasts. Mechanism study revealed that this paradoxical induction was mediated by p300-mediated histone acetylation and interaction of glucocorticoid receptor with transcription factors CREB and STAT3. Conclusively, cortisol regenerated in the fetal membranes can paradoxically induce ALOX15/15B expression and 15(S)-HETE production in human amnion fibroblasts, which may further assist in the induction of PGE2 synthesis in the inflammatory responses of the fetal membranes for parturition.


Understanding Pathway Complexity of Organic Micro/Nanofiber Growth in Hydrogen-Bonded Coassembly of Aromatic Amino Acids.
Rational engineering of one-dimensional (1D) self-assembled aggregates to produce desired materials for versatile functions remains a challenge. In this work, we report the noncovalent modulation of 1D aggregates at the micro/nanoscale using a coassembly protocol. Aromatic amino acids were employed as the model building blocks, and melamine (Mm) behaves as a modulator to form coassembly arrays with aromatic amino acids selectively. The selective self-assembly behavior between aromatic amino acids and Mm allows distinguishing and detecting Mm and aromatic amino acids from their analogues in macroscopic and microscopic scales. Dimensions and sizes of fibrous aggregates prepared from different amino acids show two opposite pathways from pristine assemblies to coassemblies induced by the addition of Mm. This pathway complexity could be controlled by the molecular conformation determined by α-positioned substituents. The developed hypothesis presents an excellent expansibility to other substrates, which may guide us to rationally design and screen 1D materials with different dimensions and sizes including the production of high-quality self-standing hydrogels.


[Role of lymphocytic choriomeningitis virus in the etiology of congenital hydrocephalus].
By the indirect immunofluorescence test, antibodies to lymphocytic choriomeningitis virus in titers of 1:32 to 1:512 detected in 12 out of 32 infants under 1 with congenital hydrocephalus. The majority of the mothers of these infants were also shown to possess these antibodies in low and moderate titers. The assumption that lymphocytic choriomeningitis virus infecting the fetus in utero may cause the development of hydrocephalus is substantiated. In 11 of 12 seropositive infants foci of chorioretinal degeneration were found.


Acquired uterine arteriovenous fistula due to a previous cornual pregnancy with placenta accreta: A case report.
The present report describes a case of an acquired uterine arteriovenous fistula, which, following surgery and postoperative pathological analysis, was confirmed as a previous cornual pregnancy with placenta accreta. The patient was a 37-year-old woman (gravida 3; para 2) who had previously delivered two children via cesarean section (in 2004 and 2010, respectively) and also had a spontaneous abortion (2008). She had experienced continuous menstrual bleeding for ~20 days and had a history of prolonged (~30 days) vaginal bleeding 13 months earlier. Other pregnancy-related diseases were excluded following a negative serum human chorionic gonadotropin test, and the diagnosis was confirmed by Doppler ultrasonography. An emergency hysterectomy was subsequently performed due to the large amount of vaginal bleeding. Postoperative pathology confirmed the uterine arteriovenous malformation and demonstrated that the cause was a previous cornual pregnancy with placental implantation. The patient successfully recovered following the surgery.


DnaC traps DnaB as an open ring and remodels the domain that binds primase.
Helicase loading at a DNA replication origin often requires the dynamic interactions between the DNA helicase and an accessory protein. In E. coli, the DNA helicase is DnaB and DnaC is its loading partner. We used the method of hydrogen/deuterium exchange mass spectrometry to address the importance of DnaB-DnaC complex formation as a prerequisite for helicase loading. Our results show that the DnaB ring opens and closes, and that specific amino acids near the N-terminus of DnaC interact with a site in DnaB's C-terminal domain to trap it as an open ring. This event correlates with conformational changes of the RecA fold of DnaB that is involved in nucleotide binding, and of the AAA+ domain of DnaC. DnaC also causes an alteration of the helical hairpins in the N-terminal domain of DnaB, presumably occluding this region from interacting with primase. Hence, DnaC controls the access of DnaB by primase.


Mutually exclusive versus co-occurring diagnostic categories: the challenge of diagnostic comorbidity.
Diagnostic comorbidity is the rule rather than the exception in both DSM-IV and ICD-10. Three types of comorbidity include true comorbidity (clinically distinct entities), artifactual comorbidity (a byproduct of the DSM/ICD strategy to split categorical diagnoses) and spurious comorbidity. DSM has established 'mutually exclusive' relationships between disorders to reduce such spurious comorbidity. Four types of mutually exclusive relationships are identified: (1) between disorders that are on different levels of the Kraepelinian-defined hierarchy (e.g., schizophrenia and major depressive disorder); (2) between categories with identical features that are split according to age or duration (schizophrenia and schizophreniform disorder); (3) between categories in which the defining features of one disorder are contained in the definition of more broadly-defined disorder (Asperger's disorder and autistic disorder), and (4) between categories in which the defining features of one disorder are an associated feature of another disorder (e.g., dysthymic disorder and schizophrenia). Although less comorbidity may be desirable to reduce diagnostic complexity, in the absence of knowledge about underlying pathophysiology, the trend in successive editions of the DSM has been to reduce diagnostic hierarchies and increase comorbidity (e.g., elimination of exclusion between panic disorder and major depression in DSM-III-R because of evidence of independence). It is important to understand that comorbidity in psychiatry does not imply the presence of multiple diseases or dysfunctions but rather reflects our current inability to apply Occam's razor (i.e., a single diagnosis to account for all symptoms).


A simple and affordable membrane-feeding method for Aedes aegpyti and Anopheles minimus (Diptera: Culicidae).
This study developed an artificial feeding (AF) method to replace direct host feeding (DHF) for the maintenance of Aedes aegypti and Anopheles minimus mosquito colonies. The procedure can be adopted by all laboratories due to its simple and affordable materials and design. The apparatus consists of heparinized cow blood contained in a 5cm diameter glass petri dish with 5cm(2) Parafilm M (Bemis(®)) stretched thinly over the top, with a pre-heated bag of vegetable oil placed underneath to keep the blood warm. Both parts are contained within an insulated Styrofoam™ box with a hole in the lid for mosquitoes to access the membrane. Mosquitoes are fed by AF for 15min at a time. Feeding rate and fecundity of Ae. aegypti mosquitoes feeding on the AF device were compared to those feeding on a live rat (DHF(r)), and of Anopheles minimus mosquitoes feeding on the AF device compared to those feeding on a human arm (DHF(h)). Aedes aegypti mosquitoes fed by AF or DHF(r) had similar feeding rates (38.2±21.5% and 35.7±18.2%, respectively) and overall egg production (1.5% difference). Anopheles minimus mosquitoes fed by the AF method had a lower feeding rate (52.0±1.0% for AF compared to 70.7±20.2% for DHF(h)) and overall egg production (40% reduction compared to DHF(h)). However, the number of eggs produced by AF-fed mosquitoes (1808 eggs per 100 mosquitoes) was still sufficient for colony maintenance, and with increased feeding time both parameters are expected to increase. Reduced feeding rate and overall egg production was observed when Ae. aegypti mosquitoes were fed on blood refrigerated for over two weeks. In conclusion, an AF device has been developed which can replace DHF for Ae. aegypti and An. minimus colony maintenance when using blood refrigerated for a maximum of two weeks.


The effects of a thermophile metabolite, tryptophol, upon protecting shrimp against white spot syndrome virus.
White spot syndrome virus (WSSV) is a shrimp pathogen responsible for significant economic loss in commercial shrimp farms and until now, there has been no effective approach to control this disease. In this study, tryptophol (indole-3-ethanol) was identified as a metabolite involved in bacteriophage-thermophile interactions. The dietary addition of tryptophol reduced the mortality in shrimp Marsupenaeus japonicus when orally challenged with WSSV. Our results revealed that 50 mg/kg tryptophol has a better protective effect in shrimp than 10 or 100 mg/kg tryptophol. WSSV copies in shrimp were reduced significantly (P < 0.01) when supplemented with 50 mg/kg tryptophol, indicating that virus replication was inhibited by tryptophol. Consequently, tryptophol represents an effective antiviral dietary supplement for shrimp, and thus holds significant promise as a novel and efficient therapeutic approach to control WSSV in shrimp aquaculture.


Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine in HIV-positive Spanish men who have sex with men (MSM).
Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine were evaluated in HIV-positive Spanish MSM. The prevalence of High Squamous Intraepithelial Lesions (HSIL) and genotypes of high-risk human papillomavirus (HR-HPV) were also determined, as well as risk factors associated with the presence of HR-HPV in anal mucosa. This is a randomised, double blind, placebo-controlled trial of the quadrivalent HPV (qHPV) vaccine. The study enrolled from May 2012 to May 2014. Vaccine and placebo were administered at 0, 2 and 6 months (V1, V2, V3 clinical visits). Vaccine antibody titres were evaluated at 7 months. Cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope) were performed at V1. Patients (n = 162; mean age 37.9 years) were screened for inclusion; 14.2% had HSIL, 73.1% HR-HPV and 4.5% simultaneous infection with HPV16 and 18. Study participants (n = 129) were randomized to qHPV vaccine or placebo. The most common adverse event was injection-site pain predominating in the placebo group [the first dose (83.6% vs. 56.1%; p = 0.0001]; the second dose (87.8% vs. 98.4%; p = 0.0001); the third dose (67.7% vs. 91.9%; p = 0.0001). The vaccine did not influence either the viral load of HIV or the levels of CD4. Of those vaccinated, 76% had antibodies to HPV vs. 30.2% of those receiving placebo (p = 0.0001). In the multivariate analysis, Older age was associated with lower HR-HPV infection (RR 0.97; 95% CI 0.96-0.99), and risk factor were viral load of HIV >200 copies/µL (RR 1.42 95% CI 1.17-1.73) and early commencement of sexual activity (RR 1.35; 95% CI 1.001-1.811). This trial showed significantly higher anti-HR-HPV antibody titres in vaccinated individuals than in unvaccinated controls. There were no serious adverse events attributable to the vaccine. In our cohort, 1 of every 7 patients had HSIL and the prevalence of combined infection by genotypes 16 and 18 was low. This suggests that patients could benefit from receiving qHPV vaccine. Older age was the main protective factor against HR-HPV infection, and non-suppressed HIV viremia was a risk factor. ISRCTN14732216 ( http://www.isrctn.com/ISRCTN14732216 ).


Effective use of magnetic resonance imaging in the assessment of children with possible growth hormone deficiency.
To present our experience with diagnosis of growth hormone (GH) deficiency in children and to determine which patients are most likely to benefit from magnetic resonance imaging (MRI). We retrospectively reviewed medical records of pediatric patients who underwent assessment for possible GH deficiency during a 6-year period and correlated clinical variables, stimulated GH responses, and MRI findings. Of 100 children who failed outpatient GH screening tests, 14 were classified as at risk for hypothalamic pituitary defects, and 86 were considered not at risk, having short stature only. Patients were further stratified by age, sex, growth variables, maximal GH response to provocative testing, and MRI findings. A significant relationship existed between the presence of risk factors, maximal GH of <5 mg/L, and sellar defects. With no risk factors, MRI scans showed normal findings in 15 of 17 patients with maximal GH of <5 mg/L, in 33 of 34 patients with GH between 5 and 10 mg/L, and in all 35 patients with GH of >10 mg/L. Abnormal MRI findings included posterior pituitary ectopy, decreased pituitary size, absent midline central nervous system structures, enlarged infundibulum, and hamartoma. In one child with a 4-year history of growth failure and a maximal GH of 3.5 mg/L, craniopharyngioma was diagnosed. MRI scans should be obtained in any child with multiple pituitary hormone deficiencies, hypoglycemia, ophthalmologic anomalies, low-stimulated GH, or acquired growth failure. Otherwise asymptomatic children with growth delay and maximal GH of >10 mg/L do not need routine MRI screening. Such a strategy could result in substantial cost savings.


Phantom nanoparticles as probes of biomolecular interactions.
A new light-scattering-based method to detect molecular interactions at the surface of low-refractive-index nanoparticles was recently proposed. Water-dispersed nanoparticles functionalized with receptors typical of immature bacteria cell walls were used to study the activity of the antibiotic vancomycin. This method subtly depends on the specific properties of the nanoparticles. Here we discuss, by comparative experiments and through theoretical evaluation, the effects of size, refractive index, electric charge, and dilution on the reliability and accuracy of the method. Quite surprisingly, perfect index matching and minimal size (i.e., maximum surface), which is almost attained in one of the colloids here employed, do not represent the ideal conditions. Rather, we show that a nanoparticle radius of 100 nm and a refractive index slightly below that of water yields the best signal/background amplitude. We also show that repulsive interactions can lead to artifacts in the adsorption isotherm, thus indicating that electrostatic stabilization should be kept at a minimum. The close agreement between the interaction strengths, as measured with two different nanoparticle systems, testifies to the reliability of the method.


Kruppel-Like Factor 4 (KLF4) and its Regulation on Mitochondrial Homeostasis.
Mitochondria are vital organelles that supply ATP and other energy metabolites to meet the bioenergetics demands of the cell. In environments of stress or increased energy requirement, mitochondria are highly dynamic and can undergo biogenesis, fusion/fission, or autophagy. The transcription factor family, Kruppel-Like Factor (KLF), is necessary to carry out normal cellular processes from proliferation to differentiation. Recently, its importance in metabolic homeostasis in various tissue types has gained much attention. A handful of evidence supports KLF4's involvement in regulating mitochondrial homeostasis in both healthy and cancer cells. In this review, we aim to summarize the available literature that demonstrates KLF4's ability to modulate the mitochondrial life cycle in: Cardiac tissue, in which KLF4-knockdown subsequently leads to Heart Failure (HF), andGlioblastoma (GBM), where its expression promotes extensive mitochondrial fusion and offers mild cell protection under serum-deprivation.


Indigenous Aphid Predators Show High Levels of Preadaptation to a Novel Prey, Melanaphis sacchari (Hemiptera: Aphididae).
The performance of four aphid predators, Hippodamia convergens Guerin-Meneville, Coleomegilla maculata DeGeer, Chrysoperla carnea Stephens and Orius insidiosus Say was compared on three prey species: Schizaphis graminum Rondani, Melanaphis sacchari (Zehntner), and Ephestia kuehniella Zeller eggs. Species predatory in both life stages (all except Ch. carnea) were reared on E. kuehniella eggs and switched to aphid prey for assessment of reproduction. Differences were greater between the E. kuehniella and aphid diets than between the two aphid species. Juvenile survival was high for all predators on all prey, except for O. insidiosus, which had survival on E. kuehniella > S. graminum > M. sacchari. The fastest development of Ch. carnea and O. insidiosus was obtained on E. kuehniella, whereas H. convergens developed fastest on S. graminum, and C. maculata did not differ among diets. S. graminum also yielded the largest H. convergens adults, whereas the largest adults of other predators were obtained on E. kuehniella. Female fecundity and egg viability were similarly high on both aphid diets for H. convergens and C. maculata, whereas, on E. kuehniella, 50% of the former entered reproductive diapause and the latter species had reduced fecundity. Reproductive success of Ch. carnea was S. graminum = M. sacchari > E. kuehniella, but it was similar among treatments for O. insidiosus, although female infertility ranged from 25 to 37.5%. We concluded that all the predators studied are preadapted to utilize sugarcane aphid as prey and have excellent potential to provide sustainable biological control of this newly invasive pest.


Percutaneous absorption of alkanoic acids I: A study of operational conditions.
The rate of penetration of propionic and butyric acids through excised porcine skin was determined in vitro in specific apparatus allowing optimal control of operational conditions. In one technique, the rate was followed by continuous pH-stat titration of acid appearing in the perfusate, in another, by periodic monitoring of [14C]propionic acid in the perfusate. With the assumption that Fick's equation applies to the process of penetration, it was found that the permeability coefficient, Kp, increases with increasing mass of neat penetrant applied per unit area to the donor side, increases with increasing concentration of penetrant in n-heptane as vehicle, increases with increasing temperature, Ea = 11.4 kcal/mol, and decreases with decreasing perfusion rate of the acceptor side when this rate is smaller than 60 mL/h.


Synthesis and characterization of mesoporous ceria with hierarchical nanoarchitecture controlled by amino acids.
In this work, we report the synthesis and characterization of mesoporous ceria with hierarchical nanoarchitectures controlled by amino acids. During the synthesis procedure, cerium oxalate precipitate was treated hydrothermally with different amino acids as crystallization modifiers, and hierarchically structured cerium oxalate precursors were obtained. Ceria can be produced after thermal decomposition of the cerium oxalate precursors. Structure and properties of the product were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, N2 adsorption analysis, and X-ray photoelectron spectroscopy (XPS) methods. The results indicate that the mesoporous ceria with hierarchical nanoarchitectures are composed of nanosized ceria crystallites as building units and possess high surface area and high concentration of oxygen vacancy. Depending on different amino acids as the crystallization modifiers, the ceria exhibit different morphologies, such as dendritic aggregation of rods, dumbbells of nanorod arrays, or aggregated spheres. It is proposed that both the type of functional side groups and the length of the side groups of the amino acids influence the morphologies of the ceria. Meanwhile, the solvent and hydrothermal treatment temperatures also play important roles in the morphological control. The method reported in this work would be regarded as a general way to fabricate mesoporous metal oxides with hierarchical nanoarchitectures.


Haloperidol Concentrations in Patients With Alzheimer's Dementia.
To investigate the relationship between clinical response and haloperidol blood concentrations in Alzheimer's dementia (AD) patients with behavior problems, 29 AD inpatients were assigned to a fixed oral dosage of haloperidol (0.5 mg, 1.0 mg, or 2.0 mg) every 12 hours for 3 weeks. BEHAVE-AD ratings and concentrations of plasma and RBC haloperidol and reduced haloperidol were obtained on Days 8, 15, and 22. Although no significant linear or curvilinear relationships were apparent between percent of change on BEHAVE-AD and plasma or RBC haloperidol concentrations, a good response (change ≥ 30%) was observed in 55% of the patients who entered the study.


Accumulation and interactions of beta-carotene and alpha-tocopherol in patients with adenomatous polyps.
The aims of the present study were: (1) to determine whether short-term supplementation of beta-carotene (BC) or vitamin E (VE; alpha-tocopherol) would result in their respective accumulation in normal colonic mucosa and in adenomatous polyps; (2) to determine whether the intake of BC would interfere with the concentration of VE in these target tissues. Blood and colonic biopsy samples were taken before and after supplementation. Eighteen volunteers with colonic adenomatous polyps were enrolled into this study. The supplementation lasted for 43 days and patients were examined over the whole period. Subjects were randomised into four groups according to the four different supplementations: placebo, natural BC (25 000 IU/day), natural VE (400 IU/day), combination BC/VE. Initially we were aiming for recruitment of 20 patients in each group, however after 2 y of study (1997-1999), we terminated the study because of slow recruitment and analysed the data. In placebo subjects after supplementation, the plasma concentrations of BC and VE remained unchanged, however only two patients were recruited in this group and therefore we did not include this group in our final analysis. In BC group, the plasma BC concentrations increased significantly (P<0.001), while VE concentrations were unchanged. In VE group, VE concentrations increased (P<0.01) and BC did not change, and in BC/VE group both BC (P<0.001) and VE levels (P<0.01) increased significantly. After supplementation, the tissue concentration of BC in normal colonic mucosa in BC group increased significantly (P<0.01) while the VE concentration did not change. In VE group, the concentration of VE in normal colonic mucosa increased slightly but did not reach statistical significance. However, VE concentration increased significantly (P<0.05) in the polyps of this group. In BC/VE group, in which patients received the combination treatment, the BC concentration of normal colonic mucosa increased (P<0.05) but, surprisingly, the VE concentration decreased significantly (P<0.01). Interestingly in the polyps, although the BC concentration increased (P<0.01), the concentration of VE was reduced moderately but did not reach statistical significance. Supplementation of BC in doses used in this study may have significantly interfered with the VE concentration in the examined tissue and probably with its metabolic pathway.


L-Glutamine enhances enterocyte growth via activation of the mTOR signaling pathway independently of AMPK.
Neonates (including human infants) require L-glutamine (Gln) for optimal intestinal health. This study tested the hypothesis that Gln enhances enterocyte growth via both mammalian target of rapamycin (mTOR) and AMP-activated kinase (AMPK) signaling pathways. Intestinal porcine epithelial cells (IPEC-1) were cultured for 3 days in Gln-free Dulbecco's modified Eagle medium containing 0 or 2 mM Gln. To determine the role of mTOR and AMPK on cell growth, additional experiments were conducted where medium contained 2 mM Gln and 10 nM rapamycin (Rap, an inhibitor of mTOR) or 1 μM compound C (an inhibitor of AMPK). IPEC-1 cell growth increased with increasing concentrations of Gln from 0 to 2 mM. Compared with 0 mM Gln, 2 mM Gln increased (P < 0.05) the amounts of phosphorylated 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6 kinase) proteins but did not affect abundances of total or phosphorylated AMPK protein. Gln also increased mRNA levels for Bcl-2, mTOR, p70S6 kinase, 4E-BP1, COX7C, ASCT2, ODC, SGLT-1, CFTR, Na(+)/K(+)-ATPase, HSP70, and ZO-1. Similarly, cells cultured with Rap and Gln exhibited higher (P < 0.05) abundances of phosphorylated 4E-BP1 and p70S6 kinase proteins than the Rap-only group, whereas abundances of phosphorylated mTOR and 4E-BP1 proteins were increased when AMPK was inhibited by compound C. Conversely, the amount of phosphorylated AMPK increased when mTOR was inhibited by Rap, suggesting a negative cross-talk between mTOR and AMPK. Collectively, these results indicate that Gln stimulates enterocyte growth by activating the mTOR signaling pathway independently of AMPK.


Midline and lateral field sound localization in the albino rat (Rattus norvegicus).
Six albino rats were used in tests of sound localization around midline and in left and right lateral field positions (i.e., 0 degree, -60 degrees, and +60 degrees azimuth). Each of the animals performed at high levels on the midline task but had great difficulty with tests in the left and right fields. Minimum audible angles for midline localization were obtained for 2 subjects and were estimated as 11.5 degrees and 13.5 degrees. Performance levels on the hemifield tests for each of the 6 animals, however, were too low to permit estimates of threshold even with speakers separated by 60 degrees. The differences between midline and lateral field sound localization are discussed.


Physiotherapeutic interventions before and after surgery for degenerative lumbar conditions: a systematic review.
Physiotherapeutic management of patients immediately following lumbar spinal surgery is common. However, there is considerable variability in the interventions provided. To assess the effect of peri-operative physiotherapeutic intervention in adults undergoing surgery for the management of degenerative lumbar conditions. The Cochrane Library, Medline, Embase, CINAHL and PEDro were searched from inception to August 2012. Randomised controlled trials investigating physiotherapeutic interventions prior to and immediately following surgery for degenerative lumbar conditions were included. Two reviewers extracted data independently using a standardised form. Risk of bias was assessed using a modified version of the Cochrane Collaboration tool. The quality of evidence was assessed using the GRADE approach, and the treatment effect size was calculated where comparable outcome measures were used across multiple trials. Four studies were included. There is very-low-quality evidence that pre- and post-operative exercise in addition to standard physiotherapeutic care may reduce pain, time taken to achieve post-operative functional milestones, and post-operative time off work. Results from one study indicated that there is no clear benefit or risk of harm from performing either prone or side-lying transfers. Very-low-quality evidence suggests that physiotherapy may improve pain and function following lumbar surgery. Due to low numbers of included studies and variation in the interventions assessed, the current evidence provides limited guidance for physiotherapeutic practice. Further research is required to determine the effectiveness of physiotherapeutic interventions in this population.